1. A case of altered mental status J. Stephen Huff, MD Associate Professor Emergency Medicine and Neurology University of Virginia Charlottesville, Virginia

2. Let’s talk about a case... 52 year-old man brought to ED by EMS CC: Frontal headache +

3. History of Present Illness 3 weeks of frontal headache Seen by primary care physician 1 week ago Cranial CT obtained no intracranial abnormalities right maxillary sinusitis started on an antibiotic (amoxicillin / clavulanate)

6. History of Present Illness 1 day prior to ED visit Headache worsened Episodes blurred vision and confusion Seen again by primary care physician Switched antibiotic to moxifloxacin

7. History of Present Illness Day of ED visit Awakened 6 AM severe headache Falls or syncope or seizures? Agitated, confused, hallucinating? Arrived ED 0840 by EMS

8. Past Medical History Psoriasis with vasculitis (digital ischemia) Non-insulin dependent diabetes Hypertension, coronary artery disease Current medications- Prednisone, celecoxib, metformin, glipizide, esomeprazole, candesartan, ASA, diltiazem, cyclobenzaprine, fluticasone / salmeterol inhaled

9. Social history (after arrival of family later) Works as truck driver Married, lives with family Past smoker > 40 pack-years Alcohol, drug use denied

10. Physical examination Restless, agitated 147/86, p 96, RR 16, Temp 36.9 SaO2 99% (room air) Will follow simple commands Responds with name Looking off into space

11. Physical examination Difficult General examination unremarkable Digit amputations left hand Psoriatic plaques Chest clear; no murmurs

12. Patient description... Restless, agitated Rolling back and forth No consistent meaningful responses Neurologic examination moves all extremities... Pupils 4 mm, equal, reactive

13. something not right Confusion Agitation Acute delirium Altered mental status

14. Differential diagnosis initial Withdrawal syndrome alcohol benzodiazepines Intoxication alcohol benzodiazepines

15. Differential diagnosis Seizures post-ictal state non-convulsive status epilepticus CNS infection? CNS structural? Systemic infection? Metabolic disturbance...may co-exist...

16. Initial approach IV access Rapid glucose determination Thiamine Laboratory and other blood tests Sedation for safety? More history?

17. Sedate the patient? What is your choice? a) midazolam (Versed) 4 mg IV b) lorazepam (Ativan) 2 mg IV c) haloperidol (Haldol) 5 mg IV d) fentanyl mcg IV e) avoid sedation if at all possible

18. ED course.... Family arrived-confirmed no history of drug or alcohol abuse pattern Family doubted ingestion Altered mental status worsening

19. Laboratory results WBC 13,700 platelets 310, 000 Na 132, bicarb 24. Cr 1.1 BUN 20 Glucose 207 Lactate 1.6 Urinalysis unremarkable Hepatic functions unremarkable

20. Differential diagnosis revisited Withdrawal syndrome Intoxication Seizures post-ictal state non-convulsive status epilepticus CNS infection? CNS structural? Systemic infection? Metabolic disturbance

21. Differential diagnosis revisited Withdrawal syndrome Intoxication Seizures post-ictal state non-convulsive status epilepticus CNS infection? CNS structural? Systemic infection? Metabolic disturbance

22. Clinical Evidence Afebrile White blood cell count indeterminate Supple neck CT a week ago showed sinusitis

23. a few words about Kernig et al Tests for neck rigidity and stiffness.... What does supple mean, anyway?

26. Jolt accentuation of headache maneuver...bottom line...

27. Pre-test probabilities? balancing act Acute bacterial meningitis? Other CNS infection? CNS structural lesion? brain abscess? parameningeal infection?

28. CNS Infection? What is your choice for next step? a) empiric antibiotics b) cranial CT c) lumbar puncture d) MRI e) a, b, and c

29. Working plan Presumed CNS infection.... Concerned about possibility of brain abscess.... Did not want to delay medical therapy

30. What medication(s) would you give this patient? a) ceftriaxone or other cephalosporin b) vancomycin c) acyclovir d) dexamethasone e) all of the above

31. a) ceftriaxone - why? b) vancomycin - why? c) acyclovir - why? d) dexamethasone - why?

32. Empiric therapy for suspected bacterial meningitis Laboratory-guided ? Age or risk-factor guided?

33. Age-guided therapy for suspected bacterial meningitis Ceftriaxone* appropriate for all outside of neonatal period (>3 months) Vancomycin for possible resistant S. pneumoniae Listeria possible at extremes of age add ampicillin if age less than 1-3 months or greater than 50 years

34. Is encephalitis a possibility? Herpes simplex encephalitis What are probabilities? Is timing as important? Should further tests be run? What? Empiric acyclovir?

35. Steroids? Are steroids useful or important in acute bacterial meningitis? Dexamethasone studies...

36. Steroids in acute bacterial meningitis Conflicting studies through the years Most recent - 301 adults with acute bacterial meningitis randomized 10 mg dexamethasone 15-20 minutes before antibiotics 10 mg every 6 hours for four days Reduction of adverse outcomes and death (26% v. 52%) Greater benefit in most ill patients.... De Gans et al (NEJM 2002; 347:1549)

37. What medication(s) would you give this patient? a) ceftriaxone or other cephalosporin b) vancomycin c) acyclovir d) dexamethasone e) all of the above

38. CT first? Risk of deterioration after LP in presence of mass lesion? pre-test probability? risk factors? adequate exam?

42. LP Lumbar puncture attempted with difficulty Procedural sedation + restraints Initial attempts failed.....options?

43. LP options Fluoroscopy? Is it important now in this case? after all, broad antibiotic coverage... a) acceptable to defer LP until later time? b) go forward at all costs to get fluid? c) defer for moment; revisit later?

44. What we did.... Ceftriaxone, Vancomycin (0915) Acyclovir Dexamethasone (1211) Invited consultants to be involved Sedation for protection and CT Procedural sedation and restraints With effort obtained clear, colorless CSF

45. CSF results 117 red blood cells protein 119 glucose 56 121 white cells 22% segmented, 77% lymphocytes

46. What type of CNS infection does this patient have? a) bacterial meningitis b) viral meningitis c) encephalitis d) another CNS infection e) cannot tell with certainty

47. Call from laboratory... Requesting India Ink test 3+ encapsulated yeast

49. Fungal meningitis... Cryptococcus neoformans most common Amphotericin or other therapy?

50. Fungal meningitis... Induction with amphotericin B Longer term therapy with fluconazole Liposomal amphotericin CSF pressures....

51. MRI Additional imaging obtained.... Rule out small masses Rule out parameningeal involvement

54. Case Conclusion Admitted to ICU Amphotericin given Others discontinued following studies Rapid improvement in confusion MRI- extensive sinusitis

55. Case Conclusion Repeat LP - OP 27-->11 cm H2O Home on intravenous amphotericin (then to fluconazole) Persistent headaches

56. Case Conclusion Headaches thought to be from ICP Improved following VP shunt

57. Cryptococcus neoformans 1/100,000 in non-HIV infected population Chronic, sub-acute, or acute Encapsulated yeast Steroid use

60. Final thoughts Empiric therapy just that, empiric Transition to definitive therapy Unusual presentation of unusual diseases... Correct diagnosis often needed for correct therapy

61. Final thoughts Think treatable causes Do not delay therapies of treatable causes for diagnostic tests.... Empiric therapy for bacterial meningitis Dexamethasone

62. Questions? J. Stephen Huff, MD jshuff@virginia.edu