Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0030567 (Parkinson's disease)
 63,064 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hypertonia is a neurological dysfunction associated with a number of central nervous system disorders, including cerebral palsy, Parkinson's disease, dystonia, and epilepsy. Genetic studies have identified a homozygous truncation mutation in Trak1 that causes hypertonia in mice. Moreover, elevated Trak1 protein expression is associated with several types of cancers and variants in Trak1 are linked to childhood absence epilepsy in humans. Despite the importance of Trak1 in health and disease, the mechanisms of Trak1 action remain unclear and the pathogenic effects of Trak1 mutation are unknown. Here we report that Trak1 has a crucial function in regulation of mitochondrial fusion. Depletion of Trak1 inhibits mitochondrial fusion, resulting in mitochondrial fragmentation, whereas overexpression of Trak1 elongates and enlarges mitochondria. Our analyses revealed that Trak1 interacts and colocalizes with mitofusins on the outer mitochondrial membrane and functions with mitofusins to promote mitochondrial tethering and fusion. Furthermore, Trak1 is required for stress-induced mitochondrial hyperfusion and pro-survival response. We found that hypertonia-associated mutation impairs Trak1 mitochondrial localization and its ability to facilitate mitochondrial tethering and fusion. Our findings uncover a novel function of Trak1 as a regulator of mitochondrial fusion and provide evidence linking dysregulated mitochondrial dynamics to hypertonia pathogenesis.
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PMID:Hypertonia-linked protein Trak1 functions with mitofusins to promote mitochondrial tethering and fusion. 2892 45

Accurate prediction of muscle and joint contact forces during human movement could improve treatment planning for disorders such as osteoarthritis, stroke, Parkinson's disease, and cerebral palsy. Recent studies suggest that muscle synergies, a low-dimensional representation of a large set of muscle electromyographic (EMG) signals (henceforth called "muscle excitations"), may reduce the redundancy of muscle excitation solutions predicted by optimization methods. This study explores the feasibility of using muscle synergy information extracted from eight muscle EMG signals (henceforth called "included" muscle excitations) to accurately construct muscle excitations from up to 16 additional EMG signals (henceforth called "excluded" muscle excitations). Using treadmill walking data collected at multiple speeds from two subjects (one healthy, one poststroke), we performed muscle synergy analysis on all possible subsets of eight included muscle excitations and evaluated how well the calculated time-varying synergy excitations could construct the remaining excluded muscle excitations (henceforth called "synergy extrapolation"). We found that some, but not all, eight-muscle subsets yielded synergy excitations that achieved >90% extrapolation variance accounted for (VAF). Using the top 10% of subsets, we developed muscle selection heuristics to identify included muscle combinations whose synergy excitations achieved high extrapolation accuracy. For 3, 4, and 5 synergies, these heuristics yielded extrapolation VAF values approximately 5% lower than corresponding reconstruction VAF values for each associated eight-muscle subset. These results suggest that synergy excitations obtained from experimentally measured muscle excitations can accurately construct unmeasured muscle excitations, which could help limit muscle excitations predicted by muscle force optimizations.
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PMID:Can Measured Synergy Excitations Accurately Construct Unmeasured Muscle Excitations? 2904 21

Following the discovery of Mirror Neuron System (MNS), Action Observation Training (AOT) has become an emerging rehabilitation tool to improve motor functions both in neurologic and orthopedic pathologies. The aim of this study is to present the state of the art on the use of AOT in experimental studies to improve motor function recovery in any disease. The research was performed in PubMed, PEDro, Embase, CINAHL and Cochrane Central Register of Controlled Trials (last search July 2015). Randomized controlled trials (RCTs) that analyse efficacy of AOT for recovery of motor functions, regardless of the kind of disease, were retrieved. The validity of the included studies was assessed using the Cochrane Collaboration tool for evaluating risk of bias. Twenty RCTs were eligible. Four studies showed AOT efficacy in improving upper limb functional recovery in participants with chronic stroke, two studies in sub-acute ones and one in acute ones. Six articles suggested its effectiveness on walking performance in chronic stroke individuals, and three of them also suggested an efficacy in improving balance. The use of AOT was also recommended in individuals with Parkinson's disease to improve autonomy in activities of daily living, to improve spontaneous movement rate of self-paced finger movements and to reduce freezing of gait. Other two studies also indicated that AOT improves upper limb motor function in children with cerebral palsy. The last two studies, showed the efficacy of AOT in improving motor recovery in postsurgical orthopedic participants. Overall methodological quality of the considered studies was medium. The majority of analyzed studies suggest the efficacy of AOT, in addition to conventional physiotherapy, to improve motor function recovery in individuals with neurological and orthopedic diseases. However, the application of AOT is very heterogeneous in terms of diseases and outcome measures assessed, which makes it difficult to reach, to date, any conclusion that might influence clinical practice.
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PMID:Action observation training to improve motor function recovery: a systematic review. 2934 Jan 83

Sialorrhea is a common distress associated with certain neurological disorders. The aim of this study is to compare the pharmacological agents used for treating sialorrhea by network meta-analysis. Electronic databases were searched for randomized clinical trials comparing active drugs with either placebo or other active drugs. Total drooling scores was the primary outcome measure. Inverse variance heterogeneity model was used for both direct and mixed treatment comparison analysis. Twenty one studies were included in the systematic review and 15 in the meta-analysis. Compared to placebo, benztropine, botulinum toxins A and B are associated with a significant reduction in the frequency and severity of drooling both in the overall neurological disorders as well as for children with cerebral palsy. Only botulinum toxin A and B were associated with significant therapeutic effects in Parkinson's disease. Benztropine and botulinum toxins A and B were observed to be effective in reducing sialorrhea associated with neurological disorders.
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PMID:Pharmacological interventions for treating sialorrhea associated with neurological disorders: A mixed treatment network meta-analysis of randomized controlled trials. 2947 76

Pseudobulbar affect, that is, pathologic laughter and crying is being increasingly recognized in adults and is seen in association with a number of diseases like Parkinson disease, dementia, traumatic encephalopathy, and others, but has not previously been described in children with cerebral palsy. The condition pseudobulbar affect may be due to lesions in (or degeneration of) the cerebro-ponto-cerebellar pathways. Here we report 2 children with cerebral palsy who have structural cerebellar injury because of their being born extremely premature who have pathologic crying and probably laughter.
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PMID:Pseudobulbar Affect in Survivors of Extreme Prematurity With Cerebellar Injury: Support for the Cerebellar Link in Pathologic Laughter and Crying. 2996 32

Neurologic disorders such as stroke and cerebral palsy are leading causes of long-term disability and can lead to severe incapacity and restriction of daily activities due to lower and upper limb impairments. Intensive physical and occupational therapy are still considered main treatments, but new adjunct therapies to standard rehabilitation that may optimize functional outcomes are being studied. Transcranial direct current stimulation (tDCS) is a noninvasive brain stimulation technique that polarizes underlying brain regions through the application of weak direct currents through electrodes on the scalp, modulating cortical excitability. Increased interest in this technique can be attributed to its low cost, ease of use, and effects on human neural plasticity. Recent research has been performed to determine the clinical potential of tDCS in diverse conditions such as depression, Parkinson's disease, and motor rehabilitation after stroke. tDCS helps enhance brain plasticity and seems to be a promising technique in rehabilitation programs. A number of robotic devices have been developed to assist in the rehabilitation of upper limb function after stroke. The rehabilitation of motor deficits is often a long process requiring multidisciplinary approaches for a patient to achieve maximum independence. These devices do not intend to replace manual rehabilitation therapy; instead, they were designed as an additional tool to rehabilitation programs, allowing immediate perception of results and tracking of improvements, thus helping patients to stay motivated. Both tDSC and robot-assisted therapy are promising add-ons to stroke rehabilitation and target the modulation of brain plasticity, with several reports describing their use to be associated with conventional therapy and the improvement of therapeutic outcomes. However, more recently, some small clinical trials have been developed that describe the associated use of tDCS and robot-assisted therapy in stroke rehabilitation. In this article, we describe the combined methods used in our institute for improving motor performance after stroke.
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PMID:The Combined Use of Transcranial Direct Current Stimulation and Robotic Therapy for the Upper Limb. 3029 60

Purpose: To identify the existing evidence evaluating the cost-effectiveness of physiotherapy treatments for people with neurological disorders.Methods: Multiple databases were searched from database inception until July 2018. Studies estimating the cost-effectiveness as incremental cost-effectiveness ratios, cost per quality-adjusted life year, cost per disability-adjusted life year and cost per other measurable results were included. Physiotherapy Evidence Database scale, and Consensus on Health Economic Criteria list were used for rating the quality of the evidence.Results: Ten studies involving 1462 participants were included. Aerobic training, progressive strength training, and a pragmatic physiotherapy program (combination of stretching, strength, and balance training) were reported as potentially cost-effective for older adults with vascular cognitive impairment, falls prevention in Parkinson's disease and multiple sclerosis respectively. Physiotherapy as an adjuvant for pain control was also reported as cost-effective for reflex sympathetic dystrophy. One study testing extra physiotherapy-by-physiotherapy assistant in cerebral palsy and two studies testing extra therapy using a robotic arm and Wii therapy for hand rehabilitation in stroke were reported as not cost-effective.Conclusions: There are limited studies that have evaluated the cost-effectiveness of physiotherapy treatments in neurological disorders. Three studies that combined extra physiotherapy-by-physiotherapy assistant and novel interventions with conventional physiotherapy were found not cost-effective.Implications for RehabilitationProgressive muscle strengthening exercise over a period of 6-month is reported to be cost-effective for falls prevention in people with Parkinson's diseaseAerobic training is reported as potentially cost-effective for older adults with vascular cognitive impairmentPhysiotherapy given as an adjuvant treatment is reported to be potentially cost-effective for reflex sympathetic dystrophy of less than 1-year durationOne study reported physiotherapy involving static stretching, aerobic exercise, strengthening exercise, and balance training as cost-effective for people with multiple sclerosisAdditional physiotherapy-by-physiotherapy assistant or family member for improving motor development in cerebral palsy and the use of novel physiotherapy techniques such as robotics or Wii plus conventional physiotherapy for improving arm function in stroke are found not cost-effectiveGroup therapy for improving physical activity in mild Alzheimer's disease is found not cost-effective.
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PMID:Economic evaluations of physiotherapy interventions for neurological disorders: a systematic review. 3061 1

Individuals post-stroke sustain motor deficits years after the stroke. Despite recent advancements in the applications of non-invasive brain stimulation techniques and Deep Brain Stimulation in humans, there is a lack of evidence supporting their use for rehabilitation after brain lesions. Non-invasive brain stimulation is already in use for treating motor deficits in individuals with Parkinson's disease and post-stroke. Deep Brain Stimulation has become an established treatment for individuals with movement disorders, such as Parkinson's disease, essential tremor, epilepsy, cerebral palsy and dystonia. It has also been utilized for the treatment of Tourette's syndrome, Alzheimer's disease and neuropsychiatric conditions such as obsessive-compulsive disorder, major depression and anorexia nervosa. There exists growing scientific knowledge from animal studies supporting the use of Deep Brain Stimulation to enhance motor recovery after brain damage. Nevertheless, these results are currently not applicable to humans. This review details the current literature supporting the use of these techniques to enhance motor recovery, both from human and animal studies, aiming to encourage development in this domain.
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PMID:Can neuromodulation techniques optimally exploit cerebello-thalamo-cortical circuit properties to enhance motor learning post-stroke? 3119 94

The deep grey matter (DGM) nuclei of the brain play a crucial role in learning, behaviour, cognition, movement and memory. Although automated segmentation strategies can provide insight into the impact of multiple neurological conditions affecting these structures, such as Multiple Sclerosis (MS), Huntington's disease (HD), Alzheimer's disease (AD), Parkinson's disease (PD) and Cerebral Palsy (CP), there are a number of technical challenges limiting an accurate automated segmentation of the DGM. Namely, the insufficient contrast of T1 sequences to completely identify the boundaries of these structures, as well as the presence of iso-intense white matter lesions or extensive tissue loss caused by brain injury. Therefore in this systematic review, 269 eligible studies were analysed and compared to determine the optimal approaches for addressing these technical challenges. The automated approaches used among the reviewed studies fall into three broad categories, atlas-based approaches focusing on the accurate alignment of atlas priors, algorithmic approaches which utilise intensity information to a greater extent, and learning-based approaches that require an annotated training set. Studies that utilise freely available software packages such as FIRST, FreeSurfer and LesionTOADS were also eligible, and their performance compared. Overall, deep learning approaches achieved the best overall performance, however these strategies are currently hampered by the lack of large-scale annotated data. Improving model generalisability to new datasets could be achieved in future studies with data augmentation and transfer learning. Multi-atlas approaches provided the second-best performance overall, and may be utilised to construct a "silver standard" annotated training set for deep learning. To address the technical challenges, providing robustness to injury can be improved by using multiple channels, highly elastic diffeomorphic transformations such as LDDMM, and by following atlas-based approaches with an intensity driven refinement of the segmentation, which has been done with the Expectation Maximisation (EM) and level sets methods. Accounting for potential lesions should be achieved with a separate lesion segmentation approach, as in LesionTOADS. Finally, to address the issue of limited contrast, R2*, T2* and QSM sequences could be used to better highlight the DGM due to its higher iron content. Future studies could look to additionally acquire these sequences by retaining the phase information from standard structural scans, or alternatively acquiring these sequences for only a training set, allowing models to learn the "improved" segmentation from T1-sequences alone.
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PMID:Quantifying deep grey matter atrophy using automated segmentation approaches: A systematic review of structural MRI studies. 3131 82

This paper presents the development of a new active assistive eating device, which aims to stabilize the movements of people living with movement disorders, such as spasticity and ataxia. Many people living with upper-body incapacities are unable to eat on their own, due to movement disorders (ex. tremors, spastic motions, lack of muscular tone), resulting from various ailments like Cerebral palsy, Parkinson's disease, Dystonia, Multiple sclerosis, strokes, and Muscular dystrophy). Our past work focused on the development of a purely mechanical device, which involved damping of the system via passive mechanical dampers. This paper extends said work by using active stabilization of user movements. The active assistance enables the design of intelligent algorithms that can assist human movements more efficiently. This active version has the benefits of being easily adjustable; the level of damping can be adjusted in real-time, depending on the user movement; different control modes are offered, and the guiding of user movements is also allowed. Firstly, the mechanical design of the device is presented, followed by the damping arrangement, the electronic design, the control algorithms and finally, the preliminary experiments are mentioned.
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PMID:Preliminary Design of an Active Stabilization Assistive Eating Device for People Living with Movement Disorders. 3137 33


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