acutemeningitis-160210083410.pptx dr. ram

ppt

1. Clinical Approach To A Patient Of Meningitis And Encephalities Mohd Saif Khan EPIDEMIOLOGY, DIAGNOSIS AND MANAGEMENT

2. Headings Background and Definition Anatomy 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. ANATOMY OF MENINGES

7. ANATOMY OF MENINGES

8. ANATOMY OF MENINGES

9. TRANSMISSION HOW DOES MENINGITIS SPREAD? An infectious agent can gain access to the CNS and cause meningeal disease via any of the 3 following major pathways : Direct contiguous spread (e.g. sinusitis , otitis media, congenital malformations, trauma, or direct inoculation during intracranial manipulation ) 1. INVASION OF THE BLOODSTREAM Invasion of the bloodstream (i.e., bacteremia, viremia , fungemia , or parasitemia ) and subsequent hematogenous seeding of the CNS 2. RETROGRADE NEURONAL PATHWAY A retrograde neuronal ( eg , olfactory and peripheral nerves) pathway ( eg , Naegleria fowleri or Gnathostoma spinigerum ) 3. DIRECT CONTIGUOUS SPREAD

10. TRANSMISSION HOW DOES MENINGITIS SPREAD? 3. DIRECT CONTIGUOUS SPREAD Local extension from contiguous extracerebral infection ( eg , otitis media, mastoiditis , or sinusitis) is a common cause. Possible pathways for the migration of pathogens from the middle ear to the meninges include the following : The bloodstream Preformed tissue planes ( eg , posterior fossa) Temporal bone fractures The oval or round window membranes of the labyrinths

11. PATHOGENESIS

12. PATHOGENESIS

13. PROGNOSIS Patients with meningitis who present with an impaired level of consciousness are at increased risk for neurologic sequelae or death . A seizure during an episode of meningitis also is a risk factor for mortality or neurologic sequelae , particularly if the seizure is prolonged or difficult to control. In bacterial meningitis, several risk factors are associated with death and with neurologic disability. A risk score has been derived and validated in adults with bacterial meningitis. This score includes the following variables, which are associated with an adverse clinical outcome   : Older age Increased heart rate Lower Glasgow Coma Scale score Cranial nerve palsies CSF leukocyte count lower than 1000/ μL Gram-positive cocci on CSF Gram stain

14. PROGNOSIS Advanced bacterial meningitis can lead to brain damage, coma, and death. In 50% of patients, several complications may develop in the days to weeks following infection. Long-term sequelae are seen in as many as 30% of survivors and vary with etiologic agent, patient age, presenting features, and hospital course. Patients usually have subtle CNS changes.

15. 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.

16. AETIOLOGY BACTERIAL MENINGITIS VIRAL MENINGITIS The most serious form of meningitis is bacterial. Even with treatment, bacterial meningitis can be fatal some of the time. If bacterial meningitis progresses rapidly, in 24 hours or less, death may occur in more than half of those who develop it, even with proper medical treatment. Determining how many people get viral meningitis is difficult because it often remains undiagnosed and is easily confused with the flu. The prognosis for viral meningitis is much better than that for bacterial meningitis, with most people recovering completely with simple treatment of the symptoms.

17. AETIOLOGY FUNGAL MENINGITIS ASEPTIC MENINGITIS Fungal meningitis is a serious form of meningitis that is normally limited to people with impaired immune systems. Aseptic meningitis is a term referring to the broad category of meningitis that is not caused by bacteria. Approximately 50% of aseptic meningitis is 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

18. BACTERIAL CAUSES Listeria monocytogenes ( >50 years old) Group A β-hemolytic streptococcus Group B β- hemolytic streptococcus Mycoplasma pneumoniae Gram – ve rods COMMON ORGANISMS: Streptococcus pneumoniae (α-hemolytic streptococcus) Neisseria meningitidis Haemophilus influenzae OTHER ORGANISMS: VIRAL CAUSES Enteroviruses Herpes simplex virus

19. ORGANISMS RISK OR PREDISPOSING FACTORS BACTERIAL PATHOGEN Age 3 months – 18 years Neisseria meningitidis 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

20. NEISSERIA MENINGITIDIS Also known as meningococcal meningitis Gram negative aerobic cocci , capsule 10% of healthy people are healthy nasopharyngeal carriers Begin as throat infection, rash Vaccination is recommended

21. NEISSERIA MENINGITIDIS STREPTOCOCCUS PNEUMONIAE Gram positive diplococci 70% of people are healthy nasopharyngeal carriers Most common in children (1 month to 4 years) Mortality: 30% in children, 80% in elderly Prevented by vaccination

22. 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

23. 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

24. NEISSERIA MENINGITIDIS HISTORY TAKING

25. NEISSERIA MENINGITIDIS HISTORY TAKING SYMPTOM SIGN MECHANISM Chills, rigors Fever  (T>38°) Endogenous cytokines (released during the immune response to the invading pathogens) affect the thermoregulatory neurons of the hypothalamus, changing the central regulation of body temperature.   Invading viruses or bacteria produce exogenous substances ( pyrogens ) that can also re-set the hypothalamic thermal set point. Nuchal rigidity  (neck stiffness) Brudzinski sign and Kernig sign Flexion of the spine leads to stretching of the meninges.   In meningitis, traction on the inflamed meninges is painful, resulting in limited range of motion through the spine (especially in the cervical spine). Altered mental status Decreased  Glasgow Coma Scale (GCS) ↑ ICP → brain herniation → damage to the reticular formation (structure in the brainstem that governs consciousness)

26. NEISSERIA MENINGITIDIS HISTORY TAKING SYMPTOM SIGN MECHANISM Focal neurological deficits, e.g. vision loss Examples: cranial nerve palsies, hemiparesis, hypertonia, nystagmus Cytotoxic edema and ↑ ICP lead to neuronal damage.   Signs or symptoms depend on the affected area (cerebrum, cerebellum, brainstem, etc.) Seizures   Inflammation in the brain alters membrane permeability, lowering the  seizure threshold . Exact seizure pathophysiology is unknown. Headache Jolt accentuation of headache: headache worse when patient vigorously shakes head Bacterial exotoxins, cytokines, and ↑ ICP stimulate nociceptors in the meninges (cerebral tissue itself lacks nerve endings that generate pain sensation). Photophobia   Due to meningeal irritation. Mechanisms unclear; pathways are thought to involve the trigeminal nerve. Nausea and vomiting   ↑ ICP stimulates the  area postrema   (vomiting centre ), causing nausea and vomiting.   Petechial rash Meningococcemia (due to  N. meningitidis )

27. 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

28. NEISSERIA MENINGITIDIS HISTORY TAKING OTHER IMPORTANT HISTORY Contact with TB patient (TB meningitis) Infection of middle ear, sinuses, lung or tooth and gum (brain abscess) Contact with infected bodily secretions (meningitis, herpes encephalitis) Sexual contact with a person infected with HIV (HIV encephalopathy) Penetrating head trauma (brain abscess) Neurosurgical complications (meningitis, brain abscess) A chronic illness, such as cancer A weakened immune system, such those with alcoholism, diabetes, HIV or people who have had organ transplant. A history of recent antibiotic use should be elicited. 40% of patients who present with acute or subacute bacterial meningitis have previously been treated with oral antibiotics (presumably because of misdiagnosis at the time of initial presentation).

29. 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 Middle ear, sinus infection Pneumonia  pneumococcus Papilledema (increase ICP) Cranial nerves examination ( III, IV, V, VI, and VII) SPECIFIC EXAMINATION

30. NEISSERIA MENINGITIDIS PHYSICAL EXAMINATION KERNIG’S SIGN (MENINGEAL STRETCH TEST)

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

32. NEISSERIA MENINGITIDIS CLINICAL FEATURES CHRONIC MENINGITIS Lymphadenopathy Papilledema and tuberculomas during funduscopy Meningismus Cranial nerve palsies 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. TUBERCULOUS MENINGITIS

33. NEISSERIA MENINGITIDIS CLINICAL FEATURES Cranial nerve palsies (III, IV, V, VI, and VII) often develop, suggesting basilar meningeal involvement . Clinical staging of tuberculous meningitis is based on neurologic status, as follows : Stage 1 - No change in mental function, with no deficits and no hydrocephalus Stage 2 - Confusion and evidence of neurologic deficit Stage 3 - Stupor and lethargy TUBERCULOUS MENINGITIS CLINICAL STAGING OF TUBERCULOUS MENINGITIS

34. NEISSERIA MENINGITIDIS CLINICAL FEATURES

35. 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) .

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

37. Anatomy Emissary veins

38. PATHOPHYSIOLOGY WBC Mechanical effects Inflammatory effects Impairment of CSF flow Occlusion of cortical blood vessels Cytokines Oxidants Proteolytic enzymes Hydrocephalus Disruption of BBB

39. Disruption of BBB Enhanced bacterial entry Enhanced WBC recruitment Overwhelming damage to neural structures Breach in piamater Infection of brain parenchyma (encephalitis) Brain abscess PATHOPHYSIOLOGY Cranial nerve palsies (VIII CN) Thrombophlebitis of cortical veins Ischemia and infarcts

40. 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, metronidazole , and IVIG Tumor Leukemia, lymphoma

41. Presentation Fever Neck stiffness Headache Only about 44% of adults with 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

42. Physical examination focal neurologic deficits.. Signs of cranial nerve palsies Meningeal signs Signs of Extracranial infection ( eg , sinusitis, otitis media, mastoiditis , pneumonia, or urinary tract infection [UTI ]) Exanthemas Symptoms of pericarditis, myocarditis, or conjunctivitis Nonblanching petechiae and cutaneous hemorrhages may be present in meningitis caused by N meningitidis (50%), H influenzae , S pneumoniae , or S aureus .

43. 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

44. D/Ds Central nervous system (CNS) vasculitis Stroke Encephalitis All causes of altered mental status and coma Leptospirosis Subdural empyema

45. Management

46. The initial treatment approach to the patient with suspected acute meningitis depends on: early recognition of the meningitis syndrome, rapid diagnostic evaluation , and emergent antimicrobial and adjunctive therapy.

47. Diagnosis

48. Lumbar puncture (LP) should be performed emergently in all patients suspected of having bacterial meningitis unless contraindicated, although it is commonly unnecessarily delayed while neuroimaging is performed to exclude mass lesions. Life-threatening brain herniation has been reported to range from less than 1% to 6% (Neurology. 1959;9(4):290–297, Ann Neurol. 1980;7(6):524–528.).

49. Typical CSF Parameters in Patients with Meningitis 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 Bacterial 100-5000 Neutrophil >100 <40 20-30 Tubercular 50-300 Lymphocyte <100 <40 18-30 Cryptococcal 20-500 Lymphocyte 50-200 <40 18-30 Characteristic CSF findings for bacterial meningitis consist of polymorphonuclear pleocytosis , hypoglycorrhachia , and raised CSF protein levels.

50. CT scan Antibiotics+Dexa Antibiotics+Dexa Stat LP Management of Adults with Acute Meningitis Syndrome ( Fulminant course (<48 h) with fever, headache, usually with impaired sensorium and stiff neck.) Blood Cultures 1. Comatose 2. Inadequate History (patient unable to provide history and no family available) 3. Risk of Mass Lesion ( papilledema , focal neurologic defects, recent head trauma, malignant neoplasm, or history of CNS mass lesion) 4. Immunosuppressed (HIV, transplant, neoplasm , steroids) No Yes LP CSF findings s/o Bacterial meningitis Continue therapy Yes negative

51. 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 .

52. 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

53. Duration of antimicrobial therapy

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

55. 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

56. 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

57. 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

58. Cryptococcal meningitis 14-day induction phase of amphotericin B, 0.7 to 1 mg/kg/day IV, with or without flucytosine , 100 mg/kg/day PO dosed every 6 hours. Consolidation therapy with fluconazole , 400 mg daily, should be continued for 8 weeks following induction. Maintenance (or suppressive) therapy with fluconazole, 200 mg per day. Risk factors: HIV patients, Organ transplant recepients Diagnosis : CSF analysis, India ink staining Detection of cryptococcal antigen ( CrAg ) by lateral flow immunoassay and latex agglutination assay.

59. Other fungal meningitis T/t of coccidioidal meningitis is oral fluconazole. Therapy for H. capsulatum meningitis consists of amphotericin B, 0.7 to 1 mg/kg/day to complete a total dose of 35 mg/kg.

60. Tuberculous meningitis Sole manifestation of TB or concurrent with pulmonary or other extrapulmonary sites of infection. Cranial nerve (CN) palsies, 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

61. 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.

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

63. Treatment The WHO guidelines recommend a first-line regimen of 2 months of HRZE(children ) or HRZS (adults ) followed by 10 months of HR.

64. 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.

65. Summary 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 priorto presentation, or coma. Empirical antibiotic therapy should begin as soon as possibleafter appropriate cultures have been obtained; these can bemodified later based on results of erebrospinal fluid (CSF) Gramstain and culture.

66. 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.

67. Thank you