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CNS Infections
EMERGENCY NEUROLOGY LECTURE SERIES
August 24, 2011
Dr .Abdullah Al-Salti R4
CNS Infections
 Case scenario
 Bacterial meningitis .
 C.T before L.P
 Dexamethasone used
 Prophylaxes.
 Viral encephalitis
 L.P procedure.
CASE 1
A 21-year-old college student was found poorly
responsive in her room. She had complained of a
headache for about 4 days that was refractory to
NSAIDs.
In the ER, temperature was 39.5°C, with BP 145/100
mmHg, HR of 112 per minute and RR of 18 per
minute.
She partly responded to verbal commands, localized
symmetrically to noxious stimuli, and moaned
incoherently.
Neurological examination showed nuchal rigidity, and
normal brainstem reflexes, with symmetric
hyperreflexia and flexor plantar responses.
CASE 1
H.P.I
ONSET, COURSE
,DURATION

 CONSTITIUSIONAL
SYMPTOMES.
First thing to do
 PMH.
 SURGICAL HISTORY
 MEDICATIONS.
 SCREEN NUEROLOGICAL
 FAMILY HISTORY.
SYSTEMS.
 HABITES.
 SYSTEMIC REVIEW.
 SOCIAL .
 WHAT IS SO FARE BEEN
DONE ?
Examination :
1.
2.
3.
4.
Focal neurological deficitst .
Signs of meninegeal irritation.
Signs of raised ICP.
General systemic exam.
Ddx:?
Investigasion ?
Treatments?
CNS INFECTIONS
CNS INFECTIONS
Overview
 Life-threatening problems with high associated mortality
and morbidity.
 Presentation may be acute, subacute, or chronic.
 Clinical findings determined by anatomic site(s) of
involvement, infecting pathogen, and host response.
 Vulnerability of CNS to the effects of inflammation & edema
mandates prompt diagnosis with appropriate therapy if
consequences to be minimized.
CNS Infections
 Meningitis
 Bacterial, viral, fungal, chemical, carcinomatous
 Encephalitis
 Bacterial, viral
 Meningoencephalitis
 Abscess
 Parenchymal, subdural, epidural
INFECTIONS
4 routes which infectious agents can enter the CNS
a) hematogenous spread
i) most common
- usually via arterial route
- can enter retrogradely (veins)
b) direct implantation
i) most often is traumatic
ii) iatrogenic (rare) via lumbar
puncture
iii) congenital (meningomyelocele)
c) local extension (secondary to established infections)
i) most often from mastoid, frontal sinuses,
infected tooth, etc.
d) PNS into CNS
i) viruses
- rabies
- herpes zoster
BACTERIAL MENINGITIS
Meningitis
refers to an inflammatory process of leptomeninges and CSF.
Meningoencephalitis
refers to inflammation to meninges and brain parenchyma.
 Meningitis classified:
a) acute pyogenic
i) usually bacterial meningitis
b) aseptic
i) usually acute viral meningitis
c) chronic
i) usually TB, spirochetes, cryptococcus.

Incidence of 3 cases/100,000 population/yr (~25,000 total cases).
COMMON BACTERIAL PATHOGENS BASED ON
PREDISPOSING FACTOR IN PATIENTS WITH MENINGITIS
Predisposing Factor
Common Bacterial Pathogens
Age
0-4 wK
4-12 wk
3 mo to 18 yr
18-50 yr
>50 yr
Streptococcus agalactiae, Escherichia coli,
Listeria monocytogenes, Klebsiella
pneumoniae, Enterococcus spp.,
Salmonella spp.
S. agalactiae, E. coli, L. monocytogenes,
Haemophilus influenzae, Streptococcus
pneumoniae, Neisseria meningitidis
H. influenzae, N. meningitidis, S. pneumoniae
S. pneumoniae, N. meningitidis
S. pneumoniae, N. meningitidis,
L..monocytogenes, aerobic gram-negative
bacilli
Clinical Features
Signs and symptoms:

rapid onset of fever

headache

photophobia

nuchal rigidity

lethargy, malaise

altered mentation

seizure

vomiting.
van de Beek D, de Gans J, Tunkel AR, et al.
Community-acquired bacterial meningitis
in adults. N Engl J Med 2006;354(1):44–53.
Clinical Features
 Study of 493 adult patients with bacterial meningitis, the presence
of the ‘‘classic triad’’ of
 fever,
 neck stiffness, and
 altered mental status was present in two-thirds of patients.
 fever WAS the most common element, in 95%.
(N Engl J Med 1993;328(1):21–8. )
 Older patients with S. pneumoniae meningitis are more likely to
have the classic triad.
Weisfelt M, van de Beek D, Spanjaard L, et al. Community-acquired bacterial meningitis
in older people. J Am Geriatr Soc 2006;54(10):1500–7.
Physical examination
 A careful neurological examination is important to
evaluate for :
 focal deficits
 increased intracranial pressure (ICP).
 Examination should include assessment for meningeal
irritation
 Brudzinski’s sign
 Kernig’s sign
 findings include purpura or petechia of the skin, which
may occur with meningococcemia.
(straightening of the knee with a flexed hip resulting in back and neck pain)
(passive flexion of the neck resulting in flexion of the hips and knees)
Bacterial meningitis
Investigations
LP
 Single most impt diagnostic test.
 Mandatory, esp if bacterial meningitis suspected.
 Tube #1 – glucose and protein
 Tube #2 – cell count and differential
 Tube #3 – gram stain and rountine culture,
cyrptococcal antigen, AFB stain and culture
 Tube #4 – VDRL, or viral studies (PCR)
CSF Characteristics
Bacterial Viral
Fungal TB
Opening
Pressure
Elevated Slight
Normal Usually
elevated or High high
Glc
Low
Normal
Low
Low
Pro
Very
high
Few
>200
Normal
High
High
None
<200
None
<50
None
20-30
PMNs
Mono
Mono
Mono
Rbcs
Wbcs
(c/mm3)
Diff
CT Before LP in Patients with
Suspected Meningitis

301 pts with suspected meningitis; 235 (78%)
had CT prior to LP

CT abnormal in 56/235 (24%); 11 pts (5%) had
evidence of mass effect

Features associated with abnl. CT were:





age >60,
immunocompromise,
H/O CNS dz,
H/O seizure w/in 7d, &
selected neuro abnls
Hasbun, NEJM
2001;345:1727
CT head Before LP(Cont.)
 96/235 pts (41%) who underwent CT had none of
features present at baseline
 CT normal in 93 of these 96 pts (NPV 97%).
 Of the 3 remaining patients, only 1 had mild mass effect
on CT, and all 3 underwent lumbar puncture with no
evidence of brain herniation
Hasbun, NEJM 2001;345:1727
Consideration for lumbar puncture
without neuroimaging
David Somand, MDa,WilliamMeurer, MD
Department of Emergency Medicine, University of Michigan, Taubman Center B1354
SPC #5303, 1500 East Medical Center Drive, Ann Arbor, MI 48109-5303, USA
 Age less than 60.
 Immunocompetent.
 No history of CNS disease.
 No recent seizure (less than 1 week).
 Normal sensorium and cognition.
 No papilledema.
 No focal neurologic defecits.
BACTERIAL MENINGITIS
Managements
APPROACH TO THE PATIENT WITH SUSPECTED
MENINGITIS
Decision-Making Within the First 30 Minutes
 Clinical Assessment
 Mode of presentation
 Acute (< 24 hrs)
 Subacute (< 7 days)
 Chronic (> 4 wks)
 Historical/physical exam clues
 Clinical status of the patient (ABCD)
 Integrity of host defenses
Management algorithm for adults with suspected bacterial meningitis.
Practice Guidelines for the Management of Bacterial Meningitis
BACTERIAL MENINGITIS
Antimicrobial Rx
 Therapy is generally IV, high dose, & bolus.
 Dosing intervals should be appropriate for drug being
administered.
 Utilize “cidal” therapy whenever possible.
 Initiate therapy promptly (ie, within 30 mins)
THE THERAPY OF MENINGITIS
CNS Penetration
Good Diffusion

Penicillins

3rd & 4th Gen Cephs

Chloramphenicol

Rifampin

TSX
Poor Diffusion





Early Gen Cephs
Clindamycin
AMGs
Tetracyclines
Macrolides
EMPIRIC THERAPY OF MENINGITIS IN
THE ADULT
Clinical Setting
Likely Pathogens
Therapy
Community-acquired
S. Pneumoniae
N. meningitidis
[Listeria]
Ceftriaxone
2 gm q12h
+
Vancomycin 1-2 gm 12h
[H. influenzae]
+/_
Ampicillin 2 gm q4h
EMPIRIC THERAPY OF MENINGITIS IN THE
ADULT
Closed head trauma
S. pneumoniae
Streptococci
Pen G 3-4 mu q4h
+
Vancomycin 1-2 gm q12h
EMPIRIC THERAPY OF MENINGITIS IN THE
ADULT
Clinical Setting
Likely Pathogens
High risk patients S. aureus
Compromised hosts
Gram negative
Therapy
Vancomycin 2-3 gm/d
+
Neurosurgical
bacilli
Ceftazidime 2 gm q8h or
Open head injury
Listeria
Cefepime 2 gm q8h
Nosocomial
Elderly
[Ceftriaxone 2 gm q12h]
[Cefotaxime 2 gm q4h]
+/Ampicillin 2 gm q4h
BACTERIAL MENINGITIS
Duration of ATB Rx
Pathogen
Duration of Rx (d)
H. influenzae
7
N. meningitidis
7
S. pneumoniae
10-14
L. monocytogenes
14-21
Group B strep
14-21
GNRs
21
NEJ1997;336:708
CORTICOSTEROIDS AND MENINGITIS
 Recent European study in adults suggested that
Rx with dexa associated with ↓ in risk of
unfavorable outcome (25%→15%, RR 0.59) & in
mortality (15%→7%, RR for death 0.48).
 Benefit primarily
pts w/S. pneumo.
 Dose of dex was 10mg IV q6h X 4d; per protocol,
dex given concurrent with or 15-20 mins before
1st dose of ATBs.
Acute bacterial meningitis
Antibiotic prophylaxis
 Is recommended for high-risk exposures to patients with
Neisseria or Hib meningitis.(potentially share secretions).
 Regimens include :
 Single-dose ciprofloxacin or ceftriaxone.
 Rifampin 600 mg every 12 hours for five doses.
 There is no indication for prophylaxis for exposure to
pneumococcal meningitis.
 Quinolone resistance has been reported to Neisseria, and
this class of antibiotics is no longer recommended for
prophylaxis in parts of the United States.
PREDICTORS OF ADVERSE CLINICAL OUTCOMES IN
PTS WITH COMMUNITY-ACQUIRED BACTERIAL
MENINGITIS
Aronin et al, AIM1998;129:862
 Retrospecitve study; 269 pts (84% culture +).
 Adverse clinical outcome in 36% of pts(Death 27%,
neuro deficit 9%).
 ↓BP, altered MS, and seizures on presentation all
independently associated with adverse clinical
outcome.
 Adverse outcomes in 5% of low risk pts (0 features),
37% of intermediate risk pts (1 feature), and 63% of
high risk pts
(2-3 features).
 Delay in administration of appropriate ATB Rx also
associated with adverse clinical outcome.
Viral Meningitis
 Very common
• clinical course is less fulminant compared to bacterial
 Often caused by enteroviruses
Polioviruses
Coxsackieviruses
Echoviruses
 Treatment is supportive
VIRAL ENCEPHALITIS
Introduction
 Encephalitis is an acute inflammatory process affecting
the brain
 Viral infection is the most common and important cause,
with over 100 viruses implicated worldwide
 Symptoms






Fever
Headache
Behavioral changes
Altered level of consciousness
Focal neurologic deficits
Seizures
 Incidence of 3.5-7.4 per 100,000 persons per year
VIRAL ENCEPHALITIS
Herpesviruses
Enteroviruses
Herpes simplex
Polioviruses
Varicella-zoster
Coxsackieviruses
Epstein Barr
Echoviruses
Cytomegalovirus
Myxo/paramyxoviruses
Togaviruses
Influenza/parainfluenzae
Eastern equine
Mumps
Western equine
Measles
Venezuelan equine
Miscellaneous
St. Louis
Adenoviruses
Powasson
LCM
California
Rabies
West Nile
HIV
Patient History
 Detailed history critical to determine the likely cause of
encephalitis.
 Prodromal illness, recent vaccination, development of few
days → Acute Disseminated Encephalomyelitis (ADEM) .
 Biphasic onset: systemic illness then CNS disease →
Enterovirus encephalitis.
 Abrupt onset, rapid progression over few days → HSE.
 Recent travel and the geographical context:
 Africa → Cerebral malaria
 Asia → Japanese encephalitis
 High risk regions of Europe and USA → Lyme disease
 Recent animal bites → Tick borne encephalitis or Rabies.
 Occupation
 Forest worker, exposed to tick bites
 Medical personnel, possible exposure to infectious diseases.
History cont.
 Season
 Japanese encephalitis is more common during the rainy season.
 Arbovirus infections are more frequent during summer and fall.
 Predisposing factors:




Immunosuppression caused by disease and/or drug treatment.
Organ transplant → Opportunistic infections
HIV → CNS infections
HSV-2 encephalitis and Cytomegalovirus infection (CMV)
 Drug ingestion and/or abuse
 Trauma
Initial Signs
 Headache
 Malaise
 Anorexia
 Nausea and Vomiting
 Abdominal pain
Developing Signs
 Altered LOC – mild lethargy to deep coma.
 AMS – confused, delirious, disoriented.
 Mental aberrations:





hallucinations
agitation
personality change
behavioral disorders
occasionally frank psychosis
 Focal or general seizures in >50% severe cases.
 Severe focused neurologic deficits.
Neurologic Signs
 Virtually every possible focal neurological disturbance has
been reported.
 Most Common





Aphasia
Ataxia
Hemiparesis.
Involuntary movements
Cranial nerve deficits (ocular palsies, facial weakness)
Other Causes of
Encephalopathy
 Anoxic/Ischemic conditions
 Metabolic disorders
 Nutritional deficiency
 Toxic (Accidental & Intentional)
 Systemic infections
 Critical illness
 Malignant hypertension
 Mitochondrial cytopathy (Reye’s and MELAS syndromes)
 Hashimoto’s encephalopathy
 Traumatic brain injury
 Epileptic (non-convulsive status)
 CJD (Mad Cow)
Differential Diagnosis
 Distinguish Etiology
 (1) Bacterial infection and other infectious conditions
 (2) Parameningeal infections or partially treated bacterial meningitis
 (3) Nonviral infectious meningitides where cultures may be negative
(e.g., fungal, tuberculous, parasitic, or syphilitic disease)
 (4) Meningitis secondary to noninfectious inflammatory diseases
VIRAL ENCEPHALITIS
DIAGNOSIS.
LP:
 CSF usually colorless
- slightly  pressure
- initially a neutrophilic pleocytosis, which rapidly converts to
lymphocytes
- proteins are 
- glucose is normal
 PCR for HSE and other viral infection is diagnostic .
VIRAL ENCEPHALITIS
DIAGNOSIS.
MRI:
 May show temporal or orbitofrontal cortex enhancement or
edema in HSE.
 In most other acute viral encephalities , neuroimaging finding
are nonspecific.
 Can exclude subdural bleeds, tumor, and sinus thrombosis.
EEG:
 Non specific
 Diffuse slowing .
 Focal abnormalities in the temporal region . HSV
Treatment.

Only HSV disease has specific therapy available. Acyclovir is
capable of improving patient outcome.
dose : 10 mg/kg intravenously every 8 hours.


Duration 14-21 days.
ganciclovir can be used in CMV infections.
pleconaril has shown promise in enteroviral.
Outcomes

Outcomes are variable depending on etiology.

EEE and St. Louis encephalitis generally have high mortality rates
and Severe neurologic sequelae among survivors.

WNV is associated with significant morbidity and morality.

Mortality of HSV encephalitis before acyclovir was 60% to 70%, and
with treatment approximately 30%.

Cognitive disability,seizures, and motor deficits are common
sequelae seen among survivors