Infections of the
Central Nervous System
E. Stolzenberg, MD, PhD
Department of Pathology
University of Oklahoma Health Sciences Center
Objectives
• Describe the microscopic and macroscopic
features of acute bacterial meningitis.
• Recognize the complications of bacterial
meningitis.
• Identify the characteristics of tertiary syphilis.
• Name the common causes of fugal meningitis.
• Recognize the histopathologic features of herpes
encephalitis.
Parameters of CNS Infection
Infectious agents: Bacteria, fungus, virus, protozoa, metazoa,
prion.
Mechanism: Acute, chronic, mixed, suppurative, abscess,
granulomatous.
Tissue involvement: Meningitis, meningoencephalitis,
encephalitis, ventriculitis, etc.
Distribution: Panencephalitis, rhombenencephalitis,
poliomyelitis, etc.
Route of entry: Blood, local infection, penetrating,
contaminated surgical procedures (eg. VP-shunt), etc.
Miscellaneous: Age, local factors, environmental factors,
underlying compromised immune system, cardiac
abnormalies, race and ethnic group, etc.
Basic Pathologic Patterns in CNS Infection
Meningitis
Meningoencephalitis
Encephalitis, Myelitis, Encephalomyelitis
Choroid plexitis
Subdural empyema and epidural abscess
Cerebritis
Ventriculitis and ependymitis
Brain abscess
Infectious Agents of the CNS
Bacteria: Pneumococcal meningitis, tuberculoma,
neurosyphilis, etc.
Fungus: Aspergillus abscess, cryptococcal meningitis,
etc.
Virus: Herpes simplex encephalitis, poliomyelitis, etc.
Protozoa: Primary amoebic meningoencephalitis,
toxoplasmosis, malarial encephalitis, etc.
Metazoa: Cysticercosis, schistosomiasis, etc.
Prion: Creutzfeldt-Jakob disease, Kuru, Fatal familial
insomnia, etc.
Acute
Bacterial
Infections
Bacterial Infections
Acute meningitis
Cerebritis
Granulomatous meningitis and granuloma
Ventriculitis and ependymitis
Brain abscess
Subdural empyema and epidural abscess
Changes associated with spirochetal infections
Acute bacterial Meningitis
Definition: An acute inflammatory process that
is limited to the meninges and subarachnoid
space.
Epidemiology:
• About 25,000 cases/year in the U.S.
• Over 70% occur in children under 5 years-old.
• Mortality without antibiotics: 90-100%
• Mortality with antibiotic treatment: 5-15%.
• Morbidity: 43%.
Pathology of Acute Bacterial Meningitis
Macroscopic:
• Cerebral edema and congested leptomeninges.
• Thrombosis, hemorrhagic infarctions.
• Purulent exudate in the subarachnoid space.
Microscopic:
• Polymorphonuclear leukocytes infiltrating the
leptomeninges, subarachnoid space and ventricles.
• Angiitis and thrombosis.
• Necrotic debris and macrophages.
• Fibrotic scarring of the leptomeninges.
Bacterial Meningitis
Grahams and Lantos, 2002
Ellison D et al., 1998
Esiri and Oppenheimer, 1989
Complications of Acute Bacterial Meningitis
• Cerebral edema leading to increased
intracranial pressure, herniation and
compromised cerebral blood supply.
• Cerebritis.
• Arterial and venous infarction of the brain.
• Mycotic aneurysm.
• Hydrocephalus, due to scarring of the
arachnoid granulations.
Complications of Bacterial Infections
Thrombosed vessel
Hemorrhagic Ventriculitis
Grahams and Lantos, 2002
Ellison D et al., 1998
Petechial hemorrhage
in meningococcemia
Infarct
Ellison D et al., 1998
Grahams Scheld WM et al., 1997
Brain Abscess
Definition: A localized suppurative infection within the brain
parenchyma.
Pathogenesis:
•
About 50% of the cases are due to localized spread of a
septic focus in the paranasal sinuses, middle ear, or dental
infection.
•
About 25% of the cases are secondary to hematogenous
spread from an infectious source outside the head. Example:
congenital heart disease with right-to-left shunt.
•
The rest are due to trauma and miscellaneous etiology such
as compromised immunity such as transplantation.
•
Bacterial profile is related to the route of spread and include
Streptococcus milleri, anaerobic bacteria, Actinomyces
israelii and others.
Bacterial Infection: Pyogenic Abscess
Ellison D et al., 1998
Syphilis
•
•
•
•
Treponema pallidum
Primary syphilis – localized disease
Secondary syphilis – systemic disease
Tertiary syphilis
– Chronic granulomas
– Aortitis
– Neurosyphilis, tabes dorsalis
• dementia, confusion, irritability, headache, tremors, incontinence
• Abnormal gait, sensory ataxia (degeneration of dorsal columns
and dorsal roots)
– Argyll Robertson pupil – pupils accommodate but don’t
react to light
• Dx: VDRL, FTA-ABS
• Rx: penicillin G
Fungal Infection
Fungal Infections of the CNS
General: They can occur as fungal meningitis or space
occupying lesions such as abscess or solid inflammatory
mass.
Shape of the fungus: The pathology is often related to the
shape of the fungus. Fungi that exist only as yeast form in
human body often cause meningitis, those with filamentous
form often cause infarction and abscess, those that can
exist as both forms can cause both.
Epidemiology: Some species are more common than the other
and the incidence is geographically related.
Predisposing factors: Unlike bacterial infections that
predisposing factors play a relatively minor role,
predisposing factors and underlying systemic disorders play
a major role. Particularly, patients are not always
immunocompromised.
Organism
Incidenc
e
Predilection
Meningitis Abscess or
Infl. mass
Infarct
Cryptococcus
+++
++++
++++
+
+
Coccidiodes
+++
++++
++++
+
+
Candida
+++
++
++
++
-
Aspergillus
++
++
+
+++
++++
Zygomycetes
++
++
+
+++
++++
Histoplasma
++
+
+
+
+
Blastomyces
++
+
+
+
-
Sporothrix
++
+
+
-
-
Paracoccidioides
+
±
+
±
-
Dermatiaceous spp
+
+++
±
++++
-
Pseudoallescheria
+
+
++
++
-
Grahams Scheld WM et al., 1997
•
•
•
•
Crytococcus neoformans and gattii
Heavily encapsulated yeast
Found in soil, pigeon droppings
Opportunistic infection: AIDS and
immunosuppressed patients (including long-term
corticosteroid use)
• Diagnosis:
– Detection of cryptococcal antigen (capsular
material) by culture of CSF, sputum, urine
– India ink: poor sensitivity
Cryptococal meningitis
Ellison D et al., 1998
Klingsberg et al., 2001
• Aspergillus fumigatus
• Mold with septate hyphae that branches at acute
angles
• Immunocompromised host, chronic
granulomatous disease
• Rare cause of fungal meningitis
Aspergillosis
Ellison D et al., 1998
• Mucor and Rhizopus spp.
• Mold with irregular nonseptate hyphae branching
at angles >90 degrees
• Ketoacidotic diabetes and leukemia patients
• Rhinocerebral, frontal lobe abscesses
• Fungi proliferate in blood vessel walls, enter the
brain through cribiform plate
• Headache, facial pain, black necrotic eschar on
face
Zygomycosis (Mucormycosis)
Grahams Scheld WM et al., 1997
Viral
Infections
Shared Aspects of Viral Infections
General: Many of them occur as viral meningitis or
meningoencephalitis, a few (such as herpes simplex
encephalitis) manifest as a necrotizing mass-like lesion.
Direct cytotoxic effects vs. necrosis and inflammation.
Distribution: Different viruses, often but not always,
have a predilection on different parts of the nervous
system.
Reactivation: Reactivation of an indolent or subclinical
infection occurs in some viruses such as herpes
simplex virus and JC virus.
CSF: There is usually marked elevation of lymphocytes
without reduction in glucose level.
Detection: The viral genome are often
detectable by molecular techniques such
as in situ hybridization (on tissue) and PCR
(on tissue and CSF). Immunostaining is
also useful.
Shared
Pathologic
Aspects of Viral
Infections
Perivascular lymphocytic infiltration- the
extent of inflammation may vary greatly.
Microglial formation and reactive gliosis.
Necrosis- usually occur as a later event
than inflammation.
CMV
Inclusion- It can be nuclear or cytoplasmic.
Demyelination is associated with some
viral infections such as HIV
encephalopathy and progressive multifocal
leukoencephalopathy (PML).
Rabies
Ellison D et al., 1998
Acute Viral Infection
Herpes Simplex Encephalitis
Ellison D et al., 1998
Herpes Simplex Encephalitis
Ellison D et al., 1998
Herpes Simplex Encephalitis
Characteristics: The only common form of encephalitis that
can occur around the year. Typically presents as space
occupying lesion in the temporal lobe.
Pathogen: Herpes simplex virus, usually type I.
Routes of entry and pathogenesis:
• Primary mucocutaneous infection.
• Establishment of latency in trigeminal ganglion or dorsal
root ganglion and reactivation of virus.
• Olfactory bulb.
Herpes Simplex Encephalitis
• Characteristic widespread,
bilateral but asymmetrical
involvement. Necrosis,
particularly in the temporal lobe
and the hippocampus.
• Cingulate gyrus may also be
involved. The brain stem is rarely
involved.
Ellison D et al., 1998
Herpes Simplex
Encephalitis
EM
Necrosis
In situ hybridization
Ellison D et al., 1998
Subacute or Chronic
Viral Infection
Subacute and Chronic Viral Infections
General: They tend to progress slowly over months or
years rather than weeks or days. The incubation period
is often longer. Reactivation of a latent infection in an
immunocompromised host is responsible in some of
them.
Virus type
Disease
Measle virus
Subacute sclerosing panencephalitis
Measle virus
Measle inclusion body encephalitis
Rubella virus
Progressive rubella panencephalitis
JC virus
Progressive multifocal leukoencephalopathy (PML)
HIV
HIV encephalitis, vacuolar myelopathy, etc.
.
Microglial nodule
Human Immunodeficiency
Virus (HIV)
Multinucleated giant cells
Calcification
Ellison D et al., 1998