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)

Four pedigrees of Machado-Joseph disease (MJD) were reported. Main clinical features of 21 patients in these pedigrees were cerebellar ataxia, limb spasticity, gaze nystagmus, facio-lingual twitchings, and external ophthalmoparesis. Amyotrophy, hypokinesia, or dystonia were manifested with advance of the illness. In patients with younger onset age, such extrapyramidal signs were dominated. Neuropathological study of one autopsied case disclosed that there were degeneration of spinocerebellar tract, anterior horn cells, pontine nuclei, dentate nucleus, red nucleus, substantia nigra, internal segment of globus pallidus, subthalamic nucleus, and motor nuclei of brain stem; neurons of cerebellar cortex and inferior olivary nucleus were preserved. From these clinical and pathological features, these 4 pedigrees satisfied the criteria of MJD, and were differentiated from hereditary olivopontocerebellar atrophy. Currently, MJD is accepted as a new entity of hereditary spinocerebellar ataxias. However, there are still controversies as to whether Azores-Portuguese MJD and Japanese MJD are identical disorder. Furthermore, the nosological relationship between MJD and a number of similar cases, as reported historically under the diagnosis of Brown type ataxia or Marie's ataxia, has not been clearly established. From reviewing such cases critically, pathological and clinical features of our cases are so similar to those of the latter, indicating that the probably identical genetic disorder has been classified under the different categories.
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PMID:[Clinicopathological study of Joseph disease: report of 4 pedigrees and its nosological consideration]. 159

Machado-Joseph disease is an autosomal dominant spinocerebellar degeneration. It expresses itself clinically with variable expression. Type one patients have early onset with a rapid progression of symptoms including spasticity, rigidity and myokymia. Type two patients are the most common phenotype with ataxia and spasticity. Type three patients develop progressive ataxia with variable amyotrophy. All patients have ophthalmoparesis and normal mental status. The neuropathology consists of neuronal loss and gliosis in the substantia nigra, motor cranial nuclei, dentate nucleus of the cerebellum, and variable neuronal loss with gliosis in the cerebellar cortex and neostriatum. The cerebral cortex is normal histologically. The inferior olivary nuclei are normal, thus separating this disease from olivopontocerebellar atrophy (OPCA). The disease has a worldwide distribution including families described in Portugal, the Azores, Spain, Italy, United States, Canada, Brazil, China, Taiwan, and Japan. The gene has not been mapped for this disease but the locus on chromosome 6p mapped for most families with OPCA has been excluded for this disorder.
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PMID:Machado-Joseph disease: an autosomal dominant motor system degeneration. 162 Jan 35

Experience is described in 25 patients from southern New England with Machado-Joseph Disease, examined serially at annual screening clinics. The disorder is dominantly inherited, with a wide range of phenotypic variation. Core clinical features described include ataxia, nystagmus, dysarthria, facial fasciculations, and lid retraction, producing a characteristic staring expression. In addition, young onset patients have spasticity, extrapyramidal rigidity, and dystonic manifestations. Late onset patients often have distal atrophy and sensory loss. Postural instability is often an early feature. We discuss the distinction of this entity from the olivopontocerebellar atrophies.
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PMID:Machado-Joseph disease in New England: clinical description and distinction from the olivopontocerebellar atrophies. 162 Jan 36

One male and two female cases in a family of Machado-Joseph disease were reported. Two cases showed typical symptoms that are characterized by bulging eyes, ophthalmoplegia, dystonia, ataxia, spasticity of extremities and amyotrophy, and were consistent with Type II (Rosenberg et al). But another one lacked diversity of the symptoms, showing mainly progressive cerebellar ataxia for over 10 years. We pointed out the existence of a new type of MJD case exhibiting only progressive cerebellar ataxia over a long period. A female patient had dyspnea and insomnia after 20 years in her clinical course, and central sleep apnea was revealed by respiratory monitor. But, the apnea and irregular respiration appeared in both awake and sleep stages. We described the importance of attention to the apnea as a new complication of Machado-Joseph disease.
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PMID:[A family of Machado-Joseph disease with a patient having frequent apnea in all day]. 191 27

Electro-oculographic recordings (EOG) were made on 26 patients with Machado-Joseph disease or at genetic risk for that disease. All patients with clinically apparent disease (ataxia, dysarthria, spasticity, or ophthalmoparesis) had abnormal eye movements. Defects in caloric response, sinusoidal tracking, opticokinetic nystagmus (OKN), refixation saccades, and presence of gaze paretic nystagmus were detected in that order of frequency. Fourteen subjects were clinically at risk but had normal neurologic examinations or minor equivocal signs. Nine of the fourteen had abnormal EOG, with sinusoidal tracking, calories, refixation saccades, OKN, and gaze paretic nystagmus being abnormal in that order. EOG may be useful in early case detection and may contribute to genetic counseling.
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PMID:Electro-oculographic findings in Machado-Joseph disease. 689 Jan 62

Affected members of 63 families with a variety of autosomal dominant late onset cerebellar ataxias (ADCA), and 29 patients with similar phenotypes but no affected relatives, were investigated for the trinucleotide (CAG) repeat expansion described in Japanese families with Machado-Joseph disease (MJD). This disorder had previously been shown to map to the region of chromosome 14 which also contains a locus causing ADCA in French families, spinocerebellar ataxia 3 (SCA3). The MJD/SCA3 mutation was identified in nine families with ADCA type I, and a further family in which affected members had parkinsonism, peripheral neuropathy, dystonia, and spasticity, but little evidence of cerebellar disease. Only one of the 10 families was British (the Drew family of Walworth); the others originated from India, Jamaica, Ghana, Brazil and France. There was no single clinical feature which distinguished patients with the MJD/SCA3 mutation from those with the CAG expansion on chromosome 6 (SCA1) or ADCA type I families with no known mutation. The CAG repeat length ranged from 13-41 copies on normal chromosomes and 62-80 copies on affected chromosomes. There was a significant inverse correlation between age of onset of symptoms and repeat length, but no significant effect of parental sex on repeat length or age of onset in offspring. DNA analysis for the MJD/SCA3 mutation is useful for diagnosis in patients with familial ataxic or extrapyramidal syndromes, and will aid genetic counselling in these disorders.
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PMID:Detection of the Machado-Joseph disease/spinocerebellar ataxia three trinucleotide repeat expansion in families with autosomal dominant motor disorders, including the Drew family of Walworth. 749 71

The authors present the clinico-pathological findings in a member of a family residing in Akita Prefecture located in the north-eastern region of Japan. Four members in three generations of the family developed ataxia. The autopsied patient was a 42-year-old woman, who, at the age of 25, had developed progressive cerebellar ataxia with pyramidal spasticity and increased deep tendon reflexes predominant in the lower extremities. However, she retained fine movement of the hands and fingers and showed no dysarthria until the age of 35. She could no longer walk unassisted at 38 years old. She showed cerebellar ataxia in both hands and legs, dysarthria, bulging eyes, progressive extraoculomotor palsy with nystagmus, bradykinesia, sensory disturbance, and dystonia in the face, upper extremities, and fingers. Deep tendon reflexes were decreased, especially in the lower extremities. Subacute generalized muscular atrophy developed at the age of 39. She became bedridden and died of pneumonia. The clinical diagnosis was Type-2 of the entity known in Japan as Machado-Joseph disease. At neuropathological examination, the brain weight was 1,250 g. The spinocerebellar system including Clarke's column and the spinocerebellar tracts were degenerated, but the cerebellar cortex and inferior olivary nucleus were spared. Slight-to-moderate degeneration was observed in the pontocerebellar system. In the dentate nucleus, most of the neurons showed what is known in Japan as "grumose degeneration", but there was no neuronal loss or gliosis. The hilus of the dentate nucleus and the superior cerebellar peduncle were intact.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[An autopsied case of type 2 Machado-Joseph's disease or spino-pontine degeneration]. 821 97

We studied a large pedigree with dominant spinocerebellar ataxia, genetically and clinically. At now, 27 members over 5 generations have been affected. Linkage study for the disease locus to D6S89 in a total of 44 individuals showed maximum lod scores of 3.99 at theta = 0.000. This result indicates that the disease locus of this pedigree locates near D6S89 on chromosome 6p (SCA 1). We studied 17 patients clinically. Mean age at onset was 37.7 +/- 8.6, and mean duration after onset was 11.3 +/- 6.8 years. Their clinical features were characterized by progressive ataxia, pyramidal involvement with hyperreflexia or spasticity, and mild posterior column involvement. Mild gaze nystagmus at early stage became unclear with the progress of illness. The frequent signs in the advanced stage were diffuse amyotropy, twitching of face or tongue, bulbar palsy, slow saccade, external ophthalmoparesis, mydriasis, coarse postural tremor, and dementia with emotional disturbance. There are so much clinical similarities between our pedigree and other SCA 1 pedigrees in the literature. Generally, SCA 1 shows hyperreflexia, spasticity, and terminal slow saccade. On the other hand, non-SCA 1 type OPCA is characterized by progressive hyporeflexia, slow eye movement from early stage, and frequent choreoathetosis. Gaze nystagmus, external ophthalmoparesis, amyotrophy, and spasticity are common in both SCA 1 and Machado-Joseph disease (MJD). However, they are more frequent in MJD than SCA 1. Moreover, extrapyramidal signs, such as dystonia, are rare is SCA 1. Based on these difference, SCA 1 could be clinically differentiated from other similar hereditary ataxias.
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PMID:[Spinocerebellar ataxia 1--clinical study of 17 patients in a large pedigree]. 836 44

The treatment of Machado-Joseph disease (MJD) has so far been purely symptomatic. Encouraged by previous publications reporting some improvement in spasticity and gait in two patients with MJD treated with sulphamethoxazole and trimethoprim (Bactrim), we carried out a double-blind, placebo controlled cross-over trial in eight patients. Three kinds of parameters were used to evaluate the treatment effect: subjective performance, neurological examination and timed tests. The results showed that Bactrim had a beneficial effect on gait and coordination and that it would be worthwhile undertaking other trials, taking into account the great clinical variability of MJD.
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PMID:Evaluation of the effect of sulphametoxazole and trimethoprim in patients with Machado-Joseph disease. 859 84

There are currently some types of autosomal dominant cerebellar ataxias such as Machado-Joseph disease (MJD), spinocerebellar ataxia types 1-5 (SCA1-5), or hereditary dentatorubropallidoluysian atrophy. It is very important for these ataxias to be clinically differentiated, but that is sometimes difficult. In particular, the differential diagnosis between MJD and SCA1 is thought to be the most difficult. Recently, both MJD and SCA1 have been proven to be related to expansions of CAG trinucleotide in their causative genes. In this study, 20 cases of MJD in 13 unrelated Japanese families were genetically and clinically examined in comparison with 20 cases of age at onset- and duration-matched Japanese SCA1. The CAG repeat number of expanded MJD and SCA1 alleles was 72.2 +/- 3.1 (mean +/- SD, n = 20) and 47.3 +/- 4.4 (n = 20), respectively, and each repeat size was inversely correlated with age at onset in both MJD and SCA1. The repeat number in leukocytes increased from parents to children with acceleration of age at onset (anticipation) in MJD. In MJD, the number of CAG repeats in the expanded allele was lower in sperm than that of leukocytes, but was more in SCA1. However, the number of peaks in the expanded allele was greater in sperm than in leukocytes in both MJD and SCA1 (increased mosaicism level). MJD was clinically characterized by a relatively higher frequency of ocular signs such as eyelid retraction, bulging eyes, ophthalmoparesis, and nystagmus, spasticity in lower limbs, and sensory and urinary disturbances in contrast to the SCA1 patients except for slow eye movement. These results indicate that the expanded CAG repeat and clinical features are correlated in both MJD and SCA1, and MJD can be differentiated from SCA1 by clinical characteristics mentioned above as well as DNA analysis.
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PMID:Analysis of CAG trinucleotide expansion associated with Machado-Joseph disease. 881 56


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