Prof Ivo Ivić CNS Restricted space for expansion of the inflammatory edema I ncrease of intracranial pressure Tissue infarction Neurological sequelae Death located within the bony armor ID: 775204
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Slide1
BacTerial infections of the central nervous system
Prof
. Ivo Ivić
Slide2CNS
Restricted
space for expansion of the inflammatory edemaIncrease of intracranial pressureTissue infarction
Neurological sequelae
Death
located within the bony armor
protect
ed
against external
mechanical
injuries
Slide3Meninges
3
layers of membranesDura mater (pachimeninges): firmly tied to boneArachnoid mater: loosely adheres to dura materPia mater Adheres to brain/spinal cordcontains blood vessels
leptomeninges
Slide43 spaces Epidural epidural abscessesSubdural subdural abscesses and effusionSubarachnoid contains CSF (purulent in bacterial meningitis)
almost pseudospaces
Meninges
Slide5Chorioid pelxus
Production
of CSF by choriod plexus: 500 mL/dayCirculatin: ventiricles subarachnoid spaceReabsorption of CSFacrahnoid (pachioni) granules
CNS is floating in the 150 ml of CSF
Cerebrospinal fluid
(CSF)
Slide6Chorioid pelxus
Bottlenecks
of CSF circulation inerventricular aperture cerebral aqueduct (Syilvii) lateral apertures (Luschka) median aperture (Magendi)
Inflammatiory adhesions
Hydocephalus
Obstructed straits of CSF circulation
Slide7Blood-brain barrier (BBB)
Consisted of mutually tighly connected capillary endothelial cellsof the brain …………………… blood-brain barrierof the chorioid plexus: ………… blood-CSF barrierInflammation: disturbed permeability of CNS capillaries
Unified
name
Slide8Arterial
side
Venous
side
M
ediates between arterial and venous circulation
Slide9Blood Brain Barier functions
Maintaning constancy of the environment of CNSProtecton of CNS from endogenous and exogeonus toxins Intact BBB disables entry (from blood to CNS) of:Immunoglobulins, Complement ,Antibotics
Entry
is enabled
Infection
of
CNS
brekas
down
BBB
Site of CNS infection: nomenclature
Infection
of
leptomeninges
Viral
–
aseptic
(
serous
) meningitis
Bacterial
-
purulent
meningitis
Infection
of
cerebral
matter
Viral
-
encephalitis
Bacterial
-
cerebritis
(
non
-
incapsulated
purulent
inflammation
)
Abscesses
(
incapsulated
pus
collection
)
Cerebral
:
usualy
within
cortex
Epidural
:
between
bone
and
dura mater
Subdural
:
between
dura
and
arachnoid
Slide11Bacterial
meningitis
Slide12Urgency
Life
threatenig
disease
Quick
diagnosis
and
therapy
are
mandatory
Maximum
30 min from suspicion to treatment
Diagnostic
lumbar
puncture
(LP) is
required
if
no
contraindication
is
present
Slide13Etiology (in order of the incidence)
Community-acquiredStr. penumoniaeN. meningitidisH. influenzaeL. monocytogenesS.aureusGram-neg. bacilli
Nosocomial Gram-neg. bacilliStr.pneum. + other streptococci S. aureus
Immunocompetent
children
and
adults
Slide14Etiology: causative agent
NeonatalE.coliStr. agalactiae (gr. B streptococcus) L. moncytogenes
Slide15Epidemiology
Developed countries
steadily
decreasing
incidence
:
Hib
and
pneumococcal
vaccine
primarily disease of adults
Undeveloped
countries
10x
higher
incidence
Crowded
living
condition
,
lack
of
vaccination
Primarly
chilhood
disease
The modes of spreading
Most
often
sporadic
diseases
Exception
:
meningococcus
A, C, W-135
S.pneumoniae
,
N.meningitidis
,
H.influenzae
Source
:
persons
with
nasopharyngeal
colonization
Modes
:
airborne
(
droplets
), close
contact
(
hands
)
L.moncytogens
Source
: animals
Mode:
ingestion
of
heavily
contaminated
food
Slide17Nosocomial
Source
:
patinets
own flora,
hospital
bacteria
Mode:
contamination
during
neurosurgery
(VP
shunt
)
Neonatal
Source
:
mother
vaginal
flora
Mode:
ingestion
/
inhalation
during
labor
Slide18The ways by which bacteria reach the meninges (subarchnoid space)
Blood borneFrom site of primary colonisation: naspoharynx, intestineinflamation: otitis media, penumonia, sinusitis, endocarditisVia blood (bacteremia)Large intracranial venous sinusesTo meninges
Slide19Contigous
(per continuitatem)2a) via formation of brain abscess From site of primary infectionsinustis, otitis mediaSpread through the bone and meningesFormation of brain abscessesLeakage of pus to subaracnoid space
Slide202b)
via pathological communication on the skull base Consequences of head trauma cribriform plate fracture= nasoliquorrheatemporal bone pyramid fracture = otoliquorrheaAgents: nasopharinegal or middle ear bacteriatypically S.pneumoniaeentry into the CNS through pathological communication
Slide21Multiplication of bacteria within CSFAttraction of neutrophils to kill bacteria Release of toxins and inflammtory cytokinesDamage of the the blood vessels
Inflammatory response within CNS
Slide22Menigitis = inflammation in the subarachnoid space
Vasculitis of the blood vessel on the surface of the brain
brain
edemaincreased intracanial pressuredecreased blood flowhypoxiadamage of cortical neural cels
Slide23Damaged permeability of BBBLeakage of serum proteins in to CSF elevated CSF proteins - proteinorrachia Altered glucose transportlowered CSF glucose – hypoglycorrachiaHypoxia -anerobic metabolismelevated lactate in CSF
Menigitis = inflammation in the subarachnoid space
Slide24Other consequences:Damage of cranial nervesStatoacustic (VIII)Oculomotor (III)Abducens (VI)Hydrocephalusfibrin in inflammatory exudateadhesinosdisturbed circulatuion and absrobtion of CSF
Menigitis = inflammation in the subarachnoid space
long intracranial route
Slide25Clinical features of bacterial meningitis
Slide26Symptoms
(
anamnestic
or
heteroanamnestic
data)
Fever
Headake
Vomiting
Signs
(
physical
examiantion
)
Neck
stiffness
(
and
other
signs
of
meningeal
irritation
)
Altered
mental
status
Focal
neurological
signs
Slide27Headake
(
meningeal
inflammation
+
increased
intracranial
pressure
)
T
he strongest that the patient had ever experienced
on a scale from 1 to 10
= p
atient
’s
“
rating
”
is100
O
ften
accompanied by
neck
pain and back
pain
C
ommon
analgesics
:
weak pain relief
Slide28Meningeal irrition (meningismus, meningeal signs)
(meningeal inflammation + increased intracranial pressure)Neck stiffnesinability to flex the neck and to touch the sternum with chin sensitivity ≈ 30%
pain
Slide29meningeal signs
inability of knee extension of semi flexed legsensitivity <10%
pain
Slide30Tripod sign = inability to sit with extended legs and with hands in the front positionsensitivity <10%
Other meningeal signs
Slide31Knee kiss sign- inability to kiss kneesitting position, leg is flexed at hip and kneesensitivity <10%amplification headache on sudden movement of the head = Head jolt signSensitivity > 95%
Other meningeal signs
Slide32Altered consciousness
Quantitaive
:
Somnolece
-
early
Coma
- late,
poor
prognosis
Qualitative
:
Confusion
and
desorientaion
Behavioral
changes
Slide33Glasgow Coma Score prognostic exam of brain injuryEye opening + Verbal response + Motor response range: 3-15 points ≤8 ponits ………. sever 9-12 points ……… moderate13-15 points ……… mild brain injury
Altered
consciousness
Slide34Unilateral nerve palsyHemiparesis / hemiplegiaFocal cerebral attacks (seizures )Unilateral papiledema or cycloplegia
Focal neurological signs
Ominous signs
Space occupying lesion(abscess)
Neglected meningitis
Slide35Other examinations/signs
Search for the rash, petechial: poor prognostic signMeningococcal infectionAsplenic patient: penumococcal or H.influenaze sepsisSearch for the source of infectionPneumoniaMiddle ear infectionSinustisInfective endocarditis
Pneumococci
- S.aureus
Slide36Search
for
prediposing
factor
head
trauma- CSF
leakage
usually
precedes
meningitis
Pneumococcal
infection
no
leakage
during
meningitis
Slide37Meningeal signs in elderly patients
Unreliable
,
often a stiff neck due to
Spondylosis
Previous
cerebrovascular
disease
Parkinson's disease
Altered
mental
status +
even
low
grade
fever
Lumbar
puncture
is
required
Slide38Meningeal signs in neonates and very joung children (≤12 months)
absence of bony suture of scull (9-18 months)No neck stiffnes : sometimes bulgin fontanelleFever + irritationperform lumbar tap
Slide39Diagnosis
Slide40Diagnostic procedures
Fundoscopic
exam
Examination
of
CSF =
lumbar
puncture
(LP)
Appearance
Cytology
Biokemistry
Gram
stained
smears
Microbiology
Blood
culture
CSF
culture
LP
L4
L3
Cauda
equina
Slide43Contraidications for LP: signs of space occupying process wthin CNS
Papiledema on fundoscopy: unilateral or bilateralFocal neurological signsImmunosupressed and HIV patientsfrequent space occupying processesRISK- incarcertion of medulla oblongata in to the foramen magnum:high intrcranial pressure from aboverelease of lumbar CSF by LPdownward moving of the brain= incarcerationsudden death or permanent neurological sequellae
Slide44CSF appearance
Normal
clear
CSF
Slightly
clodyCSF
Grossly
clody
CSF
Slide45CSF leukocytes (WBC)/mm3
Normal
: 5-7
Bacterial
meningitis
from several hundreds up to several thousand
s
>90% PMN
Exception
-
L.monocytogens
Elicit
mononuclear
respose
Lower
%
of
PMN
Slide46CSF glucose level
Normal
:
2/3
of
blood
glucose
level
is maintained at the minimum 2.5
mmol
/L (45 mg/dL)
Bacterial
meningitis:
hypoglycorrachia
Below
40%
of
blood
glucose
level
Often
< 1.5
mmol
/L (25 mg/dL)
Slide47Normal: 150 - 500 mg/L (15-50 mg/dL)Bacterial meningitis: proteinorracihaOften < 1500 mg/L
CSF protein level
Slide48Normal: 1-2,5 mmol/L (10-25 mg/dL)Bacterial meningitis: >3 mmol/L (27 mg/dL)
CSF
lactate
level
Slide49Gram stained smears of CSF
S.pneumoniae
G+ cocci, diplococci, coccci in chains
N.meningitidis
G-
diplococci
,
intra
and
extracellar
(PMN)
Slide50Algorithm for supected bacterial meningitis
Papilledema and / or focal neurological sign
Yes
No
- Obtain blood culture- LP + CSF culture
Obtain blood culture
CSF examination=Bacterial meningitis
Gram stain of CSF sediment
Visible bacteria
No bacteria
Empiric atibiotic therapy
Focused atibiotic therapy
Empiric atibiotic therapy
CT of head
Mass lesion
Yes
No
Consult neurosurgeon
LP= meningitis
Continue antibiotic
30 min
Slide51Tretament of bacterial meningitis
Slide52Empiric therapy (pending culture results)
Determinats
of
empyrical
therapy
decision
:
Age
Immunological
status
Nosocomial
or
community
acquired
Maximum
dosage
of
antibiotic
(BBB)
Intravenous route + sometimes:
intrathecal route (IT) for Vancomycin
intraventricular
route
for VP
shunt
infection
Slide53Age 3 months – 60 years
Moderetly ill patientCeftriaxon Severely ill patientCeftriaxon + Vancomycin penicillin resistant S.penumoniaeAnaphylactic allegry to penicillinVancomycin
S.pneumoniae
N.menigitidis
(
H.infunezae
b)
Slide54Ceftriaxon + AmpicilinL.monocytogenesNeonates (0-30 days)see neonatal sepsis
Age 1-3 months and >60 years,
Slide55Immunocompromised
patientCeftiaxon + Ampicilin + VacomycinNeurosurgery or VP shunt infectionVancomycin + Ceftazidime
MRSA,MRSE
Gram negative bacilli (including P.aeruginosa)
Slide56PCN resistant S.pneumoniae
Intermediately
resitant
(MIC 0,1-
1
μ
g
/mL
)
High
dose
of
ceftriaxon
to
overcome
BBB
when
inflammation
stabilizes
Highly
resistant
(MIC >
2
μ
g
/mL
)
Vancomycin
+
Rifampin
possible
IT for
vancomycin
Repeated
LP
after
24-36
hours
of
therapy
Antiinflammatory therapy of meningitis
Dexamethason :15 mg/kg IV for 4 daysreduces release of inflammatory cytokinesCSF pressure and brain edemaCSF protein levelincidece of deafness morataliyantibiotic permeability of BBB therefore short course - 4 days
30 min prior to antibiotic
Slide58Other therapeutic measures
Controle of brain edema
and increased ICP
Manitol 20% IV, glycerol PO (children)
appropriate oxygenation
neither hyperventilation, nor hypoventialtion
CO
2
= vasodilatation, brain edema
CO
2
= vasoconstriction, reduced perfusion
Control seisures
: diazepam
after first attac
not as prophylaxis
before
first attac
Slide59PROGNOSIS and COMPLICATIONS
Slide60Prognosis
D
epends
m
ostly
on early treatment
If started
within the first 24 hours of illness
full recovery
or minor curable complications
If started after 2 days of disease
serious complications are likely
Slide61Mortality
Highest with:
L.monocytogenes
age
3 months and 65 years
immunocompromised patient
mortality
L-monocyitogenes ...... 26%
S.pneumoniae ............. 19%
N.meningitidis ............. 13%
H.influenzae ................ 3%
Slide62Permanent neurological sequellae
from learning difficulties to mental retardation
from hearing impairment to deafness
seisure disorders
hydocephalus
cerebral
palsy
(
children
),
paresis
(adults)
cerebellar disfunction (adults)
Slide63PREVENTION
Slide64Vaccination
Prevents
invasive
(
bacteremic
)
infection
to
seed
CNS
H.influenzae
type
b
All
children
:
conjugated
polysaccharide
vacc
.
S.pneumoniae
All
children
: 13-valent
conjugated
polys.vaccine
Adults
: 23-valent
polysacchride
vaccine
Age
>65 y
Splenctomia
,
functional
asplenia
(
sickle
cell
disease
)
chronic
pulmonary
,
cardivascular
and
liver
disease
DM
Slide65Vaccination
N.meningitidis
type
A
and
C
Polysacharide
vaccine
,
~
3years
of
protection
N.meningitidis
type
B
Obut 50%
of
childhood
invasive
meningococal
disease
No
vaccine
available
Under
development
, to
be expected in the near future
Slide66Chemoprophylaxis
H.influenzae
:
Rifampin
/4
days
Within
6
day
of
contact
:
Household
contacts
if
at
least
1
child
aged
<2 y is
unvaccinated
Dycare
contact
children
aged
<2y ???
N.meningitidis
: single dose of Ciprofloxacin
Witin
5
days
of
contact
:
Hosehold
and
daycare
contacts
Slide67Tuberculous
meningitis
Slide68Pathogenis
Children
:
hematogenous
miliary
tb
(
primary
infection
)
Adults
:
miliary
tb
, or
rupture
of
tubercle
of
CNS (
previos
infection
)
Mostly basilar meninges are afected
Mononuclear inflammatory response
Slide69Clinical feature: subacute course
1st
week
:
mostly
general +
scarse
menigneal
symptoms
fever (if low grade, may not be noticed)
insomia
,
loss
of
apetite,
headake
,
fotophobia
,
etc
.
2nd
week
:
meningeal
+
neurological
symptoms
fever
signs
meningeal
irritaion
,
painful
expression
somolence
,
disorientation
,
pathological
nerve
reflexes
kranial
nerve
palsy
(
oculomotors
)
other
focal
neurolgical
signs
(
epi
,
hemiplegia
,
etc
.)
Slide703rd
week
:
advanced
focal
neurological
signs
sopor
,
coma
death
within
5-8
weeks
Focal
neurological
signs
:
If
absent
:
beter
prognosis
, cure is
possible
typically
within
1st
week
of
disease
If
present
:
frequent
permanent
neurological
sequellae
Slide71CSF examiantion: “viral cytology, bacterial biochemistry”
WBC
:
few
hundreds
/
mm
3
usualy
below
500
prevalence
of
lyphocytes
Proteins
:
elevated
usualy
over
1000mg/
mm
3
Glucose
:
lowered
below
2,5mmol/L (45 mg/dL)
Lactate
:
elevated
Over
3
mmol
/L
Slide72Microbiological diagnosis
Microscopy
of
CSF
sedimet
smear
Ziehl
-
Neelsen
(
acid
fast
)
stain
aproximately1/3
positive
CSF
culture
Lage
samples
(
~
10ml)
PCR
~60%
sensitivity
high specificity
Slide73Other diagnostic procedures
PPD-
usually
positive
Chest
X-
ray
positive
for
tb
almost
all
children
only
50%
adults
CT or MRI
of
brain
search
for
tuberculomas
Slide74Therapy
ATD/12
monts
Pyrazinamide
+
Rifampin
+
Isoniazid
/2
months
Followed
by
Rifampin
+
Isoniazid
/10
months
Corticosteroids
/6-8
weeks
, to:
reduce
basilar
inflamation
,
and
prevent
hydocephalus
Slide75(Infections of cerebral cortex)
BRAIN ABSCESS
Slide76Pathogensis
Direct
(
contiogus
)
spred
:
F
rom
the adjacent inflammatory foci
chronic
otitis
media
/
mastioiditis
….
temporal
lobe,
cerebellum
sinusitis
, dental
infection
………….
frontal
lobe
Inoculation
by
penetrateing
wounds
Bulit
,
pencil
Neurosurgery
more
often
solitay
abscess
Slide77Hematogenous
spread
from
:
Lung
abscess
and
empyema
Skin
infection
Abdominal
and
pelvic
infections
Bacterial
endocarditis
,
etc
.
Also freqently seen in patients with cyanotic hearth disease
More
frequently
multiple
absesses
Pathology
Week1-2: cerebritisEarly:inflammatory edema without demarcationLate: development of inflammatory capsuleInhomgenous capsule and abscess content ring enhancment by contrast on CT/MRIdamaged BBB
Early
cerebritis
Late cerebritis
Slide79Pathology
Week 2-3: foramtion of abscessliquefaction of affected tissue – isodens abscess content formation of isodense capsule (demarcation)no ring enhancement edema of the surrounding unaffected tissue
Slide80MRI vs CT
MRI is
preferred
-
better
visualise
:
early
cerebritis
satelite
lesions
small
lesion
extent
of
necrosis
,
ring
enhancement
brain
edema
brain
steam
Slide81Microbilogy: often mixed infections
Anaerobes, oral and intestinalAerobic gram positive cocci alpha-hemolytic (S.milleri)SA, etcGram negative rods - very rareImmunocompromised patients, possibility of: ToxoplasmaNocardia Fungi (Aspergilus, Cryptococcus, etc.)Cysticercus
Slide82Clinical feature
Gradual
development
of
symptoms
Fever
:
only
in
50%,
frequenty
low
grade
Headake
and
vomiting
-
the
most
prominent
Meningeal
irritaion
-
rare
,
usualy
in
case
of
:
ruture
of
abscess
in
to
subarachnoid
space
large
abscesss
of
posterior
cranial
cavity
Slide83Neurological symptoms
Reflect localisation of abscess, just as brain tumors motor and sensory deficitschanges in behavior are and personality, etc.Later symptoms:cranial nerve palsy (oculomotors)papiledemaseiszures
neurologyst/neurosurgeon most commonly establish diagnois
LP
Slide84Therapy
IV antibiotics/ 6-8 weeks + NeurosurgeryAntibiotic selection: depending on origin of infetionOptimal combination of first choice:Metronidazol + Ceftriaxon
anaerobs
G+ cocci
Slide85Pseudomonas
suspected
:
Ceftazidim
instead
of
Ceftriaxon
MSSA
suspected
:
head
trauma,
sepsis
add
Cloxacillin
(
Nafcillin
)
MRSA
suspected
:
neurosurgery
add
Vankomycin
Slide86Corticosterids
If symptoms of edema are prominent
depressed
metal status,
etc
O
therwise
should be
avoide
d:
corticosteroids improve BBB funtion, and
affect
penetration
of
antibiotics
in
to CNS
Slide87INTRACRANIAL EPIDURAL
AND SUBDURAL ABSCESS
Slide88Epidural abscess
Originate from ostemyelitis associated with:neurosurgery, sinusitis (frontal), otitis/mastoiditisS.aureus most comon causative agent
Dura mater
Slide89Symptoms
Epidural absces- slow progresivedura tightly adherent to scullSymptoms mimic brain abscessLocal symptoms of inflammation always presentswelling, erythema and pain
Slide90Subdural
abscess: rapidly progressiveAcutely ill patients, high fever, headakeMeningeal irrtation presentRapid onset of focal neurolgical signswithin1-2 days
Slide91Diagnosis and therapy(epi- and subdural abscess)
LP is
contraindicted
Urgent CT or MRI
Obtain hemoculture,
Introduce
high
dose
antibotic
IV
Consult neurosurgeon for urgent drainage
Slide92SPINAL EPIDURAL ABSCESS
Slide93Spine
canal: dura adheres lightly to vertebraeAnterior and posterior epidural space are formedConatin fat, vessels, nerve roots
Slide94Pathogenesis
direct spred from spondylitis and/or discitisSA- most comon, followed by E.coli
Consequence
of
:Hematogenous spred from various sites,Neurosurgery
Slide95Symptoms and management
Fever,
some patient are septic
Back
pain
,
spinous
processus
tenderness
Radicular
pain
Onset
of
lower
motor deficit (
praparesis
)
Compressed
spinal
cord
Urgent
CT/MRI-
drainge
is
necessary
24
hours
later
–
permanent
cord
damage
is
very
likely
Slide96Therapy
Obtain
blood
culture
Introduce
antibiotic
according
to
pressumed
agent:
MSSA:
Cloxacillin
……………… (
community
acquired
)
MRSA:
Vancmycin
……………… (
nosocomial
)
G-negative :
Ciprofloxacin
…….. (UTI)
4-6
weeks
of
therapy
Consult
neurosurgen
Urgently
if
parparesis
present