Meningitis, Encephalitis, and Brain Abscesses



Meningitis, Encephalitis, and Brain Abscesses


Kate T. Brizzi

Tracey Cho



Meningitis: Inflammation of the meninges. Encephalitis: Inflammation of the brain. Meningoencephalitis: Inflammation of brain & meninges. Aseptic meningitis: Meningitis w/neg routine bacterial cx (misnomer—causes include infectious & noninfectious agents, excluding causes of acute bacterial meningitis). Chronic meningitis: Meningitis > 1 mo. Recurrent (Mollaret) meningitis: >1 episode, nl CSF b/n. Leptomeningitis: Primarily arachnoid + pia (usual meaning of “meningitis”). Pachymeningitis: Involves primarily dura (much rarer).


OVERLAPPING CLINICAL SYNDROMES

Bacterial & aseptic meningitis, meningoencephalitis, & brain abscess Roughly four acute clinical syndromes, generally merit different w/u & mgt:



  • Acute bacterial meningitis: (+)meningeal, (±)cortical si/sx.


  • Acute aseptic meningitis: (+)meningeal, (–)cortical si/sx.


  • Acute encephalitis: (±)meningeal, (+)cortical si/sx (multifocal > focal).


  • Brain abscess: (±)meningeal, (+)cortical si/sx (focal > multifocal).

Syndromes of bacterial meningitis & encephalitis overlap, hence “meningoencephalitis.” In practice, all four frequently present similarly.

Common in all four: HA, fever, nuchal rigidity, photophobia, n/v.

Acute bacterial meningitis: Fever (77%), nuchal rigidity (83%), AMS (69%), sz (5%). At least 2/4 of these + in 95% cases. Elderly pts can be “atypical”: Lethargy, AMS, no fever, or even without neck stiffness.


Encephalitis: Fever, HA, AMS, sz, focal signs, mvmt d/os.

Aseptic meningitis: Neg routine CSF cx, CSF pleocytosis (usu lymphocytic, but not always); discomfort, lethargy, HA, f/n/v, but preserved mentation.

Brain abscess: Confusion, drowsiness, szs. Distinguish from meningoencephalitis by imaging.

Distinguishing at presentation: Sometimes clear initial distinction possible (frequent exceptions). “Classical” CSF profile can help (beware wide variability in CSF for bacterial meningitis). Decision tools may aid early triage, e.g., Bacterial Meningitis Score (BMS) (Pediatrics 2002;110:712; JAMA 2007;297:52; Curr Opin Neurol 2009;22:288).


































Bacterial Meningitis Score (Pediatrics 2002;110:712)


Predictor

Points


Positive Gram stain

2


CSF protein ≥ 80 mg/dL

1


Peripheral ANC ≥ 10,000 cells/mm3

1


Seizure at or before presentation

1


CSF ANC ≥ 1,000 cells/mm3

1


Interpretation of score (possible scores range from 0 to 6)


BMS = 0: strongly suggests aseptic meningitis (Se 74%, Sp 100%)


BMS = 1: won’t miss bacterial meningitis, but nonspecific (Se >99%, Sp 37%-73%)


BMS ≥ 2: strongly suggests bacterial meningitis (Se >99%, Sp 97%)


(Rev Med Liege 2006;61:581; Pediatrics 2002;110:712; Curr Opin Neurol 2009;22:288)


Caveats: Derived based on pedi population. Valid if inclusion/exclusion criteria are met: Inclusion criteria: CSF WBC >10 cells/mm3.


Exclusion criteria: H/o neurosurgery, immunosuppression, CSF RBC >10,000/mL, pretreated w/antibiotics within 48 h, septic shock, presence of purpura.










































Pathways for Initial Management of Acute Meningitis & Encephalitis


Meningeal si/sx only

→

Bacterial

→

Admit, w/u ABM

→

“Aseptic”

→

Admit, w/u AAM



→

Home w/f/u


Cortical ± meningeal si/sx

→

Clue(s) to etiology

→

Admit, core + focused w/u AME


→

No specific clues

→

Admit, core + broad w/u AME


ABM, acute bacterial men; AAM, acute aseptic men; AME, acute meningoencephalitis.






















































Typical CSF Findings in Meningitis & Encephalitis

Glucose (mg/dL)

Protein (mg/dL)

<10

10-45

>250

50-250


More common

BM

BM

BM

VM, NS, Lyme dz


Less common

TBM, FM

NS, VM (e.g., mumps, LCMV)

TBM


Total white blood cell count (cells/µL)

>1,000

100-1,000

5-100


More common

Bacterial meningitis

BM, VM

Early BM; TBM, NS


Less common

Mumps, LCMV

Encephalitis

Encephalitis


BM, bacterial men; VM, viral men; TBM, tuberculous men; NS, neurosyphilis; FM, fungal meningitis. Adapted from UpTo Date 2009, “Cerebrospinal fluid: Physiology & utility of an exam in dz states.”



TRIAGE IN THE EMERGENCY DEPARTMENT

Admit & emergently treat if: Suspect acute bacterial meningitis or encephalitis. Tailor w/u & Rx to clinical situation; general rules of thumb by best-fitting syndrome:



  • AME → broad-spectrum bacterial abx + acyclovir


  • ABM → dexamethasone + empiric bacterial abx + acyclovir

Admit for observation + further w/u, ± Rx: In selected cases of aseptic meningitis. Most admissions for supportive care (IVF, antiemetics, pain control). Broad ddx w/few treatable causes (˜ same ddx as encephalitis—see below); clinical suspicion for specific causes & illness severity must determine w/u scope.

Consider discharge home from ED: In selected pts w/aseptic meningitis, no universally accepted criteria currently exist, reasonable to d/c pts meeting the following criteria: (1) “Nontoxic” clinical appearance. (2) BMS = 0 (neg Gram stain, CSF
ANC < 1,000, CSF protein < 80, peripheral ANC < 10). (3) Normal serum WBC. (4) No sz during illness. (5) No cerebral (cortical) signs on neurological examination. (6) Adequate control of sx (e.g., n/v). (7) Able to arrange f/u w/PCP in 1-3 days. (8) Advise return to ED immediately in case of any clinical worsening.


ETIOLOGIES OF ASEPTIC MENINGITIS & ENCEPHALITIS


















Ddx of Aseptic Meningitis & Encephalitis


Infectious


Viruses: Enteroviruses (coxsackie, ECHO, non-polio entero)


Herpes viruses (HSV1, HSV2, VZV, CMV, EBV, HHV-6, simian herpes B virus)


Resp viruses: Adenovirus, rhinovirus, influenza types A and B, parainfluenza viruses, RSV


Arboviruses: EEE, WEE, VEE, St LE, WNV, LA, California EV, CTFV, Powassan virus, mumps, measles, rubella


HIV, HTCLV-I & II, LCMV, rotavirus, encephalomyocarditis virus, vaccinia, rabies virus, hepatitis A & B, parvovirus, vesicular stomatitis virus


Bacteria: Partially Rx’d meningitis, parameningeal infxn, endocarditis


Mycoplasma pneumonia, Mycoplasma hominis, Mycob. tuberculosis


Ehrlichiosis, brucella, Bartonella henselae, Francisella tularensis, Actinomyces


Listeria, Nocardia, Chlamydia, rat-bite fever/sodoku, Strep. moniliformis


Spirillum minus, Coxiella burnetii (Q fever), Whipple bacillus


Spirochetes: Borrelia burgdorferi (Lyme), T. pallidum (syphilis), leptospirosis


Rickettsiae: RMSF, typhus


Fungi: Crypto, Histo, Coccidioides, Sporothrix, Blastomyces, Candida, Aspergillus, zygomycosis (mucormycosis), Pseudallescheria, Paracoccidioides, dematiaceous mold


Parasites: Toxoplasma, cysticercosis (Taenia solium), trichinosis (Trichinella spiralis), Angiostrongylus, Strongyloides stercoralis, schistosomiasis, amebae (Naegleria, Acanthamoeba, Balamuthia), Trypanosoma sp., Malaria sp., Baylisascaris procyonis


Noninfectious


Drugs: TMP-SMX, NSAIDs (esp ibuprofen), amoxicillin, OKT3 (muromonab-CD3), IVIg, INH, azathioprine, intrathecal(IT)-MTX, IT-cytosine arabinoside, allopurinol, carbamazepine, sulfasalazine, Pyridium (phenazopyridine)


Demyelinating dz: MS, ADEM, NMO, transverse myelitis


Systemic dz: Collagen vascular dz, SLE, Sjögren syndrome, Wegener, PAN, CNS vasculitis, Behcet dz, sarcoidosis, Vogt-Koyanagi-Harada syndrome, Fabry dz.


Neoplastic: Leptomeningeal cancer, leukemia, lymphoma, carcinomatous meningitis, posttransplantation lymphoproliferative disorder


Vascular: Infarctions (brain, cord), CNS vasculitis (primary or secondary)


Postinfxn/vaccine: Rubeola, rubella, varicella, variola; vaccines: Rabies, pertussis, influenza, vaccinia, yellow fever


Chemical: Blood leak from brain, cord, meninges due to, e.g., angioma, AVM; can cause superficial hemosiderosis. Cholesterol leak from craniopharyngioma, teratoma, epidermoid cyst


Other: HaNDL syndrome (“headache w/neurologic deficits & CSF lymphocytosis”—?viral)



ACUTE ASEPTIC MENINGITIS & ENCEPHALITIS


WORKUP & EMPIRIC TREATMENT

General points: (1) Distinguish primary vs. post- or parainfections. (2) Mosquito & tick-borne illnesses have regional & seasonal variation. (3) WNV occurs mainly during mosquito season, affects elderly most. (4) Enterovirus, influenza, varicella: Incidence varies seasonally. (5) HSV: No significant variation by season or geography. (6) Identification of etiologic agents only possible in ˜1/3 cases even w/“aggressive” w/u.

History: Onset/pace/progression, travel, pets/animal/insect exposures/bites/scratches, sick contacts, PPD/HIV/immune status, prior similar illness, transfusion hx, recent illness, recent abx, new meds, sexual hx, rash, mouth/genital sores, arthritis, dry mouth/eyes.

Exam: See suggestions at beg of chapter. (1) Gen si/sx: HA, fever, stiff neck, photophobia, n/v, sz, MSΔs, focal si/sx, mvmt d/os. (2) Focal vs. diffuse brain involvement (by exam or imaging)—can point to etiology (e.g., arboviral infection: diffuse, w/early, rapid, HA, fever/n/v/AMS/focal signs, coma. HSV: Focal sx pointing to asymmetric
temporal & frontal lobe involvement. Fever/HA progress for days & then szs, obtundation). (3) Useful clues on exam (Table 14.1): Enlarged liver, lymphadenopathy, parotitis, rash, respiratory sx, retinitis, cerebellar ataxia, CN palsies, dementia, myorhythmia, parkinsonism, paralysis, CN palsies, ulcers of mouth & genitals, joint inflammation, dry eyes or mouth, uveitis (iridocyclitis), rash, blisters/vesicles (including on genitalia), hydrophobia, aerophobia, pharyngeal spasm, hyperactivity, tremors (eyelids, tongue, lips, limbs).


Empiric abx (while confirmatory tests are pending)



  • Empiric coverage for ABM × 48 h if: Bacterial meningitis suspected (see below) or elderly, immunocompromised, or received abx recently (even if viral meningitis more likely).


  • Suspect encephalitis: Acyclovir 10 mg/kg q8h × 14 days (until r/o HSV; see chapter Neurologic Infectious Diseases).


  • Rickettsial or Ehrlichial dz: During appropriate season, treat those w/suggestive clinical picture w/doxycycline 100 mg q12 for 10 days or until afebrile for at least 3 days.


  • ADEM: Steroids, ± IVIg, or plasmapheresis (see chapter Demyelinating Diseases of the Central Nervous system).


  • Other causes of aseptic meningitis & encephalitis less common or not treatable—target any therapies toward treatable causes if reasonable grounds for suspicion.

Diagnostic Tests: Labs: Vast ddx. Use “two-step” approach: (1) Initial w/u for dangerous/common/treatable causes (see Table 14.3) (2) Further w/u focused based on: Pace & temporal pattern of illness (acute, subacute/chronic/recurrent), clinical clues (see Table 14.1), epidemiology & risk factors (Table 14.2), initial lab results (Table 14.3). MRI w/gado: If suspect encephalitis (may help narrow ddx). EEG: If pt is confused/obtunded/comatose to r/o nonconvulsive status epilepticus.








Table 14.1 Possible Etiologies Based on Clinical Findings





















































Hepatitis: C. burnetii


Lymphadenopathy: HIV, EBV, CMV, measles, rubella, WNV, (Toxoplasma) Treponema pallidum, Bartonella sp., TB, Toxo, Trypanosoma brucei gambiense


Parotitis: Mumps virus


Rash: HIV, VZV, HHV-6, B virus, WNV, some enteroviruses, Rickettsia rickettsii, Mycoplasma pneumoniae, B. burgdorferi, T. pallidum, Ehrlichia, Anaplasma phagocytophilum


Respiratory sx: VEE, Nipah virus, Hendra virus, influenza, adenovirus, M. pneumoniae, C. burnetii, M. tuberculosis, Histo


Retinitis: CMV, VZV, HSV, WNV, B. henselae, T. pallidum


Urinary symptoms: St. Louis encephalitis virus (early)


Cerebellar ataxia: VZV (children), EBV, mumps, St LE, T. whipplei, T. brucei gambiense


Cranial nerve palsies: HSV, EBV, Listeria, TB, T. pallidum, B. burgdorferi, T. whipplei, Cryptococcus, Histo, Coccidioides sp., HIV, Lyme, VZV, CMV, HSV, sarcoid


Dementia: HIV, sCJD & vCJD, measles virus (SSPE), T. pallidum, T. whipplei


Myorhythmia: T. whipplei (oculomasticatory)


Parkinsonism: JEV, St LEV, WNV, Nipah virus, T. gondii, T. brucei gambiense


Flaccid paralysis: JEV, WNV, tick-borne encephalitis virus, enteroviruses, (enterovirus-71, coxsackieviruses), poliovirus


Rhombencephalitis: HSV, WNV, enterovirus 71, Listeria, rabies


Malignancy, CN, or spinal nerve palsies: Neoplastic meningitis


Intractable HA + mild meningeal signs: Granulomatous CNS angiitis


Ulcers of mouth & genitals, serositis, arthritis, dry eyes & mouth, uveitis, rash: Behcet’s, Sjögren’s, SLE, sarcoid


Vesicles in dermatomal pattern: VZV


Genital vesicles & ulcers: HSV2, Behcet’s


Hydrophobia, aerophobia, pharyngeal spasm, hyperactivity: Rabies


Tremors of eyelids, tongue, lips, extremities: St LE, WNV


Temporal lobe preference: HSV > VZV, EBV, HHV6, syphilis


Hydrocephalus: Bacterial, fungal, & parasitic agents, sarcoidosis


Very low CSF glucose: Tuberculosis, Cryptococcus, neoplastic, sarcoidosis


Skin rash, aphthous ulcers: HIV, VZV, HSV, EBV, CMV, JCV, Behcet’s











Table 14.2 Possible Etiologies Based on Risk Factors & Epidemiology


































































































































































Age


Neonates

HSV2, CMV, rubella virus, Listeria, T. pallidum (syphilis), Toxoplasma


Infants & children

EEE, JEV, Murray Valley EV, influenza virus, La Crosse v.


Elderly

EEE, St LE, WNV, sporadic CJD, Listeria


Animal contact


Bats

Rabies v., Nipah v.


Birds

WNV, EEE, WEV, VEE, St LE, Murray EV, JEV, Cryptococcus


Cats

Rabies v., C. burnetii, B. henselae, T. gondii Dogs Rabies v.


Horses

EEE, WEE, VEE, Hendra v.


Old World primates

B v.


Raccoons

Rabies v., B. procyonis


Rodents

EEE, VEE, tick-borne EV, Powassan v. (woodchucks), La Crosse v. (chipmunks, squirrels), Bartonella Q, LCMV


Sheep & goats

C. burnetii


Skunks

Rabies v.


Swine

JEV, Nipah v.


White-tailed deer

B. burgdorferi


Immunocompromised

VZV, CMV, HHV-6, WNV, HIV, JCV, TB, Listeria, Crypto, Histo, Toxo, Coccidioides


Agammaglobulinemia

Enteroviruses, M. pneumoniae


Ingested items


Undercooked meat

T. gondii


Raw meat, fish, reptiles

Gnathostoma species


Unpasteurized milk

Tick-borne EV, Listeria, C. burnetii Insect contact


Mosquitoes

EEE, WEE, VEE, St LE, Murray Valley EV, JEV, WNV, La Crosse v., Plasmodium falciparum


Sandflies

Bartonella bacilliformis


Ticks

Tick-borne EV, Powassan v, R. rickettsii, Ehrlichia, A. phagocytophilum, C. burnetii, B. burgdorferi


Tsetse flies

T. brucei (gambiense & rhodesiense)


Occupation


Exposure to animals

Rabies v., C. burnetii, Bartonella sp.


Exposure to horses

Hendra v.


Work w/primates

B v.


Laboratory workers

WNV, HIV, C. burnetii, Coccidioides sp.


Healthcare workers

VZV, HIV, influenza v, HIV, measles, TB


Person-to-person transmission

HSV (neonatal), HHV-6, VZV, EBV, VEE (rare), poliovirus, MMR, enteroviruses, Nipah v., B v., WNV (transfusion/transplant/breast-feeding), HIV, rabies v. (transplant), influenza v, M. pneumoniae, TB, T. pallidum (sexual intercourse, syphilis)


Recent vaccination

ADEM


Recreational activities


Camping/hunting

Mosquito, tick agents (see above)


Sexual contact

HIV, T. pallidum


Spelunking

Rabies virus, H. capsulatum


Swimming

Enteroviruses, Naegleria fowleri Season


Late summer/early fall

Mosquito, tick agents (see above), enteroviruses


Winter

Influenza v.


Transfusion & transplantation

CMV, EBV, HIV, tick-borne EV, rabies, CJD, T. pallidum, A. phagocytophilum, R. rickettsii, crypto, Histo, Coccidioides


Travel


American Northwest & Northern Midwest

Borrelia


American SW & Mexico

Coccidioides


Africa

Rabies, WNV, P. falciparum, T. brucei (gamb., rhod.)


Australia

Murray Valley EV, JEV, Hendra v.


Central America

Rabies, EEE, WEE, VEE, St LE, R. rickettsii, P. falciparum, T. solium


Europe

WNV, tick-borne EV, A. phagocytophilum, B. burgdorferi


India, Nepal

Rabies v., JEV, P. falciparum


Middle East

WNV, P. falciparum


Russia

Tick-borne encephalitis v.


South America

Rabies, EEE, WEE, VEE, St LE, R. rickettsii, B. bacilliformis (Andes mountains), P. falciparum, T. solium


Southeast Asia, China, Pacific Rim

JEV, tick-borne EV, Nipah v., P. falciparum, Gnathostoma sp., T. solium


Unvaccinated status

VZV, JEV, polio v, measles, mumps, rubella

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Aug 17, 2016 | Posted by in NEUROLOGY | Comments Off on Meningitis, Encephalitis, and Brain Abscesses

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