Subacute/Chronic meningitis Reşat ÖZARAS, MD, Prof. Infection Dept. [email protected] Admission Acute (1 day-1 week) Subacute (1 week-1 mo.) Chronic (> 1 mo. ) Subacute/Chronic meningitis • Within weeks or months • Headache, fever, neck rigidity, mental changes • Focal neurological signs are more frequent • Needs specific treatment • A diagnostic challenge A Case Study • A 48-year-old female was admitted with headache, myalgia, nausea, vomiting, fatigue, anorexia and fever for 6 weeks • Biochemistry normal • CBC normal • C-RP: 5 Xnormal, ESR 100 mm/h • No previous and family history – Immunosuppressive disorders/drugs – No similar signs & symptoms in the family • No focal neurological sign • Neck rigidity +/-, Kernig and Brudzinski + • MRI showed mild contrast enhancement at basal cranial meninges CSF • • • • • Clear Cell count: 250 /mm3, 80% lymphocytes Glucose 10 mg/dl (blood glucose 98) Protein 280 mg/L Gram and EZN staining: negative • What is your diagnosis? 2 days later • CSF TB-PCR: positive 25 days later • CSF cultures Mycobacterium tuberculosis Subacute/chronic meningitis • Infections: – TB TB • May follow a slow progress • Exposure, TST/PPD(+), immune suppression • Prodrome 2-4 weeks • Not only menengitis, • Vasculitis, space-occupying lesion (brain tuberculoma) – – – – Fever Change in mental status Hemiplegia, paraplegia Ocular nerve involvement CSF Etiology WBC(/mm3) Cell Type Viral 50–1000 Lymphocytic >45 <200 Bacterial 1000– 5000 Neutropilic 100–500 TB 50–300 Lymphocytic <45 Glucose(Mg/dL) <40 Protein(Mg/dL) 50–300 neuropathology.neoucom.edu Clinical Presentation • Most common clinical findings: – Fever – Headache – Vomiting – Nuchal Rigidity Diagnosis • CSF Examination – Usually lymphocytic pleocytosis – Elevated protein with severely depressed glucose – AFB – Culture – PCR Diagnosis • Other Studies – Brain imaging – demonstrates hydrocephalus, basilar exudates and inflammation, tuberculoma, cerebral edema, cerebral infarction • CXR – Abnormal, sometimes miliary pattern seattlechildren.org Treatment: Antimicrobial Therapy • Start as soon as there is suspicion for TB meningitis • Same Guidelines as those for pulmonary TB – Intensive Phase: 4 drug regimen of Isoniazid, Rifampin, Pyrazinamide, and Ethambutol for 2 months – Continuation Phase: Isoniazid and Rifampin for another 7 – 10 months Treatment: Adjunctive Therapy • Glucocorticoids Indicated with: – rapid progression from one stage to the next – CT evidence of cerebral edema – worsening clinical signs after starting antiTb meds – increased basilar enhancement, or moderate to advancing hydrocephalus on head CT Outcomes • Overall Poor • Only 1/3 - 1/2 of patients demonstrate complete neurologic recovery • Up to 1/3 of patients have residual severe neurologic deficits such as hemiparesis, blindness, seizure DO Another Case Study • A 30-year-old male farmer was admitted with headache, newly-onset seizures, and fever for 1 month • Biochemistry normal • CBC normal • C-RP: 5 Xnormal, ESR 50 mm/h A 30-year-old male was admitted with headache, newly-onset seizures, and fever for 1 month… • Blood cultures were obtained • MRI: normal • Diagnosed by a serology!... • Rose-Bengal test positive • Wright test positive • 2 bottles of blood culture yielded Brucella melitensis Rx • Rifampin+Doxycycline Subacute/chronic meningitis • Infections: – TB – Spirochetal diseases (syphilis, Lyme’s disease) – Brucellosis – Fungal • Cryptococcus neoformans, Aspergillus, Candida Toxoplasmosis, Neurosyphilis • Infection of the central nervous system by Treponema pallidum • Neurosyphilis can occur at any time after initial infection. utdol.com • Early NS – Asymptomatic – Symptomatic – Meningovascular • Late NS – General paresis – Tabes dorsalis A) Focal meningeal enhancement B) Significant edema in the in the left frontal lobe with left posterior frontal lobe. surrounding edema. Cerebral gumma in an HIV-infected patient with recent secondary syphilis. utdol.com Diagnosis • EIA: syphilis enzyme immunoassay • FTA-ABS: fluorescent treponemal antibody-absorbed test • TPPA: Treponema pallidum particle agglutination test Rx • Penicillin G benzathine 2.4 million units IM once