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

Chapter 15. Infectious Diseases of the Nervous System

Question

 1. A 32-year-old male intravenous drug user, whose partner was recently diagnosed with HIV, presents with headache, flu-like symptoms, fever (temperature of 39°C), and mild neck stiffness. His CSF analysis shows 0 RBCs, 15 WBCs (normal up to 5 lymphocytes/μL) with 85% lymphocytes, a protein level of 85 mg/dL (normal up to 45 mg/dL), and normal glucose level. CSF bacterial cultures are negative. Which of the following options is correct regarding this condition?

      a.  A negative HIV serology (Enzyme Immunoassay and Western blot) result rules out HIV meningitis, and no further serologic tests for HIV are needed

      b.  Acyclovir is the treatment of choice for HIV meningitis

      c.  Positive HIV serology along with clinical manifestations would confirm the diagnosis of HIV meningitis, and no other tests are required

      d.  Acute aseptic meningitis occurs only as a late manifestation of HIV

      e.  Patients with acute aseptic meningitis have preserved alertness and cognition

 2. A 20-year-old college student who lives in Connecticut presents with right-sided Bell’s palsy and is prescribed steroids and acyclovir. One week later, he presents with left-sided facial nerve paralysis. He reports that recently he went hiking in a forest nearby, and over the past 3 weeks, he has been experiencing headaches and arthralgias and does not feel well in general. His CSF shows 98 WBCs with 78% lymphocytes (normal up to 5 lymphocytes/μL), protein level of 69 mg/dL (normal up to 45 mg/dL), and normal glucose level. Which of the following is correct regarding this condition?

      a.  The causative agent is the spirochete Treponema pallidum

      b.  Antibodies against Borrelia burgdorferi are present in the CSF

      c.  Treatment of choice is isoniazid, pyrazinamide, ethambutol, and rifampin

      d.  CSF VDRL test is very sensitive but not specific for this condition

      e.  Erythema marginatum is a manifestation of this disease

 3. While on a volunteer trip to Central America, you see a patient in the hospital with diabetic ketoacidosis and a destructive lesion on his face, affecting his nose, the maxillary bone, and his right eye, with prominent proptosis. The patient rapidly deteriorates, and his condition gets complicated by cavernous sinus thrombosis. A histopathologic specimen from sinus biopsy showed nonseptated hyphae. Which among the following is not true regarding this condition?

      a.  The pathogenic agent is angioinvasive

      b.  Immunosuppressed patients are predisposed to this infection

      c.  Patients on long-term deferoxamine therapy are predisposed to this infection

      d.  Weakly acid-fast bacilli are detected

      e.  It is a zygomycosis

Questions 4–5

 4. A 52-year-old man with a history of intravenous drug use, hepatitis C, and HIV diagnosed 10 years ago comes for evaluation of progressive cognitive decline. He has been noncompliant with his antiretroviral therapy and is presumed to have HIV-associated dementia. Which of the following is correct regarding this condition?

      a.  HIV-associated dementia is most commonly seen with CD4 counts between 200 and 400 cells/mm3

      b.  Cognitive and psychomotor dysfunction are the main components of the HIV-associated dementia syndrome

      c.  More than 50% of patients have focal neurologic findings at the time of diagnosis

      d.  Cortical involvement with subcortical sparing is the neuropathologic hallmark

      e.  HIV-associated dementia is caused by an opportunistic infection

 5. Which of the following is correct regarding the treatment of this patient?

      a.  Acyclovir is a specific treatment used along with antiretroviral therapy

      b.  A complex antiretroviral regimen, with multiple medications and more frequent dosing, is required to obtain better outcomes in these patients

      c.  Amphotericin is frequently used for the treatment of HIV-associated dementia

      d.  The prognosis is usually good and antiretroviral therapy can be curative

      e.  Antiretroviral therapy can prevent this condition and improve neuropsychological performance in patients with HIV-associated dementia

 6. While you are working your 4th of July shift in the emergency department, a 62-year-old farmer with mental status changes and generalized weakness is brought by his wife. The patient has been having low-grade fevers, malaise and back pain, body aches, and headaches for the past 10 days; however, he did not want to come to the hospital. Over the past 5 days, he has developed bilateral hand tremors and difficulty walking. About 3 days ago, he became confused, and today, he was noticed to be unable to move his legs. On examination, he is lethargic and confused and noticed to be flaccid in his lower extremities, with areflexia. Which of the following is the most likely diagnosis?

      a.  Tuberculous meningitis and Pott’s disease

      b.  Subacute combined degeneration of the spinal cord

      c.  Neurosyphilis with tabes dorsalis

      d.  West Nile encephalitis

      e.  HSV encephalitis

Questions 7–9

 7. A 42-year-old woman presented with low-grade fevers of 1-month duration, headache, photophobia and neck stiffness for at least 1 week, and altered mental status on admission. A lumbar puncture was performed, and the opening pressure was 30 cm H2O. CSF analysis showed 0 RBCs, 55 WBCs with 70% lymphocytes (normal up to 5 lymphocytes/μL), protein of 60 mg/dL (normal up to 45 mg/dL), and glucose of 50 mg/dL. India ink smear was positive in the CSF. The patient eventually died, and the brain specimen is shown in Figure 15.1. Which of the following is the most likely etiologic agent?

FIGURE 15.1 Brain specimen. Courtesy of Dr. Richard A. Prayson. Shown also in color plates

      a.  Mycobacterium tuberculosis

      b.  Coccidioides immitis

      c.  Cryptococcus neoformans

      d.  Histoplasma capsulatum

      e.  Streptococcus pneumoniae

 8. Which of the following is correct regarding the condition depicted in question 7?

      a.  The most clinically useful diagnostic test is culture of the organism from the CSF

      b.  CSF antigen detection has poor sensitivity and low specificity

      c.  It commonly occurs in patients with AIDS and CD4 counts greater than 400/μL

      d.  Increased intracranial pressure is a common finding and is associated with higher mortality

      e.  It is frequently seen in early stages of HIV infection

 9. Which of the following is correct regarding treatment of the condition depicted in question 7?

      a.  Adverse effects of amphotericin, commonly used to treat this condition, include renal failure, hyperkalemia, and hypermagnesemia

      b.  Fluconazole at 200 mg daily is first-line chronic maintenance therapy

      c.  Vancomycin and ceftriaxone are the treatment of choice

      d.  CSF drainage with frequent lumbar puncture is contraindicated in this condition

      e.  Isoniazid and rifampin are first-line initial therapy

Question 10–11

10. A 50-year-old man with long-standing AIDS, noncompliant with antiretroviral therapy, presented with a seizure, mild right-sided weakness, and confusion. Brain MRI showed at least three ring enhancing lesions with surrounding edema, the most prominent one in the left subcortical white matter. A brain biopsy was obtained, and the histopathologic specimen is shown in Figure 15.2. Which of the following is correct regarding the most likely organism causing this opportunistic infection?

FIGURE 15.2 Brain specimen. Courtesy of Dr. Richard A. Prayson. Shown also in color plates

      a.  It is an encapsulated fungus

      b.  It is an intracellular protozoan

      c.  It belongs to the family of Herpesviridae

      d.  It is a mycobacterium

      e.  It is a spirochete

11. Which of the following is incorrect regarding the treatment of this opportunistic infection?

      a.  Standard therapy is sulfadiazine plus pyrimethamine

      b.  Trimethoprim-sulfamethoxazole is used for prophylaxis

      c.  Folinic acid can be used instead of sulfadiazine in sulfa-allergic patients

      d.  A patient with HIV, CD4 count of less than 100/μL, and immunoglobulin G (IgG) antibodies against this organism should receive prophylaxis

      e.  Clindamycin can be used for the treatment of this infection

12. A 49-year-old man with long-standing AIDS presents with progressive aphasia and right hemiparesis. His MRI shows a mass in the left frontal periventricular white matter, with mild contrast enhancement and surrounding edema. CSF analysis shows 20 WBCs with 90% lymphocytes (normal up to 5 lymphocytes/μL), protein of 55 mg/dL (normal up to 45 mg/dL), and normal glucose level. Epstein-Barr virus PCR in the CSF is positive. Which of the following options is correct?

      a.  This patient most likely has cerebral toxoplasmosis

      b.  CSF flow cytometry will show monoclonal B lymphocytes

      c.  Highly active antiretroviral therapy has not improved the prognosis of this condition

      d.  Cytology is 95% sensitive and specific

      e.  Corticosteroid therapy does not affect the results of brain biopsy

13. A 53-year-old man with AIDS and CD4 count of 30 cells/μL is seen for altered mental status. Over the prior 4 months, he had developed multiple focal neurologic findings, initially with left arm numbness, followed by right leg weakness, and eventually right hemiparesis. He later developed difficulty speaking and a deficit in his left visual field. About 1 week ago, he started to be confused. Brain MRI shows multiple coalescent nonenhancing white matter lesions in various locations. A brain biopsy was obtained and is shown in Figure 15.3. Which of the following is correct regarding this condition?

FIGURE 15.3 Brain specimen. Courtesy of Dr. Richard A. Prayson. Shown also in color plates

      a.  Acyclovir 10 mg/kg every 8 hours for 10 days is an effective therapy

      b.  Bilateral temporal periodic lateralized epileptiform discharges are useful for the diagnosis

      c.  The prognosis is good when specific therapy for the virus is given early

      d.  Presence of serum antibodies to this virus is specific to the diagnosis

      e.  The etiologic agent is a polyomavirus

14. A 60-year-old woman with HIV diagnosed approximately 6 years ago comes to the clinic for distal and symmetric foot pain and paresthesias that had slowly developed over the prior 12 months. She reports that she was started on new antiretroviral therapy approximately 2 months ago when her CD4 counts were found to be decreasing. Which of the following is the most likely diagnosis?

      a.  HIV neuropathy

      b.  Nucleoside analog-associated neuropathy

      c.  Cytomegalovirus polyradiculomyelitis

      d.  Acute inflammatory demyelinating polyradiculoneuropathy

      e.  Mononeuropathy multiplex

15. Muscle damage and wasting can be seen in patients with HIV. Which of the following mechanisms does not account for muscle problems in this patient population?

      a.  Mitochondrial myopathy associated with antiretrovirals

      b.  Myositis from autoimmune muscle fiber injury

      c.  Muscle wasting syndrome

      d.  Pyomyositis

      e.  Myositis from direct HIV invasion of muscle fibers

Questions 16–18

16. Which of the following is the least common cause of bacterial meningitis in neonates?

      a.  Neisseria meningitidis

      b.  Escherichia coli

      c.  Enteric gram-negative bacilli

      d.  Listeria monocytogenes

      e.  Group B streptococci

17. A 35-year-old man suffers an SAH with intraventricular extension and develops hydrocephalus. An external ventricular drain is placed. Over the next several days, he develops fever, and his CSF shows 210 WBCs/μL with 75% neutrophils (normal up to 5 lymphocytes/μL) and a protein level of 80 mg/dL (normal up to 45 mg/dL). Which of the following is the least likely pathogen causing this infection?

      a.  Staphylococcus aureus

      b.  Staphylococcus epidermidis

      c.  Pseudomonas aeruginosa

      d.  Streptococcus pneumoniae

      e.  Propionibacterium acnes

18. A 79-year-old woman with diabetes, hypertension, and chronic leg ulcers develops headaches and fever. On examination, she has neck stiffness and mild confusion. Brain CT scan is unremarkable. Lumbar puncture is performed, and CSF shows 112 WBCs/μL (normal up to 5 lymphocytes/μL) with 81% neutrophils, protein level of 60 mg/dL (normal up to 45 mg/dL), and glucose of 80 mg/dL, with a blood glucose of 198 mg/dL. CSF is sent for culture. Which empiric antibiotic regimen would you start?

      a.  Vancomycin and ceftriaxone

      b.  Vancomycin, ceftriaxone, and ampicillin

      c.  Vancomycin, ceftriaxone, and acyclovir

      d.  Ampicillin and gentamicin

      e.  Penicillin and gentamicin

19. Mycobacterium tuberculosis may invade the spinal column. Which of the following is incorrect?

      a.  The mid-thoracic region is most commonly affected

      b.  Back pain and muscle spasms are common symptoms

      c.  Spinal disease usually starts in the spinous processes

      d.  Kyphotic deformities are common

      e.  Long-standing disease may produce vertebral body destruction and collapse

20. According to the Infectious Disease Society of America guidelines, which of the following patients does not need a brain CT scan prior to an lumbar puncture for evaluation of bacterial meningitis?

      a.  A 62-year-old patient with a history of oligodendroglioma

      b.  A 35-year-old patient with HIV

      c.  A 40-year-old patient with diplopia and left pronator drift

      d.  A 45-year-old obese woman with papilledema

      e.  A 27-year-old man with a history of controlled epilepsy

21. The likelihood of a positive Gram stain result is lower with which of the following bacterial agents?

      a.  Haemophilus influenzae

      b.  Gram-negative bacilli

      c.  Streptococcus pneumoniae

      d.  Neisseria meningitidis

      e.  Listeria monocytogenes

22. While you are on a trip to South America as a volunteer health care worker, you see a 49-year-old man who has various well-demarcated hypopigmented skin lesions with hair loss and anhidrosis. He also has a few anesthetic spots, and asymmetric peripheral nerve palsies. His ulnar nerves at the ulnar grooves are palpable and thickened. A smear from a skin lesion shows weakly positive acid-fast bacilli. Which of the following is correct?

      a.  This patient has nocardiosis

      b.  The most likely cause is Mycobacterium tuberculosis

      c.  The causative organism has tropism toward nerves in warmer regions of the body

      d.  This condition most commonly causes a respiratory illness from which the organisms may spread to the skin and peripheral nerves

      e.  The tuberculoid variant occurs in patients with good cellular immunity

23. Which of the following antibiotics is appropriate treatment for the specified bacterium?

      a.  Streptococcus pneumoniae—penicillin G

      b.  Neisseria meningitidis—ceftriaxone

      c.  Listeria monocytogenes—vancomycin

      d.  Haemophilus influenzae β-lactamase positive—ampicillin

      e.  Pseudomonas aeruginosa—ceftriaxone

Questions 24–25

24. A 25-year-old man was involved in a motor vehicle accident 8 months ago and suffered head trauma, requiring multiple craniofacial surgeries. He also has a history of chronic sinusitis. He now presents with fever and change in mental status. His brain MRI is shown in Figure 15.4. Which of the following is correct regarding this condition?

      a.  It can be polymicrobial

      b.  Highly active antiretroviral therapy is the treatment of choice

      c.  CSF shows atypical lymphocytes with monoclonal B cells

      d.  He should be treated with pyrimethamine and sulfadiazine

      e.  It is caused by mycobacteria

25. Which of the following is not seen during the evolution of these lesions through different stages?

      a.  Cerebritis

      b.  Central necrosis

FIGURE 15.4 Axial CT scan

      c.  Capsule formation

      d.  Caseating granulomas

      e.  Vasogenic edema

26. A 21-year-old woman with a history of recurrent sinusitis presents with fever, diplopia and facial pain. On examination, she has proptosis of the right eye with periorbital edema, limited extraocular movements of the right eye, and reduced sensation over her right upper face and cheek. Fundoscopic examination demonstrates papilledema and retinal hemorrhages. What is the most likely diagnosis?

      a.  Superior sagittal sinus thrombosis

      b.  Meningitis

      c.  Brain abscess

      d.  Cavernous sinus thrombosis

      e.  Transverse sinus thrombosis

Questions 27–28

27. A 55-year-old man from South America who immigrated to the United States approximately 8 months ago presented with 2 months of low-grade fever, headaches, neck stiffness, and diplopia. On examination, he had bilateral cranial nerve VI palsies. CSF analysis showed 250 WBCs with 80% lymphocytes, (normal up to 5 lymphocytes/μL), 180 mg/dL of protein (normal up to 45 mg/dL), and 39 mg/dL of glucose. Brain MRI showed leptomeningeal enhancement, and a biopsy was obtained and is shown in Figure 15.5. Which of the following is the most likely etiology?

FIGURE 15.5 Leptomeningeal biopsy specimen. Courtesy of Dr. Richard A. Prayson. Shown also in color plates

      a.  Mycobacterium avium intracellulare complex

      b.  HIV

      c.  Cryptococcus neoformans

      d.  Mycobacterium tuberculosis

      e.  Mycobacterium leprae

28. Which of the following is correct regarding this condition?

      a.  A combination of at least four drugs should be used for initial treatment

      b.  CSF cultures are positive in 95% of cases

      c.  Thickened nerves and mononeuritis multiplex are common manifestations

      d.  Noncaseating granulomas are the pathologic hallmark

      e.  The etiologic organism is anaerobic

Questions 29–30

29. A 43-year-old woman from South East Asia comes to the clinic. She has multiple hypopigmented skin lesions with sensory loss to pinprick and temperature. You notice that she also has claw-hand deformities and bilateral footdrop, and her ulnar and common peroneal nerves are enlarged on palpation. A sural nerve biopsy shows granulomas and acid-fast bacilli. Which of the following is the most likely cause of the neuropathy in this patient?

      a.  Lyme disease

      b.  Hansen disease (leprosy)

      c.  Tuberculosis

      d.  Parasitic infection

      e.  Diabetes mellitus

30. Which of the following is incorrect regarding this condition?

      a.  There is a tuberculoid variant

      b.  There is lepromatous variant

      c.  The causative organism is Mycobacterium leprae

      d.  It tends to involve warmer regions of the body

      e.  The causative organism invades Schwann cells

31. A 35-year-old woman who has a history of intravenous drug use and multiple sexual partners developed right hemiparesis and aphasia. Brain MRI showed restricted diffusion in the left hemisphere but in an unusual distribution. Rapid plasma reagin was detected as positive. CSF VDRL test was also found to be reactive. Based on the information provided, which of the following best describes this patient’s disease?

      a.  Primary syphilis

      b.  Secondary syphilis

      c.  Meningovascular syphilis

      d.  Tabes dorsalis

      e.  Parenchymal syphilis

32. A 54-year-old woman has a history of abdominal pain, diarrhea, weight loss, and an undetermined form of arthritis that she developed approximately 6 months earlier. She presents with a progressive dementia and abnormal eye movements associated with rhythmic chewing movements of the nose and mouth. A duodenal biopsy is performed and shows periodic acid Schiff-positive material. Which of the following is correct?

      a.  The causative agent is Tropheryma whippelii

      b.  A positive 14–3-3 protein in the CSF makes the diagnosis

      c.  Avoiding gluten is the treatment of choice

      d.  Vitamin B12 deficiency is the major cause of these neurologic manifestations

      e.  Angiotensin-converting enzyme levels in the CSF are usually elevated in this condition

33. A 57-year-old aerospace engineer is brought to the clinic by his wife because of cognitive decline and various neurologic symptoms. Approximately 6 months ago, he stopped worrying about his job and began exhibiting odd behavior, leaving the house without showering or brushing his teeth. He progressively became apathetic and paranoid. He could not solve simple mathematical problems and was having trouble paying his bills. Over the past month, he has developed unsteady gait, ataxia and frequent falls. His wife also reports that he “jerks all over.” An MRI is obtained and is shown in Figure 15.6. Which of the following is the most likely cause?

FIGURE 15.6 Axial diffusion-weighted MRI

      a.  Progressive multifocal leukoencephalopathy

      b.  CJD

      c.  Alzheimer disease

      d.  AIDS dementia

      e.  FTD

34. Primary CNS lymphoma occurs more frequently in patients with AIDS but may also be diagnosed in immunocompetent patients. Regarding CNS lymphoma, which of the following differs between these two patient populations?

      a.  Association with Epstein Barr virus

      b.  Findings on cytology

      c.  Response to steroids

      d.  B-cell origin

      e.  MRI findings

35. A 64-year-old man who has not seen a physician in many years is brought to the hospital because he has been unsteady on his feet for the past 6 months. On examination, he has asymmetric pupils, which are poorly reactive to light. His lower extremity strength is preserved; however, his sensory examination is abnormal to vibration and proprioception, and he has gait ataxia with a broad-based gait. When he closes his eyes, he falls to the floor. Serum rapid plasma reagin (RPR) is reactive. Which of the following is correct?

      a.  This patient has secondary syphilis

      b.  RPR is very specific but not sensitive for the diagnosis of syphilis

      c.  Treatment with penicillin will cure the disease and reverse the neurologic deficits

      d.  Treatment requires intravenous penicillin G, up to 4 million units every 4 hours for 14 days

      e.  Neurologic manifestations will occur in 99% of the patients who are initially infected and left untreated

36. Regarding CJD, which of the following is correct?

      a.  Granulovacuolar degeneration and neurofibrillary tangles are seen on histopathologic specimens

      b.  The familial form is autosomal recessive caused by a mutation in the prion protein gene

      c.  It is caused by scrapie prion protein (PrP), which has decreased β-sheet content as compared with cellular prion protein (PrPC)

      d.  The EEG finding shows a repetitive periodic pattern

      e.  It is associated with very low CD4 counts

37. A 26-year-old woman is brought to the emergency department after having a seizure. As per her roommate, the patient had been behaving oddly over the past week. Approximately 3 days ago, she developed fever, and for the past 2 days, she has been confused, talking strangely, and very lethargic. Today she had a generalized tonic-clonic seizure. Her CSF was reported as “reddish” in color, with 59 WBCs (normal up to 5 lymphocytes/μL), 3500 RBCs, protein of 58 mg/dL (normal up to 45 mg/dL), and normal glucose levels. An MRI is obtained and is shown in Figure 15.7. Which is the most likely diagnosis?

      a.  West Nile encephalitis

      b.  Bacterial meningitis

      c.  HSV encephalitis

      d.  Enterovirus meningitis

      e.  Tuberculous meningitis

FIGURE 15.7 (A) Axial diffusion-weighted MRI; (B) Axial FLAIR MRI

38. A 40-year-old Italian man with progressive cognitive decline, ataxia, and tremors is brought to the emergency department because his family cannot take care of him anymore. He seems to be agitated at night and more confused than usual, and his wife reports that for the past month, he has not been able to sleep at all. His wife, who is a nurse, has also noticed that he becomes tachycardic, hypertensive, and diaphoretic, sometimes with mild fever. On the basis of supportive diagnostic information, he is thought to have a prion disease. Which of the following is the most likely diagnosis?

      a.  Fatal familial insomnia

      b.  Gerstmann-Straussler-Scheinker disease

      c.  Familial CJD

      d.  Sporadic CJD

      e.  Iatrogenic CJD

39. In HSV encephalitis, which of the following is a characteristic EEG finding?

      a.  Occipital seizures

      b.  Triphasic waves

      c.  Periodic lateralized epileptiform discharges

      d.  14- and 6-Hz spikes

      e.  3-Hz spike and wave complexes

40. An MRI is performed on a patient with HSV encephalitis. Which of the following is suggestive of this condition?

      a.  Hemorrhagic changes in the temporal lobes

      b.  T2 hyperintensity and restricted diffusion in the posterior cortical regions

      c.  Hockey-stick and pulvinar signs

      d.  Leptomeningeal enhancement in the basal regions

      e.  Diffuse white matter hyperintensity on T2 sequences

41. Which of the following is not caused by an arbovirus?

      a.  Saint Louis virus encephalitis

      b.  West Nile encephalitis

      c.  La Crosse (California) encephalitis

      d.  Japanese encephalitis

      e.  Subacute sclerosing panencephalitis

42. A 49-year-old woman with a history of liver transplantation 5 years ago presents with altered mental status. MRI of the brain shows multiple areas of restricted diffusion bilaterally, with no clear vascular distribution. A histopathologic specimen is obtained and is shown in Figure 15.8. Which of the following is the most likely diagnosis?

FIGURE 15.8 Pathologic specimen. Courtesy of Dr. Richard A. Prayson. Shown also in color plates

      a.  Cryptococcosis

      b.  Aspergillosis

      c.  Histoplasmosis

      d.  Candidiasis

      e.  HSV encephalitis

43. A 36-year-old man from South America comes to the epilepsy clinic for evaluation of new-onset partial seizures. His CT scan shows multiple cystic lesions in different locations and some small calcified masses. A biopsy was obtained and is shown in Figure 15.9. Which of the following is correct regarding this condition?

      a.  It is caused by Taenia saginata

      b.  India ink will be positive on CSF examination

      c.  Human ingestion of cooked pork meat containing the adult tapeworm leads directly to this clinical presentation

      d.  Albendazole is the treatment of choice

      e.  It is transmitted by the tsetse fly

FIGURE 15.9 Brain specimen. Courtesy of Dr. Richard A. Prayson. Shown also in color plates

44. A 20-year-old man is admitted for evaluation of fever, neck stiffness, and altered mental status. Approximately 5 days prior, he had gone swimming with his friends in a pond nearby his house. During hospitalization, he rapidly worsened and eventually died. On autopsy, a brain specimen was obtained and is shown in Figure 15.10. Which of the following is the most likely diagnosis?

FIGURE 15.10 Brain specimen. Courtesy of Dr. Richard A. Prayson. Shown also in color plates

      a.  Amebic meningoencephalitis

      b.  Viral encephalitis

      c.  Bacterial meningitis

      d.  Tuberculous meningitis

      e.  Fungal infection

Questions 45–46

45. A 24-year-old man goes camping in Connecticut and presents 5 weeks later with headache and severe pain radiating down his low back to the left leg. He also has paresthesias in his right hand and left foot. The patient recalls having a rash that started 2 weeks ago, which seems to be migrating and looks round and erythematous with a paler center. Which of the following is incorrect regarding this condition?

      a.  Ceftriaxone is used for the treatment of this condition

      b.  Doxycycline can be used for the treatment in the setting of normal CSF

      c.  Bacterial meningitis with predominance of neutrophils is a common manifestation

      d.  There are early and late neurologic manifestations of the disease

      e.  Approximately 10% of asymptomatic people in endemic areas may be seropositive for this organism

46. Which of the following neurologic presentations is not typical with this condition?

      a.  Cranial neuropathy

      b.  Mononeuritis multiplex

      c.  Aseptic meningitis

      d.  Subdural empyema

      e.  Polyradiculitis

Answer Key

1. e

2. b

3. d

4. b

5. e

6. d

7. c

8. d

9. b

10. b

11. c

12. b

13. e

14. a

15. e

16. a

17. d

18. b

19. c

20. e

21. e

22. e

23. b

24. a

25. d

26. d

27. d

28. a

29. b

30. d

31. c

32. a

33. b

34. a

35. d

36. d

37. c

38. a

39. c

40. a

41. e

42. b

43. d

44. a

45. c

46. d

Answers

 1. e

By definition, in meningitis, alertness and cognition are preserved, distinguishing it from encephalitis and meningoencephalitis.

Acute HIV meningitis is a syndrome that occurs in patients with progressive HIV disease and as CD4 count declines. It is occasionally present during the initial stages of HIV infection as part of the seroconversion syndrome and/or may be precipitated by a concomitant infection. Patients with acute HIV meningitis present with a febrile illness, headache, and symptoms of meningeal irritation. By definition, alertness and cognition are preserved. The CSF of these patients usually shows a lymphocytic pleocytosis (but usually less than 25 cells/μL) and mildly increased protein level (less than 100 mg/dL), with normal glucose levels.

In a patient with HIV, meningitis due to HIV itself is a diagnosis of exclusion; an extensive evaluation to rule out other etiologies is mandatory, including other viruses, tuberculosis, fungi, bacteria, lymphoma or meningeal carcinomatosis, and other inflammatory conditions. The diagnosis is made once other etiologies have been ruled out in a patient with signs of meningeal irritation and confirmed HIV infection. However, this syndrome may occur at early stages of infection during which HIV antibodies may not be detected. In these cases, subsequent serologic testing for HIV is required later.

Acute HIV meningitis requires no specific therapy and will eventually subside, although early initiation of treatment of antiretroviral therapy for the HIV infection itself is important.

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

 2. b

This patient has bilateral Bell’s palsy and lymphocytic meningitis, most likely associated with Lyme disease, which is caused by Borrelia burgdorferi. This spirochete is transmitted by the deer tick Ixodes and is frequently seen in the northeast United States. Clinically, the disease manifests in three stages:

–  Primary stage (within first 4 weeks of the tick bite): erythema chronicum migrans, which is a “bull’s eye rash” (not erythema marginatum, which is seen in rheumatic fever). Patients usually have constitutional symptoms during this stage.

–  Secondary stage (weeks after the rash): systemic manifestations, including cardiac involvement (cardiac conduction blocks), arthralgias and arthritis, lymphocytic meningitis, and neuropathies

–  Tertiary stage (months after the secondary stage): neuropathy, encephalomyelitis, encephalopathy, and dementia

The diagnosis of Lyme disease is based on epidemiologic data, clinical information, and CSF and serologic studies. The presence of anti–B. burgdorferi antibodies in the serum and intrathecal production of these antibodies is helpful in making the diagnosis. PCR is also available. MRI studies may show leptomeningeal enhancement in some cases.

Patients with CNS abnormalities should be treated with intravenous antibiotics such as ceftriaxone or penicillin G for up to 2 to 4 weeks. If CSF findings are unremarkable and there are no neurologic manifestations, oral doxycycline may be sufficient. Option c provides a list of medications used in tuberculosis, which is not the diagnosis in this patient. This patient does not have syphilis; therefore, CSF VDRL test is not helpful.

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

 3. d

This patient has mucormycosis, which is a zygomycosis. This fungus tends to enter through the respiratory tract, producing nasal and sinus disease and pulmonary infections. In the presence of predisposing factors and trauma, it may invade blood vessels and gain entry into the CNS, where it can produce an acute necrotizing reaction and vascular thrombosis, including sinus venous thrombosis, especially affecting the cavernous sinus. Externally, patients have a destructive inflammatory and necrotizing lesion affecting the face, especially in the nasal and maxillary areas. Diabetes mellitus and diabetic ketoacidosis are major and frequent risk factors for this condition. Other predisposing conditions include malignancies, high-dose steroids, organ transplantation, immunosuppression, and iron chelation therapy (with deferoxamine). The organisms causing this infection are mucor, rhizopus, and rhizomucor, which are fungi and not acid-fast bacilli. These fungi are seen as infrequently septated or nonseptated hyphae on histopathologic specimens.

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

 Fauci AS, Braunwald E, Kasper DL, et al. Harrison’s Principles of Internal Medicine, 17th ed. New York, NY: McGraw-Hill; 2008.

 4. b, 5. e

HIV-associated dementia is a complication of HIV occurring at late stages of the disease, in patients with CD4 counts below 200 cells/mm3, meeting the diagnostic criteria for AIDS. HIV-associated dementia is also called AIDS-dementia complex. The etiology of this condition is the retrovirus itself rather than an opportunistic infection. Progressive cognitive decline and prominent psychomotor dysfunction are the main clinical manifestations. These patients have significant difficulties with attention and concentration, along with fine motor dysfunction, gait incoordination, and tremors. However, focal neurologic findings are not common.

CSF analysis is nonspecific, frequently revealing mild lymphocytic pleocytosis and slightly elevated protein levels. Neuropathological studies show diffuse white matter pallor, activated macrophages, multinucleated giant cells, and vacuolar changes in the brain. The main findings are in the subcortical region, and the cerebral cortex is relatively spared.

Neuropsychologic testing is useful in the diagnosis and follow-up of these patients, as well as to monitor these patients while on therapy.

HIV-associated dementia can be prevented by adequate early treatment of HIV with highly active antiretroviral therapy (HAART), with the goals of attaining higher CD4 counts and suppressing the virus. Treatment of patients with HIV-associated dementia leads to improvements in neuropsychological performance.

Given the cognitive impairment of these patients, successful treatment requires the use of simpler HAART regimens, with the least number of drugs and simple dosing intervals, and using a regimen that minimizes side effects. Complex regimens are associated with poor compliance. Family or friend support is very important, and directly observed therapy may be required. Besides HAART, there are no other specific therapies for HIV-associated dementia.

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

 6. d

This patient has West Nile virus (WNV) encephalitis, which is an arboviral infection that spreads in the summer months, can occur in epidemics, and is transmitted by mosquitoes of the genus Culex. Most infected patients are asymptomatic, up to 20% may show signs of a febrile viral illness, and less than 1% develop a severe neurologic presentation; elderly patients are particularly at risk for neurologic disease and death. Patients with this neurologic presentation will have manifestations of encephalitis; however, WNV can also invade the anterior horn cells leading to flaccid weakness with areflexia, similar to poliomyelitis. WNV infection may also manifest with cranial neuropathies and tremors.

WNV encephalitis is diagnosed by serology and detection of immunoglobulin M (IgM) antibodies in the CSF. CSF PCR is less sensitive, but is diagnostic when positive. MRI is nondiagnostic. Treatment is supportive.

This patient does not have findings to support the other conditions listed.

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

 7. c, 8. d,  9. b

On the basis of the clinical history, presentation, elevated CSF opening pressure, and the presence of a positive India ink smear, this patient has cryptococcal meningitis, which is caused by the encapsulated yeast Cryptococcus neoformans. Furthermore, the histopathologic specimen demonstrates budding yeasts near blood vessels and surrounded by an inflammatory infiltrate, which is consistent with infection by this organism.

Cryptococcal meningitis usually occurs in immunocompromised patients and is an opportunistic infection seen in advanced HIV infection, usually when CD4 counts fall below 200 cells/μL. However, it may rarely be seen in otherwise immunocompetent patients; in such cases, a history of exposure to bird droppings, as occurs with roofers, may be elicited.

Patients usually present with fever, headache, neck stiffness, personality and behavioral changes, and altered mental status. Brain CT scan and MRI are performed to rule out other conditions and may demonstrate hydrocephalus, gelatinous pseudocysts, infarcts, or cryptococcomas. Lumbar puncture demonstrates an increased opening pressure, and CSF analysis shows mononuclear lymphocytosis with increased protein and low glucose levels. India ink smear is not very sensitive; however, it is useful when it is positive. Cryptococcal antigen detection in the CSF is rapid, sensitive and specific, and clinically useful, since fungal culture may take several days to weeks for a positive result to be obtained.

The initial treatment regimen is amphotericin plus flucytosine for 2 to 3 weeks. These patients should be monitored closely, since amphotericin is associated with renal failure, hypokalemia, and hypomagnesemia; and flucytosine may cause hematologic abnormalities. If the patient is doing well on amphotericin and flucytosine, or the meningitis is mild, the treatment can be switched to fluconazole 200 mg twice daily for 8 to 10 weeks. Afterward, the patient should be kept on long-term maintenance therapy with fluconazole 200 mg daily to prevent recurrences. Highly active antiretroviral therapy, by promoting immune reconstitution, plays a major role in the long-term treatment of HIV patients with cryptococcal meningitis, after the acute infection has cleared.

Mortality rate in the acute setting may be related to elevated intracranial pressure, which should be treated. Patients with increased intracranial pressure may need frequent CSF drainage by repeated lumbar punctures or even ventriculostomy.

Since this patient does not have a bacterial or tuberculous meningitis, there is no role for vancomycin, ceftriaxone, isoniazid, or rifampin.

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

10. b, 11. c

This patient has toxoplasmosis of the CNS, which is caused by Toxoplasma gondii, an intracellular protozoan. The diagnosis in this case can be suspected based on the history and clinical findings and confirmed with the histopathologic findings showing a microglial nodule, in which an encysted bradyzoite can be seen surrounded by an inflammatory infiltrate.

Cerebral toxoplasmosis is the most frequent opportunistic infection in patients with AIDS. The organism is usually acquired earlier in life and remains dormant until the immune system declines and T. gondii becomes active. This occurs in advanced stages of immunodeficiency in the setting of CD4 counts of less than 100/μL.

Patients present with headaches, focal neurologic deficits, seizures, and altered mental status that can progress to coma. Brain MRI typically demonstrates multiple ring enhancing lesions with surrounding edema. Since these cases present with a mass lesion in the brain, the differential diagnoses include primary CNS lymphoma, tuberculomas, fungal masses, or bacterial abscesses. Definitive diagnosis is made with brain biopsy; however, this is not commonly performed, and patients are typically treated empirically.

Standard therapy is sulfadiazine plus pyrimethamine. Since both agents affect the folate metabolism pathways, folinic acid should be provided to avoid hematologic complications. An alternative therapy is clindamycin, especially in patients who are allergic to the sulfa components and cannot take sulfadiazine. Long-term suppressive therapy is needed to prevent relapses. Highly active antiretroviral therapy promotes immune reconstitution, and patients whose CD4 counts rise above 200/μL may not need further suppressive therapy. Trimethoprim-sulfamethoxazole is used for prophylaxis. Patients with HIV and CD4 counts of less than 200/μL with positive immunoglobulin G (IgG) antibodies to toxoplasma should be given prophylaxis.

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

12. b

This patient has primary CNS lymphoma (PCNSL) in the setting of AIDS. These patients usually present with focal neurologic manifestations, which progress slowly over weeks to months. Since PCNSL in AIDS patients is frequently associated with Epstein-Barr virus, positive CSF PCR for this virus helps to make the diagnosis. CSF findings usually demonstrate a lymphocytic pleocytosis, elevated protein, and low to normal glucose levels. Cytology may detect atypical cells; however, this test has low sensitivity. Flow cytometry is helpful in making the diagnosis when it shows monoclonal B lymphocytes. CT scan has poor sensitivity, and MRI is a better tool, showing one or more lesions usually in the periventricular and deep regions of the brain. These lesions may have contrast enhancement, surrounding edema, and produce mass effect. Definitive diagnosis is done with brain biopsy.

Corticosteroids are helpful in the treatment of edema and mass effect, and the lesion itself tends to shrink with this treatment. However, the use of steroids should be reserved until after the brain biopsy has been obtained, since the results may be altered and the sensitivity of the biopsy reduced with corticosteroid exposure. Chemotherapy has been used, especially methotrexate; however, this therapy may be toxic and not optimal in patients with a baseline poor performance status related to the underlying disease. Radiation therapy is used as palliative treatment. The use of highly active antiretroviral therapy has improved the overall prognosis in patients with AIDS and PCNSL.

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

13. e

This patient has progressive multifocal leukoencephalopathy (PML), caused by JC virus, which is a polyomavirus. PML occurs in patients with end-stage AIDS and is the only known manifestation of JC virus. A large percentage of the general population has antibodies against this virus, certainly without clinical manifestations; and therefore, the presence of serum antibodies is not helpful for the diagnosis. Only those patients with severe immunosuppression and CD4 counts less than 200 cells/μL develop clinical manifestations; PML in immunocompetent individuals is exceedingly rare but can occur.

PML presents with a gradually progressive course of multiple focal neurologic manifestations, with visual field deficits and visual agnosias being common, given the predominant involvement of parieto-occipital regions. Seizures also occur.

The diagnosis can be suspected with the history and clinical manifestations, supported with MRI findings and CSF JC virus DNA PCR and confirmed with brain biopsy (though brain biopsy is not necessary in the setting of typical clinical, imaging, and CSF findings).

MRI shows multiple white matter nonenhancing lesions that tend to coalesce and predominate in the parieto-occipital regions. Brain biopsy is the gold standard diagnostic test; neuropathologic findings include myelin loss, giant astrocytes, and altered oligodendrocytes, with enlarged nuclei and viral inclusions. On electronic microscopy, the viral particles give a “spaghetti and meatballs” appearance. The specimen shown in Figure 15.3demonstrates enlarged oligodendrocytes with intranuclear inclusions consistent with PML. CSF JC virus DNA PCR is specific for the diagnosis, and because of the wide availability of this test, brain biopsy is rarely necessary.

Patients with PML have poor prognosis, as it denotes the presence of an already severely altered immune system. There is no specific therapy for this condition; however, some patients may improve with antiretroviral therapy and immune reconstitution. There are no specific EEG findings in PML, and acyclovir does not treat this condition.

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

14. a

This patient has HIV neuropathy, which is a distal sensory neuropathy seen in patients with HIV, more frequently as the CD4 count drops. This condition is a predominantly sensory, axonal length-dependent symmetric polyneuropathy. It is thought to be related to direct effects of the virus and cytokine upregulation. These patients should continue antiretroviral therapy for virus suppression, and the treatment is symptomatic for the neuropathic pain.

Options b to e mention other types of neuropathy that can be seen in patients with HIV. Nucleoside analog-associated neuropathy occurs over weeks following the initiation of therapy, and the treatment is to discontinue the offending drug. In this patient, the symptoms of neuropathy had evolved over months and not in direct relationship with initiation of the antiretrovirals; therefore, it is most likely that she has HIV neuropathy. Acute inflammatory demyelinating polyradiculoneuropathy can occur secondary to dysregulation of the immune system and is seen most frequently at the time of seroconversion. Cytomegalovirus polyradiculomyelitis is an uncommon syndrome seen in patients with very low CD4 counts, presenting with leg pain, sensory symptoms, and weakness, along with areflexia and sphincteric dysfunction evolving over days. Mononeuropathy multiplex can occur with HIV disease, more frequently late in the course of the illness, and may be associated with superimposed infection, lymphomatous infiltration, or vasculitis. However, clinically, this case does not represent a mononeuropathy multiplex, but rather a distal symmetric polyneuropathy.

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

15. e

HIV does not seem to invade muscle fibers directly, but rather it induces major histocompatibility complex I expression with autoimmune muscle fiber injury. This myositis can occur at any time during HIV infection. Patients on zidovudine can develop a mitochondrial myopathy. Pyomyositis is rare, but since the HIV epidemic, it has been more frequently seen. Patients with end-stage AIDS may develop a muscle wasting syndrome known as AIDS cachexia.

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

16. a, 17. d, 18. b

Bacterial meningitis can be caused by different groups of bacteria, depending on the age group, risk factors, and associated circumstances. Escherichia coli, other enteric gram-negative bacilli, Listeria monocytogenes, and group B streptococci are the most common pathogens of bacterial meningitis in neonates. In patients from 1 to 23 months of age, the most common agents are Streptococcus pneumoniaeNeisseria meningitidisStreptococcus agalactiaeHaemophilus influenzae, and Escherichia coli. In patients in the 2 to 50 years age group, the most common agents are Streptococcus pneumoniae and Neisseria meningitidis. In older adults, such as the patient depicted in question 18, Listeria monocytogenes should be considered, as well as aerobic gram-negative bacilli, Streptococcus pneumoniae and Neisseria meningitidis. Neurosurgical patients are predisposed to meningitis with aerobic gram-negative bacilli (including Pseudomonas aeruginosa), Staphylococcus aureus, and Staphylococcus coagulase negative (such as epidermidis). In the setting of CNS instrumentation, these same agents and Propionibacterium acnes should be considered. Unlike in community-acquired meningitis, Streptococcus pneumoniae is not a common cause of hospital-acquired meningitis.

Empiric antibiotic therapy should be started before specific agents are identified from CSF cultures. Usually, vancomycin and a third-generation cephalosporin (such as ceftriaxone) are initiated in adult patients with suspicion for bacterial meningitis caused by Streptococcus pneumoniaeNeisseria meningitidis, and/or Haemophilus influenzae. In the extremes of life (younger and older patients) and in immunocompromised patients, Listeria monocytogenes should be considered and, therefore, ampicillin should be added to the empiric therapy.

 Allan RT, Hartman BJ, Kaplan SL, et al. Practice guidelines for the management of bacterial meningitis. Clin Infect Dis. 2004; 39:1267–1284.

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

19. c

Tuberculosis can affect the spine, more specifically the vertebral column (Pott’s disease). The most commonly affected region is the midthoracic spine. Patients frequently present with constitutional symptoms, back pain, and muscle spasms, sometimes with findings of compressive radiculopathy or myelopathy.

Mycobacterium tuberculosis invades the body of the vertebral column, usually starting in the anterior region of the vertebral bodies, not at the spinous processes. The infectious process tends to disrupt the bone and the intervertebral spaces, leading to vertebral body destruction and collapse, as well as vertebral column deformities with kyphosis and scoliosis.

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

20. e

In patients with increased intracranial pressure, or an intracranial mass, lumbar puncture may precipitate a herniation syndrome. Therefore, in most cases, a brain CT scan is recommended before performing an lumbar puncture, in order to rule out an intracranial process. Various studies have been performed in the past to evaluate which clinical features are associated with abnormalities detected on CT scan, and based on these findings, specific guidelines have been recommended for adults undergoing CT scan before lumbar puncture.

The following are the recommended criteria for adult patients with suspected bacterial meningitis who should have a brain CT scan prior to lumbar puncture:

–  Immunocompromised patients (HIV patients, AIDS patients, patients on immunosuppressive therapy, transplant patients)

–  History of CNS disease (mass, stroke, focal infection)

–  New-onset seizure (especially within 1 week)

–  Papilledema

–  Abnormal level of consciousness

–  Focal neurologic deficit.

In this case, a known history of epilepsy does not fit the recommended criteria, and a brain CT scan does not necessarily need to be done prior to the lumbar puncture.

 Tunkel AR, Hartman BJ, Kaplan SL, et al. Practice guidelines for the management of bacterial meningitis. Clin Infect Dis. 2004; 39:1267–1284.

21. e

Gram stain results depend on multiple factors, such as the CSF concentration of bacteria and the specific bacterial agent. Approximately 90% of meningitis cases caused by Streptococcus pneumoniae, 86% of those caused by Haemophilus influenzae, 75% of those caused by Neisseria meningitidis, 50% of those caused by gram-negative bacilli, and 33% of cases caused by Listeria monocytogenes have positive Gram stain results.

Even though the yield of CSF Gram stain can be as low as 20% in patients who have received antibiotics, this test is easy to do, is rapid and inexpensive, and is recommended for all patients with suspected bacterial meningitis.

 Tunkel AR, Hartman BJ, Kaplan SL, et al. Practice guidelines for the management of bacterial meningitis. Clin Infect Dis. 2004; 39:1267–1284.

22. e

This patient has Hansen disease, or leprosy. This disease has a long incubation period (from months to decades) and is caused by Mycobacterium leprae, which is thought to spread through the respiratory tract but does not typically produce a respiratory illness. This mycobacterium has tropism toward peripheral nerves, especially in cooler areas of the body.

Leprosy has two major variants, a lepromatous variant and a tuberculoid variant, in addition to forms intermediate between the two. The lepromatous variant occurs in patients with impaired cell-mediated immunity, making it possible for the organism to spread to the skin and peripheral nerves, causing a maculopapular rash, nodules, and poorly demarcated skin lesions. The manifestations can be systemic, and patients will present with thickened nerves and multiple neuropathies. The tuberculoid form occurs in patients with good cellular immunity, in which the disease is less disseminated, the skin lesions are better localized, and the patient will also have asymmetric peripheral neuropathies with thickened nerves. The ulnar nerve is commonly affected, and the syndrome may resemble mononeuritis multiplex.

The diagnosis is supported by skin smears showing weakly positive acid-fast bacilli. Skin and/or nerve biopsies are sometimes needed. The lepromin test is an intradermal test similar to the purified protein derivative test. Chronic therapy is usually needed, using rifampin, dapsone, and clofazimine.

As opposed to tuberculosis, there is no pulmonary illness in Hansen disease. Nocardia asteroides stains partially acid-fast; however, it is associated with respiratory infections, cutaneous abscesses and fistulas, and sometimes cerebral abscesses, but not peripheral neuropathies.

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

23. b

Neisseria meningitidis should be treated with a third-generation cephalosporin, either ceftriaxone or cefotaxime, and the recommended duration of treatment is 7 days.

Streptococcus pneumoniae should be treated initially with vancomycin and ceftriaxone, and the duration of treatment is between 10 and 14 days.

Listeria monocytogenes, which is a potential cause of meningitis particularly at the extremes of age (younger and older) and in immunocompromised patients, should be treated with ampicillin for more than 21 days, or for 2 weeks after the CSF culture is sterile. Haemophilus influenzae can be treated with ampicillin if the organism is β-lactamase negative; however, if it is β-lactamase positive, a third-generation cephalosporin should be used. Pseudomonas aeruginosa is usually a hospital-acquired infection and is typically resistant to ceftriaxone. Ceftazidime and cefepime have been used to treat this infection with a duration of treatment of at least 21 days.

 Tunkel AR, Hartman BJ, Kaplan SL, et al. Practice guidelines for the management of bacterial meningitis. Clin Infect Dis. 2004; 39:1267–1284.

24. a, 25. d

This patient has multiple ring enhancing lesions, with a history and clinical findings consistent with brain abscesses. These lesions originate from invasion of brain parenchyma by bacterial organisms, commonly polymicrobial, with a combination of streptococci, staphylococci, enterobacteria, and anaerobes. The bacterial agents spread via hematogenous routes or from a contiguous infected site, such as the sinuses, ears, or teeth. They also can be encountered after open trauma or neurosurgical interventions.

Patients may present with fever, headaches, neck stiffness, focal neurologic findings, and altered mental status. The diagnosis is made on the basis of clinical suspicion and the presence of risk factors, along with clinical and radiologic findings, with the MRI showing ring enhancing lesions with surrounding edema.

Lumbar puncture may be contraindicated in the presence of mass effect; however, if a CSF sample is obtained, there may be increased WBC and protein levels, with normal to decreased glucose level. Atypical lymphocytes and monoclonal B cells are seen in lymphoproliferative disorders and not in brain abscesses.

Brain abscesses evolve through different stages, with initial cerebritis in the first few days, then the formation of central necrosis with surrounding vasogenic edema, and the subsequent formation of a capsule. The abscess eventually matures, with the development of collagenous tissue in the capsule and regression of the vasogenic edema. Caseating granulomas are not seen in cerebral bacterial abscesses.

Given that these lesions are polymicrobial, the treatment of choice is a combination of antibiotics, usually a third-generation cephalosporin (for streptococci and gram-negative bacilli), metronidazole (for anaerobes), and vancomycin (for staphylococci). The IV antibiotic regimen is continued for 6 to 8 weeks, and subsequent continuous oral antibiotics may be required for 2 to 3 months. Some cases may require surgical intervention, with stereotactic aspiration or excision. Vasogenic edema is treated with steroids and sometimes hyperosmolar agents are required.

Pyrimethamine and sulfadiazine are used for cerebral toxoplasmosis, which is not the diagnosis in this patient. Antiretroviral therapy plays no role in the treatment of cerebral abscesses. These lesions are not typically caused by mycobacteria.

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

26. d

This patient has septic cavernous sinus thrombosis, which can be a complication of bacterial sinus infections, and manifests with proptosis, compromise of the cranial nerves (CNs) traveling within the sinus (CNs V1 and V2, III, IV, and VI), retinal vein engorgement with retinal hemorrhages, and papilledema.

Patients with intracranial infections may also develop thrombosis of other sinuses such as the superior sagittal or the transverse sinuses. Diagnosis is based on clinical suspicion and radiologic studies. MRV or angiographies with venous phases are very useful. Treatment involves antibiotic therapy, covering gram-positive agents, staphylococci, gram-negative organisms, and anaerobes.

This patient’s proptosis and cranial nerve abnormalities suggest involvement of the cavernous sinus rather than the superior sagittal or the transverse sinus. Basilar meningitis can cause cranial neuropathies; however, basilar meningitis and brain abscess would not produce the constellation of neurologic manifestations that this patient has.

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

27. d, 28. a

This patient has tuberculous (TB) meningitis. This diagnosis is suspected on the basis of his epidemiologic factors, clinical findings, and CSF findings and confirmed with the leptomeningeal biopsy, which demonstrates a granulomatous inflammatory response with multinucleated giant cells and caseating necrosis, as seen in Figure 15.5.

TB meningitis is caused by Mycobacterium tuberculosis, which is an aerobic mycobacterium that spreads via respiratory droplets leading to a primary infection (usually pulmonary) and subsequent reactivation (usually in the setting of immunosuppression). TB meningitis tends to affect the base of the brain and commonly presents with fever, headache, neck stiffness, multiple cranial neuropathies (due to involvement of the basilar aspect of the brain) and altered mental status. Focal neurologic manifestations and seizures may also occur.

CSF demonstrates elevated protein level (80 to 400 mg/dL), low glucose level (less than 40 mg/dL), and lymphocytic pleocytosis (200 to 400 cells/μL). Opening pressure is usually elevated but may be normal. Acid fast bacillus (AFB) smear is diagnostic in 10% to 30% of the cases, and CSF cultures may be positive in 45% to 70%; however, the results may take between 6 and 8 weeks to become positive. PCR has higher sensitivity and may be helpful for a faster diagnosis. Brain MRI may be normal or may demonstrate meningeal enhancement, especially on the basal surface. Pathologic specimens show caseating granulomas, mononuclear inflammatory infiltrates, and multinucleated giant cells as described in this case.

Combinations of multiple anti-TB agents are used to kill the organisms and avoid inducing resistance. Commonly used medications are isoniazid, rifampin, pyrazinamide, streptomycin, and ethambutol. Usually, four drugs are initially administered for 2 months, after which the regimen can be reduced to two drugs that can be continued for several months.

Mycobacterium tuberculosis can affect the spinal cord and the brain parenchyma, where it can lead to the formation of tuberculomas. These lesions behave like space-occupying lesions, and the treatment is with anti-TB medications.

Peripheral nerves are more commonly affected by Mycobacterium leprae rather than Mycobacterium tuberculosis; in leprosy, nerve thickening occurs, and mononeuritis multiplex is a common manifestation (discussed in questions 29–30).

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

29. b, 30. d

This patient has Hansen disease, which is the cause of her neuropathy. Hansen disease, or leprosy, is caused by Mycobacterium leprae and is an important cause of neuropathy and skin disease worldwide. Most cases in the United States occur in immigrants, especially from Asia, the South Pacific, India, South America, and certain parts of Africa. Mycobacterium leprae is transmitted after prolonged and close contact with a patient with the disease, with an incubation period that is very long, lasting for years. The organism is thought to spread through the respiratory tract, from where it disseminates to other regions, especially the skin and superficial nerves, and mainly to cooler regions of the body. When invading the peripheral nerves, the mycobacterium tends to involve the Schwann cells preferentially.

There are two main variants determined by the immune reaction against this mycobacterium, and these variants are the tuberculoid and lepromatous forms. In between these, there are three borderline variants: borderline tuberculoid, borderline intermediate, and borderline lepromatous forms. The tuberculoid variant presents in patients with strong cell-mediated immunity and an intense delayed hypersensitivity reaction, causing destruction of peripheral nerves and inflammatory lesions in the skin. These patients typically have demarcated hypopigmented lesions and areas of sensory loss, especially to temperature and pinprick. Peripheral nerves are involved, indurated, hypertrophic, and palpable, and sensory loss may be prominent, leading to trauma. Nerves predominantly involved are the ulnar, radial, common peroneal, sural, and greater auricular. Claw-hand from ulnar involvement and footdrop from common peroneal involvement may be present.

The lepromatous form is present in patients with poor cell-mediated immunity with proliferation of the mycobacteria as they invade the tissues. It is characterized by skin infiltration by the mycobacteria, leading to diffuse cutaneous involvement in the coolest regions such as the pinna of the ear, tip of the nose, and dorsum of the hands and feet. Nerves may also be involved but usually at later stages.

The treatment of Hansen disease is prolonged, usually with a combination of dapsone and rifampin, sometimes with the addition of clofazimine.

 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.

31. c

This patient has manifestations of neurosyphilis, more specifically meningovascular syphilis. Syphilis is caused by the spirochete Treponema pallidum, which transmits vertically from mother to child or via sexual contact. In infected adults, three phases with a latent period and various neurologic complications are described:

–  Primary syphilis is characterized by the development of a painless chancre at the site of entry (genital region). There is asymptomatic systemic spread of the organism, and the chancre eventually disappears

–  Secondary syphilis develops approximately 2 to 12 weeks after the contact, with manifestations of systemic dissemination, including constitutional symptoms, lymphadenopathy, and rash (classically palms and soles). Syphilitic meningitis and cranial neuropathies may occur in this second stage

–  Latent period is an asymptomatic phase with serologic evidence of the disease, which may last for years

–  Tertiary syphilis is characterized by cardiovascular complications (such as aortitis), gummatous complications, and neurologic complications

Major neurologic complications include pure meningeal syphilis, meningovascular syphilis, tabes dorsalis and parenchymatous neurosyphilis. Meningeal invasion of the treponemes can lead to meningitis and meningovascular syphilis, in which there is endarteritis obliterans and vasculitis, which can lead to strokes in different arterial distributions; this can occur at any stage but often occurs within the first 4–7 years of infection with syphilis. Tabes dorsalis is the classical myelopathy with areflexia, lightning pains, sensory ataxia, loss of pain and temperature sensation, and relatively preserved strength, leading to gait instability and the development of Charcot joints. Parenchymatous syphilis (general paresis) is the encephalitic form in which patients develop progressive dementia, neuropsychiatric manifestations, speech disturbance, and pupillary abnormalities. Argyll-Robertson pupils, which accommodate but do not react to light, may be seen in patients with neurosyphilis. Manifestations of neurosyphilis may overlap in the same patient, usually presenting with a combination of findings.

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

32. a

This patient has Whipple disease, caused by Tropheryma whippelii. Whipple disease is a multisystemic disease, initially affecting the gastrointestinal tract, producing abdominal pain, diarrhea, and weight loss. It can also produce arthritis, cutaneous hypopigmentation, adrenal insufficiency, and various neurologic manifestations, including dementia, supranuclear ophthalmoplegia, ataxia, oculomasticatory myorrhythmia (such as described in this case), meningitis, neuropathy, and myopathy. Some patients with Whipple disease may present only with CNS manifestations, without the characteristic diarrhea and joint symptoms.

The diagnosis is made on the basis of gastrointestinal biopsy demonstrating periodic acid Schiff-positive macrophage inclusions. CSF-PCR for Tropheryma whippelii can also be helpful. A prolonged course of trimethoprim-sulfamethoxazole is the treatment of choice.

Angiotensin-converting enzyme is utilized for the evaluation of sarcoidosis, and the 14–3-3 protein is used in the diagnostic workup for CJD, neither of which are the diagnosis in this patient. This patient does not have vitamin B12 deficiency. She does not have celiac sprue and, therefore, avoiding gluten is not recommended.

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

33. b

This patient has CJD, which is a transmissible spongiform encephalopathy. The MRI shown in Figure 15.6 demonstrates restricted diffusion of the cortex (cortical ribboning) and the head of the caudate, which are findings not seen in the diagnoses provided in the other options. Other MRI findings seen in some CJD variants include bilateral signal hyperintensity in both thalami (especially in the pulvinar region, known as the pulvinar sign) and in the anterior portions of the putamen. The combination of anterior putamen and caudate head hyperintensity is known as the “hockey-stick” sign.

Patients with CJD present clinically with a rapidly progressive dementia, neuropsychiatric symptoms, cerebellar ataxia, and myoclonus. These patients deteriorate rapidly and inexorably die within months. The diagnosis is suspected on the basis of clinical features and supported by ancillary tests such as MRI, EEG, and CSF studies. EEG shows a typical periodic pattern. CSF 14–3-3 protein can be seen in many other causes of neuronal destruction, but for sporadic CJD, it can be up to 94% sensitive and 93% specific. CSF tau is also used in the diagnosis. Neuropathologic evaluation may be required in some cases and demonstrates significant spongiform degeneration with neuronal loss, vacuolar changes, and astrocytosis (discussed in Chapter 12).

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

34. a

Primary CNS lymphoma (PCNSL) is more frequently diagnosed in immunocompromised patients, especially in patients with AIDS. Almost all of these cases are associated with Epstein-Barr virus (EBV), and CSF EBV PCR is helpful in the diagnosis. In contrast, PCNSL in immunocompetent patients is not commonly associated with EBV.

In general, PCNSL in immunocompromised patients occurs at earlier ages than in those who are immunocompetent. It is not possible to differentiate PCNSL in immunocompromised patients versus immunocompetent patients only on the basis of imaging, CSF findings, or cytology. There is no clear evidence of differences in response to steroids in either group.

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

35. d

This patient has tabes dorsalis, which is caused by syphilis in its tertiary phase, and occurs if syphilis in its primary stages is untreated and the spirochete invades the CNS, in this case the spinal cord. However, not all cases of untreated syphilis progress to the subsequent stages, and only less than 10% of patients with untreated syphilis will develop symptomatic neuro-syphilis.

The diagnosis of syphilis is based on clinical manifestations along with supportive laboratory evidence. There are treponemal and nontreponemal tests. Nontreponemal tests are the Venereal Disease Research Laboratory (VDRL) test and the Rapid Plasma Reagin test. These tests are more sensitive but less specific than treponemal tests and become negative some time after treatment. Treponemal antibodies remain positive for life and include the fluorescent treponemal antibody, syphilis immunoglobulin G, and microhemagglutination assay among others. For the diagnosis of neurosyphilis, CSF should be analyzed, usually showing mononuclear pleocytosis with elevated protein levels. CSF VDRL is very specific for neurosyphilis but may be negative in as many as 25% of cases. Intrathecal antibody production against Treponema pallidum, oligoclonal bands, and PCR are also helpful for the diagnosis.

Treatment of neurosyphilis involves intravenous antibiotics, and the first choice is penicillin G 4 million units every 4 hours for 14 days. Antibiotic therapy may clear the infection; however, it will not reverse already established neurologic manifestations of tertiary syphilis. Follow-up CSF analysis is recommended to assess the response to therapy.

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

36. d

CJD is a prion disease, caused by conformational changes of the prion protein from cellular prion protein (PrP) to scrapie prion protein (PrP), which has an increased β-sheet content. This leads to physico-chemical changes in the protein, making it resistant to proteinases, poorly soluble in water, and with a tendency to polymerize, which leads to neuronal death. PrP has the ability to bind to PrP and induce its conformational change, therefore making this agent infective.

CJD can be sporadic or familial, caused by mutations in the prion protein gene. The familial form can be inherited in an autosomal dominant fashion. EEG is helpful in making the diagnosis, showing a repetitive periodic pattern. CJD is not necessarily associated with compromised immunity, and therefore does not depend on CD4 counts. Granulovacuolar degeneration and neurofibrillary tangles are seen in Alzheimer disease and not in CJD.

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

37. c

This patient has HSV encephalitis, likely from HSV type 1, which is the most common cause of fatal sporadic viral encephalitis in the United States. This virus is transmitted via respiratory or salivary secretions, spreading to the CNS, where it tends to affect the orbitofrontal and temporal regions. Patients present with fever, headaches, behavioral changes, altered mental status, focal neurologic findings, and seizures. CSF analysis is the most important diagnostic test, demonstrating a lymphocytic pleocytosis (10 to 1000 WBCs/μL), moderately elevated protein and normal glucose levels. Increased RBC count in the CSF or xanthochromia is seen frequently; however, this finding is neither sensitive nor specific. CSF HSV PCR is 95% sensitive and almost 99% specific for this condition; however, there may be false-negative results if the CSF is sampled in the first 24 hours of the illness. The MRI, as shown in Figure 15.7 demonstrates FLAIR T2 hyperintensities and restricted diffusion in the temporal regions—in this case, on the right side. Treatment with intravenous acyclovir 10 mg/kg every 8 hours should be started as soon as possible and continued for a minimum of 14 days.

This patient does not have West Nile virus (WNV) encephalitis, which is an arthropod-borne viral encephalitis that occurs in the summer months. WNV encephalitis is discussed in question 6. The CSF findings are not consistent with bacterial meningitis, which typically causes neutrophilic pleocytosis. Since this patient has findings of parenchymal involvement, this is an encephalitis rather than a meningitis; therefore, this is not consistent with enteroviral meningitis. Tuberculous meningitis is discussed in questions 27 and 28.

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

38. a

This patient has features suggestive of fatal familial insomnia, which is a prion disorder characterized by progressive intractable insomnia and symptoms of sympathetic hyperactivity such as hypertension, tachycardia, hyperthermia, and hyperhidrosis. Patients may also have cognitive impairment, tremor, ataxia, hyperreflexia, and myoclonus.

CJD exists in different variants, including sporadic, familial, iatrogenic, and new variant forms. The sporadic form is the typical form that was described in question 33. The familial variant is similar; however, it may present earlier, and the course is more protracted and insidious. The iatrogenic form is very rare and has been described in the past in patients who received cadaver-derived human growth hormone, and after neurosurgical procedures or corneal transplants. Gerstmann-Straussler-Scheinker is an inherited prion disease that progresses slowly over years. It is characterized by cerebellar ataxia and dysarthria, sometimes extrapyramidal features followed by dementia. These patients may also have gaze palsies, deafness, cortical blindness, extensor plantar response, and hyporreflexia in the lower extremities. The new variant CJD was first described in 1996 and is believed to occur from infection through consumption of cattle products contaminated with the agent of bovine spongiform encephalopathy. In contrast to traditional forms of CJD, new variant CJD affects younger patients (third to fourth decade of life), and the duration is more protracted.

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

39. c

Abnormal EEG findings are common in patients with HSV encephalitis. Periodic lateralized epileptiform discharges (PLEDs) in the temporal regions are characteristic and support the diagnosis. Diffuse slowing, which is nonspecific, can also be seen.

Occipital seizures can be seen in various conditions, including occipital lobe epilepsies, and in posterior reversible encephalopathy syndrome.

Triphasic waves are seen typically in hepatic encephalopathy, but they are seen also in other metabolic encephalopathies, including uremic encephalopathy. While 14- and 6-Hz spikes are normal and benign findings, 3-Hz spike and wave complexes are seen in absence epilepsy.

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

40. a

MRI is helpful in the evaluation of HSV encephalitis, demonstrating the structural lesions that occur, typically focal abnormalities in the temporal lobes with increased signal intensity on T2-weighted images (see Figure 15.7). The presence of hemorrhagic changes in the temporal regions is suggestive of HSV encephalitis, correlating with the pathologic findings of foci of hemorrhages and necrosis.

T2 hyperintensity and restricted diffusion in the posterior head regions are not typically seen in HSV encephalitis and are more consistent with posterior reversible encephalopathy syndrome. The hockey-stick and pulvinar signs are seen in CJD (see question 33). Leptomeningeal enhancement in the basal regions is nonspecific and may be seen in conditions such as tuberculous meningitis or neurosarcoidosis. Diffuse white matter hyperintensities on T2-weighted images is also nonspecific but may be seen in acute disseminated encephalomyelitis or in leukody-strophies.

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

41. e

Subacute sclerosing panencephalitis (SSPE) is a rare and late complication of measles, which is not an arbovirus. Measles can cause four major neurologic syndromes:

–  Acute encephalitis

–  Postviral encephalomyelitis

–  Measles inclusion body encephalitis, which is a rapidly progressive dementing illness with seizures, myoclonus, and coma, occurring 1 to 6 months after measles infection in patients with cell-mediated immunodeficiency

–  SSPE, which is caused by defective measles virus maturation in neural cells

Children infected in the first two years of life are the ones at the greatest risk for SSPE, which may develop 2 to 12 years after the infection. It begins with behavioral and personality changes, later causing seizures, myoclonus, spasticity, choreoathetoid and ballistic movements, ataxia, optic atrophy, quadriparesis, autonomic instability, akinetic mutism, and eventually coma. Neurons contain nuclear and cytoplasmic viral inclusion bodies, and levels of CSF and serum antibodies are elevated. MRI demonstrates T2 hyperintensity in the gray and subcortical white matter more in the posterior regions. EEG shows periodic slow-wave complexes at regular intervals and a background of depressed activity.

Regarding the arboviruses, these are arthropod-borne viruses, transmitted by mosquitoes, and more than 500 arbovirus-transmitted RNA viruses exist, including Saint Louis encephalitis virus, West Nile virus, La Crosse encephalitis virus, Japanese encephalitis virus, and Eastern and Western Equine encephalitis viruses.

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

42. b

This patient has aspergillosis, which is caused by the aspergillus fungus. This organism is capable of causing various manifestations, such as allergic syndromes, respiratory tract infections, and sinusitis. However, it may also cause an invasive syndrome that can spread to the CNS, especially in neutropenic patients, immunocompromised patients, or those on chronic steroids. Aspergillus fumigatus is the organism that causes most of the invasive syndromes, invading blood vessels, causing stroke-like syndromes, infarcts, and hemorrhagic transformation. A vasculitis-like phenomenon occurs as the fungus invades the vessel walls and may eventually progress to parenchymal disease, forming granulomas and abscesses. This fungus may invade multiple other organs and cause systemic disease.

Histopathologically, invading hyphae are detected in blood vessels, with the findings of necrosis, hemorrhage, and inflammation. The specimen shown in Figure 15.8 is a Gomori methenamine silver stain demonstrating septate hyphae that branch at acute angles, which is consistent with aspergillus infection. Aspergillosis does not typically present with meningitis.

Cryptococcus causes meningitis and not typically a vasculitis-type syndrome. Histoplasmosis causes pulmonary disease more frequently, but when it invades the CNS, it can produce a form of basilar meningitis, focal cerebritis, or granulomas. Candidiasis can also cause systemic disease, with histopathological findings of budding yeasts and pseudohyphae. This patient does not have clinical features or pathologic findings of HSV encephalitis (discussed in question 37).

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

 Fauci AS, Braunwald E, Kasper DL, et al. Harrison’s Principles of Internal Medicine, 17th ed. New York, NY: McGraw-Hill; 2008.

43. d

The specimen in Figure 15.9 shows a parasite consistent with cysticercosis. Neurocysticercosis is caused by the pork tapeworm Taenia solium and has a worldwide distribution, being endemic in Latin America, Africa, the Indian subcontinent, and parts of Asia.

Human ingestion of undercooked pork meat containing cysticerci may lead to infection with the intestinal tapeworms but does not cause the manifestations of neurocysticercosis, which occurs only with infection at a specific stage of the tapeworm life cycle. When the adult tapeworm resides in the small bowel of either the pig or the human, proglottids are released and excreted in to the feces. The eggs in these proglottids are infective to humans and animals. After humans ingest these eggs, larvae are released that penetrate the intestinal wall and migrate to various tissues, causing cysticercosis and neurocysticercosis. Clinical manifestations may occur years later, including seizures, focal neurologic symptoms, a vasculitic-type syndrome with strokes, increased intracranial pressure, headaches, hydrocephalus, and rarely coma.

Neuroimaging is helpful in the diagnosis of neurocysticercosis, showing cystic lesions that may have contrast enhancement and calcifications. The treatment of choice is albendazole. Praziquantel is an alternative. Since patients commonly have seizures, antiepileptic agents are used and may be required for life.

Taenia saginata is the beef tapeworm but does not cause neurocysticercosis.

India ink is used to detect Cryptococcus but is not useful in cysticercosis.

Cysticercosis is not transmitted by flies. The tsetse fly transmits Trypanosoma brucei, which causes African trypanosomiasis, or sleeping sickness.

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

 Fauci AS, Braunwald E, Kasper DL, et al. Harrison’s Principles of Internal Medicine, 17th ed. New York, NY: McGraw-Hill; 2008.

44. a

This patient has amebic meningoencephalitis. The diagnosis is based on clinical history and epidemiological factors and is confirmed by the histopathologic specimen, which shows an inflammatory infiltrate and trophozoites, consistent with an amebic infection.

Amebic meningoencephalitis is caused by free-living amebae, such as Naegleria fowleriAcanthamoeba, and Balamuthia mandrillaris. Patients acquire the amebae by swimming in contaminated ponds or lakes. The parasites enter the brain by passing through the cribriform plate and along the olfactory nerve to enter the frontal lobes and cause a necrotizing inflammation with destruction. Acanthamoeba can also enter the CNS through hematogenous dissemination and from a primary corneal infection acquired by using contact lenses stored in contaminated solution.

Patients with amebic encephalitis present with rapid progression of headaches, fever, neck stiffness, nausea, and vomiting and eventually develop focal neurologic findings, seizures, and altered mental status. The progression is rapid, and the disease is usually fatal.

CSF opening pressure is increased, and CSF analysis shows a neutrophilic pleocytosis, increased protein, and decreased glucose levels. Gram stain will not show the organism, but trophozoites may be seen on a wet preparation of unspun spinal fluid. Pathologically, there are findings consistent with a purulent meningitis, with microabscesses in the parenchyma, and an extensive necrotizing destruction of the parenchyma. A polymorphonuclear inflammatory infiltrate and trophozoites can be seen, such as in the histopathologic specimen shown in Figure 15.10.

 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.

45. c, 46. d

This patient has Lyme disease, which has a broad variety of neurologic presentations; however, bacterial meningitis with neutrophilic predominance is unlikely to occur. Subdural empyema is not seen in Lyme disease.

Lyme disease is caused by Borrelia burgdorferi. It is more commonly acquired in the Northeastern United States and is transmitted by a tick bite, more specifically the Ixodes tick. Lyme disease has an early phase and a late phase, and neurologic complications occur in both. In the early phase, patients may have a rash called erythema migrans, which is characteristic and has a “bull’s eye” appearance. Other nonneurologic manifestations include carditis, arthralgias, lymphadenopathy, and fever. Neurologic manifestations in the early phase include the following:

–  Aseptic meningitis: these patients have a mononuclear pleocytosis and mild elevation of protein levels in the CSF, as well as intrathecal production of antibodies against Borrelia burgdorferi

–  Encephalitis

–  Cranial neuropathy: commonly cranial nerve VII, and this can be uni- or bilateral

–  Peripheral nervous system: including mononeuritis multiplex, peripheral neuropathy, polyradiculopathy, or even a Guillain-Barre type presentation (which is not common).

Neurologic presentations in the late phase are encephalopathy, encephalomyelitis, and peripheral neuropathy.

The diagnosis of CNS Lyme disease is based on clinical and epidemiological suspicion, supported by the presence of positive serology, CSF abnormalities, and intrathecal production of antibodies. Serology is positive in 10% of people living in endemic areas, and this should be taken into account. The treatment is antibiotic therapy with intravenous ceftriaxone, up to 2 g daily for 2 to 4 weeks. For late presentations, a longer course may be required. Oral antibiotic therapy with doxycycline can be used in patients without CSF abnormalities.

 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.