neurology march 19

1. Updates in Epilepsy for GPs
Ela Akay
Consultant Neurologist
ela.akay@nuth.nhs.uk

2. Overview
• Classification of seizures
• 1st seizures
• SUDEP
• Epilepsy and antidepressants
• Epilepsy drugs – long term effects
• Pregnancy/Sodium valproate MHRA guidance
• Drug resistant epilepsy
• New antiepileptic drugs incl. Cannabidiol in epilepsy
• Local developments

3. What is epilepsy?
• Recurrent (more than one) seizures >24 h apart
• Prevalence
• 0.8% (m>f)
• Bimodal onset

4. “Partial
onset”
Simple partial Complex partial
Secondary generalised
Idiopathic generlaised
epilepsy (IGE) / Genetic
generalised epilepsy (GGE)

5. 1st seizures

6. ILAE (International league against epilepsy) definition of epilepsy

7. Remote symptomatic seizures – higher risk
for recurrence

8. 1st seizures
• Should be seen in 2 weeks (NICE) – currently 6 weeks
• Advice
• driving (6-12m depending on risk of recurrence)
• Safety (heights, baths, infant children, swimming)

9. Management of Epilepsy
• Generalised onset
• Valproate
• Lamotrigine
• Levetiracetam
• Zonisamide
• Focal onset
• Lamotrigine
• Carbamazepine
• Levetiracetam
• Zonisamide
• Topiramate

10. SUDEP
• Sudden Unexplained Death in EPilepsy
• 7-15% of deaths in Epilepsy
• >50% occur in patients with Drug resistant epilepsy
• Risk factors
• Young males
• GTCS
• Nocturnal seizures
• Poor compliance
• Bed sensors available (refer to ENS)

11. Epilepsy and antidepressants
• Theoretical increased risk of seizures
• Depression common in patients with epilepsy ~30% affected during
their life
• Benefits usually outweigh risk
High risk of seizure: amitriptyline (higher doses), clomipramine,
dosulepin
Incidence ~0.5%
Intermediate risk of
seizure:
amitriptyline, doxepin, duloxetine, imipramine,
mirtazapine, nortriptyline, trazodone, venlafaxine,
fluoxetine, sertraline
Incidence ~0.2%
Low risk of seizure: fluvoxamine, isocarboxazid, moclobemide,
phenelzine, reboxetine, sertraline,
tranylcypromine, tryptophan

12. Long term effects of AEDs
• Increased risk of osteoporosis/osteopaenia
• Particularly if on enzyme inducing AEDs e.g. carbamazepine, phenytoin,
topiramate, perampanel
• Check vitamin D, ALP, Ca every 2-5y (NICE)
• Dyslipidaemia
• Increased non HDL cholesterol with enzyme inducing AEDs (especially
carbamazepine) and sodium valproate
• No specific guidelines as to management

13. Epilepsy and Pregnancy

14. EURAP
• Launched in 1999
• 42 countries worldwide
• Physician initiated
• Prospective observational study of AED effects in pregnancy
• Follow-up each TM, birth and 1 yr postpartum (longer than most
observational studies)
• 22,721 enrolled; 12,892 prospective, 80% monoRx
• Most common AEDs: LTG, CBZ, VPA
• MCM rate overall was 5%; monoRx 4.6%; polyRx 6.9%
• 10% detected perinatally, 62% at birth, 28% in 1st yr

16. Major congenital malformations – EURAP

17. Sodium Valproate

18. Sodium Valproate – risks
• 1/10 Major congenital malformations
• 30-40% risk of neurodevelopmental problems e.g. ASD, ADHD, LD
• Risks associated with abruptly stopping valproate
• SUDEP (MBRACE report)
• Increased seizures
• Current guidance if women becomes pregnant – to be seen within 2 weeks by
a specialist

19. Pregnancy prevention programme
• Assessing patients for the potential of becoming pregnant
• Pregnancy tests before starting and during treatment as needed
• Counselling patients about the risks of valproate treatment
• Explaining the need for effective contraception throughout treatment
• Carrying out reviews of treatment by a specialist at least annually
• Risk acknowledgement form that patients and prescribers will go through
at each such review to confirm that appropriate advice has been given and
understood.
• It is important that no woman should stop taking sodium valproate without
first consulting her doctor.

20. Annual risk acknowledgement form

21. Antiepileptic drug development
Perampanel
Brivaracetam
Cannabidiol 2019

22. Control of seizures – new vs old AEDs

23. Drug resistant epilepsy
Seizure free after:
• 1st drug: 47%
• 2nd drug: 13%
• 3rd drug: 4%
• 4th + drug: <1%
1/3rd patients
have drug
resistant epilepsy

24. Common reasons ongoing
seizures/breakthrough seizures
• Misdiagnosis – commonly non epileptic attack disorder
• Non compliance
• Consider once daily AEDs
• Drug levels
• Alcohol/drugs

25. What to do in patients with DRE
• Consider re-referring back to epilepsy service
• Non pharmacological treatments
• Surgical resection
• Vagal nerve stimulation
• (Ketogenic diet)

26. Newer AEDs
• Brivaracetam
• Good if levetiracetam works but behavioural side effects
• Can switch overnight
• Esclicarbazepine
• Once daily
• Can switch from carbamazepine over 1-3 weeks and oxcarbazepine overnight
• Perampanel
• Once daily
• Can cause significant behavioural side effects

27. Cannabis and Epilepsy
• Cannabidiol (CBD) – oral solution Epidiolex
• FDA approved June 2018 for Dravet + Lennox Gastaut in pts >2y
• Cannabis – 85 active compounds
• THC (tetrahydrocannabinol) – most psychoactive
• CBD
• Cannabidivarin
• Epidiolex 99% CBD 0.1% THC
• Sativex 50/50 THC/CBD (MS related spasticity)

28. Local developments
• Tertiary services with Epileptologists in Sunderland, Middlesborough
and Newcastle
• Non-epileptic attacks service commissioned – awaiting psychology
appointment
• Epilepsy and Obstetrics clinic – in progress (currently Epilepsy
Specialist nurse present weekly)
• Adult Ketogenic diet service – in progress
• Regional Epilepsy specialist interest group