Download - INFEKSI CNS
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CNS infections
Ahmad RizalBagian Saraf FKUP / RSHS
Bandung
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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
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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
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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
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Signs and symptoms
• Headache
• Fever
• Neck stiffness (and other meningeal signs)
• Obtundation
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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
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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
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Meningococcal septicaemia
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Meningococcal septicaemia Picture: With the friendly permission of Dr. Noack (photographer) and Prof.Dittman, in whose book the picture appears (German title:"Meningokokkenerkrankungen”)
Meningococcaemia
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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
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Bacterial meningitis: antibiotics
• Ceftriaxone iv 4g; then 2g daily– cefotaxime– benzylpenecillin– chloramphenicol
• Resistant pneumococcus– add vancomycin 2g bd iv +/- rifampicin
• Listeria– ampicillin
• Pseudomonas– gentamicin
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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
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• 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
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• Other anti-inflammatory drugs?– against CSF cytokines– matrix metalloproteases– reactive oxygen species
Bacterial meningitis: treatment
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Bacterial meningitis
Delay initiating treatmentDelay recognising complications
high mortalitymore complication
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Late deterioration
• Subdural effusion
• Empyema
• Hydrocephalus
• Vasculitis: – stroke– diffuse brain injury– oedema
• systemic
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Cerebral infarction
T2 DWI
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Subdural empyema
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Vasculitis and stroke
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Vasculitis, stroke, hydrocephalus
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Acute or subacute onset global cerebral dysfunction
• Three diagnostic categories
– Infective encephalitis (typically viral)
– Encephalopathy (typically metabolic or toxic)
– ADEM
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• 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
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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?
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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
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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
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HSE
• Without treatment, mortality >70%
• Major morbidity in survivors
• Milder forms of the illness exist but are rarely correctly identified
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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
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• 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
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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
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Chronic meningitis
Signs and symptoms• Headache • Fever • Meningismus • Confusion • Hydrocephalus
In general, symptoms develop slowlyMeningismus may be mildThere may be subtle mental status changes
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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
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Causes
• Infectious: – Bacterial– Fungal– Parasitic
• Non-infectious
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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
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TBM
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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
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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
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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
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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
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TBM
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stroke
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tuberculous abcess
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TBM - diagnosis
Gold standard is microscopy: ZN staining
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TB culture
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TBM diagnosis: other
• CSF adenosine deaminase – unreliable: false positives– undefined in HIV
• PCR– good after treatment has begun
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TB
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TBM: treatment
• Quadruple therapy initially– Isoniazid– Rifampicin– Pyrazinamide– Ethambutol/streptomycin
• Steroids:– Coma– Dexamethasone 16mg/day 2-4 weeks
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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
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AIDS/HIV
• Meningitis– Cryptococcus neoformans
• Encephalitis– CMV
• Brain abcess– Toxoplasma
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Aspergillus
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Nocardia
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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
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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
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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
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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
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