DR. RAM JIBAN MENINGITIS PPT FINAL.pptx gds

ppt

1. CLINICAL APPROACH TO CASE OF MENINGITIS AND ENCEPHALITIS MODERATOR DR.ZAFAR ALAM CONSULTANT PHYSICIAN DEPARTMENT OF INTERNAL MEDICINE PRESNTED BY DR.RAM JIBAN YADAV FCPS MEDICINE RESIDENT

2. Headings A natomy Background and Definition Pathophysiology Etiology Clinical presentation Diagnosis Treatment Subacute meningitis-diagnosis and management Nosocomial meningitis

3. Meningitis is a clinical syndrome characterized by inflammation of the meninges . CNS infections Meningitis Encephalitis Leptomeningitis Pachymeningitis

4. MENINGES Leptomeningitis :- Archenoid / subachenoid Patchy meningitis :- dura mater BRAIN PARENCHYMA Focal :- cerebritis / abcess Diffuse :- encephalitis SPINA CORD :- Focal :- epidural abcess Diffuse :- myelitis Combination Meningo encephalitis Encephalo - myelitis

5. Can be caused by cancer , SLE , certain Drugs ,Head injury and Brain surgery NON- infectious causes Caused by viruses like enterovirus, arboviruses, herpes simplex viruses Caused by Fungi like Cryptococcus and Histoplasma Caused by Bacteria like Neisseria meningitis and streptococcus pneumoniae

6. Etiology Predisposing risk MC organisms Trauma or neurosurgery Staphylococcus aureus species, gram negative bacilli, Infected VP shunt Staph. epidermidis , S aureus Elderly individuals (>60 years) And pregnant women Listeria monocytogenes Neonates Streptococcus agalactiae Immunocompromized Cryptococci, Mycobacterium tuberculosis, Infectious Non-Infectious Bacteria, viruses, fungi, parasites Drugs NSAIDs, Ibuprofen metronidazole, and IVIG Anti-CD3 monoclonal antibody Azathioprine Trimethoprim-sulfamethoxazole Tumor Leukemia lymphoma Metastatic carcinomas adenocarcinomas

7. TYPES OF MENINGITIS Based on blood culture Septic meningitis Aseptic meningitis not caused by bacteria. Approximately 50% due to viral infections . Other less common causes include drug reactions or allergies, and inflammatory diseases like lupus. It occurs in individuals of all ages but is more common in children BASED ON DURATION Acute (<24 hours) Subacute (1-7 days) Chronic (>7 days) Bacterial Viral Tuberculosis, Syphilis, Fungi (especially cryptococci ), Carcinomatosis

8. PATHOGENESIS BACTEREMIA, VIREMIA, FUNGEMIA,PARASITEMIA SINUSITIS, OTITIS MEDIA, CONGENITAL MALFORMATIONS, TRAUMA, OR DIRECT INOCULATION DURING INTRACRANIAL MANIPULATION )

9. Invasion of SAS by pathogenic bacteria Multiplication and lysis of organisms Release of bacterial cell wall components (endotoxin, techoic acid) Production of inflammatory cytokines like TNF α , IL-1 β , and IL-6 Altered BBB permeability Adherence of leukocytes to endothelial cells Alterations in cerebral blood flow Production of excitatory AA, reactive O and N species ↑ Permeability of vessels Leakage of plasma proteins into CSF Leukocytes enter CSF, degranulate and release cytokines Cell injury and death Exudate obstructs outflow & resorption of CSF and Infiltrates vasculature Cerebral ischemia ↓ Blood flow ↑ Blood flow vasogenic edema Obstructive and communicating hydrocephalus Interstitial edema cytotoxic edema, stroke seizures ↑ ICP Coma DEATH Hence neuronal injury can progress even after CSF sterilization.

10. PATHOGENESIS

11. AETIOLOGY BACTERIAL VIRAL FUNGAL PHYSICAL INJURY DRUGS REACTION Severity/ treatment of illness differ depending on the cause. Thus, it is important to know the specific cause of meningitis.

12. MOST SERIOUS FORM EVEN WITH TREATMENT CAN BE FETAL SOME OF TIME. progresses rapidly, in 24 hours or less, death may occur in more than half of those who develop it, even with proper medical treatment. Confused with flue good prognosis, complete recovery CAN BE SERIOUS FORM

13. 50% 25% 10% < 10%

14. S. pneumoniae : 70% of people are healthy nasopharyngeal carriers pneumococcal pneumonia, sinusitis otitis media, alcoholism, diabetes mellitus, asplenia , HIV, hypogammaglobulinemia , complement deficiency, head trauma,CSF rhinorrhea. N. meningitidis : asplenia , complement deficiency Begin as throat infection, rash Vaccination is recommended L. monocytogenes : neonates, elderly (>60 years), pregnancy, immunodeficiency. Group B streptococcus: neonates, age> 50 years. Predisposing conditions

15. ORGANISMS RISK OR PREDISPOSING FACTORS BACTERIAL PATHOGEN Age 3 months – 18 years Neisseria meningitides ( menincococal meningitis ) Streptococcus penumoniae Haemophilus influenza Age 18 – 50 years Streptococcus penumoniae Neisseria meningitidis Haemophilus influenza Age > 50 years Streptococcus penumoniae Neisseria meningitidis Listeria monocytogenes Aerobic gram-negative bacilli Immunocompromised state Streptococcus penumoniae Neisseria meningitidis Listeria monocytogenes Aerobic gram-negative bacilli Intracranial manipulation including neurosurgery Staphylococcus aureus Coagulase negative staphylococci Aerobic gram-negative bacilli, including Pseudomonas aeruginosa Basilar skull fracture Streptococcus penumoniae Haemophilus influenza Group A streptococci

16. NEISSERIA MENINGITIDIS HISTORY TAKING

17. NEISSERIA MENINGITIDIS CLINICAL FEATURES

18. NEISSERIA MENINGITIDIS HISTORY TAKING ~25% of those who develop meningitis have symptoms that develop over 24 hours. The remainder generally become ill over one to seven days . ~25% of patients have concomitant sinusitis or otitis that could predispose to  S pneumoniae  meningitis . Occasionally, if someone has been on antibiotics for another infection, the symptoms can take longer to develop or may be less intense. If someone is developing fungal meningitis (most commonly someone who is HIV positive), the symptoms may take weeks to develop. DURATION

19. NEISSERIA MENINGITIDIS HISTORY TAKING In contrast, patients with subacute bacterial meningitis and most patients with viral meningitis present with neurologic symptoms developing over 1 – 7 days . Chronic symptoms lasting longer than 1 week suggest the presence of meningitis caused by certain viruses or by tuberculosis, syphilis, fungi (especially cryptococci ), or carcinomatosis . DURATION

20. NEISSERIA MENINGITIDIS HISTORY TAKING In contrast, patients with subacute bacterial meningitis and most patients with viral meningitis present with neurologic symptoms developing over 1 – 7 days . Chronic symptoms lasting longer than 1 week suggest the presence of meningitis caused by certain viruses or by tuberculosis, syphilis, fungi (especially cryptococci ), or carcinomatosis . DURATION

21. Penetrating head trauma (brain abscess) Neurosurgical complications (meningitis, brain abscess)

22. sickle cell anemia People with cancer, especially those receiving chemotherapy People who have received transplants and are taking drugs that suppress the immune system People living in close quarters (military barracks, dormitories) IV drug users People with shunts in place for hydrocephalus Those recently exposed to meningitis at home

23. Presentation Fever Neck stiffness Headache about 44% of adults will have bacterial meningitis Altered mentation Nausea and vomiting Photophobia Double visions Confusion Irritability Delirium Seizures Coma Symptom onset Acute (<24 hours) Subacute (1-7 days) Chronic (>7 days) Bacterial Viral Tuberculosis, Syphilis, Fungi (especially cryptococci ), Carcinomatosis

24. NEISSERIA MENINGITIDIS PHYSICAL EXAMINATION GENERAL EXAMINATION Non -toxic looking might suggestive of viral origin. Sick, toxic looking might suggest bacterial origin. Glasgow-coma scale Kernig’s sign Brudzinki’s sign Look for other source of infections: Cutaneous petachie / purpura rash  meningococcus Signs of Extracranial infection ( eg , sinusitis, otitis media, mastoiditis, pneumonia, or urinary tract infection [UTI]) Pneumonia  pneumococcus Papilledema (increase ICP) Cranial nerves examination ( III, IV, V, VI, and VII) Exanthemas Symptoms of pericarditis, myocarditis, or conjunctivitis SPECIFIC EXAMINATION

25. 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. Clinical Presentation (contd.) Petechial skin rash that accompanies meningitis due to Neisseria meningitidis . Fine petechial rash in disseminated infection and meningitis due to Staphylococcus aureus

26. Physical examination Nonblanching petechiae and cutaneous hemorrhages may be present in meningitis caused by N meningitidis (50%), H influenzae , S pneumoniae , or S aureus .

27. Nuchal rigidity : Inability to flex the neck forward due to rigidity of neck muscles, if flexion of the neck is painful but full ROM is present then NR is absent 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

28. NEISSERIA MENINGITIDIS PHYSICAL EXAMINATION KERNIG’S SIGN (MENINGEAL STRETCH TEST) Kernig’s and Brudzinski’s sign have poor sensitivity (5%) with high specificity (95%) Nuchal rigidity has low sensitivity (30%) and specificity (68%).

29. NEISSERIA MENINGITIDIS PHYSICAL EXAMINATION BRUDZINSKI’S SIGN (MENINGEAL STRETCH TEST)

30. Viral meningitis CAUSED BY ENTEROVIRUSES, HERPES SIMPLEX VIRUS (HSV), HUMAN IMMUNODEFICIENCY VIRUS (HIV), WEST NILE VIRUS (WNV), VARICELLA-ZOSTER VIRUS (VZV), MUMPS, AND LYMPHOCYTIC CHORIOMENINGITIS VIRUS (LCM) Most common Coxsackie , echovirus , other non-poliovirus enteroviruses Seasonal variation Etiology WBC Count (cells/mm 3 ) Predominant cell type Protein (mg/ dL ) Glucose (mg/ dL ) Opening Pressure (cm H 2 O) Normal 0-5 Lymphocyte 15-40 50-75 8-20 Viral 10-500 Lymphocyte Normal normal 9-20 CSF PCR Mollaret's meningitis HSV-2

31. Consiousness like irritability lethargy, change in behaviour Attriibutated to brain parenchyma

32. NEISSERIA MENINGITIDIS COMPLICATIONS 1. HEARING LOSS 2. CEREBRAL OEDEMA AND INCREASED ICP 4 . BRAIN ABSCESS 4. STROKE Infections / inflammation from subarachnoid space  via cochlear aqueduct  inner ear  Inflammatory response – damages cochlear (hair cells) Cerebral edema may be vasogenic , from increased vascular permeability, cytotoxic from cerebral hypoxia, interstitial , from increased CSF volume, or a combination of all. Increased intracranial pressure, in turn, causes decreased cerebral perfusion, hypoxia/ischemia, and neuronal necrosis. 3. DISSEMINATED INTRAVASCULAR COAGULOPATHY (DIC) Bacterial products can damage the brain and blood vessels directly. Bacterial toxins cause neuronal apoptosis , and cell wall lipopolysaccharide (endotoxin), released from bacteria, activates clotting causing disseminated intravascular coagulation (DIC) .

33. Complications Immediate complications : Septic shock with DIC Coma Seizures, which occur in 30-40% of children and 20-30% of adults Cerebral edema Septic arthritis Pericardial effusion Hemolytic anemia ( H influenzae ) Late complications : Decreased hearing or deafness Multiple seizures Focal paralysis Subdural effusions Hydrocephalus Intellectual deficits Ataxia Blindness Waterhouse- Friderichsen syndrome Peripheral gangrene

34. Management

35. Suspicion of bacterial meningitis Immunocompromised, H/O CNS disease, new onset seizures, focal deficits, papilledema, altered sensorium , delay in performing lumbar puncture. Blood culture STAT Dexamethasone + empirical antibiotic therapy CT scan head Perform lumbar puncture No C/I to lumbar puncture Yes No Blood culture and lumbar puncture STAT Dexamethasone + empirical antibiotic therapy CSF c/w pyogenic meningitis? Consider alternate diagnosis No Yes CSF gram stain positive? Dexamethasone + empirical antibiotic therapy Dexamethasone + targeted antibiotic therapy No Yes Algorithm for management of suspected meningitis

36. ↑ TLC (mean 10,600/cc vs 8900/cc). ↓ Platelet counts- systemic infection, sepsis. ** Hyponatremia (serum Na < 135mEq/l) seen in 30% cases. - Severe (Na <130) in 6%. (resolves spontaneously) - More common with L. monocytogenes and in patients with symptoms > 24 hours. Blood culture- should be taken immediately, before starting antibiotics. Positive in 74% cases. ESR, CRP and Procalcitonin elevated : distinguish acute bacterial from non bacterial meningitis.

37. Other laboratory test Gram staining of bacteria in CSF India Ink preparation CSF lactate: to distinguish bacterial from aseptic meningitis PCR Latex agglutination-based rapid tests Procalcitonin C-reactive protein Limulus lysate assay : useful test for patients with suspected gram-negative meningitis , detect ∼10 3 gram-negative bacteria/mL of CSF and as little as 0.1 ng /mL of endotoxin .

38. Initial empirical antibiotics Clinical Infectious Diseases 2004; 39:1267–84

39. Antimicrobial therapy Predisposing conditions Antibiotics Age <1 month 1 month – 2 years 2-50 years >50 years Ampicillin+cefotaxime /aminoglycoside Vanco + 3 rd Gen Cephalo Vanco + 3 rd Gen Cephalo Vanco+Ampi+3 rd Gen Cephalo Head trauma Basilar fracture Penetrating Vanco + 3 rd Gen Cephalo Vanco + Cefepime / Ceftazidime / Meropenem Postneurosurgery Vanco + Cefepime / Ceftazidime / Meropenem CSF Shunt Vanco + Cefepime / Ceftazidime / Meropenem Impaired cellular immunity Vancomycin plus ampicillin plus either cefepime or meropenem

40. Supportive treatment Analgesics Antipyretics Anticonvulsants ICP lowering measures Intubation and mechanical ventilation

41. Nosocomial meningitis Invasive Procedures ( e.g., craniotomy, placement of internal or external ventricular catheters, lumbar puncture, intrathecal infusions of medications, or spinal anesthesia ), VP shunt/EVD Complicated Head Trauma Removal of the internal ventricular catheters For MDR GNB Intraventricular antibiotic administration Not FDA approved, indications are not well defined. Vancomycin and gentamicin are most commonly given via this route

42. Lancet Neurol 2008; 7: 637–48 Clinical Infectious Diseases 2004; 39:1267–84 Duration of antibiotic therapy WHO recommendation – 5 day antibiotic therapy To be extended if- Immunocompromise Persistent fever Persistent seizures Coma

43. Role of corticosteroids 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.

44. Hence steroids to be given early, with or before 1 st dose of antibiotics to have maximum effect. Duration of this window of opportunity not described. Dose - Dexamethasone 0.15 mg/kg I.V. 6 th hourly for 4 days is the most widely recommended dose. Role of corticosteroids (contd.)

45. Management for raised ICT

46. Supportive treatment Treatment of raised ICP – Head end elevation (30 ° -45 °) IV mannitol (25-100 g 4 th hourly) i.e 1 – 1.5 g/kg IV given over 15 minutes Action: Mannitol is a hyperosmolar agent that makes the intravascular space hyperosmolar to the brain and permits movement of water from brain tissue into the intravascular compartment Intubation and hyperventilation (P a CO 2 25-30 mm of Hg). Maintain ICP below 20 mm of Hg. ANTICONVULSANT LIKE Diazepam , Lorazepam should be a dministered if patient has seizure Maintain blood pressure and urine output. Aggressive fluid resuscitation to be avoided for fear of hyponatremia.

47. Treatment of viral meningitis Generally supportive treatment is given. Pleconaril has been evaluated for enteroviral meningitis with modest benefit. Acyclovir (10 mg/kg IV every 8 hours) for HSV meningitis (controversial). Intravenous immunoglobin has been used in agammaglobulinemic patients with chronic enteroviral meningitis. Arboviruses , mumps, or LCM: No specific therapy HIV-associated meningitis should be treated with combination antiretroviral therapy. CMV meningitis : Ganciclovir

48. CHRONIC MENINGITIS Lymphadenopathy Papilledema and tuberculomas during funduscopy Meningismus Cranial nerve palsies (III, IV, V, VI, and VII) often develop, suggesting basilar meningeal involvement. hemiparesis , paraparesis , and seizures are common and should raise the possibility of MTB as the etiology of meningitis. Chest X-ray is suggestive of active or previous pulmonary TB in approximately 50% of cases Occurs most common shortly after primary infection in childhood or as part of military TB . The presentation of chronic tuberculous meningitis may be acute, but the classic presentation is subacute and spans weeks. Patients generally have a prodrome consisting of fever of varying degrees, malaise, and intermittent headaches.

49. Lab Diagnosis CSF : Pleocytosis with lymphocytic predominance, high protein levels, and low glucose levels . In all suspected case send CSF for Ziehl-Neelsen (ZN) staining for AFB, Gram staining for bacteria, India ink preparations for fungi, and antigen testing for Cryptococcus neoformans . MTB cultures can take several weeks. Xpert MTB/RIF detect MTB and rifampicin resistance simultaneously in less than 2 hours.

50. Neuroimaging in TBM CECT or MRI scan The most common findings in descending order are meningeal enhancement, hydrocephalus, basal exudates, infarcts, and tuberculomas

51. In patients who are co-infected with HIV-1, TBM has a mortality approaching 50%. HIV infected patients receiving ART are at risk for clinical deterioration after initiation of antiretroviral therapy (ART) due to immune reconstitution inflammatory syndrome (TBM-IRIS ). Defer ART to 4–6 weeks after beginning ATT. Steroid are of great use.

52. Pathophysiology of CNS tuberculosis

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

54. NEISSERIA MENINGITIDIS MANAGEMENT ANTIBIOTICS (CHRONIC MENINGITIS) INFECTION SUGGESTED TREATMENT COMMENTS PREFERRED ALTERNATIVE TUBERCULOUS MENINGITIS Mycobacterium tuberculosis Treatment is continued for 12 months. Intensive 2 months S/EHRZ and 10 months HR Pyridoxine 10- 50mg PO q24h needs to be prescribed together with Isoniazid. (Streptomycin should replace Ethambutol in TB meningitis as it crosses BBB better than Ethambutol .) CPG on management of Tuberculosis, 3rd edition, 2012; 16, 22, 40-42, 56) WHO Treatment of Tuberculosis Guidelines, 4th ed. 2009 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

55. Fungal meningitis 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( immunocompromised hosts)

56. Mode of Infection MOMOMODEmm The most common pathogen causing fungal meningitis is C. neoformans

57. Treatment HIV patients Induction : liposomal amphotericin B + flucytosine x 2 weeks followed by 1 wk of fluconazole (1200 mg/day, adult) Alternate induction : fluconazole (400-1200 mg/day, adult) + flucytosine ×2 wk Consolidation : oral fluconazole 800 mg/day ×8 wk (minimum ) Maintenance/secondary prophylaxis : oral fluconazole 200 mg/day Corticosteroids: not recommended during induction Antiretroviral therapy (ART) initiation: defer for 4–6 wk from start of antifungal treatment

58. Continued… Organ transplant patients Induction : lipid-formulation amphotericin + flucytosine ×2 wk (minimum) Consolidation : oral fluconazole 400–800 mg/day ×8 wk Maintenance : oral fluconazole 200–400 mg ×6–12 mo Immunocompetent patients Induction: amphotericin B/lipid-formulation amphotericin + flucytosine ×4 wk Consolidation : oral fluconazole 400–800 mg/day ×8 wk Maintenance: oral fluconazole 200–400 mg ×6–12 mo

59. Continued… If ICP ≥ 25 cm H2O and symptomatic- Therapeutic lumbar puncture Target-lumbar puncture (LP) to closing pressure of ≤20 cm H2O or ≤50% of opening pressure (OP) . For persistent symptoms, recheck and treat OP daily until symptoms abate or ICP stable ×2 days

60. NEISSERIA MENINGITIDIS PREVENTION AND PROPHYLAXIS PRECAUTION Completion of recommended schedule of vaccination is an effective way of protecting individuals from certain types of bacterial  meningitis (E.g. meningococcus , pneumococcus and Hib ) FOLLOW UP R epeat cerebrospinal fluid exam in patients in whom there is doubt about the success of therapy or the accuracy of the initial diagnosis Patients who respond promptly to therapy may no longer need repeat cerebrospinal fluid exams Monitor for hydrocephalus and treat the condition appropriately - hydrocephalus usually manifests within the first few weeks of infection and is treated with ventriculoperitoneal shunting Monitor for neurologic sequelae and provide appropriate supportive therapy Sequelae include hearing impairment, cranial nerve palsies and motor deficits Supportive therapy should be individually tailored Use of mask, gloves, and gowns prevents spread of disease as meningitis is a droplet infection VACCINATION

61. Approach in case of suspected meningitis/encephalitis

62. Continued

63. Management Algorithm

64. Continued…

65. Continued…

66. TAKE HOME MESSAGE Clinical triad is the hallmark of meningitis but absent in nearly half of the patients. Neuroimaging studies should precede lumbar puncture in the presence of papilledema, focal findings on neurologic examination, immunocompromise (human immunodeficiency virus [HIV]infection, malignancy, or transplant), seizures in the week prior to presentation, or coma. Empirical antibiotic therapy should begin as soon as possible after appropriate cultures have been obtained; these can be modified later based on results of cerebrospinal fluid (CSF) Gram stain and culture.

67. Patients with negative cultures and limited clinical response after 48 hours of therapy should undergo repeat lumbar puncture and head computed tomography (CT) or magnetic resonance imaging (MRI) scans. Initial combination therapy with dexamethasone and antibiotics has been associated with improved outcomes in patients with pneumococcal meningitis.