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Journal of Parkinson's Disease 2020Carbidopa (CD) and levodopa (LD) extended release (CD-LD ER) capsules are designed to combine both immediate and extended release pharmacokinetics. In the phase 3,...
BACKGROUND
Carbidopa (CD) and levodopa (LD) extended release (CD-LD ER) capsules are designed to combine both immediate and extended release pharmacokinetics. In the phase 3, randomized, double-blind, ADVANCE-PD trial, patients randomized to CD-LD ER experienced a 1.17-hour greater reduction in OFF time compared to patients randomized to CD-LD IR (p < 0.0001).
OBJECTIVE
To compare CD-LD IR optimization to CD-LD ER conversion based on patient dyskinesia status at baseline using data from the ADVANCE-PD trial.
METHODS
This was a retrospective analysis of the ADVANCE-PD study. Patients were categorized by dyskinesia status at baseline into 1) those who had No Dyskinesia (ND), 2) those who had Non-Troublesome Dyskinesia Only (NTDO), and 3) those who had Troublesome Dyskinesia (TD).
RESULTS
Comparative reductions in OFF time favoring CD-LD ER over CD-LD IR were similar for the ND (-1.08 h, p = 0.0071, n = 183) and NTDO (-1.12 h, p = 0.0104, n = 131) groups, and smaller for the TD group (-0.82 h, p = 0.2382, n = 79). Reductions in OFF time for both CD-LD ER conversion and CD-LD IR adjustment were largest within the ND group and smallest within the TD group (CD-LD ER: ND -2.86 h, NTDO -2.11 h, TD -1.36 h; CD-LD IR: ND -1.78 h, NTDO -0.99 h, TD -0.55 h).
CONCLUSION
Responses to both CD-LD IR adjustment and CD-LD ER conversion depended on baseline dyskinesia status. Significant reductions in OFF time with CD-LD ER compared to CD-LD IR were observed in the ND and NTDO groups. In the TD group, comparing CD-LD ER conversion to CD-LD IR optimization, benefits were still observed, but there was less reduction in OFF time, less reduction in troublesome dyskinesia, and fewer patients self-rated themselves much or very much improved than in the ND and NTDO groups. These data suggest that in clinical practice, the best chances for success with conversion from CD-LD IR to CD-LD ER are in patients without TD.
Topics: Aged; Aged, 80 and over; Antiparkinson Agents; Capsules; Carbidopa; Delayed-Action Preparations; Drug Administration Schedule; Drug Combinations; Dyskinesias; Female; Humans; Levodopa; Male; Middle Aged; Parkinson Disease
PubMed: 32568108
DOI: 10.3233/JPD-202010 -
Neuropsychopharmacologia Hungarica : a... Dec 2014Movement disorders are common in psychiatry. The movement disorder can either be the symptom of a psychiatric disorder, can share a common aetiological factor with it,... (Review)
Review
Movement disorders are common in psychiatry. The movement disorder can either be the symptom of a psychiatric disorder, can share a common aetiological factor with it, or can be the consequence of psychopharmacological therapy. Most common features include tic, stereotypy, compulsion, akathisia, dyskinesias, tremor, hypokinesia and disturbances of posture and gait. We discuss characteristics and clinical importance of these features. Movement disorders are frequently present in mood disorders, anxiety disorders, schizophrenia, catatonia, Tourette-disorder and psychogenic movement disorder, leading to differential-diagnostic and therapeutical difficulties in everyday practice. Movement disorders due to psychopharmacotherapy can be classified as early-onset, late-onset and tardive. Frequent psychiatric comorbidity is found in primary movement disorders, such as Parkinson's disease, Wilson's disease, Huntington's disease, diffuse Lewy-body disorder. Complex neuropsychiatric approach is effective concerning overlapping clinical features and spectrums of disorders in terms of movement disorders and psychiatric diseases.
Topics: Anxiety Disorders; Comorbidity; Compulsive Behavior; Conversion Disorder; Diagnosis, Differential; Dyskinesia, Drug-Induced; Dyskinesias; Gait; Humans; Hypokinesia; Mental Disorders; Mood Disorders; Movement Disorders; Posture; Psychotropic Drugs; Schizophrenia; Stereotypic Movement Disorder; Tic Disorders; Tourette Syndrome; Tremor
PubMed: 25577484
DOI: No ID Found -
Neuropsychobiology 2012Classical schizophrenia literature reports motor symptoms as characteristic of the disorder. After the introduction of neuroleptic drugs, the existence of genuine motor... (Review)
Review
Classical schizophrenia literature reports motor symptoms as characteristic of the disorder. After the introduction of neuroleptic drugs, the existence of genuine motor disorders was challenged. Renewed interest arose as symptoms were found in never-medicated patients. Reports focused on abnormal involuntary movements, parkinsonism, neurological soft signs, catatonia, negative symptoms, or psychomotor slowing. Since these syndromes refer to different concepts, however, the definitions are not congruent and the symptoms overlap. The prevalence rates of motor symptoms in schizophrenia are surprisingly high, and recent studies indicate a possible pathobiology. In particular, the development and maturation of the human motor system appears to be closely linked to the emergence of motor symptoms observed in schizophrenia. Post-mortem and neuroimaging results demonstrated aberrant structure and function of premotor and motor cortices, basal ganglia, thalamus, and the connecting white matter tracts. Animal models have focused on aberrant neurotransmission and genetic contributions. Findings of localized abnormal oligodendrocyte function and myelination point to the special role of the white matter in schizophrenia, and recent studies specifically found an association between motor abnormalities and white matter structure in schizophrenia. This review of the literature supports the idea that motor symptoms are closely related to the neurodevelopmental disturbances of schizophrenia and a distinct syndromal dimension with its own pathophysiology.
Topics: Basal Ganglia; Catatonia; Dyskinesias; Humans; Motor Cortex; Parkinsonian Disorders; Schizophrenia
PubMed: 22814247
DOI: 10.1159/000339456 -
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 -
Journal of Anatomy May 2000Models of basal ganglia function are described which encapsulate the principal pathophysiological mechanisms underlying parkinsonian akinesia on the one hand and... (Review)
Review
Models of basal ganglia function are described which encapsulate the principal pathophysiological mechanisms underlying parkinsonian akinesia on the one hand and abnormal involuntary movement disorders (dyskinesias) on the other. In Parkinson's disease, degeneration of the nigrostriatal dopamine system leads to overactivity of the 'indirect' striatopallidal projection to the lateral (external) segment of the globus pallidus. This causes inhibition of lateral pallidal neurons, which in turn project to the subthalamic nucleus. Disinhibition of the subthalamic nucleus leads to abnormal subthalamic overactivity and, as a consequence, overactivity of medial (internal) pallidal output neurons. Dyskinesias, such as are observed in Huntington's disease, levodopa-induced dyskinesia and ballism, share mechanistic features in common and are associated with decreased neuronal activity in both the subthalamic nucleus and the medial globus pallidus.
Topics: Animals; Basal Ganglia; Dyskinesias; Humans; Movement Disorders; Neural Pathways; Neurotransmitter Agents; Parkinson Disease
PubMed: 10923984
DOI: 10.1046/j.1469-7580.2000.19640519.x -
Journal of Neural Transmission (Vienna,... Aug 2018Cholinergic signaling plays a key role in regulating striatal function. The principal source of acetylcholine in the striatum is the cholinergic interneurons which,... (Review)
Review
Cholinergic signaling plays a key role in regulating striatal function. The principal source of acetylcholine in the striatum is the cholinergic interneurons which, although low in number, densely arborize to modulate striatal neurotransmission. This modulation occurs via strategically positioned nicotinic and muscarinic acetylcholine receptors that influence striatal dopamine, GABA and other neurotransmitter release. Cholinergic interneurons integrate multiple striatal synaptic inputs and outputs to regulate motor activity under normal physiological conditions. Consequently, an imbalance between these systems is associated with basal ganglia disorders. Here, we provide an overview of how striatal cholinergic interneurons modulate striatal activity under normal and pathological conditions. Numerous studies show that nigrostriatal damage such as that occurs with Parkinson's disease affects cholinergic receptor-mediated striatal activity. This altered cholinergic signaling is an important contributor to Parkinson's disease as well as to the dyskinesias that develop with L-dopa therapy, the gold standard for treatment. Indeed, multiple preclinical studies show that cholinergic receptor drugs may be beneficial for the treatment of L-dopa-induced dyskinesias. In this review, we discuss the evidence indicating that therapeutic modulation of the cholinergic system, particularly targeting of nicotinic cholinergic receptors, may offer a novel approach to manage this debilitating side effect of dopamine replacement therapy for Parkinson's disease.
Topics: Animals; Corpus Striatum; Dyskinesia, Drug-Induced; Humans; Interneurons; Levodopa; Parkinson Disease
PubMed: 29492663
DOI: 10.1007/s00702-018-1845-9 -
Agri : Agri (Algoloji) Dernegi'nin... Apr 2022The aim of the study was to evaluate the prevalence of scapular dyskinesia in patients with neck, back, and shoul-der pain and examine the variations in clinical...
OBJECTIVES
The aim of the study was to evaluate the prevalence of scapular dyskinesia in patients with neck, back, and shoul-der pain and examine the variations in clinical parameters cause by this combination.
METHODS
A total of 121 patients with neck, back, or shoulder pain were included in this prospective cross-sectional study. De-mographic and clinical data of the patients were recorded. It was evaluated the intensity of pain with the visual analog scale (VAS), the presence of muscle shortness with muscle shortness tests, and scapular dyskinesia with the Lateral Scapular Slide Test.
RESULTS
The prevalence of scapular dyskinesia was 41.9% in the study population. Patients were divided into groups, with or without scapular dyskinesia for evaluation, and compared. The presence of scapular dyskinesia was significantly higher in pa-tients with back and shoulder pain (p<0.05). When the distribution of scapular dyskinesia pathological types was evaluated, it was found that Type 1 was the most common in the study population. No significant difference was observed in pain intensity at rest and during activity between the groups (p>0.05), but the VAS score at night was significantly higher in patients with scapular dyskinesia (p<0.05). The pectoral, latissimus dorsi, and rhomboids muscle shortness were significantly higher in the group with scapular dyskinesia (p<0.05).
CONCLUSION
The evaluation of the presence of scapular dyskinesia in a physical examination in patients with neck, back, and/or shoulder pain will be a guide for the diagnosis and treatment of pain-related problems.
Topics: Cross-Sectional Studies; Dyskinesias; Humans; Muscles; Prevalence; Prospective Studies; Scapula; Shoulder Pain
PubMed: 35848815
DOI: 10.14744/agri.2022.87059 -
Medicina 2018Paroxysmal events are commonly encountered in toddlers. These events include a variety of conditions with different manifestations and pathophysiology. For that reason,... (Review)
Review
Paroxysmal events are commonly encountered in toddlers. These events include a variety of conditions with different manifestations and pathophysiology. For that reason, the diagnosis of these events can be challenging. In some instances, studies such as EEG and polysomnogram may be useful to differentiate between epileptic and non-epileptic events. In the majority of cases, a complete clinical history is enough to make an appropriate diagnosis. In this article, we review some of the most common paroxysmal non-epileptic events affecting toddlers, such as: tics, dyskinesias, sleep related events, etc. We also discuss diagnostic strategies and treatment options.
Topics: Child, Preschool; Diagnosis, Differential; Dyskinesias; Electroencephalography; Epilepsy; Humans; Movement Disorders; Polysomnography
PubMed: 30199366
DOI: No ID Found -
Cell Research Jan 2018In an elegant publication in Cell Research, Tan and colleagues showed that ablation of PRRT2 in cerebellar granule cells is sufficient to induce paroxysmal kinesigenic...
In an elegant publication in Cell Research, Tan and colleagues showed that ablation of PRRT2 in cerebellar granule cells is sufficient to induce paroxysmal kinesigenic dyskinesia. PRRT2 turns out to downregulate the presynaptic SNARE complex in granule cell axons, which in turn controls the activity patterns of Purkinje cells, the sole output of the cerebellar cortex.
Topics: Cerebellum; Dyskinesias; Dystonia; Humans; Membrane Proteins; Mutation; Nerve Tissue Proteins; Synaptic Transmission
PubMed: 29148542
DOI: 10.1038/cr.2017.142 -
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