Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0026838 (spasticity)
 6,471 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

During the last one-half century, electrical stimulation has become clinically significant for improving health and restoring useful function after spinal cord injury. Short-term stimulation can be provided by electrodes on the skin or percutaneous fine wires, but implanted systems are preferable for long-term use. Electrical stimulation of intact lower motor neurons can exercise paralyzed muscles and reverse wasting; improve strength, endurance, and cardiovascular fitness; and may reduce the progression of osteoporosis. Other potential therapeutic uses being investigated include reduction of spasticity, prevention of deep vein thrombosis, and improvement of tissue health. Pacing of intact phrenic nerves in high tetraplegia can produce effective respiration without mechanical ventilation, allowing improved speech, increased mobility, and increased sense of well-being. Improvement of cough has also been demonstrated. Stimulation of intact sacral nerves can produce effective micturition and reduce urinary tract infection; it can also improve bowel function and erection. It is usually combined with posterior sacral rhizotomy to improve continence and bladder capacity, and the combination has been shown to reduce costs of care. Electroejaculation can now produce semen in most men with spinal cord injury. Significant achievements have also been made in restoring limb function. Useful hand grasp can be provided in C5 and C6 tetraplegia, reducing dependence on adapted equipment and assistants. Standing, assistance with transfers, and walking for short distances can be provided to selected persons with paraplegia, improving their access to objects, places, and opportunities that are inaccessible from a wheelchair. This review summarizes the current state of therapeutic and neuroprosthetic applications of electrical stimulation after spinal cord injury and identifies some future directions of research and clinical and commercial development.
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PMID:Clinical applications of electrical stimulation after spinal cord injury. 1548 67

We report two patients diagnosed to have familial amyotrophic lateral sclerosis (FALS). A 40 year old lady had progressive weakness and atrophy of the limbs and bulbar palsy from the age of 39 years and with electrophysiological evaluation was confirmed as definite ALS. Her mother had presented in 1978 at the age of 42 years with symptoms and signs of ALS. The other patient was a 43 year old male with rapidly progressive weakness, wasting and spasticity of the limbs and bulbar palsy of 4 months duration and with electrophysiological evidence of diffuse anterior horn cell involvement. His father also had onset of illness at 43 years of age with gradually progressive spasticity and atrophy of the extremities followed by bulbar palsy. In the first instance the mother had a duration of illness of 8 years while in the second the father lived for 15 years after the onset of illness.
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PMID:Familial amyotrophic lateral sclerosis: first report from India. 1693 97

Hereditary spastic paraplegias (HSP) are neurodegenerative diseases mainly characterized by lower limb spasticity associated, in complicated forms, with additional neurological signs. We have analysed a large series of index patients (n = 76) with this condition, either from families with an autosomal recessive inheritance (n = 43) or isolated patients (n = 33), for mutations in the recently identified SPG11 gene. We found 22 truncating mutations, including the first four splice-site mutations, segregating in seven isolated cases and 13 families. Nineteen mutations were novel. Two recurrent mutations were found in Portuguese and North-African patients indicating founder effects in these populations. The mutation frequency varied according to the phenotype, from 41%, in HSP patients presenting with a thin corpus callosum (TCC) visualized by MRI, to 4.5%, in patients with mental impairment without a TCC. Disease onset occurred during the first to the third decade mainly by problems with gait and/or mental retardation. After a mean disease duration of 14.9 +/- 6.6 years, the phenotype of 38 SPG11 patients was severe with 53% of patients wheelchair bound or bedridden. In addition to mental retardation, 80% of the patients showed cognitive decline with executive dysfunction. Interestingly, the phenotype also frequently included lower motor neuron degeneration (81%) with wasting (53%). Slight ocular cerebellar signs were also noted in patients with long disease durations. In addition to a TCC (95%), brain MRI revealed white matter alterations (69%) and cortical atrophy (81%), which worsened with disease duration. In conclusion, our study reveals the high frequency of SPG11 mutations in patients with HSP, a TCC and cognitive impairment, including in isolated patients, and extends the associated phenotype.
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PMID:Mutations in SPG11 are frequent in autosomal recessive spastic paraplegia with thin corpus callosum, cognitive decline and lower motor neuron degeneration. 1807 67

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterised by progressive muscular paralysis reflecting degeneration of motor neurones in the primary motor cortex, corticospinal tracts, brainstem and spinal cord. Incidence (average 1.89 per 100,000/year) and prevalence (average 5.2 per 100,000) are relatively uniform in Western countries, although foci of higher frequency occur in the Western Pacific. The mean age of onset for sporadic ALS is about 60 years. Overall, there is a slight male prevalence (M:F ratio approximately 1.5:1). Approximately two thirds of patients with typical ALS have a spinal form of the disease (limb onset) and present with symptoms related to focal muscle weakness and wasting, where the symptoms may start either distally or proximally in the upper and lower limbs. Gradually, spasticity may develop in the weakened atrophic limbs, affecting manual dexterity and gait. Patients with bulbar onset ALS usually present with dysarthria and dysphagia for solid or liquids, and limbs symptoms can develop almost simultaneously with bulbar symptoms, and in the vast majority of cases will occur within 1-2 years. Paralysis is progressive and leads to death due to respiratory failure within 2-3 years for bulbar onset cases and 3-5 years for limb onset ALS cases. Most ALS cases are sporadic but 5-10% of cases are familial, and of these 20% have a mutation of the SOD1 gene and about 2-5% have mutations of the TARDBP (TDP-43) gene. Two percent of apparently sporadic patients have SOD1 mutations, and TARDBP mutations also occur in sporadic cases. The diagnosis is based on clinical history, examination, electromyography, and exclusion of 'ALS-mimics' (e.g. cervical spondylotic myelopathies, multifocal motor neuropathy, Kennedy's disease) by appropriate investigations. The pathological hallmarks comprise loss of motor neurones with intraneuronal ubiquitin-immunoreactive inclusions in upper motor neurones and TDP-43 immunoreactive inclusions in degenerating lower motor neurones. Signs of upper motor neurone and lower motor neurone damage not explained by any other disease process are suggestive of ALS. The management of ALS is supportive, palliative, and multidisciplinary. Non-invasive ventilation prolongs survival and improves quality of life. Riluzole is the only drug that has been shown to extend survival.
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PMID:Amyotrophic lateral sclerosis. 1919 1

In Western countries the incidence of amyotrophic lateral sclerosis (ALS) is 1.89 per 100,000 per year and the prevalence is 5.2 per 100,000. The incidence of ALS is lower among African, Asian, and Hispanic ethnicities when compared to Caucasians. The mean age of onset for sporadic ALS is about 60 years and there is a slight male predominance (male to female ratio of 1.5 to 1). Approximately two thirds of patients with ALS have the spinal form of the disease with symptoms presenting in the extremities. Patients typically have evidence of both lower motor neuron degeneration (atrophy, weakness, and fasciculations) and upper motor neuron degeneration (spasticity, weakness, and hyperreflexia). Patients with limb onset ALS typically complain of focal muscle weakness and wasting. The symptoms may start either distally or proximally in the upper and/or lower limbs. Gradually spasticity develops in the weakened atrophic limbs, affecting manual dexterity and gait. Patients with bulbar onset ALS typically present with dysarthria and dysphagia for solid or liquids. Limb symptoms can develop simultaneously with bulbar onset. In the vast majority of patients, limb weakness will occur within 1-2 years of bulbar onset ALS symptoms. A case of bulbar and sporadic limb ALS in a 70-year-old veteran, presenting with right diaphragmatic paralysis and respiratory failure, is presented.
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PMID:Respiratory failure in a 70-year-old veteran. 2022 86

Motor neuron syndromes including typical ALS develop very rarely after electrotrauma, with possible causality discussed but not confirmed. We report on a 44-year-old male who developed clinically definite ALS by the revised El Escorial criteria with onset weeks after mild electric injury. He presented with asymmetric upper limb amyotrophy and weakness beginning around the entry point of the current. Over 1 year he developed generalized wasting, weakness and fasciculations, including the bulbar and thoracic muscles, with prominent spasticity and pyramidal tract signs. Electrodiagnostic studies confirmed widespread denervation, very unstable neurogenic motor units in the bulbar, cervical, thoracic and lumbosacral segments with normal motor velocities and normal sensory parameters. This is a well-documented case of fast-progressive ALS that seems related to electric injury.
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PMID:Clinically definite ALS presenting weeks after mild electric injury: causality or coincidence? 2222 68

Amyotrophic lateral sclerosis is a neurodegenerative disorder characterized by progressive loss of upper and lower motor neurons, with a median survival of 2-3 years. Although various phenotypic and research diagnostic classification systems exist and several prognostic models have been generated, there is no staging system. Staging criteria for amyotrophic lateral sclerosis would help to provide a universal and objective measure of disease progression with benefits for patient care, resource allocation, research classifications and clinical trial design. We therefore sought to define easily identified clinical milestones that could be shown to occur at specific points in the disease course, reflect disease progression and impact prognosis and treatment. A tertiary referral centre clinical database was analysed, consisting of 1471 patients with amyotrophic lateral sclerosis seen between 1993 and 2007. Milestones were defined as symptom onset (functional involvement by weakness, wasting, spasticity, dysarthria or dysphagia of one central nervous system region defined as bulbar, upper limb, lower limb or diaphragmatic), diagnosis, functional involvement of a second region, functional involvement of a third region, needing gastrostomy and non-invasive ventilation. Milestone timings were standardized as proportions of time elapsed through the disease course using information from patients who had died by dividing time to a milestone by disease duration. Milestones occurred at predictable proportions of the disease course. Diagnosis occurred at 35% through the disease course, involvement of a second region at 38%, a third region at 61%, need for gastrostomy at 77% and need for non-invasive ventilation at 80%. We therefore propose a simple staging system for amyotrophic lateral sclerosis. Stage 1: symptom onset (involvement of first region); Stage 2A: diagnosis; Stage 2B: involvement of second region; Stage 3: involvement of third region; Stage 4A: need for gastrostomy; and Stage 4B: need for non-invasive ventilation. Validation of this staging system will require further studies in other populations, in population registers and in other clinic databases. The standardized times to milestones may well vary between different studies and populations, although the stages themselves and their meanings are likely to remain unchanged.
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PMID:A proposed staging system for amyotrophic lateral sclerosis. 2227 64

Cervical-cord damage is a complication of a difficult delivery, and results in spinal shock with flaccidity progressing to spastic paralysis. Conventionally, outlook for such patients is extremely poor and most will recover only slightly from quadriplegia and autonomic dysfunction. Here, we report a case in which the extent of damage considerably contrasted with the outcome and recovery. A full-term baby girl born by difficult vaginal delivery displayed bilateral flaccid paralysis of the lower limbs with absent spontaneous movements, weakness of both upper limbs, hyporeflexia in all limbs and axial hypotonia. MRI of cervicothoracic spine exhibited raised signal intensity in the dorsal aspects of C7 to T1 signifying myelopathy. MRI at 4 months revealed a near-total transection of the cervical cord. However, at 6 months, the child could move all lower limbs independently with a marked increase in power. There was no spasticity, wasting or incontinence. Reflexes had also returned.
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PMID:Remarkable recovery in an infant presenting with extensive perinatal cervical cord injury. 2323 Feb 49

Mitochondrial structure and function is emerging as a major contributor to neuromuscular disease, highlighting the need for the complete elucidation of the underlying molecular and pathophysiological mechanisms. Following a forward genetics approach with N-ethyl-N-nitrosourea (ENU)-mediated random mutagenesis, we identified a novel mouse model of autosomal recessive neuromuscular disease caused by a splice-site hypomorphic mutation in a novel gene of unknown function, DnaJC11. Recent findings have demonstrated that DNAJC11 protein co-immunoprecipitates with proteins of the mitochondrial contact site (MICOS) complex involved in the formation of mitochondrial cristae and cristae junctions. Homozygous mutant mice developed locomotion defects, muscle weakness, spasticity, limb tremor, leucopenia, thymic and splenic hypoplasia, general wasting and early lethality. Neuropathological analysis showed severe vacuolation of the motor neurons in the spinal cord, originating from dilatations of the endoplasmic reticulum and notably from mitochondria that had lost their proper inner membrane organization. The causal role of the identified mutation in DnaJC11 was verified in rescue experiments by overexpressing the human ortholog. The full length 63 kDa isoform of human DNAJC11 was shown to localize in the periphery of the mitochondrial outer membrane whereas putative additional isoforms displayed differential submitochondrial localization. Moreover, we showed that DNAJC11 is assembled in a high molecular weight complex, similarly to mitofilin and that downregulation of mitofilin or SAM50 affected the levels of DNAJC11 in HeLa cells. Our findings provide the first mouse mutant for a putative MICOS protein and establish a link between DNAJC11 and neuromuscular diseases.
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PMID:A splicing mutation in the novel mitochondrial protein DNAJC11 causes motor neuron pathology associated with cristae disorganization, and lymphoid abnormalities in mice. 2511 Nov 80

Amyotrophic lateral sclerosis (ALS) is a neuromuscular disease that occurs throughout the world with no racial, ethnic or socioeconomic boundaries. Despite its high morbidity and mortality, there are limited medications available for ALS that may increase survival in patients with amyotrophic lateral sclerosis by approximately 2-3 months. Inasmuch as negative effects of riluzole on muscle atrophy and wasting, weakness, muscle spasticity, dysarthria, dysphagia, and overall patient quality of life and its different adverse effects, much attention has been paid to natural products and herbal medicines. Overall scientific reports indicate that natural products have beneficial effects on patients with ALS low side effects and multiple targets. In the present paper, we review the scientific reports on beneficial role of natural polyphenolic compounds in treatment of ALS.
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PMID:Natural compounds used as therapies targeting to amyotrophic lateral sclerosis. 2560 6


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