CNS Infections

Keith B. Armitage, MDVice Chair for Education, Department of Medicine

University Hospitals Case Medical CenterCase 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

van de Beek D et al. N Engl J Med 2004;351:1849-1859

Clinical Course, Outcome, and Neurologic Findings at Discharge

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 anaphylaxis-

vancomycin; 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

de Gans J et al. N Engl J Med 2002;347:1549-1556

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

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

Hirsch M and Werner B. N Engl J Med 2003;348:2239-2247

Transmission Cycle of West Nile Virus

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