Download Bacerial infections of the central nervous system

BACTERIAL INFECTIONS OF THE
CENTRAL NERVOUS SYSTEM
Prof. Ivo Ivić
CNS



Restricted space for expansion of the inflammatory edema

Increase of intracranial pressure


located within the bony armor
protected against external
mechanical injuries
Tissue infarction
Neurological sequelae

Death
Meninges
3 layers of membranes
 Dura
mater (pachimeninges): firmly tied to bone
 Arachnoid mater: loosely adheres to dura mater
 Pia mater
 Adheres
to brain/spinal cord
 contains blood vessels
leptomeninges
Meninges
3 spaces
1. Epidural
almost
pseudospaces

epidural abscesses
2. Subdural

subdural abscesses and effusion
3. Subarachnoid

contains CSF (purulent in bacterial meningitis)
Cerebrospinal fluid
(CSF)
Chorioid pelxus
CNS is floating in the 150 ml of CSF

Production of CSF



by choriod plexus: 500 mL/day
Circulatin: ventiricles
Reabsorption of CSF

subarachnoid space
acrahnoid (pachioni) granules
Chorioid pelxus
Inflammatiory adhesions
Bottlenecks of CSF circulation
• inerventricular aperture
• cerebral aqueduct (Syilvii)
• lateral apertures (Luschka)
• median aperture (Magendi)

Obstructed straits
of CSF circulation
Hydocephalus
Blood-brain barrier (BBB)

Consisted of mutually tighly connected capillary
endothelial cells
 of
the brain …………………… blood-brain barrier
 of the chorioid plexus: ………… blood-CSF barrier

Inflammation: disturbed permeability of CNS capillaries
Arterial side
Mediates between
arterial and
venous circulation
Venous side
Blood Brain Barier functions

Maintaning constancy of the environment of CNS

Protecton 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

Bacterial meningitis
Urgency

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
Etiology (in order of the incidence)
Community-acquired






Str. penumoniae
N. meningitidis
H. influenzae
L. monocytogenes
S.aureus
Gram-neg. bacilli
Nosocomial



Gram-neg. bacilli
Str.pneum. + other streptococci
S. aureus
Immunocompetent
children and adults
Etiology: causative agent
Neonatal



E.coli
Str. agalactiae (gr. B streptococcus)
L. moncytogenes
Epidemiology
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
Nosocomial
 Source: patinets own flora, hospital bacteria
 Mode: contamination during neurosurgery (VP shunt)
Neonatal
 Source: mother vaginal flora
 Mode: ingestion/inhalation during labor
The ways by which bacteria reach the meninges
(subarchnoid space)
1. Blood borne
 From site of primary
 colonisation:
naspoharynx, intestine
 inflamation: otitis media, penumonia, sinusitis, endocarditis

Via blood (bacteremia)

Large intracranial venous sinuses

To meninges
2. Contigous (per continuitatem)
2a) via formation of brain abscess
 From site of primary infection
 sinustis,
otitis media

Spread through the bone and meninges

Formation of brain abscesses

Leakage of pus to subaracnoid space
2b) via pathological communication on the skull base
 Consequences of head trauma
 cribriform
plate fracture= nasoliquorrhea
 temporal bone pyramid fracture = otoliquorrhea

Agents: nasopharinegal or middle ear bacteria
 typically
S.pneumoniae
 entry into the CNS through pathological communication
Inflammatory response within CNS

Multiplication of bacteria within CSF

Attraction of neutrophils to kill bacteria

Release of toxins and inflammtory cytokines

Damage of the the blood vessels
Menigitis = inflammation in the subarachnoid space
 Vasculitis
of the blood vessel on the surface of the brain

brain edema

increased intracanial pressure

decreased blood flow

hypoxia

damage of cortical neural cels
Menigitis = inflammation in the subarachnoid space
Damaged permeability of BBB

Leakage of serum proteins in to CSF
 elevated

Altered glucose transport
 lowered

CSF proteins - proteinorrachia
CSF glucose – hypoglycorrachia
Hypoxia -anerobic metabolism
 elevated
lactate in CSF
Menigitis = inflammation in the subarachnoid space
Other consequences:
 Damage of cranial nerves
 Statoacustic
(VIII)
 Oculomotor (III)
 Abducens (VI)

• long intracranial route
Hydrocephalus
 fibrin
in inflammatory exudate
 adhesinos
 disturbed circulatuion and absrobtion of CSF
Clinical features
of bacterial meningitis
Symptoms (anamnestic or heteroanamnestic data)
 Fever
 Headake
 Vomiting
Signs (physical examiantion)
 Neck stiffness (and other signs of meningeal irritation)
 Altered mental status
 Focal neurological signs
Headake
(meningeal inflammation + increased intracranial pressure)

The strongest that the patient had ever experienced
 on
a scale from 1 to 10 = patient’s “rating” is100

Often accompanied by neck pain and back pain

Common analgesics: weak pain relief
Meningeal irrition (meningismus, meningeal signs)
(meningeal inflammation + increased intracranial pressure)
Neck stiffnes
 inability to flex the neck and to touch the sternum
with chin
 sensitivity ≈ 30%
pain
meningeal signs

inability of knee extension of semi flexed leg
 sensitivity
<10%
pain
Other meningeal signs

Tripod sign = inability to sit with extended legs and
with hands in the front position
 sensitivity
<10%
Other meningeal signs

Knee kiss sign- inability to kiss knee
 sitting


position, leg is flexed at hip and knee
sensitivity <10%
amplification headache on sudden movement of the
head = Head jolt sign
 Sensitivity
> 95%
Altered consciousness
Quantitaive :
 Somnolece- early
 Coma- late, poor prognosis
Qualitative:
 Confusion and desorientaion
 Behavioral changes
Altered consciousness

Glasgow Coma Score
 prognostic
exam of brain injury
 Eye opening + Verbal response + Motor response
 range:
3-15 points
≤8 ponits ………. sever
 9-12 points ……… moderate
 13-15 points ……… mild brain injury

Focal neurological signs




Unilateral nerve palsy
Hemiparesis / hemiplegia
Focal cerebral attacks (seizures )
Unilateral papiledema or cycloplegia
Ominous signs
Space occupying lesion
(abscess)
Neglected meningitis
Other examinations/signs

Search for the rash, petechial:
poor prognostic sign
 Meningococcal infection
 Asplenic patient: penumococcal or H.influenaze sepsis

Search for the source of infection
 Pneumonia
 Middle
ear infection
Pneumococci
 Sinustis
 Infective
endocarditis - S.aureus

Search for prediposing factor
 head
trauma- CSF leakage usually precedes meningitis
 Pneumococcal
infection
 no leakage during meningitis
Meningeal 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
Meningeal signs in neonates and very
joung children (≤12 months)
absence of bony suture of scull (9-18 months)
 No neck stiffnes : sometimes bulgin fontanelle
 Fever + irritation

perform lumbar tap
Diagnosis
Diagnostic procedures
1. Fundoscopic exam
2. Examination of CSF = lumbar puncture (LP)
 Appearance
 Cytology
 Biokemistry
 Gram
stained smears
3. Microbiology
 Blood
culture
 CSF culture
LP
L3
L4
Cauda equina
Contraidications for LP:
signs of space occupying process wthin CNS



Papiledema on fundoscopy: unilateral or bilateral
Focal neurological signs
Immunosupressed and HIV patients
 frequent

space occupying processes
RISK- incarcertion of medulla oblongata
in to the foramen magnum:
 high intrcranial pressure from above
 release of lumbar CSF by LP
 downward moving of the brain= incarceration
 sudden death or permanent neurological sequellae
CSF appearance
Normal clear
CSF
Slightly clody
CSF
Grossly clody CSF
CSF leukocytes (WBC)/mm3


Normal: 5-7
Bacterial meningitis
 from
several hundreds up to several thousands
 >90% PMN
 Exception- L.monocytogens
 Elicit
mononuclear respose
 Lower % of PMN
CSF 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)
CSF protein level

Normal: 150 - 500 mg/L (15-50 mg/dL)

Bacterial meningitis: proteinorraciha
 Often
< 1500 mg/L
CSF lactate level

Normal: 1-2,5 mmol/L (10-25 mg/dL)

Bacterial meningitis: >3 mmol/L (27 mg/dL)
Gram stained smears of CSF
N.meningitidis
G- diplococci, intra and extracellar (PMN)
S.pneumoniae
G+ cocci, diplococci, coccci in chains
Algorithm for supected bacterial meningitis
Papilledema and / or focal neurological sign
30 min
Yes
No
- Obtain blood culture
- LP + CSF culture
Obtain blood culture
Empiric atibiotic
therapy
CSF examination=
Bacterial meningitis
CT of head
Gram stain of CSF sediment
Mass lesion
No bacteria
Empiric atibiotic
therapy
Visible bacteria
Focused atibiotic
therapy
Yes
Consult
neurosurgeon
No
LP= meningitis
Continue antibiotic
Tretament of bacterial meningitis
Empiric 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
Age 3 months – 60 years
S.pneumoniae
N.menigitidis
(H.infunezae b)
Moderetly ill patient
 Ceftriaxon
Severely ill patient
 Ceftriaxon + Vancomycin
 penicillin
resistant S.penumoniae
Anaphylactic allegry to penicillin
 Vancomycin
Age 1-3 months and >60 years,

Ceftriaxon + Ampicilin
 L.monocytogenes
Neonates (0-30 days)
 see
neonatal sepsis
Immunocompromised patient

Ceftiaxon + Ampicilin + Vacomycin
Neurosurgery or VP shunt infection

Vancomycin + Ceftazidime
MRSA,
MRSE
Gram negative bacilli
(including P.aeruginosa)
PCN resistant S.pneumoniae
Intermediately resitant (MIC 0,1-1 μg/mL)
 High dose of ceftriaxon
 to
overcome BBB when inflammation stabilizes
Highly resistant (MIC > 2 μg/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 days
 reduces
 release
of inflammatory cytokines
 CSF pressure and brain edema
 CSF protein level
 incidece of deafness
 morataliy
 antibiotic
permeability of BBB
 therefore
short course - 4 days
30 min
prior to antibiotic
Other therapeutic measures
Controle of brain edema and increased ICP
 Manitol 20% IV, glycerol PO (children)
 appropriate oxygenation
 neither
hyperventilation, nor hypoventialtion
 CO2
= vasodilatation, brain edema
  CO2 = vasoconstriction, reduced perfusion
Control seisures: diazepam
 after
first attac
 not as prophylaxis before first attac
PROGNOSIS
and COMPLICATIONS
Prognosis
Depends mostly 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
Mortality
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%
Permanent neurological sequellae

from learning difficulties to mental retardation

from hearing impairment to deafness

seisure disorders

hydocephalus

cerebral palsy (children), paresis (adults)

cerebellar disfunction (adults)
PREVENTION
Vaccination
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

Vaccination
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
Chemoprophylaxis
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
Tuberculous meningitis
Pathogenis

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
Clinical 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.)

3rd 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
CSF examiantion:
viral cytology, bacterial biochemistry”
“

WBC: few hundreds/mm3
usualy below 500
 prevalence of lyphocytes


Proteins: elevated


Glucose: lowered


usualy over 1000mg/mm3
below 2,5mmol/L (45 mg/dL)
Lactate: elevated

Over 3 mmol/L
Microbiological diagnosis

Microscopy of CSF sedimet smear



CSF culture


Ziehl-Neelsen (acid fast) stain
aproximately1/3 positive
Lage samples (~10ml)
PCR


~60% sensitivity
high specificity
Other 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
Therapy

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
BRAIN ABSCESS
(Infections of cerebral cortex)
Pathogensis
Direct (contiogus) spred:
1. From the adjacent inflammatory foci
chronic otitis media/mastioiditis …. temporal lobe, cerebellum
 sinusitis, dental infection …………. frontal lobe

2. Inoculation by penetrateing wounds



Bulit, pencil
Neurosurgery
more often solitay abscess
Hematogenous 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: cerebritis
Early:
 inflammatory edema without demarcation
Late:
 development of inflammatory capsule
 Inhomgenous capsule and abscess content
 ring enhancment by contrast on CT/MRI

damaged BBB
Early cerebritis
Late cerebritis
Pathology

Week 2-3: foramtion of abscess




liquefaction of affected tissue – isodens abscess content
formation of isodense capsule (demarcation)
no ring enhancement
edema of the surrounding unaffected tissue
MRI vs CT

MRI is preferred- better visualise:
 early
cerebritis
 satelite lesions
 small lesion
 extent of necrosis,
 ring enhancement
 brain edema
 brain steam
Microbilogy: often mixed infections


Anaerobes, oral and intestinal
Aerobic gram positive cocci
 alpha-hemolytic
 SA,

(S.milleri)
etc
Gram negative rods - very rare
Immunocompromised patients, possibility of:
Toxoplasma
 Nocardia
 Fungi (Aspergilus, Cryptococcus, etc.)
 Cysticercus

Clinical 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
Neurological symptoms

Reflect localisation of abscess, just as brain tumors
 motor
and sensory deficits
 changes in behavior are and personality, etc.

Later symptoms:
 cranial
nerve palsy (oculomotors)
 papiledema
 seiszures
LP
neurologyst/neurosurgeon most commonly establish diagnois
Therapy

IV antibiotics/ 6-8 weeks + Neurosurgery

Antibiotic selection: depending on origin of infetion
Optimal combination of first choice:
 Metronidazol + Ceftriaxon
anaerobs
G+ cocci

Pseudomonas suspected:
 Ceftazidim

MSSA suspected: head trauma, sepsis
 add

instead of Ceftriaxon
Cloxacillin (Nafcillin)
MRSA suspected: neurosurgery
 add
Vankomycin
Corticosterids
 If symptoms of edema are prominent
 depressed

metal status, etc
Otherwise should be avoided:
 corticosteroids
improve BBB funtion, and
 affect penetration of antibiotics in to CNS
INTRACRANIAL EPIDURAL
AND SUBDURAL ABSCESS
Epidural abscess

Originate from ostemyelitis associated with:
 neurosurgery,
sinusitis (frontal), otitis/mastoiditis
 S.aureus most comon causative agent
Dura mater
Symptoms
Epidural absces- slow progresive

dura tightly adherent to scull

Symptoms mimic brain abscess

Local symptoms of inflammation always present

swelling, erythema and pain
Subdural abscess: rapidly progressive
 Acutely ill patients, high fever, headake
 Meningeal irrtation present
 Rapid onset of focal neurolgical signs

within1-2 days
Diagnosis 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
SPINAL EPIDURAL ABSCESS

Spine canal: dura adheres lightly to vertebrae

Anterior and posterior epidural space are formed
 Conatin
fat, vessels, nerve roots
Pathogenesis

direct spred from spondylitis and/or discitis
 SA-
most comon, followed by E.coli
Consequence of:
•Hematogenous spred
from various sites,
•Neurosurgery
Symptoms 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
Therapy

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