Duk№ Modified from DE Singer et at; № 133:5Щ 2D06; DN frltm et it СШ 133;593S, 2008.

XI-19. The answer is E. (Chap. 370) Numerous studies have identified key risk factors for ischemic stroke. Old age, family history, diabetes, hypertension, tobacco smoking, and cholesterol are all risk factors for atherosclerosis and therefore stroke. Hypertension is the most significant among these risk factors. All cases of hypertension must be controlled in the setting of stroke prevention. Antiplatelet therapy has been shown to reduce the risk of vascular atherothrombotic events. The overall relative risk reduction of nonfatal stroke is about 25–30% across most large clinical trials. The “true” absolute benefit is dependent on the individual patient’s risk; therefore, patients with a low risk for stroke (e.g., younger patients with minimal cardiovascular risk factors) may have a relative risk reduction with antiplatelet therapy but a meaningless “benefit.” Numerous studies have shown the benefit of statin therapy in the reduction of stroke risk even in the absence of hypercholesterolemia. Anticoagulation is the treatment of choice to prevent stroke in patients with atrial fibrillation and other potential causes of cardiocerebral emboli. However, data do not support the use of long-term vitamin K antagonists for preventing atherothrombotic stroke for either intracranial or extracranial cerebrovascular disease. The WARSS study found no benefit of warfarin (INR 1.4–2.8) over aspirin 325 mg for secondary prevention of stroke but did find a slightly higher bleeding rate in the warfarin group. A recent European study confirmed this finding. The Warfarin-Aspirin Symptomatic Intracranial Disease (WASID) study demonstrated no benefit of warfarin (INR 2–3) over aspirin in patients with symptomatic intracranial atherosclerosis, and also found higher rates of bleeding complications.

XI-20. The answer is C. (Chap. 370) Once the diagnosis of stroke is made, a brain imaging study is necessary to determine if the cause of stroke is ischemia or hemorrhage (Figure XI-20). There are no clinical findings that definitively distinguish ischemia from hemorrhage. If the stroke is ischemic, administration of recombinant tissue plasminogen activator (rtPA) or endovascular mechanical thrombectomy may be beneficial in restoring cerebral perfusion. Medical management to reduce the risk of complications becomes the next priority, followed by plans for secondary prevention. For ischemic stroke, several strategies can reduce the risk of subsequent stroke in all patients, while other strategies are effective for patients with specific causes of stroke such as cardiac embolus and carotid atherosclerosis. For hemorrhagic stroke, aneurysmal subarachnoid hemorrhage (SAH) and hypertensive intracranial hemorrhage are two important causes. The National Institute of Neurological Disorders and Stroke (NINDS) recombinant TPA (rtPA) Stroke Study showed a clear benefit for IV rtPA in selected patients with acute stroke. The NINDS study used IV rtPA (0.9 mg/kg to a 90-mg max; 10% as a bolus, then the remainder over 60 minutes) versus placebo in patients with ischemic stroke within 3 hours of onset. Subsequent studies using different dosing and timing ranges have not been as positive. rtPA is being reviewed for approval in the 3- to 4.5-hour window in Europe, but is only approved for 0–3 hours in the United States and Canada. Use of IV rtPA is considered a central component in primary stroke centers as the first treatment proven to improve clinical outcomes in ischemic stroke and is cost-effective and cost saving. Because collateral blood flow within the ischemic brain is blood pressure dependent, there is controversy about whether blood pressure should be lowered acutely. Blood pressure should be lowered if there is malignant hypertension or concomitant myocardial ischemia or if blood pressure is above 185/110 mmHg and thrombolytic therapy is anticipated. When faced with the competing demands of myocardium and brain, lowering the heart rate with a β₁-adrenergic blocker (such as esmolol) can be a first step to decreasing cardiac work and maintaining blood pressure. Endovascular mechanical thrombectomy has recently shown promise as an alternative or adjunctive

treatment of acute stroke in patients who are ineligible for, or have contraindications to, thrombolytics or in those who have failed to have vascular recanalization with IV thrombolytics. Studies have shown excellent acute and chronic recanalization rates and the FDA has approved some devices for intracerebral use. Hypothermia is a powerful neuroprotective treatment in patients with cardiac arrest and is neuroprotective in animal models of stroke, but it has not been adequately studied in patients with ischemic stroke.

FIGURE XI-20

XI-21. The answer is B. (Chap. 371) Approximately 10% of all persons over the age of 70 have significant memory loss, and in more than half the cause is Alzheimer’s disease (AD). AD can occur in any decade of adulthood, but it is the most common cause of dementia in the elderly. AD most often presents with an insidious onset of memory loss followed by a slowly progressive dementia over several years. Pathologically, atrophy is distributed throughout the medial temporal lobes, as well as lateral and medial parietal lobes and lateral frontal cortex. Microscopically, there are neurofibrillary tangles composed of hyperphosphorylated tau filaments, and accumulation of amyloid in blood vessel walls in the cortex and leptomeninges. The cognitive changes of AD tend to follow a characteristic pattern beginning with memory impairment and spreading to language and visuospatial deficits. Yet approximately 20% of patients with AD present with nonmemory complaints such as word-finding, organizational, or navigational difficulty. In the early stages of the disease, the memory loss may go unrecognized or be ascribed to benign forgetfulness. Slowly the cognitive problems begin to interfere with daily activities, such as keeping track of finances, following instructions on the job, driving,

shopping, and housekeeping. Some patients are unaware of these difficulties (anosognosia), while others remain acutely attuned to their deficits. Social graces, routine behavior, and superficial conversation may be surprisingly intact. Language becomes impaired—first naming, then comprehension, and finally fluency. In some patients, aphasia is an early and prominent feature. Word-finding difficulties and circumlocution may be a problem even when formal testing demonstrates intact naming and fluency. Visuospatial deficits begin to interfere with dressing, eating, or even walking, and patients fail to solve simple puzzles or copy geometric figures. Simple calculations and clock reading become difficult in parallel. Loss of judgment and reasoning is inevitable. Delusions are common and usually simple, with common themes of theft, infidelity, or misidentification. In end-stage AD, patients become rigid, mute, incontinent, and bedridden. Hyperactive tendon reflexes and myoclonic jerks may occur spontaneously or in response to physical or auditory stimulation. Generalized seizures may also occur. Often death results from malnutrition, secondary infections, pulmonary emboli, heart disease, or, most commonly, aspiration. The typical duration of AD is 8–10 years, but the course can range from 1 to 25 years. For unknown reasons, some AD patients show a steady decline in function, while others have prolonged plateaus without major deterioration.

XI-22. The answer is D. (Chap. 370) There is currently no robust or curative medical therapy for Alzheimer’s disease (AD). The acetylcholinesterase inhibitors donepezil, rivastigmine, and galantamine, as well as the NMDA receptor antagonist memantine are FDA approved for treatment of AD. Double-blind, placebo-controlled crossover studies with these agents have shown improved caregiver ratings of patients’ functioning with an apparent decreased rate of decline in cognitive test scores over periods of up to 3 years. The average patient on an anticholinesterase compound maintains his or her MMSE score for close to a year, whereas a placebo-treated patient declines 2–3 points over the same time period. Memantine, used in conjunction with cholinesterase inhibitors or by itself, slows cognitive deterioration and decreases caregiver burden for patients with moderate to severe AD but is not approved for mild AD. Each of these compounds has only modest efficacy for AD. Some studies have suggested a protective effect of estrogen replacement in women. However, a prospective study of a estrogen-progesterone combination increased the prevalence of AD in previously asymptomatic women. A randomized, double-blind, placebo-controlled trial of an extract of Ginkgo biloba found modest improvement in cognitive function in subjects with AD and vascular dementia. Unfortunately, a comprehensive 6-year multi-center prevention study using Ginkgo biloba found no slowing of progression to dementia in the treated group. Experimental studies are investigating chemical or vaccination strategies to interfere or inhibit amyloid protein deposition. Retrospective studies suggest a beneficial role of statins in the development of dementia. Mild to moderate depression is common in the early stages of AD and may respond to antidepressants or cholinesterase inhibitors. Newer-generation antipsychotics (risperidone, quetiapine, olanzapine) in low doses may benefit neuropsychiatric symptoms. Medications with strong anticholinergic effects should be vigilantly avoided, including prescription and over-the-counter sleep aids (e.g., diphenhydramine) or incontinence therapies (e.g., oxybutynin).

XI-23. The answer is D. (Chap. 370) All the choices given in the question are causes of or may be associated with dementia. Binswanger’s disease, the cause of which is unknown, often occurs in patients with long-standing hypertension and/or atherosclerosis; it is associated with diffuse subcortical white matter damage and has a subacute insidious course. Alzheimer’s disease, the most common cause of dementia, is also slowly progressive and can be confirmed at autopsy by the presence of amyloid

plaques and neurofibrillary tangles. Creutzfeldt-Jakob disease, a prion disease, is associated with a rapidly progressive dementia, myoclonus, rigidity, a characteristic EEG pattern, and death within 1-2 years of onset. Vitamin B₁₂ deficiency, which often is seen in the setting of chronic alcoholism, most

commonly produces a myelopathy that results in loss of vibration and joint position sense, and brisk deep tendon reflexes (dorsal column and lateral corticospinal tract dysfunction). This combination of pathologic abnormalities in the setting of vitamin B₁₂ deficiency is also called subacute combined

degeneration. Vitamin B₁₂ deficiency may also lead to a subcortical type of dementia. Recent studies

have demonstrated that elevated levels of MMA, which is a more sensitive measure of vitamin B₁₂

deficiency, may increase the risk of cognitive decline in elderly patients. The therapeutic implications of this finding are not yet clear but emphasize the importance of adequate vitamin B₁₂ intake. Multi-

infarct dementia, as in this case, presents with a history of sudden stepwise declines in function associated with the accumulation of bilateral focal neurologic deficits. Brain imaging demonstrates multiple areas of stroke.

XI-24. The answer is D.(Chap. 370) The differential diagnosis of Parkinson's disease is broad, and the disease can be difficult to diagnose, with an estimated misdiagnosis of 10-25% even by experienced physicians. This patient exhibits several atypical features that should alert the physician to search for alternative diagnoses. These include early age of onset, prominent orthostasis, autonomic symptoms of flushing and diaphoresis, and failure to respond to dopaminergic agents. In addition, recurrent urinary tract infections should prompt an evaluation for urinary retention due to autonomic dysfunction in this patient. These symptoms are most consistent with multiple system atrophy with parkinsonian features (MSA-p). The average age of onset is 50 years, and these individuals more frequently present with bilateral, symmetric tremor and more prominent spasticity than those with Parkinson's disease. Orthostasis and autonomic symptoms are typically prominent. On MPJ, one would expect to find volume loss and T2-hyperintensity in the area of the putamen, globus pallidus, and white matter. On pathologic examination, a-synuclein-positive inclusions would be seen in the affected areas. Median survival after diagnosis is 6-9 years. Dopaminergic agents are not helpful in the treatment of this disorder and are usually associated with drug-induced dyskinesias of the face and neck, rather than the limbs and trunk. Corticobasal degeneration is a sporadic tauopathy that presents in the sixth to seventh decades. In contrast to Parkinson's disease, this disorder is frequently associated with myoclonic jerks and involuntary purposeful movements of a limb. Its progressive nature leads to spastic paraplegia. Diffuse Lewy body disease has prominent dementia with parkinsonian features. Neuropsychiatric complaints including paranoia, delusions, and personality changes are more common than in Parkinson's disease. Drug-induced Parkinson's disease is not seen with nitrofurantoin, and the patient has no history of illicit drugs such as MTPT, which could cause Parkinson's disease. Finally, this is unlikely to be inadequately treated Parkinson's disease because one would expect at least an initial improvement on dopaminergic agents.

XI-25. The answer is C.(Chap. 370) Therapy for Parkinson's disease should be initiated when symptoms interfere with the patient's quality of life. Choice of initial drug therapy is usually with dopamine agonists, levodopa, or MAO inhibitors. The initial choice in most individuals is a dopamine agonist (pramipexole, ropinirole, rotigotine), and monotherapy with dopamine agonists usually controls motor symptoms for several years before levodopa therapy becomes necessary. Over this period, escalating doses are frequently required, and side effects may be limiting. It is thought that dopamine

agonists delay the onset of dyskinesias and on-off motor symptoms such as freezing. By 5 years, over half of individuals will require levodopa to control motor symptoms. Levodopa remains the most effective therapy for the motor symptoms of Parkinson's disease, but once levodopa is started, dyskinesias and on-off motor fluctuations become more common. MAO inhibitors (selegiline, rasagiline) work by decreasing the postsynaptic breakdown of dopamine. As monotherapy, these agents have only small effects and are most often used as adjuncts to levodopa. Surgical procedures such as pallidotomy and deep-brain stimulation are reserved for advanced Parkinson's disease with intractable tremor or drug-induced motor fluctuations or dyskinesias. In this setting, deep-brain stimulation can alleviate disabling symptoms.

XI-26. The answer is D.(Chap. 370) Restless legs syndrome (RLS) is a neurologic disorder that affects approximately 10% of the adult population, causing significant morbidity in some. It is rare in Asians. The four core symptoms required for diagnosis are as follows: an urge to move the legs, usually caused or accompanied by an unpleasant sensation in the legs; symptoms begin or worsen with rest; partial or complete relief by movement; worsening during the evening or night. Symptoms most commonly begin in the legs, but can spread to or even begin in the upper limbs. In about 80% of patients, RLS is associated with periodic leg movements (PLMs) during sleep and occasionally while awake. These involuntary movements are usually brief, lasting no more than a few seconds, and recur every 5-90 seconds. The restlessness and PLMs are a major cause of sleep disturbance in patients, leading to poor-quality sleep and daytime sleepiness. Primary RLS is genetic, and several loci have been found with an autosomal dominant pattern of inheritance, although penetrance may be variable. The mean age of onset in genetic forms is 27 years, although pediatric cases are recognized. The severity of symptoms is variable. Secondary RLS may be associated with pregnancy or a range of underlying disorders, including anemia, ferritin deficiency, renal failure, and peripheral neuropathy. The pathogenesis probably involves disordered dopamine function, which may be peripheral or central, in association with an abnormality of iron metabolism Diagnosis is made on clinical grounds but can be supported by polysomnography and the demonstration of PLMs. The neurologic examination is normal. Secondary RLS should be excluded, and ferritin levels, glucose, and renal function should be measured. Most RLS sufferers have mild symptoms that do not require specific treatment. If symptoms are intrusive, low doses of dopamine (pramipexole, ropinirole) may be administered before bedtime. Levodopa can be effective but is frequently associated with augmentation (spread and worsening of restlessness and its appearance earlier in the day) or rebound (reappearance sometimes with worsening of symptoms at a time compatible with the drug's short half-life). Other drugs that can be effective include anticonvulsants, analgesics, and even opiates. Management of secondary RLS should be directed to correcting the underlying disorder.

XI-27. The answer is E.(Chap. 374) The combination of upper and lower motor neuron findings is highly suggestive of ALS. Indolent presentation is typical and many patients receive alternative diagnoses before defining ALS. There is currently no curative therapy for ALS; therefore, treatable causes of motor nerve dysfunction should be ruled out. Compression of the cervical spinal cord or cervicomedullary junction from tumors in the cervical regions or at the foramen magnum or from cervical spondylosis with osteophytes projecting into the vertebral canal can produce weakness, wasting, and fasciculations in the upper limbs and spasticity in the legs, closely resembling ALS. Absence of pain or of sensory changes, normal bowel and bladder function, normal roentgenographic studies of the spine, and normal cerebrospinal fluid (CSF) all favor ALS. Another important entity in

the differential diagnosis of ALS is multifocal motor neuropathy with conduction block (MMCB). In this disorder, remarkably focal blocks in conduction regionally and chronically disrupt lower motor neuron function. Many cases have elevated serum titers of mono- and polyclonal antibodies to ganglioside GM1; it is hypothesized that the antibodies produce selective, focal, paranodal demyelination of motor neurons. MMCB is not typically associated with corticospinal signs. In contrast with ALS, MMCB may respond dramatically to therapy such as IV immunoglobulin or chemotherapy; it is thus imperative that MMCB be excluded when considering a diagnosis of ALS. A diffuse, lower motor axonal neuropathy mimicking ALS sometimes evolves in association with hematopoietic disorders such as lymphoma or multiple myeloma. Lyme disease may also cause an axonal, lower motor neuropathy, although typically with intense proximal limb pain and a CSF pleocytosis. Other treatable disorders that occasionally mimic ALS are chronic lead poisoning and thyrotoxicosis. Vitamin С deficiency may cause myalgias in addition to fatigue, lethargy, and skin findings, but motor neuron findings are not typical.

XI-28. The answer is E.(Chap. 375) Postural orthostatic tachycardia syndrome is characterized by symptomatic orthostatic intolerance and either an increase in heart rate to more than 120 beats/min or an increase of 30 beats/min with standing that subsides on sitting or lying down. There is no orthostatic hypotension. Women are affected approximately five times more often than men, and most develop the syndrome between the ages of 15 and 50. Approximately half of affected patients report an antecedent viral infection. Lightheadedness, weakness, and blurred vision combined with symptoms of autonomic over activity (palpitations, tremulousness, nausea) are common. Recurrent, unexplained episodes of dysautonomia and fatigue also occur. The pathogenesis is unclear in most cases; hypovolemia, deconditioning, venous pooling, impaired brainstem regulation, or adrenergic receptor supersensitivity may play a role. Although up to 80% of patients improve, only about 25% eventually resume their usual daily activities (including exercise and sports). Expansion of fluid volume and postural training are initial approaches to treatment. If these approaches are inadequate, then midodrine, fludrocortisone, phenobarbital, beta blockers, or cloni-dine may provide some benefit. Reconditioning and a sustained exercise program are very important. All of the other listed choices are associated with orthostatic hypotension.

XI-29. The answer is D.(Chap. 375) Complex regional pain syndrome (CRPS) types I and II are the

terms that have replaced reflex sympathetic dystrophy (RSD) or causalgia because of the absence of a proven causative role for the autonomic nervous system CRPS type I is a regional pain syndrome that usually develops after tissue trauma. Examples of associated trauma include myocardial infarction, minor shoulder or limb injury, and stroke. Allodynia, hyperpathia, and spontaneous pain occur. The symptoms are unrelated to the severity of the initial trauma and are not confined to the distribution of a single peripheral nerve. CRPS type II is a regional pain syndrome that develops after injury to a specific peripheral nerve, usually a major nerve trunk. Spontaneous pain initially develops within the territory of the affected nerve but eventually may spread outside the nerve distribution. Pain is the primary clinical feature of CRPS. Vasomotor dysfunction, sudomotor abnormalities, or focal edema may occur alone or in combination but must be present for diagnosis. Localized sweating and changes in blood flow may produce temperature differences between affected and unaffected limbs. CRPS type I has classically been divided into three clinical phases but is now considered to be more variable. Phase I consists of pain and swelling in the distal extremity occurring within weeks to 3 months after the precipitating event. The pain is diffuse, spontaneous, and either burning, throbbing, or aching in

quality. The involved extremity is warm and edematous, and the joints are tender. Increased sweating and hair growth develop. In phase II (3-6 months after onset), thin, shiny, cool skin appears. After an additional 3-6 months (phase III), atrophy of the skin and subcutaneous tissue plus flexion contractures complete the clinical picture. A variety of surgical and medical treatments have been developed for CRPS, with conflicting reports of efficacy. Clinical trials suggest that early mobilization with physical therapy or a brief course of glucocorticoids may be helpful for CRPS type I. Other medical treatments include the use of adrenergic blockers, nonsteroidal anti-inflammatory drugs, calcium channel blockers, phenytoin, opioids, and calcitonin. Stellate ganglion blockade is a commonly used invasive technique that often provides temporary pain relief, but the efficacy of repetitive blocks is uncertain.

XI-30. The answer is E(Chap. 376) Trigeminal neuralgia is a clinical diagnosis based entirely on patient history. The disorder is characterized by paroxysms of excruciating pain in the lips, gums, cheeks, and chin that resolves over seconds to minutes. It is caused by ectopic action potentials in afferent pain fibers of the fifth cranial nerve, due either to nerve compression or other causes of demyelination. Symptoms are often, but not always, elicited by tactile stimuli on the face, tongue, or lips. An elevated ESR is not part of the clinical syndrome. Elevated ESR is associated with temporal arteritis, a vasculitis associated with jaw claudication, unilateral vision loss, and symptoms of polymyalgia rheumatica. Trigeminal neuralgia is specifically notable for a lack of sensory findings on examination, unless the diagnosis is made in conjunction with another disorder such as a midbrain mass lesion or aneurysm. Deep-seated facial and head pain is more commonly a feature of migraine headache, dental pathology, or sinus disease. First-line therapy is with carbamazepine, not gabapentin. It should be started and increased gradually until pain symptoms subside; 50-75% of patients will respond to this therapy. If treatment is effective, it is continued for 1 month then tapered.

XI-31. The answer is C.(Chap. 376) Trigeminal neuralgia is a clinical diagnosis based entirely on patient history, and as such should be treated once a patient presents with the virtually pathognomonic complaints of paroxysms of excruciating pain in the lips, gums, cheeks, and chin that resolve over seconds to minutes. Carbamazepine is first-line therapy. Oxcarbazepine likely has equivalent efficacy to carbamazepine with less toxicity. Lamotrigine, orphenytoin, and baclofen are other potential therapeutic options. Surgical approaches, such as radiofrequency thermal rhizotomy, gamma-knife radiosurgery, and microvascular decompression, should be considered only when medical options fail. Steroids have no therapeutic role, as trigeminal neuralgia is not an inflammatory condition. Neuroimaging is not indicated, unless other clinical features or a focal neurologic deficit elicited on history or physical examination suggest another possible diagnosis such as intracranial mass or multiple sclerosis.

XI-32. The answer is D.(Chap. 376) Brief paroxysms of severe, sharp pains in the face without demonstrable lesions in the jaw, teeth, or sinuses are called tic douloureux, or trigeminal neuralgia. The pain may be brought on by stimuli applied to the face, lips, or tongue or by certain movements of those structures. Aneurysms, neurofibromas, and meningiomas impinging on the fifth cranial nerve at any point during its course typically present with trigeminal neuropathy, which will cause sensory loss on the face, weakness of the jaw muscles, or both; neither symptom is demonstrable in this patient. Amyotrophic lateral sclerosis (ALS) is a motor neuron disease that may present with bulbar motor findings but sensory findings (in the absence of muscle spasms) are uncommon.

XI-33. The answer is C.(Chap. 377) The MRI shows an infiltrated and collapsed second thoracic

vertebral body with posterior displacement and compression of the upper thoracic spinal cord due to metastatic breast cancer. The low-intensity bone marrow signal in panel A of Figure XI-33 signifies replacement by tumor. When a patient presents with possible myelopathy, the first priority is to distinguish between a compressive or noncompressive etiology. The common causes of compressive myelopathy are tumor, epidural abscess or hematoma, herniated disk, or vertebral pathology. Epidural compression due to malignancy or abscess often causes warning signs of neck or back pain, bladder disturbances, and sensory symptoms that precede the development of paralysis. MRI is the optimal diagnostic modality to image the spinal cord. In adults, most neoplasms are epidural in origin, resulting from metastases to the adjacent spinal bones. The propensity of solid tumors to metastasize to the vertebral column probably reflects the high proportion of bone marrow located in the axial skeleton. Almost any malignant tumor can metastasize to the spinal column, with breast, lung, prostate, kidney, lymphoma, and plasma cell dyscrasia occurring particularly frequently. The thoracic spinal column is most commonly involved; exceptions are metastases from prostate and ovarian cancer, which occur disproportionately in the sacral and lumbar vertebrae, probably resulting from spread through Batson's plexus, a network of veins along the anterior epidural space. Retroperitoneal neoplasms (especially lymphomas or sarcomas) enter the spinal canal through the intervertebral foramens and produce radicular pain with signs of root weakness prior to cord compression. Pain is usually the initial symptom of spinal metastasis and characteristically awakens patients at night. A recent onset of persistent back pain, particularly if in the thoracic spine (which is uncommonly involved by spondylosis), should prompt consideration of vertebral metastasis. Infections of the spinal column (osteomyelitis and related disorders) are distinctive in that, unlike tumor, they may cross the disk space to involve the adjacent vertebral body. Management of cord compression includes glucocorticoids to reduce cord edema, local radiotherapy (initiated as early as possible) to the symptomatic lesion, and specific therapy for the underlying tumor type. Spinal epidural abscess presents as a clinical triad of midline dorsal pain, fever, and progressive limb weakness. Risk factors include an impaired immune status (diabetes mellitus, renal failure, alcoholism, malignancy), IV drug abuse, and infections of the skin or other tissues. Two-thirds of epidural infections result from hematogenous spread of bacteria from the skin (furunculosis), soft tissue (pharyngeal or dental abscesses), or deep viscera (bacterial endocarditis). Hemorrhage into the epidural (or subdural) space causes acute focal or radicular pain followed by variable signs of a spinal cord or conus medullaris disorder. Therapeutic anticoagulation, trauma, tumor, or blood dyscrasias are predisposing conditions. Hemorrhage into the substance of the spinal cord is a rare result of trauma, intraparenchymal vascular malformation, vasculitis due to polyarteritis nodosa or systemic lupus erythematosus (SLE), bleeding disorders, or a spinal cord neoplasm. Hematomyelia presents as an acute, painful transverse myelopathy.

XI-34. The answer is B.(Chap. 377) This patient has a history and examination consistent with a myelopathy. The rapidity of onset and the lack of other antecedent symptoms (e.g., pain) make a noncompressive etiology most likely. An MRI is the initial test of choice and will easily identify a structural lesion such as a neoplasm or subluxation. Noncompressive myelopathies result from five basic causes: spinal cord infarction; systemic disorders such as vasculitis, systemic lupus erythematosus (SLE), and sarcoidosis; infections (particularly viral); demyelinating disease such as multiple sclerosis; and idiopathic. Therefore, serologies for antinuclear antibodies, viral serologies such as HIV and HTLV-I, and lumbar puncture are all indicated. Because the clinical scenario is consistent with a myelopathy, an electromyogram is not indicated.

XI-35. The answer is A.(Chap. 377) Syringomyelia is a developmental, slowly enlarging cavitary expansion of the cervical cord that produces a progressive myelopathy. Symptoms typically begin in adolescence or early adulthood. They may undergo spontaneous arrest after several years. More than half are associated with Chiari malformations. Acquired cavitations of the spinal cord are referred to as syrinx cavities. They may result from trauma, myelitis, infection, or tumor. The classic presentation is that of a central cord syndrome with sensory loss of pain and temperature sensation, and weakness of the upper extremities. Vibration and position sensation are typically preserved. Muscle wasting in the lower neck, shoulders, arms, and hands with asymmetric or absent reflexes reflects extension of the cavity to the anterior horns. With progression, spasticity and weakness of the lower extremities, and bladder and bowel dysfunction may occur. MRI scans are the diagnostic modality of choice. Surgical therapy is generally unsatisfactory. Syringomyelia associated with Chiari malformations may require extensive decompressions of the posterior fossa. Direct decompression of the cavity is of debatable benefit. Syringomyelia secondary to trauma or infection is treated with decompression and a drainage procedure, with a shunt often inserted that drains into the subarachnoid space. Although relief may occur, recurrence is common.

XI-36. The answer is A.(Chap. 378) Concussions result from blunt head trauma that causes anterior-posterior movement of the brain within the skull. Transient loss of consciousness is common, as are confusion and amnesia. Many patients do not lose consciousness but feel dazed, stunned, or confused. A brief period of both retrograde and anterograde amnesia is characteristic of concussion and it recedes rapidly in alert patients. Head imaging is typically normal. Postconcussive syndrome is a constellation of symptoms including fatigue, headache, dizziness, and difficulty concentrating that follows a concussion. The patient described fits this diagnosis; strict diagnostic criteria do not exist. Typically patients will improve over a 6- to 12-month period. Patients who were energetic and highly functioning prior to their trauma have an excellent prognosis. Treatment is aimed at reassurance and relieving prominent symptoms. Dizziness can be treated with Phenergan, which acts as a vestibular suppressant. He should avoid contact sports at least until his symptoms resolve.

XI-37. The answer is D.(Chap. 378) The head CT (Figure XI-37) shows chronic bilateral subdural hematomas of varying age. The collections began as acute hematomas and have become hypodense in comparison to the adjacent brain. Some areas of resolving blood are contained in the more recently formed collection on the left. Acute hematomas (which would be as bright as the resolving blood shown in arrows) become hypodense in comparison with adjacent brain after approximately 2 months. During the isodense phase (2-6 weeks after injury), they may be difficult to discern. Chronic subdural hematoma may present without a history of trauma or injury in 20-30% of patients. Headache is common. Other symptoms may be vague, as in this case, or there may be focal signs including hemiparesis mimicking stroke. Underlying cortical damage may serve as a seizure focus. In relatively asymptomatic patients with small hematomas, observation and serial imaging may be reasonable; however, surgical evacuation is often necessary for large or symptomatic chronic hematomas.

XI-38. The answer is D.(Chap. 378) Hemorrhages beneath the dural layer (subdural) or between the skull and the dura (epidural) are common sequelae of head trauma. They can be life-threatening, and prompt evaluation and management are imperative. Several clinical features allow these conditions to be distinguished from one another. Acute subdural hematomas typically arise from venous sources, often the bridging veins located immediately under the dura mater. As the brain volume decreases with

age, traction on these venous structures increases and even minor head trauma in the elderly can lead to a subdural hematoma. A "lucid interval" of several minutes to hours before coma supervenes is most characteristic of epidural hemorrhage, but it is still uncommon, and epidural hemorrhage is not the only cause of this temporal sequence. Subdural bleeding is typically slower than epidural bleeding due to their different sources. Small subdural bleeds are asymptomatic and often do not require evacuation. Epidural hematomas, on the other hand, can arise quickly and typically represent arterial bleeding. A lacerated middle meningeal artery from an overlying skull fracture often causes these. A rapid increase in intracranial pressure from these bleeds can necessitate arterial ligation or emergent craniotomy. Most patients with epidural bleeding are unconscious when first evaluated; a "lucid interval" can occasionally be seen.

XI-39. The answer is D.(Chap. 379) Distinguishing CNS toxoplasmosis from primary CNS lymphoma in a patient with HIV infection is often difficult. The standard approach in a neurologically stable patient is to treat the patient for toxoplasmosis for 2-3 weeks then repeat neuroimaging. If the imaging shows clear improvement, continue antibiotics. If there is no response to therapy after 2 weeks, therapy does not need to be continued and a stereotactic brain biopsy is indicated. In this immunocompromised patient who has not responded to treatment for CNS toxoplasmosis, a positive CNS EBV DNA would be diagnostic of CNS lymphoma. Whole-brain radiation therapy is part of the treatment for CNS lymphoma, which is not yet diagnosed in this patient, and should not be instituted empirically. Treatments directed at viral infections of the CNS or CNS lymphomas are not indicated at this time since a diagnosis is still yet to be made. In the absence of a change in neurologic status or evidence of mass effect on CT, there is no indication for dexamethasone. Of note, the incidence of primary CNS lymphoma appears to be increasing in immunocompetent individuals for unclear reasons.

XI-40. The answer is A.(Chap. 379) Endocrine dysfunction resulting in hypopituitarism frequently follows exposure of the hypothalamus or pituitary gland to therapeutic radiation. Growth hormone is the most sensitive to the damaging effects of WBRT, and thyroid-stimulating hormone is the least sensitive. ACTH, prolactin, and gonadotropins have an intermediate sensitivity. Other complications of radiation therapy to the brain include acute radiation injury manifest by headache, sleepiness, and worsening of preexisting neurologic defects. Early delayed radiation injury occurs within the first 4 months after therapy. It is associated with increased white matter signal on MRI and is steroid responsive. Late delayed radiation injury occurs more than 4 months after therapy, typically 8-24 months. There may be dementia, gait apraxia, focal necrosis (after focal irradiation), or the development of secondary malignancies.

XI-41. The answer is D.(Chap. 379) The postgadolinium MRI shows multiple meningiomas along the falx and left parietal cortex. Meningiomas derive from the cells that give rise to the arachnoid granulations. They are now the most common primary brain tumor, accounting for approximately 32% of the total, and occur more commonly in women than men. They are usually benign (WHO classification grade 1) and attached to the dura. They rarely invade the brain. Meningiomas are diagnosed with increasing frequency as more people undergo neuroimaging studies for various indications. Their incidence increases with age, and they are more common in patients with a history of cranial irradiation. They are most commonly located over the cerebral convexities, especially adjacent to the sagittal sinus, but can also occur in the skull base and along the dorsum of the spinal cord. Many meningiomas are found incidentally following neuroimaging for unrelated reasons. They can also

present with headaches, seizures, or focal neurologic deficits. On imaging studies they have a characteristic appearance usually consisting of a partially calcified, densely enhancing extra-axial tumor arising from the dura. The main differential diagnosis of meningioma is a dural metastasis. Total surgical resection of a meningioma is curative. Low-grade astrocytoma and high-grade astrocytoma (glioblastoma) often infiltrate into adjacent brain and rarely have the clear margins seen in Figure XI-41. Oligodendroma comprise approximately 15% of all gliomas and show calcification in roughly 30% of cases. They have a more benign course and are more responsive than other gliomas to cytotoxic therapy. For low-grade oligodendromas, the median survival is 7-8 years. Brain abscess will have distinctive ring-enhancing features with a capsule, will often have mass effect, and will have evidence of inflammation on MRI scanning.

XI-42. The answer is D.(Chap. 380) The onset of multiple sclerosis (MS) may be abrupt or insidious. Symptoms may be severe or seem so trivial that a patient may not seek medical attention for months or years. Indeed, at autopsy, approximately 0.1% of individuals who were asymptomatic during life will be found, unexpectedly, to have pathologic evidence of MS. Similarly, in the modern era, an MRI scan obtained for an unrelated reason may show evidence of asymptomatic MS. Symptoms of MS are extremely varied and depend on the location and severity of lesions within the CNS (see Table XI-42). Examination often reveals evidence of neurologic dysfunction, often in asymptomatic locations. For example, a patient may present with symptoms in one leg but signs in both.

Date: 2016-04-22; view: 731