Review: Diagnosis and treatment of paroxysmal dyskinesias revisited

Unterberger, Iris; Trinka, Eugen

doi:10.1177/1756285608095119

Cited by 42 publications

(46 citation statements)

References 59 publications

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“…Paroxysmal kinesigenic dyskinesia (PKD), one of the three main types of paroxysmal dyskinesia, is brief in its presentation ranging from seconds to 5 min and is precipitated by sudden attacks of dyskinesias induced by voluntary movements [1]. Since it is relatively uncommon, many PKD patients are misdiagnosed in clinical practice.…”

Section: Dear Editormentioning

confidence: 99%

Paroxysmal kinesigenic dyskinesia in pseudohypoparathyroidism: Is basal ganglia calcification a necessary finding?

Kwon

Jung

Choi

et al. 2015

Journal of the Neurological Sciences

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Section: Dear Editormentioning

confidence: 99%

Paroxysmal kinesigenic dyskinesia in pseudohypoparathyroidism: Is basal ganglia calcification a necessary finding?

Kwon

Jung

Choi

et al. 2015

Journal of the Neurological Sciences

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“…PNKD, the dominant type associated with KCNMA1-linked channelopathy, is commonly described as refractory to medications. However, benzodiazepines, particularly clonazepam, and some ASMs have been shown to be effective in some PNKD patients (Unterberger and Trinka, 2008). Additional therapies used to treat other movement disorders, such as acetazolamide in episodic ataxia, have demonstrated positive effects in some patients with PNKD (Silveira- Moriyama et al, 2018).…”

Section: Lessons From Animal Studies Linking Changes In Bk Channel Fumentioning

confidence: 99%

KCNMA1-linked channelopathy

Bailey

Moldenhauer

Park

et al. 2019

Journal of General Physiology

108

118

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KCNMA1 encodes the pore-forming α subunit of the “Big K+” (BK) large conductance calcium and voltage-activated K+ channel. BK channels are widely distributed across tissues, including both excitable and nonexcitable cells. Expression levels are highest in brain and muscle, where BK channels are critical regulators of neuronal excitability and muscle contractility. A global deletion in mouse (KCNMA1−/−) is viable but exhibits pathophysiology in many organ systems. Yet despite the important roles in animal models, the consequences of dysfunctional BK channels in humans are not well characterized. Here, we summarize 16 rare KCNMA1 mutations identified in 37 patients dating back to 2005, with an array of clinically defined pathological phenotypes collectively referred to as “KCNMA1-linked channelopathy.” These mutations encompass gain-of-function (GOF) and loss-of-function (LOF) alterations in BK channel activity, as well as several variants of unknown significance (VUS). Human KCNMA1 mutations are primarily associated with neurological conditions, including seizures, movement disorders, developmental delay, and intellectual disability. Due to the recent identification of additional patients, the spectrum of symptoms associated with KCNMA1 mutations has expanded but remains primarily defined by brain and muscle dysfunction. Emerging evidence suggests the functional BK channel alterations produced by different KCNMA1 alleles may associate with semi-distinct patient symptoms, such as paroxysmal nonkinesigenic dyskinesia (PNKD) with GOF and ataxia with LOF. However, due to the de novo origins for the majority of KCNMA1 mutations identified to date and the phenotypic variability exhibited by patients, additional evidence is required to establish causality in most cases. The symptomatic picture developing from patients with KCNMA1-linked channelopathy highlights the importance of better understanding the roles BK channels play in regulating cell excitability. Establishing causality between KCNMA1-linked BK channel dysfunction and specific patient symptoms may reveal new treatment approaches with the potential to increase therapeutic efficacy over current standard regimens.

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“…It has been classified into four different types on the basis of triggering factors responsible for the episodes that are (i) Paroxysmal kinesigenic dyskinesias (PKD) which is known to be triggered by sudden voluntary movements and unexpected stimulus, (ii) Paroxysmal non-kinesigenic dyskinesias (PNKD) that can be triggered by factors other than movement like stress, fatigue, and alcohol consumption, (iii) Paroxysmal exercise(exertion)-induced dyskinesias (PED) which could be triggered by prolonged exercise, and lastly (iv) Paroxysmal hypnogenic dyskinesias (PHD) in which attack can be triggered during Non-rapid eye movement sleep (Unterberger and Trinka 2008). Increased studies revealed that familial PKD can be caused by channel mutations and it has been identified that coexistence of generalized epilepsy and paroxysmal dyskinesiais caused by mutations in KCNMA1 gene.…”

Section: Paroxysmal Dyskinesiamentioning

confidence: 99%

Mutational Consequences of Aberrant Ion Channels in Neurological Disorders

2014

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Neurological channelopathies are attributed to aberrant ion channels affecting CNS, PNS, cardiac, and skeletal muscles. To maintain the homeostasis of excitable tissues, functional ion channels are necessary to rely electrical signals, whereas any malfunctioning serves as an intrinsic factor to develop neurological channelopathies. Molecular basis of these disease is studied based on genetic and biophysical approaches, e.g., loci positional cloning, whereas pathogenesis and bio-behavioral analysis revealed the dependency on genetic mutations and inter-current triggering factors. Although electrophysiological studies revealed the possible mechanisms of diseases, analytical study of ion channels remained unsettled and therefore underlying mechanism in channelopathies is necessary for better clinical application. Herein, we demonstrated (i) structural and functional role of various ion channels (Na(+), K(+), Ca(2+),Cl(-)), (ii) pathophysiology involved in the onset of their associated channelopathies, and (iii) comparative sequence and phylogenetic analysis of diversified sodium, potassium, calcium, and chloride ion channel subtypes.

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Review: Diagnosis and treatment of paroxysmal dyskinesias revisited

Cited by 42 publications

References 59 publications

Paroxysmal kinesigenic dyskinesia in pseudohypoparathyroidism: Is basal ganglia calcification a necessary finding?

Paroxysmal kinesigenic dyskinesia in pseudohypoparathyroidism: Is basal ganglia calcification a necessary finding?

KCNMA1-linked channelopathy

Mutational Consequences of Aberrant Ion Channels in Neurological Disorders

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