Post on 26-Dec-2015
Infections of the Central Nervous System
Department of PathologyUniversity of Oklahoma Health Sciences Center
E. Stolzenberg, MD, PhD
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.
AcuteBacterial
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
Ellison D et al., 1998Esiri and Oppenheimer, 1989
Grahams and Lantos, 2002
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
Infarct
Hemorrhagic Ventriculitis
Petechial hemorrhagein meningococcemia
Ellison D et al., 1998
Ellison D et al., 1998
Grahams and Lantos, 2002
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
• 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
Syphilis
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 Incidence
Predi-lection
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
ViralInfections
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.
Shared Pathologic
Aspects of Viral Infections
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.
Perivascular lymphocytic infiltration- the extent of inflammation may vary greatly.
Microglial formation and reactive gliosis.
Necrosis- usually occur as a later event than inflammation.
Inclusion- It can be nuclear or cytoplasmic.
Demyelination is associated with some viral infections such as HIV encephalopathy and progressive multifocal leukoencephalopathy (PML).
CMV
RabiesEllison 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
Ellison D et al., 1998
• 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.
Herpes Simplex Encephalitis
Ellison D et al., 1998
Necrosis In situ hybridization
EM
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.
Human Immunodeficiency Virus (HIV)
Ellison D et al., 1998
Microglial nodule
Multinucleated giant cells
Calcification