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INFEKSI CNS
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CNS infections
Ahmad RizalBagian Saraf FKUP / RSHS
Bandung
Terminology
• Primarily affects its coverings meningitis• Affects the brain parenchyma encephalitis• Affects the spinal cord myelitis• A patient may have more than one affected
area, and if all are affected, the patient has "meningoencephalomyelitis“
• Localized pockets of infection:– Within the brain or spinal cord abscess– Outside them there epidural abscess or subdural
empyema
Clinical syndromes
• Acute presentations: <2 days duration – bacterial process (pyogenic)– aggressive viral encephalitis
• Subacute presentations : broader spectrum of diagnostic possibilities– Tuberculous– Fungal– Parasitic– Viral– Non infectious: encephalopathy, ADEM, other
Change in scenario
• Increase in immuno-compromised patients– AIDS– prolonged survival of cancer patients– organ transplantation
• Increase in international travel– rapid transmission to susceptible populations– new diseases
• Widespread antibiotic use– resistant organisms
Signs and symptoms
• Headache
• Fever
• Neck stiffness (and other meningeal signs)
• Obtundation
Diagnosis
• Suspicious clinical symptoms and signs
• CT of head to rule out abscess or other space-occupying lesion, if it can be done quickly
• Lumbar puncture
• Blood cultures
Acute bacterial meningitis
• The big three: N.meningitides, S.pneumoniae, H.influenzae– Other: Listeria, pseudomonas, E.coli….
• Headache, fever, neck stiffness, obtundation• focal signs, seizures, rash, shock..• often fulminant
• CSF: high wbc (500- 20000 polymorphs), high protein, low glucose– But: partial treatment
• CT/MRI: may be normal
Meningococcal septicaemia
Meningococcal septicaemia Picture: With the friendly permission of Dr. Noack (photographer) and Prof.Dittman, in whose book the picture appears (German title:"Meningokokkenerkrankungen”)
Meningococcaemia
Bacterial meningitis: diagnosis
High index of suspicion
Prompt CSF examination
urgent smear for Gram stain
urgent latex agglutination testing for bacterial antigens (meningococcus, pneumococcus, H.infl) not a routine procedure in Bandung
Repeat CSF examination after 24 – 48 h
Bacterial meningitis: antibiotics
• Ceftriaxone iv 4g; then 2g daily– cefotaxime– benzylpenecillin– chloramphenicol
• Resistant pneumococcus– add vancomycin 2g bd iv +/- rifampicin
• Listeria– ampicillin
• Pseudomonas– gentamicin
Bacterial meningitis: steroids
– Significantly reduce mortality and neurological sequelae in adults with bacterial meningitis
– Should be used ROUTINELY in adults with suspected bacterial meningitis
– Best effect to pneumococcal infection– Give with/before 1st dose of antibiotics– 10mg dexa 6 hourly for 4 days– NOT in patients already started on antibiotics
(de Gaans, NEJM 2002; 347: 1549 – 56)– Caution: may reduce penetration through BBB
• especially vancomycin
• Don’t give in– Late stage disease – may be harmful– septic shock– post neurosurgical meningitis– immunosuppressed/i.compromised patients
• Stop if– No pathogen identified on CSF smear and suspect
fungal/other infection– No bacterial growth/other organism after 24- 48 hours
Bacterial meningitis: steroids
• Other anti-inflammatory drugs?– against CSF cytokines– matrix metalloproteases– reactive oxygen species
Bacterial meningitis: treatment
Bacterial meningitis
Delay initiating treatmentDelay recognising complications
high mortalitymore complication
Late deterioration
• Subdural effusion
• Empyema
• Hydrocephalus
• Vasculitis: – stroke– diffuse brain injury– oedema
• systemic
Cerebral infarction
T2 DWI
Subdural empyema
Vasculitis and stroke
Vasculitis, stroke, hydrocephalus
Acute or subacute onset global cerebral dysfunction
• Three diagnostic categories
– Infective encephalitis (typically viral)
– Encephalopathy (typically metabolic or toxic)
– ADEM
• Encephalopathy
– Mental status –steady decline
– Seizures –generalised
– Blood - wbc N– CSF – wbc N– EEG – diffuse slowing– MRI – often normal
• Encephalitis– Fever and headache
common– Mental status –often
fluctuates– Seizures – focal and
generalised– Focal signs common
– Blood – wbc – CSF- wbc – EEG – slow plus focal– MRI –often abnormal
Encephalitis?
• The physician addresses three important questions:
– How likely is the diagnosis of encephalitis?
– What could be the cause of encephalitis?
– Which is the best treatment plan for the patient with encephalitis?
Causes of viral encephalitis• Herpes simplex virus (HSV-1, HSV-2)
- treatable
• Other herpes viruses: VZV, CMV,EBV, human herpes virus 6 (HHV6)
• Adenoviruses
• Influenza A
• Enteroviruses, poliovirus
• Measles, mumps and rubella viruses
• Rabies
• Arboviruses— Japanese B encephalitis, West Nile encephalitis virus
• Bunyaviruses—La Crosse strain of California virus
• Reoviruses— Colorado tick fever virus
• Arenaviruses— lymphocytic choriomeningitis virus
HSE
• Most commonly identified cause of viral encephalitis in the US (10-20% of cases)
• Estimated annual incidence: 1 in 250,000 to 500,000 persons
• Cases distributed throughout the year• Biphasic age distribution, with peaks at 5-
30 and >50 years of age• HSV-1 virus causes more than 95% of
cases
HSE
• Without treatment, mortality >70%
• Major morbidity in survivors
• Milder forms of the illness exist but are rarely correctly identified
HSE
• Clinical hallmark of HSV encephalitis: acute onset of fever and focal neurological symptoms
• Differentiation of HSV encephalitis from other processes is difficult.
• CSF , CT, MRI, PCR
• High index of suspicion– Even if CSF/imaging normal
• Most common presentations include:– fever in up to 90%– severe headache– focal or generalized convulsions– alterations in behavior and consciousness– disorientation, dysphasia, and hemiparesis
more rare– motor paralysis present in < 50%
HSE
HSV treatment
• Vidarabine: 1st effective antiviral therapy
• Acyclovir: proved more potent – reduced mortality to 19-28%, compared with
50-54% with vidarabine (Whitley et al, NEJM 1992)
– dosed 10 mg/kg given 8h for 10-14 days– toxicity rare: phlebitis, rash, ↑ transaminases,
GI disturbance, neurotoxicity
Chronic meningitis
Signs and symptoms• Headache • Fever • Meningismus • Confusion • Hydrocephalus
In general, symptoms develop slowlyMeningismus may be mildThere may be subtle mental status changes
Diagnosis
• Difficult diagnosis because signs and symptoms are often non-specific. It can be suspected in any patient with a chronic encephalopathy, or a patient with new onset of hydrocephalus
• MRI or CT of head may show hydrocephalus or contrast enhancement of the basal meninges
• Lumbar puncture
Causes
• Infectious: – Bacterial– Fungal– Parasitic
• Non-infectious
Infectious: • M. tuberculosis • Cryptococcus neoformans • HIV • Treponema pallidum • Nocardia sp. • Aspergillus sp. • Taenia solium (cysticercosis) • Toxoplasma gondii
Non-infectious: • Neoplasm (esp. breast, lung) • Neurosarcoidosis • Behcet's disease • CNS vasculitis • Mollaret's meningitis
Causes
TBM
TBM
• High mortality– mainly due to complications
• hydrocephalus• infarction• ventriculitis
• Rapid diagnosis difficult• High index of clinical suspicion
– Chronicity– Basal meningitis– Systemic illness– High risk groups
Clinical features
• Fever, headache, meningismus and mental status changes
• Vomiting and other signs of increased intracranial pressure may occur
• Cranial nerve palsies occurs in approximately 25% of cases
• HIV infection is a risk factor for tuberculous meningitis• Other mycobacteria (M. avium, M. africanus) can
produce human disease, and M. avium is an opportunistic pathogen in AIDS patients
• Other involvement: – Spinal cord usually in the thoracic cord region– Tuberculous spondylitis psoas abscess, epidural abscess
Cerebrospinal fluid
• lymphocytic pleocytosis• elevated protein• reduced glucose• Staining: positive in 5 to 25%• Culture: positive in approximately 60% of cases• CSF PCR may be useful
• With treatment, the CSF returns to normal slowly. Glucose is the first to normalize, but it takes at least three weeks, and usually more
Imaging
• Contrast-enhanced CT or MRI scans show a basilar meningitis, with contrast enhancement of the meninges in the suprasellar area, prepontine cistern, or interpeduncular fossa
• Obstructive or communicating hydrocephalus may occur
TBM
stroke
tuberculous abcess
TBM - diagnosis
Gold standard is microscopy: ZN staining
TB culture
TBM diagnosis: other
• CSF adenosine deaminase – unreliable: false positives– undefined in HIV
• PCR– good after treatment has begun
TB
TBM: treatment
• Quadruple therapy initially– Isoniazid– Rifampicin– Pyrazinamide– Ethambutol/streptomycin
• Steroids:– Coma– Dexamethasone 16mg/day 2-4 weeks
Immunocompromised patients
• Multiple organisms in single or multiple organs
• Unusual organisms
• Decreased sensitivity diagnostic tests
• Atypical presentations – no fever in meningitis
• Clinical picture complicated– multi-organ failure
AIDS/HIV
• Meningitis– Cryptococcus neoformans
• Encephalitis– CMV
• Brain abcess– Toxoplasma
Aspergillus
Nocardia
Lumbar Puncture
Basically, LP should be undertaken on all patients with suspected CNS infection
Contraindications:
• signs of raised intracranial pressure—– altered pupillary responses, – Absent Doll’s eye reflex– decerebrate or decorticate posturing– abnormal respiratory pattern– Papilloedema– hypertension– bradycardia
Contraindications (cont.):
• recent (within 30 minutes) or prolonged (over 30 minutes) convulsive seizures
• focal or tonic seizures• other focal neurological signs
– hemi/monoparesis– extensor plantar responses– ocular palsies
Lumbar Puncture
Contraindications (cont.):
• Glasgow Coma Score < 13 or deteriorating level of consciousness
• Strong suspicion of meningococcal infection (typical purpuric rash in an ill child)
• State of shock• Local superficial infection• Coagulation disorder
Lumbar Puncture
Typical CSF formulas
Bacterial Viral Fungal Tuberculous
opening pressure
normal or high normal normal or high usually high
WBC count (cells/mm3)
1,000-10,000 < 300 20-500 50-500
PMN (%) >80 <20 <50 ~20
RBC count (cells/mm3)
slight increase normal normal normal
protein (mg/dl)
very high (100-500)
normal high high
Glucose < 40 normal usually < 40 < 40
Gram stain 60-90 % positive
negative negativeAFB stain + in 40-80%
culture (% positive)
70-85 25 25-50 50-80