Original Article

Neurological Sciences

, Volume 34, Issue 11, pp 1925-1931

First online:

Altered intrinsic brain activity in patients with paroxysmal kinesigenic dyskinesia by PRRT2 mutation

Altered brain activity by PRRT2 mutation
  • ChunYan LuoAffiliated withDepartment of Neurology, Sichuan University, West China Hospital
  • , Yongping ChenAffiliated withDepartment of Neurology, Sichuan University, West China Hospital
  • , Wei SongAffiliated withDepartment of Neurology, Sichuan University, West China Hospital
  • , Qin ChenAffiliated withDepartment of Neurology, Sichuan University, West China Hospital
  • , QiYong GongAffiliated withDepartment of Radiology, Huaxi MR Research Center, Sichuan University, West China HospitalDivision of Medical Imaging, Faculty of Medicine, University of Liverpool
  • , Hui-Fang ShangAffiliated withDepartment of Neurology, Sichuan University, West China Hospital Email author 

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Abstract

The proline-rich transmembrane protein 2 (PRRT2) gene has been recently identified as a causative gene of paroxysmal kinesigenic dyskinesia (PKD), with an insertion mutation c.649_650insC (p.P217fsX7) reported as the most common mutation. However, the pathogenic mechanism of the mutation of PRRT2 remains largely unknown. Resting-state functional magnetic resonance imaging is a promising approach to assess cerebral function and reveals underlying functional changes. Resting-state functional magnetic resonance imaging was performed in 4 Chinese PKD patients with p.P217fsX7 mutation, 6 Chinese PKD patients without the mutation, and 10 healthy control subjects. Voxel-based analysis was used to characterize alterations in the amplitude of low-frequency fluctuation (ALFF). When compared with the healthy control subjects, both groups of PKD patients showed alterations in spontaneous brain activities within cortical–basal ganglia circuitry. Besides, the group of patients with p.P217fsX7 mutation also exhibited increased ALFF in the right postcenral gyrus and right rolandic operculum area, while the alteration of ALFF in group of patients without the mutation additionally involved the middle orbitofrontal cortex. Direct comparative analysis between these two patient groups revealed significantly increased ALFF in the right postcentral gyrus in the group with p.P217fsX7 mutation. Increased spontaneous brain activity in the cortical–basal ganglia circuitry, especially in the motor preparation areas, is a common pathophysiology in PKD. Differences in the spatial patterns of increased ALFF between patients with and those without the mutation might reflect the distinct pathological mechanism resulting from PRRT2 mutation.

Keywords

Paroxysmal kinesigenic dyskinesia (PKD) Proline-rich transmembrane protein 2 (PRRT2) Mutation C.649_650insC Resting-state functional magnetic resonance imaging (rfMRI) Amplitude of low-frequency fluctuation (ALFF)