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Query: UMLS:C0040822 (tremor)
 18,428 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Neuropathology of hyperkinetic movement disorders can be very challenging. This paper starts with basic functional anatomy of the basal ganglia in order to appreciate that focal lesions like for instance tumor or infarction can cause hyperkinetic movement disorders like (hemi)ballism. The neuropathology of different causes of chorea (amongst others Huntington's disease, neuroacanthosis, and HLD-2) and dystonia (DYT1, PD, and Dopa-Responsive Dystonia) are described. Besides the functional anatomy of the basal ganglia a wider anatomical network view is provided. This forms the basis for the overview of the neuropathology of different forms of tremor.
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PMID:Neuropathological diagnostic considerations in hyperkinetic movement disorders. 2342 Jun 6

CHOREA CAN BE CAUSED BY A MULTITUDE OF ETIOLOGIES: neurodegenerative, pharmacological, structural, metabolic, and others. In absence of other apparent causes, exclusion of Huntington's disease is often a first step in the diagnostic process. There are a number of neurodegenerative disorders whose genetic etiology has been identified in the past decade. Molecular diagnosis has enabled genetic identification of disorder subtypes which were previously grouped together, such as the neurodegeneration with brain iron accumulation disorders and the neuroacanthocytosis syndromes, as well as identification of phenotypic outliers for recognized disorders. Correct molecular diagnosis is essential for genetic counseling and, hopefully, ultimately genetic therapies. In addition, there has recently been recognition of other disorders which can mimic neurodegenerative disorders, including paraneoplastic and prion disorders. This article focuses upon recent developments in the field but is not intended to provide an exhaustive review of all causes of chorea, which is available elsewhere. I also discuss the nomenclature of these disorders which has become somewhat unwieldy, but may ultimately be refined by association with the causative gene.
Tremor Other Hyperkinet Mov (N Y) 2012
PMID:Update on the Non-Huntington's Disease Choreas with Comments on the Current Nomenclature. 2344 May 98

Dynamic mutations are those caused by the expansion of existing polymorphic DNA repeat sequences beyond a copy number threshold. These genetic mutations can give rise to dominant, recessive or X-linked disorders, dependent upon the location of the repeat sequence with respect to the genes that are affected by the expansion. The distinguishing feature of these mutations is their instability, which is a function of the copy number of repeats and can occur in either meiosis or mitosis. For some of the resultant disorders there is a relationship between repeat copy number and age-at-onset and/or severity ofsymptoms ofthe disease. For this reason much effort is now focused on identifying the pathogenic pathways from the mutation to the disease symptoms in the hope of finding means of delaying onset, slowing progression or even preventing symptoms ofthe disease. The growing list ofneurodegenerative and neuromuscular diseases caused by dynamic mutations includes Huntington's disease (HD), spinobulbar muscular atrophy (SBMA), dentatorubral-pallidoluysian atrophy (DRPLA), a number of spinocerebellar ataxias (SCAs), oculopharyngeal muscular dystrophy (OPMD), myotonic dystrophy Type 1 and 2 (DM1 and 2), Huntington's disease-like 2 (HDL-2), Friedrich's ataxia (FRDA), Fragile X associated tremor ataxia syndrome (FXTAS), Fragile XE (FRAXE) and Fragile XA (FRAXA). This chapter aims to give a brief overview of what is currently known about each disease and the mechanisms underlying pathogenesis.
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PMID:Dynamic mutations: where are they now? 2356 Mar 5

Fragile X-associated tremor/ataxia syndrome (FXTAS) is a late-onset neurodegenerative disorder associated with FMR1 gene premutation alleles (55-200 CGG repeats). Fragile X-associated tremor/ataxia syndrome clinical core features include action tremor, gait ataxia, cognitive deficits progressing to dementia, and frequently parkinsonism. Although the pathogenic molecular mechanism of FXTAS is not completely understood, the restriction of the phenotype to the FMR1 premutation range has given rise to a model based on a RNA toxic gain-of-function. Since the identification of the first microRNAs (miRNAs) and their role in normal development, several studies have associated them with neurodegenerative diseases such as Parkinson, Alzheimer and Huntington diseases, suggesting that they play a key role in brain development, as well as in its morphogenesis. Herein, we present the characterization of miRNA expression profiles in FXTAS male patients using deep sequencing-based technologies and microarray technology. Deep sequencing analysis evidenced 83 miRNAs that were significantly deregulated whereas microarray analysis showed 31. When comparing these results, 14 miRNAs were found deregulated in FXTAS patients. MiR-424 and miR-574-3p showed significant fold change adjusted P-values in both platforms in FXTAS patients. MiR-424 has been founded substantially and specifically enriched in human cerebral cortical white matter of Alzheimer disease patients, which, together with cerebral atrophy, is a prominent imaging finding in individuals with FXTAS. The study provides the first systematic evidence of differential miRNA expression changes in FXTAS blood samples. Although further studies are necessary to better characterize the miRNA function in FXTAS disorder, our results suggest that they might contribute to its pathogenesis.
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PMID:MicroRNA expression profiling in blood from fragile X-associated tremor/ataxia syndrome patients. 2379 Jan 10

Tetrabenazine (TBZ) is a reversible inhibitor of vesicular monoamine storage that is used to treat Huntington's disease. TBZ preferentially depletes striatal dopamine (DA), and patients being treated with TBZ often experience parkinsonian side effects. The present studies were conducted to investigate the ability of TBZ to induce tremulous jaw movements (TJMs), which are a rodent model of parkinsonian tremor, and to determine if interference with adenosine A2A receptor transmission can attenuate TJMs and other motor effects of TBZ. In rats, TBZ (0.25-2.0mg/kg) significantly induced TJMs, which primarily occurred in the 3.0-7.5-Hz frequency range. The adenosine A2A antagonist MSX-3 (1.25-10.0mg/kg) significantly attenuated the TJMs induced by 2.0mg/kg TBZ in rats, and also significantly reduced the display of catalepsy and locomotor suppression induced by TBZ. In mice, TBZ (2.5-10.0mg/kg) dose dependently induced TJMs, and adenosine A2A receptor knockout mice showed significantly fewer TJMs compared to wild-type controls. MSX-3 (2.5-10.0mg/kg) also significantly reduced TBZ-induced TJMs in CD1 mice. To provide a cellular marker of these pharmacological conditions, we examined c-Fos expression in the ventrolateral neostriatum (VLS). TBZ (2.0mg/kg) significantly increased the number of c-Fos-positive cells in the VLS, which is indicative of reduced DA D2 receptor transmission, and 10.0mg/kg MSX-3 significantly attenuated the TBZ-induced c-Fos expression. These results indicate that TBZ induces tremor as measured by the TJM model, and that pharmacological antagonism and genetic deletion of adenosine A2A receptors are capable of attenuating this oral tremor.
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PMID:The vesicular monoamine transporter (VMAT-2) inhibitor tetrabenazine induces tremulous jaw movements in rodents: implications for pharmacological models of parkinsonian tremor. 2386 69

Gamma-aminobutyric acid (GABA) is the major inhibitory neurotransmitter in the central nervous system. This paper reviews the current knowledge derived from positron emission tomography and single photon emission tomography studies quantifying GABAA receptor binding in movement disorders of extrapyramidal origin, focusing on essential tremor (ET), Parkinsonism (idiopathic PD and atypical parkinsonian syndromes), dystonia, and Huntington's disease (HD). In ET, there is evidence to suggest a specific disturbance at the level of the GABAA receptor and impairment of GABAergic inhibition to be a driving force for the development of rhythmic overactivity in cerebello-thalamo-cortical networks. In dystonia, GABAA receptor binding studies have been relevant for unraveling pathophysiological mechanisms causing sensorimotor disinhibition leading to dystonic movements. The role of GABA in idiopathic PD and atypical parkinsonian syndromes is less clear, despite the fact that GABAA receptors are expressed on virtually all striatal neurons and that GABA exerts important inhibitory influences upon basal outflow pathways. In HD, reductions of GABAA receptor have been reported in the basal ganglia but were found to be less extensive compared with concomitant metabolic reductions.
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PMID:Imaging the role of GABA in movement disorders. 2399 Mar 56

Significant advances have allowed diffusion magnetic resonance imaging (MRI) to evolve into a powerful tool in the field of movement disorders that can be used to study disease states and connectivity between brain regions. Diffusion MRI is a promising potential biomarker for Parkinson's disease and other forms of parkinsonism, and may allow the distinction of different forms of parkinsonism. Techniques such as tractography have contributed to our current thinking regarding the pathophysiology of dystonia and possible mechanisms of penetrance. Diffusion MRI measures could potentially assist in monitoring disease progression in Huntington's disease, and in uncovering the nature of the processes and structures involved the development of essential tremor. The ability to represent structural connectivity in vivo also makes diffusion MRI an ideal adjunctive tool for the surgical treatment of movement disorders. We review recent studies using diffusion MRI in movement disorders research and present the current state of the science as well as future directions.
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PMID:The evolving role of diffusion magnetic resonance imaging in movement disorders. 2404 83

Deep brain stimulation (DBS) is a well established treatment for essential tremor and for the tremor associated with Parkinson's disease. The efficacy of DBS in these common tremors has led some investigators to apply the technique to rarer tremors such as such as Holmes' tremor, posttraumatic tremor, orthostatic tremor, and the tremor associated with multiple sclerosis. Likewise, DBS of the thalamus and globus pallidus directly suppresses levodopa-induced dyskinesias in Parkinson's disease, suggesting the application of DBS to other hyperkinetic states such as Huntington's disease, tardive dyskinesia, and hemiballism. Myoclonus has also been treated with DBS, especially in cases where it is associated with dystonia. This chapter reviews the reported results of DBS for these conditions. Due to the rarity of these indications, most of the literature reviewed takes the form of case reports or small single-center case series.
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PMID:Deep brain stimulation for other tremors, myoclonus, and chorea. 2411 95

Neuromodulation using deep brain stimulation (DBS) has become an established therapy for the treatment of certain disorders such as Parkinson's disease and tremors. Recent advances in surgical and imaging techniques further decrease the surgical risk associated with these procedures. Symptoms such as tremor, bradykinesia, rigidity and gait disturbances can be significantly controlled with DBS. This results in an opportunity to decrease anti-parkinsonism medications, and their dyskinetic side-effects. Following the success of DBS in the management of movement disorders, the role of this therapy is being extensively studied in more complex disorders that involve cognition and behavior. The inherent complexity in cognitive circuitry makes neuromodulation using DBS more difficult than in movement disorders. The goal of DBS surgery in these diseases is not only to slow the cognitive decline, but also restoration of function and ultimately improvement in the quality of life. DBS as a treatment for patients with advanced dementia holds significant promise in delaying or reversing the progressive cognitive decline by enhancing connectivity in the memory networks. In appropriately selected patients this potentially reversible surgical therapy can lead to a significant improvement in the quality of life and reduce the burden on patients, families and the healthcare system. This review focuses on the recent and future studies involving neuromodulation for cognitive disorders such as Alzheimer's disease and Huntington's disease.
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PMID:Modulation of mind: therapeutic neuromodulation for cognitive disability. 2488 63

Repeat-associated disorders caused by expansions of short sequences have been classified as coding and noncoding and are thought to be caused by protein gain-of-function and RNA gain-of-function mechanisms, respectively. The boundary between such classifications has recently been blurred by the discovery of repeat-associated non-AUG (RAN) translation reported in spinocerebellar ataxia type 8, myotonic dystrophy type 1, fragile X tremor/ataxia syndrome and C9ORF72 amyotrophic lateral sclerosis and frontotemporal dementia. This noncanonical translation requires no AUG start codon and can initiate in multiple frames of CAG, CGG and GGGGCC repeats of the sense and antisense strands of disease-relevant transcripts. RNA structures formed by the repeats have been suggested as possible triggers; however, the precise mechanism of the translation initiation remains elusive. Templates containing expansions of microsatellites have also been shown to challenge translation elongation, as frameshifting has been recognized across CAG repeats in spinocerebellar ataxia type 3 and Huntington's disease. Determining the critical requirements for RAN translation and frameshifting is essential to decipher the mechanisms that govern these processes. The contribution of unusual translation products to pathogenesis needs to be better understood. In this review, we present current knowledge regarding RAN translation and frameshifting and discuss the proposed mechanisms of translational challenges imposed by simple repeat expansions.
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PMID:RAN translation and frameshifting as translational challenges at simple repeats of human neurodegenerative disorders. 2521 82


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