Chapter One – Answers
The woman has retro-orbital optic neuritis. In papillitis (optic nerve head inflammation), the optic disc is red and elevated. In retro-orbital optic neuritis, the examining doctor sees nothing (on doing a fundoscopy) and the patient states that he/she sees nothing!
Although many candidates are familiar with giant cell (temporal) arteritis, they don’t know where the vascular lesion is that is responsible for this sudden visual loss; the posterior ciliary arteries are the usual culprits. The ophthalmic artery is rarely a cause. The central retinal artery is a very rare cause (if ever) and would produce a milky white retina with a cherry red macular spot. The anterior choroidal artery is an intracerebral artery that has no orbital or ocular distribution. The temporal artery per se is involved, but it is not the cause of the visual loss.
Lhermitte's sign or phenomenon is due to the presence of a lesion (demyelinating plaques in this patient) residing at the posterior columns of the cervical cord. It is neither specific nor pathognomonic for multiple sclerosis, as it can be seen in any "posterior cervical column lesion", e.g., cervical cord trauma, tumors, and spondylotic compression. Anterior dorsal spinal cord lesion would cause paraparesis and "dissociated" sensory loss in the lower limbs; this usually results from anterior spinal artery occlusion.
Cardiac emboli usually lodge themselves at the proximal middle cerebral artery (MCA) or its main stem (the MCA is a medium-sized artery) causing a devastating type of stroke. This patient has a non-dominant hemispheric infarction in the territory of the whole area supplied by the right middle cerebral artery. The patient’s speech is slurred because of the upper motor neuron facial weakness affecting the labial constants; he is not If the dominant hemisphere is involved, he would have a global type of aphasia as the whole "language cortex” is damaged. Left internal carotid artery (supplying the dominant hemisphere) occlusions have a similar presentation. Lenticulostriate perforating arteries (small branches that stem from the proximal middle cerebral artery and supply the basal ganglia and internal capsule) occlusion would cause a "lacunar" type of stroke (visual field defects should be absent). Posterior cerebral artery occlusion would cause visual field defects or anomic aphasia but not a hemiplegia-hemianesthesia pattern. Embolic anterior cerebral artery occlusion is rare and would cause weakness in the contralateral lower limb mainly.
Myasthenia gravis is an autoimmune disease directed against the post-synaptic membrane of the motor end-plate of skeletal muscles; the end-plate is simplified and less folded than normal and has fewer acetylcholine receptors. The pre-synaptic area is normal and there is a normal amount of acetylcholine formation and release. Examples of pre-synaptic diseases are Lambert-Eaton myasthenic syndrome and botulism. In both of them, there is impairment of acetylcholine release; acetylcholine formation is normal and there is a normal number of post-synaptic receptors.
The Kayser-Fleischer ring can be seen with the aid of the slit-lamp, high plus ophthalmoscope, or even by the naked eye (in some cases). It resides at the posterior surface of the cornea in its Descemet’s membrane. It is an important sign in Wilson’s disease patients who have neurological involvement.
Multiple sclerosis targets the CNS white matter with inflammatory demyelinating plaques. Later, these plaques may extend to and involve the overlying cortex. The latter may cause epilepsy, which is an uncommon late complication; this is a cortical sign in multiple sclerosis! The disease may also target the proximal areas of the spinal roots, giving rise to radicular signs. Schwann cells are the myelin-forming cells in the peripheral nervous system. The peri-venular areas are targeted by initial inflammatory cuffing and later plaque formation; the venules per se are not the primary target in multiple sclerosis.
Complex partial epilepsy is a form of focal seizure that arises from one or both temporal lobes; EEG would show epileptiform activity in one or both temporal lobes. Brain MRI usually discloses atrophy in one or both hippocampi with a dilated temporal horn of the lateral ventricle (hippocampal sclerosis).
This is a simple focal motor seizure arising from the hand motor cortical area of the left frontal lobe (the pre-central motor area).
These are formed, not simple, visual hallucinations. Formed visual hallucinations include faces, houses, cars, animals,…etc., while simple ones include lights, flashes, colors, lines…etc. The origin of such formed visual hallucinations is from the temporal lobe while simple visual hallucinations arise from the occipital cortex.
Certain midbrain lesions may cause some forms of visual hallucinations, so-called peduncular hallucinosis (but other midbrain signs should also be present).
Guillain-Barrè syndrome is primarily an acute peripheral demyelinating polyradiculopathy with or without secondary axonal degeneration. A primary axonopathic form is rare. Central demyelination occurs in multiple sclerosis.
Lambert-Eaton myasthenic syndrome (LEMS) is a disease of the membrane of the motor The presence of anti-P/Q type calcium channel antibodies (which attack the pre-synaptic area causing less release of acetylcholine) is highly sensitive and specific for LEMS of any etiology.
Paraneoplastic cerebellar degeneration is associated with anti-Yo (anti-Purkinjie cell) antibodies that are seen in ovarian cancer. Anti-Hu antibodies are seen in small-cell lung cancer and Hodgkin's disease. Anti-Ri antibodies are seen in breast cancer. Anti-Yo antibodies cross-react with cerebellar Purkinje cortical cells causing subacute pancerebellar degeneration. This woman has ovarian cancer and paraneoplastic anti-Yo-associated cerebellar degeneration.
Alzheimer's disease is a form of "cortical" type of dementia and targets primarily the central cholinergic nuclei (e.g., the nucleus basalis of Myenert). Sub-cortical type of dementia occurs in Huntington's disease, advanced Wilson's disease, advanced multiple sclerosis,…etc.
Pick's disease or dementia belongs to a group of idiopathic "frontotemporal" dementias. These disorders may be distinguished from Alzheimer's disease by:
•More prominent behavioral than cognitive dysfunction at presentation.
•Preferential atrophy of the frontal and the anterior temporal lobes on CT scans or MRIs.
•Brain biopsy showing Pick's cells and Pick's inclusion bodies and the absence of amyloid plaques and neurofibrillary tangles characteristic of Alzheimer's disease.
Wernicke's encephalopathy is produced by a deficiency of thiamin (vitamin B1), which as the pyrophosphate, is a required cofactor for the decarboxylation of pyruvic acid and ketoglutaric acid and for transferring groups in the hexose monophosphate shunt. In addition to the areas mentioned (stems a, b, c, and d), it affects the oculomotor, abducens, and vestibular nuclei. It does not affect the spinal cord.
Up to 75% of cases of subarachnoid hemorrhage (SAH) are due to a ruptured Berry's aneurysm. The peak incidence is in the and decades of life. Ruptured arteriovenous malformations comprise 10% of cases of SAH and are mainly seen during the to decades. The question did not mention any drug intake or a risk factor for subtle head trauma.
The woman has right-sided internuclear ophthalmoplegia (INO). The right eye is unable to adduct. This is due to lesions in the brainstem medial longitudinal fasciculus; this disconnects the nuclei of the ipsilateral cranial nerve from those of the contralateral cranial nerve producing dissociated or disconjugate eye movements (a characteristic feature of brainstem lesions). Convergence is intact, which differentiates INO from partial oculomotor nerve palsy. Abducens palsy would produce an inability to "abduct" the eye. In pontine horizontal gaze lesions, both eyes cannot move toward the site of the lesion. She has no limitation in the up-gaze (a midbrain sign).
Head trauma, usually a minor one, is the commonest cause of isolated cranial nerve palsy. Here, the left eye cannot be depressed in the adducted position (optimal position for an intact superior oblique muscle). Horizontal diplopia occurs in abducens palsy; angular diplopia suggests oculomotor palsy; vertical diplopia is a sign of trochlear palsy.
In sudden and isolated cranial nerve palsy, one should look at the pupil to differentiate between the medical palsy (e.g., diabetic vascular palsy, which is usually painless) and the surgical palsy (e.g., expanding Berry's aneurysm causing nerve compression and pain) because the treatment and prognosis are different. Diabetic vascular cranial nerve palsy is painful in 25% of cases (as in our patient) and is pupillary-sparing in 75% of cases (i.e., in 25% of cases, the pupil is dilated). Compressive lesions are usually painful and pupillary-involving.
Therefore, don’t always assume that sudden and painful cranial nerve palsy is due to an expanding intracranial aneurysm, or a sudden painless one is due to diabetes.
The overall picture is highly suggestive of idiopathic trigeminal neuralgia. The facial nerve has no sensory distribution on the face. Trigeminal neuralgia is not idiopathic if the patient is young, the pain is bilateral or alternating, or if there is any abnormal neurological finding (such as absent corneal reflex or facial weakness,…etc.).
The root has no deep tendon reflex "representation" in the lower limbs. The knee jerk represents while the ankle jerk represents The root supplies the muscles responsible for foot and big toe dorsiflexion; this patient has right-sided foot drop due to "lateral" inter-vertebral disc prolapse.
One of the ways to localize the lesion(s) in those with coma is the "breathing pattern". Generally, we have 5 types of breathing or respiration in comatose patients:
•Central neurogenic hyperventilation.
Cheyne-Stokes and central neurogenic hyperventilation are seen in metabolic disturbances and structural lesions at many sites of the central nervous system. Therefore, they have no localization value. Ataxic and gasping breathings are exclusively seen in pontomedullary area lesions and are useful "localizers".
The sudden onset of coma with focal brainstem signs strongly supports a diagnosis of an infratentorial (posterior fossa) lesion. Pupillary size and reactivity, ocular movements (induced by caloric testing or Doll's maneuver), motor responses to pain (e.g. decerebrate posturing), and breathing patterns are very useful for such localization. The pupils might be non-reactive (but not necessarily dilated or small). In addition, there may be gaze deviation towards the side of hemiparesis (in supratentorial lesions, there is gaze deviation away from the side of hemiparesis), disconjugate eye movements (like internuclear ophthalmoplegia), and ataxic or gasping breathing pattern.
Horner's syndrome and oculomotor nerve palsy would cause ptosis and "occlusion" of the eye; facial palsy would weaken the orbicularis oculi making complete "closure" of the eye difficult (facial palsy is not a cause of ptosis; a common mistake in examinations). This patient's meningitic process may be complicated by facial nerve palsy, or he has a middle ear infection with facial nerve involvement and secondary meningitis.
This female most likely has multiple sclerosis (MS); a constellation of optic neuritis, nystagmus, dysarthria, and the new development of transverse myelitis are highly suggestive. MS is an inflammatory demyelinating disease affecting the CNS white matter.
The overall clinical picture is highly suggestive of the lateral medullary syndrome of Wallenberg. The corticospinal tracts are located more anteriorly and medially within the medulla oblongata and therefore no weakness occurs in Wallenberg syndrome. There are crossed sensory loss (ipsilateral facial and contralateral body) which is highly characteristic of brainstem lesions.
This patient has a sensory cortical loss represented by loss of object identification put in the hand (astereognosis) and failure to identify numbers written on the palm (agraphesthesia). These are parietal cortical signs that are seen in both dominant and non-dominant parietal lobe lesions provided that the primary sensory input is normal.
This is the classical history of someone with a non-dominant (right) parietal lobe lesion causing "neglect". The patient may eagerly hunt for the examiner's face on the right when the voice is called from the left and the patient may deny that the left side of the body exists (even a dense hemiparesis may be cheerfully "overlooked").
This patient had a trauma to his left common peroneal nerve causing a left-sided foot drop.
Sodium valproate is an excellent antiepileptic medication with a broad spectrum of action (against grand mal, petit mal, and myoclonic epilepsies). Carbamazepine and phenytoin can worsen myoclonic and petit mal epilepsies. Sodium valproate is given 2-3 times per day, 500-3000 mg in divided doses. Unlike carbamazepine and phenytoin, it is not an enzyme inducer. Its side effects are alopecia, thrombocytopenia, weight gain, and a pancreatitis-like picture.
Carbamazepine is a potent enzyme inducer, including its own metabolism, and is usually given 3-4 times daily (for immediate-release preparations) and twice daily (for extended-release tablets). It can produce neural tube defects in 0.5% of pregnancies as well as craniofacial dysmorphism. A good amount of this medication is excreted in urine and is not safe for renal failure (unlike sodium valproate). It is highly effective in partial seizures and can be given as a second-line agent in generalized tonic-clonic seizures.
Phenytoin (and carbamazepine) worsens petit mal and myoclonic epilepsies. Phenytoin can be given once daily because it has a long half-life. It is a potent enzyme inducer. Unfortunately, it has many side effects in the long-term, like coarse facial features, hirsutism, pseudolymphoma, osteomalacia, and gum hyperplasia. It is usually a first-line medication in many types of epilepsies, not an add-on therapy.
Ethosuximide can cause weight loss. Other well-known side effects are depression, psychosis, skin rashes, and dyskinesia. Weight gain is seen with sodium valproate; ethosuximide and sodium valproate are given in absence attacks.
Pregabalin is related to gabapentin; the latter is excreted in the urine and is neither an enzyme inducer nor an inhibitor. It is used as an add-on therapy in focal epilepsies (with or without secondary generalization).
Topiramate decreases the effectiveness of oral contraceptive pills while the other stems (except lamotrigine) are enzyme inducers that increase the catabolism of these pills. Lamotrigine is an excellent alternative for those who wish to avoid pregnancy while taking oral contraceptive pills. Fosphenytoin is given as an intravenous infusion or intramuscular injection in status epilepticus; there is no oral preparation. Lamotrigine is also safe during pregnancy.
As is the case with other anti-epileptics, topiramate should not be withdrawn suddenly in those who receive the medication for a long time because of precipitating rebound seizures and status epilepticus. Topiramate can cause renal stones; therefore, dehydration should be avoided. It has been associated with acute myopia and acute angle-closure glaucoma, which are usually seen within 1 month of starting this medication. Choroidal effusions and anterior displacement of the lens have also been reported. If glaucoma occurs whilst the patient is on this medication:
•Seek ophthalmological advice immediately.
•Use measures to decrease the raised intra-ocular pressure.
•Stop topiramate rapidly as feasible (and use other alternatives simultaneously).
Consider withdrawing lamotrigine if any one of the following occurs: fever, flu-like illness, drowsiness, or worsening of seizure control whilst the patient is on this medication. Like all anti-epileptics, it can cause blood dyscrasias, including aplastic anemia. Concomitant sodium valproate therapy increases the plasma level of lamotrigine and increases the risk of Stevens-Johnson syndrome development; lamotrigine should be started at a low dose with gradual escalation.
Phenytoin often raises the blood level of phenobarbitone and lowers serum levels of carbamazepine, sodium valproate, clonazepam, and topiramate.
Intravenous sodium valproate can be given in status epilepticus when there is profound hypotension. Ethosuximide has no place in status epilepticus. Rectal paraldehyde is useful when there are no facilities for resuscitation, as it has a low risk for respiratory depression. Fosphenytoin can be given as an intravenous infusion or intramuscular injection (in normal saline 0.9% or glucose water 5%).
L-dopa is not contraindicated in skin basal cell carcinoma; malignant melanoma can be activated by this medication and is a contraindication.
Diabetes mellitus (not diabetes insipidus) is a cautious situation. Other cautious situations are the presence of pulmonary disease as well as renal and liver diseases; avoid sudden withdrawal. Ask patients to resume normal activities gradually.
L-dopa can cause reddish discoloration of urine. Other side effects are anorexia, vomiting, agitation, postural hypotension (labile hypertension is uncommon), dyskinesias (so-called L-dopa-induced dyskinesias; LIDs), hypomania and psychosis, depression, drowsiness, pruritis, and rarely elevated liver enzymes.
Entacapone is a COMT inhibitor; it prevents the degradation of L-dopa and potentates its action.
Long-term dopamine receptor agonist therapy is a well-known cause of retroperitoneal fibrosis. The patient’s shortness of breath may also result from pulmonary fibrosis and/or pleural effusion, both of which are side effects of dopamine agonists. Before starting ergot dopamine receptor agonists (bromocriptine, cabergoline,…etc.), you should have a baseline ESR, renal function tests, and chest X-ray. The patient should be asked to report dyspnea, persistent cough, and abdominal pain or tenderness.
Apomorphine is usually given for refractory motor fluctuations and the so-called “off periods” which are inadequately controlled by L-dopa or other dopaminergic agents; however, it usually causes dyskinesias during the "on" periods! Unfortunately, it increases the degree of any cognitive impairment present. It should be avoided in respiratory depression, CNS depression, and hepatic impairment.
Amantadine has a modest anti-Parkinsonian effect; if the response to it is not rewarding, it should be withdrawn gradually. Fluid retention and peripheral edema can be problematic; they should be avoided in heart failure. It is used only in idiopathic Parkinson's disease; it has no place in drug-induced Parkinsonism. Other side effects are confusion, hallucination, convulsions, insomnia, and inability to concentrate.
Triptans are contraindicated in ischemic heart disease, severe uncontrolled hypertension, and coronary spasm syndromes. They can cause a sensation of tingling, heaviness, and various tightness (should be discontinued if intense). They are effective as an abortive therapy in established migraine headaches not responding to conventional treatment, but should you avoid concomitant use of the "ergots".
Triptans, ergotamine, and dihydroergotamine are abortive therapies; they are not used in migraine prophylaxis. Other medications that can be used in migraine prophylaxis are pizotifen and topiramate. Clonidine should be avoided as it can aggravate depression in addition to causing severe insomnia. Methysergide is now rarely used, given the presence of safer drug regimens.
Riluzole offers a modest efficacy in amyotrophic lateral sclerosis by extending the time needed for mechanical ventilation by an average of 6 months. It is an anti-glutamate medication and is not used for spasticity per se. It can cause tachycardia, vertigo, dizziness, somnolence, and abnormalities in liver function tests. It is contraindicated in hepatic failure.
Donepezil is a reversible inhibitor of central acetylcholinesterase. It should be used with caution in asthma, COPD, hepatic impairment, peptic ulcer, sick sinus syndrome, and cardiac conduction abnormalities. It has a long half-life permitting a once-daily administration. It can exacerbate extra-pyramidal features.
Memantine is an NMDA receptor antagonist. It is licensed to be used in moderate and severe Alzheimer's disease. Be cautious in the presence of seizures, renal failure, and pregnancy. It is contraindicated in breastfeeding. It increases libido and can cause vomiting, anxiety, hypertonia, and cystitis.
Those patients, when examined early after the injury, would exhibit a confusional state; most patients are unable to incorporate and form new memories anterograde amnesia occurs for a variable period). Without obtaining a history of head trauma, most cases will be misdiagnosed as transient global amnesia rather than post-traumatic amnesia. Some degree of retrograde amnesia also occurs and usually covers a variable period of events before the trauma; however, this period of retrograde amnesia begins to shrink gradually, with the most remote memories being the first to return. In those who sustain a lapse of consciousness, the absence of anterograde amnesia should cast strong doubt on the diagnosis of post-traumatic amnesia; anterograde loss of the ability to form and store new memories is always seen following head traumas that have resulted in a loss of consciousness.
Patients with short periods of unconsciousness following cardiac arrest uncommonly exhibit prominent memory changes; memory problems are mainly seen in those who lost consciousness for more than 12 hours. Patients typically appear to have an isolated disorder of short-term memory because of the relative preservation of remote memory and immediate recall. Despite their memory disturbance, many patients exhibit a lack of concern about their environment and confabulation may be very prominent in some. A period of retrograde amnesia preceding the insult may occur.
Following a failed cardiac arrest, memory loss can be seen as an isolated syndrome; however, because watershed infarcts may co-exist, bi-brachial paresis, cortical blindness, or visual agnosia may accompany it. A highly characteristic feature in those who develop amnesic syndrome following carbon monoxide poisoning is striking affective symptoms; their brain CT scan may show hypodense areas in the basal ganglia and the cerebellar dentate nuclei.
The posterior cerebral artery supplies the medial temporal lobes, the thalami, the occipital cortex, and the upper midbrain; therefore, occlusion of one of both arteries can produce a multitude of neurological signs and symptoms. The posterior cerebral artery originates from the vertebrobasilar system, not the carotid one. The amnesic syndrome results from bilateral damage to the inferio-medial temporal i.e., to both hippocampi and adjacent structures, such as the dorsomedial thalami. This amnesia can be accompanied by alexia without agraphia, anomia, or sensory symptoms (e.g., peduncular hallucinosis). Impaired pupillary reflexes, vertical gaze palsy, or oculomotor nerve lesions can be detected on careful neurological examination, reflecting the involvement of the
Transient global amnesia may also occur in old people with risk factors for atherosclerosis, especially a prior ischemic event in the posterior cerebral arterial territory. Only 10% of patients will have recurrent attacks. Therefore, a single attack is more common, and patients can be reassured with high certainty that they will not have another one. It is a primary disorder of short-term memory that can last for minutes or days, typically for hours. The patient appears agitated and perplexed and may repeatedly inquire about their whereabouts, the time, and the nature of what they are experiencing. A highly characteristic feature during the attack is that patients retain their identity as well as their remote memories and registration ability; therefore, for inexperienced physicians, this may be diagnosed as malingering or conversion reaction, or more commonly, an unnoticed head trauma. The inability of the patient to form new memories accounts for the patient's repetitive questions (e.g., Where am I? What time is it?).
During the spell of transient global amnesia, patients appear dazed and confused and some may have a prominent agitation; the patient's obvious concern about the condition distinguishes transient global amnesia from most other organically based amnesic syndromes, but unfortunately may give rise to a suspicion that this amnesia is psychogenic. Many patients have risk factors for atherosclerotic disease and there may be a history of a prior brain ischemic event. Diffusion-weighted MRI can demonstrate many signal abnormalities during the spells; these are compatible with cerebral edema and may be related to spreading
These blackouts occur in chronic alcoholics as well as non-alcoholic individuals following heavy drinking. Before assuming that this "blackout" is due to alcohol per se, one should look for seizures, head trauma, and Wernicke's encephalopathy (all of these can complicate alcohol drinking). The disorder is self-limiting and no specific treatment is required; however, all patients should be advised about the reduction of ethanol and thiamin should be given to treat a possible Wernicke's encephalopathy.
Patients with psychogenic amnesia usually demonstrate a prior psychiatric history, additional psychiatric symptoms, or precipitating emotional stress. However, all of these can be difficult to obtain. Memory loss is patchy and inconsistent and may be strictly selective to some but not other events during such a period of amnesia. Loss of the patient's own name or identity is a highly characteristic feature of psychogenic amnesia; an exceedingly rare finding in organic amnesias. Despite such disorientation to person, orientation to place and time may well be preserved. Another characteristic feature is the relative preservation of recent memory while the old ones may be severely impaired; the reverse of the pattern that is customarily seen in organic amnesias. A rare type of dissociative amnesia is the so-called generalized amnesia, i.e., the patient forgets everything, all of a sudden!
A prior history of Wernicke's encephalopathy is present in 75% of Korsakoff's syndrome, i.e., it is absent in up to 25% of patients. Therefore, the diagnosis may be challenging in some patients. Most patients are chronic heavy alcoholics, but it also may be seen in malnutrition and famines. Residual signs of preceding Wernicke’s such as horizontal nystagmus or a mild cerebellar gait might be seen; these are helpful clues. Long-term memory is frequently but registration is characteristically intact. The patient is classically apathetic and lacks insight into his Many patients try to reassure the examiner that everything is OK and speak a lot to cover the memory gap; confabulation is often, but not always, present. All patients should receive thiamin to prevent the progression of the deficits, the existing deficits are unlikely to be reversed.
A variety of memory disturbances is usually seen in patients who survive an encephalitic process (depending on the infectious organism). Often, there is total amnesia for the period of encephalitis. Some patients may exhibit confabulation and the whole syndrome may exactly resemble that of alcoholic Korsakoff's syndrome; therefore, obtaining a thorough history is very important. The accompanying behavioral changes can overshadow memory disturbances, e.g., docility, indifference, flat affect and mood, inappropriate jocularity, and sexual illusions. Focal seizures are common.
It is a rare type of amnesic syndrome. Tumors that compress the floor or walls of the ventricle from without can produce amnesia. Malnutrition resulting from the tumor itself or its associated therapeutic modalities may cause Korsakoff's syndrome (the most important differential diagnosis in such patients but the differentiation may be challenging in some patients). Memory disturbance can be accompanied by endocrine disturbances, visual field defects, and papilledema. Amnesia may improve following neurosurgery, cranial irradiation, or both.
Limbic encephalitis presents as an amnesic syndrome that may precede the full-blown picture of the original lung tumor in weeks or months. This amnesia reflects the preferential affection of the gray matter of the hippocampus, cingulum, piriform cortex, inferior frontal lobes, insula, and amygdala. Anti-Hu antibodies may be detected in up to of patients in the serum and CSF. Depression and anxiety are very common early features. In many this amnesic state progresses to global dementia.
The CSF's non-specific findings are raised protein and mononuclear pleocytosis. The EEG's diffuse slowing or slow-wave and spikes are non-diagnostic. Brain MRI usually shows signal abnormalities in the medial temporal lobes; this contrasts with most para-neoplastic neurological syndromes where brain MRI is "normal". antibodies are the commonest antibodies to be found in this syndrome and are usually associated with small-cell lung cancer, while antibodies are found in testicular cancers; in both the prognosis is poor. The syndrome can progress, stay static, or even remit following successful treatment of the associated malignancy. Korsakoff's syndrome should always be excluded in patients who have malignancy; this group of patients is prone to developing malnutrition and the resulting thiamin deficiency is easily treatable.
Neurological changes in "normal" aging:
•Cognitive: Some degree of memory loss is expected and does not necessarily indicate dementia (so-called benign senescent
•Neuro-ophthalmologic: Some signs can be detected when the "eyes" are examined. The pupils are usually small (but regular) and react sluggishly to light (Argyll-Robertson pupil of tertiary syphilis is a differential diagnosis). The is slightly limited (and this should be differentiated from Parkinson's disease and progressive supranuclear palsy). The convergence of the globes is impaired. Bilateral partial ptosis is common.
•Motor: Loss of muscle bulk occurs, and this atrophy is best seen in the small muscles of the hands and feet (may be confused with motor neuron disease). Despite muscle atrophy, the muscle tone is increased and many elderly people assume a flexed (stooped) posture with a slow gait; this may give an impression of having Parkinson's disease.
•Sensory: Many sensory modalities are "normally" impaired to some degree; this is not equivalent to having a degenerating disease. There are impairments in vision (which increases the risk of hearing, taste, and olfaction, and the vibration sense is reduced (but the loss of joint position is never normal).
•Reflexes: Some primitive reflexes may appear (if the patient's cognition is normal, diffuse frontal lobes disease is a remote possibility). The abdominal and ankle reflexes are lost (but the loss of the knee jerks, whether symmetrical or not, should always prompt a search for a neurological disease).
Alzheimer's disease is the commonest cause of dementia and its incidence and prevalence rise with age. When adjusted for age, both sexes are equally The disease is progressive and no aborted cases have been reported. Alzheimer's disease is sporadic (and therefore, family history is usually negative); only 5% of cases are inherited as an autosomal dominant pattern (because of mutations in certain genes). Its neuritic plaques are extracellular deposits containing many types of proteins (e.g., beta-amyloid protein, presenilin-1 and 2), while the so-called neurofibrillary tangles are intracellular deposits containing tau protein (a protein).
Alzheimer's disease develops in all cases of Down's syndrome by the age of 40 years; the abnormal (extra) chromosome 21 might confer this susceptibility. Mutations in presenilin-2 and presenilin-1 (on chromosomes 1 and 14 respectively) can result in autosomal dominant Alzheimer's disease. It has been shown that the number of APOE4 alleles on chromosome 19 may influence disease development. One of the most striking features of the brains of Alzheimer's disease patients is that the cholinergic neurons are lost; there is a marked reduction in the level of choline acyltransferase (mainly seen in the hippocampus).
There is a marked reduction in the level of choline acyltransferase enzyme in the cortex and hippocampus of those patients and that is why central acetylcholinesterase inhibitors are used to increase the level of acetylcholine at these sites. In addition to PS2 genetic mutations, the abnormal PS1 gene on chromosome 14 is responsible for early-onset cases. PS2 genetic mutations are mainly seen in Volga Germans. All Down syndrome patients will develop Alzheimer's disease by the age of 40 years.
Impairment of recent memory is typically the first sign of the disease; this is often noticed by the family members. After this, most patients become disoriented to time and then to place (and the disease becomes prominent). Unfortunately, impairment in calculation and naming abilities might be prominent early manifestations in some patients; these will force the patient to leave work or to give up the management of the family finances early (and creates an early disease burden). Some Alzheimer's patients show varieties of gait abnormalities early in their course, such as short slow shuffling steps, flexed posture with a wide and difficulty in initiating walking. Visuospatial tasks can be impaired early, causing the patient to become lost easily. Depression can be prominent early in the course in many patients and may give way to a restless agitated state.
Many types of seizures, focal or generalized, can complicate the terminal stages of Alzheimer's disease; however, myoclonus is rare. Psychiatric manifestations gradually become prominent and frank psychosis can be difficult to manage; this can harm caregivers. Hemiparesis and extensor planters are rare late features despite being a cortical degenerative disease. Typically, Alzheimer's patients die after 5-10 years of their diagnosis (from inanition or infection).
Until there has been no single medication (or intervention) that can reverse (or arrest) the progression of Alzheimer's disease. Acetylcholine replacement therapy is only symptomatic and useful in mild cases for about 6 months and its long-term benefit is questionable. About 5% improvement in the baseline mini-mental status examination score can be obtained when using central acetylcholinesterase inhibitors; however, this is notable for a period of up to 6 months in early mild cases only (there is no place in severe cases). Because of its safe side effect profile and once-daily administration, donepezil is gradually becoming the drug of choice; no central acetylcholinesterase inhibitor is superior to other members of this Behavioral disturbances are very common in all stages of the disease and can be controlled cautiously with anxiolytic medications.
Most patients can continue their social, recreational, and limited professional activities early in their course. As the disease worsens, patients lose these abilities; more advanced stages can be very difficult to be managed at home. By doing injudicious actions or taking wrong decisions, patients should be protected from injuring themselves and their families. Most patients die after 5 to 10 years of their diagnosis; this is a long period of suffering, both for the patient and his/her family. Typically, Alzheimer's patients die from inanition or infection.
Pick's dementia patients are usually younger than Alzheimer's ones and loss of recent memory is not an early or prominent feature. Instead, Pick's patients have more prominent behavioral dysfunction at presentation. A very characteristic MRI feature is the preferential atrophy of frontal and temporal lobes; global cortical atrophy with compensatory hydrocephalus suggests Alzheimer's disease. The presence of Pick's cells and inclusion bodies is virtually diagnostic of Pick's dementia. The presence of prominent neuritic plaques and neurofibrillary tangles is consistent with Alzheimer's disease. The familial occurrence of frontotemporal dementia has been documented and mapped to chromosome 17.
Creutzfeldt-Jacob disease (CJD) is characterized by a rapidly progressive cortical type of dementia and startle myoclonus. It affects the cerebral cortex, basal ganglia, cerebellum, brainstem, and spinal cord; therefore, the disease is not limited to the brain. Males and females are affected equally, with a peak incidence at the age of 60-64 years. More than one member of a family is affected in 5-10% of cases only; conjugal cases are rare.
Human-to-human transmission (e.g., by corneal transplant) is very rare; human-to-animal transmission has been documented. The abnormal prion protein is present only in the CSF (not in any other body fluid); however, it is present in the liver, spleen, kidney, eye, lung, and lymph nodes. The cellular isoform is present normally in healthy neurons, but its function is still unknown. The presence of autonomic and endocrine dysfunction should point toward fatal familial insomnia.
Creutzfeldt-Jacob disease (CJD) may start as mild global cognitive impairment. Focal cortical signs may be found early in the course of the disease; in some patients, these may dominate the clinical picture. Hallucinations, depression, labile affect, euphoria, anxiety, and delusional disorders can occur. The patient's myoclonus may be induced by startle or it can be spontaneous. Extrapyramidal, pyramidal and cerebellar signs are common (reflecting the widespread involvement of the central nervous system). Visual field defects, cranial nerve and seizures are fewer common manifestations. The disease is rapidly aggressive, and fatal. Typically, it results in a coma or akinetic mutism within features of the so-called new variant CJD that you should know (an important examination theme) are:
•Earlier age of onset (mean age of affection is 30 years; the CJD peak is 60-64
•More prolonged course (the disease span is greater than 1 year; CJD is usually less than 1
•Invariable cerebellar involvement (in CJD, it is variable).
•Prominent early psychiatric manifestations (the disease can easily escape detection and is usually managed as major depression, psychosis,…etc. before other neurological signs and symptoms appear).
In the appropriate clinical setting, certain EEG changes are highly suggestive of CJD (such as periodic sharp waves or spikes); these changes are unfortunately transient and are absent in the new-variant form of the disease. MRI of the brain may show hyper-intense lesions in the basal ganglia; this is not specific at all. The CSF protein 14-3-3 is increased in CSF samples; it is a normal brain protein that is also increased in herpes simplex encephalitis and vascular dementias. The CSF total protein may be elevated; a non-specific finding. In sporadic cases, CJD can be diagnosed by immuno-detection of in brain tissues obtained by multiple biopsies.
CJD, at times, can be mistaken for early Alzheimer's disease, especially in patients with a less fulminant course and a paucity of cerebellar and signs. When subcortical involvement is prominent, Parkinson's disease appears in the differential diagnosis list. Some patients have prominent cortical focal signs early in their course that may wrongly suggest an intracranial space-occupying lesion. The mean duration of illness is 7-9 months. Although transient improvement may occur, it is invariably fatal.
Normal pressure hydrocephalus is a potentially reversible cause of a subcortical type of dementia; it "may" respond to shunting. It is usually idiopathic; however, it can follow meningitis, head trauma, or subarachnoid hemorrhage. The resulting dementia is often mild (and insidious) and is typically preceded by gait disorder and urinary incontinence. Because of the subcortical affection, focal cortical signs are rare.
The earliest manifestation of normal pressure hydrocephalus is the gait disorder; there is unsteady standing and difficulty in initiating walking in the absence of ataxia or weakness. Because urinary incontinence is a relatively late feature, many patients may be unaware of it; fecal incontinence has been reported as rare. Pyramidal signs may occur but they are uncommon features. The prominent involvement of the frontal lobes is reflected by the appearance of frontal release signs. There is no papilledema.
Characteristically, the CSF opening pressure is either normal or low; raised CAF opening pressure should cast doubt upon the diagnosis of normal pressure hydrocephalus. Brain imaging should show no obstructing mass lesion; the hydrocephalus is communicating. Delayed clearance and failure of the radio-isotope ascent over the cerebral convexities are seen in cisternography. Shunt infection, subdural hematoma, and shunt malfunction (which necessitates shunt removal) occur in 30% of patients who undergo shunting surgery.
The Lewy body type of dementia comes only second to Alzheimer's disease as causes of dementia; up to of elderly demented patients who undergo autopsy have round eosinophilic intra-cytoplasmic neuronal inclusion bodies termed Lewy which are present in the cerebral cortex and brainstem. Lewy bodies contain alpha-synuclein (a protein that is also found in Lewy bodies of Parkinson's disease) and tau (which is present in Alzheimer's disease and frontotemporal dementias). A highly distinguishing feature (from Alzheimer's disease) is that cognitive decline occurs without a prominent early loss of recent memory.
A highly characteristic feature is the fluctuating cognitive function without prominent early impairment of recent memory. Well-formed (not simple) types of visual hallucinations add to the morbidity of the disease and put pressure on the patient's caregivers. Parkinsonian features are common, especially rigidity and bradykinesia; however, tremor is uncommon and is usually mild and symmetric. Those patients may respond to donepezil, but the response is short-lived and not that prominent. Lewy body dementia patients are very sensitive to the extrapyramidal side effects of antipsychotics. Therefore, these medications should be avoided.
The mechanism behind cognitive decline in patients having an intracranial mass (or masses) is usually multi-factorial and cannot be explained by a single change; brain edema, compression of adjacent brain structures, raised intracranial pressure, and impairment of cerebral blood flow is implicated in the pathogenesis. Gliomas arising from the frontal or temporal lobes or the corpus callosum are the usual causes of this type of dementia; although such tumors tend to infiltrate the subcortical white matter extensively, they initially give rise to few neurological signs. Most patients have apathy, mental slowness, impaired and subtle personality changes; however, a careful examination can uncover many cortical signs. Focal or generalized seizures might occur.
In general, AIDS-dementia complex is the commonest neurological complication of HIV infection; actually, it is more common than opportunistic brain infections. At least 50% of patients experience a variable degree of cognitive impairment during the later or the pre-terminal course of the disease. It is an AIDS-defining illness that might be the presenting feature. HIV-1 does not appear to replicate within brain neurons or glia in vivo, and the loss of these cell types is not prominent in the brains of patients with complex. This may suggest that neuronal function is impaired by an indirect neurotoxic mechanism (by releasing certain cytokines from HIV-infected monocytes, or
The onset of AIDS-dementia complex is usually insidious with cognitive and behavioral changes (e.g., easy forgetfulness, apathy, social withdrawal) and motor symptoms (e.g., unsteady gait, leg weakness, and impairment in handwriting). The rapid downhill course suggests another or co-existent disease. At pre-terminal stages, most patients are vegetative.
Brain MRI shows diffuse cortical atrophy with ventricular dilatation and hyper-intense subcortical signals on images. The CSF can show mononuclear pleocytosis, not polymorphonuclear one. Oligoclonal CSF bands are detected; a non-specific finding which is also seen in syphilis, sarcoidosis, and multiple sclerosis. While the CSF opening pressure is always normal, its protein content is raised; the latter is the commonest CSF abnormality, which is seen in 65% of cases. Note that the CSF of these patients could be entirely normal; therefore, a normal CSF examination does not refute the diagnosis of the AIDS-dementia complex. Most patients usually die within 1-9 months from aspiration or opportunistic infections. The course could be steadily progressive or acutely exacerbated by systemic such as pulmonary infections.
General paresis of insane (GPI) was the commonest cause of dementia and psychiatric disorders related to neurosyphilis in the pre-penicillin era. Global intellectual deterioration with grandiosity, depression, psychosis, and focal weakness usually follows an initial phase of vague personality changes and memory loss. The usual terminal events are incontinence and seizures. A highly characteristic sign is the so-called trombone tremor of the tongue. There might be a dull or vacant facial expression.
After receiving penicillin, the condition may improve, or even progress. Whether the treated patient is symptomatic or not, a persistently abnormal CSF profile indicates failure of therapy; those patients should be re-treated. Follow-up visits and repeated CSF examinations are very important.
CNS infection with the JC virus (Papovavirus) results in progressive multifocal leukoencephalopathy (PML). Asymptomatic infections are very but clinical disease is very rare; in those with immune suppression, the disease occurs due to viral re-activation. The virus infects oligodendrocytes leading to diffuse and patchy demyelination that usually targets the white matter of both cerebral hemispheres (but it involves the brainstem and cerebellum to some degree). Once symptomatic, it results in death within 3-6 months. The disease is usually seen in patients with immune suppression (e.g., leukemia, lymphoma, systemic cancers, organ transplant recipients,...etc.).It is rarely seen, if ever, in immune-competent hosts.
There are no systemic features (fever, malaise,…etc.) caused by the JC virus itself, but the systemic manifestations of immune suppression might be seen, such as chest infections and oral candidiasis in AIDS patients. Altered mentation with hemiparesis and visual field defects are the classical presenting features. Seizures are characteristically absent; their occurrence should prompt the neurologist to search for an alternative/associated condition.
The CSF profile in those patients is usually normal; uncommonly, it may show raised protein or raised white cells. The usual findings on brain MRI are multifocal superficial subcortical white matter lesions located near the gray-white matter junction that lack mass effect and do not enhance following contrast administration. The diagnosis is completely secured by examining a brain biopsy specimen; however, this is rarely done in clinical practice; doing PCR (polymerase chain reaction) for the JC virus genome in the CSF can aid the diagnosis. Unfortunately, no treatment is effective.
This syndrome is uncommon in clinical practice, which is seen in malnourished alcoholics. It has a variable course; acute, subacute, or Coma finally ensues in the victims. Only symptomatic measures are used to treat it (there is no specific treatment), and cessation of drinking and improvement in nutrition is advised. The outcome is highly variable; patients may die, survive with dementia, or recover!
The disease develops over many years in those on regular hemodialysis programs. Aluminum gradually accumulates in the body due to aluminum in the dialysate fluids; this may be aggravated by aluminum-containing anti-acids. The disease has an aggressive resulting in death within 6 months. Although the EEG of patients is highly abnormal with many changes that can be detected, these changes are characteristically reversible by diazepam. The disease is now very rare because of the removal of aluminum from dialysate fluids.
Non-Wilsonian hepatocerebral degeneration should be differentiated from alcoholic cerebellar degeneration (the latter primarily affects gait). The course is usually progressive but may be punctuated by episodes of acute hepatic encephalopathy. There is no specific treatment; however, some degree of improvement following L-dopa or bromocriptine may occur. The CSF is almost always normal apart from raised glutamine level, although slightly raised protein may be found.
This type of brain hematoma is usually seen between the ages of 50-70 years. A prior history of head trauma is absent in 25% of cases. The subacute hematomas may be easily missed on brain CT scans because bilateral hematomas are isodense with the brain and there is no midline shift; the hematomas may be demonstrated by contrast CT scans or MRI. In a few cases, its demonstration requires cerebral angiography which should always be done bilaterally. Other risk factors for subdural hematoma are alcoholics, epilepsy, treatment with anticoagulants, cerebral atrophy from any cause, ventricular shunts, and long-term hemodialysis. Headache is the usual first feature to start with; seizures are uncommon.
After Alzheimer's disease and dementia with Lewy bodies, vascular dementia ranks on the list of common causes of dementia. The numbers of ischemic strokes, their brain location, and the total infarct volume required for a stroke to produce dementia are still uncertain. Almost all patients are hypertensive; normal baseline blood pressure should make you think of another diagnosis.
Pseudo-bulbar, not bulbar, palsy is common and those patients demonstrate dysarthria, dysphagia, and pathological emotionality. MRI is the imaging modality of choice. Patients without a history of hypertension require careful assessment and work-up. All patients should be tested for polycythemia, thrombocytosis, and cardiogenic emboli. The mainstay in the treatment is to prevent recurrent strokes; control hypertension and other risk factors and treat any associated disease.
Because depression is common and treatable, distinguishing between the two disorders is very important. Depression can be a feature of dementia and both disorders often coexist; adding more confusion to the clinical picture. When depression is considered, a psychiatric referral should be done. Prominent changes in sleep, appetite, sexual desire, and weight are in favor of depression. Somatic complaints are very common in depressed patients. The mood is extremely depressed in the morning hours in depression.
Glioblastoma multiforme (GM) accounts for about 20% of all intracranial neoplasms, 55% of all glial tumors, and more than 90% of supratentorial gliomas. GM is usually seen around the age of 60 years, but no age is exempt. These tumors have a slight male preponderance of 1.6:1 and almost all cases are sporadic (i.e., there is a negative family history). Most of them are in the cerebral hemispheres within their deep white matter and they quickly infiltrate the brain extensively; some time may attain an enormous size before attracting medical attention.
Characteristically, glioblastoma multiforme (GM) is a highly infiltrative tumor. Part of the lateral ventricle is usually distorted and both lateral and ventricles may be displaced contralaterally. Apart from extending to the meningeal surfaces, these highly aggressive tumors may reach into the ventricular surface causing raised CSF protein with mononuclear cell pleocytosis. Extra-cranial spread (mainly seen in the bones and lymph nodes) is very rare, except when craniotomy has been done (i.e., providing a portal for exit). A highly characteristic aggressive nature of the disease is to involve more than one lobe and spreads to the other side via the corpus callosum. Around 3-6% of GM tumors are multicentric (which increases their virulence).
The tumor may be mottled grey, red, brown, or orange depending on the degree of hemorrhage and Microscopically, there are prominent hypercellularity, cellular pleomorphism, and nuclear atypia (indicating highly aggressive malignancy). The tumor cells "arise" from anaplasia of mature astrocytes; meningiomas arise from meningothelial cells of the arachnoid mater. Cystic areas within the tumor mass are commonly seen, which impart a hypodense signal on brain imaging. The tumor vasculature may undergo sarcomatous changes with prominent reticulin and collagen interstitium, due to the elaboration of a growth factor by the tumor tissue.
These highly aggressive tumors (i.e. grade IV malignant gliomas or glioblastoma multiforme) can never be cured. Even with an aggressive multimodality approach, survival can be prolonged from 6-9 months to 12 months; a figure that is too small to have any significance given the morbidity incurred by the treatment. The multicentricity and infiltrative character defy the scalpel. Intrathecal chemotherapy has no place at all. Chemotherapeutic regimens have a marginal benefit on survival, either carmustine alone, or a combination of procarbazine, lomustine, and vincristine (PLV). Brain radiotherapy with 1500-2000 cGy increases survival by an average of 5 months only. Although surgical intervention cannot cure these tumors, de-bulking should be always done to have a pathologic specimen and to decompress the intracranial compartment.
These brain tumors usually target people in their and decades, while the decade in children is the usual age of affection. Low-grade gliomas are slowly growing tumors with infiltrative character and a tendency to form large cavities or pseudocysts. A highly characteristic feature of low-grade gliomas is that the location of the tumor is usually influenced by the age of the patient; for optic and thalamic gliomas are almost only seen in children. Fine granules of calcium can be seen in these tumors, but are more commonly seen in oligodendrogliomas; therefore, the presence of calcification is not against the diagnosis. They are surrounded by little vasogenic edema. These tumors tend to show marked enhancement after gadolinium administration.
There is diffuse infiltration of the brain hemispheres with neoplastic glial cells involving much of one cerebral hemisphere or both, with sparing of neuronal elements and without a discrete tumor mass being identified. The tumor cells compress the ventricular system and one or more large confluent areas of signal changes may appear in brain imaging. The tumor cells can cross to the other side via the corpus callosum (and also thicken the corpus callosum). Pancephalic headache, vague personality changes, impaired mentation, and seizures comprise much of the clinical picture, and florid papilledema (like other high-grade gliomas) is usually detected at the time of presentation. Enhancement in brain imaging is scanty, which differentiates it from cerebral lymphoma (the top-ranked differential diagnosis). Generally, the prognosis of these tumors is gloomy, and surgery is futile. Corticosteroids have if any effect, possibly because of the paucity of cerebral edema. The benefit of radiation is uncertain.
Oligodendrogliomas are derived from oligodendrocytes or their precursors. About 50% of oligodendrogliomas are mixed which are grossly indistinguishable from other gliomas, suggesting that their precursor cells are pluripotential. They are firm, pink-grey, multilobulated, and relatively avascular No age is exempt, but these tumors are mainly seen in the and decades. They comprise about 5% of all brain gliomas and, therefore, are relatively infrequent.
The frontotemporal area is the commonest site for oligodendroglioma; up to 70% of these tumors can be found There is little or no surrounding edema with scanty contrast enhancement on brain imaging (but the aggressive and mixed ones may show contrast enhancement). Streaks of calcification can be seen in 50% of cases upon doing brain CT scanning; a helpful clue. The typical neoplastic oligodendrocyte has a small nucleus and a halo of unstained cytoplasm (a fried egg appearance). By extending to the pial surface and to the ependymal wall, it can disseminate to the meninges, ventricles, and subarachnoid spaces.
Ependymomas arise from well-differentiated ependymal cells lining the ventricles of the brain and central canal of the spinal cord. These tumors proved to be more complex and more variable than other gliomas. Generally, they are three types: ependymoma, ependymoblastoma, and the myxopapillomatous type. The myxopapillomatous type is seen exclusively in the filum terminale of the spinal cord. The commonest site for ependymal tumors is the ventricle. The tumor cells tend to form rosettes (canals) and pseudo-rosettes (circular arrangement) around the blood vessel. There is high mitotic activity, nuclear atypia, endothelial proliferation, and necrosis (reflecting the aggressive nature of these tumors).
Meningiomas account for 15-20% of all intracranial neoplasms. Male to female ratio is 1:2 (i.e. more common in females). The highest incidence is seen in the and decades (therefore, they generally are uncommon in young people). Whether environmental or therapeutic, irradiation increases its incidence, and these radiation-induced tumors tend to occur at a younger age and to be more aggressive. Meningiomas are associated with the loss of chromosome 22 or a deletion of part of it; therefore, they can be multiple in neurofibromatosis type II (which has the same mutated chromosome).
The tumor arises from meningothelial particularly from those forming the arachnoid but the precise origin of these tumors is still not settled. Meningiomas take the shape of the space in which they grow; some tumors are flat and plaque-like, while others are rounded and lobulated. Because of their origin, they are extra-axial and compressive; "some" might be invasive, however. meningiomas are rare and arise from the covering arachnoidal cells of the choroid plexus. A characteristic feature is that the tumor cells tend to encircle each other forming whirls and to form psammoma bodies (laminated calcific concretions).
The commonest sites in descending order are the Sylvian fissure, the parasagittal surface of the frontoparietal area, the olfactory groove, the lesser wing of the sphenoid bone, the tuberculum sellae, the superior surface of the cerebellum, cerebellopontine angle, and finally the spinal cord.
Meningiomas are extra-axial in position and exert their effect mainly by compressing the underlying brain. Some are invasive and have an intra-axial component (but the bulk is extra-axial).
There are three possibilities when a meningioma has underlying brain edema (which is vasogenic edema): secretory, atypical, and frankly malignant meningiomas (which constitute no more than 5% of all meningiomas in general).
The incidence of primary cerebral lymphomas in hosts is rising with no explanation. There is a preponderance of men with the peak incidence in the through the decades, or in the and decades in AIDS patients. These tumors are usually of large B-cell type. The B-lymphoblastic cell is the tumor cell, and the fine reticulum and microgliacytes are secondary interstitial reactions derived from fibroblasts and microglia or histiocytes. T-cell lymphomas are rare tumors of the brain but do occur in both individuals and AIDS patients. The tumor is multicentric and deep within the white matter of the cerebral hemispheres. The cerebral hemispheres are the usual target (60%) and localization is common. The eye (vitreous, uvea, and retina) is involved in 20% of cases; therefore, a vitreous biopsy can make the diagnosis, but usually, it is not done in clinical practice.
It is a pinkish-grey, soft, ill-defined infiltrative mass. Its clinical course can exactly resemble that of glioblastoma multiforme but with a vastly different response to treatment. The EBV genome is found in both, immune-compromised and immune-competent patients. Because it is multi-centric and deep, surgery is ineffective, except in rare instances. Cranial irradiation and steroids produce a partial response in the majority of or rarely a complete but the tumor, unfortunately, recurs in more than 90% of cases. Generally, the survival is 10-18 months in immune-competent patients; much shorter in AIDS (or other immune-suppressed) patients.
About 80% of secondary tumors localize within the supratentorial while 20% of them occur in the posterior fossa, corresponding roughly to the relative size and weights of these portions of the brain and their blood flow. Cancers of the pelvis and colon are exceptional in this respect, tending to spread to the posterior fossa. Cancers of the and skin (except for malignant melanoma) seldom metastasize to the brain. Secondaries in the skull and dura are usually seen with prostatic cancer; actually with any tumor, but mainly seen in breast and prostate cancers, and with multiple myeloma. About 45 to 50% (usually 47%) of brain metastases are single; single metastasis tends to come from the kidney, breast, thyroid, and lung (adenocarcinoma type). Small-cell lung cancers and melanomas tend to be multiple. Metastases from malignant melanoma and choriocarcinoma tend to be hemorrhagic, but these can also be seen with cancers of the lung, thyroid, and kidney.
The presentation can be stroke-like in some, but it is usually insidious; abrupt presentation can be due to hemorrhage into the tumor or to tumor embolism causing cerebral infarction. A brain CT scan can detect secondary tumors larger than 1 cm; MRI with contrast can detect smaller ones in addition to meningeal involvement. In selected patients, solitary metastasis can be excised if the systemic disease is reasonably controlled. Intrathecal methotrexate has no place to treat secondary parenchymal malignant disease. Those with brain parenchymal metastases usually have a shorter life expectancy than those with bone or soft tissue metastases.
In meningeal carcinomatosis, there is widespread involvement of the ventricles and meninges with malignant cells. Apart from leukemia and lymphoma, this meningeal carcinomatosis is seen mainly with cancers of the lung, breast, GIT, and melanoma. Meningeal carcinomatosis generally forms 4% of all neurological metastases. Headache, backache, cranial nerve palsies, polyradiculopathies, seizures, and confusional states are the principal features. Hydrocephalus of a communicating type is seen in 50% of patients. Polyradiculopathy, especially of the cauda equina, is surprisingly common.
The clinical picture is highly suggestive of meningeal carcinomatosis; therefore, detecting the malignant cells in the CSF is the next step. This can be done by cytospin, flow cytometry, centrifugation, or Millipore filtration. Multiple large samples are usually needed. The CSF can show mononuclear pleocytosis, raised protein, and low sugar. Measuring the CSF biochemical markers of cancers (such as LDH, carcinoembryonic antigen, and beta-2 microglobulin) offers another means of making the diagnosis and following the response to treatment. These markers are most likely to be abnormal in hematological malignancies, but may also be altered in some cases of intracranial infections and parenchymal metastases.
Medulloblastoma arises from the cerebellar hemisphere in adults; in children, they are mid-cerebellar. Medulloblasts have never been identified in the fetal or human brain; nevertheless, the term is retained for no reason other than its familiarity! The clinical picture is due to both obstructive hydrocephalus and raised intracranial pressure; as a rule, symptoms have been present for 1-5 months before the diagnosis is made. Children aged 4-8 years are the victims, and male to female ratio is 3:1. These tumors and fill the ventricle. Blood-born metastases are rare; they are usually seen after craniotomy.
About 50% of choroid plexus papillomas occur in the lateral ventricles, 40% in the ventricle, and 10% in the ventricle. Surgical excision usually results in a complete cure by removing the source of excess CSF production. The antigen of the SV40 virus (which is an oncogene) is possibly involved in tumor induction. When the tumor arises from the choroid plexus of the ventricle and projects into the lateral recess of this ventricle, a cerebellopontine angle mass can be created; however, this is rare. These tumors are essentially of children.
Hemangioblastomas are usually seen in von Hippel-Lindau disease; sporadic tumors are uncommon in isolation. A highly characteristic feature of these tumors is that they are mainly seen as a cerebellar "cyst" with enhancing mural "nodule" on MRI. In a high proportion of cases, surgery can be curative. Even when the cyst and its mural nodule seem to be removed totally, recurrence can occur in 15% of cases. In 70% of spinal hemangioblastomas, the tumor is associated with syringomyelia; the tumor tends to be multiple and located mainly in the posterior column of the spinal cord.
Parinaud's syndrome is due to compression of the upper dorsal midbrain and associated hydrocephalus. Both mechanisms are operative.
Precocious puberty is seen with which is the commonest pineal tumor subtype. These tumors previously were inoperable because of the tumor site. Nowadays, the use of an operating microscope makes it possible to excise them by a or transtentorial approach. In addition to causing expansion of the pineal gland, pineoblastoma is a locally invasive tumor. Germinomas are the commonest subtype of pineal tumors, while gliomas are the least encountered.
The colloid cyst of the ventricle arises from the which are the ependymal cells of a vestigial third ventricle. The cyst is filled with a gelatinous material, which is glary and contains a variety of mucopolysaccharides. The cyst is usually 1-3 cm in size with a smooth surface; it is round or oval. Contrary to the common belief, intermittent obstructive symptoms are infrequent in clinical practice. Surgery is curative but can have many risks. Nowadays, either decompression of the cyst or placing a permanent ventricular shunt leaving the benign growth behind can produce satisfactory results. It is mainly a childhood tumor.
Acoustic neuromas are usually sporadic and unilateral; bilateral tumors are the hallmark of neurofibromatosis type II. Facial palsy indicates a late presentation or develops after surgical removal of the mass. Together with tuberculous meningitis and Guillain-Barré syndrome, an acoustic neuroma can result in a very high CSF protein. Although it is called "acoustic", it arises from the vestibular portion of the eighth cranial nerve (a misnomer). It is a tumor of Schwann cells that covers the eighth cranial nerve.
The commonest reported symptom in patients with an acoustic neuroma is hearing loss. Facial pain is rare but facial numbness is Signs of raised intracranial pressure are late and uncommon. Vertigo is seen in 30% of cases; usually mild and well-compensated. The most sensitive screening investigation is brainstem auditory evoked potentials. The reflex is the clinical screening test.
Craniopharyngiomas are mainly seen in children, but they are also seen in adults (up to the age of 60 years). Cystic components are very common and are usually calcified. The cyst is usually suprasellar, 3-4 cm in diameter, pressing down the optic chiasma, and extending up into the third ventricle. The tumor arises from the remnant of Rathke's pouch. The Rathke's pouch lies at the junction of the infundibular stem and the Calcification is seen in 70-80% of cases; a very useful clue on CT brain imaging. The underlying sella is usually flattened and enlarged.
This is the full-blown picture of the glomus jugulare tumor. It is purplish red and a highly vascular tumor arising from minute clusters of nonchromaffin paraganglioma cells (glomus bodies) found mainly in the adventitia of the dome of the jugular bulb (glomus jugulare) immediately below the floor of the middle ear. It is a very slowly progressive sometimes over 10-20 years.
This is the typical scenario of sphenoid wing meningioma. About 75% of cases are seen in women around the age of 50 years. The other stems listed are the differential diagnoses.
The patient demonstrates the classical frontal lobe syndrome due to large olfactory groove meningioma (note the loss of smell sensation). Both, olfactory groove and sphenoid wing meningiomas have a classic presentation.
Tumors in the region of the foramen magnum are of particular importance and must be differentiated from multiple sclerosis, Arnold-Chiari malformation, syringomyelia, and bony anomalies around the craniocervical junction. Failure to recognize these tumors is a serious matter since the majority are benign and i.e., potentially resectable and curable. If unrecognized, they terminate fatally by causing medullary and spinal cord compression. Together with neurofibromas and dermoid cysts, meningiomas and Schwannomas constitute the majority of foramen magnum tumors. Other tumor types are rare there. The clinical course of the above tumors usually extends over 2 years or longer with deceptive and "unexplained" fluctuations. They comprise about 1% only of all brain tumors, but they are extremely important as they are resectable.
Anti-Yo antibodies can be seen in lung but they are mainly seen in female gynecological cancers (ovarian cancer ranks at the top). Anti-Hu antibodies are associated with subacute sensory and neuronopathy. Scotomas, glares, and visual hallucinations can be seen in pan-retinal degeneration due to anti-recoverin antibodies in small-cell lung cancer, gynecological cancers, and melanomas. Anti-voltage-gated calcium channel antibodies are detected in Lambert-Eaton syndrome (in small-cell lung cancer). Antiamphiphysin antibodies may be seen in breast cancer causing stiff person syndrome (muscle spasms and rigidity).
Gradenigo-Lannois syndrome encompasses painful trigeminal and abducens palsies. In the past, infections of the petrous temporal bone (such as otitis media) were the usual causes. Nowadays, primary and secondary tumors in that area are the usual etiologies. This man most likely has an intracranial secondary tumor at the petrous temporal bone.
The patient has paraneoplastic cerebellar degeneration, which is the only stem that fits the clinical scenario. Guillain-Barré syndrome is usually seen with Hodgkin's lymphoma and results in flaccid areflexic weakness; dysphagia and facial weakness may occur but there should be no nystagmus. Vitamin deficiency needs at least 3-5 years to develop and does not result in nystagmus or dysarthria; malignancy patients are at risk of developing vitamin deficiency (i.e., Wernicke's encephalopathy and Korsakoff's amnesic syndrome).
Apart from sedative drug intoxication, the other stems can cause a confusional state with fever (not hypothermia). Alcohol and sedative drug withdrawal can cause fever, but their intoxication lowers body temperature. Other causes of hypothermia with a confusional state are hypothyroidism, hepatic encephalopathy, and hypoglycemia.
Bleeding peptic ulcer is a cause of hypotension (not hypertension). Do not forget hypertensive encephalopathy and sedative drug withdrawal.
Apart from opioid intoxication (which produces pinpoint reactive pupils), the other stems can cause dilated pupils.
Hepatic encephalopathy (and prominent hyperglycemia) can be a cause of hyperventilation, not hypoventilation.
Wernicke's encephalopathy can cause a confusional state with ophthalmoplegia and ataxia (not hemiparesis). Metabolic causes of encephalopathy (such as hypoglycemia or hyperglycemia, hepatic failure, uremia,…etc., can cause focal or multifocal neurological signs that are usually fluctuating or alternating between the right and left sides of the body.
This question highlights the importance of the past medical history of chronic illnesses. Complex partial status epilepticus presents as a confused dazed state; an EEG should be done which will reveal an ongoing seizure activity in one or both temporal lobes. Some patients may develop head injury following a seizure; a multitude of intracranial hemorrhages may occur and can precipitate catastrophic status epilepticus. A prolonged post-ictal confusional state occurs in the presence of underlying metabolic or structural encephalopathy; therefore, the recovery might be prolonged, giving a wrong impression of continued seizure activity (i.e., status epilepticus). Anti-epileptic intoxication can be iatrogenic (e.g., adding an enzyme inhibitor medication, such as clarithromycin for a simple chest infection which would enhance phenytoin toxicity) or might be intentional (suicide).
A history of diabetes mellitus may indicate a hyperosmolar nonketotic insulin-induced or sulphonylureas-induced hypoglycemia. A history of head injury is important as this may indicate a post-traumatic amnestic chronic subdural or post-traumatic epilepsy. Alcohol intake can cause acute intoxication (with alcohol or other materials, such as methyl alcohol), hypoglycemia, head injury, decompensated hepatic encephalopathy, Wernicke's encephalopathy, and a post-ictal state. Do not forget alcohol withdrawal. History of depression may indicate a recent suicidal attempt and, hence, drug poisoning should be suspected; it may also suggest an organic cause of this depression, such as hypothyroidism, Wilson's disease, decompensated cirrhosis, vitamin deficiency, or a functional state. Do not forget neuroleptic malignant syndrome in those taking conventional neuroleptics (e.g., schizophrenic patients).
Sexual history may give a clue to AIDS-dementia complex or general paresis of insane. Multi-infarct dementia might be due to multiple cardiac emboli from chronic atrial fibrillation. Vascular dementia is usually associated with chronic hypertension. Bradycardia and hypothermia can be seen in hypothyroidism which can result in dementia. Dementia with papilledema might be due to brain tumors or subdural hematomas.
Ethanol intoxication produces nystagmus, dysarthria, and limb and gait ataxia; an acute confusional state which is mainly seen in alcoholics. The severity and clinical features of ethanol encephalopathy correlate roughly with blood ethanol levels; however, chronic heavy alcoholics may have a very high blood ethanol level although they do not appear to be intoxicated. In ethanol intoxication, the plasma osmolality is characteristically raised. The plasma osmolality roughly increases by 22 mOsm/kg for every 100 mg/dL of ethanol present. Sedative-hypnotic drug poisoning can be confused with alcohol intoxication, but the former can be differentiated by the presence of ethanol odor, increased plasma osmolality (in ethanol poisoning the plasma osmolality is raised), and blood and urinary toxicology. Ethanol intoxication predisposes to head injury, lung aspiration, and seizures. Chronic alcoholism increases the risk of bacterial meningitis. The treatment is supportive only. All alcoholics should receive 100 mg of thiamin intravenously to prevent Wernicke's encephalopathy.
Stem "d" is false because confusion, if present, is usually mild. Illusions and hallucinations, usually visual, are seen in up to 25% of cases. It usually responds to diazepam 5-20 mg or chlordiazepoxide 20-25 mg orally every 4 hours.
Rum fits are usually seen within 48 hours of abstinence; however, in 70% of cases they occur within 7-24 hours of abstinence. The interval between the first and last seizure is usually 6-12 hours in up to 85% of cases. Only up to 40 % of patients will have one seizure. They abate spontaneously; however, diazepam or chlordiazepoxide is given because up to 30% of patients will develop delirium tremens. Unusual and atypical features of rum fits are the development of focal fits, prolonged duration of the fits (> 6-12 hours), more than 6 fits, status epilepticus, or a prolonged post-ictal phase. In these cases, a prompt search for a co-existent pathology is required.
Delirium tremens is the most aggressive type of all alcohol withdrawal states. It has a high mortality figure. It is usually seen within 3-5 days of abstinence and may last for up to 72 hours. In addition to the features mentioned in the question, tachycardia, and sweating may occur. The mortality rate is 15% and is mostly due to concomitant infection, pancreatitis, cardiovascular collapse, or trauma. The total requirement of diazepam to produce a calm patient may exceed 100 mg/hr.
The intoxicated patient may display respiratory depression, hypotension; reactive pupils, hypothermia, ataxia, dysarthria, and hyporeflexia may be seen in severe cases. A characteristic feature is the presence of reactive pupils; however, very large doses of phenobarbitone or glutethimide may result in large, fixed pupils. The mortality rate is low and mostly due to aspiration pneumonia (with or without systemic sepsis) or iatrogenic fluid overload and pulmonary edema. Despite severe intoxication, a patient who arrives at the hospital with adequate cardio-pulmonary function and support should survive without any sequelae. The treatment is mainly supportive while the drug is being eliminated. Forced alkaline diuresis is mainly used to increase the urinary clearance of phenobarbital, but in should be avoided as it can lead to fluid overload. Hemodialysis may be used in severe resistant cases of barbiturate poisoning or when drug elimination is impaired by renal failure.
Intermediate- or short-acting agents are more likely to produce withdrawal syndrome when stopped abruptly. The syndrome occurs within 1-3 days (for short-acting agents) and may take up to 1 week or even more to appear (for long-acting agents). Such patients may have confusion, agitation, and seizures. The diagnosis can be confirmed by the phenobarbital challenge test, which if positive, the patient should receive long-acting phenobarbital orally to maintain a calm state without signs of intoxication. In most patients, it is possible to stop it gradually after progressive decrement in the daily doses within 2 weeks. Seizures, especially myoclonic ones, should be treated aggressively with anticonvulsants. A delirium tremens-like syndrome may occur 3-8 days after abstinence (mainly seen in those taking very high and frequent doses).
a. true, as an iatrogenic overdose; also seen as an accidental overdose in addicts and in suicidal attempts.
b. true, and pontine hemorrhage is a differential diagnosis. Although needle tracks and marks might be seen, they are not diagnostic. c. true, the test is positive if the pupils dilate and the patient regains his full consciousness; however, when very large doses of opioids are taken or multiple drug ingestion is present, the pupils may slightly dilate.
d. false, with appropriate treatment, patients should recover uneventfully.
e. true, because naloxone is a short-acting agent.
The same clinical features can occur with antidepressants and antihistamine overdoses. Flushing, urinary retention, and tachycardia are also seen. Anticholinergics poisoning can be confirmed by a toxicology screen of blood and urine (mainly used in anti-psychotics or anti-depressant overdose). Symptoms usually resolve spontaneously if the patient is well-managed and supported. Although rarely needed as an anti-dote, physostigmine can produce severe bradycardia, seizures, and hypersalivation. Specific treatment is required when there is life-threatening cardiac dysrhythmia.
Their mechanism of action involves a variable combination of inhibiting the reuptake and/or increasing the release of noradrenalin and/or dopamine and, therefore, producing central stimulant and peripheral sympathomimetic effects. Cocaine can produce myocardial infarction. Strokes may occur and may be due to sudden severe hypertension, drug-induced vasculitis, or rupture of cerebral arteriovenous malformation. Beta-blockers should be avoided, especially in cocaine-induced myocardial infarctions (because of the unopposed alpha receptors stimulation). Alpha-blockers are useful in treating hypertension. Haloperidol is useful in the treatment by counteracting the psychotic manifestations of this overdose. Because amphetamines are longer-acting than cocaine, amphetamine intoxication is more likely to require treatment.
Prominent insomnia occurs in LSD victims, as well as prominent sympathetic over-activity. Changes in mental status are usually the most striking feature; alterations in affect and mood may dominate the clinical picture. Seizures are very rare, fortunately. The presence of prominent seizure activity should prompt a search for another pathology or to revise the diagnosis. Treatment with diazepam may be of benefit to calm severely intoxicated patients.
Unlike other hallucinogens (e.g., LSD), PCP poisoning is a medical emergency with many fearful and aggressive complications. Large or small pupils, horizontal and vertical nystagmus, hypertonia, hyperreflexia, and myoclonus may occur. There may be analgesia to a surprising degree. Phenothiazines reduce seizure threshold and may produce severe hypotension, and therefore, should be avoided; however, haloperidol can be used safely in such cases. Diazepam can be used for sedation and treating muscle spasms. In general, signs and symptoms resolve within 24 in some patients, it may take days or even weeks.
Many medications or drugs can easily incite a confusional state (and even coma) in elderly people when taken in larger than customary doses (whether accidental or intentional). However, other medications may confuse this population, even when prescribed in small or therapeutic doses; therefore, such patients may be wrongly diagnosed as having a serious CNS illness. Polypharmacy is a very important etiology.
Hypothyroidism is one of the causes of potentially-reversible dementia. Bilateral ptosis is seen in up to 65% of cases and is due to the low sympathetic tone of the levators. Unexplained agitation and even frank psychosis may be the presenting feature. The most characteristic neurological finding is a delayed relaxation of tendon reflexes, typically seen at the ankle joints. The CSF pressure is occasionally increased, as is the CSF protein.
The so-called activated crisis is seen in young people, while the apathetic crisis is mainly seen in the elderly. Hyper-adrenergic manifestations dominate the clinical picture; therefore, sympathomimetic drug intoxication is the top-ranked differential diagnosis. Exaggerated action tremors and hyper-reflexia are usually seen; however, extensor planters are extremely rare, and when present, should cast a doubt on the diagnosis.
The warning somatic hyper-adrenergic features might be absent; therefore, those patients may present with progressive coma; this is especially seen in those with recurrent hypos, the presence of associated autonomic neuropathy, or concomitant treatment with beta-blockers. Flaccid quadriparesis is another advanced feature. Focal, multifocal, or generalized seizures and myoclonus may be seen. Prolonged hypoglycemia at levels of 30 mg/dL, or lower, invariably leads to irreversible brain damage. The clinical picture can exactly resemble that of rostral-caudal herniation syndromes, with coma, bilateral extensor planters, and decorticate or decerebrate posturing; therefore, all such patients should have their blood sugar measured first. Somnolence might be seen; agitation may be absent. Tachycardia is seen with agitated delirium, but bradycardia is seen with somnolence.
The severity of hyperosmolarity correlates well with depression of the level of while the degree of systemic acidosis does not. Focal neurological signs and focal or generalized seizures that are not responsive to are commonly seen. The mortality rate is between 40-70% and is largely due to failure to recognize the condition in elderly patients without prior history of diabetes or who present with stroke or seizures, and coexistent diseases. In contrast to diabetic ketoacidosis, profound metabolic acidosis, and ketosis are absent. The impairment in consciousness ranges from very mild and subtle drowsiness to profound coma. Hyperosmolar non-ketotic hyperglycemia is the presenting feature of up to 40% of cases of type II diabetes mellitus in elderly people.
Hyponatremia may produce focal signs by unmasking preexisting structural brain lesions such as infarcts. Central pontine myelinolysis syndrome (in which no treatment is available) is the result of rapid correction of hyponatremia; prevention is very important by avoiding rapid correction of hyponatremia. Despite the prominent myopathic features of hypercalcemia, deep tendon reflexes are usually intact. Seizures are very rare in hypercalcemia (unlike in which seizures are very common and might be the only presenting feature). The overall clinical picture of hypercalcemia is due to the calcium-induced increase in the depolarization threshold of nerve and muscle with consequent under-excitability.
Hypocalcemic patients demonstrate positive Chvostek's sign and Trousseau's sign. These clinical signs indicate a hyper-excitability state. Prolonged hypocalcemia can cause cataracts and especially in children; in addition, basal ganglia calcification and Parkinsonian features may gradually appear. Hypocalcemic seizures can sometimes be very resistant to Chorea may occur in hypocalcemic patients; therefore, measuring serum calcium is part of the clinical work-up of chorea.
There is also small blood vessel proliferation and small petechial hemorrhages. The most commonly affected areas are mammillary bodies, periaqueductal grey matter, cerebellar vermis, and oculomotor, abducens, and vestibular nuclei. The commonest ocular manifestations are nystagmus and unilateral or bilateral lateral rectus weakness or paralysis. Ataxia primarily affects the gait; limb ataxia is highly uncommon, as is dysarthria. Up to 80% of those patients have co-existent peripheral neuropathy. Wernicke's encephalopathy is an uncommon cause of coma, but a very common cause of acute confusion. Mental status examination reveals global confusion with prominent impairment of immediate recall and recent memory. The CSF analysis is usually normal, although a mild increase in protein (<90 mg/dL) might be seen. Increased opening pressure or pleocytosis or low glucose should prompt a search for other or additional diseases.
Wernicke's encephalopathy can have many ocular findings, which can easily escape detection. Medicine textbooks usually mention "ophthalmoplegia and There are nine ocular findings in general:
•External rectus weakness or paralysis (unilateral or bilateral).
•Nystagmus, horizontal or a combined horizontal and vertical one.
•Internuclear ophthalmoplegia (a common finding).
•Conjugate gaze palsy or weakness.
•Involvement of vestibular focusing mechanisms.
•Small miotic reactive pupils (a very rare finding). Very subtle anisocoria and sluggish pupillary reactions might be seen. However, the pupils are usually spared.
Within 1 day of starting thiamin, the ocular findings usually start to disappear. The gait ataxia, together with confusion, should improve within 1 week. Nystagmus and gait ataxia disappear in 40% of cases only following successful treatment; the remaining 60% will be left with residual (mild) gait ataxia and horizontal nystagmus. Up to 75 % of cases after recovering from Wernicke's encephalopathy will develop Korsakoff's syndrome; therefore, long-term visits are important. The external ophthalmoplegia, vertical nystagmus, and confusion should be entirely reversible; failure of these to reverse back to normal should prompt a search for another or additional disease.
Vitamin vitamin deficiency can produce confusion, depression, aggression, agitation, or frank psychosis with hallucinations. A strange feature is that a tight band-like sensation around the trunk may occur, but a clear-cut sensory level is against the diagnosis. Lhermitte's sign, distal paresthesia, and (sensory) gait ataxia might be the presenting feature. Loss of ankle jerk indicates peripheral neuropathy. An abnormal CSF profile (apart from slightly raised protein) should cast doubt on the diagnosis. Vitamin should be assessed in the differential diagnosis of any unexplained cognitive impairment, myelopathy, and peripheral neuropathy, whether anemia is present or not. Neurological abnormalities present for more than a year are less likely to correct with treatment. Encephalopathy may begin to clear within 24 hours after the first vitamin injection, but full neurological recovery, when it occurs, may take several months.
Hepatic encephalopathy might gradually progress to a stupor and coma. Asterixis (negative myoclonus) indicates impairment of the parietal postural control mechanism. Focal or multifocal neurological signs that might fluctuate in severity and type might occur. Raised CSF glutamine is the most specific CSF finding. In addition, an elevated opening pressure, mild pleocytosis, and increased protein all might be CSF xanthochromia occurs when the total serum bilirubin exceeds 4-6 mg/dL. As in any metabolic encephalopathy, the EEG may show diffuse slowing with triphasic The prognosis in hepatic encephalopathy is most closely correlated with the severity of hepatocellular damage rather than neurological
In uremic encephalopathy, CSF acidosis is rare and cerebral edema is not a factor in the pathogenesis. Uncommonly, neck stiffness occurs (adding more confusion to the clinical picture). The motor manifestations are coarse tremor, asterixis, myoclonus, and tetany. Focal or generalized seizures or focal signs all are common. The CSF can show a multitude of abnormities (such as the ones described in the question) and this may wrongly suggest an infectious meningitic process. Decorticate or decerebrate posturing can occur as part of any severe encephalopathy (may be misdiagnosed as seizures). The treatment should be directed against renal failure and its cause. Control of seizures and hypertension is very important.
Dialysis disequilibrium may begin during hemodialysis or as long as 24 hours after hemodialysis. It is a rare complication of maintenance hemodialysis in patients with chronic stable renal failure. A rapid correction of systemic acidosis may also exacerbate CSF as diffuses into the CSF. If the EEG is recorded during a dialysis session, it will gradually become abnormal, sometimes before any clinical change has occurred. The EEG may reveal paroxysmal activities with spikes-and-sharp waves. Fortunately, myoclonus, asterixis, coma, and generalized seizures are uncommonly seen.
Its prevention is very important by correcting uremia more gradually or using briefer periods of dialysis at a reduced rate of blood flow.
Pulmonary encephalopathy (with high is a confusional state that ranges from mild drowsiness to deep coma. Unlike other encephalopathies complicating other organ failures, focal neurological signs are rare. Deep tendon reflexes are usually decreased; is uncommon. One of the commonest mistakes in clinical practice is to give intravenous bicarbonate to correct systemic acidosis. Bicarbonate infusion increases the production of which subsequently diffuses into the CSF and worsens the CSF acidosis leading to paradoxical clinical deterioration while systemic acidosis is improving. The treatment involves intubation and mechanical ventilation.
In tuberculous meningitis, tubercles can be seen on the surface of the brain as well as the meninges. Hydrocephalus is common (communicating or non-communicating) and the ventricular surfaces may show ependymal exudate or granular Cerebral vasculitis may complicate the picture and increases the disease morbidity by producing focal signs (such as hemiparesis). Cranial nerve palsies are in general either due to vasculitis or nerve compression due to basal fibrosis (both are very common).
Surprisingly, a history of contact with tuberculosis patients is usually absent; therefore, the diagnosis needs a high index of suspicion. Fever, confusion, and signs of meningeal irritation are the major presenting features, but all of them might be absent. Oculoparesis and optic disc swelling may occur and can wrongly be attributed to a mass lesion. In some patients, seizures can be a prominent feature. Stroke, brain edema, and spinal subarachnoid block may complicate the disease, thus increasing the already increased morbidity. Tuberculous meningitis is a very aggressive CSN infection that needs a high index of suspicion.
The CSF is usually under pressure and is clear and colorless but may show a clot upon standing due to its high protein content. Early polymorphonuclear pleocytosis may wrongly suggest a pyogenic cause. The CSF protein may reach very high levels, especially in those with spinal sub-arachnoid block. Measurement of the chloride level in the CSF was used in the past as an aid in the diagnosis, but nowadays it is too non-specific.
Unlike pyogenic meningitis (where the CSF glucose might reach zero mg/dL), the sugar level in tuberculous meningitis rarely falls below 20 mg/dL.
The inflammatory response in pyogenic meningitis is associated with the release of inflammatory cytokines, such as IL-1, IL-6, and TNF alpha, thus promoting the permeability of the blood-brain barrier, vasogenic cerebral edema, changes in cerebral blood flow, and perhaps direct neuronal toxicity. The inflammatory exudate is more marked in the basal cisterns with N. meningitidis infection. Actual bacterial invasion of the underlying brain is very rare. The burden of the pathological process is within the leptomeninges with secondary changes in the underlying brain. Many complications can alter the clinical course of pyogenic meningitis, such as stroke and hydrocephalus. Even in immune-competent hosts, the low levels of antibodies and complements in the subarachnoid space are inadequate to contain the infection.
Few pyogenic meningitis patients may have a stroke-like pattern within 1 day. Neck stiffness is absent in 20% of cases; usually in neonates and old people and in those in a deep coma. Therefore, the absence of neck stiffness is not against the diagnosis. Some patients present with seizures and cranial nerve palsies; this may be easily mistaken for a brain abscess. Hemorrhagic skin rash occurs in 50-60% of cases of N. meningitidis infections.
In pyogenic meningitis, leucopenia may indicate an immune-suppressed state or an overwhelming infection therefore, portends a very bad The causative organism can be isolated in 40-90% of cases by using blood cultures; CSF culture is positive in 80% of cases. Focal signs may indicate the presence of focal cerebritis, brain or scarring. The physician should look for para-meningeal or remote sites of such as a pulmonary abscess.
In pyogenic meningitis, the CSF appearance ranges from slightly turbid to grossly purulent. The pleocytosis is predominantly polymorphonuclear; the presence of predominant mononuclear pleocytosis is consistent with Listeria pyogenic infections. CSF white cell count of more than 50000 cells/µL usually indicates the presence of a burst brain abscess as a cause. Gram stain of CSF is positive in 60-80% of pyogenic cases; in tuberculous meningitis, acid-fast smears are positive in 20% of cases only. A useful tool in the diagnosis is PCR; PCR has been used to diagnose N. H. and L. monocytogenes meningitis. CSF culture is positive in 80% of cases.
The initial choice of antibiotic therapy is empirical and is based on the patient's age and predisposing factors. The use of steroids as a treatment adjunct is still controversial, although it is suggested to be given to children less than 2 months of age and to adults with positive CSF gram stain and features of raised intracranial pressure. Steroids have been shown to decrease hearing loss and neurological sequelae in children with H. influenzae meningitis. After using the correct antibiotic, the CSF should be sterile within 24 hours and CSF pleocytosis and the proportion of polymorphonuclear cells should decrease within 3 days. A regimen consisting of 20 mg/kg of rifampicin once daily for 4 days is used for H. influenzae infections; in N. meningitidis meningitis, it is given as 20 mg/kg twice daily for 2 days. A vaccine is available for certain strains of N. meningitidis and is recommended for military recruits, college and travelers to areas of ongoing epidemics.
The case fatality rate in Streptococcus pneumoniae infection may exceed 25%. N. meningitidis infection can be complicated by acute adrenal failure; Waterhouse-Friderichsen syndrome. A delay in initiating treatment is associated with a gloomy outcome. Seizures and focal signs predict a bad prognosis.
Syphilitic meningitis is seen within 2 years of primary syphilitic infection and affects men more than women. The infection is usually asymptomatic. The cranial nerves most frequently affected in descending order are facial, acoustic, oculomotor, trigeminal, abducens, and optic, but other cranial nerves may be involved as well. Even when asymptomatic, it should be treated to prevent the development of more serious CNS complications.
Although CSF VDRL testing is positive in 50% of cases, the blood FTA treponemal tests are almost always positive. Oligoclonal bands are not present in the normal CSF. The CSF opening pressure may be normal or slightly elevated. Although acute syphilitic meningitis is a self-limiting illness with little or no sequelae, it should be treated to prevent the future development of tertiary neurosyphilis. This CNS infection can be treated with high intravenous doses of penicillin-G for 10 days; another course of treatment should be given if the CSF cell count or protein remains elevated.
Herpes simplex encephalitis is the commonest sporadic fatal encephalitis; there is no seasonal variation. The mortality rate ranges from 40-70% and depends on many factors. People older than 40 years of age are commonly targeted; this age group is higher than that of other causes of viral encephalitides in general. HSV type 2 affects neonates when passing through an infected birth canal. HSV type II in adults usually produces viral meningitis rather than viral encephalitis. Characteristically, the infectious process involves the medial temporal and inferior frontal lobes (unilateral or bilateral affection). Intranuclear inclusions may be seen in neurons and glia. Patients who recover may show cystic necrosis of the involved areas.
The presence of herpes labialis does not reliably implicate HSV as a cause of encephalitis. The disease can be rapidly progressive and result in a coma within a few days. Acute behavioral changes may be wrongly diagnosed as acute psychosis. Seizures may occur. The commonest sequelae in survivors are memory and behavioral reflecting the predilection of HSV for the limbic system structures.
The CSF white cell count is usually between 50-100 cells/µL. HSV is one of the causes of hemorrhagic CSF. The glucose is usually normal (its level becomes low in a few cases). The virus generally cannot be isolated from the CSF but the viral DNA can be detected in the CSF by PCR. Focal paroxysmal activity in the form of spikes and waves might be seen. Brain MRI is uncommonly normal but usually, it shows abnormalities in one or both temporal lobes and the changes may extend to frontal and parietal lobes. The CSF is entirely normal in 2% of cases.
Neoplastic meningitis can complicate many systemic cancers. In descending order: acute lymphoblastic leukemia, non-Hodgkin's lymphoma, malignant melanoma, acute myeloblastic leukemia, breast carcinoma, Hodgkin's lymphoma, lung carcinoma, GIT and sarcomas. It may be the presenting manifestation or occur after many years of the illness (sometimes in an apparently cured patient). Some patients have nausea, vomiting, seizures, and gait abnormalities. Abnormal neurological signs are often more striking than the symptoms, indicating involvement at multiple levels of the neuraxis. Primary brain tumors may be associated with meningeal gliomatosis; medulloblastomas and pineal tumors have a particular propensity for meningeal dissemination.
In neoplastic meningitis, the cytology is positive in 55% of cases. Large volumes of fluid and repeated CSF samples increase the diagnostic yield. The detection of malignant cells by cytological examination is the objective. CSF beta-2 microglobulin, beta-glucuronidase, and LDH isozyme-V are sensitive CSF pleocytosis is present in 60% of cases. Untreated, neoplastic meningitis typically results in death within 2 months. In neoplastic there is ophthalmoplegia (30%), facial weakness (25%), and papilledema (10%).
Hypertensive encephalopathy results from a sudden severe rise in blood pressure, with or without pre-existent hypertension. A blood pressure of more than 250/150 mmHg is required to produce the syndrome in chronically hypertensive people. Lower levels may suffice to produce the picture in previously normotensive individuals. Co-existent renal failure appears to increase the risk of developing hypertensive encephalopathy; therefore, renal function should always be investigated. Some patients may present in a stroke-like pattern. It develops over several hours to days.
Retinal arteriolar spasm is almost invariably found upon doing fundoscopy; the most helpful and specific sign. Retinal soft exudates and hemorrhages are with or without papilledema. An elevated CSF protein might also be seen. A brain CT scan shows hypodense areas in the posterior lobes, indicating areas of brain edema. These changes are reversible upon successful drug therapy. Renal failure appears to increase the risk of developing hypertensive encephalopathy; blood urea and electrolytes should be estimated in all cases. Hypertensive encephalopathy is a diagnosis of exclusion.
The infusions of should be carefully monitored to produce the mentioned targets in the question’s stems. If the diastolic blood pressure falls below 100 mmHg in the first hour, this indicates over-treatment and hypotension. All anti-hypertensive medications should be given either by intravenous infusions or by repeated boluses; there is no place for oral medications in the acute setting. If promptly treated, full clinical recovery ensues.
Neuro-lupus is the commonest autoimmune cause of encephalopathy, which is commonly seen between the ages of 10 to 40 years. Neuropathologically, there is fibrinoid necrosis of small arterioles and capillaries causing small and discrete hemorrhages (vasculopathy). True cerebral vasculitis is very rare.
The cognitive dysfunction of neuro-lupus includes acute confusional state, schizophreniform psychosis, depression, and mania. Seizures may be focal. Diplopia, ptosis, hemiparesis, para-paresis, and chorea are less common findings. Although anti-ribosomal antibodies are supposed to be associated with lupus psychosis, it is still a controversial issue. The EEG is usually diffusely slowed or there are focal abnormalities.
A common dilemma is to differentiate cerebral lupus from steroid-induced psychosis, but in practice, cerebral lupus is by far much more common. In addition, encephalopathy in SLE may be due to infections, severe anemia, lupus endocarditis, and metabolic and electrolyte disturbances. If the patient is not receiving steroids, prednisolone should be started at doses between 60-80 Cerebral lupus has not been shown to adversely affect the overall prognosis.
After ingestion of the larvae of the pork tapeworm, the disease affects the brain in 60-90% of cases. Hydrocephalus occurs because of obstruction to the CSF pathways by intraventricular cysts or inflammatory process that causes basilar meningitis. Myelopathy and vague personality changes are the additional features. Typically, the CSF shows lymphocytic pleocytosis with many eosinophils. The opening pressure might be high due to cerebral mass lesions or very low in cases of a spinal subarachnoid block.
The indications for the treatment of cerebral cysticercosis are still controversial; however, patients with seizures and either meningitis or one or more non-calcified cysts should be treated. Intra-ventricular, subarachnoid, and racemose cysts respond very poorly to treatment. Corticosteroids can be given for raised intracranial pressure or lesions near the cerebral aqueduct or intra-ventricular foramina, as these can produce obstructive hydrocephalus. A single accessible intra-parenchymal lesion can be removed surgically; therefore, removing a mass effect. Shunting can be used to treat hydrocephalus due to lesions. Calcified cysts do not require treatment.
Although malaria is the commonest parasitic infection worldwide, cerebral involvement is rare; therefore, prophylaxis is very important. It causes occlusion of small cerebral blood vessels. It usually produces a global confusional state and seizures; focal signs are rare. The CSF may show raised protein and mononuclear pleocytosis. The mortality rate is high (20-50%, and may reach 80% in cases complicated by coma and seizures).
In addition to the pathological changes mentioned in the question, there may be cerebral infarction related to cerebral vasculitis and ventricular enlargement due to communicating hydrocephalus. Direct extension of infection may also be seen with actinomycosis and Aspergillus infections. The clinical picture may also resemble brain abscesses and neurosyphilis. A predisposing illness is usually present, such as systemic cancer, diabetes, HIV, immune suppression, organ Intravenous amphotericin B is the drug of choice, which should be used for 3 months. The treatment is long and costly. There is no intravenous preparation of nystatin.
This man has resting tremors, dysarthria, depression, and impaired liver function tests; only Wilson’s disease would fit this scenario. Hemochromatosis has no CNS neurological complications. Stem e is focal chronic encephalitis that may present as focal seizures. The patient is too young in order to develop multiple system atrophy. In addition, neither Shy-Dragger syndrome nor multiple sclerosis damages the liver.
There are cerebellar signs, extensor planter responses, and skeletal abnormalities; Friedreich's ataxia would fit this constellation. Ataxia telangiectasia is seen in infants and young children. Acquired alcoholic cerebellar degeneration develops in adults and produces isolated gait ataxia. A 6-year history would be too long for an untreated CNS malignancy.
The patient’s communicating hydrocephalus and headache had developed on the background of surgically treated breast cancer; malignant or carcinomatous meningitis is the most likely explanation. The brain imaging has excluded secondary tumors and meningioma (both of these tumors enhance with contrast administration). Cavernous sinus thrombosis results in ophthalmoplegia and proptosis. Superior sagittal sinus thrombosis does not cause hydrocephalus and would result in hemorrhagic hemispheric infarctions.
The diagnosis is straightforward. There are white matter signs which have disseminated in time and place. Dorsal column signs in one limb should always prompt a search for multiple sclerosis. The abnormal right pupil reflects optic nerve involvement. Motor neuron disease has no ocular or sensory signs. Multiple meningiomas are usually part of neurofibromatosis type II; the spinal cord compression is slowly progressive. Isolated CNS vasculitis is a differential diagnosis, but it is rare and usually affects the older age group. Argyll-Robertson pupils are found in taboparesis; in addition, there are many personality and behavioral changes resulting from frontal lobe atrophy.
Becker’s muscular dystrophy usually starts to manifest itself after the age of 10 years (i.e., when Duchenne’s patient starts to be wheelchair-bound). The absence of skin manifestations would make childhood dermatomyositis a remote possibility. Duchenne’s muscular dystrophy fits this child’s clinical scenario. Congenital myopathies are a distinct group of myopathies that have characteristic features and age group affection. Bilateral ptosis and progressive dysphagia comprise the main features of oculopharyngeal muscular dystrophy, which usually afflicts individuals older than 50 years of age.
Motor neuron disease does not result in muscle tenderness. One of the characteristic features of inclusion body myositis is the early loss of knee jerk. The absence of skin changes would cancel out adult-type dermatomyositis. Although proximal weakness may dominate the myasthenic picture, the fatigability should be painless. Adult-type polymyositis exactly fits this man’s clinical presentation; dysphagia is usually seen in acute/subacute cases.
There are rapidly progressive quadriparesis, normal sensation, and normal sphincteric functions; Guillain-Barrè syndrome is compatible with the patient’s history and findings. Myasthenic crisis is rarely the presenting feature of generalized myasthenia gravis and rarely presents as an ascending weakness without ocular abnormalities. The absence of sensory level and sphincteric disturbances would argue against acute transverse myelitis. Although the patient has had back pain, the unremarkable sensory symptoms, the flexor plantar reflexes, and the intact bladder and bowel functions all point against a compressive spinal cord pathology.
This patient has oropharyngeal dysphagia, upper motor neuron signs in both upper and lower limbs, and intact sensation and ocular movements; amyotrophic lateral sclerosis (motor neuron disease would fit this constellation). Although primary progressive multiple sclerosis can result in this constellation of signs, the patient’s age, and prominent lower motor neuron signs should make you discard this option. CNS involvement in sarcoidosis may result in a multitude of signs and symptoms, but this disease targets young people. Most patients with brain metastases die within 3-6 months; the patient’s history spans longer than this figure. Her hypermetropia and cataract are age-related; they are not related to the patient’s presentation.
This middle-aged woman has cognitive dysfunction, peripheral neuropathy, and extensor planters; vitamin deficiency would explain all of these features. Rombergism is represented by the frequent falls when she takes a shower (i.e., closing her eyes). Multifocal motor neuropathy with conduction block is a pure motor syndrome and is one of the differential diagnoses of motor neuron disease. Taboparesis, not tabes dorsalis, may have a similar presentation, but there should be no stocking peripheral neuropathy. The patient’s age and cognitive dysfunction are against the diagnosis of Friedreich’s ataxia. Even without noticing other features, the mere presence of stocking peripheral neuropathy should not make you think of multiple sclerosis.
Intermittent acute angle-closure glaucoma may have a similar picture, but the presence of rhinorrhea and the absence of vomiting during these pain attacks would cancel out this possibility. Analgesic rebound headache occurs in those who ingest over-the-counter analgesics for a long time; the headache rebounds when the medication’s blood level drops. Atypical facial pain syndrome and ice pick headache have different clinical scenarios. This patient has a cluster headache.
The patient’s history, clinical findings, and brain imaging are compatible with a diagnosis of pseudotumor cerebri (idiopathic intracranial hypertension). Tuberculous meningitis would have features of fever, lethargy, sweating, weight loss, anorexia, neck stiffness, impaired mentation,…etc. The Miller-Fischer variant of Guillain-Barre syndrome results in ocular paresis, areflexia, and ataxia. Fever, headache, seizures, and clouded consciousness are parts of Herpes simplex encephalitis. Orbital pain and proptosis would point out toward the orbital pseudotumor. Posterior fossa tumors may result in headache, vomiting, and cranial nerve palsies; such tumors raise intracranial pressure mainly by producing obstructive hydrocephalus (the patient’s brain imaging is incompatible with this).
This young woman has unilateral ptosis, bulbar weakness, and “generalized” weakness (that is fatigable); myasthenia gravis is the correct diagnosis. Relapsing-remitting multiple sclerosis should have dissemination in time and place of white matter signs. The Miller-Fischer variant of Guillain-Barrè syndrome should result in areflexia. The patient has “solid” neurological signs that are not indicative of a conversion reaction. The ptosis in myotonia dystrophica is bilateral and the weakness is distal.
The presentation is stroke-like. Cerebellar hemorrhages usually present with headache, vomiting, and gait ataxia which are followed gradually by brainstem compression signs; neck stiffness is absent and nerve palsy is unusual. Massive brainstem infarction may have a very similar presentation, it but would not explain the fundal “blood” and the recent headache. Pyogenic meningitis results in fever, headache, vomiting, and stiff neck over a few days, not a “sudden collapse”. Head trauma with extradural hematoma formation and brain herniation (resulting in nerve palsy) may exactly present as such, but the absence of head injury would cancel out this possibility. The recent severe headache might well represent “a sentinel bleed”; the dilated pupil has resulted from an expanding Berry’s aneurysm (which is usually located at the junction of the posterior cerebral artery and the posterior communicating artery). The explosive rupture of the aneurysm explains the sudden collapse and the fundal subhyaloid hemorrhage in this patient.
This smoker man has autonomic dysfunction, hyporeflexia, and proximal weakness; Lambert-Eaton myasthenic syndrome would fit this scenario. In myasthenia gravis, the deep tendon reflexes are usually normal, and there should be no autonomic dysfunction. The presence of autonomic failure would also exclude adult dermatomyositis. Chronic alcoholics may develop “acute” alcoholic myositis; however, the muscle weakness and tenderness are diffuse.
This alcoholic man presents with an acute meningitic illness which has resulted in brainstem signs; Listeria meningoencephalitis usually attacks the brainstem and should always be looked for in alcoholics. Therefore, the patient’s empirical antibiotic therapy should always include high-dose intravenous ampicillin. Tuberculous meningitis is a subacute/chronic process; rarely, it does have an acute pyogenic meningitis-like presentation. Wernicke's encephalopathy and chronic subdural hematomas do not result in fever. Acute subarachnoid hemorrhage may result in fever, not a high fever. Rupture of a large basilar artery aneurysm may produce brainstem signs in addition to neck stiffness and altered consciousness.
The overall picture is that of an expanding intracranial space-occupying lesion with raised intracranial pressure. The brain CT findings are suggestive of “chronic” subdural hematoma.
Wilson’s disease may present between the ages of 5-50 years; however, isolated CNS manifestations without hepatic involvement are extremely unusual in someone who has reached 40 years of age. The symmetrical bilateral onset of hand tremor is against idiopathic Parkinson’s disease. In drug-induced Parkinsonism (e.g., after long-term use of anti-psychotics) the tremor is symmetrical, resting, and coarse but has no postural component. Thyrotoxicosis results in exaggerated physiological tremor; the patient’s blood tests were normal.
Lowy body dementia would have produced Parkinsonism and formed visual hallucinations without prominent memory impairment. Pick’s dementia results in early behavioral and personality changes rather than memory problems. Autonomic failure is an important component of Shy-Dragger syndrome; the disease also produces pyramidal and extra-pyramidal signs. Creutzfeldt-Jacob disease results in rapidly progressive cognitive decline as well as startle myoclonus. Alzheimer’s disease is the correct diagnosis for this man.
The constellation of a subcortical type of dementia, chorea, and psychiatric manifestations in this man with a positive family history strongly solidifies the diagnosis of Huntington’s disease. Machado-Joseph disease is heredito-familial spinocerebellar ataxia which targets the younger age group. Tardive dyskinesia usually involves oro-facial and neck involuntary movements in those receiving long-term conventional neuroleptic therapy; the limbs may be involved but would not explain the father’s death. Patients with advanced Parkinson’s disease, who are taking dopaminergic agents, may develop a multitude of dyskinesias; the absence of tremors and the presence of cognitive decline as well as the patient’s age would cancel out this option away.
The presence of diabetes and cataract in this young woman who has distal weakness, bilateral ptosis, and facial wasting should prompt a search for myotonia dystrophica; panhypogammaglobulinemia is responsible for her repeated chest infections. Myasthenic weakness muscles of the eyes, face, bulbar area, and girdle musculature; the presence of isolated distal weakness and wasting should cast strong doubt on the diagnosis of myasthenia gravis. Kerns-Sayre disease patients have diabetes and ptosis, but there should be ophthalmoplegia as well. Facioscapulohumeral muscular dystrophy produces facial wasting and bilateral ptosis with weakness and wasting of periscapular and humeral muscles; early distal muscle involvement is highly unusual and should suggest an alternative diagnosis.
This young man has a fever, seizures, and impaired consciousness with mild neck stiffness; the constellation is consistent with Herpes simplex encephalitis. Pneumococcal meningitis may produce seizures at presentation, but the seizure type is usually generalized rather than complex partial in type, and the neck stiffness is usually prominent rather than mild. Patients with subdural abscesses usually have a preceding history of intracranial infection and the resulting signs are usually lateralizing (aphasia, hemiplegia,…etc.).
This is the classical presentation of pure sensory lacunar stroke involving the right thalamus. The patient’s retina shows hypertensive and diabetic retinopathic changes. Proximal middle cerebral artery or top of the basilar occlusions would result in devastating types of stroke. The lateral medullary syndrome causes vomiting, Horner’s syndrome, dysphagia, crossed spinothalamic sensory loss,…etc.
This is the classical triad of dementia, gait apraxia, and urinary incontinence (use of diapers) which is consistent with normal pressure hydrocephalus (NPH). The patient’s NPH is secondary to a previous subarachnoid hemorrhage.
The presence of an eyewitness is very important in the diagnosis of epileptic disorders. Epilepsy is a clinical diagnosis. This boy has a typical history of generalized tonic-clonic seizures. The constellation of a positive family history of the same condition, the age of the patient, and normal neurological examination and lab tests, would make idiopathic grand-mal epilepsy the most likely diagnosis.
The asymmetric onset of this coarse resting tremor and the facial expression would make idiopathic Parkinson’s disease the best option. Essential tremor has symmetrical onset and the tremor is fast and fine with a prominent postural component. Alcohol withdrawal tremor is a form of exaggerated physiological tremor and occurs when the patient abstains from drinking; the patient’s history spans several months. Encephalitis lethargica was a cause of post-encephalitic Parkinson’s disease. Paroxysmal choreoathetosis results in chorea and athetosis intermittently, on an episodic basis, and occurs in young people.
The optic and olfactory nerves are the only cranial nerves that are not located in the posterior fossa. The patient has brainstem involvement (recurrent vertigo), hyper-reflexic bladder, pyramidal dysfunction, and left-sided optic nerve atrophy (central scotoma); relapsing-remitting multiple sclerosis would be a reasonable cause of these neurological signs. Vitamin deficiency may sound reasonable but episodic brainstem dysfunction and unilateral optic nerve involvement would make this option unlikely. Devic’s disease comprises bilateral optic neuritis and long-segment transverse myelitis. Anterior spinal artery occlusion produces acute paraparesis and dissociated sensory loss in the lower limbs because of ischemic infarction of the anterior of the spinal cord. Posterior fossa meningioma cannot explain the unilateral optic nerve atrophy this patient has.
The presence of cerebellar and pyramidal dysfunctions should cast strong doubt on the diagnosis of Pick’s dementia and depressive pseudodementia. Ataxia and extensor planters as well as dementia may be encountered in Shy-Dragger syndrome, but such patients usually exhibit prominent autonomic failure in addition to the Parkinsonian features. One of the core features of progressive supranuclear palsy is gaze impairment (up and down gazes). This woman has rapid cognitive decline and myoclonus; she has Creutzfeldt-Jacob disease.
The gait description is that of spastic paraparesis; the patient must have extensor planter reflexes as well. There are absent ankle jerks, and this would narrow the differential diagnosis list. She has depression and bilateral optic nerve atrophy in addition to peripheral neuropathy (feet numbness); vitamin (cobalamin) deficiency would be consistent with all of these signs.
This very short scenario consists of refractory epilepsy, retinal phakoma, and brain “kindling” in a teen; this is tuberous sclerosis.
Locked-in patients have quadriparesis. Patients with chronic subdural hematoma usually complain of headaches and hemiparesis. Listeria infection usually prefers to target the brainstem and results in meningoencephalitis with fever and neck stiffness. Horizontal gaze paresis is a brainstem sign. Hemispheric brain secondary tumors would be expected to produce hemispheric signs. Cancer patients and those with malnutrition are at risk of thiamin deficiency; the patient’s presentation is that of Wernicke’s encephalopathy.
The presentation is relatively rapid and somewhat progressive. Did the patient develop an intracranial event and then fall onto the floor, or the reverse is true? The picture suggests a rapidly growing intracranial space-occupying mass lesion. His vision is most likely impaired because of glaucoma. Because of atrial fibrillation, he might well have been prescribed warfarin. The eye problem increases the risk of and warfarin increases the risk of hemorrhagic complications. An intracranial bleed might well have developed in this man following his fall. His fall might also have resulted from his cardiac problem (which might result in syncope). Syncope does not result in hemiparesis, vomiting, and impaired consciousness, unless it is, has resulted in head trauma and its aftermaths.
This diabetic man has a facial infection which has resulted in the rapid extension of this infection into the cavernous sinus. The phrasing of the scenario may mislead you to think of mucormycosis; this infection needs a longer time to develop. Preseptal orbital cellulitis can result in proptosis but does not result in anesthesia over the check. The Tolosa-Hunt syndrome is a non-infectious granulomatous inflammation of the cavernous sinus that is painful and usually recurrent; mild proptosis may be seen and is rare. Multiple cranial nerve palsies may result from nasopharyngeal cancer but it would take some time to progressively involve the nerves.
This is the full-fledged picture of post-partum superior sagittal sinus thrombosis. Venous infarctions tend to be hemorrhagic, do not follow the anatomy of arterial territories, and are usually epileptogenic.
The patient has Horner’s syndrome, dysphagia, as well as severe vertigo. The latter is reflected by the patient’s inability to stand and his preference for eye closure). Damage to the central vestibular apparatus results in nausea, vomiting, vertigo, diplopia, oscillopsia, and nystagmus. Acute vestibular neuronitis may have a very similar presentation, but Horner’s syndrome is not a manifestation. Pontine hemorrhage usually causes quadriparesis, prominent impairment in consciousness, pinpoint pupils and gaze paresis. Weber’s syndrome comprises unilateral cranial nerve palsy and contralateral hemiparesis.
Diabetic peripheral neuropathy starts in the feet and ascends gradually over months-years. When the patient develops hand symptoms, the lower limb process reaches the knees. This woman has no lower limb symptoms. Cervical ribs damage the lower trunk of the brachial plexus and causing sensory signs and symptoms in these dermatomes as well as global hand wasting. Cervical syringomyelia begins with dissociated sensory loss in both hands and then produces asymmetric weakness, wasting, and reflex changes. Cervical radiculopathy has a dermatomal distribution. Sensory complaints may be in the form of numbness, pins and needles, paresthesia, pain, coldness, and “heaviness”. This patient’s picture is of bilateral carpal tunnel syndrome; diabetes increases the risk of developing entrapment neuropathies. Thenar wasting is a late sign.
His conduct during the examination, the prominent vegetative symptoms, and the dysphoric mood are pointing toward depressive pseudodementia.
This is the classical story of idiopathic trigeminal neuralgia in a middle-aged woman. Conversion reaction can be a differential diagnosis in young women because of the bizarre complaints and the unremarkable clinical examination. The other stems should demonstrate abnormal neurological examination.
Patients with locked-in syndrome have damage in the basis pontis which intersects the descending pyramidal system but spares the dorsally located ascending reticular activating system. Therefore, such patients have quadriparesis but full consciousness and they respond to commands by moving the globes vertically. Man in a barrel syndrome develops after sustaining watershed infarctions with bi-brachial paresis. This is seen after prolonged pan-cerebral hypoperfusion (the brain CT scan would show bilateral wedge-shaped infractions in the watershed areas). The patient has the deafferentation condition of a persistent vegetative state.
Normal brain imaging cancels out any form of intracerebral hemorrhage (the blood appears hyperdense on brain CT scans). Malingering patients should respond to painful stimuli. Intentional aspirin overdose would take some time to develop and coma is a late sign; those patients also have hyperventilation. The normal EEG record in deep coma patients virtually excludes organic causes. The normal EEG, the normal examination, and the unremarkable brain imaging are consistent with psychogenic unresponsiveness.
The constellation of bilateral tremors, cerebellar dysfunction, and pyramidal signs would suggest a diagnosis other than idiopathic Parkinson’s disease. Advanced Alzheimer’s patients may have a similar picture, but the prominent autonomic failure would make this a remote possibility. Multi-infarct dementia encompasses focal signs and dementia, but there is no autonomic dysfunction. The presence of Parkinsonism, autonomic failure, and global cognitive dysfunction as well as pyramidal and cerebellar signs would fit the Shy-Dragger syndrome form of multiple system atrophy.
The patient’s history of recurrent muscle cramps and myoglobinuria after exercise and the normal physical examination all are indicative of myophosphorylase deficiency form of glycogen storage disease.
This woman presents with focal motor seizures due to frontal meningioma which irritates the hand motor cortical area.
The patient’s history and the brain MRI findings in this HIV-positive man are highly suggestive of progressive multifocal leukoencephalopathy (PML). The commonest features are hemiparesis and visual field defects. The characteristic imaging features of PML are the absence of surrounding brain edema and non-enhancement. The JC virus damages the CNS oligodendroglial cells with resulting demyelination. The brain lesions of Toxoplasmosis and primary CNS lymphoma show diffuse or ring-shaped gadolinium enhancement on brain MRI imaging.
The combination of his age, dementia and brain CT findings are indicative of congophilic angiopathy. Lacunar strokes are ischemic.
This is the classical diabetic vascular mononeuritis simplex of the pupillary-sparing cranial nerve palsy. This palsy is painful in 25% of cases. Sixth cranial nerve palsy results in weakness of eye abduction; there is no ptosis. Cavernous sinus thrombosis results in proptosis, chemosis, optic disc swelling,…etc. Horner’s syndrome may develop as part of a cluster headache but the history is incompatible with this diagnosis. Pontine lesions result in nerve palsy, horizontal gaze paresis, and small reactive pupils; vertical eye movements are intact.
The patient’s history defines status epilepticus. The commonest cause is the withdrawal of long-term anti-epileptic therapy. Pseudo-seizures are responsible for 25% of cases of refractory genuine epilepsy, i.e., they may complicate genuine seizures. Malingering does not result in this prolonged unresponsiveness and involuntary movements. Aversive seizures are a form of frontal lobe seizures which present with repetitive head and eye turning movements towards the contralateral side.
The patient’s history and findings are highly suggestive of transient global amnesia, which is usually seen in old or middle-aged people with a history of stroke. Bilateral hippocampal infarction is a grave event that is associated with many abnormal neurological signs. His eye movements and gait are intact and, therefore, Wernicke's encephalopathy is a very remote possibility. Hysterical patients forget many things all of a sudden, including their own names. Patients with complex partial status present in a dazed confused state; they do not respond to verbal stimulations or questions.
This subjective diplopia (in addition to ptosis) has been present for more than 2 years. The question did not mention fatigability testing. If such testing was conducted properly, it might well have revealed worsening ptosis and variable diplopia. The findings are confined to the eyes and this defines pure ocular myasthenia. Botulism is an acute process that does not present intermittently for 3 years. Progressive external ophthalmoplegia results in bilateral symmetrical ptosis and globe weakness; diplopia is mild or absent. Oculopharyngeal muscular dystrophy presents with ocular weakness and dysphagia in the or decade.
The patient has severe acne. She might well have been treated with a retinoic acid derivative. Vitamin A and its derivatives may result in pseudotumor cerebri. The enlargement in the physiological blind spot reflects papilledema (and raised intracranial pressure). Brain imaging is abnormal in hemispheric infarctions and gliomas. Hippocampal sclerosis results in complex partial seizures.
This is the classical story of rapid correction of dehydration in an alcoholic patient with chronic hyponatremia (resulting from alcohol-induced diuresis). This rapid rehydration (rapid correction of hyponatremia) results in central pontine myelinolysis. The resulting demyelination is non-inflammatory and is not confined to the pons; a misnomer.
Global aphasia and dense right-sided hemiplegia point to a (dominant) middle cerebral artery occlusion; the middle cerebral artery is a medium sized-vessel and is usually blocked by an embolus rather than by a locally formed thrombus. He has atrial fibrillation. Lacunar motor strokes present with dense hemiplegia but without aphasia. Posterior fossa lesions, such as cerebellar hemorrhages, never result in aphasia. The transverse sinus is far away from the language area. Global cerebral hypoperfusion results in watershed infarctions and diffuse neocortical death.
The combination of cognitive dysfunction and visual hallucinations (at presentation, early in the course of the dementia illness) should cast a doubt on the diagnosis of idiopathic Parkinson’s disease. Autonomic dysfunction occurs in both Shy-Dragger syndrome and Lewy body dementia; well-formed visual hallucinations favor the latter. Pick’s patients demonstrate early personality and behavioral changes rather than memory impairment. Patients with normal pressure hydrocephalus may be misdiagnosed as having Parkinson’s disease.
Asymmetric lower limb sensory and lower motor neuron signs may suggest cauda equina lesions; however, the presence of neurological signs in the upper limbs would cancel this possibility. Peripheral polyneuritis is symmetrical. Tumors at the level of the craniocervical junction may produce a motor neuron disease-like picture. However, the history is slowly progressive over several months, and even years (a characteristic feature is the involvement of the ipsilateral arm and then the ipsilateral leg which are followed by the contralateral leg and finally the contralateral arm). The distribution of the motor and sensory symptoms in this patient is compatible with mononeuritis multiplex. Option e is an acute illness; however, its chronic variant, CIDP, may present as such.
The constellation of bilateral asymmetric sensory deficits and lower motor neuron signs in both lower limbs in addition to perineal numbness should always prompt the physician to search for cauda equina lesions. The list of these lesions is long and the scenario did not give a hint; you may consider tumors (benign and malignant), disc prolapse, vertebral fractures,…etc. The presence of sensory signs and symptoms would make motor neuron disease a remote possibility. Cervical cord astrocytoma should produce signs in the upper limbs as well as upper motor neuron signs in the lower limbs. Primary progressive multiple sclerosis usually results in spastic paraparesis. The planter reflexes in subacute combined degeneration of the cord are extensors and the sensory loss in the lower limbs follows a stocking pattern.
The development of intracerebral hemorrhage in patients younger than 50 years and who are not hypertensive should prompt the physician to search for causes other than the hypertensive etiology. Drug abuse may result in ischemic or hemorrhagic strokes.
The brain CT findings are typical of an acute extradural hematoma. Subdural hematomas are crescent-shaped. Subarachnoid blood is found mainly at the basal cisterns but it may extend to the hemispheres or subdural space.
Inversion of biceps and supinator jerks reflects combined cervical myelopathy at of the cord. The other stems cannot be explained by this finding. Note that diabetic peripheral polyneuropathy is usually mildly symptomatic.
The sensory, motor, and reflex changes in the right upper limb localize the lesion to the segment of the spinal cord (on the right side); this is most likely a compressive myelopathy caused by a tumor. His lower limbs’ signs are bilateral and symmetrical. The boy’s urinary urge incontinence is a sign of hyper-reflexic bladder. Necrotizing cauda equine radiculitis is usually seen in advanced HIV infection and is caused by CMV infection. Hereditary spastic paraparesis and HTLV1-associated myelopathy do not result in isolated deficits in the segment of the spinal cord. Midline frontal lobe lesions can damage both “leg cortical areas” and can result in spastic paraparesis but this would not explain the right arm signs.
The overall picture is suggestive of a chronic basal meningitic process; tuberculous meningitis would fit this scenario. Viral meningitides are acute or recurrent infections; very rarely, a chronic infection establishes itself in immune-compromised patients.
A high spinal cord lesion would not explain the brainstem signs. The virtually normal EEG excludes non-convulsive status epilepticus and alpha coma. Hysterical unresponsiveness is canceled out by the presence of many solid neurological signs, such as the up-going planters. This man has the typical locked-in syndrome which results from damage to the basis pontis. It is a de-efferentation state; the patient is conscious and alert and has intact comprehension but he cannot communicate with others.
The presence of resting tremors in a young individual, together with psychiatric manifestations and impaired liver function tests, should always prompt a search for Wilson's disease. The patient has a positive family history of a similar problem. Ordering serum ceruloplasmin (normal in up to 5% of cases and is low in the remainder) and 24-hour urinary copper (high in all established cases) are the next best steps. Liver biopsy with measurement of the amount of copper per gm dry weight can also be used. The serum copper is low, not high (a common mistake in examinations).
The overall clinical picture is that of progressive pancerebellar dysfunction with skeletal abnormalities in a young male; only Friedreich's ataxia would fit this scenario. It is reasonable to do echocardiography (looking for hypertrophic cardiomyopathy), fasting blood sugar (10-20% are diabetic), nerve conduction study, and EMG (looking for evidence of peripheral poly-neuropathy). A Friedreich's-like picture might be seen in abetalipoproteinemia and blood film may reveal red cell acanthocytes. The CSF analysis is normal in Friedreich's ataxia. Long-standing hypothyroidism can result in an isolated cerebellar dysfunction. Muscle biopsy has no place in the diagnostic work-up of Friedreich's ataxia.
This middle-aged woman has a history of breast cancer which was successfully treated 5 years ago. Her current scenario suggests an intracranial space-occupying lesion(s) as evidenced by her headache, papilledema, and the presence of focal signs. The patient’s age, gender, and history of breast cancer all are risk factors for meningioma, which may be the cause of her recent presentation; the 6 months duration of the headache is too long for cerebral metastases. The location of this tumor would be in the parasagittal midline frontal area. This case highlights the development of a benign tumor in a patient with a remote history of cancer (which has a different treatment modality and prognosis). However, it is worth investigating systemic recurrence and metastasis by liver ultrasound and bone scan. The meningioma can be successfully removed surgically and, therefore, 4-vessel cerebral angiography might be used before surgery to delineate the cerebral and tumor vasculature.
The constellation of paroxysmal sensory symptoms with lower limbs pyramidal signs and optic disc pallor in this young woman is highly suggestive of multiple sclerosis. Imaging of the brain and spinal cord can be used to assess the number, burden, distribution, and activity of the plaques. Visual-evoked responses can be used to detect subclinical involvement of the left eye. CSF analysis can be done to detect oligoclonal bands. Nerve conduction studies and EMG have no place at all in the diagnosis or follow-up of multiple sclerosis, as it is a central (not peripheral) white matter disease.
The overall scenario points toward Duchenne's muscular dystrophy. It is wise to proceed with serum creatine phosphokinase (which is high from birth), EMG (looking for myopathic pattern), and muscle biopsy (for dystrophin). Cardiac investigations, such as ECG and echocardiography, are done to detect cardiomyopathy. There is no peripheral nerve affection in Duchenne's muscular dystrophy; therefore, nerve conduction studies would be useless.
The patient has developed polymyositis; serum muscle enzyme levels (CPK, aldolase, LDH, and AST), EMG, and muscle biopsy are the right investigations.
The patient has developed Guillain-Barrè syndrome. Nerve conduction studies (including F-wave measurement) and lumbar puncture for CSF analysis are part of the diagnostic plan. Imaging of the brain and spinal cord would be normal in Guillain-Barrè syndrome. Stool examination and serology may be positive for a positive test would predict a bad outcome in but it is not diagnostic for this demyelinating disease per se.
The constellation of pseudo-bulbar palsy, wasting of small hand muscles, absent reflexes in the upper limbs, and pyramidal signs in the lower limbs are consistent with motor neuron disease (MND). EMG would reveal high amplitude, long-duration, and polyphasic motor unit potentials. Muscle biopsy is rarely done in clinical practice; however, this shows fiber-type grouping with angular fibers and absent inflammatory infiltrate, i.e., pure neurogenic atrophy. Serum creatine phosphokinase is either normal or mildly elevated. MRI of the foramen magnum may be done to exclude a mass lesion at that level which may present as an MND-like picture.
The absence of pallor and jaundice are not against the diagnosis of subacute combined degeneration of the cord; clinical anemia is absent in 25% of cases. The psychiatric manifestations (depression), painful ataxic sensory peripheral neuropathy, optic atrophy, and pyramidal signs would fit this diagnosis. The workup should be directed to confirm the presence of vitamin deficiency (and its cause). Serum or red cell folate is not used since this vitamin deficiency is not associated with subacute combined degeneration of the cord.
This young man has cluster headaches. High-dose oral prednisolone is very effective at aborting current and future attacks and inducing remission. High-flow, high-concentration nasal oxygen, intranasal xylocaine, and are the other abortive therapeutic options.
The overall picture is consistent with pseudotumor cerebri. Documentation of the high CSF pressure (through lumbar puncture) with measurement of other CSF parameters is the best next step.
The work-up of myasthenia gravis is divided into 2 parts. First, we should confirm the diagnosis of myasthenia gravis. Next, we should look for associated diseases that might affect the overall management. Anti-acetylcholine receptor antibodies, edrophonium test, EMG (repetitive, tetanic, and single muscle fiber), and imaging (mediastinal and brain CT scan) are the investigations required to confirm the diagnosis. Blood counts, ESR, anti-nuclear antibody, rheumatoid factor, tuberculin skin testing, serum TSH, blood sugar…etc., are parts of the second purpose.
The patient’s clinical presentation is highly suggestive of spontaneous subarachnoid hemorrhage due to a ruptured Berry's saccular aneurysm. The subarachnoid blood can be visualized by a non-contrast brain CT scan in 90% of cases on the first day. If initial the brain CT scan is normal, a CSF examination is the next correct step (looking for grossly hemorrhagic CSF, raised opening pressure, and xanthochromia).
This smoker man presents with Lambert-Eaton myasthenic syndrome (LEMS). Small cell lung cancer is the commonest underlying association. Part of the investigations should be directed at detecting this chest malignancy. The presence of anti-P/Q voltage-gated calcium channel antibodies is highly sensitive and specific for LEMS of any etiology. Anti-acetylcholine receptor antibodies are found in myasthenia gravis.
The presence of high fever, clouded consciousness, and neck stiffness should always prompt a search for pyogenic meningitis. The patient’s initial brain CT scan is normal and there is no need to repeat this imaging study with a contrast; lumbar puncture and CSF analysis are the correct next step. Meanwhile, the patient should receive empirical antibiotic therapy.
This man has developed confusion and headache over 2 weeks. There are lateralizing signs; an intracranial space-occupying lesion should rank top on your differential diagnosis list; therefore, brain imaging should be the next step. At least, 20% of subacute/chronic subdural hematomas in elderly people lack a history of prior head trauma. The duration of his illness is 2 weeks; the hematoma most likely would appear isodense with the adjacent brain tissue on brain CT scans.
The age of the patient, the long duration of the tremor, the symmetry and type of the tremor, and the response to alcohol all make benign essential tremor the likely diagnosis. Generally, there is no need to do any investigation, as the diagnosis is largely clinical. A full work-up is needed if patients show atypical features, such as extensor planters or rigidity.
This man has progressive cognitive decline without focal signs or a remarkable medical examination. Alzheimer’s disease is the commonest cause of dementia and would fit this patient’s scenario. Vitamin deficiency and hypothyroidism may present as dementia, but the normal medical examination and routine blood tests would cancel out these possibilities. CSF protein 14-3-3 can be ordered if the picture is suggestive of Creutzfeldt-Jacob disease. Although brain biopsy is the gold standard investigation to diagnose Alzheimer’s disease, it is usually done postmortem. Brain imaging would show global cortical atrophy, prominent sulci, and compensatory hydrocephalus; the usual Alzheimer’s image.
The combination of chorea, global cognitive dysfunction, and a positive family history of the same illness should always prompt a search for Huntington's disease. Brain imaging would reveal atrophy of the caudate nuclei. Genetic testing is also useful. Hereditary hemochromatosis is not a dementing illness; ordering serum ferritin would be unreasonable in this man.
This young woman demonstrates percussion myotonia and she is wearing a wig (because of frontal baldness?). She is also diabetic. Myotonia dystrophica is the most likely explanation. Her dysarthria is due to tongue and pharyngeal muscles myotonia. EMG would show characteristic myotonic discharges and myopathic changes. Ischemic forearm exercise test is used in glycogen storage diseases while serum anti-acetylcholine receptor antibodies are done in myasthenia gravis. Myotonia dystrophica does not affect peripheral nerves; nerve conduction studies would be useless.
This febrile man has new onset complex partial seizures, altered mentation, and mild neck stiffness; viral encephalitis should be your top differential diagnosis. Herpes simplex is the commonest cause of sporadic viral encephalitis. The patient’s brain CT findings are consistent with this diagnosis; contrast administration would not make a big difference. CSF examination is the correct step for the time being and the patient should receive an acyclovir infusion while his investigations are being completed. Herpes simplex encephalitis may cause a hemorrhagic CSF, may lower the CSF sugar, and may be normal in 2% of cases. Brain biopsy is rarely used to diagnose this CNS infection.
Dense hemiplegia with intact language, vision, and sensation in someone with longstanding hypertension should make you think of a pure motor lacunar stroke. Most likely his lesion lies at the posterior limb of the left internal capsule. A brain CT scan is the first imaging in all cases of stroke; the other stems are part of the patient’s management plan.
This woman has the triad of dementia, gait apraxia, and urinary incontinence; this is most likely normal pressure hydrocephalus. Brain CT scan of those patients reveals communicating hydrocephalus, no cortical atrophy, and no mass lesion. Normal pressure hydrocephalus is either idiopathic, or secondary to previous meningitis, subarachnoid hemorrhage, or head trauma. Dementia is typically mild and is preceded by a gait disorder. A lumbar puncture can be used for therapeutic purposes and to predict which patient will respond to shunting. The definitive diagnosis is by isotope CSF dynamic study or what is called radionuclide cisternography (which classically shows isotope accumulation in the ventricles, delayed clearance, and failure of ascent over the cerebral convexities).
The presence of an eyewitness is very important in the diagnosis of epileptic disorders. The mother describes typical attacks of generalized tonic-clonic seizures. There is a positive family history; idiopathic generalized grand mal epilepsy is most likely the diagnosis. The scenario does not point toward any atypical features (e.g., mental retardation, focal neurological signs, prolonged post-ictal phase,…etc.). Therefore, brain imaging is not indicated. Watchful waiting is unreasonable, as the recurrence rate is high; starting an antiepileptic medication would be the correct step. Temporal lobectomy is used in medication-refractory complex partial seizures. Video-EEG is used in difficult cases of epilepsy (e.g., when there is diagnostic uncertainty or multiple types of seizures).
This man most likely has idiopathic Parkinson’s disease. The diagnosis is largely clinical. Brain imaging studies and further work-up are required when the overall picture is atypical, e.g., symmetrical onset, pyramidal signs, cerebellar dysfunction,...etc. Early non-disabling cases may require nothing other than reassurance and frequent follow-ups. However, this man is embarrassed by his appearance and requires intervention in the form of anti-Parkinsonian medications. Ablative therapies are the last resort in advanced cases.
The patient’s clinical findings are consistent with relapsing-remitting multiple sclerosis. Her current presentation is that of acute transverse myelitis, which is function-threatening and calls for high-dose methylprednisolone pluses to hasten recovery (although it does not affect the long-term disability). After finishing this steroid regimen, the patient needs long-term immune-modulator therapy (beta interferon or glatiramer acetate).
The development of rapidly progressive dementia and startle myoclonus should always prompt a search for Creutzfeldt-Jacob disease. The EEG is positive in 65% of cases and shows characteristic complexes which might be transient. CSF examination for protein 13-4-4 level is a useful aid. Brain biopsy, looking for spongiform changes and detection of can also be done in selected patients. In familial cases, the diagnosis can be secured by the detection of the mutant form of in DNA from peripheral blood lymphocytes.
There are slowly progressive myelopathy and peripheral neuropathy; the patient is pale and jaundiced and had undergone gastric surgery several years ago. This should prompt you to search for and treat subacute combined degeneration of the cord due to vitamin deficiency. Giving high-dose folate would result in deterioration, and therefore, it is contraindicated. Vitamin deficiency should be included in the differential diagnosis list of all cases of non-compressive myelopathy.
This man has von Hippel-Lindau disease; the loin mass is probably renal cell carcinoma while the cerebellar one is hemangioblastoma. The new frontal lobe mass is malignant-looking which might well represent a secondary tumor from his renal cancer. The right eye fundal mass is a retinal hemangioma. An abdominal CT scan is useful to delineate the loin mass.
This triad of confusion, ophthalmoplegia, and ataxia in an alcoholic man should always make you think of Wernicke's encephalopathy. The absence of fever and neck stiffness is incompatible with pyogenic meningitis. Profound hypoglycemia rarely presents as such. Thiamin replacement therapy should always precede glucose infusion.
His atrial fibrillation is well-controlled; he most likely takes daily warfarin in addition to a rate-controlling anti-arrhythmic. His trivial trauma might well have resulted in acute subdural hematoma; an emergency non-contrast brain CT scan should be done and the neurosurgical department should be consulted as soon as possible. Embolic hemispheric stroke unlikely results in such drowsiness over a matter of 3 hours. The other stems are part of the patient’s management plan but stem “e” is the top priority for the time
The presence of a boil within a facial area that is drained by the inferior ophthalmic vein, the rapid and devastating onset of complete ophthalmoplegia, optic disc swelling, and facial edema over 3 days are highly compatible with septic cavernous sinus thrombosis due to Staph. The phrasing of the question may misdirect you to think of rhinocerebral mucormycosis; its development and progression would take a longer time. Intravenous antibiotics against Staph. aureus should be instituted without any delay. His blood sugar should be optimized and he needs careful water and electrolyte balance. Brain imaging should be done next.
The post-partum period is a well-known risk factor for intracranial venous sinus thrombosis. The brain CT scan suggests superior sagittal sinus thrombosis. She needs brain MRV and anti-coagulation.
This is the lateral medullary syndrome due to an ischemic infarction involving a wedge-shaped area of the lateral medulla; this may result from occlusion of any of the following arteries: vertebral, posterior inferior cerebellar, upper lateral, middle lateral, and lower lateral medullary arteries. The workup should be directed toward this brainstem ischemic stroke. Brain MRV is not part of this work-up.
The patient has developed diabetic peripheral sensorimotor polyneuropathy. To confirm the provisional diagnosis, neurophysiological testing with nerve conduction studies is required. The presence of severe symptoms should suggest an alternative diagnosis or an associated disease.
The differential diagnoses are Alzheimer’s disease and depressive pseudo-dementia. However, both may co-exist. The presence of prominent vegetative symptoms (such as weight change and insomnia), attitude during the examination, and dysphoric mood favor pseudo-dementia over Alzheimer’s. A trial of anti-depressants would seem reasonable.
This is the classical story of idiopathic trigeminal neuralgia in a middle-aged woman. Imaging studies are indicated if there are atypical features, e.g., a patient is a young man, bilateral symptoms, alternating pains, sensory loss in the face, brainstem signs,…etc.). The diagnosis is largely clinical in idiopathic cases; imaging studies, including angiography, fail to detect the anomalous vascular loop which entraps the cranial nerve. The first line treatment is carbamazepine, which produces an excellent response in the majority of patients. Second-line agents are phenytoin, gabapentin, and mexiletine. Trigeminal ganglion ablation should be the last resort at all possibilities when there is a failure of all forms of medical treatment.
Patients in a persistent vegetative state (PVS) represent a subgroup of patients who suffer severe anoxic brain injury and progress to a state of wakefulness without awareness. PVS may represent a transition between coma and recovery or between coma and death. In patients who continue in PVS, life expectancy is approximately 2 to 5 years, and most patients die from infection of the lungs or urinary tract, multi-organ system failure, the sudden death of an unknown cause, respiratory failure, or underlying disease. The EEG tracing in PVS could be normal or may reveal continuous generalized slowing, intermittent generalized slowing, background slowing, background suppression, alpha, generalized periodic pattern, periodic lateralized epileptiform discharges (PLEDS), and triphasic waves. Apart from EEG, the other stems in the question have no diagnostic value in this patient.
This sudden occurrence of deep coma in the context of no history of head trauma or abnormal movements, normal examination, and unremarkable brain CT, is highly suggestive of psychogenic coma or unresponsiveness. EEG would be a useful tool; a normal EEG in comatose patients is pathognomonic of hysterical unresponsiveness. In cases of organic coma, the EEG always shows some abnormality. Intoxication is very unlikely given the rapidity of the onset of coma during their quarrel.
This is a Parkinsonian-plus syndrome. There are resting tremors, cogwheel rigidity, dementia, ataxia, and extensor planters; this is most likely Shy-Dragger syndrome, a form of multiple system atrophy. Autonomic function tests, such as the detection of prominent postural hypotension, fixed heart rate,…etc., are reasonable steps for the time being. There are no diagnostic brain imaging findings, and brain MRI or CT scan may show global brain atrophy with compensatory hydrocephalus.
The patient’s history of recurrent muscle cramps and myoglobinuria after exercise in the context of positive family history and normal physical examination is indicative of the myophosphorylase deficiency form of glycogen storage disease. An ischemic forearm exercise test would be the correct answer.
This woman has focal motor seizures in addition to headaches. The brain imaging is suggestive of meningioma. Surgical removal is the best therapeutic option. Seizures can be controlled with anti-epileptic medication. The EEG may localize the epileptic focus, but it is not the best step for the time being, as the diagnosis is obvious.
The history and the MRI findings in this immune-compromised HIV-positive man are highly suggestive of progressive multifocal leukoencephalopathy (PML). The MRI picture is incompatible with primary CNS lymphoma or toxoplasma encephalitis. CSF PCR study for JC virus may be diagnostic. Unfortunately, there is no effective treatment and most patients die within 3-6 months.
The combination of the patient’s age, dementia, and brain CT findings are compatible with congophilic angiopathy. This angiopathy has resulted in lobar hemorrhage. We cannot prevent further hemorrhagic episodes. His dementia would preclude aggressive control of risk factors and interventions. The patient’s blood pressure is well-controlled; continuation of his current medical therapy is the best intervention. Anti-coagulation is contraindicated.
This is the classical diabetic vascular mononeuritis simplex of the pupillary-sparing cranial nerve palsy. The prognosis is excellent in the majority of patients; gradual recovery occurs within 6-12 weeks. The blood sugar should be well-controlled.
The patient has developed status epilepticus following the intentional withdrawal of long-term phenytoin. The development of high fever is due to his repetitive seizure activity, not an infectious process. Therefore, CSF analysis is not indicated unless the history is suggestive of CNS infection (i.e., a few days of fever, drowsiness, neck
The history and findings are highly suggestive of transient global amnesia (TGA). TGA is usually seen in middle-aged and old people with a history of stroke, especially in the posterior circulation. In all cases, the amnesia spontaneously reverts within a few minutes to many days (usually within a few hours). So, all we need after doing this CT scan is to calm down the patient and reassure him. The other stems are useless. He has no new stroke, no complex partial seizures, and no evidence of Wernicke's encephalopathy. Occult head trauma is the most important differential diagnosis. Inexperienced physicians may diagnose malingering or hysterical conversion.
The findings are confined to the ocular muscles and the symptoms have been present for more than 2 years; this defines pure ocular myasthenia (POM). Thymectomy is contraindicated in POM. Anti-acetylcholine receptor antibodies are present in 50% of POM. Associated thyroid disease is present in 3-8% of cases; all myasthenic patients should undergo thyroid function testing.
She might well have been prescribed oral isotretinoin and/or tetracycline for her severe scarring acne. Both medications are potential risk factors for pseudotumor cerebri (idiopathic intracranial hypertension). Stopping her current anti-acne medications (and using other alternatives) and adding acetazolamide (with oral prednisolone) is the next best step.
This is the classical story of rapid rehydration in someone with chronic hyponatremia (alcohol-induced diuresis) causing central pontine myelinolysis.
This man has many risk factors for stroke, both hemorrhagic and ischemic. The presence of a rapid irregular pulse is indicative of rapid atrial fibrillation; embolic stroke involving the main stem of the left middle cerebral artery has developed. Starting with a brain CT scan and ECG are reasonable steps. This step should be followed by echocardiography, blood sugar, blood His blood pressure and diabetes need optimization and his heart rate should be controlled. After 1-2 weeks, oral anti-coagulation can be started; it is unsafe for the time being because the infracted area is large and friable (hemorrhagic transformation can ensue rapidly).
This abbreviated scenario points to Lewy body dementia. Note that because of their visual hallucinations, such patients may be given neuroleptics; these medications will deteriorate the picture further. Patients with Lewy body dementia are extremely sensitive to the side effects of neuroleptics. Their Parkinsonism does not respond to dopaminergic agents. Donepezil may be of some benefit in the short term.
She has systemic vasculitis syndrome which has resulted in mononeuritis multiplex and rapidly progressive glomerulonephritis. Mononeuritis multiplex sometimes becomes so confluent as to imitate a peripheral polyneuropathic process. Goodpasture’s syndrome is not associated with peripheral nerve vasculitis; therefore, assessing serum anti-GBM antibodies has no place in the work-up and management of this patient.
She has asymmetrical sensory deficits and lower motor neuron signs in the lower limbs, as well as urinary retention; these should prompt the physicians to think of cauda equina lesions. MRI of the lumbosacral spine (with contrast) is the correct step.
The patient is younger than the age of 50 years and does not have hypertension; spontaneous non-traumatic hypertensive intra-cerebral hemorrhage is very unlikely. The usual culprits of non-traumatic hemorrhage are cerebral arteriovenous malformation (AVM), coagulopathy, drug abuse, and hemorrhagic brain tumors (primary or secondary). The patient’s MRI is suggestive of AVM, although the report did not comment on the hemorrhage itself! Conventional cerebral angiography is required to delineate the whole cerebral vasculature and the AVM, its feeding vessels, and any associated anomalies (such as aneurysms). The AVM may be amenable to embolization with occlusion of the feeding vessels through this angiography.
The brain CT findings are typical of acute extradural hematoma. Immediate evacuation is a must.
The presence of a reflex inversion in both biceps and supinator jerks would localize the lesion to the segments of the spinal cord. This man has cervical spondylotic myelopathy which is the cause of the upper motor neuron signs in the lower limbs. The feet' sensory changes and lost ankle jerks are due to diabetic peripheral neuropathy. Both pathologies have resulted in exaggerated knee jerks, lost ankle jerks, and bilateral extensor planters. The picture is not suggestive of vitamin deficiency (which is another cause of lost ankles and up-going planters).
There is a constellation of motor, sensory, and sphincteric problems. The right upper limb findings localize the lesion to of the spinal cord. His gait is spastic. Most likely, the patient has an asymmetric compressive right-sided spinal cord lesion. He needs a cervical spine MRI (with contrast). Local lesions in the neck can result in neck stiffness, as in this patient.
The overall picture points toward subacute/chronic meningitis; her ethnicity would make tuberculous infection the likely diagnosis. Despite hydrocephalus, which is common in tuberculous meningitis, lumbar puncture, and CSF analysis should be done. Although a chest X-ray is required (looking for current or past tuberculous infection), it is not the top priority for the time being.
This is the classical picture of a lesion at the basis pontis. This lesion has disrupted the descending motor fibers responsible for horizontal eye movements as well as limb and trunk movements, but preserving the fibers of the reticular activating system intact (which are more dorsally located in the mid-pons and above). This is a locked-in syndrome (a de-efferentation state), and is usually mistaken for coma; patients respond to commands by up and down eye movements. MRI of the brainstem is required. The damage can be incurred by strokes (hemorrhagic or ischemic), tumors (benign or malignant), severe demyelination, and infection (encephalitis). The outcome is variable and is mostly related to the underlying cause and the extent of brainstem damage.
Dilated ventricles with diffuse sulcal effacement are seen in normal pressure hydrocephalus. Prominent sulci with (compensatory) hydrocephalus are non-specific signs of generalized brain atrophy (e.g., in Alzheimer's disease). Normal imaging study (and sometimes with slit-like ventricles) is the usual finding in pseudotumor cerebri (PTC), indicating diffuse brain edema). Supra-sellar contrast-enhancing mass lesions (e.g., tumor, granuloma,…etc.) are space-occupying lesions that are not consistent with the diagnosis of PTC; PTC should have no mass lesions. The presence of periventricular plaques may suggest multiple sclerosis.
The CSF parameters in idiopathic pseudotumor cerebri (PTC) should be entirely normal apart from raised opening pressure (normally 5-18 cm water). Low sugar levels can be seen in infectious, malignant, and inflammatory meningitides. High CSF proteins are encountered in tuberculous meningitis, acoustic neuroma, and Guillain-Barrè syndrome. The CSF opening pressure in idiopathic PTC pressure may widely fluctuate but never returns to the normal range. Lymphocytic pleocytosis indicates a meningitic process, e.g., tuberculous meningitis. Positive Gram stains are never a normal finding and are indicative of pyogenic meningitis.
This is myasthenia gravis. Electron microscopy shows stratification and simplification of the post-synaptic membrane (but this is not used in routine clinical practice). Peri-fascicular atrophy is characteristic of dermatomyositis, even in the absence of inflammatory infiltrate. Fiber-type grouping is seen in neurogenic atrophy (indicating chronic denervation and re-innervation). Lymphorrhage is a focal collection of lymphocytes (similar to those seen in Hashimoto thyroiditis); lymphorrhages are found in myasthenia gravis. Heavy T-cell infiltration indicates an inflammatory process, e.g., myositis. Type II fiber atrophy is characteristically described in steroid-induced myopathy (but this is not specific).
An incremental response, at 4-5 Htz, is found in up to 90% of cases of generalized myasthenia. Jittering is seen upon doing “single muscle fiber” EMG for myasthenia gravis (not in the repetitive EMG); a trick! This single muscle fiber EMG would reveal “block and jittering with normal muscle fiber density”. The EMG study could be normal only in 10% of cases of generalized myasthenia; hence, we may proceed to tetanic stimulation, or rarely, to single muscle fiber EMG. An incremental response is found in Lambert-Eaton myasthenic syndrome. Dive-bombing discharges are indicative of myotonic disorders.
This man most likely has adult-type polymyositis. High amplitude, long duration, and polyphasic MUPs are seen in neuropathic disorders (with chronic denervation and re-innervation), e.g. motor neuron disease. Prolonged insertional activity, abnormal resting discharges, pseudo-myotonic discharges, short duration, low amplitude, and polyphasic MUPs are the usual myopathic EMG findings.
Alkaline phosphatase is found in the liver, bone, placenta, and bowel. It is not elevated in muscle diseases. The other enzymes mentioned in the question are used as muscle markers, especially creatine phosphokinase.
This man has myotonia dystrophica. His dysarthria is due to myotonia of the pharyngeal and laryngeal muscles. Hypogammaglobulinemia can result in repeated chest infections (and bronchiectasis). Myotonia dystrophica has no epileptiform activity. Testicular atrophy results in elevated serum LH and FSH. About 10-20% of patients have diabetes mellitus (and its complications). Cardiomyopathy may result in dysrhythmia.
This is Friedreich's ataxia (FA). Hypertrophic cardiomyopathy can be seen and adds to the morbidity and mortality of this disease. Diabetes can occur, but not fasting hypoglycemia. The CSF parameters are always normal. FA is not a dementing illness; brain MRI may reveal cerebellar atrophy late in the course. Spinal cord atrophy occurs; the spinal cord holds the burden of the disease.
This is Wilson's disease. Low serum copper level is seen. Normal anion-gap metabolic acidosis occurs due to proximal renal tubular acidosis (this is rarely of any clinical significance). Wilson's disease does not affect the peripheral nervous system; the nerve conduction studies are normal. The 24-hours urinary copper excretion is high. Wilson’s disease is a basal ganglia disease, not a cerebellar one; however, clinically, a “pseudo-cerebellar syndrome” can occur.
This is motor neuron disease. Prolonged F-wave on nerve conduction study is seen in demyelinating disorders, e.g., Guillain-Barrè syndrome. In motor neuron disease, the CSF parameters should be normal. The serum creatine phosphokinase is either normal or slightly raised; very high levels are seen in Duchenne's muscular dystrophy and rhabdomyolysis. High-amplitude, long-duration, and polyphasic motor unit potentials on EMG are indicative of chronic denervation with re-innervation. Muscle fiber necrosis and regeneration on muscle biopsy are seen in inflammatory myositis.
This is normal pressure hydrocephalus (NPH), sometimes clinically mistaken for Parkinson's disease! In NPH, there should be no mass lesion. The CSF opening pressure and other CSF parameters should be normal. NPH is not a demyelinating peripheral nerve disease. Ragged red fibers are seen in mitochondrial cytopathies. Dilated ventricles (all ventricles) with diffuse sulcal effacement or normal sulcal width are seen in hydrocephalus.
Spongiform changes are seen in brain biopsy specimens. Increased CSF levels of protein 14-3-3 are seen, although they are not specific and can be seen in stroke, multi-infarct dementia, and Herpes simplex encephalitis. A characteristic feature of the disease is the presence of periodic bursts of high-voltage triphasic complexes on EEG. However, these EEG findings may be transient and are seen in 65% of cases only. These changes are usually bilateral, but they may be more prominent on one side. A single brain biopsy can have a negative result because is not present in all brain areas; therefore, a negative detection of a single brain biopsy specimen (not multiple) does not rule out CJD.
Inflammatory cell infiltration on muscle biopsy is not seen, as the disease is not an inflammatory myopathy. There is no muscle fiber damage; therefore, serum muscle enzyme levels are normal. The disease is a peripheral nerve and root demyelinating illness; prolonged distal latencies on nerve conduction studies are found. A single CSF neutrophil cell is against the diagnosis. Campylobacter serology may be positive, but it does not mean that the patient has GBS.
The lens-shaped hyperdense extra-axial lesion is an acute extradural hematoma. A metastatic deposit or brain abscess may appear as a rounded hypodense area in the frontal lobe with prominent surrounding edema. A crescent-shaped, isodense extra-axial lesion reflects a subacute subdural hematoma. A fractured skull may result in an underlying extradural hematoma and brain contusion. Watershed infarctions appear as wedge-shaped hypodense lesions within watershed areas.
The overall clinical picture is suggestive of pyogenic meningitis, mostly a pneumococcal one; the opening pressure should be high and there is neutrophilic pleocytosis with raised protein and low sugar.
Most likely, she has Herpes simplex encephalitis. A positive CSF cryptococcal antigen is seen in cryptococcal meningitis. Biforntal atrophy occurs in general paresis of insane. The presence of calcified spots in both calves (on plain X-ray films) points to cysticercosis. This infection is unlikely to cause such an explosive brain dysfunction; neuro-cysticercosis usually produces a progressive syndrome with seizures, hydrocephalus, personality disorders,…etc. Degeneration of the nucleus basalis of Myenert on brain biopsy is a characteristic feature of Alzheimer's disease. Slow-wave activity in the left temporal area on EEG can be seen, with or without epileptic activity and/or periodic bursts of high voltage activity.
This is the classical scenario of cluster headaches. It is not an epileptogenic disorder. Prolonged wave upon doing visual evoked potentials is characteristically seen in multiple sclerosis. Temporal, giant cell, arteritis is associated with necrotizing granulomatous changes in the temporal artery. Bilateral swelling of the medial rectus muscle is characteristically seen in dysthyroid eye disease.
The aggregation of migraine-like headaches, deep venous thrombosis, and recurrent abortions should prompt the physician to search for the anti-phospholipid syndrome (APS). The aPTT is a screening test that does not correct itself when the patient’s blood sample is mixed up with normal plasma. Another clue to APS is false positive VDRL testing. Thrombocytopenia occurs. Anemia is seen, usually Combs-positive.
Focal changes are seen in focal lesions, such as tumors. Focal temporal poly-spikes are seen in temporal lobe epilepsy. The generalized 3-per-second spike-and-wave discharges are the characteristic finding. Generalized slowing with triphasic complexes is seen in metabolic encephalopathies, such as hepatic failure or uremia. The EEG is normal in 20% of cases inter-ictally; therefore, in 80% of patients, it is abnormal.
This is idiopathic Parkinson's disease. Dilatation of a lateral ventricle is compensatory to overcome the volume loss, in an aftermath of a massive hemispheric stroke. Parkinson’s disease is a basal ganglia disease. The disease does not produce grossly visible abnormalities on brain CT scans or MRI; functional imaging can be abnormal, however. A rounded extra-axial diffusely enhancing mass with a dural tail is a meningioma. Watershed infarctions are aftermaths of ischemic encephalopathy, as in cardiac arrest.
This is the classical picture of small-cell lung cancer-associated Lambert-Eaton myasthenic syndrome. Serum anti-acetylcholine receptor antibodies are seen in myasthenia gravis.
This is giant cell arteritis with resultant right-sided arteritic anterior ischemic optic neuropathy. Thrombocytosis occurs as part of disease activity. Creatine phosphokinase should be normal (without eye involvement or severe headache, the condition is easily mistaken for polymyositis in which creatine phosphokinase is raised). Abnormalities in liver function tests are common.
This is a form of mitochondrial cytopathy; it is not an inflammatory myopathy. Heavy mononuclear cell infiltration occurs in inflammatory myositis. Non-specific fiber-type atrophy is seen in disuse atrophy. Ragged-red fibers are the classical finding; it also occurs in zidovudine-induced myopathy in HIV-treated patients. Capillaritis is found in dermatomyositis which results in peri-fascicular atrophy. Reduced dystrophin content is found in Duchenne's or Becker's muscular dystrophies.
This is most likely a relapsing-remitting type of multiple sclerosis. The brain MRI is negative in 5-10% of cases only; this fact should be kept in mind. Therefore, a normal brain MRI does not rule out the disease. During relapses, the CSF protein can be raised, and it may reach 80 mg/dL; CSF protein values greater than 100 mg/dL should cast strong doubt on the diagnosis. The audiometric testing should be normal; however, brainstem auditory evoked potentials can be abnormal. Visual evoked potentials can detect up to 70% of asymptomatic optic neuritis (this would detect dissemination in space). Expansion of the spinal cord is suggestive of transverse myelitis.
This is the classical picture of pure motor lacunar stroke syndrome. The presence of seizures, aphasia, visual field defects, and impaired sensorium should cast strong doubt against lacunar strokes.
340) c, f.
She has seronegative (or receptor antibodies negative) myasthenia gravis. Other differential diagnoses are congenital myasthenic syndromes and Eaton myasthenic syndrome (LEMS). Congenital myasthenic syndromes are very unlikely given their rarity and the patient's age at the time of presentation. Ocular signs are uncommonly seen in LEM syndrome. Serum receptor antibodies are negative in 15% of generalized myasthenia gravis. The picture is suggestive of myasthenia gravis (which is much more common than the other 2 possibilities). Therefore, proceeding to the test and repetitive (not conventional) EMG is the correct step. Note that her symptoms are and misleading. The signs may fluctuate and the patient may display subtle signs when examined. Anti-voltage-gated calcium channel antibodies are seen in LEMS, and anti-Jo1 antibodies are positive in 30% of cases of adult-type polymyositis (and usually correlate with the development of interstitial lung fibrosis). Although a brain CT scan can be obtained in myasthenia gravis to rule out central causes of her signs, securing the diagnosis with the test and repetitive EMG is the top priority for the time being. She needs a CT scan of the chest (for thymus enlargement of tumors). Thymomas may be associated with pure red cell aplasia; however, blood films and counts are not the correct steps right now, as there is no clue for the latter disease association. Myasthenia gravis does not attack peripheral nerves; it is a disease of the neuromuscular junction. Therefore, nerve conduction studies (motor or sensory) should be normal. The neuromuscular junction is not damaged by secondary or tertiary syphilis; serum VDRL has no use. Note that VDRL (false positive ones) may appear in the examination as part of abnormal investigations in autoimmune diseases, especially anti-phospholipid syndrome. Mammography or colonoscopy can be chosen if the phrasing of the question suggests dermatomyositis or paraneoplastic neurological syndromes.
341) d, f.
The description of the optic discs is consistent with early "secondary" optic atrophy (after longstanding papilledema); therefore, the underlying etiology should be found. The clinical scenario and the "normal" brain CT scan are suggestive of pseudotumor cerebri. About 10% of cases are headache-free. Headache-free pseudotumor cerebri is not uncommon, and the presenting feature is almost always a deteriorated vision over months to a year. We should proceed with brain MRV (looking for intracranial cerebral and dural venous sinus thrombosis), and CSF analysis with an assessment of the opening pressure and other CSF parameters. Conventional angiography is invasive and is not available at all centers. Visual evoked potentials are usually used in multiple sclerosis patients to detect subclinical optic nerve involvement; this patient's optic nerves are already abnormal and this investigation would be abnormal and would add nothing. Retinal fluorescein angiography can be used to differentiate genuine papilledema from pseudo-papilledema. In this patient, however, this investigation is useless. Hypothyroidism (and other endocrinopathies) may be associated with pseudotumor cerebri. The correct sequence is to confirm the presence of cerebri and then we can proceed further to detect its associations (if the clinical picture is suggestive). Blood urea and serum electrolytes (and other routine blood tests) are part of the management plan, but they would not confirm or refute the presence of pseudotumor cerebri.
342) c, e,
The patient has rapidly progressive flaccid areflexic paraparesis. He demonstrates flexor planter responses, normal sensation (including no sensory level on the trunk), dysphagia, and dyspnea. Guillain-Barré syndrome is the correct diagnosis. He is in danger of respiratory failure; therefore, we should do serial forced vital capacity testing and consult the respiratory care unit in due time if impending failure is found). Nerve conduction velocities (including F-waves for the proximal spinal roots) looking for wide-spread demyelination (EMG has no place in the management of Guillain-Barré), and lumbar puncture (looking for albuminocytological dissociation) are When the diagnosis is secured, plasma exchange or intravenous immunoglobulin therapy should be initiated (as he presents within the 2-week window). A nasogastric tube should be placed for feeding. MRI of the dorsal spine is done when the scenario is suggestive of acute transverse myelopathy (compressive or non-compressive). Steroids are not used to treat Guillain-Barré syndrome; they are a treatment option for the chronic variety of this demyelinating radiculopathy, i.e., chronic inflammatory demyelinating polyradiculopathy (CIDP).
343) e, f.
The clue lies in the age of the patient. Only taboparesis (not tabes dorsalis) and vitamin deficiency (sub-acute combined degeneration of the cord) would fit this "short" scenario. Even without knowing the clinical features, you should guess that Friedreich's ataxia, Rufsum’s disease, and ataxia telangiectasia are seen in children. Combined cauda equina and conus medullaris lesions would result in upper and lower motor neuron signs in the lower limbs. Thiamin deficiency may result in peripheral neuropathy but would not cause extensor planters (neither Wernicke's encephalopathy nor Korsakoff's syndrome produce up-going planters). Primary progressive multiple sclerosis usually presents as non-compressive myelopathy in males in their 40s or 50s; the resulting spastic paraparesis is combined with up-going planters and exaggerated ankle jerks (with clonus).
Ceruloplasmin is normal in up to 5% of cases of Wilson's disease. This abbreviated scenario points out this disease. Wilson's disease can cause resting, postural, cerebellar, and wing-beating types of tremors. The presence of unexplained "tremor" in a young person should always prompt the physician to search for Wilson's disease. Wilson's disease can cause proximal renal tubular acidosis (RTA type 2) which is almost always non-significant. Therefore, serum electrolytes (Na, K, Cl, and testing may confirm normal anion gap metabolic acidosis. A examination of the eyes will detect Kayser-Fleisher corneal ring in 98% of untreated cases (if done by an experienced ophthalmologist); the sunflower cataract will be more obvious. Serum copper, 24-hour urinary copper, and liver biopsy were not mentioned in the question, but they are the cornerstone of the diagnosis. Genetic testing for the HFE gene and serum ferritin are part of the diagnostic plan of hereditary hemochromatosis while ECG might detect cardiac dysrhythmia in that disease. Sural nerve biopsy is done in unexplained peripheral neuropathies and certain childhood neuropathies. Neither brain biopsy nor CSF examination can help us diagnose Wilson's disease. Wilson's disease does not affect skeletal muscles; muscle biopsy is useless. Brain MRI may show hyper-intense putamen, but by itself is not diagnostic of Wilson's disease.
345) d, g.
You must face a case of stroke in each examination. You should be familiar with the inclusion and exclusion criteria of this form of therapy. Mild hand weakness (the patient should have severe weakness in at least one limb or severe aphasia to include him) and high blood sugar (blood sugar more than 400 mg/dL or less than 50 mg/dL are exclusion criteria) preclude this form of therapy. Please review the whole criteria in textbooks.
346) e, f.
This woman with a history of relapsing-remitting multiple sclerosis is experiencing a mild attack of optic neuritis. These attacks do not need any specific therapy; only severe function-threatening or life-threatening relapses should be treated with high doses of bolus methylprednisolone. Three or more relapses per year preclude the continuation of beta interferon or glatiramer acetate injections (as the objective behind using them is to reduce relapse frequency). The other stems are irrelevant. Plasma exchange has a place in severe function-threatening or life-threatening relapses not responding to conventional treatment. The best steps now are options e and f. Measuring serum antibodies against her interferon is useful to see whether this failure of medical therapy is due to the development of neutralizing antibodies or to the natural progression of the disease. The baclofen pump is used to treat spastic limbs. Carbamazepine is useful to alleviate paroxysmal symptoms (such as tonic spasms of the limbs, trigeminal neuralgia,…etc.).
347) b, d.
This patient with myotonia dystrophica has a disabling grip myotonia and needs to be treated; phenytoin is a good option but should be used cautiously as he has cardiac conduction defects. Foot drop can be managed with specific ankle-foot orthosis and splints. He is frankly diabetic and GTT is an unreasonable step; he should receive anti-diabetic medications. The ptosis is progressive; lid-lifting surgery has no place except in severe cases. He may need cataract surgery instead. The other options are useless.
348) f, g.
This man has mononeuritis multiplex. Polyarteritis nodosa and granulomatosis with polyangiitis (Wegner's granulomatosis) should be the top differential diagnoses. Subacute primary axonopathy should prompt a search for vasculitic, toxic, and metabolic causes of neuropathy. SLE can result in mononeuritis multiplex; the age and sex of the patient would make this diagnosis unlikely. Options f and g are more practical. Systemic vasculitides in general result in normochromic anemia, neutrophilic leukocytosis, thrombocytosis, and high ESR. Some of them may attack the kidneys and cause azotemia. Systemic manifestations are usually non-specific with fever, weight loss, malaise, and anorexia. Malignancy can arise as a differential diagnosis.
349) d, h.
This man has autonomic neuropathy, entrapment neuropathy (bilateral carpal tunnel syndrome), and peripheral sensory neuropathy (bilateral foot pain). The differential diagnosis list of autonomic neuropathies with peripheral neuropathy is relatively short: diabetes, chronic renal failure, AIDS, primary AL amyloidosis, and porphyrias. To this list, we can add Guillain-Barré syndrome, LEMS, Sjögren's syndrome, medications, drugs, and toxins (vincristine, cisplatin, acrylamide, and thallium), and the various types of hereditary sensory autonomic neuropathy (HSAN). Don’t confuse the aforementioned mentioned causes with those that can result in isolated autonomic failures, such as acute pan-dysautonmia, postural orthostatic tachycardia syndrome and primary idiopathic anhydrosis. Hereditary motor neuropathy with liability to pressure palsy and multifocal motor neuropathy with conduction block are the differential of motor neuron disease.
The sudden occurrence of partial Brown-Sequard syndrome in this young woman should always prompt a search for multiple sclerosis (MS). In MS, Brown-Sequard syndrome is usually partial rather than complete. A compressing metastatic tumor (e.g., from breast cancer) may give a similar picture. Note the sensory loss on the lateral aspect of the right arm and left-sided extensor planter and akinesthesia; MRI of the cervical cord with gadolinium is the key imaging investigation here, as the lesion most likely lies at the left segment of the cord. The findings localize the pathology to the cervical cord; brain imaging would be useless as the initial investigation. In all cases of acute myelopathy, you should know whether this is compressive or non-compressive, as the treatment and prognosis differ a lot.
Severe cervical spondylosis is a well-known risk factor for brainstem stroke due to vertebrobasilar ischemia. Carotid and vertebrobasilar Doppler studies or transcranial Doppler studies should be done. Aspirin should be given to all ischemic stroke patients unless it is contraindicated. All risk factors for ischemic stroke should be addressed and controlled. Thrombolytic therapy is beyond its window period.
This woman's new generalized seizure should always prompt a search for hematoma expansion or the development of another hematoma that causes cortical irritation. Needless to say, hypo- or hypernatremia should not be overlooked (those inpatients need a careful fluid and electrolyte balance). In addition, look for other etiologies behind the development of these seizures, such as severe hypoxemia, medications' side effects, and interactions,…etc. Her seizures would further increase her intracranial pressure; secondary prophylaxis with anti-epileptics should be instituted while looking for and removing the culprit, if possible.
Up to 90% of the pyramidal tract decussates at the lower medulla oblongata to the contralateral side. However, in a minority of the normal population, this decussation could be very minor or even absent, as in this patient. In such individuals, a lesion in this tract above the lower medulla will not give contralateral pyramidal signs; instead, the signs will be ipsilateral. This patient has a cortical irritating tumor, which causes focal seizures at the same side of the tumor because of pyramidal non-decussation. Although the other options might be true in real practice, this congenital anomaly should not be forgotten.
The patient was diagnosed with schizophrenia and might well have been given a conventional neuroleptic. The constellation of confusion, high fever, rigidity, and dysautonomia would fit neuroleptic malignant syndrome. This syndrome develops over a few days and it is not a sudden one.
In Friedreich's ataxia (FA), there is no cognitive impairment or only mild impairment in cognition; a marked cognitive dysfunction should cast strong doubt on the diagnosis. Absent family history does not refute the diagnosis; however, its presence is a helpful clue. Diabetes mellitus occurs in 10-20% of cases and may result in polyuria and polydipsia; diabetic retinopathy may occur in the long term. Optic atrophy and/or retinitis pigmentosa may develop. FA is an autosomal recessive disease; unlike other hereditary spinocerebellar ataxias, which are autosomal dominant. FA is the commonest cause of hereditary spinocerebellar ataxia.
This middle-aged woman has acute left-sided papillitis; the list of differential diagnoses is long. Vasculitides, malignant deposits, infectious agents, sarcoidosis,…etc can produce this presentation. Multiple sclerosis is an unlikely diagnosis in this woman, given her age and the type of optic neuritis she has, but it needs to be excluded. The visual loss in giant cell arteritis is irreversible; progressive visual improvement to a remarkable degree should suggest a diagnosis other than giant cell arteritis. Foster-Kennedy comprises a slowly progressive optic atrophy on one side (the side of the compressing intracranial mass) and optic nerve head swelling on the other side (due to raised intracranial pressure).
This man has a "cluster headache-like" presentation; cluster headache neither spans the whole day nor persists for 2 years without remission. In addition, he has hypogonadism as evidenced by his soft testes and gynecomastia.
This constellation should call for imaging the sellar/suprasellar area. Brain MRI may reveal a large sellar mass with supra-sellar extension and impingement upon the left carotid artery. His serum prolactin would be very high.
Weight gain in leukemic patients may reflect hypothalamic dysfunction because of leukemic infiltration. This together with the pancephalic headache and ptosis, CNS involvement is a very likely complication. Glucocorticoids might increase the patient’s weight, but the persistent headache and ptosis would point out a way from this possibility. Vincristine may result in peripheral sensory neuropathy or autonomic neuropathy, not cranial palsies. Leukemic patients with CNS involvement need intra-thecal chemotherapy and craniospinal irradiation after securing the diagnosis by CSF cytological studies.
This patient is immune-suppressed because of cyclosporine. The triad of clouded consciousness, fever, and neck stiffness should always prompt the physician to search for meningitis (or meningoencephalitis). Cyclosporine should be withheld, and starting broad-spectrum antibiotics is the best action for the time being. Meanwhile, arrange for lumbar puncture and CSF assessment. Blood cultures are useful in bacteremic patients by isolating the offending organism. Adding another immune suppressant (azathioprine) would be the wrong step. In the absence of focal/lateralizing neurological signs or signs of grossly raised intracranial pressure, brain imaging is not justified; CSF can be done safely in those patients.
Primary progressive multiple sclerosis is reflected by the progression of symptoms over 6 months and the widespread “white matter” signs. Brain MRI with contrast is a reasonable step, looking for the disease’s plaques. CSF analysis and visual evoked potentials (looking for subclinical involvement of the left eye) are also indicated. The management of primary progressive multiple sclerosis is entirely different from that of the relapsing-remitting type.
This woman with permanent valvular atrial fibrillation has developed an embolic stroke. The infracted area is large with mass effect and midline shift. Therefore, measures to reduce the raised intracranial pressure should be instituted without delay, such as high concentration mannitol infusion,...etc. While anticoagulation is indicated, it is should be withheld for the time being as there is a very high risk of hemorrhagic transformation of this large friable infarcted area. It can be started after 1-2 weeks. Her atrial fibrillation is rapid, and she needs measures to slow it (e.g. digoxin or beta blockers). Echocardiography is required to assess her heart. Rate control and anti-coagulation are required, instead of rhythm control or DC cardioversion.
The constellation of this long-standing history, positive family history, stork-like legs, and palpable nerves in the context of little disability and no other systemic involvement is typical for Charcot-Marie-Tooth disease. Palpable nerves can also be seen in Refsum’s disease, but this disease results in retinitis pigmentosa, ataxia, and thick dry skin. Chronic inflammatory demyelinating polyradiculopathy may result in a progressive or fluctuating course with widespread motor and sensory signs; little disability and stork-like legs are not expected findings. Guillain-Barrè syndrome, whether the first attack or less commonly the relapsing form, has a rapidly progressive course with ascending flaccid paralysis. Diphtheritic neuropathy is a demyelinating form of predominantly motor peripheral neuropathy that occurs within 2-3 months of diphtheritic infection and has a rapid pace.
This is Broca's aphasia in a right-handed man; the posterior part of the lower left frontal gyrus (Broca’s area) is the damaged site.
Weight gain, not weight loss, is a side effect of valproic acid; this should be taken into account when prescribing this medication to obese epileptic patients. Alopecia occurs with valproic acid while hirsutism occurs with phenytoin.
Kayser-Fleischer ring is due to copper deposition within Descemet’s membrane of the cornea. The ring is usually reversible upon using copper chelating therapy.
CIDP, not GBS, can be a cause of palpable nerves. Charcot-Marie-Tooth disease type I is a demyelinating disease that produces palpable nerves; type II is an axonal one that does not result in nerve enlargement. Another cause of palpable nerves is leprosy.
Both carbamazepine and phenytoin can worsen petit mal epilepsy. Sodium valproate acid and ethosuximide are the first-line agents, while lamotrigine and clonazepam are second-line ones Sodium valproate acid is preferred because it is an effective agent against many types of epilepsies (which might coexist with petit mal epilepsy, such as myoclonic jerks and generalized tonic-clonic seizures).
Option “e” is papilledema. Unilateral or bilateral optic nerve head swelling in multiple sclerosis patients indicates papillitis, not papilledema. In optic neuritis, the visual acuity is remarkably reduced; optic disc swelling with preserved vision points to papilledema.
The clinical picture is suggestive of community-acquired meningitis in an otherwise healthy man. Empirical intravenous antibiotic therapy and blood cultures should be started without delay while arranging for lumbar puncture and CSF analysis. Brain imaging is required if the examination shows focal or lateralizing neurological signs. In such cases, an urgent brain CT scan is the imaging modality of choice because MRI is unsuitable for critically ill and confused patients. He has no risk factors for HIV; ordering this test without prior consent is not justified. He has no acute subarachnoid hemorrhage to prescribe nimodipine.
Dysautonomia is seen in up to 65% of cases and might produce sudden cardio-respiratory arrest as well as fluctuating blood pressure and pulse rate. Some degree of asymmetry in the neurological signs may be seen in up to 9% of cases at the time of diagnosis; however, marked or persistent asymmetry should cast a doubt on the diagnosis and should prompt a search for an alternative condition. Even at best centers, the mortality rate is around 4-5% of cases. The CSF proteins level and the nerve conduction study might be entirely normal in the week of the illness; hence, normal studies early in the course are not against the diagnosis. Follow-up studies are indicated. Some patients, around 6%, may experience relapses which might be associated with certain HLA haplotypes.
Mesial temporal (or hippocampal) atrophy is a common cause of temporal lobe epilepsy (TLE). Carbamazepine and phenytoin are effective in many patients and should be the first-line agents if no contraindication is present. Refractory TLE patients are the best candidates for surgical treatment of epilepsy in general. The EEG may show lateralized spikes in one or both temporal lobes.
Meningioma is an extra-axial tumor that is benign in a substantial number of patients.
The presence of underlying brain edema indicates that the tumor may be frankly malignant, secretary, or atypical. The tumor may stop growing but never regresses. The commonest sites are over the cerebral convexities and along the falx cerebri; the infratentorial fossa and the spine are uncommon locations. Intracranial meningiomas are associated with breast cancer; a history of breast cancer and past cranial irradiation are risk factors for meningioma development. Multiple meningiomas should always prompt a search for neurofibromatosis type II.
Anomia is a supra-tentorial sign that almost always indicates a cortical lesion in the dominant hemisphere. Certain brainstem lesions might result in anarthria, which can be easily confused with aphasia. Horizontal nystagmus may be due to peripheral vestibulopathy, but the vertical one is always central in origin. Horizontal gaze paresis is a pontine sign while the vertical one points to a midbrain lesion. Onion skin pattern of facial sensory deficit localizes the lesion to the trigeminal sensory nucleus and tract. Damage to the brainstem medial longitudinal fasciculus results in internuclear ophthalmoplegia.
The idiopathic variety is the commonest type; other causes/associations are intracranial venous sinus thrombosis, medications (tetracycline, vitamin A preparations), Addison's disease, and Cushing's syndrome. Headache-free variety is well-documented and unfortunately, those patients present lately with visual loss. The visual loss is due to secondary (not primary) optic atrophy due to long-standing papilledema. Although steroids can be a cause (long-term treatments, particularly upon withdrawal), they are the agent of choice in severe elevations of intracranial pressure. Optic nerve sheath fenestration, although done on one eye, it protects both eyes!
CNS involvement in leukemias always portends a grave prognosis, especially when present at the time of the diagnosis. Headache, backache, confusion, cranial nerve palsies, and root signs might be clues to leukemic meningitis. A single CSF sample may fail to show the blast cells, and repeated samples are required to increase the diagnostic yield. Neck stiffness in leukemias could be due to leukemic meningitis, infectious meningitis, or subarachnoid hemorrhage (due to low platelets). The patient should be put on a certain treatment protocol that entails intrathecal chemotherapy (methotrexate, cytarabine, and hydrocortisone) and craniospinal irradiation.
Nystagmus is an infratentorial sign, e.g., it is seen in posterior circulation strokes. Hemiplegia could be due to anterior or posterior circulation strokes. Seizures develop in 5-15% of stroke patients because of cortical irritation (mainly in embolic or hemorrhagic strokes).
The concept of the dominant and non-dominant hemispheres is important in localization in neurology. All aphasias result from dominant hemispheric lesions. Hemiplegia is seen in many sites damaged by a pathology (such as the cortex, internal capsule, basis pontis,…etc.). Astereognosis is a cortical sign but can be seen in both dominant and non-dominant parietal hemispheric lesions. Constructional apraxia occurs in non-dominant parietal lesions. Urinary incontinence occurs in lesions involving both mesial frontal lobes (such as normal pressure hydrocephalus).
Clarithromycin has resulted in enzyme inhibition and carbamazepine toxicity; the latter manifests as ataxia and diplopia. The same clinical scenario is consistent with the Miller-Fischer variant of Guillain-Barrè syndrome!
Motor neuron disease does not result in autonomic neuropathy. Other causes are fatal familial insomnia, vasculitides, Fabry's disease, and multiple system atrophy.
This man presents with a subacute meningitic illness on the background of a positive family history of tuberculosis; you should have a high index of suspicion of tuberculous meningitis and anti-TB medications should be started without delay while pending the result of CSF culture and ZN stains for acid-fast bacilli. The history is too long for a viral etiology. The intracranial pressure is high (normal 5-18 cm The hydrocephalus in TB meningitis could be both communicating and non-communicating. Even with successful treatment, many patients are left with a considerable degree of neurological disability.
This man has pseudo-bulbar palsy. Myasthenia gravis is a cause of bulbar palsy.
The presence of cerebellar signs, ocular palsies, marked dementia, Parkinsonian features, sensory signs and symptoms, and sphincter disturbances are against the diagnosis of motor neuron disease. The combination of amyotrophic lateral sclerosis, dementia, and Parkinsonian features is a very rare distinct clinical syndrome, and should not make you change your answer.
This woman has primary optic atrophy. Long-standing raised intracranial pressure states with papilledema (e.g., pseudotumor cerebri, space-occupying lesions, obstructive hydrocephalus,…etc,) can produce secondary optic atrophy (the optic disc is yellowish-white with indistinct margins).
Aphasia is a cortical sign. Dementia may develop in advanced multiple sclerosis and is of a subcortical type (slow thinking, apathy,…etc.).
Oligodendrogliomas are primary brain tumors that are usually supratentorial in location, less infiltrative than astrocytoma, and therefore, most of them are amenable to complete surgical excision. These tumors usually respond well to systemic chemotherapy. Tumor calcification is usually seen in 30% of cases.
Of all gliomas, glioblastoma multiforme is the most aggressive one. It infiltrates the adjacent areas diffusely which makes complete surgical excision impossible; however, de-bulking surgery is done to decrease its size, obtain a tissue diagnosis, and reduce the intracranial pressure. Gliomatosis cerebri is said to be present when there is diffuse infiltration without a clear-cut mass or enhancing area on brain MRI; it is uncommon. The prognosis is very poor. Metastasis outside the CNS is rare and is usually seen in those who were operated upon.
Donepezil is a central inhibitor of acetylcholinesterase and is used in early cases of Alzheimer's disease. About 10-20% of patients will show a modest improvement in their cognition. The medication has a long half-life and is given once per day. Tacarine (central inhibitor of acetylcholinesterase) is hepatotoxic; donepezil is not. It can cause bradycardia and, therefore, is contraindicated in those with advanced heart block.
Normal pressure hydrocephalus (NPH) is one of the causes of potentially reversible dementia. However, it is an uncommon cause (Alzheimer's disease comprises up to 50% of cases of dementia in old people). It can be idiopathic, or secondary to head trauma, subarachnoid hemorrhage, or meningitis. Brain MRI shows dilated ventricles (without prominent cortical sulci), upward bulging of the corpus callosum, and widening of the Sylvius aqueduct in the absence of an intracranial mass lesion. The definitive diagnosis is by radionuclide cisternography. Post-shunting, 30-50% of patients will show improvement in their gait and cognition.
Huntington's disease (HD) is an autosomal dominant disease and is due to trinucleotide CAG repeats expansion in the Huntingtin gene on chromosome 4. Seizures and Parkinsonian features are more common in the juvenile variant, which is rare. Patients who present with chorea in the context of a positive family history of that movement disorder should be differentiated from benign familial chorea (which has a relatively good prognosis).
Benztropine (like all other anticholinergics) is effective at treating not rigidity. However, in patients older than 60-65 years, it can produce confusional states. Amantadine can be used in early cases, either alone or with anticholinergics, and it has a mild short-lived effect that rapidly wears off. L-dopa is the pro-drug of dopamine. There are no receptors (only Tolcapone (and entacapone) is a COMT inhibitor; it enhances the effect of L-dopa therapy.
Hematomyelia is a hematoma within the substance of the spinal cord; it may result from arteriovenous malformations (AVM), coagulation defects, and vasculitis. Decompression into the subarachnoid space may occur. When an AVM is a cause, spinal angiography is done to delineate the AVM; the AVM may be amenable to surgical resection; otherwise, the treatment is symptomatic.
Tabes dorsalis is a form of tertiary syphilis. Rombergism is seen in 50% of cases, due to loss of akinesthesia (vibration and position senses should be impaired). Loss of bladder sensation causes urinary retention and overflow incontinence. Extensor planters are elicited in taboparesis or general paresis of insane, not in pure tabes dorsalis. The severe lancinating pains may cause severe abdominal pain (tabetic abdominal crises); this may bring the patient to the Emergency Room (as an acute abdomen but no surgical cause can be found). This is one of the causes of the so-called medical acute abdomen. Other causes of medical acute abdomens are familial Mediterranean fever and acute intermittent porphyria.
The rationale of giving beta interferon injections in RRMS is to decrease the severity and frequency of relapses (by one-third); the occurrence of 1 relapse after 1 year of therapy is not a reason to stop this form of therapy. The occurrence of 3 or more relapses within 1 year (that have necessitated steroid pulses) is an indication of treatment failure; beta interferon therapy should be stopped.
Levetiracetam is an anti-epileptic agent. Cocaine, quinolones, and chlorpromazine reduce seizure threshold as well.
The precise mode of action of riluzole is unknown, but it is supposed to have an anti-glutamate action that interferes with excitotoxic neuronal cell death mechanisms. It is given orally and has been found to offer a modest improvement in the survival figure. It is hepatotoxic and can cause weight loss.
Long-term dapsone therapy (e.g., treatment of leprosy or Behcet disease) can result in pure motor peripheral neuropathy. The other stems result in predominately sensory neuritis.
The distinction between demyelinating and axonal types of neuropathies is very important with respect to underlying etiology, potential treatment, and prognosis. There is no definite clinical test for this discrimination, but nerve conduction studies can answer this question. Vitamin deficiency is a cause of subacute/chronic primary peripheral axonopathy.
Anticholinesterases (such as pyridostigmine) result in symptomatic improvement only and they do not alter the disease course. Thymectomy has no place in neonatal myasthenia, congenital myasthenic syndromes, patients above the age of 65 years, myasthenia duration of more than 7 years, and pure ocular myasthenia. Intravenous immunoglobulin is used in a myasthenic (not cholinergic) crisis. Although prednisolone is effective in almost all cases, it can produce a dramatic worsening at the start of treatment if given in high doses. Cyclosporine has a modest effect as an immune-suppressive agent in myasthenia gravis.
Medications and drugs are usually overlooked as a cause of muscle weakness. The list of these medications and drugs is long; non-steroidal anti-inflammatory drugs do not result in this complication. Zidovudine can cause myopathy with ragged-red fibers due to mitochondrial toxicity. The risk of statin-induced myopathy (or myositis) is greatly increased when these agents are concomitantly ingested with cyclosporine or gemfibrozil.
Inclusion body myositis is the commonest cause of inflammatory myositis in individuals older than the age of 50 years. EMG may show evidence of denervation due to the neuropathic component of the disease (but there is no degeneration of anterior horn cells). It is resistant to immune-suppressive therapy. Occasionally, many cases are diagnosed initially as polymyositis but the failure of immune-suppressive therapy eventually points out towards to this disease’s entity. The prognosis is poor. Some cases show familial clustering. The presence of rimmed-vacuoles on biopsy specimens is highly suggestive of inclusion body myositis; there are many other distinctive features on histopathological examination, such as deposition of amyloid and presence of eosinophilic cytoplasmic inclusions.
Facioscapulohumeral muscular dystrophy is not associated with cardiac involvement, although it may be associated with sensorineural deafness, retinal detachment, and labile hypertension. Limb-girdle muscular dystrophy is uncommonly associated with cardiac involvement.
Botulism is a disease of the motor end-plate from interference of acetylcholine release. This would affect acetylcholine release at the peripheral autonomic ganglia resulting in a multitude of autonomic dysfunction signs; the CNS is preserved.
Kennedy’s disease is a form of bulbospinal muscular atrophy due to trinucleotide repeats expansion. The other stems are mitochondrial diseases.
In 30% of cases, no obvious source of infection can be found. The surrounding edema is vasogenic. Lumbar puncture is both dangerous and unnecessary. After successful treatment, around 50% of patients develop seizures.
About 5-10% of PCR-proven cases have a normal brain MRI; the CT scan is normal in of such cases. The virus cannot be cultured from the CSF but its DNA is present there. HSV can be recovered from brain biopsy specimens. The negative predictive value of a negative CSF PCR assay for HSV DNA is 98%. Acyclovir should be started without any delay when there is a clinical suspicion of HSV encephalitis (as it decreases both, the morbidity and mortality figures).
Positive CSF protein 14-3-3 in the context of rapidly progressive dementia and myoclonus is highly suggestive (but not diagnostic) of CJD; it can also be positive in HSV encephalitis and vascular dementias but is negative in Alzheimer's disease. The presence of fever, high ESR, peripheral blood neutrophilic leukocytosis, or CSF neutrophilic pleocytosis should cast doubt on the diagnosis of CJD.
When the ICP is recorded invasively through ventriculostomy, the CSF can be drained to decrease the pressure. The head of the bed should be elevated. Steroids can remarkably improve vasogenic edema associated with brain tumors or abscesses; they are useless in cytotoxic edema which occurs in ischemic or hemorrhagic strokes. Plasma osmolality should be kept below 320 mOsm/kg when using mannitol infusions.
CPM results from too rapid correction of hyponatremia or hypo-osmolality states. Partial forms are not uncommon and may present as isolated dysarthria, confusion, or even gaze palsies. Therefore, the absence of quadriparesis is not against the diagnosis. The usual picture is an acute onset of quadriparesis and pseudo-bulbar palsy in a chronically alcoholic individual, who has received rapid rehydration and correction of chronic hyponatremia.
Stem “e” is an "inclusion criterion".
Hypothyroidism is a cause of slowly progressive ataxia in long-standing cases; the other stems are causes of acute ataxia.
Kearns-Sayre syndrome is a sporadic, not an inherited, cause of ataxia; it is a mitochondrial cytopathic disease.
Enteroviruses are the commonest agents responsible for viral meningitides; the other infectious agents are considered to be "uncommon" causes.
Not every viral encephalitic process portends a gloomy prognosis. La Crosse (California) virus, Venezuelan equine encephalitis virus, and Epstein-Barr virus have a good prognosis in general. Eastern equine viral encephalitis has a case fatality rate of 50-75%, and at least 80% of survivors are left with severe neurological deficits.
Status epilepticus is a medical emergency, which has a high mortality rate. The commonest precipitating event is sudden withdrawal (self or iatrogenic) from long-term anti-epileptic therapy. Lactic acidosis is very common but does not warrant any treatment. Phenobarbitone infusion should be used as the step (after lorazepam and phenytoin). Hyperthermia, not hypothermia, occurs.
Ischemic stroke in young people is an important subject in neurology. The occurrence of this type of stroke in people younger than 45 years of age should prompt a thorough search for an underlying cause, such as atrial fibrillation, infective endocarditis, meningovascular syphilis, paradoxical embolism through a patent foramen ovale, vasculitis, anti-phospholipid syndrome,…etc. Atherosclerotic disease is very rare in this age group as a cause of ischemic stroke.
In the absence of chronic hypertension, or patients younger than 50 years of age, spontaneous "hypertensive" hemorrhage is very unlikely. Instead, one should look for other causes, such as arteriovenous malformations, coagulopathy, drug abuse, head trauma, hemorrhage in tumors,…etc. Congophilic angiopathy is responsible for lobar hemorrhages in old people.
This young man demonstrates a new onset of focal motor seizures. Intracranial space-occupying lesions should always be excluded. Brain CT scans may miss some lesions. MRI (with gadolinium) is superior to it. After head traumas, some patients may develop early and/or late focal epilepsies. A migraine-like headache with focal seizures should always prompt a search for anti-phospholipid syndrome or cerebral arteriovenous malformation. Carbamazepine is the drug of choice for focal seizures.
Aspirin has been shown to decrease stroke-related morbidity and mortality, as well as early stroke recurrence. Heparin is indicated in the persistent cardiogenic source of embolization. Heparin is associated with an increased risk of CNS (or systemic) hemorrhage, which statistically outweighs any benefit. The combination of aspirin and clopidogrel in the acute setting is still controversial.
The ocular and facial muscles in polymyositis are usually spared while the anterior neck muscles are commonly involved (causing neck drop). If this weakness is accompanied by typical skin rashes, this defines dermatomyositis. Respiratory muscles involvement is uncommon but dangerous and mainly develops in acute cases.
Cerebellar masses in children are usually malignant tumors. The pilocytic variety of low-grade astrocytoma has an excellent prognosis; a complete cure can be achieved if the tumor is removed completely. In general, infratentorial tumors tend to raise the intracranial pressure early (unlike supratentorial ones). The presence of neck stiffness with a negative Kerning's sign should make you think of a local pathology in the posterior fossa (e.g., a tumor) or the neck. The most fearful event that complicates posterior fossa masses is secondary brainstem compression (and herniation syndromes).
421,422, and 423) d, d, d.
Only pseudotumor cerebri fits the clinical picture. Apart from routine blood tests, the next step should be brain imaging, that is CT scan (which usually shows a normal brain with or without slit-like ventricles). If there is any suggestion of intra-cranial venous sinus thrombosis as the underlying cause, brain MRV (magnetic resonance venography) should be done. The raised intracranial pressure must be documented by lumbar puncture with measurement of the CSF opening pressure. The opening pressure may fluctuate widely but never returns to the normal level. Apart from identifying any underlying cause or association (such as medications, endocrinopathy,…etc.) and removing them if possible, medical treatment should be tried first aiming at reducing the raised intracranial pressure and preventing optic nerve damage (and blindness ).
431 and 432) a.
This patient presents with an ischemic stroke. The first step in the Acute and Emergency Department is the so-called ABC (airway, breathing, and circulation). Meanwhile, routine blood tests and ECG should be done while arranging his brain CT scan. Brain MRI has no place in acute strokes of any type in general. Finally, and as a specific therapy, if there are no contraindications, he may receive an r-tPA infusion. Heparin infusion is now reserved for ischemic strokes with a persistent cardiac source of emboli; its "routine" use should be discouraged. Many trainees are still using steroids as a mode of reducing brain edema; the ischemic "cytotoxic" edema does not respond to glucocorticoids. Aspirin has been shown to reduce ischemic stroke morbidity and mortality as well as its recurrence rate. This patient needs optimization of his blood sugar.
433, 434, and 435) c, c, d.
This young woman has myasthenia gravis (MG). Normal pupils would cancel out Horner's syndrome. Myasthenia gravis usually targets the ocular muscles causing variable diplopia and muscle weakness. Her double vision upon reading refers to the "fatigable" weakness of her extra-ocular muscles. Unless there is a high index of suspicion, early cases may be misdiagnosed as a conversion reaction or an anxiety disorder, because the" routine" clinical examination reveals nothing abnormal. The curtain sign of fatigable ptosis is useful in such cases. Muscle biopsy may show lymphorrhages (collection of lymphocytes). Examination under electron microscopy may show a simplification of the postsynaptic membrane; however, muscle biopsy is not routinely done. A thymic histopathological examination is done after confirming the diagnosis and doing a thymectomy to exclude the presence of thymoma (which is malignant in of cases); however, it is not used initially to confirm the clinical suspicion. Anti-Yo antibodies are seen in paraneoplastic cerebellar degeneration, and anti-PQ-type calcium channel antibodies are seen in Lambert-Eaton myasthenic syndrome. In all cases of MG, brain imaging (CT scan or MRI) should be done to exclude intracranial diseases, such as small brainstem AVMs or mass lesions which may have an MG-like presentation. Chest plain films (insensitive) and chest CT scans are parts of the work-up of MG looking for thymic enlargement. Skull X-ray has no place at all. Motor neuron disease does not target the extra-ocular muscles. Myotonia dystrophica can result in bilateral ptosis but other features usually dominate the clinical picture (hand myotonia, distal weakness, wasting,…etc.). The distribution of muscle weakness and wasting in facioscapulohumeral dystrophy is characteristic; it can result in bilateral ptosis but there is no diplopia. Dermatomyositis can be acute, subacute, or chronic and has skin manifestations (heliotrope eyelid rash, Gottron's Typically, it presents with proximal weakness and tenderness; extra-ocular muscle weakness is seen in 2% of cases only and as a mode of presentation is extremely rare.
436, 437, and 438) c, c, c.
Essential (familial) tremor is symmetric and does not involve the jaw. It may result in a gross head shaking in a yes-yes-yes or no-no-no pattern, but not an isolated "jaw" shaking. The history did not point to any possible drug ingestion or toxic exposure. This patient is likely to have idiopathic Parkinson's disease (PD). If there is any atypical feature (e.g., extensor planters, lateralizing signs, symmetric onset, prominent cognitive dysfunction at then brain imaging is indicated; brain imaging is not required in typical cases and the diagnosis is purely clinical. Toxicology is indicated when history is suggestive of toxic exposure. Lewy bodies are found in the brainstem of Parkinson's patients (and do not indicate an associated Lewy body dementia per se). In addition, stereotactic brain biopsy is not used to confirm or refute the diagnosis of PD. Functional MRI is used in research only; it is not done in everyday hospital work. Early in the course of PD, the presence of:
•A prominent postural drop in blood pressure can be a clue to multiple system atrophy (Parkinsonian plus syndrome).
•Aphasia and impairment in abstract reasoning can be a clue to a cortical dementia illness.
•Bilateral symmetric findings can be a clue to a drug-induced etiology, such as haloperidol ingestion.
•Impairment of up and down gazes can be a clue to progressive supranuclear palsy (impaired up-gaze can be seen normally in old people and Parkinson's disease, but not a combined up and down gazes impairment). "Frequent falls" are one of the prominent manifestations and usually overshadow other features of "early" progressive supranuclear palsy.
439 and c, a.
This patient may have dementia or depressive pseudodementia. The patient’s presentation is non-specific. Hypothyroidism and vitamin deficiency may result in dementia; therefore, all dementia patients should undergo serum TSH and vitamin testing. Lewy-body dementia presents with a fluctuated cognitive function, Parkinsonism, and formed visual hallucinations early in the course of the illness. All patients with a mini-mental state examination score of less than 25 need a thorough evaluation for dementia; the patient's score is too low for depressive pseudodementia. The presence of prominent vegetative symptoms (weight gain, insomnia, loss of sexual should point to depressive pseudodementia rather than Alzheimer's disease. However, dementia and depression may co-exist in elderly people. The aphasia in Alzheimer's disease is usually receptive rather than expressive. Disinhibition is seen with frontal lobe lesions, together with frontal release signs (e.g. grasp, snout, and palmo-mental reflexes). An impaired visuospatial task is a parietal lobe sign.
441 and 442) c, c.
This is the full-blown picture of Lewy Body Dementia (LBD). These patients show extreme sensitivity towards the anti-Parkinsonian side effects of neuroleptics. Therefore, such medications should be avoided, as they can cause clinical worsening. In they have been shown to increase the mortality figure. Donepezil (and other central acetylcholinesterase inhibitors) are usually ineffective (unlike Alzheimer's disease), but they are not contraindicated. hallucinations are formed, not simple ones. The Parkinsonian tremor is symmetrical from the outset disease (but it could be absent).
443, 444, and 445) d, c, b.
This patient has an acute subarachnoid hemorrhage. After doing the airway, breathing, and circulation (ABC) in the Emergency this patient should undergo brain CT scanning. The CT scan is positive in 90% of cases within the first 24 hours; it shows blood within the basal cisterns in a pattern. This positivity declines day by day; it becomes 40% by day 4 of the ictus. If there is a high index of suspicion and the initial brain CT scan is normal, a lumbar puncture should be done, looking for grossly bloody CSF and/or xanthochromia; the latter appears after 8-12 hours of the ictus. When the diagnosis of acute subarachnoid hemorrhage is made, conventional 4-vessel cerebral angiography should follow to visualize the cerebral vasculature (anterior and posterior circulations, right and left). Berry aneurysm is multiple in 20% of cases and may be associated with other vascular anomalies (such as cerebral arteriovenous malformation). The timing of the latter invasive investigation is controversial, but ideally, should be done within 48 hours of the vascular event to allow optimal treatment of the ruptured aneurysm (and its complications). MRI is unsuitable for confused and agitated patients but may have a role in subacute and chronic cases, by showing the blood metabolites in the subarachnoid space. Brain magnetic resonance angiography is a useful "screening" tool for high-risk patients, e.g., adult polycystic kidney disease patients who have a family history of a cerebral aneurysm (with/without a history of rupture). Although it is a non-sensitive test, it cannot detect aneurysms smaller than 5 mm. It should not be used as a diagnostic tool in those with subarachnoid hemorrhage (instead of conventional angiography).
446, 447, and 448) b, d, d.
Friedreich's ataxia (FA) is an autosomal recessive disease (unlike the other hereditary spinocerebellar ataxias, which are autosomal dominant). It is due to GAA trinucleotide repeat expansion of the Frataxin gene on chromosome 9. PMP22 gene duplication is seen in certain types of Charcot-Marie-Tooth disease. Preseniline-1 (and presenilin-2) gene mutation is the cause of early-onset familial Alzheimer's disease. FA is neither an epileptogenic nor a dementing disorder; therefore, the EEG recording and mini-mental state examination should be normal. Hypertrophic cardiomyopathy can be seen in FA; as a result, a double apical impulse might be seen, as well as a variety of cardiac conduction defects on 12-lead ECG. Diabetes mellitus develops in 10-20% of cases. FA, apart from causing primary optic atrophy (and retinitis pigmentosa), does not affect the other cranial nerves. The MCV (mean corpuscular volume) of 80 fL is normal and is expected to be normal in FA patients. FA is one of the causes of up-going planters and lost ankle jerks. Myoclonus and tremor are seen in spinocerebellar ataxia (SCA) type II and oculoparesis occurs in SCA type III. Cardiac involvement, diabetes, pes cavus, and scoliosis are only encountered in FA; therefore, they are useful diagnostic clues.
449, and 451) d, d, e.
Duchenne's muscular dystrophy is due to defects in the dystrophin gene (the largest gene in the body) on chromosome X. This would result in a severe quantitative defect in the dystrophin of the sarcoplasma of skeletal muscles. Dystrophin is present in the brain; this might explain the mild mental deficiency that is seen in 20% of cases. The child starts to be wheelchair-bound by the end of the 1st decade and bed-bound by the end of the 2nd decade. Respiratory failure (with death) ensues shortly thereafter. The genetic defect is not in the bone marrow; therefore, bone marrow transplantation has no place in the treatment. Gene therapy is a promising therapy. Blood counts are not used to diagnosing this type of muscle disease. The serum creatine phosphokinase is very high from birth; therefore, mild elevations (or normal levels) should cast strong doubt upon the diagnosis. EMG studies show myopathic features (short-duration, low amplitude, and polyphasic motor unit potentials); consequently, denervation and re-innervation changes should point out away from Duchenne's muscular dystrophy. Muscle biopsy with studies will confirm the diagnosis. The heart is involved late in the course.
452, 453, 454, and 455) e, d, c, e.
Peripheral polyneuropathy is a big subject. One-third of patients will be found to have a reversible cause, one-third will be found to have an irreversible cause, and one-third will be marked with an unknown cause. Sural nerve biopsy is used if the cause is unknown after doing thorough investigations or in certain hereditary cases. The patient has significant symptoms; therefore, watchful waiting would seem unreasonable. Vasculitis can be treated with steroids while vitamin replacement is used if there is a documented deficiency state; both are specific forms of treatments for peripheral neuropathy, not symptomatic ones. In advanced cases, the plaques of multiple sclerosis within the substance of the spinal cord may extend outwards to the proximal spinal roots and result in radicular signs; however, a polyneuropathy picture never develops. Some polyneuropathies may have an additional autonomic component that increases the disease morbidity, and even mortality, e.g., diabetes, amyloidosis, and acute intermittent porphyria. Vasculitides result in acute/subacute axonal type of neuropathy, which could be of a polyneuropathic type or a mononeuritis multiplex one. Tabes dorsalis targets the dorsal spinal columns and their dorsal roots; severe sensory ataxia ensues, not a peripheral neuropathic process. Intravenous immunoglobulin can be used to treat Guillain-Barré syndrome or chronic inflammatory demyelinating polyradiculopathy (CIDP). Severe painful symptoms in diabetic patients should alert the physician to search for an alternative/associated diagnosis, e.g., critical limb ischemia. Continuous burning feet pain (due to neuropathy) usually responds well to gabapentin or tricyclic anti-depressants, while the lancinating pains are usually treated with carbamazepine.
456, 457, 458, and 459) c, d, d, c.
The presence of certain features should cast strong doubt on the diagnosis of Guillain-Barré syndrome. These are striking asymmetric signs, bladder, and bowel involvement at presentation (or persistent after recovery), striking sensory signs, and the presence of neutrophil cells in the CSF. Facial weakness and dysphagia are seen in 50% of cases. Dysautonomia occurs in 65% of cases. About 20% of patients will need assisted ventilation. The mortality rate is 4-5%; 85% of patients will have an excellent degree of recovery after 6 months (demonstrating mild foot drop and absent ankle jerks only). Assistant ventilation is used when the patient has a respiratory failure. Erythromycin can be used to treat bowel C. jujeni infection, not the Guillain-Barré syndrome. Steroids are not a treatment option in Guillain-Barré syndrome; they may delay recovery. Plasma exchange and intravenous immunoglobulin infusions are equally effective when started within 2 weeks of symptom onset; however, there is no benefit in combining both of them. Some patients present in their plateau or recovery phase. The decision to treat or not to treat is the question; mild features may need nothing apart from observation. Primary or secondary axonopathy, the presence of a preceding C. jujeni infection, and the need for assistant ventilation portend a very poor prognosis of recovery.
461, and 462) e, c, b.
Acute ischemic strokes can be treated with r-tPA infusion (thrombolytic therapy) if certain inclusion and exclusion criteria are addressed. The recommended dose is 0.9 mg/kg to a maximum of 90 mg; 10% of the dose is given as an intravenous bolus and the rest is given as an intravenous infusion over 1 hour. The most fearful complication is cerebral hemorrhage.
463, 464, 465, and 466) c, a, c, d.
Myotonic dystrophy (MD) is caused by CTG trinucleotide repeats expansion on chromosome 19q. Diabetes is seen in 10-20% of cases (which can result in retinopathy in the long term). Testicular atrophy with hypergonadotrophic hypogonadism (i.e., high serum FSH and LH with low serum testosterone) and gynecomastia are part of the disease’s manifestations. Low serum levels of testosterone, FSH, and LH indicate secondary gonadal failure. Cardiac failure and conduction defects are the major causes of mortality in MD. The conduction defects can be worsened by procainamide; procainamide is better avoided as a medication for myotonia when there is cardiac involvement. There is bilateral ptosis but without frontalis overaction (unlike neurogenic causes of ptoses); the forehead is smooth (not wrinkled) in those patients. Hypogammaglobulinemia can result in recurrent chest infections (and bronchiectasis). EMG studies can show myopathic features in addition to myotonic discharges. Other family members may demonstrate cataracts only. Distal weakness and wasting occur in MD patients.
467, 468, 469, and 470) d, d, e, d.
The thymus is abnormal in the majority of cases of myasthenia gravis. Thymic hyperplasia is the commonest histological abnormality, accounting for 65% of cases. Thymoma is seen in 15% of patients (in of those patients it is malignant). Thymic atrophy is seen in late-onset cases (mostly in men after 60 years of age). Anti-acetylcholine receptor antibodies are positive in 50% of pure ocular 80-85% of generalized myasthenia, and zero percentage of congenital myasthenic syndromes (and Lambert-Eaton myasthenic syndrome). This means that 15% of cases of generalized myasthenia gravis are "seronegative" for anti-acetylcholine receptor antibodies; however, anti-MuSK antibodies are positive in 40% of those seronegative patients. When there is severe deterioration (crisis), features of a hypercholinergic state (small pupils, cramping abdominal pain and diarrhea, are useful clues to a cholinergic crisis. The cholinergic crisis is much less common than the myasthenic crisis. Thymic irradiation is not used in the treatment of myasthenia gravis. Plasmapheresis is used during a myasthenic crisis, preparing patients before surgery, and initially in severe (or rapidly worsening) cases, together with immune suppression (which has a delayed effect).
a. Idiopathic pseudotumor cerebri.
b. Superior sagittal sinus-associated pseudotumor cerebri due to Behcet’s disease.
d. Papilledema (due to venous sinus thrombosis-associated pseudotumor cerebri)
Bilateral papillitis (as part of
472) Pure Ocular
a. Pure ocular myasthenia (the features are present exclusively in the ocular muscles for more than 2 years).
b. receptor antibodies (positive in 50% of cases of pure ocular myasthenia, and 85% of cases of generalized myasthenia
Repetitive EMG (looking for a decremental response; note that tetanic EMG stimulation and single muscle fiber EMG can also be mentioned).
Mediastinal CT scan (looking for thymic enlargement due to hyperplasia; enlargement due to thymoma is seen mainly in elderly people; thymic atrophy is seen normally in the elderly population).
NB: you may also write the test.
Pure ocular myasthenia is a contraindication to thymectomy (the other contraindications are neonatal myasthenia, congenital myasthenic syndromes, disease duration >7 years, age >60 years, severe co-morbidities, and patient preference!).
a. Right-sided supratentorial peri-Sylvian meningioma (the location should be added to get a full mark; a defective description will deduct a few marks).
b. Extra-axial (the tumor arises from the meningothelial cells of the arachnoid
c. Neurofibromatosis type II (might be multiple).
Breast Cancer (should be differentiated from breast metastasis in the appropriate clinical setting).
d. Partially resected tumor (as in sphenoid wing meningiomas).
Difficult neurosurgical access (in addition, it can be used for recurrent tumors).
a. Brain MRI with and without contrast (looking for plaques and other areas’ white matter plaques; actively inflamed plaques will show contrast enhancement).
Visual evoked potentials (looking for prolonged latency of the the amplitude can be very low during an acute attack of optic neuritis but usually returns to normal after recovery, unlike the latency which is almost always prolonged in the recovery phase and subclinical attacks).
CSF analysis (looking for lymphocytic pleocytosis, raised protein, oligoclonal bands, and raised IgG index and synthetic rate; the opening pressure is normal, as is the sugar level).
b. Pulses of high-dose intravenous methylprednisolone for 3 days. (500 to 1000 mg per day).
NB: This form of intervention is done because the attack is function-threatening (in mild relapses, steroid therapy might not be needed).
c. Beta-interferon or glatiramer acetate (because she has fulfilled the criteria for relapsing-remitting multiple sclerosis; note the dissemination in time and place).
d. Spastic urinary bladder; oxybutynin (or tricyclic
Tremor; propranolol (clonazepam or high dose
Spasticity; baclofen tablets (baclofen pump, dantrolene, clonazepam, diazepam, tizanidine, and dorsal
a. Adult-type polymyositis (there are many types, e.g., childhood polymyositis, myositis associated with malignancy…etc.; therefore, elaborate when writing down the correct diagnosis to get a full mark).
b. Muscle enzymes (you may also mention serum CPK or other muscle enzymes, such as LDH, aldolase, or AST).
EMG (looking for myopathic features; nerve conduction study is a wrong answer; the disease is in the muscle not in the peripheral nerves).
Muscle biopsy (better to be taken from the clinically involved muscle, but the weakness should of grade 3 and above).
NB: If 2 out of the above 3 investigations are positive, then we can label the patient as having
c. Involvement of the respiratory muscles (especially in the acute and sub-acute forms).
Interstitial lung fibrosis (mainly seen when serum anti-Jo1 antibodies are positive).
Cardiac failure (cardiac involvement is responsible for most of the mortality).
a. Single aneurysm that is plugged in by a thrombus.
Very small aneurysm.
Bleeding from a spinal source (other causes are bleeding from a venous angioma and bleeding from cavernous angioma).
b. Re-bleeding (roughly doubles the mortality rate; the re-bleeding peaks from day 3 to 14).
Cerebral vasospasm (responsible for the delayed morbidity; also peaks from day 3 to 14).
Hydrocephalus (acute, chronic, or normal pressure hydrocephalus).
Seizures (increase the risk of re-bleeding) (other complications are SIADH and cerebral salt-losing nephropathy).
c. Ehlers-Danlos syndrome type IV.
Aortic coarctation (other associations are adult-type polycystic kidney pseudoxanthoma elasticum, cerebral arteriovenous malformations, and fibromuscular dysplasia).
477) Giant Cell
a. Arteritic anterior ischemic optic neuropathy.
b. The sudden loss of vision (it is subacute in optic
The pale optic disc (it is hyperemic in optic type)
NB: Another important feature is the altitudinal visual field defect (uncommonly, total loss of vision occurs) rather than the central scotoma in optic neuritis.
c. Temporal artery biopsy (multiple biopsies should be taken as the involvement might be patchy; 50% of cases will display the characteristic giant cells with necrosis and disruption of the internal elastic lamina; a high ESR supports the diagnosis and is an important lab parameter in the follow up; a normal ESR at the time of diagnosis is very rare but may be seen).
d. Giant cell arteritis causing right-sided arteritic anterior ischemic optic neuropathy and visual
e. Very unlikely that right-sided vision will improve (usually remains static). There is a 50% chance of involvement of the other eye within 4 months (therefore, the patient should be given a high dose of prednisolone to protect the other eye).
a. The main stem of the left middle cerebral artery (occlusion of this artery is almost always the result of an embolic material which is usually cardiac; note the global aphasia and severe weakness).
The infracted territory is large and is more than of the hemisphere (very high risk of hemorrhagic transformation; the patient presented within the 3-hour window).
NB: The initial CT scan can be normal in the 12 hours of ischemic strokes.
c. Right-sided hemianesthesia.
Right-sided homonymous hemianopia.
479) Motor Neuron Disease (MND).
a. MRI with and without contrast at the level of the foramen magnum (the most important potentially treatable differential diagnosis of MND).
b. EMG (looking for features of chronic denervation and re-innervation).
Muscle biopsy (looking for neurogenic atrophy)
NB: the serum CPK may be slightly elevated or normal.
c. Riluzole (this medication has been shown to offer a modest improvement in the survival figure).
a. Respiratory muscle involvement (mainly the diaphragm).
Pulmonary aspiration (due to oropharyngeal dysphagia).
Pulmonary thromboembolism (there is a high risk of lower limbs deep venous thrombosis).
b. Wide-spread peripheral nerve and radicular demyelination with or without secondary axonal degeneration (a primary axonopathic form is rarely seen, mainly in Orients)
NB: you may also write peripheral nerves and roots prolonged latency, conduction block, dispersion of compound muscle action potentials, and prolonged F-waves with or without secondary axonopathy).
c. Preceding Campylobacter jujeni gastrointestinal infection.
Axonal involvement (primary or secondary; other bad predictors are advanced age and a rapid downhill course).
Need for ventilatory support.
d. Sudden arrest (due to autonomic neuropathy).
Respiratory failure due to respiratory muscles involvement.
Massive pulmonary thromboembolism (due to lower limb DVT; in death can be due to septicemia associated with bed sores and severe pulmonary aspiration from pharyngeal weakness).
481) Dissociated Sensory
a. Diabetic small fiber neuropathy (this man has dissociated sensory loss which can also be caused by anterior spinal artery occlusion).
NB: dissociated sensory loss in the upper limbs can result from syringomyelia.
Primary AL amyloidosis.
b. Nerve conduction studies.
Rectal biopsy for stain.
Sural nerve biopsy.
482) Absent Ankle Jerks with Upgoing Planter
a. Subacute combined degeneration of the cord due to vitamin deficiency (vitamin deficiency alone will not get a full mark).
Taboparesis (other causes are combined pathology, e.g., cervical spondylosis with peripheral neuropathy, and combined cauda equina and conus medullaris lesions; Friedreich's ataxia is seen in young individuals; always note the patient's age in the question)
b. Pupillary size, shape, and reactivity (note that optic atrophy is seen in both, but Argyll-Roberson pupil is seen in taboparesis).
c. Blood film (macrocytosis and neutrophils, and complete blood counts for anemia,
Anti-parietal cell and anti-intrinsic factor antibodies.
VDRL (or any serological test for syphilis).
Serum vitamin level.
d. Combined such as cervical spondylosis with peripheral diabetic neuropathy (and combined cauda equina and conus medullaris lesions).
a. Mononeuritis multiplex (note the distribution of the affected nerves).
b. Nerve conduction studies for both upper and lower limbs (to examine several peripheral nerves; sometimes the affection is so confluent clinically to label the patient as having peripheral polyneuropathy).
c. Classic polyarteritis nodosa (the clue is the high blood pressure and livedo reticularis).
484) Wilson's Disease.
Sunflower cataract (also signs of chronic liver disease, such as jaundice,
b. Serum copper.
Serum (and liver biopsy)
c. L-dopa responsive dystonia (and idiopathic torsion dystonia).
a. Myotonia dystrophica.
Repeated pulmonary aspiration (due to pharyngeal myotonia).
c. Bilateral ptosis (usually partial and somewhat symmetrical but without frontalis overaction).
Premature stellate cataract (the slit-lamp examination is also used to detect mild cases and to screen other family members for this finding).
d. Phenytoin for myotonia (or procainamide; be careful when there is a cardiac conduction defect). Splints for foot drops methylphenidate for excessive daytime somnolence, cataract extraction for visual impairment, medications for
486) Friedreich's Ataxia.
a. Diabetes mellitus (10-20% of cases).
Kyphoscoliosis (and pes cavus).
c. Genetic analysis.
Fasting blood sugar.
Nerve conduction velocity.
NB: his polyuria is due to hyperglycemia.
a. Right-sided, subacute subdural hematoma (between 3 to 21 it is sub-acute; more than 21 days it is called chronic).
NB: note the isodense signal of subacute hematomas; a hyperdense signal indicates an acute one, and a hypodense one indicates a chronic course; sometimes multiple densities are seen and indicate chronicity with recurrent minor bleedings).
b. Old age.
Treatment with anticoagulants.
Alcoholics (in any patient who is liable for repeated falls or head such as Parkinson's disease and epileptic patients).
c. Surgical evacuation (small and mildly symptomatic ones may not need surgical treatment and may resolve spontaneously).
488) Normal Pressure Hydrocephalus (NPH).
a. Normal pressure hydrocephalus (note the classical triad and negative medical and drug history).
b. Head trauma.
c. Idiopathic Parkinson's disease.
d. Placement of a permanent ventricular shunt (the most difficult question to answer in NPH is whom to shunt and whom not to shunt?).
a. Pyogenic meningitis (as it is
Intravenous cannula-associated superficial
A subdural abscess (other causes are the development of brain abscess, urinary tract infection, chest infection, bed sore, and septic cortical venous thrombosis).
c. Hydrocephalus (both communicating and non-communicating).
Seizures (and mental retardation or deficiency, deafness, blindness).
Intellectual impairment (and difficulties in schooling, occupation,…etc.).
a. Brain MRI with contrast.
CSF analysis with PCR for Herpes simplex virus genome (note that the virus can be isolated from brain specimens but not from the CSF).
b. Acyclovir (10 3 times daily, as a slow intravenous
Carbamazepine (or phenytoin for seizures).
a. Silt-lamp examination that is done by an inexperienced ophthalmologist (the commonest cause in clinical practice; the ring is not easily
Dark iris (makes the detection even by those who are highly experienced).
2% of patients with CNS involvement will never display the ring (other causes are being on anti-Wilsonian medication as it is a reversible sign, and wrong diagnosis from the outset).
b. 5% of patients will have normal serum ceruloplasmin.
c. Normal anion gap metabolic acidosis, due to proximal renal tubular acidosis (but it is clinically insignificant).
a. Prolonged latency of the right (indicating a demyelinating process; note that normal values were not given in the question, but it can be concluded from the data in the question that the right one is the abnormal one).
b. Lymphocytic pleocytosis with raised protein and normal sugar (most likely indicating an acute relapse).
c. Multiple sclerosis does not affect the peripheral nerves (rarely in advanced cases, a spinal cord plaque may encroach upon the proximal emerging roots, giving rise to radicular signs).