Objective: This study aimed to delineate the morphological and functional alterations of paroxysmal kinesigenic dyskinesia (PKD) by functional magnetic resonance imaging (fMRI).

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) and sparing the cortex. However, patients of PKD often have seizures 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: Twenty patients, including 4 with a heterozygous pathogenic PRRT2 mutation, and 19 aged-matched healthy controls were recruited. The fractal dimension (FD) and cortical volume (CV) indexes were calculated to quantify the morphology alteration. The tract-template based 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 the altered network properties.

Results: In PKD patients, FD and CV of BG and the limbic system (LS) were significantly decreased. FA of anterior thalamic radiation and uncinated fasciculus were also lowered. In contrast, FD of cerebellar vermis increased in patients. The patients who need regular medication had a greater aberrance of fALFF, ReHo, and VMHC in the cerebellum, orbital frontal gyri and precuneus area, indicating a profoundly attenuated inhibition of the sensorimotor network (SMN). The cerebellum, superior and middle frontal gyri, supramarginal gyrus and parietal gyrus were regions affected mostly in PRRT2-PKD, indicating PRRT2 mutations disrupted synaptic transmission n leading to functional aberrance of the cerebellum and SMN. OXC could normalized the above dysfunction, explaining the excellent response of PRRT2-PKD to OXC.

Conclusion: This study pointed out PKD a networking disease. Our results also provide the cortical dysfunction related to PRRT2 mutations and the evidence of modulational effects by pharmacotherapy. The correlation of genetics and neurophysiology can advance our understanding of the pathogenesis of PKD.

« Back to 2022 International Congress

MDS Abstracts - https://www.mdsabstracts.org/abstract/brain-structure-alternations-and-disrupted-functional-connectivity-in-paroxysmal-kinesigenic-dyskinesia/