meningitis send to ram.pptx nepal medical college

ppt

1. MODERATOR DR. Ram babu lado khanxa ( buddhi na vayeko ) LADO CHUSUWA DOCTOR DEPARTMENT OF FUCK LOGY Presented by Lado khau Ram babbu JR - 1 M EOICINE

2. Introduction Types of meningitis Causes Clinical presentation Investigations Lumbar puncture procedure Approach in case of suspected meningitis Management Algorithm Brief overveiw of different types of meningitis

3. DEFINITION Meningitis is an inflammation of the leptomeninges (arachnoid and pia mater) surrounding the brain and spinal cord, with involvement of the subarachnoid space

4. Based on etiology

5. Based on duration Acute meningitis Subacute meningitis Chronic meningitis/Recurrent meningitis Based on blood culture Septic meningitis Aseptic meningitis

6. Bacterial Neisseria meningitis Haemophilus influenzae Listeria monocytogenes Gram negative bacilli Staphylococcus aureus Streptococcus agalactiae

7. Virus Enterovirus Herpes simplex virus Varicella zoster virus Adenovirus Arboviruses Coxsackieviruses types A and B

8. Fungal Cryptococcus neoformans / gattii Histoplasma Coccidioides Parasitic Taenia solium Naeglaria Floweri Toxoplasma Acanthamoeba

9. Drug Anti- CD3 monoclonal antibody Azathioprine lbuprofen Other NSAIDs Trimethoprim- sulfamethoxazole Malignancy Leukemia Lymphoma Metastatic carcinomas and adenocarcinomas

10. Autoimmune Sarcoidosis Systemic lyupus erythematosus Vogt-Koyanagi- Harada syndrome Other Epidermoid cyst Postvaccination

11. Symptoms Fever (7S— 95a) Headache (8o - 95a) Photophob ia (30 - 50%) Vomiting (gOa of children; 1O9s of adults) Signs Neck st •• t 5D- gO9s) Confusion (7$- 8$%) Kemig's sign“ (5s) Brudzinski's signst ($%) Focal neurological deficit (20 — 3 Ost) Fits ( 15- 3 Ose) Rash (1o — t5'x)

12. Classic triad of fever, neck stiffness, and headache seen in only 2/3^ of adults. More common in pneumococcal than other bacterial meningitis. 1 of the 3 elements present in almost all patients. Absence of all 3 rules out acute meningitis with sensitivity of 99- 100%. Usually history is of 24 to 48 hours.

13. Clinical Presentation (contd.) O - • Rash most commonly seen with meningococcal disease (92% of meningitis cases with rash). Presence of shock, rash or clustering of cases should raise suspicion of meningococcemia. Petechlal skin rash that accompanles meningitis due to Neisseria men/ngiffdfs. Fine patechlal rash in disseminated infection and menlngltis due to Staphylococcus aureus

14. Kernig's and Brudzinski's sign have poor SRFÏsitiVity (59a) with high specificity (95a) Nuchal rigidity has low sensitivity (30%) and specificïty 8n›dz1n\ki’s re¢k +gn

15. Jolt accentuation test - exacerbation of existing headache on having the patient rotate his head horizontally @2- 3 times/ sec. Sensitivity of 97%, specificity of 60% in a small study, never been further evaluated extensively.

16. TLC (mean 10,600/cc vs 8900/cc). Platelet counts- systemic infection, sepsis. ””Hyponatremia (serum Na < 135mEq/I) seen in 30°f cases. Severe (Na <JJ0J in 6%. (resolves spori£onec›us/yJ More common with L. monocytogenes and in patients with symptoms > 24 hours. Blood culture- should be taken immediately, before starting antibiotics. Positive in 74a cases.

17. Acute inflammatory markers - ESR, CRP and Procalcitonin elevated : distinguish acute bacterial from non bacterial meningitis. Diagnostic lumbar puncture - performed in all cases unless specific contraindications present- local infection at puncture site subdural abscess bleeding diathesis septic shock- diastolic BP < 60 mm of Hg mass lesion/ ventricular obstruction/ brain shift on cranial imaging

18. Indications for cranial imaging before L.P. Non contrast CT scan of the head before L.P. is indicated if one of the following is present: New onset seizure (within one week of presentation) Immunocompromised state Papilledema Focal neurological signs (excluding hearing loss) Moderate to severe impairment of consciousness (GCS <10) Absence of all these features has 97P« negative predictive value for an intra cranial abnormality that would preclude a lumbar puncture

19. Cell type Cell count Glucose Protein Normal Lymphocytes 0-4 >6D% of blood glucose < D.45 mg/dl Viral Lymphocytes 1D- 2000 Normal Normal Bacterial Polymorphs 1000- 5000 Decreased Increased Tubercular Lymphocytes/ polymorphs 50- 5000 Decreased Increased Fungal Lymphocytes 50- 500 Decreased Increased CSF findings in infectious meningitis

20. CSF latex agglutination for pneumococcal and meningococcal antigen - specificity of 95- 100d. Sensitivity 70- 100% for pneumococci, 30- 70% for meningococcci. Pneumolysin in CSF - detected by Cowan 1 Staphylococccal protein A co-agglutination method. Sensitivity and specificity of 91 and 92°A respectively.

21. tąuşm C

22. Investigations (contd.) Methods to improve diagnostic yield of microbiology Examine CSF before or shortly after antibiotics started. Submit large volume of CSF ( »5 ml) for microbiology. Gram stain and inoculation for culture as soon as possible. Centrifuge at high force ( 3000g) for 20 min and stain and culture the deposit. Subculture after 24 hr inoculation in brain heart infusion broth at 37°C with 5% COC Storage/ transport of CSF — incubate at 37°C if available or at room temperature. Do not refrigerate.

23. Overview of different types of meningitis

24. Definition- Acute purulent infection within the subarachnoid space. Meninges, subarachnoid space and brain parenchyma frequently involved together- meningoencephalitis.

25. Pus covered surface - Lcptomeninyes

26. Incidence- 0.6- 4/1,00,000 adults in developed nations. Upto 10 times higher in developing nations. Mortality 16% to 37% despite modern antibiotics.

27. In developed world MC organism in both children and adults is S. pneumoniae = 5095 N. meningitidis = 2596 Group B Streptococcus = 159f› Listeria monocytogenes =10% H. influenzae < 10% Staphylococcal species and gram negative bacilli in special circumstances.

28. Streptoœccus pneumoniae(commonest œuse worldwidg; asso<iatedwith HfV Mom•mingk/d«s(serog psA.W- 13S. C. tndX œuse epldœnks inAfdca: sm›g«x›ps B and C are rnŒe common in Eur No+th Amené AustraII4 and east Asia) GrompBflœptœoci(‹ommoncauselnneonatei) Listwio monocytogenes(neonatw elderly people and immune compromised) iscd) Common œuses of acute bacterlal menlnghls In resource poor settlngs Tubercular and cryptococcal meningitis common in HIV Maybe difficult to distinguish from acute bacterial meningitis.

29. Predisposin g conditions S. pneumoniae: pneumococcal pneumonia, sinusitis otitis media, alcoholism, diabetes mellitus, asplenia, HIV, hypogammaglobulinemia, complement deficiency, head trauma,CSF rhinorrhea. N. meningit!dis: asplenia, complement deficiency. L. monocytogenes: neonates, elderly (>60 years), pregnancy, immunodeficiency. Group B streptococcus: neonates, age> SO years.

30. Pneumococci colonize the nasopharynx and compete with resident flora. Balance effected by recent antibiotic usage, host immunity, smoking, over crowding. Invade intravascular space via the nasal epithelium. Avoid phagocytosis and complement mediated destruction mainly by virtue of polysaccharide capsule. Invade choroid plexus cells and gain access to CSF via transcytosis. Low levels of complements, antibodies and leukocytes in CSF allow rapid bacterial multiplication.

31. " Hence rtëîifó al injury can progrë ’".':«'Mven afteao9Raterilization. ’ "

32. Right 3'" nerve palsy and severe herpes IabIaIls in a patient of acute bacterial meningitis

33. Turbid C9F wlłh fibrous spider clot aner 1 hour in pyoganic meningitis

34. pneumen lao in CSF. Gram negative dipłoøocci oł menłngococci ln CAT Heuropmsenggœmnegu•enminlin C6Cofanelderłypafienłofk.cołł Gram negølive rods• H. in dueme

35. Predictor Points Present Absent CSF Gram stain 2 CSF protein > 80mg/d! 1 CSF ANC>1000/cc 1 Peripheral blood ANC » 10,000/cc 1 Seizures at or before presentation 1 Bacterial meningitis score (BMS)

36. Risk of bacterial meningitis is very low (0.1%) with BMS and it increases as the score increases:- 3% with score 1 27°A with score 2 70% with score 3 9S9£ with score * 4 It has a negative predictive value of 99.9% for acute bacterial meningitis. Validated only in age group of 29 days to 19 years. Not applicable to adults and neonates.

37. Indicators of poor prognosis in a case of bacterial meningitis are:- Evidence of systemic compromise — tachycardia (HR>120 bpm), low blood pressure, positive blood culture, raised ESR, low platelet count. Low CSF IeukDcyte count (<100/cc). Low score on GCS Advanced age

38. 5. Predisposing conditions like immunocompromised state, pneumonia, otitis, sinusitis. Cranial nerve palsy Pneumococcal meningitis- 6 times higher chance of unfavorable outcome compared to meningococcal meningitis.

39. Algorithm for management of suspected bacterial meningitis NeC8blumbBrpunMuœ

40. Antibiotics are the mainstay of treatment. Should be given as early as possible. Delay >3 hours independently associated with mortality 75 • 2 > 2 • 4 > 4 • 6 > 6 • 8 > 8 • 1g Door•to•antihiotfn ttme (hours)

41. WHO recommendation — 5 day antibiotic therapy To be extended if- lmmunocompromise Persistent fever Persistent seizures Coma

42. Mortality and rate of neurological sequelae remain high despite appropriate antimicrobial therapy. Due to adverse effects of inflammatory cytokines. Corticosteroids act by inhibiting synthesis of IL- 1 and TNF at m- RNA level decreasing CSF outflow resistance and — stabilizing the BBB. Once macrophages and microglia activated and TNF production induced, steroids have less effect.

43. Hence steroids to be given early, with or before 1” dose of antibiotics to have maximum effect. Duration of this window of opportunity not described. Dose- Dexamethasone 0.15 mg/kg I.V. 6‘ h hourly for 4 days is the most widely recommended dose.

44. Role of cort ico steroids (contd.) Randomized controlled trial of 301 adult patients from the Netherlands - 21 (16) Distribution of acores on Glasgow outcome scale at eight weeks

45. Treatment of raised ICP — Head end elevation (30°- 45°) IV mannitol (25-100 g 4 th hourly) Intubation and hyperventilation (P a CO 2 25- 30 mm of Hg). Maintain ICP below 20 mm of Hg. Maintain blood pressure and urine output. Aggressive fluid resuscitation to be avoided for fear of hyponatremia.

46. Treatment of raised ICP — Head end elevation (30°- 45°) IV mannitol (25-100 g 4 th hourly) Intubation and hyperventilation (P a CO 2 25- 30 mm of Hg). Maintain ICP below 20 mm of Hg. Maintain blood pressure and urine output. Aggressive fluid resuscitation to be avoided for fear of hyponatremia.

47. 1g•31% Cardk›respirctory faihre ñtedsankal ventilatlm Oisseminated intrcrcsoJlar caa‹:Iuktion Neurologicd complications

48. Enlarged lateral ›’c ‹triclcs in a paticnt with I ydruccpl alus - trotted by placing two shunts.

49. 2S. Cause of death

50. Neurological findings at discharge Any sequelae in surviving patients Cranial nerve palsies Hearing loss local cerebral deficitst Aphasia Hemiparesis 4- 10%

51. Prevention Vaccination and chemoprophylaxis useful fer prevention. Chemopropkyiaxis reserved for meningococcal disease. Only for close contacts, to be given as early as possible.

52. Most common organisms are S. pneumoniae and N. meningitidis. Absence of clinical triad, Kerning's and Brudzinski's sign do not rule out acute bacterial meningitis. Start antibiotics early, before lumbar puncture if need be. Empirical antibiotics based on age, predisposing condition and geographical resistance patterns. Give dexamethasone with or before 1* t dose of antibiotic. Imaging not needed before lumbar puncture in all cases. Absence of typical CSF findings do not rule out acute bacterial meningitis.

53. ViraI infection of the nervaus system can result in a myriad of clinical presentations occurring separately or in combinations including acute or chronic meningitis, encephalitis, myelitis, ganglionitis, and polyradiculitis. Viruses may also incite para— or post- infectiOUS CNS inflammatory or autoimmune syndromes such as acute disseminated encephalomyelitis (ADEM) or encephalitis associated with autoantibodies ,• ""'- "” t

54. Jbbæfiafioo:WNV,Wast Noa v us. Lyz hocytlz tI›orbnæIngitIsvInis

55. Leading cause of viral meningitis Neonates- fever, vomiting, anorexia, rash, upper respiratory tract symptoms, meningea! signs (nuchal rigidity, bulging antetrior fontanelle) +/- Severe form with hepatic necrosis, myocarditis, necrotizing enterocolitis, encephalitis Child ren, adults- fever, headache, neck stiffness, photophobia Anorexia, vomiting, rash, diarrhoea, cough, pharyngitis, myalgia h/o community enteroviral outbreaks, rash, conjunctivitis, pleurodynia, pericarditis, herpangina

56. HSV 2 meningitis Neurological complications- urinary retention, d v saesthesis, paraesthesia, neuraIg!a, motor weakness, paraparesis, difficulty in concentration, impaired hearing, usually resolve in 3- 6 months EBV meningitis Associated with pharyngitis, !v• ph adenopathy, sp1enomega !v VZV meningitis Associated with diffuse vehicular rash

57. CSF - Exceptions in Viral Mening0- encephalitis Cell counts of several thousand/ pL + low glucose 4 infections due to lymphocytic choriomeningitis virus (LCMV) and mumps virus. PMNs predominate in first 48 h of illness 4 Echovirus 9, West Nile virus (WNV) or mumps PMN pleocytosis with low glucose Cytomegalovirus (CMV) infections

58. Atypical lymphocytes in the CSF EBV infection Plasmacytoid or Mollaret- like large mononuclear WNV encephalitis Red blood cells (>500/pL) in the CSF in a nontraumatic tap HSV encephalitis

59. Empirical Antibiotics + (Acyclovir (HSV) 10mg/kg IVI q8h) for 14- 21 days Treat raised ICT Cushing's triad (HTN, Bradycardia, Irregular RR) Seizures 4 Antiepileptics

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62. Tuberculosis remains a global health problem, with an estimated 10.4 million cases and 1.8 million deaths resulting from the disease in 2015. The most lethal and disabling form of tuberculosis is tuberculous meningitis (TBM), for which more than 100,000 new cases are estimated to occur per year. In patients who are co- infected with HIV- 1, TBM has a mortality approaching 50%.

63. Diagnosis of TBM is often delayed by the insensitive and lengthy culture technique required for disease confirmation. Antibiotic regimens for TBM are based on those used to treat pulmonary tuberculosis, which probably results in suboptimal drug levels in the cerebrospinal fluid, owing to poor blood— brain barrier penetrance

64. sae also ( iar TBthoughout body Tuberculous meningitis L.atent foci in brain or Tissue destrumlon p mass effact Cranial nerva Menlngeal Art erltie & irwo!vament fibrosis vawular occlusion Hyaroceptiaius Braln infarcts

65. CSF appearance- Cog web coagulam CSF cells - leukocyte 10- 1000 cells/p.1 - Lymphocytes predominates CSF glucose - <40 mg/dl CSF Protein - markedly high (400- 5,000 ing/dl) Chloride content - increased Acid- fast stain positive in up to 30% of cases Culture is positive in 50- 70% of cases

66. A 6- month course of therapy is acceptable, but therapy should be prolonged for 9— 12 months in patients who have- an inadequate resolution of symptoms of meningitis positive mycobacterial cultures of CSF during the course of therapy. Dexamethasone therapy is recommended for patients with tuberculous meningitis. The dose is 12— 16 mg/d for 3 weeks,and then tapered over 3 weeks

67. History- 4 8 yrs old male patient had h/o low grade fever for past 2 months with h/o evening rise of temperature. Patient also had h/o weight loss & loss of appetite for last 2 months. He was brought to casualty with h/o altered sensoriom for last 2-3 days O_/E-neck stiffness present Investigations- CSF: appearance clear Protein- 600mg%(15 45mg%) Sugar-30mg% [40-70mg%) Chloride- S80mg% (116- 126mg%) Total cells 450/mm’ (sS cellsl Lymphocyte - 92% Polymorph - 8K

68. Hydrocephalus in TB meningitis on MRI A T1 - weighted MR of the brain in the s•gicIal pra}ection shows hy¢lrocephaius of the Istefol ventricle{asterisk) end fourth ventride(arrawT. Tmage B is a FLAIR sequence in axial projection and shows moderate hydro¢ephalus of the lateral venwtcles (asterlsks) with trans- ependymai edema farrowsF, and dlffuse cerebral edema and effacement of the sulcl (arroe/headk Image C is a FLAIR sequence showing hydro¢ephalus or the thfrd ventrlcle (asterIsk\ transependyrnal edema (arrzaas). and effacement of tt›e suki {arrowhead) tndfcaong cerebral edema.

69. Millan TBandbrain tuberculomas

70. Typically acquired by the inhalation of airborne fungal spores. The initial pulmonary infection may be asymptomatic or present with fever, cough, sputum production, and chest pain and may later disseminate to CNS(immunocomprom!sed hosts)

71. M o de Of I n fe ct ion The most common pathogen causing fungal meningitis is C. neoformans

72. HIV patients InduEtion. liposomal amphoter ie in B + fiuc ytosine x 2 weeks followed by 1 wk of fiuconazole (1200 mg/day, adult) Alternate induction: fluconazole (400- 1200 mg/day, ad ult) + flue ytosine x2 wk Consolidation. oral fluconazole 800 mg/day •8 wk (minimum) Maintenante/secondary prophylaxis. oral fluconazole 20O mg/day Corticosteroids: not recommended during induction Antiretroviral therapy (ART) initiation: defer for 4— 6 wk from start of antifungal treatment

73. Organ transplant patients Induction! lipid-formulation ampLiotericin + flucytosine x2 wk (minimum) Consolidation: oral fluconazole 40fI— 800 mg/day •8 wk Maintenance: oral fl uconazole 200— 400 mg •6— 12 mo ImmunocompetRnt patients Induction: amphotericin B/lipid-formulation amphotericin + fl uc y tosine x4 \vk Consolidation: ora] fîuconazole 400— 800 mg/day •8 wk Maintenance: oral fluconazole 200— 400 mg =6— T 2 mo

74. 4 If ICP a 25 cm H2O and symptomatic-Therapeutic lumbar puncture 4 Target- lumbar puncture (LP) to closing pressure of s20 cm H2O or s50% of opening pressure (OP) * . For persistent symptoms, recheck and treat OP daily until symptoms abate or ICP stable x2 days