The Pathogenesis of Paroxysmal Kinesigenic Dyskinesia: Current Concepts

Abstract

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.

An Electroencephalography Profile of Paroxysmal Kinesigenic Dyskinesia

“…Meanwhile, connections from the thalamus to the striatum and the primary motor cortex were more facilitated. [ 10 , 39 ] Furthermore, PRRT2 , the primary pathogenic gene of PKD, is highly expressed in the cerebellum, especially in granule cells (GCs), and enriched at the presynaptic membrane in the molecular layer. Cerebellar knockout of PRRT2 could result in the phenotype of PKD in mice and abnormal excitability of the cerebellum.…”

Heterozygous KCNJ10 variants affecting Kir4.1 channel cause paroxysmal kinesigenic dyskinesia

“…Although the mechanism of PKD is not yet well elucidated, it has long been established that this disease is related to the disturbance or imbalance in neural excitability based on its clinical features and electrophysiological studies 19 . Moreover, recent studies have highlighted that abnormal excitability in the cerebellum is involved in PKD.…”

“…It has been well accepted that the basal ganglia-thalamo-cortical circuit is highly associated with PKD due to its clinical manifestation. 19 However, increasing evidence from both clinical and mechanistic studies has highlighted the role of the cerebellum in PKD. 17,20,21 No genetic cause is found in more than 60% of PKD individuals, 1,5 unceasing efforts have been made to seek causative genes for PKD.…”

Identification of a de novo CACNA1B variant and a start-loss ADRA2B variant in paroxysmal kinesigenic dyskinesia

“…Paroxysmal kinesigenic dyskinesia (PKD), the most prevalent form of paroxysmal dyskinesia, is a rare neurological disorder distinguished by recurrent and transient attacks of involuntary movements triggered by sudden voluntary movement [ 1 ]. PKD can be categorized into primary and secondary types depending on its etiology.…”

“…Attacks are characterized by involuntary movements that may include dystonia, chorea, or both, and may last for seconds to minutes. Management typically involves avoidance of known triggers and treatment with medication such as anticonvulsants or benzodiazepines to reduce the frequency and severity of attacks [ 1 , 7 ]. PKD is a treatable condition and accurate diagnosis is important for optimal management and genetic counseling.…”