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

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

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

Incidence and Prevalence in the UK new cases a year cases cases of severe epilepsy

Incidence and Prevalence in the UK GP –1 - 2 new cases of epilepsy/year – cases of active epilepsy Neurologist –150 cases of epilepsy/single seizures/year –1,200 cases of active epilepsy

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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!

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 Who Should be Evaluated for Surgery

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

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

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

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 Psychosocial

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

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 Pathology and Outcome

Treatment Guidelines for Epilepsy NICE = – National Institute for Clinical Excellence (England and Wales) SIGN = – Scottish Intercollegiate Guidelines Network (Scotland) AAN = – American Academy of Neurology (USA)

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

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

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

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!