Comprehensive Review in Clinical Neurology: A Multiple Choice Question Book for the Wards and Boards

Chapter 16. Neurologic Complications of Systemic Diseases and Pregnancy

Question

 1. A 52-year-old woman with a prosthetic aortic valve presents to the emergency department with complaints of fever, chills, and generalized malaise of 3 weeks’ duration. She is found to have Staphylococcus epidermidisbacteremia, and a transesophageal echocardiogram shows an echodensity on her aortic valve. Two days after admission, she develops left hemiparesis. MRI of the brain shows multiple bilateral cortical foci of restricted diffusion, the largest being in the right MCA territory. Which of the following is incorrect regarding this patient’s condition?

      a.  Ischemic strokes due to septic emboli are the most common neurologic complication of infective endocarditis

      b.  Cerebral septic emboli lead to arteritis of the involved vessel with subsequent development of mycotic aneurysms in some cases

      c.  Hemorrhagic conversion of an ischemic infarct is the most common cause of intracerebral hemorrhage in patients with infective endocarditis

      d.  Patients with ischemic stroke due to infective endocarditis should be immediately anticoagulated to prevent further strokes

      e.  Neurologic complications are more common in patients with native valve endocarditis than in those with prosthetic valve endocarditis

 2. A 16-year-old boy with sickle cell anemia (Hemoglobin [Hb] SS disease) presents with sudden onset of left hemiparesis. He has had a fever with productive cough for 4 days. Chest radiograph shows pneumonia. CT scan of the brain shows a hypodensity in the right MCA territory. Which of the following statements is incorrect regarding this patient’s condition?

      a.  Patients with sickle cell anemia (Hb SS disease) are more likely to suffer from neurologic complications as compared to those with hemoglobin SC (Hb SC) disease

      b.  Intracerebral hemorrhage is more common than ischemic stroke in patients with Hb SS disease

      c.  Patients with Hb SS disease are at risk of developing intracerebral aneurysms with subsequent subarachnoid hemorrhage

      d.  Myelopathy and radiculopathy may be complications of vertebral body infarction in patients with Hb SS disease

      e.  In children found to have elevated cerebral blood flow velocities on transcranial Doppler ultrasonography, blood transfusion reduces the risk of ischemic stroke

Questions 3–4

 3. Which of the following statements is incorrect regarding neurologic involvement in patients with plasma cell dyscrasias and other hematological disorders?

      a.  Infiltration of vertebral bones from myeloma cells can be complicated by spinal cord and nerve root compression

      b.  POEMS syndrome (plasma cell dyscrasia with polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes) is a constellation of abnormalities seen in some patients with plasma cell dyscrasias, particularly plasmacytoma

      c.  Plasma cell dyscrasias are associated with both paraneoplastic and infiltrative neuropathies

      d.  Causes of encephalopathy in patients with plasma cell dyscrasias include hypercalcemia, hyperviscosity syndrome, and CNS infections due to their immunocompromised state

      e.  Presence of neuropathy in a patient with monoclonal gammopathy invariably indicates that the patient has multiple myeloma

 4. A 62-year-old woman presented with a 4-month history of paresthesias that began in her toes and later extended up to her shins and began involving her fingertips. Over the prior few weeks, she had noticed herself to be tripping more frequently than usual. Examination showed bilateral foot dorsiflexion and plantar flexion to be Modified Research Council grade 4/5. Wrist extension was 4/5 on the left. Otherwise, motor examination was normal. Sensory examination revealed reduced sensation to all modalities in the feet, including reduced vibratory sense and impaired proprioception. Deep tendon reflexes could not be elicited in any extremity. She had no family history of neuropathy, and there was no evidence of hammer toes or high-arched feet. EMG/NCS showed a demyelinating neuropathy with mild axon loss. Serum monoclonal protein immunofixation showed an immunoglobulin M monoclonal band. Which of the following tests would be indicated in this patient?

      a.  Genetic panel for Charcot-Marie-Tooth disease

      b.  A technetium bone scan

      c.  Antibodies against myelin-associated glycoprotein

      d.  Superoxide dismutase gene mutation

      e.  Anti-GQ1b antibodies

 5. A 62-year-old woman has been feeling tired and sluggish and had appeared pale to her husband for several days. She complained of headache and felt feverish. While at the grocery store, she is witnessed to have a generalized tonic-clonic seizure and is brought to the emergency department. Her temperature is 39.1°C. Laboratory evaluation reveals a hemoglobin level of 6.6 g/dL (normal 13 to 17 g/dL), platelet count of 30,000/μL (normal 150 to 400/μL), and creatinine level of 1.8 mg/dL (normal 0.7 to 1.4 mg/dL). Review of a peripheral smear shows evidence of red blood cell fragmentation. Coagulation tests are normal. Lactate dehydrogenase level is elevated, and serum haptoglobin level is low. What is the most likely diagnosis in this patient?

      a.  Hemolytic-uremic syndrome

      b.  Idiopathic thrombocytopenic purpura

      c.  Thrombotic thrombocytopenic purpura

      d.  Disseminated intravascular coagulation

      e.  Anti-phospholipid antibody syndrome

 6. A 42-year-old man with nonalcoholic steatohepatitis cirrhosis of the liver was brought to the emergency department by his wife, with confusion. One week earlier, he had started to show some signs of confusion, and over the prior few days, he had been sleeping most of the day, and at night, he would wake up distinctly confused and agitated. On examination, he appears restless and agitated and is mumbling incomprehensibly. Asterixis is noted on examination. An EEG shows moderate generalized slowing and triphasic waves. On reexamination a few hours later, he is somnolent but arousable to noxious stimuli. Which of the following is correct regarding the most likely cause of this patient’s encephalopathy?

      a.  A serum ammonia level can be used to assess for the severity of his condition and serially checked as a means of assessing response to therapy

      b.  Given the extent of his encephalopathy, he must also have a history of alcoholism

      c.  This patient should undergo a transjugular intrahepatic portosystemic shunt procedure to help treat his encephalopathy

      d.  Treatment for this type of encephalopathy includes reducing absorption of ammonia in the colon and may include lactulose or neomycin

      e.  A high-protein diet should be instituted in this patient

 7. A 32-year-old woman presents with unsteadiness of walking. She reports that over the prior year, her gait has become progressively more unsteady. On review of systems, she reports chronic diarrhea, significant weight loss, and multiple food intolerances, including pasta, bread, and pastries. On examination, she has bilateral dysmetria and a wide-based, lurching gait. Examination also shows reduced sensation to pinprick and light touch on her extremities distally. MRI of the brain shows cerebellar atrophy. Upper gastrointestinal endoscopy with small bowel biopsy is obtained, and pathological examination of the biopsy specimens shows atrophy of the villi. Periodic acid-Schiff (PAS) staining of the biopsies does not show PAS-positive macrophage inclusions. Which of the following statements is incorrect regarding this patient’s condition?

      a.  Other neurologic complications that could be seen include inflammatory myopathy, cognitive dysfunction, and myoclonus

      b.  There is an increased risk of seizures in patients with this condition

      c.  Her neurologic symptoms are expected to improve with a gluten-free diet

      d.  In some patients with this disorder, neurologic symptoms may be the presenting feature, without diarrhea or other gastrointestinal manifestations

      e.  This patient should be treated with a prolonged course of a sulfonamide

 8. A 24-year-old woman with ulcerative colitis is admitted to the hospital with increasing frequency of bowel movements and hematochezia. While being treated for her exacerbation, she experiences severe diffuse headache. MRV shows superior sagittal sinus thrombosis. Which of the following statements is incorrect regarding the neurologic complications of inflammatory bowel disease (IBD)?

      a.  Neurologic complications are most common during acute exacerbations of IBD but can occur at any time

      b.  Both demyelinating and axonal neuropathies can occur

      c.  Patients are at increased risk of neurologic complications from vitamin deficiencies resulting from chronic malabsorption

      d.  Patients with IBD are at increased risk of cerebral venous thrombosis, but there is not an increased risk of arterial thrombosis in these patients

      e.  Patients with recurrent facial nerve palsies, angioedema, and tongue fissuring (Melkersson-Rosenthal syndrome) should be evaluated for IBD

 9. Which of the following statements regarding the neurologic complications of renal failure are incorrect?

      a.  Uremic encephalopathy often presents with impaired concentration and attention, apathy, and, in severe cases, obtundation

      b.  Mononeuritis multiplex is the most common neuropathy seen in patients with chronic renal failure

      c.  Seizures may occur in patients with acute or chronic renal failure

      d.  Asterixis and multifocal myoclonus are often seen in uremic encephalopathy

      e.  Dialysis disequilibrium syndrome may present with a range of neurologic manifestations ranging from mild encephalopathy to fatal cerebral edema

10. Various electrolyte abnormalities can lead to a spectrum of neurologic manifestations ranging from mild encephalopathy to seizures, coma, and even cerebral edema with death. Which of the following electrolyte abnormalities is not commonly associated with CNS complications?

      a.  Hyponatremia

      b.  Hypokalemia

      c.  Hypocalcemia

      d.  Hypercalcemia

      e.  Hypomagnesemia

11. A 73-year-old woman is brought to the clinic by her daughter who is concerned about her mother’s memory. Over the prior few months, she had become more forgetful, disinterested in social activities she used to enjoy, and slept most of the day. Her gait had also become somewhat more unsteady, and her daughter had noticed that her mother was having more difficulty climbing stairs. She has also noticed weight gain, constipation, and dry skin. Which of the following laboratory tests should be ordered on this patient?

      a.  Serum growth hormone

      b.  Anti-neuronal antibody

      c.  Thyroid stimulating hormone

      d.  Vitamin D

      e.  Anti-microsomal antibodies

12. Which of the following statements is incorrect regarding the neurologic manifestations of thyroid disorders?

      a.  The most common cause of treatable mental retardation is congenital hypothyroidism; it most commonly results from dysgenesis of the thyroid gland

      b.  Pseudomyotonia (a delay in muscle relaxation following elicitation of deep tendon reflex) is a feature of hyperthyroidism

      c.  Myopathy can result from both hypothyroidism and hyperthyroidism

      d.  Tremor is present in the majority of patients with untreated hyperthyroidism

      e.  Restricted upward gaze is the most common eye movement abnormality seen in patients with thyroid eye disease

13. A 73-year-old man with non–insulin-dependent diabetes since the age of 32 presents with nonhealing, painless ulcers on his feet. On examination, he has absent vibratory sense from the toes to the knees bilaterally, reduced sensation to pinprick with a gradient up to the mid-thigh bilaterally, and impaired proprioception in the toes. Which of the following statements is correct regarding the peripheral nervous system complications of diabetes?

      a.  Sensory loss associated with significant motor weakness is the most common manifestation of diabetic polyneuropathy

      b.  A proximal predominantly motor neuropathy is the most common manifestation of diabetic polyneuropathy

      c.  Neuropathy can result from impaired glucose tolerance alone in patients not otherwise meeting laboratory criteria for diabetes

      d.  Diabetes rarely affects the autonomic nervous system

      e.  Diabetic neuropathy is reversible with adequate glycemic control

14. A 52-year-old man with recently diagnosed diabetes presents to the clinic with multiple complaints including headache, difficulty climbing stairs, and impotence. His wife reports that he is very moody and has become verbally and even physically aggressive, which is highly unusual for him. On examination, he has central obesity with abdominal striae and has multiple ecchymoses all over his body. On confrontation testing, he is found to have a bitemporal hemianopia. Hip flexors are Medical Research Council grade 4/5 bilaterally. What is the most likely diagnosis in this patient?

      a.  Hypothyroidism

      b.  Graves disease

      c.  Cushing disease

      d.  Addison disease

      e.  Hyperparathyroidism

15. Consultation is requested for a 22-year-old woman who was admitted to the orthopedic service for pathologic fracture of the right femur. She has a history of bilateral hearing loss of unclear etiology. On examination, she was noted to have reduced visual acuity, weakness of the right upper and lower facial muscles, and reduced sensation in the distribution of all three branches of the trigeminal nerve. Serum alkaline phosphatase level is elevated. What is the most likely diagnosis in this patient?

      a.  Achondroplasia

      b.  Osteopetrosis

      c.  Ankylosing spondylitis

      d.  Osteomalacia

      e.  Relapsing polychondritis

16. A 32-year-old woman is brought to the emergency department by her mother. Over the prior 2 weeks, the patient had been suffering from fever, headache, and facial rash that she had attributed to a viral illness and had not sought medical attention for. However, in the prior 2 days, the patient had become confused, with significant delusions and hallucinations. General examination revealed a rash on both her cheeks and a systolic murmur. Neurologic examination showed her to be severely encephalopathic, restless, and agitated. Otherwise, there were no focal neurologic abnormalities on examination. Laboratory evaluation showed elevated creatinine level, anemia, leucopenia, thrombocytopenia, and elevated antinuclear antibody. CSF analysis showed pleocytosis with elevated protein and normal glucose levels; CSF cultures and other testing for microorganisms were negative. What is the most likely diagnosis in this patient?

      a.  Systemic lupus erythematosus

      b.  Systemic sclerosus

      c.  Sarcoidosis

      d.  Behet syndrome

      e.  Sjgren syndrome

Questions 17–18

17. A 52-year-old woman presents with gait instability. She began to experience left lower extremity painful paresthesias 2 years earlier, which were attributed to an L5-S1 radiculopathy and not further evaluated. Subsequently, her right leg became involved. Over the following 2 years, she experienced slowly progressive sensory loss in both of her extremities and began having frequent falls a few months prior to presentation. She reported falling even when she was just leaning over the sink to wash her face. Examination showed normal cranial nerve and motor examination, reduced sensation to pinprick over the upper and lower extremities, face, and trunk, and impaired proprioception, temperature discrimination, and vibratory sense in the fingers and toes. Deep tendon reflexes were hypoactive throughout. On review of systems, she endorsed multiple complaints including dry eyes, dry mouth, and orthostatic light-headedness. NCS showed reduced amplitude of the SNAPs in the arms and legs, but motor NCS is normal. What is the most likely diagnosis in this patient?

      a.  Small fiber neuropathy due to systemic lupus erythematosis

      b.  Subacute combined degeneration due to vitamin B12 deficiency

      c.  Sensory neuronopathy due to Sjgren syndrome

      d.  Generalized sensorimotor polyneuropathy due to Sjgren syndrome

      e.  Small fiber neuropathy due to Churg-Strauss syndrome

18. Which of the following diagnostic studies would not be helpful in making the diagnosis?

      a.  Schirmer test

      b.  Anti-Ro (SSA) antibody

      c.  Anti-La (SSB) antibody

      d.  Lip biopsy

      e.  Rectal biopsy

19. Which of the following disorders is most commonly associated with atlanto-axial disloca- tion?

      a.  Rheumatoid arthritis

      b.  Systemic sclerosis

      c.  Sarcoidosis

      d.  Behet syndrome

      e.  Sjgren syndrome

Questions 20–21

20. A 44-year-old man with a history of hepatitis B infection due to blood transfusion presents to the clinic with complaints of pain in the right forearm with inability to extend his wrist or fingers and an inability to dorsiflex his left foot. He also complains of recent onset of severe abdominal pain. He is later admitted to the hospital with worsening abdominal pain and elevated serum lactate level. Because of concerns for bowel ischemia, he undergoes a mesenteric angiogram, which shows multiple mesenteric aneurysms. He later undergoes nerve biopsy, shown in Figure 16.1. Serum perinuclear anti-neutrophil cytoplasmic (P-ANCA) antibody is positive. Which of the following diagnoses is the most likely in this patient?

      a.  Churg-Strauss syndrome

      b.  Polyarteritis nodosa

      c.  Wegener granulomatosis

      d.  Kawasaki disease

      e.  Behcet syndrome

FIGURE 16.1 Nerve biopsy specimen. Courtesy of Dr. Richard Prayson. Shown also in color plates.

21. Which of the following systemic necrotizing vasculitides is not associated with the listed manifestations?

      a.  Churg-Strauss syndrome—asthma, nasal polyps, peripheral eosinophilia, peripheral neuro- pathy

      b.  Wegener granulomatosis—glomerulonephritis, inflammatory sinusitis, peripheral and cranial neuropathy

      c.  Hepatitis C—vasculitis with type 2 cryoglobulinemia

      d.  Kawasaki disease—aseptic meningitis

      e.  Polyarteritis nodosa—recurrent oral and genital ulcers

22. A 19-year-old woman from Thailand had reported to family members feeling unwell for weeks, with fevers and malaise. She had a history of erythema nodosum and mild anemia that was under investigation. Other symptoms she had previously reported included pain in the calves whenever she walked more than approximately 50 meters without rest. One morning, she is found collapsed on the floor of her apartment, unresponsive. She is taken to an emergency department where a CT scan of the brain showed an acute infarct involving the entire territory of the left MCA. MRI of the brain also shows an extensive right lateral medullary infarct. Angiogram shows significant disease of the aortic arch, bilateral severe narrowing of the subclavian arteries and left carotid, and right vertebral occlusion. What is the most likely diagnosis in this patient?

      a.  Primary angiitis of the CNS

      b.  Polyarteritis nodosa

      c.  Takayasu arteritis

      d.  Temporal arteritis

      e.  Microscopic polyangiitis

23. A 32-year-old woman from Turkey presents to the ophthalmologist, complaining of painful vision loss. Examination reveals uveitis. On review of systems, the patient endorses multiple recurrent oral and genital ulcers of several years duration. Which of the following is incorrect regarding this patient’s disorder?

      a.  The skin pathergy test is typically positive in this disorder

      b.  Headaches are the most common neurologic manifestation

      c.  Focal inflammation affecting the basal ganglia or brain stem is one pattern of CNS involvement that may occur

      d.  Increased intracranial pressure with dural venous sinus thrombosis occurs

      e.  A symmetric sensorimotor axonal polyneuropathy is a frequent occurrence in this disorder

24. Which of the following has not been associated with increased risk of venous thrombosis that may involve the CNS?

      a.  Anti-phospholipid antibody syndrome

      b.  Acquired factor VIII deficiency

      c.  G20210 A prothrombin polymorphism

      d.  Antithrombin III deficiency

      e.  Factor V Leiden

Questions 25–26

25. A 32-year-old African American woman presented to the clinic, complaining of a moderate holocephalic headache of 3 weeks’ duration. She denied a prior history of headaches. On review of systems, she endorsed a dry cough of several months’ duration, which she had not sought medical evaluation for. On examination, the patient had normal cranial nerve, motor, and sensory examination. MRI of the brain is shown in Figure 16.2. CSF analysis showed 21 WBCs/μL (normal 0 to 5 WBCs/μL), protein level of 86 mg/dL (normal 50 to 75 mg/dL), and glucose level of 86 mg/dL (normal 15 to 45 mg/dL). CT scan of the chest revealed bilateral hilar adenopathy. Bronchoscopy was performed, and pathological review of the specimens obtained showed multiple noncaseating granulomas. What is the most likely diagnosis in this patient?

FIGURE 16.2 (A) Coronal T1-weighted precontrast MRI and (B) Coronal T1-weighted postcontrast MRI

      a.  Wegener granulomatosis

      b.  Primary CNS lymphoma

      c.  Disseminated tuberculosis

      d.  Metastatic breast cancer

      e.  Sarcoidosis

26. Regarding the disorder depicted in question 25, which of the following is incorrect?

      a.  Myelopathy is the most common presentation

      b.  Corticosteroids are the mainstay of therapy

      c.  Both large and small fiber neuropathy as well as myopathy may occur

      d.  Cranial nerve (CN) VII is the most commonly involved CN

      e.  Serum angiotensin-converting enzyme levels are neither sensitive nor specific for diagnosis

27. A 52-year-old woman presents to the emergency department with episodes of severe headaches, palpitations, and diaphoresis that have been occurring daily for the past several weeks. She had seen two other physicians, one of which had ordered an MRI of the brain and an MRA of the Circle of Willis, which were normal. Her attacks had been attributed to panic disorder. While being evaluated in the ED, she experiences a similar attack. Blood pressure during the attack is 190/110 mm Hg. Which of the following statements is correct?

      a.  These symptoms are likely hot flashes due to menopause, and she should be treated with hormone replacement therapy

      b.  She is likely suffering from panic attacks and should be referred to a psychiatrist

      c.  She may be suffering from pheochromocytoma and should under go exploratory laparotomy to find the tumor

      d.  She may be suffering from pheochromocytoma and plasma free metanephrine level should be checked

      e.  She may be suffering from pheochromocytoma and should undergo 24-hour urine collection for 5-hydroxyindoleacetic acid

28. Which of the following statements is incorrect regarding the pituitary?

      a.  The anterior pituitary is derived embryologically from Rathke’s pouch, which evaginates from the oropharyngeal membrane during fetal development

      b.  The pituitary derives its blood supply from perforating branches of the basilar artery

      c.  Secretion of hormones from the anterior pituitary is controlled by the hypothalamus; the hypophyseal-portal system serves for regulation of hormone release controlled by the hypothalamus

      d.  Antidiuretic hormone and oxytocin are synthesized in the supraoptic and paraventricular nucleus of the hypothalamus and are secreted from the posterior pituitary

      e.  The classic visual field deficit occurring due to sellar lesions is a bitemporal hemianopia due to pressure on the optic chiasm

29. A 63-year-old woman undergoes transsphenoidal resection of a pituitary mass. Following surgery, she reports feeling markedly thirsty and reports urinating excessively. Her serum sodium level is noted to be 161 mmol/L (normal 135 to 146 mmol/L). Which of the following statements is correct regarding the likely cause of this patient’s hypernatremia?

      a.  Her urine osmolality is likely high

      b.  If this patient is administered desmopressin, her urine osmolality will increase

      c.  Water deprivation is the treatment of choice in this patient

      d.  Hypertonic saline is the treatment of choice for this patient

      e.  This patient’s serum sodium level is elevated because of an excess of antidiuretic hormone

30. A 62-year-old man with aneurysmal subarachnoid hemorrhage (SAH) is admitted to the ICU. Seven days into the hospitalization, he is noted to have a serum sodium concentration of 129 mmol/L (normal 135 to 146 mmol/L). Further testing reveals elevated urinary sodium and urinary osmolarity. He is noted to be hypotensive and tachycardic. Central venous pressure is low. Which of the following statements is correct?

      a.  His hyponatremia is likely due to syndrome of inappropriate antidiuretic hormone secretion (SIADH), and he should be treated with fluid restriction

      b.  His hyponatremia is likely due to cerebral salt wasting, and he should be treated with fluid restriction

      c.  His hyponatremia is likely due to SIADH, and he should be treated with intravenous fluids

      d.  His hyponatremia is likely due to cerebral salt wasting, and he should be treated with intravenous fluids

      e.  He should be treated with a loop diuretic such as furosemide

31. A 22-year-old woman delivers a healthy baby. A few hours after delivery, the woman complains of a severe headache. Shortly afterward, she becomes sleepy but is still arousable to minor stimuli. Her blood pressure is not elevated. Urine protein level is not elevated. She develops right arm and leg paresthesias. MRI of the brain does not show any abnormalities; MRA shows multifocal stenoses involving bilateral MCAs, PCAs, and left ACA. What is the most likely diagnosis in this patient?

      a.  Eclampsia

      b.  Cerebral venous sinus thrombosis

      c.  Postpartum cerebral angiopathy

      d.  Meningitis

      e.  Amniotic fluid embolism to the brain through a patent foramen ovale

32. A 32-year-old woman is 2 weeks postpartum from an uneventful pregnancy and delivery. She presents to the emergency department with a severe holocephalic headache, nausea, and two episodes of vomiting. Examination shows bilateral papilledema but is otherwise normal. She is otherwise healthy. Family history is remarkable for a history of spontaneous lower extremity deep venous thrombosis in her mother and recurrent miscarriages in her sister. Noncontrast CT scan of the brain is normal. Which of the following tests should be ordered in this patient?

      a.  CT scan of the brain with contrast

      b.  MRV

      c.  Cerebral angiogram

      d.  Transcranial Doppler ultrasonography

      e.  LP

Questions 33–34

33. A 28-year-old woman in her last trimester of pregnancy is witnessed to have a generalized tonic-clonic seizure of 2 minutes duration. She is brought to the emergency department (ED). On arrival, she is somnolent but arousable and follows simple commands. Blood pressure when is 180/100 mm Hg. Urine analysis shows 3+ proteinuria. In the ED, she has another generalized seizure of 1 minute duration. What is the most likely diagnosis in this patient?

      a.  Preeclampsia

      b.  Eclampsia

      c.  Gestational hypertension

      d.  Venous sinus thrombosis

      e.  Meningitis

34. Regarding the patient depicted in question 33, which of the following management strategies is appropriate?

      a.  Intravenous phenobarbital

      b.  Intravenous pentobarbital

      c.  Oral angiotensin-converting enzyme inhibitor for long-term blood pressure control

      d.  Oral diazepam

      e.  Intravenous magnesium sulfate

35. Which of the following statements is correct regarding the activity of neurologic disorders in pregnancy?

      a.  Pregnant women with epilepsy invariably have a worsening of seizures during pregnancy

      b.  Multiple sclerosis commonly improves during pregnancy

      c.  Multiple sclerosis relapse rates accelerate during pregnancy and then slow down after pregnancy

      d.  The majority of women with a history of migraines have increased migraine frequency during pregnancy

      e.  Myasthenia gravis typically goes into complete remission during pregnancy

36. In which of the following cases is the specified test not indicated given the patient’s presentation?

      a.  A 32-year-woman in the second trimester of pregnancy who complains of creepy-crawly feelings in her legs in the evening and at night—ferritin

      b.  A 21-year-old woman in the first trimester of pregnancy who presents to the emergency department with involuntary dancing-like movements of her right arm—anti-phospholipid antibodies

      c.  A 23-year-old woman who is planning a pregnancy but wishes to be tested for Huntington disease, given a strong family history—genetic counseling and genetic testing for Huntington disease

      d.  A 36-year-old woman in the second trimester of pregnancy who presents with a high-frequency postural tremor and palpitations—thyroid stimulating hormone

      e.  A 21-year-old woman with bipolar disorder started on risperidone after becoming manic during pregnancy presents with fever and muscle rigidity—serum copper

Answer Key

1. d

2. b

3. e

4. c

5. c

6. d

7. e

8. d

9. b

10. b

11. c

12. b

13. c

14. c

15. b

16. a

17. c

18. e

19. a

20. b

21. e

22. c

23. e

24. b

25. e

26. a

27. d

28. b

29. b

30. d

31. c

32. b

33. b

34. e

35. b

36. e

Answers

 1. d

Because of increased risk of hemorrhagic conversion, anticoagulation in patients with ischemic stroke due to infective endocarditis is warranted only in specific cases such as in patients with mechanical valves.

Infective endocarditis can lead to a variety of neurologic complications due to septic cerebral embolization, including but not limited to ischemic stroke (most common), intracranial hemorrhage (most often due to hemorrhagic conversion of an ischemic infarct), subarachnoid hemorrhage, cerebral abscess, meningoencephalitis, and seizures. Headaches and encephalopathy also occur, often as a symptom of the latter complications. Neurologic complications occur in both patients with native and prosthetic valve endocarditis, although they are more common with native valve endocarditis.

Septic cerebral emboli can lead to mycotic aneurysms by causing intraluminal arterial wall necrosis and destruction of the adventitia and muscularis with subsequent dilatation. Mycotic aneurysms are usually located at distal arterial bifurcations and are best detected by conventional cerebral angiography.

The mainstay of therapy for the neurologic complications of infective endocarditis is antibiotic therapy and acute symptomatic management (such as AEDs in patients with seizures).

 Aminoff MJ. Neurology and General Medicine, 4th ed. Philadelphia, PA: Elsevier; 2008.

 2. b

Intracranial hemorrhage is less common than ischemic stroke in patients with sickle cell anemia (Hemoglobin [Hb] SS disease).

Neurologic complications of Hb SS disease include ischemic stroke, intracranial hemorrhage, cranial neuropathies, spinal cord infarction (although rare), intracranial aneurysm formation with subarachnoid hemorrhage, ischemic optic neuropathy, optic atrophy, seizures, and headaches. Ischemic stroke is more common in children with Hb SS disease than in adults. In children, transcranial Doppler ultrasonography should be periodically performed, and when elevated velocities are detected, blood transfusions have been shown to reduce the risk of ischemic stroke. Patients with Hb SS disease are more likely than those with hemoglobin SC (Hb SC) disease to suffer from neurologic complications.

 Adams R, McKie V, Hsu L, et al. Prevention of a first stroke by transfusion in children with abnormal results on transcranial Doppler ultrasonography. N Engl J Med. 1998; 339:5–11.

 Aminoff MJ. Neurology and General Medicine, 4th ed. Philadelphia, PA: Elsevier; 2008.

 3. e, 4. c

Monoclonal gammopathy of undetermined significance (MGUS) alone can lead to neuropathy, and the presence of neuropathy in a patient with a monoclonal paraproteinemia does not necessarily indicate that the patient has multiple myeloma.

The plasma cell dyscrasias include Waldenstrm macroglobulinemia, MGUS, multiple myeloma, plasmacytomas, and others. Neurologic complications of the plasma cell dyscrasias may result from infiltration of the peripheral nervous system by abnormal plasma cells. Infiltration of vertebral bodies can lead to spinal cord or nerve root compression, and infiltration of peripheral nerves leads to a sensorimotor predominantly axonal neuropathy. Neuropathy in patients with plasma cell dyscrasias can also be due to amyloidosis or a paraneoplastic syndrome. Patients with plasma cell dyscrasias may develop encephalopathy due to hypercalcemia, hyperviscosity syndrome (due to hypergammaglobulinemia), and CNS infections, which such patients are prone to due to their immunocompromised state. CNS involvement in the plasma cell dyscrasias can occur but is relatively rare. POEMS syndrome (plasma cell dyscrasia with polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes) is a constellation of abnormalities seen in some patients with plasma cell dyscrasias.

A patient with immunoglobulin M (IgM) monoclonal gammopathy associated with antibodies against myelin-associated glycoprotein (MAG) is depicted in question 4. Patients with MGUS (which is characterized by the presence of a monoclonal protein in the absence of significant bone marrow involvement, anemia, renal failure, lytic lesions, or hypercalcemia) are at risk of developing symptomatic multiple myeloma. However, MGUS without evidence of other hematologic disorders can be associated with neuropathy. The neuropathy is often primarily demyelinating, and in some cases, particularly in patients with IgM MGUS, antibodies against MAG are detected in the serum.

Neuropathy in patients with monoclonal proteinemias can also occur because of the presence of cryoglobulins. Cryoglobulins are serum protein complexes that precipitate at specific temperatures. They occur in a variety of conditions as follows: Type I cryoglobulins are monoclonal proteins seen in the monoclonal paraproteinemias such as multiple myeloma and Waldenstrm macroglobulinemia. Type II cryoglobulins are seen in lymphoproliferative and autoimmune disorders, and infectious hepatitis. Type III cryoglobulins are seen with underlying infectious and autoimmune disorders. The most common neuropathic complication of cryoglobulinemia is generalized neuropathy, although mononeuritis or mononeuritis multiplex and cerebral vasculitis with ischemic stroke can also occur.

While Charcot-Marie-Tooth disease can present in adulthood, in the absence of family history or other evidence of a hereditary neuropathy on examination (discussed in Chapter 9), a costly genetic panel would not be of high yield. A technetium bone scan is not useful in investigating for the presence of bone lesions due to multiple myeloma (rather, plane film radiographs are used). Anti-GQ1b antibodies are typically seen in the Miller-Fisher variant of Guillain-Barr syndrome (discussed in Chapter 9). Genetic abnormalities of superoxide dismutase are detected in some patients with familial amyotrophic lateral sclerosis (discussed in Chapter 11), which is not the diagnosis in this case.

 Aminoff MJ. Neurology and General Medicine, 4th ed. Philadelphia, PA: Elsevier; 2008.

 5. c

This patient’s laboratory studies point to the presence of hemolytic anemia, renal failure, and thrombocytopenia. Given her presentation with a seizure, her history is consistent with thrombotic thrombocytopenic purpura (TTP). The diagnostic pentad of TTP includes a microangiopathic hemolytic anemia, low platelet counts, renal dysfunction, neurologic signs or symptoms, and fever, although not all five features may necessarily be present. TTP results from a deficiency of von Willebrand factor–cleaving protease, leading to abnormal platelet aggregation. Neurologic manifestations include seizures, headaches, encephalopathy, and in severe cases coma, cranial neuropathies, and focal neurologic deficits. Treatment includes emergency plasma exchange.

Hemolytic-uremic syndrome (HUS) shares several features with TTP but HUS is associated with more severe renal dysfunction. It is predominantly a disorder of childhood, often associated with an infection with Shiga toxin–producing bacteria such as certain strains of Escherichia coli and Shigella. The syndrome is typically preceded by abdominal pain and diarrhea, not present in the case depicted in question 5. Seizures, encephalopathy, cranial nerve palsies, and neuropathy may occur.

Idiopathic thrombocytopenic purpura does not typically have primary neurologic manifestations (unless intracranial bleeding occurs, which is rare even with markedly low platelet levels), and it is not associated with a hemolytic anemia. Disseminated intravascular coagulation (DIC) results in a coagulopathy; in this patient, the coagulation tests were normal. Because DIC typically occurs in the setting of a severe illness, there is often associated encephalopathy, and seizures and other neurologic manifestations may complicate the underlying illness.

Anti-phospholipid antibody syndrome is discussed in question 24.

 Aminoff MJ. Neurology and General Medicine, 4th ed. Philadelphia, PA: Elsevier; 2008.

 Bradley WG, Daroff RB, Fenichel GM, et al. Neurology in Clinical Practice, 5th ed. Philadelphia, PA: Elsevier; 2008.

 6. d

This patient’s history is consistent with hepatic encephalopathy, or portosystemic encephalopathy. Hepatic encephalopathy is seen in patients with liver cirrhosis of any cause (not only in those with alcoholic cirrhosis), and the extent of liver dysfunction, rather than the cause of cirrhosis, correlates with the degree of encephalopathy. Clinical manifestations are variable, ranging from mildly decreased attention, disorientation, and personality changes to somnolence and in severe cases coma. Asterixis, or negative myoclonus, is seen in hepatic encephalopathy and other metabolic encephalopathies. EEG findings include generalized slowing and triphasic waves (discussed also in Chapter 5).

Although hyperammonemia has been largely implicated in the pathophysiology of hepatic encephalopathy, other abnormalities of neurotransmission, including abnormal GABA and glutamate neurotransmission, and abnormalities in fatty acids are also implicated. Ammonia is normally produced in the colon and is taken to the liver through the hepatic portal vein, where it is converted to urea and excreted in the urine. With liver dysfunction, ammonia and other toxic substances are shunted to the systemic circulation (so-called portosystemic shunting). Transjugular intrahepatic portosystemic shunt, used to treat certain complications of portal hypertension such as recurrent esophageal variceal hemorrhage, increases the risk of hepatic encephalopathy, as it enhances shunting of ammonia from the liver to the systemic circulation.

Serum ammonia levels may be elevated, but hepatic encephalopathy may occur even at relatively low serum ammonia levels, due to the impaired cerebral ammonia uptake and metabolism seen in patients with cirrhosis. Clinical improvement in mental status is the best indicator of response to therapy, and serum ammonia concentrations are not reliable for this purpose. Treatment of hepatic encephalopathy includes correction of precipitating factors (hypovolemia, gastrointestinal bleed, infection, and others) and reduction of ammonia absorption from the colon by using the disaccharide lactulose, sometimes in combination with the antibiotics rifaximin or neomycin.

The pathological hallmark of hepatic encephalopathy is the Alzheimer type II astrocyte, which is seen in various areas of the cortex and subcortical regions, including the basal ganglia, thalamus, dentate of the cerebellum, and red nuclei.

 Aminoff MJ. Neurology and General Medicine, 4th ed. Philadelphia, PA: Elsevier; 2008.

 Romero-Gomez M. Pharmacotherapy of hepatic encephalopathy in cirrhosis. Expert Opin Pharmacother. 2010; 11:1317–1327.

 7. e

This patient’s history, examination, and biopsy findings are consistent with celiac disease. Sulfonamides are used for the treatment of Whipple disease rather than celiac disease; absence of periodic acid Schiff -positive macrophage inclusions on bowel biopsy makes Whipple disease less likely (see Chapter 15).

Celiac disease, also known as gluten-sensitive enteropathy, results from an immune-mediated insensitivity to gluten, a protein found in foods containing cereal grains. Chronic diarrhea with malabsorption is common, and small bowel biopsy shows atrophy of intestinal villi. Celiac disease can have a variety of neurologic manifestations; in fact, neurologic manifestations may be the only clinical features in a minority of patients. These include a predominantly axonal peripheral neuropathy, inflammatory myopathy, cerebral calcifications, and seizures. Prominent cerebellar involvement is often seen because of loss of Purkinje cells in the cerebellum. The mainstay of treatment is a gluten-free diet, although some of the neurologic manifestations, such as cerebellar atrophy, may not be reversible. Patients with celiac disease can also have neurologic complications resulting from vitamin E deficiency (discussed in Chapter 17) due to chronic malabsorption.

 Aminoff MJ. Neurology and General Medicine, 4th ed. Philadelphia, PA: Elsevier; 2008.

 8. d

Patients with inflammatory bowel diseases are at increased risk of both venous and arterial thrombosis, including ischemic stroke.

Crohn’s disease and ulcerative colitis are inflammatory bowel diseases (IBD). Neurologic complications of these disorders are most common during exacerbations (manifested by worsening diarrhea, abdominal pain, and other gastrointestinal symptoms) but can occur at any time. Patients with IBD are at an increased risk of both venous and arterial thrombosis, which may be due to activation of the coagulation cascade, impaired fibrinolysis, platelet activation, and systemic activation. Cerebral venous thrombosis and ischemic strokes may occur. Other neurologic complications include demyelinating and axonal neuropathies, myopathies, and cranial neuropathies, particularly cranial nerve VII palsy as is seen in Melkersson-Rosenthal syndrome, which also includes tongue fissuring and angioedema. White matter abnormalities resembling the demyelinating lesions of multiple sclerosis are seen in some patients with IBD; the significance of these findings is unclear. Patients with IBD can also have neurologic complications resulting from malabsorption of vitamin E, vitamin B12, or other nutrients (discussed in Chapter 17).

 Aminoff MJ. Neurology and General Medicine, 4th ed. Philadelphia, PA: Elsevier; 2008.

 Pfeiffer RF. Neurologic presentations of gastrointestinal disease. Neurol Clin. 2010; 28:75–87.

 9. b

A generalized sensorimotor polyneuropathy is the most common type of neuropathy in patients with chronic renal failure. Patients with renal failure can have a variety of neurologic signs and symptoms. Alteration in awareness from renal failure, or uremic encephalopathy, may manifest as reduced alertness, poor attention and concentration, perceptual errors, and hallucinations. In more severe cases, the patient may be obtunded. Patients with uremic encephalopathy, as with other metabolic encephalopathies, may exhibit multiple motor symptoms including asterixis, myoclonus (so-called uremic twitching, attributed to alterations in cerebral phosphate metabolism), and gait ataxia. Seizures can occur in both acute and chronic renal failure. When treating seizures in patients with renal failure, attention must be given to the pharmacokinetic changes that occur in such patients. Uremic neuropathy is typically a distal, symmetric sensorimotor axonal polyneuropathy; mononeuritis multiplex is typically not associated with renal failure itself, unless there is an underlying connective tissue disorder leading to both the renal failure and the mononeuropathies. Mononeuropathies can occur as a complication of arteriovenous shunt placement.

Dialysis disequilibrium syndrome is a spectrum of neurologic signs and symptoms occurring during or after dialysis. It is most common during initiation of urgent dialysis but may occur at any time. It is thought to result at least in part from shifts of water into the brain due to changes in the osmotic gradient. Clinical manifestations can range from mild encephalopathy to fatal cerebral edema. Other neurologic manifestations in patients with renal failure include dementia and restless legs syndrome.

 Aminoff MJ. Neurology and General Medicine, 4th ed. Philadelphia, PA: Elsevier; 2008.

10. b

Hypokalemia typically manifests with peripheral nervous system abnormalities such as muscle cramps or tetany; CNS manifestations rarely, if ever, occur.

Various electrolyte abnormalities can lead to neurologic manifestations. Hyponatremia typically causes more severe neurologic symptoms when it develops rapidly, but they can occur also in chronic hyponatremia. A nonspecific encephalopathy is the most frequent manifestation. Seizures can occur with acute hyponatremia, usually with serum sodium levels of 115 mEq/L or less. Correction of serum sodium levels is the mainstay of treatment of hyponatremia-associated seizures, but care must be taken not to correct serum sodium levels too rapidly, given the risk of central pontine myelinolysis (discussed in Chapter 3). CNS manifestations of hypernatremia typically occur with serum sodium concentrations higher than 160 mEq/L and include encephalopathy, seizures, and in severe cases coma.

Both hypokalemia and hyperkalemia are associated with peripheral rather than CNS manifestations. Hypokalemia can lead to myalgias and proximal limb weakness (with sparing of bulbar muscles). Rhabdomyolysis can occur with severe hypokalemia. Tetany may be a manifestation of hypokalemia (or hypocalcemia). Hyperkalemia is associated with muscle weakness in the context of hyperkalemic periodic paralysis (discussed in Chapter 10) or Addison disease, but rarely otherwise.

Neurologic manifestations of hypercalcemia include encephalopathy and in severe cases coma. Other manifestations include headache and rarely seizures. Hyperparathyroidism can lead to depression, encephalopathy, and myopathy. Seizures are a much more common complication of hypocalcemia. Hypocalcemia also leads to tetany, which is due to spontaneous repetitive nerve action potentials. Initial symptoms of hypocalcemia include tingling in the perioral area and the digits. In more severe later stages, tonic muscle spasms occur, beginning in the fingers and toes (carpopedal spasm) but in some cases involving more proximal musculature; when the tetany involves truncal musculature, opisthotonos is present.

Hypomagnesemia can lead to encephalopathy, tremor, myoclonus, and in severe cases seizures. Hypermagnesemia is rare, usually occurring in the setting of renal failure. Neurologic manifestations of severe hypermagnesemia include muscle weakness that when severe may progress to respiratory failure.

 Aminoff MJ. Neurology and General Medicine, 4th ed. Philadelphia, PA: Elsevier; 2008.

11. c

In a patient presenting with cognitive dysfunction, apathy, and hypersomnolence, hypothyroidism is a diagnostic possibility, and serum thyroid stimulating hormone (TSH) level should be tested. Thyroid function should be assessed in all patients presenting with cognitive dysfunction, but particularly older adults (see discussion of question 12 for other neurologic manifestations of thyroid disease). Growth hormone deficiency is unlikely to lead to the mentioned presentation; vitamin D deficiency should be checked for in older adults, but symptoms (if any) include myalgias and other pains. There is no suggestion of an autoimmune condition in this case, and a TSH would be more important to order than an anti-neuronal antibody. Anti-microsomal antibodies may be checked in the evaluation of a patient with thyroid dysfunction but would not be the first test to order. Anti-microsomal antibodies are also checked in patients with a relapsing-remitting encephalopathy or with other neurologic manifestations that raise concern for steroid-responsive encephalopathy with autoimmune thyroiditis (SREAT, or Hashimoto encephalopathy).

 Aminoff MJ. Neurology and General Medicine, 4th ed. Philadelphia, PA: Elsevier; 2008.

12. b

Pseudomyotonia, or a delay in muscle relaxation following elicitation of deep tendon reflex, is a feature of hypothyroidism.

Congenital hypothyroidism is the most treatable cause of mental retardation. Untreated, it leads to cretinism, which is manifested by cognitive dysfunction, gait dysfunction, and hearing loss. The most common cause is dysgenesis of the thyroid, but severe maternal iodine deficiency also can lead to it.

Both hypothyroidism and hyperthyroidism can lead to myopathy. Serum creatine kinase level is typically elevated. Gait dysfunction in patients with thyroid disorders could be due to cerebellar ataxia, myopathy, neuropathy, or a combination of these.

Tremor is almost universally present in patients with untreated hyperthyroidism. It is typically a postural, high-frequency tremor that is thought to result from increased β-adrenergic activity. Other abnormal movements seen in patients with hyperthyroidism include parkinsonism, dyskinesias, chorea, and myoclonus.

Thyroid eye disease in patients with Graves disease results from an immune-mediated increase in connective tissue of the orbit. Manifestations include proptosis, extraocular muscle enlargement with restricted movement, optic nerve compression, and ocular neuromyotonia. Restricted upward gaze is the most common extraocular abnormality seen in patients with thyroid eye disease, but impaired abduction, adduction, and downward gaze also occur. Eyelid retraction in patients with Graves disease may be due to overactivation of Muller muscle (a sympathetically innervated muscle) or eyelid fibrosis.

Myxedema coma, due to severe untreated hypothyroidism, typically occurs in older adults and is often precipitated by intercurrent illnesses. Clinical features include hypothermia and encephalopathy. Seizures occur in some patients.

Patients with hypothyroidism may develop diffuse peripheral neuropathy with both axonal and/or demyelinating features and entrapment neuropathy, most commonly carpal tunnel syndrome (discussed in Chapter 9), resulting from deposition of mucopolysaccharides.

Other neurologic manifestations of thyroid disease include both obstructive and central sleep apnea, headache, and hearing impairment with tinnitus.

 Aminoff MJ. Neurology and General Medicine, 4th ed. Philadelphia, PA: Elsevier; 2008.

13. c

Peripheral nervous system complications of diabetes include both small and large fiber neuropathy, autonomic neuropathy, radiculopathy (including thoracic radiculopathy), cranial neuropathies (most commonly, cranial nerves III and VI), and diabetic amyotrophy (discussed in Chapter 9). Diabetic polyneuropathy occurs in more than half of patients with diabetes. It is pathophysiologically complex but is in part related to increased activity of the aldose reductase pathway, which leads to accumulation of intraneuronal sorbitol and fructose with subsequent impairment in intracellular signaling, impaired auto-oxidation of glucose, accumulation of advanced glycation end products, oxidative stress, and impaired neuronal microvascular function.

Early in diabetes, small nerve fibers are predominantly affected, leading to positive sensory symptoms such as tingling and pain. Large-fiber involvement may also lead to positive sensory symptoms, although later in the disease, sensory loss predominates. Diabetic polyneuropathy is most commonly a distal, symmetric, sensorimotor polyneuropathy. Sensory loss is the most common clinical manifestation of diabetic polyneuropathy; motor weakness typically occurs only in advanced cases or from other complications of diabetes (discussed in Chapter 9). With involvement of nociceptive fibers, injuries may be painless, with the development of painless ulcers that often heal poorly, as in the case depicted in question 13. Charcot joints, or relatively painless progressive deformities of the foot and ankle, also occur.

Autonomic neuropathy is common in diabetics and can result in a variety of abnormalities including impotence, bladder dysfunction, abnormal pupillary reaction, orthostatic hypotension, and gastroparesis.

Neuropathy can result from impaired glucose tolerance alone in patients not otherwise meeting laboratory criteria for diabetes. In fact, impaired glucose tolerance is often found in patients with otherwise idiopathic neuropathy, and treatment including diet and exercise may halt progression of the neuropathy. Diabetic polyneuropathy is irreversible, but slowing the progression is accomplished by adequate glycemic control. Painful neuropathy is treated with medications including nonsteroidal anti-inflammatory agents, antidepressants (tricyclic antidepressants, selective serotonin reuptake inhibitors, norepinephrine serotonin reuptake inhibitors), anticonvulsants (gabapentin and pregabalin), and topical agents such as capsaicin.

Diabetic oculomotor palsy may present acutely and be associated with ipsilateral forehead pain. It results from ischemia to the third nerve; pupillomotor fibers are spared, given their more circumferential location, distinguishing it from other causes of acute oculomotor palsy such as cerebral aneurysms (see also Chapter 1). Cranial nerve VI palsy is another manifestation of diabetes.

CNS complications of diabetes may result from diabetic ketoacidosis and hyperosmolar hyperglycemic state, both of which can lead to encephalopathy and in severe cases stupor and coma. Cerebrovascular disease due to atherosclerosis and arteriosclerosis due to frequently comorbid hypertension can lead to various CNS manifestations resulting from ischemic stroke. Acute and sometimes permanent chorea can occur in patients with nonketotic hyperglycemia.

 Aminoff MJ. Neurology and General Medicine, 4th ed. Philadelphia, PA: Elsevier; 2008.

 Smith AG, Singleton R. Impaired glucose tolerance and neuropathy. Neurologist. 2008; 14:23–29.

14. c

This man’s history and examination are consistent with Cushing disease, which results from hypercortisolism in the setting of an ACTH-secreting pituitary adenoma. Neurologic manifestations of Cushing disease include headache, proximal myopathy, cognitive dysfunction, and behavioral changes, with psychosis in severe cases.

In this patient, the bitemporal hemianopia is a clue to a compressive lesion of the optic chiasm, distinguishing Cushing disease from Cushing syndrome, which can result from cortisol-secreting tumors or from ectopic ACTH production as can occur with paraneoplastic syndromes or other causes.

Hypothyroidism (discussed in question 12) can lead to weight gain, cognitive dysfunction, and proximal myopathy but not typically the skin changes and aggressive behavior depicted in question 14. Hyperthyroidism (discussed in question 12) leads to weight loss and lacks the skin findings depicted. Hypocortisolism, as occurs in primary adrenal insufficiency or Addison disease, can lead to fatigue, cognitive dysfunction, myopathic weakness, and psychiatric symptoms, but typically not weight gain. Skin manifestations in Addison disease include hyperpigmentation. Hyperparathyroidism can lead to depression, encephalopathy, and myopathy, but not the other features depicted in the case.

 Aminoff MJ. Neurology and General Medicine, 4th ed. Philadelphia, PA: Elsevier; 2008.

15. b

This patient’s history is consistent with osteopetrosis, a sclerosing bone disorder characterized by pathologically increased bone mass due to impaired bone resorption by osteoclasts. It is caused by a mutation in an ATPase or a chloride channel. Autosomal dominant and recessive forms exist, each differing in their age at presentation and clinical manifestations. Some of the younger-onset forms are severe. The majority of patients are asymptomatic, but symptoms may include bone pain, joint deformities, secondary osteoarthritis, and fractures. Many adults with osteopetrosis are asymptomatic, but cranial neuropathies may occur because of skull thickening with subsequent narrowing of cranial nerve (CN) foramina in the base of the skull. The most commonly involved CNs are CNs II (in some cases leading to optic atrophy with blindness), VII, and VIII, leading to irreversible hearing loss, as in this patient. Elevated serum alkaline phosphatase level is a clue to this diagnosis. The olfactory nerve is also commonly involved.

A bone disorder with similar neurologic complications to osteopetrosis is Paget disease. Paget disease results from excessive bone turnover and abnormal compensatory bone formation. It is often asymptomatic and diagnosed incidentally, but it may also result in cranial neuropathies (most commonly CN VIII, but also CN II), spinal stenosis with resulting myelopathy, radiculopathy, or a combination of these. Serum alkaline phosphatase level is also elevated in Paget disease.

Achondroplasia is an autosomal dominant bone dysplasia characterized by short stature. Cognition often develops normally, but in some, developmental delay may be present. Other neurologic complications include cervical myelopathy due to craniocervical junction abnormalities, radiculopathy, and hydrocephalus.

Ankylosing spondylitis is a chronic polyarticular inflammatory disorder that involves the spine and sacroiliac joints. Uveitis and aortic insufficiency may occur. Neurologic complications include vertebral fracture with secondary spinal cord injury and spinal stenosis, leading to radiculopathy and/or myelopathy. Cauda equina syndrome due to arachnoiditis may occur.

Relapsing polychondritis results from recurrent episodes of inflammation and destruction of cartilage. Episodes commonly involve not only the ears but also the upper airway. Neurologic manifestations include vertigo and hearing loss due to involvement of the vestibulocochlear system. Ocular motor palsies and optic neuritis may rarely occur. Other neurologic manifestations of relapsing polychondritis include cerebral vasculitis, peripheral neuropathy, and aseptic meningitis.

 Aminoff MJ. Neurology and General Medicine, 4th ed. Philadelphia, PA: Elsevier; 2008.

 Ruiz-Garcia M, Tovar-Baudin A, Del Castillo-Ruiz V, et al. Early detection of neurological manifestations in achondroplasia. Childs Nerv Syst. 1997; 13:208–213.

 Steward CG. Neurological aspects of osteopetrosis. Neuropathol Appl Neurobiol. 2003; 29:87–97.

16. a

This patient’s history and examination are consistent with systemic lupus erythematosis (SLE). This is an autoimmune disorder characterized by multiorgan involvement and presence of various antibodies including anti–double-stranded DNA and anti-Smith antigen. There are specific diagnostic criteria based on hematologic, dermatologic, neurologic, renal, cardiac, and serologic features.

SLE may involve both the CNS and the peripheral nervous system. Neuropsychiatric manifestations of SLE include cognitive dysfunction, depression, anxiety, and psychosis. Headaches and seizures are among the most common neurologic manifestations; others include aseptic meningitis (as is likely the case in this patient), chorea, and myelopathy. There is an increased risk of ischemic strokes due to a variety of mechanisms including cardioembolism, antiphospholipid antibody–associated thrombosis, premature intracranial atherosclerosis, and rarely secondary cerebral vasculitis. Intracerebral hemorrhage may also occur. Peripheral nervous system manifestations include cranial neuropathies, peripheral mononeuropathy or mononeuritis multiplex, demyelinating or axonal polyneuropathy, and plexopathy.

Systemic sclerosis is a multiorgan disorder that leads to fibrosis. Scleroderma is the term used to describe the skin thickening that is seen in this disorder. Subcutaneous calcinosis, Raynaud phenomenon, esophageal dysfunction, sclerodactyly, and telangiectasia (CREST) syndrome is seen in some patients with systemic sclerosis. The diagnosis is made on the basis of the presence of clinical features and antibodies against centromeres and topoisomerases. Intracerebral vasculopathy leading to TIAs, ischemic stroke, or intracranial hemorrhage may occur. Peripheral nervous system manifestations include carpal tunnel syndrome, trigeminal neuropathy, peripheral polyneuropathy, and mononeuritis multiplex.

Sarcoidosis is discussed in questions 25 and 26, Behet syndrome in question 23, and Sjgren syndrome in questions 17 and 18.

 Aminoff MJ. Neurology and General Medicine, 4th ed. Philadelphia, PA: Elsevier; 2008.

17. c, 18. e

This patient’s history and examination are consistent with a sensory neuronopathy due to Sjgren syndrome. Rectal biopsy is used to diagnose amyloidosis and is not helpful in the diagnosis of Sjgren syndrome.

Sjgren syndrome is an inflammatory multiorgan disorder primarily affecting exocrine glands (such as the salivary and lacrimal glands), leading to xerostomia and xerophthalmia (which when severe can lead to keratoconjunctivitis sicca). Sjgren syndrome often co-occurs with other autoimmune disorders. Constitutional symptoms are often present.

Peripheral nervous system involvement in Sjgren syndrome manifests most commonly as a distal predominantly sensory or mixed sensorimotor axonal polyneuropathy. A sensory neuronopathy, or dorsal root ganglionopathy, as depicted question 17, may occur, and results from involvement of the dorsal root ganglia. With sensory neuronopathy, the sensory loss may not follow a length-dependent pattern but rather can affect the face or trunk before distal segments of the limbs (discussed further in Chapter 9). Sensory ataxia is often prominent in such cases. Other manifestations of Sjgren syndrome include isolated small fiber neuropathy (without large fiber involvement), autonomic neuropathy, and cranial neuropathy. CNS manifestations of Sjgren syndrome are uncommon but include cognitive dysfunction, focal brain lesions most often affecting subcortical white matter, aseptic meningitis, optic neuritis, and myelopathy.

Diagnosis is made on the basis of the presence of symptoms of xerostomia and xerophthalmia, objective documentation of xerophthalmia with Schirmer test, serologic testing for the autoantibodies anti-Ro (SSA) or anti-La (SSB), and/or minor salivary gland biopsy. Treatment is a combination of symptomatic therapies and immunosuppressants in some cases.

This patient’s examination and nerve conduction findings are not consistent with an isolated small fiber neuropathy, in which NCS are normal. Normal motor NCS would not be seen in a sensorimotor polyneuropathy. Churg-Strauss syndrome is discussed in questions 20 and 21. Small fiber neuropathy due to systemic lupus erythematosus would not be associated with abnormal NCS, and other systemic features would be present. Vitamin B12deficiency can lead to a variety of neurologic manifestations (discussed in Chapter 17) but would not be associated with the dry eyes and mouth that this patient describes.

 Aminoff MJ. Neurology and General Medicine, 4th ed. Philadelphia, PA: Elsevier; 2008.

 Segal B, Carpenter A, Walk D. Involvement of nervous system pathways in primary Sjögren’s syndrome. Rheum Dis Clin N Am. 2008; 34:885–906.

19. a

Atlanto-axial dislocation is most common in patients with rheumatoid arthritis, a polyarticular symmetric inflammatory disorder. In addition to an inflammatory arthritis, other features include subcutaneous nodules, hypersplenism, amyloidosis, scleritis, cardiac, and pulmonary involvement. Diagnosis is made on the basis of the presence of clinical features, rheumatoid factor, and cyclic citrullinated peptide. Atlanto-axial dislocation in rheumatoid arthritis results from inflammation and resulting laxity of the ligaments, with pannus formation. Myelopathy may also occur. The most common neurologic manifestation of rheumatoid arthritis is carpal tunnel syndrome. Other neurologic manifestations of rheumatoid arthritis include headaches, compressive mononeuropathies, distal sensorimotor polyneuropathy, mononeuritis multiplex, and rarely ischemic stroke.

Systemic sclerosis is discussed in question 16, sarcoidosis in questions 25 and 26, Behet syndrome in question 23, and Sjgren syndrome in questions 17 and 18.

 Aminoff MJ. Neurology and General Medicine, 4th ed. Philadelphia, PA: Elsevier; 2008.

20. b, 21. e

The patient mentioned in question 20 has a history consistent with polyarteritis nodosa. Recurrent oral and genital ulcers are seen in Behet disease (see discussion to question 23), not in polyarteritis nodosa.

Polyarteritis nodosa, Wegener granulomatosis, Kawasaki disease, and Churg-Strauss syndrome are systemic necrotizing vasculitides involving medium and small vessels. These diseases typically involve multiple organs with often prominent constitutional symptoms. Neurologic manifestations of the systemic vasculitides of medium and small vessels include seizures, mononeuritis multiplex, cranial neuropathies (with the most frequently involved being cranial nerve VIII), and peripheral polyneuropathies. The neuropathy seen in these vasculitides is a necrotizing vasculitic ischemic neuropathy due to involvement of vasa vasorum. Figure 16.1 shows a nerve biopsy specimen demonstrating perivascular neutrophilic inflammatory infiltrate with necrosis. Arteritis of cerebral blood vessels may also lead to ischemic stroke.

Although overlap occurs in these different disorders, certain features help distinguish them. Diagnostic criteria for Churg-Strauss syndrome include asthma, eosinophilia, and sinus and pulmonary involvement. Features of Wegener granulomatosis include glomerulonephritis, paranasal sinusitis, and pulmonary involvement. The presence of granulomas on biopsy and the presence of cytoplasmic anti-neutrophil cytoplasmic (C-ANCA) antibody and antibodies to proteinase-3 allow for the diagnosis. Polyarteritis nodosa leads to a vasculopathy in multiple organ systems. It leads to prominent constitutional symptoms, renal, cardiac, and gastrointestinal involvement, and is associated with chronic hepatitis B infection. Skin manifestations include livedo reticularis, skin ulcerations, and subcutaneous nodules. Kawasaki disease is a disorder of childhood and is characterized by acute onset of fever, conjunctivitis, mucositis, polymorphous rash, lymphadenopathy, and other findings, including increased risk coronary artery aneurysms; neurologic involvement includes the occurrence of aseptic meningitis. Cryoglobulinemia is discussed in question 4. The systemic necrotizing vasculitides are treated with immunosuppression, often including corticosteroids and cyclophosphamide.

 Aminoff MJ. Neurology and General Medicine, 4th ed. Philadelphia, PA: Elsevier; 2008.

22. c

This patient’s history and angiographic findings are consistent with Takayasu arteritis, or pulseless disease, a large-vessel vasculitis most common in females of Asian descent. Commonly involved vessels include the subclavian arteries, but the aorta and cerebral vessels can also be involved, leading to ischemic stroke as in the case depicted in question 22. Takayasu arteritis manifests with constitutional symptoms and symptoms related to organ ischemia such as peripheral claudication. Treatment is with immunosuppression and in some cases surgical or endovascular treatment of vessel stenosis or occlusion.

Polyarteritis nodosa, microscopic polyangiitis, and temporal arteritis affect medium or small vessels as opposed to large ones. Temporal arteritis, or giant cell arteritis (discussed in Chapter 4), most commonly leads to headaches, but ischemic strokes or transient ischemic attacks can also occur in a minority due to involvement of the carotid and vertebral arteries.

 Aminoff MJ. Neurology and General Medicine, 4th ed. Philadelphia, PA: Elsevier; 2008.

23. e

Peripheral nervous system involvement with Behet syndrome is rare. Behet syndrome is a systemic inflammatory disorder that typically affects multiple organs, including the eyes, skin, gastrointestinal tract, joints, and vascular system. Uveitis and orogenital ulcers are characteristic manifestations. Diagnostic criteria include recurrent oral ulceration, plus two of the following: recurrent genital ulceration, eye lesions including uveitis, skin lesions (such as papulopustular lesions), or a positive pathergy skin test. Patients may also have arthritis, subcutaneous thrombophlebitis, deep venous thrombosis, and gastrointestinal lesions.

Behet syndrome is most common in younger woman of Mediterranean or east Asian descent. Diagnosis is based on clinical features; in many patients with Behet syndrome, the skin pathergy test is positive but is nonspecific. The most common CNS manifestation is headache. CNS involvement may also include focal inflammatory brain lesions most commonly affecting the basal ganglia and/or brain stem. Progressive personality change, psychiatric disorders, and dementia may develop. Increased intracranial pressure associated with venous sinus thrombosis is another potential pattern of CNS involvement. Unlike other systemic vasculitides, peripheral nervous system involvement with Behet syndrome is rare, although peripheral neuropathy or myopathy may occur.

 Al-Araji A, Kidd DP. Neuro-Behçet’s disease: epidemiology, clinical characteristics, and management. Lancet Neurol. 2009; 9:192–204.

 Aminoff MJ. Neurology and General Medicine, 4th ed. Philadelphia, PA: Elsevier; 2008.

24. b

Acquired factor VIII deficiency, or acquired hemophilia, leads to increased risk of hemorrhage rather than thrombosis.

Anti-phospholipid antibody syndrome (APLS) and most of the so-called hereditary thrombophilias, including G20210 A prothrombin polymorphism, mutation in the methylene tetrahydrofolate reductase gene (leading to hyperhomocysteinemia), and factor V Leiden, as well as others including antithrombin III, protein C, and protein S deficiency, lead to venous thrombosis. Therefore, venous sinus thrombosis is the most common neurologic manifestation of these disorders. However, arterial ischemia in the form of venous infarction is seen, as are paradoxical emboli to the cerebral vasculature from the venous system through an intracardiac right-to-left shunt. Other causes of both venous and arterial thrombosis include malignancy, heparin-induced thrombocytopenia, systemic vasculitides (discussed in questions 20 and 21) and myeloproliferative diseases (such as essential thrombocythemia, polycythemia rubra vera, and others).

APLS is a disorder of thrombosis resulting from the presence of circulating antibodies against phospholipid-bound proteins such as anticardiolipin antibodies and lupus anticoagulant antibodies. In addition to venous and less commonly arterial thrombosis, other neurologic manifestations seen in APLS include chorea, headaches, and seizures.

 Aminoff MJ. Neurology and General Medicine, 4th ed. Philadelphia, PA: Elsevier; 2008.

 Landolfi R, Di Gennaro L, Falanga A. Thrombosis in myeloproliferative disorders: pathogenetic facts and speculation. Leukemia. 2008; 22:2020–2028.

 Levy JH, Hursting MJ. Heparin-induced thrombocytopenia, a prothrombotic disease. Hematol Oncol Clin North Am. 2007; 21:65–88.

25. e, 26. a

The patient depicted in question 25 has sarcoidosis. The most commonly involved organs in sarcoidosis are the lungs. Myelopathy can occur but is relatively uncommon.

Sarcoidosis is a granulomatous, immune-mediated disorder that may involve multiple organ systems including (but not limited to) the lungs (most commonly), skin, heart, and central and peripheral nervous system. In the United States, it is more common in African American females. Neurologic signs or symptoms as the primary presentation are rare; less than 10% of sarcoidosis cases present with extrapulmonary involvement leading to diagnosis. The most common presentation of neurosarcoidosis is cranial neuropathy, with cranial nerve VII being the most frequently affected. Multiple cranial neuropathies may occur in some patients. Other neurologic manifestations include aseptic meningitis (as in the case presented in question 25), hydrocephalus, parenchymal disease/mass lesion, myelopathy, small and large fiber peripheral neuropathy, and myopathy. Hypothalamic or pituitary involvement may lead to endocrinopathy.

The diagnosis of sarcoidosis is established on the basis of the history, examination, and demonstration of noncaseating granulomas on biopsy. Serum angiotensin-converting enzyme (ACE) is neither sensitive nor specific, but increased serum ACE levels are a marker of disease activity. In patients with known systemic sarcoidosis, neurosarcoidosis is diagnosed in the setting of neurologic signs or symptoms and/or findings of LP or MRI of the brain or spine (although alternative causes, such as in CNS infections in sarcoidosis patients being treated with immunosuppressive therapy must also be considered and excluded). Diffuse leptomeningeal enhancement, often with a predominance at the base of the brain, is the classic finding, although focal parenchymal enhancing brain lesions can also occur (as shown in Figure 16.2 in the splenium of the corpus callosum) as can intramedullary or extramedullary enhancing spine lesions. Treatment is with immunosuppressive therapy including corticosteroids and, in some cases, steroid-sparing agents such as methotrexate.

Lymphoma and breast cancer are not associated with the presence of granulomas on biopsy. Wegener granulomatosis is associated with granulomas and can also lead to multiple cranial neuropathies, but a history of recurrent sinusitis and other serologic findings help distinguish Wegener granulomatosis (discussed in questions 20 and 21) from neurosarcoidosis. Biopsy specimens in tuberculosis show caseating as opposed to noncaseating granulomas.

 Aminoff MJ. Neurology and General Medicine, 4th ed. Philadelphia, PA: Elsevier; 2008.

27. d

This patient’s history is concerning for pheochromocytoma, which may present with episodes of headache, diaphoresis, and palpitations in the setting of elevated blood pressure. Pheochromocytomas are neuroendocrine tumors derived from amine precursor uptake decarboxylation (APUD) cells. Included in the group of APUD cell tumors are carcinoid tumor, paraganglioneuromas, neuroblastoma, and others. Pheochromocytomas arise from chromaffin cells and secrete catecholamines. The majority arise from the adrenal medulla, although in a minority, they arise from the sympathetic ganglia, in which case they are termed catecholamine-secreting paragangliomas. Pheochromocytomas are most commonly sporadic, although in a minority, they occur as part of other syndromes such as neurofibromatosis, von Hippel-Lindau disease, tuberous sclerosis, and Sturge-Weber syndrome (discussed in Chapter 14). They are most commonly benign but are malignant in a minority of patients. Diagnosis of pheochromocytomas may be aided by measurement of catecholamines, metanephrines, and vanillylmandelic acid in a 24-hour urine collection; measurement of plasma free metanephrines is the most sensitive test.

The differential diagnosis for patients with the presentation depicted in the case is broad, but elevated blood pressure in the setting of these symptoms warrants exclusion of pheochromocytoma before a diagnosis of anxiety or hot flashes due to menopause is made. Carcinoid syndrome can present with episodic flushing and headache associated with other symptoms; diagnosis is made by measurement of urinary 5-hydroxyindoleacetic acid.

 Aminoff MJ. Neurology and General Medicine, 4th ed. Philadelphia, PA: Elsevier; 2008.

28. b

The pituitary derives its blood supply from the superior and inferior hypophyseal arteries, which arise from the ICA.

The anterior pituitary, or adenohypophysis, is derived embryologically from Rathke’s pouch, which evaginates from the oropharyngeal membrane during fetal development. The hypothalamus modulates pituitary function, and pituitary hormones in turn modulate hypothalamic function. The pituitary derives its blood supply from the superior and inferior hypophyseal arteries, which arise from the ICA. The superior hypophyseal artery forms a capillary plexus in the hypothalamic median eminence. Blood carrying regulatory hypothalamic hormones flows from there in the hypophyseal portal vein, through the infundibulum (or pituitary stalk) to the anterior pituitary. Secretion of prolactin by the anterior pituitary is modulated by dopamine. Growth hormone–releasing hormone secreted by the hypothalamus regulates growth hormone release by the anterior pituitary. Thyrotropin-releasing hormone secreted by the hypothalamus modulates thyroid stimulating hormone release, and gonadotropic-releasing hormone secreted by the hypothalamus modulates release of follicle-stimulating hormone and luteinizing hormone from the anterior pituitary. ACTH release by the anterior pituitary is modulated by corticotrophin-releasing hormone from the hypothalamus.

Magnocellular neurons in the supraoptic and paraventricular nuclei of the hypothalamus synthesize antidiuretic hormone and oxytocin. These are then moved via axonal transport, where they are stored and released by the posterior pituitary, also called the neurohypophysis.

 Bradley WG, Daroff RB, Fenichel GM, et al. Neurology in Clinical Practice, 5th ed. Philadelphia, PA: Elsevier; 2008.

 Ropper AH, Samuels MA. Adams and Victor’s Principles of Neurology, 9th ed. New York, NY: McGraw-Hill; 2009.

29. b

Given this patient’s recent history of a neurosurgical procedure in the pituitary region, she most likely has central diabetes insipidus (DI), due to deficiency of antidiuretic hormone (ADH).

ADH is synthesized by the magnocellular and supraoptic nuclei of the hypothalamus and secreted by the posterior pituitary. Synthesis and secretion of ADH is modulated by serum osmolality; increases in serum osmolality normally lead to release of ADH, which stimulates renal tubular resorption of water.

Central DI manifests clinically with thirst, polydipsia, and polyuria. It is not uncommon following neurosurgery and may be transient. Other causes of central DI include trauma, hypoxic-ischemic insult, compressive lesions in the sellar or suprasellar region, and infiltration of the hypothalamus due to granulomatous diseases such as sarcoidosis (discussed in questions 25 and 26). In some cases, the disorder is idiopathic. In patients with DI, urine osmolality is low: the urine is dilute due to inadequate resorption of water and hence excessive excretion of water in the urine.

Central DI is distinguished from nephrogenic DI, which results from inadequate renal response to ADH. In patients with central DI, administration of desmopressin, an ADH analog, will lead to urinary concentration and therefore an increase in urine osmolality and a reduction in serum sodium concentration. In nephrogenic DI, urine osmolality does not decrease in response to desmopressin. One of the causes of nephrogenic DI is lithium carbonate.

The treatment of central DI includes allowing free access to water (allowing patients to maintain adequate intake of water) and administration of vasopressin; water restriction will worsen hypernatremia, as will hypertonic saline.

 Aminoff MJ. Neurology and General Medicine, 4th ed. Philadelphia, PA: Elsevier; 2008.

 Bradley WG, Daroff RB, Fenichel GM, et al. Neurology in Clinical Practice, 5th ed. Philadelphia, PA: Elsevier; 2008.

30. d

In the setting of subarachnoid hemorrhage, and given evidence of hypovolemia, this patient’s hyponatremia is most likely due to cerebral salt wasting. This results from excessive renal losses of sodium and is seen in patients with severe CNS dysfunction. Unlike patients with syndrome of inappropriate antidiuretic hormone secretion (SIADH) who are typically euvolemic, in cerebral salt wasting syndrome, the patient is hypovolemic, and the treatment is with salt supplementation and intravenous isotonic fluid administration. The pathophysiology of cerebral salt wasting syndrome is not clear, but it may in part relate to increased levels of atrial natriuretic peptide released from the cardiac atria.

SIADH may occur following head trauma, neurosurgery SAH and with paraneoplastic ectopic antidiuretic hormone production. Several medications may also cause SIADH. Treatment of SIADH is with fluid restriction and correction of underlying causes; in severe cases, furosemide may be used. Vasopressin receptor antagonists are being investigated in the neurocritical care setting.

 Aminoff MJ. Neurology and General Medicine, 4th ed. Philadelphia, PA: Elsevier; 2008.

 Ropper AH, Samuels MA. Adams and Victor’s Principles of Neurology, 9th ed. New York, NY: McGraw-Hill; 2009.

 Wright WL, Asbury WH, Gilmore JL, et al. Conivaptan for hyponatremia in the neurocritical care unit. Neurocrit Care. 2009; 11:6–13.

31. c

This patient’s history and imaging findings are consistent with postpartum cerebral angiopathy, a disorder along the spectrum of reversible cerebral vasoconstriction syndrome. The pathophysiology of this disorder is unclear but is related to the occurrence of multifocal vasospasm. Clinically, patients present most commonly with headache, although seizure and/or focal neurologic deficit may occur. This disorder is typically benign, responsive to calcium channel blockers and/or corticosteroids. Rarely, ischemic strokes occur.

Normal blood pressure and urine protein level distinguish postpartum cerebral angiopathy from preeclampsia (discussed in questions 33 and 34). Absence of infarcts on MRI make amniotic fluid emboli unlikely; the presence of arterial vasospasm and absence of abnormalities on MRI of the brain make cerebral venous sinus thrombosis less likely. The history is not consistent with meningitis, and the presence of vasospasm further points to the diagnosis of postpartum angiopathy.

 Calabrese LH, Dodick DW, Schwedt TJ, et al. Narrative review: reversible cerebral vasoconstriction syndrome. Ann Intern Med. 2007; 146(1):34–44.

 Turan TN, Stern BJ. Stroke in pregnancy. Neurol Clin. 2004; 22:821–840.

32. b

Given this patient’s presentation, cerebral venous sinus thrombosis should be excluded, and MRV would be the most appropriate test to order. Pregnancy and the postpartum period are hypercoagulable states, predisposing to venous sinus thrombosis. In pregnancy, levels of several of the procoagulant factors are elevated, including fibrinogen and factors VII, VIII, IX, and X. These elevations, associated with a reduction in protein S levels, increase susceptibility to venous thrombosis. Given this patient’s family history, a hereditary thrombophilia or anti-phospholipid antibody syndrome may also have contributed to her risk of thrombosis (see discussion to question 24).

Venous sinus thrombosis can occur during pregnancy or in the postpartum period. In addition to headache and other signs and symptoms of increased intracranial pressure, seizures can occur.

A CT scan with contrast would be of little utility in this case; it may show a triangular area of central hypodensity surrounded by a rim of hyperintensity in the superior sagittal sinus (the so-called empty delta sign), but absence of this sign would not exclude the diagnosis. Cerebral angiogram is not indicated, although if this patient’s condition deteriorates significantly, angiogram with venous thrombolysis may be necessary.

Transcranial Doppler ultrasonography could be used to exclude vasospasm as occurs in postpartum angiopathy (discussed in question 31), but the presence of papilledema in this case makes the diagnosis of venous sinus thrombosis more likely. Similarly, while subarachnoid hemorrhage, meningitis, and other indications for LP in the postpartum period can occur, the presence of papilledema makes an MRV of higher priority.

 Aminoff MJ. Neurology and General Medicine, 4th ed. Philadelphia, PA: Elsevier; 2008.

 Karnad DR, Guntupalli KK. Neurologic disorders in pregnancy. Crit Care Med. 2005; 33(10)(suppl):S362–S371.

33. b, 34. e

This patient’s history, laboratory findings, and elevated blood pressure are consistent with eclampsia. Preeclampsia is characterized by gestational hypertension and proteinuria, often associated with edema in the face and hands. Eclampsia is the occurrence of seizures in association with hypertension and edema during pregnancy or in the postpartum period. The pathophysiology may relate to impaired trophoblast invasion of the endometrium and immune-mediated and endocrinologic mechanisms. Associated symptoms may include headache, visual disturbance, and epigastric abdominal pain. Postpartum eclampsia is more commonly associated with complications including disseminated intravascular coagulation and respiratory distress. In more severe cases, ischemic stroke, intracerebral hemorrhage, and/or posterior reversible encephalopathy syndrome (discussed in Chapter 3) can occur.

Management of eclampsia includes delivery (which should be the priority if the pregnancy is at or close to term) and intravenous medications such as hydralazine or labetalol for blood pressure reduction (although excessive reductions should be avoided to maintain fetal blood flow). Angiotensin-converting enzyme inhibitors should be avoided given potential effects on the fetal kidney. Intravenous magnesium sulfate should be administered; it reduces vasospasm and improves cerebral perfusion. Close monitoring is necessary as magnesium toxicity may lead to maternal respiratory distress. The use of AEDs is controversial, but medications that depress the fetus, such as pentobarbital or phenobarbital, should be avoided; oral diazepam is likely to be of little utility in seizure control and may depress the fetus.

Gestational hypertension is the presence of hypertension without associated proteinuria occurring beyond 20 weeks of gestation. Venous sinus thrombosis can lead to seizures and should be on the differential diagnosis of a patient in the peripartum period presenting with seizures, but the presence of proteinuria and hypertension point to eclampsia. Similarly, the history and laboratory features make meningitis less likely.

 Kaplan PW. Neurologic aspects of eclampsia. Neurol Clin. 2004; 22:841–861.

35. b

Multiple sclerosis typically improves during pregnancy. The rate of multiple sclerosis relapses decline during pregnancy but may rebound afterward. Seizure frequency in pregnant patients with epilepsy is variable and unpredictable; approximately one-third have increased seizure frequency in pregnancy, whereas the rest have a reduction or no change in seizure frequency. The majority of women with a history of migraine have a reduction in migraines during their pregnancy, although some women may have a worsening, and migraines can occur for the first time in pregnant women without pre-existing migraines. In the latter patients, exclusion of other causes of headache such as venous sinus thrombosis (discussed in question 32) is important. The effects of pregnancy on myasthenia gravis are variable. Approximately one-third of women have significant worsening; improvement in the second and third trimesters occurs in others, and this is thought to be related to the relative immunosuppression that occurs during this period. Sudden worsening in the postpartum period may occur.

 Ciafaloni E, Massey JM. Myasthenia gravis and pregnancy. Neurol Clin. 2004; 22:771–782.

 Hughes M. Multiple sclerosis and pregnancy. Neurol Clin. 2004; 22:757–769.

 Pennel PB. Pregnancy in women who have epilepsy. Neurol Clin. 2004; 22:799–820.

 Silberstein S. Headaches in pregnancy. Neurol Clin. 2004; 22:727–756.

36. e

In question 36, the first case depicts a pregnant woman with restless legs syndrome (RLS). RLS may first present during pregnancy, and preexisting RLS often worsens during this state. RLS is associated with iron deficiency, which is not uncommon during pregnancy. Testing serum ferritin level is indicated, and iron supplementation should be initiated if the ferritin level is less than 50 ng/mL.

The second case in question 36 depicts a pregnant woman with chorea gravidarum. Previously associated most often with rheumatic fever, with the decline in incidence of rheumatic fever in recent decades, other causes such as anti-phospholipid antibody syndrome have emerged as being more common and should be checked for.

In the third case depicted in question 36, a young woman with a family history of Huntington disease wishes to be tested prior to pregnancy. Referral to a genetic counselor and genetic testing is appropriate.

In the fourth case, assessment for hyperthyroidism is indicated in the setting of new-onset tremor during pregnancy.

The fifth case depicts a patient with fever and rigidity following initiation of an antipsychotic, a story that may be consistent with neuroleptic malignant syndrome (discussed in Chapter 3). The diagnosis is a clinical one, although measurement of serum creatine kinase level is indicated as it is often elevated. Checking serum copper and ceruloplasmin levels, tests for Wilson disease (discussed in chapter 6), may be indicated as part of the initial workup of this patient’s underlying neuropsychiatric illness but would not be the first line of testing for this acute presentation.

 Russel CS, Lang C, McCambridge M, et al. Neuroleptic malignant syndrome in pregnancy. Obstest Gynecol. 2001; 98:906–908.

 Smith M, Evatt M. Movement disorders in pregnancy. Neurol Clin. 2004; 22:783–798.