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Torsion Dystonia (torsion + dystonia)

Distribution by Scientific Domains
Medical Sciences90%

Kinds of Torsion Dystonia

  • primary torsion dystonia
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    Selected Abstracts

    TorsinA in PC12 cells: Localization in the endoplasmic reticulum and response to stress

    JOURNAL OF NEUROSCIENCE RESEARCH, Issue 2 2003
    Jeffrey Hewett
    Abstract Most cases of early-onset torsion dystonia are caused by deletion of GAG in the coding region of the DYT1 gene encoding torsinA. This autosomal dominant neurologic disorder is characterized by abnormal movements, believed to originate from neuronal dysfunction in the basal ganglia of the human brain. The torsins (torsinA and torsinB) are members of the "ATPases associated with a variety of cellular activities" (AAA+) superfamily of proteins that mediate chaperone and other functions involved in conformational modeling of proteins, protection from stress, and targeting of proteins to cellular organelles. In this study, the intracellular localization and levels of endogenous torsin were evaluated in rat pheochromocytoma PC12 cells following differentiation and stress. TorsinA, apparent MW 37 kDa, cofractionates with markers for the microsomal/endoplasmic reticulum (ER) compartment and appears to reside primarily within the ER lumen based on protease resistance. TorsinA immunoreactivity colocalizes with the lumenal ER protein protein disulfide isomerase (PDI) and extends throughout neurites. Levels of torsinA did not increase notably in response to nerve growth factor-induced differentiation. None of the stress conditions tested, including heat shock and the unfolded protein response, affected torsinA, except for oxidative stress, which resulted in an increase in the apparent MW of torsinA and redistribution to protrusions from the cell surface. These findings are consistent with a relatively rapid covalent modification of torsinA in response to oxidative stress causing a change in state. Mutant torsinA may interfere with and/or compromise ER functions, especially in dopaminergic neurons, which have high levels of torsinA and are intrinsically vulnerable to oxidative stress. © 2003 Wiley-Liss, Inc. [source]

    Microstructural white matter changes in primary torsion dystonia

    MOVEMENT DISORDERS, Issue 2 2008
    Maren Carbon MD
    Abstract Primary torsion dystonia (PTD) has been conceptualized as a disorder of the basal ganglia. However, recent data suggest a widespread pathology involving motor control pathways. In this report, we explored whether PTD is associated with abnormal anatomical connectivity within motor control pathways. We used diffusion tensor magnetic resonance imaging (DT-MRI) to assess the microstructure of white matter. We found that fractional anisotropy, a measure of axonal integrity and coherence, was significantly reduced in PTD patients in the pontine brainstem in the vicinity of the left superior cerebellar peduncle and bilaterally in the white matter of the sensorimotor region. Our data thus support the possibility of a disturbance in cerebello-thalamo-cortical pathways as a cause of the clinical manifestations of PTD. © 2007 Movement Disorder Society [source]

    Molding the sensory cortex: Spatial acuity improves after botulinum toxin treatment for cervical dystonia

    MOVEMENT DISORDERS, Issue 16 2007
    Richard Walsh MB
    Abstract Disorganization of sensory cortical somatotopy has been described in adult onset primary torsion dystonia (AOPTD). Although botulinum toxin type A (BTX-A) acts peripherally, some studies have suggested a central effect. Our primary hypothesis was that sensory cortical reorganization occurs after BTX-A treatment of AOPTD. Twenty patients with cervical dystonia and 18 healthy age-matched control patients had spatial discrimination thresholds (SDTs) measured at baseline and monthly for 3 months. Mean baseline SDT (±SD) was 1.75 ±0.76 mm in the dystonia group, greater than the control group mean of 1.323 ± 0.45 mm (P = 0.05). Mean control group SDT did not vary significantly over time. A transient improvement of 23% from baseline (P = 0.005) occurred in the dystonia group 1 month after injection, which did not positively correlate with changes in physician and patient ratings of torticollis severity. The presumed mechanism of SDT improvement is a modulation of afferent cortical inputs from muscle spindles. © 2007 Movement Disorder Society [source]

    Changes in blink reflex excitability after globus pallidus internus stimulation for dystonia

    MOVEMENT DISORDERS, Issue 10 2006
    Stephen Tisch MBBS
    Abstract A pathophysiological feature of dystonia is reduced inhibition at various levels of the nervous system, which may be detected in clinically unaffected body parts. Chronic deep brain stimulation (DBS) of the globus pallidus internus (GPi) has emerged as an effective treatment for primary torsion dystonia (PTD), although its mechanism of action and impact on inhibitory abnormalities in dystonia are unknown. We sought to understand the effect of GPi DBS on brainstem excitability in patients with PTD. We measured the blink reflex from orbicularis oculi in response to paired electrical stimulation of the supraorbital nerve at interstimulus intervals of 500 and 1,000 milliseconds in 10 patients with PTD before and at intervals of 1, 3, and 6 months after bilateral GPi DBS and in 10 healthy subjects. Patients were clinically evaluated using the Burke,Fahn,Marsden dystonia rating scale. We found R2 inhibition was significantly decreased in PTD patients compared with control subjects and progressively increased after GPi DBS, which correlated with clinical improvement in dystonia. We conclude that GPi DBS for PTD results in functional reorganization of the nervous system, which includes a long-term increase in brainstem inhibition. © 2006 Movement Disorder Society [source]

    Phenotypic characterization of DYT13 primary torsion dystonia,

    MOVEMENT DISORDERS, Issue 2 2004
    Anna Rita Bentivoglio MD
    Abstract We describe the phenotype of DYT13 primary torsion dystonia (PTD) in a family first examined in 1994. A complete neurological evaluation was performed on all available family members: 8 individuals were definitely affected by dystonia. The family was re-evaluated in March 2000: at that time, 3 more individuals had developed symptoms of dystonia. Inheritance of PTD was autosomal dominant, with affected individuals spanning three consecutive generations and male-to-male transmission. Age at onset ranged from 5 to 43 years. Onset occurred either in the craniocervical region or in upper limbs. Progression was mild, and the disease course was benign in most affected individuals; generalization occurred only in 2 cases. We did not find anticipation of age at onset or of disease severity through generations. Most subjects presented with jerky, myoclonic-like dystonic movements of the neck or shoulders. DYT13-PTD is an autosomal dominant disease, with incomplete penetrance (58%). Clinical presentation and age at onset were more variable than in DYT1-PTD, and the neck was involved in most of those affected. Moreover, the individuals with generalised dystonia were not severely disabled and were able to lead independent lives. To date, this is the only family with DYT13-PTD. © 2003 Movement Disorder Society [source]

    Impaired heteronymous somatosensory motor cortical inhibition in dystonia

    MOVEMENT DISORDERS, Issue 11 2003
    Laura Bertolasi MD
    Abstract A typical pathophysiological abnormality in dystonia is cocontraction of antagonist muscles, with impaired reciprocal inhibitory mechanisms in the spinal cord. Recent experimental data have shown that inhibitory interactions between antagonist muscles have also a parallel control at the level of the sensorimotor cortex. The aim of this work was to study heteronymous effects of a median nerve stimulus on the corticospinal projections to forearm muscles in dystonia. We used the technique of antagonist cortical inhibition, which assesses the conditioning effect of median nerve afferent input on motor evoked potentials (MEPs) elicited by transcranial magnetic stimulation (TMS) in ipsilateral forearm extensor muscles at rest. Nine healthy subjects and 10 patients with torsion dystonia participated in the study. MEPs and somatosensory evoked potentials were normal in patients. In healthy subjects, median nerve stimulation at 15- to 18-msec intervals inhibited the test MEPs in forearm extensors. In dystonic patients, median nerve stimulation delivered at the same conditioning,test intervals elicited significantly less inhibition of the test MEP. On the whole, these data suggest an impaired sensory,motor integration in dystonia and, more specifically, the decreased antagonistic cortical inhibition could suggest that functional interactions between antagonist muscles are primarily impaired at the cortical level. © 2003 Movement Disorder Society [source]

    Novel Italian family supports clinical and genetic heterogeneity of primary adult-onset torsion dystonia

    MOVEMENT DISORDERS, Issue 2 2002
    Francesco Brancati MD
    Abstract We report on an Italian kindred with adult-onset primary torsion dystonia (PTD). A detailed clinical examination of the six definitely affected family members revealed a mild, purely focal phenotype. The disease involved only one body part (eyes, neck, or arm). PTD in this family was not linked to the known disease loci (DYT1, DYT6, DYT7, and DYT13), and the 3-bp deletion in the DYT1 gene was also excluded. These findings support genetic heterogeneity of PTD and indicate that a novel unassigned gene is responsible for focal dystonia in this family. © 2002 Movement Disorder Society. [source]

    Brainstem pathology in DYT1 primary torsion dystonia

    ANNALS OF NEUROLOGY, Issue 4 2004
    Kevin St. P. McNaught PhD
    DYT1 dystonia is a severe form of young-onset dystonia caused by a mutation in the gene that encodes for the protein torsinA, which is thought to play a role in protein transport and degradation. We describe, for the first time to our knowledge, perinuclear inclusion bodies in the midbrain reticular formation and periaqueductal gray in four clinically documented and genetically confirmed DYT1 patients but not in controls. The inclusions were located within cholinergic and other neurons in the pedunculopontine nucleus, cuneiform nucleus, and griseum centrale mesencephali and stained positively for ubiquitin, torsinA, and the nuclear envelope protein lamin A/C. No evidence of inclusion body formation was detected in the substantia nigra pars compacta, striatum, hippocampus, or selected regions of the cerebral cortex. We also noted tau/ubiquitin-immunoreactive aggregates in pigmented neurons of the substantia nigra pars compacta and locus coeruleus in all four DYT1 dystonia cases, but not in controls. This study supports the notion that DYT1 dystonia is associated with impaired protein handling and the nuclear envelope. The role of the pedunculopontine and cuneiform nuclei, and related brainstem other involved brainstem structures in mediating motor activity and muscle tone also suggest that alterations in these structures, in mediating motor activity and controlling muscle tone suggests that alterations in these structures could underlie the pathophysiology of DYT1 dystonia. Ann Neurol 2004 [source]