Life Long Learning in Neurology - part 5 pps

74 and OPMD typically causes ptosis, ophthalmoplegia without diplopia, and dysphagia. Ptosis and facial weakness would not be typical of acid maltase deficiency or EDMD. 11. A 5-year-old girl is diagnosed with dermatomyositis after a 3-month period of difficulty walking, difficulty arising from a chair, and the development of a characteristic rash. She states that her knees and ankles hurt, and her parents note that she has been walking on her toes. In addition to the symptoms mentioned, which of the following is more likely to be found in this child than in an adult with the same disorder? A. Elevated creatine phosphokinase (CPK) levels B. Malignancy C. Cutaneous calcinosis D. Cardiac conduction defect E. Increased mortality Correct Answer: The correct answer is C. In dermatomyositis, CPK levels may or may not show elevation in adults or children and have little correlation with the degree of disease activity. Malignancy has not been found to be associated with dermatomyositis in childhood, whereas cardiac conduction defects and other electrocardiogram abnormalities can be found across the age spectrum. Increasing age confers a higher degree of mortality. Subcutaneous calcifications, described as painful and occurring at pressure points, are more common in juvenile dermatomyositis than adult onset-cases. 12. An 8-year-old boy with myalgia and exercise intolerance says that he can generally walk as far as he wants on level ground, but within minutes of trying to run, climb a steep hill, or swim he develops painful cramps and muscle swelling. If he immediately stops exerting himself and rests briefly, he can resume the activity. Which of the following is the most likely diagnosis? A. Acid maltase deficiency B. Carnitine palmitoyltransferase II (CPT II) deficiency C. Myoadenylate deaminase (MADA) deficiency D. Myophosphorylase deficiency (McArdle's disease) E. Myotonic dystrophy, type 1 (DM1) Correct Answer: The correct answer is D. Myophosphorylase deficiency typically presents in childhood with painful cramps and muscle swelling that begin shortly after intense exertion, and patients usually describe a "second-wind phenomenon" whereby they can rest briefly after the cramps begin and then resume the previous activity. This is thought to be due to increased utilization of free fatty acids. In contrast, patients with CPT deficiency have defective utilization of free fatty acids and do not experience the second-wind phenomenon. It remains controversial whether MADA deficiency causes muscle pain and fatigue (or whether it is an incidental finding in patients with these symptoms), but the reported cases have involved patients who presented in late adolescence to middle age. Acid maltase deficiency and myotonic dystrophy are not associated with exertional muscle pain and swelling. 13. Which of the following syndromes is sometimes caused by dystrophin deficiency? A. Cataracts with normal muscle function B. Intermittent head drop C. Isolated myotonia D. Isolated quadriceps myopathy E. Oculopharyngeal weakness Correct Answer: The correct answer is D. Mutations of the dystrophin gene have been demonstrated in a small number of patients whose only clinical manifestation was a mild, slowly progressive myopathy confined to the quadriceps muscle. Dystrophin deficiency has not been associated with any of the other syndromes listed. 14. A 12-year-old boy is brought to the physician after he noted a problem participating in sports, which began about 3 months earlier. While playing soccer, he noted difficulty at the beginning of a game chasing a ball or running to receive a pass. After about 15 minutes, improvement would occur. His coach attributed his performance to poor conditioning and recommended that he run sprints. When seen by the physician, he is a normal-appearing boy with normal muscle development and strength. However, when asked to grip the examiner's hand, he has trouble relaxing his grip. When asked to repeat this maneuver several times, his function improves. What is the most likely genetic defect causing this problem? A. Point mutation in a sodium channel gene B. Deletion in a sodium channel gene C. Point mutation in a chloride channel gene D. Point mutation in a potassium channel gene E. Deletion in a chloride channel gene 75 Correct Answer: The correct answer is C. The phenotype described is myotonia congenita, autosomal recessive type (as evidenced by later onset) caused by a point mutation at a muscle chloride channel gene CLCN1 (chromosome 7q35). 15. Current literature suggests approximately what percentage of patients who develop weakness or substantial elevations of CPK on statin therapy? A. 20% B. 10% C. 5% D. 1% E. 0.1% Correct Answer: The correct answer is D. These symptoms are consistent with myopathy rather than myalgias. 16. In a normal individual, the forearm ischemic lactate test would be expected to produce which of the following results? A. Increase (threefold to fivefold) in ammonia, increase (threefold to fivefold) in lactate B. Increase (threefold to fivefold) in ammonia, no change in lactate C. No change in ammonia, increase (threefold to fivefold) in lactate D. No change in ammonia, increase (less than twofold) in lactate E. No change in ammonia, no change in lactate Correct Answer: The correct answer is A. The physiological response to the forearm ischemic lactate test in a normal individual is a threefold to fivefold rise above baseline in both lactate and ammonia. A rise in lactate without a rise in ammonia is diagnostic of myoadenylate deaminase (MADA) deficiency. A variety of defects in the glycolytic chain result in a rise in ammonia without a rise in lactate. 17. A 65-year-old man comes to the physician because of a progressive problem with walking, which he believes has been going on about 1 year. In the past he noted some difficulty getting up from a chair; more recently, on several occasions his left leg buckled, and he fell once. He has a history of mild low back pain when walking attributed to spinal stenosis and non-insulin dependent diabetes mellitus, which is controlled. His muscles do not hurt. On physical examination, there is left quadriceps atrophy and mild right forearm atrophy on the volar aspect. Knee extension is 2/5 on the left as is wrist flexion on the right. The left patellar reflex is present but depressed; the right is normal. Serum CPK is normal. Inclusion body myositis is clinically suspected. Which of the following findings would be most consistent with that diagnosis? A. Positive antinuclear antibody B. Concurrent interstitial lung disease C. Rimmed vacuoles and amyloid deposition within muscle fibers on biopsy D. Macrophage invasion of muscle fibers E. Presence of membrane attack complex deposition on small blood vessels Correct Answer: The correct answer is C. IBM is an inflammatory disease whose histopathological findings include mononuclear cell invasion of nonnecrotic muscle fibers, rimmed vacuoles within muscle fibers, and intracytoplasmic or intranuclear amyloid deposits on Congo red staining or tubulofilamentous inclusions on electron microscopy. Macrophages are found in the inflammatory infiltrate of IBM as well as polymyositis, dermatomyositis, and in muscular dystrophies. Membrane attack complexes on small blood vessels are appreciated in dermatomyositis. A positive antinuclear antibody may be seen in association with any inflammatory myopathy and is therefore not specific. 18. A 58-year-old woman was found to have a serum CK level twice the upper limit of normal in the course of an "executive physical" and laboratory screening. She has no history of medical illness and denies any weakness or pain. Physical examination is normal. What additional test should be ordered? A. EMG B. No test necessary C. Serum carnitine D. Serum lactate E. Urine myoglobin Correct Answer: The correct answer is B. It is extremely unusual for a slight (threefold or less) elevation in serum CK to be associated with an underlying myopathy in the absence of pain or objective weakness. 19. A 3-year-old boy is brought to the physician for weakness that was noted in the first year of life. Recently his parents became concerned when he was playing outside in the snow and then found that he was unable to swallow or talk for a few hours. On physical examination, percussion over the thenar eminence produces a prolonged contraction of the finger flexors. Which of the following is associated with this condition? A. Warm-up phenomenon 76 B. Prominent muscle pain C. Chloride channel abnormality D. Family history of this problem in a parent E. Abnormal nerve conduction velocities Correct Answer: The correct answer is D. Paramyotonia congenita, which is cold sensitive, is an autosomal dominant channelopathy caused by a point mutation in a voltage-gated sodium channel gene. In contrast with myotonia congenita, the warm-up phenomenon is not present. Muscles can be stiff, but myalgias are uncommon. Routine nerve conduction studies are unrevealing. 20. Which of the following agents had by far the greatest incidence of fatal rhabdomyolysis? A. Lovastatin B. Simvastatin C. Atorvastatin D. Cerivastatin E. Pravastatin Correct Answer: The correct answer is D. Cerivastatin (Baycol) was withdrawn from the market. 21. All of the following should be avoided as muscle biopsy sites except: A. A muscle recently studied by needle EMG B. A muscle with Medical Research Council (MRC) grade 2 strength C. A muscle with MRC grade 5 strength D. The gastrocnemius muscle E. The vastus lateralis muscle Correct Answer: The correct answer is E. For practical purposes, the vastus lateralis is the best choice of muscle to biopsy in the lower extremities. The gastrocnemius should be avoided because its tendon insertion extends throughout the muscle, which may lead to difficulty with interpretation. Muscles that are severely weak (MRC grade 3 or less) should not be sampled because they are likely to show only nonspecific "end stage" changes. Histopathological abnormalities may not be evident in muscles that are clinically normal (MRC grade 5). Needle insertion can cause artifacts, so muscles recently studied by needle EMG should be avoided. 22. In a 3-year-old boy previously diagnosed with Duchenne muscular dystrophy (DMD) based on typical clinical features and a positive family history, which of the following would be a reason to doubt the diagnosis? A. Areflexia B. Large quadriceps muscles C. Normal CK levels D. Normal motor nerve conduction studies E. Recent improvement in motor function Correct Answer: The correct answer is C. The serum CK level is always more than 10 times the upper limit of normal in the first 3 years of life in children with DMD; if the level is lower than that, the diagnosis should be questioned. Early in the course of DMD, nerve conduction studies are normal. Although "pseudohypertrophy" is most likely to affect calf muscles, it can sometimes occur in quadriceps, gluteal, deltoid, and other muscles. Reflexes are typically reduced or absent in patients with DMD. Between 3 and 6 years of age, there may be some evidence of transient improvement, presumably because the pace of normal development temporarily outstrips the pace of disease progression. 23. The diagnosis of primary myopathic carnitine deficiency is typically based on which of the following? A. Muscle biopsy B. Hepatic carnitine levels C. Nerve conduction studies D. Serum carnitine levels E. Serum CK levels Correct Answer: The correct answer is A. Primary myopathic carnitine deficiency by definition has normal liver and serum carnitine levels. This is a rare disorder, which can only be diagnosed by muscle biopsy. Muscle pathology reveals abnormal accumulation of lipids; muscle carnitine levels are less than 2% to 4% of normal. Nerve conduction studies are normal. Serum CK is often normal, but it may be elevated; this is a nonspecific abnormality. 24. A 65-year-old diabetic man is seen by a physician for a 4-month history of difficulty walking, with his right leg tending to buckle when he stands. He is followed over several months and then develops difficulty with the other leg, as well as difficulty using his hands. He has no complaints of pain or cramps. Myopathic changes are seen on EMG, and a muscle biopsy shows, among several features, endomysial inflammation with invasion of nonnecrotic muscle fibers. A diagnosis of polymyositis (PM) is made, and he is treated with prednisone, starting at 80 mg daily 77 and tapered to 20 mg daily over 6 months. However, he fails to make much improvement on this regimen. CPKs showed a twofold elevation from normal prior to treatment and have not changed after 6 months. What is the most likely cause of the treatment failure? A. Prednisone tapered too rapidly B. Secondary steroid-induced myopathy C. Superimposed neuropathy D. Probable missed inclusion body myositis (IBM) E. Muscles too necrotic Correct Answer: The correct answer is D. Failure to respond to a fairly vigorous course of immunosuppressive treatment-in this case prednisone-suggests a possible diagnosis of IBM (PM and DM can occasionally be poorly responsive to prednisone; this does not in and of itself exclude an autoimmune myositis). Both PM and IBM can show endomysial inflammation of nonnecrotic muscle fibers. High elevations of CPK (greater than 10-fold of normal) are characteristic of PM but not of IBM. A steroid-induced myopathy is unlikely given the pattern of both distal and proximal weakness. 25. A 5-year-old girl is brought to the physician for an episode of weakness and difficulty getting out of bed. Her physician has been watching her closely for a few years for any signs of motor problems because her father and older brother both have a history of episodes of muscle weakness. One week prior to her appointment, she had a viral infection, went to bed without eating much, and then awakened the next day and was unable to arise from bed. Her mother attributed this to the "flu," and the child improved. However, she continued to complain of sore muscles and was brought to the doctor. On examination, she is a normal-appearing child with normal intelligence, normal motor development, strength, and reflexes. A genetic cause-a mutation in sodium channel gene SCN4A-is found. Which of the following problems is also linked to a mutation in this gene? A. Paramyotonia congenita B. Myotonia congenita C. Hypokalemic periodic paralysis (hypoPP) D. Andersen-Tawil syndrome E. Thyrotoxic periodic paralysis Correct Answer: The correct answer is A. Although paramyotonia congenita and hyperkalemic periodic paralysis (hyperPP) have a common abnormal gene, the point mutations identified are different. Phenotypically, however, many patients with hyperPP have myotonia, and patients with paramyotonia congenita can have periodic paralysis. The other disorders listed have involvement of different genes: CLCN1 (myotonia congenita), CACNL1S (most common mutation in hypoPP), KCNJ2 (Andersen-Tawil syndrome), except for thyrotoxic periodic paralysis, for which the genetic basis is not known. 26. A 7-year-old girl had been healthy and exhibited normal developmental milestones until age 3, when she began to complain of fatigue after running. At age 5, she suddenly said that she couldn't see anything shortly after running a race. The symptoms resolved within an hour, but she had two similar episodes over the next few months. Her family thought she was just making excuses not to compete but grew concerned when she began having unprovoked episodes of weakness on the left side of her body associated with headaches, nausea, and vomiting, typically lasting 12 hours or less. They brought her to the ED when one episode failed to resolve after 2 days. Examination revealed diffuse proximal weakness with superimposed left hemiparesis. A head CT scan showed hypodensities in the right parietal and left occipital lobes, and MRI showed increased signal on T2 and diffusion- weighted imaging sequences but normal apparent diffusion coefficient (ADC). Which of the following serum abnormalities is most likely? A. Increased glucose B. Increased lactate C. Reduced ammonia D. Reduced carnitine E. Reduced potassium Correct Answer: The correct answer is B. The mild proximal weakness and recurrent episodes of strokelike symptoms are typical of MELAS (mitochondrial encephalomyopathy, lactic acidosis, and strokelike episodes). As the name implies, lactic acidosis is characteristic of this disorder. 27. A 75-year-old man who had been on simvastatin therapy for 2 years comes to the physician because of muscle aches and pains for 2 months. He has a history of coronary artery disease with a previous myocardial infarction. Atenolol and a daily 81-mg aspirin have also been prescribed. On physical examination, shoulder girdle muscles are tender to palpation. Reflexes are normal. Serum CPKs are normal. The patient agrees to enter a research study regarding statins, and his drug therapy is stopped. He is then restarted on either a statin or a placebo in 3 months. He undergoes a muscle biopsy, which shows lipid-filled vacuoles in muscle fibers without evidence of 78 macrophages. When the study is unblinded, he is found to have been placed back on active drug. Based on this evidence, the researchers implicated which of the following in this patient's myopathy? A. Mitochondrial respiratory chain dysfunction B. Inflammatory infiltration of muscle C. Age-related degeneration of myofiber D. Elevated mevalonate levels E. Hydrophilicity of statin agent Correct Answer: The correct answer is A. The cause of toxicity to muscle caused by statins is not known, although several leading theories are discussed by the authors. In a small study similar to the scenario presented above, deposition of lipids without evidence of inflammation was found in muscle biopsies, suggesting a metabolic/mitochondrial-based etiology. Low mevalonate levels are believed to be causative of statin-induced myopathy; limited evidence implicates the more lipophilic agents over hydrophilic ones in causing muscle problems. 28. A 40-year-old man is referred to a physician for continued workup after being treated in the ED for an episode of diffuse weakness the week before. In the ED, a random check of electrolytes revealed serum potassium of 1.7 mEq/L during the episode; intravenous potassium was given, and he recovered. There is no family history of a similar problem. The patient is a nonsmoker and nondrinker who exercises frequently. In the 3 months leading up to this attack, he had noticed a 15-lb weight loss despite eating normally. He also had complained to his primary care physician of feeling "shaky and sweaty all over." This was attributed to anxiety. On physical examination, he is a thin man who is somewhat restless and perspiring. Vital signs are: blood pressure 130/70, P-115 R-15 afebrile. Neurological examination is unremarkable except for a fine tremor with the hands outstretched. Strength and reflexes are normal. Which of the following preliminary treatments is an appropriate measure for this patient at this juncture? A. Beta blockers B. Acetazolamide C. Thiazide diuretics D. Oral potassium E. Corticosteroids Correct Answer: The correct answer is A. The patient described has thyrotoxic periodic paralysis with a clinical attack of weakness identical to that seen in hypokalemic periodic paralysis. The condition is believed to possibly be linked to a genetic susceptibility and is seen, in contrast to hyperthyroidism without periodic paralysis, more commonly in males. Definitive treatment is ablation of the overactive thyroid, but stabilizing treatment includes beta blockers. Acetazolamide and the other treatments mentioned, except for potassium, are ineffective in the setting of acute weakness. 29. Cardiac conduction defects are least likely in which of the following conditions? A. Duchenne muscular dystrophy (DMD) B. Emery-Dreifuss muscular dystrophy (EDMD) C. Myotonic dystrophy, type 1 (DM1) D. Myotonic dystrophy, type 2 (DM2) E. Oculopharyngeal muscular dystrophy (OPMD) Correct Answer: The correct answer is E. Cardiac conduction defects are common in DMD, EDMD, DM1, and DM2; they are not typical of OPMD. 30. A 55-year-old woman is referred to a physician because of a 3-month history of weakness. She reports particular difficulty in combing her hair, changing a light bulb, and going up stairs. Physical examination reveals symmetrical weakness in pectoral muscles and hip flexors. Inspection reveals a purplish discoloration over the eyelids, and a clinical diagnosis of dermatomyositis (DM) is made, confirmed by EMG and muscle biopsy. She is treated with high-dose prednisone and responds well with improvement in symptoms, but predictably she develops weight gain and elevated blood sugars. Her physician decides to initiate treatment with methotrexate, 7.5 mg weekly. The presence of which of the following would preclude the use of this treatment in DM? A. Elevated CPKs B. Membrane attack complex C. Anti-Jo-1 antibodies D. Anti-Mi-2 antibodies E. Antinuclear antibody Correct Answer: The correct answer is C. Elevated CPKs are characteristic of DM, as is identification of membrane attack complex on histopathological studies. Anti-Mi-2 antibodies may be present and generally occur in patients with a more rapid and florid onset and subsequent good response to therapy. Conversely, anti-Jo-1 antibodies are 79 associated with interstitial lung disease; since methotrexate can cause pulmonary fibrosis, it is not recommended in patients with anti-Jo-1 antibodies. 31. Which of the following is the most common cause of recurrent myoglobinuria in adults? A. Carnitine palmitoyltransferase II deficiency (CPT II) B. Lactate dehydrogenase (LDH) deficiency C. Limb-girdle muscular dystrophy (LGMD) D. Myotonic dystrophy, type 1 (DM1) E. Phosphofructokinase (PFK) deficiency Correct Answer: The correct answer is A. Adult CPT II deficiency is the most frequent cause of recurrent myoglobinuria. Myoglobinuria occurs less frequently in PFK deficiency than it does in myophosphorylase deficiency. Myoglobinuria is typical of LDH deficiency, but LDH deficiency is rare. Myoglobinuria is not a typical feature of DM1 or LGMD. 32. A 25-year-old man has noted progressively deteriorating strength over the past 5 years. Even before that, his hands had a tendency to stiffen up when he was trying to turn a door knob. He also had difficulty relaxing his grip when opening cans. His examination is notable for bilateral cataracts, a long face, wasting of the temporalis muscles, a thin neck, distal weakness and atrophy in all four limbs, and sustained contraction after percussion of the thenar eminence. He most likely has a condition that has which of the following patterns of inheritance? A. Autosomal dominant B. Autosomal recessive C. Maternally inherited D. Nonhereditary E. X-linked recessive Correct Answer: The correct answer is A. This patient has typical features of DM1, which has an autosomal dominant pattern of inheritance, with variable penetrance. 33. A 9-year-old boy began having generalized tonic-clonic seizures, and a few months later he began to experience involuntary jerking movements of the neck and limbs. Valproic acid was started for presumed juvenile myoclonic epilepsy. Several months later, he developed diffuse weakness. His treatment was changed from valproic acid to topiramate, and he was placed on carnitine, but the weakness progressed and his performance in school began to deteriorate. Examination reveals diffuse weakness, atrophy, gait ataxia out of proportion to weakness, myoclonus, and bilateral hearing loss. The boy's 13-year-old sister recently developed myoclonus and generalized tonic-clonic seizures. They have no other siblings. Their 34-year-old mother was recently diagnosed with limb-girdle muscular dystrophy (LGMD) because of a 5-year history of slowly progressive proximal weakness, and their 29-year-old maternal uncle has been having more and more trouble climbing stairs and lifting objects for the past 3 years but refuses to see a doctor. A muscle biopsy would be most likely to show which of the following? A. Abnormal accumulation of lipids on oil red O stain B. Absence of staining with antidystrophin antibodies C. Absence of staining with antiemerin antibodies D. Increased deposition of PAS-positive material E. Ragged red fibers on modified-Gomori trichrome stain Correct Answer: The correct answer is E. This patient has myoclonus, epilepsy, ataxia, cognitive deterioration, and hearing loss, all of which are features of the clinical syndrome of MERRF (myoclonic epilepsy and ragged red fibers). This patient's family history is consistent with maternal inheritance, as would be expected with MERRF. Ragged red fibers are characteristic of this condition (and other mitochondrial disorders). Lipid accumulation on oil red O staining is characteristic of disorders of lipid metabolism, and PAS-positive deposits are characteristic of disorders of glycogen metabolism. Antidystrophin staining is used to diagnose dystrophinopathies, and antiemerin staining is used to diagnose EDMD. 34. Intravenous immunoglobulin (IVIG) has been used in the treatment of refractory myositis. Which of the following statements concerning IVIG and muscle disease is true? A. It is an effective monotherapy. B. It is effective in myotonic dystrophy. C. Systemic side effects are rare. D. Inclusion body myositis responds to IVIG. E. It predisposes to diabetes. Correct Answer: The correct answer is B. The authors state that IVIG has been studied in DM in at least one small prospective trial and found to be effective and muscle biopsies are improved. IBM is poorly responsive to the 80 therapy. Monotherapy with IVIG in inflammatory muscle disease is not recommended. Systemic side effects are, in fact, common, although there is no relationship to diabetes. 35. A 23-year-old man has had gradually progressive weakness of the shoulder girdle for the past 5 years. Examination reveals a pouting appearance, a transverse smile, inability to whistle, weakness of eye closure, pectoral muscle atrophy resulting in axillary creases, scapular winging, and atrophy of the biceps and triceps muscles with relative sparing of deltoid and distal upper extremity muscles. Lower extremity muscles are strong. CK levels are only mildly elevated, and EMG shows nonspecific myopathic features. Which of the following abnormalities is most likely in this patient? A. Deletion of D4Z4 repeats B. Expansion of trinucleotide CTG repeats C. Insertion in the dystrophin gene D. Point mutation in the calpain-3 gene E. Substitution (A to G) in the dysferlin gene Correct Answer: The correct answer is A. This patient has typical features of facioscapulohumeral dystrophy (FSHD). Current methods for DNA testing of FSHD are highly specific and (in patients with a typical phenotype) sensitive. They demonstrate deletions of an integral number of 3.3 kilobase repetitive elements known as D4Z4 repeats (on chromosome 4q35). These repeats do not contain expressed DNA; the deletions are thought to alter chromosomal structure and influence the expression of one or more genes elsewhere on the chromosome. 36. A 45-year-old man was diagnosed with MERRF based on clinical features and muscle biopsy. Which of the following relatives is at risk for developing the disease? A. His brother's son B. His daughter C. His daughter's son D. His sister's daughter E. His son's daughter Correct Answer: The correct answer is D. MERRF is caused by mutations in mitochondrial tRNA, so it is maternally inherited. This man's mother must have had the mutation and transmitted it to him and all of his siblings. Because it is maternally inherited, he and his brother cannot transmit it to their children, but his sister can transmit it to her children. 37. A 30-year-old man is seen in the ED for an episode of weakness that began when he awakened that day. He had been followed by a physician since his teenage years for spells of weakness that occurred primarily in the morning. Medical history was significant for alcohol abuse. On the day prior to presenting to the ED, he recalled drinking a 12-pack of beer. His physician had prescribed "two pills," which he had not been taking. On examination when first seen in the ED, he is profoundly weak in all four limbs and areflexic; he is then given an electrolyte infusion and recovers strength and reflexes over a few hours. Without treatment, what is the most likely outcome of this disease? A. Eventual muscle atrophy and distal weakness B. Failure of respiratory muscles and death C. Decreasing severity of attacks with age D. Death from cardiac arrest E. Dysphagia with aspiration Correct Answer: The correct answer is C. HypoPP, the most common of the periodic paralyses, occurs later in life than the hyperkalemic type. Attacks, which may include alcohol as a trigger, tend to mitigate with age. Permanent weakness is not common and is typically proximal in distribution; respiratory and pharyngeal involvement is possible in severe attacks but is not the rule. Cardiac arrest can occur in the setting of profound hypokalemia (of any cause) but would be considered to be rare. 38. A 65-year-old woman is sent to the physician after developing weakness and muscle pain approximately 6 months earlier. She notes difficulty in combing her hair and in arising from a chair. She describes a feeling of tenderness and pain when she massages her muscles. On physical examination, there is grade 4/5 weakness symmetrically of both shoulder abductors and hip flexors, and there is reflux of water upon trying to swallow. After a detailed evaluation, the patient is diagnosed with polymyositis (PM) and starts high-dose prednisone therapy. Her strength improves in approximately 4 months. After 1 year of therapy, she reports to her physician a gradual increase in difficulty climbing stairs and arising from a chair. On physical examination, she is cushingoid in appearance. Hip flexion in 3/5 bilaterally. Which of the following suggests a relapse of PM rather than a steroid- induced myopathy? A. Presence of pain in muscles B. Predominately proximal weakness C. Prednisone dose under 40 mg daily 81 D. Normal CPK level E. Abnormal spontaneous activity on EMG Correct Answer: The correct answer is E. Patients on long-term therapy for PM with prednisone may develop steroid-induced myopathies that, like the initial disease, can cause proximal weakness. These can be difficult to distinguish on clinical grounds (pattern of weakness or pain). Relapse of PM may cause an increase in serum CPK and would be more likely to show signs of muscle irritability on EMG. 39. A 13-year-old girl with normal birth and early development has had slowly progressive exercise intolerance, and her mother notes that she is tending to walk on her toes. The patient's father died of a cardiac arrest at age 35; he had also tended to walk on his toes. He had never complained of difficulty walking, but he had never been very physically active. The patient's examination reveals mild scapular winging and weakness of the biceps and triceps muscles bilaterally with incipient elbow contractures. Strength is relatively preserved in the deltoid and distal upper extremity muscles. Her distal leg muscles are weak, and she has contractures of the Achilles tendons. Serum CK levels are 3 times the upper limit of normal, and EMG shows mild myopathic features. Her electrocardiogram is normal. Genetic testing reveals a mutation in the lamin A/C gene. What further testing is necessary? A. Cardiac evaluation B. Cervical spine x-rays including flexion and extension views C. Glucose tolerance test D. Muscle biopsy E. MRI of the brain Correct Answer: The correct answer is A. This patient has typical features of EDMD, with an autosomal dominant inheritance pattern. This was confirmed by mutation analysis, so there is no need for a muscle biopsy. Because the cardiac involvement in EDMD is potentially fatal, patients with this condition should have their cardiac status evaluated even if they are asymptomatic and they have a normal electrocardiogram. There is no particular reason to screen with the other tests listed. 40. An 8-year-old girl began to complain of fatigue with exercise, and her parents had noticed that her eyelids were droopy for the past few months. Examination revealed bilateral ptosis, ophthalmoparesis, pigmentary retinopathy, bilateral hearing loss, mild proximal weakness, and ataxia. Serum CK and EMG were normal; spinal fluid protein was increased. Muscle biopsy showed ragged red fibers. Which of the following associated features is most likely? A. Cataracts B. Heart block C. Intestinal pseudo-obstruction D. Seizures E. Strokes Correct Answer: The correct answer is B. Progressive external ophthalmoplegia, pigmentary retinopathy, and onset before 20 years of age are characteristic features of Kearns-Sayre syndrome. Ataxia, mild proximal weakness, and sensorineural hearing loss are also common, and spinal fluid protein is usually elevated. The other classic feature is cardiac conduction block. NEURO-OTOLOGY Aug 2006 TYPE A QUESTIONS (ONE BEST ANSWER) 1. A 62-year-old man with history of diabetes and hypertension awoke one morning with a sensation of severe spinning, nausea, and vomiting. He was unable to stand or walk and had to crawl to the bathroom to vomit. He has no hearing loss. Upon evaluation in the emergency department, the patient has spontaneous horizontal-torsional nystagmus, with the fast phase toward the left side and more intense on left gaze. The nystagmus is greater when visual fixation is removed. Where is the most likely location of the lesion? A. Left labyrinthine inputs to left vestibular nuclei B. Right labyrinthine inputs to right vestibular nuclei C. Left vestibular nuclei D. Right vestibular nuclei E. None of the above Correct Answer: The correct answer is B. The patient has a peripheral nystagmus. The direction of the nystagmus indicates hypofunction of the right labyrinth or vestibular nerve carrying inputs from the semicircular canals to the ipsilateral vestibular nuclei. 2. A 43-year-old woman with history of migraine had an episode of acute-onset vertigo, oscillopsia, imbalance, and vomiting 4 months ago. At that time, she was given the diagnosis of "an inner ear problem" and was treated with meclizine. Although her acute symptoms significantly improved in the next 3 days, she has continued to experience gait instability, particularly when she moves her head abruptly. She has no hearing loss. Video electronystagmography reveals bilateral gaze-evoked nystagmus and impaired smooth pursuit. Caloric responses 82 are normal. During posturography, the results of the sensory organization testing are normal, but the motor control testing and postural-evoked responses are abnormal. Which of the following is the most likely cause of the patient's persistent symptoms? A. Partially compensated vestibular neuritis B. Benign positional vertigo C. Cerebellar lesion D. Migraine-related motion sickness E. Anxiety disorder Correct Answer: The correct answer is C. Despite the history suggestive of an acute vestibular lesion, the presence of gaze-evoked nystagmus is indicative of a cerebellar lesion, which may explain the persistence of the patient's symptoms. The normal caloric responses and the results of the posturography are also consistent with a cerebellar, rather than vestibular, lesion. Migraine-associated motion sickness, benign positional vertigo, and anxiety disorders do not produce gaze-evoked nystagmus. 3. A 35-year-old woman is evaluated for episodes of vertigo and oscillopsia, which are triggered by loud noises. She also has the sensation of hearing her heart beat and her own voice in her right ear. Which of the following is the most likely finding on examination of this patient? A. Horizontal nystagmus elicited by Valsalva maneuver B. Gaze-evoked-nystagmus elicited by hyperventilation C. Horizontal-torsional nystagmus elicited by jugular compression D. Vertical-torsional nystagmus elicited by tragal compression E. Direction-changing horizontal nystagmus elicited by noise Correct Answer: The correct answer is D. The history of vertigo induced by loud noises, pulsatile tinnitus, and autophony suggest a superior canal dehiscence as a cause for the patient's symptoms. In these patients, loud sounds, Valsalva maneuver, or positive pressure applied to the external auditory canal produces a vertical-torsional nystagmus, with the slow phase directed upward with torsional motion of the superior pole of the eye away from the affected ear. Conversely, negative pressure on the external auditory canal or jugular venous compression causes a vertical-torsional nystagmus in the opposite direction. Superior canal dehiscence does not typically produce horizontal or gaze-evoked nystagmus. 4. A 68-year-old man comes to the office for evaluation of a 2-year history of progressive left-sided hearing loss. There is no history of vertigo or other neurological symptoms. Neurological examination is normal except for the left-sided hearing loss. On bedside examination with a 512-Hz tuning fork, bone conduction is better than air conduction on the left, and Weber testing lateralizes to the left. Formal audiometric testing shows hearing loss to air-conducted stimuli on the left, normal findings to air-conducted stimuli on the right, and normal findings on bone-conducted stimuli bilaterally. Which of the following is the most likely cause of this patient's hearing loss? A. Acoustic neuroma B. Autoimmune hearing loss C. Noise exposure D. Otosclerosis E. Presbycusis Correct Answer: The correct answer is D. This patient's findings are consistent with a conductive hearing loss on the left. Otosclerosis is a common cause of adult-onset progressive conductive hearing loss. All of the other listed possibilities are causes of sensorineural, rather than conductive, hearing loss. 5. A 28-year old woman comes to the emergency department because of severe and persistent vertigo, nausea, and vomiting, which she first noted when she awakened from sleep 3 hours ago. She has no significant medical history. She denies diplopia, dysarthria, or focal motor or sensory symptoms. On examination she is afebrile with normal vital signs. She appears uncomfortable and vomits intermittently. She states that moving her head in any direction seems to make her vertigo worse. She has right-beating and torsional nystagmus seen on lateral gaze; no vertical nystagmus is present. The remainder of her neurological and otological examination is normal. Treatment with low-dose parenteral lorazepam and prochlorperazine causes a reduction in her acute symptoms. Which of the following is the most appropriate next step in treatment for this patient? A. Particle repositioning maneuver B. Methylprednisolone C. Salt restriction D. Sumatriptan E. Triamterene/hydrochlorothiazide Correct Answer: The correct answer is B. This patient's symptoms of acute vertigo and nausea are most consistent with vestibular neuritis. A recent study of patients with vestibular neuritis found that a course of 83 methylprednisolone, starting with 100 mg/d and tapering to 10 mg/d over 3 weeks, significantly improved the results of caloric testing in these patients 1 year later. Therefore, a course of steroids should be considered in this patient. The worsening of her symptoms with movement is a nonspecific finding; the persistent nature of her symptoms is not consistent with benign paroxysmal positional vertigo, and particle repositioning maneuver, therefore, is not indicated. She does not have a history of paroxysmal vertiginous attacks with tinnitus and hearing loss to support a diagnosis of Ménière's disease, so treatment for this condition with salt restriction or diuretic therapy is not indicated. Her history also does not suggest a diagnosis of migraine; therefore, sumatriptan therapy is not appropriate. 6. An 18-year-old woman with a history of migraine and anxiety is evaluated for persistent dizziness following an acute illness 4 months ago. At that time, she had headache, fever, severe nausea and vomiting, and diarrhea for approximately 5 days. Approximately 7 days into the illness, she developed an episode of vertigo, oscillopsia, and vomiting. Although the severe symptoms resolved in 2 days, she continued to feel weak and remained in bed for the following 10 days. Since then, she has complained of chronic dizziness. This occurs primarily when she stands from a sitting position or after trying to exercise. Because of her persistent symptoms, she stopped all physical activities and had become increasingly depressed. Neurological examination is normal. She has no hearing loss. Upon standing from a sitting position, she has the sensation of shortness of breath, chest pressure, and exacerbation of her headache and dizziness. This coincides with an increase in heart rate from 70 beats per minute while sitting to 120 beats per minute while standing. Her symptoms do not worsen with head movement. Her symptoms improve and her heart rate decreases after sitting down. Which of the following is the most likely diagnosis? A. Phobic postural vertigo B. Migraine-associated motion sickness C. Hyperventilation D. Postural intolerance E. Somatization disorder Correct Answer: The correct answer is D. The presence of excessive tachycardia upon standing is consistent with postural intolerance (postural tachycardia syndrome). In this case, it probably reflects deconditioning, hyperadrenergic state (including anxiety), and perhaps some volume depletion, given the history of vomiting and diarrhea. Although the other diagnoses are possible in this patient, the consistent association with standing and decreased severity with sitting suggests a primarily hemodynamic cause. 7. A 32-year-old man awoke one morning with a sensation of severe spinning, nausea, and vomiting. He has no hearing loss. Upon evaluation in the emergency department 6 hours after onset of symptoms, he has severe gait ataxia and spontaneous horizontal nystagmus with a slow phase toward the right side. The nystagmus worsens upon looking to the left, and there is a small amount of right-beating nystagmus on right gaze. Which of the following is the most likely cause? A. Right vestibular neuritis B. Left medial cerebellar infarction C. Right lateral medullary infarction D. Right posterior vestibular artery infarction E. Left internal auditory artery infarction Correct Answer: The correct answer is B. The characteristics of the nystagmus (pure horizontal) with a bilateral gaze-evoked component suggest a central nystagmus, in this case reflecting vestibular imbalance due to a cerebellar lesion. Lateral medullary infarction primarily affects utricular inputs to the inferior portions of the ventricular nuclear complex, eliciting skew deviation. The posterior vestibular artery supplies the posterior semicircular canal. Therefore, infarction in its distribution is unlikely to explain the horizontal nystagmus in this patient. 8. A 38-year-old woman with a history of migraine is evaluated for sensation of positional disequilibrium and nausea over the past 3 weeks. She has spontaneous oscillopsia that worsens with head movement. Examination reveals downbeat nystagmus. Which of the following is the most appropriate next diagnostic test? A. Electronystagmography B. Dix-Hallpike maneuver C. Genetic testing for episodic ataxia type 2 D. Magnetic resonance imaging (MRI) of the head E. Posturography Correct Answer: The correct answer is D. The presence of vertical nystagmus suggests a central nervous system lesion. Therefore, an MRI of the head is the most appropriate first diagnostic test. Electronystagmography and posturography would have only a confirmatory role in this case. The history and findings are not those of benign positional vertigo. Although episodic ataxia type 2 is associated with migraine, a structural brain lesion should be excluded first. [...]... amitriptyline) and calcium channel blockers, should be avoided 35 A 57 -year-old man is evaluated for a 3-month history of episodic spinning sensation triggered by turning in bed, arising from bed in the morning, or extending his neck to look upward Each episode lasts 20 to 30 seconds Occasionally, he uses meclizine to relieve nausea He has no hearing loss The Dix-Hallpike maneuver shows evidence of left posterior... canalith repositioning treatment (CRT) Which of the following statements is correct regarding the use of meclizine in this clinical setting? A Use of meclizine prevents vestibular compensation following CRT B Meclizine should be discontinued at least 2 days prior to CRT C Meclizine can be used to reduce nausea during CRT D Meclizine is as effective as CRT in these patients E Meclizine should always... patient 29 A 52 -year-old man comes to the office because of a 6-year history of episodes of dizziness, left-sided tinnitus, and hearing loss He has had a total of 10 attacks of dizziness, consisting of several hours of vertigo with nausea and vomiting He also has tinnitus, which he describes as a "roaring" sound in the left ear during each attack Progressively decreased hearing in his left ear has... would be expected by pure-tone testing, the presence or absence of this finding would still not preclude definitive imaging Similarly, acoustic reflex testing, auditory brain stem response, or cochlear emissions can help with localization, but findings on these tests would not eliminate the need for MRI 23 A 62-year-old man with history of hypertension is brought to the emergency department for the acute... answer is C Meclizine may be helpful to relieve nausea in patients undergoing canalith repositioning maneuvers for posterior SCC BPPV Vestibular compensation is not an issue in BPPV Meclizine is less effective than CRT in these patients Meclizine does not interfere with the benefits of CRT in BPPV 36 A 24-year-old woman comes to the office because she is about to go on a 7-day cross-country bus ride... helpful in improving symptoms of oscillopsia during predictable and unpredictable head movements In one study the use of vestibular exercises was the main factor involved in improvement in visual symptoms, regardless of age or time from onset; this benefit was not seen with placebo exercises 39 A 57 -year-old woman presents with a history of positional vertigo, elicited by rolling over in bed, getting out... prevent recurrent episodes leading to hearing loss Correct Answer: The correct answer is B Intratympanic administration of gentamicin is used for Ménière's disease affecting only one ear Recurrent episodes of vertigo may occur after 6 to 18 months and can be controlled with additional intratympanic injections The long- term hearing outcome in these patients is comparable to that in patients who only receive... answer is D Head shaking is a useful bedside test to detect asymmetry in velocitystorage mechanisms following peripheral vestibular lesions Vestibular imbalance is detected by the presence of horizontal-rotatory nystagmus Vertical nystagmus after horizontal head shaking (cross-coupling) indicates a central lesion 20 A 28-year-old man has had a feeling of mild disequilibrium since recovering from an acute... neurological examination is unremarkable except for short anterograde amnesia Early during hospitalization, he remained in supine position to facilitate healing of the vertebral fracture When he first sat up, he had an episode of spinning sensation associated with nausea that lasted less than 1 minute Since then, he has continued to experience similar events whenever he turns his head while lying supine or tries... bilateral sensorineural hearing loss Mutation of a gene encoding which of the following proteins is the most likely cause of this patient's hearing loss? A Connexin 26 B Endothelin-3 C Endothelin receptor type B D Type IV collagen E Usherin 92 Correct Answer: The correct answer is A This patient has nonsyndromic congenital hearing loss Mutations of the gap junction protein connexin 26 account for half of . should be avoided. 35. A 57 -year-old man is evaluated for a 3-month history of episodic spinning sensation triggered by turning in bed, arising from bed in the morning, or extending his neck to. gradual increase in difficulty climbing stairs and arising from a chair. On physical examination, she is cushingoid in appearance. Hip flexion in 3 /5 bilaterally. Which of the following suggests. examination, he is a thin man who is somewhat restless and perspiring. Vital signs are: blood pressure 130/70, P-1 15 R- 15 afebrile. Neurological examination is unremarkable except for a fine