Neurological management of epilepsy Flashcards
What is epilepsy?
the tendency to have recurrent epileptic seizures
What are epileptic seizures?
-abnormal synchronous firing of a large number of cortical neurons, causing symptoms
-Common (0.5-1% of the population)
-Important cause of injury, mortality, unplanned hospital admissions
-Linked to poor outcomes for education, employment, mental health and stigma
Briefly summarise the NICE neurological management pathway
-Patient presents with suspected seizure(s), usually to GP or A&E
-Refer to specialist for diagnosis and decision to start treatment
-Exceptionally, start treatment before seeing specialist
-Clinician takes history, examines patient, arranges appropriate investigation
-Diagnosis and classification of epilepsy
-Explanation, discussion, provision of information
-Decision to treat; special consideration for particular groups of patients
-Ongoing treatment
-Depending on response and outcome, possible referral to tertiary service
-Stopping treatment
What information should be provided to people with epilepsy?
-epilepsy in general, diagnosis, treatment
-risk management, first aid, safety
-psychological issues
-education and employment issues
-road safety and driving
-lifestyle
-issues relevant to women (contraception and pregnancy)
-voluntary organisations, support groups
What is the general information regarding pharmacological treatment? (NICE guidelines)
-provide information about indications, side effects and license status
-drug treatment strategy should be individualised
-diagnosis of epilepsy needs to be critically evaluated if events continue
-consistent supply of a particular ASM is needed
treat with single ASM (mono therapy)
-if an ASM has failed a second drug should be started as mono therapy
-combination therapy should be considered when mono therapy has not resulted in seizure freedom
-when prescribing sodium valproate to women, there is a risk of malformation and neurodevelopment impairments in an unborn child
What were Kwan and Brodie’s findings (2000)?
-Follow-up of 525 patients diagnosed and treated at a single centre
-63% became seizure-free for >12 months
-Subgroup of 470 who were treatment-naïve when first seen
-47% seizure-free for >12 months with the first drug tried (monotherapy)
-14% with the second drug tried (monotherapy)
-3% on therapy with two drugs
-“Idiopathic” aetiology and fewer seizures before starting treatment predicted good outcome
-No evidence that any particular drug was preferable
What were Marson et al., (2007) findings?
-Subdivided patients into “partial (focal-onset) seizures”, or “generalised or unclassifiable” (assumed to include a subset with IGE/GGE)
-Generalised or unclassifiable (results were similar for IGE/GGE subgroup)
-Valproate better tolerated than topiramate and more efficacious than lamotrigine
-NB adverse effects of valproate during pregnancy
-Partial (focal)
-Lamotrigine better tolerated than carbamazepine and equally efficacious
-Lamotrigine better tolerated than topiramate
-Both better than gabapentin
What did the meta-analysis conducted by Nevitt et al (2017) show?
-Very large meta-analysis – 77 trials, 17961 patients (36 and 12391 had usable data on outcomes)
-Primary outcome ‘time to withdrawal of allocated treatment‘
-Secondary outcomes were ‘time to achieve 12-month remission’, ‘time to first seizure post-randomisation’, and ‘occurrence of adverse events‘
-Primary outcome, partial (focal) seizures
-Levetiracetam better than carbamazepine and lamotrigine ,Lamotrigine better than all others
Carbamazepine better than gabapentin and phenobarbitone
-Generalised onset seizures
Sodium valproate better than carbamazepine, topiramate and phenobarbitone
What do NICE guidelines state about ASM’s?
Anti-epileptic drug treatment strategy should be individualised according to seizure type, epilepsy syndrome, co-medication and co-morbidity, lifestyle, and preferences of the person, their family and/or carers as appropriate.
What are pharmacological treatment options for focal (‘partial’) seizures?
-Levetiracetam, lamotrigine, carbamazepine
-Levetiracetam has no interactions with other drugs and usually well tolerated
What are pharmacological treatment options for generalised seizures?
-In men: sodium valproate, lamotrigine, levetiracetam
-In women: lamotrigine, levetiracetam
-Ethosuximide for frequent absence seizures uncontrolled by above drugs
-Topiramate is poorly tolerated in trials but anecdotally starting with very low dose, escalating slowly and aiming for low continuing dose is better tolerated
What is the evidence for polytherapy?
-Kwan and Brodie – 3% seizure-free two drugs
-Luciano and Shorvon, Annals of Neurology, 2007
-155 patients with epilepsy for >5 years, mostly polytherapy
-Adding or substituting a drug rendered 28% seizure-free
-Almost all trials of new drugs are as add-on versus placebo in similar patients, 28% seizure-free not usual
What should be considered when continuing pharmacological treatment? (NICE guidelines)
-look for adverse effects
-continuing ASM therapy should be planned by the specialist
-if management is straightforward, ASMs can be continued/prescribed by primary care provider (prescribed)
How can adherence to treatment be optimised?
-understanding of their condition and the rationale of treatment
-reducing stigma associated with the condition
-using simple medication regimens
-positive relationships with healthcare professionals
When is blood test monitoring indicated?
-detection of non-adherence to the prescribed medication
-suspected toxicity
-adjustment of phenytoin dose
-management of pharmacokinetic interactions
-specific clinical conditions, for example, status epilepticus, organ failure and certain situations in pregnancy
What is the evidence for stopping drug treatment?
-MRC Antiepileptic Drug Withdrawal Study Group, Lancet, 1991
-1031 patients seizure-free on drug treatment for >2 years
-Randomised to slow drug withdrawal vs continued treatment
-2 years after randomisation, 78% of those continuing treatment and 59% of those withdrawn from treatment remained seizure free
Later, the differences between the two groups diminished
-Lamberink at al., Lancet Neurology, 2017
Meta-analysis, 45 studies including 7082patients (10 studies with 1769 suitable)
-46% relapsed (9% did not regain seizure control after treatment restarted)
What are predictors of more likely seizure recurrence?
-Longer epilepsy duration before remission
-Shorter seizure-free interval before antiepileptic drug withdrawal
-Younger age at onset of epilepsy
-History of febrile seizures
-Higher number of seizures before remission
-Absence of a self-limiting epilepsy syndrome
-Developmental delay
-Epileptiform abnormality on electroencephalogram (EEG) before withdrawal
What is phenobarbital used for?
-partial and generalised convulsive seizures
-anxiety disorders
-sedation
-sleep disorders
What is phenytoin used for?
-partial and generalised convulsive seizures
What is primidone used for?
-partial and generalised convulsive seizures
What is ethosuximide used for?
Absent seizures
What is diazepam used for?
-convulsive disorders
-status epilepticus
What is carbamazepine used for?
-partial and generalised convulsive seizures
What is valproate used for?
-partial and generalised convulsive seizures
-absent seizures
What is clonazepam used for?
-Lennox-Gastaut syndrome
-myoclonic seizures
What is clobazam used for?
-Lennox-Gastaut syndrome
What is vigabatrin used for?
-infantile spasms
-complex partial seizures
What is lamotrigine used for?
-partial and generalised seizures
-Lennox-Gastaut syndrome
What is oxcarbazepine used for?
-Partial seizures
What is gabapentin used for?
-partial and generalised seizures
What is levetiracetam used for?
-partial and generalised convulsive seizures
-juvenile myoclonic epilepsy
-partial seizures
What are ASMs that should be avoided for women?
-valproate (higher teratogenic risk)
-phenytoin (cosmetic effects)
What are some hepatic enzyme inducing ASMs?
-phenytoin
-carbamazepine
-barbiturates
-oxzcarbazepine
-topiramte
How do ASMs affect girls and women of childbearing potential (NICE guidelines)?
-Risk of ASMs causing malformations and neurodevelopment impairments in unborn child.
-Enrol in a pregnancy prevention programme
-Management of pregnancy, labour and postpartum including breastfeeding
What step should be ensured for communication between PwE and HCPs?
-Ensure there is an accessible point of contact with specialist services
-Comprehensive care plan
-Lifestyle issues as well as medical issues
-Epilepsy specialist nurses (ESNs) should be an integral part of the network of care
-HCPs have a responsibility to educate others
