Acute non viral infections

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

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

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

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

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

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 Grocott Pseudo Hyphae From: Neuropathology Illustrated 1.0

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

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

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% Blood vessel with infected RBCs From: Neuropathology Illustrated 1.0 From: Neuropathology Illustrated 1.0

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 CT Multiple abscesses Basal ganglia abscess From: Neuropathology Illustrated 1.0

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

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

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