EPILEPSY

1. EPILEPSY Dr Sadik AL Ghazawi Associated professor Neurologist MRCP,FRCP UK

2. ‘The Sacred Disease’

3. ‘The Sacred Disease’

4. Historical Background The term “epilepsy” is derived from Greek epilepsia: a taking hold of or seizing. Ancient accounts over 2500 years ago by Babylonians and Egyptians. Detailed descriptions in On the Sacred Disease attributed to Hippocrates in the 5th century BC. Use of “Sacred” possibly meant to be ironic. Late 19th century: -Jackson: Model of focal seizures; aura evolving to psychosomatic or convulsive seizure. Use of aura for localizing seizure onset.

5. Historical Background • Late 20th century: • Widespread use of simultaneous video-EEG . • Neuroimaging • Development of new antiepileptic drugs based on seizure mechanisms. • Emergence of epileptology as a defined specialty within neurology and development of comprehensive epilepsy programs including epilepsy monitoring units and epilepsy surgery.

6. Historical Background • 21st century: • Identification of genetic basis of many syndromic epilepsies. • Neurostimulation devices: Vagus Nerve Stimulation (VNS), Responsive NeuroStimulation (RNS), Deep Brain Stimulation (DBS). • Use of laser ablation in epilepsy surgery.

7. Definitions Seizure is the clinical manifestation of an abnormal, excessive, and hypersynchronous electrical discharge of a population of cortical neurons. Epilepsy: A brain disease characterized by recurrent seizures that are unprovoked by systemic or neurologic insults.

8. Epilepsy syndrome: a particular form of epilepsy, often implying specific causes, clinical manifestations, and prognosis. Aura: The earliest part of a seizure and typically the only subjective experience recalled by the patient.

9. Definitions Convulsion: The motor manifestations of a seizure, usually consisting of rhythmic tonic followed by clonic movements and postures. Semiology: Abnormal sensations, emotions, behaviors, loss of consciousness, muscle spasms, convulsions that accompany the brain seizure activity.

10. Postictal period: Time between the end of the seizure and recovery to the baseline state. Status epilepticus: Five or more minutes of continuous or recurrent seizures without recovery.

11. Definitions Sudden Unexpected Death in Epilepsy (SUDEP): Sudden, unexpected , witnessed or unwitnessed, nontraumatic, and nondrowning death of patients with epilepsy with or without evidence of a seizure and in whom postmortem examination does not reveal a structural or toxicological causes.

12. Definitions Automatisms: 1- nonpurposeful, stereotyped, and repetitive behaviors that commonly accompany focal impaired awareness seizures (in the semiologic classification, they define automotor seizures). 2-The behavior is inappropriate for the situation. Patients are usually amnestic to their automatisms. 3-Automatisms could be oral or manual.

13. ILAE OFFICIAL REPORT Epilepsy is a disease of the brain defined by any of the following conditions 1. A least two unprovoked (or reflex) seizures occurring >24 h apart 2. One unprovoked (or reflex) seizure and a probability of further seizures similar to the general recurrence risk (at least 60%) after two unprovoked seizures, occurring over the next 10 years. 3. Diagnosis of an epilepsy syndrome Epilepsy is considered to be resolved for individuals who had an age-dependent epilepsy syndrome but are now past the applicable age or those who have remained seizure-free for the last 10 years, with no seizure medicines for the last 5 years. ILAE: International League Against Epilepsy

14. Asses Risk of further seizures Berg AT, Shinnar S. Neurology 1991; 41:965-972 Hauser WA et al. N Engl J Med 1998; 338:429-434

15. Seizures: Classification Generalized or Focal • Generalized abnormalities on EEG • 1-No lesion or diffuse abnormalities on MRI • 2-No aura • 3-Bilaterally symmetrical onset • 4-Often < 30 seconds • Focal abnormalities on EEG • 1-May have focal lesion on MRI • 2-Auras sometimes present • 3-Focal clinical features during seizure • 4-May be longer (1-2 minutes)

16. ILAE 2017 Classification of Seizure Types Expanded Version1 Focal Onset Generalized Onset Motor tonic-clonic epileptic spasms Non-Motor behavior arrest Motor tonic-clonic clonic tonic myoclonic myoclonic-tonic-clonic myoclonic-atonic atonic epileptic spasms2 Non-Motor (absence) typical atypical myoclonic eyelid myoclonia Motor Onset automatisms atonic2 clonic epileptic spasms2 hyperkinetic myoclonic tonic Non-Motor Onset autonomic behavior arrest cognitive emotional sensory Unknown Onset Unclassified3 focal to bilateral tonic-clonic 1 Definitions, other seizure types and descriptors are listed in the accompanying paper and glossary of terms. 2 These could be focal or generalized, with or without alteration of awareness 3 Due to inadequate information or inability to place in other categories Impaired Awareness Aware From Fisher et al. Instruction manual for the ILAE 2017 operational classification of seizure types. Epilepsia doi: 10.1111/epi.13671

17. Location of Focal Epilepsy

18. PastRecentCurrent2017 Terminology Focal ---- Simple Partial ---- Focal without impairment--- Focal Aware of awareness Psychomotor---- Complex Partial--- Focal with impairment--- Focal impaired of awareness awareness Grand Mal----Tonic-Clonic----- Tonic-Clonic -------- Tonic-Clonic OR OR focal to Focal evolving to bilateral tonic-clonic a bilateral, convulsive seizure Petit MalAbsence---- Absence ----- Non-Motor (Absence) Fisher et al. Instruction manual for the ILAE 2017 operational classification of seizure types. Epilepsiadoi: 10.1111/epi.13671. Berg AT, et al. Epilepsia 2010; 51(4): 676-85

19. Etiology of Epilepsies 1-Genetic (previously called idiopathic) 2-Structural/Metabolic (previously called symptomatic) 3-Unknown cause (previously called cryptogenic)

20. 1-

22. 2-

24. Epilepsy syndromes per ILAE 4- conditions associated with seizures but not a diagnosis of epilepsy A- febrile seizures B- benign neonatal seizures 5- Epilepsies of unkown cause.

25. Provoked seizures Provoking factors include acute CNS or systemic alterations that lead to increased excitation of the brain resulting in a seizure.

26. Epidemiology 50 million people worldwide are affected by epilepsy. In 30% of these patients, the seizures are not controlled by any available medical therapy. Even among patients whose seizures are controlled, significant medication side effects are common. In addition to the medical burden of epilepsy, the social and economic stress of refractory epilepsy can be devastating to the patient and family.   1-2% of World’s population affected ~50 Million worldwide.

27. Epidemiology There is a bimodal incidence for both seizures and epilepsy with highest rate in the( first year) of life and increasing again (after age 60).

28. 1. 2. History from Patient ? Routine EEG 3. 4. History from witness of event MRI

29. History: Risk factors for epilepsy : 1.        Family history (genetic predisposition to seizure disorder) 2.        Birth history and complications, cognitive and motor development 3.        Infant or childhood seizures (e.g. febrile seizures are associated with temporal lobe epilepsy) 4.        Past history of CNS infections, stroke, head trauma, cancer.

30. History:  Detailed description of the event: Seizures are generally brief and have stereotyped patterns. 1.        What was the patient doing at time of the event (e.g. occur out of sleep)? 2.        Were there any warning symptoms/aura and were they focal ? 3.        Did he/she loose consciousness? 4.        What other symptoms were present? (SOB, chest pain, etc. may suggest different diagnosis )

31. 5.        How long did the events last (most seizure last < 3 minutes)? 6.        Description of the movements; falling to the ground, convulsion/myoclonus/posturing, head turn, eye movements , automatisms. 7.        Did he/she loose bowel/bladder control or bite their tongue? 8.        Was there postictal confusion, hemi-paresis, aphasia?

32. History Generalized Tonic-Clonic seizures: 1-Can arise from a partial seizure (focal to bilateral tonic clonic) or as a generalized seizure from the beginning (primarily generalized) 2-Strained cry--------- 3-Generalized tonic-------- then clonic activity 4-Duration: 1-2 minutes 5-Post-ictal phase

33. History Absence Seizures: 1-Cessation of activity, staring, clonic twitches of perioral and eyelid muscles 2-Brief: 10-20 seconds 3-No post-ictal period 4-Multiple per day 5-No associated developmental delay 6-EEG: 3 Hz spike and wave ++++++++ 7-Can be confused with focal impaired awareness seizures.

34. History Semiology of focal epilepsies: Temporal lobe: Déjà vu, Epigastric rising sensation, oral and manual automatisms, olfactory or auditory hallucinations, impaired consciousness, impaired language if dominant side.

35. Frontal lobe: hypermotor activity, bicycling, brief, recurrent, out of sleep, quick regain of consciousness. Occipital lobe: elementary visual hallucinations. Parietal lobe: Quick propagation to other areas causes different semiologies.

36. History DD,The history can suggest other possible diagnosis for transient neurological symptoms and/or loss of consciousness.   1.        Syncope (presyncopal symptoms, precipitating maneuvers, orthostatic BP, abnormal ECG) 2.        Sleep disorders such as narcolepsy/cataplexy 3.        Stroke ( is rare in stroke, but can occur with posterior circulation stroke) 4.        Migraine

37. History 5.        Paroxysmal Vertigo 6.        Transient global amnesia 7.        /drug related “blackouts” 8.        Movement disorder (e.g. myoclonus, dyskinesias) 9-Psychiatric (nonepileptic seizures, panic attacks, hyperventilation)

38. Suggestive of a Seizure • 1-Duration: 1-2 minutes • 2-Clustering • 3-Tongue-biting • 4-Incontinence • 5-Stereotyped • 6-Amnesia • 7-Arising out of true sleep • 8-Eyes open • 9-Post-ictal dysfunction

39. Seizure vs Syncope Syncope 1-visual, auditory fading 2-10-30 seconds 3-minimal post-ictal phase 4-pallor & diaphoresis 5-flaccidity 6-Provocation by prolonged standing, hunger, heat, pain, micturition, cough Seizure • 1-aura • 2-duration: 1-2 min • 3-post-ictal phase x several minutes • 4-tonic-clonic activity, limb posturing • 5-tongue-biting • 6-Incontinence • 7-Guttural, strained cry

40. Physical Exam 1-Mental status 2-Focal features 3-Signs of tongue biting 4-Signs of infection or trauma

41. Diagnostic Workup 1-Labs: Electrolytes, glucose, LFT, KFT, CBC, toxic screen ?, CPK ? , CSF ? 2-Imaging: MRI preferred to CT scan. 3-EEG: as soon as available.

42. Electroencephalogram EEG right temporal lobe epilepsy- T6 sharp waves

43. Electroencephalogram EEG childhood abcense epilepsy – 3 Hz spike and wave

44. Electroencephalogram EEG Lennox- Gastaut syndrome – slow (<3 Hz) spike and wave and slow background ( and developmental delay and refractory seizures)

45. Status Epilepticus • Lowenstein in 1999 Defined status has having a seizure for 5 minutes or longer or multiple seizures without full return to baseline

47. Treatment of Epilepsy

48. Seizure First Aid • 1-Don't hold the person down or try to stop his movements. • 2-Time the seizure with your watch. • 3-Clear the area around the person of anything hard or sharp. • 4-Loosen ties or anything around the neck. • 5-Put something flat and soft, like a folded jacket, under the head. • 6-Turn him or her gently onto one side. • 7-Do not try to force the mouth open with any hard implement or with fingers. • 8-Be friendly and reassuring as consciousness returns.

49. Choosing an Anti-Epileptic Drug (AED) 1-Type of seizures (generalized vs. focal) 2-Can medication be loaded? 3-Other comorbidities 4-Medication interactions (including contraceptives) 5-Short and Long Term Adverse Effects 6-Teratogenicity 7-Daily, BID, or TID dosing 8-Cost and Insurance coverage 9-Formulation (liquids, crushable, sprinkles, etc.)

50. Medications for seizure type Focal Generalized Carbamazepine Oxcarbazepine Phenytoin Phenobarbital Gabapentin Lacosamide Pregabalin Tiagabine Vigabatrin Ethosuximide (Absence) Valproate Lamotrigine Levetiracetam Topirimate Zonsiamide Felbamate Rufinamide (Tonic)