1. Subacute/Chronic meningitis Reşat ÖZARAS, MD, Prof. Infection Dept. rozaras@yahoo.com

2. Admission Acute (1 day-1 week) Subacute (1 week-1 mo.) Chronic (> 1 mo. )

3. 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

4. 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

5. 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

6. CSF Clear Cell count: 250 /mm 3, 80% lymphocytes Glucose 10 mg/dl (blood glucose 98) Protein 280 mg/L Gram and EZN staining: negative

7. What is your diagnosis?

8. 2 days later CSF TB-PCR: positive

9. 25 days later CSF cultures Mycobacterium tuberculosis

10. Subacute/chronic meningitis Infections: –TB

11. TB May follow a slow progress Exposure, TST/PPD(+), immune suppression Prodrome 2-4 weeks

12. Not only menengitis, Vasculitis, space-occupying lesion (brain tuberculoma) –Fever –Change in mental status –Hemiplegia, paraplegia –Ocular nerve involvement

15. CSF Etiology WBC(/mm 3 ) Cell Type Glucose(Mg/dL)Protein(Mg/dL) Viral50–1000Lymphocytic>45<200 Bacterial 1000– 5000 Neutropilic<40100–500 TB50–300Lymphocytic<4550–300

17. neuropathology.neoucom.edu

18. Clinical Presentation Most common clinical findings: –Fever –Headache –Vomiting –Nuchal Rigidity

19. Diagnosis CSF Examination –Usually lymphocytic pleocytosis –Elevated protein with severely depressed glucose –AFB –Culture –PCR

20. Diagnosis Other Studies –Brain imaging – demonstrates hydrocephalus, basilar exudates and inflammation, tuberculoma, cerebral edema, cerebral infarction CXR –Abnormal, sometimes miliary pattern

21. seattlechildren.org

23. 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

24. 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

25. 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

26. 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

27. 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!...

28. Rose-Bengal test positive Wright test positive 2 bottles of blood culture yielded Brucella melitensis

29. Rx Rifampin+Doxycycline

30. Subacute/chronic meningitis Infections: –TB –Spirochetal diseases (syphilis, Lyme’s disease) –Brucellosis –Fungal Cryptococcus neoformans, Aspergillus, Candida Toxoplasmosis,

31. Neurosyphilis Infection of the central nervous system by Treponema pallidum Neurosyphilis can occur at any time after initial infection.

32. utdol.com

33. Early NS – Asymptomatic – Symptomatic – Meningovascular Late NS – General paresis – Tabes dorsalis

34. B) Significant edema in the left posterior frontal lobe. A) Focal meningeal enhancement in the left frontal lobe with surrounding edema. Cerebral gumma in an HIV-infected patient with recent secondary syphilis. utdol.com

35. Diagnosis EIA: syphilis enzyme immunoassay FTA-ABS: fluorescent treponemal antibody-absorbed test TPPA: Treponema pallidum particle agglutination test

36. Rx Penicillin G benzathine 2.4 million units IM once