Case Files Neurology - part 8 pdf

food-borne but can also present with intravenous drug use, surgery, and wounds. The difference is that patients present with a descending paralysis, beginning with the Dozen Ds of cranial nerve progression—dry mouth, double vision, pupil dilation, droopy eyelids, facial droop, diminished gag reflex, dysphagia, dysarthria, dysphonia, difficulty lifting head, descending paralysis, and diaphragmatic paralysis. Rapid administration of botulism antitoxin halts wors- ening, although mechanical ventilation can still be required. Tick paralysis pro- duces a rapidly ascending paralysis with areflexia, ataxia, and respiratory insufficiency much like Guillain-Barré syndrome, particularly in children with a history of outdoor exposure. Removal of the discovered female tick can be cur- ative by elimination of the source of the neurotoxin. Clinical Presentation The mean interval from onset of Guillain-Barré syndrome to the most severe degree of impairment is 12 days, with 98% of patients reaching the end point of clinical worsening (nadir) by 4 weeks. The mean time to improvement starts at 28 days, and clinical recovery usually occurs by 200 days. Eighty-five percent of patients recover completely, although up to 15% have permanent deficits. Three to eight percent of patients die in spite of intensive care man- agement. A major cause of mortality in elderly victims is arrhythmias. The history should be meticulous to identify corroborating symptomatol- ogy and triggers as discussed above, and to rule out other causes of acute flac- cid paralysis. The physical examination should focus on the vital signs, reflexes, and extent of weakness in the extremities, diaphragm, and cranial nerves. Fever and mental status changes are unusual, and signal hypoxic res- piratory failure or a different etiology. The principal laboratory test is the lum- bar puncture showing rising protein levels up to 400 mg/L with no associated increase in cell count (albuminocytologic dissociation), although protein ele- vation may not be seen until 1–2 weeks after onset, and 10% remain normal. Antibodies and stool culture for C. jejuni are frequently checked. Other help- ful tests include sedimentation rate, antiganglioside antibodies, anti-GQ1b antibodies for Miller Fisher presentations, and pregnancy test. Presence of anti-GM1 antibodies signals a poorer prognosis. Nerve conduction studies show early changes indicative of nerve root demyelination. MRI of the brain and spine can show anterior nerve root enhancement, which is more specific for Guillain-Barré syndrome, but should be obtained for difficult cases to rule out secondary causes, such as malignancy, vasculitic, or viral infection, and spinal cord pathology. Measurement of respiratory strength (FVC) is crucial for cases with respiratory involvement as above. Electrocardiograph (ECG) should be performed to screen for atrioventricular block, ST segment changes, and arrhythmias. The patient should be admitted for further monitoring and treatment. If the etiology is still unclear and the patient continues to deteriorate, consultation with a neurologist is indicated. CLINICAL CASES 333 Treatment Intubation and mechanical ventilation should be considered for FVC less than 15 mL/kg with intensive care monitoring for arrhythmias and blood pressure instability. Because of the immune-mediated pathogenesis of the disease, the only proven therapies are IV immune globulin therapy (5 days) and plasma exchange (10 days), both of which can hasten recovery by 50% if initiated early in the course of the disease. There is no data to support the use of steroids. Complications of immobility, hospitalization, and respiratory insufficiency should be avoided by implementing prophylactic measures for deep venous thrombosis, decubitus ulcers, gastritis, and aspiration. Recurrence is rare but can occur in up to 5% of cases. Comprehension Questions Match the following etiologies (A–E) to the clinical situation [39.1] to [39.4]: A. Acute inflammatory demyelinating polyneuropathy B. Acute stroke C. Myasthenia gravis D. Inflammatory myopathy E. Tick paralysis F. Transverse cord myelitis [39.1] A 19-year-old man, who works at a hamburger stand, develops diar- rhea, and 2 weeks later experiences gait difficulties and foot tingling. [39.2] An 18-year-old woman comes back from a camping trip complaining of blurry vision, facial weakness, and difficulty swallowing followed by arm then leg weakness. [39.3] A 62-year-old man with hypertension and diabetes presents with acute right face, arm, leg weakness, slurred speech, and right-sided hyperreflexia. [39.4] A 34-year-old woman presents with fatigable muscle weakness with climbing stairs or blow drying her hair. This is associated with some shortness of breath, which improves with rest. Answers [39.1] A. AIDP is the most common presentation of Guillain-Barré syn- drome, with up to 40% of patients seropositive for C. jejuni, which is found in poorly cooked meats. [39.2] E. Tick paralysis presents with ascending paralysis and resolves with removal of the tick. 334 CASE FILES: NEUROLOGY [39.3] B. Unilateral face, arm, leg weakness and dysarthria in a patient with risk factors for vascular disease is consistent with an acute cerebrovas- cular event. [39.4] C. Myasthenia gravis is an acquired neuromuscular junction disorder caused by antibody-mediated impairment of the skeletal muscle acetylcholine receptor. CLINICAL CASES 335 CLINICAL PEARLS ❖ The majority of Guillain-Barré cases are associated with a history of preceding C. jejuni or other flu-like or gastrointestinal syndrome. ❖ Most Guillain-Barré patients experience proximal lower extremity weakness with ascending paralysis within hours to days. ❖ One should be wary that the examination can worsen rapidly from one visit to the next with the possibility of respiratory failure. ❖ Significant autonomic instability can accompany Guillain-Barré symptoms and require intensive care monitoring. ❖ IV immunoglobulin and plasma exchange are the two therapeutic options that have been shown to improve recovery. REFERENCES Hughes RA, Cornblath DR. Guillain-Barré syndrome. Lancet 2005 Nov 5;366(9497):1653–1666. Miller A. Guillain-Barré syndrome. Available at: http://www.emedicine.com/ EMERG/topic222.htm. This page intentionally left blank ❖ CASE 40 A 31-year-old woman presents with a 3-month history of muscle soreness, cramps, and muscle fatigue with climbing stairs and carrying objects. The patient has recently noted a rash on her cheeks, necks, chest, and back and swelling around her eyes. Her review of symptoms is significant for recent sensitivity of her fingers to cold temperatures, difficulty swallowing certain foods and pills, and some shortness of breath with exertion. The physical examination is significant for an erythematous rash across her cheeks, neck, chest, and back and mild lid edema. The cardiac exam is significant for occa- sional skipped beats. The neurologic examination shows proximal muscle weakness of the patient’s deltoids, biceps, hip flexors, and knee flexors. The sensory and coordination examination is normal. Laboratory studies are nor- mal except for elevated serum creatine kinase of 770 (normal 50–200). Electromyography and nerve conduction studies reveal an irritative myopathy and normal nerve conductions. ◆ What is the most likely diagnosis? ◆ What is the next diagnostic step? ◆ What is the next step in therapy? ANSWERS TO CASE 40: Dermatomyositis Summary: A young woman complains of subacute onset of proximal muscle weakness and myalgias, skin rash, and a clinical history of Raynaud phenom- ena, dysphagia, and cardiac arrhythmia. Diagnostic studies reveal an irritative and damaging myopathy that is likely inflammatory in etiology. ◆ Most likely diagnosis: Dermatomyositis ◆ Next diagnostic step: Skeletal muscle biopsy ◆ Next step in therapy: Immunomodulatory therapy; cardiac and respiratory evaluation Analysis Objectives 1. Describe the most common types of inflammatory myopathies. 2. Be familiar with the diagnostic workup of inflammatory myopathies. 3. Be familiar with the treatment and management of dermatomyositis. Clinical Considerations The patient presented in this case has a subacute onset of proximal muscle pain and weakness, some swallowing (dysphagia) difficulties, and rash. This clini- cal presentation is consistent with dermatomyositis. The two most common inflammatory myopathies are dermatomyositis and polymyositis. Both diseases share the common symptom of proximal muscle weakness. Dermatomyositis differs from polymyositis by its immunopathogenesis but also by the involvement of skin, with rash, discoloration, and tissue calcification. Inclusion body myositis (IBM) is another inflammatory myopathy that shares some features with polymyositis and dermatomyositis. However, IBM occurs in older patients, usually >50 years of age, and affects men more than women. Inclusion body myositis tends to present with a more gradual onset of weak- ness, which can date back several years by the time of diagnosis. It generally follows a more indolent course and is more refractory to therapy. APPROACH TO DERMATOMYOSITIS Definitions Heliotrope rash: Bluish-purple discolorations on the face, lids, neck, shoul- ders, upper chest, elbows, knees, knuckles, and back of patients with dermatomyositis. 338 CASE FILES: NEUROLOGY Gottron nodules: Flat-topped raised nonpruritic lesions found over the dorsum of the metacarpophalangeal, proximal interphalangeal, and dis- tal interphalangeal joints. Anti-Jo-1 antibody: Antibody that recognizes a cytoplasmic histidyl trans- fer RNA synthetase. Creatine kinase (CK): An enzyme found primarily in the heart and skele- tal muscles, and to a lesser extent in the brain. Significant injury to any of these structures will lead to a measurable increase in CK levels. Raynaud phenomenon: A condition resulting from poor circulation in the extremities (i.e., fingers and toes). In a person with Raynaud phenome- non, when his or her skin is exposed to cold or the person becomes emo- tionally upset, the blood vessels under the skin spasm, and the blood flow slows. This is called vasospasm. These areas can become cyanotic and cold. Clinical Approach Polymyositis and dermatomyositis are frequently considered together because they have similar clinical, laboratory, and pathologic features and because they progress at the same tempo. Although inclusion body myositis shares some features with polymyositis and dermatomyositis, it generally follows a more indolent course and is more refractory to therapy. Epidemiology and Clinical Features Dermatomyositis is more rare than polymyositis, affecting 10 people out of every 1 million. Although there is a juvenile form of this disease that begins between the ages of 5 and 15 years, it most commonly begins between the ages of 40 and 60 years. Dermatomyositis has a subacute (somewhat short and rel- atively severe) onset, usually worsening over a period of days or weeks, although it might also last for months. The distinguishing characteristic of dermatomyositis is a rash accompany- ing, or more often, preceding muscle weakness. The rash is described as patchy, bluish-purple discolorations on the face, neck, shoulders, upper chest, elbows, knees, knuckles, and back. Some patients might also develop hard- ened bumps of calcium deposits under the skin. Trouble with swallowing (dys- phagia) might also occur. In approximately one-fourth of adult cases, muscles ache and are tender to the touch. In the juvenile form, these myalgias can be seen in as many as 50 percent. Polymyositis also causes varying degrees of decreased muscle function. The disease has a more gradual onset compared to dermatomyositis and gen- erally begins in the second decade of life. Polymyositis rarely affects people younger than18 years of age. Like dermatomyositis, difficulty with swallow- ing occurs and is more common with polymyositis, which can affect nutrition CLINICAL CASES 339 as well increase the risk of aspiration pneumonia. Approximately one-third of patients with polymyositis or dermatomyositis experience muscle tenderness and cramps. The chief clinical feature of polymyositis and dermatomyositis is progres- sive, painless symmetrical proximal muscle weakness, with symptoms possi- bly dating back to 3 to 6 months by the time of the diagnosis. Upper-extremity muscle weakness manifests as difficulty in performing activities that require holding the arms up, such as hair washing, shaving, or reaching into overhead cupboards. Neck muscle weakness may lead to difficulty raising the head from a pillow or even holding it up while standing. Involvement of pharyngeal mus- cles may result in hoarseness, dysphonia, dysphagia, and nasal regurgitation after swallowing. Lower-extremity proximal muscle weakness manifests as difficulty climbing stairs and rising from a seated or squatting position. Patients will often seek chairs with armrests to push off from or grab the sink or towel bar to rise from the toilet. Other Clinical Features Weakness is the major complaint, but proximal myalgias and constitutional symptoms such as fever, fatigue, and weight loss can occur. Interstitial pneumonitis occurs in approximately 10% of patients with polymyositis, usually developing gradually over the course of the illness. Myocardial involvement in polymyositis and dermatomyositis is well described. The reported frequency of congestive heart failure (with or without cardiomegaly) ranges from fewer than 5% of patients to 27–45%. Electrocardiographic abnor- malities are more common, with left anterior fascicular block and right bundle-branch block representing the most frequent conduction defects. Both polymyositis and dermatomyositis were associated with an increased risk of malignancy, with a threefold risk demonstrated in patients with der- matomyositis and a 1.4-fold risk for patients with polymyositis. The types of malignancy generally reflected those expected for age and sex although ovar- ian cancer was overrepresented in women with dermatomyositis, and both groups of patients displayed a greater-than- expected occurrence of non- Hodgkin lymphoma. Cutaneous Features of Dermatomyositis In dermatomyositis, patients can have an erythematous, often pruritic rash over the face, including the cheeks, nasolabial folds, chin, and forehead. Heliotrope (purplish) discoloration over the upper eyelids with periorbital edema is characteristic (Fig. 40–1), as is the shawl sign, which describes the pattern of an erythematous rash in V distribution on the chest and across the shoulders. Gottron papules—flat-topped raised nonpruritic lesions found over the dorsum of the metacarpophalangeal, proximal interphalangeal, and 340 CASE FILES: NEUROLOGY distal interphalangeal joints—are virtually pathognomonic for dermatomyositis (Fig. 40–2). Often pinkish to violaceous, sometimes with a slight scale, they are distinguished from cutaneous lupus in that lupus has a predilection for the dorsum of the fingers between the joints. Calcinosis Cutis Children with dermatomyositis are also particularly prone to calcinosis cutis, which is the development of dystrophic calcification in the soft tissues and muscles, leading to skin ulceration, secondary infection, and joint contracture. Calcinosis cutis occurs in up to 40% of children with dermatomyositis and less commonly in adults; there is no proven therapy to prevent this complication. Inclusion Body Myositis Inclusion body myositis tends to present with a more gradual onset of weak- ness, which can date back several years by the time of diagnosis. Although the muscle weakness is proximal, distal muscle groups can also be affected, and CLINICAL CASES 341 Figure 40–1. Heliotrope rash. (With permission from Kasper DL, Braunwal E, Fauci A, et al. Harrison’s principles of internal medicine, 16th ed. New York: McGraw-Hill; 2004: Fig. 49–3.) asymmetry of involvement is characteristic. Atrophy of the deltoids and quadriceps is often present, and weakness of forearm muscles (especially fin- ger flexors) and ankle dorsiflexors is typical. Peripheral neuropathy with loss of deep tendon reflexes can be present in some patients. Diagnosis Because both polymyositis and dermatomyositis are relatively rare, there is not a clearly defined approach to diagnosing these conditions. The diagnosis is further complicated by the similarity of these diseases to other, more com- mon diseases and disorders. Both polymyositis and dermatomyositis are often diagnosed by ruling out other conditions. Laboratory studies include a creatine kinase serum level. The laboratory hallmark of polymyositis and dermatomyositis, although not specific to either of these, is a dramatic elevation of the serum creatine kinase, often in the range of 1,000 to 10,000 mg/dL. Although early in the disease process milder eleva- tions can be seen. In inclusion body myositis, creatine kinase elevations tend to be less striking, often increasing only to the 600 to 800 mg/dL range; 20% to 30% of patients with inclusion body myositis can have a normal creatine kinase at presentation. With initiation of effective treatment, creatine kinase levels decrease rapidly, and periodic measurements are used to follow up dis- ease activity over the course of the long term. Caution is advised when inter- preting creatine kinase elevations, as levels can remain mildly elevated with clinically quiescent disease. Therefore, the degree of elevation does not nec- essarily correlate with the degree of muscle weakness, although disease exac- erbation is often associated with increased levels. Elevated serum levels of 342 CASE FILES: NEUROLOGY Figure 40–2. Gottron papules. (With permission from Kasper DL, Braunwal E, Fauci A, et al. Harrison’s principles of internal medicine, 16th ed. New York: McGraw-Hill; 2004: Fig. 49–4.) [...]... generally absent in inclusion body myositis Autoantibodies present in polymyositis and dermatomyositis include the myositis specific autoantibodies anti-Jo-1, seen in 20% of patients, and the less commonly encountered anti-PL-7, anti-PL-12, anti-OJ, and anti-EJ These antibodies recognize cytoplasmic transfer RNA synthetases (for transfer RNA synthetase), and they are markers of the subset of polymyositis... abnormalities observed ◆ What is most likely diagnosis? ◆ What is the next diagnostic step? ◆ What is the next step in therapy? 360 CASE FILES: NEUROLOGY ANSWERS TO CASE 42: Median Nerve Mononeuropathy A 45-year-old right handed office secretary with hypothyroidism presents with a 5-month complaint of numbness and pain of her right index and middle fingers, worsened with activity of the fingers The symptoms... can also counsel patients and caregivers about end-of-life issues Comprehension Questions [41.1] Which of the following diagnostic studies is critical to diagnosing ALS? A B C D Cerebrospinal fluid (CSF) analysis Electroencephalograph (EEG) EMG/NCV Genetic testing [41.2] What percentage of ALS cases are familial? A B C D 10% 25% 50% 100% 356 CASE FILES: NEUROLOGY [41.3] Which of the following clinical... There is no evidence of neuropathy or myopathy ◆ What is the most likely diagnosis? ◆ What is the next diagnostic step? ◆ What is the next step in therapy? 350 CASE FILES: NEUROLOGY ANSWERS TO CASE 41: Amyotrophic Lateral Sclerosis Summary: A 64-year-old relatively healthy man presents with progressive skeletal muscle weakness of both upper extremities and lower extremity His examination and diagnostic... the incidence is 1–3 cases per 1000 subjects per year; prevalence is approximately 50 cases per 1000 subjects in the general population Incidence can increase as high as 150 cases per 1000 subjects per year, with prevalence rates greater than 500 cases per 1000 subjects in certain high-risk groups Whites are probably at highest risk The syndrome appears to be very rare in other non-white racial groups... Department of Anatomy Upper motor neuron pathways: a tutorial Available at: http://d-mis-web.ana.bris.ac.uk/calnet/UMN/page2.htm This page intentionally left blank ❖ CASE 42 A 45-year-old right-handed office secretary presents with a 5-month complaint of numbness and pain of her right index and middle fingers, which is worse with driving or typing on her keyboard at work The symptoms often awake the... http://www.neuro.wustl edu/neuromuscular/ Rendt K Inflammatory myopathies: narrowing the differential diagnosis Cleve Clin J Med 2001 Jun; 68( 6):505, 509–514, 517–519 This page intentionally left blank ❖ CASE 41 A 64-year-old male comes to a neurologist with an 11-month history of progressive weakness He first noticed weakness of his right hand with difficulty holding onto things This progressed to... chronic and/or untreated cases, the muscles at the base of the thumb can waste away 362 CASE FILES: NEUROLOGY Not infrequently, patients report symptoms in the whole hand Many patients with CTS also complain of a tight or swollen feeling in the hands and/or temperature changes (e.g., hands being cold/hot all the time) Many patients also report sensitivity to changes in temperature (particularly cold) and... 2003 Nov;15(6):730–736 CLINICAL CASES 357 Traynor BJ, Codd MB, Corr B, et al Clinical features of amyotrophic lateral sclerosis according to the El Escorial and Airlie House diagnostic criteria: a populationbased study Arch Neurol 2000 Aug;57 (8) :1171–1176 University of Bristol Department of Anatomy Upper motor neuron pathways: a tutorial Available at: http://d-mis-web.ana.bris.ac.uk/calnet/UMN/page2.htm... patients when ALS presents in the sixth and seventh decades, especially in women The incidence (number of new cases per 100,000 per year) and prevalence (the number of existing cases per 100,000 per year) are 1–2 cases and 4–6, respectively There is an overall male predominance of 1.5 to 1 in sporadic cases, with a ratio of 3–4 to 1 when ALS presents in the third and fourth decades, and 1 to 1 when ALS presents . myositis specific autoanti- bodies anti-Jo-1, seen in 20% of patients, and the less commonly encountered anti-PL-7, anti-PL-12, anti-OJ, and anti-EJ. These antibodies recognize cyto- plasmic transfer. Bluish-purple discolorations on the face, lids, neck, shoul- ders, upper chest, elbows, knees, knuckles, and back of patients with dermatomyositis. 3 38 CASE FILES: NEUROLOGY Gottron nodules: Flat-topped. myelitis [39.1] A 19-year-old man, who works at a hamburger stand, develops diar- rhea, and 2 weeks later experiences gait difficulties and foot tingling. [39.2] An 1 8- year-old woman comes back