EPILEPSY

1. EPILEPSY DR. MANSOUR AL MOALLEM

2. Definitions : An epileptic seizure is an abnormal and excessive focal or generalized discharge of neurons usually accompanied by an observable behavioral abnormality. It is a symptom of the brain hyper-excitability which may affect otherwise normal individuals (e.g. with ECT, head trauma).

3. Epilepsyis a prediposistion to recurrent epileptic seizure, with various etiologies. Seizures are paroxysmal discrete events although they may recur in close succession without an intervening return to normal consciousness producing a state called statusepilepticus . Generalized convulsive status epilepticus may be life threatening if not terminated within a few hours.

4. Seizures usually spontaneous or provoked by nonspecific factors increasing brain excitability such as sleep deprivation, drug or alcohol ingestion or withdrawal or hypoglycemia. Rare patients have their seizures provoked consistently by specific sensory stimuli (e.g. flickering lights, video games or television, a specific piece of music, reading, immersion in hot water, etc.): the reflex epilepsy.

5. Epidemiology of Epilepsy • 5% - 7% will have a seizure at sometime during their life • 1% - 2% of the population suffers from epilepsy • Peak age incidence: newborn, first decade, elderly • In only 50% is an etiology identifiable • 80% respond well to treatment

6. Is Epilepsy Inherited ? Genetic factors play only a minor role in most type of epilepsy. Certain inherited diseases, which are rare, have epilepsy as one of their manifestations. Absence seizures have a tendency to run in families. In general, a child with an epileptic parent has about a 5% chance of developing epilepsy.

7. Major Causes of Seizures in Different Age Groups

8. Classification of SeizuresInternational classification of seizures Classification of SeizuresInternational classification of seizures • Partial (focal) seizures - with or without secondary generalization) 1-Simple Partial a) motor b) sensory c) autonomic d) psychic

9. Classification of Seizures (cont) 2-Complex Partial (with or without automatisms) a) impairment of consciousness at onset b) simple partial onset followed by impairment of consciousness

10. Classification of Seizures (cont) • Genleraized seizures a) Tonic-clonic (Grand Mal) b) Absence (typical Petit Mal or atypical) c) Myoclonic d) Clonic e) Atonic

11. Simple Partial Seizures (Focal) • Seizure in which the first clinical and EEG changes indicates initial activation of a system of neurons limited to part of one cerebral hemisphere but where there is no alteration of consciousness. • Clinical symptoms, is determined by the anatomical location of the seizure focus. May be: motor signs, sensory symptoms, autonomic signs and symptoms, psychic symptoms. • May evolve to complex partial or secondarily generalized tonic-clonic seizure.

12. Complex Partial Seizures (Psychomotor) • Impaired consciousness associated with automatic behaviour • The phases (in temporolimbic seizure): stare, stereotyped automatisms, reactive automatisms • May evolve from simple partial seizure and to a secondarily generalized tonic-clonic seizure • Occur in 40% of patients with epilepsy • Most common seizure type seen in adult • 50% of patients have onset in childhood • Drugs control seizure in less than ½ of patients • Disabling psychosocial disturbances develop in 1/3

13. Tonic-Clonic Seizure (Grand Mal) • Abrupt loss of consciousness (may be vague ill-described warning but no true aura • Sudden sharp bilaterally symmetricalcontraction muscles, cry, fall, head extension, cyanosis. May be tongue-biting and incontinence • Bilaterally symmetrical clonic jerks, may be salivation and frothing at the mouth • Deep respiration and relaxation of muscles • Post-ictal period of depressed consciousness, usually awakens with muscle stiffness and sometimes headache

14. Absence Seizures (Petit Mal) • Sudden onset brief (usually <10 sec) interruption of ongoing activities • Blank stare, usually unresponsive when spoken to • May have stereotyped motor automatisms (mild clonic or tonic), especially if prolonged • Abrupt onset and abrupt cessation • No post-ictal confusion or other symptoms

15. Atypical Absence Seizures • Alteration of consciousness which may not be complete (some activities may continue in obtunded child. • May have loss of tone of face and neck muscles and/or myoclonic twitching of the eyelids and mouth. • Onset and cessation gradual.

16. Myoclonic Seizures • Sudden very brief shock-like muscular contractions. • May be generalized or confined to the face and trunk, to one or more extremities, or to individual muscles or group of muscles. • May be regularly repetitive or sporadic. • May occur in other neurological conditions as well as epilepsy.

17. Tonic Seizure • Brief generalized tonic contraction; head extension, stiffening of all four extremities. • Tachycardia; apnea, then cyanosis. • Frequently seen in Lennox-Gastaut Syndrome, especially during slow wave sleep.

18. Clonic Seizures • Rapidly repetitive bilateral jerking of extremities and facial muscles and loss of consciousness. • May be accompanied by autonomic changes. • Post-ictal phase is usually short.

19. Atnoic Seizures (Drop Attacks) • Sudden diminution in muscles tone, which may be fragmentary. • Extremely brief or no loss of consicouness. • May occur repetitively in a rythmic, successive manner. • Atonic seizure frequently seen in Lennox-Gastaut Syndrome; drop attacks may occur in neurological condition other than epilepsy.

20. Pseudoseizures • Atypical features (e.g. Partial preservation of consciousness during convulsion) • Tendency to occur in company. • Triggered by emotional upset. • Urinary incontinence, tongue-biting, injury are unusual. • Poor psychosocial history. • Unresponsive to appropriate AED therapy.

21. Pseudoseizures (cont) • 5-20% of outpatient epilepsy population have pure pseudoseizures. • 20-30% of uncontrolled epileptic also have pseudoseizures. • 20-30% of pseudoseizure patients also have epilepsy. • F:M 3-4: 1 • 85% of cases are between 15 and 25 years old.

22. Differential Diagnosis • Syncope • Psychogenic pseudoseizures • Panic/anxiety/HV attacks • Movement disorders • Sleep disorders (narcolepsy, parasomnias) • Hypoglycemia • TIA΄s • Migraine • Pheochromocytoma

23. Investigations • Electroencephalogram EEG • CT scan brain / MRI brain

24. Treatment The Principles : 1-Accurate diagnosis 2-Accurate seizure classification and if possible syndromic diagnosis 3-Select the most effective drug for seizure type 4-Begin with monotherapy 5-Allow the adequate time to assess the effect of the drug 6-If the seizure are not controlled, obtain blood levels 7-Change gradually to a second drug if the first drug Does not control the seizures

25. Mechanisms of Action of Anti-epileptic Drugs

26. Antiepileptic Drugs of Choice

27. Legends

28. Factors associated with an increased probability of seizure recurrence following medication withdrawal • Longstanding, severe epilepsy, initial difficult to control • Structural brain damage and neurological handicap • Partial seizures and mixed seizures • Persistent epileptic findings on EEG • Specific syndromes which are known not remit e.g. juvenile myoclonic epilepsy • Adult onset epilepsy

29. Surgical Treatment of Epilepsy • Seizure uncontrolled with medical therapy or intolerable side effects • Good cognitive function • Identifiable focus (except for callosotomy) • Social support system

30. International Classification of Epilepsies and Epilepsy Syndromes 1- Localization-related (focal, local, partial) epilepsies and epileptic syndromes A. Idiopathic with age-related onset 1. Benign childhood epilepsy with centrotemporal spikes 2. Childhood epilepsy with occipital paroxysms B. Symptomatic

31. 2-Generalized epilepsies and epileptic syndrome A- Idiopathic with age-related onset 1. Benign neonatal epilepsy 2. Childhood absence epilepsy (pyknolepsy) 3. Juvenile myoclonic epilepsy (impulsive petit mal) 4. Juvenile absence epilepsy with generalized tonic-clonic seizures on awakening

32. B- Secondary (idiopathic or symptomatic) 1. West syndrome (infantile spasms) 2. Lennox-Gastaut syndrome C- Symptomatic 1. Nonspecific etiology (early myoclonic encephalopathy 2. Specific syndromes (epileptic seizures that may complicate many diseases, e.g.Ramsy Hunt syndrome, Unverrichs disease

33. STATUS EPILEPTICUS What is the defenition?

34. STATUS EPILEPTICUS Definition. Seizure persists for 30 minutes, OR two or more sequential seizure without full recovery of the consciousness between the seizures.

35. Epidemiology 60 per 100,000 individuals per year in the general population Bimodal distribution, high value during the first year of life and over the age of 60 Mortality around 22% (pediatric 3%, adult 26% and elderly 38%) Determined by: age seizure duration etiology

36. Etiology. Majority of patient with SE did not have a history of epilepsy (38% of children, 40-50% of adult and 30% of elderly did not a history of epilepsy). In adult: Low anticonvulsant drug level 34% Remote symptomatic ( hemorrhage, tumor) 25% CVA 22% In children: Infection Fever Electrolyte disturbance

37. Why high morbidity & mortality…

38. Metabolic Complication Associated with status epilepticus Metabolic & others Lactic acidosis Hypercapnia Hypoglycemia Hyperkalemia Hyponatremia Dehydration leukocytosis

39. Medical complication SE (cont) Autonomic Hyperpyrexia Failure of cerebral autoregulation Vomiting Incontinence Renal .Prerenalasotemia Renal failure from rhabdomyolysis

40. Medical complication SE (cont) Cardiac/Respiratory Hypoxia Arrhythmia High blood pressure High output failure Pulmonary edema Pneumonia Cognitive Intellectual impairment with memory loss

41. How you treat…

42. Management.The goal should always be immediate diagnosis and termination of seizures. History: From the companion/previous notes Examination: General / systemic / Neurological Investigations: (1) CBC / deferential Electrolytes Blood sugar

43. Investigations (cont) EEG ECG / X-ray / ABG CT scan brain or MRI brain

44. Treatment Monitor vital signs I.V. line 02 Anti-epileptic drugs (AED) The drug should be administered I.V. forrapid absorption without reacting with other medications or solutions.

45. Specific Drug Compounds. 1- Benzodiazepines (BZD) Diazepam / Lorazepam / Midazolam Work by enhancing GABA ergic inhibition by binding to the BZD-GABA, and barbiturate receptor complex. High lipid solubility, they enter the brain quickly, but they redistributed to other areas of the body, reducing their clinical effect.

46. Specific drugs compound (cont) They have good efficacy (70-80%) to terminate all type of seizure but with high rate of relapse due to short half-life. Adverse effects respiratory suppression, hypotention, sedation, and local tissue irritation.

47. Diazepam. Half-life 15 minutes 5-10 mg I.V., it can be repeated Lorazepam. Half-life 2-3 hours (less lipid soluble + bind more tight to GABAergic receptor) Effect last for 6-12 hrs 4-8 mg I.V. Midazolam More lipid soluble than the other two, so shorter half life with higher relapse. Good for continue I.V. infusion with titration accordingly. 0.2 mg /kg followed by 0.1- 0.2mg /kg/hr

48. 2- Phenytoin High lipid soluble with long duration Control 60-80% Non sedative Cannot mixed with glucose, it precipitate out of solution Loading dose 18-20 mg/Kg at rate not exceed 50 mg/min; if no response, it can be repeated with half the dose. Adverse effect : arrhythmia/ hypotention

49. IF NO RESPONSE, Refractory status epilepticus Intensive Care Unit Consider potential incubation and mechanical ventilation. Avoid the use of neuromuscular junction blockade as it can mask ongoing motor manifestation. A short acting non- depolarizing agent such as vecuronium is preferred.

50. Drugs Therapy Cont.. 3- Phenobarbital Dosage 15-30 mg/Kg Adverse side effects -respiratory depression -hypotention -sedation -cardiac depression