Transcript CNS_Carlson_11_24_03

CNS Infections
Margrit Carlson, M.D.
November 2003
How are infections in the
CNS different?

Separated by the blood brain barrier

Immunologically distinct

Unique anatomic considerations dictate
the spread of infection within the CNS

Closed space

Limited capacity for regeneration or
compensation for injury
Blood Brain Barrier

Between blood and brain formed by the
tight junctions of the cerebral capillary
endothelium

Between blood and CSF formed by the
tight junctions of the choroid plexus
epithelium
Immune Response in the CNS

Access of immune effector cells to CNS
is limited by the BBB

T lymphocytes can enter and exit the
CNS in small numbers

Low expression of MHC molecules limits
antigen presentation
Entry into the CNS
Bypassing the blood brain barrier
 direct
extension from a local focus,
sinuses
middle ear or mastoid
dental source
 foreign body
 trauma
Entry through the BBB

direct penetration of the choroid plexus
epithelium into the CSF (meningitis)

direct penetration of the capillary
endothelium into the brain parenchyma
(encephalitis)

disruption of the tight junctions

transportation across the barrier inside
leukocytes
Types of infections
Meningitis- subarachnoid
 Encephalitis-brain parenchyma
 Abscess
subdural
brain
epidural

Cerebrospinal Fluid in
Meningitis
Pressure
Normal 180mm
Glucose
Protein
2/3 of serum up to50
WBC
0-5
Bacterial
I
<40
50-1500
50-5000P
Viral
N
N
N
<100L
Chronic
I
10-45
45-500
25-1000L
I=Increased
N =Normal
P=polymorphonuclear leukocytes
L=Lymphocyte
CSF Parameters
Pressure
Normal 180mm
Glucose
2/3 of serum
Protein
50
WBC
0-5
Abscess
I
N
30-200
10-500 L
Encephalitis N
N
20-125
20-200 L
I=Increased N =Normal
P=polymorphonuclear leukocytes
L=Lymphocyte
Acute Meningitis

19 yo student is seen for sore throat x2
days. His symptoms worsen and he
develops a terrible headache and
photophobia. He is brought to the ER
the next morning by his roommate. In
the ER he is hypotensive, confused,
complaining of headache and
photophobia. He has a seizure.

He is given antibiotics and taken for a
CT scan which is unremarkable.

CSF
RBC 10
WBC 1230 93% PMNs
glucose 33
protein 276
Acute meningitis
Meningeal signs and symptoms worsen
over a few days

symptoms: headache, fever, neck
stiffness, photophobia and vomiting.

signs: nuchal rigidity, altered level of
consciousness, seizures and cranial
nerve palsies(sensorineural hearing
loss)
Bacterial Meningitis

0-4 weeks Streptococcus agalactiae,
E. coli, Listeria monocytogenes

4-12 weeks H. influenzae, E. coli,
L. monocytogenes, S.agalactiae,

3mo-18 years H. influenzae, N.
meningiditis, S. pneumoniae

18-50 years S. pneumoniae, N.
meningiditis

36 YO G3P2, 33 week IUP brought in by
her sister for chest pain and confusion
increasing over the last 3 days.

PE: temp was 38.5, she had
photophobia but no nuccal rigidity. A
vesicular rash was seen on her L chest

CSF: 320 RBC, 460 WBC, 50% lymphs
and 34% monos

protein 623, glucose 91

Her MRI had diffuse meningeal
enhancement
Meningitis in the
Immunocompromised Host
Bacterial Syphilis, Listeria, Nocardia
Viral
VZV, HSV
Fungal
cryptococcus,
coccidioidomycosis,
histoplasmosis
Mycobacterial
tuberculosis
44 yo construction worker had upper
respiratory symptoms 1 month ago. He
has had worsening fevers, a constant
headache and photophobia for a month.
His thinking has been slowed and he
had an episode of aphasia lasting 1 day.
glucose 27
protein 203
RBC
<1
WBC
203
 45%lymphs/40% mono/5% eos
 MRI: enhancement of the basal
cisterns, along the midbrain, pons, right
optic tract, and the right caudate head.

CSF:
Chronic meningitis

Gradual onset and progression

Focal symptoms

Increased intracranial pressure

History of exposure

Immunocompromised ?
Symptoms of Increased
Intracranial Pressure
headache
 nausea, vomiting
 altered mental status
 ataxia
 incontinence
 papilledema
 3rd or 6th nerve palsy

Infectious causes of chronic
meningitis

Coccidioidomycosis, Cryptococcus,
Histoplasmosis, Sporotrichosis

Tuberculosis

Syphilis, Lyme Disease

HIV, Enterovirus
Non-infectious causes of
Chronic Meningitis

Behcet’s disease

Systemic lupus erythematosis

Sarcoidosis

Carcinomatous or lymphomatous
meningitis

Granulomatous angiitis
Complications of Chronic
Meningitis

hydrocephalus

vasculitis, cerebrovascular occlusion

cranial nerve palsies
32 yo Hispanic man has new onset
confusion developing over 24 hours,
aphasia, hallucinations and seizures
following a bone marrow transplant for
CML. He has no known ill contacts. He
has had mucositis
Putting it all together
Sudden or gradual onset?
 Meningeal symptoms, encephalopathy?
 Focal findings?
 Fever ?
 Predisposing conditions and exposures
 Imaging
 LP results

 CSF:
glucose 67
protein 158
RBC 179
WBC 124 25% P /74% L
 His MRI shows diffuse periventricular
white matter disease and enhancement
in the temporal lobes.
Acute Encephalitis
Fever
 Headache
 Altered level of consciousness: lethargy,
confusion, stupor, coma
 Seizures
 Hypothalamic or pituitary dysfunction

Causes of Acute Encephalitis

Herpes simplex, Varicella zoster

California, St Louis, Japanese, Western
and Eastern equine encephalitis viruses

Enteroviruses (coxsackie, echo and
enteroviruses)

Post measles, post influenza
encephalomyelitis
HSV Pathogenesis

Retrograde transport of virus from
mucous membranes to the sensory
ganglia and rarely to the CNS

Anterograde transport from the sensory
ganglia to the periphery during
cutaneous exacerbations
33 yo with AIDS,CD4 cells 5, brought in
by his partner who has noticed he has
become more forgetful and withdrawn
over the last 3-6 months.
He’s had no fevers or headache. No
recent infections. He has been off
antiretrovirals because of side effects.

MRI showed diffuse atrophy

CSF
glucose
protein
RBC
WBC
88
78
<1
12
74% lymphs
26% monos
Chronic Encephalitis

Predominantly viral

Non-viral: Neurosyphilis, Lyme disease,

Neurotropic viruses:
Retroviruses: HTLV I and II, HIV
Herpes viruses: HSV, VZV and CMV
Chronic Encephalitis
Other:
JC virus: Progressive multifocal
leukoencephalopathy
Subacute Sclerosing panencephalitis
(Measles)
Rubella
Creutzfeldt-Jakob
HIV Encephalopathy
AIDS Dementia Complex
7-27% of persons with CD4<200 have
some impairment including:
 decreased attention and concentration
 psychomotor slowing
 personality change, loss of initiative,
drive, animation
 hyperreflexia, ataxia, frontal release
signs
Pathogenesis of ADC
HIV is present in the CSF and brain in
primary infection.
 HIV infects cells of monocyte lineage
(macrophages, microglia, multinucleated
giant cells).
 Viral burden (HIV qPCR) in CSF or brain
correlates with neurologic disease.

Pathogenesis of ADC
Release of neurotoxins from
macrophages (nitric oxide, arachidonic
acid, quinolinic acid).
 Cytokine mediated release of
neurotoxins.
 Direct toxicity of viral proteins, i.e.
gp120.

73 yo man with a fever who is brought in
by his wife because he is confused and
unable to move his right side.
He was complaining of a headache for a
few days. He started vomiting this
morning and was bumping into the wall
on his way to the bathroom.
Brain Abscess

hematogenous spread through the
blood brain barrier

direct extension via the the emissary
veins into the cerebral venous
circulation
Development of an abscess

Local area of cerebritis, inflammation
and edema (1-3 days)

Expansion and development of a
necrotic center (4-9 days)

Formation of a ring enhancing capsule
by gliosis and fibrosis (14 days)
Clinical Presentation
Headache with gradual worsening
 Fever <50%
 Focal neurologic signs
 Seizures
 CSF: elevated protein, normal glucose
and mild leukocytosis
 Increased ICP: Nausea,vomiting,
lethargy

Brain Abscess

Location

Source

Organism

Treatment
Brain Abscess
Paranasal Sinuses
Otogenic Infection
Frontal lobe
Temporal lobe,
cerebellum
Hematogenous spread Multiple lesions
MCA distribution
Post traumatic
Site of wound
Post operative
Site of surgery
Pathogens
Sinuses
Streptococci, Haemophilus,
Bacteroides, Fusobacterium
Otogenic as above, and Pseudomonas
Endocarditis Staphylococcus, Viridans
streptococci
Lung abscess Streptococci, anaerobes,
Actinomyces
Trauma
Staph aureus

A 28 YO father of 3 develops worsening
sinus headaches and is seen repeatedly
at an outside ER. He has low grade
fevers. His headache becomes
excruciating and he subsequently
becomes unresponsive during his
evaluation.
Brain Abscess in the
Immunocompromised
AIDS
Toxoplasmosis, Tuberculoma,
Cryptococcoma, Coccidiodomycosis,
Blastomycosis
 Transplant
Aspergillus, Nocardia, Candida,
Zygomycetes in addition to the above

35 YO man with 2 weeks of worsening
headache, low grade fever and rash.
He also has had myalgias and L knee
pain and swelling.
 He has no recent travel or outdoor
activities, not sexually active x 6 months


CT Scan is unremarkable

CSF: 2 RBC, 25 WBC;20%segs, 60%
lymphs, 20% monocytes, glucose 64,
protein 45.
Fever, Headache,Rash and
mild CSF pleocytosis

Enterovirus

Primary HIV

Epstein Barr

Secondary syphilis

Mycoplasma

Drug Reaction
Neurosyphilis
Primary, chancre 10-90 days
 Secondary,rash 4-10 weeks later (up to
6 months after initial infection
 Meningeal within 1st year after infection
 Meningovascular 4-7 years later
 Parenchymal disease decades later

Syphilis
50-75% of exposed partners were
infected.
 30-70% of those with secondary syphilis
have CSF mononuclear pleocytosis,
elevated protein or + RPR in CSF
 25% untreated patients have
recurrances
 1/3 of untreated patients develop late
sequelae
