INFECTIONS OF THE CENTRAL NERVOUS SYSTEM

1. INFECTIONS OF THE CENTRAL NERVOUS SYSTEM

2. Meningitis • Encephalitis • Brain abscess

3. MENINGITIS A medical emergency!

4. Clinical features that suggest the diagnosis of acute meningitis • Headache • Irritable • Neck stiffness • Photophobia • Fever • Vomiting • Varying levels of consciousness • Rash

5. Groups in which clinical features are not so specific • Neonates (first few weeks of life) • Elderly • Immunosuppressed

6. Incidence: Primary meningitis: spread via the bloodstream Secondary meningitis: Ears, sinuses, trauma, Surgery Main pathogens: Neisseria meningitidis Strept. Pneumoniae Haemophilus influenzae BACTERIAL

7. N meningitidis (meningococcus) and meningococcal meningitis • The most common cause of acute bacterial meningitis • Most cases in children and young adults • Gram negative diplococcus • 3 main serological types A, B. C • Person to person transmission • Reservoir nasopharynx (2-25% carriage) • Respiratory droplet spread • Incubation period 1-3 days

8. Higher carriage rates in: • Children • Overcrowding • Schools, universities, other institutions • military

9. Most cases are sporadic • Close family contacts of cases at risk • Outbreaks may occur in eg, schools • Group B serotype traditionally most frequent cause • Group C serotype has become increasingly common • Epidemics occur in eg, Africa, South America

10. Nasopharyngeal carriage Bloodstream infection Meningitis

11. CLINICAL FEATURES • May be sore throat • Progression from headache, drowsiness, signs of meningitis • Haemorrhagic skin rash (non-blanching) • Sepsis complicated by intravascular coagulation, shock, acute renal failure • Bleeding into organs may occur eg, adrenal gland causing Waterhouse Friderichsen syndrome • Gangrene of peripheral limbs

12. TREATMENT OF ACUTE BACTERIAL MENINGITIS KEYPOINTS: • Once the diagnosis is clinically suspected don’t delay treatment • If the causative agent is not clear eg, no rash, give ceftriaxone or cefotaxime • This provides cover of the 3 main causes until a microbiological diagnosis is made • If meningococcal meningitis confirmed then a change to high doses of benzylpenicillin can be considered • Chloramphenicol can be an alternative if allergy to beta lactams

13. MICROBIOLOGICAL DIAGNOSIS • If possible collect Cerebrospinal fluid (may not be, if raised intracranial pressure) • Blood culture, both before antibiotic therapy • Sample from petechial skin lesion may yield meningococcus • CSF subjected to cell count, gram stain of deposit, and culture on chocolate agar in CO2 atmosphere

14. CSF Abnormalities in Meningitis

15. Additional lab investigations • Latex agglutination test on CSF to detect meningo polysaccharide antigen • PCR to amplify bacterial DNA in blood (EDTA sample) or CSF which may be positive even after start of antibiotics • Save serum sample for antibody tests with a subsequent “convalescent” sample • Set up antibiotic sensitivities to penicillin, cephalosporins, ampicillin, chloramphenicol and others

16. Some features of meningococcal isolate • Gram: gram negative cocci some within neutrophils (intracellular) • Grows within 24-48 hours best on chocolate agar in CO2 • Will agglutinate with group specific antisera eg, B, C • Caution needed in lab as making suspensions can be a hazard to the lab worker (may acquire pathogen)

17. MENINGOCOCCAL MENINGITIS • Notifiable to public health authorities • Close contacts in home, school/university, nursery should be given antibiotic prophylaxis • Rifampicin X 2 days (ciprofloxacin is used but not licensed) • Hospital contacts only need prophylaxis if contact with secretions, eg, mouth to mouth resuscitation • Vaccine against group C now widely in use and for overseas travellers group A vaccine may be indicated

18. Pneumococcal meningitis • Strep pneumoniae is the cause, a capsulate gram positive coccus • Highest incidence in those at extremes of age, infants <3yrs and elderly • Alcoholism, debilitation, malnutrition, hyposplenism • May spread from middle ear or sinus infection • Or following trauma causing basal skull #

19. Pneumococcal meningitis: clinical features • Acute onset with rapid development of loss of consciousness • Skin rash not a feature • May be a history of ear infection, splenectomy • Bacteraemia a feature • Higher mortality than other causes • High incidence of complications in survivors

20. Microbiological investigations • CSF and blood cultures should be taken • Gram stain of CSF deposit shows gram positive cocci in short chains • Culture on blood and choc agar in CO2 gives alpha haemolytic (green) colonies with “draughtsmen” • Direct sensitivities for penicillin, cefotaxime, ceftriaxone, ampicillin

21. Treatment • High doses of penicillin eg, 1.2g (2mill units) 2 hourly • Note some strains have reduced susceptibility to penicillin, and some are resistant! • Need to review to find a potential underlying risk factor • Polyvalent vaccine for risk groups eg, before splenectomy

22. Haemophilus influenzae meningitis • Gram negative coccobacillus, capsulated strains (type b used predominate) • Peak incidence 2 years old, range 3 months to 5 years • Incidence has declined greatly since the successful introduction of Hib vaccine • More insidious onset, no rash, lower mortality • Diagnostic approach as for other causes • Treament with cefotaxime or ceftriaxone

23. Other bacterial causes of meningitis in adults and children • Post trauma or surgery Staph aureus, streps, anaerobes, coliforms, Pseudomonas • Immunocompromised Listeria monocytogenes • Others M tuberculosis, Leptospira, Borrelia burgdorferi

24. Tuberculous meningitis • Higher incidence in immigrant populations who come from countries with a higher incidence of TB • Insidious onset • High frequency of complications, cranial nerve palsies • Delayed diagnosis makes complications more likely • CSF shows predominantly lymphocytic response but polymorphs also present • High protein, low/absent sugar • Treat: probably with 3 agents eg, isoniazid, rifampicin, pyrazinamide • Note occasional reports of MDR TB

25. CSF Abnormalities in Meningitis

26. NEONATAL MENINGITIS • Group B streptococcus (S agalactiae) and Esch coli are the principal causes • Travel via the bloodstream but direct infection may occur • Premature rupture of membranes, pre-term delivery (“VLBW”) are risk factors • May complicate maternal infection • High morbidity and mortality • Clinical features can be non-specific • Early onset Group B infection more common than late onset disease • Other causes: Listeria, Staph, Salmonella, other GNB • Treat: Cephalosporin, or penicillin + aminoglycoside

27. BACTERIAL VIRAL FUNGAL, OTHER

28. VIRAL MENINGITIS • Primarily affects children and young adults • Milder signs and symptoms • May start as respiratory or intestinal infection then viraemia • CSF shows raised lymphocyte count (50-200/cu mm); protein and sugar usually normal • Full recovery expected

29. Causes of viral meningitis • Enteroviruses: Echo, coxsackie A ,B, polio • Paramyxovirus: mumps • Herpes simplex, VZV • Adenoviruses • Other: arboviruses, lymphocytic choriomeningitis, HIV

30. Diagnosis: viral meningitis • Examination of CSF • Storage at -700C of CSF for subsequent virus isolation • Additionally throat swab, stool, paired sera

31. CSF Abnormalities in Meningitis

32. Fungal meningitis • Cryptococcus neoformans is main cause • HIV and immunosuppressed pts at risk • Insidious onset of headache, fever, neck stiffness • Diagnosis made on CSF examination • Shows raised lymphocyte count, protein, low sugar, capsulate yeasts, antigen • Treat with amphotericin B +flucytosine

33. CSF Abnormalities in Meningitis

34. ENCEPHALITIS • Affects children and adults mostly • A variety of symptoms and signs • Drowsiness, confusion, coma, fits, nerve palsies, paresis • May have sequelae eg, memory loss, motor impairment, death • EEG, brain scan, CSF exam, brain biopsy may establish diagnosis

35. Causes of encephalitis • Sporadic: • Herpes simplex, mumps, VZV, EBV rabies • Epidemic: • Togaviruses: equine, louping ill, Japanese B, enteroviruses • Post-infectious: • Measles, rubella, post-vaccination • Degenerative: • Measles (SSPE), vCJD, JC virus (PML)

36. Herpes simplex encephalitis • Most common cause of sporadic encephalitis in previously healthy • May be evidence of herpes infecion of skin, mucosae • Causes severe haemorrhagic encephalitis affecting temporal lobe, • Focal signs and epilepsy features • High mortality so treatment urgently needed with aciclovir

37. Other causes • VZV • Mumps • Rabies • Mycoplasma pneumoniae • Rickettsiae • Toxoplasma

38. Subacute sclerosing panencephalitis (SSPE) • A rare complication of measles infection • Usually affects children • Intellectual impairment, involuntary movements • High titres of measles antibody • Brain biopsy shows measles virus • Fatal outcome

39. Prion diseases • Degenerative disorders • Long incubation periods • Slow progressive spongiform encephalopathy • Fatal outcome

40. Kuru: occurred in New Guinea, diue to cannibalism, eating human brain • Sporadic Creutzfeldt-Jacob disease (CJD): rare degenerative disease in over 50’s • Recipients of growth hormone at increased risk, use of surgical instruments contamined with prion protein • Prions are (Prp) proteins in abnormal configuration resistant to destruction • Mutations of genes encoding these proteins can be inherited

41. New variant CJD • In 1980’s emergence of bovine spongiform encephalopathy (BSE) • Could be experimentally transmitted from brains of sheep with scrapie • Similarities between BSE and nvCJD • Occurs in young people rapidly fatal • Possibly acquired from eating infected beef/ beef products • Diagnosis on brain biopsy (? Tonsillar tissue) • No treatment

42. Brain abscess • Can arise from direct inoculation of infection following trauma, surgery; from spread of infection of ear or sinuses; or haematogenous spread from eg, lungs, heart (endocarditis) • May be non-specific signs, neurological symptoms • Needs urgent investigation by CT/MRI scan • Surgical treatment +antibiotics

43. Causes of brain abscess • Ear: mixed anaerobes, coliforms • Sinus: pneumococci, streptococci • Trauma/surgery: Staph aureus • Chest: strep, staph, pneumococci

44. Diagnosis and treatment • Examination of pus aspirated from abscess • CSF • Blood cultures • Surgical drainage a priority • Antibiotics chosen with good penetration of CNS

45. Guillain-Barre syndrome • Infectious polyneuritis • Paraesthesiae, progressive weakness of limbs, respiratory failure • High CSF protein • Post infectious • Various infections implicated including Campylobacter, EBV, Mycoplasma • Recovery likely to occur with supportive care

46. Congenital CNS infections • Intrauterine infections: toxoplasma, rubella, cytomegalovirus, syphilis • During birth: herpes simplex, hepatitis B HIV