Epilepsy — Written Clinical Reasoning

SAQ 1 — Acute Status Epilepticus Management (15 marks, 20 minutes)

Prompt: Outline your immediate and acute management of this patient, addressing airway, first-line pharmacological therapy, second-line therapy, and concurrent investigation for the underlying cause. Justify each step with reference to evidence and guideline thresholds. [1]

Model Answer

Immediate assessment and stabilisation (3 marks): [1]

1. This is convulsive status epilepticus (SE) — continuous seizure activity for over 5 minutes. The ILAE 2015 operational definition sets t1 (the treatment threshold) at 5 minutes and t2 (the consequence threshold) at 30 minutes for convulsive SE [1]. This patient is at 12 minutes — well into established SE — and the clock is running toward neuronal injury.
2. Airway and oxygen — apply high-flow oxygen (15 L via non-rebreather mask), head tilt, jaw thrust, suction secretions. His saturation of 90 per cent reflects hypoventilation from ongoing seizure activity and airway compromise; rapid seizure termination will restore it.
3. Glucose — finger-prick glucose is 4.2 mmol/L, which is normal; hypoglycaemia is excluded as a cause. Do not delay treatment for further bloods.
4. Call for senior emergency and ICU support — this patient is at high risk of needing intubation.

First-line pharmacological therapy (4 marks): [1]

The first-line treatment of SE is a benzodiazepine. The standard adult dose is intravenous lorazepam 0.1 mg/kg (4 mg typical) repeated once at 5 to 10 minutes if seizure activity persists. However, paramedics were unable to establish intravenous access, and this patient has been convulsing for 12 minutes. [1]

The correct first-line agent in this situation is intramuscular midazolam 10 mg. The RAMPART trial (Silbergleit et al., NEJM 2012, PMID 22335736) randomised patients to IM midazolam versus IV lorazepam in the prehospital setting and found IM midazolam was superior: 73.4 per cent versus 63.4 per cent seizure-free on ED arrival [2]. The reason is that the median time to drug administration was 1.2 minutes for IM midazolam versus 4.8 minutes for IV lorazepam (because establishing IV access in a convulsing patient is slow). The faster administration more than compensated for the slightly slower drug absorption from the IM route.

Establish IV access concurrently with the IM midazolam administration; if the patient is still convulsing at 5 to 10 minutes after the first benzodiazepine dose, give a second benzodiazepine dose — IV lorazepam 4 mg if IV access is now available. [1]

Second-line pharmacological therapy (3 marks): [1]

If the patient is still convulsing after two benzodiazepine doses (i.e. established benzodiazepine-refractory SE), the next step is a non-benzodiazepine antiepileptic drug. The ESETT trial (Kapur et al., NEJM 2019, PMID 31774955) randomised patients with benzodiazepine-refractory convulsive SE to levetiracetam 60 mg/kg, fosphenytoin 20 mg PE/kg, or valproate 40 mg/kg and found all three were equivalent (47 per cent, 45 per cent, 46 per cent respectively terminating SE and improving consciousness at 60 minutes) [3].

For this patient, intravenous levetiracetam 60 mg/kg (approximately 4500 mg over 5 minutes) is a reasonable first choice because it has the most favourable safety profile, minimal drug interactions, and is not an enzyme inducer. Fosphenytoin 20 mg PE/kg would be appropriate if levetiracetam is unavailable or if there is a prior good response to phenytoin; valproate 40 mg/kg should be avoided given his hepatic status is unknown and levetiracetam is equally effective. [1]

Refractory SE (anaesthetic infusion) — only if second-line fails: [1]

If the patient is still convulsing after the second-line agent (typically beyond 40 minutes), he has refractory SE and requires intubation, mechanical ventilation, anaesthetic infusion (propofol infusion 1-2 mg/kg bolus then 30-200 microgram/kg/min, or midazolam infusion, or thiopentone), continuous EEG monitoring, and ICU admission. [1]

Concurrent investigation of the underlying cause (5 marks): [1]

New-onset status epilepticus in a 62-year-old demands a structural or metabolic cause search. The investigations and their rationale: [1]

Given the 6-month history of morning confusion and a 40-pack-year smoking history, a structural lesion (primary or secondary brain tumour, prior stroke, subdural haematoma) is the leading diagnostic consideration. His type 2 diabetes and hypertension also raise the possibility of cerebrovascular disease. [1]

SAQ 2 — Women with Epilepsy: Preconception Counselling (10 marks, 15 minutes)

Prompt: A 26-year-old woman with idiopathic generalised epilepsy presents for preconception counselling. She has had generalised tonic-clonic seizures and myoclonic jerks since age 14. She has been seizure-free for 3 years on sodium valproate 1500 mg daily and lamotrigine 200 mg daily. She and her partner want to start a family in 12 months. Outline your integrated management plan. [1]

Model Answer

Problem list (2 marks): [1]

1. Idiopathic generalised epilepsy (most consistent with juvenile myoclonic epilepsy) — well-controlled on combination therapy
2. Preconception management required — valproate is contraindicated in pregnancy
3. The teratogenic and neurodevelopmental risks of valproate must be balanced against the risk of breakthrough seizures
4. Contraception, folic acid supplementation, and surveillance planning
5. Counselling on driving, lifestyle, and the lifelong nature of her epilepsy [1]

Switch from valproate (3 marks): [1]

Valproate is now prohibited in women of childbearing potential in Australia (TGA) and Europe (EMA) unless a formal Pregnancy Prevention Programme is met. The malformation rate is 30-40 per cent (neural tube defects, cardiac defects, orofacial clefts) and there is consistent evidence of neurodevelopmental harm — IQ reduction of 6-9 points and a 5-fold increase in autism spectrum disorder. The SANAD II trial confirmed valproate is the most effective generalised AED but the prohibition in pregnancy stands [4].

The plan:

1. Withdraw valproate gradually over 2 to 4 months, 12 months before planned conception.
2. Optimise lamotrigine monotherapy (titrate upward to a typical target of 300-500 mg daily based on trough levels). Lamotrigine has the most reassuring pregnancy safety data.
3. If lamotrigine monotherapy fails to maintain seizure freedom, add or switch to levetiracetam, which also has substantial pregnancy safety registry data.
4. Counsel explicitly that the new regimen may be less effective — accept some increase in seizure risk in exchange for fetal safety. The shared decision-making conversation must cover this trade-off.
5. Aim for at least 6 months of seizure freedom on the final preconception regimen before trying to conceive. [1]

Folic acid and preconception care (2 marks): [1]

• Folic acid 5 mg daily — start now and continue through the first trimester to reduce neural tube defect risk. This is recommended for all women with epilepsy on AEDs, especially those previously on valproate or carbamazepine.
• Effective contraception during the transition period (preferably a levonorgestrel IUD or copper IUD; the combined oral contraceptive pill interacts with enzyme-inducing AEDs but levetiracetam and lamotrigine do not reduce OCP efficacy — however, OCP use accelerates lamotrigine clearance and reduces its level, so monitor levels if an OCP is used).
• Lifestyle advice: avoid sleep deprivation (a major seizure precipitant in JME), minimise alcohol, and ensure partner and family are aware of seizure first aid. [1]

Pregnancy surveillance (2 marks): [1]

• Trimesterly review with neurology and obstetric medicine.
• Lamotrigine trough levels at each trimester — lamotrigine clearance rises 50-70 per cent in the second and third trimesters due to oestrogen-induced glucuronidation; the dose must be titrated upward to maintain the pre-pregnancy trough level.
• If levetiracetam is used, monitor levels similarly.
• High-resolution fetal anatomy ultrasound at 18-20 weeks.
• Counsel that the postpartum period requires rapid dose reduction back to pre-pregnancy levels (within 1-2 weeks) to avoid maternal drug toxicity, and that breastfeeding is safe with lamotrigine and levetiracetam. [1]

Counselling and prognosis (1 mark): [1]

• JME is typically lifelong — most patients require AED therapy for life. Do not counsel her that the epilepsy is curable.
• The recurrence risk of breakthrough seizures in pregnancy is highest in the peripartum and postpartum periods due to falling drug levels, sleep deprivation, and non-adherence.
• SUDEP risk stratification — she is currently low risk (seizure-free), but this rises if seizures return. Counsel honestly.
• Document all discussions in writing, including the signed acknowledgement of valproate risk if a Pregnancy Prevention Programme was previously in place. [1]