Linda J. Stephen

Epilepsy in elderly people

The prevalence and incidence of epilepsy are highest in later life with around 25% of new cases occurring in elderly people, many of whom will have concomitant neurodegenerative, cerebrovascular, or neoplastic disease. Difficulties accepting the diagnosis are frequently compounded by its unpredictable nature. Those affected commonly lose confidence and independence. Seizures in older people can result in physical injury, adding to low morale. Complete control is achievable in around 70% of patients with antiepileptic drug treatment. Optimum management requires rapid investigation, accurate diagnosis, effective treatment, sympathetic education, and assured support. The emergence of seizure disorders in old age places an increasing burden on health-care facilities and costs. A coordinated programme among health-care workers is advised to maintain the independence and improve the quality of life of this vulnerable patient population.

Does the Cause of Localisation‐Related Epilepsy Influence the Response to Antiepileptic Drug Treatment?

Summary: Purpose: We investigated the response to antiepileptic drug (AED) therapy in patients with localisation‐related epilepsy associated with different underlying causes.

Bone density and antiepileptic drugs: a case-controlled study

This case-controlled study explored the relationship between bone mineral density (BMD) and long-term treatment with antiepileptic drugs (AEDs) in older adults with epilepsy. Seventy-eight patients (47 post-menopausal females, 31 males, aged 47-76 years) with epilepsy participated in the study. Each had only ever received treatment with either enzyme-inducing (n = 52) or non-inducing (n = 26) AEDs. Individuals were matched for age, sex, height and weight with a drug-naive control. All patients underwent bone densitometry at the lumbar spine and femoral neck and had blood sampling and urine collected for a range of bone markers. Male patients had lower BMD than controls at the lumbar spine (P < 0.01) and neck of the femur (P < 0.005). Female patients had significantly reduced bone density at the femoral neck (P < 0.05) only. AED usage was independently associated with an overall reduction in bone density at femoral sites and contributed to just over 5% of the variance at the femoral neck. Duration of treatment and type of AED were not independent factors for reduction in BMD. This case-controlled study supports the hypothesis that long-term AED therapy is an independent risk factor for reduced BMD in epileptic patients. Adults receiving treatment for epilepsy are at higher risk of osteoporosis and should be offered bone densitometry.

Mortality in adults with newly diagnosed and chronic epilepsy: a retrospective comparative study

BACKGROUND People with epilepsy are at increased risk of premature death compared with the general population. Many clinicians are unsure whether and when this issue should be broached with their patients. We analysed mortality in patients with newly diagnosed and chronic epilepsy over a 20-year period. METHODS Patients who attended the epilepsy service at the Western Infirmary in Glasgow, UK between 1981 and 2001, with newly diagnosed epilepsy (n=890) or referred after receiving unsuccessful treatment elsewhere (n=2689) were included in the study. Mortality data were obtained from the General Registrar Office for Scotland. Causes of death were ascertained from death certificates and primary care and health authority records. The two patient cohorts were compared with age-matched and sex-matched Scottish comparison groups. Standardised mortality ratios (SMR) were calculated for each epilepsy type, 10-year age band, and cause of death category. FINDINGS Newly diagnosed patients had a 42% increase in mortality (SMR 1.42, 95% CI 1.16-1.72) compared with the comparison group. Increased mortality was recorded in those who had not responded to treatment, with no increase in risk observed in patients who were seizure free. In the chronic epilepsy cohort, there was more than double the expected number of deaths (2.05, 1.83-2.26). The incidence of sudden unexpected death in epilepsy was 1.08 and 2.46 per 1000 patient-years in patients with newly diagnosed and chronic epilepsy, respectively. The greatest excess in mortality was reported in patients younger than 30 years. INTERPRETATION Mortality risks and preventive strategies should be discussed with patients with epilepsy when treatment fails or is refused despite recurrent seizures.

Sudden unexpected death in epilepsy: A search for risk factors

Sudden unexpected death in epilepsy (SUDEP) is the commonest cause of seizure-related mortality in people with refractory epilepsy. Of the 6140 patients registered with the Epilepsy Unit at the Western Infirmary in Glasgow between 1982 and 2005, 529 had died, 62 (11.7%) of whom succumbed to SUDEP. All but 2 deaths occurred at home; 3 were witnessed. Two living controls were matched with each SUDEP case for year of birth, gender, and syndromic classification. Mean duration of epilepsy was significantly longer in cases compared with controls (P=0.001). More people succumbing to SUDEP had had a seizure within the previous year (P=0.007). There were no significant associations between SUDEP and a history of generalized tonic-clonic seizures, drug polytherapy, and current use of carbamazepine. There is an urgent need for a large-scale, prospective, international, community-based study of SUDEP to explore more closely the risk factors to plan preventive strategies.

Hormone Profiles in Young Adults with Epilepsy Treated with Sodium Valproate or Lamotrigine Monotherapy

Summary:  Purpose: Treatment with sodium valproate (VPA) may be associated with polycystic ovarian syndrome (PCOS) in some women with epilepsy. By comparing hormone profiles in young adults taking VPA or lamotrigine (LTG) as monotherapy, this study aimed to explore whether a pharmacologic effect of VPA could be responsible for this observation.

Topiramate in Refractory Epilepsy: A Prospective Observational Study

Summary: Purpose: This prospective observational study explored the efficacy and tolerability of topiramate (TPM) in patients with refractory epilepsy attending a single outpatient clinic.

Seizure freedom with more than one antiepileptic drug

Many people with epilepsy take antiepileptic drug (AED) polytherapy, although supportive evidence for the success of this strategy is sparse. Of 2881 treated patients registered in our database, 1617 (56%) have been seizure-free for at least the previous year, with 21% taking more than one AED (287 on two, 86%; 42 on three, 13%; 3 on four, 1%). There were 40 effective duotherapies and 28 triple therapies. Treatment with two or three but not four AEDs may be a useful therapeutic option for patients not responding to monotherapy. Further explorations of the best regimens for individual seizure types and epilepsy syndromes is required.

Pharmacotherapy of epilepsy: newly approved and developmental agents.

This article discusses seven newly available antiepileptic drugs (AEDs) and agents in phase III development.Lacosamide, licensed as an adjunctive treatment for partial-onset seizures, primarily acts by enhancing sodium channel slow inactivation. At daily doses of 200–600 mg, the drug significantly reduced partial-onset seizures in adults with refractory epilepsy. The most common adverse effects are CNS related.Rufinamide, available as adjunctive treatment for seizures associated with Lennox-Gastaut syndrome, has an unclear mechanism of action, although it does block voltage-dependent sodium channels. Coadministration of valproic acid significantly increases rufinamide circulating concentrations. The drug has been shown to have efficacy for partial-onset, primary generalized tonic-clonic, tonic-atonic, absence and atypical absence seizures. Adverse effects are mainly somnolence, nausea and vomiting.Eslicarbazepine acetate, a carbamazepine analogue, was recently licensed as adjunctive treatment for partial-onset seizures. Eslicarbazepine acetate acts at voltage-gated sodium channels, although the precise mechanism of action is unclear. The drug had efficacy for partial-onset seizures in three randomized, double-blind, placebo-controlled studies, using 400, 800 or 1200mg/day. Adverse effects include dizziness and somnolence.Retigabine (ezogabine) exerts its anticonvulsant effect through the opening of neuronal voltage-gated potassium channels. Following significant seizure reduction rates at dosages of 600, 900 and 1200mg/day, license applications have been submitted for its use as adjunctive treatment for patients with partial-onset seizures. Dose-related adverse effects include somnolence, confusion and dizziness.Brivaracetam is the n-propyl analogue of levetiracetam. Mixed results have been obtained in phase III studies in patients with partial-onset seizures, and further trials in children, patients with photosensitive epilepsy and patients with partial-onset seizures are ongoing. Dizziness, headache and somnolence are the most common adverse effects reported.Perampanel was designed as an AMPA-type glutamate receptor antagonist. Following encouraging results from phase II studies in patients with refractory partial-onset seizures, recruitment for phase III trials is almost complete.Ganaxolone is a neurosteroid with potent antiepileptic activity that modulates GABAA receptors in the CNS. Ganaxolone has shown promise in a variety of seizure types. Dizziness and somnolence have been reported in some patients.The availability of new AEDs has widened the choices for clinicians treating patients with epilepsy. However, given the minimal improvement in prognosis and disappointing efficacy outcomes in double-blind, placebo-controlled, dose-ranging regulatory trials, it seems unlikely that these novel agents will have a major impact on outcomes for people with epilepsy.

Peripheral retinal dysfunction in patients taking vigabatrin

Objective: To assess the wide-field multifocal electroretinogram (WF-mfERG) for assessment of retinal function in vigabatrin-treated patients. Methods: Thirty-two adults who had taken vigabatrin for at least 3 years for localization-related epilepsy underwent WF-mfERG, ERG, logMar visual acuity and color vision evaluation, Humphrey visual field analysis (static perimetry), and funduscopy. The group was matched with a cohort of patients who had never received vigabatrin. Results were compared with a normative data set (120 drug-free controls) with respect to potential bilateral abnormalities in response timing. Results: There were no significant differences between groups in visual acuity or color vision testing. Of the vigabatrin patients, 19 (59%) had bilateral visual field defects compared to none of the controls. Using WF-mfERG, all patients on vigabatrin with visual field defects showed abnormalities (100% sensitivity) and only 2 of the 13 patients without a field defect showed retinal abnormalities (86% specificity). Conclusions: WF-mfERG may be useful for detecting retinal pathology in patients taking vigabatrin. The majority of previous reports based on subjective testing may have underestimated the prevalence of peripheral retinal toxicity related to the drug.