Roy Beran, MD, is a consultant neurologist and visiting medical officer at Liverpool Hospital, Fairfield Hospital, Braeside Hospital, Royal Rehabilitation Hospital, HMAS Penguin Naval Hospital and the Mater and St Luke’s Hospitals in Sydney. He holds academic appointments at Griffith University, Queensland, and the University of New South Wales (NSW). His qualifications include MBBS from the University of NSW, and an MD in the area of neuro-epidemiology with specific focus upon epilepsy. Additionally he has law degrees from Macquarie and Sydney Universities.
His clinical interests include general neurology, but particularly epilepsy, sleep medicine, and therapeutics, with particular reference to clinical drug trials. His major interest in legal medicine is the focus upon the interface of medicine and the law, the ethics of clinical drug trials and the impact of law.
Dr. Beran was elected to the presidency of the Australian College of Legal Medicine (ACLM) in 2002. Besides involvement with ACLM, he also contributes to the World Association of Medical Law, the Australian Academy of Forensic Sciences, the Australian and New Zealand Institute of Health Law and Ethics and served on the Commission for Economic Aspects of Epilepsy for the International League Against Epilepsy, and the International Bureau for Epilepsy Commission on Epilepsy and the Law. He has written and edited several books on epilepsy and the law.
Here we have two presentations:
- The case that appeared originally in 110 Puzzling Cases of Epilepsy, edited by Dieter Schmidt, MD, and Steven C. Schachter, MD, (Martin Dunitz, Publisher, London, 2002).
- A review of the case by Dr. Beran with updated material regarding the patient and the use of new medication. / Editor’s Note
The patient was first seen when he was aged 35 years, when he moved from interstate. He developed epilepsy at the age of 18 months in the setting of pneumonia. His birth was difficult and complicated by perinatal cyanosis.
His typical seizures were complex partial, although he also had simple partial seizures that occasionally progressed to secondarily generalised tonic–clonic seizures. The most frequent episodes were described as losing contact with his environment and having automatisms, especially of his left upper limb. When first seen he had tried phenobarbital, primidone, phenytoin, carbamazepine, valproate, vigabatrin and lamotrigine.
A significant reason for his move interstate was psychosocial disintegration. He had a failed marriage and had moved back to live with his elderly mother. He was unemployed and had virtually lost contact with his daughter and former wife. Two years after the initial consultation, he would still experience seizures provoked by correspondence received from his daughter, and he coped with this by taking short-acting benzodiazepine medication half an hour before reading the letters. This approach prevented further such seizures.
In 1997, he had been seizure-free for almost 2 years on a combination of valproate (1 g twice daily), vigabatrin (1 g twice daily) and lamotrigine (100 mg twice daily). As a consequence, he was given permission to resume driving. This revitalized his self-confidence and he was able to return to full employment. Through the greater social contact that employment provided, he met, courted and married his second wife, moved into separate accommodation and now lives a full and independent life.
Examination and investigation
When reports of visual field defects associated with the use of vigabatrin emerged, he underwent formal visual field testing with Goldmann and Humphries perimetry, which confirmed bilateral upper quadrant nasal field defects.
Vigabatrin-associated visual field defect, symptomatic partial epilepsy.
Treatment and outcome
The visual field findings were discussed with the patient and he was given the option of stopping the vigabatrin and considering an alternative antiepileptic medication. After discussion with his wife, the patient opted for continuing vigabatrin and ongoing monitoring of the field defect to determine its progression. He based this decision on the fact that he was symptom-free and enjoying a full and active life. He was extremely afraid that cessation of vigabatrin might cause recurrence of seizures.
As of June 2000, he was taking valproate 1 g twice daily, lamotrigine 100 mg twice daily and vigabatrin 1 g twice daily. His field defect remained stable.
This is the case of a mature man whose life had been devastated as a result of the consequences of epilepsy, with loss of marriage, job, independence and self-esteem. This has been successfully modified and reversed by combination therapy, including vigabatrin, but he was found to have visual field defects, presumed to be associated with vigabatrin.
What did I learn from this case?
The first lesson to be learnt from this case is the beneficial use of short-acting benzodiazepines to treat situationally related reflex epilepsy. This man experienced seizures in response to the emotions provoked by contact from his estranged daughter. Taking the benzodiazepines half an hour before such provocation, at a time that was appropriate (he would be unable to drive if the benzodiazepine caused sedation), gave him protection from these seizures and allowed him to maintain his seizure-free status.
The second lesson to be absorbed from this case is the devastating social burden of epilepsy. Conversely, the message that this case provides is how the maintenance of seizure-freedom can allow a patient who was rendered totally isolated and dependent from uncontrolled seizures to resume a full and active life.
The final message from this case is the need to respect the patient as an autonomous agent who has the right to determine what they do or do not accept as treatment options. The patient had visual restriction to 40°, which is really quite substantial, and had the opportunity to see his own fields as mapped out by a neuro-ophthalmologist.
In discussing this issue with the patient, we could not guarantee that he would remain seizure-free if we stopped vigabatrin or that an alternative treatment regimen would be as effective. Furthermore, we could not provide confirmation that stopping vigabatrin would reverse the deficit, nor could we advise that maintenance of vigabatrin would result in further deterioration.
In the face of all these negatives and in the absence of any symptoms or clinical signs with examination, such as visual confrontation, this patient made the informed decision to remain on his medications, including vigabatrin. He has been followed for more than 3 years and has maintained the identical constriction of visual fields that we have learned to associate with vigabatrin, without progression.
It could thus be argued that he has exercised his right of autonomy and informed consent, despite our fears for his potential loss of vision. His decision would appear to have been correct because his lifestyle has remained intact and his vision has not deteriorated.
Here we present an update from Dr. Beran sent to us in August 2008
I have reviewed the case of the patient with vigabatrin therapy and visual field defects. The patient was reviewed on 9th February 2005 with feedback from visual field testing being that his visual fields were continuing to restrict whilst on vigabatrin. On this basis the patient was advised that it would be preferable to stop the vigabatrin if he wished to preserve his remaining visual fields status.
In my letter to his treating primary, family physician, I wrote “…It must be stated from the outset that the decision to continue with the Sabril (vigabatrin) was not made lightly and was an informed consent by both (the patient and his wife) and was sufficiently outstanding to be published as a case of interest in a text on epilepsy used to show people patient’s rights to make decisions.
Having found that his fields are diminishing (the patient) would now like to come off the medication and I think this makes sense. I have discussed with them (the patient and his wife) the option of using other medications or alternatively trying to come off the vigabatrin and see if it makes any change….”
The patient was advised to drop by one tablet every two weeks, such that it would take six weeks before stopping the vigabatrin. The patient was to be reviewed in nine weeks but I made the point that “…if his pattern of epilepsy changes at all during this time then I want to see them immediately rather than waiting until his next visit because there are other medications which can be introduced. I have also made it totally clear to the patient that he should not drive whilst this is happening and I was quite pleased to hear that he has acted responsibly and cancelled his licence already because of the visual fields restriction….”
The patient was to remain on sodium valproate and lamotrigine with levels measured.
The patient was seen one week after starting the reduction of Sabril, dropping only one tablet, as he began having seizures. His blood levels had shown a low level for lamotrigine although it remained within my therapeutic window of 40 – 60 µmol/L, and his valproate was also within the therapeutic range. It was thus decided to increase his lamotrigine to 100 mg mane and 200 mg nocte while leaving his valproate at 1 gram b.d.
The patient was seen a month later following a further seizure, at which stage total valproate was 641 µmol/L with a free level of 57 µmol/L and lamotrigine was 65.3 µmol/L. The patient had continued to reduce vigabatrin and was taking I b.d. In the absence of toxicity he remained on that dose and was reviewed a month later. At this time his lamotrigine level was 68 µmol/L (somewhat supra-therapeutic) while valproate revealed a total valproate of 600 µmol/L with a free level of 62 µmol/L and unremarkable full blood count and biochemistry. He was now completely off the vigabatrin and maintained on sodium valproate and lamotrigine alone.
He was reviewed a month later following a further seizure and levetiracetam (Keppra) was introduced to the regimen, commencing at 500 mg b.d.
He was reviewed a month later and was seizure free and when seen two months later was still seizure free. He was now complaining of waking in the morning with headaches thought to be essentially tension in type but he was found to be hypertensive with a blood pressure of 195/100 mmHg.
His levetiracetam was increased to 500 mg I mane and II nocte, recognising that his valproate levels were a total of 551 µmol/L with a free level of 59 µmol/L, which was thought to be satisfactory and the lamotrigine was a little elevated at 68.1 µmol/L.
When reviewed a month later both his valproate and lamotrigine levels had risen with a total valproate of 755 µmol/L and a free level of 70 µmol/L and a lamotrigine level of 73 µmol/L, which is well above my therapeutic window of 40 – 60 µmol/L. This was thought to possibly explain the patient’s complaint of excessive fatigue. In line with this his lamotrigine was reduced to 100 mg b.d. to complement the valproate 500 mg II b.d. and levetiracetam 500 mg mane and 1 gram nocte.
The patient was seen a month later, at which time his valproate level was a total of 623 µmol/L with a free level of 55 µmol/L and lamotrigine had dropped to 53.3 µmol/L, both within my therapeutic window. The patient was seizure free.
He was seen three months later and had two further seizures and thus his levetiracetam was increased to 500 mg II b.d. with valproate maintained at 500 mg II b.d. and lamotrigine at 100 mg b.d.
He was seen a month later and was seizure free without episodes.
When seen three months later he was likewise seizure free without difficulty.
He had significant problems at work because of his seizures and much discussion revolved around the Australians with Disabilities Act, particularly in the light of his employer being a Government Department. This gave him reassurance to cope with his work situation.
The patient was not seen again for more than one year, at which time he presented not for seizures but rather for migrainous type headaches. He was still remaining seizure free. At this time he remained on levetiracetam 1 gram b.d., valproate 1 gram b.d. and lamotrigine 100 mg b.d. In addition to his anti-epileptic medications he was also on Domperidone 10 mg b.d. for oesophageal reflux, rabeprazole sodium 20 mg b.d. for abdominal discomfort and perindopril erbumine 4 mg I mane for hypertension. By the time the patient was seen his headaches had abated and the patient remained seizure free.
The patient was followed from that time forward and at the time of preparing this update was 15 months seizure free on combination therapy with sodium valproate 1 gram b.d., lamotrigine 100 mg b.d. and levetiracetam 1 gram b.d. while maintaining the Perindopril 5 mg mane. He was maintaining three monthly reviews and had had his eyes tested six months earlier with confirmation of definite tunnel vision, which has persisted since he stopped the vigabatrin two years earlier.
The patient remained employed and had unilaterally surrendered his driver’s licence because of his visual field defects. He was satisfied with his quality of life, the problems encountered with his employer having evaporated as his epilepsy came under better control.
Lessons learnt from this case have not changed from the time of the initial preparation of this report although the patient has accepted that he must suspend the vigabatrin -- and that was met with some difficulty finding the correct combination to provide seizure control.