6.7.

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

Figure 1. Purulent exudate covers the cerebral hemispheres

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 o Mild cases: lymphocytes, plasma cells, and
macrophages.
o Florid cases: well-formed granulomas, often with
central caseous necrosis and giant cells.

Figure 2. Exudates settle along the base of the brain, around

cranial nerves, and the openings of the fourth ventricle.
Figure 5. Epithelioid cell granulomas with Langhans giant
cells, lymphocytic infiltrates, and central caseous necrosis.

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

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 immunocompetent host: cell mediated immune reaction
with lymphocytes and epitheloid cell granulomas
Morphology: Microscopy
 Parenchymal lesions consist of aggregates of
organisms within expanded perivascular (Virchow-
Robin) spaces associated with minimal or absent
inflammation or gliosis
 Infiltrates consist of chronic inflammatory cells and
fibroblasts admixed with cryptococci
Figure 5: cryptococci present in perivascular space
Figure 6: Brain section looks like “Swiss Cheese” due to cystic
dilatation (organism grows in the subarachnoid and
perivascular spaces. Presents with a gelatinous material within
the subarachnoid space and small cysts within the parenchyma
(“Soap Bubble Appearance”)
 Diagnosis
 CSF analysis:
 mononuclear pleocytosis
 elevated protein
 low glucose
 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
1. Meningovascular Neurosyphilis
Morphology: Involves the base of the brain and variably also
the cerebral convexities and spinal leptomeninges
Meningovascular Lesions
 Lymphoplasmacytic infiltrates
 Intimal thickening of small and medium-size
leptomeningeal and parenchymal arteries (endarteritis
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
Mattus Medina Pamintuan Panday Parabuac Rejante
o Insidious but progressive loss of mental and
physical functions
o Mood alterations (including delusions of
grandeur), terminating in severe dementia
2. Paretic Neurosyphilis
 Loss of neurons with proliferations of microglia,
gliosis, and iron deposits (perivascularly and in the
neuropil, presumably from damage to the
microcirculation)
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)
 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
4. As the disease progresses, confusion, coma, and
seizures develop
Signs of Meningitis
1. Kernig sign (knee pain with hip flexion)
2. Brudzinski sign ( upon flexion of neck there is
spontaneous similar movement of the hips and knees
3. Increased CSF with changes in biochemical
composition of CSF
Table 1: Cerebrospinal (CSF) Findings
COMPLICATIONS OF MENINGITIS
 Scarring and obstruction of CSF leading to hydrocephalus
o Organization of fibrinopurulent exudate into fibrous
tissue >>> Block the exits of the 4th ventricle
 Cranial nerve injury due to constriction may lead to
neurologic deficits
 Destruction of brain parenchyma lead to mental deficits,
sensory defects
 Epilepsy
 Abscess Formation
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Figure 7: Vascular narrowing after meningitis
Figure 8: Postmeningitic Hydrocephalus
 TB Meningitis: Epithelioid cell granulomas destroy
the pia and invade the brain.
 Obliterative Endarteritis: Inflammatory infiltrates in
arterial walls and marked intimal thickening >>
Arterial occlusion and infarction of underlying brain.
 Long-Standing Cases: Dense, fibrous adhesive
arachnoiditis
 Tuberculoma: Tumor-like mass, single or multiple
well-circumscribed intraparenchymal mass. May
cause significant mass effect.
ACUTE ASEPTIC (VIRAL) MENINGITIS
 Generally of viral etiology
o 70% of cases, a pathogen can be identified,
most commonly an enterovirus
 Clinical Manifestations: meningeal irritation, fever,
and alterations of consciousness of relatively acute
onset.
o Less fulminant course: self-limiting
 Usually associated with:
o encephalitis
o meningoencephalitis
 Source of Infection:
o Secondary infection in the coarse of SVI
(measles, varicella, mumps)
o Primary infection which maybe
 Sporadic (HSV)
 Epidemic (arthropod transmitted
arbovirus)
 Nonspecific gross findings
 Microscopic findings:
o No abnormality or
o Mild to moderate infiltration of the
leptomeninges with lymphocytes.
 CSF:
o Lymphocytic pleocytosis,
o Moderate protein elevation
o Sugar content is nearly always normal.
REVIEW: VIRUSES
 Obligate intracellular organisms.
 Use cellular machinery for their replication and damage or
kill the cells they infect.
 Additional brain damage is caused by the cell-mediated
immune reaction that they elicit.
 Routes of Viral Infection
Mattus Medina Pamintuan Panday Parabuac Rejante
o Respiratory tract (Mumps, Measles)
o Gastrointestinal tract (Enteroviruses)
o By inoculation from insect bites (Arthropod-borne
viruses)
o From animal bites (Rabies)
 Most viruses reach the CNS via the bloodstream.
 Some viruses travel to the CNS along nerves
o Herpes simplex virus(HSV)
o Varicella-zoster virus (VZV)
o Rabies
 Some viruses have a predilection for certain groups of
neurons.
o Poliomyelitis attacks anterior horn cells
o Varicella-zoster involves sensory ganglion cells
PATHOGENESIS
Viruses
Activation of T-Lymphocytes
Release of Potent Cytokines
(INF-Gamma, IL-2, TNF,
Lymphotoxin)
Mobilization of Macrophages
Attack Virus assault the host
Causing severe vascular and
tissue injury
 Parenchymal viral infection of the brain associated with
meningeal inflammation = Meningoencephalitis
 Simultaneous involvement of the spinal cord =
Encephalomyelitis.
Viral encephalitis:
 Characteristic Histologic Features:
o Perivascular and parenchymal mononuclear cell
infiltrates (lymphocytes, plasma cells, and
macrophages)
o Glial cell reactions (including the formation of
microglial nodules, and neuronophagia).
 Viral infection of neurons and glial cells by viruses
impairs neurological function and may cause seizures,
focal neurologic deficits and coma.
 Early phase:
o Neutrophilic infiltration initially of lymphocytes
and macrophages.
o Infiltrates the arachnoid membrane and the brain
diffusely but are more concentrated around blood
vessels.
Figure 9: Perivascular Cuffing
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 Microscopic:
 The encephalitides caused by various arboviruses differ in
epidemiology and prognosis, but the histopathologic
picture is similar, except for variations in the severity and
extent of the lesions within the CNS
 Lymphocytic meningoencephalitis
 Perivascular cuffing (tendency for inflammatory cells to
accumulate perivascularly)
 Neurophagia (single-cell neuronal necrosis with
phagocytosis of the debris)
 Microglial nodules (small aggregates of microglial cells
around foci of necrosis)
Figure 10: Activated microglial cells proliferate diffusely and
form clusters around small foci of necrotic brain tissue
Clinical Manifestations:
(microglial nodules). These are histological clues of viral
 Generalized neurologic deficits, such as seizures,
infection
confusion, delirium, and stupor or coma
 Focal signs such as reflex asymmetry and ocular
palsies

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

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Figure 13: Adult HSV encephalitis (gross) - diffuse softening
and edema, hemorrhagic necrosis of the inferior frontal and
temporal lobes
Microscopic findings:
(1) Acute phase:
 Meningeal and perivascular mononuclear cells
 Increased microglia
 Focal necrotizing vasculitis
 Eosinophilic intranuclear inclusions in glial cells and
neurons
Figure 14: Intranuclear eosinophilic amorphous or droplet-like
bodies surrounded by a clear halo (pointed structures)
(2) End stage:
 Brain atrophy and gliosis
 Brain destruction is more severe than any other viral
encephalitis
CSF Findings:
 Pleocytosis (early neutrophils, late lymphocytes)
 Elevated protein (depends on the degree of brain
necrosis)
 Glucose is normal
III. HERPES SIMPLEX VIRUS TYPE 2 (HSV-2)
 HSV-2 infection of the brain is usually manifested in
adults as meningitis
 Severe encephalitis develops in as many as 50% of
neonates born by vaginal delivery to women with active
primary HSV genital infections
 HSV-2 may cause an acute, hemorrhagic, necrotizing
encephalitis in AIDS patients
NEONATAL HSV INFECTION
 70% are caused by HSV type II (herpes genitalis)
 Acquired during vaginal delivery
 HSV transmitted across the placenta
 Acquired by babies in the NB nursery or at home
Figure 15: Neonatal HSV encephalitis. (Gross) Diffuse
necrotizing encephalitis. In time, the lesions evolve into cystic
encephalomalacia with microcephaly.
Mattus Medina Pamintuan Panday Parabuac Rejante
IV. CYTOMEGALOVIRUS (CMV)
 Infected pregnant mother may transmit the virus to the
fetus, causing a generalized fetal CMV infection
 CMV infection may develop at any stage during
pregnancy and may continue after delivery
 CNS infection occurs in fetuses and immunosuppressed
individuals
 In utero infection: periventricular necrosis  severe brain
destruction  microcephaly with periventricular
calcification
 Infected neurons and glial cells enlarge and develop
cytoplasmic and intranuclear inclusions
Figure 16: Cytomegaly and intranuclear inclusions
Figure 17: (Gross: Congenital CMV, cortical atrophy and
calcifications) heavily infected areas become necrotic and
calcify. Lesions have a predilection for the walls of the
ventricles. Infection before mid-gestation may derange the
process of neuronal migration, causing microcephaly and
cortical dysplasia.
Cytomegalovirus Encephalitis
 Rare in adults and usually occurs as part of a
generalized CMV infection in immunocompromised
patients
 Most common opportunistic viral pathogen in
patients with AIDS, affecting the CNS in 15-20% of
cases
V. POLIOMYELITIS
 Poliovirus infection causes a subclinical or mild
gastroenteritis.
 Secondarily invades the nervous system in vulnerable
persons
Morphology
 Acute cases
 Mononuclear cell perivascular cuffing
 neuronophagia of the anterior horn motor neurons of
the spinal cord.
 Postmortem examination in long-term survivors of
symptomatic poliomyelitis shows loss of neurons and
gliosis in the affected anterior horns of the spinal cord,
some residual inflammation, atrophy of the anterior
(motor) spinal roots, and neurogenic atrophy of
denervated muscle.
Clinical Features.
 Initial manifestation: meningeal irritation and a CSF
picture of aseptic meningitis
 May progress to involve the spinal cord where it causes
loss of motor neurons producing flaccid paralysis with
muscle wasting and hyporeflexia in the corresponding
region of the body—the permanent neurologic residue
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 In acute disease, death can occur from paralysis of the VII. HUMAN IMMUNODEFICIENCY VIRUS
respiratory muscles, and a myocarditis sometimes  60% of patients with AIDS develop neurologic
complicates the clinical course. dysfunction during the course of their illness
 sis or paralysis  Infects and destroys CD4 lymphocytes, causing immune
follows (when it involves the innervation of the deficiency
 Neurologic Dysfunction due to:
compromise may occur and cause long-term morbidity)  Direct or indirect effects of HIV
 Opportunistic infection
Post-polio syndrome  Primary CNS lymphoma
 25 to 35 years after the resolution of the initial illness. If there is CNS lymphoma you should rule out the
 Progressive weakness associated with decreased muscle possibility of immunodeficiency of whatever cause
mass and pain  AIDS patients are susceptible to opportunistic infections
 CNS toxoplasmosis
VI. RABIES  Cryptococosis and other mycoses
 Severe encephalitis  CMV encephalitis
 Transmitted to humans by the bite of a rabid animal, a  Papovavirus infections (PML)
dog or various wild animals  AIDS patients develop cerebral and other extranodal B-
Morphology cell lymphomas
Gross:  Directly cause aseptic meningitis, encephalitis,
Brain shows intense edema and vascular congestion leukoencephalopathy, myelopathy, neuropathy, and
myopathy
Microscopic:
 Widespread neuronal degeneration Patterns of inflammation:
 Inflammatory reaction; most severe in the brainstem (basal  Aseptic meningitis
ganglia, spinal cord, dorsal root ganglia may also be  Encephalitis
infected)  Meningoencephalitis
 Regions most severely affected: midbrain, floor of fourth
ventricle (part in the medulla) 1. ASEPTIC HIV 1 MENINGITIS
o occurs 1-2 weeks of seroconversion in about 10% of
patients; antibodies to HIV can be demonstrated and
the virus can be isolated from the CSF
o mild lymphocytic meningitis, perivascular
lymphocytic inflammation, and some myelin loss in
the hemispheres.
o Among the cell types of the CNS, only microglia have
the appropriate combination of CD4 and a chemokine
receptor (CCR5 or CXCR4) to allow for the efficient
infection by HIV.
o During the chronic phase, an HIV encephalitis is
o commonly found when symptomatic individuals
come to autopsy.

2. HIV 1 MENINOENCEPHALITIS (SUBACUTE

ENCEPHALITIS)
Figure 18: Negri bodies = Pathognomonic microscopic finding o Presents with AIDS-dementia complex
for Rabies o Cognitive changes, both mild and florid enough to be
 Cytoplasmic, round to oval, eosinophilic inclusions in termed, HIV associated dementia, appear to have
pyramidal neurons of the hippocampus and Purkinje persisted into the era of effective anti-HIV treatment
cells of the cerebellum (sites usually devoid of regimens.
inflammation)
 Contains rabies virus HIV Encephalitis
 Causes AIDS-dementia complex: progressive memory
Clinical Features: loss, intellectual deterioration, behavioral changes, and
 Virus enters the CNS by ascending along the peripheral motor deficits
nerves from the wound site  Damage to neurons and oligodendrocytes occurs
 Incubation period (bet 1 and 3 months) depends on the indirectly through the release of toxic cytokines and
distance between the wound and the brain alterations of the blood-brain barrier
 The disease begins with nonspecific symptoms (malaise,
headache, fever) but the conjunction of these symptoms Morphology:
with local paresthesias around the wound is diagnostic. Gross
 As the infection advances, the affected individual exhibits  Meninges are clear
extraordinary CNS excitability; the slightest touch is  Ventricular dilation with sulcal widening
painful, with violent motor responses progressing to  Normal cortical thickness
convulsions. Contracture of the pharyngeal musculature Microscopic:
on swallowing produces foaming at the mouth, which  Diffuse myeline damage (spongy myelinopathy, gliosis)
may create an aversion to swallowing even water  Neuronal loss
(hydrophobia).  Vascular damage
 There is meningismus, and as the disease progresses,  Microglial nodules
flaccid paralysis.  Lymphocytic infiltrates
 Periods of alternating mania and stupor progress to coma
and death from respiratory center failure.

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 BRAIN ABSCESS
 Arise by:
1. Direct extension from infection in
neighborhood, e.g., middle ear-mastoid, paranasal sinuses,
open wounds
2. Hematogenous, particularly from endocarditis and
bronchial-pulmonary infections
Figure 19: chronic inflammatory reaction with widely  Predisposing conditions:
distributed infiltrates of microglial nodules, sometimes with  Acute bacterial endocarditis >> multiple abscesses
associated foci of tissue necrosis and reactive gliosis  Cyanotic CHD: right-to-left shunt >> pulmonary
filtration of organisms is lost
 Chronic pulmonary sepsis (bronchiectasis).
**Streptococci and staphylococci: most common organisms in
non-immunosuppressed
 CSF findings:
 increased pressure;
 white cell count and protein level are elevated
 Sugar content is normal.

Figure 20: HIV envelope glycoproteins cause the membranes
of HIV-infected macrophages to fuse >>> form multinucleated
giant cells (Black Arrow)= hallmark of HIV encephalitis. )
Microglial nodules are also found in the vicinity of small blood
vessels.
Pathogenesis:
Destruction of brain tissue  progressive loss of neurological
function Pus and edema of surrounding tissue causes ICP to
elevate  Increased ICP and progressive herniation can be
fatal.
Morphology:

 An important component of the microglial nodules the

macrophage-derived multinucleated giant cell.
 In some cases there is also a disorder of white matter
characterized by multifocal or diffuse areas of myelin
pallor, axonal swelling, and gliosis.

Congenital HIV infection

 Caused when an HIV infected mother transmits the
infection to the fetus
 More severe than the adult form may result in
microcephaly
 Distinctive feature of congenital AIDS: basal ganglia
calcification
Pathogenesis
 Virus is carried into the brain by infected CD4
lymphocytes and perivascular monocytes
 Microglial cells pick up free viral particles
 The only cells that harbour HIV in the brain are
perivascular monocytes and microglia
 Brain damage is caused mainly by activated monocytes
and microglial cells producing:
 Cytokines (such as TNF)
 Neurotoxins (such as glutamate and NO
produced by activated monocytes and
microglial cells)
VIII. SUBACUTE SCLEROSING PANENCEPHALITIS
(SSPE)
 Rare
 Progressive clinical syndrome characterized by cognitive
decline, spasticity of limbs, and seizures.
 It occurs in children or young adults, months or years
after an initial, early-age acute infection with measles.
 Probably due to persistent infection of the CNS by an
altered measles virus
Figure 21: (Gross) Discrete lesions with central liquefactive
necrosis, a surrounding fibrous granulation tissue capsule, and
edema.
I. CEREBRAL TOXOPLASMOSIS
 Etiology: Toxoplasma gondii
 One of the most common causes of neurologic symptoms
and morbidity in patients with AIDS.
 Clinical symptoms are subacute, evolving during a 1- or 2-
week period, and may be both focal and diffuse.
 Primary maternal infection with toxoplasmosis ( early in
the pregnancy)  cerebritis in the fetus production of
multifocal cerebral necrotizing lesions  calcify 
producing severe damage
Morphology:
 Gross: Brain shows abscesses most involving the
cerebral cortex (near the gray-white junction) and
deep gray nuclei
 Microscopy: Acute lesions consist of central foci of
necrosis with variable petechiae surrounded by acute
and chronic inflammation, macrophage infiltration,
and vascular proliferation

Microscopic Findings:
 Widespread gliosis and myelin degeneration
 Viral inclusions, largely within the nuclei of
oligodendrocytes and neurons

Mattus Medina Pamintuan Panday Parabuac Rejante UERM 2015B Page 8 of 8