Objective: To delineate the cortical function of paroxysmal kinesigenic dyskinesia (PKD) and correlate with the genotypes of patients.

Background: PKD is characterized by episodic involuntary movements triggered by initiation of movements. PKD was conventionally regarded as a movement disorder involving the basal ganglia (BG). However, the patients often have epilepsy and respond excellently to antiepileptic drugs, like oxacarbazepine (OXC). PRRT2 mutations, the most common genetic etiology of PKD, can also cause epilepsy syndromes. These facts suggest the brain cortex is affected in PKD.

Method: 20 patients, including  4 with a pathogenic PRRT2 mutation, and 19 age-matched healthy controls were evaluated by functional magnetic resonance imaging. The fractal dimension (FD) and cortical volume (CV) indexes were calculated to quantify the morphology alteration. The diffusion tensor images (DTI) parameters included fractional anisotropy (FA) and mean diffusivity (MD). The local functional abnormalities were analyzed using fractional amplitude of low frequency fluctuations (fALFF), regional homogeneity (ReHo) and voxel-mirrored homotopic connectivity (VMHC). Structural covariance networks were used to examine network properties.

Results: In PKD patients, FD and CV of BG and the limbic system (LS) reduced significantly, FA of anterior thalamic radiation and uncinate fasciculus also decreased, but FD of the cerebellar vermis increased. The patients who need regular medication had a greater aberrance of fALFF/ReHo/VMHC in the cerebellum, orbital frontal and precuneus gyri, indicating attenuated inhibition of the sensorimotor network (SMN). The values of FD co-variated with a small group of neighboring regions, but not a large group. This echoed the relatively benign nature of PKD as compared with epilepsy. The cerebellum, supramarginal gyrus and parietal gyrus were regions affected most in PRRT2-PKD, indicating the pathogenic impacts of PRRT2 mutations on the cerebellum and SMN. OXC could normalize above dysfunction, explaining the excellent response of PRRT2-PKD to OXC.

Conclusion: This study pointed out PKD a network disease with BG, LS, SMN and cerebellum the majorly affected functional regions. Our results also provide the cortical dysfunction related to PRRT2 mutations and the effect of pharmacotherapy modulational. The correlation between genetics and neurophysiology can advance our understanding of the pathogenesis of PKD.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/correlations-between-genetics-and-cortical-dysfunction-of-paroxysmal-kinesgenic-dyskinesia/