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1. Acute central nervous system infections 14-Aug-24 1

2. Outline Introduction Acute bacterial Meningitis Meningioencephalitis Cerebritis and brain abscess Epidural abscess Cerebral malaria Referrences 14-Aug-24 2

3. Introduction Central nervous system infections involving the brain, spinal cord, optic nerves, and their covering membranes. CNS is extremely resistant to infection due to a combination of protective effects of its bony structures, the meninges, and the blood-brain barrier. 14-Aug-24 3

4. Cont... However, once infection has initiated, the CNS is generally more susceptible to infection than most other tissues. Host defense mechanisms that are normally seen in other areas of the body are inadequate in the CNS. 14-Aug-24 4

5. Cont... Acute CNS infections that warrant neurointensive care admission fall broadly into three categories meningitis, encephalitis, and abscesses. 14-Aug-24 5

6. Cont... The microorganisms that cause CNS infections include a wide range of bacteria, mycobacteria, yeasts, fungi, viruses, spirochaetes (e.g., neurosyphilis), and parasites (e.g., cerebral malaria and strongyloidiasis). 14-Aug-24 6

7. 1. Acute Bacterial Meningitis Inflammatory response to pyogenic bacterial invasion of the pia mater, the arachnoid membranes, and surrounding the CNS. Involves the entire length of the neuraxis including the brain, spinal cord, optic nerves, and their covering membranes. 14-Aug-24 7

8. Cont... Bacteria invade the CNS following direct inoculation of the brain parenchyma or by spread from a focus of infection outside the CNS. Hematogenous spread is the most common route, and the upper respiratory tract is the most common source of entry of microorganisms. 14-Aug-24 8

9. Pneumonia, Sinusitis, Otitis media, Alcoholism, Diabetes Cont... Immunosuppression associated with conditions, such as Malignancy Connective tissue diseases, Sickle cell disease Organ transplantation Splenectomy Dialysis Steroids and Other immunosuppressive therapy. 14-Aug-24 9

10. Cont... Because of the blood–brain barrier, immunoglobulin and complement protein levels and leukocytes are significantly lower in CSF than in serum and interstitial fluid. 14-Aug-24 10

11. Cont... Subsequent phagocytosis by neutrophils are hindered by the relative paucity of complement and immunoglobulins and the intrinsic fluid nature of CSF which is less facilitating to phagocytosis as compared to solid tissues. 14-Aug-24 11

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13. Cont... S. pneumoniae and N. meningitidis are the most common causes of community-acquired acute bacterial meningitis. In mastoiditis-associated meningitis, sinusitis, or otitis media, anaerobes often play a role. L. monocytogenes is usually acquired via contaminated food. 14-Aug-24 13

14. Cont... Though an absolute increase in the number of cases of H. influenzae non-b and S. pneumoniae serotypes not in the vaccine (“replacement phenomena”) has been seen, this increase in absolute number is small. 14-Aug-24 14

15. Cont.... The incidence of meningitis due to N. meningitidis has decreased with the tetravalent (serogroups A, C, W-135, and Y) vaccine, but the vaccine does not provide lasting immunity and does not include one of the major serotypes, serotype B. 14-Aug-24 15

16. Cont... L. monocytogenes accounts for approximately 8% of acute bacterial meningitis cases in those with predisposing factors: Age older than 50, Diabetes, chronic illness, Malignancy, and Immunosuppressed state. 14-Aug-24 16

17. Cont ABM is still a severe infection resulting in a high mortality (nearly 20%) and morbidity worldwide. The overall case fatality rate is six fold higher in S. pneumoniae than in N. meningitidis infection. Sequelae, hearing disability, or neurologic deficits are reported in 30–50% of patients. 14-Aug-24 17

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20. Cont... Classic triad of fever, altered mental status, and neck stiffness is present in only 40–45% of cases. Headache was the most common complaint (87%), followed by neck stiffness (83%), fever (77%), and altered mental status (69%). 14-Aug-24 20

21. Cont... Focal neurologic signs and seizures are present, respectively, in 25% and 5% of patients. Kernig’s and Brudzinski’s signs elicited in only about 50 % of children and only 5 % of adults with acute bacterial meningitis. A rash is noted in 8% of cases; nearly all patients with purpura are infected with N. meningitidis. 14-Aug-24 21

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23. Cont... CSF opening pressure: Normal opening pressure ranges from 1 to 10 cm H2O in young children, 6–20 cm H2O after 8 years of age, and up to 25 cm H2O in obese patients. CSF Color: Xanthochromia also occurs when CSF protein concentrations are greater than 150 mg/dL. 14-Aug-24 23

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25. Cont... Approximately 75 % of patients with acute bacterial meningitis will have a positive gram stain, and this percentage may drop to about 50 % among patients who have received significant doses of prior antimicrobial therapy. 14-Aug-24 25

26. Cont... Generally, the gram stain is positive in 90 % of untreated patients with pneumococcal meningitis, 86 % of patients with meningitis due to H. influenzae , and approximately 75 % of cases due to N. meningitidis. 14-Aug-24 26

27. Cont... CRP can be measured in CSF and, when greater than 100 μg/mL, may be useful in differentiating bacterial from viral meningitis. CSF lactate has high sensitivity and specificity in differentiating bacterial from viral meningitis. While at a cut-off value of 3mmol/L. 14-Aug-24 27

28. Cont... The major value of CT and MRI scans in patients with acute bacterial meningitis is in the investigation of complications, such as cerebral infarction, vasculitis, abscess, subdural effusion, subdural empyema or hydrocephalus. 14-Aug-24 28

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30. Treatments The penetration of the blood–brain barrier is a function of both the properties (e.g., lipid solubility, molecular size, and molecular structure) of the antimicrobial itself and the degree or extent of the inflammation of the meninges. 14-Aug-24 30

31. Cont... Fortunately, in inflamed meninges therapeutic concentrations of penicillins, cephalosporins, and vancomycin can be achieved for treatment of the vast majority of cases of bacterial meningitis. 14-Aug-24 31

32. Cont... The penetration of the 3rd generation cephalosporins is signifi cantly better than that of the earlier generation cephalosporins. Sulfa agents and vancomycin, in the presence of inflamed meninges, may reach sufficient concentrations to be of therapeutic value. 14-Aug-24 32

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35. 2. Viral Meningitis and Encephalitis The most common viral pathogens are enteroviruses, which cause approximately 85% of cases of viral CNS infections. Other include arboviruses, HSV, cytomegalovirus, varicella-zoster virus, rotavirus, coronavirus, influenza viruses A and B, West Nile virus, and Epstein-Barr virus. 14-Aug-24 35

36. Cont... Enteroviruses are transmitted from person to person by the fecal-oral route and their activity tends to be increased in areas of overcrowding, poverty, and generally poor hygienic conditions. 14-Aug-24 36

37. Cont... Most cases of enteroviral meningitis or encephalitis are self-limiting with supportive treatment. However, arbovirus, West Nile virus, and Eastern equine virus infections are associated with a less favorable prognosis. 14-Aug-24 37

38. Cont... HSV is the most common cause of sporadic encephalitis. Patients with HSV type I encephalitis. The most common manifestations include headache, fever, cognitive disorders, impaired consciousness, seizures, and focal neurological deficits. 14-Aug-24 38

39. Cont... In contrast to other viral encephalitides, HSV type 1 and 2 encephalitis are treatable. More than 90% of HSV encephalitis in adults is due to HSV type 1, whereas HSV type 2 predominates in neonatal HSV encephalitis (greater than 70%). 14-Aug-24 39

40. Cont... HSV encephalitis is the result of reactivation of a latent infection (two-thirds of cases) or a severe case of primary infection (one-third). Without effective treatment, the mortality rate may be as high as 85%, and survivors often have significant residual neurologic deficits. 14-Aug-24 40

41. Cont... In the case of HSV, the distribution involves the medial part of the temporal lobe bilaterally with one temporal lobe generally much more involved than the other. 14-Aug-24 41

42. Cont... Autopsy studies showed the presence of virus in the olfactory bulbs, olfactory tracts, and the tracts of the limbic system which end in the hippocampus, amygdala, insula, cingulate gyrus, and olfactory cortex. 14-Aug-24 42

43. Cont... Viral meningitis is an acute illness characterized by fever, headache, stiff neck, photophobia, and varying degrees of nonspecific symptoms such as malaise, myalgia, nausea, vomiting, abdominal pain, or diarrhea. 14-Aug-24 43

44. Cont... Generally, neither disturbance of mental status nor abnormal neurological signs are characteristic of viral meningitis. The presence of obtundation, disorientation, seizures , or localized neurologic signs should suggest brain parenchymal involvement and a diagnosis of encephalitis or meningoencephalitis. 14-Aug-24 44

45. Cont... PCR is the gold standard for the diagnosis of HSV‐1 encephalitis with a sensitivity of 96% and a specificity of 99%. Because PCR can be falsely negative in the very early stage of infection, it is wise to continue acyclovir therapy in this setting and to test a repeat sample within three to five days. 14-Aug-24 45

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47. Cont... MRI imaging is a useful test for ascertaining HSV encephalitis and for differentiating post infectious encephalomyelitis from viral encephalitis. 14-Aug-24 47

48. Cont... A diagnosis of HSV encephalitis is supported by MRI findings showing bilateral temporal lobe involvement that is generally asymmetrical. CT imaging may reveal frontotemporal changes in HSV encephalitis. 14-Aug-24 48

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50. Cont... Diffusion restriction on diffusion weighted imaging (DWI) is more sensitive than FLAIR in the early phase of infection. 14-Aug-24 50

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52. Cont... On EEG, patients with HSV‐1 are significantly more likely to have periodic discharges and focal slowing in the frontotemporal and occipital areas, compared with patients with encephalitis of other etiologies. 14-Aug-24 52

53. Treatments No specific drug or serologic therapy is currently available for enterovirus or arbovirus infections. In general, viral meningitis due to enteroviruses is clinically mild, and most patients usually recover within 7–10 days without antiviral therapy. 14-Aug-24 53

54. Cont... Before antiviral agents became available for the treatment of HSV encephalitis, the disease was fatal in approximately 70 % of patients, with an additional 20–25 % surviving with severe disabilities. 14-Aug-24 54

55. Cont... The dose of acyclovir is 10 mg/kg IV every 8 h for 14–21 days. Foscarnet 120 to 200 mg/kg/day divided every 8 to 12 hours for 2 to 3 weeks is the treatment of choice for acyclovir-resistant HSV. 14-Aug-24 55

56. 3. Brain Abscess The incidence estimated at 1.3–100,000, with the rates slightly higher in children between 5 and 9 years of age and after the age of 60 years. 14-Aug-24 56

57. Cont... The most common predisposing conditions for the development of a brain abscess are infections in the middle ear, paranasal sinuses, mastoids, and teeth (dental abscess). 14-Aug-24 57

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59. Cont... Approximately 20 % of brain abscesses arise from a contiguous focus; 25 % are associated with hematogenous spread from a distant focus, such as a pyogenic lung abscess or bronchiectasis, and 25 % occur following trauma. 14-Aug-24 59

60. Cont... Brain abscesses develop as localized areas of cerebritis (i.e., poorly demarcated areas of encephalitis), initially consisting of bacteria in the brain parenchyma together with inflammation and edema. 14-Aug-24 60

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62. Cont... 1. Early cerebritis: There is little mass effect and minimal enhancement. 2. Late cerebritis: Characterized by the development of a necrotic center. Early abscesses,associated with a significant amount of edema and intense enhancement. 3. Early encapsulation: There is a well-defined mass with intense ring enhancement. 4. Late encapsulation: Mature abscesses have a collagen capsule, with less cerebritis and edema. The length of time required to form a mature abscess varies from weeks to months 14-Aug-24 62

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65. Cont... Streptococci are implicated in 60% to 70% of cases and include anaerobic as well as microaerophilic streptococci. Other anaerobes, particularly Bacteroides species and Prevotella species, are found in up to 40% of cases, usually in mixed culture. 14-Aug-24 65

66. Cont... Staphylococcus aureus is the underlying cause of 25 % of brain abscesses and often associated with trauma, endocarditis, or following a neurosurgical procedures 14-Aug-24 66

67. Cont... In patients with HIV infection, reactivation of toxoplasmosis ( most common infectious cause of focal brain lesions) can lead to brain abscesses. In approximately 25 % of cases no under- lying etiology can be established. 14-Aug-24 67

68. Cont... Headache is the most common symptom, in approximately 70% of cases. C lassic triad of focal neurological signs , fever , and headache is present in less than 50 % of cases. Fever is present in 40–50 % of cases. 14-Aug-24 68

69. Cont... Seizures are observed in approximately 25–45 % of patients by the time they present. The seizures are most often generalized and associated with frontal lobe lesions. 14-Aug-24 69

70. Cont... Sensitivity and specificity of MRI in differentiating abscess from tumor to 94% and 95%, respectively. 14-Aug-24 70

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73. Cont... Steroids are indicated only if significant cerebral edema is present, particularly if it is accompanied by rapid neurologic deterioration. 14-Aug-24 73

74. Cont... Neurosurgical approach summary (i) Total resection through craniotomy is now rarely considered first, except for patients with a large multilobulated abscess and severe cranial hypertension; (ii) Stereotactic aspiration by neuro‐navigation, either CT or MRI guided, is indicated for all patients with microbiologically undocumented brain abscess ≥1 cm; 14-Aug-24 74

75. Cont... (iii) An abscess size ≥2.5 cm is considered as a stand alone indication for drainage, Other indications for neurosurgery include placement of an external ventricular catheter for drainage of intraventricular abscess rupture and in selected cases of large cerebral or cerebellar abscess with hydrocephalus. 14-Aug-24 75

76. 4 . Spinal epidural abscess The epidural space is area posterolateral to the spinal cord between the dura and the vertebral column. Most SEAs occur in the thoracic area. 14-Aug-24 76

77. Cont... The infectious agent in SEAs is Staphylococcus aureus about 50% of the time. However, Streptococcus , gram-negative bacilli, anaerobes, fungi, and tuberculosis can also present with epidural abscess. Two third is hematogenous spread. 14-Aug-24 77

78. Cont... The classic presentation is a triad of fever, back pain / tenderness, and neurological deficits. The following staging system has been described: 1. Stage 1: Focal neck or back pain at the level of the spine affected. 2. Stage 2: Radicular pain and paresthesias. 14-Aug-24 78

79. Cont... 3. Stage 3: Motor weakness, sensory deficits, and bladder/bowel dysfunction 4. Stage 4: Progression to paralysis 14-Aug-24 79

80. Cont... MRI reveal an enhancing lesion with compression of the underlying neural tissue. Pus will be hyperintense on T2-weighted images and hypointense on T1-weighted images with restricted diffusion. Diskitis and osteomyelitis occur in 80% of patients and may be demonstrated on CT images as well as MRI. 14-Aug-24 80

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82. Cont... Surgical intervention for removal of pus and granulation tissue forms the basis of therapy, followed by a prolonged course of parenteral antimicrobials. If the patient has neurological signs at presentation, immediate surgical decompression of the spinal cord is absolutely essential. 14-Aug-24 82

83. 5. Cerebral malaria Cerebral malaria, in particular, is the most prominent and serious of these complications. Attributable mortality remains relatively high (20 %) and is often associated with delays in diagnosis and treatment. 14-Aug-24 83

84. Cont... As P . falciparum trophozoites mature in the red blood cells, they induce the formation of small knobs on the surface of the red cell. These knobs bind to adhesion molecules on the microvascular endothelial cells, leading to sequestration . 14-Aug-24 84

85. Cont... Sequestration is an important mechanism causing coma and death in cerebral malaria. The second important factor in the pathogenesis of cerebral malaria is the increase in cytokine production . 14-Aug-24 85

86. Cont... The end result of cytoadherence, rosetting, and rigidity is the enhancement of sequestration of P . falciparum -parasitized erythrocytes in the cerebral vasculature, stagnation of the cerebral blood flow... 14-Aug-24 86

87. Cont... and secondary ischemia leading to tissue hypoxia, lactic acidosis, hypoglycemia, and prevention of delivery of nutrients to the tissues. In the CNS, this process results in delirium, impaired consciousness, convulsions, paralysis, coma, and, ultimately, rapid death if not treated. 14-Aug-24 87

88. Cont... Quinine, 1.5–2 g, IV, over 4 h, q8h, for adults, and 25 mg/kg for children, then po, as soon as possible, for 3–10 days. It warrants hospital monitoring. Artesunate, 2.4 mg kg, IV, followed by the same dose at 12 and 24 h, then once daily until the patient is able to take artesunate (2 mg kg/day) po, to complete 7 days. 14-Aug-24 88

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90. Cont... Intravenous corticosteroids are associated with poor outcomes and are absolutely contraindicated. Mannitol therapy as adjunctive treatment for brain swelling in adult cerebral malaria prolongs coma duration and may be harmful. 14-Aug-24 90

91. Cont... Approximately 12 % of patients with cerebral malaria may have lasting neurologic sequelae, including cortical blindness, tremor, cranial nerve palsies, and sensory and motor deficits . 14-Aug-24 91

92. 6. Referrences 14-Aug-24 92

93. Thank you 14-Aug-24 93