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)

Two female patients with clinical features resembling spinal muscular atrophy were presented. Patient 1 presented with hypotonia and proximal weakness of extremities at age 4 months. Electromyography revealed motor neuronopathy suggestive of spinal muscular atrophy. Patient 2 presented with severe hypotonia, motor weakness, and joint contractures since birth. Muscle biopsy findings were consistent with spinal muscular atrophy. However, deletions in the survival motor neuron gene and the neuronal apoptosis inhibitor protein gene were not found in both patients. They finally manifested clinical features unlike spinal muscular atrophy: epileptic seizure, cardiomyopathy, and spasticity. The clinical course of each patient was not like that of spinal muscular atrophy type I. Mitochondrial respiratory chain complex enzyme activities in cultured skin fibroblasts were measured. Respiratory complex I enzyme activity was decreased, suggestive of isolated complex I deficiency in both patients. In conclusion, in patients who have clinical features resembling spinal muscular atrophy but no deletions in the spinal muscular atrophy gene, the possibility of the mitochondrial respiratory chain complex I deficiency should be considered.
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PMID:Mitochondrial respiratory complex I deficiency simulating spinal muscular atrophy. 1716 96

Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) was originally found among inhabitants of the Charlevoix-Saguenay region of northeastern Quebec in Canada. This disease is a neurodegenerative disorder characterized by early-onset spastic ataxia, dysarthria, nystagmus, distal muscle wasting, finger and foot deformities, and retinal hypermyelination. The principal neuropathology comprises atrophy of the upper vermis and the loss of Purkinje cells in the cerebellum. The SACS gene was originally reported to consist of a single gigantic exon spanning 12.8 kb with an 11.5-kb open reading frame (ORF), and to encode the protein sacsin. Recently, eight exons upstream from the original gigantic one, however, have been found, and the new ORF has elongated to 13.7 kb. To date, at least 28 mutations have been found in Quebec and non-Quebec patients including ones in Italy, Japan, Spain, Tunisia, and Turkey, and ARSACS thus shows a worldwide occurrence. Although most of the mutations reported have been in the gigantic exon, the genotype is now expanding upstream from this gigantic exon. Therefore, the new exons upstream of the gigantic one should be analyzed when a case is clinically compatible with ARSACS, even without any mutation in the gigantic exon. Although Quebec patients show a homogeneous phenotype, non-Quebec patients exhibit some atypical clinical features, as follows: slightly later onset than that in Quebec patients, absence of retinal hypermyelination, intellectual impairment, and lack of spasticity. Thus, since ARSACS shows the clinical diversity, the SACS gene should be analyzed not only in typical cases as Quebec patients but also in atypical cases as non-Quebec patients. As more SACS mutations are identified worldwide, the clinical spectrum of 'sacsinopathies' will expand, and a finer genotype-phenotype correlation study will become possible and shed light on the molecular mechanism underlying ARSACS.
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PMID:Sacsinopathies: sacsin-related ataxia. 1785 17

Motor neuron diseases (MNDs) are progressive neurodegenerative disorders characterized by selective death of motor neurons leading to spasticity, muscle wasting and paralysis. Human VAMP-associated protein B (hVAPB) is the causative gene of a clinically diverse group of MNDs including amyotrophic lateral sclerosis (ALS), atypical ALS and late-onset spinal muscular atrophy. The pathogenic mutation is inherited in a dominant manner. Drosophila VAMP-associated protein of 33 kDa A (DVAP-33A) is the structural homologue of hVAPB and regulates synaptic remodeling by affecting the size and number of boutons at neuromuscular junctions. Associated with these structural alterations are compensatory changes in the physiology and ultrastructure of synapses, which maintain evoked responses within normal boundaries. DVAP-33A and hVAPB are functionally interchangeable and transgenic expression of mutant DVAP-33A in neurons recapitulates major hallmarks of the human diseases including locomotion defects, neuronal death and aggregate formation. Aggregate accumulation is accompanied by a depletion of the endogenous protein from its normal localization. These findings pinpoint to a possible role of hVAPB in synaptic homeostasis and emphasize the relevance of our fly model in elucidating the patho-physiology underlying motor neuron degeneration in humans.
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PMID:hVAPB, the causative gene of a heterogeneous group of motor neuron diseases in humans, is functionally interchangeable with its Drosophila homologue DVAP-33A at the neuromuscular junction. 1794 96

Loss of function, muscle pain and secondary muscoloskeletal complaints are common symptoms of patients with neuromuscular disease. Many patients develop a progressive handicap. Physiotherapeutic treatment is often used in the management of neuromuscular diseases. Different therapeutic strategies are useful depending on the stage and pathophysiology of the disease and with regard to the extent of the patient's handicap. The aims of the physiotherapy and realistic targets should be discussed critically with the patient at the beginning of the treatment. We propose different physiotherapeutic strategies depending on the stage of the underlying disease: 1) Patient is able to walk--active phase: education in self-training with regard to the risks of exhaustion. Manual and physical treatment of mycofascial complaints. 2) Progressive functional loss--assistive phase: support of compensation and daily functioning. 3) Patient in wheelchair or bedbound, loss of most voluntary functions--passive phase. The knowledge of the pathopysiology of the underlying disease is essential for the development of therapeutic strategies. Loss of upper neurons leads to the development of spasticity and muscle hypertonia whereas muscular atrophy and weakness is a prominent feature of lower motor neuron loss. Overtreatment and exhaustive training may lead to secondary muscle damage in primary myopathies. Training in short sessions with intervals between may have protective effects.
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PMID:[Basic principles of non-respiratory physiotherapy for neuromuscular diseases]. 1831 80

n-Hexane and methyl n-butyl ketone share a common metabolite, 2,5-hexanedione, a potent neurotoxin. Neurotoxic effects to both peripheral and central nervous systems may occur after occupational exposure or recreational abuse of n-hexane. Initial clinical manifestations include numbness and tingling sensation in the toes and fingers, followed by progressive weakness and areflexia, particularly in the distal limbs. Chronic low-dose n-hexane exposure, often observed in industrial workers, apparently causes axonal loss with sensory impairment. Subacute high-dose n-hexane exposure, often observed in glue-sniffers, can cause axonal swelling and secondary demyelination with muscle wasting and weakness. Electrophysiological studies demonstrate prominent prolongation of distal latencies, slowing of nerve conduction velocities, and conduction block with temporal dispersion particularly in severely intoxicated patients. Pathological hallmarks include giant axonal swelling with secondary demyelination and relative loss of large myelinated fibers. Giant axons are accumulated by 10 nm neurofilaments. The clinical course tends to be biphasic with "coasting" for 2-3 months, followed by a slow recovery for about 1-2 years after cessation of exposure to n-hexane. Prognosis is usually favorable. Severely affected patients may develop sequelae of muscle wasting, foot drop, and spasticity. Increased awareness of the n-hexane neurotoxicity in industrial workers and glue sniffers as well as use of safe solvents and adequate ventilation systems are important for preventing n-hexane toxicity.
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PMID:Polyneuropathy induced by n-hexane intoxication in Taiwan. 1856 21

Hereditary spastic paraplegias (HSP) constitute a heterogeneous group of neurodegenerative disorders characterized by slowly progressive spasticity of the lower extremities. Only a few different mutations in the SPG10 gene, KIF5A, have been described in pure dominant forms of the disease. We sequenced the motor domain of KIF5A in a large panel of 205 European HSP patients with either pure or complicated forms of the disease. We identified eight different heterozygous missense mutations, seven novels, in eight different families of French origin. Residue R280 was a mutational hot spot. Interestingly, the patients in 7/8 families had a complex phenotype, with peripheral neuropathy, severe upper limb amyotrophy (Silver syndrome-like), mental impairment, parkinsonism, deafness and/or retinitis pigmentosa as variably associated features. We report the largest series of SPG10 families described so far, which extends both the mutational spectrum of the disease and its phenotype, which now includes complicated forms of HSP. SPG10 mutations were found in 10% of our complicated forms of HSP, suggesting that mutations in KIF5A represent the major cause of complicated AD-HSP in France.
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PMID:Complicated forms of autosomal dominant hereditary spastic paraplegia are frequent in SPG10. 1885 58

We identified a family in Mali with two sisters affected by spastic paraplegia. In addition to spasticity and weakness of the lower limbs, the patients had marked atrophy of the distal upper extremities. Homozygosity mapping using single nucleotide polymorphism arrays showed that the sisters shared a region of extended homozygosity at chromosome 19p13.11-q12 that was not shared by controls. These findings indicate a clinically and genetically distinct form of hereditary spastic paraplegia with amyotrophy, designated SPG43.
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PMID:Hereditary spastic paraplegia and amyotrophy associated with a novel locus on chromosome 19. 2003 86

Autosomal recessive spastic ataxia of Charlevoix-Saguenay, more commonly known as ARSACS, is an early-onset cerebellar ataxia with spasticity, amyotrophy, nystagmus, dysarthria, and peripheral neuropathy. SACS is the only gene known to be associated with the ARSACS phenotype. To date, 55 mutations have been reported; of these, only five in Italian patients. We found two novel homozygous nonsense mutations in the giant exon of SACS gene in two unrelated patients with classical ARSACS phenotype. Characterization of the homozygous nature of the mutations through genotyping of the parents, quantitative DNA analysis and indirect STS studies permitted us to confirm in one of the cases that uniparental isodisomy of the paternal chromosome 13 carrying the mutated SACS gene played an etiologic role in the disease.
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PMID:Two novel homozygous SACS mutations in unrelated patients including the first reported case of paternal UPD as an etiologic cause of ARSACS. 2085 69

Spinal muscular atrophy (SMA) is an autosomal recessive anterior horn cell disease that results in progressive muscular weakness and atrophy without sensory involvement. A wide clinical spectrum that ranges from early death to essentially normal adult live exists. We describe a case of two 12 years olds, who represent two of three surviving non-identical quadruplets, born at 25 weeks gestational age. A diagnosis of hypotonic cerebral palsy (CP) was made in early childhood and early intervention services were initiated. At 3 years of age, MRI's showed white matter changes. Both briefly attained Gross Motor Functional Classification Scale (GMFCS) 3 status, but by 12 years of age their ambulatory abilities had decreased to Level 4. Physical Medicine and Rehabilitation (PM&R) physicians were consulted. On exam, distal lower extremities atrophy, hypotonia, hyporeflexia, and muscle weakness were noted. Neither child had upper motor neuron signs or spasticity. Cognition was normal. Neuromuscular disorder was suspected and genetic testing confirmed spinal muscular atrophy in both patients. While prior MRI/CT demonstrated static encephalopathy, recognition of symptoms and signs consistent with neuromuscular disease should have led to a secondary diagnosis. Therapeutic and surgical treatment decisions may have differed. Fragmentation of care and lack of a comprehensive team approach also contributed to the delay in recognition of their dual diagnosis.
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PMID:Cerebral palsy masking spinal muscular atrophy. 2179 63

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


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