A Diabetic Male with AMS, Fever, and Hallucinations

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

2. Edward P. Sloan, MD, MPHAssociate ProfessorDepartment of Emergency MedicineUniversity of Illinois College of MedicineChicago, IL

3. Attending PhysicianEmergency MedicineUniversity of Illinois HospitalOur Lady of the Resurrection HospitalChicago, IL

6. Global Objectives • Maximize patient outcome • Utilize health care resources well • Optimize evidence-based medicine • Enhance ED practice

7. Sessions Objectives • Present case • Review key concepts • Consider relevant questions • Examine treatment options • Develop reasonable Rx strategies

8. 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

9. 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.”

10. 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

11. 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

12. 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?

13. 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

14. 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

15. 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

16. 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

17. 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

18. 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) +

19. 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

20. Fever, AMS Differential Dx Encephalitis Meningitis Meningoencephalitis Encephalomyelitis Sepsis

21. Viral Encephalitis Etiologies Arboviruses: mosquitoes, ticks Herpes viruses: Herpes simplex Epstein-Barr CMV Varicella zoster Measles virus

22. Encephalitis Pathophysiology Brain inflammation Usually caused by a viral etiology Focal, multi-focal, or diffuse Cerebral edema, hemorrhage, neuronal death

23. Encephalitis Pathophysiology Blood borne CNS infection Diffuse encephalitis Transmitted thru other tissue Focal infection DNA or RNA viruses

24. 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

25. 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

26. Varicella Encephalitis Bad if related to chicken pox Adults and children In zoster, less severe unless immunocompromised Both types are rare

27. Epstein-Barr Encephalitis Related to mononucleosis Fatigue, sore throat, HA, fever 1% encephalitis rate Usually mild

28. CMV Encephalitis 5-10% complication rate In HIV patients, 50% complicated Significant mortality

29. 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

30. 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

31. Arbovirus Encephalitis Eastern equine Western Equine St Louis California Japanese B West Nile

32. 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

33. Arbovirus Motor Sx Motor disorders common Severe general weakness Ataxia, voluntary motor problems Tremor, partial paralysis Dysphagia, Broca’s aphasia Hearing and visual symptoms

34. Encephalitis Sx Sudden onset Meningismus Stupor, coma Seizures, partial paralysis Confusion, psychosis Speech, memory symptoms

35. 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

36. 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

37. Ruling Out Viral Meningitis Self limited Headache, photosensitivity Stiff neck Fever, N/V, fatigue also common Confusion, psychosis not seen Exclude mycoplasma, legionnella

38. Treating Viral Encephalitis Antibiotics for presumed meningitis Acyclovir for presumed HSV Dx Steroids? Supportive therapies Seizure Rx Sedation Airway control Pain and fever meds

39. 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)

40. Encephalitis Pt Outcome 25% relapse rate in HSV disease ? Due to relapse or new viral illness Poorer outcome with: Age < 1, > 55 Immunocompromise Pre-existing neurological problem Specific virus virulence Coma does not = bad outcome

41. 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)

42. Encephalitis Vaccines Measles vaccine Varicella vaccine Rabies vaccine, immunoglobulin Japanese encephalitis vaccine Experimental West Nile Virus vaccine

43. 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

44. 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

45. West Nile Ecology

46. West Nile Ecology

47. U.S. counties reporting any WNV-infected birdsin1999(N = 28 counties)

48. U.S. counties reporting any WNV-infected birdsin2000(N = 136 counties)

49. U.S. counties reporting any WNV-infected birdsin2001(N = 328 counties)

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