1. Central nervous system infection Dr. Koukeo Phommasone

2. CNS infection Meningitis Encephalitis Myelitis Focal Central Nervous System Syndrome – Brain abscess – Subdural empyema – Epidural abscess

3. ¦¾À¹©¢º¤ CNS infection Virus: EV, HSV, VZV, CMV, Mumps, JE, Dengue Bacteria: HIB, S. pneumoniae, N. meningitidis, S. suis, M. tuberculosis… Fungi: Cryptococcus Protozoa Parasites: Angiostrongylus cantonensis, … ນອກນັ້ນຍັງມີສາຍເຫດຈຳນວນໜຶ່ງທີ່ບໍ່ ແມ່ນພະຍາດຊຶມເຊື້ອທີ່ພາໃຫ້ມີອາການຄື CNS infection ເຊັ່ນ : Neoplastic diceases, intracranial tumors and cysts, medications, collagen vascular disorders, and other systemic illnesses

5. º¾¡¾­¦½Á©¤¢º¤² ະຍາດ Ä¢É (fever) À¥ñ®¹ö¸ (headache) ¦½ªò®Ò©ó (altered mental status) Focal neurologicdeficits Meningismus ອາການທີ່ເວົ້າມາຂ້າງເທີງນີ້ ແມ່ນ nonspecific, ມັນຂຶ້ນກັບ pathogenesis, infectious agents and area of CNS involvement and age of the patient headache; photophobia; stiff neck; Kernig’s and Brudzinski’s signs +; opisthotonus

6. Meningitis vs Encephalitis Meningitis Fever Headache Meningismus Altered mental status Encephalitis Fever Headache Altered mental status Mental status changes early in the disease course, prior to coma Focal or diffuse neurologicsigns (seizures and hemiparesis) Both share many features Meningoencephalitis

7. Definitions of WHO Bacterial meningitis Clinical description – Acute onset of fever (usually >38.5 rectal, >38 axillary) – Headache and – One of the following signs: neck stiffness, altered consciousness or other meningeal signs Acute encephalitis syndrome (AES) Clinical case definition – Acute onset of fever and at least one of: Change in mental status (including symptoms such as confusion, disorientation, coma, inability to talk New onset of seizure ( including simple febrile seizure)

8. Meningitis and encephalitis Life-threatening disease Signs and symptoms are not specific Physical examination may not be sufficient to accurately identify patient with meningitis, especially in infants and young children Lumbar puncture result may be difficult to distinguish bacterial meningitis from viral meningitis Suspected bacterial meningitis is a medical emergency and need empirical antimicrobial treatment without delay Physicians who prescribe the initial dose of antibiotics should be aware of guidelines for antibiotics and adjunctive steroids

9. LP contraindication Mass in the brain (eg. Brain tumor or abscess) causing raised intracranial pressure Skin or soft tissue sepsis at the proposed LP site Severe coagulopathy or severe thrombocytopenia Risk for either mass or raised ICP recent head injury a known immune system problem localizing neurological signs evidence on examination ofraised ICP MRI or CT brain prior to LP Focal neurological signs, papilloedema, falling level of consciousness with falling pulse, rising BP and/or vomiting

10. Brainherniation

12. Typical CSF in meningitis PyogenicTuberculosisViral AppearanceOften turbidOften fibrin web Usually clear Predominant cells polymorphsmononuclear Cell count/mm 3 90-100010-100050-1000 Protein (g/L)>1.51-5<1 glucose<1/2 plasma >1/2 plasma Normal opening pressure: 50-190 mmH 2 O (depends on age) Appearance :clear; turbid; yellow or bloody

13. LP Cell count: 0-5/mm 3 in children and adult, maybe up to 32/mm 3 (mean of 8-9/mm 3 ) in neonates – False positive eleviation of CSF white bloodcell counts : traumatic LP, intracerebral or subarchnoidhemorrage

14. LP done at Mahosot Physicians decide to do Lumbar Puncture according to clinical symptoms/signs No contraindication for LP Informed written consent

15. LP doneatMahosot Lab staff assist the physician for LP CSF drop on agar plate, CSF collection in 3 tubes : adult: 8ml children: 3ml Blood collection: (haemoculture, glucose and serology)

16. CSF Hemoculture Cell count, Glucose, Protein, GS, ZN, Auramine, India ink Classical bacteriological &TB culture Bacteria PCR Bacteriological tests Fungus & parasites Viral tests S. pneumoniae H. influenzae N. meningitidis S. suis Rickettsia Scrub typhus Murine typhus Spotted fever Malaria film Cryptococcal Ag & culture Serum RDT for murine and scrub typhus Serology for Angiostrongyluscantonensis and Gnathostomaspinigerum Panbio ELISA: Dengue (NS1, IgM, IgG), JE IgM Viral PCR Viral culture EV, HSV, VZV, CMV, Dengue, JE, Nipha, Influenxa A Mumps, measles, TBE, West Nile, Inluenza B, Panflavivirus

17. Total included patients 2003-2009: 840 patients Few bacteria isolated from CSF: 6% (67% AB before LP) virus positive samples : 15.3% Viral causesTested POS % EV PCR345 CSF72% HSV PCR344 CSF30.9% VZV PCR385 CSF20.5% CMV PCR243 CSF41.6% Mumps PCR344 CSF20.9% JEV PCR 344 CSF20.9% JE culture200 CSF10.5% JEV IgM700 CSF486.8% Dengue344 sera4 (3D1,1D4)1.2%

18. Treatment of meningitis Mahosot Microbiology Review Antibiotic recommendation – Ceftriaxone 80-100 mg/kg/day divided into 2 daily doses (50kg adult 2g IV every 12 h) – Or in neonates: Aged 0-7 days cefotaxime100-150 mg/kg/day (dose interval every 8-12h) or aged 8-28 days 150-200 mg/kg/day IV (dose interval 6-8h)

19. And if Listeria is suspected (usually in infant < 1 month old) give ampicillin Treatment of meningitis Mahosot Microbiology Review Age0-7 days8-28 days<15 y>15 y Daily dose IV150 mg/kg/day200 mg/kg/day300 mg/kg/day12 g/day Dose intervalEvery 8hEvery 6-8hEvery 6hEvery 4 h

20. If ceftriaxone is not available give chloramphenicol Treatment of meningitis Mahosot Microbiology Review Age0-7 days8-28 days<15 y>15 y Daily dose IV25 mg/kg/day50 kg/day75-100mg/kg/day4-6g/day Dose interval24h12-24h6h If suspected rickettsial disease add in: oral doxycycline 4 mg/kg stat followed by 2mg/kg every 12h for 1 week. In adult doxycycline 200 mg loading dose followed by 100 mg every 12h

21. Adjunctive treatment with dexamethasone Neurological sequelae are common in survivors of meningitis (hearing loss, cognitive impairement, developmental delay) Adjuvant therapy with dexamethasone reduces the mortality and neurological sequelae among adults with bacterial meningitis in the developed world There have been few clinical trials in Asian patients – unclear whether should be given ? Systemic steroids (dexamethasone, 10 mg IV) are important adjunctive treatment for patients with suspected bacterial meningitis and should be given with the first dose of antibiotics and continued every 6 h for 4 days (but unclear whether beneficial in developing countries)

22. Prevention Viral meningitis: Immunoprophylaxis - JEV Bacterialmeningitis:Vaccine available for Hib, 7 serotype of S. pneumoniae and N. meningitidis group A, C, Y and W135 Chemoprophylaxis for bacterial meningitis patients/contacts – Haemophulus influenzae Eradication of nasopharyngeal colonization of Hib – Rifampicin 20 mg/kg daily for 4 days (2 days of rifampicin is efficacious as 4 days’ treatment – Ampicillin and chloramphenicol, unlike ceftriaxone and cefotaxime, do not effectively eliminate nasopharyngeal colonization – Rifampicin is Not recommended in pregnant women Chemoprophylaxis is not currently recommended for daycare contacts 2 y old or older unless two or more cases occur in the daycare center within 60 days-period For children <2 y, the CDC recommends prophylaxis for daycare contacts

23. – Neisseria meningitidis Chemoprophylaxis: – Ceftriaxone IM 250 mg in adult and 125 mg in children – Ciprofloxacin 500 mg oral in adult single dose – in adults, rifampin 600 mg bid for 2 days. In children 1 month or older 10 mg/Kg and infant youngerthan 1 month 5m/kg Chymoprophylaxis is recommended for household contacts, daycare center members, any person exposed to the patient’s oral secretion Chemoprophylaxis is not recommended for school, work or transport contacts High dose penicillin or chloramphenicol do not reliably eradicate meningococci from the nasopharynx of colonized patients – S. pneumoniae: the risk of secondary pneumococcal disease in contacts of infected patient has not been defined – Streptococcus agalactiae All pregnant should be screenat 35-37 weeks gestation for anogenital colonization with group B streptococci

24. Microbiology Laboratory Mahosot Hospital Thank you for your attention