Download Aseptic Meningitis

Bacterial and Non-Bacterial CNS
Infections
EMERGENCY NEUROLOGY LECTURE
SERIES
JULY 7, 2010
Dr. Abdullah Al-Salti R3
CNS INFECTIONS
Overview
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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
OUT LINE
1.
2.
3.
4.
Bacterial meningitis
Aseptic Meningitis
Viral Meningitis
Viral encephalitis
CNS Infections

Meningitis
• Bacterial, viral, fungal, chemical,
carcinomatous
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Encephalitis
• Bacterial, viral
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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.
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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
Age
0-4 wk
4-12 wk
3 mo to 18 yr
Common Bacterial Pathogens
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
18-50 yr
S. pneumoniae, N. meningitidis
>50 yr
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
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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.
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Other studies have shown the classic triad to be less
common, with estimates ranging from 21% to 51%.
All cases studied had at least one of the three signs; the
absence of the all components of the classic triad excludes the
diagnosis in immunocompetent individuals.
Physical examination

A careful neurological examination is important to
evaluate for :
• focal deficits
• increased intracranial pressure (ICP).
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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.
Bacterial meningitis
Investigations
LP
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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
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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:
•
•
•
•
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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.)
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Neuro abnls included altered MS, inability to
answer 2 consecutive questions or follow 2
consecutive commands, gaze palsy, abnl visual
fields, facial palsy, arm or leg drift, & abnl
language
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
Department of Neurology, University of Michigan, Taubman Center 1914 SPC #5316, 1500 E.
Medical Center Drive, Ann Arbor, MI 48109-5316, USA
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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
Acute bacterail meninigits
MRI
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Not generally useful in acute diagnosis
(Pt cooperation; logistics).
Very helpful in investigating potential
complications developing later in
clinical course such as venous sinus
thrombosis or subdural empyema.
Laboratory Testing Helpful in Distinguishing
Bacterial from Viral Meningitis.
CSF lactate .

Elevated CSF lactate concentrations may be useful in
differentiating bacterial from nonbacterial meningitis in
patients who have not received prior antimicrobial therapy.
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study of 78 patients with acute meningitis in which CSF
lactate concentrations of >4.2mmol/L were considered to be a
positive discriminative factor for bacterial meningitis .
Sens
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Spec
PPV
NPV
96%,
100%, 100%, 97%.
Furthermore, other factors (e.g., cerebralhypoxia/ischemia,
anaerobic glycolysis,vascular compromise,and metabolism of
CSF leukocytes) also may elevateCSF lactate concentrations.
Therefore, measurement of CSF lactate concentrations is not
recommended for patients with suspected communityacquired bacterial meningitis.
Practice Guidelines for the Management of Bacterial Meningitis
Allan R. Tunkel,1 Barry J. Hartman,2 Sheldon L. Kaplan,3 Bruce A. Kaufman,4 Karen
L. Roos,5 W. Michael Scheld,6and Richard J. Whitley7
Laboratory Testing Helpful in Distinguishing
Bacterial from Viral Meningitis.
C-reactive protein (CRP).
 Serum CRP concentrations were capable of
distinguishing Gram stain–negative bacterial
meningitis, with a sensitivity of 96%, a specificity of
93%, and a negative predictive value of 99%.

Measurement of serum CRP concentration may be
helpful in considering withholding antimicrobial
therapy, on the basis of the data showing that a
normal CRP has a high negative predictive value in
the diagnosis of bacterial meningitis. Provided the
CSF Gram stain result is negative.
Practice Guidelines for the Management of Bacterial Meningitis
Allan R. Tunkel,1 Barry J. Hartman,2 Sheldon L. Kaplan,3 Bruce A.
Kaufman,4 Karen L. Roos,5 W. Michael Scheld,6and Richard J. Whitley7
Laboratory Testing Helpful in Distinguishing
Bacterial from Viral Meningitis.
procalcitonin concentration.
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Elevated serum concentrations of the polypeptide procalcitonin,
which are observed in patients with severe bacterial infection,
were shown to be useful in differentiating between bacterial and
viral meningitis .
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In a study of 59 consecutive children hospitalized for meningitis ,
the sensitivity of measurements of the serum procalcitonin
concentration (using a cutoff of 15.0 mg/L) for the diagnosis of
bacterial meningitis was 94%, and the specificity was 100%.
In adults, serum concentrations 10.2 ng/mL had a sensitivity and
specificity of up to 100% for the diagnosis of bacterial meningitis .
At present, because measurement of serum procalcitonin
concentrations is not readily available in clinical laboratories,
recommendations on its use cannot be made at this time.
Practice Guidelines for the Management of Bacterial Meningitis
Allan R. Tunkel,1 Barry J. Hartman,2 Sheldon L. Kaplan,3 Bruce A. Kaufman,4 Karen L. Roos,5 W.
Michael Scheld,6and Richard J. Whitley7
Laboratory Testing Helpful in Distinguishing
Bacterial from Viral Meningitis.
PCR.
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In patients who present with acute meningitis, an important
diagnostic consideration is whether the patient has enteroviral
meningitis.
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Enteroviral RT-PCR has been tested in clinical settings by
numerous investigators and has been found to be more
sensitive than viral culture for the detection of enterovirus, with
a sensitivity and specificity of 86%–100% and 92%–100%,
respectively.
lead to shortened patient hospitalization, decreased use of
antimicrobial therapy for treatment of bacterial meningitis, and
reduced need for ancillary diagnostic tests .
Practice Guidelines for the Management of Bacterial Meningitis
Allan R. Tunkel,1 Barry J. Hartman,2 Sheldon L. Kaplan,3 Bruce A. Kaufman,4 Karen L. Roos,5 W.
Michael Scheld,6and Richard J. Whitley7
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
Overall Goals in Management
1. To promptly recognize the patient with an
acute CNS infection syndrome
2.
To rapidly initiate appropriate empiric
therapy
3.
To rapidly and specifically identify the
etiologic agent, adjusting therapies as
indicated
4. To optimize management of complicating
features
BACTERIAL MENINGITIS
Antimicrobial Rx
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Therapy is generally IV, high dose, & bolus.
Dosing intervals should be appropriate for
drug being administered.
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Utilize “cidal” therapy whenever possible.
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Initiate therapy promptly (ie, within 30 mins)
THE THERAPY OF MENINGITIS
CNS Penetration
Poor Diffusion
Good Diffusion
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Penicillins
3rd & 4th Gen Cephs
Chloramphenicol
Rifampin
TSX
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Early Gen Cephs
Clindamycin
AMGs
Tetracyclines
Macrolides
EMPIRIC THERAPY OF MENINGITIS IN THE
ADULT
Clinical Setting
Likely Pathogens
Community-acquired
S. pneumoniae
N. meningitidis
[Listeria]
[H. influenzae]
Ceftriaxone
2 gm q12h
+
Vancomycin 1-2 gm 12h
+/Ampicillin 2 gm q4h
Closed head trauma
S. pneumoniae
Streptococci
Pen G 3-4 mu q4h
+
Vancomycin 1-2 gm
q12h
Therapy
EMPIRIC THERAPY OF MENINGITIS IN THE
ADULT
Clinical Setting
Likely Pathogens
High risk patients
S. aureus
Compromised hosts Gram negative
Neurosurgical
bacilli
or
Open head injury
Listeria
Nosocomial
Elderly
Therapy
Vancomycin 2-3 gm/d
+
Ceftazidime 2 gm q8h
Cefepime 2 gm q8h
[Ceftriaxone 2 gm q12h]
[Cefotaxime 2 gm q4h]
+/Ampicillin 2 gm q4h
SPECIFIC THERAPY FOR KNOWN PATHOGENS
Pathogen
Recommended Therapy
S. pneumoniae*
N. meningitidis
Streptococci
Pen G 18-24 mu/d
or
Ampicillin 12 gm/d
[Chloro 75-100 mg/kg/d]
[Ceftriaxone 2-4 gm/d]
H. influenzae
Cefotaxime 12 gm/d
[Ceftriaxone 2-4 gm/d]
Group B strep
Pen G 18-24 mu/d
or
Ampicillin 12 gm/d
[plus aminoglycoside]
SPECIFIC THERAPY FOR KNOWN PATHOGENS
(continued)
S. aureus
Nafcillin 12 gm/d
[Vancomycin 2-3 gm/d]
Listeria
Ampicillin 12 gm/d
or
Pen G 18-24 mu/d
[plus aminoglycoside]
Gram negative
bacilli
Cefotaxime 12 gm/d
[Ceftriaxone 2-4 gm/d]
Pseudomonas
Ceftazidime 6-8 gm/d or
Cefepime 6 gm/d
[plus aminoglycoside]
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
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Role of steroids still somewhat uncertain.
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.
CORTICOSTEROIDS AND MENINGITIS
(Cont)
Only pts with cloudy CSF, + CSF GmS,
or CSF WBC count >1000 were enrolled
 Accompanying editorial raised concerns
about use of steroids in pts with DRSP
who are being Rx’ed with vanc b/o ↓ in
CNS conc of vanc with concurrent steroid
use.
 Practically speaking, almost all pts with
presumed bacterial meningitis are
candidates for at least 1 dose of dexa

NEJM 2002;347:1549
Acute bacterial meningitis
Antibiotic prophylaxis
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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.
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
Department of Neurology, University of Michigan, Taubman Center 1914 SPC #5316, 1500 E.
Medical Center Drive, Ann Arbor, MI 48109-5316, USA
PREDICTORS OF ADVERSE CLINICAL OUTCOMES IN
PTS WITH COMMUNITY-ACQUIRED BACTERIAL
MENINGITIS
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Retrospecitve study; 269 pts (84% culture +).
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Adverse clinical outcome in 36% of pts(Death 27%, neuro deficit
9%).
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↓BP, altered MS, and seizures on presentation all independently
associated with adverse clinical outcome.
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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.
Aronin et al, AIM1998;129:862
Aseptic Meningitis
Aseptic Meningitis
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All non-bacterial causes of meningitis
Typically less ill appearing than bacterial
meningitis
Most common cause is viral
• HSV
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Consider especially in infants presenting with seizure
Usually HSV type II
Treat with acyclovir
• Enterovirus (coxsackie, echovirus)
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Typically occurs during late summer and fall
Spread via respiratory secretions and fecal-oral
Affects all ages
Generally self-limited illness
Aseptic Meningitis
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Other Viral
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HIV
Lymphocytic choriomeningitis virus
Arbovirus
Mumps
CMV
EBV
VZV
Adenovirus
Measles
Rubella
Rotavirus
Influenza and parainfluenza
Aseptic Meningitis
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Other infectious
• Borrelia burgdorferi
• Mycobacterium tuberculosis
• Treponema pallidum
• Mycoplasma pneumoniae
• Rickettsia, erlichia, brucella
• Chlamydia
Aseptic Meningitis
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Fungal
• Cryptococcus
• Coccidiodes
• Histoplasmosis
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Parasitic
• Angiostrongylus
• Toxoplasmosis
Aseptic Meningitis
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Medication
• NSAID’s
• Bactrim
• Pyridium
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Malignancy
• Lymphoma and leukemia
• Metastatic carcinoma
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Autoimmune
• Sarcoid
• Behcet’s
• SLE
Viral Meningitis
•
Very common
clinical course is less fulminant compared to
bacterial
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Often caused by enteroviruses
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Polioviruses
Coxsackieviruses
Echoviruses
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Treatment is supportive
VIRAL ENCEPHALITIS
Introduction
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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
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•
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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
Herpes simplex
Varicella-zoster
Epstein Barr
Cytomegalovirus
Myxo/paramyxoviruses
Influenza/parainfluenzae
Mumps
Measles
Miscellaneous
Adenoviruses
LCM
Rabies
HIV
Enteroviruses
Polioviruses
Coxsackieviruses
Echoviruses
Togaviruses
Eastern equine
Western equine
Venezuelan equine
St. Louis
Powasson
California
West Nile
Patient History
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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
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Recent animal bites → Tick borne encephalitis or
Rabies.
Occupation
• Forest worker, exposed to tick bites
• Medical personnel, possible exposure to infectious diseases.
History cont.
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Season
• Japanese encephalitis is more common during the rainy
season.
• Arbovirus infections are more frequent during summer and fall.
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Predisposing factors:
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•
•
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Immunosuppression caused by disease and/or drug treatment.
Organ transplant → Opportunistic infections
HIV → CNS infections
HSV-2 encephalitis and Cytomegalovirus infection (CMV)
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Drug ingestion and/or abuse
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Trauma
Initial Signs
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Headache
Malaise
Anorexia
Nausea and Vomiting
Abdominal pain
Developing Signs
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Altered LOC – mild lethargy to deep coma.
AMS – confused, delirious, disoriented.
Mental aberrations:
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hallucinations
agitation
personality change
behavioral disorders
occasionally frank psychosis
Focal or general seizures in >50% severe
cases.
Severe focused neurologic deficits.
Neurologic Signs
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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
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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
Brain biopsy :

Reserved for patients who are worsening, have an
undiagnosed lesion after scan, or a poor response to
acyclovir.
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.
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WNV is associated with significant morbidity and morality.
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Mortality of HSV encephalitis before acyclovir was 60% to 70%, and
with treatment approximately 30%.
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Cognitive disability,seizures, and motor deficits are common
sequelae seen among survivors
Bacterial and Non-Bacterial CNS
Infections
EMERGENCY NEUROLOGY LECTURE
SERIES
JULY 7, 2010
Dr. Abdullah Al-Salti R3