This document discusses central nervous system infections such as meningitis (infection of the meninges), encephalitis (infection of the brain parenchyma), and myelitis (infection of the spinal cord). It describes the signs and symptoms, diagnoses, causes and treatments of different types of CNS infections including acute bacterial meningitis, viral encephalitis such as herpes simplex encephalitis, tuberculous meningitis, and chronic meningitis. It emphasizes the importance of prompt diagnosis and treatment to reduce mortality and complications of these serious infections.
This document discusses central nervous system infections such as meningitis (infection of the meninges), encephalitis (infection of the brain parenchyma), and myelitis (infection of the spinal cord). It describes the signs and symptoms, diagnoses, causes and treatments of different types of CNS infections including acute bacterial meningitis, viral encephalitis such as herpes simplex encephalitis, tuberculous meningitis, and chronic meningitis. It emphasizes the importance of prompt diagnosis and treatment to reduce mortality and complications of these serious infections.
This document discusses central nervous system infections such as meningitis (infection of the meninges), encephalitis (infection of the brain parenchyma), and myelitis (infection of the spinal cord). It describes the signs and symptoms, diagnoses, causes and treatments of different types of CNS infections including acute bacterial meningitis, viral encephalitis such as herpes simplex encephalitis, tuberculous meningitis, and chronic meningitis. It emphasizes the importance of prompt diagnosis and treatment to reduce mortality and complications of these serious infections.
This document discusses central nervous system infections such as meningitis (infection of the meninges), encephalitis (infection of the brain parenchyma), and myelitis (infection of the spinal cord). It describes the signs and symptoms, diagnoses, causes and treatments of different types of CNS infections including acute bacterial meningitis, viral encephalitis such as herpes simplex encephalitis, tuberculous meningitis, and chronic meningitis. It emphasizes the importance of prompt diagnosis and treatment to reduce mortality and complications of these serious infections.
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CNS infections
Ahmad Rizal, dr., SpS (K), Ph.D
Bagian 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 Meningococcaemia
Meningococcal septicaemia Picture: With the friendly permission of Dr. Noack (photographer) and Prof.Dittman, in whose book the picture appears (German title:"Meningokokkenerkrankungen”) 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 Bacterial meningitis: steroids • 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: treatment • Other anti-inflammatory drugs? – against CSF cytokines – matrix metalloproteases – reactive oxygen species Bacterial meningitis Delay initiating treatment Delay recognising complications
high mortality more 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 • Encephalitis – Fever and headache common – Mental status –steady – Mental status –often decline fluctuates – Seizures –generalised – Seizures – focal and generalised – Focal signs common
– Blood – wbc – Blood - wbc N – CSF- wbc – CSF – wbc N – EEG – slow plus focal – EEG – diffuse slowing – MRI –often abnormal – MRI – often normal 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
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 HSE • 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% 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 slowly
Meningismus may be mild There 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: • Neoplasm (esp. breast, lung) • Neurosarcoidosis • Behcet's disease • CNS vasculitis • Mollaret's meningitis 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 TBM tuberculomas 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
• 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 Typical CSF formulas Bacterial Viral Fungal Tuberculous opening normal or high normal normal or high usually high pressure WBC count 1,000-10,000 < 300 20-500 50-500 (cells/mm3) PMN (%) >80 <20 <50 ~20 RBC count slight increase normal normal normal (cells/mm3) protein very high normal high high (mg/dl) (100-500) Glucose < 40 normal usually < 40 < 40 60-90 % AFB stain + in Gram stain negative negative positive 40-80% culture (% 70-85 25 25-50 50-80 positive)
