Transcript Endovascular Infections - What's New in Medicine

Encephalitis
and Meningitis
John Lynch MD MPH
Harborview Medical Center &
University of Washington
http://bit.ly/1wb7KOz
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 EDs
Head CT normal
CSF
WBC 58 per microliter (all WBCs)
Glucose 53 mg/dl
Protein 48 mg/dl
Selected Causes of Encephalitis-Viral
Viruses
Comments
HSV 1 and 2
Type 1 most common cause of
sporadic encephalitis
Elderly and
immunocompromised, rash
may be absent
Myelitis, brainstem encephalitis
Parkinsonian movement
disorder, flaccid paralysis
VZV
Enteroviruses, Parechoviruses
WNV, JEV, SLEV
Selected Causes of EncephalitisBacterial
Viruses
M pneumoniae
M tuberculosis
B henselae
T pallidum
Rickettsia, Erlichiosis,
Anaplasmosis
Infectious endocarditis
Comments
parainfectious
immunocompromised,
immigrants
seizures, retinal disease
imaging may mimic HSVE
Geographic distribution
Infarcts in vascular
distributions
Selected Causes of EncephalitisNon-infectious
Viruses
NMDA receptor
Comments
Young women, movement
disorder, autonomic
instability, ovarian
teratoma
Leucine rich glioma
Older men, faciobrachial
inactivated-2 (LGI1; VGKC) 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 encephalitis
B. HHV6 encephalitis
C. Leucine rich glioma inactivated 1
encephalitis
D. Rhomboencephalitis 2nd to L
monocytogenes
E. 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 normal
CSF: 28 WBCs (40% polys), glucose 57, protein
56
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
HSV Encephalitis
Most common cause of sporadic encephalitis in US
Occurs any time of year
Bimodal 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
Fever
Headache
Change in level of consciousness
Dysphasia
Personality changes
Seizures
Mild 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
Mortality
Untreated 70%
Treated 28%
Neurological, neuropsychiatric
sequelae in more than 50%
Diagnostic Algorithm
Metabolic Evaluation and Directed Physical Exam
CT FIRST?
YES
Empiric Acyclovir
NO
CT
LP
Not OK
OK
MR
Continue treatment
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 pneumoniae
B. Naegleria fowleri
C. N meningococcus
D. L monocytogenes
E. B henselae
F. 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
meningitis
Can 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.
IDSA Meningitis Treatment Guidelines
Question
What is the most likely etiology?
A. S pneumoniae
B. Naegleria fowleri
C. N meningococcus
D. L monocytogenes
E. B henselae
F. MRSA
Causes of Meningitis by Age
Age 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 20042011
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 pneumoniae
B. Naegleria fowleri
C. N meningococcus
D. L monocytogenes
E. B henselae
F. 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 (6691%) 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
0.4-0.9/100,000
Brouwer NEJM 2014
Brain Abscess
• 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
Brouwer NEJM 2014