Search

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.

Paroxysmal dyskinesias (PD) are rare movement disorders characterized by recurrent attacks of dystonia, chorea, athetosis, or their combination, with large phenotypic and genetic heterogeneity. 3-Hydroxy-isobutyryl-CoA hydrolase (HIBCH) deficiency is a neurodegenerative disease characterized in most patients by a continuous decline in psychomotor abilities or a secondary regression triggered by febrile infections and metabolic crises. We describe two PD patients from two pedigrees, both carrying a homozygous c.913A > G, p.Thr305Ala mutation in the HIBCH gene, associated with an unusual clinical presentation. The first patient presented in the second year of life with right paroxysmal hemidystonia lasting for 30 minutes, without any loss of consciousness and without any triggering factor. The second patient has presented since the age of 3 recurrent exercise-induced PD episodes which have been described as abnormal equinovarus, contractures of the lower limbs, lasting for 1 to 4 hours, associated with choreic movements of the hands. Their neurological examination and metabolic screening were normal, while brain magnetic resonance imaging showed abnormal signal of the pallidi. We suggest that HIBCH deficiency, through the accumulation of metabolic intermediates of the valine catabolic pathway, leads to a secondary defect in respiratory chain activity and pyruvate dehydrogenase (PDH) activity and to a broad phenotypic spectrum ranging from Leigh syndrome to milder phenotypes. The two patients presented herein expand the spectrum of the disease to include unusual paroxysmal phenotypes and HIBCH deficiency should be considered in the diagnostic strategy of PD to enable adequate preventive treatment. [ABSTRACT FROM AUTHOR]

RHOBTB2 was first described as epileptogenic when it presents a missense variant in 2016 and studied more specifically in 2018. It is a gene that causes rare, but potentially severe childhood epileptic encephalopathy. In 2021, research confirmed that heterozygous mutations of RHOBTB2 included other clinical signs besides these encephalopathies. Thus, these infantile epilepsies are mainly associated with highly variable phenotypes, with developmental delay, post-traumatic encephalitis, paroxysmal movement disorders and iconographic brain damage. In this work, after presenting a clinical case, we will recall the role of RhoGTPases on neuronal development. We will then discuss a study which highlighted the neurodevelopmental impact of mutations on the RHOBTB2 gene by carrying out work on Drosophila melanogaster flies. Finally, we will compare the presented clinical case with a literature review.

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]

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]

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.

Background: The diagnosis of psychogenic paroxysmal movement disorders (PPMD) can be challenging, in particular their distinction from the primary paroxysmal dyskinesias (PxD) remains difficult.Methods: Here we present a large series of 26 PPMD cases, describe their characteristics, contrast them with primary PxD and focus on their distinguishing diagnostic features.Results: Mean age at onset was 38.6 years, i.e. much later than primary PxD. Women were predominantly affected (73%). Most subjects (88.4%) had long attacks, and unlike primary PxD there was a very high within-subject variability for attack phenomenology, duration and frequency. Dystonia was the most common single movement disorder presentation, but 69.2% of the patients had mixed or complex PxD. In 50% of PPMD cases attack triggers could be identified but these were unusual for primary PxD. 42.3% of patients employed unusual strategies to alleviate or stop the attacks. Response to typical medication used for primary PxD was poor. Precipitation of the disorder due to physical or emotional life events and stressors were documented in 57.6% and 65.3% of the cases respectively. Additional interictal psychogenic signs were documented in 34.6% and further medically unexplained somatic symptoms were present in 50% of the cases. 19.2% of patients had a comorbid organic movement disorder and 26.9% had pre-existing psychiatric comorbidities.Conclusion: Although the phenotypic presentation of PPMD can be highly diverse, certain clinical characteristics help in distinguishing this condition from the primary forms of PxD. Recognition is important as multidisciplinary treatment approaches led to significant improvement in most cases. [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]

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 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]

Paroxysmal dyskinesias are rare disorders characterized by various involuntary movements induced by triggers such as fatigue, emotional stress, caffeine, sudden movement and others. Except for primary, genetical ly determined diseases, there are secondary paroxysmal dyskinesias caused most commonly by multiple sclerosis. In this article, we describe a case of a young man with sudden onset attacks of kinesigenic paroxysmal dystonia without any other symptoms. The diagnosis of clinically isolated syndrome in multiple sclerosis was made and demyelinating plaque within the cervical spine was suggested as the cause of dyskinesia. We discuss in detail diagnostic steps, treatment and outcome of this patient in context of literature available about this condition. [ABSTRACT FROM AUTHOR]

• Both the clinical course and the management of PxDs in pregnancy are uncovered issues. • Retrospective data show an improvement of movement disorder during pregnancy. • Antidyskinetic drug discontinuation resulted in good pregnancy outcome in PRRT2 -PxD. [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]

Most movement disorders, reflecting degenerative disorders, develop in a slowly progressive fashion. Some movement disorders, however, manifest with an acute onset. We wish to give an overview of the management and therapy of those acute-onset movement disorders. Drug–induced movement disorders are mainly caused by dopamine–receptor blockers (DRB) as used as antipsychotics (neuroleptics) and antiemetics. Acute dystonic reactions usually occur within the first four days of treatment. Typically, cranial pharyngeal and cervical muscles are affected. Anticholinergics produce a prompt relief.Akathisia is characterized by an often exceedingly bothersome feeling of restlessness and the inability to remain still. It is a common side effect of DRB and occurs within few days after their initiation. It subsides when DRB are ceased.Neuroleptic Malignant Syndrome is a rare, but life–threatening adverse reaction to DRB which may occur at any time during DRB application. It is characterised by hyperthermia, rigidity, reduced consciousness and autonomic failure. Therapeutically immediate DRB withdrawal is crucial.Additional dantrolene or bromocriptine application together with symptomatic treatment may be necessary. Paroxysmal dyskinesias are childhood onset disorders characterised by dystonic postures, chorea, athetosis and ballism occurring at irregular intervals. In Paroxysmal Kinesigenic Dyskinesia they are triggered by rapid movements, startle reactions or hyperventilation. They last up to 5 minutes, occur up to 100 times per day and are highly sensitive to anticonvulsants. In Paroxysmal Non–Kinesiogenic Dyskinesia they cannot be triggered, occur less frequently and last longer.Other paroxysmal dyskinesias include hypnogenic paroxysmal dyskinesias, paroxysmal exertional dyskinesia, infantile paroxysmal dystonias, Sandifer's syndrome and symptomatic paroxysmal dyskinesias. In Hereditary Episodic Ataxia Type 1 attacks of ataxia last for up to two minutes, may be accompanied by dysarthria and dystonia and usually respond to phenytoin. In Type 2 they can last for several hours, may be accompanied by vertigo, headache and malaise and usually respond to acetazolamide. Symptomatic episodic ataxias can occur in a number of metabolic disorders, but also in multiple sclerosis and Behcet's disease. [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.

Paroxysmal dyskinesias represent an unusual group of movement disorders featuring intermittent involuntary paroxysmal movements including dystonia, chorea, athetosis, ballismus, or a combination of these. Secondary paroxysmal dyskinesias are rare. We report on two patients: a male with Wilson's disease who presented paroxysmal kinesigenic dyskinesias in the titration period with d -penicillamine, and a female who initially developed paroxysmal kinesigenic dyskinesias and turned out to have a subacute sclerosing panencephalitis. Carbamazepine had a remarkable beneficial effect on paroxysmal symptoms in both of them but it does not replace the treatment of the underlying illness. [ABSTRACT FROM AUTHOR]

Copyright of Arquivos de Neuro-Psiquiatria is the property of Thieme Medical Publishing Inc. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Abstract: Neuroacanthocytosis (NA) comprises a genetically heterogeneous group of disorders characterized by dysfunction of the erythrocyte membrane, presenting with acanthocytes and several neurological manifestations. We report the case of a 42-year-old woman with NA who in addition had episodes consistent with paroxysmal dyskinesias. She was diagnosed with NA featuring mild chorea, weakness of the right lower extremity and myoclonic jerks. However, one year after onset she presented attacks of paroxysmal abnormal movements, consistent with paroxysmal kinesigenic dyskinesias. Carbamazepine markedly reduced the frequency and severity of the attacks. Our case illustrates that paroxysmal dyskinesias can be a hitherto unrecognized manifestation of neuroacanthocytosis responsive to carbamazepine. [Copyright &y& Elsevier]

Abstract: Idiopathic paroxysmal dyskinesias (PxD) are characterized by attacks of hyperkinetic movement, with no inter-ictal symptoms. We report two cases, one with paroxysmal kinesigenic dyskinesia and another with paroxysmal exercise-induced dystonia, both of whom had myoclonus and dystonia between attacks. This previously unreported association highlights the heterogeneity of paroxysmal movement disorders. [Copyright &y& Elsevier]

The article describes the case of a 48-year-old male patient with paroxysmal exertion-induced dyskinesia (PED). The medical history of the patient and the symptoms he manifested are presented. Physical examination, laboratory tests and imaging done on the patient are mentioned. Background information on the condition is provided.

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.