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11/8 CNS Infections
Neuro
133
Medical
Graduate
11/08/2011

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Cards

Term
location of nervous system infections

(general)
Definition
can be focal, multifocal, or diffuse

-brain, SC, nerve root, plexus, peripheral nerve, muscle
Term
time course of nervous system infections
Definition
subacute

typically present clinical manifestations like a mass lesion with a subacute course
Term
classification of neurologic infections
Definition
by site of infection

by organism
Term
classification of neurologic infections

by site of infection
Definition
meningeal

parenchymal (brain, spinal cord)

peripheral nerve

muscle
Term
classification of neurologic infections

by organism
Definition
bacterial

viral

fungal

parasitic
Term
parenchymal infections
Definition
encephalitis

cerebritis

abscess

granuloma
Term
bacterial meningitis

clinical features
Definition
headache, abrupt onset (acute)

fever

stiff neck - meningeal signs

photophobia

nausea/vomiting
Term
meningeal signs
Definition
Brudsinski's = doc passively flexes pt head forward and pt involuntarily flexes one or both hips
-more specific
-may be only subtle hip flexion

Kernig's = pain on extension of the knee while hip is flexed (from stretching out meninges)
Term
bacterial meningitis

macroscopic pathology
Definition
*hallmark = meningeal inflammation*

-swollen brain
-congested meninges
-purulent exudate (pus) in subarachnoid space around ventricles

(meninges look like they have a bad cold)
Term
bacterial meningitis

microscopic pathology
Definition
lots on PMNs and necrotic debris in subarachnoid space and ventricles

(1 wk) PNMs replaced by macrophages and lymphocytes; fibroblast proliferation
Term
bacterial meningitis

secondary pathology
Definition
perivascular inflammation - inflammatory cells infiltrate meningeal and cortical blood vessels; may cause thrombosis, infarction

fibrous organization can obstruct CSF outflow, causing hydrocephalus
Term
bacterial meningitis

pathophysiology - route of entry
Definition
bacteria colonize mucosal surfaces of nasopharynx
Term
bacterial meningitis

pathophysiology - transport to the nervous system
Definition
bacteria get transported from nasal mucosa to blood vessels (in phagocytic vacuoles across epithelial cells)

spread to choroid plexus via bloodstream (mechanism unknown)

cross BBB into subarachnoid space
Term
bacterial meningitis

pathophysiology - inflammatory response
Definition
in subarachnoid space, bacteria trigger inflammatory cytokine release

cell wall and lipopolysachharide surface components of bacteria induce meningeal inflammation

cytokines upregulate blood vessel endothelial cell adhesion molecules - PMN infiltration into CSF

PNMs degranulate and release other inflammatory mediators and toxic oxygen metabolites
Term
bacterial meningitis

pathophysiology - cellular damage
Definition
damage directly from bacterial toxins and toxins released from PNMs

edema from cellular damage and increased vascular permeability from inflammatory products
Term
bacterial meningitis

CSF findings
Definition
++ WBC >1000; mostly NEUTROPHILS

+ protein >100

+ opening pressure 200-500

- glucose <40%serum glucose

often + gram stain

- glucose
Term
bacterial meningitis

likely organisms

age 0-12 weeks
Definition
group B strep

e. coli

listeria monocytogenes
Term
bacterial meningitis

likely organisms

age 3m - 50y
Definition
strep pneumo

neisseria meningitides

h. flu
Term
bacterial meningitis

likely organisms

age >50 years
Definition
strep pneumo

listeria

gram (-) bacilli
Term
bacterial meningitis

likely organisms

head trauma, neurosurgery
Definition
staph - from skin irritation

gram (-) bacilli

strep pneumo
Term
bacterial meningitis

likely organisms

immunocompromised
Definition
listeria

gram (-) bacilli

strep pneumo

h. flu
Term
bacterial meningitis

treatment
Definition
empiric antibiotics

steroids?

symptom management
Term
bacterial meningitis

empirical antibiotic treatment
Definition
3rd generation cephalosporin PLUS

vancomycin (to cover resistance)

if immune comp, ADD ampicillin (listeria)
Term
bacterial meningitis

role of steroids in treatment
Definition
administration of steroid (dexamethasone) either before antibiotics or concurrently MAY help improve efficacy of the antibiotics
Term
bacterial meningitis

symptom management
Definition
important to manage these symptoms as they arise:

-intracranial pressure
-seizures
-SIADH (hyponatremia)
-systemic complications (aspiration pneumonia)
Term
viral meningitis

clinical features
Definition
acute but less aggressive than bacterial meningitis

headache, abrupt onset (acute); fever; stiff neck - meningeal signs; photophobia; nausea/vomiting
Term
viral meningitis

pathology
Definition
vascular congestion

scant infiltrate of lymphocytes (NOT neutrophils as with bact) in the meninges, perivascular spaces, choroid plexus

less intense inflammatory reaction than bacterial meningitis
Term
viral meningitis

pathophysiology - route of entry
Definition
enteroviruses traverse the intestinal lining cells to Peyer's patches in the lamina propria

viral replication --> minor viremia

numerous organ systems seeded, more replication --> major viremia
Term
viral meningitis

pathophysiology - transport to nervous system
Definition
CNS can be seeded either at time of minor or major viremia

viral transport thought to be passive (exact mechanism unknown)
Term
viral meningitis

pathophysiology - mechanism of infectivity
Definition
virus replicates in choroid plexus and spreads through CSF

more replication in ependymal and meningeal cells causes cell destruction
Term
viral meningitis

pathophysiology - inflammatory response
Definition
replication in ependymal and meningeal cells incites inflammatory response

mediated by lymphocytes and monocytes

focal destruction of ependymal lining, meningeal fibrosis, inflammation of choroid plexus

inflammatory response much less destructive than the neutrophilic response in bacterial meningitis
Term
viral meningitis

CSF findings
Definition
+ WBCs 10-200; most lymphocytes

mildly + protein <100

normal opening pressure <200

normal glucose >50% serum glucose

gram stain negative
Term
CSF findings

bacterial vs. viral meningitis
Definition
no clinical or CSF feature RELIABLY discriminates between bacterial and viral meningitis
Term
viral meningitis

common viral causes
Definition
non-polio enterviruses (coxsackie, echovirous)

poliovirus

mumps
Term
viral meningitis

treatment
Definition
no specific viral meningitis treatment

empiric antibiotics for bacterial meningitis continued from onset until CSF cultures have been negative for at least 24-48 hours

symptom management
Term
fungal meningitis

clinical features
Definition
similar to bacterial meningitis
-fever, headache, mental status changes

more indolent course - progression over weeks to months or even years

more common in immunocompromised individuals
Term
fungal meningitis

pathology
Definition
moderate thickening and opacification of meninges

scant meningeal inflammation microscopically
-lymphocytes, plasma cells, eosinophils, multinucleated giant cells
Term
fungal meningitis

CSF findings
Definition
+ WBCs <800

+ protein - up to 500

+ opening pressure

- glucose 10-40

organisms visualized under microscope
Term
fungal meningitis

diagnoses
Definition
LP with typical CSF findings

fungal cultures

fungal serology (especially for cryptococcal antigen)
Term
fungal meningitis

common fungal causes
Definition
cryptococcus (HIV, older)*
histoplasma
blastomyces
coccidioides
candida
aspergillus
mucormycosis (DB)*
paracoccidioides
Term
fungal meningitis

treatment
Definition
amphotericin B

flucytosine during initial therapy
-especially in AIDS patients

fluconazole maintenance therapy in AIDS patients
Term
TB meningitis

clinical features
Definition
several week prodrome of headache, malaise, personality change, low-grade fever

gradual increase in headache, more continuous, nausea, vomiting, stiff neck, confusion, cranial nerve abnormalities, papilledema

strokes may occur

seizures in 10%

progression to stupor and coma; death within 2 months if untreated
Term
TB meningitis

macroscopic pathology
Definition
gelatinous subarachnoid exudate (pus)
-thickest in Sylvian fissures and at base of the brain (esp. brainstem and optic chiasm)
Term
TB meningitis

microscopic pathology
Definition
exduate: lymphocytes, mononuclear cells, epitheliod nodules, a few multinucleated giant cells and tubercles
Term
TB meningitis

microscopic pathology: tubercles
Definition
central area of caseous necrosis surrounded by epithelioid macrophage reaction and peripheral ring of lymphocytes
Term
TB meningitis

diagnosis
Definition
CSF

mycobacterial cultures and acid-fast stain (take a loooong time)

PCR
Term
TB meningitis

CSF findings
Definition
+ WBCs 100-300; most lymphocytes

+ protein 100-500

+ opening pressure

- glucose <45 (in 80% of patients)
Term
TB meningitis

treatment
Definition
isoniazid

PLUS 2 more:
rifampin, ethambutol, pyrazinamide, streptomycin
Term
viral encephalitis

clinical features
Definition
diffuse inflammation of the brain parenchyma

acute onset, incubation period usually <1week (can be up to 3)

similar to meningitis: fever, headache, mental status change

*mental status changes* occur earlier

neck stiffness and meningeal signs less prominent

seizures may occur

prodromal viral syndrome (nausea, vomiting, myalgia)
Term
viral encephalitis

common epidemic causes
Definition
arborviruses

enteroviruses

most common in later spring, summer, early fall
Term
viral encephalitis

sporadic causes
Definition
herpes simplex virus (HSV) most common

70% mortality if left untreated
20% mortality with early treatment
Term
viral encephalitis

pathophysiology - routes of entry
Definition
arborviruses: injected directly into bloodstream by their vector (mosquito, tick)

enteroviruses: enter through intestines from fecal-oral contamination

(less commonly by respiratory droplets)
Term
viral encephalitis

pathophysiology - transport to nervous system
Definition
must penetrate host defenses to reach the bloodstream

typically seed one or more intermediate organ systems before reaching CNS (accounts from prodrome)l sites for viral replication

create high viral titers to overcome BBB and nervous system defenses
Term
viral encephalitis

pathophysiology - mechanism of infectivity
Definition
virus attaches to neuron membrane and deliver their genome

co-opt neuron's cellular machinery to replicate viral genome and make new viral particles
Term
viral encephalitis

pathophysiology - immune response
Definition
predominant immune response is cellular - helps limit the spread of virus but may compound the tissue damage and exacerbate symptoms
Term
viral encephalitis

pathology
Definition
neuronal cell bodies destroyed and engulfed by macrophages ("neuronophagia")

perivascular cuffing by lymphocytes, macrophages, plasma cells

microglial proliferation, form nodules and rod cells appear

inclusion bodies in nuclei or cytoplasm (only with some viruses)
Term
viral encephalitis - HSV

pathophysiology - route of entry
Definition
infects peripheral nerves or cranial nerves
Term
viral encephalitis - HSV

pathophysiology - transport to nervous system
Definition
neuronal spread

travels up infected peripheral or cranial nerve and across synapses to enter the CNS (often after a latent period of many years)
Term
viral encephalitis - HSV

pathophysiology - mechanism of infectivity
Definition
same as other viral encephalopathies

preferentially involves the temporal lobes
Term
viral encephalitis

diagnosis
Definition
CSF

antibody testing for arboviruses

PCR for HSV, west nile

MRI, EEG for HSV
Term
viral encephalitis

CSF findings
Definition
+ WBCs 50-550, lymphocytic predominance

moderate + protein

+ opening pressure

normal or moderate - glucose

RBCs in 20-40% of HSV
Term
viral encephalitis

treatment
Definition
arboviruses - no treatment

HSV - acyclovir

*all patients should be treat with acyclovir until it is clear that they do dont have HSV
Term
subacute sclerosing panencephalitis
(SSPE)
Definition
rare, late complication of measles

defective virus maturation in neural cells

children infected in first 2 years of life at greatest risk

interval between initial infection and manisfestations 2-12 years

three stages
Term
SSPE

clinical features
Definition
1: change in personality or behavior

2: myoclonus, seizures, spasticity, choreoathetosis, ataxia, chorioretinitis

3: optic atrophy, quadriparesis, autonomic instability, akinetic mutism, coma

-affect gray and white matter; can cause just about any neurologic manifestation
Term
SSPE

pathology
Definition
intranuclear inclusion bodies in neurons
Term
bacterial abscess

clinical features
Definition
focal, subacute process (progression over weeks)

-headache
-focal deficits
-altered thinking
-fever in ~50%
-nausea/vomiting in ~50%
Term
bacterial abscess

pathophysiology - route of entry
Definition
hematogenous spread from a distant site of infection (especially lungs or heart)

or can arise from a contiguous infectious site
Term
bacterial abscess

pathophysiology - transport to nervous system
Definition
hematogenous spread (usually leads to location within the white matter near the junction with gray matter)
Term
bacterial abscess

pathophysiology - mechanism of infectivity
Definition
begins as a microscopic focus of septic microvascular injury that grows into a localized region of encephalitis, eventually necrotizing and getting walled off by a fibrous capsule

expands toward ventricle (this side of wall is thinest), and can ultimately rupture its contents into the ventricle (cause a meningitis)
Term
bacterial abscess

pathology
Definition
4 stages

1. days 1-3: focal cerebritis
2. days 4-9: late cerbritis
3. days 10-13: early encapsulation
4. days 14+: late encapsulation
Term
bacterial abscess

pathology - focal cerebritis
Definition
days 1-3

ill-defined region on hyperemia surrounded by edema

early parenchymal necrosis, vascular congestion, petechial hemorrhage, microthromboses, perivascular fibrinous exudate, PMNs
Term
bacterial abscess

pathology - late cerebritis
Definition
day 4-9

adjacent foci of necrosis become confluent resulting in a necrotic, purulent center surrounded by a narrow irregular later of inflammatory granulation tissue containing PMNs, lymphocytes, macrophages
Term
bacterial abscess

pathology - early encapsulation
Definition
days 10 - 13

fibroblast proliferation, reactive astrocytosis, capillary formation

early abscess capsule consists of granulation tissue that includes lymphocytes, plasma cells, monocytes, macrophages, numerous newly formed blood vessels, and scattered fibroblasts
Term
bacterial abscess

pathology - late encapsulation
Definition
days 14 onward

more firm, well encapsulated abscess consisting of 5 layers:
1) necrotic center
2) granulation tissue with proliferating fibroblasts and capillaries
3) lymphocytes and plasma cells in granulation tissue
4) dense fibrous tissue with embedded astrocytes
5) gliosis and edema
Term
bacterial abscess

diagnosis - cerebritis stage
Definition
non-enhancing focal region of low density on CT

non-enhancing hypointensity on MRI
Term
bacterial abscess

diagnosis - adscess/capsule stage
Definition
ring-enhancing mass with surrounding edema (CT, MRI)
Term
bacterial abscess

typical organisms
Definition
alpha-hemolytic and non-hemolytic strep

staph aureus

enterobacter

anaerobes
Term
bacterial abscess

treatment
Definition
total excision or aspiration under stereotactic CT or MRI guidance in conjunction with systemic antibiotic treatment

aspiration is more common

antibiotics tailored to specific cultured organism OR 3rd gen cephalosporin plus metronidazole (anaerobes) for empiric treatment
Term
NON-bacterial abscess

types of organisms
Definition
FUNGI: mucormycosis, aspergillus, candida, crptococcus

PARASITES: entamoeba, toxoplasma
Term
normal CSF values

WBC
Definition
0 - 5 cells/mm3
Term
normal CSF values

predominent cell type
Definition
lymphocytes
Term
normal CSF values

protein
Definition
15 - 45 mg/dL
Term
normal CSF values

glucose
Definition
>50% of serum glucose
Term
normal CSF values

gram stain
Definition
negative
Term
normal CSF values

cultures
Definition
negative
Term
normal CSF values

CSF pressure
Definition
<200 mm H2O
Term
CSF meningitis pathologies

WBCs
Definition
bact: >1000

viral: 10-200

fungal: 50-800

TB: 100-300
Term
CSF meningitis pathologies

predominant cell type
Definition
bact: neutrophils

viral: lymphocytes

fungal: lymphocytes

TB: lymphocytes
Term
CSF meningitis pathologies

protein
Definition
bact: >100

viral: 15-100

fungal: 40-500

TB: 100-500
Term
CSF meningitis pathologies

glucose
Definition
bact: <40% serum

viral: normal

fungal: 10-40

TB: <45
Term
CSF meningitis pathologies

gram stain
Definition
bact: postive

viral: negative

fungal: positive

TB: negative
Term
CSF meningitis pathologies

cultures
Definition
bact: positive

viral: negative

fungal: positive

TB: positive (eventually)
Term
CSF meningitis pathologies

CSF pressure
Definition
bact: 200-500

viral: normal

fungal: mild elev

TB: elevated
Term
*neurologic infections key points*

meningitis
Definition
FEVER

HEADACHE

meningeal signs
Term
*neurologic infections key points*

viral encephalitis
Definition
headache

MENTAL STATUS CHANGES
Term
*neurologic infections key points*

abscess
Definition
headache

FOCAL FINDINGS
Term
*neurologic infections key points*

PCR test
Definition
can be used for:

TB, HSV, west nile
Term
*neurologic infections key points*

biopsy
Definition
abscess

HSV
Term
TB

granulomas
Definition
granuloma/tuberculoma

TB's version of an abscess

parenchymal involvement

spherical/multilobar lesions with a caseous center surrounded by a granulomatous reaction comprised of giant cells, lymphcytes, and fibrosis
Term
syphilis

clinical features
Definition
1o: chancre at site of inoculation

2o: asymptomatic; flu-like symptoms; rash; lymphadenopathy; mucosal lesions

latent - months to years

3o: on in 10-30% on untreated patients
Term
syphilis

neurologic syndromes
Definition
aseptic meningitis

meningovascular syphilis

general paresis

tabes dorsalis
Term
syphilis

aseptic meningitis
Definition
only in ~5% of people

occurs in 2o syphilis or in the first 2 years of latent syphilis

cranial nerve involvement is common
Term
syphilis

meningovascular syphilis
Definition
type of 3o syphilis; usually 1-10 years after innoculation

headache, apathy, irritability, insomnia, focal deficits

lymphocyte and plasma cell proliferation in meninges and around blood vessels

combo of meningitis and stroke manifestations
Term
syphilis

general paresis
Definition
10-20 years after initial inoculation

dementia, psychiatric manifestations, seizures, myoclonus, abnormal pupils, dysarthria, UMN findings, incontinence, death

thickened fibrotic meninges, loss of cortical neurons, gliosis, marked proliferation of rod-shaped microglia

(like SSPE, can cause almost any brain manifestation)
Term
syphilis

tabes dorsalis
Definition
15-20 years after inoculation

dramatic loss of proprioception/vibrational sense

lighting-like pains, ataxia

chronic inflammation of dorsal roots and ganglia, with degeneration of posterior columns
Term
syphilis

diagnosis
Definition
RPR, VDRL: non-specific serologic test; present in blood of almost all 2o patients, but reverts to normal in 25% of late stage patients

FTA, MHA-TP: specific antibody tests; present in almost all 2o patients, persists throughout life (even after treatment)
Term
syphilis

protocol for diagnosing
Definition
serum FTA test

-if negative = NOT neurosyphilis

-if positive = do LP
Term
syphilis

CSF findings
Definition
+ WBCs

+ protein

+ VDRL in spinal fluid

...ANY of the above are an indication for treat for presumed neurosyphilis
Term
syphilis

treatment
Definition
high-dose intravenous penicillin

(when at 3o stage; presence of neurologic syndromes)
Term
lyme disease

neuro manifestations
Definition
1o and 2o similar to syphilis
(3o more controversial)

most common neurologic manifestation = subacute or chronic meningitis, oftern with cranial nerve involvement (especially one of both CN VII)
Term
herpes varicella-zoster virus
VZV /("shingles")

clinical presentation
Definition
(primary infection is chicken pox)

sharp, burning pain in dermatomal distribution

followed by rash in same area 2-5 days later

post-herpetic neuralgia (pain lasting >4weeks) in 10%, but in 50% of patients over age 60
Term
VZV

pathophysiology
Definition
after chicken pox, remains latent in dorsal root ganglion cells

re-activated years later and spreads along the nerve root

more common in elderly and immunocompromised
Term
VZV

diagnosis
Definition
diagnosis is primarily clinical

may do cultures, microscopic examination, or antibody testing on vesicular scrapings from rash

VZV culture or PCR from spinal fluid
Term
VZV

treatment
Definition
acyclovir, famciclovir, valacyclovir all REDUCE DURATION of rash and post-herpetic neuralgia is started within 72 hours

steroids may be helpful, but not definite
Term
VZV

other neurologic manifestations from spread
Definition
spread to spinal cord - myelitis

spread to motor branches of nerve roots - radicualr weakness

spread to neighboring cranial nerves

spread to blood vessels - stroke
(V1 branch of CN V is not far from carotid arteries)
Term
HIV

4 factors predisposing to neurologic involvement
Definition
1. patients are at increased risk for many opportunistic infections and tumors that affect the nervous system

2. HIV itself has a predilection for both the CNS and PNS and may produce symptoms directly

3. antigenic cross-reactivity can cause the inflammatory reaction provoked by HIV infection results in neurologic damage

4. many of the meds to treat HIV can have neurotoxic effects
Term
HIV

neurologic manifestations
Definition
encephalopathy

opportunistic infections: toxo, crypto, EBV/CNS lymphoma, JC virus/PML, VZV, CMV/polyradiculopathy

vacuaolar myelopathy (HIV attacking spinal cord directly)

peripheral neuropathies
Term
PML

progressive multifocal leukoencephalopathy
Definition
disease of white matter caused by JC virus (an opportunistic papova-virus)

can produce mass lesions - may present with progressive, focal symptoms, subacute time course

MRI looks like MS

histo: giant astrocytes, oligodendrocytes with enlarged nuclei and viral inclusions
Term
HIV

approach to mass lesions
Definition
solitary lesion on MRI = biopsy

multiple lesions on MRI = check toxo titers
(-) toxo titer = biopsy
(+) toxo titer = treat empirically for toxo...biopsy if no clinical response after 10-14 days

if PML or CNS lymphoma...treat with HAART
Term
cysticercosis
Definition
parasite that has a predilection for the nervous system

most common parasitic infection of the CNS

"pork tapeworm" that causes neruo disease when humans replace pigs in the life cylce of the parasite via fecal-oral contamination (usually from produce washed in contaminated water)
Term
cysticercosis

clinical features
Definition
may or may not be symptomatic, but usually don't occur until long after the infection is established (1-35 years!)

seizures, headache

stroke, encephalitis

may present with ICP features if cyst obstructs CSF flow

may have focal deficits depending on location of individual cysts
Term
cysticercosis

pathophysiology
Definition
4 stages:

1-cysticercus provkes edema form surrounding brain parenchyma

2-thin walled cyst containing fluid and a live larva develops over several months

3-inflammatory reaction from surrounding brain damages cyst-->fills with caseous material; larva dies and cyst contents released

4-cyst itself degenerates and becomes calcified and inacive

cysts often resolve spontaneously after the inflammatory reaction begins
Term
cysticercosis

pathology
Definition
anywhere from one to several hundred cysts in CNS: parenchyma (esp. gray), meninges, ventricles

after arg dies, surrounded by neutrophils, lymphocytes, macrophages, foreign body cells, eosinophils

cyst becomes zone of granulation tissue --> dense collagenous capsule --> fibrotic/calcified
Term
cysticercosis

treatment
Definition
albendazole

AEDs if seizures develop

shun (and resection) if hydrocephalus
Term
antigen studies
Definition
bacterial meningitis

fungal meningitis (esp cryptococcal)
Term
antobody studies
Definition
arboviruses - encephalitis
Term
PCR
Definition
TB meningitis

HSV
Term
is it SAH or bacterial meningitis?
Definition
both = qualitatively different and "worst headache of life"

CT will show SAH in 95% of patients within 48 hours

LP: if no WBC, NOT meningitis; RBC hallmark of SAH
Term
major antibiotics used to treat nervous system infections
Definition
ceftriaxone

acyclovir

isoniazid

amphotericin
Term
ceftriaxone
Definition
3rd generation cephalosporin

bacterial meningitis

empiric treatment of abscess
Term
acyclovir
Definition
HSV

VZV
Term
isoniazid
Definition
TB
Term
amphotericin
Definition
fungal meningitis
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