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Short, intermittent episodes of disuse muscle atrophy (DMA) may have negative impact on age related muscle loss. There is evidence of variability in rate of DMA between muscles and over the duration of immobilization. As yet, this is poorly characterized. This review aims to establish and compare the time-course of DMA in immobilized human lower limb muscles in both healthy and critically ill individuals, exploring evidence for an acute phase of DMA and differential rates of atrophy between and muscle groups. MEDLINE, Embase, CINHAL and CENTRAL databases were searched from inception to April 2021 for any study of human lower limb immobilization reporting muscle volume, cross-sectional area (CSA), architecture or lean leg mass over multiple post-immobilization timepoints. Risk of bias was assessed using ROBINS-I. Where possible meta-analysis was performed using a DerSimonian and Laird random effects model with effect sizes reported as mean differences (MD) with 95% confidence intervals (95% CI) at various time-points and a narrative review when meta-analysis was not possible. Twenty-nine studies were included, 12 in healthy volunteers (total n = 140), 18 in patients on an Intensive Therapy Unit (ITU) (total n = 516) and 3 in patients with ankle fracture (total n = 39). The majority of included studies are at moderate risk of bias. Rate of quadriceps atrophy over the first 14 days was significantly greater in the ITU patients (MD -1.01 95% CI -1.32, -0.69), than healthy cohorts (MD -0.12 95% CI -0.49, 0.24) (P < 0.001). Rates of atrophy appeared to vary between muscle groups (greatest in triceps surae (-11.2% day 28), followed by quadriceps (-9.2% day 28), then hamstrings (-6.5% day 28), then foot dorsiflexors (-3.2% day 28)). Rates of atrophy appear to decrease over time in healthy quadriceps (-6.5% day 14 vs. -9.1% day 28) and triceps surae (-7.8% day 14 vs. -11.2% day 28), and ITU quadriceps (-13.2% day 7 vs. -28.2% day 14). There appears to be variability in the rate of DMA between muscle groups, and more rapid atrophy during the earliest period of immobilization, indicating different mechanisms being dominant at different timepoints. Rates of atrophy are greater amongst critically unwell patients. Overall evidence is limited, and existing data has wide variability in the measures reported. Further work is required to fully characterize the time course of DMA in both health and disease., (© 2022 The Authors. Journal of Cachexia, Sarcopenia and Muscle published by John Wiley & Sons Ltd on behalf of Society on Sarcopenia, Cachexia and Wasting Disorders.)

Disuse atrophy, caused by situations of unloading such as limb immobilisation, causes a rapid yet diverging reduction in skeletal muscle function when compared to muscle mass. While mechanistic insight into the loss of mass is well studied, deterioration of muscle function with a focus towards the neural input to muscle remains underexplored. This study aimed to determine the role of motor unit adaptation in disuse-induced neuromuscular deficits. Ten young, healthy male volunteers underwent 15 days of unilateral lower limb immobilisation with intramuscular electromyography (iEMG) bilaterally recorded from the vastus lateralis (VL) during knee extensor contractions normalised to maximal voluntary contraction (MVC), pre and post disuse. Muscle cross-sectional area was determined by ultrasound. Individual MUs were sampled and analysed for changes in motor unit (MU) discharge and MU potential (MUP) characteristics. VL CSA was reduced by approximately 15% which was exceeded by a two-fold decrease of 31% in muscle strength in the immobilised limb, with no change in either parameter in the non-immobilised limb. Parameters of MUP size were reduced by 11% to 24% with immobilisation, while neuromuscular junction (NMJ) transmission instability remained unchanged, and MU firing rate decreased by 8% to 11% at several contraction levels. All adaptations were observed in the immobilised limb only. These findings highlight impaired neural input following immobilisation reflected by suppressed MU firing rate which may underpin the disproportionate reductions of strength relative to muscle size. KEY POINTS: Muscle mass and function decline rapidly in situations of disuse such as bed rest and limb immobilisation. The reduction in muscle function commonly exceeds that of muscle mass, which may be associated with the dysregulation of neural input to muscle. We have used intramuscular electromyography to sample individual motor unit and near fibre potentials from the vastus lateralis following 15 days of unilateral limb immobilisation. Following disuse, the disproportionate loss of muscle strength when compared to size coincided with suppressed motor unit firing rate. These motor unit adaptations were observed at multiple contraction levels and in the immobilised limb only. Our findings demonstrate neural dysregulation as a key component of functional loss following muscle disuse in humans., (© 2022 The Authors. The Journal of Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society.)