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.

Background     Intraspinal microstimulation (ISMS) is a novel electrical stimulation technique that has demonstrated mobility restoration in animals with spinal cord injury (SCI). This project investigated: 1) the capacity of ISMS to restore functional walking in rats with SCI through 4 weeks of stimulation, and 2) the degree of walking deficit caused by ISMS surgery. Methods     Thirteen Sprague Dawley rats were divided into three groups: 1) rats with hemi-section SCI (hSCI) and no implants (control group), 2) rats with hSCI and passive ISMS implants (ISMS sham group), and 3) rats with hSCI and implants with active electrical stimulation (ISMS group). All groups were trained to walk on a horizontal ladder and their performance was quantified pre- and post-surgery. Results     We hypothesized that the rats with active ISMS implants would demonstrate the greatest improvement in functional walking compared to both control groups, and that the ISMS sham group would underperform the most. The preoperative functional walking scores of control, sham and ISMS rats were 5.7±0.2, 5.5±0.3 and 5.7±0.1, respectively (7-point scale; mean ± standard error). The post-surgery scores were 3.2±0.9, 2.6±0.6 and 3.3±0.8 for control, sham, and ISMS rats, respectively. Conclusions     As the difference between the post-surgery functional walking scores of ISMS and control rats was not statistically significant, this may indicate that four weeks of ISMS stimulation is not enough to cause rehabilitative effects. Additionally, the ISMS sham group demonstrated impaired functional walking compared to the hSCI control group as predicted. Future studies will employ a larger sample size to fully elucidate this trend and utilize thinner microwires to mitigate cellular damage.