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Movement Disorders : Official Journal... Sep 2019Individual genetic variation can have a major impact on the clinical manifestation of a movement disorder and its response to treatment. Advances in gene discovery and... (Review)
Review
Individual genetic variation can have a major impact on the clinical manifestation of a movement disorder and its response to treatment. Advances in gene discovery and increasing availability of diagnostic genetic testing have led to the identification of a growing number of patients with well-defined hereditary movement disorders. Establishing a genetic diagnosis may greatly impact patient counseling and shape therapeutic decisions. Further, assignment of a movement disorder to a specific genetic defect holds promise for the development of causal treatment approaches and individualized therapies, especially as the first gene-targeted approaches have recently entered clinical trials. However, important gaps remain, that is, genetic testing results are often inconclusive, gene-specific treatment options are still exceedingly rare, and designing clinical trials to demonstrate disease modification continues to pose a major challenge. © 2019 International Parkinson and Movement Disorder Society.
Topics: DNA Mutational Analysis; Genetic Testing; Genotype; Humans; Movement Disorders; Precision Medicine
PubMed: 30970153
DOI: 10.1002/mds.27699 -
European Journal of Internal Medicine Sep 2019Paraneoplastic syndromes include, by definition, any symptomatic and non-metastatic condition associated with a neoplasm. Paraneoplastic movement disorders are a... (Review)
Review
Paraneoplastic syndromes include, by definition, any symptomatic and non-metastatic condition associated with a neoplasm. Paraneoplastic movement disorders are a heterogeneous group of syndromes encompassing both hyperkinetic and hypokinetic conditions, characterized by acute/sub-acute onset, rapidly progressive evolution, and multifocal localizations with several overlapping features. These movement disorders are immune-mediated, as shown by the rapid onset and by the presence of antineuronal antibodies in biological samples of patients, fundamental for the diagnosis. Antineuronal antibodies could be targeted against intracellular or neuronal surface antigens. Paraneoplastic movement disorders associated with anti-neuronal surface antigens antibodies respond more frequently to immunotherapy. The underlying tumors may be different, according to the clinical presentation, age, and gender of patients. Our search considered articles involving human subjects indexed in PubMed. Abstracts were independently reviewed for eligibility criteria by one author and validated by at least one additional author. In this review, we sought to critically reappraise the clinical features and the pathophysiological mechanisms of paraneoplastic movement disorders, focusing on diagnostic and therapeutic strategies. Our main aim is to make clinicians aware of paraneoplastic movement disorders, and to provide assistance in the early diagnosis and management of these rare but life-threatening conditions.
Topics: Algorithms; Humans; Movement Disorders; Paraneoplastic Syndromes, Nervous System
PubMed: 31200996
DOI: 10.1016/j.ejim.2019.05.023 -
Der Nervenarzt Jun 2024
Topics: Humans; Movement Disorders; Conversion Disorder; Germany
PubMed: 38874600
DOI: 10.1007/s00115-024-01646-0 -
Acta Neurologica Scandinavica Oct 2022Movement disorders have been carefully clinically defined, based on clinico-pathological series; however there is often diagnostic and prognostic uncertainty, especially... (Review)
Review
Movement disorders have been carefully clinically defined, based on clinico-pathological series; however there is often diagnostic and prognostic uncertainty, especially in early stage disease. Blood-based biomarkers for Alzheimer's disease (AD), particularly p-tau181 and p-tau217, may be useful in the movement disorder clinic, especially in identifying corticobasal syndrome due to AD pathology and in identifying Parkinson's disease (PD) patients at high risk for the future development of dementia. Serum or plasma neurofilament light (NfL) may be useful in separating Parkinson's plus syndromes (progressive supranuclear palsy-PSP, multiple system atrophy - MSA, and corticobasal syndrome-CBS) from PD. NfL is also a prognostic biomarker, in that the level of baseline or cross-sectional plasma/serum NfL is associated with a worse prognosis in PD and PSP. The development of protein aggregation assays in cerebrospinal fluid and multiplex assays which can measure 100 s-1000s of proteins in blood will provide new tools and insights for movement disorders for clinicians and researchers. The challenge is in efficiently integrating these tools into clinical practice and multi-modal approaches, where biomarkers are combined with clinical, genetic, and imaging data may guide the future use of these technologies.
Topics: Biomarkers; Cross-Sectional Studies; Diagnosis, Differential; Humans; Multiple System Atrophy; Parkinson Disease; Protein Aggregates; Supranuclear Palsy, Progressive
PubMed: 36156206
DOI: 10.1111/ane.13700 -
Continuum (Minneapolis, Minn.) Aug 2023This article reviews common sleep-related movement disorders, including their clinical description, epidemiology, pathophysiology (if known), and evaluation and... (Review)
Review
OBJECTIVE
This article reviews common sleep-related movement disorders, including their clinical description, epidemiology, pathophysiology (if known), and evaluation and management strategies. This article will provide the reader with a good foundation for approaching concerns that are suggestive of sleep-related movement disorders to properly evaluate and manage these conditions.
LATEST DEVELOPMENTS
α2δ Ligands, such as gabapentin enacarbil, can be used for the initial treatment of restless legs syndrome (RLS) or in those who cannot tolerate, or have developed augmentation to, dopamine agonists. Another option is the rotigotine patch, which has a 24-hour treatment window and may be beneficial for those who have developed augmentation with short-acting dopamine agonists. IV iron can improve RLS symptoms even in those whose serum ferritin level is between 75 ng/mL and 100 ng/mL. At serum ferritin levels greater than 75 ng/mL, oral iron will likely have minimal absorption or little effect on the improvement of RLS. Research has found an association between RLS and cardiovascular disease, particularly in people who have periodic limb movements of sleep.
ESSENTIAL POINTS
RLS is the most common sleep-related movement disorder. Its pathophysiology is likely a combination of central iron deficiency, dopamine overproduction, and possibly cortical excitation. Treatment includes oral or IV iron. Dopaminergic medications can be very effective but often lead to augmentation, which limits their long-term use. Other sleep-related movement disorders to be aware of are sleep-related rhythmic movement disorder, nocturnal muscle cramps, sleep-related propriospinal myoclonus, sleep bruxism, and benign myoclonus of infancy.
Topics: Humans; Restless Legs Syndrome; Dopamine Agonists; Parasomnias; Sleep; Iron; Myoclonus; Movement Disorders; Ferritins
PubMed: 37590826
DOI: 10.1212/CON.0000000000001269 -
The Canadian Journal of Neurological... Jul 2022Mercury (Hg) exists in the environment as inorganic (metallic Hg vapor, mercurous and mercuric salts) or organic (bonded to a structure containing carbon atoms) forms.... (Review)
Review
Mercury (Hg) exists in the environment as inorganic (metallic Hg vapor, mercurous and mercuric salts) or organic (bonded to a structure containing carbon atoms) forms. Neurotoxic effect of Hg is known for years. While the organic form (methylmercury (meHg)) led to the Minamata incidence in Japan and "wonder-wheat" disaster in Iraq, the "mad hatters" and "Danbury shakes" were related to the inorganic elemental form (Hg vapor). Human exposure to toxic Hg continues in the modern world to a large extent by artisanal gold mining, biomass combustion, chloralkali production, and indigenous medicine use to name a few. Heavy industrial use of Hg contaminates air and landfills, affecting the aquatic ecosystem and marine food chain. A detailed social and occupational history with a high index of clinical suspicion is required to not miss this toxic etiology for movement disorders like ataxia, tremor, or myoclonus. In this review, we have discussed the past and present global health impact of Hg from a movement disorder perspective. The connection of Hg with neurodegeneration and autoimmunity has been highlighted. We have also discussed the role of chelating agents and the preventive strategies to combat the neurotoxic effects of Hg in the modern world.
Topics: Ecosystem; Humans; Mercury; Methylmercury Compounds; Mining; Movement Disorders
PubMed: 34346303
DOI: 10.1017/cjn.2021.146 -
European Journal of Neurology Apr 2022The scientific literature on COVID-19 is increasingly growing. (Review)
Review
BACKGROUND AND PURPOSE
The scientific literature on COVID-19 is increasingly growing.
METHODS
In this paper, we review the literature on movement disorders in the context of the COVID-19 pandemic.
RESULTS
First, there are a variety of transient movement disorders that may manifest in the acute phase of COVID-19, most often myoclonus, with more than 50 patients described in the literature. New onset parkinsonism, chorea, and tic-like behaviours have also been reported. Movement disorders as a side effect after COVID-19 vaccination are rare, occurring with a frequency of 0.00002-0.0002 depending on the product used, mostly manifesting with tremor. Current evidence for potential long-term manifestations, for example, long COVID parkinsonism, is separately discussed. Second, the pandemic has also had an impact on patients with pre-existing movement disorder syndromes, with negative effects on clinical status and overall well-being, and reduced access to medication and health care. In many parts, the pandemic has led to reorganization of the medical system, including the development of new digital solutions. The movement disorder-related evidence for this is reviewed and discussed.
CONCLUSIONS
The pandemic and the associated preventive measures have had a negative impact on the clinical status, access to health care, and overall well-being of patients with pre-existing movement disorders.
Topics: COVID-19; COVID-19 Vaccines; Humans; Movement Disorders; Pandemics; SARS-CoV-2; Post-Acute COVID-19 Syndrome
PubMed: 34918437
DOI: 10.1111/ene.15217 -
Medicinal Research Reviews Sep 2021Movement disorders are a group of neurological conditions characterized by abnormalities of movement and posture. They are broadly divided into akinetic and hyperkinetic... (Review)
Review
Movement disorders are a group of neurological conditions characterized by abnormalities of movement and posture. They are broadly divided into akinetic and hyperkinetic syndromes. Until now, no effective symptomatic or disease-modifying therapies have been available. However, since many of these disorders are monogenic or have some well-defined genetic component, they represent strong candidates for antisense oligonucleotide (ASO) therapies. ASO therapies are based on the use of short synthetic single-stranded ASOs that bind to disease-related target RNAs via Watson-Crick base-pairing and pleiotropically modulate their function. With information arising from the RNA sequence alone, it is possible to design ASOs that not only alter the expression levels but also the splicing defects of any protein, far exceeding the intervention repertoire of traditional small molecule approaches. Following the regulatory approval of ASO therapies for spinal muscular atrophy and Duchenne muscular dystrophy in 2016, there has been tremendous momentum in testing such therapies for other neurological disorders. This review article initially focuses on the chemical modifications aimed at improving ASO effectiveness, the mechanisms by which ASOs can interfere with RNA function, delivery systems and pharmacokinetics, and the common set of toxicities associated with their application. It, then, describes the pathophysiology and the latest information on preclinical and clinical trials utilizing ASOs for the treatment of Parkinson's disease, Huntington's disease, and ataxias 1, 2, 3, and 7. It concludes with issues that require special attention to realize the full potential of ASO-based therapies.
Topics: Humans; Huntington Disease; Nervous System Diseases; Oligonucleotides, Antisense; Parkinson Disease
PubMed: 32656818
DOI: 10.1002/med.21706 -
Journal of Neurology, Neurosurgery, and... Jul 2021Sleep and circadian rhythm disturbances are central features of many movement disorders, exacerbating motor and non-motor symptoms and impairing quality of life.... (Review)
Review
Sleep and circadian rhythm disturbances are central features of many movement disorders, exacerbating motor and non-motor symptoms and impairing quality of life. Understanding these disturbances to sleep is clinically important and may further our understanding of the underlying movement disorder. This review evaluates the current anatomical and neurochemical understanding of normal sleep and the recognised primary sleep disorders. In addition, we undertook a systematic review of the evidence for disruption to sleep across multiple movement disorders. Rapid eye movement sleep behaviour disorder has emerged as the most reliable prodromal biomarker for the alpha synucleinopathies, including Parkinson's disease and multiple system atrophy, often preceding motor symptom onset by several years. Abnormal sleep has also been described for many other movement disorders, but further evidence is needed to determine whether this is a primary or secondary phenotypic component of the underlying condition. Medication used in the treatment of motor symptoms also affects sleep and can aggravate or cause certain sleep disorders. Within the context of movement disorders, there is also some suggestion of a shared underlying mechanism for motor and sleep pathophysiology, with evidence implicating thalamic and brainstem structures and monoaminergic neurotransmission. This review highlights the need for an understanding of normal and abnormal sleep within the movement disorder clinic, an ability to screen for specific causes of poor sleep and to treat sleep disturbance to improve quality of life. Key sleep disorders also act as important biomarkers and have implications in diagnosis, prognosis and the development of future therapies.
Topics: Circadian Rhythm; Humans; Movement Disorders; Quality of Life; Sleep; Sleep Wake Disorders
PubMed: 33741740
DOI: 10.1136/jnnp-2020-325546 -
Parkinsonism & Related Disorders May 2021The emerging science of fatigue has soundly endorsed the need for its unified definition, shared terminology and increased recognition in neurological illnesses.... (Review)
Review
The emerging science of fatigue has soundly endorsed the need for its unified definition, shared terminology and increased recognition in neurological illnesses. Nevertheless, the real impact of fatigue remains under-recognized. Fatigue describes a sense of tiredness, lack of energy or need for increased effort often perceived as overwhelming, pervasive, and disabling. It is a common feature of chronic medical conditions and neurological diseases, including Parkinson's disease (PD) and other hypokinetic, hyperkinetic, and functional movement disorders (FMD). While there is solid evidence for the burden of fatigue in PD, knowledge of fatigue in other movement disorders (MDS) is still limited. Lack of consensus definition, rigorous measures and the high prevalence of potential confounders such as apathy, depression and sleepiness are the main obstacles in studying fatigue in MDS. This review of the prevalence, impact, and clinical correlates of fatigue in common MDS summarizes current hypotheses for the pathophysiological mechanisms underlying fatigue and gives a brief overview of treatment options. Fatigue is a prevalent, disabling, primary non-motor symptom (NMS) in MDS, including atypical and secondary parkinsonisms, dystonia, essential tremor (ET) and a hallmark feature of FMD. We report the hypothesis that fatigue is a perceptual disorder of the sensorimotor system. Given the relevance of this burdensome symptom, fatigue deserves greater clinical and research attention to better understand its manifestation and pathophysiology and to improve diagnosis and treatment.
Topics: Fatigue; Female; Humans; Male; Movement Disorders
PubMed: 33839028
DOI: 10.1016/j.parkreldis.2021.03.018