John Lynch MD MPH Harborview Medical Center & University of
Washington Encephalitis and Meningitis
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Case 25 year old woman with a headache and change in mental
status. LP finds WBC 88 per microliter.
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Central Nervous System Infections Signs and symptoms Fever
Headache Altered mental status Focal neurological findings
Nonspecific Infectious and noninfectious etiologies
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CNS Infections Risk factors Geographic location, travel Time of
year Environments (dormitories, barracks) Concomitant illness (HIV,
diabetes, alcoholism) Medications (immunosuppressants, chemo,
prophylactic medications)
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CNS Infections Physical examination Identify contraindications
to LP mass lesion with midline shift infected lumbar area
disordered coagulation (PLT 1.5) Identify concomitant sites of
pathology Define the site and the syndrome
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CNS Infection Syndromes Acute meningitis Subacute or chronic
meningitis Acute encephalitis Chronic encephalitis Space occupying
lesion Toxin mediated Encephalopathy with systemic infection
Postinfectious
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Case 25 year old woman with a headache and change in mental
status. LP finds WBC 88 per microliter, HSV PCR negative. D/c to
home, improved on topiramate after 5 days.
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Encephalitis Inflammation of the brain Pathological diagnosis
+/- neurons infected Cardinal features Altered mental status Can
mimic psychiatric disease Other features Headache, fever, nausea,
vomiting Seizures, focal neurological deficits
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Neuroimaging in Encephalitis Normal Focal inflammation Diffuse
inflammation
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Encephalitis Etiology Infectious More than 100 infectious
etiologies identified Most commonly viruses Para- or
post-infectious Etiology not established in ~50% of cases
Diagnostics not adequate Emergence of new etiologies
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Encephalitis etiology? Season: late summer, early fall
enteroviruses parechoviruses tick and mosquito-borne agents
Geographic exposure Relapsing fever vs Borreliosis JEV in Asia/SE
Asia Consult public health
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Encephalitis etiology? Underlying medical problems HIV:
toxoplasmosis (CD4
Anti-NMDAR Encephalitis 80% of patients are female Associated
with ovarian teratoma Females >11 yrs More common in people of
African and Asian ancestry Prominent psychiatric symptoms early
(can resemble phencyclidine or ketamine intox) Patients often
require ICU care and prolonged hospitalization
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Clinical Findings in NMDARE-1 Prodrome Headache Fever Nausea
and vomiting Diarrhea URI symptoms
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Clinical Findings in NMDARE-1 Early Seizures Psychiatric
symptoms Short-term memory loss Language abnormalities
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Clinical Findings in NMDARE-1 Late Involuntary movements
Catatonia Coma Autonomic and breathing instability
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Diagnosis NMDARE Serum: antibodies to N-terminal domain of NR1
subunit of NMDAR CSF Mild to moderate mononuclear pleocytosis OCBs
in 60% Antibodies to NMDAR, more sensitive than serum
antibodies
NMDARE Treatment Immunotherapy Corticosteroids Rituximab +/-
cyclophosphamide Identification and removal of tumor (empiric
oophorectomy)
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NMDARE Prognosis Recover or mild sequelae ~75%, can take >18
months Severely disabled ~20% Die ~4% Relapse ~20-25% No tumor
identified Not treated with immunosuppression Rapid taper of
immunosuppression
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Case 2 70 yo man with CAD, AF on warfarin. Comes into the ED
ill x 3-4 days (fever, MS changes, nausea, vomiting, diarrhea).
Neurological examination: confused and left facial weakness
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Case 2 70 yo man with CAD, AF on warfarin. Comes into the ED
ill x 3-4 days (fever, MS changes, nausea, vomiting, diarrhea).
Neurological examination: confused and left facial weakness WBC
17,000, head CT normal CSF: 28 WBCs (40% polys), glucose 57,
protein 56
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Question What is the most likely diagnosis? A.Herpes
encephalitis B.HHV6 encephalitis C.Leucine rich glioma inactivate 1
encephalitis D.Rhomboencephalitis due to L monocytogenes E.NMDA
receptor encephalitis
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HSV Encephalitis Most common cause of sporadic encephalitis in
US Occurs any time of year Bimodal age distribution 25-30% 40 yo
Most due to HSV-1 Primary ~30% Reactivation ~60% HSV-2 in
immunosuppressed (Mollarets?) Steroids, TNF-alpha blockers are risk
factors
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Clinical Findings in HSVE Fever Headache Change in level of
consciousness Dysphasia Personality changes Seizures Mild or
atypical cases in PCR era
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HSVE Treatment Acyclovir 10mg/kg IV q8hrs 14-21 days course
Continue till CSF HSV PCR negative Prolonged PO treatment after IV?
Study in adults pending Study in neonates found better
neurodevelopmental outcomes after 6 months of treatment
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HSVE Prognosis Mortality Untreated 70% Treated 28%
Neurological, neuropsychiatric sequelae in more than 50%
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Diagnostic Algorithm Metabolic Evaluation and Directed Physical
Exam CT FIRST? YES CT Empiric Acyclovir LP MR Not OKOK Continue
treatment NO
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Meningitis Inflammation of the leptomeninges (the pia,
arachnoid, and dura mater). Meningitis reflects inflammation of the
arachnoid mater and the cerebrospinal fluid (CSF) in both the
subarachnoid space and in the cerebral ventricles.
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Types of Meningitis Bacterial (N meningitidis, S pneumoniae)
Viral (enteroviruses, arbovirus, HSV) Fungal (cryptococcus,
histoplasma) Parasitic (A cantonensis) Non-infectious (SLE, vancer,
drugs, injury)
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Case 3 12 yo male living in Alabama with headache, neck
stiffness, nausea, vomiting x 1. Only medical history is sinusitis
treated with home remedies. Started on broad empiric antibiotics
and acyclovir. The next day he started to hallucinate and soon
became unresponsive and died a day later.
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Question What is the most likely etiology? A. S pneumoniae
B.Naegleria fowleri C.N meningococcus D.L monocytogenes E.B
henselae F.MRSA
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Primary Amebic Meningoencephalitis (PAM) Very rare form of
parasitic meningitis (31 US cases/10 yrs) The ameba is found
worldwide in warm freshwater, hot springs, water heaters and warm
industrial waters The ameba enters the body through the nose
(cannot infect by drinking water) Uniformly fatal in 1-12 days
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Fungal Meningitis Cryptococcus- inhalation of soil contaminated
with bird droppings Histoplasma- environments with heavy
contamination of bird/bat droppings, Ohio and Mississippi Rivers
Blastomyces- soil with rich decaying matter, northern Midwest
Coccidioides- SW US, Central and S America (and E Washington),
African Americans, Filipinos, pregnant women, immunocompromised at
higher risk Candida- usually hospital acquired
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Viral Meningitis Summer and fall months = enteroviruses Fecal
contamination and respiratory secretions Person to person spread
Others: mumps, EBV, HSV, VZV, measles, influenza, arboviruses, LCMV
Risk groups: Infants