Objective: To determine which nerve excitability outcome measures are potential biomarkers for ALS via systematic review and meta-analysis. Methods: Potential studies were identified from the following databases: MEDLINE, PubMed Central, CINAHL Plus, EMBASE, HealthSTAR, Scopus, and Web of Science up to March 2020. Only studies performed in human participants and assessing median motor axons were included. Forest Plot analyses using a random-effects model to determine pooled effect (Z-score), heterogeneity (I2) and Cohen's d were used to identify potential biomarkers. Results: From 2866 studies, 26 (patients=942, controls=719) were used in the systematic review and 23 in the meta-analysis. Seven nerve excitability indices met the three criteria for: significant Z-score, heterogeneity I2<40% and Cohen's d >0.2 (in descending rank order): TEd 90-100 ms, strength-duration time constant (SDTC), superexcitability, TEd 40-60 ms, resting I/V slope, 50% depolarizing, and subexcitability. A sensitivity analysis restricted to patients with *early* ALS indicated that four indices are potential early biomarkers of ALS (Z ranging from 2.99 to 2.16, in descending rank order): TEd 10-20 ms, TEd 90-100 ms, superexcitability, and SDTC. Conclusion: Seven excitability indices differentiate ALS patients from healthy controls, four of which may serve as early biomarkers for ALS. The candidate biomarkers may be used to monitor disease progression, predict survivability, and measure treatment response in clinical trials. High quality diagnostic test accuracy studies are warranted to firmly establish the utility of these indices in individuals suspected of an ALS diagnosis.

Purpose To determine the role of moderate-to-vigorous physical activity (MVPA) and sedentary behavior in flow-mediated dilation (FMD) and glucose metabolism during late pregnancy. Methods Seventy normotensive, euglycemic pregnant women (31.6 ± 2.9 yr) in their third trimester (28–39 wk) were recruited. After a fasted blood sample; FMD was measured (brachial artery Doppler ultrasonography, normalized for the shear stimulus [area under the curve]). Anterograde and retrograde shear rate were estimated. Physical activity (MVPA) and sedentary behavior were assessed via accelerometry for seven consecutive days (Actigraph wGT3X-BT). We categorized the women as active (>150 min·wk−1) or inactive (<150 min·wk−1) according to their accelerometry data. Data were corrected for age and gestational age. Results On average, women were sedentary 67.1% ± 8.2% of their waking hours. Active pregnant women (>150 min·wk−1 MVPA, n = 32) engaged in 266.7 ± 99.3 min·wk−1 MVPA, whereas inactive pregnant women (<150 min·wk−1 MVPA, n = 38) engaged in 76.1 ± 42.5 min·wk−1 MVPA. The FMD response (normalized to the magnitude of shear stress stimulus) was greater in active compared with inactive pregnant women (6.5 ± 4.4 a.u. vs 3.9 ± 3.5 a.u.; F = 4.619; P = 0.005). The MVPA in active pregnant women was inversely correlated with insulin concentrations (r = −0.556; P = 0.03). In inactive pregnant women, higher amounts of sedentary behavior were associated with lower amounts of retrograde shear rate (r = 0.504; P = 0.02), retrograde blood flow (r = 0.499; P = 0.02), and retrograde velocity (r = 0.508; P = 0.02) during baseline, but not correlated with the FMD response. Conclusions Engaging in MVPA during pregnancy is associated with improved FMD and a lower insulin concentration. Sedentary behavior was not associated with FMD responses.

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