TUBERCULOUS MENINGITIS Dr Shreedhar Paudel April, 2009

TUBERCULOUS MENINGITIS…… Infection of meninges by Mycobacterrium Serious complication of childhood tuberculosis Common between 6 months to 24 months age May lead to serious disabling neurological sequale

TUBERCULOUS MENINGITIS…… PATHOGENESIS – Usually reaches the meninges through hematogenous route – May occur as a part of miliary tuberculosis

TUBERCULOUS MENINGITIS…… PATHOLOGY – The meningeal surface is covered with yellow grayish exudates and tubercles – The subarachnoid space and arachnoid villi are obliterated leading to poor absorption of CSF – The thick exudates may block the CSF pathway causing hydrocephalus – There might be thrombophlebitis and tuberculous encephalopathy

Clinical Features Prodromal stage ( stage of invasion) – Insidious onset with vauge symptoms – Fever, anorexia, disturbed sleep – Frequent vomiting, headache, photophobia Stage of meningitis – Features of meningitis with focal neuroligical deficits Stage of coma – Fever, loss of consciousness and altered respiratory pattern

Diagnosis….. LP and evaluation of CSF – Raised CSF pressure: CM of water ( normal 3-4 CM of water) – CSF may be clear with formation of cobweb coagulum on standing ( like suspended pellicle ) – Protein: >40 mg/dl – Sugar: < 2/3 rd of blood sugar level – Cell count: /μL, predomonance of lymphocytes – AFB stain and C/S

Diagnosis….. CT Head – May identify Basal exudates Inflammatory granuloma Infarct lesions Hydrocephalus PCR for Mycobacterium Other tests: Chest X- Ray, HIV ELISA

TUBERCULOUS MENINGITIS Differential Diagnosis – PURULENT MENINGITIS, – PARTIALLY TREATED MENINGITIS – ENCEPHALITIS, – TYPHOID ENCEPHALOPATHY, – BRAIN ABSCESS, – BRAIN TUMOR, – CHRONIC SUBDURAL HEMATOMA, – AMEBIC MENINGOENCEPHALITIS.

TREATMENT OF TUBERCULOSIS MENINGITIS Antitubercular treatment for 12 weeks INITIAL PHASE-- 2 MTHS: HRZE CONTINUATION PHASE--10 MTHS: HRE – DOSE OF DRUGS ISONIAZID: 5mg/kg/day RIFAMPICIN: 10mg/kg/day ETHAMBUTOL: 15-20mg/kg/day PYRAZINAMIDE: 30-40mg/kg/day

TREATMENT OF TUBERCULOSIS MENINGITIS…… STEROID THERAPY – DEXAMETHASONE IV- 1-2 WEEKS – ORAL PREDNISONE FOR 6 WEEKS – TAPER SLOWLY OVER 2 WEEKS REDUCE THE INTENSITY OF CEREBRAL EDEMA REDUCE THE DEVELOPMENT OF ARACHNOIDITIS REDUCE FIBROSIS AND SPINAL BLOCK SUPPORTIVE AND SYMPTOMATIC THERAPY

Prognosis Depends on – Age of the patient – Stage of the disease at diagnosis – Adequacy of treatment – Presence of complications Untreated cases die within 4-8 weeks 20-25% mortality and 25% of survivors would have neurological deficits in stage 2 50% mortality and 100% neurological deficits among survivors in stage 3

ENCEPHALITIS An inflammatory process of the central nervous system with dysfunction of the brain

ENCEPHALITIS… Encephalopathy is the cerebral dysfunction due to other causes than inflammatory response – Due to circulating toxins – Poisions – Abnormal metabolites – Intrinsic biochemical disorders

ENCEPHALITIS… ETIOLOGY – VIRAL: Measles, Mumps, Rubella, Enterovirus, HSV, CMV, EBV, Japanese B, WEST NILE, RABIES, DENGUE, HIV OTHER: RICKETTSIA, Cryptococcus TOXOPLASMA, MALARIA BACTERIAL: Mycobacterium, Salmonella, Shigella, Leptospirosis REYE’S SYNDROME

Clinical Features ONSET: SUDDEN SIGNS AND SYMPTOMS: FEVER, HEADACHE, VOMITING, ALTERED MENTAL STATUS, IRRITABILITY, APATHY, COMA Typical features – Increased ICP Papilloedema Evidence of brain stem dysfunctions Focal neurological deficits, Respiratory/ Cardiac arrest due to Herniation of cerebellum

Clinical Features … DECEREBRATION, DECORTICATION, EXTRAPYRAMIDAL SYMPTOMS: JAPANEASE B TEMPORAL OR FRONTAL LOBE FEATURES: HSV

ENCEPHALITIS DIAGNOSIS – HISTORY OF EXPOSURE – LP – CSF EVALUATION – PCR – SEROLOGICAL TESTS – TOXICOLOGICAL SCREENING – CT/ MRI

MANAGEMENT OF ENCEPHALITIS MANAGEMENT OF ABC SYMPTOMATIC: ICT, FEVER, SHOCK, SEIZURES SPECIFIC TREATMENT – HSV: ACYCLOVIR 30 MG/KG/DAY IN 3 DIVIDED DOSE FOR 10 DAYS – Focal neurological deficits, RBCs in CSF and focal involvement of temporal lobe on CT are important diagnostic clues for herpes simplex encephalitis

REYE’S SYNDROME Acute self limiting metabolic insult resulting in generalised mitochondrial dysfunction due to inhibition of fatty acid beta-oxidation. Precipitated by use of aspirin in viral acute respiratory infections

REYE’S SYNDROME PATHOGENESIS – DYSFUNCTION OF LIVER, KIDNEY, CNS – GENERALISED MYOCARDIAL DYSFUNCTION – INHIBITION OF B-OXIDATION OF FATTY ACIDS – HYPERAMMONEMIA, NEUROHYPOGLYCAEMIA – COMMON AGE IS 2MTHS – 15 YEARS – RAPID PROGRESSION

CLINICAL FEATURES STAGE I - MILD CONFUSION, VOMITING, ANOREXIA STAGE II – DELIRIUM, IRRITATION, DISORIENTATION STAGE III – COMA STAGE IV – APNEA, NON REACTING PUPIL, SHOCK

DIAGNOSIS HYPERAMMONEMIA, ABNORMAL LFT, INCREASED PROTHROMBIN TIME GENERALISED SLOW WAVES IN EEG HYPOGLYCEMIA LIVER BIOPSY SHOWS FATTY CHANGES AND GLYCOGEN DEPLETION BUT NO NECROSIS

TREATMENT LOW PROTEIN DIET WITH ADEQUATE CALORY TREATMENT OF HEPATIC FAILURE TREATMENT OF RAISED ICT TREATMENT OF HYPOGLYCAEMIA SUPPLEMENTATION OF VITAMIN K, FFP TREATMENT OF ACIDOSIS, HYPOXIA AND DYSELECTROLYTEMIA

PROGNOSIS POOR PROGNOSIS 25-70% MORTALITY SURVIVORS MAY HAVE NEUROLOGICAL SEQUALE