Aseptic Meningitis


  Normal Bacterial Viral Fungal Tb Abscess
WBC/mL 0–5 >1000* <1000 100–500 100–500 10–1000
%PMN 0–15 >80* <50 <50 <50 <50
%lymph >50 <50 >50 >80 ↑ monos variable
Glucose 45–60 <40 45–65 30–45 30–45 45–60
Ratio ≥ 0.6 ≤0.4 45–65 <0.4 <0.4 0.6
Protein 15–45 150–1000 50–100 100–500 100–500 >50
Pressure 6–20 20–50 variable >20 >20 variable

Background

  1. A serious inflammation of the membranes covering the brain
  2. Can have numerous causes

General Findings

  1. All have similar general findings
  2. Specific etiologic agents have varying histories

Tuberculous Meningitis

  • 300 - 400 cases/ year in the US
    • 15-40% mortality
       
  • Pathophysiology
    • Tubercles form in brain, meninges, adjacent bone
      • From primary TB or reactivation
    • Subependymal tubercle ruptures into subarachnoid space
    • If untreated: Death in 5-8 wks
       
  • Symptoms/ findings
    • Very hard to diagnose
      • Must have high index of suspicion
    • Stage I
      • Lasts 2-3 wks
      • Malaise, headache, lassitude
      • Low-grade fever
      • No mental status changes
    • Stage II
      • Severe/ protracted headache
      • Vomiting
      • Meningismus
      • Confusion/ altered concsciousness
      • Cranial nerve signs (often isolated)
      • Abnormal involuntary movements
        • Tremor, chorea
    • Stage III
      • Disease becomes rapidly progressive
      • Confusion  coma  seizures
      • Occasional hemiparesis
      • Frequent SIADH
         
  • Diagnostic testing
    • TB skin test positive in most cases
      • Negative test DOES NOT rule out disease
    • CXR abnormal in 50%
    • CSF Findings
      • Usual cell count: 100-500 (lymphocytes)
      • Protein: Elevated (100-5000)
        • If subarachnoid block, may be 2-6 g
        • Xanthochromia = poor prognosis
      • Glucose low (<45 in 85% of pts)
      • AFB smears/ cultures (CSF)- minimum of 3, (4 is better)
        • Use last fluid collected
        • Collect 10-15 ml
        • Can take several weeks
      • PCR tests - variable sensitivity
        • May be very useful
        • MUCH faster than cultures
    • CT Scan
      • Basilar meningeal enhancement with ANY hydrocephalus is strong evidence for TB meningitis
    • MRI better for brainstem, midbrain, basal ganglia, spinal cord
       
  • Treatment
    • Initial INH, rifampin, pyrazinamide + ethambutol or streptomycin; 2 month tx course
      • INH: 10 mg/kg/qD until good result, then 5 mg/kg/qD
      • Rifampin: 10 mg/kg/qD (600 mg in adults)
      • Pyrazinamide: 15-30 mg/kg/qD (max 2 g)
        AND
      • Ethambutol: 15-25 mg/kg/qD (Caution: Optic neuritis) OR
      • Streptomycin: 15 mg/kg/qD IM, (max 1 g)

 

Fungal Meningitis

  • Can be several pathogens
    • Cryptococcal meningitis common in AIDS patients (60%)
      • Rare with CD4 counts >100
    • Candida
    • H. capsulatum
    • C immitis
       
  • Physical findings
    • Rarely impressive
      • Focal neuro deficit in 6%, altered mental status in 24%
    • Indolent course
      • Fever, malaise headache
      • Meningeal signs, vomiting, photophobia are rare
    • When course rapid/ fulminant, death often occurs
       
  • Diagnostic testing
    • Blood, urine, sputum cultures
    • CSF findings
      • WBC count usually low (<50, mononuclear cells)
      • Opening pressure often high (>200) in 70%
      • Protein and glucose often minimally abnormal
      • India ink stain positive (75%)
      • CSF culture is definitive diagnostic test
      • Cryptococcal antigen assay: 90% accurate
    • CT Scan if focal findings
      • Hydrocephalus
      • Lymphomas
         
  • Treatment
    • Cryptococcus (AIDS patients)
      • Induction phase (2 wks)
        • Amphotericin B: 0.7- 1 mg/kg/qD IV can add
        • Flucytosine: 25 mg/kg PO QID
      • Consolidation phase (8 wks)
        • Fluconazole: 400 mg/qD IV/PO or
        • Itraconazole: 400 mg/qD IV/PO (an alternative if fluconazole is not tolerated)
      • Maintenance phase
        • Fluconazole: 200 mg/qD IV/PO
           
    • Cryptococcus (non-AIDS patients)
      • Induction (2 wks)
        • Amphotericin B: 0.7- 1 mg/kg/qD IV and
        • Flucytosine: 25 mg/kg PO QID
      • Consolidation (10 wks minimum)
        • Fluconazole: 400 mg/day IV/PO
           
    • Other fungal pathogens
      • C immitis
        • Fluconazole: 400 mg/qD PO (some use up to 1000 mg/qD)
        • Some add intrathecal amphotericin B
      • H capsulatum
        • Amphotericin B: 0.7- 1.0 mg/kg/qD IV then
        • Fluconazole: 800 mg/qD PO x 9-12 months
      • Candida sp
        • Amphotericin B: 0.7 mg/kg/qD IV plus
        • Flucytosine: 25 mg/kg PO QID

 

Lyme Meningitis

  • Typically occurs in the fall
    • History of outdoor activity or tick bite
      • Often seen 2-3 months after skin rash
         
  • Clinical findings
    • Fatigue/ malaise common
    • Fever low-grade or absent
    • Headache is persistent and worsens with time
    • Photophobia/ neck stiffness (may last weeks)
    • DO NOT see Kernig and Brudzinski signs or severe nuchal rigidity
    • Cranial neuropathy (usually CN VII)
    • May see meningoencephalitis findings
      • Memory/ concentration problems
      • Emotional lability
         
  • Diagnostic testing
    • CSF findings
      • WBC count: Usually lower (<100), lymphocytes
      • Glucose level usually normal
      • Protein: Normal to minimally elevated
      • CSF antibodies to B. burgdorferi (compared to serum levels)
      • CSF PCR testing (cannot prove active infection)
         
  • Treatment
    • IV antibiotics (14-28 days)
      • Ceftriaxone 2 g/qD (single dose) OR
      • Cefotaxime: 2 g/ IV q8 hrs OR
      • Penicillin G: 20 million units/qD in 4-6 divided doses
    • NO role for corticosteroids

 

Other Etiologies

  1. Syphilitic meningitis
    • May present as primary infection or as late as 2 yrs later
       
  2. Drug-induced meningitis
    • Probably a hypersensitivity reaction (Types 1 & 3)
    • Other etiologies/ pathophysiology unclear
    • Treatment
      • STOP OFFENDING AGENT
      • Search for other causes of meningitis
 

Admit Orders: Meningitis (Adult)

1. Admit to:

2. Diagnosis: Meningitis.

3. Condition:

4. Vital Signs: q1h. Call physician if BP systolic >160/90, <90/60; P >120, <50; R>25, <10; T >39°C or less than 36°C

5. Activity: Bed rest with bedside commode.

6. Nursing: Respiratory isolation, inputs and outputs, lumbar puncture tray at bedside.

7. Diet: NPO

8. IV Fluids: D5 ½ NS at 125 cc/h with KCL 20 mEq/L.

9. Special Medications:

No known immunodeficiency:

-Ceftriaxone (Rocephin) 2 g IV every 12 hours OR

-Cefotaxime (Claforan) 2 g IV every four to six hours PLUS

-Vancomycin 30 to 60 mg/kg IV per day in two or three divided doses PLUS

-In adults >50 years of age, ampicillin 2 g IV every four hours.

Impaired cell-mediated immunity:

-Vancomycin 30 to 60 mg/kg IV per day in two or three divided doses PLUS

-Ampicillin 2 g IV every four hours PLUS EITHER

-Cefepime (Maxipime) 2 g IV every eight hours OR

-Meropenem (Merrem) 2 g IV every eight hours.

Nosocomial Meningitis:

-Vancomycin 30 to 60 mg/kg IV per day in two or three divided doses PLUS

-Ceftazidime (Fortaz) 2 g IV every eight hours OR

-Cefepime (Maxipime) 2 g IV every eight hours OR

-Meropenem (Merrem) 2 g IV every eight hours.

Allergy to beta-lactams:

-Vancomycin 30 to 60 mg/kg IV per day in two or three divided doses PLUS

-Moxifloxacin (Avelox) 400 mg IV once daily PLUS

-If Listeria coverage is required (>50 and/or in those with defects in cell-mediated immunity), TMP-SMX: 10 to 20 mg/kg (of TMP component) IV per day divided q6-12h.

10. Symptomatic Medications:

-Dexamethasone (Decadron) 0.4 mg/kg IV q12h x 2 days to commence with first dose of antibiotic.

-Heparin 5000 U SC q12h or pneumatic compression stockings.

-Famotidine (Pepcid) 20 mg IV/PO q12h.

-Acetaminophen (Tylenol) 650 mg PO/PR q4-6h prn temp >39°C.

-Docusate sodium 100-200 mg PO qhs.

11. Extras: CXR, ECG, CT scan.

12. Labs: CBC, CMP. Blood C&S x 2. UA with micro, urine C&S. Antibiotic levels peak and trough after 3rd dose, VDRL.

Lumbar Puncture:

CSF Tube 1: Gram stain, C&S for bacteria (1-4 mL).

CSF Tube 2: Glucose, protein (1-2 mL).

CSF Tube 3: Cell count and differential (1-2 mL).

CSF Tube 4: Antigen tests for S. pneumoniae, H. influenzae (type B), N. meningitides, E. coli, group B strep, VDRL, cryptococcal antigen, toxoplasma titers. Fungal cultures, AFB (8-10 mL).