Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011168 (dysphagia)
 15,644 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We report a 68-year-old man with progressive speech disturbance and dementia. He was well until 1995, when he noted an onset of difficulty in speech. He was able to name simple objects and understand language, however, he showed great difficulty in spontaneous speech. In 1998, he visited our service. He was alert and oriented, but he showed moderate degree of dementia. He did not appear to have aphasia but he showed marked dysarthria and slurred speech. He showed limb-kinetic apraxia in his right hand. He showed moderate restriction in his vertical gaze, masked face, and dysphagia. He walked normally. No rigidity, ataxia, or abnormal involuntary movement was noted. He showed grasp response and he was bradykinetic. He was treated with levodopa without effect. His condition deteriorated slowly and he was admitted to our service because of fever on February 13, 1999. He was alert but almost mute. He was unable to look upward or downward. Oculocephalic response was preserved. Axial rigidity was noted but no limb rigidity was present. He walked with small steps. Retropulsion was present. Deep tendon reflexes were diminished and the plantar response was flexor bilaterally. Laboratory examinations were unremarkable and his fever went down within a few days by supportive treatment. He was discharged to his home, where his condition deteriorated further. He developed cardiopulmonary arrest on May 3, 1999 and was brought into ER again. Cardiopulmonary resuscitation was unsuccessful and he was pronounced dead at 7:30 in the morning on the same day. The patient was discussed in a neurological CPC. The chief discussant arrived at the conclusion that this patient had corticobasal degeneration. But he felt that the differential diagnosis from atypical progressive supranuclear palsy, in which cortical pathology and symptoms predominated as in corticobasal degeneration, would be extremely difficult. Most of the participants felt that this patient had corticobasal degeneration, but a few thought that he had atypical PSP. Post-mortem examination revealed asymmetric cortical atrophy, which was accentuated in the left motor cortical area. Microscopic examination of the precentral cortex revealed neuronal loss and gliosis. Ballooned neurons and astrocytic plaques were also seen. The substantia nigra showed marked neuronal loss. Neuropil threads were observed in the nigra. Those threads were positive for anti-tau immunohistochemistry. The internal segment of the globus pallidus, the subthalamic nucleus, and the cerebellar dentate nucleus showed mild to moderate neuronal loss. A few neurofibrillary tangle-positive neurons were seen in these structures. Neuropil threads were also seen throughout. Pathologic changes were consistent with the diagnosis of corticobasal degeneration. One of the participants pointed out that he was able to walk at the time when he was showing marked speech disturbance and limb-kinetic apraxia, which was rather unusual for PSP suggesting corticobasal degeneration.
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PMID:[A 68-year-old man with speech disturbance as the initial symptom followed by bradykinesia and dementia. Clinical conference]. 1144 73

Leigh disease is a subacute neurodegenerative disorder characterized by symmetric necrotic lesions in the basal ganglia, cerebellum, thalamus, brain stem, and optical nerves and caused by altered oxidative phosphorylation. We describe the clinical, biochemical, neuroimaging, and molecular studies of a 19-year-old boy with early-onset Leigh disease manifesting as severe extrapyramidal disorder with generalized dystonia and choreoathetosis. He was born of healthy parents after an uneventful pregnancy and delivery. At the age of 2 1/2 years, after a minor respiratory infection, he developed unstable, broad-based gait and tremor of the hands. These symptoms persisted for the next several years, when ataxia became more prominent. Difficulty in swallowing, dysarthria, trunk dystonia, and marked dyskinesia of the arms and hands gradually developed. Nystagmus, transient ptosis, and strabismus also appeared. Abnormal laboratory findings included elevated plasma and cerebrospinal fluid lactate and pyruvate, with an abnormal lactate/pyruvate ratio. Cranial computed tomography and magnetic resonance imaging demonstrated signs of cerebellar atrophy, bilateral and symmetric hypodensities in the lentiform nucleus and thalamus, and transient hyperintensities of cerebral peduncles in T2-weighted sequences suggestive of Leigh disease. Muscle biopsy revealed isolated fiber atrophy, necrotic fibers undergoing phagocytosis, and no ragged-red fibers. The measured catalytic activity of cytochrome c oxidase in skeletal muscle homogenates demonstrated a partial cytochrome c oxidase deficiency No abnormalities in the mitochondrial genome and in the SURF-1 gene were found. The boy is currently receiving levodopa therapy, creatine monohydrate, and a high dosage of thiamine and lipoic acid, his condition is stabilized, and extrapyramidal symptoms are less pronounced.
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PMID:Cytochrome c oxidase partial deficiency-associated Leigh disease presenting as an extrapyramidal syndrome. 1151 Sep 39

Altered function of the ubiquitin pathway has been implicated in the etiology of neurodegeneration. For example, gracile axonal dystrophy (gad) mutant mice, which harbor a deletion within the gene encoding ubiquitin C-terminal hydrolase L1 (Uch-L1), display sensory ataxia followed by posterior paralysis and lethality. We previously showed that mice homozygous for a targeted deletion of the related Uch-L3 gene are indistinguishable from wild-type. To assess whether the two hydrolases have redundant function, we generated mice homozygous for both Uch-L1gad and Uch-L3Delta3-7. The double homozygotes weigh 30% less than single homozygotes and display an earlier onset of lethality, possibly due to dysphagia, a progressive loss in the ability to swallow food. This is consistent with histological analysis that revealed axonal degeneration of the nucleus tractus solitarius (NTS) and area postrema (AP) of the medulla. The NTS is essential for central nervous system control of swallowing. The double homozygotes also display a more severe axonal degeneration of the gracile tract of the medulla and spinal cord than had been observed in Uch-L1gad single homozygotes. In addition, degeneration of dorsal root ganglia cell bodies was detected in both the double homozygotes and Uch-L3Delta3-7 single homozygotes. Given that both Uch-L1gad and Uch-L3Delta3-7 single homozygotes display distinct degenerative defects that are exacerbated in the double homozygotes, we conclude that Uch-L1 and Uch-L3 have both separate and overlapping functions in the maintenance of neurons of the gracile tract, NTS and AP. This study is the first to successfully document dysphagia in the mouse and is a potentially valuable resource for understanding human neurodegenerative disorders that cause swallowing defects.
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PMID:Loss of Uch-L1 and Uch-L3 leads to neurodegeneration, posterior paralysis and dysphagia. 1155 33

Paraneoplastic cerebellar degeneration with anti-Yo antibodies is a rare but disabling neurodegenerative disease that may point to an occult ovarian cancer. Symptoms usually accompanying paraneoplastic cerebellar degeneration include truncal and limb ataxia, dysarthria, dysphagia, nystagmus, vertigo, and diplopia. The pathogenesis of paraneoplastic neurological syndromes is unknown. Treatment results of the neurological symptoms are disappointing. The present case illustrates how neurological symptoms pointed to an occult ovarian cancer.
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PMID:Paraneoplastic cerebellar degeneration: neurological symptoms pointing to occult ovarian cancer. 1158 46

A 68-year-old man presented with Wallenberg's syndrome consisting of ataxia, dysphagia, hypesthesia on the left side of the body, and Horner's syndrome on the right. Magnetic resonance (MR) imaging revealed a right lateral medullary infarction and small multiple lacunae scattered in the upper medulla. Neurological symptoms improved in a week and the patient was discharged with mild residual hypesthesia on the left side. However, 31 days later, he was emergently admitted after suddenly becoming apneic and losing consciousness. MR imaging detected no new lesion. The patient was placed under ventilation support for 48 hours before regaining normal respiratory function. Medullary infarction sometimes causes catastrophic respiratory failure, but Wallenberg's syndrome caused by lateral medullary infarction is rarely associated with central respiratory dysfunction, and delayed onset of central respiratory dysfunction is extremely unusual. Delayed onset of central respiratory failure is a life-threatening complication of the medullary infarction causing Wallenberg's syndrome, which in general is not recognized.
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PMID:Delayed central respiratory dysfunction after Wallenberg's syndrome--case report. 1176 Mar 86

The hereditary spastic ataxias (HSA) are a group of clinically heterogeneous neurodegenerative disorders characterized by lower-limb spasticity and generalized ataxia. HSA was diagnosed in three unrelated autosomal dominant families from Newfoundland, who presented mainly with severe leg spasticity, dysarthria, dysphagia, and ocular-movement abnormalities. A genomewide scan was performed on one family, and linkage to a novel locus for HSA on chromosome 12p13, which contains the as-yet-unidentified gene locus SAX1, was identified. Fine mapping confirmed linkage in the two large families, and the third, smaller family showed LOD scores suggestive of linkage. Haplotype construction by use of 13 polymorphic markers revealed that all three families share a disease haplotype, which key recombinants and overlapping haplotypes refine to about 5 cM, flanked by markers D12S93 and GATA151H05. SAX1 is the first locus mapped for autosomal dominant HSA.
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PMID:A locus for autosomal dominant hereditary spastic ataxia, SAX1, maps to chromosome 12p13. 1177 73

The nosology and aetiology of sporadic adult-onset ataxia are poorly understood. The aim of the present study was to answer the following questions: (i) How many sporadic ataxia patients have a genetic cause? (ii) How many sporadic ataxia patients suffer from multiple system atrophy (MSA)? (iii) Is there a specific association between sporadic ataxia and serum anti-glutamic acid decarboxylase (GAD) or antigliadin antibodies? and (iv) What are the clinical features of patients with unexplained sporadic ataxia? The study was performed in 112 patients who met the following inclusion criteria: (i) progressive ataxia; (ii) onset after 20 years; (iii) informative and negative family history (no similar disorders in first- and second-degree relatives; parents older than 50 years); and (iv) no established symptomatic cause. Thirty-two patients (29%) met the clinical criteria of possible (7%) or probable (22%) MSA. The Friedreich's ataxia mutation was found in five patients (4%), the spinocerebellar ataxia (SCA) 2 mutation in one (1%), the SCA3 mutation in two (2%) and the SCA6 mutation in seven (6%). The disease remained unexplained in 65 patients (58%). We did not detect anti-GAD antibodies in any of our patients. Antigliadin antibodies were present in 14 patients, 10 patients with unexplained ataxia (15%) and 4 patients with an established diagnosis (9%). Patients with unexplained sporadic ataxia had a median disease onset of 56.0 years. Decreased vibration sense (62%), decreased or absent ankle reflexes (40%), increased ankle reflexes (39%), dysphagia (38%) and extensor plantar responses and/or spasticity (34%) were the most frequent extracerebellar symptoms. Compared with MSA, disease progression was significantly slower.
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PMID:The aetiology of sporadic adult-onset ataxia. 1196 Aug 86

CAG repeat expansions with loss of CAT interruptions in the coding region of the ataxin-1 gene are associated with spinocerebellar ataxia type 1 (SCA1). For molecular genetic diagnosis it is necessary to define the limits of normal and pathological size ranges. In most studies, normal alleles as measured by PCR range from 6-39 units with interruptions of 1-3 CAT trinucleotides that are thought to be involved in the stability of the trinucleotide stretch during DNA replication. Expanded alleles have been reported to carry 39-81 CAG trinucleotides without stabilising CAT interruptions. To evaluate the limits between normal and disease size ranges we analysed the repeat length and composition of the SCA1 gene in 15 individuals with alleles ranging from 36 and 41 triplets for genotype-phenotype correlation studies. We found the 39 trinucleotide-allele to be either interrupted by CAT repeats or formed by a pure CAG stretch. The clinical features of individuals carrying 39 uninterrupted CAG repeats did not differ from the SCA1 phenotype in general with dysphagia, pale discs, pyramidal signs and cerebellar tremor being more frequent as compared to other SCA genotypes. In contrast, the interrupted 39 trinucleotide-allele is not correlated with the SCA1 phenotype.
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PMID:Spinocerebellar ataxia type 1 (SCA1): phenotype-genotype correlation studies in intermediate alleles. 1197 25

Spinocerebellar ataxia is a group of diseases with autosomal dominant inheritance heterogenous both clinically and genetically. So called dynamic mutations underlie most these nosological units. The clinical patterns of various SCA types have not yet been defined completely. The purpose of the present report was description of the typical symptoms and signs of type 1 SCA. Seventeen patients from 13 families (M-2, F-15) were studied clinically in detail. The diagnosis was confirmed by DNA analysis. The assessment included neurological status, cognitive functions, the results of EEG, EMG, SEP, VEP, BAER and MRI examinations. The pedigrees indicated autosomal dominant inheritance pattern. The mean age at onset was 35.5 +/- 6.8 years (range 23-45 years) and it suggested negative correlation with the number of CAG repetitions. Cerebellar syndrome limb and truncal, ataxia and dysarthria was present in all cases. Six patients had nystagmus, 3 had slow saccades, 2 had gaze limitation upward, and lateral and 6 had dysphagia. Signs of pyramidal system involvement were found in 10 cases, one had athetotic movements, one had orthostatic hypotension. Two patients had dementia features, 9 had some decline of intellectual functions, mainly with difficulties of memorization, learning and concentration. In 16 cases MRI demonstrated vermis atrophy and atrophy of cerebellar hemispheres, 14 had fourth ventricle dilatation, 8 had flattening of pons base, 8 had narrowing of cervical spinal cord, 8 had dilated CSF spaces over frontal lobes and in 6 cases lateral ventricles were dilated. Electrophysiological peripheral nervous system investigations showed in 16 cases long-standing damage to the motor and sensory peripheral neurons at the level of nerve trunks, more pronounced in sensory nerves. In 13 cases peripheral neuron damage was subclinical. SEP showed in all patients disturbed function of ascending sensory pathways at peripheral and spinocortical levels.
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PMID:[Clinical picture of spinocerebellar ataxia type I (SCA1)]. 1198 14

The term acanthocytosis is derived from the Greek for "thorn" and is used to describe a peculiar spiky appearance of erythrocytes. Acanthocytosis is found to be associated with at least three hereditary neurological disorders that are generally referred to as neuroacanthocytosis. Abetalipoproteinaemia is an autosomal recessive condition, characterised by absence of serum apolipoprotein B containing lipoproteins leading to fat intolerance and fat-soluble vitamin deficiency. This results in a progressive spinocerebellar ataxia with peripheral neuropathy and retinitis pigmentosa. Chorea-acanthocytosis is also an autosomal recessive condition and is characterised by chorea, orofaciolingual dyskinesia, dysphagia, dysarthria, areflexia, seizures and dementia. Some of its features, including choreic movements, peripheral neuropathy with areflexia, elevated serum creatine kinase levels and myopathy are shared by another form of neuroacanthocytosis, McLeod syndrome. Patients affected by this X-linked disorder also show abnormal expression of Kell blood group antigens and a permanent haemolytic state. In addition to these cases, acanthocytosis is occasionally associated with other neurological disorders, such as Hallervorden-Spatz disease. For each of the neuroacanthocytosis syndromes we review the main clinical features and their molecular bases. The recent molecular genetics findings are the first step towards the understanding of the pathogenetic mechanisms and eventually the search for effective treatments.
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PMID:Clinical features and molecular bases of neuroacanthocytosis. 1218 48


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