To determine the features, causes, risk factors and outcome of acquired neuromuscular paralysis in critically ill patients. Retrospective review of all confirmed cases of acquired polyneuropathy and myopathy examined by our Neurology service in the Intensive Care Unit (ICU), at King Fahad National Guard Hospital, Riyadh, Kingdom of Saudi Arabia over a period of 5 years. All patients had comprehensive electrophysiological studies and one third had muscle and nerve biopsies. Thirty cases were included, 8 cases of polyneuropathy, 15 cases of myopathy and 7 cases of mixed neuropathy and myopathy. Absent deep tendon reflexes and absent sensory potential on nerve conduction studies were significantly suggestive of neuropathy. The level of creatine phosphokinase was not of great diagnostic value. Most polyneuropathy and myopathy cases had passed through a stormy ICU course with sepsis and multiorgan failure. The use of high doses of steroids was more associated with myopathy. Seven patients died in ICU, the others were discharged to the wards after a mean ventilation period of 40 days. One patient became chronic ventilator dependent. From this series and available literature, it seems that symptomatic myopathy is more frequent than polyneuropathy and some risk factors are common for both (sepsis and multiorgan failure) while the use of steroids is more associated with ICU myopathy. Treating sepsis and stopping corticosteroids results in the improvement of most of the cases.

Sirs: We read the article by Dr. Mohammadi and colleagues dealing with parameters that correlate with the severity of early stage critical illness polyneuropathy (CIP) with great interest [5]. The authors performed nerve conduction studies and electromyography in 20 consecutive patients with severe sepsis or septic shock from day 1 to day 14 after onset of sepsis. The essential finding was a reduction in the amplitude in the compound action potential of the median and/or peroneal nerve which was reduced in 75% of patients already at day 1, and in 88% of patients at day 7. Remarkably, the reduction in the amplitude of the compound motor action potential correlated with the serum concentrations of endotoxin and interleukin-2-receptors. We have recently shown a direct interaction of endotoxin with heterologously expressed voltage-gated skeletal muscle sodium channels in vitro [4]. Endotoxin reduced sodium channel availability at depolarized membrane potentials during acute application of high concentrations (C50 ng/ml) and after prolonged exposure (1 h) to a clinically relevant concentration (300 pg/ml). After 24 h of in vitro incubation with 300 pg/ml endotoxin, the reduction of sodium channel availability was irreversible and independent from the membrane potential. In septic patients, CIP and critical illness myopathy (CIM) often coexist [2, 3], and the incidence in patients with sepsis or septic shock varies between 70% and 80% [1]. Taken together, the results of the clinical study performed by Dr. Mohammadi and colleagues, and our in vitro study on the interaction of endotoxin with voltage-gated sodium channels suggest that endotoxin might be a crucial factor in the development of neuromuscular sequelae of sepsis already at a very early stage after onset of sepsis. This highlights the need for development of anti-endotoxin strategies to prevent CIM and CIP.

Objective To investigate the peripheral nerve and muscle function electrophysiologically in patients with persistent neuromuscular symptoms following Coronavirus disease 2019 (COVID-19). Methods Twenty consecutive patients from a Long-term COVID-19 Clinic referred to electrophysiological examination with the suspicion of mono- or polyneuropathy were included. Examinations were performed from 77 to 255 (median: 216) days after acute COVID-19. None of the patients had received treatment at the intensive care unit. Of these, 10 patients were not even hospitalized. Conventional nerve conduction studies (NCS) and quantitative electromyography (qEMG) findings from three muscles were compared with 20 age- and sex-matched healthy controls. Results qEMG showed myopathic changes in one or more muscles in 11 patients (55%). Motor unit potential duration was shorter in patients compared to healthy controls in biceps brachii (10.02±0.28 vs 11.75 ± 0.21), vastus medialis (10.86±0.37 vs 12.52±0.19) and anterior tibial (11.76±0.31 vs 13.26±0.21) muscles. All patients with myopathic qEMG reported about physical fatigue and 8 patients about myalgia while 3 patients without myopathic changes complained about physical fatigue. Conclusions Long-term COVID-19 does not cause large fibre neuropathy, but myopathic changes are seen. Significance Myopathy may be an important cause of physical fatigue in long-term COVID-19 even in non-hospitalized patients.

Background Diagnosis of intensive care unit acquired weakness (ICUAW) is challenging. Pathogenesis of underlying critical illness polyneuromyopathy (CIPNM) remains incompletely understood. This exploratory study investigated whether longitudinal neuromuscular ultrasound examinations and cytokine analyses in correlation to classical clinical and electrophysiological assessment contribute to the understanding of CIPNM. Methods Intensive care unit patients were examined every 7 days until discharge from hospital. Clinical status, nerve conduction studies, electromyography as well as ultrasound of peripheral nerves and tibial anterior muscle were performed. Cytokine levels were analyzed by a bead-based multiplex assay system. Results Of 248 screened patients, 35 patients were included at median of 6 days (IQR: 8) after admission to intensive care unit. Axonal damage was the main feature of CIPNM. At the peak of CIPNM (7 days after inclusion), nerve ultrasound showed cross-sectional area increase of tibial nerve as a sign of inflammatory edema as well as hypoechoic nerves as a possible sign of inflammation. Cytokine analyses showed signs of monocyte and macrophage activation at this stage. Fourteen days after inclusion, cytokines indicated systemic immune response as well as profiles associated to neovascularization and regeneration. Conclusions Exploratory neuromuscular ultrasound and cytokine analyses showed signs of inflammation like macrophage and monocyte activation at the peak of CIPNM followed by a systemic immune response parallel to axonal damage. This underlines the role of both axonal damage and inflammation in pathogenesis of CIPNM.

Peripheral nerve changes in critically ill patients are common, sepsis being the most important risk factor. The aim of our study is to investigate interval neurophysiological changes in non septic mechanically ventilated critically ill patients, a group who has not been the focus of previous studies. Consecutive non septic mechanically ventilated critically ill patients were included. Baseline nerve conduction studies (NCS) were done within 3 days of intensive care unit admission, and 48 hours after the initiation of mechanical ventilation, and were followed up 7-8 days later. Sural and ulnar sensory, and median and peroneal motor nerves were tested. Nine patients were studied, five (56%) showed significant changes in their NCS compared to baseline. The peroneal and sural nerve amplitudes significantly dropped in all of the five affected patients, with drop of those of the median motor nerves in two, and ulnar sensory nerves in three patients. In conclusion, interval changes in peripheral nerves can exist in critically ill mechanically ventilated non septic patients. The pattern is similar to critically ill patients with sepsis. Theories of possible pathophysiology of critical illness neuropathy should not merely depend on the presence of sepsis as a trigger and other mechanisms should be investigated.