Neurofrailty: A Study of Late-onset Epilepsy and Its Associations

A Prospective Population-based Longitudinal Observational Cohort Study of Late-onset Epilepsy, and Subsequent Stroke and Dementia.

We don't know a great deal about why some people develop seizures in adulthood, but some researchers think that it might tell us something about the brain. A small number of people with first seizure in adulthood go on to experience problems like stroke or dementia later in life. However, stroke and dementia are common diseases, so we don't know whether there is a real association between these conditions. When people develop their first seizure in adult life, this is sometimes called Late-Onset Epilepsy. Through the NeuroFrailty study, we will observe 'brain health' over the years following the onset of a seizure, and I hope that it might give us more information about people with these kinds of seizures.

The NeuroFrailty study involves observing people from the time of diagnosis of first seizure. At this time, we will look at investigations such as blood tests, blood pressure, brain scans, alongside other diagnoses which might tell us whether there are differences compared to people without seizures. For some people, we will also look in greater depth at lifestyle including exercise, driving, family planning, and memory assessments.

Over the following years, we will look at how things change: for example whether there are changes in memory, new diagnoses, medication changes and how lifestyle has changed. Because there is so little research in this area, it is very difficult to predict what might happen. For example, some people can experience worse memory because of medication side effects; on the other hand, good seizure control following a diagnosis can sometimes lead to improved memory. Over years, it may become clear that some diseases are more likely in people with late-onset epilepsy than in people without such a diagnosis. You will receive a yearly newsletter to keep you updated on everything we learn about late-onset epilepsy.

Purpose and Background

Most of the time, we do not know why an adult develops epilepsy. Some researchers think there may be a connection between epilepsy which starts in adulthood, and increased risk of stroke or dementia in the future. However, there is very little research or evidence in this area, so we cannot say whether this is true.

What does taking part involve?

This study is an observational study, which means that the management of participants' seizure disorder will not be affected if they choose to take part in this study. The purpose of this study is to watch participants over the course of several years, to find out more about seizures which start in adulthood.

Participants can choose the level of involvement that is right for them.

1. LOW involvement. A researcher will check hospital and General Practice (GP records) once or twice per year, for the LIMITED AND SPECIFIC purpose of checking: medications, any new diagnoses, investigations associated with stroke risk (such as cholesterol, blood pressure, heart trace) and any brain scans that have been performed. I will not have access to more detailed information, such as conversations between a participant and their GP.
2. HIGH involvement. This involves being contacted by telephone once per year for 15-30 minutes to ask questions assessing memory and enquiring about lifestyle, such as exercise, smoking and alcohol use.
3. VERY HIGH involvement. These participants will be contacted for a longer telephone conversation 30-45 minutes once per year about their experience of how epilepsy has affected home life, work and medications.

If someone decides in the future that they don't want to be involved, they can withdraw from the study. However, once the study is completely finished, the information will be completely anonymous, which means that I won't be able to find individual's information in order to delete it.

Glossary Seizure disorder = any disorder which involved having experienced at least one seizure. First seizure and epilepsy both can be classed as a form of seizure disorder.

Neurofrailty = A condition whereby a person is at risk of stroke or dementia.

Study Overview

• Status: Recruiting
• Conditions: Stroke; Dementia; Late Onset Epilepsy

• Study Type: Observational
• Enrollment (Estimated): 360

Contacts and Locations

• Study Contact: Name: Jasmine Wall, MB BChir; Phone Number: via switchboard; Email: jasmine.wall@lthtr.nhs.uk

Study Locations

• United Kingdom
  • Lancashire
    • Preston, Lancashire, United Kingdom, PR2 9HT
      • Recruiting
      • Lancashire Teaching Hospitals NHS
      • Contact: Kina Bennett; Phone Number: (+44) 01772 522031; Email: kina.bennett@lthtr.nhs.uk
      • Contact: Research Access; Email: research.access@lthtr.nhs.uk
      • Principal Investigator: Jasmine Wall

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Case participants will be identified through consecutive adult cases of first seizure or new diagnosis of epilepsy without a 'lesional' cause identified in the regional area served by Preston tertiary neurology centre.

Control participants will be identified through consecutive adult cases of migraine without a 'lesional' cause, identified in the regional area served by Preston tertiary neurology centre.

Description

Inclusion criteria for case participants includes:

• diagnosis of LOE or first seizure after the age of 18.
• diagnosis confirmed or established at a tertiary neurology centre.
• sequential cases will be used; in the unlikely event that eligible cases outstrip capacity, an annual cap of the first 150 patients per year per cohort will be used.

Inclusion criteria for control participants includes:

• established diagnosis of migraine.
• with or without therapeutic medications with antiepileptic properties.

Exclusion Criteria

Exclusion criteria for case participants includes:

• a 'lesional' attributable cause for seizures including malignancy, stroke (excluding transient ischaemic attack), hypoxic brain injury, trauma, vascular or congenital abnormality of likely aetiological significance.
• people with migraine or headache syndrome can be included in case group - the presence or absence of a seizure syndrome is mutually exclusive between case and control groups, not the presence or absence of migraine.

Exclusion criteria for control participants includes:

• diagnosis of epilepsy or confirmed seizure.
• 'lesional' attributable cause for seizures including malignancy, stroke (excluding transient ischaemic attack), hypoxic brain injury, trauma.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
Case (Late-onset epilepsy); Observational study - no intervention. Participants with first seizure or new diagnosis of epilepsy, in adulthood. Inclusion criteria for cases includes: diagnosis of LOE or first seizure after the age of 18.; diagnosis confirmed or established at a tertiary neurology centre.; sequential cases will be used; in the unlikely event that eligible cases outstrip capacity, an annual cap of the first 150 patients per year per cohort will be used. Exclusion criteria for cases includes: another 'lesional' attributable cause for seizures including malignancy, stroke (excluding transient ischaemic attack), hypoxic brain injury, trauma, vascular or congenital abnormality of likely aetiological significance.; people with migraine or headache syndrome can be included in case group - the presence or absence of a seizure syndrome is mutually exclusive between case and control groups, not the presence or absence of migraine.
Control (migraine); Inclusion criteria for controls includes: established diagnosis of migraine.; with or without therapeutic medications with antiepileptic properties. Exclusion criteria for controls includes: diagnosis of epilepsy or confirmed seizure.; 'lesional' attributable cause for seizures including malignancy, stroke (excluding transient ischaemic attack), hypoxic brain injury, trauma. However, in both cases and controls, people with dementia, alcohol excess, recreational drug use or pre-existing small vessel disease will be included, as excluding these conditions would bias against the inclusion of the population who may benefit from this research and against the inclusion of patients with high risk of small vessel disease.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
At the time of onset, do people with late-onset epilepsy have higher prevalence of cerebrovascular disease risk factors compared to a control population?	Including HbA1c, hypertension / blood pressure, total cholesterol, triglycerides, MRI changes	3 years
Quality of Life - how of chronic illness is mediated	How is the experience of chronic illness in LOE mediated through the immediate experience of seizures (holidays, swimming), socioeconomic factors (unemployment, insurance, driving, family planning) and long-term risk of associated comorbidity	3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
What is the absolute and relative incidence of stroke and dementia in people after the onset of LOE compared to the background population?	As described	3-5 years
Which anti-epileptic drugs are used in current practice in LOE, and how are they tolerated?	As described	3 years

Collaborators and Investigators

• Sponsor: Lancashire Teaching Hospitals NHS Foundation Trust
• Investigators: Principal Investigator: Jasmine Wall, MB BChir, University of Lancaster

Study record dates

Study Major Dates

• Study Start (Actual): May 5, 2022
• Primary Completion (Estimated): January 12, 2027
• Study Completion (Estimated): January 12, 2027

Study Registration Dates

• First Submitted: February 9, 2024
• First Submitted That Met QC Criteria: February 9, 2024
• First Posted (Actual): February 16, 2024

Study Record Updates

• Last Update Posted (Actual): February 16, 2024
• Last Update Submitted That Met QC Criteria: February 9, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Epilepsy; Dementia
• Other Study ID Numbers: 288703

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: We will facilitate requests to share the full, anonymised dataset where made by an external investigator who is part of a formal research group with the appropriate expertise such as a statistician.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No