Dark White Matter: Evidence of a Peri-Ictal MRI Sign from a Systematic Review

The radiological finding of Dark White Matter (DWM)-characteristic diffuse subcortical white matter hypointensity on T2/FLAIR sequences-is underrecognized, but has important clinical implications. Recent systematic evidence shows that over 60% of previously published cases showed seizures in association with DWM findings-it is also particularly predictive of the underlying etiology, particularly non-ketotic hyperglycemic hyperosmolar state (NKH). Based on our previous work, we reinterpret the data, focusing only on patients with seizures and DWM, to summarize the most essential and distinguishing features of these patients. Both cortical and subcortical abnormalities in DWM are more frequently associated with anti-MOG encephalitis. DWM with or without cortical involvement is more commonly found in NKH among patients with seizures. This updated systematic review will describe the proposed pathophysiological mechanisms, clinical associations, and implications for DWM in patients with seizures, and highlight how early recognition of DWM may allow for targeted diagnostic strategies and treatment options. We expanded our previous search with details regarding seizure features, our results show that DWM is associated with repetitive seizures and Status Epilepticus (both convulsive and non), in line with other peri-ictal MRI abnormalities associated with prolonged seizure activity. DWM-associated seizures are mostly focal, rather than generalized. Moreover, the high percentage of clinical recovery at follow-up suggests that DWM may be predictive of a good outcome, especially in NKH cases, although this needs to be confirmed in future studies.