1. A Diabetic Male with AMS, Fever, and Hallucinations

2. Edward P. Sloan, MD, MPH Associate Professor Department of Emergency Medicine University of Illinois College of Medicine Chicago, IL

3. Attending Physician Emergency Medicine University of Illinois Hospital Our Lady of the Resurrection Hospital Chicago, IL

4. Edward P. Sloan, MD, MPH, FACEP EMS Presentation… 51 year old 0028 CFD EMS call for AMS Per family, high temp, flu-like symptoms Fever and hallucinations Hot, flushed, diaphoretic, O x 1 VS 140/P, HR 120, RR 30 Glucose 300 Hx DM, HTN Recent viral illness

5. Edward P. Sloan, MD, MPH, FACEP ED Presentation… August 2002, Illinois, 1:01 AM ED Presentation non-verbal, moaning Temp 102.2 Viral Sx, N/V/D for 2 days Taking NSAIDs, refused PMD admit Responds to verbal, moans “Help me.”

6. Edward P. Sloan, MD, MPH, FACEP ED History… ED Presentation non-verbal, moaning Temp 102.2 Viral Sx, N/V/D for 2 days Taking NSAIDs, refused PMD admit Responds to verbal, moans “Help me.” No drugs or EtOH history Hx psoriasis

7. Edward P. Sloan, MD, MPH, FACEP ED Physical Exam… Agitated, confused, combative, diaphoretic Pupils 2-3 mm, non-reactive; airway OK Neck supple, no thyromegaly Cardiopulmonary: tachycardia, tachypnea Abdomen non-tender Neuro: CN grossly normal, no motor weakness, tremor, intermittent nystagmus on central gaze Skin: old psoriasis, no new rash

8. Edward P. Sloan, MD, MPH, FACEP Clinical Questions What are the differential diagnoses? What are the etiologies? What tests must be performed? What therapies must be provided? What consultations are required? What outcome is likely?

9. Edward P. Sloan, MD, MPH, FACEP Lumbar Puncture Are there settings in which a lumbar puncture is NOT to be performed? Why? What are they?

10. Edward P. Sloan, MD, MPH, FACEP Meningitis Rx What is the optimal initial treatment strategy for the management of presumed meningitis? Why? What microbes are we treating?

11. Edward P. Sloan, MD, MPH, FACEP Encephalitis Rx What is the optimal initial treatment strategy for the management of presumed encephalitis? When should we empirically give acyclovir? What clinical or lumbar puncture findings suggest the need for acyclovir?

12. Edward P. Sloan, MD, MPH, FACEP ED Management… DDx: Viral Sx, AMS R/o encephalitis, meningitis, sepsis Need to R/o West Nile Virus (Illinois) 1:15 Haldol, ativan 1:25 RSI with etomidate, pavulon, sux 4:40 Ceftriaxone 2 gr IV 4:55 Acyclovir 1 gr IV over 1 hour

13. Edward P. Sloan, MD, MPH, FACEP ED Diagnostics… WBC 11,900 Hb 16.1 Glu 313, Bicarb 25, chem ok 7.33 / 39 / 79 / 22 / 97% CXR: no clear infiltrate EKG: sinus tach UA: no UTI CT: no lesions LP: Unable x 2

14. Edward P. Sloan, MD, MPH, FACEP Consultations… Neuro consult: LP under fluoro, EEG ID consult: R/o septic shock, resp failure R/o staph, given psoriasis R/o pneumococcal pneumonia R/o meningitis R/o toxic or metabolic encephalopathy Add vancomycin, obtain 2-D echo

15. Edward P. Sloan, MD, MPH, FACEP Hospital Course… LP by neurosurgery: 20 WBC, 20 RBC, glu 137, protein 32 ID: viral synd, R/o aseptic meningitis Day 3: Possible sub-endocardial AMI Day 3: Seizure, rx with fosphenytoin Rocephin changed to cefipime, levaquin Day 9: More responsive, temp to 102.6 Day 10: Maculopapular rash

16. Edward P. Sloan, MD, MPH, FACEP Hospital Course… EEG: Non-specific diffuse slowing ECHO: LV dysfunction Blood cultures negative Repeat CT: maxillary sinus fluid PCR negative for herpes simplex virus Tests for systemic vasculitides negative Ab for myeloperoxidase Ab for proteinase-3

17. Edward P. Sloan, MD, MPH, FACEP Hospital Course… Legionella Ag in urine negative Mycoplasm antibody titre negatvie Chlamydia pneumoniae IgG, IgA positive HIV Ab negative Day 11: West Nile Arbovirus (CSF) +

18. Edward P. Sloan, MD, MPH, FACEP Patient Outcome… PM & R Consult: Comprehensive rehab Pt extubated, improved neurologically Pt able to understand plan Discharge on day 26: nursing home/rehab care able to speak, ambulate beginning to meet needs Seen in ED by same EM MD, doing well

19. Edward P. Sloan, MD, MPH, FACEP Fever, AMS Differential Dx Encephalitis Meningitis Meningoencephalitis Encephalomyelitis Sepsis

20. Edward P. Sloan, MD, MPH, FACEP Viral Encephalitis Etiologies Arboviruses: mosquitoes, ticks Herpes viruses: Herpes simplex Epstein-Barr CMV Varicella zoster Measles virus

21. Edward P. Sloan, MD, MPH, FACEP Encephalitis Pathophysiology Brain inflammation Usually caused by a viral etiology Focal, multi-focal, or diffuse Cerebral edema, hemorrhage, neuronal death

22. Edward P. Sloan, MD, MPH, FACEP Encephalitis Pathophysiology Blood borne CNS infection Diffuse encephalitis Transmitted thru other tissue Focal infection DNA or RNA viruses

23. Edward P. Sloan, MD, MPH, FACEP Arbovirus Encephalitis Mosquitoes or ticks (vectors) Vector-transmitted infection Mosquitoes 10% encephalitis rate if infected 150 to 3000 cases per year Ticks Rocky Mountain spotted fever Non-US Russian encephalitis

24. Edward P. Sloan, MD, MPH, FACEP Herpes Virus Encephalitis Able to lie dormant and reactivate HSV causes 10-20% of all cases 2 per 1,000,000 persons per year Usually HSV-1 from oral herpes Children, both HSV-1 and –2 Only treatable cause of encephalitis

25. Edward P. Sloan, MD, MPH, FACEP Varicella Encephalitis Bad if related to chicken pox Adults and children In zoster, less severe unless immunocompromised Both types are rare

26. Edward P. Sloan, MD, MPH, FACEP Epstein-Barr Encephalitis Related to mononucleosis Fatigue, sore throat, HA, fever 1% encephalitis rate Usually mild

27. Edward P. Sloan, MD, MPH, FACEP CMV Encephalitis 5-10% complication rate In HIV patients, 50% complicated Significant mortality

28. Edward P. Sloan, MD, MPH, FACEP Other Encephalitis Causes Rabies Severe, fatal 16 cases between 1980-91; 8 US Measles, influenza Adenoviruses 30% mortality rate if encephalitis Symptoms of meningitis, coma Parasites: raccoons, toxoplasmosis

29. Edward P. Sloan, MD, MPH, FACEP What is ADEM? Acute disseminated encephalomyelitis Non-infectious encephalitis 2-3 weeks after a viral illness 1/3 of encephalitis cases Varicella, URIs are common causes Autoimmune reaction, white matter Myelin sheath damage, as in MS

30. Edward P. Sloan, MD, MPH, FACEP Arbovirus Encephalitis Eastern equine Western Equine St Louis California Japanese B West Nile

31. Edward P. Sloan, MD, MPH, FACEP Arbovirus Encephalitis Sx St Louis & West Nile common in US Less than 1% cause CNS symptoms Sx 2-14 days post-exposure Fever, HA, N/V, lethargy West Nile Virus: Maculopapular rash, morbilliform rash Loss of muscle tone and weakness

32. Edward P. Sloan, MD, MPH, FACEP Arbovirus Motor Sx Motor disorders common Severe general weakness Ataxia, voluntary motor problems Tremor, partial paralysis Dysphagia, Broca’s aphasia Hearing and visual symptoms

33. Edward P. Sloan, MD, MPH, FACEP Encephalitis Sx Sudden onset Meningismus Stupor, coma Seizures, partial paralysis Confusion, psychosis Speech, memory symptoms

34. Edward P. Sloan, MD, MPH, FACEP Encephalitis Diagnosis Find treatable etiologies CT: no changes early MRI: early HSV changes detectable EEG: temporal lobe HSV changes LP: elevated WBCs and protein Labs: Leukocytosis, LFTs, coags, chem, tox Viral cultures

35. Edward P. Sloan, MD, MPH, FACEP Encephalitis Serum Ab Tests Virus only at 2-4 days (too early) Serum Ab titres Low early levels 4-fold increase in convalescent tires Obtained 3-5 weeks after sx onset PCR: will replicate virus DNA Quick results (hours) Sensitivity equal to viral culture

36. Edward P. Sloan, MD, MPH, FACEP Ruling Out Viral Meningitis Self limited Headache, photosensitivity Stiff neck Fever, N/V, fatigue also common Confusion, psychosis not seen Exclude mycoplasma, legionnella

37. Edward P. Sloan, MD, MPH, FACEP Treating Viral Encephalitis Antibiotics for presumed meningitis Acyclovir for presumed HSV Dx Steroids? Supportive therapies Seizure Rx Sedation Airway control Pain and fever meds

38. Edward P. Sloan, MD, MPH, FACEP Viral Encephalitis Anti-virals Acyclovir for presumed HSV, HZ Foscarnet (Foscavir) When resistant to Acyclovir If adverse reaction to Acyclovir Foscarnet or gancyclovir in CMV Ribavirin (Virazole)

39. Edward P. Sloan, MD, MPH, FACEP Encephalitis Pt Outcome 25% relapse rate in HSV disease ? Due to relapse or new viral illness Poorer outcome with: Age 55 Immunocompromise Pre-existing neurological problem Specific virus virulence Coma does not = bad outcome

40. Edward P. Sloan, MD, MPH, FACEP Encephalitis Pt Outcome Outcome related to mental status at the time anti-viral Rx initiated Early use is warranted Long-term sequelae can occur Motor, speech, cognitive Emotional, personality changes Sensory problems (vision, hearing)

41. Edward P. Sloan, MD, MPH, FACEP Encephalitis Vaccines Measles vaccine Varicella vaccine Rabies vaccine, immunoglobulin Japanese encephalitis vaccine Experimental West Nile Virus vaccine

42. Edward P. Sloan, MD, MPH, FACEP West Nile Virus Encephalitis Mosquito-borne, expanding area 1/5 mild febrile illness 1/150 meningitis, encephalitis Advanced age is greatest risk factor Clues as to likely WNV infection: Infected birds or cases identified Late summer Profound muscle weakness

43. Edward P. Sloan, MD, MPH, FACEP West Nile Virus Encephalitis IgM Ab testing via Elisa useful Test of serum or CSF False positives can occur Other flaviviral infections (dengue) Prior vaccination (yellow fever) Rapid reporting is essential

44. West Nile Ecology

45. Edward P. Sloan, MD, MPH, FACEP West Nile Ecology

46. Edward P. Sloan, MD, MPH, FACEP U.S. counties reporting any WNV-infected birds1999 birds in 1999 (N = 28 counties)

47. Edward P. Sloan, MD, MPH, FACEP U.S. counties reporting any WNV-infected birds2000 birds in 2000 (N = 136 counties)

48. Edward P. Sloan, MD, MPH, FACEP U.S. counties reporting any WNV-infected birds2001 birds in 2001 (N = 328 counties)

49. U.S. Counties Reporting WNV-Positive Dead Birds, 2002* 15,745 birds 1,888 counties 42 states & D.C.

50. Edward P. Sloan, MD, MPH, FACEP 2003

51. Edward P. Sloan, MD, MPH, FACEP June 2004

52. Edward P. Sloan, MD, MPH, FACEP West Nile Virus

53. Edward P. Sloan, MD, MPH, FACEP WNV Encephalitis Diagnosis Leukocytosis, lymphocytopenia Hyponatremia CSF pleocytosis, lymphocytes Elevated CSF protein Normal CT MR: enhanced leptomeninges or periventricular areas

54. Edward P. Sloan, MD, MPH, FACEP Encephalitis MR Findings Inflamed portion of the temporal lobe, involving the uncus and adjacent gyrus, in brightest white on MR. Inflamed portion of the temporal lobe, involving the uncus and adjacent parahippocampal gyrus, in brightest white on MR. parahippocampal

55. Edward P. Sloan, MD, MPH, FACEP WNV Antibody Diagnosis ELISA detection of WNV IgM 95% CSF WNV IgM rate IgM does note cross BBB CSF IgM suggests CNS infection 90% remain positive if tested within 8 days on symptom onset

56. Edward P. Sloan, MD, MPH, FACEP WNV Antibody Diagnosis Asymptomatic pts common In endemic area, IgM could be high Acute, convalescent titres Viral culture low yield Real-time PCR: 55% CSF positive, 10% serum

57. Edward P. Sloan, MD, MPH, FACEP WNV Encephalitis Pt Outcome Overall, 4-14% mortality Age > 70, 15-29% mortality DM, immunosuppression also predict worse outcome

58. Edward P. Sloan, MD, MPH, FACEP WNV Encephalitis Prevention Reducing the # of vector mosquitoes Draining standing water sites Methoprene spraying (no maturation) Adulticides (organophos, pyrethroids) Prevent mosquito bites 50% DEET, 10% DEET in children Permethrin to clothing, fabrics Citronella (less effective)

59. Edward P. Sloan, MD, MPH, FACEP Key Learning Points AMS, fever, weakness: encephalitis Know clues for West Nile virus Early use of ceftriaxone, acyclovir Supportive care essential Consultation for best diagnostics Reportable public health disease Prevention is best approach

60. Edward P. Sloan, MD, MPH, FACEP Key Learning Points No LP if there is a herniation risk Abnormal posturing, exam Abnormal CT Ceftriaxone 2 gr, vancomycin 1 gr LP in encephalitis: WBCs, lymphocytes, no bacteria Acyclovir with any encephalitis risk

61. Questions? www.FERNE.org edsloan@uic.edu 312 413 7490 destin_ sloan_ams_wnv_2004