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Internal Med MKSAP Neurology

Terms in this set (56)

* The diagnosis of Lambert-Eaton myasthenic syndrome, a neuromuscular junction disorder that causes progressive proximal muscle weakness and areflexia, precedes the clinical recognition of cancer in up to 50% of patients.

This patient most likely has Lambert-Eaton myasthenic syndrome, as suggested by his history of proximal upper and lower limb weakness, the presence of autonomic symptoms (dry eyes/mouth, erectile dysfunction), and the finding of absent deep tendon reflexes on examination. These are characteristic signs and symptoms of the syndrome. Lambert-Eaton myasthenic syndrome is a neuromuscular junction disorder caused by disordered calcium channel function on the presynaptic nerve terminal. In most patients with this disorder, antibodies to voltage-gated P/Q-type calcium channel receptors exist. Lambert-Eaton myasthenic syndrome is typically a paraneoplastic syndrome, caused by or associated with an underlying malignancy, particularly small cell lung cancer. The diagnosis of Lambert-Eaton myasthenic syndrome precedes the clinical diagnosis of cancer in up to 50% of affected patients; therefore, in patients with newly diagnosed Lambert-Eaton myasthenic syndrome, a thorough search for an underlying cancer should be performed. If no evidence of malignancy is found, these patients should be evaluated serially for occult malignancy. In addition to elevated levels of voltage-gated P/Q-type calcium channel antibodies, the diagnosis can be confirmed through electrodiagnostic studies, particularly repetitive nerve stimulation studies, which show an increase in the muscle action potential (increment) after brief exercise.

Elevated levels of antibodies against acetylcholine receptors are present in 90% of patients with generalized myasthenia gravis. Myasthenia gravis is an autoimmune disorder that results in neuromuscular transmission failure, causing weakness of limb and cranial muscles. The diagnosis is confirmed through electrodiagnostic testing, including repetitive nerve stimulation studies and, in some patients, single-fiber electromyography. The presence of an elevated acetylcholine receptor antibody level may provide additional confirmatory evidence supporting the diagnosis of myasthenia gravis. In this patient, the absence of any bulbar signs or symptoms, such as ptosis, visual symptoms (blurred vision or diplopia), or dysphagia, in conjunction with absent deep tendon reflexes, would argue against myasthenia gravis.
* First-line pharmacotherapy for mild Alzheimer dementia is an acetylcholinesterase inhibitor.

This patient should receive donepezil. The Folstein Mini-Mental State Examination (MMSE) discriminates well between the major stages of dementia used for prognosis and management purposes. The MMSE score range of 21 to 25 corresponds to mild dementia, 11 to 20 to moderate dementia, and 0 to 10 to severe dementia. This patient has Alzheimer dementia and is at a mild to moderate stage of impairment. The most appropriate medication with which to begin treatment is an acetylcholinesterase inhibitor of which there are currently three: donepezil, rivastigmine, and galantamine. Multiple large, prospective, randomized, double-blind, placebo-controlled studies have shown in patients with mild, moderate, or severe Alzheimer dementia the efficacy of donepezil (and its superiority to placebo) in the preservation of instrumental and functional activities of daily living and in the reduction of caregiver stress. Other studies have found that patients treated with donepezil have improved cognitive function compared with those treated with placebo. Donepezil was safe and well tolerated in this patient group.

Memantine is also used to treat Alzheimer dementia, but only in patients with moderate to severe impairment. There is no evidence that memantine has any effect in earlier stages of Alzheimer dementia or that it alters the course of the disease. With a score of 24/30 on the MMSE, this patient has mild dementia, which makes memantine an inappropriate treatment. In patients with severe dementia, memantine can be used alone or added to an acetylcholinesterase inhibitor.
* Because trigeminal neuralgia usually presents after age 40 years, its diagnosis in a younger patient should prompt an evaluation for secondary causes, such as multiple sclerosis, posterior fossa tumors, and vascular or aneurysmal compression of the trigeminal nerve. Everyone should get an MRI, 10% have intracranial lesion.

This patient, whose history is most compatible with a diagnosis of trigeminal neuralgia, should have an MRI of the brain. In 90% of patients with trigeminal neuralgia, idiopathic disease presents after age 40 years. Trigeminal neuralgia in a patient this young should prompt evaluation for secondary causes, such as multiple sclerosis, posterior fossa tumors, and vascular or aneurysmal compression of the trigeminal nerve. In light of her history of transient paresthesias 3 years ago, multiple sclerosis is high among the diagnostic possibilities for this patient. An MRI can show the demyelination typical of multiple sclerosis.

Trigeminal neuralgia is a unilateral condition characterized by brief episodes of lancinating pain in the distribution of one or more divisions of the trigeminal nerve, invariably V2 and/or V3. The pain is excruciating and often described as sudden, sharp, superficial, and stabbing or burning in quality. The pain is paroxysmal and usually lasts 2 to 3 seconds and may occur in volleys of jabs or stabs of pain. The paroxysms are often punctuated by pain-free periods lasting seconds to hours. Characteristically, the painful episodes are associated with trigger zones, particularly around the mouth and nostrils, and the pain may be triggered by trivial stimuli, such as wind on the face, brushing the teeth, shaving, chewing, or even talking.

Up to 10% of patients with trigeminal neuralgia may harbor an intracranial lesion; therefore, an MRI should be obtained for every patient with trigeminal neuralgia, even those who respond to medication and whose examination findings are normal.
* Myasthenic crisis, a potentially life-threatening neurologic emergency characterized by muscle weakness severe enough to necessitate intubation, typically requires plasma exchange therapy.

This patient has a rapidly progressive neurologic disorder with weakness of limb, bulbar, and respiratory muscles and should undergo plasma exchange. Given the absence of sensory loss and normal deep tendon reflexes, myasthenia gravis is the most likely diagnosis. Because of the rapid progression of the disease and the involvement of respiratory and bulbar muscles, the patient should be admitted to the hospital for management of a myasthenic crisis. Myasthenic crisis is a potentially life-threatening neurologic emergency characterized by weakness that is severe enough to necessitate intubation. Electromyographic studies, including repetitive stimulation of motor nerves, are indicated to establish a diagnosis of myasthenia gravis.

Plasma exchange is the treatment of choice in patients with myasthenic crisis. Myasthenia gravis is an autoimmune disorder that results from antibody-mediated attacks on the postsynaptic neuromuscular junction. This process may impair neuromuscular transmission by functional blockade of the acetylcholine receptor, by accelerating the degradation of acetylcholine receptors, and by causing damage to the postsynaptic membrane of the neuromuscular junction. Plasma exchange presumably removes these circulating antibodies.

Prednisone is an effective therapy in the treatment of patients with myasthenia gravis. However, it is not appropriate as the initial, sole therapy in patients in the midst of a myasthenic crisis. A worsening of muscular weakness is seen in some patients within the first 3 weeks of the initiation of this medication. Even if this complication does not occur, the beneficial effects from prednisone typically do not occur for 3 to 4 weeks after drug initiation. In a patient with myasthenic crisis, prednisone is often initiated after the patient has been stabilized and is improving with plasma exchange. Used in this fashion, prednisone should reach maximum efficacy by the time the beneficial effects of plasma exchange have waned (6-8 weeks).
* Approximately 90% of patients who present in an ambulatory care setting with a chief symptom of recurrent, moderately severe headache have a form of migraine.

This patient most likely has migraine without aura. Approximately 90% of patients in an ambulatory care setting with a chief symptom of recurrent, moderately severe headache have a form of migraine. Her 6-year history of episodic headache meets the International Classification of Headache Disorders criteria for migraine. There is no single criterion that is necessary or sufficient to make the diagnosis of migraine. In this particular example, this patient does not have unilateral or throbbing pain, and there is no associated photophobia, phonophobia, or vomiting, features that are often considered necessary for the diagnosis. Her headache is preceded by premonitory symptoms (yawning and irritability), which occur in approximately 75% of patients with migraine. In addition, her attacks are triggered by stress and changes in barometric pressure, both of which are frequent triggers for migraine. Depression is a comorbid disorder that often leads to a misdiagnosis of tension-type headache.

Chronic migraine (previously referred to as "transformed" migraine) is a very common cause of chronic daily headaches and is defined as headaches occurring on more than 15 days per month that meet the diagnosis of migraine without aura or respond to ergots or triptans (migraine-specific drugs) on at least 8 of those days. This patient does not meet the diagnostic criteria for this type of headache.
* Guillain-Barré syndrome is a disorder associated with rapidly progressive extremity weakness, paresthesias, and areflexia.

This patient should undergo electromyography (EMG). She has a rapidly progressive disorder affecting the peripheral nervous system, most compatible with a clinical diagnosis of Guillain-Barré syndrome. Patients with Guillain-Barré syndrome typically develop paresthesias distally in the lower extremities that are followed by limb weakness and gait unsteadiness. In addition to sensory loss and limb weakness, deep tendon reflexes are characteristically absent or markedly reduced. The diagnosis is confirmed by EMG, which usually shows a demyelinating polyradiculoneuropathy. Cerebrospinal fluid (CSF) analysis characteristically shows albuminocytologic dissociation, whereby the spinal fluid cell count is normal but the spinal fluid protein level is elevated. CSF analysis may also yield normal results early in the course of the disease. However, a normal CSF cell count is useful in excluding other infectious conditions, such as polyradiculoneuropathies associated with HIV and cytomegalovirus infection, infection due to West Nile virus, and carcinomatous or lymphomatous nerve root infiltration. By definition, symptoms in patients with Guillain-Barré syndrome peak within 4 weeks of onset. Poor prognostic features include rapid symptom progression, respiratory failure, EMG evidence of axonal degeneration, and advanced age. Intravenous immune globulin and plasma exchange are equally efficacious in the treatment of Guillain-Barré syndrome.
* Thunderclap headache is a potential neurologic emergency that requires urgent imaging of the cerebral vasculature with either magnetic resonance or CT angiography after a noncontrast CT scan of the head and a lumbar puncture have excluded subarachnoid hemorrhage.

* A lumbar puncture with subsequent cerebrospinal fluid analysis is necessary in any patient with thunderclap headache and normal findings on a CT scan to fully evaluate a possible subarachnoid hemorrhage.

This patient should undergo CT angiography of the head and neck. She has experienced a thunderclap headache, which is a severe and explosive headache that is maximal in intensity at or within 60 seconds of onset. Every thunderclap headache must be immediately evaluated to detect potentially catastrophic conditions, especially subarachnoid hemorrhage. Most of the other causes of thunderclap headache, such as an unruptured cerebral aneurysm, a carotid or vertebral artery dissection, cerebral venous sinus thrombosis, and reversible cerebral vasoconstriction syndrome, can be excluded by noninvasive angiography. Therefore, CT angiography of the head and neck is the most appropriate next step in management. CT angiography can detect unruptured aneurysms as small as 3 mm in diameter and thus is adequate to exclude this diagnosis. Magnetic resonance angiography (MRA) would also be appropriate in this setting. Both CT angiography and MRA can be performed with a venous phase to exclude cerebral venous sinus thrombosis. Given that most causes of thunderclap headache can be excluded by such noninvasive angiography and that prior cerebrospinal fluid analysis has shown no evidence of a subarachnoid hemorrhage in this patient, conventional cerebral angiography, in which a catheter is inserted into a large artery and advanced through the carotid artery, is unnecessary.
* Multiple sclerosis begins as a relapsing-remitting disorder in 85% of patients and a primary progressive disorder in 15% of patients; those with the relapsing-remitting type have a greater than 50% risk of developing a secondary progressive disease course.

This patient experienced an episode of transient neurologic dysfunction (an attack) at disease onset and thus has relapsing-remitting multiple sclerosis (MS). Eighty-five percent of patients with MS have this type of disease onset. In relapsing-remitting MS, relapse frequency declines over time, and relapses do not become more severe with increasing disease duration; however, recovery from individual events may be slower and less complete.

Primary progressive MS, which the other 15% of patients with MS have at disease onset, is defined as gradually worsening neurologic function over more than 1 year without recovery. This patient has recovered completely from two neurologic episodes and is currently asymptomatic. Therefore, he cannot be classified as having primary progressive MS.

Secondary progressive MS is characterized by gradual, unremitting development of new symptoms over months to years in a patient who previously had a relapsing-remitting course. The lifetime risk of conversion from relapsing-remitting to secondary progressive disease is greater than 50%, but the onset and rate of the progressive phase are highly variable and not predictable for individual patients. The median time from MS onset until conversion to the secondary progressive phase typically ranges from 10 to 15 years. The establishment of a secondary progressive course is a risk factor for substantial disability, such as loss of independent ambulatory function; the median time from MS onset to the point at which unilateral gait assistance (such as a cane) is required is 15 to 25 years. This patient first had transient symptoms only 6 months ago and thus cannot be characterized as having secondary progressive disease.

Benign MS is defined loosely as no or minimal neurologic impairment 15 or more years after MS onset. This category may encompass as many as 20% of all patients with MS. The definition of benign MS is controversial because continued follow-up of such patients often uncovers late progressive disease and disability accrual. However, a small minority of patients with MS live a long and essentially unrestricted life. The factors that predict a benign course early in the disease have not yet been identified. This patient's MS diagnosis is too recent to be categorized as benign at this point.
Epilepsy is classified as partial or generalized on the basis of the areas of the brain involved at onset. Seizures that present in adulthood are usually partial in onset; partial seizures in which the patient maintains full awareness are classified as simple partial, whereas those involving an alteration of consciousness, as in this patient, are classified as partial complex. The most common site of onset for partial seizures is the temporal lobe. As described by this patient, temporal lobe events often begin with an aura of déjà vu, a rising epigastric sensation, or autonomic disturbances. Although automatisms, such as lip smacking, are occasionally reported in absence seizures, these features are atypical for that type of seizure and are more suggestive of partial complex ones. In this patient, the age of onset, duration (several minutes) of the event, presence of oral automatisms, and reported postictal confusion and speech impairment all suggest a partial complex seizure.

Absence, generalized tonic-clonic, and myoclonic seizures are all manifestations of generalized epilepsy and are correlated with generalized epileptiform discharges on an electroencephalogram. Absence seizures are characterized by brief periods of staring and unresponsiveness, typically lasting seconds, with an immediate return to normal awareness. Absence seizures usually present in childhood. The length of this patient's episodes, his confusion before returning to normal awareness, and his age argue against absence seizure being the diagnosis.

Generalized tonic-clonic (grand mal) seizures are characterized by stiffening of the trunk and extremities followed by generalized symmetric jerking. Such features were not reported in this patient.

Myoclonic seizures consist of brief, shock-like muscle jerks without loss of awareness. These features are not consistent with the history this patient provides.
* First-line medications used to treat essential tremor include propranolol, primidone, gabapentin, and topiramate.

This patient should be treated with propranolol. She has a history and examination findings consistent with the presence of essential tremor. Essential tremor primarily occurs when a patient maintains a posture, such as when the hands are outstretched. Essential tremor also may be present during movement, particularly postural adjustments. Autosomal dominant transmission occurs in approximately half of patients with this condition. Essential tremor most commonly affects the upper extremities; however, the legs, head, trunk, face, and vocal cords may be involved. Up to 15% of patients with essential tremor have major disability associated with this condition. Progression of essential tremor is typically slow, with intermittent lengthy periods of stable symptoms. Features that may be predictive of a more severe essential tremor include a positive family history of tremor, longer tremor duration, voice tremor, and unilateral tremor onset. Alcoholic beverage consumption suppresses symptoms in most patients with this condition.

Treatment options for essential tremor are often limited and frequently only partially effective. It has been estimated that 50% of patients with essential tremor have no response to medical treatment. First-line medications used to treat essential tremor include propranolol, primidone, gabapentin, and topiramate. Propranolol is typically the drug of choice in most patients with essential tremor because of its effectiveness, which has been established in multiple well-designed randomized clinical trials.
* Acetazolamide is the option of first choice for the medical treatment of idiopathic intracranial hypertension.

This patient should be treated with acetazolamide. She has idiopathic intracranial hypertension, a disease that primarily affects young obese women. She has a progressive daily headache associated with pulsatile tinnitus and transient visual obscurations, the most common symptoms of this disease. She also has papilledema and impaired lateral gaze to the left on presentation. These signs and symptoms suggest the possibility of a left sixth cranial nerve palsy. Abducens nerve palsies are sometimes seen in patients with idiopathic intracranial hypertension because of compression of the sixth cranial nerve as a result of elevated intracranial pressure. Definitive diagnosis is established by an elevated cerebrospinal fluid (CSF) pressure and normal results on CSF analysis. Because there is not yet evidence of visual field or visual acuity impairment, urgent surgical intervention is not necessary and medical therapy is appropriate. However, all patients with suspected idiopathic intracranial hypertension must undergo a thorough ophthalmologic evaluation, including formal visual perimetry testing, to detect enlargement of the blind spots or visual field defects that are not detected by confrontation visual field testing at the bedside.

Acetazolamide is the medical option of first choice for the treatment of idiopathic intracranial hypertension. Although its exact mechanism of action is unclear, acetazolamide is a carbonic anhydrase inhibitor that decreases the production of CSF and relieves intracranial hypertension.