Nature , A number sign is used with this entry because of evidence that autosomal dominant torsion dystonia-4 DYT4 is caused by heterozygous mutation in the TUBB4A gene on chromosome 19p NOTE: OMIM is intended for use primarily by physicians and other professionals concerned with genetic disorders, by genetics researchers, and by advanced students in science and medicine. While the OMIM database is open to the public, users seeking information about a personal medical or genetic condition are urged to consult with a qualified physician for diagnosis and for answers to personal questions.
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Central Nervous System. Dystonia - PS - 27 Entries. Cassandra L. Creation Date:. Victor A. Edit History:. Clinical Features. Molecular Genetics. Dystonia 4, torsion, autosomal dominant.
Dystonia: diagnosis and management
Dystonia 13, torsion. Dystonia, childhood-onset, with optic atrophy and basal ganglia abnormalities. Dystonia 2, torsion, autosomal recessive. Dystonia 9. GLUT1 deficiency syndrome 2, childhood onset. Dystonia Paroxysmal nonkinesigenic dyskinesia 2. Paroxysmal nonkinesigenic dyskinesia 1. Dystonia, myoclonic. Dystonia 6, torsion. Dystonia-1, torsion.
Dystonia, DOPA-responsive, with or without hyperphenylalaninemia. AR , AD. Episodic kinesigenic dyskinesia 1. Episodic kinesigenic dyskinesia 2.
Dystonia 4, Torsion, Autosomal Dominant Type
Dystonia-7, torsion. Dystonia 28, childhood-onset. Dystonia, primary torsion. Dystonia 26, myoclonic. Dystonia-Parkinsonism, X-linked. Autosomal dominant. The visuosensory neurons in the superficial layer of the superior colliculus exert inhibitory influences on the pre-motor neurons in the intermediate and deep layer of the superior colliculus 53 , The deep layer in turn projects via the tecto-reticulospinal and tectospinal pathways to the upper cervical spinal cord 55 , 56 , 57 , Prolonged duration firing of visuosensory neurons because of impaired GABA inhibition would cause hyperexcitability of the pre-motor neurons in the deep layer of the superior colliculus.
These hyperexcitable premotor neurons could stimulate motor neurons in the upper cervical spinal cord perhaps resulting in the abnormal, jerky head spasms characteristic of cervical dystonia. The findings from our study that superior collicular processing is disrupted in both patients and relatives harbouring the endophenotype an abnormal TDT , supports the hypothesis that disrupted superior collicular processing is involved temporal discrimination.
As an abnormal TDT is a mediational endophenotype for cervical dystonia, we might assume that disordered sensory processing in the superior colliculus is also involved in the pathogenesis of this condition. While the results of this study support a model of reduced superior collicular GABAergic activity as contributing to sensory processing abnormalities and motor features of cervical dystonia, our study cannot determine the exact level at which this deficit arises; this GABAergic deficit may, in fact, be upstream of the superior colliculus.
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Further research is required to determine this. A Dynamic Causal Modelling DCM study may be instructive in this regard as it may identify where the superior colliculus fits within a given brain network and how these connections are impacted by abnormal TDTs and dystonia. All experiments were performed in accordance with relevant guidelines and regulations.
To examine any functional differences between those with a normal TDT versus those with an abnormal TDT the study was planned to have an equal representation from the following four groups; cervical dystonia patients, relatives with abnormal TDT, relatives with normal TDTs and healthy controls. Sixty-four, age- and sex-matched participants 16 cervical dystonia patients, 16 first-degree relatives with abnormal TDT, 16 relatives with normal TDT and 16 healthy controls were recruited.
The mean age of study participants was Forty-two were women. All participants had normal cognition, normal visual acuity, absence of sensory symptoms and a normal sensory examination. Sixteen cervical dystonia patients 10 women; four familial, 12 sporadic mean age Thirteen patients were receiving regular botulinum toxin injections for their dystonia at the time of scanning.
Amongst the group receiving regular botulinum toxin injections, three patients were taking regular clonazepam and four patients were on anti-depressant medication. Of those not receiving regular botulinum toxin injections, none were taking regular medications. Thirty-two unaffected first-degree relatives were recruited 22 women, mean age Seven had first-degree relatives with familial cervical dystonia; 25 had first-degree relatives with sporadic cervical dystonia.
All were clinically examined by two neurologists with expertise in dystonia; none had any evidence of dystonia or dystonic tremor.
From hospital staff and relatives of the research team sixteen healthy control participants were recruited 10 women; mean age Visual and tactile TDT testing was carried out in a single session, in a sound-proofed, darkened room. This method and has been previously described Kimmich et al. Structural and functional MRI images were acquired from all 64 age- and sex-matched participants that participated in the behavioural experiment 16 cervical dystonia patients, 32 first-degree relatives and 16 healthy controls.
Billington et. Their study was statistically powered to show differences between loom and recede in a cohort of ten participants aged between 20—40 years. To ensure full coverage of the superior colliculi we orientated the slices parallel to the brainstem at the height of the pons. The first four volumes from each run were discarded to avoid T1 equilibrium effects. The visual paradigm, based on 41 was an event-related design developed in Presentation Software Neurobehavioral Systems Inc.
To increase the perceived effect of 3-dimensional movement, thus increasing the likelihood of superior colliculus activation, a patch covered the right eye for the duration of the experiment. Participants were presented with three stimulus conditions: looming, receding and random motion Fig. Experimental visual stimulus paradigm. Screen capture of the sequence of events that occurs during each of the three conditions incorporated into the experimental paradigm.
The colour of the vertical lines indicates the trial type: loom green , recede yellow , random blue. In the looming-motion condition, the size of the sphere expands during motion towards the outer vertical lines before disappearing. The receding-motion condition is the reverse of the looming-motion condition; the sphere begins at its maximum diameter and contracts towards the inner vertical lines before disappearing. The random-motion condition consists of an unchanging sphere volume with randomly moving points that maintain the same velocity of the previous conditions.
Statistical parametric mapping software SPM12 www. Briefly, pre-processing consisted of resetting the origin, realignment, unwrapping, co-registration, segmentation and normalisation. The origin was reset to the anterior commissure to align functional and anatomical images in the same plane The first four images from each session were discarded to allow for equilibrium magnetisation. EPI blood oxygen level-dependent BOLD images were re-aligned and re-sliced using a six parameter spatial transformation with the first non-discarded image as a reference.
Estimated motion parameters calculated during the re-alignment step were saved for later use as nuisance regressors in the first level general linear model. Co-registration of functional and structural T1-weighted images was completed automatically and confirmed by careful visual inspection to ensure accurate alignment. The unified segmentation routine was employed to perform the segmentation bias correction and spatial normalisation.
Region of interest ROI analysis at the individual level was carried out on unsmoothed data. A single general linear model GLM was created for each subject which incorporated the regressors of interest loom, recede and random motion and nuisance regressors to account for discontinuity between recordings. The duration of each event corresponded to the timing of stimulus movement and was set to one second. The time-period between stimulus offset and the button press response was excluded from each event to avoid modelling an early motor preparatory response. The six movement parameters estimated during the re-alignment procedure were included as nuisance regressors to account for unwanted movement.
A whole brain one-sample and two-sample t-test using condition estimates beta values from a first level effect GLM analysis was performed to compare whole brain activation associated with each experimental condition loom, recede, random motion. A set of contrast images for each participant was generated for testing at group level.
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The contrast images were generated at the first level and then submitted to second level analysis. A repeat 2 nd level analysis was calculated for each group incorporating the contrasts examined in the whole group analysis. Imaging of the superior colliculus is difficult due its small size, its proximity to major blood vessels and anatomical variation that exists between subjects Accurate delineation of superior collicular anatomical boundaries is necessary to ensure optimal region of interest analysis To achieve this, we identified the anatomical landmarks of the superior colliculus during neuropathological dissection of human brainstem specimens.
A consultant neuropathologist dissected the brainstem specimen and identified the anatomical boundaries of left and right superior colliculus Fig. Using these pre-defined anatomical boundaries, we created 3-D regions of interest ROIs using Mango image processing software Lancaster, Martinez; www. Region of interest anatomical definition: A Human cadaver brainstem specimen used during a neuro-pathological dissection.
A consultant neuropathologist dissected the brainstem specimen and identified the anatomical landmarks of the left and right superior colliculi. B Superior collicular 3-D regions of interest on T1-weighted structural brain images. Three radiological views are shown; axial, coronal and sagittal respectively. Mango image processing software Lancaster, Martinez; www. Structural T1-weighted images were used for ROI definition. The axial-plane centre point was defined as a point equidistant from the posterior surface of the superior colliculus to the anterior border of the superior colliculus posterior border of the posterior commissure.
On the sagittal plane a vertical line was drawn from the superior border of the superior colliculus to the indentation between the superior and inferior colliculi: where this line crossed a line equidistant to the medial and lateral border of the superior colliculus our centre-point was set. The three stimulus types looming, receding and random motion were modelled at the first level and incorporated into a second level analysis. To calculate the change in BOLD signal over time within the region of interest, percent signal change time courses were estimated for individual subjects.
By comparing contrast of conditions as opposed to conditions within subjects, we reduced the potential for noise that may arise from inter-subject variability. Participants were grouped according to normal or abnormal TDT for correlation analysis. All data generated or analysed during this study are included in this published article Albin, R.
The functional anatomy of basal ganglia disorders. Trends Neurosci. DeLong, M.
DYSTONIA 4, TORSION, AUTOSOMAL DOMINANT; DYT4 | kecaheretu.tk
Primate models of movement disorders of basal ganglia origin. Galardi, G. Basal ganglia and thalamo-cortical hypermetabolism in patients with spasmodic torticollis. Acta Neurol. Wilson, B. Animal models for dystonia. Nelson, A. Delnooz, C. Altered striatal and pallidal connectivity in cervical dystonia. Brain Struct. Neychev, V. The basal ganglia and cerebellum interact in the expression of dystonic movement. Brain , — Vidailhet, M. Pathophysiology of dystonia. The functional neuroanatomy of dystonia. Hendrix, C. Toward a network model of dystonia.
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Sadnicka, A. Quartarone, A. Emerging concepts in the physiological basis of dystonia. Hallett, M. Charness, M. Brain mapping in musicians with focal task-specific dystonia. Abnormal plasticity of sensorimotor circuits extends beyond the affected body part in focal dystonia. Psychiatry 79 , — Hinkley, L.
Hand Ther. Belvisi, D. Abnormal experimentally- and behaviorally-induced LTP-like plasticity in focal hand dystonia. Zittel, S. Normalization of sensorimotor integration by repetitive transcranial magnetic stimulation in cervical dystonia. Poisson, A. Patel, N. Alleviating manoeuvres sensory tricks in cervical dystonia. Psychiatry 85 , —4 Conte, A.
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Non-motor symptoms in patients with adult-onset focal dystonia: Sensory and psychiatric disturbances. Kimmich, O. Sporadic adult onset primary torsion dystonia is a genetic disorder by the temporal discrimination test. Brain , —63 Dean, P. Event or emergency? Two response systems in the mammalian superior colliculus. Furigo, I. The role of the superior colliculus in predatory hunting. Neuroscience , 1—15 Terry, H.
Vagnoni, E. Threat modulates perception of looming visual stimuli. Yilmaz, M. Rapid innate defensive responses of mice to looming visual stimuli. Wu, L. Tectal neurons signal impending collision of looming objects in the pigeon. Liu, Y. Neuronal responses to looming objects in the superior colliculus of the cat.
Billington, J. Neural processing of imminent collision in humans. Fischl, B. Automatically Parcellating the Human Cerebral Cortex. Cortex 14 , 11—22 Hammers, A. Three-dimensional maximum probability atlas of the human brain, with particular reference to the temporal lobe. Brain Mapp. Shattuck, D. Construction of a 3D probabilistic atlas of human cortical structures.
Neuroimage 39 , —80 Poldrack, R. Region of interest analysis for fMRI. PLoS One 8 , e Dynamic cortical gray matter volume changes after botulinum toxin in cervical dystonia.
Dresel, C. Botulinum toxin modulates basal ganglia but not deficient somatosensory activation in orofacial dystonia. Sensorimotor network in cervical dystonia and the effect of botulinum toxin treatment: A functional MRI study. Kendler, K. Endophenotype: a conceptual analysis.