Approach to Seizure Internal Medicine ELS

1. Approach to SeizureInternal Medicine ELS Najwa Al-Bustani Neurology Resident July 22-2011

2. Outline: • Definitions. • Classification. • Etiology. • Evaluation. • Differential Diagnosis. • Risk of recurrence. • When to start AED. • How to choose AED. • Status Epilepticus: • Definition. • Pathophysiology. • Etiology. • Work-up. • Management. • Prognosis.

3. Definition: • Seizure defined by the International League Against Epilepsy (ILAE) as: • A transient occurrence of signs and/or symptoms due to abnormal excessive or synchronous neuronal activity in the brain. • Epilepsy: tendency for recurrent spontaneous/unprovoked seizures.

6. Classification:

7. Etiology:

9. Evaluation: • History: • From a witness if possible >> ictal + pot-ictal period. • Emphasize on any auras >> localization. • New onset vs recurrent. • Look for precipitating factors: trauma, sleep deprivation, drugs, metabolic causes. • Family and developmental history. • Compliance to AED (if known for epilepsy).

12. Physical Examination: • Vitals: BP-postural changes, HR. • Complete neuro. Exam >> look for focal deficit. • Neurocutaneous lesions. • Dysmorphic features.

13. Work-up: • CBC, renal + liver function, Ca, Mg, Glucose, CK, Toxicology screen, AED levels. • EKG = all patients. • ? L.P if infection is suspected. • CT scan = all patients. • MRI brain = selected cases.

14. Cortical dysplasia – left parietal Mesial temporal sclerosis

15. Work-up: • EEG: • Positive in 20-59% after 1st seizure. • Sensitivity in predicting recurrence after first seizure ranges 48-61% & specificity (patients without epileptiform abnormalities who do not experience recurrence) has been 71-91%. • If done within 24 hours increases sensitivity by 15%. • Sleep deprived increase sensitivity by 25%.

16. Differential Diagnosis: Continuum June 2010 - Epilepsy

17. Medlink Neurology

18. Continuum June 2010 - Epilepsy

19. Risk of recurrence: • After 1st unprovoked seizure in adults ranges from 31-56% over 2-5 years of follow-up. • After 2nd seizure >> 73%, and 76% after 3rd. • Clinical factors that can increase risk of recurrence: symptomatic etiology, abnormal neuro exam., 1st seizure during sleep.

20. When to treat: • Early treatment is justifiable for whom any seizure have significant consequences related to driving, working and general saftey. • Recurrent seizures. • Epileptiform abnormalities in EEG: generalized spike and wave >> JME.

21. How to choose AED:

22. Status Epilepticus

23. Definition: • Generalized, convulsive SE in adults refers to > 30 minutes of: (International League Against Epilepsy and the Epilepsy Foundation of America – 1993) • Continuous seizures OR • Two or more discrete seizures between which there is incomplete recovery of consciousness. • Operational definition for clinical practice: continuous or intermittent seizures lasting more than 5 min, without full recovery of consciousness between seizures. • Refractory SE: when seizures fail to response to adequate doses of at least 2 AED.

24. Pathophysiology: • Development of SE is not clearly understood. • Failure of mechanisms that normally abort an isolated seizure. • Abnormally persistent, excessive excitation >>> Glutamate. • Ineffective recruitment of inhibition >>> GABA.

25. Systemic & Central Pathophysiology:

26. Etiology:

27. Classification & Manifestation

28. Classification & Manifestation

29. Epilepsia Partialis Continua: • Continuous focal motor seizure (usually clonic movements) that remains confined to a specific body part. • Can last up to several months and consciousness is preserved. • Associated conditions include non-ketotic hyperglycemia, hepatic encephalopathy, uremic encephalopathy, hyponatremia, Rasmussen syndrome, focal cortical lesions. • Classically refractory to treatment – treat underlying cause.

30. Physical Exam.: • Suspect subtle status epilepticus in any patient who does not regain consciousness within 20-30 minutes of cessation of generalized seizure activity. • Subtle movements (eg, nystagmoid jerks of the eyes or twitching of the shoulder) may be seen in subtle status.

31. Diagnostic Work-up: • History, neurological exam and labs as discussed before. • LP: • If infection is suspected. • Neuroimaging: • Performed once seizures are under control. • CT head to R/O SAH, neoplasm, stroke etc.

32. Diagnostic Work-up: • EEG (esp. Continuous with video): • Crucial, but should not delay treatment. • Identify subtle or nonconvulsive seizure activity. • Monitor response to treatment. • Determine seizure type (focal vs generalized). • Suggest etiology or prognosis. • Differentiate seizures from non-epileptic events.

33. Management of S.E

34. Treatment Goal: • Immediate diagnosis and termination of seizures. • Prevent neurologic and systemic pathology. • For an anti-seizure drug to be effective in status epilepticus, the drug must be administered intravenously to provide quick access to the brain without the risk of serious systemic and neurologic adverse effects.

35. Ideal Agent: If Exists • Easy to administer. • Prompt onset, long-acting • 100% effective. • No depression of cardio-resp. function or mental status. • No other adverse effects.

36. Management S.E

37. Management: • Seizures > 5 mins: • IV Lorazepam @ 0.1 mg/kg (no faster than 2 mg/min); typically does not exceed 6 mg. • Lorazepam does not last more than 45 mins usually, so loading with phenytoin or fosphenytoin is standard practice.

38. Management: • Give IV phenytoin @ 20 mg/kg, no faster than 50 mg/min to avoid hypotension. Note that phenytoin is not compatible with glucose containing solutions (it will precipitate out). • Alternatively, IV fosphenytoin can be used – 20 mg PE/kg (1.5 FosPHT:1 PHT), no faster than 150 mg PE/min (lower risk of peripheral infusion site complications). • Cardiac monitoring required >> risk of hypotension and cardiac arrhythmias. • Additional maximal load of 10 mg/kg.

39. Management: • If seizures persist >> refractory SE >> INTUBATION is required. Order urgent EEG. Initiate one of the following: • IV phenobarbital 20 mg/kg slow push (<100 mg/min). • IV pentobarbital 5 mg/kg (<50 mg/min), then 0.5 mg/kg/h to 5 mg/kg/hr. • IV propofol 1 to 2 mg/kg bolus. This dose may be repeated in 5 minutes if seizures persist. Initial rate of 2 mg/kg/hr, max 5 mg/kg/hr.

40. Management: • Other options for refractory SE include: • IV Midazolam 0.2 mg/kg given over 20 to 30 seconds. This dose may be repeated in 5 minutes if seizures persist. Continuous infusion at 0.05 to 2 mg/kg/h • Not routinely available: • IV Valproate bolus of 25 mg/kg to 30 mg/kg at 3 mg/kg/min. • IV Levetiracetam 20 mg/kg IV over 15 minutes.

41. Management: • AEDs such as PHT, CBZ are usually maintained during the treatment of status epilepticus, so that when the anaesthestic is terminated, there can be longer term protection. • Continue previous AED.

42. Prognosis: • Mortality of SE >> 22% (highest for myoclonic SE, up to 86% esp. if within 24 hr of circulatory arrest). • RF for mortality: increased age, longer duration of seizures (esp. > 1 hr) and aetiology of SE (cerebral anoxia particularly bad). • Recurrence rate 25 %, especially if progressive neurologic disease. • Refractory SE (30% of all SE) >> higher mortality and morbidity.

43. CASES

44. 42 year old male, s/p resection of left frontal astrocytoma, recently D/C from hospital. On Dilantin and Dexamethasone. • At home: wife witness jerky movement of Rt. UE >> LE with aphasia >> LOC >> GTC sz. X 2 min. • US arrived >> decreased LOC, vitals stable >> ER. • In ER >> another GTC sz. X 1 min. • What will you do ?

45. You are the resident on-call covering RVH/MNI. • Nurse from 3-north calls you regarding: • 45 year old male, known for TLE, admitted for work-up for possible surgery, he takes: Tegretol, Keppra, Clobazam. Med.s on hold to record his seizures. • For last 30 minutes had 4 episodes of starring and lip smacking, and few minutes ago GTC sz >> received Ativan 2mg IV. • Now confused, vitals stable. • What to do next Dr. ?

46. 60 year old male, s/p liver Tx on immunosuppresion. • Fever and confusion since AM. • Wife witness lip smacking and starring for few seconds X 2. • Had episode of GTC sz. X 45 seconds. • Regained consciousness but confused. • In ER >> febrile, disoriented, aphasic. • What will you do next ?

47. THANK YOU