1. Esther Sammler ST4 in Neurology Dundee Oncology Foundation Doctors ‘ Lunchtime Teaching

2. Background Seizures Manifestation of an abnormal and excessive synchronized discharge of set of neurons Epilepsy Brain disorder with an enduring predisposition to generate unprovoked epileptic seizures (in practice: < 2 more) Epidemiology Lifetime prevalence of seizures is 1-5% Incidence of epilepsy in general population is 1%

3. ILAE* Classification of Seizures Seizur es Partial Simple Complex With 2 0 generalization Generaliz ed Absence Myoclonic Atonic Tonic Tonic-Clonic ILAE* International League against Epilepsy

4. Causes of epilepsy / seizures Varies within age groups and geographical distribution Genetic and congenital conditions predominate in early childhood Inherited predispositions, hippocampal sclerosis, alcohol & drug abuse, trauma in older children and young adults Tumors and sporadic infections at all ages, but malignant brain tumors >30 Cerebrovascular and degenerative diseases in the elderly

5. Incidence of epilepsy depending on age

6. Precipitating causes Stress Sleep deprivation and fatigue Sleep / wake cycle Alcohol and alcohol withdrawal Metabolic disturbances Toxins and drugs Menstrual cycle

7. Prognosis of epilepsy 60 – 70% enter prolonged remission Predictors of an adverse outcome – Early onset – Symptomatic epilepsy – Neurological deficit / learning disabilities – Failure of Antiepileptic drug treatment

8. Burdens of Epilepsy on the Individual Physical morbidity (burns, fractures etc.) Psychological stress (e.g. loss of control, fear, overprotection) Social stress (stigma, education, work, driving, relationships, social life) Psychiatric illness (depression, anxiety) Co-morbidities

9. Healthcare Burden Random series (n=1628) of pts on AED therapy 65% on montherapy, 35% on polytherapy OVER LAST 12 MONTHS 28% attended specialist service 87% seen by GP 9% no contact 18% attended A&E (43% ever) 9% required hospital admission (47% ever) Hart et al. The nature of epilepsy in the general population. Epilepsy Res 1995;21:43-9

10. Diagnosis of epilepsy Wide differential diagnosis Misdiagnosis is common For example, 74 pts with dx of epilepsy were investigated with tilt-table, prolonged ECG, blood pressure monitoring and EEG monitored carotid sinus massage and an alternative cardiological cause was found in 31, including 13 on AED treatment)* Conditions most commonly mistaken are syncope and pseudoseizures Precise and detailed personal and witnessed accounts of prodrome, onset, evolution, and recovery period There is no shame in deferring a diagnosis if uncertain Zaidi et al. Misdiagnosis of epilepsy: many seizure like attacks have a cardiovascular cause. J Am Coll Cardiol 2000; 36:1

11. Common reasons for misdiagnosis Incomplete history No eye witness account Not taking full clinical picture into account Over-interpretation of minor EEG abnormalities

12. Investigations in adult-onset epilepsy Classification of epileptic seizures and co- morbidities will guide investigations The main role of investigations in new onset epilepsy is to attempt to identify aetiology and identify underlying cause in symptomatic seizures – Cerebral Imaging – EEG – ECG – Blood tests

13. Management of first seizure Clear history of epileptic seizure Focal onset clinically (all patients > 25 years) – Detailed brain imaging in all – EEG Generalized onset clinically (all patients > 25 years) – EEG – No need for imaging unless atypical ECG and bloods General safety and driving advice No AED treatment if first seizure event Refer to neurology

14. Management of pt with established epilepsy Take careful and complete hx – Seizure semiology (witness!) and possible trigger factor – Previous seizure pattern in terms of frequency and clinical presentation – AED: Any recent changes? Compliance? Previous AED? – AED serum levels: please don’t! possible exception phenytoin Investigate as appropriate Assure that AED are written up, available and appr. formulation! Neurology registrar on call (bleep 4968) always happy to discuss Safety and driving advice

15. DVLA – Medical rules for drivers First fit Group 1 liscence: 6 months off driving from the date of the seizure if the licence holder has undergone assessment by an appropriate specialist and no relevant abnormality has been identified on investigation, for example EEG and brain scan where indicated. Till 70 licence restored, provided no further attack and otherwise well. (Special consideration may be given when the epileptic attack is associated with certain clearly-identified, non-recurring provoking causes) Fit in established epilepsy: 12 months of driving http://www.dft.gov.uk/dvla/medical.aspx

16. Seizures in oncological patients Epilepsy and malignancy are common conditions in the general population and may co-exist New onset seizures in pt with known malignancy = “brain metastasis” 4% of pts with epileptic seizures have intracranial malignancy 30-40% of pts with brain tumors present with fits 10-30% of pts with brain tumors will seize at some point

17. Seizures in oncological patients Primary CNS tumors Metastasis – 10x more frequent than primary CNS tumors – Melanomas, lung, breast, kidney,ect Infiltrative Lesions – Meningeal carcinomatosis, Gliomatosis cerebri, Intravascular lymphomatosis Paraneoplastic syndromes (limbic encephalitis) Metabolic disorders and Infections Chemotherapy Radiotherapy

18. Investigations Tailored to patient Detailed imaging (MRI including gadolinium contrast) CSF analysis (up to 3 LP’s with up to 10-15ml CSF) Biochemistry (in particular Na, K, Ca, Mg, blood glucose) Infection screen

19. Treatment There is no evidence for prophylactic antiepileptic treatment Complex interactions between AED and chemotherapeutics – Enzyme inducing AED: phenytoin, phenobarbital, primidone, carbamazepine, and to lesser extent, oxacarbamazepine and topiramate – Enzyme inhibiting AED: Valproate, Zonisamide, Felbamate Increased risk of adverse effects AED with beneficial pharmocokinetic profile: – Levetiraectam – Gabapentin – Pregabalin – Vigabatrin Other Tx (surgery, radiotherapy, ect)

20. AED potential for producing interactions HighMediumLow Carbamazepine Phenotoin Phenobarbital Primidone Valproate Felbamate Lamotrigene Oxcarbazepine Tiagabine Topiramate Ethosuximide Clonazepam Clobazam Zonisamide Vigabatrin Gabapentin Levetiracetam* Pregabalin Vecht et al., Lancet Neurol. 2003;2:404-409

21. Take home message Seizures in oncological patients is red flag and warrant immediate assessment for underlying cause EEG only in special situations helpful (non-convulsive status epilepticus, encephalopathy,…) Treatment of status epilepticus as in general population No prophylactic AED treatment Safety and driving advice

22. Thank you