CNS Infections

1
CNS Infections

• Keith B. Armitage, MD
• Vice Chair for Education, Department of Medicine
• University Hospitals Case Medical Center
• Case Western Reserve University

2
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?

3
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-
  lt 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

4
Mortality Rates Associated with
Community-Acquired Bacterial Meningitis over the
Past 90 Years
5
Clinical Course, Outcome, and Neurologic Findings
at Discharge
van de Beek D et al. N Engl J Med
20043511849-1859
6
Multivariate Analysis of Factors Associated with
an Unfavourable Outcome
7
(No Transcript)
8
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 gt 100 wbc with neutrophilic
  predominance, low glucose, high protein but 5-10
  near normal associated with bad outcome
• Blood cultures- always

9
(No Transcript)
10
For every patient with suspected acute community
acquired bacterial meningitis, consider five
medications

• Three meds you always give
• Two you consider

11
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 anaphylaxis- vancomycin plus FQ, TMP-SMX, or
  chloramphenicol
• Vancomycin 1 gram

12
Two you consider

• Ampicillin
• Age gt 60
• Risk factors- alcoholism or impaired immune
  status
• Acyclovir
• Overlap in presentation with encephalitis

13
Corticosteroids in meningitis
14
Cerebrovascular Complications in Bacterial
Meningitis
15
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 20023471549-1556
16
Outcomes Eight Weeks after Admission, According
to Culture Results
de Gans J et al. N Engl J Med 20023471549-1556
17
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 20023471549-1556
18
Adverse Events
de Gans J et al. N Engl J Med 20023471549-1556
19
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

20
Steroids Summary

• For known or suspected Streptococcus pneumonia
• Given with first dose
• Efficacy in developing countries not known

21
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

22
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

23
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?

24
MRI Study of the Brain Showing a Heterogeneous
Mass in the Right Frontal Lobe That Compresses
the Right Lateral Ventricle
25
Differential Diagnosis of Ring-Enhancing Brain
Lesions
26
Microbiologic Pathogens in Brain Abscesses,
According to Major Primary Source of Infection
27
Therapy of brain abscess

• Drainage
• Vancomycin, ceftriaxone, metronidazole
• Consider primary source
• Adjacent infection
• Endocarditis
• Atrial septal defect
• Pulmonary AVMs

28
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

29
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?

30
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?

31
Encephalitis Rule 1

• In any patient with suspected encephalitis-
  administer acyclovir

32
Encephalitis Rule 2

• There is no rule 2.

33
Encephalitis

• Role of HSV PCR
• Other diagnostic tests
• West Nile, Arbovirus panel, Enterovirus
• ? EBV, CMV, other Herpesvirus

34
Treatable Diseases Mimicking Herpes Simplex
Encephalitis in a Study of 432 Patients
35
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 CMCbut

36
Approximate Global Distribution of Medically
Important Members of the Japanese Encephalitis
Serogroup of Flaviviruses
37
Transmission Cycle of West Nile Virus
Hirsch M and Werner B. N Engl J Med
20033482239-2247
38
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.

39
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?

40
Cryptococcal meningitis

• Dont 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

41
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.

42
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.

43
(No Transcript)
44

• Friedlander R et al. N Engl J Med
  20033482125-2132
• van de Beek D et al. N Engl J Med 200635444-53
• Solomon T. N Engl J Med 2004351370-378
• Crumpacker C et al. N Engl J Med 2003349789-796