1. Sean Wilde Margriet Greidanus March 29 2012

2. Outline:  Practical ED based Approach  Some important keys and pearls  Discuss thinking about altered MS in presentation categories  Practice it with cases  Discussion of selected diagnoses Important not to miss Not covered in other topics

3. Disorders of Consciousness Hypervigilent Obtunded Drowsy/Lethargic Stupor Coma Confused

4. Look ‘em up  Dementia Chronic, slowly progressive, non-emergent  Delerium Acute, fluctuating, **investigate** 25% hyperactive 50% hypoactive 25% mixed  Assessment Tools: GCS AVPU ACDU Simplified Motor Scale Confusion Assessment Method (CAM)

5. CAM for Delerium Acute onset and/or Fluctuating Course AND Inattention WITH EITHER Disorganized thinking OR Altered Level of Consciousness 91-97% sensitivity 85-94% specificity J Am Geriatr Soc. 2008 May ; 56(5): 823–830

6. Beware: “Grandpa’s just a little confused today”

7. Approach to the Clearly Altered

8. 2 Causes of altered LOC Arousal (R.A.S.) Behavior (Cerebral activity)

9.  Bihemispheric dysfunction Usually metabolic Diffuse cerebral disease (infection, edema)  Brainstem dysfunction Reticular activating system Brainstem lesions Herniation

10. Step 1: Unleash the A(BC)-Team

11. Unclear history? C-spine

12. Step 2: Absent an emergent A or B… Look for neurological findings before you sedate/paralyze

13. Step 3: Emergent Interventions  Dextrose Only if glucose < 4 1 amp (25g) D50  Oxygen  Narcan Reasonable if any clinical/historical suspicion of narcotic use 0.4-2mg IV/SC ○ Start small, increase. Full dose in code. Response? Ongoing boluses vs infusion (2/3 effective dose)  Thiamine If worried about nutritional deficiency Q- Before or after glucose? A- In the ED, who cares  No Flumazenil Risk of seizure induction The Coma Cocktail: Do DON’T, or don’t DON’T?

14. GCS < 8: When Wouldn’t I Intubate?  If the airway is acutely threatened, or oxygenation/ventilation poor, then yes.  Otherwise, the indication for intubation is urgent, but not emergent.  Look first for rapidly reversible or self- limited causes of decreased LOC Hypoglycemia, opioid overdose Post-ictal, EtOH intoxication

15. Step 4: Full vitals with ACURATE temperature  Temperature can quickly direct your differential  Rectal most accurate  Can still trick you. Rechecks

16. Emergent Temperature Control  Think of it like Blood Pressure Healthy body can autoregulate Thermal damage occurs when regulation fails Hypo/Hyperthermia in an altered patient is a critical finding requiring emergent correction!

17. Other emergent considerations  Treat shock state  Antibiotics Sepsis, meningitis Often indicated empirically  Steroids Meningitis Adrenal crisis  Benzos Seizures, agitation

18. Step 5: Details Secondary Survey History  Evidence of trauma  Evidence of infection  Signs of shock  Toxidromes  Focal neuro symptoms  Brainstem reflexes  Seizure related injuries  Onset, course, symptoms  Meds/substance use  Medical history  Trauma

19. Step 6: Work-up Most of the TimeWhen Indicated  CBC, ERChem, LFTs, INR, PTT  Calcium, TSH  ABG  EKG  Blood cultures  Urinalysis/culture/tox  CT head  EtOH, ASA, apap, osm, toxic alcohols  Trauma films/CT  Chest x-ray  Lumbar Puncture  MRI  EEG

20. Step 7: Diagnosis and Management  Supportive Care  Correct physiologic abnormalities  Treat underlying cause  Antidote?

21. Think in presenting Categories… Focal and Altered Hot and Altered Cold and Altered Trauma and Altered Bradycardic and Altered Shock and Altered Sudden vs. progressive But don’t fixate or exclude too early

22. So, what should I memorize?

23. Common Causes Rare Dangerous Treatable X

24. Most Common Causes PediatricsAdults  CNS infections  Trauma  Toxic ingestions  DKA  Severe dehydration  Congenital malformations  Metabolic disorders  Prolonged seizures  Infections / sepsis  Trauma  Intoxication/Withdrawal  Toxic ingestions  Seizures  Hypoglycemia  Intracranial bleeding  Hypoxia/CO2 narcosis  Electrolyte abnormalities

25. Cases

26. The Hot and Altered Patient  Infectious  Toxidromes Sympathomimetic, anti-cholinergic Psychotropic meds  Environmental Exertional or exposure Heat Stroke  Other Febrile illnesses Thyrotoxicosis, thyroid storm Neoplasms Inflammatory conditions

27. Toxidrome differentiation Look at the Skin  Diaphoretic: sympathomimetic  Dry: anti-cholinergic ○ decreased bowel sounds ○ urinary retention

28.  Serotonin Syndrome Rapid onset Myoclonus Ocular clonus Increased reflexes (hyperkinesia) Difference b/wn upper and lower extremities  Neuromuscular Malignant Syndrome Onset over days Bradykinesia Lead pipe rigidity (think Parkinson’s) Extremity exam: upper = lower.

29. Heat Illnesses  Spectrum from mild (cramping, rash) to severe (coma and death)  Exertional heat stroke Young, healthy athletes Acute onset, exertion in high heat  Non-Exertional heat stroke Typically young or elderly in heat waves Slow onset, abnormal lytes common.

30. Water Intoxication  Acute Hyponatremia (<125) N&V, malaise, dizziness, fatigue Peripheral edema Progression to cerebral edema  Risk Factors: Exercise > 4hours Female Low body mass index Free water consumption

31. Non-Convulsive Status Epilepticus  Persistent neurological seizure activity without obvious visible seizure activity  Difficult diagnosis Controversial and developing clinical and EEG criteria  Add to DDx of “Altered/Comatose/Bizarre behavior of no obvious cause”

32. Non-Convulsive Status Epilepticus

34. NCSE- Risk Factors  Known epilepsy Even remote Under-medicated  CNS infections (all types)  Any recent or remote seizure risk factors Stroke, tumor, neurosurg, CNS catastrophe/trauma Drug intoxication/withdrawal  Recent witnessed convulsive seizure

35. NCSE- When to suspect  Altered MS with no other obvious cause  Prolonged post-ictal period >1-2 hours  Subtle motor activity Minor tremors, twitching or eye deviations  Awake but altered with: Slowing, disorientation Somatomotor symptoms Automatisms Sensory hallucinations Prolonged prodromal aura New confusion or abnormal behavior in the elderly

36. J Neurol Neurosurg Psychiatry 2003;74:189–191 Most predictive Clues  Ocular movement abnormalities  History of seizures  Remote seizure risk factors: Stroke Neoplasia Dementia Previous neurosurgery Small study Poor design Not much else out there

37. NCSE- Management approach  Urgent EEG/Neurology to confirm/categorize if at all unclear of dx.  Treatment less urgent than convulsive NCSE still probably damages neurons, but not nearly as much as convulsive Mostly from animal studies and case series  Benzos are first line for all types 4mg IV lorazepam X 2.  Treatment diverges then if it is Absence

38. NCSE- If Benzo’s fail… Altered but preserved consciousness Impaired Consciousness Comatose (esp post grand mal) VPA Phenobarb Avoid: Phenytoin Carbamazapine Phenytoin Phenobarb VPA (std Status tx) Full standard status Tx Rapid progression to GA (midaz, propofol) Could be Absence

39. Case #2 Altered Elderly

40. Salicylate Toxicity  Early signs Hearing changes, tinnitus Tachypnea Can be febrile  Late CNS toxicity AG Metabolic acidosis  Consider in: Septic appearing elderly (most common misdiagnosis) Herbal OD (wintergreen) Any sick pt with AG metabolic acidosis and resp alkalosis.

41. Suspected Meningitis Approach  Blood cultures during ABCs  Antibiotics and dexamethasone Ceftriaxone 2g IV Vancomycin 1g IV  CT  LP  Antivirals Acyclovir 10mg (0.15-0.3mg/kg)

42. CT before LP if:  Age > 60  Immunocompromised  Altered or decreasing LOC  Seizure within 1 week  Known CNS disease AVN, tumor, stroke  Malignancy Hx  Papilledema  Focal neurological finding (incl. aphasia) 97% negative predictive value for abnormal CT N Engl J Med 2001, Hasbun et al.

43. Steroids in meningitis  Bacterial lysis increases CNS inflammation  Steroids attenuate if given before/concurrently  Demonstrated benefit in Strep Pneumo (adults) and H. Influenza (Peds)  Probably no harm in others  Only Dexamethasone studied  Caution in overtly immunocompromised

44. Gaham, Can J Emerg Med 2003;5(5):348-9 Viral or Bacterial?

45.  Caution in interpreting CSF Significant overlap of findings Normal is not always reassuring Gram stain – 80% sensitive at best  Organism in blood culture: 50-91% of time  Empiric Acyclovir? No good guidelines Reasonable if high viral suspicion Probably not as urgent as antibiotics

46. Case #3 Cold and Altered

47. Adrenal Crisis  Severe hypotension Fluid/pressor refractory  Dehydration and hypoglycemia  Abdominal Pain / GI symptoms  CNS disturbance Confusion, disorientation, lethargy  Sepsis With or without fever Can be hypothermic

48. Myxedema Coma  Metabolic, multi-organ dysfunction  Features: Mental status changes Hypotension Hypothermia (<35.5)  Clues 90% elderly women in winter Bradycardia, hypoventilation Hypothyroid body habitus Pleural/cardiac effusions Absence of shivering Delayed reflexes (esp relaxation phase)

49. Some definitions  Meningitis: Infection/inflammation in subarachnoid space Meningeal signs and symptoms  Encephalitis: Infection and inflammation in brain parenchyma Distinct neurologic abnormalities  Encephalopathy: Global brain dysfunction Altered LOC as primary feature Movement disorders and eye findings prominent Multiple forms/causes

50. Viral Encephalitis: Suspect in  New psychiatric symptoms  Cognitive deficits Aphasia Amnesia Acute confusional state  Seizures  Movement Disorders  Often fever and meningeal signs

51. Viral Encephalitis  HSV-1  Herpes Zoster Virus  CMV  Epstein-Barr  Arboviruses West Nile, Equine viruses, etc  Rabies

52. Viral encephalitis HSV Prominent psychiatric features Memory disturbance aphasia  Acyclovir 10mg/kg IV q8H  MRI/EEG  PCR studies on CSF

53. Case #4 Focal and Altered

54. Glioblastoma

55. Brain Abscess  Consider in well looking pt with: Triad ○ Headache (100%) ○ Fever (50%) ○ neuro deficits/seizures (33%) Possible meningeal symptoms (up to 50%) Signs/symptoms of increased ICP (50%)  ~60% with clear source  ID consult- multidrug coverage incl anaerobes

56. Thiamine Deficiency  Anyone with a chronic nutritional deficiency is at risk 2-3 weeks of deficiency to develop Sx  EtOH abuse Poor intake Increased demand (EtOH metabolism)  GI surgery (weeks to months ago) Absorbed in duodenum  Cancer/AIDS  Severe systemic disease

57. Consider Thiamine in any of…  Staple diet of polished rice  Chronic EtOH abuse and malnutrition  GI surgical procedures  Chronic vomiting/diarrhea  Cancer/chemotherapy  Systemic disease state  Magnesium depletion  Unbalanced nutrition

58. Multiple Presentations  Dry beriberi Wernicke’s encephalopathy ○ Progresses to Korsakoff’s syndrome Distal polyneuropathy  Wet beriberi (Asians higher risk) High output (common) ○ CHF, orthopnea, pulmonary/peripheral edema Low Output ○ Hypotension, lactic acidosis, no edema  Infantile Beriberi 2-12 months, soy formula or breastfed by deficient mother

59. “Classic” Wernicke’s Encephalopathy  Mental Status changes (82%) Confusion to coma spectrum Can mimic acute psychosis  Occular Abnormalities (29%) Nystagmus Various gaze palsies Optic disk edema/retinal hemorrhages  Motor Disturbances (29%) Incoordination (cerebellar and vestibular dysfunction) Gait ataxia  All the above (<10%)  None of the above (19%)

61. Bottom Line?  Thiamine is cheap and safe  You can miss a lot of subtle presentations of deficiency  Give it liberally in the altered patient  How much?

62. High dose or normal dose?  100mg IV daily is standard prophylactic dose  Lancet neurology 2007 review High dose “suggested” for probable cases based on suggestion of retrospective studies 500mg over 30min TID X 2-3 days, then taper Not clearly demonstrated  Cochrane Review No validated regimen in the literature  Timing? Prolonged glucose administration without thiamine can be harmful No demonstrated harm from a single bolus of glucose pre- thiamine

63. Common Encephalopathies  Uremic  Hepatic  Wernicke’s  Herpes (HSV)  Hypertensive  Hypoxic/hypercapneic  Toxic  Numerous other rarer causes

64. Hepatic Encephalopathy  Hx Liver disease  Asterixis  Stigmata of Liver Disease  Precipitants: GI bleed (may be occult) SBP  Serum ammonia level  Treat with NG lactulose infusion

65. Uremic Encephalopathy  Missed Dialysis  Increased BUN/Creatinine ratio  Asterixes  Needs emergent Dialysis

66. Interesting Diagnosis: Case  15yo F  Brought in by principle on school Ski trip  Sitting on chair lift and suddenly asked “where are we?”  Unable to recall any events since waking that morning.  Continues to ask the same questions over and over again shortly after being answered

67.  Recalls her name, hometown, friends and family  Still able to ski down at her regular ability  Well prior, no PMhx or meds  No known trauma/ingestions  Other than memory, completely normal Physical, ROS and Neurological exam.

68. Transient Global Amnesia Benign, temporary loss of anterograde memory with sparing of immediate recall, remote memories and deeply imprinted identity and skills.

69. TGA: Features  Isolated short-term memory loss  Inability to imprint new memories  Frequent perseveration “Broken record” Orientation questions  Preserved consciousness  Otherwise completely normal exam  HA, nausea, emesis may be present  Duration typically 2-12 hours Always < 24hrs

70. I swear I don’t remember what happened… TGA Triggers:  Physical Exertion Swimming Sex Valsalva  Drug Use Viagra Marijuana  Emotional/psychological stress

71. TGA: Causes  Possibly due to intracranial venous stasis Ischemia of memory centres Based on studies of inducibility of stasis in sufferers  Probably not epilepsy, migraine variant  Is not a TIA  Higher risk in young with migraine hx.

72. TGA: Hodge and Warlow Criteria (1990)

73. TGA: DDX considerations  R/O Delirium!!  TIA/CVA Suspect posterior circulation  Migraine variant  Complex Partial Seizures Aura, automatisms Non-convulsive status  Transient epileptic amnesia EEG if lasts <1hr / resolves with benzos  Fugue (psychogenic amnesia) Preserved new memories Loss of self-identity and auto-biographical memories  Rule out trauma

74. TGA: Prognosis  Excellent  Small recurrence rate  Not associated with long term complications or risks  TIA/CVA risk is same as general population

75. TGA: Ix and Management  If all criteria met: No Ix needed Reassurance and support for patient and distressed family members is the primary management  Duration < 1 hour EEG: consider transient epileptic event  Duration > 24 hours Look for something else  Any suspicion of other neuro or systemic findings warrants full lab and imaging investigation Metabolic Posterior CVA

76. Approach to Altered Patient: Summary  Develop a standard approach  Manage and diagnose concurrently Think first of the rapidly reversible Early neuro exam- is it focal? Low threshold for empiric infection tx  Think in presenting categories that work for you  Have a list of what to always think about in unclear cases.