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

Hypertonia, which results from motor pathway defects in the central nervous system (CNS), is observed in numerous neurological conditions, including cerebral palsy, stroke, spinal cord injury, stiff-person syndrome, spastic paraplegia, dystonia and Parkinson disease. Mice with mutation in the hypertonic (hyrt) gene exhibit severe hypertonia as their primary symptom. Here we show that hyrt mutant mice have much lower levels of gamma-aminobutyric acid type A (GABA(A)) receptors in their CNS, particularly the lower motor neurons, than do wild-type mice, indicating that the hypertonicity of the mutants is likely to be caused by deficits in GABA-mediated motor neuron inhibition. We cloned the responsible gene, trafficking protein, kinesin binding 1 (Trak1), and showed that its protein product interacts with GABA(A) receptors. Our data implicate Trak1 as a crucial regulator of GABA(A) receptor homeostasis and underscore the importance of hyrt mice as a model for studying the molecular etiology of hypertonia associated with human neurological diseases.
 ...
PMID:Trak1 mutation disrupts GABA(A) receptor homeostasis in hypertonic mice. 1638 Jul 13

In recent years, a number of potential new therapeutic indications of botulinum toxin injections have emerged, amongst which sialorrhea has attracted considerable attention. Based on open-label and controlled studies, botulinum toxin can be used to improve sialorrhea in patients with Parkinson's disease, parkinsonian syndromes, motor neuron disease and cerebral palsy. The toxin can be injected blindly based on anatomic landmarks of the salivary glands, or localization can be facilitated by use of ultrasound guidance. There are few reported adverse effects. However, many more carefully designed, controlled studies are still required to address the specific questions related to selection of patients, the optimal injection technique, the appropriate dose of botulinum toxin and its long-term effects.
 ...
PMID:Botulinum toxin treatment of sialorrhea: comparing different therapeutic preparations. 1641

Irving S. Cooper was a pioneer in the field of functional neurosurgery. During his very productive and controversial career, he proposed the surgical treatment of Parkinson disease (PD) by ligating the anterior choroidal artery to control tremor and rigidity. Subsequently, he developed seminal techniques for chemopallidectomy and cryothalamectomy for PD. He also attempted to use electrical stimulation of the cerebellum or the thalamus to treat spasticity. Cooper continued his work on brain stimulation until his death in 1985. He made video recordings of nearly all of his patients during his tenure (1977-1985) at New York Medical College. Cooper's clinical video recordings were reviewed, and selected footage was compiled into a video history of Cooper's surgical management of various movement disorders. Included are pre-, post-, and some intraoperative recordings that Cooper made to document his treatment of patients with PD, tremor, Wilson disease, cerebral palsy, chorea, dystonia musculorum deformans, and some rarer entities.
 ...
PMID:Irving S. Cooper and the early surgical management of movement disorders. Video history. 1660 79

Chancellor MB, Anderson RU, Boone TB: Pharmacotherapy for neurogenic detrusor overactivity. Am J Phys Med Rehabil 2006;85:536-545. Patients with neurogenic detrusor overactivity are a heterogeneous group with voiding dysfunction secondary to neurologic injury or disease. The neurogenic detrusor overactivity syndrome, which may include urinary frequency, urgency, and incontinence, frequently contributes to a loss of independence, or even institutionalization. Urodynamic assessment provides the best method of quantifying and classifying neurogenic detrusor overactivity dysfunction in patients with primary diagnoses as diverse as Parkinson's disease, cerebral palsy, multiple sclerosis, spinal cord injury, and spina bifida. For many patients, management of urinary symptoms includes pharmacotherapy with an anticholinergic agent. Several novel approaches to managing neurogenic detrusor overactivity, including intravesical instillation of anticholinergic agents, vanilloids, and neurotoxins, are being investigated. For most patients, however, flexible dosing with an anticholinergic agent, with clean intermittent catheterization when indicated, has been shown to reduce the risks of urologic complications, improve levels of continence, and enhance patient quality of life in both children and adults.
 ...
PMID:Pharmacotherapy for neurogenic detrusor overactivity. 1671 24

Our 15 years of research have generated the first short- and long-term efficacy data for speech treatment (Lee Silverman Voice Treatment; LSVT/LOUD) in Parkinson's disease. We have learned that training the single motor control parameter amplitude (vocal loudness) and recalibration of self-perception of vocal loudness are fundamental elements underlying treatment success. This training requires intensive, high-effort exercise combined with a single, functionally relevant target (loudness) taught across simple to complex speech tasks. We have documented that training vocal loudness results in distributed effects of improved articulation, facial expression, and swallowing. Furthermore, positive effects of LSVT/LOUD have been documented in disorders other than Parkinson's disease (stroke, cerebral palsy). The purpose of this article is to elucidate the potential of a single target in treatment to encourage cross-system improvements across seemingly diverse motor systems and to discuss key elements in mode of delivery of treatment that are consistent with principles of neural plasticity.
 ...
PMID:The science and practice of LSVT/LOUD: neural plasticity-principled approach to treating individuals with Parkinson disease and other neurological disorders. 1711 54

This study examined the relative benefit of three interventions (i.e. physiological, behavioural, and pragmatic) designed to facilitate speech recognition software use. Participants were 15 adults with dysarthria associated with a variety of aetiological conditions, including cerebral palsy, Parkinson's disease, and motor neuron disease. Results suggested no clear dysarthric profile that would preclude at least some degree of speech recognition system use. Participants demonstrated systematic improvement in their dictation rates regardless of treatment order. The physiological treatment produced significantly higher dictation rates overall than the behavioural--but not the pragmatic--treatment. This finding suggests that improvement was not simply a function of software training, at least for the physiological treatment. This conclusion also was supported by changes in the participants' speech production during a post-treatment assessment.
 ...
PMID:Facilitating use of speech recognition software for people with disabilities: a comparison of three treatments. 1736 26

Seven children between 2 and 15 years of age with cerebral palsy and upper extremity dystonia were enrolled in an open-label, dose-escalation pilot clinical trial of botulinum toxin type B (Myobloc), injected into the biceps and brachioradialis muscles of I or both arms. The primary outcome measure was the change in maximum speed of hand movement during attempted forward reaching. Escalating doses of 12.5, 25, and 50 U/kg per muscle were injected at each of 3 visits. Reaching speed improved in response to injection, and dystonia scores on the Burke-Fahn-Marsden dystonia scale, the Unified Dystonia Rating Scale, and the Unified Parkinson's Disease Rating Scale improved. There was not a dose-related effect on efficacy. There were no serious adverse events. Two children reported transient weakness. These results support the use of botulinum toxin type B as a safe and effective treatment for upper extremity dystonia in children with cerebral palsy. Larger controlled trials are needed to confirm these results.
 ...
PMID:Botulinum toxin type B improves the speed of reaching in children with cerebral palsy and arm dystonia: an open-label, dose-escalation pilot study. 1760 20

Spasticity is a complex disorder characterized by a velocity-dependent increase in muscle tone associated with exaggerated deep tendon reflexes. It can be caused by numerous diffuse or focal cerebral and spinal pathologic conditions. Spasticity indicates upper motor neuron dysfunction and if severe, can lead to considerable motion restriction and eventually to more serious disability. The therapeutic interventions available to treat spasticity are often of limited benefit. In the last decade, many open-label and several double-blind, placebo-controlled, studies have demonstrated the effectiveness of intramuscular botulinum toxin (BTX) injections for the management of spasticity caused by multiple sclerosis, brain / spinal cord injury, cerebral palsy, and stroke. BTX can also be beneficial in the treatment of spasticity, or a mixture of spasticity and rigidity, in many neurodegenerative conditions; including Parkinson disease, progressive supranuclear palsy, corticobasal degeneration, frontotemporal dementia and parkinsonism linked to chromosome 17, and in various sporadic and familial spinocerebellar ataxia syndromes. Currently, two BTX serotypes, which are serologically different but share a common subunit structure, are commercially available: type A (Botox(R), manufactured by Allergan, Inc, Irvine, California, USA; and Dysport(R), distributed by Beaufour-Ipsen Pharmaceuticals, Paris, France); and type B (manufactured by Elan Corporation, Dublin, Ireland, and available in the United States as MyoBloc(R) and in Europe as NeuroBloc(R)). BTX primarily affects the neuromuscular junction by inhibiting acetylcholine release. Dosages vary considerably depending on the particular preparation used, the muscle injected, the severity of the condition, and the duration of treatment.
 ...
PMID:Treatment of spasticity with botulinum toxin. 1761 18

Sialorrhea or excessive salivation, and drooling, are common and disabling manifestations in different neurological disorders. A review is made of the literature, based on a PubMed search, selecting those articles describing clinical trials involving the injection of botulinum toxin A in the salivary glands of patients with different diseases characterized by sialorrhea. The most frequently treated diseases were infant cerebral palsy (30%), Parkinson's disease (20%) and amyotrophic lateral sclerosis (15%). Over half of the authors injected the product into the parotid glands, 9.5% into the submaxillary glands, and 38% into both. The total doses of toxin injected varied from 10-100 units of Botox or 30-450 units of Dysport according to the different authors. A reduction was observed in the production of saliva following these injections, and the duration of the therapeutic effect was 1.5-6 months. Six articles (30%) described the presence of adverse effects such as dysphagia, xerostomia and chewing difficulties. Most of the clinical studies involved small patient samples, with no blinding or randomization, and no control group. Moreover, no data are available on the efficacy and adverse effects of treatment in the context of long-term prospective studies. The effective therapeutic dose and ideal form of application remain to be established, and require the conduction of further controlled clinical trials involving large sample sizes.
 ...
PMID:Salivary gland application of botulinum toxin for the treatment of sialorrhea. 1797 75

Hypertonia, which is characterized by stiff gait, abnormal posture, jerky movements, and tremor, is associated with a number of neurological disorders, including cerebral palsy, dystonia, Parkinson's disease, stroke, and spinal cord injury. Recently, a spontaneous mutation in the gene encoding trafficking protein, kinesin-binding 1 (Trak1), was identified as the genetic defect that causes hypertonia in mice. The subcellular localization and biological function of Trak1 remain unclear. Here we report that Trak1 interacts with hepatocyte-growth-factor-regulated tyrosine kinase substrate (Hrs), an essential component of the endosomal sorting and trafficking machinery. Double-label immunofluorescence confocal studies show that the endogenous Trak1 protein partially colocalizes with Hrs on early endosomes. Like Hrs, both overexpression and small-interfering-RNA-mediated knockdown of Trak1 inhibit degradation of internalized epidermal growth factor receptors through a block in endosome-to-lysosome trafficking. Our findings support a role for Trak1 in the regulation of Hrs-mediated endosomal sorting and have important implications for understanding hypertonia associated with neurological disorders.
 ...
PMID:Hypertonia-associated protein Trak1 is a novel regulator of endosome-to-lysosome trafficking. 1867 23


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>