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

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

3. J. Stephen Huff, MD History of Present Illness 3 weeks of frontal headache Saw primary care physician 1 week ago Cranial CT obtained –no intracranial abnormalities –right maxillary sinusitis –started on an antibiotic (amoxicillin / clavulanate)

4. J. Stephen Huff, MD

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. J. Stephen Huff, MD 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. J. Stephen Huff, MD 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. J. Stephen Huff, MD 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. J. Stephen Huff, MD 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. J. Stephen Huff, MD Physical examination Difficult General examination unremarkable Digit amputations left hand Psoriatic plaques Chest clear; no murmurs

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

13. J. Stephen Huff, MD something not right something not right Confusion Agitation Acute delirium Altered mental status

14. J. Stephen Huff, MD Differential diagnosis initial Withdrawal syndrome –alcohol –benzodiazepines Intoxication –alcohol –benzodiazepines

15. J. Stephen Huff, MD Differential diagnosis Seizures –post-ictal state –non-convulsive status epilepticus CNS infection? CNS structural? Systemic infection? Metabolic disturbance...may co-exist...

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

17. J. Stephen Huff, MD 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. J. Stephen Huff, MD ED course.... Family arrived-confirmed no history of drug or alcohol abuse pattern Family doubted ingestion Altered mental status worsening

19. J. Stephen Huff, MD 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. J. Stephen Huff, MD Differential diagnosis revisited Withdrawal syndrome Intoxication Seizures –post-ictal state –non-convulsive status epilepticus CNS infection? CNS structural? Systemic infection? Metabolic disturbance

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

22. J. Stephen Huff, MD Clinical Evidence Afebrile White blood cell count indeterminate Supple neck CT a week ago showed sinusitis

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

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

27. J. Stephen Huff, MD Pre-test probabilities? balancing act Acute bacterial meningitis? Other CNS infection? CNS structural lesion? –brain abscess? –parameningeal infection?

28. J. Stephen Huff, MD 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. J. Stephen Huff, MD Working plan Presumed CNS infection.... Concerned possibility of brain abscess.... Did not want to delay medical therapy

30. J. Stephen Huff, MD 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. J. Stephen Huff, MD a) ceftriaxone - why? b) vancomycin - why? c) acyclovir - why? d) dexamethasone - why?

32. J. Stephen Huff, MD Empiric therapy for suspected bacterial meningitis Laboratory-guided ? Age or risk-factor guided?

33. J. Stephen Huff, MD 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. J. Stephen Huff, MD Is encephalitis a possibility? Herpes simplex encephalitis What are probabilities? Is timing as important? Should further tests be run? What? Empiric acyclovir?

35. J. Stephen Huff, MD Steroids? Are steroids useful or important in acute bacterial meningitis? Dexamethasone studies...

36. J. Stephen Huff, MD 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. J. Stephen Huff, MD 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. J. Stephen Huff, MD CT first? Risk of deterioration after LP in presence of mass lesion? –pre-test probability? –risk factors? –adequate exam?

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

43. J. Stephen Huff, MD 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. J. Stephen Huff, MD 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. J. Stephen Huff, MD CSF results 117 red blood cells protein 119 glucose 56 121 white cells –22% segmented, 77% lymphocytes

46. J. Stephen Huff, MD 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. J. Stephen Huff, MD Call from laboratory... Requesting India Ink test 3+ encapsulated yeast

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

50. J. Stephen Huff, MD Fungal meningitis... Induction with amphotericin B Longer term therapy with fluconazole Liposomal amphotericin CSF pressures....

51. J. Stephen Huff, MDMRI Additional imaging obtained.... Rule out small masses Rule out parameningeal involvement

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

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

56. J. Stephen Huff, MD Case Conclusion Headaches thought to be from ICP Improved following VP shunt

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

58. J. Stephen Huff, MD

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

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

62. J. Stephen Huff, MDQuestions? jshuff@virginia.edu ferne_pv_2007_lectures_huff_infection_062307_finalcd