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Abstract 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.

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]

Introduction: Paroxysmal dyskinesias and episodic ataxias are often caused by mutations in genes related to cell membrane and synaptic function. Despite the exponential increase in publications of genetically confirmed cases, management remains largely clinical based on non-systematic evidence. Areas covered: The authors provide a historical and clinical review of the main types of paroxysmal dyskinesias and episodic ataxias, with recommendations for diagnosis and management of patients suffering from these conditions. Expert opinion: After secondary paroxysmal dyskinesias, the most common paroxysmal movement disorders are likely to be PRRT2-associated paroxysmal kinesigenic dyskinesias, which respond well to small doses of carbamazepine, and episodic ataxia type 2, which often responds to acetazolamide. Familial paroxysmal non-kinesigenic dyskinesias are largely caused by mutations in PNKD and have poor response to therapy but improve with age. Exercise-induced dyskinesias are genetically heterogeneous, caused by disorders of glucose transport, mitochondrial function, dopaminergic pathways or neurodegenerative conditions amongst others. GNAO1 and ADCY5 mutations can also cause paroxysmal movement disorders, often in the context of ongoing motor symptoms. Although a therapeutic trial is justified for classic cases and in limited resource settings, genetic testing may help direct initial or rescue therapy. Deep brain stimulation may be an option for severe cases. [ABSTRACT FROM AUTHOR]

Paroxysmal dyskinesias (PxD) comprise a group of heterogeneous syndromes characterized by recurrent attacks of mainly dystonia and/or chorea, without loss of consciousness. PxD have been classified according to their triggers and duration as paroxysmal kinesigenic dyskinesia, paroxysmal nonkinesigenic dyskinesia and paroxysmal exertion-induced dyskinesia. Of note, the spectrum of genetic and nongenetic conditions underlying PxD is continuously increasing, but not always a phenotype–etiology correlation exists. This creates a challenge in the diagnostic work-up, increased by the fact that most of these episodes are unwitnessed. Furthermore, other paroxysmal disorders, included those of psychogenic origin, should be considered in the differential diagnosis. In this review, some key points for the diagnosis are provided, as well as the appropriate treatment and future approaches discussed. [ABSTRACT FROM AUTHOR]

Limb shaking syndrome (LSS) is a rare presentation of transient ischemic attacks (TIAs), usually secondary to a critical carotid stenosis compromising intracranial circulation, first described 40 years ago. Two additional cases are described herein, aiming to add on to previous descriptions, and to warn physicians about this potentially harming and rather uncommon condition.

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]

Abstract: Thyroid hormones are known to be essential for growth, development and metabolism. Recently mutations in the SLC16A2 gene coding for the monocarboxylate thyroid hormone transporter 8, MCT8, have been associated with Allan–Herndon–Dudley syndrome (AHDS), an X-linked condition characterized by severe mental retardation, dysarthria, athetoid movements, muscle hypoplasia and spastic paraplegia. Here we describe in detail the clinical and biochemical features in a boy affected by AHDS with severe neurological abnormalities and a novel de novo SLC16A2 gene insertion, 1343–1344insGCCC, resulting in a truncated protein lacking the last four transmembrane domains (TMDs) as well as the carboxyl cytoplasmic end. He presents mental retardation, axial hypotonia, hypertonia of arms and legs, paroxysmal dyskinesias, seizures. The endocrine phenotype showed low serum total and free thyroxine (T4), very elevated total and free triiodothyronine (T3) and normal thyrotropin (TSH) with blunted response to thyrotropin-releasing hormone (TRH). The latter finding was unexpected and suggested that the lack of functional MCT8 was counterbalanced at the thyrotrope cell level by high serum T3 concentration and/or by increased intrapituitary type 2 deiodinase (D2) activity. Our case constitutes a relevant contribution to better characterize this disorder and to elucidate the functional consequences of SLC16A2 gene mutations. [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]

Paroxysmal dyskinesias (PD) are thought to be rare movement disorders. The overwhelming majority of reported cases are primary. Secondary PD has seen reported to occur in some conditions, mainly in multiple sclerosis and head trauma. The anatomic origin of the lesion is also rarely seen at the spinal cord. Our objective was to describe four patients with paroxysmal dystonia secondary to spinal lesions during the recovering phase of a neuromyelitis optica (NMO) bout. In the reviewed literature, we do not find any report of PD related to NMO.Discinesias paroxísticas (DP) são distúrbios do movimento raros. A maioria dos casos relatados é de origem primária. DP secundárias têm sido relatadas em algumas condições, principalmente na esclerose múltipla e no trauma craniano. A origem anatômica da lesão também é raramente observada na medula. O objetivo deste trabalho foi descrever quatro pacientes com distonia paroxística secundária a lesões medulares, ocorrida durante a fase de recuperação do surto de neuromielite óptica (NMO). Na literatura consultada, não encontramos qualquer relato de DP secundárias à NMO.

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Hyperkinetic movement disorders such as tremors are not uncommon in patients with multiple sclerosis (MS). The classical feature is intention tremor, whereas rest tremors appear not to occur. Treatment is mainly invasive, with options of Gamma Knife surgery, thalamotomy or deep brain stimulation depending on individual circumstances. Deep brain stimulation is the only option for patients who require a bilateral intervention. All treatment recommendations have only low evidence. Tremors can also be cured spontaneously by a subsequent strategic MS lesion. Paroxysmal dyskinesias are rarer than tremors. The rarest MS movement disorder is symptomatic paroxysmal choreoathetosis, tonic spasms or 'brain stem fits'; attacks are short but frequent, up to 200 per day and generally respond well to carbamazepine.