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)

An autosomal dominant striatonigral degeneration is present in a family of Portuguese ancestry numbering in excess of 329 persons in eight generations. The illness begins in the second, third, or fourth decade, and progresses for about 15 years with parkinsonian rigidity, spasticity, spastic dysarthria, and abnormalities of eye movement. Neuropathologic findings are severe neuronal loss and astrocytic gliosis in the corpus striatum and substantia nigra, with a moderate neuronal loss in the dentate nucleus of the cerebellum and nucleus ruber of the midbrain. This is a new genetic entity, distinct from other autosomal dominant neurologic disorders such as nigrospinodentatal degeneration, olivopontocerebellar degeneration, dystonia musculorum deformans, Machado's disease, and Huntington's disease.
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PMID:Autosomal dominant striatonigral degeneration. A clinical, pathologic, and biochemical study of a new genetic disorder. 94 67

Hand muscle reflexes to stretch or electric stimulation of mixed nerves consist of two main components, the short latency reflex (SLR, M1) or Hoffmann reflex (HR) and the long latency reflex (LLR, M2). The SLR is most likely a spinal, monosynaptic reflex and all the evidence presently available supports a transcortical pathway of the LLR. Investigations in normal subjects demonstrate that the LLR is a reflex mediated by fast conducting muscle and cutaneous afferents. Group II muscle afferents do not significantly contribute to this reflex and it cannot be explained by repetitive excitation of spinal oligosynaptic pathways. These findings should not be uncritically generalized to other muscle groups, because the central and peripheral mechanisms apparently differ according to the body region and mode of stimulation. The LLR of hand muscles is most likely involved in skillful movements of the fingers. It is believed to assist rapid compensatory responses to unexpected disturbances. In addition to the main component of the LLR, which is called LLR II, the study of electrically elicited thenar reflexes following stimulation of the median nerve disclosed further LLR components, the LLR I and the LLR III. The latter reflexes are rarely seen in normal subjects but have a significance in several diseases. Several abnormalities could be demonstrated in different diseases. Enhanced HR and reduced LLR are found in spasticity of various origin. Enhanced LLR I are frequently seen in Parkinson's disease, essential tremor and reflex myoclonus. Absent or reduced LLR II is found in Huntington's disease and in different focal brain lesions but not in symptomatic choreatic syndromes of other origin. Delayed latencies of the LLR II or absent LLR II have been described in multiple sclerosis. Enhanced LLR III may occur in cerebellar diseases. The method to elicit LLR of thenar muscles by electric stimulation may prove to be useful for clinical neurophysiology.
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PMID:Physiology and clinical applications of hand muscle reflexes. 228 56

Hallervorden Spatz syndrome (HSS), described in 1.922, is a rare progressive disorder recessively inherited involving the basal ganglia. It is manifested clinically by mental deterioration, rigidity, choreoathetosis and spasticity evident during the first two decades of life. Increased concentration of iron in the globus pallidus and substantia nigra has been demonstrated convincingly. the objective of this paper is to describe two venezuelan children with this syndrome. Patient 1 is a 14-year-old boy with progressive impairment of language, mental deterioration and slowing of voluntary movements started at the age of 8 years. Patient 2 is a young girl first examined at 8 years of age because of psychomotor development delay, progressive impairment of gait, rigidity of the limbs, progressive dystonia and mental deterioration. Multiple test were performed, including metabolic studies, CT scan and magnetic resonance imaging in the brain. These two cases may lead us to think that besides the Huntington Disease, the HSS is also an entity to be taken into consideration in a young patient with movement disorder, mental deterioration and progressive course.
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PMID:[Hallervorden-Spatz syndrome in 2 Venezuelan patients]. 791 58

The development of neuroprotective agents for the prevention of neuronal loss in acute conditions such as stroke and epilepsy or chronic neurodegenerative disorders including Parkinson's disease, Alzheimer's disease, Huntington's chorea, and motor neuron disease is currently focusing on drugs that inhibit excitatory amino acid neurotransmission or exhibit antioxidant properties. Unfortunately, potent antagonists at the N-methyl-D-aspartate (NMDA) type glutamate receptor, which is thought to mediate excitotoxic neuronal injury, e.g., MK-801 or phencyclidine (PCP), share a high probability of inducing psychotomimetic side effects. Further, these drugs have been associated with acute neurotoxicity in vitro and in vivo, precluding their clinical use. In contrast, low affinity NMDA receptor antagonists like amantadine and its dimethyl derivative, memantine, have been administered clinically for the management of Parkinson's disease, dementia, neuroleptic drug-induced side effects, and spasticity. These agents have only rarely induced significant psychotomimetic side effects. Recent pharmacologic advances have helped to elucidate how high drug affinity for the PCP binding site of the NMDA receptor may enhance psychotogenicity. Low affinity and associated fast voltage-dependent channel unblocking kinetics are likely to be responsible for the better tolerance of amantadine and memantine compared with MK-801 and PCP. Further factors apparently modulating psychotogenicity of glutamate receptor antagonists include differential actions on neuronal populations in various brain regions and interactions with neurotransmitter receptors other than the NMDA type glutamate receptor.
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PMID:Psychotogenicity and N-methyl-D-aspartate receptor antagonism: implications for neuroprotective pharmacotherapy. 901 83

CAG repeat expansions have been identified as the disease-causing dynamic mutations in the coding regions of genes in several dominantly inherited neurodegenerative disorders, including spinobulbar muscular atrophy, Huntington's disease, dentatorubral-pallidoluysian atrophy, spinocerebellar ataxia type 1, 2 and 6 and Machado-Joseph disease. The CAG repeat expansions are translated to elongated polyglutamine tracts and an increased size of the polyglutamine tract correlates with anticipation, the cardinal feature, seen in all these diseases. Autosomal dominant pure spastic peraplegia (ADPSP) is a degenerative disorder of the central motor system clinically characterized by slowly progressive and unremitting spasticity of the legs, hyperreflexia and Babinski's sign. Like the established CAG repeat diseases ADPSP is characterized by both inter- and intrafamilial variation and anticipation. Using the Repeat Expansion Detection (RED) method, we have analyzed 21 affected individuals from six Danish families with the disease linked to chromosome 2p21-p24. We found that 20 of 21 affected individuals showed CAG repeat expansions versus two of 21 healthy spouses, demonstrating a strongly statistically significant association between the occurrence of the repeat expansion and the disease (Fisher's test, P < 10(-5)) suggesting that a CAG repeat expansion is involved presumably as a dynamic mutation in ADPSP linked to chromosome 2p21-p24. The size of the expansion is estimated to be > or = 60 CAG repeat copies in the affected individuals. The CAG repeat expansion is very likely translated and expressed as indicated by the detection of a polyglutamine-containing protein in an ADPSP patient.
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PMID:CAG repeat expansion in autosomal dominant pure spastic paraplegia linked to chromosome 2p21-p24. 930 57

Autosomal dominant hereditary spastic paraplegia (HSP) is genetically classified into three types, all of which are characterized by insidiously progressive spasticity of the lower extremities. Patients with a complicated form of autosomal recessive HSP associated with hypoplasia of the corpus callosum have been reported by Iwabuchi et al. Here we report a 64-year-old patient with a pure form of autosomal dominant HSP with thinning of the corpus callosum. He had been well until 12 years of age, when spasticity and weakness of the lower extremities began to develop. His symptoms gradually worsened and he had difficulty in walking at the age of 44. When he was 56 years old, he visited our hospital. Eleven family members over five generations have been affected, and anticipation, i.e., an apparent decrease in age of onset, has been observed. On admission, he had mild cataracts, equinovarus and pes cavus, and neurological examination revealed spastic paraplegia. However, the intelligence test was normal, and nystagmus, ataxia of the extremities, involuntary movement, orthostatic hypotension or urinary disturbance was not observed. Trinucleotide repeat diseases, such as Huntington's disease, spinocerebellar ataxia type 1, spinocerebellar ataxia type 2, Machado-Joseph disease and dentatorubral-pallidoluysian atrophy, were excluded by DNA analysis. Brain MRI at the age of 64 revealed marked thinning of the corpus callosum. We considered this patient had a pure form of HSP. However, thinning of the corpus callosum has never been reported in autosomal dominant HSP.
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PMID:[A case of autosomal dominant, pure form spastic paraplegia with thinning of the corpus callosum]. 980 90

A consanguineous family affected by an autosomal recessive, progressive neurodegenerative Huntington-like disorder, was tested to rule out juvenile-onset Huntington disease (JHD). The disease manifests at approximately 3-4 years and is characterized by both pyramidal and extrapyramidal abnormalities, including chorea, dystonia, ataxia, gait instability, spasticity, seizures, mutism, and intellectual impairment. Brain magnetic resonance imaging (MRI) findings include progressive frontal cortical atrophy and bilateral caudate atrophy. Huntington CAG trinucleotide-repeat analyses ruled out JHD, since all affected individuals had repeat numbers within the normal range. The presence of only four recombinant events (straight theta=.2) between the disease and the Huntington locus in 20 informative meioses suggested that the disease localized to chromosome 4. Linkage was initially achieved with marker D4S2366 at 4p15.3 (LOD 3.03). High-density mapping at the linked locus resulted in homozygosity for markers D4S431 and D4S394, which span a 3-cM region. A maximum LOD score of 4.71 in the homozygous interval was obtained. Heterozygosity at the distal D4S2366 and proximal D4S2983 markers defines the maximum localization interval (7 cM). Multiple brain-related expressed sequence tags (ESTs) with no known disease association exist in the linkage interval. Among the three known genes residing in the linked interval (ACOX3, DRD5, QDPR), the most likely candidate, DRD5, encoding the dopamine receptor D5, was excluded, since all five affected family members were heterozygous for an intragenic dinucleotide repeat. The inheritance pattern and unique localization to 4p15.3 are consistent with the identification of a novel, autosomal recessive, neurodegenerative Huntington-like disorder.
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PMID:Localization of the gene for a novel autosomal recessive neurodegenerative Huntington-like disorder to 4p15.3. 1084 1

We describe here familial dyskinesia and facial myokymia (FDFM), a novel autosomal dominant disorder characterized by adventitious movements that sometimes appear choreiform and that are associated with perioral and periorbital myokymia. We report a 5-generation family with 18 affected members (10 males and 8 females) with FDFM. The disorder has an early childhood or adolescent onset. The involuntary movements are paroxysmal at early ages, increase in frequency and severity, and may become constant in the third decade. Thereafter, there is no further deterioration, and there may even be improvement in old age. The adventitious movements are worsened by anxiety but not by voluntary movement, startle, caffeine, or alcohol. The disease is socially disabling, but there is no intellectual impairment or decrease in lifespan. A candidate gene and haplotype analysis was performed in 9 affected and 3 unaffected members from 3 generations of this family using primers for polymorphic loci closely flanking or within genes of interest. We excluded linkage to 11 regions containing genes associated with chorea and myokymia: 1) the Huntington disease gene on chromosome 4p; 2) the paroxysmal dystonic choreoathetosis gene at 2q34; 3) the dentatorubral-pallidoluysian atrophy gene at 12p13; 4) the choreoathetosis/spasticity disease locus on 1p that lies in a region containing a cluster of potassium (K+) channel genes; 5) the episodic ataxia type 1 (EA1) locus on 12p that contains the KCNA1 gene and two other voltage-gated K+ channel genes, KCNA5 and KCNA6; 6) the chorea-acanthocytosis locus on 9q21; 7) the Huntington-like syndrome on 20p; 8) the paroxysmal kinesigenic dyskinesia locus on 16p11.2-q11.2; 9) the benign hereditary chorea locus on 14q; 10) the SCA type 5 locus on chromosome 11; and 11) the chromosome 19 region that contains several ion channels and the CACNA1A gene, a brain-specific P/Q-type calcium channel gene associated with ataxia and hemiplegic migraine. Our results provide further evidence of genetic heterogeneity in autosomal dominant movement disorders and suggest that a novel gene underlies this new condition.
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PMID:Familial dyskinesia and facial myokymia (FDFM): a novel movement disorder. 1131 Jun 26

We report an adult-onset case of Huntington disease presenting with spasticity and cerebellar ataxia. The patient, a 47-year old woman, was admitted to our clinic because of progressive involuntary movements. Her elder brother suffered from the similar symptoms. Neurologically, she had quick temper, dementia, generalized chorea, spasticity and truncal ataxia. MRI demonstrated atrophy of caudate, midbrain, pons and cerebellum. From these clinical and MRI findings, she was suspected to have a form of spinocerebellar degeneration (SCD), particularly DRPLA. However, DNA analysis showed CAG repeats in huntington gene was expanded (47/20). Accordingly she was diagnosed as having adult-onset Huntington disease, mimicking SCD. This case indicates Huntington disease may present atypical clinical features and it is crucial to determine CAG repeat size in huntington gene for the patient with dementia and/or movement disorders, etiology of which is unknown. The relationships between clinical phenotypic variations and huntington gene expression are not determined.
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PMID:[A case of adult-onset Huntington disease presenting with spasticity and cerebellar ataxia, mimicking spinocerebellar degeneration]. 1282 May 45

Huntington's disease is an autosomal dominant progressive neurodegenerative disorder characterized by involuntary movements, cognitive decline, and behavioral disorders leading to functional disability. In contrast to patients with adult onset, in which chorea is the major motor abnormality, children often present with spasticity, rigidity, and significant intellectual decline associated with a more rapidly progressive course. An unusual early-onset Huntington's disease case of an 11-year-old boy with severe hypokinetic/rigid syndrome appearing at the age of 2.5 years is presented. Clinical diagnosis was confirmed by polymerase chain reaction study of the expanded IT-15 allele with a compatible size of 102 cytosine-adenosine-guanosine repeats L-Dopa mildly ameliorated rigidity, bradykinesia, and dystonia. We conclude that Huntington's disease should be included in the differential diagnoses of regressive syndromes of early childhood.
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PMID:Unusual early-onset Huntingtons disease. 1288 81


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