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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 Neural Transmission (Vienna,... Aug 2018The purpose of review is to review the current status of positron emission tomography (PET) molecular imaging of serotonergic system in Parkinson's patients who... (Review)
Review
The purpose of review is to review the current status of positron emission tomography (PET) molecular imaging of serotonergic system in Parkinson's patients who experience levodopa-induced (LIDs) and graft-induced dyskinesias (GIDs). PET imaging studies have shown that Parkinson's disease is characterized by progressive loss of dopaminergic and serotonergic neurons. Parkinson's patients who experienced LIDs and GIDs have an aberrant spreading of serotonergic terminals, which lead to an increased serotonergic/dopaminergic terminals ratio within the putamen. Serotonergic terminals convert exogenous levodopa into dopamine in a non-physiological manner and release an abnormal amount of dopamine without an auto-regulatory feedback. This results in higher swings in synaptic levels of dopamine, which leads to the development of LIDs and GIDs. The modulation of serotonergic terminals with 5-HT and 5-HT receptors agonists partially reduced these motor complications. In vivo PET studies confirmed that abnormal spreading of serotonergic terminals within the putamen has a pivotal role in the development of LIDs and GIDs. However, glutamatergic, adenosinergic, opioid systems, and phosphodiesterases 10A may also play a role in the development of these motor complications. An integrative multimodal imaging approach combining PET and MRI imaging techniques is needed to fully understand the mechanisms underlying the development of LIDs and GIDs.
Topics: Dyskinesia, Drug-Induced; Humans; Parkinson Disease; Positron-Emission Tomography; Serotonergic Neurons
PubMed: 29264660
DOI: 10.1007/s00702-017-1823-7 -
Developmental Medicine and Child... Dec 2017To evaluate the actual evidence of efficacy of oral pharmacological treatments in the management of dyskinetic cerebral palsy (CP). (Review)
Review
AIM
To evaluate the actual evidence of efficacy of oral pharmacological treatments in the management of dyskinetic cerebral palsy (CP).
METHOD
A systematic review was performed according to the American Academy for Cerebral Palsy and Developmental Medicine (AACPDM) and Preferred Reporting Items for Systematic Reviews and Meta-Analyses methodology. Articles were searched for in PubMed/MEDLINE, Scopus, Web of Science, Cochrane Library, Database of Reviews of Effectiveness, OTSeeker, Physiotherapy Evidence Database, REHABDATA, and ClinicalTrials.gov.
RESULTS
Sixteen articles met the eligibility criteria. Eight studies on trihexyphenidyl and two on levodopa showed contradictory results. Low efficacy was reported for diazepam, dantrolene sodium, perphenazine, and etybenzatropine. Tetrabenazine, gabapentin and levetiracetam should be studied in more detail. The updated available evidence does not support any therapeutic algorithm for the management of dyskinetic CP.
INTERPRETATION
This lack of evidence is partially owing to the inconsistency of classifications of patients and of outcome measures used in the reviewed studies. Further randomized, double-blind, placebo-controlled pharmacological trials, optimized for different age groups, based on valid, reliable, and disease-specific rating scales are strongly needed. Outcome measures should be selected within the framework of the International Classification of Functioning, Disability and Health.
WHAT THIS PAPER ADDS
Evidence to prove (or disprove) the efficacy of oral drugs in dyskinetic cerebral palsy is low. The most investigated drugs, trihexyphenidyl and levodopa, show contradictory results. Tetrabenazine, levetiracetam, and gabapentin efficacy should be studied in more detail. Lack of evidence is partially due to the inconsistency of classifications and outcome measures used. Outcome measures should be selected within the framework of the International Classification of Functioning, Disability and Health in next clinical trials.
Topics: Anticonvulsants; Cerebral Palsy; Dyskinesias; Humans; Neurotransmitter Agents; Outcome Assessment, Health Care
PubMed: 28872668
DOI: 10.1111/dmcn.13532 -
Journal of Veterinary Internal Medicine Jul 2017Myoclonus is a sudden brief, involuntary muscle jerk. Of all the movement disorders, myoclonus is the most difficult to encapsulate into any simple framework. On the one... (Review)
Review
Myoclonus is a sudden brief, involuntary muscle jerk. Of all the movement disorders, myoclonus is the most difficult to encapsulate into any simple framework. On the one hand, a classification system is required that is clinically useful to aid in guiding diagnosis and treatment. On the other hand, there is need for a system that organizes current knowledge regarding biological mechanisms to guide scientific research. These 2 needs are distinct, making it challenging to develop a robust classification system suitable for all purposes. We attempt to classify myoclonus as "epileptic" and "nonepileptic" based on its association with epileptic seizures. Myotonia in people may be divided into 2 clinically and molecularly defined forms: (1) nondystrophic myotonias and (2) myotonic dystrophies. The former are a group of skeletal muscle channelopathies characterized by delayed skeletal muscle relaxation. Many distinct clinical phenotypes are recognized in people, the majority relating to mutations in skeletal muscle voltage-gated chloride (CLCN1) and sodium channel (SCN4A) genes. In dogs, myotonia is associated with mutations in CLCN1. The myotonic dystrophies are considered a multisystem clinical syndrome in people encompassing 2 clinically and molecularly defined forms designated myotonic dystrophy types 1 and 2. No mutation has been linked to veterinary muscular dystrophies. We detail veterinary examples of myotonia and attempt classification according to guidelines used in humans. This more precise categorization of myoclonus and myotonia aims to promote the search for molecular markers contributing to the phenotypic spectrum of disease. Our work aimed to assist recognition for these 2 enigmatic conditions.
Topics: Animals; Dog Diseases; Dogs; Dyskinesias; Myoclonus; Myotonia
PubMed: 28557061
DOI: 10.1111/jvim.14771 -
Annals of Clinical and Translational... Apr 2022To quantitatively evaluate upper limb ataxia using a novel pen-like sensor device in patients with spinocerebellar ataxia (SCA) and to assess its validity, reliability,...
OBJECTIVE
To quantitatively evaluate upper limb ataxia using a novel pen-like sensor device in patients with spinocerebellar ataxia (SCA) and to assess its validity, reliability, and sensitivity to disease progression.
METHODS
We designed a cross-sectional and longitudinal study of patients with SCA and healthy controls. Upper limb ataxia was evaluated using a device that measures the three-dimensional position every 10 msec. Participants were instructed to move a pen-like part of the device iteratively between two buttons. We evaluated the time, length, velocity, and variation coefficient of the stroke, and calculated the distortion index using the mean squared error. The following scales were also evaluated: Scale for the Assessment and Rating of Ataxia (SARA), the International Cooperative Ataxia Rating Scale (ICARS), and the nine-hole pegboard test. Subjects were followed 12 months after the baseline evaluation.
RESULTS
A total of 42 patients with SCA and 33 healthy controls were enrolled and evaluated. For all ataxia indices measured using the device there were significant differences between healthy controls and patients with SCA. Among the ataxia indices, the distortion index showed the strongest correlation with the SARA and ICARS upper limb score (Pearson's r = 0.647 and 0.722, respectively). Test-retest reliability was high for most of the ataxia indices. In the longitudinal analysis, the distortion index showed high standardized response mean and adjusted effect size, regardless of disease severity.
INTERPRETATION
Our study demonstrated that the distortion index is a reliable functional marker that is sensitive to longitudinal change in patients with SCA.
Topics: Ataxia; Cerebellar Ataxia; Cross-Sectional Studies; Humans; Longitudinal Studies; Reproducibility of Results; Spinocerebellar Ataxias
PubMed: 35293156
DOI: 10.1002/acn3.51528 -
Tremor and Other Hyperkinetic Movements... 2022Chorea can be due to a large number of etiologies. Unilateral chorea is classically related to a contralateral structural lesion, e.g. of the putamen or subthalamic... (Review)
Review
BACKGROUND
Chorea can be due to a large number of etiologies. Unilateral chorea is classically related to a contralateral structural lesion, e.g. of the putamen or subthalamic nucleus, however, based upon personal impressions, we have observed that systemic disease, in particular metabolic or autoimmune conditions, can also lead to a unilateral or markedly asymmetric presentations. We sought to investigate this impression by reviewing the literature.
METHODS
A PubMed search was conducted using the terms asymmetric" AND "chorea" OR "hemichorea" OR "unilateral" AND "chorea" OR "monochorea" OR "right greater than left" AND "chorea" OR "left greater than right" AND "chorea" OR "right more than left" AND "chorea" OR "left more than right" AND "chorea" as well as "hemiballismus" NOT "stroke" NOT "infarct" NOT "dyskinesia. A total of 243 sources were felt to meet criteria and were reviewed.
RESULTS
The most common etiology of reported hemi- or asymmetric chorea was diabetic non-ketotic hyperglycemic hemichorea/hemiballismus. Other common diagnoses were Sydenham's disease, antiphospholipid syndrome and drug-induced chorea. The vast majority of patients with hemi- or asymmetric chorea had acquired rather than genetic, degenerative or congenital causes.
CONCLUSION
Despite the potential limitations of our literature review, the evidence presented here supports the observation that the vast majority of asymmetric or unilateral chorea presentations are due to acquired causes, and in this situation an exhaustive search for reversible etiology should be undertaken. However, presentation with symmetric, generalized chorea does not exclude reversible causes, and investigations should address these in addition to genetic and neurodegenerative etiologies.
Topics: Chorea; Dyskinesias; Humans; Movement Disorders; Putamen; Subthalamic Nucleus
PubMed: 35136702
DOI: 10.5334/tohm.675 -
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 -
NeuroImage Apr 2019Parkinson's disease causes a characteristic combination of motor symptoms due to progressive neurodegeneration of dopaminergic neurons in the substantia nigra pars... (Review)
Review
Parkinson's disease causes a characteristic combination of motor symptoms due to progressive neurodegeneration of dopaminergic neurons in the substantia nigra pars compacta. The core impairment of dopaminergic neurotransmission has motivated the use of functional magnetic resonance imaging (fMRI) in patients with Parkinson's disease to elucidate the role of dopamine in motor control and cognition in humans. Here we review the main insights from functional brain imaging in Parkinson's disease. Task-related fMRI revealed many disease-related alterations in brain activation patterns. However, the interpretation of these findings is complicated by the fact that task-dependent activity is influenced by complex interactions between the amount of dopaminergic neurodegeneration in the task-relevant nuclei, the state of medication, genetic factors and performance. Despite these ambiguities, fMRI studies in Parkinson's disease demonstrated a central role of dopamine in the generation of movement vigour (bradykinesia) and the control of excessive movements (dyskinesia), involving changes of both activity and connectivity of the putamen, premotor and motor regions, and right inferior frontal gyrus (rIFG). The fMRI studies addressing cognitive flexibility provided convergent evidence for a non-linear, U-shaped, relationship between dopamine levels and performance. The amount of neurodegeneration in the task-relevant dopaminergic nuclei and pharmacological dopamine replacement can therefore move performance either away or towards the task-specific optimum. Dopamine levels also strongly affect processing of reward and punishment for optimal learning. However, further studies are needed for a detailed understanding of the mechanisms underlying these effects.
Topics: Cognitive Dysfunction; Dopamine; Executive Function; Humans; Hyperkinesis; Hypokinesia; Neuroimaging; Parkinson Disease; Reward
PubMed: 30465864
DOI: 10.1016/j.neuroimage.2018.11.021 -
CMAJ : Canadian Medical Association... Nov 2016
Review
Topics: Age of Onset; Antiparkinson Agents; Carbidopa; Deep Brain Stimulation; Drug Combinations; Dyskinesias; Humans; Levodopa; Life Expectancy; Parkinson Disease; Practice Guidelines as Topic; Risk Assessment
PubMed: 27221269
DOI: 10.1503/cmaj.151179 -
Medicine Jun 2021Sit-to-stand (STS) motion is one of the most important and energy-consuming basic motions in everyday life. Kinematic analysis provides information regarding what... (Observational Study)
Observational Study
Sit-to-stand (STS) motion is one of the most important and energy-consuming basic motions in everyday life. Kinematic analysis provides information regarding what strategy or motion pattern is used by the healthy people, and through which, we can understand and obtain the law of the STS motion. The objective of this article is to study the law of STS motion through the experiment to determine a suitable description of STS motion in healthy adults, so as to provide a starting point and bases for future design and control of STS assistive devices.Thirty healthy adult subjects participated in this study and carried out STS motion experiment of standing up naturally. The STS motions were recorded using a high-definition camera. The experimentally collected kinematic data and a link segment model of the human body were used to obtain the coordinates of joints and to calculate the coordinates, velocity, and momentum of center of gravity; the postures of human body during STS are also obtained. The relationship between human body parameters and motion parameters is analyzed by using Pearson correlation method.The STS motion is divided into 4 phases; the phases are differentiated in terms of STS motion characteristics and postures, and momentum of center of gravity of human body. The main factors determining the differences in STS motion among individuals are horizontal distance between hip joint and ankle joint, lower leg length, thigh length, and the length of the transition period. The horizontal distance between hip joint and ankle joint is positively correlated with the duration from motion begin to trunk stops flexing forward (P = .021 < .05), but not so with the duration from motion begin to the end of phase 2 (P = .15 > .05).The results suggest that when designing the sit-to-stand assistive devices, one should pay attention to the whole-body posture control in STS motion, such as the posture guidance of trunk and lower leg, and should carry out specific training according to different STS phases. Sit-to-stand assistive devices should provide the same horizontal distance between hip joint and ankle joint for different individuals during the STS motion. Transition period should be properly controlled, and the degree of freedom of the lower leg should not be limited.
Topics: Adult; Algorithms; Ankle Joint; Biomechanical Phenomena; Body-Weight Trajectory; Dyskinesias; Hip Joint; Human Body; Humans; Leg; Male; Movement; Postural Balance; Posture; Range of Motion, Articular; Self-Help Devices; Thigh; Torso
PubMed: 34087893
DOI: 10.1097/MD.0000000000026208