Epilepsy — Clinical Case

DCE Long Case

Patient brief (provided to trainee)

Patient: Ms Sarah Chen, 29 years old, marketing manager. [1]

Presenting complaint: Recurrent focal impaired awareness seizures despite multiple antiepileptic drugs, currently under evaluation at the epilepsy surgery service. She is in the clinic today for review and discussion of the surgical pathway. [1]

History of presenting complaint: First seizures at age 13 years with episodes of a rising epigastric sensation lasting 30 seconds followed by impaired awareness with lip-smacking and fumbling hand automatisms, lasting 1 to 2 minutes, with postictal confusion of 10 to 15 minutes. Had three to four seizures per month on average, occasionally progressing to a bilateral tonic-clonic seizure. Has been tried on sodium valproate (poorly tolerated, weight gain and tremor), lamotrigine (rash at 200 mg daily requiring discontinuation), carbamazepine (worsened her mood and produced hyponatraemia to 124 mmol/L), and currently on levetiracetam 1500 mg twice daily for the past 2 years with ongoing focal impaired awareness seizures at 4 to 6 per month and one bilateral tonic-clonic seizure 3 months ago. Reports a memorable febrile convulsion at age 18 months requiring hospital admission. [1]

Past history:

• Depression (diagnosed at 18, currently on sertraline 100 mg daily)
• Migraine with aura since age 16
• Menstrual cycle irregularity
• Appendicectomy age 22 [1]

Current medications:

• Levetiracetam 1500 mg twice daily
• Sertraline 100 mg daily
• Combined oral contraceptive pill (ethinyloestradiol 30 microgram / levonorgestrel 150 microgram) [1]

Family history:

• Father with epilepsy (focal, well-controlled)
• Mother with hypothyroidism [1]

Social history:

• Lives with her partner
• Drinks 6 to 10 standard drinks per week
• Does not drive (seizure-related restriction for 5 years)
• Works part-time due to seizures [1]

Examination findings (trainee elicits):

• Alert, cooperative, oriented. Fluent speech with normal comprehension and naming
• Cutaneous examination: no neurocutaneous stigmata
• Cranial nerves: intact. Visual fields full to confrontation. Fundi normal
• Motor: tone, power 5/5 in all four limbs, symmetrical reflexes, flexor plantar responses
• Sensation intact to all modalities. Coordination intact. Gait normal
• Mild postictal nose-rubbing during the consultation after a brief aura [1]

Investigations (provided):

• Interictal EEG: left anterior temporal spikes
• Video-EEG monitoring: 4 habitual seizures captured, all with left temporal ictal onset
• MRI brain (3 Tesla, epilepsy protocol): left hippocampal sclerosis — left hippocampal atrophy (volume 1.8 mL versus 3.2 mL right) with T2/FLAIR hyperintensity and loss of internal architecture
• FDG-PET: left temporal hypometabolism
• Neuropsychology: impaired verbal memory (worse than expected for age and education) with intact visuospatial memory
• Visual fields: full
• WADA test: left hemisphere language dominant, memory support from right hemisphere adequate for surgery [1]

Candidate's structured presentation (model)

Opening statement: [1]

"Ms Chen is a 29-year-old marketing manager with a 16-year history of drug-resistant focal impaired awareness seizures arising from left mesial temporal sclerosis, with concordant presurgical data. She has comorbid depression on sertraline, migraine with aura, and is on a combined oral contraceptive pill. She does not drive due to seizure-related restrictions. [1]

Her seizures are characterised by a rising epigastric aura followed by impaired awareness with orofacial automatisms and postictal confusion, with occasional progression to bilateral tonic-clonic seizures. She has failed four antiepileptic drugs and continues to have 4 to 6 seizures per month on levetiracetam 1500 mg twice daily. [1]

Her main problems are:

1. Drug-resistant mesial temporal lobe epilepsy from left hippocampal sclerosis — concordant presurgical data supporting surgical evaluation
2. Recurrent seizures with secondary bilateral tonic-clonic generalisation — high SUDEP risk
3. Comorbid depression on sertraline, which complicates AED choice and prognosis
4. Driving restriction and occupational limitation — major psychosocial impact
5. Reproductive considerations — contraception, future pregnancy planning, and AED-contraception interactions
6. Long-term prognosis and the question of surgical referral" [1]

Management plan: [1]

1. Referral for anterior temporal lobectomy with amygdalohippocampectomy. This is the most appropriate next step. She meets the ILAE definition of drug-resistant epilepsy (failure of two appropriately chosen and tolerated AEDs; she has failed four). Her presurgical data are fully concordant — the structural lesion (left hippocampal sclerosis on MRI), the electrical data (left temporal ictal onset on video-EEG), the metabolic data (left temporal hypometabolism on FDG-PET), and the neuropsychological data (impaired verbal memory localising to the left temporal lobe) all point to the same epileptogenic zone. The WADA test confirms that the right hemisphere can support memory after left temporal resection. The Wiebe randomised controlled trial demonstrated that 58 per cent of patients with this syndrome achieve seizure freedom at 1 year with surgery compared with 8 per cent with continued medical therapy [1]. She does not require invasive EEG monitoring because the non-invasive data are concordant.

2. Continue current AED regimen preoperatively. Do not change levetiracetam while awaiting surgery — breakthrough seizures are dangerous and complicate surgical planning. The preoperative period is also an opportunity to confirm adherence (consider checking a levetiracetam level). [1]

3. Depression management. Sertraline is a reasonable SSRI for her depression and is compatible with levetiracetam. Address the bidirectional relationship — depression is common in epilepsy (lifetime prevalence 30 per cent) and worsens quality of life, medication adherence, and seizure control. After surgery, depression may improve with seizure freedom but may also transiently worsen in the postoperative period; close follow-up is required. [1]

4. Contraception review. Levetiracetam does not reduce OCP efficacy (it is not an enzyme inducer), so her current combined OCP is effective. If she is switched to lamotrigine postoperatively for monotherapy, the OCP will reduce lamotrigine levels — she would need dose adjustment. If she is switched to carbamazepine (unlikely, given her history), the OCP would be unreliable. [1]

5. Driving. She does not currently drive due to ongoing seizures. After successful surgery with seizure freedom, she would become eligible to drive after the regulatory seizure-free period (6 months in Australia). This is a major quality-of-life benefit of surgery that should be discussed. [1]

6. SUDEP risk stratification and counselling. Her annual SUDEP risk is elevated (approximately 1 in 200) because of ongoing bilateral tonic-clonic seizures. Seizure freedom after surgery would substantially reduce this risk. Document the SUDEP discussion. [1]

7. Pregnancy planning. She is on sertraline (relatively safe in pregnancy), levetiracetam (reasonable safety profile in pregnancy), and a combined OCP. If she plans pregnancy, the levetiracetam would be continued (it is one of the safer AEDs in pregnancy), the OCP stopped, folic acid 5 mg started, and levetiracetam trough levels monitored trimesterly. If surgery achieves seizure freedom, AED withdrawal may be considered after 1 to 2 years, ideally before pregnancy to minimise fetal exposure. [1]

Examiner discussion questions

Q: "She has been tried on four AEDs. Is there any role for further drug trials before surgery?" [1]

"There is no role for further drug trials in this patient before surgical evaluation, and the evidence is clear. Once two appropriately chosen and tolerated AEDs have failed to achieve seizure freedom, the chance of achieving seizure freedom with each subsequent drug trial is under 10 per cent. Continuing to trial drugs introduces further delay — the average delay from onset of drug-resistant focal epilepsy to surgical referral is over 20 years, during which time the patient accumulates psychosocial harm and SUDEP risk. Her presurgical data are concordant, the syndrome (mesial temporal lobe epilepsy with hippocampal sclerosis) is the best-characterised surgically remediable syndrome, and the Wiebe randomised trial showed surgery is dramatically superior to continued medical therapy. The correct action is surgical referral now, not further drug trials. Drug trials would be appropriate only if the presurgical data were discordant or if she declined surgery." [1]

Q: "What are the risks of temporal lobectomy she should be counselled about?" [1]

"The risks fall into surgical and functional categories. Surgical risks include stroke in approximately 1 to 2 per cent of cases (due to manipulation of the anterior choroidal or middle cerebral artery branches), infection in 1 to 2 per cent, haematoma requiring evacuation in under 1 per cent, and mortality under 0.5 per cent. Functional risks include a superior quadrantanopia in up to a quarter of patients (due to interruption of Meyer's loop of the optic radiation), which is usually asymptomatic but may affect driving eligibility if bilateral or severe. The most important cognitive risk is verbal memory decline, which occurs in some patients with dominant (left) temporal resection and pre-existing impaired verbal memory — though this is weighed against the natural memory decline of ongoing seizures. She has already had WADA testing to confirm that the right hemisphere can support memory after surgery, which provides additional safety. Naming difficulty (anomia) is also common after dominant temporal lobectomy. She should be counselled on these risks and the benefits, and the discussion should be documented." [1]

Q: "If she becomes seizure-free after surgery, would you withdraw her AEDs?" [1]

"This is a shared decision. After anterior temporal lobectomy, the standard approach is to continue AEDs for at least 1 to 2 years postoperatively, then consider withdrawal in patients who have remained seizure-free. The recurrence risk after withdrawal is approximately 20 to 40 per cent over 5 years — so the decision must weigh the desire to come off medication against the risk of seizure recurrence (and its driving, occupational, and SUDEP implications). In her favour are seizure freedom from surgery, a single epileptogenic focus that has been resected, and no bilateral epileptiform abnormalities on EEG. Against her are her long epilepsy duration (16 years) and the bilateral tonic-clonic seizures. The decision should be individualised and reviewed in a multidisciplinary epilepsy surgery clinic. If withdrawal is chosen, it should be slow over 3 to 6 months to avoid precipitating withdrawal seizures. If she plans pregnancy, withdrawal before conception (if appropriate) would minimise fetal drug exposure." [1]

Q: "What are the specific considerations for her depression in this context?" [1]

"Depression is the commonest psychiatric comorbidity in epilepsy — the lifetime prevalence is approximately 30 per cent, and the bidirectional relationship (depression increases seizure risk and vice versa) is well established. In Ms Chen's case, the depression predates the AED trials and is currently managed on sertraline 100 mg daily, which is reasonable. Three issues deserve attention. First, surgery itself can transiently worsen mood in the early postoperative period — a minority of patients develop new-onset depression or anxiety in the first 6 months after temporal lobectomy, even with seizure freedom. Close psychiatric follow-up in the postoperative period is essential. Second, levetiracetam is well known for behavioural side effects — irritability, depression, and rarely suicidal ideation — and her mood should be monitored. If postoperative seizure freedom is achieved, levetiracetam withdrawal (when appropriate) may improve her mood further. Third, depression is an independent risk factor for SUDEP — so treating her depression is itself a safety intervention. I would involve a clinical psychologist or psychiatrist as part of the multidisciplinary team both before and after surgery." [1]

DCE Short Case — Neurological Examination in Epilepsy

Instruction

"Examine this patient's neurological system. They have a long-standing seizure disorder. You have 7 minutes for examination and 8 minutes for discussion." [1]

Key signs the patient demonstrates

• Phenytoin toxicity — gum hypertrophy, lateral gaze-evoked nystagmus, mild limb ataxia, coarse facial features
• Sensorimotor signs — subtle right upper limb hyperreflexia (the patient had a left frontal arteriovenous malformation resected 5 years ago, with residual focal motor seizures)
• No cutaneous stigmata of a neurocutaneous syndrome (compare with the long case above)
• Surgical scar — left frontal craniotomy scar under the hairline [1]

Systematic examination routine

1. Observe from the end of the bed: posture, gait, communication, surgical scars, cutaneous stigmata
2. Cutaneous examination: ash-leaf macules (tuberous sclerosis), port-wine stain (Sturge-Weber), café-au-lait macules (NF1)
3. Stigmata of drug toxicity: gum hypertrophy (phenytoin), tremor (valproate), hirsutism (phenytoin), ataxia (phenytoin, carbamazepine)
4. Cranial nerves: visual fields, fundoscopy, facial power, tongue and palate
5. Motor: tone, power, reflexes, plantar responses — looking for lateralised signs
6. Sensory: cortical sensory testing (graphaesthesia, stereognosis) for parietal involvement
7. Coordination and gait: cerebellar signs of chronic AED toxicity
8. Speech and cognition: fluency, comprehension, naming, orientation, recall — temporal lobe epilepsy may produce material-specific memory impairment [1]

Presentation template

"I examined Mr Singh's neurological system. He is a 45-year-old man who is alert and cooperative. [1]

On general inspection, I note gum hypertrophy affecting the lower gums, a coarse lateral gaze-evoked nystagmus on extreme lateral gaze in both directions, and a mild wide-based gait. There is a surgical scar in the left frontal region under the hairline. These findings together are consistent with chronic phenytoin use and previous left frontal neurosurgery. [1]

Cranial nerve examination is otherwise intact — visual fields full to confrontation, pupils equal and reactive, fundi normal, facial sensation and power symmetrical, tongue and palate symmetrical. [1]

Motor examination reveals normal tone. Power is 5 out of 5 in all four limbs. Reflexes are brisk in the right upper limb with a right extensor plantar response. Sensation is intact to all modalities. Coordination is impaired by mild bilateral dysmetria on finger-nose testing. Gait is mildly wide-based. [1]

His speech is fluent with normal comprehension and naming. Orientation and short-term recall are intact. [1]

In summary, this patient has clinical features of chronic phenytoin toxicity — gum hypertrophy, nystagmus, ataxia, and bilateral dysmetria — and a residual right upper motor neuron sign (brisk reflexes and extensor plantar) consistent with his previous left frontal AVM resection. The phenytoin toxicity warrants dose review, a free phenytoin level, and consideration of switching to a modern non-enzyme-inducing AED such as levetiracetam or lacosamide, especially given the long-term risks of phenytoin including osteoporosis, peripheral neuropathy, and cerebellar atrophy." [1]

Discussion questions

Q: "Why is phenytoin a difficult drug to use long-term?" [1]

"Phenytoin has a narrow therapeutic index and saturable, zero-order pharmacokinetics — small dose increases can produce disproportionate rises in serum levels and toxicity. The long-term complications are extensive: gingival hypertrophy (which requires dental surveillance), hirsutism, coarse facies, cerebellar atrophy with chronic ataxia, peripheral neuropathy, megaloblastic anaemia from folate interference, and osteoporosis or osteomalacia from vitamin D acceleration. It is a powerful enzyme inducer, complicating the management of other drugs including the combined oral contraceptive pill, warfarin, and many antimicrobials. Modern epilepsy guidelines (NICE NG217, SIGN 143) recommend against phenytoin as a first-line agent for new-onset epilepsy; it is now reserved for those already established on it or for specific indications such as certain acute situations. Switching to a non-enzyme-inducing agent such as levetiracetam or lacosamide is appropriate in most long-term patients, with careful cross-titration to avoid breakthrough seizures or phenytoin withdrawal. The SANAD trial established lamotrigine as a better-tolerated first-line focal agent than carbamazepine [3], and both are preferred to phenytoin."

Q: "How would you counsel him about driving?" [1]

"Mr Singh does not currently drive because of his ongoing seizures. To regain a private vehicle licence in Australia, he must be seizure-free for 6 months (or 3 months if there is a clearly treated provoking factor). For a heavy vehicle licence, he would need to be seizure-free for 10 years and off AEDs for the preceding 2 years. My role is to inform him of the legal obligation to notify the licensing authority of his seizure disorder and to document this advice in the medical record. In most Australian states the patient self-notifies; mandatory clinician reporting applies in some jurisdictions. I would also counsel him on the rationale — a seizure at the wheel carries a high risk of fatal injury to him and others — and on the role of AED optimisation in achieving seizure freedom. If his phenytoin toxicity is contributing to breakthrough seizures, the switch to a more reliable agent may itself improve his seizure control and bring him closer to driving eligibility." [1]

Q: "He had a first seizure 6 months ago after a 5-year seizure-free interval. Would you restart or adjust his AED?" [1]

"A breakthrough seizure after a long seizure-free interval warrants a structured assessment. The first step is to identify precipitants — common ones include AED non-adherence (the commonest), sleep deprivation, alcohol, intercurrent infection, hyponatraemia (especially on carbamazepine or oxcarbazepine), drug interactions lowering AED levels, and progression of the underlying cause (a recurrent AVM, in his case, would warrant imaging). I would check a free phenytoin level, electrolytes, and consider an MRI brain if there is any concern about progression. If the phenytoin level is subtherapeutic and the cause is non-adherence or interaction, I would optimise the existing regimen. If the level is therapeutic and the cause unclear, I would consider switching to a more effective and better-tolerated agent. Critically, he must not drive for 6 months from the date of the breakthrough seizure. The MESS trial reminded us that immediate treatment reduces early recurrence but does not alter long-term remission [4] — so the goal in breakthrough seizures is rapid return to seizure freedom, with shared decision-making on long-term therapy."