Nerve excitability measured with the TROND protocol in amyotrophic lateral sclerosis: a systematic review and meta-analysis.

This meta-analysis assessed the 30+ nerve excitability indices generated by the TROND protocol to identify potential biomarkers for amyotrophic lateral sclerosis (ALS). A comprehensive search was conducted in multiple databases to identify human studies that tested median motor axons. Forest plot analyses were performed using a random-effects model to determine the pooled effect (Z-score), heterogeneity (I2), and Cohen's d for potential biomarker identification. Out of 2,866 studies, 23 studies met the inclusion criteria, incorporating data from 719 controls and 942 patients with ALS. Seven indices emerged as potential biomarkers: depolarizing threshold electrotonus (TEd) 90-100 ms, strength-duration time constant (SDTC), superexcitability, TEd 40-60 ms, resting I/V slope, 50% depolarizing I/V, and subexcitability (ranked by the magnitude of the difference between patients and controls from largest to smallest). In a sensitivity analysis focusing on patients with larger compound muscle action potentials (CMAPs), only four indices were potential biomarkers: TEd 10-20 ms, TEd 90-100 ms, superexcitability, and SDTC. Among the extensive range of 30+ excitability indices generated by the TROND protocol, we have identified seven indices that effectively differentiate patients with ALS from healthy controls. Furthermore, a smaller subset of four indices shows promise as potential biomarkers when the CMAP remains relatively large. However, most studies were considered to be at moderate risk of bias due to case-control designs and absence of sensitivity and specificity calculations, underscoring the need for more prospective diagnostic test-accuracy studies with appropriate disease controls.NEW & NOTEWORTHY This meta-analysis uncovers seven potential axonal excitability biomarkers for lower motor neuron pathology in ALS, shedding light on ion channel dysfunction. The identified dysfunction aligns with the primary pathology-protein homeostasis disruption. These biomarkers could fill a gap to detect presymptomatic spread of the disease in the spinal cord and monitor treatments targeting protein homeostasis and limiting spread, toward enhancing patient care.

Physical Activity in Pregnancy Is Associated with Increased Flow-mediated Dilation.

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) or inactive (<150 min·wk) 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 MVPA, n = 32) engaged in 266.7 ± 99.3 min·wk MVPA, whereas inactive pregnant women (<150 min·wk MVPA, n = 38) engaged in 76.1 ± 42.5 min·wk 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.