Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0013362 (dysarthria)
 3,768 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This is the first large scale case series of motor neurone disease (MND) in Thailand. Seventy-seven patients were identified between 1978 and 1984 at Siriraj Hospital Medical School, Bangkok, Thailand. Fifty-five patients were male (71.43%) and the mean age of the patients was 51.55 (SD 14.26) years with the range of 17 to 78 years. Clinical classification of MND was categorized as progressive bulbar palsy (PBP), 26 patients (33.77%); amyotrophic lateral sclerosis (ALS), 42 patients (54.54%); and progressive spinal atrophy (PSA), 9 patients (11.69%). The mean age of PBP, ALS and PSA were in the order of 57.61 (SD 12.09), 52.81 (SD 11.18), and 28.11 (SD 9.44) years. Progressive spinal atrophy group was younger than PBP and ALS groups significantly at the P-value less than 0.05 by analysis of variance and Duncan tests. Fifty-three patients (72.60%) were resident in Bangkok and the central part of Thailand. The main presenting symptoms were wasting of the small muscles of both hands, leg weakness, and speech and/or swallowing difficulties. These symptoms were found in 62 patients (81.58%). Nearly half of the patients (48.68%) came to our care within six months of onset, 22.8 per cent presented with asymmetry of motor wasting, while limb and trunk fasciculation was seen in 73.61 per cent. Dysarthria, dysphagia and tongue fasciculation were recorded as 51.32, 48.68, 60.53 per cent respectively. Exaggerated deep tendon reflexes were noted as 65.79 and 80.26 per cent over the upper and lower limbs, while Babinski sign was elicited in only 23.3 per cent of the patients.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Motor neurone disease in Thailand: the clinical aspects of 77 patients. 194 Jul 1

Two sisters presented with progressive muscle cramps, as well as wasting and weakness of the legs with onset after age 20. They also showed intention tremor of the upper extremities and dysarthria starting during the first decade. The older patient also had fasciculations; the younger, hyperreflexia. Total plasma beta-hexosaminidase (Hex) activity with 4-methylumbelliferyl-acetyl-glucosamine as substrate was reduced to 1.4% and 2.7% of the control in the 2 patients, respectively. Hex A activity measured by 4-methylumbelliferyl-N-acetylglucosamine-6-O-sulphate as substrate was 9.9% and 12.8% of the mean control value in the 2 patients, respectively. Hex B activity was undetectable in both patients. Leukocyte total Hex activity was 7-8% of normal; residual Hex A activity in the 2 patients was 17.8% and 16.3% of normal controls, respectively. Fibroblastic residual Hex A activity in the 2 patients was 9.6% and 22% of normal mean value, respectively. Appendiceal ganglion cells contained membranous cytoplasmic bodies in the younger patient. Thin layer chromatography of the appendiceal extract from one patient (III/2) showed a marked increase of GM2 ganglioside, and some increase of GM3 ganglioside. Northern blots performed on fibroblast cell lines from both patients for the demonstration of alpha and beta locus messenger RNA showed no difference between patients and control. These patients have a rare form of adult-onset progressive motor neuron disease presumably due to abnormal beta subunits, causing severe deficiency of both Hex A and Hex B. The phenotypic expression of this disease is similar to motor neuron disease due to alpha locus mutations, which suggests that the Hex A deficiency, even though only a partial one, may be the important pathogenic factor.
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PMID:Adult onset motor neuronopathy in the juvenile type of hexosaminidase A and B deficiency. 297 15

A male patient was suspected as olivo-ponto-cerebellar atrophy from the clinical and computed tomographic features at 34 years of age. Afterwards, his dysarthria and limb ataxia were slowly and steadily worsened. He was finally bed-ridden and unresponsive, and died of hyperpyrexia and general wasting at 37 years of age. It was noted that laboratory investigation gave lower values of urinary 17-ketosteroids and 17-hydroxycorticosteroids in comparison with those of normal subjects. Pathological investigation in autopsy showed that he had pathological features consistent with adrenoleukodystrophy accompanying the olivo-ponto-cerebellar atrophy; diffuse demyelination in the cerebrocerebellear white matter, distorted architecture and cytoplasmic striations in the adrenal cortex, and in addition, a pseudosystemic degeneration of the olivo-ponto-cerebellar system and subcortical gray matter.
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PMID:An adult case of adrenoleukodystrophy with features of olivo-ponto-cerebellar atrophy: I. Clinical and pathological studies. 347 76

An 81-year-old man from a family with a history of oculopharyngeal muscular dystrophy (OPMD) involving 6 members over 4 generations is described. The patient first noted drooping of his eyelids at the age of 65. Dysphagia and dysarthria occurred soon thereafter. At age 78, impairment of gait developed and progressive wasting occurred in the limbs with an initial distal distribution. Electromyography of several limb muscles displayed a mixed myopathic and neurogenic pattern with giant potentials. Examination at autopsy revealed slight loss of neurons in the anterior horns of the spinal cord, with scanty ghost cells, neuronophagia, and central chromatolysis. By light microscopy the limb muscles showed moderate small-group atrophy with severe myopathy and target fibers. The viscerocranial muscles, including the ocular, vocal, and tongue muscles, demonstrated only myopathic change with the typical features of progressive muscular dystrophy. Advanced replacement by fibrous connective tissue and fat had occurred in both the viscerocranial and the lower limb muscles. The significance of neurogenic involvement in OPMD is discussed.
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PMID:An autopsy study of a familial oculopharyngeal muscular dystrophy (OPMD) with distal spread and neurogenic involvement. 725 32

Sixteen members of a family with a history of autosomal dominant progressive external ophthalmoplegia (adPEO) with hypogonadism were examined. The muscular involvement commenced cranially and descended in relation to increasing disease duration. The neuromuscular signs were PEO, dysarthria, dysphonia, limb muscle weakness with wasting, absence of Achilles tendon reflexes, and distal vibration sensory loss. The electromyogram (EMG) was myopathic in facial and proximal limb muscles. Neurogenic involvement was suspected in a few tibial anterior muscles. Neurography showed signs of axonal neuropathy correlated to clinical signs. F-responses were reduced in number or absent in peroneal nerves, and did not correlate to clinical signs or disease duration. Muscle biopsies in advanced cases had structural abnormalities of mitochondria, ragged-red fibers, and focal cytochrome c oxidase deficiency. A combination of muscle-nerve involvement with PEO, Achilles tendon areflexia, distal vibration sensory impairment, myopathic EMG, and abnormally low sural nerve responses seems to be typical of this type of mitochondrial disorder.
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PMID:Muscle-nerve involvement in autosomal dominant progressive external ophthalmoplegia with hypogonadism. 860 26

1. Amyotrophic lateral sclerosis (ALS) is a degenerative disorder characterized by selective damage to the neural system that mediates voluntary movement. Although the pathophysiologic process of ALS remains unknown, about 5 to 10% of cases are familial. According to genetic linkage studies, the familial ALS (FALS) gene has been mapped on chromosome 21 in some families and recent work identified some different missense mutations in the Cu/Zn superoxide dismutase gene in FALS families. 2. We recently identified five mutations in six FALS families. The mutations identified in our FALS families are H46R, L84V, I104F, S134N, and V148I. The H46R mutation that locates in the active site of Cu/Zn SOD gene is associated with two Japanese families with very slow progression of ALS. On the other hand, the L84V mutation associated with a rapidly progressive loss of motor function with predominant lower motor neuron manifestations. 3. In the family with the V148I, the phenotype of the patient varied very much among the affected members. One case had weakness of the lower extremities at first and died without bulbar paresis. The second case first noticed wasting of the upper limbs with bulbar symptoms, but the third had weakness of upper extremities without developing dysarthria nor dysphagia until death. These mutations account for 50% of all FALS families screened, although Cu/Zn SOD gene mutations are responsible for less than about 13-21% in the Western population. 4. Our results indicate that the progression of disease with mutations of Cu/Zn SOD is well correlated with each mutation. The exact mechanism by which the abnormal Cu/Zn SOD molecules selectively affect the function of motor neurons is still unknown.
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PMID:Molecular analyses of the Cu/Zn superoxide dismutase gene in patients with familial amyotrophic lateral sclerosis (ALS) in Japan. 987 71

A patient with polymyositis manifesting severe myocardial damage and conduction block is described. A 57-year-old man presented dysarthria, dysphagia, proximal-dominant muscle weakness and wasting of the extremities. Muscle biopsy revealed degeneration and regeneration of muscle fibers and infiltration of mononuclear cells. After admission, muscle weakness rapidly progressed and mechanical ventilation was needed for respiratory failure. Simultaneously, cardiac symptom developed and resulted in bradycardia and trifascicular conduction block, which required a pacemaker. Echocardiogram revealed diffuse hypokinesia, ventricular enlargement and thickened wall. Marked elevations of serum CK-MB, cardiac myosin light chain I and cardiac troponin T were observed. High dose administration of methylprednisolone resulted in improvement of muscular and cardiac symptoms, and prevented complete heart block. Immediate and high dose of steroid therapy was considered to be effective for severe myocarditis in polymyositis.
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PMID:[A patient of polymyositis with severe myocardial damage and conduction block]. 1039 Oct 81

Although there are indications that beta-blockers affect the skeletal muscle in therapeutic dosages, their influence on mitochondrial disorders is unknown. A 52-year-old woman developed double vision, myalgias, muscle cramps, and hip and thigh muscle stiffness. Clinical neurologic examination revealed ptosis, dysarthria, sore neck muscles, weakness and wasting of the thighs, and generally brisk tendon reflexes. Lactate stress testing was significantly abnormal. Needle electromyography was nonspecifically abnormal and myopathic. Muscle biopsy showed mild myopathic changes, target fibers, and a single COX-negative fiber. Probable mitochondrial disorder was diagnosed. The patient had been on 30 mg of propranolol during 7 years for arterial hypertension. Shortly after discontinuation of the drug, her double vision gradually disappeared, myalgias and muscle cramps gradually resolved, and the patient reported an increase in muscle mass on repeated follow-ups. Long-term administration of propranolol may aggravate a mitochondrial disorder. Discontinuation of propranolol may result in a gradual resolution of these adverse reactions.
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PMID:Mitochondrial disorder aggravated by propranolol. 1686 49

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

One week after a flu-like prodrome, an 18-month-old boy developed acute severe, symmetrical, painless weakness and wasting of the shoulder girdle and upper limbs, drooling, dysphagia, dysarthria, atrophy and fasciculations of the tongue. Milder paresis involved the mimic muscles and the neck extensors. The legs were intact with brisk reflexes. The flail immobile upper limbs produced the appearance that the boy was restrained in a narrow barrel. Electrodiagnostic findings suggested demyelinating motor neuropathy sparing the legs. CSF (45 days after onset) was normal. Initial recovery was observed but 70 days after onset the child suffered severe relapse and died from respiratory arrest. This is another rare case of the pharyngeal-cervical-brachial variant of Guillain-Barre syndrome in infancy with an unusual relapsing course leading to a fatal outcome.
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PMID:The "Child in the Barrel syndrome"--severe pharyngeal-cervical-brachial variant of Guillain-Barre Syndrome in a toddler. 1956 2


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