7.2 Patho6 - Cns Infection 2015b
7.2 Patho6 - Cns Infection 2015b
7.2 Patho6 - Cns Infection 2015b
2 CNS INFECTIONS
Dr. Tilbe
FORMS OF CNS INFECTIONS Pathogenesis
A. Meningitis
The organisms that cause bacterial Meningitis colonize the
Infection limited to subarachnoid space
nasopharynx.
(leptomeningitis)
Or spread into the brain (meningoencephalitis)
B. Encephalitis Goes into the blood stream and enter the Subarachnoid
Inflammation of brain; most often due to virus space
Maybe diffuse (entire brain involved) or localized to a
part of the brain
C. Brain Abscess When bacteria die, lipids and oligosaccharides, including
Localized purulent infection of the brain endotoxin, are released from their walls (SEPSIS)
Typically caused by bacteria attracting circulating granulocytes and monocytes into the
Maybe solitary or multiple ( usually in sepsis ) CSF and cause vascular injury.
MENINGITIS
Maybe acute or chronic Lysed granulocytes and monocytes release lysosomal
Maybe purulent or serous (lymphocytic or aseptic) based enzymes and free radicals (destroy neural tissue and
on CSF findings damage blood vessels). Polyunsaturated fatty acids
Maybe infectious or non infectious released from the membranes of dying neutrophils also
Types of infectious meningitis: cause increased vascular permeability.
o Acute pyogenic (bacterial) meningitis,
o Aseptic (usually acute viral meningitis)
o Chronic (usually tuberculous, spirochetal, or Increased permeability (cerebral edema)
cryptococcal) Vasculitis (ischemia)
Sepsis Death from gram-negative shock
ACUTE BACTERIAL MENINGITIS
Route of Infection
Diagnosis: CSF EXAMINATION (Cornerstone)
o Hematogenous dissemination (More Common)
o Cloudy or frankly purulent CSF
o Direct extension(sinusitis, mastoiditis, brain abscess,
o Abundant neutrophils ( as high as 90,000
penetrating injury, congenital defect)
neutrophils/mm3)
o Cranial bone fracture due to trauma
o Elevated protein level
o During surgery
o Organisms are abundant
o Markedly reduced glucose content (used up by
Etiology
neutrophils)
o Neisseria meningitidis (most common in children)
o Streptococcus pneumoniae (most common in adults)
Morphology
o Hemophilus influenzae (children)
o Exudate is within the leptomeninges over the surface of
o Gram (-) bacteria ( E coli, Klebsiella, Enterobacter) in
the brain.
immunosuppressed following trauma or brain surgery
o The location of the exudate:
o E coli and group B streptococcus in neonates
H. influenzae meningitis: usually basal
Pneumococcal meningitis: cerebral convexities
Age Prevalence
near the sagittal sinus.
o Neonates: Escherichia coli and the group B streptococci
o Newborn and Elderly: Streptococcus pneumoniae and
Listeria monocytogenes.
o Infants : S. pneumoniae
o Adolescents and in young adults: Neisseria
meningitides
Clinical Features:
o Symptoms of headache, malaise, mental confusion,
and vomiting.
o Moderate CSF pleocytosis and elevated protein
concentration
o Most serious complications:
Arachnoid Fibrosis producing hydrocephalus
Obliterative Endarteritis producing arterial
occlusion and infarction
B. FUNGAL MENINGOENCEPHALITIS
primarily seen in immunocompromised patients
most common fungi involved:
Figure 3. Neutrophilic exudation of the subarachnoid space Candida albicans
Mucor
CHRONIC MENINGITIS Aspergillus fumigates
Onset: Insidious Cryptococcus neoformans
Duration: Weeks to Months hematogenous dissemination
Seen in: composed of three main patterns of fungal infection in the
o Tuberculosis CNS:
o Fungal Disease chronic meningitis
o Syphilis vasculitis
Sources parenchymal invasion
A. TB : Ruptured tubercles into the CSF or
hematogenous dissemination Parenchymal Invasion:
B. Fungal and Cryptococcal: hematogenous spread usually in the form of granulomas or abscesses
from lungs mostly encountered fungi:
C. Syphilis: manifestation of tertiary stage of syphilis. Candida:
a commensal fungi which rarely causes disease in
normal people
A. TUBERCULOUS MENINGOENCEPHALITIS infection is caused by organisms that are already
present in the intestines and other location
Morphology: Macroscopic
in neonates, it is transmitted from external
Subarachnoid space contains gelatinous or fibrinous
sources
grayish-white exudates.
most disseminated infections are nosocomial and
Often found at the base of the brain obliterating the
the key risk factors are catheters and antibiotics
cisterns and casing the cranial nerves.
causes meningitis, multiple microabscesses or
Most common pattern of involvement: Diffuse
extensive brain necrosis
Meningoencephalitis
at first inflammation consists of neutrophils;
later stage consists of epitheloid cells and giant
cells
C. CRYPTOCOCCAL MENINGITIS
hematogenous spread from the lungs
an opportunistic infection commonly seen in
immunocompromised
occurs as chronic meningitis/meningoencephalitis with
meningeal fibrosis hydrocephalus (due to CSF flow
obstruction)
may be fulminant and fatal in as little as 2 weeks or
indolent, evolving over months and years
can cause dementia and focal neurologic deficits
oval yeast about the size of a red cell, surrounded by a
Figure 4: Tuberculous exudates at the base of the brain gelatinous capsule
present in bird droppings, vegetables, and soil
Morphology: Microscopy immunosuppressed host: inflammation is absent or mild
o Caseating granuloma
3. Tabes Dorsalis
Damage to the sensory nerves in the dorsal roots
results in:
o Impaired joint position sense and resultant
ataxia (locomotor ataxia)
o Loss of pain sensation, leading to skin and
joint damage (Charcot joints)
o absence of deep tendon reflexes.
Histologic Findings
Obliterative endarteritis (Heubner arteritis)
Figure 5: cryptococci present in perivascular space
Perivascular inflammatory reaction rich in plasma
cells and lymphocytes
Cerebral gummas (plasma cell-rich mass lesions) may
occur in the meninges and extending into the cerebral
parenchyma
Symptoms of Meningitis
1. fever (more than 40C (bacterial); less than 40C (viral)
2. Onset: sudden for bacterial with prodrome for viral
3. Meningeal irritation and neurologic impairment:
headache, photophobia, irritability, clouding of
consciousness, neck stiffness
Figure 6: Brain section looks like “Swiss Cheese” due to cystic 4. As the disease progresses, confusion, coma, and
dilatation (organism grows in the subarachnoid and seizures develop
perivascular spaces. Presents with a gelatinous material within
the subarachnoid space and small cysts within the parenchyma Signs of Meningitis
(“Soap Bubble Appearance”) 1. Kernig sign (knee pain with hip flexion)
2. Brudzinski sign ( upon flexion of neck there is
Diagnosis spontaneous similar movement of the hips and knees
CSF analysis: 3. Increased CSF with changes in biochemical
mononuclear pleocytosis composition of CSF
elevated protein
low glucose Table 1: Cerebrospinal (CSF) Findings
mucoid encapsulated yeasts can be visualized in the
CSF by India ink preparations
PAS and mucicarmine as well as silver stains (tissue
sections)
antigens can be detected by latex agglutination
D. NEUROSYPHILIS
tertiary stage of syphilis infection
3 forms:
a. Meningovascular Neurosyphilis
b. Paretic Neurosyphilis
c. Tabes Dorsalis
COMPLICATIONS OF MENINGITIS
Scarring and obstruction of CSF leading to hydrocephalus
1. Meningovascular Neurosyphilis o Organization of fibrinopurulent exudate into fibrous
Morphology: Involves the base of the brain and variably also tissue >>> Block the exits of the 4th ventricle
the cerebral convexities and spinal leptomeninges Cranial nerve injury due to constriction may lead to
neurologic deficits
Meningovascular Lesions Destruction of brain parenchyma lead to mental deficits,
Lymphoplasmacytic infiltrates sensory defects
Intimal thickening of small and medium-size Epilepsy
leptomeningeal and parenchymal arteries (endarteritis Abscess Formation
obliterans- Heubner arteritis).
Parenchymal Lesions
Tabes dorsalis (rot of the spinal cord): Inflammation
and degeneration of dorsal roots and posterior
columns
General paresis of the insane (dementia paralytica)
o Encephalitis due to invasion of the brain by
spirochetes
PATHOGENESIS
Viruses
Activation of T-Lymphocytes
Mobilization of Macrophages
Figure 8: Postmeningitic Hydrocephalus
Severe Cases:
Necrotizing vasculitis with associated focal
hemorrhages
Viral Encephalitis:
CSF Findings
Usually colorless
Slightly elevated pressure
Figure 11: Activated microglial cells encircle degenerating Initially there is a neutrophilic pleocytosis
neurons (neuronophagia). Single-cell neuronal necrosis with lymphocytic pleocytosis
phagocytosis of the debris. Protein level is elevated
Sugar content is normal
Certain viruses cause intranuclear and cytoplasmic
inclusions.
These inclusions consist of packed viral particles and II. HERPES SIMPLEX VIRUS TYPE 1 (HSV-1)
products of their replication. ENCEPHALITIS
Viruses that cause inclusions are Most common in children and young adults
o Herpes simplex 10% of the patients have a history of prior herpes
o Cytomegalovirus Alterations in mood, memory, and behavior (most
o Varicella-zoster commonly observed clinical presenting symptoms)
o Papovaviruses Location: inferior and medial regions of the temporal
o Measles lobes and the orbital gyri of the frontal lobes (initial and
Intranuclear inclusions, e.g. herpetic infection (Cowdry most severely affected.
body) Most common year-round viral encephalitis
Cytoplasmic inclusions, e.g. rabies (Negri body) Most people become primarily infected with HSV in their
Nuclear and cytoplasmic inclusions e.g. (cytomegalovirus) teens or twenties
HSV type 1 is transmitted by the saliva
MORPHOLOGY:
Gross: Necrotizing and often hemorrhagic
Microscopic: Cowdry type A intranuclear viral inclusion
bodies in both neurons and glia
PATHOGENESIS:
Initial HSV infection stomatitis virus remains latent in the
trigeminal ganglion reactivated virus can spread in the:
Skin (along the branches of the trigeminal nerve)
Figure 12: Viral inclusion bodies sores on the lips (herpes labialis)
Brain infecting the meninges of the anterior and
Direct indications of viral infection: middle cranial fossae
o Viral inclusion bodies From the meninges, HSV extends to the adjacent brain
o Identification of viral pathogens by affects the temporal and inferior frontal lobes (first and more
ultrastructural, immunocytochemical, and severely) then spreads to the rest of the brain
molecular methods.
Presumptive indirect evidence: ADULT HSV ENCEPHALITIS
o An immune-mediated disease, such as Limited to the brain
perivenous demyelination following systemic Symptoms: fever, confusion, coma and seizures
viral infections Involvement of the frontal and temporal lobes – bizarre
behavior, personality changes, anosmia and gustatory
I. ARTHROPOD-BORNE VIRAL hallucinations
ENCEPHALITIS Survivors may have Korsakoff’s amnesia, dementia and
Arboviruses are an important cause of epidemic seizures
encephalitis
They are capable of causing serious morbidity and high
mortality
All have animals hosts and mosquito vectors except for
tick-borne type
Microscopic findings:
(1) Acute phase:
Meningeal and perivascular mononuclear cells
Increased microglia
Focal necrotizing vasculitis
Eosinophilic intranuclear inclusions in glial cells and
neurons
Clinical Features.
Initial manifestation: meningeal irritation and a CSF
picture of aseptic meningitis
May progress to involve the spinal cord where it causes
Figure 15: Neonatal HSV encephalitis. (Gross) Diffuse loss of motor neurons producing flaccid paralysis with
necrotizing encephalitis. In time, the lesions evolve into cystic muscle wasting and hyporeflexia in the corresponding
encephalomalacia with microcephaly. region of the body—the permanent neurologic residue
Pathogenesis:
Destruction of brain tissue progressive loss of neurological
function Pus and edema of surrounding tissue causes ICP to
Figure 20: HIV envelope glycoproteins cause the membranes elevate Increased ICP and progressive herniation can be
of HIV-infected macrophages to fuse >>> form multinucleated fatal.
giant cells (Black Arrow)= hallmark of HIV encephalitis. )
Microglial nodules are also found in the vicinity of small blood Morphology:
vessels.
Microscopic Findings:
Widespread gliosis and myelin degeneration
Viral inclusions, largely within the nuclei of
oligodendrocytes and neurons