Paroxysmal Kinesigenic Dyskinesia Patients Research Articles

Clinical Manifestations in Paroxysmal Kinesigenic Dyskinesia Patients with Proline-Rich Transmembrane Protein 2 Gene Mutation

Background and PurposeGiven the diverse phenotypes including combined non-dyskinetic symptoms in patients harboring mutations of the gene encoding proline-rich transmembrane protein 2 (PRRT2), the clinical significance of these mutations in paroxysmal kinesigenic dyskinesia (PKD) is questionable. In this study, we investigated the clinical characteristics of PKD patients with PRRT2 mutations.MethodsFamilial and sporadic PKD patients were enrolled and PRRT2 gene sequencing was performed. Demographic and clinical data were compared between PKD patients with and without a PRRT2 mutation.ResultsAmong the enrolled PKD patients (8 patients from 5 PKD families and 19 sporadic patients), PRRT2 mutations were detected in 3 PKD families (60%) and 2 sporadic cases (10.5%). All familial patients with a PRRT2 gene mutation had the c.649dupC mutation, which is the most commonly reported mutation. Two uncommon mutations (c.649delC and c.629dupC) were detected only in the sporadic cases. PKD patients with PRRT2 mutation were younger at symptom onset and had more non-dyskinetic symptoms than those without PRRT2 mutation. However, the characteristics of dyskinetic movement did not differ between the two groups.ConclusionsThis is the first study of PRRT2 mutations in Korea. The presence of a PRRT2 mutation was more strongly related to familial PKD, and was clinically related with earlier age of onset and common non-dyskinetic symptoms in PKD patients.

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

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.

Clinical analysis of nine cases of paroxysmal exercise-induced dystonia

This study was aimed to analyze the clinical features of paroxysmal kinesigenic dyskinesia (PKD) and extend the understanding of this disease. From August, 2008 to October, 2010, 9 patients were diagnosed with PKD in the Department of Neurology of the First Affiliated Hospital of Zhejiang University, China. The data involving clinical demographic characteristics, somatosensory evoked potentials, results of electromyography, video electroencephalography (EEG), brain magnetic resonance imaging (MRI) and computerized tomography (CT) were collected. All PKD patients exhibited unilateral or bilateral recurrent episodic dyskinetic attacks triggered by sudden voluntary movements. The duration of the attacks ranged from several seconds to one minute. The attack frequency ranged from approximately once in several months to more than 10 times in a day. Patients suffered from no conscious disorders during the attack, and no neurological signs were found during the period between attacks. No abnormal somatosensory evoked potentials were found. Routine EEG, video EEG monitoring or brain imaging showed normal findings. Classical treatment for anti-epilepsy, including carbamazepine and topiramate, was administered to the patients and proved to be effective. It was concluded that PKD is characteristically triggered by sudden voluntary movement; no abnormal electroneurophysiological findings are observed in PKD, and antiepileptic drugs are effective in treating the disorder.

PRRT2 c.649dupC Mutation Derived from De Novo in Paroxysmal Kinesigenic Dyskinesia

PRRT2 was recently identified as a causative gene for paroxysmal kinesigenic dyskinesia (PKD), and the c.649dupC mutation was shown to be a "high frequency" mutation. This mutation was also identified in many sporadic cases. This might be attributed to the incomplete penetrance of c.649dupC. Alternatively, c.649dupC might derive from de novo. The aim of this study is to elucidate the possibility concerning de novo mutagenesis of PRRT2 mutations in PKD. Nine sporadic Chinese PKD patients including one Mongolian patient were recruited. Direct sequencing of PRRT2 was performed in them and their parents. Haplotype analysis was conducted to confirm the biological relationship. A novel mutation, c.133_136delCCAG, was identified in one Han patient and his unaffected mother. The c.649dupC mutation was detected in another Han patient and his unaffected father. To our interest, c.649dupC was detected in the Mongolian patient but not in his parents. Haplotype analysis confirmed the biological relationship among the trio. No mutations were identified in the remaining six patients. These findings demonstrate the heterogeneity of PKD, and the de novo mutagenesis of PRRT2 gene might indicate the genetic instability of this region.

Clinical manifestations of 20 Taiwanese patients with paroxysmal kinesigenic dyskinesia.

We compared the clinical manifestations and response to medications between familial and sporadic patients with paroxysmal kinesigenic dyskinesia (PKD), and also between patients with autosomal dominant (AD) and autosomal recessive (AR) inheritance. This retrospective cohort study included 9 familial and 11 sporadic Taiwanese patients with PKD diagnosed during a 10-year period at one of two hospitals. The mean duration of follow-up was 3.8 +/- 2.7 years. Each patient was interviewed and their medical records, as well as videotape recordings of PKD attacks in 6 patients, were used for analysis. Patients were treated with either carbamazepine or phenytoin, and the efficacy of sodium valproate was tested in 5 patients. No single distinguishing feature in terms of clinical manifestations or therapeutic response was found to differentiate among familial, and sporadic cases, or between AD and AR inheritance. Carbamazepine and phenytoin were superior to sodium valproate in treating both familial and sporadic PKD patients, and both drugs resulted in almost complete remission of attacks. Our findings indicate that the sporadic and familiar forms of PKD, as well as the AR and AD inherited types, are similar in terms of clinical manifestations and response to treatment. The functional status and prognosis of our Taiwanese patients suggest that PKD is a relatively benign entity.

Study of paroxysmal kinesigenic dyskinesia with fMRI

To detect the differences in subcortical structures between patients with paroxysmal kinesigenic dyskinesia (PKD) and normal subjects during movement preparation and execution. The PKD patients performed a movement task, in which a CUE signal (preparation) indicated the movement sequence prior to the appearance of an imperative GO signal (execution). Event-related functional magnetic resonance imaging (fMRI) and 3dDeconvolve program of AFNI were used to estimate the hemodynamic response function and to generate activation maps. During movement preparation, the activated brain areas in PKD patients were less than those of normal subject, and there was no activation in basal ganglia in PKD patients. During execution, the activation was also less in PKD patients except in bilateral M1. During intermission, abnormalities of the brain still exist in PKD patients when during preparing or performing movement. The movement circuit in the brain displays an unusual state. The attack may be caused by reducing of inhibition in brain areas.