Epilepsy

1. Epilepsy Prof. Magdy Dahab August 26th, 2009 Prof. Magdy Dahab

2. What Is Epilepsy? • A syndrome of recurring episodes of electrical activity of the central nervous system called seizures. • Seizures may vary from mild and unnoticeable to full-scale convulsive seizures. Prof. Magdy Dahab

3. Some Common Symptoms of Epilepsy • Uncontrollable movements of the body • Disorientation -Confusion • Sudden fear • Loss of consciousness Prof. Magdy Dahab

4. What Causes Epilepsy? • In over 70% of cases, no cause for epilepsy has been identified. • The other 30% can result from many other possibilities. • Head injuries • Lack of oxygen during birth • Genetic conditions • Lead poisoning • Severe Infections (Meningitis and Encephalitis) • Problems during development of the brain Prof. Magdy Dahab

5. Seizures • “Provoked” • Metabolic disorders • Hypoglycemia • Electolyte imbalance • Withdrawal from massive amounts of alcohol or sedatives • Massive sleep deprivation • High fever • Hypoxia • Substance abuse • Excessive use of stimulants Prof. Magdy Dahab

6. Seizures • “Unprovoked” • Birth trauma • Anoxia • Brain tumors • Infectious diseases in the mother • Parasitic infections • Genetic • Vascular diseases affecting the brain’s blood vessels • Neurotransmitter GABA (gamma-amino butyric acid) imbalance Prof. Magdy Dahab

7. Epilepsy • 1-2% of people with epilepsy will have a diagnosable genetic etiology for their seizure occurrence • The general incidence of epilepsy is between 1% and 4% • Two major type so seizures: Generalized and Partial • Generalized – uncontolled discharge of neurons on BOTH sides of brain. Seizure starts in one area and spreads across the brain. • Partial – abnormal electrical activity involving only a small part of the brain - although sometimes a partial seizure can spread to the whole brain Prof. Magdy Dahab

8. Generalized Seizures • Tonic-clonic seizures • “grand mal” – massive discharge of neurons on both cerebral hemispheres. Body becomes rigid and jerks. “Tonic-clonic” means “stiffness-violent” “grand mal” means “great sickness” • Absence seizures • Non-convulsive. Person may be unaware of surroundings and stare off. Lasts only 5-30 seconds • Atonic seizures • Loss of muscle tone – causes person to fall down • Myoclonic seizures • Involves motor cortex and causes twitching or jerking of certain body parts. • Status epilepticus • Frequent, long-lasting electrical activity with no regaining of consciousness between attacks. Very dangerous and requires immediate medical attention. Prof. Magdy Dahab

9. Partial seizures • Simple partial seizures • “Jacksonian” or “focal” seizures. • Short seizures with no loss of consciousness • People may see, hear or smell something odd & their body may jerk. • Complex partial seizures • “Psychomotor” seizures • A seizure with a change, but no loss, in consciousness. • People may hear or see things or have a memory resurface. Déjà vu may occur. Prof. Magdy Dahab

10. Diagnosis • Diagnosis requires a thorough evaluation of patients medical history describing seizure characteristics and frequency. • People suffering from epilepsy -brain waves have a characteristically abnormal rhythm. • Another way epilepsy is diagnosed is through an electroencephalograph (EEG). Prof. Magdy Dahab

11. Overview of Epileptic Syndromes Focal Seizures • 60% 0f Epilepsy • Focal Cortical Disturbance • Their origin usually determines the clinical picture • Focal Spikes on eeg Primary Generalised Seizures • Origin unclear either sleep spindles or hypersynchrony • Commence bilaterally • Spike and wave • No aura Prof. Magdy Dahab

12. Cerebral cortex regions Functional Areas of the Brain Prof. Magdy Dahab

13. Example of Primary Generalised Epilepsy • Childhood absence seizure

14. Complex partial seizures Epilepsy; Commonsense Logical Disabling

15. Examples of Focal Seizures Focal motor seizure that becomes secondarily generalised. Likely focus in right frontal lobe

16. Cellular Electrophysiology Membrane Potential The Na+ / K+ Pump http://www.biologymad.com/NervousSystem/nerveimpulses.htm

17. Cellular Electrophysiology • Selectively Permeable Membrane - Channels • Depolarising Shift • Epileptic Focus

19. Principles of Epidemiology • Incidence Rate= new cases per year [n per 100,000 per year] • For epilepsy is around 50 per 100,000 • Point Prevalence = All cases with active epilepsy at a point in time [n per 1000]. • For epilepsy is 4-6 per 1000 • Active Epilepsy = to have had a seizure or treatment in the last 5 yrs Prof. Magdy Dahab

20. Conditions that may look like a seizure • Syncope • “Psychogenic” seizures • Breath-holding spells • Paroxysmal REM sleep behavior • Panic attacks Prof. Magdy Dahab

21. International classification of epilepsies • Originally established in 1989 – currently under revision • Current system comprises two major categories: • Localization-related syndromes • Idiopathic • Symptomatic • Generalized-onset syndromes • Idiopathic with age-related onset • Idiopathic &/or symptomatic • Symptomatic • Nonspecific etiology • Specific syndromes Prof. Magdy Dahab

22. Complex partial seizures • stare into space/engage in automatisms, such as grimacing, gesturing, chewing, lip smacking • last 3 minutes or less • post-ictal: somnolence, confusion, headache for up to several hours Prof. Magdy Dahab

23. Generalized tonic-clonic seizure • No aura • tonic phase x 10-20 seconds: • sudden LOC, loss of posture, arms flex, eyes deviate upward • extension of back, neck, arms, legs • involuntary crying out • ends with tremors which merge c clonic phase Prof. Magdy Dahab

24. Generalized tonic-clonic seizure • Clonic phase x 90 seconds: • brief, violent, generalized flexor contractions alternating with progressively longer muscle relaxation • cyanosis • cheek or tongue biting, salivation • loss of bowel, bladder control Prof. Magdy Dahab

25. Generalized tonic-clonic seizure • Post ictal phase x minutes to hours • headache • mild confusion • sore muscles • may sleep and feel refreshed Prof. Magdy Dahab

26. Evaluation of single seizure • History of event • Medical History • Family History • Social History • Physical Examination • Neurological Examination • Laboratory Evaluation • EEG • MRI • Routine lab work Prof. Magdy Dahab

27. Treatment and Prognosis • Antiepileptic (anticonvulsant) medications • Carbamazepine (Tegretol) • Clobazam (Frisium) • Clonazepam (Rivotril) • Diazepam (Valium) • Divalproex sodium (Depakote) • Ethosuximide (Zarontin) • Phenobarbital (many different names) • Phenytoin (Dilantin) • Valproic Acid (Depakene) Prof. Magdy Dahab

28. Special topics in the Management of Epilepsy 1. Woman and Epilepsy Pregnancy and epilepsy. • Pre-conceptual Care- • ensure pregnancies are planned [high dose oestrogen pills if necessary, 4 packs of COC consecutively with 4 day pill free interval, Depo-provera every 10 weeks not 12.] • Discuss modification of AED to reduce number and total dose • Advise oral folic acid 5mg daily when intending pregnancy Belfast Register ….www.epilepsyandpregnancy.com Prof. Magdy Dahab

29. Special Topics in the Management of Epilepsy Ante-Natal Care • Continue 5mg Folic acid until at least 12 weeks • Adjust AED if necessary on medical grounds • Monitoring of plasma levels is not usually necessary [SIGN guidelines] • Offer serum screening at 16weeks and anomaly scan at 18-22 weeks • Prescribe oral vit K 20mg a day from 36weeks in on enzyme inducing AED • Prolonged seizures can be controlled by IV Diazepam [ rectally is OK if IV access not possible] Belfast Register ….www.epilepsyandpregnancy.com Prof. Magdy Dahab

30. Special Topics in the Management of Epilepsy Intra-Partum Care • Continue usual AED regime during labour • Control seizures with i.v. diazepam • Early decision for LSCS if seizures uncontrolled • Offer same range of analgesics as available to other mothers • Give infant vitamin K 1mg IM at birth Prof. Magdy Dahab

31. Special Topics in the Management of Epilepsy Post Partum Care • Encourage breast feeding • Offer advice for safe settings for feeding, bathing etc. • Review AED and contraceptive regimens • Encourage pre-conceptive care for future pregnancies Prof. Magdy Dahab

32. Special topics in the Management of Epilepsy Catamenial seizures- “the clustering of epileptic seizures in relation to the menstrual cycle” • Seizure control is worse in anovulatory cycles • Oestrogen- inhibits GABA, potentiates glutaminergic transmission, increases neuronal metabolism and discharge rates and promotes kindling. • Progesterone- its metabolites are barbiturate like ligands at GABA receptor, reduces neuronal transmission and discharge rate, suppresses kindling and inhibits epileptic discharges • Seizures likely when oestrogen/progesterone ratio is highest Prof. Magdy Dahab

33. Sexual dysfunction in epilepsy Hypo sexuality – • surveys suggest 22-67% reduction in sexual interest Erectile Dysfunction – • occurs in 57%[ Toone et al 1989], up to 83% in TLE Sexual Functioning in Males [1989] • Previous SI 56% [compared to 98% controls] • S.I. in the previous month 43% [compared to 91% in controls] • Previous erectile dysfunction 57% [compared to 18% controls] Prof. Magdy Dahab

34. Social Aspects of Epilepsy • Occupational – Unemployment, poor job-seeking skills, Non competitive, unskilled manual employment as a result of disadvantaged education, pressure of keeping current job • Social – Social isolation as a result of no driving licence, unable to drink alcohol, stigma • Tiredness • Over protective parents Prof. Magdy Dahab

35. Employment Disability Discrimination Act 1995 & 1996Disability is defined as; “a physical or mental impairment which has a substantial and long term adverse effect upon one’s ability to carry out normal day to day activities.” Substantial is more than minor and long term is longer than 12 months Exclusions; Hay fever, tendency to set fires or steal, physical or sexual abuses of others Disability Discrimination Help Line Tel: 0345 622644 Prof. Magdy Dahab

36. Driving Collapse at the wheel- • CVA 8% • Heart 9% • Diabetes 17% • Blackout 22% • Epilepsy 38% • Others 7% Group1 Driving Licence- Must be 1 yr seizure free with a medical review before restarting or only nocturnal seizures for 3 yrs Group 2- Withdrawn for 10 yrs and can be re-issued if 10yrs seizure freedom and has not taken AD during the time or does not have a continuing liability to epileptic seizures Prof. Magdy Dahab

37. Driving AED Withdrawal Risk of developing seizure increases by 40% so advise patients not to drive during withdrawal and for 6 months afterwards Confidentiality • If patients continues to drive inform patient not to • If continues to drive advise if continues will inform DVLA [copy of warning letter to patient and GP] • If still continues advise will inform DVLA and do so [occurs very exceptionally] Prof. Magdy Dahab

38. Overview of established Anti Epileptic Drugs Carbamazepine • Partial Epilepsy – Not for Absence or Myoclonic Jerks • Start at 100-200mg a day increase slowly • S/E- diplopia, nausea, headache, dizziness • Idiosyncratic reactions possible [up to 10%] • Monitoring needed- increase ‘Chrono’ dose • Beware of interactions Prof. Magdy Dahab

39. Overview of established Anti Epileptic Drugs Clobazam • Used intermittently • Extra cover for catamenial seizures, stressfull events , clusters of attacks • Dose- 10mg [SLS] once or twice a day for 3 days Prof. Magdy Dahab

40. Overview of established Anti Epileptic Drugs Clonazepam • Limited role due to tolerance, sedation and withdrawal seizures • Usually reserved for refractory seizures especially Myoclonic jerks Prof. Magdy Dahab

41. Overview of established Anti Epileptic Drugs Ethosuximide • Indication – Absence seizures [hence paediatric field usually] • Introduce slowly 500mg daily increasing to 1-2 g a day • Side Effects – GI and CNS Prof. Magdy Dahab

42. Overview of established Anti Epileptic Drugs Gabapentin • Add on therapy for partial seizures only • Dose starts at 300mg a day and increases to 1800-2400 mg a day with t.d.s dosing • No interactions[ not metabolised] • Side effects – well tolerated occas. drowsiness, dizziness, diploplia, ataxia and headaches • ? Efficacy Prof. Magdy Dahab

43. Overview of established Anti Epileptic Drugs Lamotrigine • Broad spectrum and first line [ less teratogenic than VPA] • Dosing – slow to minimise side effects usually 25mg a day increasing every 2 weeks, b.d. dosing. Max dose around 400mg a day. • Interactions – VPA , CBZ and PHT • Idiosyncratic reactions in up to 5% Prof. Magdy Dahab

44. Overview of established Anti Epileptic Drugs Piracetam • Need a wheelbarrow ! • Indications – refractory myoclonus • Dose – 7.2g in t.d.s. dosage, increasing weekly to 12-24 g/day!! • No known interactions Prof. Magdy Dahab

45. Overview of established Anti Epileptic Drugs Phenytoin • Was considered first line for partial seizures • Poor side effect profile- rash , liver toxicity. blood dyscrasias, cosmetic changes, neurotoxicity etc • Dosing difficulties – saturation kinetics • Many interactions Prof. Magdy Dahab

46. Overview of established Anti Epileptic Drugs Phenobarbitone [and Mysoline] • World-wide best seller for partial seizures • Side –effects largely unacceptable- effects on cognition, mood and behaviour. Also arthritic changes, dupytrons contracture, frozen shoulder • Interactions- accelerates metabolism of many lipid soluble drugs Prof. Magdy Dahab

47. Overview of established Anti Epileptic Drugs Sodium Valproate • Broad Spectrum and Powerful [ no-longer first line in women] • Dose – 300- 500mg a day, usually bd dosage • Side effects- tremor, wt. gain, POS, possible hepatotoxicity, blood dyscrasias and pancreatitus • Interactions- can inhibit liver enzymes Prof. Magdy Dahab

48. Overview of established Anti Epileptic Drugs Vigabatrin • Tertiary Care Initiation • Peripheral field loss [permanent in up to 40%] • Used for very resistant cases or in infantile spasms Prof. Magdy Dahab

49. Overview of the Newer Anti Epileptic Drugs Topiramate • Second line – Broad Spectrum [5 mechanisms of action] • Dose starts at 25mg a day -2 in 3 tolerate it slowly increased to 200-400mg a day • Side effects- Irritability, drowsiness, headaches, dizziness, cognitive slowing, speech impairment, weight loss and paraesthesia. • Beware of kidney stones [occurs in 4 %] Prof. Magdy Dahab

50. Overview of the Newer Anti Epileptic Drugs Oxcarbazepine- analogue of CBZ • Indications – same as CBZ, may worsen absence and myoclonic epilepsy. • Dose – start at 300mg a day and increase to 900 – 2400mg a day as needed • Side effects – hyponatraemia, headaches, occas. rashes and teratogenicity Prof. Magdy Dahab