1. Acute non viral infections Bacterial Fungal Parasitic

2. Bacterial Infections of the CNS Neonatal bacterial meningitis –Common organisms Gram negative bacilli Streptococci –30-60% mortality –Significant long-term morbidity 35%

3. Common etiologic agents of bacterial meningitis Most common –Neisseria meningitidis –Group B Streptococcus Other Gram Positive –Listeria monocytogenes –Staphylococcus aureus Other Gram Negative –E. Coli –Citrobacter –Klebsiella –Pseudomonas –Proteus –Salmonella

4. Bacterial meningitis: Gross findings Edematous brain +/- herniation Hemorrhage and infarction Opacity of meninges –Subdural empyema Ventriculitis Obstructive hydrocephalus From: Neuropathology Illustrated 1.0

5. Meningitis From: Neuropathology Illustrated 1.0 Vessels cuffed by leukocytes Empyema From: Neuropathology Illustrated 1.0 Skull Pus

6. Bacterial meningitis: Microscopic findings Meningeal infiltrate with abundant neutrophils macrophages, fibrin and cell debris Extension into the Virchow- Robin space Vascular thrombosis and infarction (more common in neonates) From: Neuropathology Illustrated 1.0

7. Brain Abscess: Clinical Increasing CNS pressure + localizing signs If direct spread: frontal or temporal lobes Hematogenous spread: gray-white junction 50% morbidity –20% mortality

8. Brain Abscess: Pathogenesis Half result from direct spread from sinus –Etiology Streptococcus, Bacteroides, Actinomyces, aerobic gram negative bacilli 25% result from hematogenous spread –Children with congenital heart defects –Adults lung abcess or endocarditis Streptococcus –Etiologies: Toxoplasma, Nocardia, Listeria, Gram negative bacilli, mycobacteria, fungi

9. CT: Ring enhancing mass Well encapsulated abscess From: Neuropathology Illustrated 1.0

10. Brain Abscess: Microscopic progression 1-2 days: suppurative encephalitis 2-7 days: focal encephalitis with central necrosis 5-14 days: early encapsulation From: Neuropathology Illustrated 1.0

11. Epidural abscess Mostly in spinal canal Biconvex shape on MRI Direct extension most common Staphylococcus aureus

12. Tuberculosis meningitis Diffuse symptoms over 2-3 weeks –Later cranial nerves involved or increased CSF pressure –Decreased glucose and increased protein –PCR of CSF is diagnostic Gelatinous subarachnoid exudate –Sylvian fissure and base of brain –+/- tubercles with focal findings Abundant macropahges and necrotizing granuloma

13. From: Neuropathology Illustrated 1.0 Fite stained mycobacteria Leptomeningeal inflammation Tuberculosis meningitis

14. Syphilis Asymptomatic CNS involvement –CSF pleocytosis Meningitis –1-2 years post primary infection –Rarely symptomatic Meningovascular syphilis –Peak incidence 7 years post primary infection –Chronic meningitis and multifocal arteritis Parenchymatous neurosyphilis and Tabes Dorsalis –Peak incidence 10-20 years after initial infection –General paresis of the insane Gummatous neurosyphilis

15. From: Neuropathology Illustrated 1.0 Chronic infarcts secondary to end-arteritis Plasmacytic infiltrate Spirochetes Parenchymatous neurosyphilis

16. Lyme Disease Borrelia burgdorferi Stage 1: Days to weeks –Maculopapular rash Stage 2: Weeks to months –Meningitis with cranial nerve palsies Stage 3: Months to years –Axonopathy, encephalopathy, polyarthritis

17. Fungal Infections of the CNS Usually associated with immunosuppression Mostly hematogenous dissemination –Rare direct extension (mucormycosis) Yeasts - Leptomeningitis Hyphae - Hemorrhagic infarcts From: Neuropathology Illustrated 1.0

18. Aspergillosis Airborne spores from soil –Hemtogenous from lung –Direct extension from paranasal sinuses Necrotizing angiitis Usually CSF without detectable bug

19. Aspergillosis From: Neuropathology Illustrated 1.0 Branched Hyphae Grocott Stain H&E

20. Mucormycosis Most common form: Rhinocerebral –Direct extension from sinuses –Poorly controlled diabetic Hematogenous dissemination of Mucor is less common but usually from lung From: Neuropathology Illustrated 1.0 Early Abscess Broad Hyphae

21. Cryptococcosis Primary infection is usually pulmonary Meningitis versus abscess –Dilation of Virchow-Robin Space From: Neuropathology Illustrated 1.0

22. Cryptococcosis Encapsulated organism Stains with PAS & Mucicarmine Encapsulated organisms From: Neuropathology Illustrated 1.0

23. Candidiasis Usually systemic nidus –Intestinal overgrowth secondary to antibiotics –Catheterization or surgery Seldom in immunologically intact Microabcesses with hematogenous dissemination From: Neuropathology Illustrated 1.0 Grocott Pseudo Hyphae

24. Coccidioidomycosis or Histoplasmosis Soil organisms Inhaltion leades to primary pulmonary nidus –Pregnancy, diabetes or other immunosuppression From: Neuropathology Illustrated 1.0 Encapsulated 50 micron cyst

25. Parasitic Infections Amebic Infections –Cerebral amebic abscess –Primary amebic meningoencephalitis –Granulomatous amebic encephalitis

26. Cerebral amebic abscess Entamoeba histolytica –Common intestinal parasite –CNS abscess is rare and late complication –Hematogenous dissemination of trophozoites –Trophozoites identifiable in abscess wall

27. Primary amebic meningoencephalitis In immunocompetent host, etiologic agent –Naegleria fowleri –Ubiquitous environmental contaminant that seeds nasal passages Follows swimming in fresh water –Ascends into CNS through cribiform plate –Acute fulminant presentation with death in 72 hours

28. Amoebic Encephalitis From: Neuropathology Illustrated 1.0 Nucleated amoebae Hemorrhagic encephalitis

29. Granulomatous amebic encephalitis In immunocompromised host –Acanthamoeba or Balamuthia madrillaris Hematogenous dissemination into CNS from lower respiratory tract or skin –Subacute or chronic disease Focal deficits or seizures Usually fatal

30. Cerebral Malaria Any of four species of malaria 1-10% of P. falciparum have CNS involvement –Usually in children –Incubation period 1-3 weeks –Clinical presentation secondary to increased intracerebral pressure Pathogenesis –Occlusion of CNS capillaries by infected RBCs –Mortality 20-50% From: Neuropathology Illustrated 1.0 Blood vessel with infected RBCs

31. Cerebral Toxoplasmosis: Postnatally-acquired Definitive host is cat Infection of immunocompetent human is asymptomatic –High seropositivity (20-40% in US) CNS disease associated with compromised cell mediated immunity Ring enhancing lesions Pathology: –Necrotizing abscesses with coagulative necrosis and PMNs

32. Cerebral Toxoplasmosis From: Neuropathology Illustrated 1.0 CT Multiple abscesses Basal ganglia abscess

33. Toxoplasmosis From: Neuropathology Illustrated 1.0 Immunostained Tachyzoites H&E Tachyzoites

34. Cerebral Toxoplasmosis: Congenital Only a minority of cases show classical triad –hydrocephalus, calcifications and chorioretinits Results from transplacental spread in primary maternal infection Pathology –Multifocal necrosis Periventricular and sub-pial tachyzoites –Microcephaly

35. Cysticercosis Commonest parasitic infection of CNS –Larval form of pork tapeworm Taenia solium –Humans are usually definitive host –Pig intermediate host Cysts = Cysticerci most commonly in muscle –1-2 cm in diameter with single scolex –Calcifies

36. Cysticercosis From: Neuropathology Illustrated 1.0 H&E Scolex MRI Multiple cysts

37. Schistosomiasis Man definitive host –Adult schistosomes inhabit blood vessels –Large numbers of ova in blood CNS involvement rare –Retrograde passage of ova though pelvic veins –Spinal cord involvement From: Neuropathology Illustrated 1.0