PRAFUS (prospective)
Research type
Research Study
Full title
Predicting recurrence after first unprovoked seizure (prospective)
IRAS ID
279362
Contact name
Tony Marson
Contact email
Sponsor organisation
The Universtiy of Liverpool
Duration of Study in the UK
2 years, 11 months, 29 days
Research summary
10% of the population will have at least one seizure in their lifetime, and around half will have a further seizure and therefore a subsequent diagnosis of epilepsy. We are currently unable to reliably predict those individuals that will have a recurrence after a first unprovoked seizure. This uncertainty is associated with serious physical, psychological and social consequences for patients and their families. If we are able to accurately identify those at highest risk of further seizures, both patients and clinicians would be better informed regarding treatment decisions, appropriate counselling and identifying those at highest risk of further seizures that may be willing to participate in clinical trials of new treatments.
We will prospectively identify 100 patients from the first seizure clinic and analyse information from their MRI brain and EEG tests that have been performed as part of routine clinical care for all of these patients. In addition to these standard clinical investigations, we will take blood and saliva samples from all participants, to measure novel markers of inflammation which we believe may be linked to seizure predisposition. In a sub-set of 40 patients, we will perform advanced MRI sequences in addition to standard clinical sequences, at the UoL MRI scanning facility as part of a nested exploratory study. The information from these tests together with clinical information recorded in the electronic patient records will be combined with the goal of accurately predicting patients that go on to have further seizures. We will follow patients up with telephone questionnaires at intervals of 6, 12, 18 and 24 months.
We anticipate the results from this study will serve as a proof of concept that will inform the further development of robust predictive tools that could be applied in the care and assessment of patients presenting with their first unprovoked seizure.
Lay summary of study results: In a study following patients over time, MRI scans showed abnormalities in 60% of patients and 33.3% of healthy controls. Half of the patients had seizures again within two years, and those with abnormal MRIs were more likely to experience this (75% compared to 45%, which was statistically significant). Advanced imaging found that in patients, the right side of the brain's thalamus was pushed inward, while the amygdala bulged outward, compared to controls. There was also shrinkage in specific parts of the thalamus. Additionally, patients with FUS (a type of seizure disorder) had lower measures of brain connectivity in several white matter pathways, and this connectivity was even worse in those with recurring seizures.
Lay summary of study results:
This research studied people who experienced a first unprovoked seizure—a type of seizure that happens without an obvious trigger like a high fever, infection, or head injury. Many people who have one seizure may never have another, but some go on to develop epilepsy, which is a condition where seizures keep happening.
Knowing who is more likely to have another seizure is very important. It helps doctors give better advice to patients about driving, working, and whether to start anti-seizure medication (ASM). It also helps decide when to make a formal diagnosis of epilepsy.
The study had two parts:
Systematic Review and Meta-analysis
The first part looked at data from 58 previous studies involving over 12,000 people. The goal was to find out how many people have another seizure and what factors increase the risk.
About 27% had another seizure within 6 months.
This went up to 43% within 2 years.
People with an abnormal electroencephalogram (EEG)—a test that records brain waves—were more likely to have another seizure.
Other possible risk factors included having a seizure during sleep, being male, having a family history of epilepsy, or having signs of a previous brain problem.
Brain Imaging Study
The second part was a new study of 40 patients with a first seizure and 60 healthy volunteers. All participants had detailed brain scans using magnetic resonance imaging (MRI).
MRI found brain changes in 60% of the patients with a seizure, compared to 33% of healthy people.
Half of the patients had another seizure within 2 years.
Those with abnormal MRI findings were much more likely to have another seizure (75% vs 45%).
New, more advanced MRI methods showed subtle brain changes in areas that help control movement and awareness, such as the thalamus and amygdala.
People who had another seizure showed more disruption in the brain’s white matter “wiring”—the connections that link different parts of the brain.
What does this mean?
These results suggest that certain tests done after a first seizure—especially brain scans and EEG—can help doctors predict who is most at risk of having another seizure. That could help patients make more informed decisions about their lives and treatment.
The research also suggests that newer types of MRI scans could one day be used to find hidden brain changes early on, before epilepsy fully develops.
Why is this important?
Making the right diagnosis early can prevent unnecessary treatment for people at low risk, and offer early help to those at high risk. This could also improve clinical trials for new treatments aimed at stopping epilepsy from developing in the first place.REC name
North East - Tyne & Wear South Research Ethics Committee
REC reference
20/NE/0078
Date of REC Opinion
28 Apr 2020
REC opinion
Further Information Favourable Opinion