John Lynch MD MPH Harborview Medical Center & University of Washington
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Transcript of John Lynch MD MPH Harborview Medical Center & University of Washington
John Lynch MD MPHHarborview 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.
Central Nervous System Infections
• Signs and symptoms– Fever– Headache– Altered mental status– Focal neurological findings
• Nonspecific• Infectious and noninfectious etiologies
CNS Infections
• Risk factors– Geographic location, travel– Time of year– Environments (dormitories, barracks)– Concomitant illness (HIV, diabetes, alcoholism)– Medications (immunosuppressants, chemo,
prophylactic medications)
CNS Infections
• Physical examination– Identify contraindications to LP• mass lesion with midline shift• infected lumbar area• disordered coagulation (PLT <50K, INR >1.5)
– Identify concomitant sites of pathology– Define the site and the syndrome
CNS Infection Syndromes
• Acute meningitis• Subacute or chronic meningitis• Acute encephalitis• Chronic encephalitis• Space occupying lesion• Toxin mediated• Encephalopathy with systemic infection• Postinfectious
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.
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
Neuroimaging in Encephalitis
• Normal• Focal inflammation• Diffuse inflammation
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
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
Encephalitis etiology?Underlying medical problems–HIV: toxoplasmosis (CD4 <200)–Transplant: LCMV, WNV, rabies– Immunosuppression: VZV, HHV6, WNV,
toxoplasmosis
More clues–Rash: VZV, JJV6, WNV, borrelia, erlichia,
anaplasma–Retinitis: WNV, B henselae, syphilis–Parkinsonism: WNV, SLEV, JEV–Flaccid paralysis: WNV, JEV, tick-borne
encephalitis virus
Case
Ongoing abnormal mental status leading to admission to psychiatric floor. Two weeks later develops seizures and is transferred to the neurology service at the local university hospital. Unresponsive, eyes closed, hyperventilating, resists passive eye opening, no response to visual threat.
Case
EEG with EDsHead CT normalCSF
WBC 58 per microliter (all WBCs)Glucose 53 mg/dlProtein 48 mg/dl
Selected Causes of Encephalitis-Viral
Viruses CommentsHSV 1 and 2 Type 1 most common cause of
sporadic encephalitisVZV Elderly and
immunocompromised, rash may be absent
Enteroviruses, Parechoviruses Myelitis, brainstem encephalitisWNV, JEV, SLEV Parkinsonian movement
disorder, flaccid paralysis
Selected Causes of Encephalitis-Bacterial
Viruses CommentsM pneumoniae parainfectiousM tuberculosis immunocompromised,
immigrantsB henselae seizures, retinal diseaseT pallidum imaging may mimic HSVE Rickettsia, Erlichiosis, Anaplasmosis
Geographic distribution
Infectious endocarditis Infarcts in vascular distributions
Selected Causes of Encephalitis- Non-infectious
Viruses CommentsNMDA receptor Young women, movement
disorder, autonomic instability, ovarian teratoma
Leucine rich glioma inactivated-2 (LGI1; VGKC)
Older men, faciobrachial seizures, hyponatremia
Case
Subsequently developed high fever, hypertension, tachycardia
CSF and serum with NMDAR antibodies
Ovarian US showed “dermoid” (teratoma)
Question
What is the most likely diagnosis?A. Herpes encephalitisB. HHV6 encephalitisC. Leucine rich glioma inactivated 1
encephalitisD. Rhomboencephalitis 2nd to L
monocytogenesE. NMDA receptor encephalitis
Anti-NMDAR Encephalitis
Population-based study of encephalitis in England = 4% of all cases
California Encephalitis Project = most common cause of encephalitis in those under 30 years of age
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
Clinical Findings in NMDARE-1
Prodrome–Headache–Fever–Nausea and vomiting–Diarrhea–URI symptoms
Clinical Findings in NMDARE-1
Early– Seizures– Psychiatric symptoms– Short-term memory loss– Language abnormalities
Clinical Findings in NMDARE-1
Late– Involuntary movements– Catatonia– Coma– Autonomic and breathing
instability
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
Diagnosis NMDARE
• MRI: non-specific abnormalities• EEG: slowing, electrographic seizures• Pelvic and transvaginal ultrasound:
teratoma
NMDARE Treatment
• Immunotherapy–Corticosteroids–Rituximab +/- cyclophosphamide
• Identification and removal of tumor (empiric oophorectomy)
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
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
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 normalCSF: 28 WBCs (40% polys), glucose 57, protein 56
Question
What is the most likely diagnosis?A. Herpes encephalitisB. HHV6 encephalitisC. Leucine rich glioma inactivate 1 encephalitisD. Rhomboencephalitis due to L monocytogenesE. NMDA receptor encephalitis
HSV Encephalitis
Most common cause of sporadic encephalitis in USOccurs any time of yearBimodal age distribution– 25-30% <20yo– 50-70% >40 yo
Most due to HSV-1– Primary ~30%– Reactivation ~60%
HSV-2 in immunosuppressed (Mollaret’s?)Steroids, TNF-alpha blockers are risk factors
Clinical Findings in HSVE
FeverHeadacheChange in level of consciousnessDysphasiaPersonality changesSeizuresMild or atypical cases in PCR era
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
HSVE Prognosis
MortalityUntreated 70%Treated 28%
Neurological, neuropsychiatric sequelae in more than 50%
Diagnostic Algorithm
Metabolic Evaluation and Directed Physical Exam
CT FIRST?
YES
CTEmpiric AcyclovirLP
MR
Not OK OK
Continue treatment
NO
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.
Types of Meningitis
• Bacterial (N meningitidis, S pneumoniae)• Viral (enteroviruses, arbovirus, HSV)• Fungal (cryptococcus, histoplasma)• Parasitic (A cantonensis)• Non-infectious (SLE, vancer, drugs, injury)
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.
Question
What is the most likely etiology?A. S pneumoniaeB. Naegleria fowleriC. N meningococcusD. L monocytogenesE. B henselaeF. MRSA
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
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
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 <1 month old and immunocompromised
HSV-2 Meningitis
More commonly associated with aseptic meningitisCan be recurrent (Mollaret’s syndrome)– Prophylactic valacyclovir RCT– Slightly higher recurrence rates on
tx– 3x higher recurrence after
stopping prophy Aurelius CID 2012
Case 4
20 yo male, sexually active and daily IC drug use, in the ED with 2 days of fever and HA. He has photophobia, mild meningismus and a normal neurological exam.
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Question
What is the most likely etiology?A. S pneumoniaeB. Naegleria fowleriC. N meningococcusD. L monocytogenesE. B henselaeF. MRSA
Causes of Meningitis by AgeAge Group Causes
Newborns Group B Streptococcus, E coli, L monocytogenes
Infants and children S pneumo, N meningitidis, H influenzae type B
Adolescents and young adults N meningitidis, S penumo
Older adults S pneumo, N meningitidis, L monocytogenes
Trends in Meningitis in the USA,1998-2007
Thigpen NEJM 2011
Trends in Meningitis, England 2004-2011
Okike Lancet Infect Disease 2014
Non-CNS Infection Meningitis
• Shiga-toxin-producing E coli outbreak in N Germany in 2011 (3500 people)• ~25% developed HUS, ~100
developed neurological disease (cognitive impairment, aphasia, seizures)
Magnus Brain 2012
Case 5
58 yo man presents with mental status change, fever, headache. CSF with 40 WBCs, mostly lymphocytes, normal glucose and protein.
Case 5
58 yo man presents with mental status change, fever, headache. CSF with 40 WBCs, mostly lymphocytes, normal glucose and protein.
www.eurorad.org
Question
What is the most likely etiology?A. S pneumoniaeB. Naegleria fowleriC. N meningococcusD. L monocytogenesE. B henselaeF. MRSA
Listeria monocytogenes rhomboencephalitis
• Typical biphasic pattern– Non-specific prodrome– Followed by asymmetrical CN palsies, cerebellar
signs and diminished consciousness• Prognosis depends on extent of disease– Abx early, survival ~70%– Even then, ~60% have neurological sequelae
• Though rhomboencephalitis is not specific to Listeria, is must be strongly suspected
Meningitis Prevention
• In developed countries the meningococcal serogroup C vaccine = decrease meningitis and sepsis
• Historically there has been a hole with serogroup B due to similarity to human Ag
• New vaccine: 4CMenB (2012) showed good immunogenicity and good protection (66-91%) in neonates. This is the vaccine used in Princeton and Santa Barbara this year.
Case 6
30 yo woman with left arm, neck and face tingling and numbness, chronic mild bilateral headache and mild difficulty hearing and speaking. Neurological exam was normal.
Naddaf WMJ 2014
Case 6
30 yo woman with left arm, neck and face tingling and numbness, chronic mild bilateral headache and mild difficulty hearing and speaking. Neurological exam was normal.
MRI should a 9x12 mm ring-enhancing lesion in the parietal lobe. An internal soft tissue component was c/w a scolex. The pt had traveled to Mexico multiple times over the last 10 years.
Naddaf WMJ 2014
Taenia solium (neurocysticercosis)
Naddaf WMJ 2014
Brain Abscess
Brouwer NEJM 2014
0.4-0.9/100,000
Brain Abscess
Brouwer NEJM 2014
• Predisposing factors– Underlying disease (ex. HIV infection)– Immunosuppression– Disruption of barriers (surgery, trauma, dental
infection)– Systemic source of infection (bacteremia,
endocarditis)• Contiguous spread ~1/3, hematogenous
spread in ~1/2, rest unk