Transcript Slide 1

CNS Infections
Keith B. Armitage, MD
Vice Chair for Education, Department of Medicine
University Hospitals Case Medical Center
Case Western Reserve University
Case 1
• A 54 year old woman with a history of
hypertension and diabetes presents to the
UH ED with fever, headache, confusion,
leukocytosis and recent earache. What is
your initial management approach to this
patient?
Acute Community-Acquired
Bacterial Meningitis in Adults
• 4-6 cases per 100,000 adults per year
• Streptococcus pneumonia and Neisseria
meningitides account for 80%
• Listeria monocytogens 8 %; Haemophilus influenza- < 5 %
• Almost all patients present with two of the
following:
– Headache, fever, stiff neck, altered mental status
• For Strep pneumo- historical case fatality 20- 37
%; morbidity 30 %
• May be lower in the steroid era
Mortality Rates Associated with Community-Acquired Bacterial Meningitis over the Past 90 Years
Clinical Course, Outcome, and Neurologic Findings at Discharge
van de Beek D et al. N Engl J Med 2004;351:1849-1859
Multivariate Analysis of Factors Associated with an Unfavourable Outcome
Suspected Acute Community
Acquired Bacterial Meningitis:
Management issues
• Timing of antibiotics and LP
– Do not delay atbx (2 hours from suspected infection
to atbx); delays associated with worse outcomes
– Safety of LP- obviously avoid if increased ICP is
suspected
– Criteria for LP without CT
• Absence of seizures, immunosupressioin, signs of space
occupying lesions, impaired consciousness
– CSF usually has > 100 wbc with neutrophilic
predominance, low glucose, high protein; but 5-10 %
near normal= associated with bad outcome
• Blood cultures- “always”
For every patient with suspected acute
community acquired bacterial
meningitis, consider five medications:
• Three meds you always give
• Two you consider
Three meds you always give
• Dexamethasone
• 10 mg 30 minutes before
or after the first dose of
antibiotics (for suspected
or known pneumococcal
meningitis)
• NEJM 2002- mortality and
morbidity decreased
• Ceftriaxone 2 grams (or
cefotaxime)
• Meropenam
• PCN anaphylaxisvancomycin; plus FQ,
TMP-SMX, or
chloramphenicol
• Vancomycin 1 gram
Two you consider
• Ampicillin
• Age > 60
• Risk factors- alcoholism or impaired immune status
• Acyclovir
• Overlap in presentation with encephalitis
Corticosteroids in meningitis
Cerebrovascular Complications in Bacterial Meningitis
Random Assignment to Treatment, Withdrawal from Treatment, and Follow-up among 301 Adults
with Bacterial Meningitis
de Gans J et al. N Engl J Med 2002;347:1549-1556
Outcomes Eight Weeks after Admission, According to Culture Results
de Gans J et al. N Engl J Med 2002;347:1549-1556
Unfavourable Outcome at Eight Weeks According to the Score on the Glasgow Coma Scale on
Admission
de Gans J et al. N Engl J Med 2002;347:1549-1556
Adverse Events
de Gans J et al. N Engl J Med 2002;347:1549-1556
Steroids: Summary
• Benefit for Streptococcus pneumonia in
patients who are moderately ill
• NNT 10; RR .59
• Trend towards benefit for other groups
– 301 patients in the trial
• New ‘standard of care’ for patients with
suspected acute community-acquired
meningitis in whom Streptococcus
pneumonia has not been ruled out
Steroids: Summary
• For known or suspected
Streptococcus pneumonia
• Given with first dose
• Efficacy in developing countries not
known
Other Management
• Repeat imaging and LP in cases of
deterioration in the face of appropriate
therapy
• MRI may be needed to detect subdural
empyema
• Vaccination- Strep pneumo, NM, H flu
• Neisseria meningitidis prophylaxis
Nosocomial Meningitis
• Need to cover MRSE, MRSA, PSA
• Vancomycin
• Antipseudomonal beta-lactam
– Cefipime, ceftazidime, meropenam
• NOT ceftriaxone
• Aztreonam for PCN anaphylaxis
• Consider IT therapy for resistant pathogens,
ventriculitis
– Almost no clinical trials
Case #2
• A 34 year old woman presents with a
history of several days of headache,
followed by a seizure, decreased level of
consciousness, and focal weakness on
exam. Imaging shows a ring enhancing
lesion. What is your initial management?
MRI Study of the Brain Showing a Heterogeneous Mass in the Right Frontal Lobe That
Compresses the Right Lateral Ventricle
Differential Diagnosis of Ring-Enhancing Brain Lesions
Microbiologic Pathogens in Brain Abscesses, According to Major Primary Source of Infection
Therapy of brain abscess
• Drainage
• Vancomycin, ceftriaxone, metronidazole
• Consider primary source
– Adjacent infection
– Endocarditis
– Atrial septal defect
– Pulmonary AVMs
Differential diagnosis of brain
abscess
– Epidural and subdural empyema
– Septic dural sinus thrombosis
– Mycotic cerebral aneurysms
– Septic cerebral emboli with associated
infarction
– Acute focal necrotizing encephalitis (most
commonly due to herpes simplex virus)
– Metastatic or primary brain tumors
– Pyogenic meningitis
Case 3
• A 76 year old woman presents with
subacute onset of fever and change in
mental status, which has worsened
significantly over the past 24 hours. She
is found to have pyuria and bacteuria.
What is your initial management?
Case #3
• Initial evaluation shows normal labs,
including white blood cell count, and an
unremarkable head CT. An LP is
preformed and reveals a modest CSF
pleocytosis with lymphocytic
predominance and near normal glucose
and protein. Additional management?
Encephalitis Rule #1
• In any patient with suspected
encephalitis- administer acyclovir
Encephalitis Rule #2
• There is no rule 2…………….
Encephalitis
• Role of HSV PCR
• Other diagnostic tests
– West Nile, Arbovirus panel, Enterovirus
– ? EBV, [CMV], other Herpesvirus
Treatable Diseases Mimicking Herpes Simplex Encephalitis in a Study of 432 Patients
West Nile Virus
• Cuyahoga County- summer 2002
– 221 cases of WNV illness, including 11 fatalities
and 155 cases of West Nile-associated
neurologic disease
• Most per capita cases in the US
• Encephalitis, meningitis, “polio-like” transverse
myelitis
– Adverse outcomes associated with advanced
age
– No established therapy
• Planned clinical trial of WNV immunoglobulin at UH
CMC…but
Approximate Global Distribution of Medically Important Members of the Japanese Encephalitis
Serogroup of Flaviviruses
Transmission Cycle of West Nile Virus
Hirsch M and Werner B. N Engl J Med 2003;348:2239-2247
Case #4
• 69 year old man presents with headache
and nausea. He takes weekly
methotrexate for RA. He has subjective
chills but no documented fever. CNS
imaging is negative. A temporal artery
biopsy is done and corticosteroids are
initiated.
Case #4
• Patient presents five days later with
worsening symptoms. On this admission,
LP is completed revealing lymphocytic
pleocytosis with low glucose and elevated
protein. Your diagnosis?
Cryptococcal meningitis
• Don’t forget Cryptococcal meningitis
• Presentation of infection due to
Cryptococcus neoformans can be subtle in
patients with mild immunosupression
• CSF CRAG, Serum CRAG, India Ink
• AmphotericinB; later fluconazole
• Other fungal infections- Histoplasmosis,
sporothrix
Case #5
• A 22 year old woman presents with low
grade fever, headache and mild
photophobia. Her temp is 100.8; other
vitals stable. CSF shows a normal
glucose, moderate protein elevation and
90 wbc, 80 % lymphocytes. What is your
diagnosis.
Viral Meningitis
• Enterovirus!
•
•
•
•
Young adults
Summer months
Fecal oral transmission
benign
• HSV
• Recurrent
• Not encephalitis…..
• HIV seroconversion
• Aseptic meningitis syndrome
• Drugs, partially treated, malignancy, etc.
•
Friedlander R et al. N Engl J Med 2003;348:2125-2132
van de Beek D et al. N Engl J Med 2006;354:44-53
Solomon T. N Engl J Med 2004;351:370-378
•
Crumpacker C et al. N Engl J Med 2003;349:789-796