The first paper from my PhD is out! . A systematic review on #neuroimaging in self-limiting #rolandic #epilepsy ( #RE). Thanks to @EpilepsiaOpen So why would you investigate the neuroimaging of an epilepsy where clinical MRI is normal? https://doi.org/10.1002/epi4.12468 #thread 1/23

RE affects around 10-20 per 100,000 school-age children. Interestingly twice as many boys develop the epilepsy compared to girls. Seizures are generally infrequent and are believed to arise from the central sulcus AKA the Rolandic fissure. 2/23

Also, there can be cognitive problems which include reading disability ( #RD), attention deficit hyperactivity disorder ( #ADHD), developmental language ( #DLD) and developmental coordination disorders ( #DCD). These can lead to problems with schoolwork/daily life. 3/23

RE is a bit of a mystery. The epilepsy is self-limiting, which means most children will become seizure-free. This can occur with or without the use of antiseizure medication. Fortunately, the majority of children with RE will be in seizure remission by 15 years. 4/23

So what causes it? Hands up, we don’t really know. There is a small proportion of RE cases where the cause is associated with channelopathy. Otherwise, RE is presumed to be genetic in origin. 5/23

It is suspected that a genetic abnormality results in abnormal neurodevelopment which impacts the function of the central sulcus. It is also assumed that brain structure may be altered, resulting in a cortical lesion. Both of these processes could impact cognition. 6/23

In children *without* seizures but with similar cognitive problems, there is data to support that these problems are a result of disordered neurodevelopment. Controlled neuroimaging studies have demonstrated evidence for altered cortex, subcortical volumes and white matter. 7/23

It is important to note that cognitive disorders can also be seen in children with epilepsies of a structural cause. So there is always the possibility that RE could be the result of an undetectable lesion (using current clinical neuroimaging) which may persist. 8/23

Therefore RE has two genetic, aetiological hypotheses, one which influences neurodevelopment and the other lesional. Many RE research groups have performed computational neuroimaging studies to investigate this. 9/23

Most studies were performed during active epilepsy and a few included children with RE in seizure remission. 10/23

So why study seizure remission?In RE, it remains unclear whether the seizures have a “damaging” effect on the child's brain. Studies which include seizure remission can help us collect the best evidence to answer this question. 11/23

This paper presents the MR neuroimaging evidence to support a disorder of neurodevelopmental in children who develop RE. Please keep in mind that these are group analyses and there was no available data for meta or mega-analysis. Maybe @enigmabrains could investigate this? 12/23

This review is a synthesis of computationally derived data from controlled whole-brain analyses. Only statistically significant values corrected for multiple comparisons were reported. The review has provided some answers to several questions. Intrigued? Then read on!13/23

Are there significant differences between the brain of a child with RE compared to healthy children? Yes, statistically significant differences can be detected. 14/23

Where are the differences? Reproducible differences can be detected within and outside the central sulcus. Yes, you read it correctly, differences can be detected outside of the location where the seizures are meant to be generated. 15/23

Is it just the cortex ? Another surprise! Reproducible differences can be detected in white matter structures and subcortical grey matter volumes, in particular the putamen. 16/23

Does age have an influence?The data indicate that the amounts of differences seen in the brains of children with RE will reduce as they get older. Younger children (under 10 yrs) have more differences compared to older children (over 10 yrs). 17/23

When the seizures stop is there evidence for damage? Neuroimaging in seizure remission has a small evidence base but the current data would suggest a reduction in differences with healthy controls. 18/23

Overall, the study demonstrates evidence for a disorder of neurodevelopment and it does not support the theory that seizures in RE lead to damage. 19/23

This review raises interesting questions of what constitutes a “lesion” and what are the mechanisms behind a "focal" epilepsy. Do the altered regions outside of the proposed ictogenic zone, play a part in the seizure mechanism or is it a co-existing feature? 20/23

Further work is required to investigate the relationship between cortex, subcortical structures, white matter and the development of an idiopathic self-limiting seizure disorder. 21/23

Moral of the story: Systematic review is the epilepsy researchers friend. 22/23

Many thanks to @palneurolab @epilepsy_london and @kingsioppn for their help and support to get this work to publication. This work would have not been possible without the generous financial support of the @Waterloo Foundation. #rolandicepilepsy #neuroimaging 23/23