Do Seizures Damage the Brain?
From a slow drip in chronic epilepsy to a flood during status epilepticus.
For 150 years clinicians have debated whether seizures harm the brain. Longitudinal imaging now lets us measure it directly, across the whole spectrum, from the subtle atrophy of chronic epilepsy to the dramatic injury of prolonged status epilepticus. The answers shape how urgently we treat, when we operate, and whether the brain can be protected.
ml of grey matter lost per year, logarithmic scale
During status epilepticus (NORSE), grey matter is lost around 80 times faster than in normal ageing and 20 times faster than in Alzheimer’s disease. Redrawn from our preprint.
The slow drip
In chronic focal epilepsy the brain shrinks about twice as fast as in normal ageing. The loss concentrates in regions wired to the seizure focus, a network process, and it does not simply track how many seizures a person has.
The sudden flood
During prolonged status epilepticus, and especially NORSE, grey matter is lost rapidly and largely irreversibly. Blood and CSF markers of neurodegeneration rise in parallel and fall once the seizures stop, and histology confirms neuronal loss.
It can be halted
Successful epilepsy surgery stops the progressive atrophy in its tracks. That is strong evidence the damage is driven by the disease itself, and that removing the source can protect the brain.
Not only loss
The picture is not all decline. The brain also compensates, with hypertrophy of structures such as the contralateral amygdala and hippocampus, hinting at reorganization that might one day be harnessed.
Two studies, both open to collaborators.
Answering this question at scale takes shared data. We lead two multicentre imaging efforts, and both actively welcome new sites.
IMPOSE
We lead this studyIMPOSE pools serial MRI and fluid biomarkers from people who had status epilepticus, to find who is vulnerable to brain injury, by how much, where, and what protects them. Our pilot showed grey-matter loss during NORSE far beyond any other condition. We are inviting centres to contribute their cases.
ENIGMA-Longitudinal
We lead this analysis within ENIGMA-EpilepsyWe are assembling the largest multicentre longitudinal MRI cohort in epilepsy, to map how the brain changes over time and to test the impact of treatment. We welcome cohorts with repeated MRI in people with epilepsy to take part.
Our work on this topic, in the literature.
Brain damage during new-onset refractory status epilepticus
Rapid, largely irreversible grey-matter loss during NORSE, around 80 times normal ageing, mirrored by fluid biomarkers and confirmed on histology.
Brain hypertrophy in mesial temporal lobe epilepsy
Showed that epilepsy does not only shrink the brain, some structures enlarge, pointing to compensation and reorganization.
Longitudinal hippocampal morphology around temporal lobe surgery
Tracked how hippocampal shape changes before and after epilepsy surgery, refining what is disease and what is treatment.
Seizures beget more than seizures
A synthesis of the cellular, structural, individual and societal toll of seizures, the conceptual backbone for this whole question.
Different MRI atrophy progression trajectories in epilepsy
Used subtype and stage inference to reveal distinct trajectories of brain change across people with epilepsy.
Neuronal antibodies in cryptogenic NORSE
A systematic search found no hidden antibody cause in most cryptogenic NORSE, sharpening where to look next.
Resective surgery prevents progressive cortical thinning
Successful surgery halted the ongoing atrophy of temporal lobe epilepsy, evidence that the damage may be preventable.
Progressive cortical thinning in focal epilepsy
The foundational study, brain atrophy in epilepsy runs at roughly twice the rate of normal ageing.