New-onset seizures in older people: Clinical features, course and outcomes.

OBJECTIVE: The incidence of epilepsy increases with age. With current demographic trends, this presents a healthcare challenge. We investigated the clinical spectrum of first seizures, evaluated neuroimaging and EEG findings, and determined clinical outcomes, including anti-seizure medication (ASM) response in older people. In addition, we sought to understand the relative effects of age and frailty on ASM response. METHODS: A retrospective single centre cohort study of 207 cases ≥60 years' old, 113 of whom were eventually diagnosed with a first seizure in a specialist epilepsy clinic. RESULTS: 65/113 (57.5%) presented with either focal aware or focal impaired awareness seizures. Stroke was the most common aetiological association (31.9%, 36/113), and odds of seizure recurrence did not significantly differ between aetiologies. 55/86 (64.0%) who started an ASM had no seizure recurrence. 14/48 (29.2%) who underwent EEG had epileptiform abnormalities, however EEG result directly affected management in only 4/48 (8.3%). The most common MRI findings were small vessel disease (37/93, 39.8%), stroke (27/93, 29.0%) and global atrophy (14/93, 15.1%). Increasing age and frailty did not affect the odds of seizure recurrence or of experiencing ASM side effects. Severity of small vessel disease or atrophy did not affect odds of seizure recurrence. CONCLUSION: Our data inform the management of first seizures in older people and provisionally support the use of ASMs in patients with increasing age and frailty, despite concerns over polypharmacy and comorbidity. Our findings should be replicated in larger cohorts.

The long-term retention of pregabalin in a large cohort of patients with epilepsy at a tertiary referral centre.

Pregabalin (PGB) is a new antiepileptic drug (AED) which is a structural, non-functional analogue of gamma-aminobutyric acid. It acts at presynaptic calcium channels to modulate neurotransmitter release in the CNS. While the efficacy and tolerability of PGB have been demonstrated in several randomised controlled trials, few studies have addressed long-term outcome in large groups of patients. A cohort of patients attending a tertiary referral centre for epilepsy was identified as having started taking PGB. Patients' data were obtained through medical records. Of 402 patients included, 42% of patients were still taking PGB at last follow-up. The estimated 2.5-year retention rate was 32%. Males appeared more likely to continue on PGB therapy than females. The common adverse experiences (AEs) leading to withdrawal were CNS-related, psychiatric AEs and weight gain. Published retention rates for levetiracetam appear to be higher, and those for gabapentin lower, than the rates estimated for PGB.

First report of Creutzfeldt-Jakob disease occurring in 2 siblings unexplained by PRNP mutation.

Sibling concurrence of pathologically confirmed prion disease has only been reported in association with pathogenic mutation of the prion protein gene (PRNP). Here, we report 2 siblings with classic neuropathologic features of sporadic Creutzfeldt-Jakob disease unexplained by PRNP mutation or known risk factors for iatrogenic transmission of prion infection. Possible explanations include coincidental occurrence, common exposure to an unidentified environmental source of prions, horizontal transmission of disease, or the presence of unknown shared genetic predisposition.

The socioeconomic, cultural, and emotional implications of starting or withholding treatment in a patient with a first seizure.

The decision to treat or not treat individuals who have suffered a single epileptic seizure is based on clinical factors, which are considered within the individual's social, cultural, and emotional environment. Even if optimally communicated, individuals and their carers will make different decisions about first seizures and their treatment, as they will judge the risks and benefits of treatment (or its deferment) in this wider context. There is a significant body of literature that describes the impact of established epilepsy on aspects of an individual's overall quality of life (QoL), and more recently evidence is emerging about the factors that may be important in 2 years after a single seizure on and off treatment. Little research, however, has considered the importance of nonclinical factors in individual's choices at the time of a first seizure, and in particular in an individual's decision to use or not use treatment. Understanding these issues may improve communication of risks and benefits to individuals, and may offer insight into the mechanisms by which social and socioeconomic disadvantage occur in epilepsy.

Antiepileptic drugs: generic versus branded treatments.

Antiepileptic drugs (AEDs) are relatively cheap but high volumes of prescriptions mean that substantial drug-budget savings may be possible by switching from innovator brands to cheaper generic drugs. Such savings have been achieved in many other treatment areas. However, more caution may be needed in the case of epilepsy because of the narrow therapeutic range of most AEDs; clinical principles of prescribing, which include making only cautious and gradual changes to dosing; the health and socioeconomic impact of breakthrough seizures or toxicity; and the need for long-term consistency of supply. Many physicians and patient groups are insufficiently reassured by current definitions of similarity between generics and innovator brands. Switching to the cheapest generic AED may offer drug-budget savings that outweigh any risk to patient safety. But to date, this cost-benefit analysis has not been done. We propose that all changes to established principles of treating epilepsy are evidence based and that the risks of switching are clearly defined.

Socioeconomic variation in incidence of epilepsy: prospective community based study in south east England.

OBJECTIVE: To determine the incidence of epilepsy in a general practice population and its variation with socioeconomic deprivation. DESIGN: Prospective surveillance for new cases over an 18 or 24 month period. PARTICIPANTS: All patients on practice registers categorised for deprivation with the Carstairs score of their postcode. SETTING: 20 general practices in London and south east England. MAIN OUTCOME MEASURE: Confirmed diagnosis of epilepsy. RESULTS: 190 new cases of epilepsy were identified during 369 283 person years of observation (crude incidence 51.5 (95% confidence interval 44.4 to 59.3) per 100 000 per year). The incidence was 190 (138 to 262) per 100 000 in children aged 0-4 years, 30.8 (21.3 to 44.6) in those aged 45-64 years, and 58.7 (42.5 to 81.0) in those aged > or =65 years. There was no apparent difference in incidence between males and females. The incidence showed a strong association with socioeconomic deprivation, the age and sex adjusted incidence in the most deprived fifth of the study population being 2.33 (1.46 to 3.72) times that in the least deprived fifth (P=0.001 for trend across fifths). Adjustment for area (London v outside London) weakened the association with deprivation (rate ratio 1.62 (0.91 to 2.88), P=0.12 for trend). CONCLUSIONS: The incidence of epilepsy seems to increase with socioeconomic deprivation, though the association may be confounded by other factors.

Economic evaluation of epilepsy treatment: a review of the literature.

This article provides an overview of methods used and findings from economic analyses in epilepsy. Cost-effectiveness studies have evaluated different drugs for monotherapy and add-on therapy, and compared alternative treatment modalities for refractory epilepsy. The methodological characteristics of these studies are examined, and their results are compared and interpreted. Health outcome measures are defined and data sources described. Methods for assessing the direct and indirect costs, and/or cost savings, with a treatment's use, are explored. Directions for future research are identified and discussed.