Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0002736 (amyotrophic lateral sclerosis)
 19,048 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Mutations in the gene progranulin (PGRN) were recently identified as the cause of some forms of frontotemporal dementia with ubiquitin-positive intraneuronal inclusion pathology (FTLD-U). The DNA-binding protein, TDP-43, was determined to be a component of these ubiquitinated inclusions in FTLD-U and amyotrophic lateral sclerosis (ALS) with dementia (ALS-D). These findings raise many interesting questions as to the shared pathology and possible common pathologic process between ALS and FTLD-U. This study examines the immunoexpression of PGRN in ALS patients using immunohistochemical analysis of post-mortem tissue. Available brain and spinal cord sections of eight ALS patients, including one case with severe dementia, and eighteen control-aged brains were stained with anti-PGRN antibodies. We found increased staining for PGRN in motor tracts with vacuolar degeneration and glial cells in ALS sample spinal cord and brainstem sections compared to controls. Variable upper motor neuron staining and reactive glia were seen in ALS motor cortex samples. Frontal lobe and hippocampal sections showed no consistent differences from control tissues with the exception of the ALS-dementia case, which showed PGRN immunoexpression in non-motor cortical areas. These results describe a pattern of increased PGRN expression in areas of active degeneration in ALS. The meaning of this association is unclear, but may indicate a potential role for PGRN in the variable expression of motor and cognitive deficits in the ALS-FTD spectrum.
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PMID:Progranulin (PGRN) expression in ALS: an immunohistochemical study. 1884 8

Frontal lobe functions, in particular working memory (WM) and verbal fluency, have been found to be deficient in amyotrophic lateral sclerosis (ALS). To study the neural correlates of WM-impairment, ALS patients and healthy age-matched controls were subjected to two working memory tasks following the 2-back paradigm, one requiring the storage of figural information, the other storage of spatial information. A significant proportion of ALS patients were unable to perform the WM-tasks. Those who could showed worse performance in the spatial task than the controls. Event-related brain potentials recorded during the task revealed a topographical change of the working memory effect in the ALS patients. Thus, behavioral and electrophysiological data suggest an alteration of working memory, in particular for spatial information, in ALS. Additionally, the patients also took part in two Go/Nogo tasks (spatial, figural) using the same stimulus material but defining targets prior to the experiment instead of a working memory manipulation. Here, an anteriorization of the nogo-P3 was found which has been established as an index of impaired inhibitory functions.
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PMID:A neurophysiological analysis of working memory in amyotrophic lateral sclerosis. 2196 13

Despite growing interest, the frequency and characteristics of frontal lobe functional and behavioral deficits in Chinese people with amyotrophic lateral sclerosis (ALS), as well as their impact on the survival of ALS patients, remain unknown. The Chinese version of the frontal assessment battery (FAB) and frontal behavioral inventory (FBI) were used to evaluate 126 sporadic ALS patients and 50 healthy controls. The prevalence of frontal lobe dysfunction was 32.5%. The most notable impairment domain of the FAB was lexical fluency (30.7%). The binary logistic regression model revealed that an onset age older than 45 years (OR 5.976, P = 0.002) and a lower educational level (OR 0.858, P = 0.002) were potential determinants of an abnormal FAB. Based on the FBI score, 46.0% of patients showed varied degrees of frontal behavioral changes. The most common impaired neurobehavioral domains were irritability (25.4%), logopenia (20.6%) and apathy (19.0%). The binary logistic regression model revealed that the ALS Functional Rating Scale-Revised scale score (OR 0.127, P = 0.001) was a potential determinant of an abnormal FBI. Frontal functional impairment and the severity of frontal behavioral changes were not associated with the survival status or the progression of ALS by the cox proportional hazard model and multivariate regression analyses, respectively. Frontal lobe dysfunction and frontal behavioral changes are common in Chinese ALS patients. Frontal lobe dysfunction may be related to the onset age and educational level. The severity of frontal behavioral changes may be associated with the ALSFRS-R. However, the frontal functional impairment and the frontal behavioral changes do not worsen the progression or survival of ALS.
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PMID:Frontal lobe function and behavioral changes in amyotrophic lateral sclerosis: a study from Southwest China. 2524 95