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The New England Journal of Medicine Jul 2022
Topics: Chorea; Dyskinesias; Humans; Hyperglycemia; Ketosis
PubMed: 35856799
DOI: 10.1056/NEJMicm2116217 -
Journal of Neural Transmission (Vienna,... Jul 2019In the differential diagnosis of Parkinson syndromes, the response to L-Dopa is an essential criterion for the diagnosis of idiopathic Parkinson's syndrome (IPS), and... (Review)
Review
In the differential diagnosis of Parkinson syndromes, the response to L-Dopa is an essential criterion for the diagnosis of idiopathic Parkinson's syndrome (IPS), and the presence of L-Dopa-induced dyskinesia (LID) is considered a supportive criterion. This implies that in the presence of LID an atypical Parkinson-syndrome (APS) is unlikely. However, dyskinesia, and in particular LID, can also be present in APS such as MSA and PSP, although less frequently, and with varying clinical appearance. We conclude that whilst presence of dyskinesia provides support for a diagnosis of IPD, they do not allow reliable differentiation from APS.
Topics: Diagnosis, Differential; Dyskinesia, Drug-Induced; Dyskinesias; Humans; Levodopa; Multiple System Atrophy; Parkinson Disease; Supranuclear Palsy, Progressive
PubMed: 31087195
DOI: 10.1007/s00702-019-02012-0 -
Expert Opinion on Drug Safety Dec 2019: Dyskinesia is a motor complication of Parkinson's disease (PD) characterized by clinical heterogeneity and complex pathogenesis and associated with long-term levodopa... (Review)
Review
: Dyskinesia is a motor complication of Parkinson's disease (PD) characterized by clinical heterogeneity and complex pathogenesis and associated with long-term levodopa therapy. Recent and controversial views on the management of PD patients have suggested that overall dyskinesia rates, and particularly troublesome dyskinesia, may be declining due to more conservative levodopa dosing regimens, widespread availability and early introduction of deep brain stimulation, and use of continuous drug delivery strategies. Nevertheless, anti-dyskinetic agents continue to be evaluated in clinical trials and recent efforts have focused on non-dopaminergic drugs.: In this review, the authors discuss the clinical phenomenology and current understanding of dyskinesia in PD with a focus on up-to-date therapeutic strategies to prevent and manage these drug-related involuntary movements.: The way dyskinesia in PD is currently managed should be changed and attention should be focused toward a more personalized medicine rather than a one-fits-all-approach. The correct identification of dyskinesia types and tailored treatments are crucial for a better management of these involuntary movements together with a holistic approach which considers additional influencing factors. The future for dyskinesia treatment is likely to be found in non-dopaminergic approaches, first set into motion by the introduction of amantadine.
Topics: Animals; Antiparkinson Agents; Deep Brain Stimulation; Drug Delivery Systems; Dyskinesia, Drug-Induced; Dyskinesias; Humans; Levodopa; Parkinson Disease
PubMed: 31619083
DOI: 10.1080/14740338.2019.1681966 -
Expert Opinion on Drug Delivery 2023Parkinson's disease (PD) is the second most common neurodegenerative disease and is growing in prevalence and disability. The standard treatment for PD is oral levo-dopa... (Review)
Review
INTRODUCTION
Parkinson's disease (PD) is the second most common neurodegenerative disease and is growing in prevalence and disability. The standard treatment for PD is oral levo-dopa (LD) with carbidopa (CD). As PD progresses, despite higher doses of LD/CD, plasma levels of LD fluctuate, and may be associated with motor fluctuations and dyskinesia.
AREAS COVERED
The development of two new subcutaneous preparations of LD/CD (ND0612 and ABBV-951) for the treatment of motor fluctuations in PD is described in detail. Both reduce motor fluctuations and dyskinesia with minor infusion site adverse events. A third subcutaneous preparation, DIZ102, is in early-stage development.
EXPERT OPINION
The premise for using continuous release LD in advanced PD is that steady state levels of LD will prevent motor fluctuations/dyskinesia, but this is not the whole story, and will limit the benefits of subcutaneous continuous release LD. With its present pump system ND0612 cannot be used as monotherapy, whereas ABBV-951 can be. Having to combine with oral LD/CD will complicate the use of ND0612. Both ND0612 and ABBV-951 only cause modest reductions in OFF time. It is not clear whether these subcutaneous preparations will have more benefits than the intestinal gel, which also reduces OFF time and dyskinesia.
Topics: Humans; Carbidopa; Levodopa; Parkinson Disease; Neurodegenerative Diseases; Drug Combinations; Dyskinesias; Antiparkinson Agents
PubMed: 37634938
DOI: 10.1080/17425247.2023.2253146 -
Oxidative Medicine and Cellular... 2022Tardive dyskinesia (TD) is a prevalent movement disorder that significantly impacts patients with schizophrenia (SCZ) due to extended exposure to antipsychotics (AP).... (Review)
Review
Tardive dyskinesia (TD) is a prevalent movement disorder that significantly impacts patients with schizophrenia (SCZ) due to extended exposure to antipsychotics (AP). Several genetic polymorphisms, including superoxide dismutase (SOD) and DRD3 9ser, have been suggested as explanations why some patients suffer from TD. . A PubMed search was used to search relevant articles using the following keywords: "Tardive Dyskinesia and Superoxide Dismutase". Fifty-eight articles were retrieved. Among them, 16 were included in this review. . Overall, 58 studies were retrieved from PubMed. Most studies investigated the association between TD and the SOD-related polymorphisms. In addition, previous studies reported an association between TD occurrence and other genetic polymorphisms. . This study found that the risk of TD is associated with altered SOD levels and several genetic polymorphisms, including VAL 66 Met and DRD3 9ser.
Topics: Humans; Tardive Dyskinesia; Antipsychotic Agents; Polymorphism, Genetic; Schizophrenia; Superoxide Dismutase
PubMed: 36338339
DOI: 10.1155/2022/5748924 -
Journal of Neurology Nov 2022Movement disorders of the mouth encompass a spectrum of hyperactive movements involving the muscles of the orofacial complex. They are rare conditions and are described... (Review)
Review
Movement disorders of the mouth encompass a spectrum of hyperactive movements involving the muscles of the orofacial complex. They are rare conditions and are described in the literature primarily in case reports originating from neurologists, psychiatrists, and the dental community. The focus of this review is to provide a phenomenological description of different oral motor disorders including oromandibular dystonia, orofacial dyskinesia and orolingual tremor, and to offer management strategies for optimal treatment based on the current literature. A literature search of full text studies using PubMed/Medline and Cochrane library combined with a manual search of the reference lists was conducted until June 2021. Results from this search included meta-analyses, systematic reviews, reviews, clinical studies, case series, and case reports published by neurologists, psychiatrists, dentists and oral and maxillofacial surgeons. Data garnered from these sources were used to provide an overview of most commonly encountered movement disorders of the mouth, aiding physicians in recognizing these rare conditions and in initiating appropriate therapy.
Topics: Dyskinesias; Dystonic Disorders; Humans; Mouth; Movement Disorders
PubMed: 35904592
DOI: 10.1007/s00415-022-11299-1 -
Experimental Neurology May 2022Gamma oscillations comprise a loosely defined, heterogeneous group of functionally different activities between 30 and 100 Hz in the cortical and subcortical local... (Review)
Review
Gamma oscillations comprise a loosely defined, heterogeneous group of functionally different activities between 30 and 100 Hz in the cortical and subcortical local field potential (LFP) of the motor network. Two distinct patterns seem to emerge which are easily conflated: Finely-tuned gamma (FTG) oscillations - a narrowband activity with peaks between 60 and 90 Hz - have been observed in multiple movement disorders and are induced by dopaminergic medication or deep brain stimulation (DBS). FTG has been linked with levodopa or DBS-induced dyskinesias, which makes it a putative biomarker for adaptive DBS. On the other hand, gamma activity can also present as a broad phenomenon (30-100 Hz) in the context of motor activation and dynamic processing. Here, we contrast FTG, either levodopa-induced or DBS-induced, from movement-related broadband gamma synchronisation and further elaborate on the functional role of FTG and its potential implications for adaptive DBS. Given the unclear distinction of FTG and broad gamma in literature, we appeal for more careful separation of the two. To better characterise cortical and subcortical FTG as biomarkers for dyskinesia, their sensitivity and specificity need to be investigated in a large clinical trial.
Topics: Deep Brain Stimulation; Dyskinesias; Humans; Levodopa
PubMed: 35143832
DOI: 10.1016/j.expneurol.2022.113999 -
The British Journal of Oral &... Jun 2020Oromandibular dystonia (OMD) is characterised by sustained or repetitive involuntary movements of the jaw, face, and tongue. People with the condition may present to... (Review)
Review
Oromandibular dystonia (OMD) is characterised by sustained or repetitive involuntary movements of the jaw, face, and tongue. People with the condition may present to their dentist, general practitioner, or a secondary care specialist with non-specific symptoms including jaw or facial pain, bruxism, subluxations or dislocations of the jaw; fractured teeth or dental restorations, or both; or jaw tremor. Many clinicians are not aware of the disorder and this can lead to delayed diagnoses, unnecessary complications, and inappropriate treatment. OMD is an important diagnosis not to miss because referral for specialist management can provide good long-term results. To aid early, accurate diagnosis, this paper focuses on the key clinical features of the disorder and its dental and medical mimics.
Topics: Dyskinesias; Dystonia; Humans; Tongue Diseases
PubMed: 32143935
DOI: 10.1016/j.bjoms.2020.02.018 -
Journal of Parkinson's Disease 2022Levodopa-induced dyskinesia (LID), a frequent complication of Parkinson's disease (PD), occurs in ∼30% of patients after five years' treatment with levodopa. In... (Review)
Review
Levodopa-induced dyskinesia (LID), a frequent complication of Parkinson's disease (PD), occurs in ∼30% of patients after five years' treatment with levodopa. In atypical parkinsonism, LID occurs less frequently than in PD. Lower frequency of LID in atypical parkinsonism has traditionally been attributed to lower amounts of levodopa used by these patients; however, recent studies have shown lower frequency of LID in atypical parkinsonism compared with PD when adjusting for levodopa dose. The mechanism of LID is complex but requires pulsatile levodopa stimulation, progressive presynaptic dopaminergic degeneration, and a relatively intact postsynaptic dopaminergic system. The globus pallidus internus (GPi), the main inhibitory nucleus of the basal ganglia, may play a major role in the development and treatment of LID. Surgical lesioning of the posteroventral GPi is directly antidyskinetic; animal models showing GPi-associated striatal neurons are directly responsible for the development of LID. However, other cortical areas, particularly the primary sensory and motor cortices may also play a role in LID. In some cases of atypical parkinsonism, particularly progressive supranuclear palsy and corticobasal degeneration, severe degeneration of the GPi, a so-called "autopallidotomy," may explain the absence of LID in these patients. In other atypical parkinsonisms, such as PD dementia and dementia with Lewy bodies, the lower incidence of LID may partly be attributed to more striatal degeneration but likely also relates to the degeneration of the motor cortex and resultant network dysfunction. Overall, atypical parkinsonism serves as a natural model that may ultimately reveal more effective therapies for LID.
Topics: Animals; Antiparkinson Agents; Basal Ganglia; Dyskinesias; Globus Pallidus; Levodopa; Parkinson Disease; Parkinsonian Disorders
PubMed: 36120793
DOI: 10.3233/JPD-223491 -
Drugs Jul 2022Motor symptoms are a core feature of Parkinson's disease (PD) and cause a significant burden on patients' quality of life. Oral levodopa is still the most effective... (Review)
Review
Motor symptoms are a core feature of Parkinson's disease (PD) and cause a significant burden on patients' quality of life. Oral levodopa is still the most effective treatment, however, the motor benefits are countered by inherent pharmacologic limitations of the drug. Additionally, with disease progression, chronic levodopa leads to the appearance of motor complications including motor fluctuations and dyskinesia. Furthermore, several motor abnormalities of posture, balance, and gait may become less responsive to levodopa. With these unmet needs and our evolving understanding of the neuroanatomic and pathophysiologic underpinnings of PD, several advances have been made in defining new therapies for motor symptoms. These include newer levodopa formulations and drug delivery systems, refinements in adjunctive medications, and non-dopaminergic treatment strategies. Although some are in early stages of development, these novel treatments potentially widen the available options for the management of motor symptoms allowing clinicians to provide an individually tailored care for PD patients. Here, we review the existing and emerging interventions for PD with focus on newly approved and investigational drugs for motor symptoms, motor fluctuations, dyskinesia, and balance and gait dysfunction.
Topics: Antiparkinson Agents; Drugs, Investigational; Dyskinesias; Humans; Levodopa; Parkinson Disease; Quality of Life
PubMed: 35841520
DOI: 10.1007/s40265-022-01747-7