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

Because linkage has been reported between HLA and the locus for hereditary ataxia in some families, we studied a 3-generation kindred in which several individuals had dominantly inherited spinopontine atrophy. Affected family members had upper and lower limb ataxia, hypoactive reflexes, loss of proprioception, dysarthria, dysphagia, and pronounced extraocular movement abnormalities. Linkage analysis, based on 25 markers in 28 people, gave strongly negative results with both HLA (z less than -2.0 for theta less than 0.15) and GLO1 (z less than -2.0, theta less than or equal to 0.01). The highest LOD score was for linkage to GPT on chromosome 16 (z = 0.42, theta = 0.0). To assess the relationship between HLA linkage and phenotype, 4 published kindreds with adequate clinical and neuropathological descriptions were used for comparison to the present family. Persons in the 3 families showing evidence for HLA linkage had clinical and pathologic changes consistent with olivopontocerebellar atrophy, type 1. The conditions in the 2 "nonlinked" families were phenotypically distinct from the HLA-linked condition with respect to extraocular movement findings and peripheral sensory nervous system signs. They differed markedly from each other in neuropathologic changes.
 ...
PMID:Linkage analysis in spinopontine atrophy: correlation of HLA linkage with phenotypic findings in hereditary ataxia. 347 98

Spinocerebellar ataxia type 4 (SCA4), also known as 'hereditary ataxia with sensory neuropathy', represents a very rare, progressive and untreatable form of an autosomal dominant inherited cerebellar ataxia (ADCA). Due to a lack of autopsy cases, no neuropathological or clinicopathological studies had yet been performed in SCA4. In the present study, the first available cerebellar and brainstem tissue of a clinically diagnosed and genetically-confirmed German SCA4 patient was pathoanatomically studied using serial thick sections. During this systematic postmortem investigation, along with an obvious demyelinization of cerebellar and brainstem fiber tracts we observed widespread cerebellar and brainstem neurodegeneration with marked neuronal loss in the substantia nigra and ventral tegmental area, central raphe and pontine nuclei, all auditory brainstem nuclei, in the abducens, principal trigeminal, spinal trigeminal, facial, superior vestibular, medial vestibular, interstitial vestibular, dorsal motor vagal, hypoglossal, and prepositus hypoglossal nuclei, as well as in the nucleus raphe interpositus, all dorsal column nuclei, and in the principal and medial subnuclei of the inferior olive. Severe neuronal loss was seen in the Purkinje cell layer of the cerebellum, in the cerebellar fastigial nucleus, in the red, trochlear, lateral vestibular, and lateral reticular nuclei, the reticulotegmental nucleus of the pons, and the nucleus of Roller. In addition, immunocytochemical analysis using the anti-polyglutamine antibody 1C2 failed to detect any polyglutamine-related immunoreactivity in the central nervous regions of this SCA4 patient studied. In view of the known functional role of affected nuclei and related fiber tracts, the present findings not only offer explanations for the well-known disease symptoms of SCA4 patients (i.e. ataxic symptoms, dysarthria and somatosensory deficits), but for the first time help to explain why diplopia, gaze-evoked nystagmus, auditory impairments and pathologically altered brainstem auditory evoked potentials, saccadic smooth pursuits, impaired somatosensory functions in the face, and dysphagia may occur during the course of SCA4. Finally, the results of our immunocytochemical studies support the concept that SCA4 is not a member of the CAG-repeat or polyglutamine diseases.
 ...
PMID:Spinocerebellar ataxia type 4 (SCA4): Initial pathoanatomical study reveals widespread cerebellar and brainstem degeneration. 1636 39

Sporadic ataxia affecting multiple systems, such as cerebellar, extrapyramidal, and autonomic systems, is known as multiple system atrophy cerebellar type (MSA-C), while similar multisystem involvements are seen in certain types of hereditary ataxia, such as spinocerebellar ataxia type 3 (SCA3). Dysphagia is a common symptom that can predispose to aspiration pneumonia, a major cause of death in patients with these diseases. Although the progressions of dysphagia in patients with MSA-C have been reported sporadically, those in SCA3 have not been reported. We retrospectively compared the results of repetitive videofluoroscopic examinations in patients with SCA3 (n = 6) and in those with MSA-C (n = 7). The result showed that the gross progression of dysphagia was significantly slower in patients with SCA3 than in those with MSA-C, but the maximum progression speeds were not significantly different. The dysphagia severities were not associated with impaired activity of daily living evaluated by the Barthel index in MSA-C, but were associated in SCA3. Despite the small number of patients enrolled, these data suggest that physicians should monitor swallowing functions in patients with SCA3 after mild dysphagia develops because it may progress as rapidly as it does in MSA-C.
 ...
PMID:Differential Progression of Dysphagia in Heredity and Sporadic Ataxias Involving Multiple Systems. 2661 69

Friedreich ataxia (FRDA) is a multisystem neurodegenerative disorder and the most common hereditary ataxia. Dysphagia (swallowing impairment) is present in 98% of individuals with FRDA and is characterized by lingual and pharyngeal dysfunction (manifesting in impaired bolus preparation and transfer, and post-swallow residue in the mouth and pharynx), delayed swallow initiation, and entry of material into the airway (penetration/aspiration). Dysphagia severity correlates with disease severity and duration however no longitudinal studies describe changes in function in FRDA. The aim of this study was to investigate the progression of dysphagia in FRDA over one year. Fifty-nine individuals with FRDA and confirmed dysphagia were recruited and 23 of them underwent a second assessment 12 months later. Assessments of swallowing related quality of life, oral motor function (Frenchay Dysarthria Assessment 2nd Ed [FDA-2]) and functional swallowing via videofluoroscopy were conducted. Trials of thin liquid, puree and biscuit were interpreted using the Bethlehem Assessment Scale and the Penetration-Aspiration Scale by two blinded raters. Data from the videofluoroscopy revealed a decline in tongue function, pharyngeal clearance and cricopharyngeal function on solid food. However, severity of penetration/aspiration did not increase. Swallowing-related quality of life and oral-motor function remained stable. A decline in function was observed at three anatomical sites considered important for safe and effective swallowing (tongue, pharyngeal, and cricopharyngeal). However, these deficits did not translate into any meaningful functional decline in swallowing related health over 12 months for individuals with FRDA.
 ...
PMID:Changes detected in swallowing function in Friedreich ataxia over 12 months. 3157 56