questions_Neurology

Educational objective: Review clinical presentations and diagnosis of myasthenia gravis.

This patient appears to have myasthenia gravis. The diagnostic approach to this condition begins with a physical examination and then proceeds to more specific testing. The major aim of the physical examination is to demonstrate fatigability of the different muscle groups.

Once it has been shown that muscles weaken with exercise and improve with rest, the diagnosis of myasthenia gravis can be confirmed most easily by an IV injection of tensilon (anticholinesterase inhibitor – edrophonium chloride). Tensilon begins to act in 30 to 60 seconds, and its effect lasts 5 to 10 minutes. This potentiation of the muscarinic effects of acetylcholine is not without risk (especially in the elderly) so atropine (0.5-2.0 mg) should be available if severe cholinergic reaction occurs (signs include sweating, increased weakness and increase in the volume of respiratory secretions, laryngospasm, bradycardia, hypotension, nausea and vomiting). To minimize risk, a test dose of 1 mg should be given; after 1 minute an additional 4 mg of tensilon should be given. If no change in the examination is noted in one minute, the additional 5 mg is given and the response quantified. Quantifying the response can be a problem. Grip strength with a dynamometer is useful if grip muscles are affected, since this can be quantified and the response repeated.

Educational objective: Review clinical features and diagnostic procedures for Lambert-Eaton syndrome.

Lambert-Eaton syndrome shares the same pathologic site with myasthenia gravis (the neuromuscular junction) and has a similar pathophysiology (an autoimmune disease). Lambert-Eaton syndrome is usually associated with malignancy. Up to 70% of patients have associated small cell lung cancer, and this disease must be ruled out in every patient with presenting symptoms of Lambert-Eaton syndrome.

Clinical presentations of the Lambert-Eaton syndrome include weakness that is typically seen early in the hip girdle, making it difficult for the patient to rise from a chair or to climb the stairs. Less dramatic is shoulder girdle weakness. Involvement of the bulbar muscles or diplopia is rare, but ptosis is frequently seen. Symptoms are also likely to be more prominent in the morning; autonomic dysfunction may cause erectile dysfunction and dry mouth. Repetitive nerve stimulation at high rates (20-50 cycles per second) produces an increase in response, in contrast to the progressive weakness in myasthenia.

Over 95% of the patients with Lambert-Eaton syndrome have antibodies against P/Q-type calcium channels. These antibodies are found in less than 5% of patients with myasthenia gravis.

Ischemic optic neuropathy is caused by occlusion of the posterior ciliary arteries with edema of the optic disk within a day of onset of symptoms. The disk is typically pale and swollen with nearby splinter hemorrhages. There is a loss of visual acuity. Visual field defects often involve either the inferior or superior fields. The majority of older patients with ischemic optic neuropathy have an underlying vascular disease, hypertension or diabetes.

Although there is no specific treatment for this disorder, it must be distinguished from giant cell arteritis; and affected patients should be referred for treatment. Without treatment, the optic nerve becomes infarcted in one third of patients.

In central retinal artery occlusion, the infarcted retina is pale and masks the underlying choroidal circulation except at the macula, where the thinness of the tissue allows it to be seen, hence the so-called “cherry red spot.” A thrombus or embolism from the heart or from the carotid artery is responsible. An afferent pupillary defect may also be present. In diabetes, one may have the sudden onset of floaters and flashing lights, a finding that raises concerns about posterior vitreous detachment, vitreous hemorrhage, or retinal detachment. These symptoms require urgent referral.

Heroin mixed with talc to increase the quantity of the drug and injected in the vein can cause talc to pass the pulmonary capillary barrier and embolise throughout the body. Emboluses are small and clinically significant when a large number (in multiple episodes) obliterates enough of the retinal circulation to cause symptomatic loss of the visual field.

The symptoms of Huntington’s disease are typically noted during the fourth decade of life, although presentation in childhood and onset delayed until later in life have been reported. Involuntary movements are usually the first symptom. Chorea is the most common movement disturbance, but myoclonus, athetosis, dystonia and Parkinsonism are also observed.

Psychiatric disorders can start before movement disorders. Depression is the most common psychiatric disorder in Huntington’s disease and prevalence is estimated between 30-50%. Psychosis with frank hallucinations and delusions may occur early. Obsessive-compulsive disorder and alterations in personality such as poor impulse control are also observed.

Dementia is an inevitable occurrence in patients with Huntington’s disease, although the time of onset and severity may vary. Relative preservation of verbal skills often leads to underestimation of the extent of cognitive decline.

Hippocampus, frontal and temporal lobes demonstrate the most striking cortical loss in patients with Alzheimer’s disease. Major association areas are also involved with significant cortical atrophy. Relatively spared areas include the motor and sensory cortex as well as the visual cortex.

Dyzigotic twins are 2-3 times less concordant for Alzheimer’s disease than monozygotic twins. Dementia occurs in the other twin within 5 years only in about 50% of patients studied. It has also been shown that genetic influences are more pronounced in cases of early onset of the disease. The APOE4 gene mutations are shown to be associated more with late onset disease rather than in those found in twins. Twins studies cannot rule out environmental influences in any given disease.

Alzheimer’s disease has a well-known association with advanced age. It has been found to be more frequent in women and in persons who have suffered severe head injury (including injuries occurring up to 35 years prior to diagnosis of Alzheimer’s disease in 15-20% of cases). There is also possible, but yet unproven, association with thyroid gland disorders. Epidemiological data on the risk in patients with a family history of sporadic cases are conflicting, and as of today this is not a separate risk factor. However, some families do carry specific genes that increase the incidence of Alzheimer’s disease.

Criteria for the clinical diagnosis of Alzheimer disease include the following:

Impairment of the two areas of cognition Progressive decline in the memory function No disturbance in consciousness No systemic disease or disorder that could account for dementia

Although changes in personality and myoclonus may occur in patients with Alzheimer’s disease, these changes are not required for diagnosis.

Dependence for activities of daily living is late in occurrence and is not included in the diagnostic criteria.

Alzheimer’s disease can be definitely diagnosed only by brain biopsy, but clinical characteristics can identify most patients with the disease. Neurofibrillary tangles (swollen neurons filled with submicroscopic filamentous structures that are approximately 10 nm in diameter), and neuritic amyloid plaques (clusters of degenerating neurons which are associated with extracellular arrays of linear filaments of amyloid) are main features of the pathology in affected patients. The most affected cell group is large neurons (greater than 90 mm2). More than 60% of such cells are lost during the progression of the disease. Magnetic resonance imaging usually shows atrophy of the cortex and hippocampal area as well as loss of the cortical markings, enlarged ventricles and enhancements of the meninges. There is no effective pharmacologic therapy for Alzheimer’s disease; care for every case should include attention to the safety of the patient, needs of the family and primary caregiver, as well as symptomatic management of the patient.

Educational objective: Review serious warning signs in patients with headache.

There are several historic features in patients with headache that should prompt investigation into possible serious underlying pathology.

Sudden onset – reaching maximum intensity in seconds or minutes warrants aggressive investigation. Subarachnoid hemorrhage would be a possibility. Cluster headaches may reach maximum within minutes, but those are transient and accompanied by ipsilateral autonomic signs.

No similar headaches in the past – The “first” or “worst” headaches of life sometimes are associated with intracranial bleeding or CNS infections.

Concomitant infection – non-intracranial locations may serve as sources for development of meningitis or intracranial abscesses. Altered mental status – in any extent suggests serious underlying pathology.

Headache with vigorous exercise - especially when minor trauma has occurred - raises the possibility of carotid artery dissection or intracranial hemorrhage.

Location of pain – pain that spreads between the shoulders and into the lower neck may be a sign of spinal meningeal irritation by infection or blood and is not typical for benign process.

Educational objective: Review serious signs on physical examination of patient with headache.

Physical findings suggestive of serious CNS causes of headache are as follows:

• Nuchal rigidity – indicating meningitis or subarachnoid hemorrhage.
• Toxic patient – with headache may indicate systemic illness affecting the CNS.
• Decreased level of consciousness – increases the likelihood of meningitis, encephalitis, intracranial hemorrhage, or other space-occupying lesion.
• Papilledema – indicative of increased intracranial pressure (tumor etc.)
• Neurologic abnormalities – if new must be evaluated for serious illness. Subtle signs only may be seen, such as slight pupillary asymmetry, unilateral pronator drift, or extensor plantar response.
• Neurologic deficits may also be seen with migraine, but those are usually perceived by the patient (symptom) rather than demonstrated on exam (sign), and are usually recurrent and short lived (less than 60 min).

However, it is important to recognize the true neurologic signs of those produced by patients with malingering, conversion disorders, etc. Such signs may be sensory deficits that do not follow dermatomal distribution as in this question.

• - Pregnant women
• - Those scheduled for a urologic procedure
• - Those having had a bladder catheter removed
• - Young children with gross vesicoureteral reflux
• - Some patients with struvite stones (removal of the stones is preferable)

Educational objective: Review the features and therapy of cluster headache.

This patient has headache typical of cluster headache. Treatment is divided into abortive and preventive aspects.

Abortive therapy can be difficult because of the brief nature of the episodes, but several medications have been successful. Inhalation of 100% oxygen (7 L/min for 15 minutes) aborts the episode in a majority of patients. Sumatriptan appears to be helpful also, as well as indomethacin and other NSAID's in some patients.

Prophylactic therapy should be started as soon as possible at the onset of a cluster episode. Prednisone is highly effective but should not be used chronically because of its side effects. Lithium is particularly effective for the chronic form of cluster headaches. Ergotamine, cyproheptadine, and indomethacin are also effective. Methysergide is effective and does not cause fibrosing syndromes in these patients due to the intermittent use of the drug.

Educational objective: Review the features and therapy of TMJ dysfunction.

Clinical features of this patient suggest temporomandibular joint dysfunction syndrome (TMJ). This condition is characterized by acute or chronic musculoskeletal pain with dysfunction of the masticatory system. Many patients complain of headache. The typical headache associated with TMJ presents as unilateral ear or preauricular pain that radiates to the jaw, temple, or neck. The pain is dull, deep, continuous, and usually worse in the morning. It is typically associated with a limitation of jaw motion and deviation of the jaw upon opening. Physical examination may demonstrate tenderness of the muscles of mastication, and sometimes clicking of the joint. The condition may be hard to differentiate from tension-type headache. The treatment primarily involves therapy of the joint disorder itself. Most cases can be treated with local heat, physical therapy, dental hygiene, NSAID's, and dietary measures. Occasional patients may require surgery. Antibiotics are not indicated in this patient since there is no suggestion of infection (no fever, long history, mild, relatively non-progressing pain).

Educational objective: Review clinical features of essential tremor.

Essential tremor is the most common type of tremor and is increasing in prevalence with advancing age. There is a bimodal pattern of distribution with peaks in the second and sixth decades of life. Essential tremor is one of the action tremors, but when severe it may persist at rest (confusion with Parkinson’s tremor is then more likely). Tremor is of relatively slow frequency (4-8 Hz) and is slowing in frequency, but it increases in amplitude with aging. Also, there is a familial form of essential tremor. Most commonly it affects the upper extremities, but it can affect head and neck, and often interferes with activities of daily living (eating, writing, or fastening buttons). It is aggravated by stress, emotion, exercise, and fatigue. Lower extremities are usually spared, and rare instances of lower extremity tremor are termed orthostatic tremor, which is characterized by slow tremor while trying to stand quietly. A curious fact about familial and essential tremors is that a few drinks of alcohol in 50-75% of cases can suppress them temporarily.

All features of the patient’s tremor point to essential tremor. Parkinson’s tremor is predominantly a resting tremor, which is clearly not the case in this patient. Calcium channel blockers are not associated with development of tremors, and the patient is not taking any other drug. Physiologic tremor may be hard to distinguish from essential tremor, but is usually faster in frequency and less common.

Educational objective: Review appropriate therapeutic modalities for essential tremor.

Essential tremor is treated most commonly with propranolol, which is shown to be effective if given in a daily dose between 120-240 mg over a long period of time. Therapeutic effects appear to be due to action in the central nervous system and not due to peripheral beta-adrenergic blockade (this is demonstrated by the inability of beta-blockers to relieve tremor when infused intra-arterially into the limb). The anticonvulsant primidone (25-50 mg initially, and raised slowly) has been found to be effective in controlling essential tremor and should be tried in patients who do not respond to or cannot tolerate propranolol.

Valproate is used in treatment of orthostatic tremor but has no role in essential tremor. L-dopa is used in treatment of Parkinson’s disease.

Alcohol temporarily relieves tremor of essential type in 50-75% of patients, but when tremor returns it may be even worse; it is in no way treatment for this clinical problem.

Educational objective: Review clinical features of normal pressure hydrocephalus.

This patient presents with the typical triad of normal pressure hydrocephalus: abnormal gait (ataxic or apractic), dementia (usually mild to moderate), and urinary incontinence. In this syndrome neuroimaging studies of the brain reveal enlarged lateral ventricles (hydrocephalus) with little or no cortical atrophy. Stretching of the corpus callosum by enlarged ventricles is also visible as well as depression of the floor of the third ventricle. This is communicating hydrocephalus (sylvian duct is patent, and may, indeed, be enlarged). There is relatively little increase of CSF pressure due to the indolent course of the process. The exact physiologic cause of the syndrome is unknown.

Diffuse cortical atrophy (more pronounced in frontal and parietal regions) is seen in Alzheimer’s disease. Mass lesion of the frontal lobe may cause a wide variety of symptoms. Personality changes should raise suspicion of frontal process. Enlarged lateral ventricles with atrophic nucleus caudatus is seen in Huntington’s disease.

This young patient presents with a neurologic disease, which should prompt a search for the metabolic cause. His eye demonstrates Kayser-Fleischer ring. Young patients (less than 30) presenting with this kind of neurologic picture and Kayser-Fleischer rings invariably suffer from Wilson’s disease (Kayser-Fleischer rings have been reported in cases of primary biliary cirrhosis and biliary atresia). Therapy for Wilson’s disease is life-long and consists of two phases. At first it is necessary to remove tissue copper that has accumulated; in the second phase the goal is prevention of reaccumulation. Copper removal may be accomplished by the use of potent chelators. The drug of choice for this initial phase is D-penicillamine. Chelation with this drug greatly increases the urinary excretion of copper to above 1200 ìg/day (normal – 30ìg/day). About 30% of patients cannot tolerate long-term therapy and trientine is used as a second-line agent. The dose is usually 250-500 mg three times daily. Chelation with tetrathiomolybdate is a new option with which there is little experience, but it appears to be preferable for patients with neurologic symptoms.

Prevention of reaccumulation during the maintenance phase can be achieved with either lower doses of the same chelators used in initiation phase or zinc. Oral zinc acetate (50 mg three times a day) has been used successfully to prevent the reaccumulation of copper in patients who have already responded to Penicillamine, and in patients who have responded poorly to Penicillamine. Zinc either inhibits resorption of copper in the intestine or promotes copper loss in the stool.

Patients with Wilson’s disease should also be maintained on a low copper diet and avoid liver, shellfish, nuts, dried fruits, chocolate, cocoa, and mushrooms.

Dimercaprol was the first drug used successfully to treat Wilson’s disease, but is now very rarely used.

The clinical picture and peripheral blood smear point to lead poisoning (basophilic stippling of the red blood cells is visible). Symptoms include abdominal pain, irritability that is followed by lethargy (coma, convulsions and death may occur in most serious cases). Anorexia, anemia, ataxia and slurred speech are also common symptoms. These symptoms usually start manifesting when blood lead level exceeds 3.9 ìmol/L (80ìg/dL). Subclinical lead poisoning with lower blood lead levels may manifest as mental retardation and language deficits, cognitive function, behavioral difficulties, poor school performance, and poor balance.

Sources of lead are paints, plumbing fixtures, and leaded gasoline (this is practically eliminated in US by use of unleaded gasoline). Exposure is relatively rare today due to greatly diminished use of lead caused by important regulatory actions. However, there are still some segments of the population exposed to lead through paint in old housing. Some professional exposure also still remains a risk (battery manufacturing, painting, and paint removal, demolition business).

Treatment includes preventing further exposure, reporting to appropriate agencies (OSHA if occupational or some community board if environmental). Pharmacologic agents include chelating agents (most commonly CaEDTA, but also dimercaprol, penicillamine, and succimer).

Vitamin B12 is given in cases of the macrocytic anemia and peripheral neuropathy caused by vitamin B12 deficiency.

Quinine and related medications are used in treatment of malaria, babesia, and recumbent leg muscle cramps.

Steroids have no place in treatment of lead poisoning.

The condition depicted is chronic subdural hematoma. The lesion is visible in the right frontoparietal region as a crescent of diminished density. Acute subdural hematoma would present as a similar crescent but density of the fluid would be higher (blood) than in this case (cells disintegrated and debris mostly resorbed). Epidural hematoma presents as a collection of blood that usually has a convex inner surface (toward the brain) because of the higher pressure under which blood is entering the epidural space. Also, epidural hematomas are most of the time limited to one cranial bone since dura is tightly attached to the areas of cranial sutures.

Normal pressure hydrocephalus is manifested on CT-scanning as big dilated lateral ventricles with no asymmetry and no other pathology. Localization and shape of the lesion make diagnosis of a brain tumor highly unlikely.

Herpetic encephalitis is characterized by lesions in the temporal and parietal lobes of the brain and clearly affects brain and not pericerebral structures.

Educational objective: Review of the option for blood pressure control in patients with ischemic cerebral infarct.

Intravenous labetalol is generally considered to be the medication of choice if pharmacologic therapy is given for hypertension control in the patients suffering ischemic cerebral infarct. The main advantage is that labetalol allows for rapid and safe titration to the goal blood pressure.

Intravenous nitroprusside should be considered second-line therapy since it carries an added risk of increasing intracranial pressure.

Calcium channel blocker nimodipine has been suggested to be particularly beneficial because of intracerebral vasodilatation and prevention of arterial spasms, but there is still no data confirming benefit.

The rest of the medications offered as an options in this question should not be routinely used in patients with acute stroke because of inability to be adjusted rapidly enough possibly resulting in hypotension and aggravating ischemic brain injury.

Educational objective: Review appropriate therapy for acute angle closure glaucoma.

Acute angle closure glaucoma is characterized by severe ocular pain. It is caused by forward displacement of the iris that narrows the angle between the iris and cornea and causes difficulties with aqueous humor outflow. Differential diagnosis includes anterior uveitis and other forms of glaucoma (miotic, traumatic or neovascular). Diagnosis is usually based on clinical picture and examination.

Slit lamp examination reveals shallow anterior chamber with hazy anterior chamber fluid.

Acute angle closure glaucoma is an emergency, and hyperosmotic agents are used to cause resorption of ocular fluid back into the blood stream (carefully if patient has a history of congestive heart failure or renal failure).

The intravenous agent of choice is mannitol (20% - 1-2 g/kg over 30 minutes).

Oral agents include glycerin (50% - 1-2 g/kg) or isosorbide (1.5-2 g/kg).

Carbonic anhydrase inhibitors (acetazolamide) are used to decrease production of aqueous humor. Â-blockers, miotics and corticosteroids are also used but only as adjunctive therapy.