Epilepsy in older people

Sen, Arjune; Jetté, Nathalie; Husain, Masud; Sander, Josemir W.

doi:10.1016/s0140-6736(19)33064-8

Cited by 197 publications

(193 citation statements)

References 137 publications

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“…In accordance with typical practice in DRE management, the decision of how to introduce a new ASM was largely based on patient and ASM factors but was also highly physician dependent 3,5 . We did not find that age and sex influenced the decision to favor substitution over addition despite the potential for the elderly and women of reproductive age to be more prone to the adverse effects of polytherapy 5,17 . Benzodiazepines were preferentially introduced as add‐on treatment, consistent with their recommended use 18 .…”

Section: Discussionmentioning

confidence: 54%

Starting a new anti‐seizure medication in drug‐resistant epilepsy: Add‐on or substitute?

Janmohamed

Lawn²,

Spilsbury

et al. 2020

Epilepsia

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ObjectivesRandomized studies in drug‐resistant epilepsy (DRE) typically involve addition of a new anti‐seizure medication (ASM). However, in clinical practice, if the patient is already taking multiple ASMs, then substitution of one of the current ASMs commonly occurs, despite little evidence supporting this approach.MethodsLongitudinal prospective study of seizure outcome after commencing a previously untried ASM in patients with DRE. Multivariable time‐to‐event and logistic regression models were used to evaluate outcomes by whether the new ASM was introduced by addition or substitution.ResultsA total of 816 ASM changes in 436 adult patients with DRE between 2010 and 2018 were analyzed. The new ASM was added on 407 (50.1%) occasions and substituted on 409 (49.9%). Mean patient follow‐up was 3.2 years. Substitution was more likely if the new ASM was enzyme‐inducing or in patients with a greater number of concurrent ASMs. ASM add‐on was more likely if a γ‐aminobutyric acid (GABA) agonist was introduced or if the patient had previously trialed a higher number of ASMs. The rate of discontinuation due to lack of tolerability was similar between the add‐on and substitution groups. No difference between the add‐on and substitution ASM introduction strategies was observed for the primary outcome of ≥50% seizure reduction at 12 months.SignificanceAdding or substituting a new ASM in DRE has the same influence on seizure outcomes. The findings confirm that ASM alterations in DRE can be individualized according to concurrent ASM therapy and patient characteristics.

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Section: Discussionmentioning

confidence: 54%

Starting a new anti‐seizure medication in drug‐resistant epilepsy: Add‐on or substitute?

Janmohamed

Lawn²,

Spilsbury

et al. 2020

Epilepsia

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“…Interestingly, many of the neurovascular risk factors that are associated with aging are also mechanisms involved in epilepsy 78 . Epilepsy is also associated with a higher incidence in the elderly and the most common risk factor associated with acquiring epilepsy late in life is cerebrovascular disease 79 . Thus, although often overlooked, altered cerebral blood flow regulation is centrally involved in epilepsy and can be both a potential cause and, as outlined here, consequence of seizures.…”

Section: Discussionmentioning

confidence: 99%

In vivo assessment of mechanisms underlying the neurovascular basis of postictal amnesia

Farrell

Colangeli

Dudok

et al. 2020

Sci Rep

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Long-lasting confusion and memory difficulties during the postictal state remain a major unmet problem in epilepsy that lacks pathophysiological explanation and treatment. We previously identified that long-lasting periods of severe postictal hypoperfusion/hypoxia, not seizures per se, are associated with memory impairment after temporal lobe seizures. While this observation suggests a key pathophysiological role for insufficient energy delivery, it is unclear how the networks that underlie episodic memory respond to vascular constraints that ultimately give rise to amnesia. Here, we focused on cellular/network level analyses in the CA1 of hippocampus in vivo to determine if neural activity, network oscillations, synaptic transmission, and/or synaptic plasticity are impaired following kindled seizures. Importantly, the induction of severe postictal hypoperfusion/hypoxia was prevented in animals treated by a COX-2 inhibitor, which experimentally separated seizures from their vascular consequences. We observed complete activation of CA1 pyramidal neurons during brief seizures, followed by a short period of reduced activity and flattening of the local field potential that resolved within minutes. During the postictal state, constituting tens of minutes to hours, we observed no changes in neural activity, network oscillations, and synaptic transmission. However, long-term potentiation of the temporoammonic pathway to CA1 was impaired in the postictal period, but only when severe local hypoxia occurred. Lastly, we tested the ability of rats to perform object-context discrimination, which has been proposed to require temporoammonic input to differentiate between sensory experience and the stored representation of the expected object-context pairing. Deficits in this task following seizures were reversed by COX-2 inhibition, which prevented severe postictal hypoxia. These results support a key role for hypoperfusion/hypoxia in postictal memory impairments and identify that many aspects of hippocampal network function are resilient during severe hypoxia except for long-term synaptic plasticity.

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“…These rates are substantially higher than the 1.2% in the general population. 15 16 At the same time, the prevalence of Alzheimer’s in people with epilepsy is six times higher than those without epilepsy. 17 As the population ages and the global burden of neurologic disease increases, dementia will likely continue to grow as a comorbidity and cause of death in people with epilepsy, contributing to an increase in epilepsy mortality rates in the future.…”

Section: Discussionmentioning

confidence: 99%

Why are epilepsy mortality rates rising in the United States? A population-based multiple cause-of-death study

et al. 2020

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IntroductionEpilepsy mortality rates are rising. It is unknown whether rates are rising due to an increase in epilepsy prevalence, changes in epilepsy causes of death, increase in the lethality or epilepsy or failures of treatment. To address these questions, we compare epilepsy mortality rates in the USA with all-cause and all-neurological mortality for the years 1999 to 2017.ObjectivesTo determine changes in US epilepsy mortality rates versus all-cause mortality, and to evaluate changes in the leading causes of death in people with epilepsy.DesignRetrospective population-based multiple cause-of-death study.Primary outcomeChange in age-adjusted epilepsy mortality rates compared with mortality rates for all-cause and all-neurological mortality.Secondary outcomeChanges in the leading causes of death in epilepsy.ResultsFrom 1999 to 2017, epilepsy mortality rates in the USA increased 98.8%, from 5.83 per million in 1999 to 11.59 per million (95% CI 88.2%–110.0%), while all-cause mortality declined 16.4% from 8756.34 per million to 7319.17 per million (95% CI 16.3% to 16.6%). For the same period, all-neurological mortality increased 80.8% from 309.21 to 558.97 per million (95% CI 79.4%–82.1%). The proportion of people with epilepsy who died due to neoplasms, vascular dementia and Alzheimer’s increased by 52.3%, 210.1% and 216.8%, respectively. During the same period, the proportion who died due to epilepsy declined 27.1%, while ischaemic heart disease as a cause of death fell 42.6% (p<0.001).ConclusionsEpilepsy mortality rates in the USA increased significantly from 1999 to 2017. Likely causes include increases in all-neurological mortality, increased epilepsy prevalence and changes in the underlying causes of death in epilepsy, led by increases in vascular dementia and Alzheimer’s. An important finding is that ischaemic heart disease and epilepsy itself are declining as underlying causes of death in people with epilepsy.

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Epilepsy in older people

Cited by 197 publications

References 137 publications

Starting a new anti‐seizure medication in drug‐resistant epilepsy: Add‐on or substitute?

Starting a new anti‐seizure medication in drug‐resistant epilepsy: Add‐on or substitute?

In vivo assessment of mechanisms underlying the neurovascular basis of postictal amnesia

Why are epilepsy mortality rates rising in the United States? A population-based multiple cause-of-death study

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