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Epilepsy

Epilepsy in

Seizure after stroke is common and late-onset have higher recurrence rate and poorer prognosis. Patients with post- stroke epilepsy are difficult to rehabilitate and are more likely to be hospitalised for an extended period of time. Second generation antiepileptic drugs have emerged as a favoured drug in post-stroke epilepsy in older patients.

Akram Malik Medical student, School of Medicine, Heath park, Cardiff CF14 4XW Ajit Verma Specialist registrar, Acute Stroke Unit, Nevill Hall Hospital, Gwent Health Care NHS Trust, Brecon Road, Abergavenny, Gwent NP7 7EG Bella Richard Locum Consultant Physician, Acute Stroke Unit, Nevill Hall Hospital, Gwent Health Care NHS Trust, Brecon Road, Abergavenny, Gwent NP7 7EG Pradeep Khanna Chief of Staff, Community/Lead Clinician, Stroke Care, Nevill Hall Hospital, Gwent Health Care NHS Trust, Brecon Road, Abergavenny, Gwent NP7 7EG email [email protected]

t has been known for quite some time that epilepsy is a stroke regardless of time of onset of seizures following recognised complication of and the stroke. It may also be defined as recurrent seizures that stroke is the commonest cause of epilepsy in older following stroke with confirmed diagnosis of epilepsy.5 I 1 people. Post-stroke epilepsy may represent up to 11% of In 1981, the International League against Epilepsy all adult and 45% of seizures starting after 60 (ILAE) divided it into two major classes (Table 1). Partial- years of age.2, 3 onset seizures begin in a focal area of the cerebral Patients with post-stroke epilepsy are difficult to cortex, whereas generalised-onset seizures have an onset rehabilitate and are more likely to be hospitalised for an recorded simultaneously in both cerebral hemispheres. extended period of time. The condition has implications on Some seizures are difficult to fit into a single class and social and mental health as well as on quality of life such they are considered unclassified seizures. as driving eligibility. Because of lack of consensus, relevant and comparable studies, clinical guidelines are difficult to Early and late onset seizures formulate and clinicians often find it difficult to manage this problem. The decision to initiate antiepileptic drug According to time of onset, early seizures are defined as (AED) treatment after a first or a second should be seizures within 24 hours—1 month in various studies.6,7,8 A individualised, primarily based on functional impact of the cut off time of 2 weeks seems to be widely accepted, but first seizure episode and the patient’s preference.4 up to 45% of post-stroke seizures occur within the first 24 The aim of this review article is to highlight hours. Late-onset seizure is described as seizure occurring epidemiology, pathophysiology, risk predictors and, in 7 particular, the management strategy of epilepsy in stroke. 2 weeks after the stroke. Epilepsy develops in about one third of early onset and half of late-onset seizures. The differentiation is important because early seizures may Definition and classification have other causes such as acid–based balance, electrolyte imbalance, hypoxia etc. Late seizures may be regarded as Seizure is defined as abnormal uncontrolled electrical real post-stroke seizures. activity in the brain that may lead to , loss of consciousness, thought disturbances or a constellation of signs and symptoms. It can be either provoked or Epidemiology unprovoked. Provoked seizures are mostly due to fever, metabolic disturbances, drugs or alcohol. Stroke is one of the commonest causes of epilepsy Epilepsy is characterised by recurrent unprovoked accounting for about 11% of all aetiologies.2,6 In the seizures. Post-stroke seizure is defined as single or elderly population, more than 40% of seizures are related multiple convulsive episode/s after stroke. It is thought to stroke.2,3 These seizures have also been reported as to be related to reversible or irreversible damage due to a predictor of future stroke and are secondary to small

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Box 1: ILAE classification of seizures Box 2: The risk predictors for likely seizure

Partial seizures a. Simple partial seizures • Stroke subtype: haemorrhagic stroke and b. Complex partial seizures (associated loss of cerebral venous thrombosis are associated with consciousness) higher incidence of seizures than ischaemic c. Partial seizures with secondary generalisation stroke7 • Stroke location: cortical location makes Primary generalised seizures patients more prone for stroke than sub-cortical a. (petit mal) locations6 b. Tonic-clonic (grand mal) • Stroke severity: total anterior circulation stroke c. Tonic (TACI) is more likely to result in seizures and d. Atonic lacunar stroke is least likely to give rise to this e. Myoclonic complication7 • Early and late onset seizures: late onset seizure is associated with a higher risk of developing vessel disease. Seizure occurring after the age of 60 years epilepsy. Late onset seizure has a peak within 6 with no past history of stroke had a 2⋅89 relative hazard to 12 months after the stroke and has a higher of a subsequent stroke compared with a control group incidence of recurrence rate of up to 90% in 9 (p<0.0001). Risk of epilepsy in stroke is 17–fold higher both ischaemic and haemorrhagic stroke.11,12 than the age-matched general population.10

Diagnostic challenges seizure.13 The picture gets further complicated by the finding that 12–38% of healthy individuals develop EEG Mostly post-stroke seizures are focal (simple partial) or abnormalities with increasing age.14 with secondary generalisation. In about one third of cases they can present as generalised tonic clonic seizures. Often patients are unable to recognise symptoms Management or even after recognition are unable to convey it to the clinician because of reasons such as expressive dysphasia. The general principles of management and investigations It is often difficult to get an eye witness account because are similar to other causes of epilepsy. Hypoglycaemia most of the patients are elderly individuals living and metabolic abnormalities should be excluded. DVLA in isolation. guidelines should be followed for driving issues and For clinicians it becomes difficult to differentiate patients should avoid swimming, water sports and between transient ischaemic attacks and seizures or vice- fire hazards. There is huge psychosocial distress on versa. Todd’s paralysis after seizure can also be perceived patients and families; therefore, patient education and as stroke recurrence. The presentation can be atypical multidisciplinary input has a paramount role. such as behavioural change, acute confusional state and AEDs are the mainstay of treatment, but the current syncope. The key to diagnosis is a high degree of suspicion available evidence does not support prophylactic use of 5 with careful history taking. AED in stroke patients including haemorrhagic .

Limited role of EEG First generation antiepilectics (EEG) has a very limited value in the setting of post-stroke epilepsy. In a study, EEG abnormalities were found in 17% of stroke patients, This drug is mostly well tolerated and has a broad spectrum among these only 2% eventually suffered a post-stroke of activity and is drug of choice for generalised seizure

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in the NICE guidelines. It was indicated in a survey that • Osteoporosis and osteopenia secondary to first line AED, it was the preferred drug by physicians for the elderly in including , valproate and carbamazepine19 the UK.15 • General problems such as poor compliance, cognitive decline and swallowing difficulty etc. Phenytoin Phenytoin should be avoided in post-stroke epilepsy Elderly patients because of its pharmacokinetics and interaction with Recently three important randomised controlled trials warfarin and antiplatelet agents. There are some performed in elderly patients compared concerns that it might hamper functional outcome in to (including one that also assessed ischaemic stroke.16 ).21-24 These studies show that elderly patients are more likely to become seizure free on a lower dosage of AED Carbamazepine because of reduced hepatic clearance, renal elimination, It has been considered drug of first choice for partial lower serum albumin levels and altered protein binding, seizures by NICE. Extended release carbamazepine leading to better retention of AED in comparison with appears to be a better tolerated drug than intermediate- younger populations. But side effects are more common in release form.17 elderly patients because of these properties.19,24 Lamotrigine and gabapentin were better tolerated drugs Treatment of first seizure? in the elderly in these studies. Based on these findings, the There is no study to date answering the question International League against Epilepsy has recommended conclusively. NICE guidance suggests that AEDs should lamotrigine and gabapentin as first-line monotherapy 25 be given when an individual has a history of more than agents for artial seizures in older adults. Furthermore these one seizure,18 but there is a high risk of seizure recurrence two drugs do not interact with anticoagulants, antiplatelet in elderly people and underlying structural disease.19 The agents and do not affect bone health. Gabapentin remains Scottish Intercollegiate Guidelines Network (SIGN) 2003 the only drug specifically evaluated in post-stroke epilepsy, favours that after a clearly documented seizure, following demonstrating a high rate of long-term seizure freedom, a full and frank discussion about the risks and benefits but lamotrigine is among the recommended first-line drugs of treatment, AED therapy can be commenced.20 Few for generalised and partial seizures in the SIGN guidelines 26 18 clinicians follow a pragmatic approach to treat early- for epilepsy. NICE suggests its use as an alternative drug. onset seizures for 1 month and to stop treatment if no There is also preliminary evidence to suggest that further seizure activity.16 can be well tolerated in post-stroke epilepsy in elderly patients.27 Start low, go slow Prognosis Pharmacotherapy aims to achieve complete seizure control on the lowest possible dose to avoid side effects. It is a matter of debate whether early seizures impact on Therefore, it is essential to start low and go slow. The physical outcome and mortality after stroke. Overall, a important issues to consider during drug selection are: majority of studies suggest that late seizure and recurrent • Possible drug interactions, especially with warfarin and seizures hamper long-term neurological outcome. AEDs other antiepileptic drugs. Phenytoin and carbamazepine are more likely to achieve seizure control in post-stroke are hepatic enzyme inducers and mutually interact epilepsy than in most other forms of symptomatic or 28 with warfarin. It is difficult to keep plasma therapeutic cryptogenic seizures. ranges of each drug leading to poor seizure control and bleeding risk Particular problems in elderly • Knowledge of pharmacokinetics and adverse drug reactions due to physiological/ pathological decline in Epilepsy incidence increases with age. Incidence of elderly people epilepsy in older people is higher than any other age

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group except first year of life. The estimated incidence in 1184–86 10. So E, Annoyers J, Hauser W, et al. Population- based a population over 65 years old is estimated to be about study of seizure disorders after cerebral infarction. 100 per 100000 annually. 2004; 62(suppl 2): 524–29 11. Sung C, Chu N. Epileptic seizures in itracerebral As opposed to a younger population more than 70% haemorrhage, J Neurol Neurosurg Psychiatry 1989; of the elderly population have an underlying structural 52: 1273–76 cause for unprovoked seizures, the most common being 12. Sung C, Chu N. Epileptic seizures in thrombotic stroke. J Neurol 1990; 237: 166–70 cerebrovascular disease. There is >90% chances of seizure 13. Carrera E, Miaechel P, Despland PA, et al. Continuous recurrence.19 assessment of electrical activity in acute stroke. Neurology 2006; 67: 99–104 Most of the seizures in elderly patients are focal 14. Hopkins A, Garman A, Clarke C. The first seizure in adult seizures with rapid secondary generalisation whereas life: value of clinical features, electroencephalography and computerised scanning in prediction of seizure primary generalised idiopathic seizures are commonest in recurrence. Lancet 1988; 331: 721–6 younger patients. There is more risk of traumatic injuries 15. Cooper J, Watt R, Feely M. Current antiepileptic prescribing in elderly patients with epilepsy; A survey because of osteoporosis and frailty. Management is often of geriatricians. Age and Ageing 2005; 34(suppl 1) challenging because of comorbidities and polypharmacy i32 leading to significant drug interactions. 16. Goldstein LB, Common drugs may influence motor recovery after stroke. Neurology 1995; 43: 865–71 17. Flicker DM, Privilera M, Krauss G, et al. Improved tolerability and efficacy in epilepsy patients with Conclusion extended-release carbamezipne. Neurology 2005; 65: 593–95 18. NICE- Clinical guidelines 20, Diagnosis and Seizures after stroke is a common problem. The diagnosis management of epilepsy in adults and children in is clinical and EEG has a very limited role because of low primary and secondary care. October 2004. http:// sensitivity and specificity. Newer antiepileptic drugs are guidance.nice.org.uk/CG20/Guidance/pdf/English (accessed 5th May 2009) emerging as favoured drugs in post-stroke epilepsy in 19. Ramsay R, Rowan A, Prior F. Special considerations older patients. Further larger studies are needed to address in treating elderly patients with epilepsy. Neurology 2004; 62 (suppl 2): 524–29 many unresolved issues in this field. 20. SIGN; clinical guidelines 70: Diagnosis and management of epilepsy in adults 2003. www.sign. ac.uk. We have no conflict of interest 21. Bodie M, Overstall P, Giorgi L. The UK Lamotrigine elderly study group. Mulicentre double blind randomised comparison between lamotrigine and References: carbamazepine in elderly patients with newly diagnosed epilepsy. Epilepsy Res 1999; 37: 81–7 1. Luhdorf K, Jensen LK, Plesner AM. Etiology of seizures 22. Rowan AJ, Ramsay RE, Colins JF, et al. New onset in the elderly. Epilepsia 1986; 27: 458–63. geriatric epilepsy in randomised study of gabapentin, 2. Hauser WA, Annegers JF, Kurland LT. Incidece of lamotrigine and carbamazepine. Neurology 2005; 64: epilepsy and unprovoked seizures in Rochester, 1868–73 Minnesota; 1935-1984. Epilepsia 1993; 34: 453–68 23. Seatre E, Preuca E, Isojarvi J, Gjerstad I. An international 3. Forsagen L, Bucht G, Erikson S, Bergmark L. Incidence multicentre double-blind double- dummy randomised and clinical characterization of unprovoked seizures trial comparing Lamotrigine and slow release in the adults: a populations based study. Epilepsia carbamazepine for treating newly diagnosed epilepsy 1996; 37: 224–29 in the elderly. 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