Infections Of The Central

Nervous System(CNS)
Ⅰ. Pathogen: virus, bacterial, fungal,
spirochetal, parasitic organisms,
etc.
Ⅱ. Category:
1. Depending on the pathogen:
2. Depending on duration:
(1)acute infection
(2)subacute infection
(3)chronic infection
3. Depending on the position of foci:
(1) Parenchymatitis: encephalitis,
myelitis, myelencephalitis, etc.
(2)Pia-arachnitis: meningitis, spinal
meningitis,etc.
(3)Meningoencephalitis:
 Ⅲ Pathway of infection
1. Respiratory pathway
2. Blood circulation pathway
3. Direct pathway
4. Reverse infection via nervous
stem
 Major Routes of CNS Invasion
• Hematogenous spread is the most common
route of CNS invasion.
• Seeding of blood with agents may come from
– Superficial or deep abscesses
– GI / GU tracts
– Respiratory system - especially lung
abscess
– Bacterial endocarditis
 Diagnostic test for meningitis :
lumbar puncture….
A lumbar puncture collects
cerebrospinal fluid to check for
the presence of disease or
injury.

A spinal needle is inserted,

usually between the 3rd and 4th
lumbar vertebrae in the lower
spine.

Permits the urgent distinction of bacterial meningitis

from viral meningitis and examination of the CSF allows
precise diagnosis.
 CSF Changes in CNS Infections
Key Normal CSF Values
• CSF composition is
• Pressure: 80-180 mmH2O
maintained within
• Cells: <5/ cubic mm. All
very narrow limits.
mononuclear
• CSF composition
• Protein: <40 mg/dl
changes in CNS
– May rise slightly with age
infections
• Glucose: about 2/3 of
– Often diagnostic in
blood glucose. <50% of
meningitis blood glucose is abnormal
– Unreliable in brain
abscess
 Diagnosis of CNS Infection

 Standard neurodiagnostic procedures

include:
• CSF examination
• EEG
• scanning

 These can be normal in early stages of the

disease

∴ Other diagnostic evaluations should be

initiated immediately
Herpes simplex Virus
encephalitis (HSE)
 This is the commonest and gravest form
of acute viral encephalitis. The incidence is
0.2-0.5/100,000 population in U.S. Between
30 and 70 percent of these are fatal, and
majority of patients survivals are left with
serious neurological abnormality.
HSE occurs sporadically throughout the
year and in patients of all ages and in all the
part of the world.
Ⅰ. Etiology and Mechanism
Herpes simplex viruses (HSV-1and HSV-
2) are belong to DNA virus. HSE is due
almost always to HSV-1, which is also
the cause of common herpetic lesions of
the oral mucosa. HSV-2 may also cause
acute encephalitis, usually in the
neonate and in relation to genial herpetic
infection in the mother .
 Ⅱ. Pathology
The lesions take the form of an
intense hemorrhagic necrosis of the
inferior and medial parts of the
temporal lobes and the medial-orbital
parts of the frontal lobes and the limbic
lobes.
 These lesions are usually bilateral but not
symmetrical, which is so characteristic that
the diagnosis can be made by gross
inspection or by their location and
appearance on image studies. In the acute
stages of the disease, intranuclear
eosinophilic inclusions are found in neurons
and glial cell, characteristically.
 Ⅲ. Clinical feature:

1. Acute onset: symptoms evolved over

several days.
2. Acute encephalitis: fever, headache,
seizures, confusion, stupor and coma.
3. Symptoms and findings about
impairments of intermedial parts of
the frontal and temporal lobes:
olfactory or gustatory hallucinations,

anosmia, temporal lobe seizures,

personality change, bizarre or
psychotic behavior or delirium,
aphasia and hemiparalysis.
4. Aseptic meningitis: signs of meningeal
irritation such as rigidity neck, Kernig’s
sign(+).
5. Some patients have the history of
herpetic lesions of the oral mucosa.
Ⅳ. Assistant test:

1. CSF: increased pressure, a pleocytosis

(range 10 to 500 cells/mm3 usually less
than 200). Mainly the cells are lymphocytes,
but occasionally there is a significant
number of neutrophils. The protein content
is increased in most case. Rarely, the CSF
glucose levels maybe reduced to slightly
less than 40 ㎎ /dL.
Increased ICP is transmitted through the subarachnoid space
to the optic nerve sheath, blocking axoplasmic flow and venous
return in the optic nerve causing engorgement and
elevation (swelling) of the optic disk.
This classic sign of ICP takes several hours to days to develop
and is often not present in the early hours of ICP increasing.
Normal ICP in adults is less than 200 mm H2O.
Normal Papilledema
 2. CT or MRI scans: showing
hypodensity of the affected areas,
among them scattered with many
small hyperdensity shadows.
3. PCR: The detection of HSV antigen
in the CSF by the application of PCR is
useful in diagnosis, which is suitable
for the early stage diagnosis.
MRI scans of HSE
Ⅴ.Diagnosis:
Principle:
1. Clinical manifestation: acute onset;
encephalitis syndrome; the change of
mental; meningitis syndrome.
2. Assistant test: abnormal change of
CSF and CT/MRI scans, and detection of
HSV-Ag(+).
Ⅵ. Treatment:
1. Treatment to pathogen
Acyclovir: 30 ㎎ / ㎏ , intravenously
daily (continued for 10 to14 days).
2. Treatment to symptoms
Lower the temperature and control
the seizures and decrease the ICP,
etc.
 3. General treatment.

 Cortical hormone: early enough and

short stage use.
 Nervous cells nutrient,
 Supportive treatment and recovering
treatment.
Tuberculous Meningitis
 Usually subacute – may be
fulminant
 Affects all ages
– Classically: a disease of
the young
– Increasingly affects
older adults
Alcoholics, indigent
Immigrants (3rd world
countries)
 Increased in AIDS
 Pathogenesis 1 tuberculosis
 Inhalation of organisms

 Replication in regional lymphatics

 Spread to hilar nodes Systemic infection

Activation of cell-mediated Granuloma formation

immunity (6 weeks) Eradication /containment

Reactivation at < 1% of cases per year

• Classically a complication of miliary TB
– Onset within months of primary infection
– More common in children
 Now is usually a disease of older adults

– Due to reactivated infection

– Usually pulmonary
– Can also be extrapulmonary
– May begin by reactivation within brain
TBC meningitis without signs of systemic infection
 Pathogenesis 2
tuberculous meningitis
 Granuloma adjacent to
ventricle or meninges

 Rupture

 Seeding of CSF

 Ventriculitis Basilar
Meningitis
 Basilar Meningitis in Tuberculosis

• Hydrocephalus
 Cranial nerve palsies

 Involvement of vessels

within inflamed meninges

( vasculitis )
– Arterial and venous
thrombosis
– Brain infarction
MRI scans of TBM
 Tuberculous Meningitis: CSF
 Differs from bacterial meningitis
– Mixed pleocytosis with lymphocytic predominance
– Low glucose
– High protein
 Organisms may hard to find
– <30% yield by AFB stain
– 70% by culture (takes up to 6 weeks)
– PCR is major means of rapid diagnosis
 Treatment: comprehensive

 Antituberculosis drugs :key treatment

early, alliance , full dose , long time,
draught are principle of drug use .
 Treatment to symptoms.
 Supporting treatment
Fungal Infection Of
CNS
 General Feature
1. Fungal infection of the CSF may
arise without obvious predisposing
cause, but frequently they
complicated some other disease
process, such as AIDS, organ
transplantation, severe burns.
2. Fungal meningitis develops insidiously
over a period of several days or weeks.
They have the similar symptoms and signs,
such as involvement of several cranial
nerves, arteries with thrombosis and
infarction of brain, multiple cortical or
subcortical microabscesses, and
hydrocephalus complicated with
meningitis. Often the patient is a febrile or
has only intermittent fever.
3. CSF: increased pressure; moderate
pleocytosis ( usually <1000 cells/ ㎜ 3,
lymphocytes predominate); in the acute
case, a pleocytosis above 1000 cells/ ㎜ 3
and a predominant polymorphonuclear;
subnormal glucose; elevated protein.
Cryptococcosis
Meningitis
 Ⅰ. Pathology:

A granulomatous meningitis is present,

in addition, there may be small granulomas
and cysts within the cerebral cortex. The
cortical cysts contain a gelatinous material
and large numbers of organism; the solid
granulomatous nodules are composed of
fibroblasts grail cells, aggregates of
organisms, and areas of necrosis.
 Ⅱ. Clinical Feature
1. Subacute onset.
2. In the majority case, early complaints
are headache, nausea, and vomiting.
3. Half patients with mental changes.
4.Some case present with symptoms of

increasing intracranial pressure due to

hydrocephalus ( papilledema in half such

patients).
5. Some patients are present with a
confused state, dementia, cerebellar
ataxia or spastic, usually without other
focal neurologic deficit.
6. Meningovascular lesion may be
superimposed on the clinical feature.
7. A pure motor hemiplegia (likely due to
hypertensive lacune infarct ) is present.
 Ⅲ. Assistant test.
1. CSF: increased pressure, a variable
lymphocytic pleocytosis (usually<15 cells/mm3);
the initial CSF formula may display
polymorphonuclear cells, but it rapidly changes to
a lymphocytic predominance; the reduced
glucose; high level protein ;special diagnosis
depends on finding cryptococcus neoformans in
the CSF: India-ink preparation are distinctive and
diagnostic in experienced hands.
2. CT scan: may find out large sick foci.
 Ⅳ.Treatment
1. Treatment to the fungal organisms.
(1). Amphotericin B: 0.5-0.7mg/kg,

intravenous daily.
(2). Flucytosine: 150mg/kg/day oral.

These two drugs can be used

together to increase the effect and
to reduce the side-effect.
 2. Treatment to symptoms.
Decrease ICP by dehydration, relieve
pain, protect the optic nerve and prevent
cerebral rupture are more importent.
 3. Supporting treatment.
Attention: Vitamin B1 、 B6 and
B12 are forbidden, because they are
helpful for Cryptococcus growing.
CNS INFECTION OF HIV
 Epidemiology
Leading cause of death in the world
 In 1998, 2.3 million AIDS related deaths accounting

for 4.2% of all deaths in the world

 Fourth leading cause of disability adjusted life years

lost, a measure that assesses the impact of the

disease on both length and quality of life
 Tuberculosis (TB), the former leading microbial killer,

was estimated to have killed 1.8 million people in

1998, but 400,000 of these deaths were in HIV-
infected individuals
 HIV infection is now responsible for more than 20% of

all deaths in people with TB.

 In 2003 the number of newly affected
individuals are about 5 million
 4.2 million adults and 700,000
children under the age of 15
 In 2003 approximately 3 million
deaths due to AIDS globally
 2.5 million adults and 500,000
children under the age of 15
 AIDS

 Neurologic symptoms and signs present in more than one

half of AIDS patients during course of disease and can be
the presenting manifestation in 10%
 Result from direct effects of HIV, opportunistic infections
and from treatment toxicity
 Pathogen of opportunistic infections:
Brain: Listeria, CMV , toxoplasmosis , PML, VZV,
aspergillosis
Meninges: Cryptococcosis, syphilis, TB, Herpes 1 and 2
Spinal Cord: VZV, syphilis, HSV, CMV ,etc. multiplex
 Neurologic infectious disease are important
cause of morbidity and mortality.
Underrecognition of infectious etiologies in
setting of increasing populations of
immunocompromised hosts, drug resistance,
international travel all contribute to morbidity.
 Bacterial meningitis most commonly caused by
S. pneumonia and N. meningitidis in <50 yrs.
 Ceftriaxone resistance has been reported.
 Controversy remains about use of steroids.
 Encephalitis is divided into sporadic and
epidemic.
NEUROPATHOLOGY OF
HIV INFECTION
1.Central Nervous System
Mechanism of CNS infection is unclear, but HIV
seems unable to cross blood-brain barrier alone.
It probably crosses in macrophages and T cells
and most directly affects subcortical structures
(basal ganglia, thalamus, brain stem).
AIDS dementia complex (ADC), a subcortical
dementia,is different from cortical dementia such
as Alzheimer's
disease.
 Toxoplasma gondii
toxoplasmosis results in CNS dysfunction
- altered cognition
- Headache
- focal neurological deficits
- Encephalitis
- Seizures
The best prevention is away from pet (such as
cat).
 Cerebellar disorders� cerebellar lesions always
result from opportunistic infections such as
toxoplasmosis and progressive multifocal
leukoencephalopathy or primary CNS lymphoma
 Recently, the relationship between stroke and
AIDS was reported.
 The most common cause of cerebral infarction in
both clinical and autopsy series was nonbacterial
thrombotic endocarditis.
 Intracerebral hemorrhages were usually associated
with thrombocytopenia, primary CNS lymphoma,
and metastatic KS.
2.spinal cord pathology
- HIV myelitis
- opportunistic infections
- lymphomas
- vacuolar myelopathy� affect the dorsolateral

white matter tracts.

3.Neuromuscular disturbances
 Neuromuscular disturbances may first appear as
movement disorders.
 A neurological examination can be performed to

provide a diagnosis and prognosis.

This may include the level of the lesion,
neuromuscular deficits, need for assistive devices,
ADL （ aids to daily living ） and functional abilities.
 Various quality of life assessments can be used

with the HIV population

 4.Peripheral Nervous System
 Sensory
 early and middle stages:
- distal lower extremities are largely involved
- paresthesia and decreased temperature sensitivity
advanced stages:
- patient has decreased ankle and knee reflexes
- diminished temperature and vibration sensitivity and
proprioception, and hyperesthesia
 Motor
resembles Guillain-Barreá syndrome (progressive
muscle weakness paralysis, decreased deep
tendon reflexes). splints and ankle-foot orthoses may
prevent deformities
 Distal symmetrical polyneuropathy (DSP)
most common form of neuropathy in HIV infection
 signs & symptoms
Numbness
Burning
paresthesias in the feet
 symptoms are typically symmetrical and so severe
that patients have contact hypersensitivity and gait
disturbances
 upper extremity involvement and distal weakness
may occur later in the course of DSP
 Neurological Examination will show
- sensory loss to pain and temperature in a
stocking-glove distribution
- increased vibratory thresholds,
- diminished ankle reflexes compared with knee
reflexes.
- concurrent CNS disorders and neuropathy,
characterized by hyperactive knee reflexes and
depressed ankle reflexes.
 Distal symmetrical polyneuropathy (DSP)
- Incidences of DSP increases with advancing
immunosuppression, in parallel with decreased
CD4 counts
- Thirty-five percent of patients with AIDS may
present with electrophysiological or clinical
abnormalities.
- Pathological evidence of DSP is present in almost
all patients who die of AIDS.
5.Autonomic Nervous System
 arrhythmias ��especially tachycardia
 abnormal blood pressure �� orthostasis and
with isometric exercises
 dementia
 myelopathy
 peripheral sensory neuropathies
 Treatment

 Treatment for CNS impairments include an

eclectic blend of rehabilitation strategies.
 No special and effective treatment, so that
prevention is the most important treatment.
Kaposi’s sarcoma
 CSF Changes in Meningitis
Viral Tuberculous Fungal

Cells Lymphs Lymphs + Lymphs

(+ poly’s) poly’s
Protein Mildly Midrange elevated
Elevated Elevated
Glucose Normal <50% blood <50% blood

Specific PCR Culture (20 ml) Culture (20ml)

Diagnosis (Serology)
Thanks