Professor Ley Sander Department of Clinical and Experimental Epilepsy UCL Institute of Neurology National Hospital for N

1. The Medical and Surgical Treatment of Epilepsy Professor Ley Sander Department of Clinical and Experimental Epilepsy UCL Institute of Neurology National Hospital for Neurology & Neurosurgery Queen Square, London WC1N 3BG

2. The Treatment of Epilepsy • The incidence and prevalence • Aetiologies and risk factors • Aims of treatment • Clinical settings • Principles of treatment • Medical treatment • Surgical treatment • Guidelines • Conclusions

3. Incidence and Prevalence • Incidence of new cases of epilepsy: • 50/100,000/year • Incidence of single seizures: • 20 - 30/100,000/year • Prevalence of active epilepsy • 5 - 10/1,000(50% because on AEDs) • Severe epilepsy: 1 - 2/1,000 • Cumulative Incidence(lifetime prevalence): • 2 - 5%

4. Incidence and Prevalence in the UK • 30 000 new cases a year • 300 000 - 400 000 cases • 72 000 - 80 000 cases of severe epilepsy

5. Incidence and Prevalence in the UK • GP • 1 - 2 new cases of epilepsy/year • 10 - 12 cases of active epilepsy • Neurologist • 150 cases of epilepsy/single seizures/year • 1,200 cases of active epilepsy

6. Epilepsy: Aetiologies and Risk Factors • Risk factors varies with age and geographic location • Congenital, developmental and genetic conditions in childhood, adolescence and young adults • Head trauma, infection and tumours at any age although tumours more likely over age 40 • Cerebrovascular disease common in elderly • Endemic infections are associated with epilepsy in certain areas • malaria, neurocysticercosis, paragonomiasis, • no adequate large scale study of attributable risk yet

7. Antiepileptic Treatment • AEDs are mainstay treatment • Non-pharmacological options feasible in only few selected cases • Surgery • Curative • Palliative • Ketogenic diet (children) • Behaviour modification • Avoidance therapy in cases with clear precipitants

8. Aims of Antiepileptic Treatment • Complete seizure freedom • 50% seizure reduction of little benefit • No adverse effects • long term treatment - long term effects ? • cognitive effects debilitating • teratogenicity • Non-obtrusive treatment • once or twice daily • No PK or PD interactions • Maintenance of a normal lifestyle • Reduction in morbidity and mortality

9. AED Treatment: Clinical Settings • Prophylactic Treatment • Newly Diagnosed Epilepsy • Single seizure • Recurrent seizures • Chronic Epilepsy

10. Prophylactic use of AEDs • Often advocated after • Head injury • Craniotomy • There are considerable compliance problems • There is no evidence of a protective effect of this policy • No place for this! • Better wait for the event to happen

11. Is it Epilepsy ? • Newly diagnosed or suspected cases at Primary Care level • > 50% not epilepsy • commonest differential diagnosis: syncope • Chronic cases • 15 - 20% not epilepsy • mostly psychological in nature • Careful diagnostic assessment a must in all cases

12. The Single Seizure • A controversial area! • Single unprovoked attack usually not treated: practice to defer treatment until 2 or more seizures, although patients at high risk may be treated after a first attack • Incidence of epilepsy much greater than of single seizures • Community-based studies show that overall risk of a second seizure greater than previously accepted • selection bias • Patients • Seizure type • time to entry bias

13. The Single Seizure • AED treatment following a single seizure reduce risk of recurrence in the short term although long term prognosis not changed • This may eventually lead to changes in the way single seizures are managed • treatment after first seizure • - for six months, for a year? • tailored treatment and not symptomatic • Meanwhile, involve patient and or guardians in the decision

14. Recurrent Seizures • Treatment recommended after two or more seizures • Exceptions: - Long interval between seizures - Clear identifiable precipitant factor - Patient against treatment - Unlikely compliance

15. Precipitating Factors • Fever • Drugs • Alcohol • Photo-Sensitivity • Sleep Deprivation • Reflex Mechanisms • Acute Metabolic Stress • Emotional Stress/Major Life Events

16. Starting an AED • Starting AED treatment is a major event and should not be undertaken without careful evaluation of all relevant factors • Therapy is a long term prospect • All implications must be fully explained to the individual and or guardian • Paramount that the patient or guardians are kept informed about the treatment process and the rationale behind it

17. Starting Treatment • Treatment should always be started with a single drug at a small dose • All common side-effects must be discussed • teratogenicity and contraception if applicable • Importance of compliance should be stressed • Careful titration is a must - start low, go slow

18. Choice of AEDs treatment • Choice of AED influenced by: • Type of seizure and or epileptic syndrome • Individual circumstances of patient • Side effect profile of drug • Personal preferences • No clear cut evidence based medicine is available! • Clinical practice is based more on dogmatic teaching than on scientific knowledge • Empirical rather than rational

19. Principles of AED treatment • Diagnosis clearly established • Appropriate first line drug for syndrome and patient • One drug at a time as a rule: • If first drug ineffective add another first line drug and then withdraw first drug • Combination therapy only when single drug ineffective

20. What Is Chronic Epilepsy ? • Active 2 years after onset • Failed 2 first line AEDs • Great number of seizure in early history

21. Chronic Epilepsy 1 • Review history of epilepsy - Obtain and review old notes if possible - Interview patient and witness - Classify seizures • Review diagnosis - Non-epileptic events - Identifiable aetiology - High resolution MRI scanning • Question Compliance • Check serum AED levels • Review past and present AED treatment for efficacy and side-effects

22. Chronic Epilepsy 2 • Select the AED that is most likely to be efficacious and with the least side-effects • Adjust the dose of the selected drug to the optimum • Attempt to reduce and taper other AEDs • If seizures continue despite a maximally tolerated dose of a first-line drug: - Check compliance • tablet count, serum levels, counselling • Commence another first-line AED if there is one that has not been used to its optimum

23. Chronic Epilepsy 3 • If seizures continue try a combination of two AEDs • If combination unhelpful, AED which appears most effective and with fewer side-effects should be continued and the other AED replaced • If this drug is effective, withdrawal of the initial agent should be considered; if not, it should be replaced by another AED • Consider the possibility of surgical treatment • Consider using an experimental AED

24. Inappropriate use of AEDs • Inappropriate treatment of people who do not have epilepsy • Inappropriate drug treatment of patients who do have epilepsy • JME easily treated with some AEDs but poorly controlled with others • Partial epilepsies often misdiagnosed as generalised epilepsy • Incorrect dosages or inappropriate use of polytherapy • Overzealous adherance to “therapeutic” AED drug levels

25. AED drug levels monitoring • Measurement of AED levels: • drug toxicity occurs and needs to be documented • suspected non-compliance • suspected drug interactions • during pregnancy (free levels) • during systemic illness • phenytoin therapy • Not a guide to dosing!

26. Who Should be Evaluated for Surgery • Partial seizures: simple, complex, sec gen. • Stereotyped onset • No non-epileptic attacks • No contraindication for Neurosurgery • Active epilepsy for >2-3 yr, despite 3 + AEDs • Inadequate seizure control: > 1-2 c p s /month • Acceptance of best risk / benefit ratio

27. Best risk vs benefit ratio of temporal lobe epilepsy surgery • MedicalSurgical • Chance of seizure control • 10% 70% • Risk • Morbidity from seizures 1/100 long-lasting impairment • Psychosocial handicap hemiparesis, aphasia • 1/100 Annual mortality 1/20 quandrantanopia prevents driving

28. Range of Epilepsy Surgery • 70% Anterior temporal lobe resection • 20% Extra-temporal cortical resection • Lesionectomy • 10% Palliative Procedures • Hemispherectomy • Corpus callosotomy • Subpial transection • Vagal Nerve Stimulation

29. Components of Presurgical Evaluation • Convergence of data • One epileptogenic & dysfunctional area • Rest of brain normal • Clinical • Neuro-Imaging • EEG • Neuropsychology • Neuropsychiatry • Psychosocial

30. Psychosocial • Realistic expectations? • Improvement in life from seizure control? • Intelligence, memory will not improve • Not more attractive, employable • Need to continue AEDs after • Social support • Family, friends, community, finances

31. Neuro-imaging • Fundamental • MRI predicts nature and extent of pathology • Unusual to resect area with normal imaging • Poor results if imaging normal

32. Pathology and Outcome • TLE: Anterior Temporal Lobe resection • Focal pathology: 70% seizure free, 25% >90% reduced • DNT, cavernoma>HS>AVM>trauma>MCD • 20% seizure free if no focal pathology • Extra Temporal Lobe • Focal pathology: 60% seizure free, 20% >90% reduced • DNT, cavernoma, glioma>AVM>trauma • MCD 20-30% seizure free, if focal • <20% seizure free if no focal pathology

33. Treatment Guidelines for Epilepsy • NICE = www.nice.org.uk – National Institute for Clinical Excellence (England and Wales) • SIGN = www.sign.ac.uk – Scottish Intercollegiate Guidelines Network (Scotland) • AAN = www.aan.com– American Academy of Neurology (USA)

34. Primary Care Guidelines for Epilepsy • Referral of ALL who experience a suspected seizure • Seen within 14 days by specialist • Risk and safety precautions documented • Care Plan in place • At least a yearly review • Early re-referral if • Treatment failure • Seizures not controlled • Diagnostic uncertainty • Considering pregnancy • Considering drug withdrawal

35. Managing People With Epilepsy • Holistic issues: • Interest and continuity of care • Clear plan • Information provision • SUDEP • Easy access - Practical Issues: • Cooking, Bathing, Driving, Contraception, Conception - Reasonable Expectations: • Prognosis, Independent Living, Employment

36. AED Treatment: Conclusions • Correct diagnosis and classification paramount to treatment • AEDs are mainstay treatment • Treatment empirical rather than rational! • > 70% of patients become seizure free • Potential complications: toxicity • Low threshold for s/effects

37. AED Treatment: Conclusions • Potential for misuse of AEDs not to be dismissed • New AEDs may be better tolerated, but more effective? • Chronic side effect profile of new AEDs not fully known • Surgical treatment very successful but only possible in a few selected cases • Consider stopping AED if seizure free for years • New treatment still needed!