Dystonia is defined as a neurological syndrome characterized by involuntary sustained or intermittent muscle contractions causing twisting, often repetitive movements, and postures. Paroxysmal dyskinesias are episodic movement disorders encompassing dystonia, chorea, athetosis, and ballism in conscious individuals. Several decades of research have enhanced the understanding of the etiology of human dystonia and dyskinesias that are associated with dystonia, but the pathophysiology remains largely unknown. The spontaneous occurrence of hereditary dystonia and paroxysmal dyskinesia is well documented in rodents used as animal models in basic dystonia research. Several hyperkinetic movement disorders, described in dogs, horses and cattle, show similarities to these human movement disorders. Although dystonia is regarded as the third most common movement disorder in humans, it is often misdiagnosed because of the heterogeneity of etiology and clinical presentation. Since these conditions are poorly known in veterinary practice, their prevalence may be underestimated in veterinary medicine. In order to attract attention to these movement disorders, i.e., dystonia and paroxysmal dyskinesias associated with dystonia, and to enhance interest in translational research, this review gives a brief overview of the current literature regarding dystonia/paroxysmal dyskinesia in humans and summarizes similar hereditary movement disorders reported in domestic animals.

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Abstract Novel genetic aetiologies for epileptic encephalopathies and movement disorders have been discovered by using next-generation sequencing methods. The phenotypic and genotypic variability in these conditions is very wide. The aim of this study was to discover novel genetic causes and phenotypes of childhood-onset drug-resistant epilepsy and epileptic or developmental encephalopathies that occur separately or together with movement disorders, and familial movement disorders. Furthermore, the use of whole-exome sequencing (WES) as a diagnostic tool in clinical practice was evaluated. Altogether, 12 children with undefined aetiology, who fulfilled the inclusion criteria, were included in the study. GABRG2 gene was identified as a genetic cause of epileptic encephalopathies. Novel GABRG2-associated phenotypes included progressive neurodegeneration, epilepsy in infancy with migrating focal seizures, and autism spectrum disorder. New pathogenic variants, GABRG2 p.P282T and p.S306F, were discovered. The pathogenic NACC1 variant caused focal epilepsy, developmental disability, bilateral cataracts, and dysautonomia. The novel phenotype associated with the NACC1 p.R298W variant included hyperkinetic movement disorder. SAMD9L was found to be the genetic cause for the familial movement disorder. The phenotype associated with the novel SAMD9L p.I891T variant was very variable. Neuroradiological findings included cerebellar atrophy and periventricular white matter changes. After publication of these results, SAMD9L was reported to be one of the most common genetic aetiologies of childhood bone marrow failure and myelodysplastic syndrome. The pathogenic homozygous MTR variant was found to cause early-onset epileptic encephalopathy that occurred together with movement disorder and haematological disturbances. Drug resistant seizures responded to cofactor and vitamin treatments. Whole-exome sequencing for 10 patients with drug-resistant epilepsy or epileptic or developmental encephalopathy provided a genetic diagnosis for two patients (20%). This study confirmed that, for epileptic encephalopathies and movement disorders in which the genetic causes and phenotypes are heterogeneous and sometimes treatable, WES is a useful tool for diagnostics and in the search for novel aetiologies, which might turn out to be more common than expected. / Tiivistelmä Uusien sekvensointimenetelmien käyttöönotto on mahdollistanut epileptisten enkefalopatioiden ja liikehäiriöiden uusien geneettisten syiden löytymisen. Näissä sairausryhmissä geenien ja ilmiasujen vaihtelevuus on suurta. Tutkimuksen tarkoituksena oli löytää uusia geneettisiä syitä ja ilmiasuja lapsuusiällä alkavissa vaikeahoitoisissa epilepsioissa ja epileptisissä tai kehityksellisissä joko itsenäisesti tai yhdessä liikehäiriön kanssa esiintyvissä enkefalopatioissa sekä perheittäin esiintyvissä liikehäiriöissä. Lisäksi selvitettiin eksomisekvensoinnin käyttökelpoisuutta kliinisessä diagnostiikassa näiden potilasryhmien kohdalla. Tutkimukseen osallistui yhteensä 12 sisäänottokriteerit täyttävää lasta, joiden sairauden syy oli jäänyt tuntemattomaksi. GABRG2-geenin mutaatiot aiheuttivat epileptisiä enkefalopatioita, joiden uutena ilmiasuna oli etenevä taudinkuva, johon liittyivät aivojen rappeutuminen, migroiva imeväisiän paikallisalkuinen epilepsia sekä autismikirjon häiriö. Tutkimuksessa löydettiin uusia GABRG2-mutaatioita: p.P282T ja p.S306F. NACC1-geenin mutaatio aiheutti epilepsian, kehitysvammaisuuden, molemminpuolisen kaihin ja autonomisen hermoston toiminnan häiriön. Hyperkineettinen liikehäiriö oli uusi NACC1 p.R298W -mutaatioon liittyvä ilmiasu. SAMD9L-geenin mutaatio aiheutti perheessä esiintyvän liikehäiriön. Neurologinen ja hematologinen ilmiasu olivat hyvin vaihtelevia. Aivojen kuvantamislöydöksiin sisältyi pikkuaivojen rappeutumista ja valkoisen aivoaineen muutoksia aivokammioiden ympärillä. Näiden tutkimustulosten julkaisemisen jälkeen SAMD9L-geenin mutaatioiden on todettu olevan yksi yleisimmistä perinnöllisistä luuytimen vajaatoiminnan ja myelodysplasian syistä. Homotsygoottinen MTR-geenin mutaatio aiheutti varhain alkaneen epileptisen enkefalopatian, liikehäiriön ja hematologisen häiriön. Kofaktori- ja vitamiini hoidot vähensivät epileptisiä kohtauksia, joihin tavanomainen lääkitys ei tehonnut. Geneettiset syyt ja ilmiasut ovat epileptisissä enkefalopatioissa ja liikehäiriöissä hyvin vaihtelevia, ja osaan on olemassa spesifi hoito. Eksomisekvensointi on käyttökelpoinen diagnostiikan ja uusien geneettisten syiden etsimisen apuna. Tässä tutkimuksessa eksomisekvensoinnin avulla kymmenestä potilaasta kahdelle (20%) saatiin varmistettua geneettinen diagnoosi.

Objective: To determine the effects of head position and of different postural control demands on head tremor measures in participants with essential tremor. Methods: Seventeen participants with essential tremor (ET) of the head and 17 control participants took part. Individuals held their heads in varying degrees of rotation, flexion, and extension. Subsequently, individuals sat and stood in different postures, incorporating different foot placements (feet apart and together), surfaces (solid and foam), and vision conditions (eyes open and closed). Neck muscle activity was recorded from three muscles bilaterally (trapezius, sternocleidomastoid, splenius capitis). Three-dimensional head and thorax positions were recorded using an Optotrak system, and head angular velocity with respect to thorax was calculated by differentiating tilt-twist angles. Fourier analysis was used to determine tremor power. Results: ET participants showed sharp peaks at their tremor frequency in spectral plots of kinematic data, whereas CN participants did not. Electromyography data was too noisy for frequency analysis. ET participants displayed increased tremor power in head positions 25° from neutral compared to neutral and positions 50° from neutral. Tremor power increased with increasing difficulty of posture for both participant groups. Removal of vision resulted in decreased tremor power in ET participants; power was significantly decreased in the easier postures, and progressively less so with increasing difficulty of posture. Interestingly, tremor direction was inconsistent in both groups, and two ET participants displayed multiple tremor peaks. Conclusions: The tilt-twist method is a feasible way of measuring head kinematics. Changing stiffness of the neck likely mediates the effect of head position on head tremor power, with the resultant interplay of the central driver and the mechanical resonance driving the amplitude changes. Decreasing stability of posture increases head tremor, likely due to the associated increase in postural sway and stress on the postural control system. Vision appears to exacerbate head tremor through the addition of tremor-related visual noise and an implicit task to stabilize vision; this is possible evidence of a visuomotor deficit. However, stabilizing vision becomes less important with increasing difficulty of posture, resulting in a narrowing gap in tremor power between vision and no vision conditions. / Thesis (Master, Rehabilitation Science) -- Queen's University, 2011-03-31 18:16:59.927

The intention of this analysis was to identify patients with treated Wilson disease (WD) and residual neurological symptoms in order to determine whether or not they were undergoing any treatment in addition to the common decoppering medication. Moreover, the effects of any symptomatic medication were analyzed. Two samples of WD patients were investigated either by a mailed questionnaire survey (n = 135) or by a retrospective analysis (n = 75). A considerable proportion of patients still suffered from neurological symptoms (n = 106, 50.5%), of whom a relatively small proportion was treated symptomatically (n = 33, 31.1%). The documented effects varied substantially, with anticholinergics and botulinum toxin (against dystonia) and primidone (against tremor) apparently being the most promising compounds. Further studies are required to analyze the symptomatic treatment of WD patients with residual neurological symptoms in more detail. / Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich.

Context: Most of the patients suffering from any neurological disorder pose ambulatory disturbance at any stage of disease which may result in falling without showing any warning sign and every patient is different from another. So there is a need to develop a mechanism to detect shaky motion. Objectives: The major objectives are: (i) To check different gait parameters in walking disorders using Shimmer platform (R). (ii) Wearing SHIMMER wireless sensors on hip, waist and chest, to check which one is the most suitable. (iii) To draw effective conclusion/results based on calibrated data in real time and offline processing in EyesWeb/Matlab.To develop an effective mechanism/algorithm for security warning and activating alarm systems. Methods: Our thesis project is related to analyze real-time gait of the patient suffering from Parkinson's disease for actively responding to the shaky movements. Based on real world data, we have developed a mechanism to monitor a real time gait analysis algorithm to detect any gait deviation. This algorithm is efficient, sensitive to detect miner deviation and not hard coded i.e. user can set Sampling Rate & Threshold values to analyze motion. Researchers can directly use this algorithm in their study without need to implement themselves. It works on pre-calculated threshold values while initial sampling rate is set to 100MHz. Results: Accelerometers putting on the chest shows high unnecessary acceleration during fall, suggest putting on waist position. Also, if a patient initiates steps with energy, his/her gait may become more stable as shown in the conscious gait. Results show that after DBS surgical procedure, the patient still experiences postural instability with fall. So it is evident to show that such patients may have reduced cognition even after surgery. Another finding is that such patients may lean left or right during turning. Conclusions: We have presented a real time gait analysis algorithm, capable of detecting the motion of the patient with PD to actively respond to the shakier motion setting threshold values. Our proposed algorithm is easy to implement, reusable and can affectively generate healthcare alarms. Additionally, this system might be used by other researchers without the need to implement by themselves. The proposed method is sensitive to detect fall therefore objectively can be used for fall risk assessment as well .The same algorithm with minor modifications can be used for seizure detection in other disorders mainly epileptic seizers to alert health providers for emergency. / Any malfunctioning of neurons in the nervous system is called Neurological disorder. Over 100 neurological disorders have been discovered throughout the world. In our study, we have chosen one disorder: Falling in Parkinson’s disease. Experiments can be performed on different gait parameters like body velocity, time ratio, ground slope, stance/swing, body gestures and gait patterns. Sensors can be put on hips, knees, thighs, limbs, neck, head, chest or any other suitable body part to capture motion data for further pre-and post-processing. Pre-processing is real time gait analysis through time domain and frequency domain to trigger various security steps and messages for patient care. Post -processing is offline analysis of motion data in different tools such as EyesWeb, BioMOBIUS and Matlab for calculations, analysis and plotting of motion to take decisions to formulate a mechanism for patient activity detection and monitoring. The area which we choose is pretty interesting, pertaining to rehabilitation, wellness and healthcare for older people. Other related keywords may include keywords may be helpful using one or combination of more than one. WSN, BAN or WBAN, biosensors, neurological disorders, gait analysis, fall detection, fall avoidance, Parkinson’s disease, wireless accelerometer, ambulatory monitoring, freezing of gait and fall risk assessment. Most of the patients suffering from any neurological disorder in later stages of disease pose ambulatory disturbance especially falling. Such patients may fall without showing any warning sign and every patient is different from another. So there is a need to develop a mechanism to detect shaky motion to avoid such patients from falling. Therefore, a real time gait analysis algorithm is implemented to trigger security alarms. In order to assess & evaluate gait analysis, accurate, reliable & consistent measurement tools need to be utilized. Even slight deviation in the data monitoring through measurement tools is not encouraged to use [21]. Gait disturbance can be measured using 3 axis accelerometers like SHIMMER(R) for real time motion analysis. In the wireless sensor network, SHIMMER platform provides wireless Body Area Network (BAN) to capture motion data. This data can be saved in CSV (Comma Separated Version) file for post processing or a 2 GB MicroSD card can be used to capture data in the SHIMMER accelerometer itself. The use of accelerometer is more suitable due to the fact that we are 66 capturing data from postural instability. One two or combinations of accelerometers can be put on different body parts. SHIMMER Gyroscope is more suitable for jerky motion with disease such as epilepsy. Mostly accelerometers and gyroscopes are used for gait analysis [4]. Defining our research work, this study is carried out on the patient with Parkinson’s disease (PD), to study various gait parameters, test wireless accelerometers on different body parts, and implementing an algorithm to trigger a security alarm system by setting a threshold value. Criteria for setting threshold value are calculating standard deviation and employed by different researchers like [3]. The main motivation to perform this experimental research work is to avoid the patient with PD from falling during unstable shaky gait. Security alarms can be activated whenever a patient poses a shakier gait. Two types of alarms or sirens can be activated in the lgorithm. First, to activate Warning Alarms when the value from motion data exceeds maximum threshold value 1 and second to activate Emergency Alarms when the value from motion data exceeds maximum threshold value 2. Later on airbag can be put on the patient’s hip position to avoid him/her from injury and hip fracture. The results show the proposed system is fairly simple to implement in the real time environment, flexible to adjust to any necessary change in the future.The major advantage of this algorithm is its reusability. Algorithm is not hard coded because a user can set his own sampling rate or threshold value or both, and check results. This algorithm is further modifiable to trigger airbag, a security push button, SOS calls, messages, siren activation system, automatic email forwarding, health care alert, and many more. The same algorithm with minor modifications can be used for fall avoidance or health care assurance on other disorders mainly in epileptic seizers to alert health providers in case of emergency, can be used for other seizures and disorders such as epilepsy, etc. Overall, this report presents the analysis of an experiment to measure the usability of wireless accelerometer data to monitor the activity of the patient suffering from Parkinson disease. Our research and experimental work can be quoted toward fall risk assessment. / Inam-ul-Haq Lindblomsvagen 37233 Ronneby +46 760609660

The intention of this analysis was to identify patients with treated Wilson disease (WD) and residual neurological symptoms in order to determine whether or not they were undergoing any treatment in addition to the common decoppering medication. Moreover, the effects of any symptomatic medication were analyzed. Two samples of WD patients were investigated either by a mailed questionnaire survey (n = 135) or by a retrospective analysis (n = 75). A considerable proportion of patients still suffered from neurological symptoms (n = 106, 50.5%), of whom a relatively small proportion was treated symptomatically (n = 33, 31.1%). The documented effects varied substantially, with anticholinergics and botulinum toxin (against dystonia) and primidone (against tremor) apparently being the most promising compounds. Further studies are required to analyze the symptomatic treatment of WD patients with residual neurological symptoms in more detail. / Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich.

La dystonie cervicale (DC) est un trouble du mouvement caractérisé par des postures et des mouvements anormaux du cou et de la tête. Dans la DC, les instabilités posturales ont été associées à une altération des sensations proprioceptives. La présente étude explore l'interaction entre les exigences proprioceptives et attentionnelles du contrôle postural dynamique dans la DC. Des participants sains et atteints de la DC ont effectué une tâche de limite de la stabilité posturale avec et sans vision, ainsi qu'une tâche secondaire cognitive de soustraction. Ces deux tâches ont été effectuées seules (tâche unique) ou simultanément (tâche double). La force de réaction au sol a été recueillie à l'aide d'une plateforme de force AMTI. Les limites fonctionnelles de la stabilité ont été quantifiées comme étant l'excursion maximale du centre de pression (COP) pendant l'inclinaison volontaire du corps dans quatre directions différentes. Les limites de la stabilité des patients DC étaient, en moyenne, plus petites que celles des témoins sains dans toutes les conditions. Cependant, leurs limites antéropostérieures étaient significativement réduites par rapport aux témoins dans la condition de tâche unique sans vision. De plus, les coûts attentionnels de la posture des patients étaient significativement plus élevés que ceux des sujets témoins dans la condition visuelle. Nos résultats soutiennent la théorie selon laquelle l'intégration sensorimotrice et les déficiences proprioceptives affectent le contrôle postural dynamique dans la DC. En outre, nos résultats suggèrent que les patients utilisent diverses stratégies pour s’adapter aux défis posturaux complexes imposés par la vie quotidienne. / Cervical dystonia (CD) is a movement disorder characterized by abnormal postures and movements of the neck and head. Postural instabilities in CD have been associated with impaired proprioceptive processing. The present study used a dual task paradigm to explore the interaction between the proprioceptive and attentional demands of dynamic postural control in CD. Healthy and CD participants performed a postural stability limit task with and without vision as well as a secondary cognitive subtraction task. These two tasks were performed alone (single task) or simultaneously (dual-task). Ground reaction force was collected using an AMTI force platform and center of pressure (COP) displacements were analysed. The functional limits of stability were quantified as the maximum COP excursion during voluntary leaning in four different directions. CD patients achieved, on average, smaller mean postural stability limits compared to healthy controls in all sensory-attentional conditions. However, their anteroposterior stability limits were significantly smaller compared to controls when vision was removed, particularly in the single task condition. Additionally, patients with CD decreased their stability limits relative to healthy controls when concurrently performing the attentional task under the visual condition. Thus, the attentional postural cost of CD patients was greater than the controls. Our results support the theory that sensorimotor integration and proprioceptive impairments affect dynamic postural control in CD. Furthermore, our findings suggest that CD patients use various adaptive strategies to cope with the sensory-attentional challenges imposed by complex postural situations in daily life.

Parkinson’s disease and Essential tremor are the two most prevalent movement disorders in the world, but due to overlapping clinical symptoms, accurate differential diagnosis is difficult. As a result, approximately 60% of patients with movement disorders symptoms will have their diagnosis changed at least once before death. By their subjective nature, clinical exams are inherently imprecise, leading to the desire to create an objective, quantifiable test for movement disorders; a test that currently is elusive. Eye movements have been studied for a century, and are widely appreciated to be quantifiably affected in those with neurological disease. Through a collaborative effort between the VA hospital and VCU, over 1,000 movement disorder subjects had their eye movements recorded, utilizing an SR Research Eyelink 2. Patients with Parkinson’s disease exhibited an ocular gaze tremor during fixation, normal reflexive saccades, and reduced blink rate. Subjects with Essential tremor exhibited slowed saccadic dynamics, with increased latencies, in addition to a larger number of square wave jerk interruptions of otherwise stable fixation. After diagnostic features of each disorder were identified, prospective data collection could occur in a blinded fashion, and oculomotor features used to predict clinical diagnoses. It was determined that measures of fixation stability were capable of almost perfectly differentiating subjects with PD, and a novel, combined parameter was capable of similar results in ET. As a group, it appears as if these symptoms do not progress as the disease does, but subanalyses show that individual patients on constant pharmaceutical doses tracked over time do slightly change and progress. The near perfect separation of disease states suggest the ability of oculomotor recording to be a powerful biomarker to be used for the differential diagnosis of movement disorders. This tool could potentially impact and improve the lives of millions of people the world over.

Le syndrome des mouvements en miroir congénitaux (MMC) est une maladie génétique caractérisée par l’existence de mouvements involontaires symétriques d’une main qui reproduisent à l’identique les mouvements volontaires de l’autre main. Deux structures sont impliquées dans la physiopathologie de cette maladie : le corps calleux (CC) et le faisceau corticospinal (FCS). Deux gènes ont été liés aux MMC à ce jour : DCC et RAD51. Tandis que DCC joue un rôle crucial dans le guidage des axones commissuraux, RAD51 intervient dans la réparation de l’ADN, et son rôle dans le développement du système moteur était inattendu.Chez la souris, nous avons étudié le rôle de RAD51 et DCC dans le développement du FCS et du CC, ainsi que l’implication de ces deux structures dans la latéralisation du contrôle moteur. Nous avons prouvé que DCC contrôle le guidage du FCS à la ligne médiane de façon indirecte. RAD51 intervient dans le développement du neocortex, mais son rôle précis dans le développement du système moteur demeure inconnu. Nous avons par ailleurs comparé un groupe de patients MMC à des volontaires sains afin d’étudier la latéralisation de l’activité corticale lors de la préparation motrice. L’activation et les interactions inter-hémisphériques des aires motrices sont anormales dès la préparation du mouvement chez les patients MMC. L’inhibition de l’aire motrice supplémentaire (AMS) chez les volontaires sains reproduit les défauts d’interactions inter-hémisphériques observés chez les patients. Ces résultats suggèrent que l’AMS est impliquée dans la préparation des mouvements latéralisés, potentiellement en modulant les interactions entre les deux hémisphères via le CC. / Mirror movements are involuntary symmetrical movements of one side of the body that mirror voluntary movements of the other side. Congenital mirror movements (CMM) is a rare genetic disorder transmitted in autosomal dominant manner, in which mirror movements are the only clinical abnormality. Two structures are involved in the physiopathology of CMM: the corpus callosum (CC) and the corticospinal tract (CST). The two main culprit genes identified so far are DCC and RAD51. While the role of DCC in commissural axons guidance during development is well known, RAD51 is involved in DNA repair, and its link with CMM was totally unexpected. In mice, we investigated the role of RAD51 and DCC in the development of the CC and CST, as well as the role of these two structures in motor lateralization. We showed that DCC controls CST midline crossing in an indirect manner. Our work clarified the role of RAD51 in neocortex development, but how RAD51 influences motor system development remains unknown. We compared a group of CMM patients with healthy volunteers to investigate the lateralization of cortical activity during movement preparation. We showed that activation of motor/premotor areas and interhemispheric interactions during movement preparation differed between the CMM patients and healthy volunteers. Transient inhibition of the supplementary motor area (SMA) in the healthy volunteers resulted in abnormal interhemispheric interactions during movement preparation, reminiscent of the situation observed in the patients. These results suggest the SMA is involved in lateralized movements preparation, potentially by modulating interhemispheric interactions via the CC.