Infections, CNS | The Massachusetts General Hospital Handbook of Neurology

Authors: Flaherty, Alice W.; Rost, Natalia S.

Title: Massachusetts General Hospital Handbook of Neurology, The, 2nd Edition

> Table of Contents > Adult Neurology > Infections, CNS

Infections, CNS

A. Abscess and focal cerebritis

1. H&P: Headache, focal deficits, altered mental status. Seizures occur in 40%. Fever, neck stiffness, vomiting, and papilledema are uncommon. Look for other infections, especially ear, nose, mouth, lung, and heart. Ask about HIV risk factors.
2. DDx: Tumor, granuloma.
3. Causes: Anaerobic streptococci are most common. Posttraumatic or surgical cases are more likely to be Staphylococcus or Enterobacteriaceae. Many abscesses are polymicrobial.
4. Tests: CT or MRI with contrast should show ring-enhancing cavity, edema, mass effect. Blood cultures, CXR, consider echocardiogram. LP is contraindicated.
5. Rx:
- a. Surgery: Needle aspiration or excision of abscess, ideally before Abx initiated.
- b. Abx: Treat for 6 wks. Adjust Abx on basis of abscess cultures.
  - 1) Ear or unknown source: Ceftriaxone 2 g IV q12h (or cefotaxime 2 g IV q4-6h) + metronidazole 500 mg IV q6h. Some also use penicillin 4-5 MU IV q4-6h.
  - 2) HIV-positive: Add coverage for toxoplasmosis; see below.
  - 3) Post head trauma or surgery: Vancomycin 1 g IV q12h + ceftazidime 2 g IV q8h or cefepime 2 g IV q12h.
- c. Steroids: Only if severely high ICP because steroids may decrease antibiotic penetration.

B. Cryptococcosis

A fungus, Cryptococcus neoformans, the most common cause of fungal meningitis. Cryptococcal meningitis may be an emergency because pts can die suddenly from high ICP.

1. H&P: HIV, immunosuppression, pigeon exposure. Headache, fever, meningeal signs, confusion, signs of high ICP. Seizures uncommon.
2. DDx: Other meningitides.
3. Tests: CSF (see p. 19). CSF India ink stain is positive in 75%. Serum and CSF cryptococcal Ag. CT/MRI usually normal.
4. Rx: Regimens vary; consider amphotericin B and flucytosine, then fluconazole. Consider serial LPs for high ICP.

C. Cysticercosis

A helminth, the pig tapeworm Taenia solium.

1. H&P: Country of origin, seizures, headache, signs of raised ICP.
2. DDx: Other parasitic dz.
3. Tests: Stool ova and parasites. Blood serology better than CSF, but slow. Consider long-bone x-ray series to look for calcified muscle cysts. CT/MRI appearance depends on stage. Chronic, inactive lesions are calcified, nonenhancing, usually at gray-white junction. Active, degenerating cysts enhance and have edema.
4. Rx: Albendazole 15 mg/kg qd for 8 d. Regimens vary; praziquantel 50 mg/kg divided tid for 12-14 d is an alternative. Consider steroids because dying cysts cause inflammation. Surgery for cyst removal or shunting is often necessary for posterior fossa or intraventricular cysts. If cysts are inactive, rx may not help. Treat seizures.
- a. Macular cysts: Rule them out before albendazole (check acuity and fundi).
- b. Ventricular cysts: Consider surgery.
- c. ID consult is often helpful.

D. Empyema, CNS

An IMMEDIATE SURGICAL EMERGENCY. Usually see HA out of proportion to neurological deficit.

1. Brain subdural empyemas: Frequently from sinusitis or trauma. Unlike subdural blood, they are better seen on MRI than CT (restricted diffusion). Consult ENT preoperatively for sinus drainage during the same procedure. Watch for sinus thrombosis.
2. Spinal cord empyemas: Never do an LP in a pt. with fever and back pain until you have ruled out empyema with MRI.

E. Human immunodeficiency virus (HIV)

See also Infection, p. 219.

1. Incidence: 50% of HIV pts. have a CNS or PNS problem; this can be the presenting complaint.
2. Headache: Have a very low threshold for MRI + gadolinium and LP. All pts. with HA and fever should get both.

P.56

3. Focal brain sx: Consider toxoplasmosis, lymphoma, progressive multifocal leukoencephalopathy (PML), Cryptococcus, VZV encephalitis, tuberculoma, neurosyphilis, clot, bleed, bacterial abscess.
4. Nonfocal/encephalitic sx:
- a. HIV dementia complex: Subcortical dementia with psychomotor slowing; often psychosis, frontal, corticospinal, or basal ganglia signs.
- b. Encephalitis: CMV, HSV, HIV.
- c. Metabolic encephalopathies.
5. Meningeal sx: Meningitis from HIV (primary infection), Cryptococcus, TB, syphilis, bacterial, lymphomatous.
6. Cranial neuropathy: CNS lesion, meningitis, peripheral neuropathy.
7. Spinal cord sx: B₁₂ deficiency, HTLV-1, HSV or VZV myelitis; vacuolar myelopathy.
8. Peripheral nerve sx: Can be immune mediated, drug induced, or infectious (e.g., CMV or VZV radiculopathy).
- a. Lumbosacral polyradiculopathy (cauda equina syndrome): Subacute leg weakness with inability to walk back pain, early bowel and bladder problems.
  - 1) DDx: Usually CMV. Consider also lymphomatous meningitis, neurosyphilis, spinal cord mass.
  - 2) Tests: LP shows >100 WBCs/ L (often with high PMNs), high protein, normal or low glucose. EMG shows axonal and demyelinating lesion.
  - 3) Rx: Ganciclovir or foscarnet.
- b. Distal symmetric peripheral neuropathy (DSPN): From nucleoside reverse transcriptase inhibitors (NRTIs), e.g., didanosine (ddI) or zalcitabine (ddC), or from Kaposi's chemotherapy (vincristine, cisplatin).
9. Myopathy: From zidovudine (AZT).

F. Lyme dz

1. H&P:
- a. Early (3 d-1 mo): Erythema migrans in ~70%.
- b. Middle (up to 9 mo): Heart block myocarditis, recurrent arthritis, recurrent meningitis, radiculoneuritis and cranial neuritis (especially peripheral 7th-nerve lesion).
- c. Late: Fatigue, mild encephalopathy, MS-like lesions on MRI, neuropathy, seizures.
2. Tests: CSF Lyme Ab titer (only test CSF if seropositive).
3. Rx:
- a. Isolated 7th palsy or mild neuropathy: Doxycycline 100 mg bid 21-28 d or amoxicillin 500 mg tid 21-28 d.
- b. More serious neurological sx: Ceftriaxone 2 g IV q12h 2-6 wk.

G. Meningitis

1. Bacterial meningitis is an emergency: It may be necessary to give IV Abx empirically before the LP. LP can be done up to 2 h after first dose without destroying culture results.
2. H&P: Prior focal signs, earache, cough, gastroenteritis, immunosuppression, trauma. HA, fever, stiff neck, rash, photophobia, fundi, stiff neck, runny ear or nose.

P.57
- a. Brudzinski's sign: Bending chin to chest hips and knees flex.
- b. Kernig's sign: Pain on straight leg raise. Could also be nerve compression.
3. Tests: CT (consider contrast), LP (technique, p. 224; CSF findings, p. 19), blood cultures, CBC, HIV test, CXR. Consider testing nasal discharge for glucose, chloride to r/o CSF leak.
4. DDx of meningitis: Tumor + fever, abscess, toxic exposure.

5. Bacterial meningitis:

a. Respiratory precautions if you suspect N. meningitidis.
b. Dexamethasone 20 min before, or at least with, the first Abx dose, at 0.15 mg/kg every 6 h for 2-4 d, or until pathogen determined. Helps H. influenzae primarily. No point in starting it after the first dose of Abx.

c. Empiric Abx: These suggestions do not apply outside the US and are heavily influenced by vaccine use. Adjust on basis of culture and sensitivities.

Table 9. Empiric antibiotics for bacterial meningitis. (Adapted from Tunkel AR, et al. Clin Infect Dis. 2004;39:1267-1284.)

Patient	Likely Pathogens	Antibiotics
18-50 yr	Pneumococcus, meningococcus	Vancomycin 0.5 g IV q6h + ceftriaxone 2 g IV q12h
>50 yr	Pneumococ., meningococ, gram-neg bacilli, Listeria	Vancomycin 1 g IV q6h + ceftriaxone 2 g IV q12h + ampicillin 2 g IV q4h
Immunocom-promised	Listeria, pneumococ., H. influenzae	Vancomycin 1 g IV q 6h + ceftriaxone 2 g IV q12h + ampicillin 2 g IV q4h
Head trauma, surgery, shunt	Staphylococcus, gram-neg. bacilli, pneumococ.	Ampicillin 2 g IV q4h + vancomycin 1 g IV q12h + cefepime 2 g IV q12h

6. Viral meningoencephalitis:
- a. Herpes simplex encephalitis:
  - 1) HSV encephalitis is an emergency: Acyclovir should be started empirically before HSV PCR is back.
  - 2) H&P: Viral prodrome; then rapid progression of floridly abnormal behavior, amnesia, seizures, hemiplegia, coma.
  - 3) Tests: HSV PCR in CSF; high CSF RBCs, monocytes, and protein. MRI may show ant. temporal lobe edema, uncal herniation. EEG often shows periodic lateralized epileptiform discharges.
  - 4) Rx: Acyclovir 10 mg/kg IV q8h for 7-10 d. Watch closely for signs of uncal transtentorial herniation.
- b. Others: Varicella, enterovirus, mumps, arboviruses (e.g., eastern equine encephalitis, St. Louis encephalitis), rabies.
7. Tuberculous meningitis and tuberculomas:
- a. H&P: Recent TB exposure, HIV risk factors. Slow onset of headache, low-grade fever, then meningismus and focal neurological signs. In young pts. but not in secondary reactivation, it is usually associated with disseminated dz.
- b. Tests: CSF shows lymphocytosis, low glucose, high protein, and positive AFB cultures (after 4-6 wk). AFB stain is frequently negative. PPD is negative in 1/3 of pts.; CXR shows pulmonary TB in about 75%. Molecular tests are controversial.
- c. Rx: If suspicious, must start rx before CSF cultures come back. Check with an ID specialist for current recommendations, but typical practice starts with isoniazid, rifampin, pyrazinamide, and ethambutol. Give pyridoxine supplements; watch for hypersensitivity, liver dysfunction, and neuropathy. Steroids are sometimes used if there is high ICP, encephalopathy, or evidence of vasculitis.
8. Chronic or recurrent meningitis:
- a. DDx of chronic meningitis:
  - 1) Noninfectious: Neoplasm, sarcoid, vasculitis, lupus, Vogt-Koyanagi-Harada syndrome, Beh et's dz, chronic benign lymphocytic meningitis, Mollaret's meningitis, chemical meningitis, post-SAH .
  - 2) Infectious: TB, fungal, cysticercosis, HACEK organisms, Lyme, brucellosis, syphilis.
- b. Tests:
  - 1) Blood:
    - a) General: Electrolytes, LFTs, CBC, ESR, ANA, RF, ACE, SIEP, VDRL.
    - b) Antibodies to Brucella, toxoplasmosis, Cryptococcus, Lyme, histoplasmosis, coccidiomycosis.
    - c) Antigen: Cryptococcus.
  - 2) CSF:
    - a) Cultures: Bacterial, mycobacterial, fungal cultures. Consider volume, >10 cc; prolonged (HACEK organisms), CO₂ (Brucella), or anaerobic (Actinomyces) incubations.
    - b) Assays: Cryptococcal Ag and Ab, India ink prep for fungi, AFB, VDRL, HSV PCR.
    - c) Cytology: Mollaret's cells, flow cytometry.
  - 3) Imaging: MRI for parameningeal abscess; consider CXR, spine, skull films.
  - 4) Other: PPD, sputum AFB, stool fungi, meningeal biopsy.

H. Progressive multifocal leukoencephalopathy (PML)

Hemiparesis, visual field cut, ataxia, cognitive changes over days to weeks. From JC virus infection; usually with HIV. Usually no mass effect or enhancement, unlike lymphoma, toxo). No specific rx; HIV rx helps some.

I. Syphilis

A spirochete, Treponema pallidum.

1. H&P: Other sexually transmitted dz, genital lesions, HIV.

P.59
- a. Early meningitis: 6-12 mo after primary infection.
- b. Meningovascular: Cranial neuropathies, especially 7th and 8th, arteritis, stroke.
- c. Tabes dorsalis: Sharp leg pains, Argyll-Robertson pupils, proprioceptive ataxia, overflow incontinence, dropped reflexes.
- d. General paresis of the insane: May present with any psychiatric sx. Tabes and meningovascular syphilis are uncommon. Often see brisk DTRs, expressionless face, dysmetria.
2. DDx: Cryptococcal, TB, or carcinomatous meningitis, CNS sarcoid, Lyme, vasculitis.
3. Tests: Serum fluorescent treponemal absorption test positive in 90%. RPR and serum VDRL may be negative. CSF VDRL nearly always positive, with high protein and lymphocytes. HIV test.
4. Rx: 24 MU penicillin G IV, 3-4 MU 10-14 d.

J. Toxoplasmosis

An intracellular protozoan, Toxoplasma gondii.

1. H&P: Immunosuppression, focal deficits, HA, confusion, fever, seizures.

2. DDx: Lymphoma, bacterial abscess, viral or fungal encephalitis, PML.

3. Tests: CT/MRI enhancing, usually ring enhancement, with edema. LP (see p. 19). Toxoplasmosis titer (Ab not usually useful). HIV test, CD4 count.

4. Rx (often empiric for 2 weeks before brain bx): Acutely, pyrimethamine 200 mg PO 1; then pyrimethamine 50-75 mg PO qd + leucovorin 10-20 mg PO qd + sulfadiazine 1-1.5 g PO q6h >6 wk, then half-dose pyrimethamine + sulfa indefinitely.