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
From: Neuropathology Illustrated 1.0
Vessels cuffed by leukocytes
Empyema
From: Neuropathology Illustrated 1.0
Skull
Pus
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 1.0From: 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
From: Neuropathology Illustrated 1.0
Fite stained mycobacteria
Leptomeningeal inflammation
Tuberculosis meningitis
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
From: Neuropathology Illustrated 1.0
Chronic infarcts secondary to end-arteritis
Plasmacytic infiltrate Spirochetes
Parenchymatous neurosyphilis
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– Hemtogenous from lung– Direct extension from paranasal sinuses
• Necrotizing angiitis
• Usually CSF without detectable bug
Aspergillosis
From: Neuropathology Illustrated 1.0Branched Hyphae
Grocott Stain
H&E
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
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
Encapsulated organisms
From: Neuropathology Illustrated 1.0
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
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
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
From: Neuropathology Illustrated 1.0
From: Neuropathology Illustrated 1.0
Nucleated amoebae
Hemorrhagic encephalitis
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%
From: Neuropathology Illustrated 1.0From: Neuropathology Illustrated 1.0
Blood vessel with infected RBCs
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
From: Neuropathology Illustrated 1.0
CT Multiple abscesses
Basal ganglia abscess
Toxoplasmosis
From: Neuropathology Illustrated 1.0
From: Neuropathology Illustrated 1.0
Immunostained Tachyzoites
H&E Tachyzoites
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
From: Neuropathology Illustrated 1.0From: Neuropathology Illustrated 1.0
H&E ScolexMRI Multiple cysts
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