RITE 2021 Flashcards

Question

In mediating the affective component of pain, which of the following structures plays the largest role? A. amygdala B. caudate nuclease C. hippocampus D. nucleus accumbens E. pulvinar

Answer 1

amygdala amygdala lies in the anterior pole of the temporal lobe, just deep to the uncus, and is an important structure in processing the emotional significance of stimuli, including pain.

Answer 2

DNA test for deletion of chromosome 15q11-q13 Angelman syndrome, disorder from loss of function of the imprinted UBE3A gene on chromosome 15q11-q13, which can be caused by a mutation on the maternal allele (the most common cause), a 5- to 7-Mb deletion of the maternally inherited chromosomal region, paternal uniparental disomy of chromosome 15, or an imprinting effect. MECP2 gene = Rett syndrome.

Answer 3

subependymal giant cell astrocytoma patients with tuberous sclerosis have a variety of systemic and cns tumors. in the brain, astrocytic hamartomas called tubers and candle gutterings are present. Subependymal giant cell astrocytomas (SEGA) are true neoplasms arising in the vicinity of the foramen of Monro.

Answer 4

cerebral amyloid angiopathy this patient has consecutive occipital lobar hemorrhages. multiple hemorrhages restricted to lobar, cortical, or cortico-subcortical regions are characteristic of probably CAA according to the Modified Boston Criteria. Diagnosis also can be suggested by a single lobar hemorrhage accompanied by focal or disseminated superficial siderosis in a patient age >55yrs in the absence of other likely causes of hemorrhage or superficial siderosis. The 5yr interval between hemorrhages in this patient argues against hemorrhagic venous infarction from cSVT or hemorrhagic metastases. the lobar location of the lesions is atypical for hypertensive intracranial hemorrhage. hemorrhagic conversion of cerebral infarcts is possible but less likely than a cerebral amyloid angiopathy given the appearance of the hemorrhage

Answer 5

Parkinson disease In the coronal image, bilateral electrodes can be seen creating an artifact at the vertex that extends down to the medial pallidal region. the cross sections of the tracts of the electrodes project symmetrical dark dots in the T2 axial image. The dots are located in the globus pallidus.

Answer 6

transient global amnesia patient unable to form new memories, which is classic for an amnestic disturbance. she has retrograde and anterograde amnesia. although the event had a sudden onset similar to a stroke or transient ischemic attack, bilateral impairment is required for amnesia

Answer 7

serum ferritin level <75 RLS can be secondary to iron deficiency anemia. eval of any patient with RLS should include workup to rule out iron deficiency anemia

Answer 8

NMDA receptor antibody symptoms consistent with typical presentation of NMDA-R encephalitis. EEG reveals extreme delta brushes with rhythmic delta activity and superimposed beta, which has been seen in close association with this syndrome

Answer 9

enlarged polyphasic motor unit action potentials patients with ALS have normal sensory responses but decreased motor amplitudes on nerve conduction studies. EMG shows enlarged polyphasic motor unit potentials and reduced recruitment. reduced sensory and motor responses are seen in association with peripheral nerve lesion distal to the DRG. slowed conduction velocity without temporal dispersion is seen in type 1 Charcot-Marie-Tooth disease.

Answer 10

order an ECT to assess for an increased QTc interval from chlorpromazine as dihydroergotamine can increase the QTc interval further antiemetics are used to treat nausea associated with migraine, however they are also associated with increased risk of QT prolongation and torsades de pointes

Answer 11

short head of the biceps femoris short head of the biceps femoris is innervated by the common peroneal nerve in the thigh. this muscle would be spared ina lesion of the peroneal nerve at the fibular head

Answer 12

voltage-gated calcium channel spinocerebellar ataxia type 6 (SCA6) is a degenerative disorder of the cerebellum with autosomal dominant inheritance pattern and characterized by nearly selective and progressive death of Purkinje cells. underlying gene mutation consists of an expansion of a trinucleotide CAG repeat in the 3' region of the CACNA1A gene, encoding the 1a subunit of the neuronal P/Q-type voltage gated calcium channel. affected individuals have 20-33 CAG repeats. characteristic findings include adult onset, slowly progressive cerebellar ataxia, dysarthria, and nystagmus. patients often present with gait unsteadiness, stumbling, imbalance, and dysarthria.

Answer 13

optic nerve a unilateral prolonged P100 latency suggests dysfunction of the ipsilateral optic nerve. retinal disorder would demonstrate absent response ipsilaterally

Answer 14

systemic lupus erythematosus may present acutely with fever and joint swelling. butterfly rash. lyme dz rarely causes sz or confusion and has different rash. MELAS might also cause signs of stroke but would not have systemic findings listed here

Answer 15

serum glucose hypoglycemia can present with signs of focal neurologic dysfunction and mimi stroke.

Answer 16

diffusion-weighted imaging CJD MRI higher specificity and sensitivity for 14-3-3 protein showing hyperintensity in the cortical gyri (cortical ribboning), caudate, and thalamus in DWI

Answer 17

hypertensive hemorrhage uncontrolled longstanding hypertension is the most common cause of spontaneous pontine hemorrhage. much like the vasculature of the basal ganglia, the penetrating arteries extending into the pons from the basilar artery are subject to lipohyalinosis because of poorly controlled hypertension

Answer 18

carbamazepine paroxsymal kinesigenic dyskinesia may be sporadic or inherited in an autosomal dominant fashion. it responds well to low-dose anticonvulsants, such as carbamazepine

Answer 19

immediately discuss the case privately with the junior resident, then notify the program director soon after

Answer 20

metachromatic leukodystrophy AR disorder in which neurocognitive symptoms can be primary presentation in the late juvenile onset forms, with relatively subtle signs on neuro examination. long tract signs are common. imaging studies usually demonstrate involvement of the periventricular and deep white matter with relative sparing of the U fibers.

Answer 21

hypohidrosis infrequent side effect of zonisamide, particularly in children and can lead to symptoms of heatstroke due to impaired heat dissipation mechanisms and produce hyperthermia

Answer 22

radial radial neuropathy characterized by wrist drop, finger drop, weakness of elbow flexion when the arm is half pronated (brachioradialis), weakness of elbow supination (supinator) and sensory loss of the dorsal lateral aspect of the hand finger abduction can appear weak when tested in a wrist drop position and may mistakenly suggest ulnar nerve pathology

Answer 23

electroconvulsive therapy may improve both mood and motor symptoms in patients with advanced Parkinson disease and major depression; also considered safter than TCAs in patients with cardiac conduction disturbances. anticholinergics not effective in treating major depression and may cause cardiac side effects, memory loss, and confusion in the elderly.

Answer 24

neurosarcoidosis enhancing, nodular, patchy, diffuse abnormalities shown are most characteristic of neurosarcoidosis. toxo produces inflammatory lesions, which may enhance but are rarely restricted to gray matter. cerebrotendinous xanthomatosis is a white matter disease.

Answer 25

williams syndrome neurodevelopment disorder caused by deletions on chromosome 7. patients are generally very friendly with excellent social and language skills. marked impairment is noted in tests of visual processing, affecting both the dorsal and ventral streams. nonneuro symptoms include cardiovascular abnormalities, hyperacusis, endocrine disorders, and hypercalcemia

Answer 26

increasing cardiorespiratory fitness use of supplements such as gingko biloba and coconut oil has not been proven to provide cognitive protection, but improving cardiorespiratory fitness has been shown in many studies to help reduce the risk of dementia, possibly by improving white matter integrity. a dairy-free diet and feeding and caring for a pet do not reduce the risk of developing cognitive issues

Answer 27

almost all patients outgrow this form of epilepsy in adolescence self-limited epilepsy with central temporal spikes (SeLECTS) trileptal

Answer 28

opsoclonus-myoclonus-ataxia syndrome myoclonic encephalopathy of infancy, characteristic opsoclonus myoclonus begins with limbs, worse with activity, low amplitude up to half have underlying occult neuroblastoma

Answer 29

INTRACRANIAL HYPOTENSION MRI shows prominent thickening and enhancement of the dura, with small subdural effusions seen on the T2-weighted axial image sx of postural headache

Answer 30

collateral sprouting large motor unit potentials results from collateral sprouting from adjacent axons. reinnervation typically takes at least 3 months to be noted on needle EMG

Answer 31

prolonged dopamine D2 receptor blockade tardive dyskinesia (TD) primarily involves tongue, lips, and jaw. results from chronic exposure to dopamine receptor blocking agents - drugs primarily used to treat psychosis. some antiemetics, including metoclopramide or prochlorperazine

Answer 32

entorhinal cortex dentate gyrus and entorhinal cortex both contain cells whose axons project to the hippocampal formation. fibers from the entorhinal cortex reach the hippocampal formation via the perforant and alveolar pathways. the hippocampal formation does not receive any olfactory input. projections from the cingulate cortex do not terminate on the hippocampal formation, rather htey synapse on cells in the presubiculum and entorhinal cortex. the hippocampus projects to the thalamus

Answer 33

Return the call and explain the patient’s condition cannot be discussed without her consent. As much as the medical team might sympathize with family members in this type of situation, the patient’s wishes must be honored, especially when the patient is mentally competent. This principle of confidentiality is protected under HIPAA.

Answer 34

perinatal hypoxia/ischemia The image shows numerous thin-walled cysts of varying sizes, characteristic of severe multicystic encephalomalacia due to intrauterine hypoxia/ischemia. The formation of cysts in the brain reflects cavitation, which is the end stage of maturation of infarcts. The infarcts must be weeks old, and therefore, reflect intrauterine events. The threadlike strands within the cysts are gliovascular remnants and thus signify an event that occurred after astrocytes were capable of participating in the reaction, roughly after 27 weeks’ gestation.

Answer 35

watershed infarcts of both anterior/middle cerebral artery territories This patient experienced a severe hypotensive episode during which perfusion to the brain was compromised. Watershed regions of the brain lying between major vascular supplies are likely to become ischemic. The border zone between the anterior and middle cerebral artery territories can experience “watershed infarcts” under these circumstances. Both sensory and motor function of the upper extremities is controlled by the frontoparietal cortex; an infarction can result in a syndrome of sensory loss and paralysis of the arms, sometimes referred to as the “man in the barrel syndrome.”

Answer 36

generalized polyspikes Patients with juvenile myoclonic epilepsy (JME) may have a variety of interictal abnormalities, but polyspikes are specific for this disorder. JME comprises up to 10% of all epilepsies, with median age 2021 RITE | 41 at onset 15 years. Hallmark features are myoclonic jerks with retained consciousness and generalized tonic-clonic seizures. Only one third of patients with JME have absence seizures.

Answer 37

misclassification bias Misclassification bias is a form of error that results from systematic inaccuracy in measurement, and it applies to either dichotomous or continuous measures. This error is also known as information bias. Interviewer bias and diagnostic bias are two examples of misclassification bias. The radiologists in this example may not be using consistent criteria to assess the degree of stenosis. Lack of standardized criteria could easily lead to diagnostic bias, which is the problem of the cases with stenosis being classified as not having stenosis (and vice versa). Similarly, those with exposure may be classified as unexposed (and vice versa). Selection bias refers to variability in participant enrollment, which is reduced by using a multicentered trial.

Answer 38

loss of muscle tone with emotional upset This patient gives a classic history for narcolepsy. She has three of the typical clinical features of narcolepsy: excessive daytime sleepiness, hypnagogic hallucinations, and sleep paralysis. She should be questioned about the presence of cataplexy, which is present in narcolepsy type 1. Narcolepsy type 2 does not have cataplexy and usually has normal CSF levels of hypocretin.

Answer 39

dimethyl fumarate Several new platform therapies have recently become available and are approved for patients with relapsing forms of multiple sclerosis. However, all approved agents have either contraindications or clinical warnings requiring the clinician to tailor therapy precisely for each patient. Fingolimod is associated with probable sudden cardiac death and would be contraindicated in a patient with heart block. Natalizumab, which has black box warnings for development of progressive multifocal leukoencephalopathy, would not warrant the risk/benefit ratio in a patient with clinically mild disease. Alemtuzumab is now approved for multiple sclerosis but would not be used in patients with mild disease. Methotrexate has generally weak data and has been used off-label. Dimethyl fumarate, a novel oral agent approved for relapsing-remitting multiple sclerosis, would be an appropriate agent in this setting.

Answer 40

retinal hemorrhage and subdural hematoma Nonaccidental head trauma, previously called “shaken baby syndrome,” is a misnomer because traumatic injury occurs with impact, not just shaking. The most common findings at autopsy are retinal hemorrhage and subdural hematoma, although often only a small amount of the latter. Stippling of soot around a wound is typical of medium-range gunshot wounds.

Answer 41

Parkinson disease This patient’s clinical presentation is consistent with idiopathic Parkinson disease. Typically, speech characteristics are hypophonic (low volume, whispering, mumbling), hypokinetic, and monotone. Alcohol abuse causes an ataxic dysarthria with excess, equal stress, and a slow rate. Pseudobulbar palsy results in a spastic dysarthria with a strained and harsh voice quality that is hypernasal and monotone. Myasthenia gravis causes a flaccid dysarthria with a breathy voice, hypernasal quality, and an imprecise articulation. Tourette syndrome results in a hyperkinetic dysarthria, with sudden variations in loudness and a harsh hypernasal quality.

Answer 42

cyanotic congenital heart disease Two large studies have demonstrated that cyanotic congenital heart disease is the most important predisposing factor for the development of intracerebral abscesses in children. Most brain abscess due to congenital heart disease develop in children over age 2 years with tetralogy of Fallot, transposition of great arteries, or similar single ventricle physiology with right to left shunts.

Answer 43

Kearns-Sayre syndrome Chronic progressive external ophthalmoplegia is characteristic of Kearns-Sayre syndrome (KSS). Features of both KSS and oculopharyngeal muscular dystrophy (OPMD) include ptosis, ophthalmoplegia, dysphagia, and proximal weakness. Hearing loss, cerebellar ataxia, and cardiac conduction defects are not features of OPMD but are seen with KSS. MELAS is characterized by a history of migraine and stroke-like episodes.

Answer 44

posterior cortical atrophy This patient has progressive difficulty with higher level visual processing, including symptoms of Balint syndrome (simultagnosia, oculomotor apraxia and optic ataxia). Of the choices given, her clinical syndrome is most compatible with posterior cortical atrophy. In most cases, posterior cortical atrophy is felt to be a variant early-onset Alzheimer disease, presenting with prominent initial involvement of the occipitoparietal cortex and prominent symptoms of abnormal cortical visual processing.

Answer 45

alpha-galactosidase Fabry disease, an X-linked defect in alpha-galactosidase, is characterized by painful peripheral neuropathy with autonomic manifestations, a typical rash in the lower half of the body, and accumulation of glycolipids in the endothelium of cerebral vessels and renal glomerular arterioles. Patients have a higher risk of cardiovascular events in adulthood. arylsulfatase A - metachromatic leukodystrophy cholesterol esterase - Cholesteryl ester storage disease (CESD) is caused by deficient lysosomal acid lipase (LAL) activity hexosaminidase A - Tay-Sachs porphobilinogen deaminase - Acute intermittent porphyria (AIP)

Answer 46

depletion of substance P in the sensory nerves Capsaicin produces a release (and subsequent depletion with repeated applications) of substance P at the afferent sensory neurons.

Answer 47

multiple sclerosis This combination of findings represents classic multiple sclerosis. Posterior column findings are particularly important diagnostically. Although acute disseminated encephalomyelitis may occur in adolescents and adults, encephalopathy is characteristically present. Neuromyelitis optica spectrum disorder has less significant brain involvement, and spinal cord changes are typically more longitudinally extensive. Combined system degeneration spares the eyes and does not produce the imaging changes noted. Adrenoleukodystrophy with adolescent onset is usually myelitic but almost always affects young men and does not manifest the additional findings or imaging changes noted here.

Answer 48

craniectomy Breach rhythm is a finding seen in patients with skull defects that alters the conductance between the brain and the recording electrode over the scalp.

Answer 49

amyloid angiopathy Cerebral amyloid angiopathy is a common cause of lobar intracerebral hemorrhage in elderly patients and is implicated as a potential cause of chronic microbleeds on gradient echo MRI. Hypertensive hemorrhages usually affect the small penetrating arteries and cause deep brain hemorrhages. Arteriovenous malformations usually present between the ages of 10 to 40 years. In dural arteriovenous fistulas, MRI findings are usually normal. Capillary telangiectasia is most commonly found in the pons and associated with a small amount of hemorrhage and gliosis.

Answer 50

Niemann-Pick disease type C Niemann-Pick disease type C is characterized by autosomal recessive inheritance with gradual and progressive neurologic deterioration. Patients have variable hepatosplenomegaly, and progressive neurodegeneration. Findings include vertical supranuclear (usually downgaze) palsy, ataxia, dystonia, seizures, gelastic cataplexy, and dementia.

Answer 51

spirometry Respiratory muscle weakness associated with ventilatory failure is a potentially serious complication in patients with acute inflammatory demyelinating polyradiculopathy. Spirometry is the most effective measure of respiratory muscle function in these patients. Oxygen saturation is not a sensitive marker for impending respiratory dysfunction in neuromuscular disorders.

Answer 52

sporadic Creutzfeldt-Jakob disease is a rapidly progressive dementing illness with characteristic hyperintensity of the caudate and putamen seen on MRI studies, positive 14-3-3 protein, and periodic sharp wave complexes on EEG. The variant form, which can be caused by ingestion or iatrogenic exposure to contaminated material, typically has a psychiatric presentation. The sporadic form is the most common and presents with multifocal neurologic symptoms and dementia. In a patient with no family history, the sporadic form is the most likely etiology.

Answer 53

posterior communicating artery aneurysm The angiogram shows a posterior communicating artery aneurysm. Mycotic aneurysm, associated with bacterial endocarditis, occurs in more distal, smaller vessels. Arteriovenous malformation is a high-flow abnormal tangle of vessels causing early shunting into the venous connection. A dural sinus venous thrombosis is an occlusion of portions of the venous drainage of the brain. The angiogram shows a normal caliber internal carotid artery, without stenosis.

Answer 54

antibody formation Antibody formation is a significant clinical concern and eventually obviates treatment benefit in approximately 5% of patients. Unilateral spasticity or a limited number of muscles needing treatment would make treatment with botulinum toxin easier. Absence of fixed contractures would be preferable as botulinum toxin will not address this non–neurotransmitter-mediated phenomenon

Answer 55

moyamoya syndrome Moyamoya syndrome can be a primary genetic disorder or secondary to various conditions, including radiation therapy involving the circle of Willis, sickle cell disease, neurofibromatosis, and Down syndrome. Primary moyamoya syndrome is especially frequent in those of Japanese ancestry.

Answer 56

branch retinal artery occlusion and sensorineural hearing loss Susac syndrome is a clinical triad of retinal branch occlusion, hearing impairment, and MRI changes that resembles multiple sclerosis. Punched-out lesions in the corpus callosum are typical. Other MRI abnormalities include hyperintense scattered subcortical T2 lesions, leptomeningeal enhancement, and focal lesions in the basal ganglia and the thalamus. In neuromyelitis optica, the lesions tend to be in the optic nerves, spinal cord, and the periventricular white matter. Behçet disease and Sneddon syndrome are other multiple-system vasculitides that are not associated with the clinical triad and imaging findings presented. Herpes simplex virus encephalitis is associated with fever, seizures, and positive CSF herpes simplex virus PCR.

Answer 57

notify the chief resident and program director to discuss the situation and offer to cover call if needed The first resident is considered an impaired provider after consuming alcohol while on call and should not take call. The second resident has an obligation to ensure both the chief resident and program director are informed.

Answer 58

vitamin K deficiency associated with phenytoin exposure Fetal vitamin K deficiency with hemorrhagic complications occurs in 10% of neonates born to mothers receiving antiepileptic drugs that induce liver metabolism of vitamin K, including phenobarbital and phenytoin. Women taking enzyme-inducing antiepileptic drugs should be treated with vitamin K, 10 to 20 mg daily, during the last month of pregnancy. Infants should receive 1 mg IM at birth and fresh-frozen plasma, if needed.

Answer 59

increased levels of total tau, increased levels of phosphorylated tau, and decreased levels of beta-amyloid (1-42) This patient has clinical signs and symptoms of Alzheimer dementia. Alzheimer disease is characterized by extracellular beta-amyloid plaque depositions. CSF level of beta-amyloid (1-42) is decreased due to what is thought to be a reduction of clearance of beta-amyloid from the brain to the CSF/blood as well as aggregation and plaque deposition in the brain, further reducing the amount found in the CSF. Another pathologic hallmark of Alzheimer dementia is intraneuronal inclusions of the microtubule-associated protein tau. Total tau increases with age but is significantly elevated in Alzheimer dementia. Tau is markedly hyperphosphorylated in Alzheimer dementia and the level in the CSF is also very high and can act to differentiate this form from other forms of dementia. The combination of these three CSF biomarkers significantly increases the diagnostic validity for sporadic Alzheimer dementia, yielding a combined sensitivity of >95% and a specificity of >85%

Answer 60

rapid eye movements Sawtooth waves are seen only in REM sleep; thus, rapid eye movements with faster background are seen. N2 findings such as vertex transients and sleep spindles may be seen during REM but are infrequent.

Answer 61

amiodarone Amiodarone has been associated with drug-induced postural tremor. Beta-blockers such as propranolol and sotalol may improve postural tremor. Diltiazem, verapamil, and digoxin have not been associated with tremor.

Answer 62

reduced recruitment of motor unit action potentials With acute (<1 week) nerve root compression, the only EMG abnormality seen may be reduced recruitment of motor unit potentials. Fibrillation potentials usually are not seen for 7 to 10 days after the onset of injury. Fasciculation potentials and large polyphasic motor unit action potentials reflect chronicity.

Answer 63

temozolomide Rationale: Once diagnosed with high-grade glioma (glioblastoma multiforme), patients should be offered standard treatment consisting of surgical resection, radiation therapy, and temozolomide. MGMT gene promoter methylation is used to help predict the response to treatment.

Answer 64

ruptured aneurysm Rationale: Ruptured aneurysm would be the most likely cause of subarachnoid hemorrhage in this age group. The high-density material that outlines the subarachnoid space around the brain indicates recent bleeding. There is hydrocephalus, but it is not idiopathic; rather, it is caused by the subarachnoid hemorrhage. The air with pneumocephalus would have a much lower density than any of the structures seen on the image. There is no focal area of infarction or subarachnoid blood to suggest clear vascular malformation or intraparenchymal lesion to indicate reversible cerebral vasoconstriction AVM rupture. Its shape rules out the other types of hemorrhage listed. There are no bone fractures to indicate trauma. Drug overdose and bacterial meningitis would not clearly explain the subarachnoid hemorrhage.

Answer 65

somatic symptom disorder Rationale: Somatic symptom disorder, previously known as somatoform disorder, is defined as one or more somatic symptoms that are distressing or result in a significant disruption of daily life. Patients have excessive thoughts, feelings, or behaviors related to the somatic symptoms or associated health concerns manifested by one or more of the following symptoms: disproportionate and persistent thought about the seriousness of the symptoms; persistent high level of anxiety about health or symptoms; or excessive time and energy devoted to these symptoms or health concerns. To be diagnosed with somatic symptom disorder, the patient must be persistently symptomatic, typically for at least 6 months.

Answer 66

discrete demyelination with axon loss Axon loss is increasingly recognized as an integral part of the disease process (along with demyelination) in multiple sclerosis

Answer 67

Rett syndrome Rationale: Stereotypic midline hand movements such as wringing or rubbing are hallmark features of Rett syndrome. Most patients will also have oral bruxism or intermittent hyperventilation. Affected children are normal initially but lose purposeful hand movements and declining head circumference sometime between age 6 and 18 months. Dravet syndrome is an epilepsy syndrome with onset in the first year of life but does not include acquired microcephaly or stereotypic hand movements.

Answer 68

empty pituitary sella This midsagittal T1-weighted MRI scan shows an empty pituitary sella, a frequent finding in patients with idiopathic intracranial hypertension. This finding is not fully sensitive or specific, as it also can be present incidentally in patients without pathologically elevated intracranial pressure. The scan does not show descent of the cerebellar tonsils that is characteristic of Chiari type I malformation. Diseases intrinsic to the chiasm and optic nerve, such as a primary glioma, can cause optic disc swelling, but these findings are not present on this scan. Typical imaging findings for olfactory groove meningioma include a homogeneously enhancing mass with a dural tail. A large arteriovenous malformation can present with papilledema, but prominent flow voids would be visible on the scan.

Answer 69

anterior spinal Rationale: Medial medullary syndrome is most commonly associated with infarction in the anterior spinal artery distribution at the level of the medulla. An occlusion at this level may result in ipsilateral cranial nerve XII paralysis (fascicle of cranial nerve XII), contralateral hemiparesis (pyramid), and contralateral loss of position and vibratory sensation (medial lemniscus). A bilateral lesion in this vascular territory results in quadriparesis, bilateral loss of proprioception and vibration, and complete paralysis of the tongue.

Answer 70

discitis Rationale: Pediatric neurologists are frequently asked to evaluate a child who refuses to walk. Causes can range from benign behavioral problems to acute neurologic problems; also possible are non-neurologic abnormalities that simulate a neurologic deficit but require immediate intervention. Childhood discitis can affect children of all ages and can be seen in the thoracic, lumbar, or sacral spines; however, it most commonly occurs in the lumbar region in children younger than age 5 years. Physical examination, laboratory tests, and imaging studies aid in the diagnosis. Proper interpretation of history, clinical presentation, and study results can prevent unnecessary invasive intervention. Presentation varies with age; a child may refuse to bear weight on the lower extremities or may present with back or abdominal pain and/or a limp, whereas an infant or toddler may present with irritability. The etiology appears to be a bacterial infection, usually caused by Staphylococcus aureus. Most children improve rapidly with a 4- to 6-week course of antibiotics. Although not routinely necessary, immobilization decreases symptoms and, in the case of osseous destruction, prevents progression of spinal deformity. Biopsy of the infected disk space is reserved for children refractory to IV antibiotics. Follow-up should include plain radiographs at regular intervals for 12 to 18 months to ensure resolution of the destructive process. Elevated erythrocyte sedimentation rate would be unusual in the case of vertebral fracture. The absence of focal findings on neurologic examination is not consistent with epidural abscess, spinal syrinx, or transverse myelitis.

Answer 71

siponimod Rationale: Siponimod, similar to other S1P modulators like fingolimod, can lead to temporary bradycardia immediately following the first dose, although a 5-day titration appears to mitigate first-dose bradycardia. Fingolimod has been shown to cause bradycardia. ECG monitoring is required prior to the first dose. Patients with Mobitz type II second- or third-degree heart block were excused from siponimod clinical trials. Some patients become symptomatic and may even experience syncope. While dimethyl fumarate, glatiramer, interferon-beta 1a, and teriflunomide have their own set of side effects, none would be contraindicated in this patient with bradycardia.

Answer 72

topiramate Rationale: Topiramate increases the risk of developing calcium oxalate and calcium phosphate stones but not other types of stones due to its carbonic anhydrase inhibitory activity. This leads to metabolic acidosis, hypercalciuria, hypocitraturia, and elevation of urinary pH, all of which are favorable to kidney stone formation.

Answer 73

touching the chin Rationale: This patient describes cervical dystonia. So-called “sensory tricks” (geste antagoniste), usually involving touching the chin, back of the neck, or cheek, have reportedly alleviated these symptoms in up to 90% of patients with cervical dystonia.

Answer 74

Medicare fraud Rationale: Overbilling or under billing is considered Medicare fraud. HIPAA addresses patient privacy and security of medical information not billing.

Answer 75

rivastigmine Rationale: Dementia with Lewy bodies (DLB) is considered the second most common form of dementia, although some experts believe vascular dementia to be the second most common form. DLB is often underdiagnosed and/or misdiagnosed as Alzheimer disease or Parkinson-related dementia. Core features are cognitive decline and at least one of the following findings: fluctuations in cognition, visual hallucinations, and/or parkinsonism. Other associated characteristics include neuroleptic sensitivity, repeated falls, syncope, transient loss of consciousness, REM sleep behavior disorder, depression, delusions, and nonvisual hallucinations. Increased caution is essential when using neuroleptic agents in these patients due to associated physical and cognitive decline and increased mortality. Symptoms of the parkinsonian syndrome (akinesia, rigidity, tremor) usually can be improved with levodopa, with a maximum dose of 300 mg/day due to the potential for psychiatric side effects. Cholinergic deficits are associated with visual hallucinations; thus, cholinesterase inhibitors may be especially useful in treatment of DLB as they often result in resolution of hallucinations, improved cognition, and decreased behavioral disturbances. Although neuroleptic sensitivity has been reported with both typical and atypical antipsychotic medications, visual hallucinations and delusions can be improved with atypical neuroleptics (clozapine, risperidone, quetiapine). Clozapine seems to be the drug of first choice. Doses of 12.5 to 50 mg three times/day can be used. Atypical neuroleptics rarely worsen parkinsonian symptoms and level of consciousness. Decreases in neuroleptic sensitivity often can be achieved by a dose reduction, although discontinuing the drug is sometimes necessary. Haloperidol is a typical antipsychotic with a higher risk of neurologic worsening.

Answer 76

blockade of T-type calcium channels This patient has absence epilepsy confirmed by an EEG that demonstrates 3-Hz generalized spike wave discharges. First-line treatment of childhood absence epilepsy is ethosuximide. The prevailing hypothesis for the mechanism of action for ethosuximide is that it produces a blockade of thalamic low-threshold “transient” or “tiny,” so-called T-type, calcium channels.

Answer 77

lead Rationale: Lead has a direct effect on porphyrin metabolism by inhibiting gamma-aminolevulinic acid dehydratase. Lead toxicity produces a motor neuropathy that affects predominantly, but not exclusively, the radial nerve. Other associated findings include abdominal pain, bluish discoloration of the gums just below the teeth, microcytic hypochromic anemia with basophilic stippling of the red cells, and increased coproporphyrin levels.

Answer 78

frontal lobes Rationale: Sequential hand movements and simple rhythm tapping are considered tests of frontal lobe function, but these can be impaired in lesions affecting the frontal-subcortical circuits (frontal cortex to basal ganglia to thalamus and back to frontal cortex). Performance of go/no-go tasks are frequently used to investigate response inhibition. Recent neuropsychological and neuroimaging studies have shown that the presupplementary motor area and ventrolateral prefrontal cortex are crucial for response inhibition. Therefore, all of these exam techniques are able to measure frontal lobe function.

Answer 79

pantothenate kinase-associated neurodegeneration Rationale: Pantothenate kinase-associated neurodegeneration (formerly Hallervorden-Spatz disease) is a progressive neurodegenerative disease with neuroaxonal dystrophy, rust-brown discoloration of the globus pallidus and pars reticularis of the substantia nigra due to accumulation of iron-containing pigment, and onset usually before age 15 years. These changes are due to mutations in the novel panto-thenate kinase (PANK2) gene. The other disorders listed would not show the characteristic gross pathology seen in the image.

Answer 80

increased tau with decreased beta-amyloid Increased CSF tau levels in patients with Alzheimer disease are thought to occur after being released from dying and damaged neurons. The CSF levels of beta-amyloid 1-42 are decreased secondary to the accumulation of amyloid in the neuritic plaques. This pattern has been shown to have sensitivity and specificity of 85% in predicting conversion from mild cognitive impairment to Alzheimer disease.

Answer 81

optic nerve hypoplasia The coronal T2-weighted MRI scan shows absence of the septum pellucidum. In the context of an infant with severe visual loss, the most likely diagnosis is septo-optic atrophy (DeMorsier syndrome). This imaging finding is not associated with retinal astrocytoma, as seen in tuberous sclerosis. There is no mass lesion or hydrocephalus to suggest the infant might have papilledema. There are no brain lesions visible on the scan to suggest the infant may have a retinal arteriovenous malformation, as occurs with Walker-Warburg syndrome. The imaging features seen here are not associated with neurofibromatosis.

Answer 82

clinically isolated syndrome Rationale: Clinically isolated syndrome is the term used to describe an initial clinical neurologic event suggestive of demyelination. This patient does not have either a clinical history of a prior episode or radiographic evidence of dissemination in time such as enhancing and nonenhancing lesions. The patient does not have oligoclonal bands. In this context, this patient does not meet clinical the 2017 McDonald criteria for multiple sclerosis. Patients with a clinically isolated syndrome and MRI evidence of dissemination in space are at high risk for subsequent demyelinating attacks (dissemination in time) and therefore ultimately fulfill the diagnostic criteria for multiple sclerosis.

Answer 83

2 years Rationale: After 2 years of age, asynchronous sleep spindles are considered abnormal.

Answer 84

history of nocturnal seizures Rationale: After presentation with a first seizure, clinical risk factors for recurrence include prior brain insult, an EEG with epileptiform abnormalities, a significant abnormality on imaging studies of the brain, and nocturnal seizure. Hyponatremia and other electrolyte disturbances can cause symptomatic seizures, but these cease after correction of the abnormality. Seizures can be seen with cocaine abuse, as an acute toxic effect, but remote cocaine use does not increase the risk of epilepsy. Seizure type has no relation to risk of epilepsy. History of migraine does not increase the risk of epilepsy.

Answer 85

contact a different neurology attending to staff the case and report the current issue concerning the neurology attending on call Rationale: The case should be staffed with a neurologist if possible and the neurology attending should be reported so that the situation can be clarified. Perhaps the attending was not aware that he/she was on call.

Answer 86

pericallosal aneurysm Rationale: There is a saccular or ovoid enlargement arising along the course of the left anterior cerebral artery just anterior genu of the corpus callosum. Its appearance is characteristic of a saccular aneurysm.

Answer 87

alpha-galactosidase Rationale: Fabry disease is an X-linked disease with reduced alpha-galactosidase enzyme activity. It is characterized by painful peripheral neuropathy with autonomic manifestations, a typical rash in the lower half of the body, and accumulation of glycolipids in the endothelium of cerebral vessels and glomerular arterioles.

Answer 88

corticobasal degeneration Rationale: All the neurodegenerative disorders listed share the core clinical feature of parkinsonism. Asymmetric rigidity is seen in all but progressive supranuclear palsy (PSP), which manifests as symmetric axial rigidity. The inability to recognize his arm as his own is consistent with alien limb syndrome, which may be seen in corticobasal syndrome referable to the parietal lobe dysfunction, frontal and callosal lesions. Corticobasal degeneration (CBD) is confirmed at autopsy with tau-positive lesions. Both CBD and PSP are tauopathies.

Answer 89

lack of clear external secondary gain Rationale: Both factitious disorder and malingering are characterized by assuming the sick role and the intentional production of symptoms. The major difference between the two is that a malingerer’s production of symptoms is entirely motivated by external secondary gain, whereas a patient with factitious disorder is motivated only by the emotional comfort of being seen as ill and needy. A history of emotional or other trauma is common in factitious disorder, but it may not be present, nor is this a way to distinguish it from malingering.

Answer 90

CASPR2 Rationale: Peripheral nerve hyperexcitability (PNH), also referred to as Isaac syndrome, is characterized by muscle cramps and stiffness, as well as marked myokymia causing undulating wave-like spontaneous muscle activity that is evident on examination. CASPR2 is an autoantigen of encephalitis and PNH previously attributed to VGKC antibodies. Antibodies are found in approximately 50% of patients. NMDA and GABA-A receptor antibodies are associated with encephalitis. Voltage-gated calcium channel antibodies are associated with Lambert-Eaton myasthenic syndrome, and sodium channel antibodies are implicated in some autoimmune polyneuropathies.

Answer 91

observation Rationale: A child who presents with more than six café-au-lait spots that are >0.5 cm in diameter and axillary freckling meets the diagnostic criteria for neurofibromatosis type 1. Optic gliomas associated with this condition usually are detected before age 6 years. Once an optic glioma is confirmed, the current recommendation is for patients to undergo eye examinations every 3 to 4 months for the first year after diagnosis and at increasing intervals after a year. In the absence of documented visual abnormalities, observation is the usual treatment modality as regression of the tumor is possible. Enlarging optic gliomas may be treated with chemotherapy (carboplatin and vincristine). Radiotherapy should be avoided as it has been associated with the development of secondary peripheral nerve sheath tumors in the treatment field.

Answer 92

visuospatial and calculation Rationale: The pathology in frontotemporal dementia is predominately located in frontal and anterior temporal lobes in the most common forms. Visuospatial and calculation skills are located predominantly in the right and left parietal cortex, respectively. The parietal lobes are more often spared in frontotemporal dementia conditions. Executive, language, and memory domains are more likely to be impaired in conditions affecting frontal and temporal lobes.

Answer 93

acute disseminated encephalomyelitis Rationale: A perivascular/perivenular pattern of demyelination is typical of ADEM. Acute hemorrhagic leukoencephalitis is characterized by perivascular hemorrhage, often with accompanying necrotizing vasculitis and demyelination. Multiple sclerosis (MS), neuromyelitis optica (NMO), and progressive multifocal leukoencephalopathy (PML) are demyelinating processes, though demyelination is not perivascular in distribution. Both MS and NMO also tend to have accompanying lymphocytic perivascular inflammation, whereas PML has a JC virus-specific viral cytopathic effect.

Answer 94

dystrophinopathy This image of a muscle biopsy specimen shows degenerating fibers undergoing phagocytosis, as well as hypercontracted fibers, excessive fibrosis, and varied fiber size. The proliferation of connective tissue, especially, is most consistent with a dystrophic process such as Duchenne muscular dystrophy due to dystrophin deficiency. Kugelberg-Welander syndrome is a spinal motor neuron atrophy that has a neurogenic appearance in muscle biopsy specimens. Nemaline rod myopathy contains classic eosinophilic inclusions in the muscle fibers. The clinical scenario and histopathology do not suggest an inflammatory myopathy such as dermatomyositis or polymyositis.

Answer 95

2- to 2.5-Hz spike-and-wave Rationale: Lennox-Gastaut syndrome is characterized clinically by frequent generalized seizures of mixed type in association with mental retardation and a slow spike-and-wave EEG pattern with increasing disorganization during sleep. The pattern is called slow spike-and-wave because it is slower than that seen in association with childhood absence epilepsy (3 to 3.5 Hz).

Answer 96

neuromyelitis optica Rationale: The spinal lesion shown is multisegmental, elongated, and located in the lower cervical and thoracic levels. The pattern and extent of the lesion is atypical for multiple sclerosis in its size and extent and is most characteristic of a form of transverse myelitis.

Answer 97

colloid cyst Patients with colloid cysts tend to present with headaches from obstructive hydrocephalus, but they may have syncope and sometimes sudden death occurs. The cysts are bright on noncontrast T1 studies and do not enhance with contrast. The cyst contents are proteinaceous and do not suppress on T2 FLAIR sequence images. The epithelium is pseudostratified, ciliated, and has goblet cells but may be flattened and unrecognizable. The lining seen here is not consistent with the epithelium in a papilloma or craniopharyngioma. A Rathke cleft cyst may have a similar lining but would be in the pituitary, not the third ventricle.

Answer 98

hypertension Rationale: Stroke prevention requires management of the major risk factors, including hypertension, hyperlipidemia, diabetes mellitus, and tobacco use, as well as antithrombotic therapy. Hypertension, the most common modifiable stroke risk factor, affects about one third of US adults over 20 years of age.

Answer 99

thyroid eye disease Rationale: The coronal CT scan shows abnormal thickening of the extraocular muscles, especially the right medial, inferior, and lateral rectus muscles, and the left medial and inferior rectus muscles. The findings are characteristic of thyroid eye disease but are not seen in idiopathic intracranial hypertension or meningioma. Carotid cavernous fistula can cause diplopia and proptosis but typically not such pronounced extraocular muscle hypertrophy. Myasthenia gravis is not accompanied by imaging abnormalities.

Answer 100

OCRELIZUMAB Rationale: This patient fulfills the McDonald criteria for primary progressive multiple sclerosis (MS), as she has a history of more than 1 year of progressive symptoms and has two of the three criteria: an abnormal MRI of the brain consistent with MS and positive oligoclonal bands. The third criterion is an abnormal MRI of the spinal cord consistent with MS. Historically, no therapy has demonstrated efficacy in primary progressive MS. In January 2017, a phase 3 randomized controlled trial of ocrelizumab for primary progressive MS was published in the New England Journal of Medicine. The percentage of patients with 12-week confirmed disability progression was 32.9% with ocrelizumab versus 39.3% with placebo (P=0.03). The percentage of patients with 24-week confirmed disability progression was 29.6% with ocrelizumab versus 35.7% with placebo (P=0.04). By week 120, performance on the timed 25-foot walk worsened by 38.9% with ocrelizumab versus 55.1% with placebo (P=0.04); the total volume of brain lesions on T2-weighted MRI scans decreased by 3.4% with ocrelizumab and increased by 7.4% with placebo (P<0.001); and the percentage of brain-volume loss was 0.90% with ocrelizumab versus 1.09% with placebo (P=0.02). FDA approval for ocrelizumab in the treatment of primary progressive MS was granted in March 2017.

Answer 101

opsoclonus-myoclonus-ataxia syndrome Rationale: The darting random eye movements are consistent with opsoclonus, and the rapid presentation and symptom complex is most consistent with opsoclonus-myoclonus-ataxia syndrome. Typical nystagmus with rapid lateral eye movements is seen in other forms of acute ataxia such as postinfectious cerebellar ataxia. Opsoclonus is not associated with ataxia telangiectasia or neuropathy, ataxia, retinitis pigmentosa, and ptosis (NARP); these disorders also have a slower onset.

Answer 102

primary CNS lymphoma The photomicrographs show a primary CNS lymphoma. Elderly patients may present with primary CNS lymphoma as either a single mass or with multiple brain masses. The neuroimaging appearance may vary widely and may mimic metastatic disease or glioblastoma. Diffusely enhancing lesions may be located in periventricular regions and may even cross the corpus callosum, further mimicking a glioma. Lesions may be highly necrotic, but the monotonous cytologic features, coupled with the immunostaining profile (in this case positivity for a B cell marker, CD20), clarify the diagnosis. Elderly patients with primary CNS lymphoma typically do not have AIDS but do have some degree of more subtle immunocompromise due to advanced age; most have B cell lymphomas. Primary CNS lymphomas may also be seen in immunocompromised patients with Epstein-Barr virus.

Answer 103

CT of the abdomen and pelvis Rationale: Femoral neuropathy or a high lumbar plexus lesion associated with retroperitoneal pain in a patient with coagulopathy suggests a retroperitoneal hemorrhage. Imaging studies such as a CT abdomen and pelvis are required to confirm the diagnosis.

Answer 104

order evaluation for epilepsy surgery Rationale: This patient has frequent partial complex seizures, most likely from a unilateral mesial temporal focus, and reports having continued seizures despite what appears to have been adequate trials of two anticonvulsants. In this situation, patients are unlikely to respond adequately to a trial of a third anticonvulsant. Referral to an epilepsy center for video-EEG monitoring as part of an assessment for possible epilepsy surgery is most appropriate.

Answer 105

dextromethorphan Rationale: Serotonin syndrome is a potentially life-threatening drug interaction that results from excess central serotonergic tone. It is chiefly a clinical diagnosis based in part on recognition of a clinical triad of mental status changes, hyperautonomaticity, and neuromuscular changes. The abuse potential of dextromethorphan, a popular antitussive, is well-known because its primary metabolite possesses a pharmacodynamic profile similar to phencyclidine. Dextromethorphan also enhances central serotonergic tone by blocking its reuptake and increasing its release. Cases of serotonin syndrome resulting from combining dextromethorphan with serotonin reuptake inhibitors and monoamine oxidase inhibitor medications have been reported.

Answer 106

follow his wishes and discuss palliative care/hospice with the patient and his parents Rationale: This cognitively competent 18-year-old patient can direct his own health care decisions, and his wishes should be followed despite the wishes of his parents.

Answer 107

processing speed Rationale: Individuals with multiple sclerosis generally display a pattern of subcortical dysfunction on neuropsychological testing with impairments noted in information processing efficiency, initial learning of new information, and working memory. Impairments in encoding of information, visuospatial skills, semantic fluency, and orientation to time are generally observed in patients with Alzheimer disease.

Answer 108

obsessive-compulsive disorder Rationale: This patient presents with multiple simple tics, both motor (blinking) and vocal tics (sniffing), though not specific vocalizations. The duration of symptoms is unknown; therefore, a diagnosis of Tourette syndrome cannot be made formally as the criteria for diagnosis (history of tics for >1 year) have not been met. Several psychiatric disorders have shown association with tics, including attention-deficit/hyperactivity disorder (ADHD) and probably most prominently, obsessive-compulsive disorder. Given the presentation and patient age, factitious disorder is unlikely. The incidence of the other psychiatric disorders appears to be no higher in the population with tics than in the population at large.

Answer 109

bacterial abscess Rationale: The image shows a right frontal lesion with internal restricted diffusion and a solid rim of contrast enhancement. These features are most concerning for a bacterial abscess. Glioblastoma most often has an irregular rim of enhancement and its internal contents do not restrict diffusion. Metastases are most often solidly enhancing. In tumefactive demyelination, restricted diffusion and enhancement are variable, and there may be an incomplete or irregular rim of enhancement. Cavernous malformations do not show rim enhancement and their internal contents do not restricted diffusion.

Answer 110

tumefactive demyelinating lesion Rationale: The photomicrograph shows sheets of macrophages, typical of a demyelinating lesion. Given the presentation of a solitary mass lesion, the diagnosis is consistent with tumefactive demyelinating lesion, thought to represent a form of multiple sclerosis (MS). The neuroimaging findings are an important clue, as an incomplete ring is most typically seen with demyelinating lesions, whereas a complete ring may be seen with glioblastoma or brain abscess, among others. Although the cells here may superficially resemble oligodendroglioma or renal cell carcinoma, these macrophages have foamy cytoplasm-containing phagocytosed myelin debris. No neoplastic cells are present, nor are there neutrophils typical of brain abscess.

Answer 111

discontinue ethambutol Rationale: Ethambutol is a standard antituberculous medication frequently used for the first 2 months of treatment. Optic neuropathy is one of the disabling side effects, usually seen a couple of months after initiation of treatment. Because ethambutol-induced optic neuropathy is most commonly retrobulbar and bilateral, abnormalities of the optic discs and the pupils might not be evident on funduscopic exam. The risk is higher in patients with impaired renal function, use of a higher dose, and longer duration of treatment. Early recognition of this side effect and discontinuation of ethambutol may restore vision, particularly when ethambutol is no longer indicated. Isoniazid-induced optic neuropathy may also occur, albeit much less likely than with ethambutol.

Answer 112

left gaze palsy Rationale: This patient has a spontaneous hemorrhage into the tegmentum of the left pons, most likely secondary to hypertension. In this location, ipsilateral involvement of cranial nerve VI and VII nuclei and their fascicles would be expected. A lesion of the sixth nerve nucleus causes both an ipsilateral abduction deficit and contralateral adduction deficit when attempting to look ipsilaterally. Contralateral adduction is preserved for near stimuli. Horner syndrome relates to involvement of the ipsilateral descending sympathetic fibers. The corticospinal tract is ventral to the lesion. Moreover, if upper motor neuron function was affected, it would involve the right hemibody, not the left. The nuclei and fibers of cranial nerves IV and XII are above and below the level of the lesion, respectively.

Answer 113

ANENCEPHALY Rationale: Folate deficiency in pregnancy may lead to neural tube defects such as anencephaly. Agenesis of the corpus callosum and holoprosencephaly are midline patterning defects, and lissencephaly and polymicrogyria are disorders of neuronal migration.

Answer 114

lateralized periodic discharges Rationale: Lateralized periodic discharges (LPDs), formerly known as periodic lateralized epileptiform discharges (PLEDs), are seen after an acute or subacute cerebral insult such as a stroke and are often associated with focal seizures. Burst suppression represents a severe disturbance of cerebral function and may be seen in a variety of contexts, including anesthesia and global anoxic injury. Rhythmic midtemporal discharges and small sharp spikes are benign variants and commonly misinterpreted as epileptiform abnormalities.

Answer 115

LOWER TRUNK PLEXOPATHY Rationale: In a patient with a traumatic brachial plexopathy, absence of ulnar motor and sensory responses and motor median responses is consistent with lower trunk brachial plexopathy. With C8-T1 root avulsion, denervation in weak and atrophic muscles is seen but sensory nerve conduction studies are normal as the dorsal root ganglia are not involved. Mononeuropathies could have motor and sensory responses involved for each mixed nerve mononeuropathy. A cervical myelopathy would have normal sensory responses.

Answer 116

TACROLIMUS Rationale: This patient has a primary motor process as demonstrated by his normal sensory nerve responses. The inability to directly stimulate muscle is a very rare finding seen in critical illness myopathy or in a patient with periodic paralysis during an episode. In this clinical context, the patient has critical illness myopathy. The principal risk factor for acute critical illness myopathy is use of high-dose corticosteroids in the ICU setting. Tacrolimus has been implicated as a cause of toxic neuropathy but not a myopathy. Ciprofloxacin has been implicated as a trigger for myasthenia but not a myopathy. Statin myopathies tend to be subacute and often associated with creatine kinase levels more than 10 times normal. Short-term use of propofol has not been associated with acute neuropathy or myopathy, although high-dose propofol can result in propofol infusion syndrome and rhabdomyolysis.

Answer 117

IDENTIFICATION OF POSITIVE FEATURES ON EXAMINATION THAT ARE TYPICAL OF A FUNCTIONAL DISORDER Rationale: The DSM-5 diagnostic criteria for a conversion disorder includes motor or sensory symptoms that do cause distress for the patient, positive physical signs of internal inconsistency with recognized disease, and symptoms that are not better explained by another medical or mental disorder. Unlike previous editions, the DSM-5 has excluded the requirement for a psychological stressor that is often not found as well as determination that a patient is “not feigning,” which is nearly impossible to prove. There is no element of duration needed to make the diagnosis.

Answer 118

ACETYLCHOLINESTERASE INHIBITOR Rationale: Acetylcholinesterase inhibitors (AChEIs) such as rivastigmine, donepezil, and galantamine have demonstrated benefit on global cognitive measures in Alzheimer dementia and diffuse Lewy body disease in double-blind, placebo-controlled trials. These agents are also effective at reducing hallucinations and delusions in these patients. Combined dopamine and serotonin receptor antagonists (risperidone), postsynaptic dopamine (D2) blockers (haloperidol), combined norepinephrine and serotonin receptor antagonists (tricyclic antidepressants), and gamma aminobutyric acid (GABA) enhancers (clonazepam) are not first-line agents. Dopamine antagonists/blockers could actually induce severe parkinsonism in this patient and should be avoided.

Answer 119

NATALIZUMAB Rationale: Natalizumab, an mAb against alpha 4 integrin, has been shown to be effective in suppressing multiple sclerosis activity but was withdrawn from the market because several treated patients developed progressive multifocal leukoencephalopathy (PML). Controlled trials have shown considerable efficacy in preventing relapses. While well-tolerated, three cases of PML occurred in the context of three clinical trials encompassing some 3,300 patients using this drug in multiple sclerosis and Crohn disease. As of March 2013, almost 350 patients developed PML among >100,000 patients treated.

Answer 120

norepinephrine Rationale: Classic symptoms of narcolepsy type 1 (narcolepsy with cataplexy) include excessive daytime sleepiness and abruptly falling without loss of consciousness or sustaining injury during periods of heightened excitement. Most patients with this syndrome have low or undetectable levels of hypocretin in CSF. Narcolepsy type 2 (narcolepsy without cataplexy) often have normal CSF levels of hypocretin.

Answer 121

NMDA glutamate receptors Rationale: Memantine is a moderate affinity, noncompetitive, voltage-dependent NMDA receptor antagonist with fast on/off kinetics that inhibits excessive calcium influx induced by chronic overstimulation of the NMDA receptor.

Answer 122

24 hours after rtPA administration Patients with acute stroke are at increased risk for deep venous thrombosis (DVT) and pulmonary embolism. According to the 2007 AHA guidelines for the early management of adults with ischemic stroke, subcutaneous administration of anticoagulants is recommended for the treatment of immobilized patients to prevent DVT, but the ideal timing for starting these medications is not known. Initiation of anticoagulant therapy within 24 hours of treatment with IV rtPA is not recommended. Aspirin and DVT prophylaxis should be started after a 24-hour head CT scan confirms no hemorrhagic conversion of the ischemic stroke with tPA.

Answer 123

rhinorrhea Rationale: Patients with cluster headaches often describe ipsilateral rhinorrhea and tearing during severe paroxysms of pain. A history of neck trauma would be important if large artery dissection is suspected, as this can also cause retro-orbital pain but not “clusters” of episodic, brief, severe retro-orbital pain separated by years, as described by this patient. This patient’s symptoms are not suggestive of trigeminal neuralgia, which can be triggered by touching the cheek or teeth brushing. In addition, this patient’s symptoms are not highly suggestive of migraine, which can be associated with photophobia and sonophobia, and sometimes preceded by a visual aura.

Answer 124

demyelinating sensorimotor polyneuropathy Rationale: Understanding the distinction between inherited metabolic diseases that affect the CNS only, such as Canavan disease, and those that affect both, such as metachromatic leukodystrophy, can be useful. Metachromatic leukodystrophy is a lysosomal storage disorder that affects both the CNS and the peripheral nervous system. It is typically associated with demyelinating sensorimotor polyneuropathy with uniformly slow motor and sensory conduction velocities. Nerve conduction studies typically are not normal in metachromatic leukodystrophy. Axonal sensorimotor neuropathy is a nonspecific pattern seen in a wide variety of conditions. Motor neuronopathy would be expected in spinal muscular atrophy. Sensory neuronopathy may be seen in other genetic disorders such as Friedreich ataxia.

Answer 125

sodium Rationale: Depolarization of action potentials causes an initial negative departure from baseline due to rapid opening of voltage-sensitive sodium channels. Closing of these channels due to an intrinsic inactivation time constant, as well as slow opening of voltage-sensitive potassium channels, results in repolarization of the neuron.

Answer 126

advertise the study, informing patients to contact the investigator if interested Rationale: A series of guidelines including the Belmont Report, the Helsinki Principle, and 45 CFR 46 guide ethical conduct for investigators. According to these guidelines, a colleague may not disclose any information regarding a patient’s name, contact information, or diagnosis to a researcher without the patient’s consent prior to release. Even the ability to opt out of a research study is not permissible if the information above is provided to the researcher without consent.

Answer 127

transactivating responsive sequence DNA-binding protein Rationale: Transactivating responsive sequence DNA-binding protein (TDP-43) is a protein encoded by the TARDBP gene on chromosome 1. Numerous studies have linked this protein to ALS, frontotemporal dementia with motor neuron disease and frontotemporal dementia with ubiquitin inclusions. Microtubule-associated protein tau and valosin-containing protein have also been found in some patients with frontotemporal dementia but rarely in those also exhibiting motor neuron disease.

Answer 128

cardiomyopathy This patient has Friedreich ataxia, the most common autosomal recessive inherited ataxia. The underlying mutation is an expansion repeat of both alleles of chromosome 9. Cardiomyopathy is the most common cause of death in these patients.

Answer 129

glatiramer acetate Rationale: Lipoatrophy is a potentially disfiguring dermatologic condition associated with glatiramer acetate, which is given by subcutaneous injection. It is not associated with any of the interferons or natalizumab. Lipoatrophy occurs at glatiramer injection sites and may be permanent. Glatiramer injections should be discontinued at affected areas.

Answer 130

facial recognition Rationale: Bilateral lesions of the fusiform (occipitotemporal) gyri produce prosopagnosia, the inability to recognize people by looking at their face.

Answer 131

absent tibial H reflex Rationale: The H reflex is the electrophysiologic equivalent of a monosynaptic tendon stretch reflex at the ankle.

Answer 132

NOTCH3 gene mutation Rationale: This patient’s presentation is most consistent with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) due to a mutation in the NOTCH3 gene on chromosome 19. This disorder is often associated with progressive focal neurologic deficits. Migraines are a common clinical feature as well.

Answer 133

consult with the hospital ethics team Rationale: In a nonemergent situation, parents direct the health care of their children. In this situation, there is no compelling reason to contradict their wishes emergently; however, in cases where decisions would have deleterious medical consequences, ethics consultation is appropriate. Lumbar puncture should not be performed in a patient with a suspected mass lesion (new seizure, hemiparesis) without first obtaining imaging studies.

Answer 134

nonconvulsive status epilepticus Rationale: Nonconvulsive status epilepticus can be prolonged and is associated with fairly abrupt deterioration in mental function and a paroxysmal EEG. These features differentiate nonconvulsive status epilepticus from the dementias.

Answer 135

Bartonella henselae Rationale: Bartonella henselae is the bacteria that causes cat scratch disease. Although this is usually a mild, self-limited febrile illness with adenopathy, it occasionally causes significant cerebritis with various lesions seen in the cortex, white matter, and/or basal ganglia. Presenting features may include seizures and encephalopathy.

Answer 136

Lisch nodules Rationale: The presence of macrocephaly, multiple café-au-lait spots, and axillary freckling suggests neurofibromatosis type 1 (NF1). The ophthalmologic finding seen in association with NF1 is Lisch nodules, defined as pigmented hamartomatous nevi affecting the iris and present in most people with NF1 after age 12 years.

Answer 137

leptomeningeal carcinomatosis Rationale: Contrast enhancement along the leptomeninges is most readily seen overlying the cerebellar folia up to the vermis bilaterally, indicating leptomeningeal carcinomatosis. A basilar meningitis could appear similarly. Intracranial hypotension results in generalized thickening with enhancement of the pachymeninges. Subarachnoid hemorrhage would typically be visible on the noncontrast images.

Answer 138

ROPINIROLE Augmentation in patients with restless leg syndrome occurs when symptoms develop earlier in the day, usually with increased severity, and occasionally with involvement of the upper extremities. This phenomenon has been reported in patients treated with levodopa and dopamine agonists. The pathophysiology of augmentation is unknown.

Answer 139

potassium Rationale: Potassium has the highest intracellular concentration at the resting membrane potential, followed by sodium, chloride, and calcium.

Answer 140

Sjogren syndrome Rationale: This patient has a sensory neuronopathy. The most common causes of sensory neuronopathy includes Sjögren syndrome, anti-Hu paraneoplastic syndrome, and toxic exposures such as platinum-based chemotherapies.

Answer 141

5-hydroxytryptamine receptor 2A Rationale: Serotonin syndrome is life-threatening condition associated with serotonin toxicity in the CNS and is caused by conditions in which multiple medications affect 5-hydroxytryptamine receptors, more commonly 2A. Patients in all age groups can be affected. Selective serotonin reuptake inhibitors (SSRIs) are the most common medications implicated in this condition, but dihydroergotamine affecting various serotonin receptors can also contribute to this condition. Symptoms typically appear within the first 6 to 24 hours after initiation of the drug. Increased deep tendon reflexes and spontaneous or induced clonus are the most common, but one or all of the following symptoms may also be present: hyperthermia, agitation, akathisia, dry mucous membrane, flushed skin, and increased bowel sounds. Management is discontinuation of the offending agent, supportive care, sedation with benzodiazepine, and administration of cyproheptadine, a histamine-1 receptor antagonist with nonspecific 5-HT1A and 5-HT2A antagonistic properties.

Answer 142

3,4-diaminopyridine Rationale: Lambert-Eaton myasthenic syndrome is characterized by impaired release of acetylcholine from the nerve terminal at the neuromuscular junction due to blockade of the voltage-gated calcium channel by autoantibodies directed against the channel. The potassium channel blocker, 3,4-diaminopyridine, enhances the release of acetylcholine by increasing the duration of the action potential, thus improving strength.

Answer 143

alpha-synucleinopathy Rationale: REM sleep behavior disorder can precede the onset of dementia in patients with dementia with Lewy bodies. Presence of this sleep disorder with dementia is most commonly seen with dementia with Lewy body disease, an alpha synucleinopathy.

Answer 144

attention deficit Rationale: This patient’s history and clinical presentation is consistent with an acute confusional state, a state of altered attention that is relatively abrupt in onset and of short duration. Impaired, fluctuating, or reduced attention is the main underlying neuropsychiatric or cognitive impairment causing this condition. Cognitive deficits such as memory and comprehension deficits, motor abnormalities, hallucinations, delusions, mood alterations, sleep-wake cycle disturbances, and other neurovegetative alterations are commonly associated but do not define the condition.

Answer 145

ceruloplasmin Rationale: Gastric bypass may reduce absorption of copper, resulting in myelopathy, which is frequently associated with a neuropathy. This patient has a myelopathy characterized by corticospinal tract and dorsal column dysfunction due to copper deficiency, similar to subacute combined degeneration from vitamin B12 deficiency. In copper deficiency myelopathy, serum copper is proportionately decreased relative to serum ceruloplasmin, whereas serum zinc levels are frequently elevated.

Answer 146

normal EEG for age Rationale: A 3-Hz slow wave activity can be seen as a normal finding during hyperventilation in a child. Simple absence seizures are associated with 3-Hz spike-and-wave discharges during hyperventilation.

Answer 147

aromatic L-amino acid decarboxylase Rationale: Tyrosine and tryptophan are converted to dopamine and serotonin by the enzyme aromatic L-amino acid decarboxylase (AADC). A deficiency of this enzyme results in a severe combined deficiency of dopamine and serotonin, as seen in this patient’s CSF evaluation by the reduced levels of their metabolites (5HIAA, HVA, and MHPG). The most common signs and symptoms are hypotonia, oculogyric crisis, and developmental delay. Additional findings may include sweating, feeding and/or swallowing difficulties, dysarthria, and ptosis.

Answer 148

burst suppression Rationale: Unresponsive patients often show generalized slow waves. The specific coma patterns include alpha and beta frequency coma, spindle coma, and burst suppression patterns. The burst suppression pattern consists of episodic bursts of activity, alternating with intervals of suppression. This pattern is often seen after a severe insult to the brain, such as a hypoxic or anoxic insult, in which case the pattern usually indicates a poor prognosis. This pattern can also be seen with potentially reversible conditions, such as anesthesia, drug intoxication, and hypothermia.

Answer 149

ulnar Rationale: C8 root fibers contribute to the lower trunk/medial cord of the brachial plexus from which the ulnar nerve is derived. Hence, the signs and symptoms can be similar to an ulnar neuropathy.

Answer 150

court-appointed guardian Rationale: Implied consent to medical treatment in the ICU is appropriate in emergency situations, as patients would otherwise be harmed by the delay needed to obtain informed consent from a surrogate. However, the concept of implied consent for emergency treatment does not extend to other procedures or interventions performed on the same patient in the absence of an emergency. For example, tracheostomy and percutaneous endoscopic gastrostomy (PEG), while necessary, are elective not emergency procedures. Therefore, informed consent from a surrogate decision maker is necessary. The hospital attorney does not have legal authority to approve treatment decisions, and as a representative of hospital interests, cannot appropriately advocate for a patient’s interests. Life-sustaining therapies cannot be withdrawn based on a decision of the ICU team alone; thus, a surrogate decision maker is required. A hospital ethics team can represent a patient’s interests and decide whether recommended treatment is ethically permissible. A judge will seriously consider the recommendations of the hospital ethics team when approving a guardian for the patient. The ICU team may make the same recommendations to the hospital ethics team or appointed guardian that would be made to family members in a similar situation, including withdrawal of life-sustaining treatment or insertion of a tracheostomy and PEG.

Answer 151

failure of neuromuscular transmission at a number of endplates Rationale: The decremental response to 2- to 3-Hz repetitive nerve stimulation in patients with myasthenia gravis is due to failure of neuromuscular transmission at a number of endplates, resulting in fewer muscle fiber action potentials contributing to the compound muscle action potential. Decreased presynaptic calcium influx occurs in Lambert-Eaton myasthenic syndrome. Impaired fusion of acetylcholine-containing vesicles to the presynaptic membrane occurs in botulism.

Answer 152

bromocriptine Rationale: Bromocriptine is a dopamine receptor agonist that activates postsynaptic dopamine receptors. It is the treatment of choice for neuroleptic malignant syndrome, a life-threatening reaction to neuroleptic medication to which elderly patients have a relative vulnerability.

Answer 153

orthostatic tremor Rationale: Orthostatic tremor or “shaky leg” syndrome is a disorder that occurs in middle-aged or elderly adults. Characteristic findings include a feeling of unsteadiness in the legs and a fear of falling when standing. Other associated symptoms include difficulty in initiating walking and leg discomfort when standing. Symptoms are caused by a high-frequency tremor in the weight-bearing muscles and are reduced with walking and relieved with sitting. Symptoms of Parkinson disease most commonly originate in the upper extremities. Lumbar stenosis is frequently worse with walking and while in an upright posture. Functional disorder is a diagnosis of exclusion and should be considered only after evaluation and empiric treatment of orthostatic tremor, which is best performed by EMG in the leg muscles while standing, revealing a high-frequency (16- to 18-Hz) tremor.

Answer 154

DPPX Rationale: DPPX (dipeptidyl-peptidase-like protein 6) autoimmune encephalitis is a newly described entity characterized by relatively indolent but progressive cognitive decline (short-term memory, executive function, delirium), psychiatric features (psychosis, depression), central hyperexcitability (hyperekplexia, myoclonus, rigidity), brain stem-cerebellar dysfunction, sleep disturbance (hypersomnia, sleep apnea, periodic limb movements, insomnia), autonomic involvement (gastrointestinal dysmotility, bladder/bowel dysfunction), cardiac dysrhythmias, and temperature dysregulationures. Weight loss and diarrhea frequently precede or accompany the neurologic symptoms. In published series, two patients had B-cell neoplasia (chronic lymphocytic leukemia, gastric lymphoma). A syndrome of progressive encephalomyelitis, rigidity, and myoclonus has also been described in patients with DPPX autoantibody disease. DPPX is a regulatory (inhibitory) protein of the voltage-gated Kv4.2 potassium channel complex, expressed in neuronal dendrites and soma throughout the CNS, autonomic nervous system, and mesenteric neurons. Its ubiquitous presence accounts for the widespread symptoms in this disorder. Early and continued treatment with immunotherapy (corticosteroids, IVIg, plasma exchange, rituximab, and cyclophosphamide) often leads to substantial recovery.

Answer 155

HYPERTENSIVE SMALL VESSEL DISEASE Rationale: The radiograph shows a hypertensive bleed. These hemorrhages are typically located in deep penetrating vessels (particularly the lenticulostriate artery) and result from hypertension-induced pseudoaneurysm formation and subsequent vessel rupture. Amyloid angiopathy typically produces lobar hemorrhage. An arteriovenous malformation is highly unlikely to present at age 75 and is much less likely than a hypertensive bleed. Prostate cancer is highly unlikely to metastasize to the brain, and the patient is not known to be immunocompromised, making a hemorrhagic Aspergillus abscess extremely unlikely.

Answer 156

PET scan Rationale: Functional imaging such as PET imaging provides a measure of how the brain metabolizes glucose functioning. In patients with frontotemporal dementia (FTD), PET scans typically show frontal and anterior temporal regional hypometabolism. In patients with probable Alzheimer disease, however, the PET pattern reveals bilateral posterior temporal and parietal hypometabolism. Each disorder shows a distinct pattern on PET imaging. EEGs are more nonspecific in patients with dementia and typically show only generalized slowing and frontal slowing in both disorders. Routine CSF analysis and cerebral angiography show similar results in patients who likely have Alzheimer disease and in patients with FTD. Routine MRI could show differential frontal atrophy in patients with FTD and hippocampal atrophy in the patients with probable Alzheimer disease, but the findings are subtle.

Answer 157

hereditary spastic paraplegia Rationale: Hereditary spastic paraplegia (HSP) is a clinical syndrome characterized by progressive lower extremity spastic weakness, often accompanied by subtle loss of vibratory sensation in the toes. Of the known genetic causes, mutation in the SPAST gene is the most common and results in autosomal dominant HSP. HSP may be difficult to distinguish clinically from other causes of progressive myelopathy; therefore, structural and metabolic causes of progressive myelopathy must be excluded. Primary lateral sclerosis can closely resemble HSP but is unlikely to be associated with a long course, vibratory sense loss, and the absence of upper extremity or bulbar signs or symptoms. Pain and sensory symptoms are often the most prominent initial features of spinal cord dural AV fistula. Multiple sclerosis is unlikely given the MRI findings.

Answer 158

Chiari type II malformation Rationale: A Chiari type II malformation is a syndrome of hindbrain crowding, which includes hydrocephalus, midbrain beaking, flattening of the pons, an S-shaped medulla, and almost always a lumbosacral meningomyelocele. Chiari type I malformation equates to chronic tonsillar herniation. A Dandy-Walker malformation is characterized by agenesis of the cerebellar vermis and enlargement of the fourth ventricle and posterior fossa. Aqueductal stenosis would not show intrinsic gross abnormalities of the brain stem or cerebellum.

Answer 159

Lennox-Gastaut syndrome Rationale: Lennox-Gastaut syndrome is characterized by multiple seizure types that are often intractable with associated intellectual disabilities. Interictal EEG typically shows a slow spike-and-wave pattern.

Answer 160

primidone Rationale: This patient has essential tremor (ET), characterized by a high-frequency postural and action tremor of the upper extremities. ET commonly interferes with upper extremity activities, such as writing, drinking liquids, and using utensils. Both propranolol and primidone have demonstrated benefit in reducing ET in double-blind, placebo-controlled studies (class A evidence). Propranolol is contraindicated in this patient because of her history of asthma. Topiramate and gabapentin can be used as second-line agents for ET, although evidence for their effectiveness is limited. Amantadine is not effective in ET.

Answer 161

natalizumab Rationale: Natalizumab, an mAb against alpha 4 integrin, has been shown to be effective in suppressing multiple sclerosis activity but was withdrawn from the market because several treated patients developed progressive multifocal leukoencephalopathy (PML). Controlled trials have shown considerable efficacy in preventing relapses. While well-tolerated, three cases of PML occurred in the context of three clinical trials encompassing 3,300 patients using this drug in multiple sclerosis and Crohn disease. As of March 2013, approximately 350 cases of PML have been reported among >100,000 patients treated.

Answer 162

Lambert-Eaton myasthenic syndrome Rationale: Electrophysiologic studies in a patient with Lambert-Eaton myasthenic syndrome will show small compound muscle action potentials. Nerve conduction studies and needle EMG are usually normal. Incremental response of CMAP amplitude of 100% or more is seen after brief exercise. In myasthenia gravis, exercise causes a decremental response with slow stimulation and a small increment with brief exercise (a normal finding). Exercise does not affect CMAP amplitude in peripheral nerve disease or myopathy.

Answer 163

FIBROUS DYSPLASIA The CT scan, displayed in bone windows, shows abnormal fibrous and osseous tissue replacing normal bone in the sphenoid, temporal, and orbital bones. These findings are characteristic of fibrous dysplasia. Multiple myeloma can have a range of imaging abnormalities, including punched-out lytic lesions, diffuse osteopenia, or a solitary plasmacytoma. Bony metastatic lesions would not be this diffuse. A chordoma stems from remnant of embryonic notochord tissue and is positioned in or near the midline along the vertebral column.

Answer 164

PLEXIFORM NEUROFIBROMAS Rationale: The image shows cutaneous neurofibromas in a patient with neurofibromatosis type 1. Angiomyolipomas are seen in patients with tuberous sclerosis, breast cancer in Li-Fraumeni and Cowden syndrome, and renal cell carcinoma in von Hippel-Lindau syndrome. Bilateral vestibular schwannomas are seen in neurofibromatosis type 2.

Answer 165

CONDUCT AN ASSESSMENT FOR UNDERLYING CAUSES Any patient with Alzheimer disease who presents with an acute onset of confusion and behavioral changes first warrants a workup to assess for the underlying cause. Even mild changes in metabolic status, medications, or an infection such as of the urinary tract may precipitate confusion and behavioral changes.

Answer 166

WARFARIN THERAPY SHOULD BE CONTINUED AT THE CURRENT DOSE Rationale: For patients on anticoagulant therapy undergoing a surgical intervention, the risk of bleeding from anticoagulant therapy should be weighed against the risk of thromboembolism. If a patient’s INR is not supratherapeutic, the risk of bleeding from a simple dental extraction is considered low. It is recommended that anticoagulant therapy not be interrupted. Local measures such as pressure and/or a local hemostatic agent should be used for bleeding control.

Answer 167

SEIZURE Rationale: Daily doses of 400 mg or more of tramadol may provoke seizure activity.

Answer 168

MEAN SLEEP LATENCY OF 110 pg/mL, if measured, are also required. A single episode of sleep-onset REM is not diagnostic of narcolepsy and can occur with sleep deprivation alone. Oxygen desaturation is indicative of sleep apnea and does not occur in narcolepsy. Periodic leg movements may disrupt sleep but are not associated with narcolepsy. An increased percentage of slow-wave (N3) sleep may be seen in disorders that disrupt sleep (rebound sleep), but this is not a criterion for a diagnosis of narcolepsy.

Answer 169

T11-L2 Sympathetic outflow arises from the thoracolumbar regions of the spinal cord. For bladder relaxation, sympathetic fibers arise from T11-L2 and synapse in the inferior mesenteric plexus. Postganglionic cells release norepinephrine in the detrusor urinae muscle.

Answer 170

dorsal ulnar cutaneous study Rationale: Ulnar nerve axonal lesions are more difficult to localize than those with focal demyelination. In the latter, focal slowing or conduction block (drop in amplitude with proximal stimulation) localizes the lesion quite precisely. In an ulnar axonal lesion, all sensory and motor responses distal to the injury will be reduced. The dorsal ulnar cutaneous (DUC) sensory study can be useful distinguishing a lesion at the wrist from a lesion at the elbow since it leaves the ulnar nerve prior to the wrist. An abnormality in the dorsal ulnar cutaneous nerve cannot result from a lesion at the wrist and must be proximal to its take off from the ulnar nerve. The ulnar sensory, mixed ulnar cutaneous, motor study to FDI, and motor study to ADM would all be reduced with lesions both at the elbow and at the wrist.

Answer 171

initiate palliative measures Rationale: The factors of greatest importance are the patient has submitted an advance directive stating that she does not wish to have aggressive treatment and that her husband is her health care proxy. Further, two types of written advance directives are generally recognized: the living will and the durable power of attorney. Both have the advantage of providing direction to a surrogate in the event a patient is unable to decide independently. Both are appropriate as legal instruments for the withdrawal of life-sustaining care.

Answer 172

pyrimethamine plus sulfadiazine Rationale: Toxoplasma encephalitis is the most likely diagnosis based on the patient’s positive HIV status, clinical presentation, multiple lesions on imaging, and serology. Fungal or bacterial abscesses and primary CNS lymphoma are statistically much less likely. Given that meningitis and lymphoma are not likely, lumbar puncture is unlikely to be helpful and may be dangerous. Tuberculosis (TB) can present with ring-enhancing lesions in the brain, but in this setting usually presents as a meningitis. PPD skin testing is positive in up to 80% of patients, and chest radiograph is positive in about 50% of adult patients with HIV who are infected with TB. Because of the high likelihood of toxoplasmosis in this patient, empiric antibiotic therapy with pyrimethamine and sulfadiazine is appropriate. If the patient improves after 2 weeks of therapy, the medications should be continued for at least 6 weeks. If he fails to improve after 2 weeks, then brain biopsy should be considered to rule out other disorders.

Answer 173

metachromatic leukodystrophy Rationale: Metachromatic leukodystrophy is characterized by extensive white matter demyelination that spares the subcortical U fibers. Confluent periventricular demyelination is also present. The anterior white matter is more severely affected. Ceroid lipofuscinosis spares white matter relative to gray matter. Leigh disease primarily affects basal ganglia structures. Binswanger disease occurs in adults in association with chronic cerebrovascular disease.

Answer 174

HAMARTOMA IN THE TUBER CINEREUM Rationale: Both the location of the lesion and the history of precocious puberty suggest a hamartoma in the tuber cinereum. In the sagittal image, the intact pituitary gland can be seen in the sella, above the suprasellar cistern.

Answer 175

iron Rationale: Iron deficiency can cause (secondary) restless legs syndrome. Evidence also suggests an abnormality in brain iron that somehow translates to a hypodopaminergic state in idiopathic restless legs syndrome. Ferritin goals for this syndrome are high (>75 to 100 ng/mL).

Answer 176

alpha-1 receptor antagonism Rationale: According to the American Association of Sleep Medicine guidelines for the treatment of nightmare disorders in adults, prazosin, an alpha-1 adrenergic receptor antagonist, is considered the first-line choice for the treatment of nightmares in patients with PTSD (level A evidence). Clonidine, an alpha-2 adrenergic receptor antagonist, may be considered, but its use lacks this level of evidence. Dopamine antagonists, benzodiazepines, and beta-blockers all have some evidence for efficacy for this disorder but also lack strong evidence when compared with prazosin.

Answer 177

botulinum toxin Rationale: Level A evidence (established as effective for the given condition in at least two class 1 studies) supports the use of botulinum toxin type A for the treatment of localized/segmental spasticity in children and adolescents. There is insufficient published data to support or refute the use of phenol, tizanidine, oral baclofen, continuous intrathecal baclofen, or botulinum toxin type B.

Answer 178

thiamine deficiency Rationale: This patient has the classic symptoms of Wernicke encephalopathy characterized by confusion, extraocular motility deficits, nystagmus, and ataxia. Because the patient appears to be homeless, with no known family or friends, it is likely he is malnourished, resulting in nutritional deficiencies with or without alcoholism. The administration of glucose without concurrent administration of thiamine is a precipitant of the acute syndrome

Answer 179

IV methylprednisolone Rationale: This patient presents with an acute transverse myelitis of currently unknown etiology. Treatment with high doses of IV corticosteroids is indicated and can be initiated before a full diagnostic workup is complete so long as there is a low suspicion of infection. Plasma exchange, IVIg, and cyclophosphamide may be appropriate second-line treatment, depending on the patient’s response to steroids and the underlying etiology. Ocrelizumab beta-interferon is not appropriate for the acute management of this patient even if she is diagnosed with MS.

Answer 180

anterior choroidal Rationale: The anterior choroidal artery arises from the internal carotid, near the posterior communicating artery. It enters the inferior horn of the lateral ventricle through the choroidal fissure and ends in the choroid plexus. In addition to the choroid plexus, it supplies portions of the hippocampus and posterior limb of the internal capsule.

Answer 181

falling toward the side of the affected ear Rationale: Patients with acute unilateral peripheral vestibular loss veer and fall toward the side of the lesion. Falling toward the side of the unaffected ear, normal results on head impulse test, skew eye deviation, and vertical nystagmus are typical of central vestibular disorders.

Answer 182

anti-muscle-specific tyrosine kinase antibodies Rationale: Approximately 40% of patients with myasthenia gravis (MG) who are antibody-negative for the anti-acetylcholine receptor-binding antibody are positive for anti-muscle–specific tyrosine kinase (MuSK) antibodies. Anti-MuSK antibody-positive MG can clinically resemble anti-acetylcholine antibody-positive MG, but patients with anti-MuSk MG may have an atypical presentation, such as prominent facial, bulbar, and neck involvement with relative sparing of ocular muscles. Anti-MuSK antibody-positive MG is also less likely to present with thymic hyperplasia or neoplasia and does not respond to thymectomy. Anti-acetylcholine receptor-blocking antibodies are found almost exclusively in the setting of positive anti-acetylcholine receptor-binding antibodies and are of little value in this setting.

Answer 183

temporalis Rationale: The trigeminal nerve supplies the muscles of mastication—the temporalis, masseter, medial and lateral pterygoids, mylohyoid, anterior belly of the digastric, tensor veli palatini, and tensor tympani muscles. The facial nerve supplies the frontalis, corrugator, orbicularis oculi, nasalis, buccinator, orbicularis oris, mentalis, and platysmas.

Answer 184

valproic acid Rationale: In a meta-analysis of 11 studies involving 556 women with epilepsy treated with valproic acid (VPA), 593 women treated with other antiepileptic drugs (AEDs), 120 women with untreated epilepsy, and 329 healthy controls, the calculated incidence of polycystic ovary syndrome in women treated with VPA was higher than that in women treated without VPA (10 studies included, P<0.05, OR 3.04, 95% CI 2.09-4.43)

Answer 185

carbidopa/levodopa trial Rationale: A levodopa challenge should be considered when the diagnosis of Parkinson disease is in doubt. The other tests listed are not clinically useful in distinguishing Parkinson disease from other parkinsonian syndromes based on insufficient evidence from clinical studies.

Answer 186

offer advice based on the information provided and allow the colleague to direct care Rationale: Direct patient care in a state one does not hold a license may be considered illegal and would not be a billable service. The exchange of medical information and advice, however, directly to a licensed physician in that state is allowed assuming they then use your advice and continue to direct care themselves. Each state licenses its physicians and the risk of practicing into other states from a legal standpoint varies by state. Interstate compacts are being evaluated which will only allow licensing to be expedited in other states.

Answer 187

right anterior temporal lobe Rationale: Capgras delusions and psychosis are typically thought to originate in the temporal lobe. Lesions in the occipitoparietal, posterior cingulate, and the superior parietal lobule are unlikely to cause these delusions. Frontal pathology occasionally makes it difficult to resolve conflicting information, which may result in delusional ideas. A tumor in the left dorsolateral frontal lobe causing a seizure would typically cause speech arrest due to involvement of the Broca area.

Answer 188

positive serum NMO-IgG (aquaporin-4) antibody Rationale: The combined eye and spinal cord involvement in this young woman is suggestive of neuromyelitis optica (NMO). A positive NMO IgG antibody (aquaporin-4) is 73% sensitive and 91% specific for NMO. The presence of elevated CSF myelin basic protein, elevated CSF IgG index, abnormal visual evoked potentials and urinary retention are all consistent with demyelinating disease but are not specific and can be seen in a number of demyelinating and inflammatory CNS disorders.

Answer 189

galactosemia Rationale: Galactosemia is caused by the absence of galactose-1-phosphate uridylyltranserase (GALT) enzyme and results in elevated erythrocyte galactose-1-phosphate levels. In most instances, the diagnosis is made during the newborn screen prior to onset of symptoms, and treatment is initiated by switching the affected neonate to a lactose-free formula. If left untreated, neonates may present with abnormal liver function, failure to thrive, hyperbilirubinemia, and hypoglycemia. Neurologic complications include neonatal encephalopathy and seizures. Urine test for reducing substances is positive, secondary to presence of sugars other than glucose in the urine. Although methylmalonic acidemia and maple syrup urine disease may present with encephalopathy in the newborn period, the presence of reducing substances in the urine would be unusual. Maple syrup urine disease may present with hypoglycemia and opisthotonus. Methylmalonic acidemia can present with seizures. Phenylketonuria, if untreated, can present with seizures in early life and later difficulties in development. Glutaric aciduria type I is associated with developmental delay and can present with dystonia. All the disorders listed require dietary changes to prevent accumulation of toxic substances.

Answer 190

HHV-6 encephalitis Rationale: HHV-6 is the etiologic agent of roseola, a virus that is nearly universally acquired during childhood. It establishes lifelong infection, including within the CNS. HHV-6 encephalitis is also a well-known complication of bone marrow transplant. HHV-6 reactivation causes a characteristic limbic encephalitis syndrome, characterized by memory loss, insomnia, SIADH, and temporal lobe epilepsy.

Answer 191

serratus anterior Rationale: Damage to the long thoracic nerve can occur with surgical procedures of the neck, resulting in scapular winging due to weakness of the serratus anterior muscle.

Answer 192

temporal sharp waves Rationale: Clinical manifestations of complex partial seizures arising from the temporal lobe include a sensation of an abnormal smell, masticatory movements, automatisms, and confusion. The EEG would show focal sharp waves arising from the temporal lobe.

Answer 193

anterior inferior cerebellar Rationale: The internal acoustic or labyrinthine artery usually arises from the anterior inferior cerebellar artery (AICA) but can also arise directly from the basilar artery. It supplies the inner ear. Vertebrobasilar or AICA ischemia can cause unilateral deafness.

Answer 194

cerebellar metastasis Rationale: Signs and symptoms of elevated intracranial pressure in conjunction with focal neurologic deficits in a patient with known malignancy should raise suspicion of intracranial metastases. Brain metastases occur in as many as 20% of patients with cancer, whereas paraneoplastic disease occurs in <1% of patients. The other disorders listed also would be less likely in this setting.

Answer 195

globus pallidum, pars interna Rationale: Axonal fibers arising from the subthalamic nucleus terminate on the globus pallidum, internal segment, and the substantia nigra, pars reticulata. Neurons of the subthalamus contain glutamate and exert excitatory input into the globus pallidum, pars internal. This connection is one component of the indirect pathway that decreases thalamocortical excitation. Lesions of the subthalamic nucleus result in hemibalissmus secondary to decreased function of the indirect pathway. The subthalamic nucleus is also a deep brain stimulation target in Parkinson disease.

Answer 196

central cores Rationale: This patient’s presentation is typical of a congenital myopathy. Of the choices, central cores are the most typically seen on histology associated with this most benign of congenital myopathies: central core disease. Inflammation is not typical of any congenital myopathy.

Answer 197

MIRTAZAPINE Rationale: Selective serotonin reuptake inhibitors (SSRIs) are very effective in treating the depression associated with dementia; however, most SSRIs (except paroxetine) can exacerbate symptoms of insomnia. This patient with Alzheimer disease presents with both depression and insomnia. Mirtazapine is an effective antidepressant and sleep agent as well as appetite stimulant. Although trazodone and nortriptyline are very good for addressing sleep disorders, side effects from doses high enough to treat depression generally preclude use in patients with dementia. The selective norepinephrine reuptake inhibitor (SNRI) venlafaxine can also worsen insomnia.

Answer 198

aspirin and clopidogrel Rationale: This patient presented with a transient ischemic attack with an ABCD score of 6 (1 point for blood pressure >140/90 mm Hg, 2 for unilateral weakness, 2 for symptom duration >1 hour, and 1 for a history of diabetes mellitus); this score places him at high risk (17.8%) for ischemic stroke within 90 days. In a study conducted at 114 centers in China that analyzed the post-event course of patients who had a minor stroke (NIH score <3) or a high-risk transient ischemic attack (ABCD2 score greater than or equal to 4), the combination of aspirin and clopidogrel for 21 days reduced the risk of ischemic stroke from 11.7% to 8.2% compared to aspirin alone over the first 3 months after the event.

Answer 199

notch Rationale: Cerebral autosomal dominant arteriopathy with cerebral infarcts and leukoencephalopathy (CADASIL) is due to a mutation of the NOTCH3 gene, which encodes for a protein that is critically involved in neural determination and neuritogenesis. Notch is a transmembrane receptor that is internalized after cleavage of its cytoplasmic domain by presenilin; it then is translocated to the nucleus where it controls expression of a variety of transcription factors. Studies in zebrafish, mice, and humans report that notch works in conjunction with other angiogenic pathways to pattern and stabilize the vasculature.

Answer 200

right-sided Horner syndrome Rationale: This patient has a lateral medullary syndrome, which is usually caused by occlusion of the posterior inferior cerebellar artery or a vertebral dissection. It is characterized by ipsilateral facial anesthesia, contralateral body anesthesia, ipsilateral Horner syndrome, vertigo, dysarthria, ipsilateral cerebellar dysfunction, and hiccups. Right-sided tongue weakness would be associated with a medial medullary syndrome. Sixth nerve involvement and gaze palsies are associated with pontine lesions. An abnormal head impulse test is more consistent with a peripheral vestibular nerve lesion.

Answer 201

medical team Rationale: The standard of best interest states that the medical team is obligated to act on behalf of the child, which in this case is removal of life support. However, when conflict exists and cannot be reasonably resolved over the course of several days to weeks, it may be necessary to involve the hospital ethics team. The ethics team can be helpful in determining how to best resolve issues, although a dialogue between the medical team and family is considered ideal to navigate the many difficult decisions that removing life support from a child requires. Occasionally, the medical team has an ethical obligation to act in the best interest of a child when the family may be too distraught to think through their grief. Ideally, the team is patient, calm, and comforting to the family. However, they must be repeatedly clear in their understanding about the lack of meaningful recovery and the need to act in the child’s best interest rather than in the family’s interest, which may be based on unrealistic expectations.

Answer 202

mild cognitive impairment Rationale: This patient’s memory impairment, when paired with normal activities of daily living, is most consistent with amnestic mild cognitive impairment. This disorder may represent the prodromal phase of Alzheimer disease.

Answer 203

radial Rationale: The terminal branches of the posterior cord of the brachial plexus are the radial and axillary nerves. The long thoracic nerve arises from C5-7, the median nerve is formed from the lateral and medial cord, the musculocutaneous nerve is a terminal branch of the lateral cord, and the ulnar nerve is a terminal branch of the medial cord.

Answer 204

delayed sleep phase syndrome Rationale: A late sleep-onset time and late rise time on weekends in a teenager/young adult suggests delayed sleep phase syndrome. Wrist actigraphy is particularly helpful in diagnosing disorders of circadian rhythm.

Answer 205

hamartin Rationale: Tuberous sclerosis complex is among the causes of infantile spasms. The principal criteria for the diagnosis of this multiple-system genetic disease include hypomelanotic macules, cortical tubers, and subependymal nodules. This genetic disorder has been linked to mutations in one of either two genes, TSC1 and TSC2, which encode for the proteins hamartin and tuberin. Altered expression of frataxin is associated with Friedrich ataxia, neurofibromin with neurofibromatosis type 1, merlin with neurofibromatosis type 2, and fukutin with Fukuyama congenital muscular dystrophy.

Answer 206

failure to point to objects to indicate she wants something Rationale: Lack of indicative pointing is typical of autistic children, whereas even preverbal children with other causes of delay generally point at objects and “share attention”. Late walking is not typical of autism but indicates overall delay in development. Sleep difficulties are common in autistic children but are also common in children with delays, as well as in toddlers with normal development. Stranger anxiety may persist into toddlerhood in otherwise normally developing children.

Answer 207

frontal subcortical executive circuit Rationale: Normal confrontation naming, when verbal fluency is impaired on animal naming, supports an executive defect. Such a finding could be the result of a lesion anywhere along the dorsolateral frontal subcortical circuit pathway.

Answer 208

amantadine Rationale: Only amantadine has been shown to clearly reduce levodopa-induced dyskinesias while not worsening and at times improving the primary symptoms of Parkinson disease. Pramipexole, ropinirole, and apomorphine are direct-acting dopamine agonists that help with Parkinson disease symptoms but when simply added to levodopa increase dyskinesias. Selegiline is a selective MAOI that can increase ON time in Parkinson disease but has not been shown to help with dyskinesias. Haloperidol is a dopamine receptor blocker that can reduce dyskinesias but will worsen the symptoms of Parkinson disease.

Answer 209

campylobacter jejuni infection Rationale: The clinical picture is typical of acute motor axonal polyneuropathy (AMAN), an axonal form of Guillain-Barré syndrome, which is closely associated with preceding bacterial diarrhea caused by C jejuni infection. Lead intoxication and elevated plasma very long chain fatty acids do not cause acute weakness. Cytomegalovirus infection is more closely associated with the AIDP variant of Guillain-Barré syndrome. Streptococcal pharyngitis does not commonly precede Guillain-Barré syndrome in children.

Answer 210

ciliary ganglion Rationale: This patient has a light-near dissociation, which is not seen in disorders of the oculomotor or optic nerve. The absence of other neurologic findings in this case would make a midbrain tectal or superior colliculus lesion unlikely. Slow nonuniform constriction of the pupil is consistent with an Adie’s pupil that is due to an abnormality of the ciliary ganglion or short ciliary nerves.

Answer 211

hold warfarin for 2 weeks and then restart warfarin Rationale: Anticoagulant therapy is often prescribed in patients at high risk of thromboembolism from atrial fibrillation and a mechanical prosthetic heart valve. However, hemorrhagic complications may still occur despite close monitoring. Anticoagulant therapy should be resumed if the benefit of preventing recurrent thromboembolism outweighs the risk of recurrent hemorrhage. Although the risk of ongoing bleeding and hematoma expansion is high in the first couple of days, it steadily declines thereafter. Resumption of anticoagulant therapy may be considered 7 to 14 days after the onset of intracerebral hemorrhage, particularly for high-risk patients. Dabigatran is associated with a higher risk of thromboembolism and bleeding in patients with mechanical heart valves, and thus is not recommended. Left atrial appendage closure may help reduce the risk of intra-atrial clot formation associated with atrial fibrillation but probably is unlikely to prevent perivalvular clots with a mechanical heart valve.

Answer 212

indomethacin Rationale: Paroxysmal hemicrania (PH) is one of the autonomic-based headaches comprising the trigeminal autonomic cephalalgias. PH is side-locked, repeats multiple times daily (on average about 11), lasts <30 minutes, and is associated with autonomic phenomena and pain in a V1 distribution. In contrast to cluster headache and SUNCT (which lasts <10 minutes and recurs up to 100 times daily), PH is more common in women and typically responsive to indomethacin. High-flow oxygen is effective for cluster headaches, which predominantly affect men, have a longer duration than PH and SUNCT, often occur at night, and do not respond to indomethacin. Triptans are effective to abort episodes of cluster headache but not usually PH or SUNCT. Oxycodone may provide pain relief but is not an effective headache abortive agent.

Answer 213

propranolol Rationale: Fingolimod is a sphingosine-1-phosphate receptor (S1PR) modulator approved for the treatment of relapsing-remitting multiple sclerosis. Its primary therapeutic effect is down-regulation of S1PRs expressed on lymphocytes in secondary lymphoid tissue. This reduces egress of autoreactive lymphocytes from lymph nodes into the peripheral circulation, thereby reducing their entry into the CNS. Oral fingolimod demonstrated superior efficacy to both placebo and weekly intramuscular interferon beta-1a in reducing relapses and MRI activity in controlled studies in patients with relapsing-remitting MS. Adverse effects of oral fingolimod include first-dose bradycardia, atrioventricular block, and QT interval prolongation due to activation of S1PRs on atrial myocytes. Bradycardia, with an average reduction of heart rate of 8 beats/min, typically occurs within 6 hours of the first dose, although it can occur up to 24 hours later. The FDA has mandated that patients be observed in a clinical setting for their initial dose of fingolimod. Because of its first-dose cardiac effects, fingolimod is not recommended for patients receiving heart rate-lowering agents (beta-blockers such as propranolol, calcium channel blockers) or those with significant QTc prolongation. Patients at risk for QT prolongation or those on concomitant QT-prolonging agents should be monitored for 24 hours with continuous ECG following initiation of fingolimod.

Answer 214

initiate cardiac telemetry Rationale: Rhabdomyolysis can be a neuromuscular emergency, with hyperkalemia resulting in cardiac dysrhythmias such as ventricular tachycardia. Therefore, cardiac monitoring should be initiated, followed by checking potassium levels. Initiating IV fluids at twice maintenance levels is generally recommended, with normal saline solution used in adults and older children. Dialysis is not a first-line treatment for rhabdomyolysis. This patient had a rapid onset of hyperCKemia with onset of fever. Viral myositis is far more common, but genetic disorders such as LPIN1 can cause a metabolic myopathy and recurrent rhabdomyolysis in which later testing may be indicated.

Answer 215

generalized polyspike and wave Rationale: The description of this patient’s episodes is consistent with juvenile myoclonic epilepsy, which has an interictal pattern of generalized polyspike and wave discharges.

Answer 216

pantothenate kinase (PANK2) Rationale: This patient’s findings are most consistent with pantothenate kinase-associated neurologic disorder, associated with mutations in PANK2. This disorder, formerly referred to as Hallervorden-Spatz syndrome, is now called PANK2-associated disorder due to Julius Hallervorden’s association with Nazi experimentation. Frataxin (FRDA) is associated with Friedreich ataxia, superoxide dismutase (SOD) with familial ALS, pyruvate dehydrogenase (PDH) with a syndrome of lactic acidosis, seizures and neurologic deterioration, and ataxia telangiectasia, mutated (ATM) with ataxia telangiectasia

Answer 217

midbrain Rationale: Midbrain lesions cause midposition pupils since they interrupt both the descending sympathetic pathways as well as the exiting parasympathetic fibers from the Edinger-Westphal nucleus. Reactivity to light is controlled by the pretectal nucleus. Dysfunction of the respiratory centers in the midbrain can cause central neurogenic hyperventilation.

Answer 218

tuberculoid leprosy Rationale: The clinical and pathologic features described are characteristic of tuberculoid leprosy, typically associated with a relatively intact immune system, thus a prominent inflammatory reaction and very few demonstrable organisms. Single or few anesthetic macules or plaques with well-defined borders are typical. Lepromatous leprosy occurs in an immunocompromised host, with skin lesions consisting of multiple nonanesthetic symmetrically distributed macules or papules, progressing to diffuse infiltration of skin. Cryoglobulinemia would produce vasculitic changes and perineuritis in peripheral nerves. Chronic immune demyelinating polyneuropathy and hereditary neuropathy with liability to pressure palsies are characterized by onion bulbs and tomaculae, respectively, on nerve biopsy. Sarcoidosis, though also showing granulomatous inflammation, would not contain demonstrable microorganisms, bacilli, or otherwise.

Answer 219

serum Lyme ELISA with reflex Western blot Rationale: When insufficiently treated, acute Lyme disease can result in chronic Lyme neuroborreliosis. Although acute Lyme disease can cause a seventh nerve palsy, other etiologies can as well. A tick bite alone does not objectively confirm a diagnosis of Lyme neuroborreliosis. Acute brain MRI eliminates a structural CNS lesion but not Lyme neuroborrelisois. The next step is to objectively confirm whether a patient has active Lyme disease by first checking serum Lyme ELISA with reflex Western blot. To have Lyme neuroborreliosis, a patient must have had systemic Lyme disease, which would be supported by an elevated serum ELISA and positive IgG Western blot. If the presence of these antibodies is confirmed, treatment with antibiotics using CSF/serum Lyme index as a guide should be initiated. If results are negative, treatment for Lyme neuroborreliosis is without foundation and another etiology needs to be investigated. SPECT brain imaging has not been shown to be either sensitive or specific for Lyme neuroborreliosis.

Answer 220

provide medical information without patient authorization Rationale: HIPAA regulations define when protected health information (PHI) can be shared with health care providers. Information can be shared without patient authorization when being communicated to another health care provider for the purposes of medical treatment. An authorization is a detailed document that gives covered entities permission to use PHI for specified purposes, generally treatment, payment, or health care operations, or to disclose PHI to a third party as specified by the individual. An authorization must specify a number of elements, including a description of the PHI to be used and disclosed, the person authorized to make the use or disclosure, the person to whom the covered entity may make the disclosure, an expiration date, and, in some cases, the purpose for which the information may be used or disclosed. With limited exceptions, covered entities may not condition treatment or coverage on the individual providing an authorization.

Answer 221

dabigatran Rationale: Numerous anticoagulant medications have been developed and approved for secondary stroke prevention in patients with nonvalvular atrial fibrillation. These medications have different mechanisms of action. Dabigatran directly inhibits factor IIa (thrombin). Apixiban and rivaroxaban directly inhibit factor Xa. Edoxaban is a once-daily factor Xa inhibitor. Warfarin acts by inhibiting the synthesis of vitamin K–dependent clotting factors, which include factors II, VII, IX, and X, and the anticoagulant proteins C and S.

Answer 222

1F receptor agonist Rationale: A unique feature of lasmiditan is that it works on 1F receptors that lack vasoconstrictor activity; it was deemed effective for treating migraine in a preliminary randomized placebo-controlled trial.

Answer 223

trisomy 21 (Down syndrome) Rationale: Fifteen percent of children with trisomy 21 (Down syndrome) have atlantoaxial instability. Other heritable conditions with similar predisposition are Klippel-Feil, Morquio, and Larsen syndromes, achondroplasia, and previous cervical spinal surgery. The other conditions listed are not associated with an increased incidence of cervical spine anomalies and would not warrant screening radiographs.

Answer 224

dopamine transporter SPECT scan Rationale: The dopamine transporter scan (DaT scan) uses a radiopharmaceutical agent paired with SPECT (single photon emission computed tomography) imaging to measure availability of striatal dopamine. It cannot distinguish among the various conditions that cause depleted dopamine in the striatum, but an abnormal study indicates a disorder of dopaminergic neurons. Essential tremor alone should not cause an abnormal DaT scan. In the absence of a familial history of Parkinson disease, genetic testing is unlikely to be helpful. None of the other studies listed can help distinguish Parkinson disease from essential tremor.

Answer 225

Parkinson disease dementia Rationale: Rivastigmine is approved to treat mild to moderate Parkinson and Alzheimer disease. Donepezil is approved for treatment of mild to severe Alzheimer disease. Galantamine is approved for mild to moderate Alzheimer disease.

Answer 226

opioids Rationale: Opioid toxicity is the only medication listed that is associated with constricted pupils. PCP, cocaine, cannabis, and amphetamine toxicity presents with dilated pupils.

Answer 227

zonisamide Rationale: Of the medications listed, only zonisamide does not alter warfarin metabolism. Carbamazepine, topiramate, and phenytoin induce warfarin metabolism, whereas valproic acid inhibits warfarin metabolism.

Answer 228

loss of cerebral autoregulation Rationale: This patient most likely has a milder form of cerebral hyperperfusion syndrome. The full-blown syndrome may be seen after revascularization of an artery (either with surgery or stenting) and consists of headache, neurologic deficit, and seizures. This patient had a number of the key risk factors for developing this syndrome: poorly controlled blood pressures perioperatively, high-grade stenosis, and recent history of endarterectomy on the contralateral side. The syndrome is believed to result from loss of cerebral autoregulation, resulting in hyperdynamic blood flow through the revascularized blood vessel.

Answer 229

air embolus Rationale: This presentation is an example of a catastrophic air embolus resulting from cardiopulmonary bypass. Brain death has occurred as a result of global cerebral hypoperfusion. This syndrome occasionally results from chest trauma or after a neurosurgical procedure in which a patient undergoes surgery with the head above the heart. The CT scan shows air diffusely within the cerebral vessels. Despite the coagulopathy associated with all major surgeries, the risk of subarachnoid bleeding and cerebral venous sinus thrombosis is not increased with this type of surgery or with the use of cardiopulmonary bypass.

Answer 230

VITAMIN B12 Rationale: Breastfed infants of mothers who follow an exclusively vegan diet are at risk for vitamin B12 deficiency and megaloblastic anemia. These infants can also present with a number of neurologic abnormalities during infancy, including failure to thrive, developmental regression, microcephaly, hypotonia, tremors, and seizures.

Answer 231

PERIODIC LIMB MOVEMENTS IN SLEEP Rationale: This patient’s clinical presentation is consistent with restless legs syndrome, a clinical entity distinct from periodic limb movements of sleep. The latter is present on polysomnography in up to 90% of patients with restless legs syndrome. Sleep latency is also typically prolonged on polysomnogram in these patients.

Answer 232

TARDIVE DYSKINESIA Rationale: Sydenham chorea (chorea minor or St. Vitus dance) is a neurologic disorder consisting of abrupt, purposeless, nonrhythmic involuntary movements, muscular weakness, and emotional disturbances. Involuntary movements disappear during sleep but may occur at rest and interfere with voluntary activity. Grimacing and inappropriate smiling are common. Handwriting usually becomes clumsy and provides a convenient way of following the patient’s course. Speech is often slurred. The specific antibody tests used to diagnose streptococcal infections most often are those directed against extracellular products, including ASO, anti-DNAse B, antihyaluronidase (antidiphosphopyridine nucleotide [anti-DPNase]), and antistreptokinase. The diagnosis can be made, however, when “pure” chorea is the sole manifestation due to the rarity with which this syndrome occurs by any other cause. These preliminary studies suggest that streptococci and other microbes may induce antibodies that functionally disrupt the basal ganglia pathways; this leads not only to classic chorea but also to behavioral disorders in children without evidence of classic chorea. Resolution of movements during sleep would argue against a seizure disorder. Stereotypies do not affect speech. Huntington disease would not be associated with normal exam between movements and typically presents as parkinsonism in childhood. Tardive dyskinesia would more commonly involve orobuccal movements.

Answer 233

BENIGN PAROXYSMAL VERTIGO Rationale: This is a classic presentation of benign paroxysmal vertigo in a child, a syndrome that occurs in children in the first 5 years of life and is a frequent precursor of migraine. Investigations (MRI, EEG) are normal. The episodes usually resolve by the end of the first decade.

Answer 234

FORMAL DRIVING SKILLS EVALUATION Rationale: Determining the ability to drive following stroke is a difficult task. Numerous studies suggest the most reliable determinant of driving ability is the roadside test. The simulated driving test and the roadside test are more predictive than neuropsychological measures and neurologist opinion.

Answer 235

VARICELLA ZOSTER VIRUS Rationale: Varicella zoster virus can cause a necrotizing myelopathy within 1 to 2 weeks after presentation with a dermatomal rash. The myelopathy typically occurs in the thoracic cord and is the result of reactivation of the virus in the dorsal root ganglia, but with centripetal migration into the cord rather than along the nerve. Diagnosis is confirmed by identification of the virus by PCR in the CSF. Herpes simplex virus 1 is associated with herpes encephalitis and does not cause myelopathy. Human herpesvirus 6 (HHV6) causes a posttransplant acute limbic encephalitis. Cytomegalovirus can cause a transverse myelitis, typically in immunocompromised patients. Herpes simplex virus 2 can lead to an ascending myelitis or sacral radiculitis in patients with genital herpes, but this is a rare development.

Answer 236

OCCIPITAL LOBE FROM THE TEMPORAL LOBE Rationale: This patient exhibits classic visual object agnosia. Disconnection of the visual cortex from the language area in the temporal lobe is responsible. Since holding the object revealed its identity, the parietal posterior central gyrus to the temporal language areas is intact. Temporal or parietal disconnection to frontal lobes or the Broca area would not cause a visual object agnosia, as the visual input could arrive in the Wernicke area for naming and gnosis.

Answer 237

UPPER TRUNK Rationale: Lesions of the upper trunk of the brachial plexus will cause weakness in the proximal upper extremity with abnormal sensory nerve action potentials on nerve conduction studies in the radial and median nerves. The deltoid muscle is innervated by the axillary nerve which arises from the upper trunk/posterior cord. The biceps is innervated by the musculocutaneous nerve which arises from the upper trunk/lateral cord.

Answer 238

INCREASED INTRAVENTRICULAR PRESSURE Rationale: Frontal predominant generalized rhythmic delta activity (GRDA), previously known as frontal intermittent rhythmic delta activity (FIRDA), can be seen with a variety of lesions, including posterior fossa lesions, encephalopathy, intracranial lesions, and increased intraventricular pressure. REM sleep is associated with a low-voltage desynchronized EEG, whereas NREM stage 3 sleep is associated with >20% delta activity in a 30-second epoch. There is no frontal predominance of this slow activity.

Answer 239

POSTERIOR COMMUNICATING ARTERY ANEURYSM Rationale: This patient’s symptoms of a third cranial nerve palsy involving the pupil are most consistent with, and concerning for, aneurysmal compression of cranial nerve III by a posterior communicating artery or carotid artery aneurysm. Myasthenia gravis should not affect the pupil or cause retro-orbital pain. Thyroid ophthalmopathy should not affect the pupil and is most likely bilateral. Extraocular weakness is not consistent with a hypertensive microvasculopathy such as retinal artery occlusion.

Answer 240

PONS Rationale: Wave I is clearly generated by the distal vestibulocochlear (VIII) cranial nerve. Wave II has been classically attributed to the cochlear nuclei or proximal vestibulocochlear nerve. The generator of wave III is poorly localized, but classically has been attributed to the superior olive, which resides in the pons. The generator of wave V has been attributed to the inferior colliculus in the midbrain. Wave VI has been attributed to the medial geniculate nucleus of the thalamus. Wave VII has been attributed to the temporal lobe (Heschl’s gyrus). The absence of all waves except wave I bilaterally best localizes to a pontine lesion involving the bilateral cochlear nuclei.

Answer 241

RIGHT TROCHLEAR (FOURTH) Rationale: Closed head injury is a common cause of fourth cranial nerve palsy. Fourth nerve palsy causes ipsilateral hyperdeviation that increases in contralateral gaze and with ipsilateral head tilt. Patients typically tilt their head to the side opposite that of the affected fourth nerve as a compensatory mechanism to improve the diplopia.

Answer 242

DIPHENHYDRAMINE Rationale: The use of IM diphenhydramine or IM anticholinergic medications typically relieves symptoms of neuroleptic-induced acute dystonia. Bromocriptine is used in neuroleptic malignant syndrome. IM chlorpromazine and olanzapine are used in the management of acute psychosis and would actually worsen this issue as they are dopamine blockers like haloperidol. Levodopa is not given IM and is not used for the treatment of acute secondary dystonia. Because this is not an inflammatory medicated side effect, prednisone would not be beneficial.

Answer 243

HEXOSAMINIDASE A Rationale: Global developmental delay and a macular cherry-red spot are characteristic of Tay-Sachs disease, which is caused by a deficiency of hexoaminidase A. Sphingomyelinase is deficient in Niemann-Pick disease, glucocerebrosidase is deficient in Gaucher disease, arylsulfatase is deficient in metachromatic leukodystrophy, and alpha-galactosidase is deficient in Fabry disease.

Answer 244

OLANZAPINE Rationale: Although all atypical and many typical antipsychotic medications are known to cause weight gain and exacerbate diabetes mellitus, numerous studies in both the dementia and schizophrenia literature report that olanzapine causes the most weight gain.

Answer 245

BLOOD TRANSFUSION Rationale: The Stroke Prevention Trial in Sickle Cell Anemia (STOP I) enrolled children with sickle cell anemia but no history of stroke and mean blood flow velocities in the internal carotid or middle cerebral artery >200 cm/sec. Subjects were randomized to standard care or transfusions to reduce hemoglobin S concentration to <30% of total hemoglobin. The study was stopped early because the risk of stroke was 92% lower in the transfusion group. Hydroxyurea may have a role after 1 year of transfusions. The benefit of aspirin for this patient is unknown. The availability of hematopoietic stem cell transplants is limited. Revascularization procedures are a consideration for patients with moyamoya disease.

Answer 246

SIPONIMOD Rationale: Siponimod is a functional antagonist of sphingosine 1-phosphate receptor subtypes 1 and 5. Fingolimod has a similar mechanism of action at the sphingosine 1-phosphate receptor but nonselectively binds to all sphingosine 1-phosphate receptor subtypes, except for subtype 2. Antagonism of the sphingosine 1-phosphate receptor prevents lymphocytes from leaving the lymph nodes. The increased selectivity of siponimod results in reduced symptomatic bradycardia compared with fingolimod. In a phase 2 study, siponimod 2 mg was shown to reduce MS active lesions by 72% compared with placebo at 3 months. In a phase 3 study (EXPAND), siponimod was shown to reduce worsening disability in secondary progressive MS by 21% at 3 months. However, siponimod requires testing of the CYP2C9 genotype prior its initiation. Patients with two alleles of CYP2C9 1* or two alleles of CYP2C9 2* or a mixture of one CYP2C9 1* allele and one CYP2C9 2* allele can metabolize siponimod normally and do not require a dose adjustment. Patients with one of those alleles and one CYP2C9 3* allele require half-dose siponimod. Patients with two CYP2C9 3* alleles should not be treated with siponimod, as they will not metabolize the medication and subsequently develop substantially elevated levels.

Answer 247

CEREBELLAR HEMANGIOBLASTOMA Rationale: The lesions shown have a typical intensely enhancing nodule with a nonenhancing cyst-like fluid collection surrounding it, suggesting cerebellar hemangioblastoma. Resolving hematoma would not have the intense focus of enhancement and would have differing signal intensity. Cerebellar abscess would have prominent vasogenic edema, which is absent. Anaplastic astrocytoma would have a more infiltrative appearance than this lesion.

Answer 248

RYANODINE RECEPTOR Rationale: Malignant hyperthermia is a potential complication seen in patients with central core myopathy associated with the administration of certain anesthetic drugs such as succinylcholine and halothane. Screening for susceptibility to malignant hyperthermia is now done by testing for mutations in the ryanodine receptor RYR1 gene.

Answer 249

FRONTOTEMPORAL LOBAR DEGENERATION WITH MOTOR NEURON DISEASE (FTLD-MND) Rationale: The image shows small ubiquitinated inclusions in the cytoplasm of neurons of the dentate gyrus of the mesial temporal lobe. Because no tau immunoreactive inclusions were seen, Alzheimer disease, Pick disease, and FTDP-17 can be eliminated because all are tauopathies. FTDP-17 usually presents with more extrapyramidal symptoms and is an autosomal dominant condition. FTLD-U is a sporadic condition that accounts for approximately 50% of all cases of frontotemporal lobar degeneration. TDP43 immunoreactive neuronal inclusions are characteristic of FTLD-MND. Motor signs may be subtle as in this patient, limited to fasciculations of the upper extremities.

Answer 250

SCN1A Rationale: This patient’s history is most consistent with Dravet syndrome, which in nearly 70% of patients is associated with truncation or missense mutations of the sodium channel gene SCN1A, which encodes for the alpha 1 pore-forming subunit of the sodium channel.

Answer 251

PARKIN Rationale: Early-onset Parkinson disease often requires genetic testing. Phenotypically, patients have a similar presentation to idiopathic Parkinson disease. The Parkin gene is the most commonly identified mutation.

Answer 252

OSTEOMYELITIS WITH ABSCESS Rationale: The images show T1 hypointensity at L3 and L4 that diffusely enhances along with the intervening disk. There is also notable extension of the enhancement into the paravertebral soft tissues and epidural space. These findings are typical of a pyogenic osteomyelitis with discitis and epidural abscess. Multiple myeloma, metastatic disease, and trauma are not typically associated with enhancement of intervening disks or this pattern of fluid infiltration in the epidural space.

Answer 253

VENTRAL HORN Rationale: The synapse of the afferent axons for the muscle stretch reflex is located in the anterior (ventral) horn. The muscle stretch reflex is monosynaptic directly from sensory neuron to an alpha motor neuron. The dorsal root ganglion contains cell bodies of the pseudo-unipolar sensory neurons. The intermediate column contains synapses related to sympathetic function, whereas the substantia gelatinosa is the site of synapse for afferent fibers that form the spinothalamic tract. The substantia gelatinosa sits within the zone of Lissauer.

Answer 254

LEAVE A MESSAGE, REQUESTING THE PATIENT CALL THE OFFICE Rationale: Because the patient is anxious about test results, reassuring him promptly is the best course of action. However, medical information should not be left on voicemail nor exchanged via unsecure email. Rather, the patient should be advised to call the office again. Results can be delivered over the phone as long as the patient’s identity is confirmed. Sending results to a home address may delay the communication of information and can violate HIPAA if written consent has not been obtained.

Answer 255

CAVUM SEPTUM PELLUCIDUM Rationale: An anterior cavum septum pellucidum lies between the transverse fibers of the genu of the corpus callosum and the anterior commissure. Constantly present in the human fetus, it tends to become obliterated near term. In adults, the cavity is found in about 20% of brains studied at autopsy. It has no proven clinical significance.

Answer 256

ANKYLOSING SPONDYLITIS Rationale: The CT scans shown demonstrate a pattern referred to as “bamboo spine.” The pattern is formed by diffuse syndesmophytic ankylosis as a result of interspinous ligament calcifications, diffuse ossification of the spinal ligaments, joints, and enthesophyte formation. Although the images show osteopenia that can be seen with osteoporosis, this is not the best answer. Rheumatoid arthritis is associated with enlarged pannus formation not seen on this study. Diffuse idiopathic skeletal hyperostosis is associated with bone proliferation along the tendinous and ligamentous insertions of the spine, resulting in calcification of the anterior and posterior longitudinal ligament and large anterior and posterior osteophytes not seen on this study. Spondylosis is a term for typical degenerative changes of aging of both the spinal disks and associated formation of adjacent osteophytes not seen on this study.

Answer 257

HEREDITARY NEUROPATHY WITH LIABILITY TO PRESSURE PALSIES Rationale: Hereditary neuropathy with liability to pressure palsies may present in childhood. Other family members may or may not be symptomatic. Electrophysiologic studies reveal conduction blocks at sites of pressure and mild diffuse slowing.

Answer 258

PROGRESSIVE SUPRANUCLEAR PALSY Rationale: A key feature of all five neurodegenerative disorders presented here is parkinsonism. While many patients with parkinsonism can fall, patients with progressive supranuclear palsy (PSP) have truncal/axial rigidity and tend to fall backward as opposed to the appendicular rigidity seen in the other neurodegenerative disorders presented here. Spilling food is a common presentation of PSP due to an inability to look down while eating. PSP and corticobasal degeneration are both associated with frontotemporal dementia and obsessive-compulsive behaviors, but corticobasal degeneration has appendicular rigidity with forward and side falls. Falls in multiple-system atrophy may be due to dysautonomia but would not explain the other clinical symptoms.

Answer 259

START HIGH-DOSE STEROIDS Rationale: There should be a high suspicion for temporal arteritis (also referred to as giant cell arteritis) in this patient. The gold standard for diagnosis is tissue confirmation by temporal artery biopsy. However, treatment with steroids should be started immediately when there is strong clinical suspicion and should not be delayed while awaiting biopsy, especially if vision loss has occurred.

Answer 260

MICROGLIA Rationale: Microglia are the resident macrophages of the brain. They share antigens with circulating monocytes, and both cell lines are probably derived largely from the same bone marrow precursors. The microglia are activated by injury to become large scavengers identical to macrophages. When activated, they may undergo mitosis. These cells play no role in maintaining the blood-brain barrier but are conspicuous at the circumventricular organs where the blood-brain barrier is absent

Answer 261

CYTOTOXIC EDEMA Rationale: The principle of diffusion MRI is in the microscopic motion of water protons. In acute stroke settings there is a shift of extracellular water into the intracellular space, thereby reducing the apparent diffusion coefficient (ADC).

Answer 262

CYTOLOGY Rationale: These findings are consistent with leptomeningeal spread of non-Hodgkin lymphoma. Although the patient is immunocompromised, it is much less likely that she has tuberculous meningitis or cytomegalovirus infection. The clinical manifestations are not those associated with paraneoplastic disease. The patient is not likely to have meningeal involvement by neurosarcoid.

Answer 263

LOSS OF TEMPERATURE SENSATION AT THE LEVEL OF THE LESION Rationale: A syrinx causes a central cord syndrome, characterized by loss of pain and temperature sensation at the level of the lesion secondary to crossing spinothalamic fibers in the ventral commissure. Posterior columns are spared. A large syrinx may start to compress the anterior horn gray matter, which can produce weakness in the area of numbness. Typically, there are no bladder symptoms.

Answer 264

MYOCLONIC EPILEPSY OF INFANCY Rationale: Myoclonic epilepsy of infancy is a generally benign generalized myoclonic seizure disorder occurring in otherwise healthy infants, some of whom (about 25%) have a history of isolated febrile convulsions. Episodes do not occur in clusters and are not associated with tonic-clonic seizures.

Answer 265

CAVERNOUS MALFORMATION Rationale: The lesion in the left temporal lobe has a heterogenous appearance on T2-weighted images, with a rim of surrounding hypointensity, findings most characteristic of a cavernous angioma. Glioma causes T2 hyperintensity and mass effect, with or without pathologic enhancement. Mesial temporal sclerosis causes volume loss and T2 hyperintensity. Dysembryonic neuroepithelial tumor often has nodular and cystic components

Answer 266

SUMATRIPTAN Rationale: This patient’s symptoms are most compatible with migraine. Although he may ultimately require preventive medication in an attempt to reduce the frequency, duration, or severity of attacks, his current frequency of two headaches per month warrants an initial trial of abortive therapy with a migraine-specific agent such as triptan. If the headaches do not respond well to abortive therapy, if he is intolerant of side effects of abortive medication, or if the headaches increase in frequency, then a prophylactic agent would be appropriate.

Answer 267

POSTERIOR INFERIOR CEREBELLAR ARTERY Rationale: The posterior inferior cerebellar artery, a branch of the vertebral artery, supplies the dorsolateral portions of the medulla and the posterior inferior portions of the cerebellum. Occlusion results in Wallenberg syndrome with loss of pain and temperature in the ipsilateral face and contralateral body, weakness of the ipsilateral soft palate, paralysis of the ipsilateral vocal cord, ipsilateral ataxia, and an ipsilateral Horner syndrome.

Answer 268

CARPAL TUNNEL SYNDROME Rationale: This patient has signs and symptoms of a distal symmetric polyneuropathy, the clinically mild features of this disorder at the present time make it unlikely that his hand paresthesias and thenar findings are part of the same problem. This, together with prominent thenar wasting, makes a carpal tunnel syndrome more likely. Carpal tunnel syndrome is common in patients with diabetes mellitus.

Answer 269

BLOOD CULTURES Rationale: The classic presentation for acute bacterial meningitis consists of fever, headache, stiff neck, and altered mental status. The most likely etiology in this patient is bacterial pneumonia due to her history of productive cough, fever, and chills. When bacterial meningitis is suspected, blood cultures should be obtained first because they are positive about 66% of the time and may be positive when CSF cultures are negative. Once cultures are obtained, empiric antimicrobial therapy should be initiated, either prior to or in conjunction with lumbar puncture. A delay in administration of antimicrobial therapy is associated with increased morbidity and mortality. The yield on Gram stain and cultures of CSF may be diminished by prior antimicrobial therapy, with CSF cell count, glucose, and protein concentration, as well as bacterial PCR studies affected. If there is strong concern for potential herniation due to lumbar puncture, then CT or MRI studies should be obtained first. If the patient is being treated with antimicrobial therapy, there is no risk in delaying lumbar puncture to obtain imaging studies. Therapeutic hypothermia currently is not a recommended treatment for bacterial meningitis.

Answer 270

LEFT TEMPORO-OCCIPITAL LOBE WITH CORPUS CALLOSUM SPARING Rationale: This patient presents with an inability to recognize individual objects (object agnosia). This unusual presentation is secondary to unilateral left temporo-occipital lesions. Facial recognition (prosopagnosia) is usually spared as that typically occurs with right temporo-occipital involvement. The corpus callosum is usually spared. Another common finding that was not mentioned is some degree if not a complete right homonymous hemianopsia. Damage to the left occipital lobe and splenium of the corpus callosum can cause a pure alexia without agraphia due to the right occipital lobe’s inability to send visual information to the language centers of the brain on the left side. This patient can read and write. Simultagnosia, or the inability to perceive more than one item or feature at a time, is usually caused by bilateral lesions to the occipitoparietal lobes. When combined with optic apraxia and ocular ataxia, it is more commonly known as Balint syndrome.

Answer 271

ALEXANDER DISEASE Rationale: Alexander disease is characteristically accompanied by macro- cephaly; it is also the only macrocephalic leukodystrophy that exhibits contrast enhancement on imaging studies. This infant’s head circum- ference is in the 95th percentile, and her MRI scans show a frontal pre- dominant white matter abnormality that affects the subcortical U fibers in the frontal lobes. There also is prominent contrast enhancement.

Answer 272

RIGHT PONS Rationale: With lower extremity somatosensory evoked potentials, the generator of the scalp-positive potential at about 40 msec is the cerebral hemisphere, mostly the primary sensory cortex. The presence of a response at the popliteal fossa on the left indicates an intact left lower extremity peripheral somatosensory response. The presence of the left N21 response indicates intact somatosensory conduction at the lumbar spine gray mater. The absence of the P40 response on the left indicates a lesion of somatosensory conduction after the lumbar spinal cord gray matter either but before or at the primary sensory cortex. With upper extremity somatosensory evoked potentials, the generator of the scalp-negative potential at about 20 msec is the cerebral hemisphere, mostly the primary sensory cortex. The presence of a response at Erb’s point on the left indicates an intact left upper extremity peripheral somatosensory response. The presence of the left N13 response indicates intact somatosensory conduction at the cervical spine gray matter. The absence of the left N20 response indicates a lesion of somatosensory conduction after the cervical spinal cord gray matter either before or at the primary sensory cortex. When considering both the upper and lower extremities, somato- sensory and subsequent N20 response indicates a lesion in the right brain stem, thalamus, or somatosensory cortex.

Answer 273

PONTINE HORIZONTAL AND VERTICAL T2 HYPERINTENSITIES Rationale: Multiple-system atrophy is characterized by combinations of autonomic instability, cerebellar signs, and parkinsonism. Horizontal and vertical T2 hyperintensities in the pons may be seen in multiple-system atrophy, called the hot cross buns sign. Midbrain atrophy is seen in progressive supranuclear palsy. Caudate atrophy is seen in Huntington disease. Unilateral cortical atrophy would be consistent with corticobasal syndrome, and FLAIR hyperintensities in the putamen and globus pallidus may be seen in carbon monoxide poisoning.

Answer 274

IMMUNOSUPPRESSIVE THERAPY Rationale: The photomicrograph shows acutely branching septate hyphae, which most likely represent an opportunistic aspergillosis infection. Patients with aspergillosis commonly are neutropenic and receiving immunosuppressive therapy for neoplasms. The organism initially infects the lung and then spreads hematogenously to involve other organs. The brain is second only to the lung as a site of visceral involvement and frequently manifests as hemorrhagic infarctions.

Answer 275

INCREASED CHIN EMG TONE AND LIMB MOVEMENTS DURING REM SLEEP Rationale: During REM sleep, there is normally loss of muscle tone with decreased EMG activity. REM sleep behavior disorder is characterized by increased tone and limb movements during REM sleep, resulting in movements that may end with patients falling out of bed or unintentionally hurting their bed partner. Although patients with periodic leg movements may experience abnormal movements during sleep, these movements are simpler, stereotyped, patterned, with no associated shouting vocalizations. A posterior alpha rhythm below the normal range suggests encephalopathy, unlikely in this patient with a normal waking neurologic examination.

Answer 276

MIGRATION ANOMALY Rationale: The signal of the deformity-producing tissue is the same as in cortex; thus, this lesion represents heterotopic gray matter. Neoplasm would have had high signal. The lesion is not limited to the basal ganglia, eliminating hemorrhage as the etiology. There is no sign of chronic infarction. The study does not include the hippocampi; therefore, mesial temporal sclerosis cannot be diagnosed.

Answer 277

MULTIPLE SCLEROSIS Rationale: The imaging findings alone are less specific than when considered in the clinical context of this patient, which includes longstanding vision loss in the left eye and weakness in the left arm and leg. Together, the history and imaging findings provide strong evidence to support a diagnosis of multiple sclerosis but not CADASIL, diffuse axonal injury, metastases, or the typically monophasic illness ADEM.

Answer 278

PROLACTINOMA Rationale: Bromocriptine and cabergoline are dopamine agonists that function by the same mechanism as prolactin inhibitory factor (PIF, which is dopamine) to inhibit prolactin synthesis and release by prolactin-secreting pituitary adenomas (prolactinomas). Bromocriptine or cabergoline treatment decreases tumor cell cytoplasmic volume without actually killing adenoma cells. Therefore, the prolactinoma may re-expand if bromocriptine is withdrawn. Bromocriptine has no significant role in neuro-oncology other than in suppression of prolactin-secreting tumors.

Answer 279

RILUZOLE Rationale: This patient’s presentation meets the criteria for probable ALS. Level A evidence indicates that riluzole slows progression of ALS to a modest degree. IVIg is used for multifocal motor neuropathy with conduction block, which may resemble ALS. The presence of upper motor neuron findings on examination and the absence of conduction block on nerve conduction studies exclude this diagnosis. There is no role for methylprednisolone, mexilitene, or gabapentin in the treatment of ALS.

Answer 280

COMPULSIVE BEHAVIOR Rationale: A variety of impulse control behaviors, including gambling and other compulsive behaviors, have been reported in patients with Parkinson disease, apparently related to dopamine agonist therapy. Patients should be advised about these behaviors before starting agonist therapy and should be monitored during follow-up visits.

Answer 281

DONEPEZIL Rationale: Typical cholinesterase inhibitor (donepezil, rivastigmine, galantamine) side effects include nausea, vomiting, and diarrhea. Even after prolonged treatment, patients can later develop GI side effects leading to poor oral intake, weight loss, and a failure to thrive phenotype. Cholinesterase inhibitors are basal forebrain activators that can lead to vivid nightmares. These medications are also nodal blockers and can lead to bradycardia and syncopal events over time. Donepezil can worsen depression symptoms: asthenia, fatigue, and somnolence. Melatonin, trazodone, and mirtazapine typically aid with sleep and do not cause sleep disturbances. Mirtazapine usually promotes appetite. Memantine can cause increased sedation and somnolence.

Answer 282

IDARUCIZUMAB Rationale: Idarucizumab has been shown to reverse the anticoagulant effect of dabigatran. Andexanet is a potential drug developed to neutralize the anticoagulant effect of apixaban, rivaroxaban and edoxaban and was FDA approved in 2019.

Answer 283

HEMICRANIA CONTINUA Rationale: A hemicrania continua is one of the primary headache disorders that can begin in childhood; it is a trigeminal autonomic cephalgia. There is a constant unilateral headache with intermittent exacerbations that are reminiscent of both migraine and cluster headache. It specifically responds to indomethacin, which can be used as both treatment and diagnosis.

Answer 284

KCNQ2 Rationale: Benign idiopathic neonatal convulsions are an autosomal dominant disorder that has been strongly linked to potassium channel defects resulting from mutations in KCNQ2 and KCNQ3. A normal examination makes hypoxia unlikely, as most infants with hypoxia are lethargic; those with metabolic disorders are also lethargic or even unresponsive. Benign rolandic epilepsy presents in adolescence

Answer 285

HYPERAMMONEMIA Rationale: Valproic acid is associated with idiosyncratic hyperammonemia. Valproate-associated hyperammonemic encephalopathy (VHE) is characterized by a decreasing level of consciousness, focal neurologic deficits, cognitive slowing, asterixis, drowsiness, and lethargy. The pathophysiology is poorly understood but a disturbance of urea cycle metabolism has been postulated; this is independent of hepatic function.

Answer 286

MULTIFOCAL MOTOR NEUROPATHY Rationale: The image shows a normal distal ulnar-ADM CMAP with temporal dispersion and conduction block found with proximal stimulation below the elbow. This phenomenon is seen in an acquired demyelinating process, such as acute or chronic inflammatory demyelinating polyneuropathy, or multifocal motor neuropathy. The patient has progressive weakness with fasciculations supporting a lower motor neuron disorder. ALS is a motor neuronopathy that results in loss of motor neurons; demyelination is not a feature. The predominant pathology in diabetic sensorimotor polyneuropathy is axonal, which results in low-amplitude sensory and motor potentials, but not demyelination/conduction block. Myasthenia gravis, as a disorder of the neuromuscular junction, typically demonstrates normal CMAPs; conduction block/demyelination is not seen. Likewise, metabolic myopathy does not demonstrate conduction block/demyelination in motor nerves

Answer 287

WIDESPREAD NEUROFIBRILLARY TANGLES AFFECTING BRAINSTEM AND DEEP GRAY NUCLEI Rationale: The combination of postural instability and falls, bradykinesia, dysarthria, gaze abnormalities, and a frontal-subcortical type of dementia points to a parkinsonian disorder, but Parkinson disease is unlikely given the absence of response to levodopa. This combination of symptoms is most consistent with progressive supranuclear palsy (PSP), a sporadic, predominantly male disorder. Supranuclear gaze abnormalities, postural instability with frequent serious falls, and lack of response to levodopa are characteristic of PSP. PSP is a tauopathy characterized neuropathologically by neurofibrillary tangles within brain stem and deep gray nuclei. Lewy bodies are not a feature of PSP. Pick disease (with Pick bodies in the dentate fascia) is a form of frontotemporal degeneration not typically associated with movement disorder. Selective loss of spiny neurons in the caudate nucleus is a key finding in Huntington disease but not a feature of PSP. Cortical plaques and tangles are the essential neuropathologic findings in Alzheimer disease. Plaques are not characteristic of PSP. The neurofibrillary tangles of PSP are predominantly subcortical and have a different morphology (globose) than those usually seen in Alzheimer disease, although both are composed of tau filaments.

Answer 288

LUMBAR SPINAL STENOSIS Rationale: Spinal stenosis in the lumbar region can present with pain in the posterior thigh and calf of both legs after walking one to two blocks or standing 5 to 10 minutes. Pain typically abates with sitting and rest. The patient’s examination results and the fact that he can ride an exercise bicycle without discomfort suggest that peripheral vascular disease and deep venous thrombosis are less likely.

Answer 289

RELEASE THE RESULTS BUT ONLY AFTER THE PATIENT SIGNS A MEDICAL RELEASE OF INFORMATION FORM Rationale: A patient has the right to access all medical information in his/her medical chart. However, documentation of this access is required to ensure that the information has been accessed appropriately. Printing from the electronic medical record may record the provider doing so and without required documentation may be seen to violate the minimum necessary requirements.

Answer 290

intranuclear oligodendrocytic inclusions Rationale: Progressive multifocal leukoencephalopathy (PML) is an opportunistic viral infection with tropism for oligodendrocytes. Since May 2010, 49 confirmed cases of PML have been documented among patients receiving natalizumab worldwide. In addition to general characteristics of a demyelinating disease shared with active multiple sclerosis (such as abundant foamy macrophages, astrocytic atypia, and relative sparing of axons) intranuclear oligodendrocytic viral inclusions are only seen in PML. Perivascular inflammatory infiltrates are not typically a feature of PML.

Answer 291

a small sac-like outpouching on the anterior communicating artery Rationale: The presenting signs and symptoms strongly suggest a ruptured saccular or berry aneurysm, which frequently occurs on the anterior communicating artery. This disorder primarily occurs in the elderly and would be unusual in a young person. Fusiform aneurysms of the basilar artery typically become atherosclerotic and are much less likely to bleed. Microscopic Charcot-Bouchard aneurysms of deep penetrating arteries and arterioles are primarily associated with hypertensive intraparenchymal hemorrhages. Congophilic material accumulates in cortical and leptomeningeal arteries in amyloid angiopathy, which may cause subarachnoid hemorrhage but nearly always occur in association with a lobar parenchymal hemorrhage. Laminar cortical necrosis results from ischemic-hypoxic injury to pyramidal cortical neurons and is not related to subarachnoid hemorrhage.

Answer 292

ANTICHOLINERGIC Rationale: Choice of an antidepressant often is based on the side effect profile. Antidepressants that are strongly anticholinergic should be avoided in patients with underlying cognitive disorders, as they are more likely to result in worsening of cognitive function.

Answer 293

KETOGENIC DIET Rationale: GLUT1 deficiency, a pathogenic variant of the SLC2A1 gene, has an autosomal dominant inheritance pattern and is almost always de novo, though sometimes one parent is affected. Common presenting signs and symptoms include eye movement disorders (usually in infancy), seizures, movement disorders, and developmental impairments. This disorder results in abnormal glucose transport across the blood-brain barrier, resulting in insufficient energy substrate in the brain. Because the disorder is caused by impaired cerebral glucose transport, a ketogenic diet (ie, a high-fat, low-protein, low-carbohydrate diet in which ketone bodies [breakdown products from fatty acid metabolism] become the chief source of energy to the brain) provides a work-around solution for the deficit. 2021 RITE | 204 Early identification and treatment is thought to lead to better long-term outcome in terms of cognition, motor skills, and epilepsy.

Answer 294

CARDIAC DYSRHYTHMIA Rationale: Hypothermia protocols for unresponsive patients who survive out-of-hospital cardiac arrest due to ventricular fibrillation or pulseless ventricular tachycardia are considered standard of care by leading organizations, including the American Heart Association. In a Scandinavian study of 986 patients treated with hypothermia, cardiac dysrhythmias occurred in up to one third of patients. Seizures, electrolyte abnormalities, bleeding, and skin injury were less common.

Answer 295

INTRACRANIAL VENOUS SINUS THROMBOSIS WITH INFARCTIONS Rationale: Chemotherapy used for leukemia, particularly L-asparaginase, may cause significant hypercoagulability, specifically secondary to antithrombin III deficiency. Venous sinus thromboses with infarctions in a venous distribution are the result.

Answer 296

ALPHA-SYNUCLEIN Rationale: This patient most likely has Lewy body dementia, which is related to abnormal processing of alpha-synuclein. Clinical features typically include distinctive visual hallucinations, parkinsonism, cognitive fluctuations, dysautonomia, sleep disorders, and neuroleptic sensitivity. Alpha-synuclein is a normal synaptic protein that may play a role in vesicle production. In patients with Lewy body dementia, an insoluble form of alpha-synuclein is a major component of the Lewy bodies.

Answer 297

ZONISAMIDE Rationale: Antiepileptic drugs that have carbonic anhydrase inhibition, such as zonisamide and topiramate, have been associated with nephrolithiasis and should be avoided in patients with a history of kidney stones.

Answer 298

SOLEUS Rationale: The soleus is innervated by S1 and thus would be spared in an L5 radiculopathy. The tensor fascia latae, tibialis anterior, peroneus longus, and tibialis posterior are all innervated by L5.

Answer 299

HYPOSMIA Rationale: The treatment of Parkinson disease is made more challenging by its association with many nonmotor problems, including autonomic failure, cognitive and behavioral disturbances, and pain. Hyposmia, though typically not noticed or reported by patients later diagnosed with Parkinson disease, is an early-onset problem affecting most patients. REM sleep behavior disorder can also precede motor manifestations by many years. Later nonmotor problems include orthostatic hypotension and peripheral edema due to autonomic dysfunction and frequently made worse by use of dopaminergic medications, erectile dysfunction in male patients, as well as other urogenital complaints, and later behavioral complications such as visual hallucinations.

Answer 300

PITUITARY APOPLEXY

Answer 301

SPASMUS NUTANS Rationale: Spasmus nutans is a rare disorder of unknown etiology that presents in the first year of life in which nystagmus (often “shimmering” and pendular) appears to be the primary feature; head nodding and sometimes a head tilt appear to be compensatory actions. The head nodding often becomes worse when the infant is regarding an object. Investigations for posterior fossa tumors, retinal disease, and other underlying causes of nystagmus or similar eye movement abnormalities are necessary, but if these causes are excluded then a diagnosis of spasmus nutans can be made. The disorder is self-limited, with infants outgrowing it by around age 3 years. Most affected children have minimally impaired visual acuity, and one third will have orthotropia and normal stereovision in the long run.

Answer 302

INTRACTABLE HICCUPS Rationale: An area postrema syndrome, characterized by intractable hiccups, nausea, and vomiting, occurs in up to 43% of patients with neuromyelitis optica spectrum disorder.

Answer 303

MEDIAN NEUROPATHY AT THE WRIST Rationale: Median neuropathy at the wrist (carpal tunnel syndrome) presents with hand and arm pain with nocturnal exacerbations. The hallmark of diagnosis is the presence of slowing sensory and motor axons of median in the segment of nerve traversing the carpal tunnel. The ulnar and radial sensory and motor axons are spared.

Answer 304

NORMAL HEAD IMPULSE TEST Rationale: Cerebrovascular disease is always a concern in older individuals presenting with acute-onset vertigo, especially with underlying stroke risk factors. Brain MRI scans may be normal within the first 48 hours in cases of posterior circulation stroke. In this setting, the presence of skew eye deviation, normal head impulse test, or direction-changing nystagmus in eccentric gaze is highly sensitive and specific for acute brain stem or cerebellar stroke.

Answer 305

CYSTICERCOSIS Rationale: The image shows the larval form of the pork tapeworm Taenia solium, the causative agent in cysticercosis. The larval form is called cysticercus. Neurocysticercosis is more likely to affect the ventricular system than amebiasis, coccidioidomycosis, tuberculosis, or nocardiosis. The diagnosis is made by confirmation of a large complex infectious agent. Amebiasis will demonstrate an abscess with organisms resembling macrophages. Coccidioidomycosis will usually show a parenchymal lesion with ~30-micron spherules filled with 2-5-micron endospores and a surrounding inflammatory reaction, usually granulomatous. Nocardia will show a parenchymal abscess with gram-positive, acid-fast beaded, filamentous bacilli. Tuberculosis will demonstrate granulomatous abscess with acid-fast “red snappers.” Only neurocysticercosis will show the large (1 to 2 cm) complex organism foreign to the human body as shown.

Answer 306

SENSORINEURAL HEARING LOSS Rationale: A delayed-onset progressive hearing loss may occur in those children with an asymptomatic congenital cytomegalovirus infection that may not be noted until a delay in language development occurs. Hearing loss may occur in up to 11% of children with an asymptomatic congenital cytomegalovirus infection.

Answer 307

JOUBERT SYNDROME Rationale: This patient’s presentation and MRI findings are typical for Joubert syndrome in which there is hypoplasia of the cerebellar vermis. The most common features of this syndrome include hyperpnea, hypotonia, oculomotor apraxia, ataxia, and intellectual disability. Seizures are among the neurologic manifestations of the disorder. The molar tooth sign seen on the MRI scan is the result of thickening and horizontalization of the superior cerebellar peduncle and a deep interpeduncular fossa; this sign is also seen in several other disorders, including Dekaban-Arima syndrome, Senior-Loken syndrome, and COACH (cerebellar vermis hypoplasia, oligophrenia, ataxia, coloboma, and hepatic fibrosis).

Answer 308

ANTERIOR INTEROSSEOUS NEUROPATHY Rationale: The anterior interosseous nerve innervates the flexor digitorum profundus to the index and middle fingers, the flexor pollicis longus, and the pronator quadratus, with resultant weakness in flexion of the distal phalanges of the thumb and index finger along with weakness in forearm pronation. Normal needle EMG findings in the extensor indicis proprius argue against C8 radiculopathy, whereas normal findings in the pronator teres argue against a more diffuse median neuropathy and place the lesion within the distribution of the anterior interosseous nerve, locating it distal to the median innervation of the pronator teres.

Answer 309

HYPOTHYROIDISM Rationale: This patient most likely has hypothyroidism, which may present with progressive cognitive impairment and systemic symptoms including weight gain, hoarseness, lethargy, and cold intolerance. Screening for hypothyroidism is considered standard for patients presenting with dementia.

Answer 310

CT OF THE CHEST, ABDOMEN, AND PELVIS WITH CONTRAST Rationale: This patient’s presentation is consistent with opsoclonus- myoclonus-ataxia syndrome (OMS), also referred to as “dancing eyes” or Kinsbourne syndrome. In patients this age, OMS most often is a paraneoplastic manifestation of occult neuroblastoma. The most common initial misdiagnosis is acute cerebellar ataxia of childhood, a benign condition. The most helpful test in determining etiology is CT of the chest, abdomen, and pelvis using oral contrast and fine-cut images.

Answer 311

GABRG2 Rationale: Genes linked to childhood absence epilepsy include GABRG2, GABRA1, and CLCN2, which encode for the gamma 2 subunit of the GABAA receptor, the alpha 1 subunit of the GABAA receptor, and chloride channel protein 2, respectively.

Answer 312

RADIATION-INDUCED PLEXOPATHY Rationale: Multiplets and doublets (previously called myokymic discharges) are rhythmic, grouped, spontaneous, repetitive discharges of the same motor unit (grouped fasciculations). The firing frequency within the burst is typically 5 to 60 Hz. These findings are suggestive of a radiation-induced plexopathy.

Answer 313

HER RISK OF POSTPARTUM MS RELAPSES IS INCREASED Rationale: Multiple sclerosis has no meaningful impact on pregnancy itself, the ability to conceive, delivery, or fetal status and well-being. An increased relapse rate, about 70% higher during the first 3 months postpartum compared to the prepregnancy rate, has been consistently observed. MS is not an inherited disease; the child of a mother with MS has only a 2% to 2.5% higher risk for developing the disease than the general population.

Answer 314

PARASOMNIA Rationale: Sleep-related eating disorder is characterized by recurrent episodes of involuntary eating and drinking occurring as a partial arousal during sleep. Patients usually eat unusual foods and have little or no memory of the event. Most also have concurrent obstructive sleep apnea, periodic limb movements of sleep, or other sleep disorders.

Answer 315

GLATIRAMER ACETATE Rationale: Interferon beta, natalizumab, and dimethyl fumarate are classified as FDA category C for pregnancy. Each is associated with either embryolethality or teratogenicity in animal studies, although this has not been proven in humans. Teriflunomide is category X for pregnancy. At this time, glatiramer acetate is considered the safest agent to use during pregnancy and lactation.

Answer 316

CYCLOSPORINE Rationale: Myopathies that occur in association with HMG-CoA reductase inhibitors used for lipid-lowering therapies are common clinical problems. Manifestations of muscle toxicity include myalgias, myopathy with weakness, sometimes with severe rhabdomyolysis that may be fatal, and subclinical myopathy defined as isolated creatine kinase (CK) elevations without myalgias or weakness. General reviews of statin myopathies cite a 2% to 7% incidence of myalgias and 0.1% to 1.0% incidence of weakness or elevated CK (>10 times the upper limit of normal). Statin and fibrate combination therapy has greater toxicity, with a 2% incidence of weakness or elevated CK (>10 times the upper limit of normal). Statin and cyclosporine combination therapy has an estimated 32% incidence of myotoxicity.

Answer 317

ALPHA 2 RECEPTOR AGONIST Rationale: Alpha 2 receptors are presynaptic noradrenergic receptors that, when stimulated, reduce firing of the locus coeruleus outflow neurons; clonidine is an agonist to the alpha 2 receptor.

Answer 318

SUPERFICIAL PERONEAL Rationale: The history of left foot drop suggests an L5 root lesion versus a peroneal neuropathy. Nerve conduction studies of the superficial peroneal nerve would be helpful in localizing the site of the lesion.

Answer 319

OLANZAPINE Rationale: The treatment of motor and vocal tics has been directed primarily toward the dopaminergic system. Typical dopamine receptor antagonists, including haloperidol and pimozide, are effective in the control of motor and vocal tics. One randomized, double-blind, controlled study reported that pimozide was superior to haloperidol with respect to efficacy and side effects. Because pimozide and other neuroleptics may cause prolongation of the QTc interval, ECG is recommended prior to initiating therapy and with dose escalation. Other atypical neuroleptics, including ziprasidone, olanzapine, and risperidone, have been shown in controlled trials to reduce motor and vocal tics.

Answer 320

REPORTING IS MANDATORY EVEN IF THE INJURIES MAY NOT BE RELATED TO SUSPECTED MALTREATMENT Rationale: Physicians and other health care professionals must report instances in which nonaccidental trauma is suspected. Physicians are not obligated to prove the abuse, and testing to rule out other causes should not postpone reporting. Glutaric aciduria, Menkes disease, and hemophilia may present with intracranial or subdural bleeding but are less likely in this situation. Retinal hemorrhages are unusual in these conditions. Physicians are protected from liability for reporting in good faith, even if the allegation is ultimately not supported

Answer 321

FEMORAL Rationale: The femoral nerve innervates the hip flexors and knee extensor muscles; thus, injury would produce EMG changes in the vastus lateralis, iliopsoas, and rectus femoris muscles.

Answer 322

STROKE Rationale: Stroke, including hemorrhagic and ischemic events, accounts for 60% of all cases of status epilepticus in the elderly and is the most common cause of new-onset seizures in the sixth and seventh decade. Brain tumors are the most common cause in the fourth and fifth decade, and trauma the most common cause in the second and third decades.

Answer 323

PICK DISEASE Rationale: Pick disease shows atrophy that typically involves the frontal and temporal lobes but may show striking sparing of the superior temporal gyrus, as illustrated in the image. This is a tauopathy; thus, the rounded intracytoplasmic inclusions will show immunoreactivity with tau immunostains. Herpes simplex encephalitis would not be expected to show anti-tau immunostaining and does not specifically spare the superior temporal gyrus. The rounded inclusions are typical for Pick bodies and not for Alzheimer disease. Lewy bodies stain better with anti–alpha-synuclein, and diffuse Lewy body disease would not show knifelike atrophy of the inferior portions of the temporal lobe.

Answer 324

DEFORMED AND LOW-LYING TONSILS Rationale: The cerebellar tonsils descend below the foramen magnum. This patient has a Chiari type I malformation. The fourth ventricle is of normal size without cysts. The tectal area is normal.

Answer 325

NUCLEUS AMBIGUUS Rationale: The nucleus ambiguus is the source of brachial motor outflow to the laryngeal and pharyngeal muscles. The dorsal motor nucleus of the vagus is the source of parasympathetic outflow to most of the viscera. The nucleus tractus solitarius receives afferent visceral sensory information.

Answer 326

BRAIN MRI Rationale: The American College of Radiology Appropriateness Criteria should be referenced frequently when selecting imaging studies. The American Academy of Neurology is among the many medical specialties that contribute to and cooperate with creating and maintaining this important clinical decision support resource, as it is multidisciplinary, outcomes- and evidence-based, free, and continuously updated. Cranial ultrasound is not effective in children older than a few months of age. The sutures that provide the acoustic window for ultrasound energy to get past the skull to interrogate the intracranial tissues have closed. CT angiography is not the most appropriate option because it is costly and requires rapid injection of iodinated contrast. It also is poor for evaluation of brain tissue because it is effectively a noncontrast CT with respect to the brain. Contrast is infused very rapidly and imaged while in the arteries before much reaches the capillaries where it can provide useful brain enhancement. CT angiography also delivers a high dose of radiation for little information relevant in a pediatric patient. Head CT is not the most appropriate exam, as it exposes a child to radiation with less than optimal diagnostic performance. MRI is the most appropriate choice because there is no radiation exposure, it provides the best performance in diagnosis, and it is cost effective.

Answer 327

CNS TOXOPLASMOSIS Rationale: The location in the basal ganglia and positive HIV status make toxoplasmosis the most likely diagnosis. This can be confirmed by stereotactic biopsy. Patient age in the third decade and its multifocal nature make glioblastoma multiforme unlikely. Oligodendrogliomas typically are seen near the cortical surface and have regions of calcification. There are no abnormal flow voids to suggest arteriovenous malformation. Cavernous malformations typically would not have this enhancement pattern or degree of surrounding edema.

Answer 328

CAVERNOUS ANGIOMA (CAVERNOMA). Rationale: The lesion in the left hippocampus has the imaging characteristics of a cavernous angioma, with a rim of low-intensity hemosiderin surrounding a cluster of high-intensity, fluid-containing vessels. The absence of draining veins rules out both arteriovenous malformation and venous angioma. Astrocytoma and oligodendroglioma do not have the imaging characteristics present in this patient’s MRI scan.

Answer 329

SKIN BIOPSY Rationale: Cranial nerve deficits and hypothalamic involvement are common neurologic complications of sarcoidosis. Enhancing lesions along the meninges, predominantly in the skull base and the spinal cord, is due to granulomatous infiltration. Diagnosis is made by demonstration of noncaseating granulomas in involved tissue.

Answer 330

FRAGILE X-ASSOCIATED TREMOR ATAXIA SYNDROME Rationale: Fragile X-associated tremor ataxia syndrome (FXTAS) is an X-linked CGG trinucleotide repeat disorder that localizes to the FMR gene (fragile X mental retardation), which encodes an RNA-binding protein (FMRP) involved in translational regulation. The full mutation, with expansion to >200 repeats, leads to hypermethylation of the repeat and failure of transcription and translation of FMR. This ultimately leads to the absence of FMRP and translation dysregulation of multiple genes. Men may become symptomatic after age 50 years, with intention tremor, ataxic gait, and/or parkinsonism. Friedreich ataxia, dentatorubral-pallidoluysian atrophy, or spino- cerebellar ataxia type 3 are unlikely in this patient given his age, absence of other clinical features, and history of intellectual disability in his daughter’s son. Patients with Charcot-Marie-Tooth disease may have postural and action tremor but not cerebellar ataxia.

Answer 331

UPBEAT AND TORSIONAL Rationale: Benign paroxysmal positional vertigo (BPPV) originates most commonly from the posterior semicircular canals. The Dix-Hallpike maneuver may elicit characteristic nystagmus, which is fatigable, occurs with the affected ear downward, and is upbeat and torsional in quality. There is typically a latency period of several seconds until onset. Gaze-evoked nystagmus is associated with central lesions.

Answer 332

NUSINERSEN Rationale: This patient has tongue fasciculations, suggesting a motor neuron or motor nerve process. In the presence of proximal hypotonia, this presentation would be most consistent with spinal muscular atrophy (SMA), an autosomal recessive disorder most often caused by mutations in the SMN1 gene. Because the patient has never been able to sit, she would be classified as SMA type 1. In the ENDEAR study of patients with SMA type 1, a significantly greater proportion of subjects treated with nusinersen achieved motor milestones compared with the control group (51% vs 0%). In the treatment group, 22% of subjects developed full head control, 10% could independently roll from a supine to prone position, 8% could sit independently, with half of those being able to sit and pivot, and one subject was able to stand with minimal to moderate support. In the CHERISH study, the effectiveness of nusinersen was studied in later-onset SMA in patients ages 2 to 12 years. Of those in the treatment group, 57% showed improvement in motor function by 3 or more points at month 15, compared with about 20% of the controls. The FDA approved nusinersen for SMA in December 2016. Nusinersin causes alternative splicing of the SMN2 gene to increase the amount of functional SMN protein produced. Alpha-glucosidase alfa is an enzyme replacement treatment for acid maltase deficiency (Pompe disease). Eteplirsen has been approved for treatment of patients with Duchenne muscular dystrophy with particular exon deletions. Idebenone is a coenzyme q10 analog that may improve respiratory function in patients with Duchenne muscular dystrophy. Edaravone has been approved for ALS.

Answer 333

TAU Rationale: This patient has clinical manifestations of parkinsonism with bradykinesia, postural instability, and rigidity. However, he also has impaired voluntary eye movements, with an intact oculocephalic reflex, and retropulsion. This presentation is most consistent with progressive supranuclear palsy, which is pathologically characterized by tau inclusions in the substantial nigra. Alpha-synuclein inclusions are seen in the substantial nigra in Parkinson disease and in cortical neurons in dementia with Lewy bodies.

Answer 334

GLIOBLASTOMA MULTIFORME Rationale: The clinical history and MRI scan are most consistent with a high-grade glioma (glioblastoma multiforme). The lesion is intra-axial and therefore unlikely to represent a meningioma, which is almost always extra-axial and dural-based. Primary CNS lymphoma is rare in a young immunocompetent person and usually enhances more uniformly. Cerebral abscess usually is ring enhancing with a necrotic center, and the history and radiographic appearance is not that of demyelinating disease.

Answer 335

RECURRENT ARTERY OF HEUBNER . Rationale: The recurrent artery of Heubner, which is also one of the medial lentriculostriate arteries, is the largest perforating branch from the proximal anterior cerebral artery. It supplies the head of caudate nucleus, paraterminal gyrus, anterior portion of the lentiform nucleus, and the anterior limb of the internal capsule.

Answer 336

PHYSICAL ABUSE Rationale: Physical abuse in women is associated with a 50% to 70% increase in gynecologic, CNS, and stress-related back problems. Additional findings include chronic neck and back pain, migraine, and other headache types. Certain signs and symptoms should raise the index of suspicion for a history of abuse or neglect, including injuries to the head, back, chest, abdomen, or genitals, injuries in different stages of healing, physical injury during pregnancy, discomfort when asked about relationships, unexplained injuries or history of inappropriate to injuries, and chronic pain without apparent etiology. The American Medical Association recommends that all patients should be screened for abuse and neglect. The focal aspect of pain associated with evidence of missing hair and bruises in various stages of healing make physical abuse the most likely diagnosis in this situation.

Answer 337

SIGMOID SINUS Rationale: Venous blood from the superior sagittal sinus travels to the confluence (torcula). Venous blood from the inferior sagittal sinus is joined by the great cerebral vein, forms the straight sinus, and empties into the torcula. From the torcula, venous blood flows to the transverse sinus, the sigmoid sinus and then the inferior jugular vein.

Answer 338

TAU Rationale: Chronic traumatic encephalopathy (CTE) is a progressive neurodegenerative condition found in individuals exposed to repeated mild traumatic brain injury, especially athletes and military veterans. Symptoms include impairment in attention, executive function, and memory, as well as behavioral changes including impulsivity and explosive anger. Mood changes such as depression and anxiety are also common. This condition is classified as a tauopathy, but the distribution of neurofibrillary tau tangles in perivascular regions and at the depths of the cerebral sulci distinguish CTE from other tauopathies.

Answer 339

INTERVAL FROM SYMPTOM ONSET TO DISEASE PLATEAU Rationale: Both Guillain-Barré syndrome and chronic inflammatory demyelinating polyneuropathy are acquired demyelinating autoimmune neuropathies. CSF analysis and electrodiagnostic findings are quite similar and do not distinguish one disorder from the other. The interval between symptom onset and disease plateau is the main distinguishing feature; most patients with Guillain-Barré syndrome reach a plateau within 4 weeks of disease onset.

Answer 340

VALPROIC ACID Rationale: Lamotrigine is efficacious for treatment of focal and generalized seizures, including the Lennox-Gastaut syndrome. It is metabolized in the liver. Valproate inhibits metabolism and increases considerably the half-life of lamotrigine. Lamotrigine is started at a dose of 50 mg/d for 2 weeks in patients not receiving valproate and 25 mg every other day for 2 weeks in patients receiving the drug. The incidence of serious rash is 0.3% in adults and 1% in children. Concurrent administration with valproate and rapid escalation of the dose increase the risk of this complication.

Answer 341

SPHINGOSINE-1-PHOSPHATE Rationale: Fingolimod is an immunomodulator that downregulates sphingosine-1-phosphate receptors on lymphocytes in secondary lymphoid tissue. Two other drugs in this class include siponimod and ozanimod. These drugs prevent egress of potentially autoreactive lymphocytes from lymph nodes into the peripheral circulation, thereby reducing their entry into the CNS. Oral fingolimod demonstrated superior efficacy to both placebo and weekly IM interferon beta-1a in reducing relapses and MRI activity in controlled studies in patients with relapsing-remitting multiple sclerosis. Adverse effects of oral fingolimod include bradycardia, atrioventricular block, macular edema, and rare fatal infections (disseminated varicella zoster, herpes simplex encephalitis).

Answer 342

CHOREA GRAVIDARUM Rationale: This patient has sydenham chorea, a poststreptococcal autoimmune disorder that typically begins within 2 to 6 months of group A beta-hemolytic streptococcal pharyngitis. Most patients recover within 6 months, although some have a more prolonged course. Girls who recover may present years later with recurrent chorea, either during pregnancy or while on hormone (estrogen) or contraceptive therapy.

Answer 343

GREATER THAN 70 CAG REPEATS IN THE HUNTINGTIN GENE Rationale: This patient has manifestations of juvenile Huntington disease. The adult-onset form of the disorder is associated with more than 40 CAG repeats in the huntingtin gene. Like many trinucleotide repeat disorders, earlier onset is often reported in subsequent generations (termed anticipation), as the repeat expands.

Answer 344

EPILEPSY IS MUCH MROE COMMON IN RETT SYNDROME THAN IN AUTISM Rationale: Approximately 80% of individuals with Rett syndrome have epilepsy compared with only 25% of patients with autism. Autopsies on the brains of individuals with Rett syndrome show a pathology different than autism, even though children with Rett syndrome often exhibit autistic-like behaviors, such as repetitive hand movements, prolonged toe walking, body rocking, and sleep problems. Characteristics typical of Rett syndrome include normal development until 6 to 18 months, followed by regression in cognition, behavior, social, and motor skills throughout their lifetime. Delayed growth and small head circumference are also characteristic. Functioning level typically ranges between severe and profound intellectual and development disabilities. Musculoskeletal findings include shakiness of the torso and possibly the limbs, hypoactivity, and an unsteady stiff-legged gait. Respiratory difficulties include hyperventilation, apnea, and air swallowing. Teeth grinding and difficulty chewing are also characteristic.

Answer 345

DEFECT IN THE RELEASE OF ACETYLCHOLINE Rationale: Infantile botulism usually presents between 3 and 18 weeks of age and is caused by the Clostridium botulinum toxin, which blocks acetylcholine release. Clinical features include constipation, hypotonia, areflexia, poor suck, impaired pupillary response to light, and ophthalmoplegia. Breastfed infants are most likely to be affected. Diagnosis is made by EMG with repetitive nerve stimulation, causing an incremental response, and isolation of C botulinum toxin in the stool.

Answer 346

HYPERNATREMIA Rationale: The same transporter that resorbs sodium also resorbs lithium, and lithium excretion is increased during periods of hypernatremia such as that caused by dehydration or by eating excessive salty foods. Sodium-wasting diuretics, NSAIDs, and ACE inhibitors can increase lithium levels and cause toxicity

Answer 347

CAVERNOUS ANGIOMA Rationale: Cavernous angiomas in the brain, also known as hemangiomas, are most commonly seen in young adults and typically present as headache or seizure. There are both sporadic and hereditary forms. Angiomas are often supratentorial but may be seen elsewhere. The risk of catastrophic bleeding is much less than with arteriovenous malformations. The ring of hemosiderin seen in histologic sections around these lesions is also seen on MRI (ferruginous penumbra). Angiomas are well-circumscribed with very little brain intervening between vessels, typically just around the edges.

Answer 348

VERBAL FLUENCY Rationale: Multiple sclerosis can cause myriad cognitive symptoms, including slowed processing speed and reaction time, retrieval-type memory loss, and mood and personality changes. Aphasia is atypical; however, changes in verbal fluency as demonstrated by decreased word list generation are common. Less frequently, mild deficits in confrontational naming can be seen.

Answer 349

SLOW RECOVERY OF VOLTAGE-GATED SODIUM CHANNELS Rationale: The mechanism of action that carbamazepine, lamotrigine, phenytoin, topiramate, valproic acid, and zonisamide share is slow recovery of voltage-gated sodium channels.

Answer 350

CT ANGIOGRAPHY OF THE NECK Rationale: The patient describes an episode of transient monocular vision loss (amaurosis fugax). Given the patient’s multiple vascular risk factors, the most likely etiology is carotid artery stenosis and therefore, vascular imaging to assess for stenosis should be undertaken. Given the patient’s age, cardioembolism is certainly possible but carotid stenosis tends to be a more likely etiology. The history is not consistent with giant cell arteritis as there are no progressive loss of vision, headache, jaw pain or constitutional symptoms, so analysis of erythrocyte sedimentation rate is not likely to help. While a dilated eye exam may show evidence of ischemia, it would not reveal the cause of the ischemia.

Answer 351

PREGABALIN Rationale: Diabetic sensorimotor neuropathy, defined as a distal axonal neuropathy, is the most common type of polyneuropathy and can be associated with autonomic features as well as pain. Improved glycemic control can prevent progression but is not effective at controlling pain. There is level A evidence recommending pregabalin for symptomatic treatment of pain.

Answer 352

CARDIOMYOPATHY Rationale: Cardiomyopathy is the most common cause of death associated with Friedreich ataxia. Pneumonia or urosepsis may occur but are not as common as a cause of death. Seizures, malignant hyperthermia, and diaphragmatic weakness are not characteristics of this disease.

Answer 353

GLUCOCORTICOIDS Rationale: The most appropriate management for natalizumab-induced progressive multifocal leukoencephalopathy (PML) is discontinuation of the medication and initiation of plasma exchange. Treatment can restore immunocompetence but result in immune reconstitution inflammatory syndrome (IRIS), characterized by acute neurologic deterioration and brain edema that occurs 3 to 6 weeks after stopping natalizumab. The optimal treatment for IRIS is high-dose glucocorticoids followed by a slow taper.

Answer 354

HOLOPROSENCEPHALY Rationale: This image shows cyclopia with a fused single eyeball and a superior proboscis. Cyclopia occurs with midline cleavage defects, and clefting of the lip or palate is usually also present. Alobar holoprosencephaly is also part of this spectrum of midline cleavage abnormalities with a single globular hemisphere, a single ventricle, and fused basal ganglia. The other conditions listed do not have an externally evident associated phenotype.

Answer 355

CARBIDOPA/LEVODOPA Rationale: This patient presents with dystonia affecting the lower extremities that becomes worse later in the day, consistent with a diurnal variation. The diagnosis is dopa-responsive dystonia, which is most commonly caused by a mutation in GTP cyclohydrolase (GCH1). As dopa-responsive dystonia in children can have a variable presentation, it is generally recommended that pediatric patients with a primary dystonia, as described in this patient with normal MRI and no history of delivery or pregnancy complications, first be given carbidopa/levodopa. These patients typically respond to low doses of levodopa and continue to respond to medication, even as adults. Although the other medications listed may treat dystonia, response to low doses of carbidopa/levodopa can aid in the diagnosis of dopa-responsive dystonia, may eliminate the need for multiple medications, and reduce side effects associated with polypharmacy. Because it is so sensitive to carbidopa/levodopa, higher doses of other agents can be avoided.

Answer 356

MIDDLE CEREBRAL ARTERY STROKE Rationale: Seizures in the newborn are most commonly symptomatic of an acute injury, either generalized or fragmentary. Acute arterial ischemic stroke in the newborn can manifest as transient focal seizures without associated hemiparesis, which is often delayed for a number of weeks. Encephalopathy would be characteristic of the other conditions listed and a greater likelihood of variously distributed weakness appearing as part of the initial presentation. More persistent seizures are likely as well.

Answer 357

NEUROSARCOIDOSIS Rationale: Neurologic involvement can occur in 5% to 10% of patients with sarcoidosis, with manifestations such as motor and sensory deficits, progressive visual loss, and cranial nerve palsies. Cognitive impairment can range from mild memory loss to progressive dementia. Sarcoidosis appears to have a predilection for the hypothalamus and basal forebrain, resulting in hypopituitarism, hyperphagia, and hypersomnolence.

Answer 358

MELATONIN Rationale: This patient most likely has REM sleep behavior disorder, characterized by vivid dreams and abnormal motor activity during REM sleep. This disorder is seen most commonly in concert with parkinsonism. Melatonin is recommended for an initial therapeutic trial to treat the sleep disorder; clonazepam may also be effective as a first-line therapy.

Answer 359

POSTGANGLIONIC SYMPATHETIC AXONS Rationale: The QSART quantitatively assesses postganglionic sympathetic sudomotor axons and sweat gland functions. The response has a usual onset latency of 1 to 2 minutes. There is no significant difference when sides are compared in normal individuals.

Answer 360

BLOCKAGE OF CSF FLOW Rationale: The image shows cerebellar tonsillar herniation with associated syringohydromyelia, a disorder that occurs in approximately half of patients with Chiari type I malformations. Syrinx formation is believed to occur as a result of craniospinal pressure dissociation due to blockage of CSF flow in the subarachnoid space at the level of the foramen magnum. This leads to pressure backup into the venous system, with initial engorgement of the Virchow-Robin spaces. The excess fluid then dissipates into the substance of the spinal cord leading to spinal cord edema. As fluid accumulates beyond the resorption power of the parenchyma, it dissipates into and dilates the central canal, leading to syrinx formation.

Answer 361

MENIERE DISEASE Rationale: Episodic vertigo associated with progressive hearing loss and tinnitus is most compatible with Ménière disease, a syndrome felt to be due to endolymphatic hydrops. Superior semicircular canal dehiscence is a variant of perilymphatic fistula and is characterized by sound, pressure-induced vertigo, and oscillopsia. About 50% of patients have autophony (hearing one’s own voice unusually loudly, or even hearing one’s heartbeat or eye movements). A diagnosis of vestibular migraine requires that International Headache Society criteria for migraine be met, in addition to episodic or fluctuating symptoms suggestive of a balance disorder. Migraine symptoms should occur during, or in temporal relation to, episodes of vertigo or imbalance with no other explanation for these symptoms. Vestibular neuronitis typically causes a monophasic prolonged episode of vertigo and would not be associated with the recurrence and progressive hearing loss of Ménière disease. Vestibular schwannoma should be considered in any patient with progressive unilateral hearing loss, as in this patient, though the episodic vertigo described in this patient would be less typical for vestibular schwannoma

Answer 362

REPRODUCTION OF SYMPTOMS Rationale: Tilt-table testing confirms a diagnosis only if a patient’s syncopal or presyncopal symptoms are reproduced along with hypotension and/or bradycardia. Therefore, a combination of subjective and objective signs is required

Answer 363

NEUROCYTOMA Rationale: The lesion shows cortical thickening and in the context of a chronic seizure disorder would most likely represent focal cortical dysplasia (FCD) type II in the Palmini classification. Type I FCD does not show this radiographic abnormality. The other tumors listed are also associated with seizures but are likely to show progression over a 21-year span. This image is not typical, particularly with the lack of contrast enhancement, which is characteristic of these tumors.

Answer 364

EXPLAIN THAT AN ORGAN PROCUREMENT ORGANIZATION WILL CONDUCT AN EVALUATION Rationale: Organ donation most commonly occurs in the context of severe brain injury and brain death. Public awareness and support of organ donation and transplant have increased in the last decade. As a result, families often recognize that the patient’s circumstances may be such that organ donation is a possibility. The family’s request is not illegal, nor does it indicate they are inappropriate decision makers for the patient because the patient has previously indicated the desire to be an organ donor. Although it usually is considered improper for physicians to raise the topic of organ donation with family members before brain death has been determined, it is proper to respond to family requests about organ donation whenever they are made. Organ donation can occur even for “coroner’s cases,” as a coroner can be in the operating room at the time organs are removed for transplant. Because patients must be evaluated for medical suitability for organ donation, and because conversations with families about organ donation require considerable skill, physicians should work closely with representatives of organ procurement organizations when organ donation is considered a possibility.

Answer 365

GUANOSINE TRIPHOSPHATE CYCLOHYDRASE Rationale: Segawa disease is a dopa-responsive dystonia that predominantly results from a mutation in the gene that encodes guanosine triphosphate cyclohdrase I (GTPCH). GTPCH is an enzyme involved in the synthesis of the biopterins, essential cofactors in the synthesis of the neurotransmitters dopamine and serotonin. A deficiency of GTPCH is one of several pediatric neurotransmitter disorders that affect the synthesis of dopamine and serotonin. The others are tyrosine hydroxylase deficiency, aromatic L-amino acid decarboxylase deficiency, and sepiapterin reductase deficiency. Sepiapterin reductase deficiency can also produce a dopa-responsive dystonia. In this disorder, CSF demonstrates a low level of BH4 and an accumulation of dihydrobiopterin and sepiapterin. Succinic semialdehyde dehydrogenase deficiency affects GABA metabolism and is also included as a pediatric neurotransmitter disorder. Dopamine beta-hydroxylase converts dopamine to norepinephrine. The clinical syndrome resulting from a deficiency of this enzyme includes severe orthostatic hypotension and hypotonia but not dystonia.

Answer 366

MEPERIDINE Rationale: This patient has multifocal myoclonus, most likely secondary to opioid therapy. Meperidine is particularly prone to produce neuro-excitatory effects due to the activity of the neurotoxic metabolite, normeperidine. For this reason, meperidine should be avoided as long-term analgesic therapy.

Answer 367

restarting the fingolimod within 6 hours of first-dose cardiac monitoring then resuming her usual daily dose Rationale: Fingolimod is one of the robust disease-modifying drugs for multiple sclerosis. Because of its potentially fatal cardiac complications, careful cardiac monitoring along with other standard blood testing is necessary. Similarly, first-dose cardiac monitoring is also indicated if fingolimod therapy is interrupted for more than 2 weeks.

Answer 368

synaptic potentials in pyramidal cortical neurons Rationale: The electrical fields that generate EEG signals are the result of inhibitory and excitatory postsynaptic potentials (IPSPs and EPSPs) on the apical dendrites of cortical neurons. Pyramidal neurons contribute to the plurality of the signal.

Answer 369

pimavanserin Rationale: Pimavanserin is the only FDA-approved medication for treatment of psychosis associated with Parkinson disease. Clozapine, haloperidol, quetiapine, and risperidone have been used for this purpose. Haloperidol, quetiapine, and risperidone can increase extrapyramidal symptoms due to dopamine antagonism.

Answer 370

ANTIBIOTICS ONLY Rationale: Antibiotic therapy is the mainstay of medical treatment for ischemic stroke occurring as a complication of embolism from bacterial endocarditis. There is no established role for antiplatelet agents or anticoagulants in the treatment of ischemic stroke occurring as a complication of embolism from bacterial endocarditis.

Answer 371

ONION BULB FORMATION Rationale: This image shows onion bulb formation, a development that results from repeated episodes of demyelination and remyelination. Onion bulbs are especially conspicuous in hypertrophic Charcot-Marie-Tooth disease, Dejerine-Sottas disease and Refsum disease. Approximately one half of patients with chronic inflammatory demyelinating polyradiculoneuropathy also show variable numbers of onion bulbs.

Answer 372

DECREASED HEMOGLOBIN WITH ELEVATED MEAN CORPUSCULAR VOLUME Rationale: Vitamin B12 deficiency may cause combined system degeneration affecting posterior columns and lateral corticospinal tracts. Dementia and peripheral neuropathy may also be seen. Decreased hemoglobin and elevated mean corpuscular volume are compatible with a macrocytic anemia that may be a hematologic manifestation of vitamin B12 deficiency. Copper deficiency may also cause a myeloneuropathy similar to subacute combined degeneration from B12 deficiency. The serum copper level would be decreased. In hypothyroidism, the relaxation phase of reflexes is prolonged; the reflexes are not hyperactive. Elevated bilirubin and alkaline phosphatase are found in liver disease and may contribute to hepatic encephalopathy but would not explain the full constellation of symptoms seen here.

Answer 373

DEMYELINATING DISEASE Rationale: The elongated lesion demonstrating hyperintensity on the T2-weighted image shown is most consistent with multiple sclerosis (MS) and represents focal demyelination. Degenerative myelomalacia may have these signal characteristics and ill-defined margins, but there is no adjacent spurring or other degenerative bony disease to have caused this problem. Ependymoma would be seen as a more focal mass with cord enlargement. Syrinx has well-defined cavity margins, although it would have a signal intensity similar to the lesion pictured. The lesion in a vitamin B12 deficiency involves the dorsal columns and lateral corticospinal tracts. MS cord lesions are usually one to two segments, or less, in length.

Answer 374

SPINOCEREBELLAR ATAXIA Rationale: The MRI scan shows no features of either Chiari type I or II malformation. Olivopontocerebellar atrophy (OPCA) would typically also demonstrate more prominent pontine atrophy as well. There is no history of phenytoin use.

Answer 375

SEGMENTAL ARTERIAL NARROWING Rationale: This patient presents with a secondary thunderclap headache syndrome in association with multifocal neurologic deficits. After several days of headache, an aneurysmal subarachnoid bleed should be detectable by lumbar puncture, brain CT, or brain MRI. Carotid artery dissection is unlikely in the absence of neck pain and in the presence of multifocal deficits not confined to a single arterial territory. Similarly, the multifocal nature of the presentation and the absence of parenchymal blood makes a vascular malformation unlikely. Cortical vein thrombosis is typically associated with parenchymal hemorrhage, seizure, or acute stroke on MRI, and is therefore also unlikely. This patient’s presentation is most consistent with diffuse cerebral vasoconstriction syndrome, which has been associated with the use of SSRIs and vasoactive drugs. The likely finding on cerebral catheter or MR angiography is segmental arterial narrowing, which is usually reversible over time.

Answer 376

IMMUNE RECONSTITUTION INFLAMMATORY SYNDROME Rationale: Treatment of HIV with combination antiretroviral therapy sometimes results in transient paradoxical worsening of infectious processes, a disorder known as immune reconstitution inflammatory syndrome (IRIS). The rapid dysregulated restoration of the immune system in these patients with resultant worsening of active or subclinical infectious processes is often seen in the setting of infection by intracellular pathogens such as mycobacteria (tuberculous and non-tuberculous), Cryptococcus, cytomegalovirus, herpes simplex virus, varicella zoster virus, and JC virus. The inflammatory reaction usually is self-limited but occasionally may be severe enough to result in long-term sequelae and fatal outcomes. This patient has progressive multifocal leukoencephalopathy (PML), as CSF testing was positive for the JC virus, the causative agent of PML on PCR testing.