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Paroxysmal kinesigenic dyskinesia (PKD) is a movement disorder characterized by recurrent and transient episodes of involuntary movements, including dystonia, chorea, ballism, or a combination of these, which are typically triggered by sudden voluntary movement. Disturbance of the basal ganglia‐thalamo‐cortical circuit has long been considered the cause of involuntary movements. Impairment of the gating function of the basal ganglia can cause an aberrant output toward the thalamus, which in turn leads to excessive activation of the cerebral cortex. Structural and functional abnormalities in the basal ganglia, thalamus, and cortex and abnormal connections between these brain regions have been found in patients with PKD. Recent studies have highlighted the role of the cerebellum in PKD. Insufficient suppression from the cerebellar cortex to the deep cerebellar nuclei could lead to overexcitation of the thalamocortical pathway. Therefore, this literature review aims to provide a comprehensive overview of the current research progress to explore the neural circuits and pathogenesis of PKD and promote further understanding and outlook on the pathophysiological mechanism of movement disorders. © 2023 International Parkinson and Movement Disorder Society. [ABSTRACT FROM AUTHOR]

Background: Paroxysmal kinesigenic dyskinesia (PKD) is the most common type of paroxysmal dyskinesias. Only one‐third of PKD patients are attributed to proline‐rich transmembrane protein 2 (PRRT2) mutations. Objective: We aimed to explore the potential causative gene for PKD. Methods: A cohort of 196 PRRT2‐negative PKD probands were enrolled for whole‐exome sequencing (WES). Gene Ranking, Identification and Prediction Tool, a method of case–control analysis, was applied to identify the candidate genes. Another 325 PRRT2‐negative PKD probands were subsequently screened with Sanger sequencing. Results: Transmembrane Protein 151 (TMEM151A) variants were mainly clustered in PKD patients compared with the control groups. 24 heterozygous variants were detected in 25 of 521 probands (frequency = 4.80%), including 18 missense and 6 nonsense mutations. In 29 patients with TMEM151A variants, the ratio of male to female was 2.63:1 and the mean age of onset was 12.93 ± 3.15 years. Compared with PRRT2 mutation carriers, TMEM151A‐related PKD were more common in sporadic PKD patients with pure phenotype. There was no significant difference in types of attack and treatment outcome between TMEM151A‐positive and PRRT2‐positive groups. Conclusions: We consolidated mutations in TMEM151A causing PKD with the aid of case–control analysis of a large‐scale WES data, which broadens the genotypic spectrum of PKD. TMEM151A‐related PKD were more common in sporadic cases and tended to present as pure phenotype with a late onset. Extensive functional studies are needed to enhance our understanding of the pathogenesis of TMEM151A‐related PKD. © 2021 International Parkinson and Movement Disorder Society [ABSTRACT FROM AUTHOR]

Background Paroxysmal kinesigenic dyskinesia (PKD) is a rare involuntary movement disorder characterized by transient and recurrent dystonic or choreoathetoid attacks triggered by sudden voluntary movements. Since 2011, progress in genetics and pathophysiology has been made. Our study aimed to investigate and analyze the characteristics of social behavior, quality of life and related factors in patients with PKD in China. Methods A cross - sectional study was conducted regarding health - related behaviors in 188 patients with PKD by using the Chinese Version of Symptom Check List-90 (SCL-90) and World Health Organization Quality of Life - 100 (WHOQoL - 100) questionnaires. Psychometric symptoms, mental health, quality of life and related factors were all investigated and analyzed. Results A total of 120 valid questionnaires were statistically analyzed. Compared with Chinese norm, patients with PKD showed significantly higher scores in global severity index (GSI, P = 0.000) and SCL-90 scores (somatization, obsessive - compulsive, interpersonal sensitivity, depression, anxiety, hostility, phobic anxiety, paranoid ideation, psychoticism; P = 0.000, for all). Patients with PKD also showed significantly lower scores than Chinese norm in general quality of life (P = 0.000) and four domains of WHOQoL - 100 (physiological domain, psychological domain, independence domain, social relationship domain; P = 0.000, for all). Pearson and partial correlation analysis showed that quality of life of PKD patients was in positive correaltion with complex PKD and remission (P = 0.016, 0.000), while was in negative correaltion with somatization, obsessive - compulsive, interpersonal sensitivity, depression, anxiety, hostility, phobic anxiety, paranoid ideation and psychoticism (P = 0.000, for all). The results of multiple linear regresssion analysis showed that lower quality of life was in association with remission (P = 0.024) and depression (P = 0.000). The degree of impact was R2 value 0.423 for remission and R2 value 0.398 for depression. Conclusions The prevalence of psychometric symptoms and poor quality of life in PKD patients were studied and the efforts to recognize and detect comorbid interictal psychological distress were important, especially for the patients with higher depression score and without remission trend. [ABSTRACT FROM AUTHOR]

Background Paroxysmal kinesigenic dyskinesia (PKD) is a disorder characterized by recurrent and brief dystonic or choreoathetoid attacks that are induced by sudden voluntary movement with highly clinical and genetic heterogeneity. We aimed to investigate the clinical features of PKD in a large Chinese population. Methods One hundred and ninety five patients diagnosed as primary PKD were recruited. For all of the participants, neurological examinations were conducted and clinical manifestations were recorded and summarized in self-made uniform registration form for PKD patients. Clinical characteristics were statistically analyzed and compared between familial and sporadic PKD patients. Results Among all of the 195 PKD patients in the present study, the gender ratio was 4.42 : 1 (male : female). The average age of onset was (12.32 ± 3.49) years. There were 162 patients (83.08%) manifestated with pure form and 33 (16.92%) with complicated form of PKD. Among them 16 patients (8.21%) had essential tremor (ET), and 144 patients (73.85%) had premonitory symptom. The percentage of patients manifested as dystonia, chorea and mixed form during episodic attacks were 68.72% (134/195), 4.10% (8/195) and 27.18% (53/195) respectively. There were 134 cases (68.72%) had facial involvement. It was recorded that 115 (58.97%), 54 (27.69%) and 26 (13.33%) patients had frequency of attack < 10 times/d, 10-20 times/d and > 20-30 times/d respectively. The percentages of patients whose duration of attack < 10 s, 10-30 s and > 30-60 s were 60% (117/195), 29.74% (58/195) and 10.26% (20/195) respectively. There were 64 patients (32.82%) with family history of PKD and 131 (67.18%) were sporadic PKD patients. Up to 40% (78/195) of patients did not require/take medications, as they had minor clinical manifestations or concerns about the side effects of anticonvulsants. Among 117 patients (60% ) prescribed with anticonvulsants, 114 patients showed a good response, including complete control (N = 106) and partial control (N = 8), and 3 patients were nonresponsive. In comparison with sporadic PKD patients, familial PKD patients had earlier age of onset (t = 2.376, P = 0.019) and shorter duration of attack (χ2 = 7.731, P = 0.021) respectively. Conclusions We summarized the clinical characteristics of PKD patients in mainland China. Through the analysis of large sample data, we hope to improve and standardize the diagnosis and treatment of PKD clinically. [ABSTRACT FROM AUTHOR]