Infections of the Central Nervous System

1
Infections of the Central Nervous System
E. Stolzenberg, MD, PhD
Department of Pathology University of Oklahoma
Health Sciences Center

2
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.

3
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.
4
Basic Pathologic Patterns in CNS Infection
Meningitis Meningoencephalitis Encephalitis,
Myelitis, Encephalomyelitis Choroid
plexitis Subdural empyema and epidural
abscess Cerebritis Ventriculitis and
ependymitis Brain abscess
5
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.
6
AcuteBacterialInfections
7
Bacterial Infections
Acute meningitis Cerebritis Granulomatous
meningitis and granuloma Ventriculitis and
ependymitis Brain abscess Subdural empyema and
epidural abscess Changes associated with
spirochetal infections
8
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.

9
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.

10
Bacterial Meningitis
Grahams and Lantos, 2002
Ellison D et al., 1998
Esiri and Oppenheimer, 1989
11
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.

12
Complications of Bacterial Infections
Thrombosed vessel
Hemorrhagic Ventriculitis
Grahams and Lantos, 2002
Petechial hemorrhage in meningococcemia
Ellison D et al., 1998
Infarct
Ellison D et al., 1998
Grahams Scheld WM et al., 1997
13
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.

14
Bacterial Infection Pyogenic Abscess
Ellison D et al., 1998
15
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
  dont react to light
• Dx VDRL, FTA-ABS
• Rx penicillin G

16
Fungal Infection
17
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.
18
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
19

• 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

20
Cryptococal meningitis
Klingsberg et al., 2001
Ellison D et al., 1998
21

• Aspergillus fumigatus
• Mold with septate hyphae that branches at acute
  angles
• Immunocompromised host, chronic granulomatous
  disease
• Rare cause of fungal meningitis

22
Aspergillosis
Ellison D et al., 1998
23

• Mucor and Rhizopus spp.
• Mold with irregular nonseptate hyphae branching
  at angles gt90 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

24
Zygomycosis (Mucormycosis)
Grahams Scheld WM et al., 1997
25
ViralInfections
26
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.
27
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. Inclusio
n- It can be nuclear or cytoplasmic. Demyelination
is associated with some viral infections such as
HIV encephalopathy and progressive multifocal
leukoencephalopathy (PML).
CMV
Rabies
Ellison D et al., 1998
28
Acute Viral Infection
29
Herpes Simplex Encephalitis
Ellison D et al., 1998
30
Herpes Simplex Encephalitis
Ellison D et al., 1998
31
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.

32
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
33
Herpes Simplex Encephalitis
EM
In situ hybridization
Necrosis
Ellison D et al., 1998
34
Subacute or Chronic Viral Infection
35
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.
36
Human Immunodeficiency Virus (HIV)
Microglial nodule
Multinucleated giant cells
Calcification
Ellison D et al., 1998