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
From: Neuropathology Illustrated 1.0
Meningitis
Pus
Vessels cuffed by leukocytes
Skull
Empyema
From: Neuropathology Illustrated 1.0
Bacterial meningitis:
Microscopic findings
• Meningeal infiltrate with
abundant neutrophils
macrophages, fibrin and cell
debris
• Extension into the VirchowRobin 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
– 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
– Hemtogenous from lung
– Direct extension from paranasal sinuses
• Necrotizing angiitis
• Usually CSF without detectable bug
Aspergillosis
H&E
Branched Hyphae
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
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
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
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
Blood vessel with infected RBCs
Pathogenesis
– Occlusion of CNS capillaries by infected
RBCs
– Mortality 20-50%
From: Neuropathology
From:Illustrated
Neuropathology
1.0
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
H&E Tachyzoites
Toxoplasmosis
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
MRI Multiple cysts
From: Neuropathology Illustrated 1.0
H&E Scolex
From: Neuropathology Illustrated 1.0
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