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Pharmacogenomics Oct 2020Tardive dyskinesia (TD) is an iatrogenic involuntary movement disorder occurring after extended antipsychotic use with unclear pathogenesis. is a liver enzyme involved...
Tardive dyskinesia (TD) is an iatrogenic involuntary movement disorder occurring after extended antipsychotic use with unclear pathogenesis. is a liver enzyme involved in antipsychotic metabolism and a well-studied gene candidate for TD. We tested predicted CYP2D6 metabolizer phenotype with TD occurrence and severity in our two samples of European chronic schizophrenia patients (total n = 198, of which 82 had TD). TD occurrence were associated with extreme metabolizer phenotype, controlling for age and sex (p = 0.012). In other words, individuals with either increased and no CYP2D6 activity were at higher risk of having TD. Unlike most previous findings, TD occurrence may be associated with both extremes of CYP2D6 metabolic activity rather than solely for poor metabolizers.
Topics: Adult; Antipsychotic Agents; Cytochrome P-450 CYP2D6; Female; Humans; Liver; Male; Middle Aged; Schizophrenia; Tardive Dyskinesia; White People
PubMed: 32969762
DOI: 10.2217/pgs-2020-0065 -
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 -
Neurotherapeutics : the Journal of the... Oct 2020Tardive syndrome (TS) is an iatrogenic, often persistent movement disorder caused by drugs that block dopamine receptors. It has a broad phenotype including movement... (Review)
Review
Tardive syndrome (TS) is an iatrogenic, often persistent movement disorder caused by drugs that block dopamine receptors. It has a broad phenotype including movement (orobuccolingual stereotypy, dystonia, tics, and others) and nonmotor features (akathisia and pain). TS has garnered increased attention of late because of the Food and Drug Administration approval of the first therapeutic agents developed specifically for this purpose. This paper will begin with a discussion on pathogenesis, clinical features, and epidemiology. However, the main focus will be treatment options currently available for TS including a suggested algorithm based on current evidence. Recently, there have been significant advances in TS therapy, particularly with the development of 2 new vesicular monoamine transporter type 2 inhibitors for TS and with new data on the efficacy of deep brain stimulation. The discussion will start with switching antipsychotics and the use of clozapine monotherapy which, despite the lack of higher-level evidence, should be considered for the treatment of psychosis and TS. Anti-dyskinetic drugs are separated into 3 tiers: 1) vesicular monoamine transporter type 2 inhibitors, which have level A evidence, are approved for use in TS and are recommended first-choice agents; 2) drugs with lower level of evidence for efficacy including clonazepam, Ginkgo biloba, and amantadine; and 3) drugs that have the potential to be beneficial, but currently have insufficient evidence including levetiracetam, piracetam, vitamin B, melatonin, baclofen, propranolol, zolpidem, and zonisamide. Finally, the roles of botulinum toxin and surgical therapy will be examined. Current therapies, though improved, are symptomatic. Next steps should focus on the prevention and reversal of the pathogenic process.
Topics: Antioxidants; Antipsychotic Agents; Deep Brain Stimulation; Disease Management; Dopamine Antagonists; Humans; Neuroprotective Agents; Tardive Dyskinesia; Vesicular Monoamine Transport Proteins
PubMed: 32720245
DOI: 10.1007/s13311-020-00898-3 -
The lived experience of chronic pain and dyskinesia in children and adolescents with cerebral palsy.BMC Pediatrics Mar 2020To explore the lived experience of chronic pain and dyskinesia in children and adolescents with cerebral palsy.
BACKGROUND
To explore the lived experience of chronic pain and dyskinesia in children and adolescents with cerebral palsy.
METHODS
A convergent parallel mixed methods design was undertaken. First, a quantitative cross-sectional study of participants able to self-report their quality of life was undertaken. This study characterised pain chronicity, intensity, body locations, and quality of life. Second, semi-structured interviews were undertaken with a subset of children and adolescents experiencing chronic pain.
RESULTS
Twenty-five children and adolescents took part in the cross-sectional study, 23 of whom experienced chronic pain and 13 of moderate intensity. Pain was often located in multiple bodily regions (6/21), with no trends in quality of life outcomes detected. Eight participated in semi-structured interviews, which identified three key themes including 'lives embedded with dyskinesia', 'real world challenges of chronic pain', and 'still learning strategies to manage their pain and dyskinesia'.
CONCLUSIONS
A high proportion of children and adolescents with cerebral palsy and dyskinesia who were able to self-report experienced chronic pain. The physical and emotional impacts of living with chronic pain and dyskinesia existed along a spectrum, from those with lesser to greater extent of their impacts. Children and adolescents may benefit from targeted chronic pain education and management within bio-psychosocial models.
Topics: Adolescent; Cerebral Palsy; Child; Chronic Pain; Cross-Sectional Studies; Dyskinesias; Female; Humans; Male; Quality of Life
PubMed: 32183802
DOI: 10.1186/s12887-020-2011-8 -
Developmental Medicine and Child... May 2023To create a shortened, more user-friendly Second Edition of the Dyskinesia Impairment Scale (DIS-II) to assess dystonia and choreoathetosis, and evaluate its construct...
AIM
To create a shortened, more user-friendly Second Edition of the Dyskinesia Impairment Scale (DIS-II) to assess dystonia and choreoathetosis, and evaluate its construct validity and reliability.
METHOD
Scale development included an online expert meeting (n = 21) and iterative discussions within the research group (n = 6). A Rasch measurement model analysis on DIS scores from individuals with dyskinetic cerebral palsy or inherited/idiopathic dystonia (n = 123, 74 males, mean age 14 years, SD 5 years) was performed to evaluate the construct validity and reliability of the DIS-II.
RESULTS
The DIS-II evaluates dystonia and choreoathetosis in action and rest in 11 body regions, with action items scored from 0 to 3 and rest items 0 to 2. The number of videos to record are reduced from 26 to 14 and the items to score are reduced from 144 to 88. Rating scale functioning, goodness-of-fit evaluation, principal component analysis, and targeting met the predefined quality criteria of the study and construct validity was therefore considered good. Furthermore, person reliability indicated that the DIS-II can separate individuals into eight distinct ability levels.
INTERPRETATION
The DIS-II provides valid and reliable measures for dystonia and choreoathetosis, and reduces the administration and scoring time compared with the DIS. The DIS-II logit scores (interval level data) enhance comparison over time and between individuals in clinical practice and research.
WHAT THIS PAPER ADDS
Compared with the Dyskinesia Impairment Scale (DIS), the shortened edition (DIS-II) requires half of the number of videos to be scored. The DIS-II has a simplified rating scale, requiring scoring of 88 instead of 144 items. The DIS-II has shown excellent reliability and good construct validity. The interval properties of the DIS-II are superior to the ordinal level outcome measures of the DIS.
Topics: Male; Humans; Adolescent; Dystonia; Reproducibility of Results; Severity of Illness Index; Dyskinesias; Cerebral Palsy; Dystonic Disorders; Psychometrics
PubMed: 36310446
DOI: 10.1111/dmcn.15444 -
Neuropharmacology Oct 2023Many patients with Parkinson's disease (PD) experiencing l-DOPA-induced dyskinesia (LID) receive adjunct treatment with dopamine agonists, whose functional impact on LID...
Many patients with Parkinson's disease (PD) experiencing l-DOPA-induced dyskinesia (LID) receive adjunct treatment with dopamine agonists, whose functional impact on LID is unknown. We set out to compare temporal and topographic profiles of abnormal involuntary movements (AIMs) after l-DOPA dose challenges including or not the dopamine agonist ropinirole. Twenty-five patients with PD and a history of dyskinesias were sequentially administered either l-DOPA alone (150% of usual morning dose) or an equipotent combination of l-DOPA and ropinirole in random order. Involuntary movements were assessed by two blinded raters prior and every 30 min after drug dosing using the Clinical Dyskinesia Rating Scale (CDRS). A sensor-recording smartphone was secured to the patients' abdomen during the test sessions. The two raters' CDRS scores were highly reliable and concordant with models of hyperkinesia presence and severity trained on accelerometer data. The dyskinesia time curves differed between treatments as the l-DOPA-ropinirole combination resulted in lower peak severity but longer duration of the AIMs compared with l-DOPA alone. At the peak of the AIMs curve (60-120 min), l-DOPA induced a significantly higher total hyperkinesia score, whereas in the end phase (240-270 min), both hyperkinesia and dystonia tended to be more severe after the l-DOPA-ropinirole combination (though reaching statistical significance only for the item, arm dystonia). Our results pave the way for the introduction of a combined l-DOPA-ropinirole challenge test in the early clinical evaluation of antidyskinetic treatments. Furthermore, we propose a machine-learning method to predict CDRS hyperkinesia severity using accelerometer data.
Topics: Humans; Antiparkinson Agents; Dopamine Agonists; Dyskinesia, Drug-Induced; Dystonia; Hyperkinesis; Levodopa; Oxidopamine; Parkinson Disease
PubMed: 37315840
DOI: 10.1016/j.neuropharm.2023.109630 -
Journal of the Neurological Sciences Apr 2022Dystonia and tremor frequently co-occur. In some cases, they have shared biological mechanisms, while in others dystonia and tremor are two comorbid conditions. The term... (Review)
Review
Dystonia and tremor frequently co-occur. In some cases, they have shared biological mechanisms, while in others dystonia and tremor are two comorbid conditions. The term "dystonic tremor" is used to describe tremor in those who have dystonia. Two mutually exclusive definitions of "dystonic tremor" were proposed. According to one definition, dystonic tremor is the tremor in the dystonic body part. An alternate definition of dystonic tremor entails irregular and jerky oscillations that have saw tooth appearance with or without overt dystonia. This paper outlines the differences in two definitions of dystonic tremor and identifies their limitations. Given the diverse views defining "dystonic tremor", this paper will use the term "tremor in dystonia". In addition, we will outline different ways to separate the subtypes of tremor in dystonia. Then we will discuss pathophysiological mechanisms derived from the objective measures and single neuron physiology analyses of tremor in dystonia. This article is part of the Special Issue "Tremor" edited by Daniel D. Truong, Mark Hallett, and Aasef Shaikh.
Topics: Dystonia; Dystonic Disorders; Essential Tremor; Humans; Tremor
PubMed: 35259651
DOI: 10.1016/j.jns.2022.120199 -
Journal of Neurology Jul 2022Movement disorders can be associated with anti-neuronal antibodies.
BACKGROUND
Movement disorders can be associated with anti-neuronal antibodies.
METHODS
We conducted a systematic review of cases with documented anti-neuronal antibodies in serum and/or cerebrospinal fluid published in PubMed before April 1, 2020. Only patients with at least one movement disorder were included. We used random forests for variable selection and recursive partitioning and regression trees for the creation of a data-driven decision algorithm, integrated with expert's clinical feedback.
RESULTS
Three hundred and seventy-seven studies met eligibility criteria, totaling 844 patients and 13 antibodies: amphiphysin, GAD, GlyR, mGluR1, ANNA-2/Ri, Yo/PCA-1, Caspr2, NMDAR, LGI-1, CRMP5/CV2, ANNA-1/Hu, IgLON5, and DPPX. Stiffness/rigidity/spasm spectrum symptoms were more frequently associated with amphiphysin, GAD, and GlyR; ataxia with mGluR1, ANNA-2/Ri, Yo/PCA-1, Caspr2, and ANNA-1/Hu; dyskinesia with NMDAR and paroxysmal movement with LGI1; chorea/choreoathetosis with CRMP5/CV2, IgLON5, and NMDAR; myoclonus with GlyR and DPPX; tremors with ANNA2/Ri and anti-DPPX; and parkinsonism with IgLON5 and NMDAR. Data-driven classification analysis determined the following diagnostic predictions (with probability selection): psychiatric symptoms and dyskinesia predicted NMDAR (71% and 87%, respectively); stiffness/rigidity/spasm and ataxia, GAD (67% and 47%, respectively); ataxia and opsoclonus, ANNA-2/Ri (68%); chorea/choreoathetosis, CRMP5/CV2 (41%). These symptoms remained the top predictors in random forests analysis. The integration with an expert opinion analysis refined the precision of the approach. Breast and lung tumors were the most common tumors. On neuroimaging, cerebellar involvement was associated with GAD and Yo/PCA-1; temporal involvement with Caspr2, LGI-1, ANNA-1/Hu.
CONCLUSION
Selected movement disorders are associated with specific anti-neuronal antibodies. The combination of data-driven and expert opinion approach to the diagnosis may assist early management efforts.
Topics: Autoantibodies; Cell Adhesion Molecules, Neuronal; Cerebellar Ataxia; Chorea; Humans; Movement Disorders; Spasm
PubMed: 35024921
DOI: 10.1007/s00415-021-10934-7 -
Journal of Neuroengineering and... Feb 2021Interventions to reduce tremor in essential tremor (ET) and Parkinson's disease (PD) clinical populations often utilize pharmacological or surgical therapies. However,... (Review)
Review
Interventions to reduce tremor in essential tremor (ET) and Parkinson's disease (PD) clinical populations often utilize pharmacological or surgical therapies. However, there can be significant side effects, decline in effectiveness over time, or clinical contraindications for these interventions. Therefore, alternative approaches must be considered and developed. Some non-pharmacological strategies include assistive devices, orthoses and mechanical loading of the tremorgenic limb, while others propose peripheral electrical stimulation. Specifically, peripheral electrical stimulation encompasses strategies that activate motor and sensory pathways to evoke muscle contractions and impact sensorimotor function. Numerous studies report the efficacy of peripheral electrical stimulation to alter tremor generation, thereby opening new perspectives for both short- and long-term tremor reduction. Therefore, it is timely to explore this promising modality in a comprehensive review. In this review, we analyzed 27 studies that reported the use of peripheral electrical stimulation to reduce tremor and discuss various considerations regarding peripheral electrical stimulation: the stimulation strategies and parameters, electrodes, experimental designs, results, and mechanisms hypothesized to reduce tremor. From our review, we identified a high degree of disparity across studies with regard to stimulation patterns, experimental designs and methods of assessing tremor. Having standardized experimental methodology is a critical step in the field and is needed in order to accurately compare results across studies. With this review, we explore peripheral electrical stimulation as an intervention for tremor reduction, identify the limitations and benefits of the current state-of-the-art studies, and provide ideas to guide the development of novel approaches based on the neural circuitries and mechanical properties implied in tremor generation.
Topics: Electric Stimulation Therapy; Humans; Male; Tremor
PubMed: 33588841
DOI: 10.1186/s12984-021-00811-9 -
International Journal of Molecular... Jan 2023Dystonia is a movement disorder in which patients have involuntary abnormal movements or postures. Non-motor symptoms, such as psychiatric symptoms, sleep problems and...
Dystonia is a movement disorder in which patients have involuntary abnormal movements or postures. Non-motor symptoms, such as psychiatric symptoms, sleep problems and fatigue, are common. We hypothesise that the gut microbiome might play a role in the pathophysiology of the (non-)motor symptoms in dystonia via the gut-brain axis. This exploratory study investigates the composition of the gut microbiome in dystonia patients compared to healthy controls. Furthermore, the abundance of neuro-active metabolic pathways, which might be implicated in the (non-)motor symptoms, was investigated. We performed both metagenomic and 16S rRNA sequencing on the stool samples of three subtypes of dystonia (27 cervical dystonia, 20 dopa-responsive dystonia and 24 myoclonus-dystonia patients) and 25 controls. While microbiome alpha and beta diversity was not different between dystonia patients and controls, dystonia patients had higher abundances of and , and a lower abundance of compared to controls. For those with dystonia, non-motor symptoms and the levels of neurotransmitters in plasma explained the variance in the gut microbiome composition. Several neuro-active metabolic pathways, especially tryptophan degradation, were less abundant in the dystonia patients compared to controls. This suggest that the gut-brain axis might be involved in the pathophysiology of dystonia. Further studies are necessary to confirm our preliminary findings.
Topics: Humans; Dystonia; Gastrointestinal Microbiome; RNA, Ribosomal, 16S; Mental Disorders; Dystonic Disorders; Dyskinesias
PubMed: 36768705
DOI: 10.3390/ijms24032383