Associations of Patient Mood, Modulators of Quality of Life, and Pharmaceuticals with Amyotrophic Lateral Sclerosis Survival Duration.

Associations of modulators of quality of life (QoL) and survival duration are assessed in the fatal motor neuron disease, Amyotrophic Lateral Sclerosis. Major categories include clinical impression of mood (CIM); physical health; patient social support; and usage of interventions, pharmaceuticals, and supplements. Associations were assessed at p < 0.05 and p < 0.001 significance thresholds using applicable methods (Chi-square, t-test, ANOVA, logistical regression, random forests, Fisher's exact test) within a retrospective cohort of 1585 patients. Factors significantly correlated with positive (happy or normal) mood included family support and usage of bi-level positive airway pressure (Bi-PAP) and/or cough assist. Decline in physical factors like presence of dysphagia, drooling, general pain, and decrease in ALSFRS-R total score or forced vital capacity (FVC) significantly correlated with negative (depressed or anxious) mood (p < 0.05). Use of antidepressants or pain medications had no association with ALS patient mood (p > 0.05), but were significantly associated with increased survival (p < 0.05). Positive patient mood, Bi-PAP, cough assist, percutaneous endoscopic gastrostomy (PEG), and accompaniment to clinic visits associated with increased survival duration (p < 0.001). Of the 47 most prevalent pharmaceutical and supplement categories, 17 associated with significant survival duration increases ranging +4.5 to +16.5 months. Tricyclic antidepressants, non-opioids, muscle relaxants, and vitamin E had the highest associative increases in survival duration (p < 0.05). Random forests, which examined complex interactions, identified the following pharmaceuticals and supplements as most predictive to survival duration: Vitamin A, multivitamin, PEG supplements, alternative herbs, antihistamines, muscle relaxants, stimulant laxatives, and antispastics. Statins, metformin, and thiazide diuretics had insignificant associations with decreased survival.

A Comprehensive Examination of Percutaneous Endoscopic Gastrostomy and Its Association with Amyotrophic Lateral Sclerosis Patient Outcomes.

There is literature discord regarding the impact of percutaneous endoscopic gastrostomy (PEG), or "feeding tube", on amyotrophic lateral sclerosis (ALS) outcomes. We assess one of the largest retrospective ALS cohorts to date (278 PEG users, 679 non-users). Kruskal-Wallis and Kaplan-Meier analysis compared cohort medians and survival duration trends. A meta-analysis determined the aggregate associative effect of PEG on survival duration by combining primary results with 7 published studies. Primary results (p < 0.001) and meta-analysis (p < 0.05) showed PEG usage is associated with an overall significant increase in ALS survival duration, regardless of onset type. Percent predicted forced vital capacity (FVC %predict) ≥50 at PEG insertion significantly increases survival duration (p < 0.001); FVC %predict ≥60 has the largest associative benefit (+6.7 months, p < 0.05). Time elapsed from ALS onset until PEG placement is not predictive (p > 0.05). ALSFRS-R survey assessment illustrates PEG usage does not slow functional ALS pathology (p > 0.05), but does stabilize weight and/or body mass index (BMI) (p < 0.05). Observed clinical impression of mood (CIM), was not impacted by PEG usage (p > 0.05). Overall results support PEG as a palliative intervention for ALS patients with ≥50 FVC %predict at PEG insertion.

A Metadata Analysis of Oxidative Stress Etiology in Preclinical Amyotrophic Lateral Sclerosis: Benefits of Antioxidant Therapy.

Oxidative stress, induced by an imbalance of free radicals, incites neurodegeneration in Amyotrophic Lateral Sclerosis (ALS). In fact, a mutation in antioxidant enzyme superoxide dismutase 1 (SOD1) accounts for 20% of familial ALS cases. However, the variance among individual studies examining ALS oxidative stress clouds corresponding conclusions. Therefore, we construct a comprehensive, temporal view of oxidative stress and corresponding antioxidant therapy in preclinical ALS by mining published quantitative experimental data and performing metadata analysis of 41 studies. In vitro aggregate analysis of innate oxidative stress inducers, glutamate and hydrogen peroxide, revealed 70-90% of cell death coincides to inducer exposure equivalent to 30-50% peak concentration (p < 0.05). A correlative plateau in cell death suggests oxidative stress impact is greatest in early-stage neurodegeneration. In vivo SOD1-G93A transgenic ALS mouse aggregate analysis of heat shock proteins (HSPs) revealed HSP levels are 30% lower in muscle than spine (p < 0.1). Overall spine HSP levels, including HSP70, are mildly upregulated in SOD1-G93A mice compared to wild type, but not significantly (p > 0.05). Thus, innate HSP compensatory responses to oxidative stress are simply insufficient, a result supportive of homeostatic system instability as central to ALS etiology. In vivo aggregate analysis of antioxidant therapy finds SOD1-G93A ALS mouse survival duration significantly increases by 11.2% (p << 0.001) but insignificantly decreases onset age by 2%. Thus, the aggregate antioxidant treatment effect on survival in preclinical ALS is not sufficient to overcome clinical heterogeneity, which explains the literature disparity between preclinical and clinical antioxidant survival benefit. The aggregate effect sizes on preclinical ALS survival and onset illustrate that present antioxidants, alone, are not sufficient to halt ALS, which underscores its multi-factorial nature. Nonetheless, antioxidant-treated SOD1-G93A ALS mice have significantly increased motor performance (p < 0.05) measured via rotarod. With a colossal aggregate preclinical effect size average of 59.6%, antioxidants are promising for increasing function/quality of life in clinical ALS patients, a premise worth exploration via low-risk nutritional supplements. Finally, more direct, quantitative measures of oxidative stress, antioxidant levels and bioavailability are key to developing powerful antioxidant therapeutics that can assert measurable impacts on redox homeostasis in the brain and spinal cord.