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Leo F McCluskey

Publications and source records attributed to Leo F McCluskey.

4 recordsLinked to original sources
PubMed2006

Ubiquitinated TDP-43 in frontotemporal lobar degeneration and amyotrophic lateral sclerosis.

Ubiquitin-positive, tau- and alpha-synuclein-negative inclusions are hallmarks of frontotemporal lobar degeneration with ubiquitin-positive inclusions and amyotrophic lateral sclerosis. Although the identity of the ubiquitinated protein specific to either disorder was unknown, we showed that TDP-43 is the major disease protein in both disorders. Pathologic TDP-43 was hyper-phosphorylated, ubiquitinated, and cleaved to generate C-terminal fragments and was recovered only from affected central nervous system regions, including hippocampus, neocortex, and spinal cord. TDP-43 represents the common pathologic substrate linking these neurodegenerative disorders.

Amino Acid Sequence↗
PubMed2006

Amyotrophic lateral sclerosis: diffusion-tensor and chemical shift MR imaging at 3.0 T.

PURPOSE: To prospectively determine whether diffusion-tensor magnetic resonance (MR) imaging in conjunction with two-dimensional chemical shift imaging can assist in identifying upper motor neuron involvement and whether disease severity and duration can be predicted based on imaging parameters in patients with amyotrophic lateral sclerosis (ALS). MATERIALS AND METHODS: Institutional review board approval and informed consent were obtained for this HIPAA-compliant study. Fifteen patients with ALS (12 men, three women; mean age, 57.3 years) with clinical evidence of upper motor neuron involvement and 10 healthy control subjects (five men and five women; mean age, 49.4 years) were studied. Fractional anisotropy (FA) and apparent diffusion coefficient (ADC) were measured from the corticospinal tracts at the level of the internal capsule. Average N-acetylaspartate (NAA)/creatine-phosphocreatine (Cr) and NAA/choline-containing compounds (Cho) ratios were calculated from the precentral gyrus. Student t test, multiple linear regression analysis, and Spearman correlation coefficients were employed to quantify relationships between imaging and clinical parameters. RESULTS: Patients with ALS exhibited significantly reduced FA values and NAA/Cr and NAA/Cho ratios compared with values in control subjects (P<.05) for both affected and nonaffected sides of the brain. ADC was elevated significantly in the affected side (P<.05) and was an independent predictor of disease duration after adjusting for age; however, FA values and NAA/Cr ratios for the affected side were even stronger predictors of disease duration. Moderate but statistically significant correlation was found between the FA values for the affected side and the ALS Functional Rating Scale Revised (ALSFRS-R) score (r=0.51, P<.05). The NAA/Cr ratio also correlated with both the ALSFRS-R and upper motor neuron scores (r=0.50 and 0.54, respectively; P<.05). CONCLUSION: Diffusion-tensor and two-dimensional chemical shift MR imaging spectroscopy can be used to identify upper motor neuron involvement and predict disease duration in patients with ALS.

Adult↗
PubMed2003

Nocturnal oximetry: utility in the respiratory management of amyotrophic lateral sclerosis.

OBJECTIVE: Current recommendations are to institute nocturnal nasal ventilation for amyotrophic lateral sclerosis patients with a forced vital capacity (FVC) of <50% of predicted normal. The purpose of this study was to determine whether this is appropriate. DESIGN: A total of 87 nocturnal oximetry evaluations were performed on 78 consecutive amyotrophic lateral sclerosis patients symptomatic for sleep-disordered breathing. Nocturnal oximetry measurements were compared for those with FVC >50% vs. those with FVC of <50% of normal. FVC was measured sitting and supine. RESULTS: A considerable number of these symptomatic patients manifested evidence of nocturnal hypoxemia as measured by oximetry. However, there was no significant difference between patients with sitting percentage-predicted FVC above and below 50% predicted in minimum oxygen saturation, mean oxygen saturation, percentage of time spent with oxygen saturation of <88%, and number of events per hour. There was no significant difference between patients with supine percentage-predicted FVC above and below 50% predicted in minimum oxygen saturation, mean oxygen saturation, percentage of time spent with oxygen saturation of <88%, and number of events per hour. CONCLUSION: The recommendation that FVC be <50% of normal is inappropriate for justifying introduction of nocturnal nasal ventilation. Many patients are symptomatic at higher FVC and manifest evidence of nocturnal hypoxemia. Nocturnal oximetry adds additional practical information for justifying earlier respiratory intervention for symptomatic patients.

Amyotrophic Lateral Sclerosis↗