Mitochondria are key structures providing most of the energy needed to maintain homeostasis. They are the main source of adenosine triphosphate (ATP), participate in glucose, lipid and amino acid metabolism, store calcium and are integral components in various intracellular signaling cascades. However, due to their crucial role in cellular integrity, mitochondrial damage and dysregulation in the context of critical illness can severely impair organ function, leading to energetic crisis and organ failure. Skeletal muscle tissue is rich in mitochondria and, therefore, particularly vulnerable to mitochondrial dysfunction. Intensive care unit-acquired weakness (ICUAW) and critical illness myopathy (CIM) are phenomena of generalized weakness and atrophying skeletal muscle wasting, including preferential myosin breakdown in critical illness, which has also been linked to mitochondrial failure. Hence, imbalanced mitochondrial dynamics, dysregulation of the respiratory chain complexes, alterations in gene expression, disturbed signal transduction as well as impaired nutrient utilization have been proposed as underlying mechanisms. This narrative review aims to highlight the current known molecular mechanisms immanent in mitochondrial dysfunction of patients suffering from ICUAW and CIM, as well as to discuss possible implications for muscle phenotype, function and therapeutic approaches.

Multiple Sclerosis (MS) is a heterogeneous immune mediated disease of the central nervous system (CNS). Fatigue is one of the most common and disabling symptom of MS. It interferes with daily activities on the level of cognition and motor endurance. Motor fatigue can either result from lesions in cortical networks or motor pathways (“primary fatigue”) or it may be a consequence of detraining with subsequent adaptions of muscle and autonomic function. Programmed exercise interventions are used frequently to increase physical fitness in MS-patients. Studies investigating the effects of training on aerobic capacity, objective endurance and perceived fatigability have yielded heterogenous results, most likely due to the heterogeneity of interventions and patients, but probably also due to the non-uniform pathophysiology of fatigability among MS-patients. The aim of this review is to summarize the current knowledge on the pathophysiology of motor fatigability with special reference to the basic exercise physiology that underlies our understanding of both pathogenesis and treatment interventions.

Qualitative assessment by the Heckmatt scale (HS) and quantitative greyscale analysis of muscle echogenicity were compared for their value in detecting intensive care unit-acquired weakness (ICU-AW). We performed muscle ultrasound (MUS) of eight skeletal muscles on day 3 and day 10 after ICU admission. We calculated the global mean greyscale score (MGS), the global mean z-score (MZS) and the global mean Heckmatt score (MHS). Longitudinal outcome was defined by the modified Rankin scale (mRS) and Barthel index (BI) after 100 days. In total, 652 ultrasound pictures from 38 critically ill patients (18 with and 20 without ICU-AW) and 10 controls were analyzed. Patients with ICU-AW had a higher MHS on day 10 compared to patients without ICU-AW (2.6 (0.4) vs. 2.2 (0.4), p = 0.006). The MHS was superior to ROC analysis (cut-off: 2.2, AUC: 0.79, p = 0.003, sensitivity 86%, specificity 60%) in detecting ICU-AW compared to MGS and MZS on day 10. The MHS correlated with the Medical Research Council sum score (MRC-SS) (r = −0.45, p = 0.004), the mRS (r = 0.45; p = 0.007) and BI (r = −0.38, p = 0.04) on day 100. Qualitative MUS analysis seems superior to quantitative greyscale analysis of muscle echogenicity for the detection of ICU-AW.

Rationale: Antral peristalsis is responsible for gastric emptying. Its failure is called gastroparesis and often caused by dysfunction of enteric neurons and interstitial cells of Cajal (ICC). Current treatment options, including gastric electrical stimulation, are non-satisfying and may improve symptoms but commonly fail to restore gastric emptying. Herein, we explore direct optogenetic stimulation of smooth muscle cells (SMC) via the light-gated non-selective cation channel Channelrhodopsin2 (ChR2) to control gastric motor function.