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 seizure:
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: /1000

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

6. Idiopathic/ cryptogenic
Etiology of Seizures
Idiopathic/ cryptogenic
65.5%
Vascular 10.9%
Congenital 8.0%
Trauma 5.5%
Neoplastic 4.1%
Degenerative 3.5%
Infection 2.5%

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

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 Absence Tonic-clonic Tonic Clonic Myoclonic Atonic
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 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, Oxcarbazepine and 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 Ketogenic Diet Experimental Drugs
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 hour fast
Families educated daily
Ratio (fat: carbs and protein)
4:1 more strict
3:1 for infants, adolescents
Calories %
Fluids %
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 (intracarotid amobarbital 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

51. Outcome after epilepsy surgery
Anterior temporal lobectomy
70-80% seizure free
Neocortical resection
With lesion: 50-80% seizure free
Without lesion: 30-50% seizure free
Hemispherectomy
Significant improvement
Corpus Callosotomy
Significant improvement for drop attacks

52. Complications of surgery
Low rate of complications
Infections
Bleeding
Anesthesia
Function

53. Vagus Nerve Stimulator
Computer attached to vagus in neck, delivers electricity to stop seizures.
Reduces seizures 30-40%. NOT a cure.
Well-tolerated and safe.
Hoarseness during stimulation that improves.

55. Deep Brain Stimulation
Trans-cranial Magnetic stimulation
Intracranial stimulation
Hippocampus
Thalamus
Cerebellum

56. Transcranial Magnetic Stimulation

57. Deep Brain Stimulation

58. Alternative Treatments
Diets
Supplements
Herbs
Cognitive-behavioral therapies
Yoga
Acupuncture