CNS

Infections
CNS Infection is a neurologic
emergency!
⚫ Acute (< 1 wk) – bacterial / viral meningitis; viral
encephalitis
⚫ Subacute ( 1-2 wks)
⚫ Chronic (> 2 wks) – TB, fungal meningitis

⚫ Brain abscess: usually presents to the hospital 11-12
days after onset of symptoms
⚫ CNS infections treatable and mostly fatal if untreated
or suboptimally treated
Census of Neuroinfections by the CNS
Infection Council, PNA: 2011-12
⚫ 7 participating institutions
⚫ 9 training programs
⚫ 1629 cases (ave of 814/yr)
⚫ 23 categories

2011-12 Census: n=1629
⚫ Bact. Meningitis – 34.3%
⚫ TBM – 30.7%
⚫ Brain abscess – 9.8%
⚫ Viral encephalitis -7.7%
⚫ Viral, unspecified – 3.6%
⚫ Others – 3.5%
⚫ Crypto meningitis – 2.8%
⚫ Meningitis, unspecified – 1.3%

⚫ TORCH – 1.0%
⚫ Ventriculitis – 0.9%
⚫ Subdural empyema – 0.9%
⚫ Tuberculoma – 0.9%
⚫ Viral Meningitis – 0.7%
⚫ Cavernous sinus thrombophlebitis – 0.6%
⚫ Shunt infection – 0.3%
⚫ Tetanus – 0.2%
⚫ Cerebral schisto – 0.2.%
⚫ Neurocysticercosis – 0.2%
⚫ Toxoplasmosis – 0.2%
⚫ Cerebral malaria – 0.1%
⚫ TB abscess – 0.1%
⚫ Intraspinal abscess – 0.1%
⚫ NeuroSY – 0
⚫ Epidural abscess - 0
Adult: n=542
⚫ TB Meningitis – 43%
⚫ Bacterial Meningitis – 19.4%
⚫ Viral encephalitis – 10.3%
⚫ Brain abscess – 9.2%
⚫ Crypto meningitis – 8.1%

CNS Infection Census in Selected Training Institutions (2011-2012), Pedia

Category PCMC 2011 PCMC 2012 UST Pedia 2011 UST Pedia 2012 PGH Pedia 2011 PGH Pedia 2012 TOTAL Percent

Bact. Meningitis 50 38 15 15 169 166 453 41.70%

TB Meningitis 25 4 4 3 136 95 267 24.60%
Brain Abscess 5 9 1 2 42 50 109 10.00%
Viral Encephalitis 28 31 6 4 69 6.30%
Viral (unspecified) 26 32 58 5.30%
Others 21 36 57 5.20%
TORCH 3 3 5 5 16 1.50%
Ventriculitis 13 2 15 1.40%
Meningitis (unspec.) 9 5 14 1.30%
Subdural empyema 10 3 13 1.20%
Tuberculoma 3 4 7 0.60%
Shunt Infection 1 4 5 0.50%
Crypto Meningitis 1 1 0.10%
Viral Meningitis 1 1 0.10%
Cerebral schisto 1 1 0.10%
Intraspinal Abscess 1 1 0.10%
TOTAL 147 107 26 24 399 384 1087 100%
Pedia: n=1087
⚫ Bacterial Meningitis – 41.7%
⚫ TB Meningitis – 24.6%
⚫ Brain abscess – 10%
⚫ Viral enceph – 6.3%
⚫ Viral (unspec) – 5.3%
⚫ TORCH – 1.5%

⚫ Crypto meningitis – 0.1%


Adult Pedia
⚫ TB Meningitis – 43% ⚫ TB Meningitis – 24.6%
⚫ Bact. Meningitis – 19.4% ⚫ Bact Meningitis – 41.7%
⚫ Crypto meningitis – 8.1% ⚫ Crypto meningitis – 0.1%
⚫ Viral – 10.3% ⚫ Viral – 11.6%
⚫ Brain abscess – 9.2% ⚫ Brain abscess – 10%


Is there a CNS infection?
⚫ High index of suspicion
⚫ Important clues: fever + any of the ff: headache and
vomiting, altered sensorium, neurologic deficits,
seizures, neck rigidity.
⚫ Fever may be absent
⚫ Is it a meningitis or an encephalitis?
Meningitis
⚫ Fever, headache, neck rigidity

⚫ vomiting
⚫ Relatively preserved mental status at onset except in
fulminant cases.
⚫ No focal signs except if complicated by infarction
from arteritis
Encephalitis (viral)
⚫ Fever
⚫ Mental and/or behavioral change prominent at onset
of illness.
⚫ No or minimal neck rigidity, unless it is a
meningoencephalitis
⚫ Acute course

Brain abscess
⚫ Headache
⚫ Drowsiness and confusion
⚫ Seizures
⚫ Focal signs
⚫ (+) focus of infection: ear, sinus, lung, heart valves
⚫ Signs of increased intracranial pressure
Major types of meningitis
⚫ Acute (< 1 wk): bacterial, viral
⚫ Chronic (> 2 wks): TB, fungal
Before doing LP, look for:
⚫ Papilledema
⚫ Focal signs
⚫ Signs of herniation

CSF exam
⚫ Adults: 10 cc
⚫ 1st bottle – 2 cc – protein and glucose
⚫ 2nd bottle* – 7 cc – Microbiology
⚫ 3rd bottle – 1 cc – cell count

⚫ *Centrifuge for 1 hr at 1000 rpm. Decant
supernatant and save for future use. Use
sediments for stains and cultures.
Stains and cultures
⚫ Stains: G/S, AFB stain, india ink
⚫ Cultures: C/S, TB culture, Saboraud’s culture

To the supernatant do the ff:
⚫ Latex cryptococcal antigen test (LCAT or more
commonly called CALAS – cryptococcal antigen latex
agglutination system)
⚫ Latex tests for bacterial antigens
⚫ PCR – for TB (or get a 4th bottle exclusively for TB
PCR)


Normal CSF Findings
⚫ Opening pressure < 180 mm H20
⚫ (+) Queckenstedt test
⚫ WBC 0-5/cu ml
⚫ RBC 0-5/cu ml
⚫ Protein 15-45 mg%
⚫ Sugar not less than 60% of RBS
 Meningitis: CSF picture
bacterial TB / fungal viral

WBC >1000/ <500/cu <500/cu
cu.ml. ml ml
Diff. count PMNs Lymphos. Lymphos.

protein increased increased

N or sl.
increased
sugar decreased decreased Normal
Other tests
⚫ If bacterial meningitis is the impression, do a blood
culture
After results of routine CSF analysis
are known -
⚫ If profile is bacterial: start empiric therapy while
waiting for the stains and C/S.
⚫ If profile is TB / fungal: start tx for TB while waiting
for the result of the latex cryptococcal agglutination
test (LCAT).
⚫ If the LCAT is negative, continue tx for TB
⚫ If the LCAT is positive, repeat test. If positive again,
treat for crypto.
Crytococcal Antigen Latex
Agglutination System (CALAS)
⚫ + Predictive value = 90%
⚫ - Predictive value = 100%

(based on validation study done at UERM in 1983)
From Harrison’s Principles of Internal Medicine, 19th ed: Chap. 164
Isolation Rate of Organisms in the CSF in
Meningitides: UERM Study, 1981.
Punsalan R., et. al.
bacterial TB crypto

stains 75% 0% 58%

cultures 90% 14% 100%

Strep pneumoniae on gram stain
Neisseria
Meningitides
TB bacilli on AFB stain (sputum)
Adjunctive Tx: Bact. Meningitis
⚫ Dexamethasone 10 mg q 6 hrs for 4 days
⚫ Start 20 min before 1st dose of antibiotics (no later
than the 1st dose of antibiotics
⚫ European trial showed benefit
⚫ 3 trials in low income countries (Sub-Saharan Africa,
Southeast Asia: no benefit
Crytococcal Antigen Latex
Agglutination System (CALAS)
⚫ + Predictive value = 90%
⚫ - Predictive value = 100%

Punsalan, R: Validation Study of the Latex Cryptococcal
Antigen Test in Meningitis, 1983



Streptococcus pneumoniae on blood agar culture
TB bacilli on culture
Cryptococcus neoformans on culture
From Harrison’s Principles of Internal Medicine, 19th ed, chap. 164
Isolation Rate of Organisms in the CSF in
Meningitides: UERM Study, 1981
bacterial TB crypto

stains 75% 0% 58%

cultures 90% 14% 100%

TBM Tx
⚫ Initiate with INH (300mg/d), rifampicin (10mg/kg/d),
PZA (30mg/kg/d in divided doses), ethambutol (15-25
mg/kg/d)
⚫ d/c etham when sensitivity is known
⚫ d/c PZA after 8 wks if good clinical response
⚫ Continue INH and Rif for another 6-12 months. 6
months acceptable but prolong to 9-12 months for
those with inadequate resolution of symptoms and
those with (+) culture.
⚫ Dexamethasone (for HIV neg. pxs): 12-16 mg/day for 3
weeks, then taper in 3 weeks
Tx of Crypto Meningitis
⚫ For non-HIV infected, non-transplant pxs:
Induction phase: Amphotericin B deoxycholate
0.7-1.0 mg/kg/d for 6 wks
Consolidation phase: Fluconazole 400 mg/d for 8
wks
Maintenance phase: Fluconazole 200 mg/d for 6-12
months
Clinical Practice Guidelines for the Management
of Cryptococcal Disease: 2010 Update by the Infectious
Diseases Society of America
Tx of crypto – con’t
⚫ For HIV-infected pxs:
Induction: AmBd (0.7-1.0 mg/kg/d) for 4-6 wks
Consolidation: fluconazole 400 mg/d for 8 wks
Maintenance: fluconazole 200 mg/d indefinitely

Clinical Practice Guidelines for the Management

of Cryptococcal Disease: 2010 Update by the Infectious
Diseases Society of America
Tx of Crypto – con’t
⚫ For organ transplant patients:
⚫ Induction Phase: Liposomal AmB 3-4 mg/kg/d or
AmB Lipid Complex 5 mg/kg/d
⚫ Consolidation Phase: Fluconazole 400-800 mg (6-12
mg/kg) per day orally for 8 wks
⚫ Maintenance Phase: Fluconazole 200-400 mg per day
for 6-12 months

Viral Meningitis
⚫ Most common causes: enterovirus (85%), HSV-2,
arbovirus, HIV
⚫ No local data on etiology
⚫ PCR amplification of viral nucleic acid – dx test of
choice
⚫ Treatment is symptomatic in most cases
⚫ IV Acyclovir may be beneficial for HSV, and severe
EBV or VZV infection, followed by oral acyclovir,
famciclovir or valaciclovir .
From Harrison’s Principles of Internal Medicine, 19th ed. : Chap 164
Arboviral encephalitis in the
Philippines: Japanese Encephalitis

⚫ A flavivirus
⚫ No specific treatment
⚫ Prevention through vaccination
Viral encephalitis



⚫ Herpes or non-herpes?
Why the need to dx HSE?
⚫ It is the only treatable encephalitis
⚫ early tx means good prognosis
⚫ Acyclovir, while relatively safe, is expensive
Herpes simplex encephalitis
⚫ Clinical syndrome of encephalitis
⚫ EEG: focal periodic sharps from frontal and / or
temporal area(s).
⚫ CT scan: hypodensity from same areas
⚫ MRI: focal abnormality from same areas
⚫ PCR: now the dx. Test of choice
EEG in HSE
MRI of HSE
MRI/CT findings in HSE
⚫ Focal findings in the ff. brain regions:
⚫ Frontal
⚫ temporal
⚫ Cingulate
⚫ Insula
PCR as a diagnostic test for
HSE:
⚫ Sensitivity: 98%
⚫ Specificity: 94%
⚫ + Predicitive value: 95%
⚫ - Predictive value: 98%
Other dx tests
⚫ CSF culture – not useful
⚫ CSF serology and antigen detection: for HSV, useful
after the 1st wk of illness and when PCR negative
⚫ Brain biopsy – for those with negative CSF PCR +
focal abnormalities on imaging + progressive
deterioration despite therapy
“There have been recent small
outbreaks of poliomyelitis associated
with vaccine strains of virus that have
reverted to virulence through mutation
or recombination with circulating wild-
type enteroviruses in Hispaniola,
China, the Philippines, Indonesia,
Nigeria, and Madagascar.” (From
Harrison’s Principles of Internal
Medicine, 18th ed, chap 381 –
Meningitis, Encephalitis, Brain Abscess
and Empyema)
Tx of suspected encephalitis
⚫ Treat presumptively as HSE with acyclovir, esp. with
focal features
⚫ D/C tx if PCR negative for herpes except for severe
encephalitis due to H-Z and EBV.
Herpes simplex encephalitis -
Tx
⚫ Acyclovir IV 10mg/kg q 8h for 14-21 days.
⚫ Neonates: 20 mg/kg q 8h for 21 days.
Other possible treatable viral
encephalitides
⚫ CMV: ganciclovir, valganciclovir, cidofovir or
foscarnet
⚫ California encephalitis: ribavarin
Prevention
⚫ Vaccines: West Nile virus (WNV) vaccines are
currently undergoing clinical testing
(ClinicalTrials.gov, identifier NCT00746798 and
00442169).
Thank you!