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A 66‐year‐old British man was referred to our department because of a 2.5 year history of bilateral paroxysmal weakness of the lower limbs. It occurred when he walked for about 10 minutes, so he would stop in place and spontaneously rest for up to 15 minutes. When carbamazepine 200 mg/day was administered, the severity and frequency of the symptoms reduced by half and resolved when the dose was increased to 300 mg/day. Even if no involuntary movement is observed, paroxysmal exercise‐induced dyskinesia should be considered in patients with paroxysmal painless gait disturbance, and a therapeutic trial of anticonvulsants may be helpful. [ABSTRACT FROM AUTHOR]

Historically, the syndrome of primary paroxysmal dyskinesias was considered a group of disorders as a result of ion channel dysfunction. This proposition was primarily based on the discovery of mutations in ion channels, which caused other episodic neurological disorders such as epilepsy and migraine and also supported by the frequent association between paroxysmal dyskinesias and epilepsy. However, the discovery of the genes responsible for the 3 classic forms of paroxysmal dyskinesias disproved this ion channel theory. On the other hand, novel gene mutations implicating ion channels have been recently reported to produce episodic movement disorders clinically similar to the classic paroxysmal dyskinesias. Here, we review the clinical and pathophysiological aspects of the paroxysmal dyskinesias, further proposing a pathophysiological framework according to which they can be classified as synaptopathies (proline-rich transmembrane protein 2 and myofibrillogenesis regulator gene), channelopathies (calcium-activated potassium channel subunit alpha-1 and voltage-gated sodium channel type 8), or transportopathies (solute carrier family 2 member 1). This proposal might serve to explain similarities and differences among the various paroxysmal dyskinesias in terms of clinical features, treatment response, and natural history. © 2017 International Parkinson and Movement Disorder Society. [ABSTRACT FROM AUTHOR]

Paroxysmal dyskinesias ( PDs) are a group of episodic movement disorders with marked variability in clinical manifestation and potential association with epilepsy. PRRT2 has been identified as a causative gene for PDs, but the phenotypes and inheritance patterns of PRRT2 mutations need further clarification. In this study, 10 familial and 21 sporadic cases with PDs and PDs-related phenotypes were collected. Genomic DNA was screened for PRRT2 mutations by direct sequencing. Seven PRRT2 mutations were identified in nine (90.0%) familial cases and in six (28.6%) sporadic cases. Five mutations are novel: two missense mutations (c. 647C>G/p. Pro216Arg and c. 872C>T/p. Ala291Val) and three truncating mutations (c. 117delA/p. Val41TyrfsX49, c. 510dupT/p. Leu171SerfsX3 and c. 579dupA/p. Glu194 ArgfsX6). Autosomal dominant inheritance with incomplete penetrance was observed in most of the familial cases. In the sporadic cases, inheritance was heterogeneous including recessive inheritance with compound heterozygous mutations, inherited mutations with incomplete parental penetrance and de novo mutation. Variant phenotypes associated with PRRT2 mutations, found in 36.0% of the affected cases, included febrile convulsions, epilepsy, infantile non-convulsive seizures ( INCS) and nocturnal convulsions ( NC). All patients with INCS or NC, not reported previously, displayed abnormalities on electroencephalogram ( EEG). No EEG abnormalities were recorded in patients with classical infantile convulsions and paroxysmal choreoathetosis ( ICCA)/paroxysmal kinesigenic dyskinesia ( PKD). Our study further confirms that PRRT2 mutations are the most common cause of familial PDs, displaying both dominant and recessive inheritance. Epilepsy may occasionally occur in ICCA/ PKD patients with PRRT2 mutations. Variant phenotypes INCS or NC differ from classical ICCA/ PKD clinically and electroencephalographically. They have some similarities with, but not identical to epilepsy, possibly represent an overlap between ICCA/ PKD and epilepsy. [ABSTRACT FROM AUTHOR]

Background and aims: This review focuses on some paediatric dystonias such as transient dystonias, new primary paediatric-onset dystonias, dopamine biosynthesis defects and new paroxysmal disorders. It is designed to provide practical help for neurologists and neuropediatricians to make appropriate diagnoses and plan the management of these disorders. Material and methods: Literature searches were performed and original papers, meta-analyses and review papers were reviewed. Conclusion: Paediatric onset dystonia is an increasingly interesting group of conditions that provides an expanding area of neuroscientific knowledge. Given the long life expectancy of children, appropriate treatment at the correct moment will have an important, lasting effect on the personal, social and healthcare domains. [ABSTRACT FROM AUTHOR]

Background and purpose:Mutations in neuronal Kv7 (KCNQ) potassium channels can cause episodic neurological disorders. Paroxysmal dyskinesias with dystonia are a group of movement disorders which are regarded as ion channelopathies, but the role of Kv7 channels in the pathogenesis and as targets for the treatment have so far not been examined.Experimental approach:In the present study, we therefore examined the effects of the activators of neuronal Kv7.2/7.3 channels retigabine (5, 7.5, 10 mg kg−1 i.p. and 10, 20 mg kg−1 p.o.) and flupirtine (10, 20 mg kg−1 i.p.) and of the channel blocker 10,10-bis(4-pyridinylmethyl)-9(10H)-anthracenone (XE-991, 3 and 6 mg kg−1 i.p.) in the dt sz mutant hamster, a model of paroxysmal dyskinesia in which dystonic episodes occur in response to stress.Key results:Retigabine (10 mg kg−1 i.p., 20 mg kg−1 p.o.) and flupirtine (20 mg kg−1 i.p.) significantly improved dystonia, while XE-991 caused a significant aggravation in the dt sz mutant. The antidystonic effect of retigabine (10 mg kg−1 i.p.) was counteracted by XE-991 (3 mg kg−1 i.p.).Conclusions and Implications:These data indicate that dysfunctions of neuronal Kv7 channels deserve attention in dyskinesias. Since retigabine and flupirtine are well tolerated in humans, the present finding of pronounced antidystonic efficacy in the dt sz mutant suggests that neuronal Kv7 channel activators are interesting candidates for the treatment of dystonia-associated dyskinesias and probably of other types of dystonias. The established analgesic effects of Kv7 channel openers might contribute to improvement of these disorders which are often accompanied by painful muscle spasms.British Journal of Pharmacology (2006) 149, 747–753. doi:10.1038/sj.bjp.0706878; published online 3 October 2006 [ABSTRACT FROM AUTHOR]