Recent Advances in the Diagnosis and Treatment of Epilepsy

1. Recent Advances in the Diagnosis and Treatment of Epilepsy Salah Mesad, M.D.

2. Epilepsy & Seizures • New onset seizures • Established seizure disorder • Questionable seizures • Drug-resistant seizures • Discontinuation anti-epileptic drugs (AEDs)

3. Epilepsy and Seizures • Epilepsy: a tendency toward recurrent seizures unprovoked by systemic or neurologic insults • A seizure: the clinical manifestation of an abnormal and excessive excitation of a population of cortical neurons

4. Seizures & Epilepsy • Seizure: Single provoked or unprovoked episode Unprovoked seizure risk: 1/100 • Epilepsy: Two or more unprovoked seizures 50 million people worldwide, 2 million in US Prevalence: 2.7-40/1000

5. Epilepsy Incidence Male Female Total Incidence (per 100,000 Person-Years) Age (y)

6. Infection2.5% Degenerative3.5% Neoplastic 4.1% Trauma 5.5% Congenital 8.0% Idiopathic/cryptogenic 65.5% Vascular 10.9% Etiology of Seizures

7. Classification of Seizures Seizures may be classified in a number of ways; by etiology, age of onset, pathological basis, and so on. The usual classification involves a combination of clinical and EEG features.

8. Partial Simple Complex Secondarily generalized Generalized Absence Atonic Clonic Tonic Tonic-clonic Myoclonic Classification of Seizures

9. Epidemiology of Seizures Generalized TC (23%) Complex Partial (36%) Simple Partial (14%) Unclassified (3%) Myoclonic (3%) Other Generalized (8%) Absence (6%)

10. Focal Seizures-Clinical

11. Diagnostic Approach • History taking from the patient, family, caregivers and eyewitnesses • Past treatments and diagnostic workups • Family history • Physical and neurological examination

12. Questions need to be answered • Seizure or not? • Focal onset? • Evidence of CNS dysfunction? • Identifiable precipitant? • Seizure type? Syndrome? • Studies? • Start anti-epileptic drug (AED)?

13. Event/Seizure Types Single Recurrent Nonepileptic Epileptic • Syncope • Migraine • Psychogenic • Toxic • Cerebrovascular • Metabolic Generalized Partial • Absence • Tonic-clonic • Tonic • Clonic • Myoclonic • Atonic Simple Complex Secondarily Generalized

14. Diagnostic Approach • Initial tests • Blood work • EEG • Head CT • Brain MRI

15. EEG

16. EEG

17. Video-EEG Monitoring • Continuous and simultaneous EEG and video monitoring • Done mostly as an inpatient

18. Video-EEG Monitoring • To confirm the diagnosis and to rule out other nonepileptic events • Ultimately the goal is to try to record actual seizures to indentify and localize seizure onset(s) (esp. for drug resistant cases) • AEDs might need to be reduced or stopped temporarily • Sleep deprivation might be necessary • Characterize epilepsy type • Pre-surgical evaluation

19. Neuroimaging • Routine screening • CT • MRI • Surgical candidate • MRI • PET • SPECT • MEG • MRS • fMRI

20. MRI

21. Mesial Temporal Sclerosis

22. Developmental Malformation

23. PET

24. SPECT

25. MEG

26. MRS

27. Non-Epileptic Events • Physiological • Psychological • A patient can have both types of seizures • Beware of pseudo-pseudo-seizures

28. Non-epileptic events • Physiologic (other medical conditions) • Referred to other medical specialist • Psychological or pseudoseizures • Referred to psychiatry and neuropsychologist who work with this type of stress-seizure • Psychiatric medication, psychotherapy, education

29. Anti-epileptic drug treatment • Bromides:1800’s • Phenobarbital: 1912 • Phenytoin: 1938 • Primidone: 1954 • Carbamazepine: 1974 • Valproate: 1978 • Ethosuximide (Zarontin) • Benzodiazepines

30. Antiepileptic drugs • Felbamate and Gabapentin: 1993 • Lamotrigine: 1994 • Topiramate: 1996 • Tiagabine: 1997 • Levetiracetam, Oxcarbazepineand Zonisamide: 2000 • Pregabalin (Lyrica)

31. Anti-epileptic Drugs • Lacosamide (Vimpat) • Rufinamide (Banzel) • Vigabatrin (Sabril)

32. Anti-epileptic Drugs • Mechanisms of actions • Side effects • interactions

33. Mechanisms of Actions • Enhancement GABAergic receptors • Sodium channels blocking • Decrease of glutamate release • Decrease of GABA catabolism • Decrease of GABA uptake • Effects on Calcium cannels • Carbonic anhydrase inhibition • UNKNOWN

34. Epilepsy Treatment • Establish the diagnosis • Education • Address psychosocial issues • Lifestyle/non-medication treatments • Medical treatments

35. Epilepsy medical treatment: principles • Mono-therapy where possible • Introduced slowly • Education improves compliance • If the first medication doesn’t work, substitute another • If initial therapy is ineffective, refer for further assessment

36. Drugs for Generalized Epilepsy • Depakote • Lamictal • Topamax • Zonegran • Keppra • Rufinamide

37. Drugs for Partial Seizures • Carbamazepine • Oxcarbazepine • Gabapentin • Lamotrigine • Leveitiracetam • Phenytoin • Valproate

38. Reason for drug failure • Misdiagnosis such as Non-epileptic seizures, Cardiogenic, Migraine, etc. • Incorrect drug for seizure type • PGE v. Partial epilepsy • Non-diagnosed brain lesion such as tumor • Refractory epilepsy • Inadequate dose and low levels • Non-optimal scheduling timing of dose • Excessive dose (e.g., sedation) • Inappropriate combinations

39. Noncompliance & AED Failure • Reasons for Noncompliance • Forgetting individual doses (midday; bedtime) • Lowering dose to reduce toxicity • Fear of medication’s effects • Denial of epilepsy • Complicated dosing regimen • Frequent seizures and postictal confusion • Cost • Memory and visual problems

40. Medical Intractability • Seizures persists despite trial of several AEDs in various combinations at adequate and tolerated doses and levels over a period of time. • Significantly and aversely affecting cognitive functions and quality of life.

41. The consequences of refractory epilepsy are numerous • Seizure-related injuries • Increased seizure severity • Adverse effects with long-term AED use • Depression and anxiety • Cognitive and memory impairment • Increased mortality and morbidity • Impaired ability to obtain education, to work, drive, establish families, and develop and maintain social relations

42. Non-pharmacological • Surgery • Focal resection • hemispherectomy • Callosotomy (palliative) • Ketogenic Diet • Experimental Drugs • Brain Stimulation

43. Ketogenic Diet • Low carb, high protein/fat • Usually in children, for 2 years. • Works best in children with generalized epilepsies (Lennox-Gastaut)

44. Ketogenic Diet • Traditionally started gradually in the hospital after a 24-48 hour fast • Families educated daily • Ratio (fat: carbs and protein) • 4:1 more strict • 3:1 for infants, adolescents • Calories 60-100% • Fluids 85-100% • Solid foods and/or formula • Requires dietician support • Strong family commitment

45. Pre-surgical Evaluation • Video EEG monitoring to record several of patient’s typical seizures • Neuroimaging • Neuropsychological evaluation • Additional tests depending on individual situation, such as neuro-ophthalmology

46. Pre-surgical Evaluation • Neuropsychological Evaluation • Pre-operative baseline • Aid in localization • Predicting risk of cognitive decline with surgery • Psychological evaluation

47. Pre-surgical Evaluation • Wada test (intracarotidamobarbital procedure; IAP) • Language lateralization • Memory lateralization • prediction of postoperative decline

48. Epilepsy Surgery • Intra-cranial EEG monitoring • Depth electrodes • Subdural electrodes • Uni-or bilateral coverage

50. Types of Epilepsy Surgery • Temporal Lobectomy • Extratemporal Resections • Hemispherectomy • Corpus Callosotomy