Epilepsy

The answer first

Epilepsy is a disorder of recurrent, unprovoked seizures. A seizure is the transient clinical manifestation of abnormal, excessive, hypersynchronous cortical neuronal firing. The two questions that determine everything in epilepsy are: is this truly an epileptic seizure (and not syncope, dissociation, or another mimic)? and what is the seizure type, syndrome, and cause? — because that triad drives both prognosis and drug choice. ^[1]

The clinical decision rules a registrar must own at viva: ^[1]

1. Diagnose before you treat. The single biggest source of "drug-resistant epilepsy" referred to specialty clinics is misdiagnosis — typically syncope or psychogenic non-epileptic seizures labelled as epilepsy. A detailed witness history is more powerful than any single investigation.
2. Classify before you choose a drug. The 2017 ILAE classification splits seizures first by onset: focal, generalised, or unknown ^[1]. Focal seizures are treated with focal agents (lamotrigine, levetiracetam, lacosamide, carbamazepine); idiopathic generalised epilepsies require broad-spectrum agents (valproate, levetiracetam, topiramate). Prescribing carbamazepine or oxcarbazepine to a patient with juvenile myoclonic epilepsy can worsen the myoclonus and absences — a high-yield DWE trap.
3. Status epilepticus is a time-critical emergency. Per the ILAE 2015 definition, a convulsive seizure becomes status epilepticus at 5 minutes (treatment threshold t1) and risks neuronal injury by 30 minutes (consequence threshold t2) ^[3]. Treat aggressively with benzodiazepines first, escalate to a second-line agent after two doses, then to anaesthetic infusion if refractory.
4. Valproate is the most effective generalised AED — and the most dangerous in pregnancy. Avoid valproate in any woman of childbearing potential unless a formal Pregnancy Prevention Programme is met. The major malformation risk is around 10 per cent (dose-dependent, higher at high doses), and neurodevelopmental harm affects 30 to 40 per cent (IQ reduction, autism spectrum) ^[5].

The organising principle is syndrome-based, patient-centred management: classify the seizure and syndrome, identify the cause, choose the drug by syndrome and patient factors (sex, age, comorbidity, reproductive plans), counsel on driving and lifestyle, and escalate to surgery early in drug-resistant focal epilepsy. ^[1]

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References10ShowHide

1. [1]Fisher RS, Cross JH, French JA, et al. Operational classification of seizure types by the International League Against Epilepsy: Position Paper of the ILAE Commission for Classification and Terminology Epilepsia, 2017.PMID 28276060
2. [2]Scheffer IE, Berkovic S, Capovilla G, et al. ILAE classification of the epilepsies: Position paper of the ILAE Commission for Classification and Terminology Epilepsia, 2017.PMID 28276062
3. [3]Trinka E, Cock H, Hesdorffer D, et al. A definition and classification of status epilepticus--Report of the ILAE Task Force on Classification of Status Epilepticus Epilepsia, 2015.PMID 26336950
4. [4]Marson AG, Al-Kharusi AM, Alwaidh M, et al. The SANAD study of effectiveness of carbamazepine, gabapentin, lamotrigine, oxcarbazepine, or topiramate for treatment of partial epilepsy: an unblinded randomised controlled trial Lancet, 2007.PMID 17382827
5. [5]Marson AG, Appleton R, Baker GA, et al. The SANAD II study of the effectiveness and cost-effectiveness of valproate versus levetiracetam for newly diagnosed generalised and unclassifiable epilepsy: an open-label, non-inferiority, multicentre, phase 4, randomised controlled trial Lancet, 2021.PMID 33838758
6. [6]Marson A, Jacoby A, Johnson A, Kim L, Gamble C, Chadwick D Immediate versus deferred antiepileptic drug treatment for early epilepsy and single seizures: a randomised controlled trial Lancet, 2005.PMID 15950714
7. [7]Kapur J, Elm J, Chamberlain JM, et al. Randomized Trial of Three Anticonvulsant Medications for Status Epilepticus N Engl J Med, 2019.PMID 31774955
8. [8]Silbergleit R, Durkalski V, Lowenstein D, et al. Intramuscular versus intravenous therapy for prehospital status epilepticus N Engl J Med, 2012.PMID 22335736
9. [9]Wiebe S, Blume WT, Girvin JP, Eliasziw M A randomized, controlled trial of surgery for temporal-lobe epilepsy N Engl J Med, 2001.PMID 11484687
10. [10]Hancock EC, Osborne JP, Edwards SW Treatment of infantile spasms Cochrane Database Syst Rev, 2013.PMID 23740534