Acute non viral infections Bacterial Fungal Parasitic

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

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

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

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

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

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

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

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

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

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

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

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

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 10-20 years after initial infection General paresis of the insane Gummatous neurosyphilis

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

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

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

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

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

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

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

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

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

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

Parasitic Infections Amebic Infections Cerebral amebic abscess Primary amebic meningoencephalitis Granulomatous amebic encephalitis

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

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

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

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

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

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

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

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

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

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

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

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