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Flashcards in 4. CNS Infections Deck (24):
1

A 47 year-old M has confusion for the 12 weeks. On exam he exhibits ataxia and weakness of his left arm and his family says that he has been apathetic and speaking less. He is HIV+, but has not taken HAART for several years. MRI of the brain shows confluent white matter T2 hyperintensity. What is the most likely diagnosis?

Progressive multifocal leukoenceophalopathy

  • Caused by JC virus
    • Infects oligodendrocytes
  • Diagnosis
    • JC virus PCR in CSF
  • Treatment
    • Start HAART

2

What medicine used to treat multiple sclerosis has resulted in cases of progressive multifocal leukoencephalopathy, several of them fatal?

Natalizumab (Tysabri)

3 risk factors for who gets PML on natalizumab:

  1. Prior exposure to JC virus is requirement
    1. Antibody test to determine exposure to JC virus
  2. Prior immunosuppresion double risk
  3. Number of natalizumab infusions
  • Red arrow = demyelination due to MS
  • Blue arrow = PML

3

A 33-year-old HIV-positive woman has diplopia for the past 3 weeks. She comes to the hospital with a headache and fever. She then has a seizure. MR imaging of her brain shows multiple ring-enhancing lesions. Her CD4 count is 90/microliter. She has...

Toxoplasmosis

  • Parasitic infection caused by toxoplasma gondii
  • Source
    • Ingestion of infected meat
    • Feces of infected cat
    • Vertical transmission from mother to fetus
  • 1/3 of world's population is carrier of toxoplasma
    • During first week after exposure, infection typically causes mild, flu-like illness or no illness
    • Afterwards, the parasite rarely causes any symptoms in healthy adults
  • Treatment
    • Suspected infection should be empirically treated with sulfadiazine and pyrimethamine
    • If not clinical or radiographic improvement, biopsy

Primary CNS lymphoma

  • Caused by EBV
  • Often clinically and radiographically indistinguishable from toxoplasmosis
  • Diagnosis
    • Patients should be tested for antibody to toxoplasmosis
      • If this is negative, then CNS lymphoma is likely the diagnosis
    • CSF for EBV PCR
  • Patients typically die in 6 months

4

A 33-year-old HIV-positive woman has a low-grade fever and has had an indolent headache for the past 3 months. On exam, she seems cognitively slowed and has a stiff neck. An LP shows 200 WBC. An India ink stain of the CSF is shown below.

  1. Which of the following is the most likely diagnosis?
  2. What is the preferred treatment?

  1. Cryptococcus neoformans
  2. IV amphotericin, then fluconazole continued for 3 months after CSF is sterilized

Cryptococcus:

  • Yeast that typically presents as lung infection
  • In immunocompromised patients, can cause cryptococcal meningitis
    • Indolent course with headaches, mental status changes, meningeal signs
  • Diagnosis:
    • CSF
      • India ink stain positive in 75%
      • Crytococcal antigen via latex agglutination test positive in 95%
    • Often, LP reveals elevated opening pressure and papilledema

5

What are the neurological symptoms associated with HIV?

Myopathy, neuropathy, myelopathy, meningitis, dementia, retinitis (due to CMV), stroke

6

A 26 year-old, healthy woman has the onset of confusion over the course of 1 day. She has a seizure and is brought to the hospital. She is febrile and delirious. An LP reveals a normal opening pressure, and 20 WBC (90% lymphocytes) and 10,000 RBC. A CT of her brain is below.

  1. Which of the following infectious agents is the most likely cause for her findings?
  2. You are unable to do additional imaging studies. What should you do for this patient?

  1. Herpes simplex virus I
  2. Treat the patient for HSV encephalitis with IV acyclovir

HSV encephalitis

  • Most common cause of sporadic encephalitis in the US
  • Signs and symptoms:
    • Fever, headache, confusion, personality changes, olfactory/gustatory hallucinations
    • Focal seizures, motor disturbances
    • EEG may show periodic lateralized epileptiform discharges (PLEDs) at temporal lobe
  • Location in brain:
    • Frontal and temporal lobes
      • Massive swelling and patients are at risk for uncal herniation
  • Diagnosis:
    • LP shows bloody CSF, elevated WBC (lymphocytes)
    • HSV PCR
  • Treatment
    • IV acyclovir as soon as diagnosis is suspected

7

A 55 year-old Jamaican man, tells you that he is able to move his arms when dancing, but his legs feel weak so that he cannot lift them off the floor. You confirm this weakness on exam and he is hyperreflexic in the legs with upgoing toes. You tell him presentation is most consistent with infection with what agent...

Human T-lymphotropic Virus Type I (HTLV-I)

  • Causes tropical spastic paraparesis
  • Chronic myelopathy common in the Caribbean and Africa
    • In US, found in IV drug users

8

A 67 year-old man develops a severe burning pain in a band around the right side of his torso just below the nipple. Within 48 hours, a rash composed of numerous vesicles has appeared in this area. The responsible infectious agent is...

Varicella zoster virus

  • Occurs from reactivation of varicella infection in dorsal root ganglia
    • Usually in thoracic dermatome
    • Zoster ophthalmicus = when occurs in V1 distribution
  • Treatment
    • 1 week of acyclovir or valacyclovir
  • Can sometimes infect cerebral arteries causing stroke
  • Can infect spinal cord directly leading to severe myelopathy

9

What are the CNS viral infections and their clinical characterisics?

PML

  • Slowly progressive demyelinatino of CNS in HIV

Herpes

  • Common, temporal/frontal lobe hemorrhage, treat ASAP

HIV

  • Can affect any level of the nervous system

HTLV

  • Infects spinal cord in people from the Caribbean

Zoster

  • Painful vesicular rash

CMV

  • Can cause infection in utero
  • In immunosuppressed, can cause encephalitis
  • Associated with retinitis

Rabies

  • Occurs after bite from infected animal
  • Can cause encephalitis that leads to psychiatric disturbances followed by seizures and death or fatal paralysis due to infection of spinal cord

Polio

  • Directly infects anterior horn cells of spinal cord

West Nile

  • Directly infects anterior horn cells of spinal cord

10

A 56 year-old previously healthy woman has the onset of headache and mental confusion over the course of one day. She is febrile and with nucal rigidity on examination. She asks to be taken to a dark, quiet room. An LP reveals a normal opening pressure, and 2000 WBC, 90% neutrophils, and 60 RBC. A gram stain shows gram positive spherical cells. Which of the following infectious agents is the most likely cause for her findings?

Streptococcus pneumoniae (Pneumococcus)

  • Characterized by:
    • Nuchal rigidity
    • Photophobia
    • Phonophobia
  • Vaccine is available

11

What is the most common cause of bacterial meningitis in neonates?

Streptococcus agalactiae (Group B strep)

12

A 28 year-old woman presents with severe headache, nuchal rigidity, and a fever of 101 degrees. On physical exam, you notice papilledema. You are suspicious for bacterial meningitis, and order blood cultures. You then start her empirically on broad spectrum antibiotics. What is the next best step in management?

Head CT

  • Steps in meningitis work-up:
    1. Blood cultures
    2. Empirically start broad-spectrum antibiotics
      • Cefoxatime/ceftriaxone + vancomycin
    3. LP
      • HOWEVER, if patient has focal neurological deficits, papilledema, immunocompromise, history of CNS disease, or altered mental status, you MUST get a head CT first
      • Doing a CT in a patient with a mass can cause herniation!

13

A 43-year-old man is brought to the ED with a 3-day history of earache and headache. He was not able to be awakened in the morning. He was intubated for airway protection. On physical examination, he had a decreased level of consciousness and neck stiffness, BP of 120/70, HR of 120/minute, Temp of 41oC. What is likely to be a finding in the CSF of this patient?

Cloudiness of CSF, increased WBC, increased opening pressure, decreased glucose, increased protein, polymorphonuclear pleocytisis

  • Bacterial meningitis
    • Organisms in adults
      • N. meningitidis, S. pneumoniae, H. influenzae
      • L. monocytogenes in age > 50
    • Organisms in children
      • GBS, E. coli, L. monocytogenes
    • Kernig's sign = pain when thigh is bent at hip and knee at 90 degrees
    • Brudzinski's sign = involuntary lifting of legs when flexing neck

14

Though is remains a subject of controversy, what symptom have steroids been shown to help in patients with bacterial meningits?

Prevent hearing loss

  • Steroids have shown to reduce morbidity from meningitis (such as deafness)
  • Steroids should be given prior to first dose of antibiotics

15

A 67 year-old man from rural China develops severe low back pain followed by weakness of his legs and incontinence. His MRIs show pathologic fracture of T12 with herniation of disc material into the spinal canal. Which of the following is the most likely diagnosis?

Pott's disease (Mycobacterium tuberculosis)

  • Tuberculosis infection of the vertebral bodies
  • Commonly localized in lower thoracic or upper lumbar spine
  • Results from hematogenous spread of TB from other sites (pulmonary)

Tuberculosis of CNS has 3 clinical categories:

  1. Meningitis
  2. Intracranial tuberculomas
    • Usually affects basal areas of the brain
    • Fever, malaise, stupor and coma, seizures, hemiparesis
  3. Spinal tuberculous arachnoiditis

Treatment:

  • Isoniazid (INH), rifampin, and pyrazinamide for 12 months

16

A patient is being treated with izoniazid and rifampin for tuberculosis. What supplement must they take to prevent a peripheral neuropathy?

Pyridoxine (vitamin B6)

  • Excess of vitamin B6 can also lead to periphearl neuropathy

17

An IV heroin user develops severe low back pain followed by weakness of his legs and incontinence. On exam, you detect a sensory level at about T10. His temp is 100.9 and he won’t lie down on the examination table because of his back pain. Which of the following is the most likely diagnosis?

Spinal epidural abscess

 

18

What are the characteristics of brain abscesses?

Result from direct infection from an adjacent site:

  • SInuses - result in frontal lobe abscess
  • Middle ear infection or mastoiditis - result in temporal lobe abscess

Abscesses typically present with focal neurologic defecits (unlike meningitis)

Radiographic appearance:

  • Ring-enhancing
    • Seen in abscesses, tumors, MS
  • Presence of multiple abscesses in brain suggest hematogenous spread from a systemic source
  • Intense edema and inflammatory response indicates early formation

19

A 65-year-old man has had general weakness with increasing loss of higher mental functions for the past 3 years. On physical examination he walks with a widened gait, and he has a positive Romberg test. Laboratory studies show that a VDRL is positive in the serum. What pathological findings might exist in the spinal cord?

Atrophy of dorsal columns

 

20

Which abnormality of the pupil can be seen in patients infected with treponema pallidum?

Small, irregular pupils that do not react to light, but do constrict with accommodation

  • Argyll Robertson pupils = pathognomonic for neurosyphilis
    • Pupil accomodates but does not react = prostitute pupil

Stages of syphilis:

  • Primary syphilis = 2-6 weeks
    • Painless chancre
  • Secondary syphilis = 2-6 weeks
    • Flu-like symptoms, rash on palms, soles, condylomata lata
  • Tertiary syphilis = 10-30 years later
    • Meningitis/vasculitis - can cause MCA stroke
    • Tabes dorsalis - destruction of dorsal root ganglia
      • Loss of sensation and pain in legs and abdomen
    • General paresis - encephalitic infection
      • Dementia and psychiatric symptoms

Diagnosis

  • Non-treponemal tests
    • RPR, VDRL
    • Detect antibodies to cardiolipin (non-specific marker for syphilis)
    • Correlate with disease activity and response to treatment
    • Nontreponemal test for confirmation
  • Treponemal tests
    • T. pallidum particle agglutination (TP-PA) test, T pallidum hemagglutinin assay (TPHA), and fluurescent treponemal antibody-absorption (FTA-ABS) test, treponemal enzyme immunoassays and immunochemoluminescence (EIA) tests
    • Detect antibodies specific to T. pallidum
    • Do NOT correlate with disease activity or response to treatment
    • Treponemal test for screening

21

  1. How do you diagnose neurosyphilis?
  2. What is the treatment for neurosyphilis?

  1. LP for CSF
    • High WBC (lymphocytes), high protein, oligoclonal bands
  2. IV or IM penicillin for 14 days
    1. Follow-up blood tests at 3, 6, 12, 24, 36 months to make sure infection is gone
    2. Re-evaluate CSF every 6 months for 3 years to ensure successful treatment
      1. Defined as decrease in lymphocyte count and protein, decreased in VDRL titer

22

A 45 year-old woman wakes up and notices the left side of her mouth is drooping. A week later, the same thing happens to the right side of her face. On exam, she is unable to smile on either side, she cannot fully close either eye and cannot raise her eyebrows. You tell her presentation is most consistent with infection with what agent...

Borrelia burgdorferi (Lyme disease)

Lyme disease

  • Caused by infection with Borrelia burgdorferi (Gram negative spirochete)
  • Stages of infection:
    1. Stage 1 = acute infection
      • Erythema migrans
    2. Stage 2 = within weeks
      • Flu-like symptoms, meningitis, cardiac pathology
    3. Stage 3 = within months
      • Sensory neuropathy, subtle cognitive changes
  • Treatment
    • Oral doxycycline
    • If neurological symptoms - IV ceftriaxone

23

A 26 year-old man from Mexico has a seizure. He denies any family history of seizures, any trauma, or any history of infections. His head CT is shown below. You immediately suspect he suffers from a brain infection with this incredibly disturbing and horrifying infectious agent?

Taenia solium

  • Pork tapeworm that causes cysticercosis
    • Infection by fecal-oral route
  • Common in India and South America
    • Primary cause of acquired epilepsy
  • Can infect muscles, brain, or eyes
    • ​Racemos neurocysticercosis (grapelike)
      • Can grow within ventricular system (4th ventricle), leading to obstruction of CSF flow and hydrocephalus
      • Shunting of ventricular system may be required
  • Treatment
    • Albendazole + steroids

Naegleria fowleri

  • "Brain-eating amoeba" found in warm bodies of fresh water (ponds, lakes, rivers, hot springs)

24

A 53 year-old previously healthy man has had a rapid decline in mental function over the past 4 months. On exam he exhibits profound dementia along with myoclonus. He startles very easily whenever you approach. An EEG shows periodic biphasic synchronous sharp-wave complexes that are superimposed upon a slow background rhythm. An MRI shows bilateral areas of increased signal intensity predominantly affecting the basal ganglia.

  1. Which of the following is the most likely diagnosis?
  2. Which set of pathologic findings is most typical for the underlying disease process? 

  1. Creutzfeldt-Jakob disease (CJD)
  2. Spongiform degeneration of the grey matter caused by neuronal loss

Caused by conformational change of prion protein

  • On MRI:
    • "Double hockey stick" sign
    • "Cortical ribboning" sign

Clinical manifestation:

  • Rapid onset dementia with myoclonus
  • Mostly sporadic but can be familial, infectious (mad cow disease), iatrogenic (infected surgical instruments or transplant tissue)

Diagnosis:

  • CSF shows 14-3-3 protein
    • Not specific for CJD
  • EEG shows periodic sharp waves