MENINGITIS infection neuromedicine presentation

Meningitis is inflammation of meninges, this ppt deals with all aspects of it.

1. MENINGITIS PRESENTED BY: DR. SHRIKANT SARAL PG1 (GENERAL MEDICINE) RKDF MEDICAL COLLEGE HOSPITAL & RESEARH CENTRE SOURCE: HARRISON’S TEXTBOOK OF INTERNAL MEDICINE

2. Meningitis is infection within sub-arachnoid space where inflammatory reaction may involve meninges, sub-arachnoid space and brain parenchyma. TYPES OF MENINGITIS CHRONIC SUBACUTE ACUTE BACTERIAL VIRAL Meningitis may result in decreased consciousness, seizures, raised intracranial pressure and stroke

3. BACTERIAL MENINGITIS

4. Neisseria meningitidis causes fulminant meningitis leading to death within hours . The risk of invasive disease following nasopharyngeal colonization depends upon bacterial virulence and host defence especially classical and alternate complement pathways . In patients with chronic and debilitating disease such as diabetes, cirrhosis, alcoholism, UTI, neurosurgical procedures, head trauma with CSF rhinorrhea or otorrhea. Meningitis complicating endocarditis may be due to viridans streptococci, S. aureus, Streptococcus bovis, the HACEK group or enterococci. Group B streptococcus or streptococcus agalactiae causes meningitis in neonates and >50 years. L. monocytogens is causes of meningitis in neonate <1 moth of age, pregnant women, individuals > 60 years, and immune- compromised. It is spread by ready-to-eat foods. H. influenza type b incidence is decreased due to conjugate vaccination. S. aureus and coagulase negative staphylococci causes meningitis in invasive neurosurgical procedures particularly shunting procedures for hydrocephalus and O mmaya reservoir for intrathecal chemotherapy.

5. DESPITE ANTIBIOTIC THERAPY, MORTALITY RATE REMAINS ~20%.

6. PATHOGENESIS

7. PATHOGENESIS THE MAIN EVENT IN PATHOGENESIS OF BACTERIAL MEINGITIS IS INFLAMMATORY RESPONSE GENERATED BY INVADING BACTERIA WHICH CAUSES NEUROLOGICAL MANIFESTATIONS AND COMPLICATIONS Bacterial colonization of Nasopharynx and transport as vacuoles across membrane to invade intravascular space by separating apical tight junctions. Bacteria reaches blood stream where it avoids phagocytises because of polysaccharide capsule Blood borne bacteria reaches intraventricular choroid plexus and infect CSF where they can rapidly multiply Bacteria multiply rapidly in CSF because of – Absence of effective host response system – that is few white blood cells, complement proteins and immunoglobulin that prevent effective opsonization. Fluid nature of CSF which is less conductive of phagocytosis

8. Lysis of bacteria and release of cell wall components into SAS result in stimulation of inflammatory response Release of inflammatory cytokines and chemokines- TNF- α , IL-1 β by microglia, astrocytes, monocytes, leukocytes Increase in protein concentration and phagocytosis

9. Altered blood brain barrier permeability Up regulate selectins expression and increasing leucocyte adhesion to vascular epithelial cells Neutrophilic degranulation Production of excitatory amino acids and reactive nitrogen and oxygen species VASOGENIC EDEMA Leakage of serum proteins into SAS HYDROCEPHALUS INTERSTITIAL EDEMA Cell injury and Cell death CYTOTOXIC EDEMA Leakage of plasma proteins into CSF INCREASED INFLAMMATORY EXUDATE RAISED INTRACRANIAL PRESSURE AND COMA

10. CLASSICAL TRIAD FEVER HEADACHE NUCHAL RIGIDITY KERNIG SIGN BRUDZINSKI SIGN CLINICAL PRESENTATION

11. RAISED INTRACRANIAL PRESSURE SIGNS- DETERIORATING LEVEL OF CONSCIOUSNESS PAPILLEDEMA DILATED POORLY REACCTIVE PUPILS SIXTH NERVE PALSIES DECEREBRATE POSTURING CUSHING REFLEX CEREBRAL HERNIATION COMA

12. OTHER CLINICAL FEATURES Nausea Vomiting Photophobia SEIZURES – focal, generalized and status epilepticus Rash of meningococcemia

13. DIAGNOSIS Blood cultures Lumbar puncture for CSF examination CSF PCR ASSAY NEUROIMAGING MRI > CT BETWEEN L3 AND L4

14. DIFFERENTIAL DIAGNOSIS Viral meningo-encephalitis Rickettsial disease Sub-acute meningitis Ehrlichioses Focal suppurative CNS infections – subdural and epidural empyema and brain abscess Subarachnoid haemorrhage Hypersensitivity meningitis, chemical meningitis, pituitary apoplexy, carcinomatous meningitis, meningitis associated with SLE, behcet’s and VKH syndrome.

15. TREATMENT Bacterial meningitis is a medical emergency, empirical antibiotic therapy should be initiated within 60 minutes of patient’s arrival. EMPIRICAL THERAPY Dexamethasone + 3/4 th generation cephalosporin + vancomycin + acyclovir + doxycycline (during tick season) for <3 and >55 year olds – AMPICILLIN for listeria monocytogens In patients with otitis, sinusitis, mastoiditis – METRONIDAZOLE In patients with hospital acquired infection – CEFTAZIDIME OR MEROPENAM

16. ANTIBIOTICS USED IN EMPIRICAL THERAPY OF MENINGTIS

17. ANTIMICRPOBIAL THERAY OF CNS BACTERIAL INFECTION BASED ON PATHOGEN

18. ADJUVANT THERAPY Dexamethasone - started 15-20 minutes before initiation of antibiotic therapy and given 6 hourly for 4 days. For raised ICP – a. 30-45 degree head elevation b. intubation c. hyperventilation d. mannitol BAD PROGNOSIS DECREASED LVEL OF CONSCIOUSNESS ON ADMISSION ONSET OF SEIZURESS WITHIN 24 HOURS OF ADMISSION SIGNS OF RAISED ICP YOUNG AGE AND AGE>50 COMORBIDITIES NEED FOR MECHANICAL VENTILATION DELAY IN INITIATION OF TREATMENT

19. VIRAL MENINGITIS

20. PRESENTING FEATURES HEADACHE NUCHAL RIGIDITY CONSTIITUTIONAL SIGNS ETIOLOGY ENTEROVIRUS VARICELLA ZOSTER HSV 2>1 HIV ARBOVIRUS DIAGNOSIS CSF EXAMINATION CSF PCR VIRAL CULTURE SEROLOGICAL STUDIES NEUROIMAGING

21. CSF FINDINGS IN VIRAL MENIGITIS Pleocytosis Slightly elevated protein – 20-800 mg/dl Normal glucose concentration Mild elevated pressure 10-35 cm of H2O Elevated cells – lymphocyte predominant

22. DIFFERENTIAL DIAGNOSIS Untreated or partially treated bacterial meningitis Early stages of sub-acute meningitis Para-meningeal infections Neoplastic meningitis Meningitis secondary to non-infectious inflammatory disease Meningitis related to Mycoplasma, Listeria, Brucella, Coxiella, Leptospira and Rickettsia spp.

23. BACTERIAL MENINGITIS SCORE The probability of bacterial meningitis is 0.3% or less with CSF pleocytosis who have- Negative CSF Gram stain CSF neutrophil count <1000 cells/ Μ l CSF protein <80 mg/dl Peripheral absolute neutrophil count <10,000 cells/ Μ l No prior history or current presence of seizures.

24. TREATMENT Conservative Hospitalization is done based on immunity status of patient and severity of presenting features Immunoglobulin in immune-compromised patients either IV or intrathecal Intravenous acyclovir 15-30 mg/kg/day in 3 divided doses, followed by Oral acyclovir 800mg Q5d Famiciclovir 500mg tid Valacyclovir 1000 mg tid For 7-14 days

25. SUBACUTE MENINGITIS CAUSES – Mycobacterium tuberculosis C. Neoformans H. Capsulatum C. Immitis Trepanoma pallidum

26. After inhalation of aerosolized droplet nuclei, during haematogenous dissemination of tubercle bacilli in course of primary infection- millet seed sized miliary tubercles form in parenchyma of brain which enlarge and caseate. The bacterial antigens then produce intense inflammation that leads to production of thick exudate filling basilar cisterns. Fungal infections are acquired by inhalation of airborne fungal spores which caused dormant pulmonary infection. When there is breech in cell mediated immunity, the fungus disseminate to CSF. Syphilis manifest as painless chancre at site of inoculation and invade CNS in early course of disease. Cranial nerves VII and VIII are involved frequently.

27. CSF FINDINGS IN TUBERULAR MENINGITIS Cob web appearance Elevated opening pressure Lymphocytic pleocytosis 10-500 cells/ μ l Raised protein 1-5 g/L Decreased glucose 20-40 mg/dl IN FUNGAL MENINGITIS Mononuclear or lymphocytic pleocytosis Raised protein Decreased glucose Eosinophil in C . Immitis meningitis

28. TREATMENT For tubercular meningitis – for 9-12 months Isoniazid 300mg/d 2. Rifampicin 10 mg/kg/day 3. Pyrazinamide 30 mg /kg/ day 4. Ethambutol 15-25 mg/kg/ day 5. Pyridoxine 50 mg/d Dexamethasone therapy for HIV negative patients – 12-16 mg/d for 3 weeks.

29. FOR FUNGAL MENINGITIS – Induction therapy – AMPHOTERICIN B 0.7 MG/KG/DAY + FLUCYTOSINE 100 mg/kg/day for 4-6 weeks Followed by Flucytosine 400 mg/day for 8 weeks. For H. Capsulatum - AMPHOTERICIN B 0.7-1 MG/KG/DAY FOR 4-12 WEEKS Till fungal culture are negative. FOLLOWED BY ITRACONAZOLE 200 MG BD/TDS FOR 9 MONTHS For C. Immitis – FLUCONAZOLE 1000MG/ DAY OR IV AMPHOTERICIN B Followed by lifelong fluconazole therapy to prevent relapse. Hydrocephalus is most common complication of fungal meningitis.

30. For syphilitic meningitis – Aqueous penicillin G 3-4 million units IV for 10-14 days Followed by 2.4 million benzathine penicillin G IM once a week for 3 weeks. CSF should be re-examined at 6 month interval for 2 years.

31. CHRONIC MENINGITIS Chronic meningitis is diagnosed when a characteristic neurological syndrome exists for >4 weeks and is associated with a persistent inflammatory response in CSF. Causes of chronic meningitis can be divided into 5 categories – Meningeal infections Malignancy Autoimmune inflammatory disorders Chemical meningitis Parameningeal infections

32. EMPIRICAL TREATMENT TREATMENT IS BASED ON DIAGNOSIS OF CAUSATIVE AGENT. HOWEVER, EMPIRICAL THERAPY INCLUDES – ANTIMICROBIAL AGENT + AMPHOTERICIN B/ FLUCYTOSINE (FOR FUNGAL INFECTIONS) + GLUCOCORTICOIDS (FOR NON INFECTIOUS INFLAMMATORY CAUSES)