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 Vessels cuffed by leukocytes Empyema Pus Skull
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 Meningitis
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 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 Necrotizing angiitis
Hemtogenous from lung
Direct extension from paranasal sinuses
Necrotizing angiitis
Usually CSF without detectable bug

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

23. Candidiasis Usually systemic nidus Seldom in immunologically intact
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. Amoebic Encephalitis Nucleated amoebae Hemorrhagic encephalitis
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. Toxoplasmosis H&E Tachyzoites Immunostained Tachyzoites
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 CNS involvement rare
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