Objective: The present study utilized multi-modal MRI study to investigate the structural and functional alterations in genetically confirmed familial cortical myoclonic tremor with epilepsy type 1 patients carrying heterozygous pathogenic (TTTCA)n insertion in the SAMD12 gene.

Background: Intronic pentanucleotide (TTTCA)n insertion was recently identified as the genetic cause of familial cortical myoclonic tremor with epilepsy. However, our knowledge to its pathophysiology was still limited.

Method: Here, we enrolled 31 familial cortical myoclonic tremor with epilepsy type 1 patients carrying heterozygous pathogenic (TTTCA)n insertion in the SAMD12 gene and 31 age- and gender-matched healthy controls. Multi-modal MRI metrics were compared, including gray matter volume, fractional anisotropy of diffuse tensor imaging, percent amplitude fluctuation (a new derivative of amplitude of low frequency fluctuation) of resting-state functional MRI.

Results: No significant group difference was found on gray matter volume and fractional anisotropy. For the resting-state functional MRI metric percent amplitude fluctuation, two-way ANOVA showed no significant main effect of “Group”, but showed significant interaction effect of “Frequency by Group” in four regions including the vermis, left cerebellar lobule, right anterior cingulate gyrus, and left precentral gyrus. The lowest frequency band (0 – 0.01 Hz) exhibited significant increased percent amplitude fluctuation in patients in three subcortical regions (two in cerebellum and one in the cingulate), while the highest frequency band (0.198 – 0.25 Hz) exhibited decreased percent amplitude fluctuation in the precentral gyrus in patients. Further analysis revealed that the interaction effect was mainly contributed by the lowest (0 – 0.01 Hz) and highest (0.198 – 0.25 Hz) frequency bands resting-state functional MRI. While the structural damage was not prominent, the cerebellum and motor cortex showed a frequency-dependent abnormality of intrinsic activity.

Conclusion: The distinct change of spontaneous brain activity, i.e., increased ultra-low frequency amplitude in the cerebellum and the decreased higher frequency amplitude in the motor cortex might be a pathophysiological feature in familial cortical myoclonic tremor with epilepsy type 1 patients.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/multi-modal-mri-in-patients-with-genetically-confirmed-familial-cortical-myoclonic-tremor-with-epilepsy-type-1/