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Movement Disorders : Official Journal... Mar 2022Paroxysmal kinesigenic dyskinesia (PKD) is the most common type of paroxysmal dyskinesias. Only one-third of PKD patients are attributed to proline-rich transmembrane...
BACKGROUND
Paroxysmal kinesigenic dyskinesia (PKD) is the most common type of paroxysmal dyskinesias. Only one-third of PKD patients are attributed to proline-rich transmembrane protein 2 (PRRT2) mutations.
OBJECTIVE
We aimed to explore the potential causative gene for PKD.
METHODS
A cohort of 196 PRRT2-negative PKD probands were enrolled for whole-exome sequencing (WES). Gene Ranking, Identification and Prediction Tool, a method of case-control analysis, was applied to identify the candidate genes. Another 325 PRRT2-negative PKD probands were subsequently screened with Sanger sequencing.
RESULTS
Transmembrane Protein 151 (TMEM151A) variants were mainly clustered in PKD patients compared with the control groups. 24 heterozygous variants were detected in 25 of 521 probands (frequency = 4.80%), including 18 missense and 6 nonsense mutations. In 29 patients with TMEM151A variants, the ratio of male to female was 2.63:1 and the mean age of onset was 12.93 ± 3.15 years. Compared with PRRT2 mutation carriers, TMEM151A-related PKD were more common in sporadic PKD patients with pure phenotype. There was no significant difference in types of attack and treatment outcome between TMEM151A-positive and PRRT2-positive groups.
CONCLUSIONS
We consolidated mutations in TMEM151A causing PKD with the aid of case-control analysis of a large-scale WES data, which broadens the genotypic spectrum of PKD. TMEM151A-related PKD were more common in sporadic cases and tended to present as pure phenotype with a late onset. Extensive functional studies are needed to enhance our understanding of the pathogenesis of TMEM151A-related PKD. © 2021 International Parkinson and Movement Disorder Society.
Topics: Adolescent; Child; Female; Humans; Male; Chorea; Dystonia; Membrane Proteins; Mutation; Phenotype
PubMed: 34820915
DOI: 10.1002/mds.28865 -
Journal of Back and Musculoskeletal... 2023Kinesio taping (KT) is one of the treatment methods used on patients with shoulder impingement syndrome (SIS). There are different results regarding its effectiveness in... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Kinesio taping (KT) is one of the treatment methods used on patients with shoulder impingement syndrome (SIS). There are different results regarding its effectiveness in the literature.
OBJECTIVE
To investigate the effects of scapular KT combined with a conventional physiotherapy program on scapular dyskinesia, shoulder pain, upper extremity function, and well-being in patients with SIS.
METHODS
The study was conducted with 60 outpatients diagnosed with SIS, aged 40-65 years. The patients were divided into two groups: KT [conventional physiotherapy program + scapular KT (targets scapular retraction and is applied along the inferior-medial edge of the scapula, starting from the processus coracoids), n= 30] and control [conventional physiotherapy program, n= 30]. In before- and after-treatment evaluations, the Lateral Scapular Slide Test (LSST) for scapular dyskinesia, a Visual Analogue Scale (VAS) for shoulder pain, and the Disabilities of the Arm, Shoulder, and Hand (DASH) for upper extremity function were used. In addition, at the end of treatment, a Kinesio taping Satisfaction Survey, created by the researchers, was filled out by the KT group for the assessment of well-being.
RESULTS
The interaction effect of Group*Time was not statistically significant in all outcome measures (p> 0.05). However, the main effect of both group and time was statistically significant in the DASH-Function/Symptom, VAS-Rest, VAS-Activity, and VAS-Night (p< 0.05). Moreover, only the main effect of time was statistically significant in LSST-1 and LSST-3 (p< 0.05). In the KT group, the satisfaction level was 8.50 ± 1.69 and the recommendation level was 8.72 ± 1.81.
CONCLUSION
Both conventional physiotherapy programs and additional scapular KT improved scapular dyskinesia, reduced pain, and increased the upper extremity function. Adding scapular KT to treatment did not change the results, but it had positive psychological effects and yielded a high satisfaction rate.
Topics: Humans; Shoulder Impingement Syndrome; Shoulder Pain; Scapula; Physical Therapy Modalities; Athletic Tape; Dyskinesias; Treatment Outcome
PubMed: 37694348
DOI: 10.3233/BMR-220396 -
Neurological Sciences : Official... Oct 2022Tremor-like movements in patients with the grasp phenomenon are reported rarely.
OBJECTIVE
Tremor-like movements in patients with the grasp phenomenon are reported rarely.
METHODS
We clinically and neuroradiologically studied four patients with tremor-like movements related to the grasp phenomenon.
RESULTS
All of the patients were women aged between 61 and 98 years. In the present cases, tremor-like movements were observed in the right arm and/or leg. The movements occurred suddenly in three of the patients and chronically in one. The movements were stereotypic, often rhythmical, tremor-like, and accompanied with groping or picking-like movements. All of the patients displayed the grasp phenomenon, including grasp reflex and/or instinctive grasping reaction ipsilateral to the movements. Two patients had a recent broad infarct ipsilateral to the movements. One patient had meningioma contralateral to the movements, which had been surgically resected. The other patient did not have any radiologically proven cerebral lesions, although she had a history of focal seizures contralateral to the movements.
CONCLUSIONS
It was suggested that their abnormal movements were closely related to the grasp phenomenon. We concluded that their characteristic tremor-like movements, a "tremor-like grasp phenomenon," was a variation of the grasp phenomenon that was due to hyperexcitation of the frontal lobe contralateral to the movements.
Topics: Aged; Aged, 80 and over; Dyskinesias; Female; Frontal Lobe; Hand Strength; Humans; Male; Middle Aged; Movement; Tremor
PubMed: 35819560
DOI: 10.1007/s10072-022-06261-y -
The Lancet. Neurology Sep 2019A large and ever-growing number of medications can induce various movement disorders. Drug-induced movement disorders are disabling but are often under-recognised and... (Review)
Review
A large and ever-growing number of medications can induce various movement disorders. Drug-induced movement disorders are disabling but are often under-recognised and inappropriately managed. In particular, second generation antipsychotics, like first generation agents, are associated with potentially debilitating side-effects, most notably tardive syndromes and parkinsonism, as well as potentially fatal acute syndromes. Appropriate, evidence-based management is essential as these drugs are being prescribed to a growing population vulnerable to these side-effects, including children and elderly people. Prevention of the development of drug-induced movement disorders is an important consideration when prescribing medications that can induce movement disorders. Recent developments in diagnosis, such as the use of dopamine transporter imaging for drug-induced parkinsonism, and treatment, with the approval of valbenazine and deutetrabenazine, the first drugs indicated for tardive syndromes, have improved outcomes for many patients with drug-induced movement disorders. Future research should focus on development of safer antipsychotics and specific therapies for the different tardive syndromes and the treatment of drug-induced parkinsonism.
Topics: Antipsychotic Agents; Disease Management; Dyskinesia, Drug-Induced; Humans
PubMed: 31279747
DOI: 10.1016/S1474-4422(19)30152-8 -
Journal of Psychopharmacology (Oxford,... Jan 2021Dystonia is by far the most intrusive and invalidating extrapyramidal side effect of potent classical antipsychotic drugs. Antipsychotic drug-induced dystonia is... (Review)
Review
Dystonia is by far the most intrusive and invalidating extrapyramidal side effect of potent classical antipsychotic drugs. Antipsychotic drug-induced dystonia is classified in both acute and tardive forms. The incidence of drug-induced dystonia is associated with the affinity to inhibitory dopamine D2 receptors. Particularly acute dystonia can be treated with anticholinergic drugs, but the tardive form may also respond to such antimuscarinic treatment, which contrasts their effects in tardive dyskinesia. Combining knowledge of the pathophysiology of primary focal dystonia with the anatomical and pharmacological organization of the extrapyramidal system may shed some light on the mechanism of antipsychotic drug-induced dystonia. A suitable hypothesis is derived from the understanding that focal dystonia may be due to a faulty processing of somatosensory input, so leading to inappropriate execution of well-trained motor programmes. Neuroplastic alterations of the sensitivity of extrapyramidal medium-sized spiny projection neurons to stimulation, which are induced by the training of specific complex movements, lead to the sophisticated execution of these motor plans. The sudden and non-selective disinhibition of indirect pathway medium-sized spiny projection neurons by blocking dopamine D2 receptors may distort this process. Shutting down the widespread influence of tonically active giant cholinergic interneurons on all medium-sized spiny projection neurons by blocking muscarinic receptors may result in a reduction of the influence of extrapyramidal cortical-striatal-thalamic-cortical regulation. Furthermore, striatal cholinergic interneurons have an important role to play in integrating cerebellar input with the output of cerebral cortex, and are also targeted by dopaminergic nigrostriatal fibres affecting dopamine D2 receptors.
Topics: Antipsychotic Agents; Cholinergic Antagonists; Cholinergic Neurons; Dopamine D2 Receptor Antagonists; Dyskinesia, Drug-Induced; Dystonia; Extrapyramidal Tracts; Humans; Interneurons; Muscarinic Antagonists; Neuronal Plasticity; Receptors, Dopamine D2
PubMed: 32900259
DOI: 10.1177/0269881120944156 -
Neurology Mar 2022The main culprit gene for paroxysmal kinesigenic dyskinesia, characterized by brief and recurrent attacks of involuntary movements, is . The location of the primary...
BACKGROUND AND OBJECTIVES
The main culprit gene for paroxysmal kinesigenic dyskinesia, characterized by brief and recurrent attacks of involuntary movements, is . The location of the primary dysfunction associated with paroxysmal dyskinesia remains a matter of debate and may vary depending on the etiology. While striatal dysfunction has often been implicated in these patients, evidence from preclinical models indicates that the cerebellum could also play a role. We aimed to investigate the role of the cerebellum in the pathogenesis of -related dyskinesia in humans.
METHODS
We enrolled 22 consecutive right-handed patients with paroxysmal kinesigenic dyskinesia with a pathogenic variant of and their matched controls. Participants underwent a multimodal neuroimaging protocol. We recorded anatomic and diffusion-weighted MRI, as well as resting-state fMRI, during which we tested the aftereffects of sham and repetitive transcranial magnetic stimulation applied to the cerebellum on endogenous brain activity. We quantified the structural integrity of gray matter using voxel-based morphometry, the structural integrity of white matter using fixel-based analysis, and the strength and direction of functional cerebellar connections using spectral dynamic causal modeling.
RESULTS
Patients with had decreased gray matter volume in the cerebellar lobule VI and in the medial prefrontal cortex, microstructural alterations of white matter in the cerebellum and along the tracts connecting the cerebellum to the striatum and the cortical motor areas, and dysfunction of cerebellar motor pathways to the striatum and the cortical motor areas, as well as abnormal communication between the associative cerebellum (Crus I) and the medial prefrontal cortex. Cerebellar stimulation modulated communication within the motor and associative cerebellar networks and tended to restore this communication to the level observed in healthy controls.
DISCUSSION
Patients with -related dyskinesia have converging structural alterations of the motor cerebellum and related pathways with a dysfunction of cerebellar output toward the cerebello-thalamo-striato-cortical network. We hypothesize that abnormal cerebellar output is the primary dysfunction in patients with a pathogenic variant resulting in striatal dysregulation and paroxysmal dyskinesia. More broadly, striatal dysfunction in paroxysmal dyskinesia might be secondary to aberrant cerebellar output transmitted by thalamic relays in certain disorders.
TRIAL REGISTRATION INFORMATION
ClinicalTrials.gov identifier: NCT03481491.
Topics: Cerebellar Diseases; Cerebellum; Chorea; Dystonia; Humans; Magnetic Resonance Imaging; Membrane Proteins; Nerve Tissue Proteins
PubMed: 35058336
DOI: 10.1212/WNL.0000000000200060 -
Journal of Neuroimaging : Official... Mar 2021Paroxysmal kinesigenic dyskinesia (PKD) is a rare movement disorder of the nervous system, and little is known about its pathogenesis. Currently, the diagnosis of PKD... (Review)
Review
Paroxysmal kinesigenic dyskinesia (PKD) is a rare movement disorder of the nervous system, and little is known about its pathogenesis. Currently, the diagnosis of PKD is primarily based on clinical manifestations, with little objective evidence. Neuroimaging has been used to explore the pathological changes in cerebral structure and function associated with PKD. The current review highlights recent advances in neuroimaging to provide a better understanding of the neural mechanisms and early diagnosis of this disorder. Several studies utilizing single-photon emission computed tomography (CT), positron emission tomography, and structural and functional magnetic resonance imaging have found significant localized abnormalities in the caudate nucleus, putamen, pallidum, thalamus, and frontoparietal cortex in PKD patients. These studies have also revealed alterations in interhemispheric functional connectivity between the brain regions of bilateral cerebral hemispheres such as the putamen, primary motor cortex, supplementary motor area, dorsal lateral prefrontal cortex, and primary somatosensory cortex in these patients. In addition, proline-rich transmembrane protein 2 gene mutations can affect the functional organization of the brain in PKD. These results suggest that the neural mechanisms of PKD are associated with the disruption of both structural and/or functional properties in basal ganglia-thalamo-cortical circuitry and interhemispheric functional connectivity. PKD can be considered a circuitry/network disorder and is not restricted to localized structural and/or functional abnormalities. Multimodal neuroimaging combined with gene analysis can provide additional valuable information for a better understanding of the pathogenesis and early diagnosis of this disorder.
Topics: Brain; Dystonia; Humans; Magnetic Resonance Imaging; Neuroimaging
PubMed: 33227178
DOI: 10.1111/jon.12811 -
Schizophrenia Research Jan 2024Abnormal movements are intrinsic to some forms of endogenous psychoses. Spontaneous dyskinesias are observed in drug-naïve first-episode patients and at-risk subjects....
Abnormal movements are intrinsic to some forms of endogenous psychoses. Spontaneous dyskinesias are observed in drug-naïve first-episode patients and at-risk subjects. However, recent descriptions of spontaneous dyskinesias may actually represent the rediscovery of a more complex phenomenon, 'parakinesia' which was described and documented in extensive cinematographic recordings and long-term observations by German and French neuropsychiatrists decades before the introduction of antipsychotics. With the emergence of drug induced movement disorders, the description of parakinesia has been refined to emphasize the features enabling differential diagnosis with tardive dyskinesia. Unfortunately, parakinesia was largely neglected by mainstream psychiatry to the point of being almost absent from the English-language literature. With the renewed interest in motor phenomena intrinsic to SSD, it was timely not only to raise awareness of parakinesia, but also to propose a scientifically usable definition for this phenomenon. Therefore, we conducted a Delphi consensus exercise with clinicians familiar with the concept of parakinesia. The original concept was separated into hyperkinetic parakinesia (HPk) as dyskinetic-like expressive movements and parakinetic psychomotricity (PPM), i.e., patient's departing from the patient's normal motion style. HPk prevails on the upper part of the face and body, resembling expressive and reactive gestures that not only occur inappropriately but also appear distorted. Abnormal movements vary in intensity depending on the level of psychomotor arousal and are thus abated by antipsychotics. HPk frequently co-occurs with PPM, in which gestures and mimics lose their naturalness and become awkward, disharmonious, stiff, mannered, and bizarre. Patients are never spontaneously aware of HPk or PPM, and the movements are never experienced as self-dystonic or self-alien. HPk and PPM are highly specific to endogenous psychoses, in which they are acquired and progressive, giving them prognostic value. Their differential diagnoses and correspondences with current international concepts are discussed.
Topics: Humans; Delphi Technique; Psychotic Disorders; Movement Disorders; Tardive Dyskinesia; Antipsychotic Agents
PubMed: 36357299
DOI: 10.1016/j.schres.2022.09.024 -
Neurology India 2022Dopamine deficiency causes Parkinson's disease (PD), and on treatment, levodopa is the gold standard. Various drug-metabolizing enzymes and drug receptors are believed...
BACKGROUND
Dopamine deficiency causes Parkinson's disease (PD), and on treatment, levodopa is the gold standard. Various drug-metabolizing enzymes and drug receptors are believed to be involved in prompting dyskinesias due to the extended usage of levodopa. Shreds of evidence in genomic studies have presented that ADORA2A receptor antagonism has beneficial outcomes to avoid these drug-induced side effects.
OBJECTIVE
The aim of this study was to study the polymorphisms of rs2298383, rs35060421, and rs5751876 in the ADORA2A in patients diagnosed as PD and describe their possible relationships with levodopa-induced dyskinesias (LID).
METHODS
One-hundred and seventy-two patients were recruited and separated as the study and the control group. DNA was achieved from peripheral venous blood, high resolution melting analysis, and reverse-transcriptase PCR was performed.
RESULTS
The allele differences among the groups were not statistically significant. Although it was not statistically significant, the rs35060421 allele was observed to repeat more frequently. However, we did not find an association between such polymorphisms of ADORA2A and LID.
CONCLUSIONS
Although this result showed that a higher sample number might produce different results as possible, current results in the Turkish sample indicated that these alleles of ADORA2A might not be related to LID in patients.
Topics: Antiparkinson Agents; Dopamine Plasma Membrane Transport Proteins; Dyskinesias; Humans; Levodopa; Parkinson Disease; Polymorphism, Genetic
PubMed: 35532631
DOI: 10.4103/0028-3886.344646 -
CNS Spectrums Aug 2019Tardive dyskinesia (TD) was first described in 1964, but treatment for this sometimes poorly characterized condition lagged decades as it was labored by medico-legal... (Review)
Review
Tardive dyskinesia (TD) was first described in 1964, but treatment for this sometimes poorly characterized condition lagged decades as it was labored by medico-legal implications. TD has often been lumped with other medication-induced disorders and incorrectly classified as extrapyramidal symptoms. TD is likely to be under-recognized for many of these reasons. Though diverse in its presentations, TD is distinct in terms of time course, pathophysiology, and phenomenology.
Topics: Humans; Tardive Dyskinesia
PubMed: 31482777
DOI: 10.1017/S1092852919001263