CNS Infection¶
source:: Pocket Medicine, 2022
ACUTE BACTERIAL MENINGITIS¶
Definition¶
- Inflammation of tissue around the brain/spinal cord
- Usually arising from nasopharynx (hematogenous spread), bacteremia, or direct inoculation (surgery, contiguous infection, trauma, foreign body [eg, CSF shunt])
Microbiology in Bacterial Meningitis (NEJM 2011;364:2016)¶
| Pathogen | |
|---|---|
| S. pneumoniae (30-60%) | Look for preceding infection (bacteremia, pneumonia, endocarditis) Drug-resistant S. pneumoniae: ˜40% PCN-resistant (even intermediate resistance problematic) ˜<10% 3rd-gen. cephalosporin-resistant |
| N. meningitidis (10-35%) | Primarily in age <30 y; associated petechiae or purpura ↑ risk in asplenia, complement defic., HIV, SCT, unvaccinated Vaccine rec for all age 11-18 y, HIV infection, asplenia, C5-9 deficiency |
| H. influenzae (<5%) | ↑ risk in asplenia, complement defic., HIV, SCT, unvaccinated, CSF leak, trauma/surgery, mastoiditis Vaccine rec for all children; markedly ↓ incidence |
| L. monocytogenes (5-10%) | ↑ in immunosupp (glucocorticoids, transplant), elderly, malignancy, pregnant, cirrhosis. Outbreaks a/w contaminated dairy & raw veg. |
| GNBs (1-10%) | More common in health care associated meningitis (E. coli, Klebsiella sp., Pseudomonas aeruginosa) |
| Staphylococci (5%) | Preceding infection (endocarditis, bacteremia), post CNS surgery, foreign bodies (CSF) shunt, intrathecal pump) |
| Mixed infection | Suspect parameningeal focus or CSF leak, post CNS surgery |
| ### Clinical manifestations (Lancet 2016;339:16) | |
| - Headache (84%), fever (74%), stiff neck (74%), photosensitivity, GCS <14 (71%), nausea (62%), seizure (23%); 95% have 2 of 4: HA, fever, stiff neck, ΔMS | |
| - Presentation may be atypical (eg, lethargy w/o fever) in elderly and immunosupp. |
Physical exam (CID 2002;35:46; Am J Emerg Med 2013;31:1601)¶
- Nuchal rigidity (Se 30%, Sp 68%), Kernig's sign (Se 5%, Sp 95%), Brudzinski's sign (Se 5%, Sp 95%), jolt sign (HA worsens w/ horizontal rotation) (Se 64%, Sp 43%)
- ± Focal neuro findings (˜30%; hemiparesis, aphasia, visual field cuts, CN palsies)
- ± HEENT findings: sinus tenderness, clear rhinorrhea (CSF leak)
- ± Skin and joint findings: petechial rash (N. meningitidis), genital or oral ulcers (HSV), arthritis with joint effusion (N. meningitidis)
Sequential management of bacterial meningitis¶
- Blood cx, initiate empiric antibiotics, consider corticosteroids (vide infra)
- CT head if indicated (see below)
- LP ASAP (if not contraindicated); yield of CSF cx unlikely to be changed if obtained w/in ˜4 h of initiation of abx
Diagnostic studies (NEJM 2017;388:3036)¶
- Blood cultures ×2 before abx
- WBC count: >10,000 in >90% of bacterial meningitis in healthy hosts
- Head CT to r/o mass effect before LP if ≥1 high-risk feature: immunosupp., h/o CNS disease, new-onset seizure, focal neuro findings, papilledema, GCS <15 (CID 2004;39:1267)
- Lumbar puncture with opening pressure (NEJM 2006;355:e12)
- Send CSF for cell count and differential, glucose, protein, Gram stain, bacterial cx
- Additional CSF studies based on clinical suspicion: AFB smear/cx (or MTb PCR), cryptococcal Ag, fungal cx, VDRL, PCR (HSV, VZV, enteroviral), cytology
- CSF Gram stain has 30-90% Se; cx 80-90% Se if LP done prior to abx though abx should not be delayed for LP if there is concern for bacterial meningitis
- Rule of 2s: CSF WBC >2k, gluc <20, TP >200 has >98% Sp for bacterial meningitis
- Repeat LP only if no clinical response after 48 h of appropriate abx or CSF shunt
- Metagenomic next-generation sequencing ↑ dx yield (NEJM 2019;380:2327)
Typical CSF Findings in Meningitis¶
| Type | Appearance | Pressure (cm H2O) | WBC/mm3 Predom Type | Glc (mg/dL) | TP (mg/dL) |
|---|---|---|---|---|---|
| Normal | Clear | 9-18 | 0-5 lymphs | 50-75 | 15-40 |
| Bacterial | Cloudy | 18-30 | 100-10,000 polys | <45 | 100-1000 |
| TB | Cloudy | 18-30 | <500 lymphs | <45 | 100-200 |
| Fungal | Cloudy | 18-30 | <300 lymphs | <45 | 40-300 |
| Aseptic | Clear | 9-18 | <300 polys → lymphs | 50-100 | 50-100 |
| ### Empiric Treatment of Bacterial Meningitis (Lancet 2012;380:1693) |
| Adults <50 y | Ceftriaxone + vancomycin (trough 15-20), consider acyclovir IV |
|---|---|
| Adults >50 y | Ceftriaxone + vancomycin + ampicillin, consider acyclovir IV |
| Immunosuppressed | [Cefepime or meropenem] + vanc ± amp (not nec. if on meropenem), consider acyclovir IV & fungal coverage |
| Healthcare assoc. infection (eg, surgery, CSF shunt) | [Cefepime or meropenem or ceftazidime] + vancomycin |
| - When possible, organism-directed Rx, guided by sensitivities or local patterns of drug resistance should be used | |
| - Confirm appropriate dosing as higher doses are often needed in meningitis (though may need to be adjusted for renal function) | |
| - Corticosteroids: If causative organism is unknown, dexamethasone 10 mg IV q6h × 4 d recommended prior to or with initiation of abx. Greatest benefit in S. pneumoniae and GCS 8-11 (↓ neuro disability & mortality by ˜50%). Avoid in crypto (NEJM 2016;374:542). | |
| - Prophylaxis: for close contacts of Ptw/N. meningitidis; rifampin (600 mg PO bid × 2 d) or ciprofloxacin (500 mg PO × 1) or ceftriaxone (250 mg IM × 1). | |
| - Precautions: droplet precautions until N. meningitidis is ruled out |
ASEPTIC MENINGITIS¶
Definition¶
- Clinical/lab evidence of meningeal inflammation with negative bacterial cx (CSF & blood)
Etiologies (Neurology 2006;66:75)¶
- Viral: enteroviruses are most common cause (summer/fall; rash, GI, URI sx), HIV, HSV, VZV, mumps (parotitis), lymphocytic choriomeningitis virus (rodent exposure), encephalitis viruses, adenovirus, polio, CMV, EBV, WNV
- Focal bacterial infection: brain/epidural/subdural abscess, CNS septic thrombophlebitis
- Partially treated bacterial meningitis
- Other infectious: TB, fungal (cryptococcus, coccidiodes), Lyme, syphilis, leptospirosis
- Neoplasm: intracranial tumors (or cysts), lymphomatous or carcinomatous meningitis
- Drug-induced meningitis: NSAIDs, IVIG, antibiotics (TMP-SMX, PCN), anti-epileptics
- Systemic autoimmune illness: SLE, sarcoidosis, Behçet's, Sjögren's syndrome, RA
- Mollaret's: recurrent lymphocytic meningitis, spontaneously resolving (often HSV-2)
Diagnosis¶
- Obtain LP for CSF analysis: lymphocytic pleocytosis common in viral etiologies (see Typical CSF Findings in Meningitis table above)
- Consider CSF cytology and MRI brain/spine to evaluate for malignancy
- Consider serum autoimmune and serum viral testing in appropriate settings if CSF is unrevealing and there is no improvement with empiric treatment
Empiric treatment¶
- Suspected bacterial meningitis: see empiric treatment of bacterial meningitis above
- Suspected viral meningitis: if concern for HSV meningoencephalitis → IV acyclovir
- Unclear etiology: consider initiation of empiric bacterial meningitis treatment while observing and awaiting CSF studies
ENCEPHALITIS (NEJM 2018;379:557)¶
Definition¶
- Inflammation of brain parenchyma characterized by impaired cerebral function (AMS, neurologic deficits) often due to primary viral infection or post-viral inflammation
Etiologies (specific etiology found in <20% of cases; Neurology 2006;66:75; CID 2008;47:303)¶
- HSV-1 all ages/seasons. If sxs recur after Rx, consider viral relapse vs. autoimmune encephalitis b/c high rates of autoimmune disease wks later (Lancet Neurol 2018;17:760)
- VZV 1° or reactivation; ± vesicular rash; all ages (favors elderly), all seasons
- Arboviruses: evaluate for exposure to vector/geography. Mosquitoes: West Nile, Eastern/Western equine, St. Louis, La Crosse; Ixodes tick: Powassan.
- Enteroviruses (coxsackie, echo): preceding URI/ GI sx; peaks in late summer/early fall
- Other infectious: CMV, EBV, HIV, JC, measles, mumps, rabies, adeno, influenza, Lyme
- Non-infectious: autoimmune/paraneoplastic (anti-NMDAR, anti-Hu, anti-Ma2, anti-CRMP5, anti-mGluR5), post-infxn demyelination (eg, ADEM)
Clinical manifestations¶
- Fever + ΔMS (subtle to severe), seizure, focal neuro deficit, HA in meningoencephalitis
Diagnostic studies (CID 2013;57:1114)¶
- CSF analysis: lymphocytic pleocytosis; PCR for HSV (95% Se & Sp), VZV; consider other PCR based on risk factors (CMV/EBV, HIV, JC, adeno/enterovirus, WNV)
- Consider testing for autoimmune etiologies and serologic viral testing in appropriate settings if CSF is unrevealing and there is no improvement with empiric HSV/VZV Rx
- MRI (CT if unavailable); HSV temporal lobe; W. Nile & Powassan thalamic hyperintensity
- EEG to r/o seizure; findings in encephalitis are nonspecific (temporal lobe focus in HSV)
Treatment¶
- HSV/VZV: IV acyclovir 10 mg/kg IV q8h; consider empiric treatment given frequency
BELL'S PALSY¶
Definition & clinical manifestations¶
- Acute idiopathic unilat. facial nerve palsy (CN VII), often presumed HSV reactivation
- P/w unilateral facial muscle weakness, hyperacusis, ↓ taste, lacrimation, & salivation
- Risk factors: pregnancy (preeclampsia), obesity, HTN, diabetes, preceding URI
Diagnosis (Otol Head Neck Surg 2013;149:656)¶
- Labs, imaging, EMG not needed in routine cases
- Ddx: Bilateral: Lyme, GBS, sarcoid. Additional neuro sx: stroke, tumor. Rash: herpes zoster. Other: otitis media, HIV, Sjögren.
Treatment and Prognosis (CMAJ 2014;186:917)¶
- 70% recover spontaneously w/in 6 mos, >80% recover with glucocorticoid treatment
- Oral corticosteroids started w/in 72 hrs of sx onset improve odds of recovery; dose varies based on severity (House-Brackmann grading). No conclusive data on antivirals.
- If eyelid closure is compromised, eye protection is crucial to prevent trauma
HERPES ZOSTER (SHINGLES)¶
Definition & etiology¶
- Painful vesicular rash in a peripheral nerve distribution due to reactivation of VZV
- Spread by contact with active lesion (prior to crusting) in uncomplicated zoster or via airborne transmission in disseminated zoster
Clinical manifestations & complications¶
- Uncomplicated: pain in a dermatomal distribution → dermatomal eruption of erythematous papules → vesicles → crusted plaques in varying stages of evolution
- Disseminated: vesicles across multiple dermatomes, visceral organ involvement (pneumonia, hepatitis, CNS) seen in immunosupp. (eg, transplant, malignancy)
- Zoster opthalmicus: ocular involvement (V1 of CN V) requires urgent ophtho eval
- Post-herpetic neuralgia: neuropathic pain lasting >90 d after dx
Diagnosis¶
- Clinical diagnosis if uncomplicated
- Confirm with PCR (most sensitive), DFA, and viral culture (allows for resistance testing) of vesicular fluid (scrape from unroofed vesicle)
Treatment & prevention¶
- Uncomplicated: acyclovir, valacyclovir, or famciclovir x 7 d; initiate w/in 72 h of onset for greatest benefit; consider after 72 h if new lesions present; minimal benefit after crusting
- Superimposed bacterial cellulitis is common; if suspected, treat with appropriate antibiotics
- Disseminated/immunosupp.: IV acyclovir, eval for visceral spread, droplet precautions
- Prevention: Shingrix (2 doses) for all Pts >50; consider in younger if immunosupp.