Central Nervous System

Infections
Gonzalo B. Roman Jr.,MD.,FPSP
Routes of Infections

1. Hematogenous spread – the most

common
2. Direct implantation – usually
traumatic
3. Local extension – mastoiditis,
infected tooth
4. Peripheral nervous system – rabies,
herpes simplex
Damage to nervous tissues

1. direct injury of neurons or glia by the

infectious agents
2. indirectly through:
- the elaboration of microbial toxins
- destructive effects of the
inflammatory response
- the influence of immune mediated
mechanisms
ACUTE MENINGITIS

 Leptomeningitis or meningitis refers to

inflammatory process of the leptomeninges
and CSF within the subarachnoid space.
 Meningoencephalitis applies to inflammation
of the meninges and brain parenchyma.
 Meningitis can be:
1. infectious
2. chemical
3. tumor – meningeal carcinomatosis
Classified into:

1. acute pyogenic (usually bacterial)

2. aseptic (usually viral)
3. chronic (tb, fungal etc)
Acute Pyogenic Meningitis
The microorganism that cause acute pyogenic
meningitis vary with the age of the patient.
 Neonates – Escherichia coli and group B
streptococci
 Infants and children – S. pneumoniae
 Adolescents and young adults – Neisseria
meningitides
 Elderly – Streptococcus pneumonia and
Listeria monocytogenes
Clinical evidence of meningeal
irritation
- headache
- photophobia
- irritability
- clouding of consciousness
- neck stiffness.
CSF FINDINGS

- cloudy or frankly purulent CSF

- increased opening pressure
- pleocytosis (as many as 90,000
neutrophils/mm3)
- raised protein level
- markedly reduced glucose content
ACUTE ASEPTIC MENINGITIS

-- Absence of recognizable organism by

traditional methods.
-- Generally viral in nature.
-- Clinical course is less fulminant compared
to bacterial meningitis
-- CSF findings:
- lymphocytic pleocytosis
- protein elevation is only moderate
- sugar content is nearly always normal
Acute Aseptic Meningitis

- enterovirus
- echovirus, coxsackievirus and
nonparalytic poliomyelitis are
responsible for up to 80% of these
cases.
- patients usually recover
- DRUG INDUCED ASEPTIC
MENINGITIS e.g. NSAIDS, Antibiotic
Acute Aseptic Meningitis -
Morphology
- No distinctive macroscopic
characteristic except for brain swelling.
- Microscopically – usually normal or
only mild to moderate infiltration of the
leptomeninges with lymphocytes.
Brain Abscess

May arise by:

1. direct implantation of organisms
2. local extension from adjacent foci
(mastoiditis, paranasal sinusitis)
3. hematogenous spread (usually from a
primary site in the heart, lungs or
distal bones or after tooth extraction)
Predisposing condition

- acute bacterial endocarditis

- cyanotic congenital heart disease
(right to left shunt with loss of
pulmonary filtration)
- chronic pulmonary sepsis
(e. g. bronchiectasis)
Brain abscess

Streptococci and staphylococci are

the most common offending
organisms.
Most commonly affected brain
regions

in descending order of frequency

- frontal lobes
- parietal lobes
- cerebellum
Brain abscess - histology

 Exuberant granulation tissue

 Fibrous capsule
 Reactive gliosis just outside capsule
CSF findings

- increased opening pressure

- elevated white cell count
- elevated protein
- normal sugar
Subdural empyema
- Bacterial or fungal infection of the
subdural space usually from previous
infection of skull bones or air sinuses.
- can present as SOL.
- A thrombophlebitis may develop in the
bridging veins that cross the subdural
space, resulting in venous occlusion and
infarction of the brain.
Subdural empyema
- With treatment (surgical drainage, antibiotics)
resolution of the empyema occurs.
- A thickened dura may be the only residual
findings.
- Most patients are febrile, with headache and
neck stiffness and if untreated may develop
focal neurologic signs, lethargy and coma.
- CSF profile is similar to brain abscess.
Extradural Abscess

 Associated with osteomyelitis

 May cause compression of underlying
neural tissues
Tuberculosis
 Generalized complaints of headache, malaise,
mental confusion, and vomiting.
 CSF :
 moderate pleocytosis (mononuclear cells, or a
mixture of PMN & mononuclear cells.
 protein is elevated
 sugar is moderately reduced or normal
 The most serious complication of chronic
meningitis is arachnoid fibrosis,
Tuberculosis
 Most common pattern of involvement is
a diffuse meningoencephalitis
 Subarachnoid space contains gelatinous
or fibrinous exudates, most often at the
base of the brain, obliterating the
cisterns and encasing cranial nerves.
 Obliterative endarteritis
 Adhesive arachnoiditis
 Tuberculoma
Neurosyphilis

 Tertiary stage of syphilis

 10% of patients with untreated infection.
 Its major form of expression are:
1. meningovascular
neurosyphilis
2. paretic neurosyphilis
3. tabes dorsalis
Meningovascular neurosyphilis
 chronic meningitis - base of the brain
and cerebral convexities and spinal
leptomeninges
 obliterative endarteritis (Huebner arteritis)
acco. by a distinctive perivascular
inflammatory reaction rich in plasma
cells and lymphocytes.
 Cerebral gummas
Paretic Neurosyphilis
 invasion of the brain by Treponema pallidum
 insidious but progressive loss of mental and
physical functions with mood alterations
terminating in severe dementia
 Inflammatory meningeal lesions associated with
parenchymal damage in the cerebral cortex
(esp. frontal lobe)
 Often with associated hydrocephalus with
damage to the ependymal lining and proliferation
of subependymal glia – granular ependymitis.
Tabes dorsalis
 damage by the spirochete to the sensory
nerves in the dorsal roots:
 impaired joint position,
 position sense and resultant ataxia (locomotor
ataxia)
 loss of pain sensation, leading to the skin and
joint damage (Charcot joints);
 other sensory disturbances, particularly the
characteristic “lightning pains”
 absence of deep tendon reflexes
Viral Meningoencephalitis

 parenchymal infection with meningeal

inflammation (meningoencephalitis)
 sometimes with simultaneous
involvement of the spinal cord
(encephalomyelitis)
Viral Meningoencephalitis
 Characteristic histologic features are:
 perivascular and parenchymal mononuclear
cell infiltrates (lymphocytes, plasma cells
and macrophages)
 glial cell reactions (including the formation
of microglial nodules)
 neuronophagia

 Direct indications of viral infection are

the presence of viral inclusion bodies.
Viral Meningoencephalitis
 Viral tropism.
 The capacity of some viruses for latency is
especially important in neurologic disease (ex.
Herpes zoster).
 may be followed by an immune-mediated
disease, such as perivenous demyelination.
 Intrauterine viral infection may cause congenital
malformation as occurs with rubella.
 A slowly progressive degenerative disease
syndrome may follow many years after a viral
illness; an example is post encephalitic
parkinsonism.
Arthropod-Borne Viral
Encephalitis (Arboviruses)
 Impt. cause of epidemic encephalitis esp. in tropics
 In western hemisphere, the most important types are:
- Eastern and Western equine
- Venezuelan
- St. Louis
- La Crosse
 Elsewhere in the world
- Japanese B (Far East)
- Murray Valley (Australia and New Guinea)
- tick-borne
Arthropod-Borne Viral
Encephalitis
 CSF
- usually colorless
- slightly elevated pressure
- initially, a neutrophilic pleocytosis
that rapidly convert to
lymphocytes
- elevated protein
- normal sugar
Herpes Simplex Virus Type 1
 Encephalitis that occurs in any age group
but is most common in children and young
adults.
 Only 10% present with history of prior
herpes.
 most commonly observed clinical
presenting symptoms are alterations in
mood, memory and behavior.
Herpes Simplex Virus Type 1
 usually involve the inferior and medial
regions of the temporal lobes and the
orbital gyri of the frontal lobes.
 infection is necrotizing and often
hemorrhagic
 perivacular inflammatory infiltrates are
usually present, and Cowdry type A
intranuclear viral inclusion bodies may be
found in both neurons and glia.
Herpes Simplex Virus Type 2

 HSV-2 is responsible for most cases of

herpetic viral meningitis.
 generalized and usually severe
encephalitis
 infection is acquired during passage
through the birth canal rather than
transplacentally.
Varicella-Zoster Virus
 Primary infection ( chickenpox), ordinarily without
any evidence of neurologic involvement.
 Reactivation in adults (shingles) usually
manifests as painful vesicular skin eruption in the
distribution of a dermatome.
 Usually self-limited but may be persistent
(postherpetic neuralgia syndrome)
 Overt CNS involvement is rare.
 Granulomatous arteritis
 In immunosuppressed patients, may cause acute
encephalitis with demyelination and subsequent
necrosis.
Cytomegalovirus
 Occurs in two groups of individuals:
1. fetus
2. immunosuppressed
 Outcome of in-utero infection is
periventricular necrosis that produces
severe brain destruction followed later by
microcephaly and periventricular
calcification.
Cytomegalovirus
 CMV is the most common opportunistic viral
pathogen in patients with AIDS affecting the
CNS in15% to 20% of cases
 most common pattern of involvement is
subacute encephalitis.
 Tendency for the virus to be localized in the
paraventricular subependymal regions of the
brain. This results in a severe hemorrhagic
necrotizing ventriculoencephalitis and a choroid
plexitis
Cytomegalovirus

 Can also attack lower spinal cord and

roots – RADICULONEURITIS
 Intranuclear and intracytoplasmic
inclusions
Poliomyelitis
 picorna group of enteroviruses.
 CNS infection manifest initially with
meningeal irritation and a CSF picture of
aseptic meningitis.
 Attack of the anterior horns with loss of
motor neurons produces a flaccid
paralysis with muscle wasting and
hyporeflexia
Poliomyelitis

 Death can occur from paralysis of the

respiratory muscles
 A myocarditis sometimes complicates
the clinical course
 Mononuclear cell perivascular cuffs and
neuronophagia of the anterior horn motor
neurons of the spinal cord.
Rabies

 Severe encephalitis.
 Usually transmitted to man by a rabid
dog.
 Exposure to bats, even without a bite,
has now been identified as a risk factor
 Virus enters the CNS by ascent along
the peripheral nerves from the wound
site
Rabies
 Nonspecific symptoms of malaise, headache
and fever, but the conjunction of these
symptoms with local paresthesias around the
wound is diagnostic.
 In advanced cases, the patient exhibits
extraordinary CNS excitability
 There is meningismus and as the disease
progresses, flaccid paralysis. Periods of
alternating mania and stupor progress to coma
and death from respiratory center failure.
Rabies
 Brain -intense edema & vascular congestion.
 Widespread neuronal degeneration and
inflammatory reaction most severe in the basal
ganglia, midbrain and floor of the fourth
ventricle, particularly in the medulla.
 Negri bodies are intracytoplasmic, round to
oval, eosinophilic inclusions and can be found in
pyramidal neurons of the hippocampus and
Purkinje cells of the cerebellum.,
HIV

 60% of patients with AIDS develop

neurologic dysfunction.
 Neuropathologic changes
 direct or indirect effects of HIV-1
 opportunistic infection

 primary CNS lymphoma.

 Aseptic meningitis
HIV Meningoencephalitis

 Manifest as dementia (AIDS dementia

complex)
 Mental slowing, memory loss, mood
disturbances and motor abnormalities e.g.
ataxia, incontinence, seizures
Vacuolar Myelopathy

 Disorder of the spinal cord

 In 20 to 30% of AIDS patients
 Vit. B12 level is normal
AIDS-Associated Myopathy &
Peripheral Neuropathy
 Muscle fiber necrosis and phagocytosis
 Interstitial infiltration with HIV positive
macrophages
 Peripheral neuropathy
 Acute & chronic inflammatory demyelinating
polyneuropathy
 Distal symmetric polyneuropathy
 Polyradiculopathy
 Mononeuritis multiplex
 Sensory neuropathy
AIDS in children

 Microcephaly with mental retardation

 Motor development delay
 Most frequent morphologic abnormality
is calcification of large and small vessels
and parenchyma within the basal ganglia
and deep cerebral white matter
 Loss of hemispheric myelin
 Microglial nodules
Progressive Multifocal
Leukoencephalopathy
 Polyomavirus (JC virus, totally unrelated
to Creutzfeld-Jakob disease).
 Preferentially infects oligodendrocytes
 Almost invariably in immunosuppressed
individuals
Progressive Multifocal
Leukoencephalopathy
 Patches of irregular, ill-defined destruction
of the white matter ranging in size from
millimeters to an entire lobe of the brain
 The cerebrum, brain stem, cerebellum and
occasionally the spinal cord can be
involved.
 patch of demyelination in the center of
which are scattered lipid-laden
macrophages and a reduced number of
axons
Subacute Sclerosing
Panencephalitis (SSPE)
 Dawson inclusion body encephalitis.
 Rare progressive syndrome characterized by cognitive
decline, spasticity of limbs and seizures.
 Occurs in children or young adults, months or years
after an initial, early-age acute infection with measles.
 Thought to represent a persistent but nonproductive
infection of the CNS by altered measles virus;
 Microscopically, there is widespread gliosis and myelin
degeneration; viral inclusions, largely within the nucleus
of oligodendrocytes and neurons.
Fungal Meningoencephalitis
 Encountered primarily in immunocompromised
patients.
 The brain is involved only late in the disease
 More often are: Candida albicans, Mucor,
Aspergillus fumigatus and Cryptococcus
neoformans.

 Three basic pattern of fungal infection:

1. Chronic meningitis
2. Vasculitis
3. Parenchymal invasion.
Fungal Meningoencephalitis

 Vasculitis is most frequently seen with

Mucor and Aspergillus
 Parenchymal invasion, either in the form
a granuloma or abscess can occur with
most of the fungi. The most commonly
encountered are Candida and
Cryptococcus.
Other Infectious diseases

 Protozoal disease (including malaria,

toxoplasmosis, amebiasis and trypanosomiasis),
rickettsial infection (typhus and Rocky Mountain
spotted fever), and metazoal diseases (esp.
cysticercosis and echinococcosis) may also
involve the CNS.
 Cerebral toxoplasmosis has assumed greater
importance with the AIDS epidemic.
Transmissible Spongiform
Encephalitis (Prion Disease)
This group of diseases include:
Creutzfeldt-Jacob disease (CJD)
Gerstmann-Straussler-Scheinker syndrome
Fatal familial insomnia
Kuru in humans
Scrapie in sheep and goats
Mink transmissible encephalopathy
Bovine spongiform encephalopathy
(mad cow disease)
Transmissible Spongiform
Encephalitis (Prion Disease)
 predominantly characterized by “spongiform
change” caused by intracellular vacuoles in
neural cells.
 Clinically, most of these patients present with
dementia.
 The most common type is CJD which occurs in
sporadic and familial forms.
 Associated with abnormal forms of a specific
protein, termed prion protein (PrP) and are both
infectious and transmissible.
Transmissible Spongiform
Encephalitis (Prion Disease)
 Accumulation of PrPsc in neural tissue
appears to be the cause of the pathology
of these diseases, but how this material
cause the development of cytoplasmic
vacuoles and eventual neuronal death is
still unknown.