Clinical Significance of Asymmetry on Electrodiagnostic Testing to detect Polyneuromyopathy in Critically Ill Patients: a cross-sectional study

Clinical Significance of Asymmetry on Electrodiagnostic Testing to detect Polyneuromyopathy in Critically Ill Patients: a cross-sectional study | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article Clinical Significance of Asymmetry on Electrodiagnostic Testing to detect Polyneuromyopathy in Critically Ill Patients: a cross-sectional study José Roberto de Deus Macedo, Paulo Eugênio Silva, Marilia Mendes Rodrigues, and 4 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6619019/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 18 You are reading this latest preprint version Abstract Background: In search of simplified nerve conduction studies as screening electrophysiological tests in Intensive Care Unit (ICU), previous studies have suggested that unilateral electrophysiological evaluations may be sufficient for screening probable critical illness polyneuro and/or myopathy (CIP/CIM) in ICU - also called as neuromuscular electrophysiological disorder (NED) - since quantitative statistical analyses did not detect significant bilateral differences, at first reinforcing its symmetrical manifestation as established. This study aimed to investigate the presence of asymmetry in the onset of NED and the relevance of bilateral electrophysiological assessments for correct screening to avoid diagnostic and analysis errors. We also investigated possible effects of laterality and focal lesions of the central nervous system on NED. Methods : From Abril to October 2024, a cross-sectional observational study of critically ill patients admitted in ICU was conducted. All participants underwent bilateral nerve conduction study for the motor peroneal nerve to investigate asymmetry. Different from previous studies, bilateral Compound Muscle Action Potential (CMAP) records were analyzed based on the electrodiagnostic criterion for asymmetry. Results: 41 patients were enrolled, in which 82 assessments were carried out. NED was identified in 34 (83%) participants. Based on electrodiagnostic criterion, asymmetries were observed in 12 (29%) participants, with diagnostic divergence in 5 (12%), in which NED could be overlooked if the evaluation were unilateral. Patients with NED had a two-fold odds ratio of asymmetry between bilateral electrodiagnostic assessments compared to patients without NED. We also identified a possible match between brain anatomical landmarks and the worst CMAP on the contralateral side, with an attributable risk of 17% in patients with NED. Conclusion: This study suggests that electrodiagnostic screening tests for neuromuscular electrophysiological disorders in critically illness participants in ICU should be performed bilaterally to avoid diagnostic error and analysis bias, due to the clinical relevance of asymmetry in the development of this dysfunction. The impact of cerebral laterality and focal brain lesions on electrodiagnostic asymmetry in the early phase of NED needs to be further studied. Biological sciences/Neuroscience Health sciences/Diseases Health sciences/Medical research Health sciences/Neurology Bilateral Evaluation Asymmetry Compound Muscle Action Potential Neuromuscular Electrophysiological Disorders Clinical Diagnosis Critical Illness Polyneuropathy Critically Ill Patients Figures Figure 1 Figure 2 Figure 3 Figure 4 BACKGROUND Critical Illness Polyneuropathy (CIP) is recognized as the most prevalent peripheral polyneuropathy in the Intensive Care Unit (ICU) 1–3 . It manifests as a distal sensory-motor axonopathy symmetrically impacts the limbs and respiratory muscles 2 . In conjunction with Critical Illness Myopathy (CIM), which often occurs concurrently 2,4,5 , these conditions are identified as principal contributors to intensive care unit-acquired weakness (ICUAW) 6,7 . In turn, this syndrome is described as the main physical manifestation of Post-Intensive Care Syndrome (PICS) 8,9 . The incidence of ICUAW varies between 40% and 57% 10–12 , potentially leading to long-term sequelae and correlating with increased mortality rates even following hospital discharge 2,6 . Evidence of clinical and/or neurophysiological axonopathy can persist for up to five years post-discharge 13 , with extreme cases resulting in quadriplegia 14 . Emerging evidence suggests that implementing early rehabilitation within the ICU setting can help maintain physical functionality and potentially enhance outcomes for those suffering from ICUAW 15,16 . However, the successful application of early rehabilitation strategies hinges critically upon early diagnostic capabilities. Nerve conduction study (NCS) and needle-electromyography (nEMG) are tools used to differentiate CIP and CIM, as well as from deconditioning, characterized by muscle weakness in the absence of electrophysiological alterations - all of them with different prognoses 17,18 . Nevertheless, nEMG cannot confirm CIM in unconscious patients - under sedation and/or in coma. Moreover, both NCS and nEMG necessitate considerable time, costly equipment, and specialized expertise 2,18 . To address these challenges, simplified screening tests have been proposed for bedside analysis within the ICU 1,19,20 . The nerve conduction study for the motor peroneal nerve is particularly notable for its high sensitivity in screening for probable CIP/CIM 1 - hereafter referred to as neuromuscular electrophysiological disorder (NED) 20 . Studies have reported an absence of statistically significant differences in electrophysiological findings between the right and left sides of the body, which reinforces the concept of NED’s symmetrical manifestation. Consequently, they recommend that screening tests be conducted unilaterally to optimize the cost-benefit ratio 17,21 , a practice already adopted in some studies 1,20 . Nevertheless, since the mid-19th century when Paul Broca and Carl Wernicke 22 introduced the concept of cerebral lateralization, numerous evidence have accrued demonstrating that the nervous system exhibits substantial functional asymmetry. Despite disuse-induced immobility caused by coma or sedation affecting both sides of the body equally, it is conceivable that laterality and unilateral central nervous system lesions (e.g., stroke, trauma) could precipitate an initially asymmetric electrophysiological expression of NED, potentially driven by synergistic interactions among distinct injury mechanisms. The hypothesis was that NED, though established as a symmetrical disease, may initially manifest asymmetrically in critically ill patients and this possibility should not be neglected, due to the risk of analysis errors. This study aimed to investigate the presence of asymmetry in NED development and the relevance of conducting bilateral electrophysiological assessments for its diagnostic screening in critically ill patients in ICU. Moreover, we intended to evaluate the impact of laterality and brain focal lesion on asymmetry. METHODS Study design This research employed a cross-sectional observational study design focusing on critically ill patients admitted to the ICU. It was conducted and reported following the STROBE statement for observational studies 23 . Setting The study was carried out in a general, surgical and trauma ICU of a tertiary public referral hospital in the Federal District, Brazil. Data collection occurred between April and October 2024. The study received ethical approval from the local ethics committee (HB/IGESDF, Brasília, Brazil, protocol 63620622.2.0000.8153) and adhered to the Declaration of Helsinki. As all participants were intubated and sedated at enrollment, written informed consent was obtained from the closest responsible family member for the patients. Participants The study included critically ill participants aged 18 years or older who were admitted to the ICU. All participants had to be sedated and mechanically ventilated for at least three days. Exclusion criteria included pre-existing neuromuscular diseases, detection of peripheral demyelinating neuropathy, use of neuromuscular blocking agents, brain death, pregnancy, a body mass index (BMI) greater than 35 kg/m², orthopedic deformities, or other lower limb conditions (such as edema, fractures, or amputations) that could preclude bilateral nerve conduction studies. Variables The primary outcome was to assess the amplitude difference in neuromuscular activation between both sides and detect the presence of asymmetry using electrophysiological criterion. Secondary outcomes involved evaluating whether unilateral anatomical landmarks in the central nervous system - such as ischemia, hemorrhage, or concussion - contributed to asymmetrical reductions in compound muscle action potential (CMAP) and the incidence of NED. Participants’ clinical characteristics (age, sex), comorbidities (diabetes, hypertension, chronic obstructive pulmonary disease, etc.), hospitalization diagnosis, severity score - Simplified Acute Physiology Score 3 (SAPS 3), Sequential Organ Failure Assessment score (SOFA), Ramsay Sedation Score, presence of sepsis and septic shock (defined according to Sepsis-3 criteria), and PaO 2 /FiO 2 ratio were collected and analyzed. Nerve Conduction Study of the Motor Peroneal Nerve (PENT) A purely electrophysiological diagnostic approach for NED was used, via PENT, which has a high sensitivity for detecting NED, ranging from 92% up to 100% 1,17,21,24 . All participants underwent bilateral PENT performed by a single experienced intensivist using a Neuro-MEP-Micro® electroneuromyograph. The low-pass filter was set at 3Hz and the high-pass filter was set at 10 kHz. Sensitivity and sweep were set at 3 mV and 2 ms, respectively. Stimulation was performed at two sites to record distal motor latencies, record amplitude, and calculate conduction velocity of each nerve. Amplitudes were measured from baseline to negative peak. For testing, surface recording electrodes (Ambu® Neuroline 715) were placed over the belly and tendon of the extensor digitorum brevis. The peroneal nerve was stimulated over the anterior region of the ankle slightly lateral to the tendon of the tibialis anterior muscle, 6 to 8 cm from the recording electrodes, and below the head of the fibula for recording motor conduction velocity. Incremental electrical stimulation of the peroneal nerve was applied until the best CMAP amplitudes were obtained, with motor conduction velocity and latency duly recorded. Diagnostic Criteria for NED CMAP results 80% below Katirj's normal standard (≥3 mV for age 20-50 years old; ≥2,5 mV for age 51-90 years old) were considered abnormal 25 . Axonopathy-related measures of motor conduction velocity were evaluated by Tan’s criteria (80% above lower limit normal, if CMAP 50% of normal) 26 . The expected pattern indicative of NED was axonopathy, characterized by reduction in CMPA amplitude with normal or mildly reduced nerve conduction velocity 2 . Diagnostic Criteria for Asymmetry We use the electrophysiological criterion for asymmetry which is the CMAP amplitude difference of more than 50% comparing side to side (i.e., a 50% [0,5x] drop from the higher side to the lower or a 100% [2x] increase from the lower side to the higher) 27 . To assess the bilateral symmetry of CMAPs, we calculated the right/left CMAP records ratio (r/l), and constructed a histogram to visualize the distribution of these ratios and better identify patterns of symmetry and asymmetry. Values in the range between 0.5 and 2 were considered “symmetry” (difference ≤50% between bilateral CMAP records). When the values were exactly the same, we had what we called perfect symmetry (r/l =1.0). Vertical lines were plotted to define a symmetry zone (0.5 ≤ ratio ≤ 2) around perfect symmetry (r/l = 1), where the bilateral CMAP amplitudes are considered symmetrical. Thus, “asymmetry” occurred when the ratios were outside this specified interval. Additionally, values outside this range indicate respectively a unfavorable CMAP asymmetry to the right (r/l 2) side. All the results were reviewed by an expert neurophysiologist. Study size Based on data inferences from our non-publisehd pilot study, a medium effect size (Cohen's d = 0.4) was hypothesized for the difference between groups. An a priori power analysis was conducted using GPower (version 3.1.9.7) for a chi-square goodness-of-fit test on contingency tables. With a significance level (α) of 0.05 and a desired power (1 – β) of 0.8, the analysis indicated a required sample size of 81 assessments. Statistical analysis Given the non-normality of most variables (by the D'Agostino-Pearson test), non-parametric statistical tests were employed. Quantitative results were presented as medians and interquartile ranges, while qualitative variables were described by absolute and relative frequencies of occurrence. To examine differences between quantitative variables was used the Mann-Whitney U test. The Wilcoxon signed-rank test was employed to compare paired quantitative variable data (right versus left sides). Fisher's exact test was used to compare proportions. Statistical differences were considered significant at p<0.05. RESULTS We enrolled forty-one participants leading to eighty-two assessments (bilateral assessments). Further details are available in the flow diagram (Figure 1). Sample characteristics are presented in Table 1. Table 1. Characterization of the critically ill patients with and without criteria for neuromuscular electrophysiological disorders diagnosis. Variables Sample Size (n=41) Non-NED (n=7) NED (n=34) Age (years) 44 (36-59) 37 (25 - 41) 48,50 (40 – 60.50) Sex - n (%) male 30 (73.17%) 5 (71.43%) 25 (73.53%) BMI (kg/m 2 ) 23 (21 - 28) 28 (22 - 30) 23 (20 - 27) SAPS 3 score, on admission 58 (49 – 66.50) 62 (49 - 67) 58 (49 - 68) SOFA score, on assessment 7 (6 - 9) 8 (6 - 9) 7 (6 - 8) Reason for ICU admission - n (%) Traumatic brain injury 14 (34.14%) 4 (57.14%) 10 (29.41%) Hemorrhagic stroke 5 (12.20%) 1 (14.29%) 4 (11.76%) Ischemic stroke 2 (4.87%) 0 (0%) 2 (5.88%) Subarachnoid hemorrhage 2 (4.87%) 0 (0%) 2 (5.88%) Abdominal trauma 2 (4.87%) 0 (0%) 2 (5.88%) Thoracic trauma 3 (7.31%) 1 (14.29%) 2 (5.88%) Heart surgery 2 (4.87%) 0 (0%) 2 (5.88%) Myocardial infarction 2 (4.87%) 0 (0%) 2 (5.88%) Cancer 3 (7.31%) 1 (14.29%) 2 (5.88%) Bradycardia 1 (2.44%) 0 (0%) 1 (2.94%) Others 5 (12.20%) 0 (0%) 5 (14.71%) Type 2 diabetes - n (%) 2 (4.87%) 0 (0%) 2 (5.88%) HIV - n (%) 1 (2.44%) 0 (0%) 1 (2.94%) Drug addiction - n (%) 2 (4.87%) 0 (0%) 2 (5.88%) Mechanical ventilation days, on assesssment 8 (5 – 12.50) 4 (3 - 9) 9 (6 - 13) ICU length of stay (days), on assesssment 6 (2 – 10.50) 3 (2 - 7) 7 (3 - 11) Hospital length of stay (days), on assesssment 9 (5 - 14) 6 (4 - 9) 11 (6 - 15) Sepsis - n (%) 41 (100%) 7 (100%) 34 (100%) Lung 35 (85.36%) 7 (100%) 28 (82.35%) Abdomen 3 (7.31%) 0 (0%) 3 (8.82%) CNS 2 (4.87%) 0 (0%) 2 (5.88%) Mediastinum 1 (2.44%) 0 (0%) 1 (2.4%) Septic Schock - n (%) 14 (34.14%) 4 (57.14%) 10 (29.41%) GCS - n (%), on admission 10 – 14 12 (29.27%) 1 (14.29%) 11 (32.35%) 6 – 9 29 (70.73%) 6 (85.71%) 23 (67.65%) RASS score, on assessment -5 (-5 - -4) -5 (-5 - -4) -5 (-5 - -4) Using norepinephrine - n (%) 14 (34.14%) 4 (57.14%) 10 (29.41%) dosage (mcg/kg/min) 0.13 (0.08 – 0.39) 0.1 (0.06 – 0.13) 0.15 (0.07 – 0.52) Lactate, dosage (mmol/L) 1.4 (1.15 – 1.65) 1.3 (1.2 – 1.4) 1.4 (1.1 – 1.72) P/F rate, on assessment 284 (234 - 338) 292 (210 - 332) 277 (235 - 344) Renal failure - n (%), on assessment 4 (9.76%) 0 (0%) 4 (11.76%) Legend : The table presents the personal and clinical characteristics of the total sample and the groups with and without clinical criteria for neuromuscular electrophysiological disorders. Qualitative variables are presented as absolute (n) and relative (%) frequencies, and quantitative variables are presented as medians and interquartile ranges (IQR), using non-parametric analysis. The Mann-Whitney U test and Fisher's exact test revealed no significant differences (p < 0.05) between NED and Non-NED groups. Items in bold indicate the subpopulation of neurological patients: n=23 (56%). Abbreviations: NED = neuromuscular electrophysiological disorders, Non NED = without neuromuscular electrophysiological disorders, BMI = body mass index, SAPS 3 = Simplified Acute Physiology Score 3, SOFA = Sequential Organ Failure Assessment, ICU = intensive care unit, HIV = human immunodeficiency virus, CNS = central nervous system, GCS = Glasgow Coma Scale, RASS = Richmond Agitation Sedation Scale, P/F = ratio between the partial pressure of arterial oxygen and the fraction of inspired oxygen. Critical Illness Polyneuromyopathy Out of the total participants, 34 (83%) individuals were diagnosed with NED. They were significantly older than those in the Non-NED group. The reason for ICU admission was almost evenly split between neurological and non-neurological conditions, with a slight predominance of neurological conditions, particularly among the Non-NED participants (Table 1). Electrophysiological Recordings and Bilateral Assessment The analysis of electrophysiological parameters (Figure 2) revealed a significant decrease in CMAP amplitude in the NED group compared to the Non-NED group; however, conduction velocity and latency remained similar between the groups, consistent with a typical axonopathy pattern. Regarding the quantitative statistical analysis of bilateral records, statistically significant inter-side differences were absent. Detailed analyses across groups showed a reduction in CMAP amplitude exceeding 50% in the NED group, with a slightly more pronounced reduction on the right side. Specifically, the median CMAP on the right side decreased from 3.8 mV to 1.35 mV in the NED group - a 64% reduction. On the left side, the median dropped from 3.1 mV in the Non-NED group to 1.35 mV, achieving a 56% reduction. Bilateral Asymmetries in Electrophysiological Recordings With regard to the CMAP symmetry ratio (r/l), as depicted in the histogram (Fig. 3), 29 (71%) participants fell within the symmetry zone, which included three participants with no recordable CMAP or "electrical silence". The histogram indicated that based on electrophysiological criterion, 12 (29%) participants - practically one-third of the sample - exhibited asymmetries in CMAP recordings from bilateral lower limb assessments. Among them, five (12%) had diagnostic divergences: one side indicated NED, while the contralateral side did not. Patients with NED had a two-fold odds ratio of asymmetry compared to the Non-NED group. The median of the symmetry ratio in the Non-NED group was very close to 1 (r/l = 1.05), whereas it was 0.79 in the NED group (Figure 2, bottom right corner). This suggests a tendency towards a more pronounced reduction in CMAP on the right side in the NED group - below the perfect symmetry line where r/l = 1. Matches between Anatomical Landmarks and Electrophysiological Recordings We explored potential correlations between cerebral anatomical landmarks due to hemispheric injury and CMAP reduction in contralateral muscles - under corticospinal influence (Figure 4). Among the eighteen neurological participants in the sample with anatomical landmarks from trauma or stroke, twelve were in the left cerebral hemisphere and six in the right. Corticospinal correspondence between focal hemispheric lesion and the side of the body with the most pronounced electrophysiological impairment was observed in 50% of cases (6:12) and 33% of cases (2:6), respectively (Figure 4). Splitting the matches by groups, we found the same proportions: 6 matches (50%) out of 12 observations in the NED group, compared to 2 matches (33%) out of 6 observations in the Non-NED group (Figure 4). This suggests a 17% attributable risk in the NED group for a match between the hemispheric anatomical landmark and more pronounced contralateral peripheral electrodiagnostic dysfunction - corresponding corticospinal side. From this 17% attributable risk, we derived an indicator called the number needed to match (NNM), calculated as 6. This implies that for every 6 participants with a brain anatomical landmark, one participant is expected to exhibit a match between the side of the focal brain injury and the worst peripheral electrodiagnostic record on the contralateral body side. DISCUSSION This study highlights the presence of clinically relevant electrophysiological asymmetry at the onset of NED among critically ill patients. Recognizing this asymmetry in diagnostic screenings is crucial, as neglecting it can lead to diagnostic errors and inaccurate research findings. Our results reinforce the high incidence of NED in critically ill patients with sepsis and multi-organ dysfunction syndrome; and underscore the potential influence of laterality and focal CNS lesions on NED progression. Symmetry vs Asymmetry Our findings initially align with previous research that did not identify statistically significant differences in bilateral CMAP records of peripheral nerves 17,21 . In neurophysiology, the assessment of neuromuscular electrical dysfunction via bilateral CMAP comparison is fundamentally determined by the identification of asymmetry, which is established on electrophysiological criteria instead of relying solely on statistical parameters 27 . Unlike the previous ones, this study used the electrophysiological criterion for asymmetry adopted by neurophysiology: difference in CMAP amplitude greater than 50% inter-sides 27 . It revealed a high occurrence of CMAP asymmetry, identified in 12 (29%) participants, with diagnostic divergence between sides in 5 (12%) cases - where one side was NED compatible and the other, normal. Supporting our observations, Latronico (2022) 24 similarly observed diagnostic divergence of 12%, advocating for contralateral nerve assessment only after a normal initial PENT. The clinical significance of our findings supports using clinical parameters alongside statistical analysis to evaluate effects 28 , strengthening the recommendation for bilateral electrodiagnostic evaluations in critical illness research, to avoid diagnostic errors and reduce analysis bias. Influence of laterality and focal CNS lesions Our findings also indicate an increased risk of spinal-cortical correspondence between focal CNS lesions and worsening CMAP recordings among NED participants. This is coupled with a slightly more pronounced reduction in neuromuscular electrical activity on the right side for those with NED compared to unaffected patients. The intricate interplay between the central nervous system (CNS) and peripheral system involves complex scientific challenges, not yet explored in the CIP/CIM scenario, particularly the potential for asymmetrical development of this condition. While not the primary etiological factor, laterality, driven by cerebral dominance, potentially predisposes one hemisphere to structural and metabolic fragilities, which could modulate disease progression and affect otherwise symmetrical peripheral nerve damage 22 . This aligns with existing research on asymmetries in neurodegenerative disorders 22 . Axonal transport, essential for the proper function of the nervous system, allows the CNS to exert significant control over the maintenance and functional integrity of peripheral nerves 29 . The CNS modulates peripheral axonal neuroregeneration through trophic signaling, mirroring the reciprocal influence of peripheral axonal stimuli on CNS neuroplasticity 30 . Schweickert et al. (2009) 31 correlated early motor rehabilitation in the ICU with reduced duration of delirium and more ventilator-free days, suggesting a negative interaction between ICU-induced delirium and ICUAW. Prospective studies in ICU indicate that both septic encephalopathy and CIP occur together in 70% of cases, septic encephalopathy appearing first, suggesting an association between both dysfunctions 32 . Recent evidence suggests that central nervous system involvement with failure of coordinated repetitive firing within the motor neurons can be a very early event, preceding electrical failure in axons and muscle fibers, strengthening CNS engagement with NED 33 . In PICS, the interplay of physical (ICUAW), cognitive (dementia), and mental (depression and delirium) impairments may underline the close relationship between brain dysfunctions and peripheral axonopathy 8 . Despite the scarcity of robust scientific evidence, all these distinct entities may provide clues into the interaction of the laterality and focal brain with the asymmetric progression of NED, possibly by disproportionately affecting contralateral descending pathways 34 . NED incidence Our study reported an 83% incidence of NED, significantly higher than the 47% reported in a systematic review of ICUAW 12 . This higher incidence can be justified by the sample, which included neurological patients with sepsis and multiple-organ dysfunctions 35 , with reports of incidences approaching 100% as severity and organ failures increase 5 . Berek et al. (1996) 36 and Latronico et al. (2022) 24 described a CIP frequency of 82% and 79% respectively among similar populations. Study limitations Some limitations should be addressed in our study. There was no diagnostic confirmation of ICUAW, since we worked with uncooperative participants - under sedation or coma 11 . Nevertheless, electrophysiological disorders are associated with deleterious outcomes in critically ill participants, even in the absence of weakness 18,37 . We applied only bilateral assessment of motor peroneal nerve by PENT, without sensory evaluation of the sural sensitive nerve to confirm CIP diagnosis 17,21 . Indeed, reduced CMAP is observed in both axonopathy (CIP) and myopathy (CIM). However, although reduced sensory nerve action potential (SNAP) confirms CIP, it does not exclude CIM and may be blunted or masked due to local oedema, low surface temperatures, or electromagnetic interference 1 . Motor changes precede sensory changes, so that normal SNAP does not rule out axonopathy at the onset of dysfunction 1,38 . Moreover, CIM and CIP are normally associated 1 and several researchers argue that the differentiation between them is not very relevant in ICU 1,17,39 . The limited setting and cross-sectional nature reduce generalizability to other contexts. Future perspectives Future multicenter studies with larger cohorts are needed to further document neuropathological asymmetry in NED progression and its clinical implications. Research should explore advanced neurophysiological tools 34 to track CNS dysfunction and assess peripheral axonopathies in critically ill patients, extending follow-up beyond hospital discharge. CONCLUSIONS Electrodiagnostic screening tests for neuromuscular electrophysiological disorders in critically illness patients in ICU should be performed bilaterally to avoid diagnostic error and analysis bias, due to the clinical relevance of asymmetry in its development. The impact of cerebral laterality and focal brain lesions on electrodiagnostic asymmetry in the onset of critical illness polyneuromyopathy needs to be further studied. Abbreviations NED Neuromuscular electrophysiological disorder Non-NED Without neuromuscular electrophysiological disorder CMAP Compound muscle action potential SNAP Sensory nerve action potential r/l Right/left CMAP ratio PENT Nerve conduction study for the motor peroneal nerve NCS Nerve conduction study EMG Needle-electromyography CIP Critical illness polyneuropathy CIM Critical illness myopathy CIP/CIM Critical illness polyneuro and/or myopathy ICUAW Intensive care unit-acquired weakness PICS Post-intensive care syndrome CNS Central nervous system ICU Intensive care unit SAPS 3 Simplified Acute Physiology Score 3 SOFA Sequential organ failure assessment BMI Body mass index GCS Glasgow Coma Scale RASS Richmond Agitation Sedation Scale MV Mechanical ventilation OR Odds ratio Declarations Acknowledgements This research was made possible by the generous support of the Fundação de Apoio à Pesquisa do Distrito Federal (Fapdf project # 00193-00002152/2023-95), the Ministério da Ciência, Tecnologia e Inovação (MCTI), the Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq). We also thank the Hospital de Base/IGESDF neurophysiologist and ICU team. Author contributions Concept and Design: JRDM and PES. Aquisition, analysis and interpretation of the data: all authors. Drafting the manuscript: JRDM, PES and EFM. Graphics: JRDM, PES and EFM. Critical revision of the manuscript for important intellectual content: all authors. Supervision: RNMF and EFM. All authors read and approved the final manuscript. Funding The contributions from Financiadora de Serviços e Projetos (Finep) allowed for the purchase of essential electromyography equipment, facilitating the successful completion of this study. Availability of data and materials The data sets used and analyzed during the current study are available from the corresponding author upon reasonable request. Ethics approval and consent to participate This study was conducted in accordance with the ethical principles outlined in the Declaration of Helsinki and was approved by the Institutional Review Board of HB/IGESDF, under protocol number 63620622.2.0000.8153. Written informed consent was obtained from the closest responsible family member for each included patients. Consent for publication Written informed consent for publication was obtained. Competing interests All authors declare no competing interests. REFERENCES Latronico, N. et al. Simplified electrophysiological evaluation of peripheral nerves in critically ill patients: The Italian multi-centre CRIMYNE study. Crit. Care 11 , R11 (2007). Latronico, N. & Bolton, C. F. Critical illness polyneuropathy and myopathy: A major cause of muscle weakness and paralysis. Lancet Neurol. 10 , 931–941 (2011). Bolton, C. F. Neuromuscular manifestations of critical illness. Muscle and Nerve 32 , 140–163 (2005). Latronico, N. Neuromuscular alterations in the critically ill patient: Critical illness myopathy, critical illness neuropathy, or both? Intensive Care Med. 29 , 1411–1413 (2003). Park, S.-H., Jeong, Y.-J. & Kim, N.-H. Critical illness neuromyopathy. Ann. Clin. Neurophysiol. 22 , 61–66 (2020). Vanhorebeek, I., Latronico, N. & Van den Berghe, G. ICU-acquired weakness. Intensive Care Med. 46 , 637–653 (2020). Hadda, V. et al. Trends of loss of peripheral muscle thickness on ultrasonography and its relationship with outcomes among patients with sepsis. J. Intensive Care 6 , 1–10 (2018). Inoue, S. et al. Post‐intensive care syndrome: its pathophysiology, prevention, and future directions. Acute Med. Surg. 6 , 233–246 (2019). Oshima, T. & Hatakeyama, J. Nutritional therapy for the prevention of post-intensive care syndrome. J. Intensive Care 12 , 1–8 (2024). Stevens, R. D. et al. Neuromuscular dysfunction acquired in critical illness: a systematic review. Intensive Care Med. 33 , 1876–1891 (2007). Fan, E. et al. An official american thoracic society clinical practice guideline: The diagnosis of intensive care unit-acquired weakness in adults. Am. J. Respir. Crit. Care Med. 190 , 1437–1446 (2014). Appleton, R. T. D., Kinsella, J. & Quasim, T. The incidence of intensive care unit-acquired weakness syndromes: A systematic review. J. Intensive Care Soc. 16 , 126–136 (2015). Van Aerde, N. et al. Five-year impact of ICU-acquired neuromuscular complications: a prospective, observational study. Intensive Care Med. 46 , 1184–1193 (2020). de Sèze, M. et al. Critical illness polyneuropathy. A 2-year follow-up study in 19 severe cases. Eur. Neurol. 43 , 61–69 (2000). Liu, M., Luo, J., Zhou, J. & Zhu, X. Intervention effect of neuromuscular electrical stimulation on ICU acquired weakness: A meta-analysis. Int. J. Nurs. Sci. 7 , 228–237 (2020). Silva, P. E. et al. Neuromuscular electrical stimulation in critically ill traumatic brain injury patients attenuates muscle atrophy, neurophysiological disorders, and weakness: A randomized controlled trial. J. Intensive Care 7 , 1–13 (2019). Kelmenson, D. A., Quan, D. & Moss, M. What is the diagnostic accuracy of single nerve conduction studies and muscle ultrasound to identify critical illness polyneuromyopathy: a prospective cohort study. Crit. CARE 22 , (2018). Hermans, G. et al. Predictive value for weakness and 1-year mortality of screening electrophysiology tests in the ICU. Intensive Care Med. 41 , 2138–2148 (2015). Silva, P. E. et al. Towards innovative electrodiagnosis tests to investigate neuromuscular excitability dysfunction in critically ill patients: an agreement study. Res. Biomed. Eng. (2023). Silva, P. E. et al. Neuromuscular electrophysiological disorders and muscle atrophy in mechanically-ventilated traumatic brain injury patients: New insights from a prospective observational study. J. Crit. Care 44 , 87–94 (2018). Moss, M. et al. Screening for critical illness polyneuromyopathy with single nerve conduction studies. Intensive Care Med. 40 , 683–690 (2014). Lubben, N., Ensink, E., Coetzee, G. A. & Labrie, V. The enigma and implications of brain hemispheric asymmetry in neurodegenerative diseases. Brain Commun. 3 , fcab211 (2021). Vandenbroucke, J. P. et al. Strengthening the Reporting of Observational Studies in Epidemiology (STROBE): explanation and elaboration. PLoS Med. 4 , e297 (2007). Latronico, N. et al. Validation of the peroneal nerve test to diagnose critical illness polyneuropathy and myopathy in the intensive care unit: The multicentre Italian CRIMYNE-2 diagnostic accuracy study. F1000Research 3 , (2022). Katirji, B. Electromyography in Clinical Practice: A Case Study Approach. 40, 244 (Mosby, 2007). Tan, F. C. EMG Secrets . 178 (Hanley & Belfus, 2002). Preston, D. C. & Shapiro, B. E. Electromyography and Neuromuscular Disorders . 466, 476 (Elsevier, 2005). Sharma, H. Statistical significance or clinical significance? A researcher’s dilemma for appropriate interpretation of research results. Saudi J. Anaesth. 15 , 431–434 (2021). Maday, S., Twelvetrees, A. E., Moughamian, A. J. & Holzbaur, E. L. F. Axonal transport: cargo-specific mechanisms of motility and regulation. Neuron 84 , 292–309 (2014). Nagappan, P. G., Chen, H. & Wang, D. Y. Neuroregeneration and plasticity: A review of the physiological mechanisms for achieving functional recovery postinjury. Mil. Med. Res. 7 , 1–16 (2020). Schweickert, W. D. et al. Early physical and occupational therapy in mechanically ventilated, critically ill patients: a randomised controlled trial. Lancet 373 , 1874–1882 (2009). Bolton, C. F., Young, G. B. & Zochodne, D. W. The neurological complications of sepsis. Ann. Neurol. 33 , 94–100 (1993). Latronico, N. & Friedrich, O. Electrophysiological investigations of peripheral nerves and muscles: a method for looking at cell dysfunction in the critically ill patients. Crit. CARE 23 , 33 (2019). Souron, R. et al. Relationship between intensive care unit-acquired weakness, fatigability and fatigue: What role for the central nervous system? J. Crit. Care 62 , 101–110 (2021). Witt, N. J. et al. Peripheral nerve function in sepsis and multiple organ failure. Chest 99 , 176–184 (1991). Berek, K. et al. Polyneuropathies in critically ill patients: a prospective evaluation. Intensive Care Med. 22 , 849–855 (1996). Kelmenson, D. A. et al. Electrophysiological abnormalities can differentiate pre-hospital discharge functional status in critically ill patients with normal strength. Intensive care medicine vol. 42 1504–1505 (2016). Kamble, N., Shukla, D. & Bhat, D. Peripheral Nerve Injuries: Electrophysiology for the Neurosurgeon. Neurol. India 67 , 1419–1422 (2019). Tankisi, H., de Carvalho, M. & Z’Graggen, W. J. Critical Illness Neuropathy. J. Clin. Neurophysiol. Off. Publ. Am. Electroencephalogr. Soc. 37 , 205–207 (2020). Additional Declarations No competing interests reported. Cite Share Download PDF Status: Under Review Version 1 posted Editorial decision: Revision requested 23 Feb, 2026 Reviews received at journal 22 Feb, 2026 Reviews received at journal 21 Feb, 2026 Reviews received at journal 18 Feb, 2026 Reviews received at journal 11 Feb, 2026 Reviews received at journal 05 Feb, 2026 Reviews received at journal 03 Feb, 2026 Reviewers agreed at journal 03 Feb, 2026 Reviewers agreed at journal 30 Jan, 2026 Reviewers agreed at journal 30 Jan, 2026 Reviewers agreed at journal 29 Jan, 2026 Reviewers agreed at journal 29 Jan, 2026 Reviewers agreed at journal 29 Jan, 2026 Reviewers invited by journal 29 Jan, 2026 Editor assigned by journal 11 Aug, 2025 Editor invited by journal 22 May, 2025 Submission checks completed at journal 21 May, 2025 First submitted to journal 08 May, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-6619019","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":583265990,"identity":"344caa1d-e7f3-4bd7-aa3b-91aea1655862","order_by":0,"name":"José Roberto de Deus Macedo","email":"","orcid":"","institution":"Health Sciences and Technologies PhD Program, Faculdade de Ciências e Tecnologias em Saúde (FCTS), Campus UnB Ceilândia, University of Brasilia, DF","correspondingAuthor":false,"prefix":"","firstName":"José","middleName":"Roberto de Deus","lastName":"Macedo","suffix":""},{"id":583265991,"identity":"b553d833-8fb5-4590-aa61-64bc0a944e10","order_by":1,"name":"Paulo Eugênio Silva","email":"","orcid":"","institution":"Department of Physical Medicine \u0026 Rehabilitation, Hospital de Base do Distrito Federal, Instituto de Gestão Estratégica de Saúde do Distrito Federal (IGESDF), DF","correspondingAuthor":false,"prefix":"","firstName":"Paulo","middleName":"Eugênio","lastName":"Silva","suffix":""},{"id":583265992,"identity":"150c65c6-0bf8-4505-8011-a3c2ce031363","order_by":2,"name":"Marilia Mendes Rodrigues","email":"","orcid":"","institution":"Department of Physical Medicine \u0026 Rehabilitation, Hospital de Base do Distrito Federal, Instituto de Gestão Estratégica de Saúde do Distrito Federal (IGESDF), DF","correspondingAuthor":false,"prefix":"","firstName":"Marilia","middleName":"Mendes","lastName":"Rodrigues","suffix":""},{"id":583265993,"identity":"349736bd-0e1c-49c5-a7b5-e54ba1bc1674","order_by":3,"name":"Ana Clara Wimmer Macedo","email":"","orcid":"","institution":"Centro Universitário do Planalto Central Aparecido dos Santos (Uniceplac) School of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Ana","middleName":"Clara Wimmer","lastName":"Macedo","suffix":""},{"id":583265994,"identity":"0e08aac1-d70b-4dd6-8a34-5458bafefb3e","order_by":4,"name":"Marta Rodrigues Carvalho","email":"","orcid":"","institution":"Neurophysiology Division, Hospital de Base do Distrito Federal, Instituto de Gestão Estratégica de Saúde do Distrito Federal","correspondingAuthor":false,"prefix":"","firstName":"Marta","middleName":"Rodrigues","lastName":"Carvalho","suffix":""},{"id":583265995,"identity":"90509648-5362-42f7-8f3a-b73741b9f2ff","order_by":5,"name":"Rubens Nelson Morato Fernandez","email":"","orcid":"","institution":"Neurophysiology Division, Hospital de Base do Distrito Federal, Instituto de Gestão Estratégica de Saúde do Distrito Federal","correspondingAuthor":false,"prefix":"","firstName":"Rubens","middleName":"Nelson Morato","lastName":"Fernandez","suffix":""},{"id":583265996,"identity":"9a9deb44-d48e-4342-b34c-9f3010b007e7","order_by":6,"name":"Emerson Fachin-Martins","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAvklEQVRIiWNgGAWjYDAC5gMgUoKBgb2BgZmB4QARWtgSgEQCUAvPAdK0gCxKIFILPxt34ufKHxZ58jPfmD0uYLiTT1CLZBvvZskzCRLFBrdzzI1nMDyzbCCkxeB+7wbJhgSJxA3SOWbSPAyHDQjaYn+Md/NPkJb5M88QqcWAjXcb2JaGGzxEapE4xrvNsiEN6LAzaWXSMwyeEdbCD/T+zQabusT57Ye3SRdU3CGsBd2dpGoYBaNgFIyCUYAVAAAtNDje4cHukwAAAABJRU5ErkJggg==","orcid":"","institution":"Health Sciences and Technologies PhD Program, Faculdade de Ciências e Tecnologias em Saúde (FCTS), Campus UnB Ceilândia, University of Brasilia, DF","correspondingAuthor":true,"prefix":"","firstName":"Emerson","middleName":"","lastName":"Fachin-Martins","suffix":""}],"badges":[],"createdAt":"2025-05-08 09:23:35","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6619019/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6619019/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":101633196,"identity":"a306a49e-4f7f-4e73-9ab2-79cc4652fd5f","added_by":"auto","created_at":"2026-02-02 05:58:18","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":100832,"visible":true,"origin":"","legend":"\u003cp\u003eFlowchart. Enrollment, eligibility and analysis.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eLegend:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAbbreviations: NED = neuromuscular electrophysiological disorder, Non-NED = without neuromuscular electrophysiological disorder, BMI = body mass index, MV = mechanical ventilation.\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-6619019/v1/48742fbe7a0f587ced518823.png"},{"id":101633198,"identity":"3d8c2f89-55d5-4f36-b7f2-bdea5f18e86a","added_by":"auto","created_at":"2026-02-02 05:58:18","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":95075,"visible":true,"origin":"","legend":"\u003cp\u003ePanel with four graphs showing bilateral recordings of electrical activity in the peroneal nerve.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eLegend\u003c/strong\u003e:\u003c/p\u003e\n\u003cp\u003eConduction velocity (top left), latency (top right), and CMAP (bottom left) are presented as box plots of the variables obtained by group (Non-NED \u003cem\u003eversus\u003c/em\u003e NED) and by right (white) and left (gray) sides. In the bottom right corner, the right-left symmetry ratio for each group is shown, with a horizontal dotted line indicating perfect symmetry between recordings (ratio = 1.00) – an outlier value (r/l = 23) was excluded from the graph to enhance visualization of the box plot. The Mann-Whitney test identified a significant difference (p\u0026lt;0.05) between groups for CMAP (indicated by brackets), with no significant difference (p\u0026gt;0,05) between the right and left sides as examined by the Wilcoxon matched-pairs rank test. Abbreviations: NED = neuromuscular electrophysiological disorder, Non-NED = without neuromuscular electrophysiological disorder, CMAP – compound muscle action potential.\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-6619019/v1/6765803dadfe5ae1de95f825.png"},{"id":101633199,"identity":"897289da-2268-41fc-af50-337367e49622","added_by":"auto","created_at":"2026-02-02 05:58:18","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":144380,"visible":true,"origin":"","legend":"\u003cp\u003eHistogram of the frequency distribution of the symmetry ratio between the bilateral CMAP\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eLegend: \u003c/strong\u003eDistribution of the r/l between the CMAP obtained from the right and left peroneal nerves. The dashed vertical lines highlight the symmetry ratio value corresponding to perfect symmetry (r/l = 1.0), as well as the lower and upper limit values considered as the boundaries of the symmetry zone (0.5 \u0026lt; r/l \u0026lt; 2). It also indicates the r/l = 0 value, which corresponds to a symmetry ratio without a CMAP signal recorded on the right side and unilateral CMAP recorded on the left nerve. For algebraic reasons, a CMAP equal to zero on the left peroneal nerve and unilateral CMAP recorded on the right nerve could not be calculated. However, in this sample, there were no participants with this condition, thus avoiding a symmetry ratio value tending to infinite. The dashed vertical lines also delineate the asymmetry zone on the left side of the histogram, indicating a predominance of CMAP signal intensity in the left lower limb, while on the right side, the upper limit of the symmetry zone marks the beginning of the asymmetry zone with a predominance of the CMAP amplitude in the right lower limb. Four participants from the clinical group were not included in the histogram and were described below the identification of each “zone” in the graph: three participants who did not have CMAP records (*), and one whose symmetry ratio was an upper outlier (r/l = 23) (**). In the table, regarding the distribution of asymmetry in NED versus Non-NED groups, the percentage occurrence of 32% and 14% respectively is verified, resulting in an OR for NED = 2,3 (#). Abbreviations: CMAP = compound muscle action potential, NED = neuromuscular electrophysiological disorder, Non-NED = without neuromuscular electrophysiological disorder, r/l = symmetry ratio, OD = odds ratio.\u003c/p\u003e","description":"","filename":"3.png","url":"https://assets-eu.researchsquare.com/files/rs-6619019/v1/32866d8ba0ba479c19c3b155.png"},{"id":101633200,"identity":"73f3a975-e209-4811-a002-94417a849371","added_by":"auto","created_at":"2026-02-02 05:58:18","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":183268,"visible":true,"origin":"","legend":"\u003cp\u003eCorticospinal matches between the worst record of bilateral CMAP and a brain anatomical landmark.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eLegend\u003c/strong\u003e: Schematic representation of the corticospinal tract and its decussation to illustrate the possibility of an anatomical landmark worsening the NED condition in muscles under its corticospinal influence. Of the 18 participants in the sample with anatomical landmarks, 6 had landmarks in the right cerebral hemisphere and 12 in the left. These anatomical landmarks corresponded to 6 (50%) and 2 (33%) of the worst records on right and left sides respectively (6 from the left hemisphere with the muscle on the right side, and 2 from the right hemisphere with the muscle on the left side, making a total of 8 (44%) matches in 18 observations. When separating the matches by groups with or without clinical criteria for NED diagnosis, we observed 6 (50%) matches in 12 observations in the NED group, compared to 2 (33%) matches in 6 observations in the non-NED group. This indicates an attributable risk of 17%, favorable to the NED group, that there is such a match between the hemispheric anatomical landmark and the contralateral side of the muscle where the worst electrophysiological recording occurred. This results in an indicator of the number needed to match (NNM) of 6, that means that for every 6 participants with a brain anatomical landmark, one participant would be expected to have a match between the side of the focal lesion in the NCS and the worst electrodiagnostic recording of NED on the corresponding corticospinal side. Abbreviations: NED = neuromuscular electrophysiological disorder, Non-NED = without neuromuscular electrophysiological disorder.\u003c/p\u003e","description":"","filename":"4.png","url":"https://assets-eu.researchsquare.com/files/rs-6619019/v1/cb91f07eb559f954416450ed.png"},{"id":101753219,"identity":"2d0a4873-ada1-406c-acc8-84cda2e9d681","added_by":"auto","created_at":"2026-02-03 10:39:27","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1438814,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6619019/v1/bde419d2-ca3d-4af1-b40e-e15908e7e41f.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Clinical Significance of Asymmetry on Electrodiagnostic Testing to detect Polyneuromyopathy in Critically Ill Patients: a cross-sectional study","fulltext":[{"header":"BACKGROUND","content":"\u003cp\u003eCritical Illness Polyneuropathy (CIP) is recognized as the most prevalent peripheral polyneuropathy in the Intensive Care Unit (ICU)\u0026nbsp;\u003csup\u003e1–3\u003c/sup\u003e. It manifests as a distal sensory-motor axonopathy symmetrically impacts the limbs and respiratory muscles \u003csup\u003e2\u003c/sup\u003e. In conjunction with Critical Illness Myopathy (CIM), which often occurs concurrently \u003csup\u003e2,4,5\u003c/sup\u003e, these conditions are identified as principal contributors to intensive care unit-acquired weakness (ICUAW) \u003csup\u003e6,7\u003c/sup\u003e. In turn, this syndrome is described as the main physical manifestation of Post-Intensive Care Syndrome (PICS) \u003csup\u003e8,9\u003c/sup\u003e. The incidence of ICUAW varies between 40% and 57% \u003csup\u003e10–12\u003c/sup\u003e, potentially leading to long-term sequelae and correlating with increased mortality rates even following hospital discharge \u003csup\u003e2,6\u003c/sup\u003e. Evidence of clinical and/or neurophysiological axonopathy can persist for up to five years post-discharge \u003csup\u003e13\u003c/sup\u003e, with extreme cases resulting in quadriplegia \u003csup\u003e14\u003c/sup\u003e.\u003c/p\u003e\n\u003cp\u003eEmerging evidence suggests that implementing early rehabilitation within the ICU setting can help maintain physical functionality and potentially enhance outcomes for those suffering from ICUAW \u003csup\u003e15,16\u003c/sup\u003e. However, the successful application of early rehabilitation strategies hinges critically upon early diagnostic capabilities. Nerve conduction study (NCS) and needle-electromyography (nEMG) are tools used to differentiate CIP and CIM, as well as from deconditioning, characterized by muscle weakness in the absence of electrophysiological alterations - all of them with different prognoses \u003csup\u003e17,18\u003c/sup\u003e. Nevertheless, nEMG cannot confirm CIM in unconscious patients - under sedation and/or in coma. Moreover, both NCS and nEMG necessitate considerable time, costly equipment, and specialized expertise \u003csup\u003e2,18\u003c/sup\u003e. To address these challenges, simplified screening tests have been proposed for bedside analysis within the ICU \u003csup\u003e1,19,20\u003c/sup\u003e. The nerve conduction study for the motor peroneal nerve is particularly notable for its high sensitivity in screening for probable CIP/CIM \u003csup\u003e1\u003c/sup\u003e - hereafter referred to as neuromuscular electrophysiological disorder (NED)\u003csup\u003e20\u003c/sup\u003e. Studies have reported an absence of statistically significant differences in electrophysiological findings between the right and left sides of the body, which reinforces the concept of NED’s symmetrical manifestation. Consequently, they recommend that screening tests be conducted unilaterally to optimize the cost-benefit ratio \u003csup\u003e17,21\u003c/sup\u003e, a practice already adopted in some studies \u003csup\u003e1,20\u003c/sup\u003e.\u003c/p\u003e\n\u003cp\u003eNevertheless, since the mid-19th century when Paul Broca and Carl Wernicke \u003csup\u003e22\u003c/sup\u003e introduced the concept of cerebral lateralization, numerous evidence have accrued demonstrating that the nervous system exhibits substantial functional asymmetry. Despite disuse-induced immobility caused by coma or sedation affecting both sides of the body equally, it is conceivable that laterality and unilateral central nervous system lesions (e.g., stroke, trauma) could precipitate an initially asymmetric electrophysiological expression of NED, potentially driven by synergistic interactions among distinct injury mechanisms. The hypothesis was that NED, though established as a symmetrical disease, may initially manifest asymmetrically in critically ill patients and this possibility should not be neglected, due to the risk of analysis errors. This study aimed to investigate the presence of asymmetry in NED development and the relevance of conducting bilateral electrophysiological assessments for its diagnostic screening in critically ill patients in ICU. Moreover, we intended to evaluate the impact of laterality and brain focal lesion on asymmetry.\u003c/p\u003e"},{"header":"METHODS","content":"\u003cp\u003e\u003cstrong\u003eStudy design\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis research employed a cross-sectional observational study design focusing on critically ill patients admitted to the ICU. It was conducted and reported following the STROBE statement for observational studies \u003csup\u003e23\u003c/sup\u003e.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSetting\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe study was carried out in a general, surgical and trauma ICU of a tertiary public referral hospital in the Federal District, Brazil. Data collection occurred between April and October 2024. The study received ethical approval from the local ethics committee (HB/IGESDF, Brasília, Brazil, protocol 63620622.2.0000.8153) and adhered to the Declaration of Helsinki. As all participants were intubated and sedated at enrollment, written informed consent was obtained from the closest responsible family member for the patients.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eParticipants\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe study included critically ill participants aged 18 years or older who were admitted to the ICU. All participants had to be sedated and mechanically ventilated for at least three days. Exclusion criteria included pre-existing neuromuscular diseases, detection of peripheral demyelinating neuropathy, use of neuromuscular blocking agents, brain death, pregnancy, a body mass index (BMI) greater than 35 kg/m², orthopedic deformities, or other lower limb conditions (such as edema, fractures, or amputations) that could preclude bilateral nerve conduction studies.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eVariables\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe primary outcome was to assess the amplitude difference in neuromuscular activation between both sides and detect the presence of asymmetry using electrophysiological criterion. Secondary outcomes involved evaluating whether unilateral anatomical landmarks in the central nervous system - such as ischemia, hemorrhage, or concussion - contributed to asymmetrical reductions in compound muscle action potential (CMAP) and the incidence of NED. Participants’ clinical characteristics (age, sex), comorbidities (diabetes, hypertension, chronic obstructive pulmonary disease, etc.), hospitalization diagnosis, severity score - Simplified Acute Physiology Score 3 (SAPS 3), Sequential Organ Failure Assessment score (SOFA), Ramsay Sedation Score, presence of sepsis and septic shock (defined according to Sepsis-3 criteria), and PaO\u003csub\u003e2\u003c/sub\u003e/FiO\u003csub\u003e2\u003c/sub\u003e ratio were collected and analyzed.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eNerve Conduction Study of the Motor Peroneal Nerve (PENT)\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eA purely electrophysiological diagnostic approach for NED was used, via PENT, which has a high sensitivity for detecting NED, ranging from 92% up to 100% \u003csup\u003e1,17,21,24\u003c/sup\u003e. All participants underwent bilateral PENT performed by a single experienced intensivist using a Neuro-MEP-Micro® electroneuromyograph. The low-pass filter was set at 3Hz and the high-pass filter was set at 10 kHz. Sensitivity and sweep were set at 3 mV and 2 ms, respectively. Stimulation was performed at two sites to record distal motor latencies, record amplitude, and calculate conduction velocity of each nerve. Amplitudes were measured from baseline to negative peak. For testing, surface recording electrodes (Ambu® Neuroline 715) were placed over the belly and tendon of the extensor digitorum brevis. The peroneal nerve was stimulated over the anterior region of the ankle slightly lateral to the tendon of the tibialis anterior muscle, 6 to 8 cm from the recording electrodes, and below the head of the fibula for recording motor conduction velocity. Incremental electrical stimulation of the peroneal nerve was applied until the best CMAP amplitudes were obtained, with motor conduction velocity and latency duly recorded.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eDiagnostic Criteria for NED\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eCMAP results 80% below Katirj's normal standard (≥3 mV for age 20-50 years old; \u0026nbsp;≥2,5 mV for age 51-90 years old) were considered abnormal \u003csup\u003e25\u003c/sup\u003e. Axonopathy-related measures of motor conduction velocity were evaluated by Tan’s criteria (80% above lower limit normal, if CMAP \u0026lt;50% of normal; or 90% above, if CMAP \u0026gt;50% of normal)\u003csup\u003e26\u003c/sup\u003e. The expected pattern indicative of NED was axonopathy, characterized by reduction in CMPA amplitude with normal or mildly reduced nerve conduction velocity\u003csup\u003e2\u003c/sup\u003e.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eDiagnostic Criteria for Asymmetry\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eWe use the electrophysiological criterion for asymmetry which is the CMAP amplitude difference of more than 50% comparing side to side (i.e., a 50% [0,5x] drop from the higher side to the lower or a 100% [2x] increase from the lower side to the higher) \u003csup\u003e27\u003c/sup\u003e. To assess the bilateral symmetry of CMAPs, we calculated the right/left CMAP records ratio (r/l), and constructed a histogram to visualize the distribution of these ratios and better identify patterns of symmetry and asymmetry. Values in the range between 0.5 and 2 were considered “symmetry” (difference ≤50% between bilateral CMAP records). When the values were exactly the same, we had what we called perfect symmetry (r/l =1.0). Vertical lines were plotted to define a symmetry zone (0.5 ≤ ratio ≤ 2) around perfect symmetry (r/l = 1), where the bilateral CMAP amplitudes are considered symmetrical. Thus, “asymmetry” occurred when the ratios were outside this specified interval. Additionally, values outside this range indicate respectively a unfavorable CMAP asymmetry to the right (r/l \u0026lt; 0,5) or left (r/l \u0026gt; 2) side.\u003c/p\u003e\n\u003cp\u003eAll the results were reviewed by an expert neurophysiologist.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eStudy size\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eBased on data inferences from our non-publisehd pilot study, a medium effect size (Cohen's d = 0.4) was hypothesized for the difference between groups. An a priori power analysis was conducted using GPower (version 3.1.9.7) for a chi-square goodness-of-fit test on contingency tables. With a significance level (α) of 0.05 and a desired power (1 – β) of 0.8, the analysis indicated a required sample size of 81 assessments.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eStatistical analysis\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eGiven the non-normality of most variables (by the D'Agostino-Pearson test), non-parametric statistical tests were employed. Quantitative results were presented as medians and interquartile ranges, while qualitative variables were described by absolute and relative frequencies of occurrence. To examine differences between quantitative variables was used the Mann-Whitney U test. The Wilcoxon signed-rank test was employed to compare paired quantitative variable data (right versus left sides). Fisher's exact test was used to compare proportions. Statistical differences were considered significant at p\u0026lt;0.05.\u0026nbsp;\u003c/p\u003e"},{"header":"RESULTS","content":"\u003cp\u003eWe enrolled forty-one participants leading to eighty-two assessments (bilateral assessments). Further details are available in the flow diagram (Figure 1).\u003c/p\u003e\n\u003cp\u003eSample characteristics are presented in Table 1.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 1.\u0026nbsp;\u003c/strong\u003eCharacterization of the critically ill patients with and without criteria for neuromuscular electrophysiological disorders diagnosis.\u003c/p\u003e\n\u003cdiv align=\"Left\"\u003e\n \u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"532\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" style=\"width: 38.9098%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eVariables\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 20.4887%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eSample Size\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e(n=41)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 19.3609%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eNon-NED\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e(n=7)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 21.2406%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eNED\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e(n=34)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" style=\"width: 38.9098%;\"\u003e\n \u003cp\u003eAge (years)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 20.4887%;\"\u003e\n \u003cp\u003e44 (36-59)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 19.3609%;\"\u003e\n \u003cp\u003e37 (25 - 41)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 21.2406%;\"\u003e\n \u003cp\u003e48,50 (40 \u0026ndash; 60.50)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"bottom\" style=\"width: 38.9098%;\"\u003e\n \u003cp\u003eSex - n (%) male\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 20.4887%;\"\u003e\n \u003cp\u003e30 (73.17%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 19.3609%;\"\u003e\n \u003cp\u003e5 (71.43%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 21.2406%;\"\u003e\n \u003cp\u003e25 (73.53%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"bottom\" style=\"width: 38.9098%;\"\u003e\n \u003cp\u003eBMI (kg/m\u003csup\u003e2\u003c/sup\u003e)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 20.4887%;\"\u003e\n \u003cp\u003e23 (21 - 28)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 19.3609%;\"\u003e\n \u003cp\u003e28 (22 - 30)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 21.2406%;\"\u003e\n \u003cp\u003e23 (20 - 27)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"bottom\" style=\"width: 38.9098%;\"\u003e\n \u003cp\u003eSAPS 3 score, on admission\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 20.4887%;\"\u003e\n \u003cp\u003e58 (49 \u0026ndash; 66.50)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 19.3609%;\"\u003e\n \u003cp\u003e62 (49 - 67)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 21.2406%;\"\u003e\n \u003cp\u003e58 (49 - 68)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"bottom\" style=\"width: 38.9098%;\"\u003e\n \u003cp\u003eSOFA score, on assessment\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 20.4887%;\"\u003e\n \u003cp\u003e7 (6 - 9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 19.3609%;\"\u003e\n \u003cp\u003e8 (6 - 9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 21.2406%;\"\u003e\n \u003cp\u003e7 (6 - 8)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"bottom\" style=\"width: 38.9098%;\"\u003e\n \u003cp\u003eReason for ICU admission - n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 20.4887%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 19.3609%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 21.2406%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 7.14286%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 31.7669%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eTraumatic brain injury\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 20.4887%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e14 (34.14%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 19.3609%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e4 (57.14%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 21.2406%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e10 (29.41%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 7.14286%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 31.7669%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eHemorrhagic stroke\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 20.4887%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e5 (12.20%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 19.3609%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e1 (14.29%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 21.2406%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e4 (11.76%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 7.14286%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 31.7669%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eIschemic stroke\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 20.4887%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e2 (4.87%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 19.3609%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0 (0%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 21.2406%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e2 (5.88%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 7.14286%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 31.7669%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eSubarachnoid hemorrhage\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 20.4887%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e2 (4.87%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 19.3609%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0 (0%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 21.2406%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e2 (5.88%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 7.14286%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 31.7669%;\"\u003e\n \u003cp\u003eAbdominal trauma\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 20.4887%;\"\u003e\n \u003cp\u003e2 (4.87%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 19.3609%;\"\u003e\n \u003cp\u003e0 (0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 21.2406%;\"\u003e\n \u003cp\u003e2 (5.88%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 7.14286%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 31.7669%;\"\u003e\n \u003cp\u003eThoracic trauma\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 20.4887%;\"\u003e\n \u003cp\u003e3 (7.31%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 19.3609%;\"\u003e\n \u003cp\u003e1 (14.29%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 21.2406%;\"\u003e\n \u003cp\u003e2 (5.88%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 7.14286%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 31.7669%;\"\u003e\n \u003cp\u003eHeart surgery\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 20.4887%;\"\u003e\n \u003cp\u003e2 (4.87%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 19.3609%;\"\u003e\n \u003cp\u003e0 (0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 21.2406%;\"\u003e\n \u003cp\u003e2 (5.88%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 7.14286%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 31.7669%;\"\u003e\n \u003cp\u003eMyocardial infarction\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 20.4887%;\"\u003e\n \u003cp\u003e2 (4.87%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 19.3609%;\"\u003e\n \u003cp\u003e0 (0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 21.2406%;\"\u003e\n \u003cp\u003e2 (5.88%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 7.14286%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 31.7669%;\"\u003e\n \u003cp\u003eCancer\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 20.4887%;\"\u003e\n \u003cp\u003e3 (7.31%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 19.3609%;\"\u003e\n \u003cp\u003e1 (14.29%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 21.2406%;\"\u003e\n \u003cp\u003e2 (5.88%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 7.14286%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 31.7669%;\"\u003e\n \u003cp\u003eBradycardia\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 20.4887%;\"\u003e\n \u003cp\u003e1 (2.44%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 19.3609%;\"\u003e\n \u003cp\u003e0 (0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 21.2406%;\"\u003e\n \u003cp\u003e1 (2.94%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 7.14286%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 31.7669%;\"\u003e\n \u003cp\u003eOthers\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 20.4887%;\"\u003e\n \u003cp\u003e5 (12.20%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 19.3609%;\"\u003e\n \u003cp\u003e0 (0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 21.2406%;\"\u003e\n \u003cp\u003e5 (14.71%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"bottom\" style=\"width: 38.9098%;\"\u003e\n \u003cp\u003eType 2 diabetes - n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 20.4887%;\"\u003e\n \u003cp\u003e2 (4.87%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 19.3609%;\"\u003e\n \u003cp\u003e0 (0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 21.2406%;\"\u003e\n \u003cp\u003e2 (5.88%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"bottom\" style=\"width: 38.9098%;\"\u003e\n \u003cp\u003eHIV - n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 20.4887%;\"\u003e\n \u003cp\u003e1 (2.44%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 19.3609%;\"\u003e\n \u003cp\u003e0 (0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 21.2406%;\"\u003e\n \u003cp\u003e1 (2.94%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"bottom\" style=\"width: 38.9098%;\"\u003e\n \u003cp\u003eDrug addiction - n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 20.4887%;\"\u003e\n \u003cp\u003e2 (4.87%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 19.3609%;\"\u003e\n \u003cp\u003e0 (0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 21.2406%;\"\u003e\n \u003cp\u003e2 (5.88%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" style=\"width: 38.9098%;\"\u003e\n \u003cp\u003eMechanical ventilation days,\u003c/p\u003e\n \u003cp\u003eon assesssment\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 20.4887%;\"\u003e\n \u003cp\u003e8 (5 \u0026ndash; 12.50)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 19.3609%;\"\u003e\n \u003cp\u003e4 (3 - 9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 21.2406%;\"\u003e\n \u003cp\u003e9 (6 - 13)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" style=\"width: 38.9098%;\"\u003e\n \u003cp\u003eICU length of stay (days),\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eon assesssment\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 20.4887%;\"\u003e\n \u003cp\u003e6 (2 \u0026ndash; 10.50)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 19.3609%;\"\u003e\n \u003cp\u003e3 (2 - 7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 21.2406%;\"\u003e\n \u003cp\u003e7 (3 - 11)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" style=\"width: 38.9098%;\"\u003e\n \u003cp\u003eHospital length of stay (days),\u003c/p\u003e\n \u003cp\u003eon assesssment\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 20.4887%;\"\u003e\n \u003cp\u003e9 (5 - 14)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 19.3609%;\"\u003e\n \u003cp\u003e6 (4 - 9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 21.2406%;\"\u003e\n \u003cp\u003e11 (6 - 15)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"bottom\" style=\"width: 38.9098%;\"\u003e\n \u003cp\u003eSepsis - n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 20.4887%;\"\u003e\n \u003cp\u003e41 (100%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 19.3609%;\"\u003e\n \u003cp\u003e7 (100%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 21.2406%;\"\u003e\n \u003cp\u003e34 (100%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 7.14286%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 31.7669%;\"\u003e\n \u003cp\u003eLung\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 20.4887%;\"\u003e\n \u003cp\u003e35 (85.36%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 19.3609%;\"\u003e\n \u003cp\u003e7 (100%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 21.2406%;\"\u003e\n \u003cp\u003e28 (82.35%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 7.14286%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 31.7669%;\"\u003e\n \u003cp\u003eAbdomen\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 20.4887%;\"\u003e\n \u003cp\u003e3 (7.31%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 19.3609%;\"\u003e\n \u003cp\u003e0 (0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 21.2406%;\"\u003e\n \u003cp\u003e3 (8.82%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 7.14286%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 31.7669%;\"\u003e\n \u003cp\u003eCNS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 20.4887%;\"\u003e\n \u003cp\u003e2 (4.87%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 19.3609%;\"\u003e\n \u003cp\u003e0 (0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 21.2406%;\"\u003e\n \u003cp\u003e2 (5.88%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 7.14286%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 31.7669%;\"\u003e\n \u003cp\u003eMediastinum\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 20.4887%;\"\u003e\n \u003cp\u003e1 (2.44%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 19.3609%;\"\u003e\n \u003cp\u003e0 (0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 21.2406%;\"\u003e\n \u003cp\u003e1 (2.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"bottom\" style=\"width: 38.9098%;\"\u003e\n \u003cp\u003eSeptic Schock - n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 20.4887%;\"\u003e\n \u003cp\u003e14 (34.14%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 19.3609%;\"\u003e\n \u003cp\u003e4 (57.14%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 21.2406%;\"\u003e\n \u003cp\u003e10 (29.41%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"bottom\" style=\"width: 38.9098%;\"\u003e\n \u003cp\u003eGCS - n (%), on admission\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 20.4887%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 19.3609%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 21.2406%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 7.14286%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 31.7669%;\"\u003e\n \u003cp\u003e10 \u0026ndash; 14\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 20.4887%;\"\u003e\n \u003cp\u003e12 (29.27%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 19.3609%;\"\u003e\n \u003cp\u003e1 (14.29%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 21.2406%;\"\u003e\n \u003cp\u003e11 (32.35%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\" style=\"width: 7.14286%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 31.7669%;\"\u003e\n \u003cp\u003e6 \u0026ndash; 9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 20.4887%;\"\u003e\n \u003cp\u003e29 (70.73%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 19.3609%;\"\u003e\n \u003cp\u003e6 (85.71%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 21.2406%;\"\u003e\n \u003cp\u003e23 (67.65%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"bottom\" style=\"width: 38.9098%;\"\u003e\n \u003cp\u003eRASS score, on assessment\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 20.4887%;\"\u003e\n \u003cp\u003e-5 (-5 - -4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 19.3609%;\"\u003e\n \u003cp\u003e-5 (-5 - -4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 21.2406%;\"\u003e\n \u003cp\u003e-5 (-5 - -4)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" style=\"width: 38.9098%;\"\u003e\n \u003cp\u003eUsing norepinephrine - n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 20.4887%;\"\u003e\n \u003cp\u003e14 (34.14%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 19.3609%;\"\u003e\n \u003cp\u003e4 (57.14%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 21.2406%;\"\u003e\n \u003cp\u003e10 (29.41%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 7.14286%;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 31.7669%;\"\u003e\n \u003cp\u003edosage (mcg/kg/min)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 20.4887%;\"\u003e\n \u003cp\u003e0.13 (0.08 \u0026ndash; 0.39)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 19.3609%;\"\u003e\n \u003cp\u003e0.1 (0.06 \u0026ndash; 0.13)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 21.2406%;\"\u003e\n \u003cp\u003e0.15 (0.07 \u0026ndash; 0.52)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"bottom\" style=\"width: 38.9098%;\"\u003e\n \u003cp\u003eLactate, dosage (mmol/L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 20.4887%;\"\u003e\n \u003cp\u003e1.4 (1.15 \u0026ndash; 1.65)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 19.3609%;\"\u003e\n \u003cp\u003e1.3 (1.2 \u0026ndash; 1.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 21.2406%;\"\u003e\n \u003cp\u003e1.4 (1.1 \u0026ndash; 1.72)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"bottom\" style=\"width: 38.9098%;\"\u003e\n \u003cp\u003eP/F rate, on assessment\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 20.4887%;\"\u003e\n \u003cp\u003e284 (234 - 338)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 19.3609%;\"\u003e\n \u003cp\u003e292 (210 - 332)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\" style=\"width: 21.2406%;\"\u003e\n \u003cp\u003e277 (235 - 344)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" style=\"width: 38.9098%;\"\u003e\n \u003cp\u003eRenal failure - n (%),\u003c/p\u003e\n \u003cp\u003eon assessment\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 20.4887%;\"\u003e\n \u003cp\u003e4 (9.76%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 19.3609%;\"\u003e\n \u003cp\u003e0 (0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 21.2406%;\"\u003e\n \u003cp\u003e4 (11.76%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"5\" valign=\"bottom\" style=\"width: 100%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eLegend\u003c/strong\u003e:\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eThe table presents the personal and clinical characteristics of the total sample and the groups with and without clinical criteria for neuromuscular electrophysiological disorders. Qualitative variables are presented as absolute (n) and relative (%) frequencies, and quantitative variables are presented as medians and interquartile ranges (IQR), using non-parametric analysis. The Mann-Whitney U test and Fisher\u0026apos;s exact test revealed no significant differences (p \u0026lt; 0.05) between NED and Non-NED groups. Items in bold indicate the subpopulation of neurological patients: n=23 (56%). Abbreviations: NED = neuromuscular electrophysiological disorders, Non NED = without neuromuscular electrophysiological disorders, BMI = body mass index, SAPS 3 = Simplified Acute Physiology Score 3, SOFA = Sequential Organ Failure Assessment, ICU = intensive care unit, HIV = human immunodeficiency virus, CNS = central nervous system, GCS = Glasgow Coma Scale, RASS = Richmond Agitation Sedation Scale, P/F = ratio between the partial pressure of arterial oxygen and the fraction of inspired oxygen.\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003e\u003cstrong\u003eCritical Illness Polyneuromyopathy\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eOut of the total participants, 34 (83%) individuals were diagnosed with NED. They were significantly older than those in the Non-NED group. The reason for ICU admission was almost evenly split between neurological and non-neurological conditions, with a slight predominance of neurological conditions, particularly among the Non-NED participants (Table 1).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eElectrophysiological Recordings and Bilateral Assessment\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe analysis of electrophysiological parameters (Figure 2) revealed a significant decrease in CMAP amplitude in the NED group compared to the Non-NED group; however, conduction velocity and latency remained similar between the groups, consistent with a typical axonopathy pattern.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eRegarding the quantitative statistical analysis of bilateral records, statistically significant inter-side differences were absent. Detailed analyses across groups showed a reduction in CMAP amplitude exceeding 50% in the NED group, with a slightly more pronounced reduction on the right side. Specifically, the median CMAP on the right side decreased from 3.8 mV to 1.35 mV in the NED group - a 64% reduction. On the left side, the median dropped from 3.1 mV in the Non-NED group to 1.35 mV, achieving a 56% reduction.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eBilateral Asymmetries in Electrophysiological Recordings\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWith regard to the CMAP symmetry ratio (r/l), as depicted in the histogram (Fig. 3), 29 (71%) participants fell within the symmetry zone, which included three participants with no recordable CMAP or \u0026quot;electrical silence\u0026quot;.\u003c/p\u003e\n\u003cp\u003eThe histogram indicated that based on electrophysiological criterion, 12 (29%) participants - practically one-third of the sample - exhibited asymmetries in CMAP recordings from bilateral lower limb assessments. Among them, five (12%) had diagnostic divergences: one side indicated NED, while the contralateral side did not. Patients with NED had a two-fold odds ratio of asymmetry compared to the Non-NED group. The median of the symmetry ratio in the Non-NED group was very close to 1 (r/l = 1.05), whereas it was 0.79 in the NED group (Figure 2, bottom right corner). This suggests a tendency towards a more pronounced reduction in CMAP on the right side in the NED group - below the perfect symmetry line where r/l = 1.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMatches between Anatomical Landmarks and Electrophysiological Recordings\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe explored potential correlations between cerebral anatomical landmarks due to hemispheric injury and CMAP reduction in contralateral muscles - under corticospinal influence (Figure 4).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAmong the eighteen neurological participants in the sample with anatomical landmarks from trauma or stroke, twelve were in the left cerebral hemisphere and six in the right. Corticospinal correspondence between focal hemispheric lesion and the side of the body with the most pronounced electrophysiological impairment was observed in 50% of cases (6:12) and 33% of cases (2:6), respectively (Figure 4). Splitting the matches by groups, we found the same proportions: 6 matches (50%) out of 12 observations in the NED group, compared to 2 matches (33%) out of 6 observations in the Non-NED group (Figure 4). This suggests a 17% attributable risk in the NED group for a match between the hemispheric anatomical landmark and more pronounced contralateral peripheral electrodiagnostic dysfunction - corresponding corticospinal side. From this 17% attributable risk, we derived an indicator called the number needed to match (NNM), calculated as 6. This implies that for every 6 participants with a brain anatomical landmark, one participant is expected to exhibit a match between the side of the focal brain injury and the worst peripheral electrodiagnostic record on the contralateral body side.\u003c/p\u003e"},{"header":"DISCUSSION","content":"\u003cp\u003eThis study highlights the presence of clinically relevant electrophysiological asymmetry at the onset of NED among critically ill patients. Recognizing this asymmetry in diagnostic screenings is crucial, as neglecting it can lead to diagnostic errors and inaccurate research findings. Our results reinforce the high incidence of NED in critically ill patients with sepsis and multi-organ dysfunction syndrome; and underscore the potential influence of laterality and focal CNS lesions on NED progression.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSymmetry vs Asymmetry\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eOur findings initially align with previous research that did not identify statistically significant differences in bilateral CMAP records of peripheral nerves \u003csup\u003e17,21\u003c/sup\u003e. In neurophysiology, the assessment of neuromuscular electrical dysfunction via bilateral CMAP comparison is fundamentally determined by the identification of asymmetry, which is established on electrophysiological criteria instead of relying solely on statistical parameters \u003csup\u003e27\u003c/sup\u003e. Unlike the previous ones, this study used the electrophysiological criterion for asymmetry adopted by neurophysiology: difference in CMAP amplitude greater than 50% inter-sides \u003csup\u003e27\u003c/sup\u003e. It revealed a high occurrence of CMAP asymmetry, identified in 12 (29%) participants, with diagnostic divergence between sides in 5 (12%) cases - where one side was NED compatible and the other, normal. Supporting our observations, Latronico (2022) \u003csup\u003e24\u003c/sup\u003e similarly observed diagnostic divergence of 12%, advocating for contralateral nerve assessment only after a normal initial PENT. The clinical significance of our findings supports using clinical parameters alongside statistical analysis to evaluate effects \u003csup\u003e28\u003c/sup\u003e, strengthening the recommendation for bilateral electrodiagnostic evaluations in critical illness research, to avoid diagnostic errors and reduce analysis bias.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eInfluence of laterality and focal CNS lesions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eOur findings also indicate an increased risk of spinal-cortical correspondence between focal CNS lesions and worsening CMAP recordings among NED participants. This is coupled with a slightly more pronounced reduction in neuromuscular electrical activity on the right side for those with NED compared to unaffected patients. The intricate interplay between the central nervous system (CNS) and peripheral system involves complex scientific challenges, not yet explored in the CIP/CIM scenario, particularly the potential for asymmetrical development of this condition. While not the primary etiological factor, laterality, driven by cerebral dominance, potentially predisposes one hemisphere to structural and metabolic fragilities, which could modulate disease progression and affect otherwise symmetrical peripheral nerve damage \u003csup\u003e22\u003c/sup\u003e. This aligns with existing research on asymmetries in neurodegenerative disorders \u003csup\u003e22\u003c/sup\u003e. Axonal transport, essential for the proper function of the nervous system, allows the CNS to exert significant control over the maintenance and functional integrity of peripheral nerves \u003csup\u003e29\u003c/sup\u003e. The CNS modulates peripheral axonal neuroregeneration through trophic signaling, mirroring the reciprocal influence of peripheral axonal stimuli on CNS neuroplasticity \u003csup\u003e30\u003c/sup\u003e. Schweickert et al. (2009) \u003csup\u003e31\u003c/sup\u003e correlated early motor rehabilitation in the ICU with reduced duration of delirium and more ventilator-free days, suggesting a negative interaction between ICU-induced delirium and ICUAW. Prospective studies in ICU indicate that both septic encephalopathy and CIP occur together in 70% of cases, septic encephalopathy appearing first, suggesting an association between both dysfunctions \u003csup\u003e32\u003c/sup\u003e. Recent evidence suggests that central nervous system involvement with failure of coordinated repetitive firing within the motor neurons can be a very early event, preceding electrical failure in axons and muscle fibers, strengthening CNS engagement with NED \u003csup\u003e33\u003c/sup\u003e. In PICS, the interplay of physical (ICUAW), cognitive (dementia), and mental (depression and delirium) impairments may underline the close relationship between brain dysfunctions and peripheral axonopathy \u003csup\u003e8\u003c/sup\u003e. Despite the scarcity of robust scientific evidence, all these distinct entities may provide clues into the interaction of the laterality and focal brain with the asymmetric progression of NED, possibly by disproportionately affecting contralateral descending pathways \u003csup\u003e34\u003c/sup\u003e.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eNED incidence\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eOur study reported an 83% incidence of NED, significantly higher than the 47% reported in a systematic review of ICUAW \u003csup\u003e12\u003c/sup\u003e. This higher incidence can be justified by the sample, which included neurological patients with sepsis and multiple-organ dysfunctions \u003csup\u003e35\u003c/sup\u003e, with reports of incidences approaching 100% as severity and organ failures increase \u003csup\u003e5\u003c/sup\u003e. Berek et al. (1996) \u003csup\u003e36\u003c/sup\u003e and Latronico et al. (2022)\u0026nbsp;\u003csup\u003e24\u003c/sup\u003e described a CIP frequency of 82% and 79% respectively among similar populations.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eStudy limitations\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eSome limitations should be addressed in our study. There was no diagnostic confirmation of ICUAW, since we worked with uncooperative participants - under sedation or coma \u003csup\u003e11\u003c/sup\u003e. Nevertheless, electrophysiological disorders are associated with deleterious outcomes in critically ill participants, even in the absence of weakness \u003csup\u003e18,37\u003c/sup\u003e. We applied only bilateral assessment of motor peroneal nerve by PENT, without sensory evaluation of the sural sensitive nerve to confirm CIP diagnosis \u003csup\u003e17,21\u003c/sup\u003e. Indeed, reduced CMAP is observed in both axonopathy (CIP) and myopathy (CIM). However, although reduced sensory nerve action potential (SNAP) confirms CIP, it does not exclude CIM and may be blunted or masked due to local oedema, low surface temperatures, or electromagnetic interference \u003csup\u003e1\u003c/sup\u003e. Motor changes precede sensory changes, so that normal SNAP does not rule out axonopathy at the onset of dysfunction \u003csup\u003e1,38\u003c/sup\u003e. Moreover, CIM and CIP are normally associated \u003csup\u003e1\u003c/sup\u003e and several researchers argue that the differentiation between them is not very relevant in ICU \u003csup\u003e1,17,39\u003c/sup\u003e. The limited setting and cross-sectional nature reduce generalizability to other contexts.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFuture perspectives\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eFuture multicenter studies with larger cohorts are needed to further document neuropathological asymmetry in NED progression and its clinical implications. Research should explore advanced neurophysiological tools \u003csup\u003e34\u003c/sup\u003e to track CNS dysfunction and assess peripheral axonopathies in critically ill patients, extending follow-up beyond hospital discharge.\u003c/p\u003e"},{"header":"CONCLUSIONS","content":"\u003cp\u003eElectrodiagnostic screening tests for neuromuscular electrophysiological disorders in critically illness patients in ICU should be performed bilaterally to avoid diagnostic error and analysis bias, due to the clinical relevance of asymmetry in its development. The impact of cerebral laterality and focal brain lesions on electrodiagnostic asymmetry in the onset of critical illness polyneuromyopathy needs to be further studied.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"433\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003eNED\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003eNeuromuscular electrophysiological disorder\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003eNon-NED\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003eWithout neuromuscular electrophysiological disorder\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003eCMAP\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003eCompound muscle action potential\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003eSNAP\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003eSensory nerve action potential\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003er/l\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003eRight/left CMAP ratio\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003ePENT\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003eNerve conduction study for the motor peroneal nerve\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003eNCS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003eNerve conduction study\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003eEMG\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003eNeedle-electromyography\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003eCIP\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003eCritical illness polyneuropathy\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003eCIM\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003eCritical illness myopathy\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003eCIP/CIM\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003eCritical illness polyneuro and/or myopathy\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003eICUAW\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003eIntensive care unit-acquired weakness\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003ePICS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003ePost-intensive care syndrome\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003eCNS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003eCentral nervous system\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003eICU\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003eIntensive care unit\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003eSAPS 3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003eSimplified Acute Physiology Score 3\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003eSOFA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003eSequential organ failure assessment\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003eBMI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003eBody mass index\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003eGCS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003eGlasgow Coma Scale\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003eRASS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003eRichmond Agitation Sedation Scale\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003eMV\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003eMechanical ventilation\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003eOR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003eOdds ratio\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis research was made possible by the generous support of the Funda\u0026ccedil;\u0026atilde;o de Apoio \u0026agrave; Pesquisa do Distrito Federal (Fapdf project # 00193-00002152/2023-95), the Minist\u0026eacute;rio da Ci\u0026ecirc;ncia, Tecnologia e Inova\u0026ccedil;\u0026atilde;o (MCTI), the Conselho Nacional de Desenvolvimento Cient\u0026iacute;fico e Tecnol\u0026oacute;gico (CNPq). We also thank the Hospital de Base/IGESDF neurophysiologist and ICU team.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eConcept and Design: JRDM and PES. Aquisition, analysis and interpretation of the data: all authors. Drafting the manuscript: JRDM, PES and EFM. Graphics: JRDM, PES and EFM. Critical revision of the manuscript for important intellectual content: all authors. Supervision: RNMF and EFM. All authors read and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe contributions from Financiadora de Servi\u0026ccedil;os e Projetos (Finep) allowed for the purchase of essential\u0026nbsp;electromyography equipment, facilitating the successful completion of this study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe data sets used and analyzed during the current study are available from the corresponding author upon reasonable request.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was conducted in accordance with the ethical principles outlined in the Declaration of Helsinki and was approved by the Institutional Review Board of HB/IGESDF, under protocol number 63620622.2.0000.8153. Written informed consent was obtained from the closest responsible family member for each included patients.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWritten informed consent for publication was obtained. \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll authors declare no competing interests.\u003c/p\u003e"},{"header":"REFERENCES","content":"\u003col\u003e\n \u003cli\u003eLatronico, N. \u003cem\u003eet al.\u003c/em\u003e Simplified electrophysiological evaluation of peripheral nerves in critically ill patients: The Italian multi-centre CRIMYNE study. \u003cem\u003eCrit. Care\u003c/em\u003e\u003cstrong\u003e11\u003c/strong\u003e, R11 (2007).\u003c/li\u003e\n \u003cli\u003eLatronico, N. \u0026amp; Bolton, C. F. Critical illness polyneuropathy and myopathy: A major cause of muscle weakness and paralysis. \u003cem\u003eLancet Neurol.\u003c/em\u003e\u003cstrong\u003e10\u003c/strong\u003e, 931\u0026ndash;941 (2011).\u003c/li\u003e\n \u003cli\u003eBolton, C. F. Neuromuscular manifestations of critical illness. \u003cem\u003eMuscle and Nerve\u003c/em\u003e\u003cstrong\u003e32\u003c/strong\u003e, 140\u0026ndash;163 (2005).\u003c/li\u003e\n \u003cli\u003eLatronico, N. Neuromuscular alterations in the critically ill patient: Critical illness myopathy, critical illness neuropathy, or both? \u003cem\u003eIntensive Care Med.\u003c/em\u003e\u003cstrong\u003e29\u003c/strong\u003e, 1411\u0026ndash;1413 (2003).\u003c/li\u003e\n \u003cli\u003ePark, S.-H., Jeong, Y.-J. \u0026amp; Kim, N.-H. Critical illness neuromyopathy. \u003cem\u003eAnn. Clin. Neurophysiol.\u003c/em\u003e\u003cstrong\u003e22\u003c/strong\u003e, 61\u0026ndash;66 (2020).\u003c/li\u003e\n \u003cli\u003eVanhorebeek, I., Latronico, N. \u0026amp; Van den Berghe, G. ICU-acquired weakness. \u003cem\u003eIntensive Care Med.\u003c/em\u003e\u003cstrong\u003e46\u003c/strong\u003e, 637\u0026ndash;653 (2020).\u003c/li\u003e\n \u003cli\u003eHadda, V. \u003cem\u003eet al.\u003c/em\u003e Trends of loss of peripheral muscle thickness on ultrasonography and its relationship with outcomes among patients with sepsis. \u003cem\u003eJ. Intensive Care\u003c/em\u003e\u003cstrong\u003e6\u003c/strong\u003e, 1\u0026ndash;10 (2018).\u003c/li\u003e\n \u003cli\u003eInoue, S. \u003cem\u003eet al.\u003c/em\u003e Post‐intensive care syndrome: its pathophysiology, prevention, and future directions. \u003cem\u003eAcute Med. Surg.\u003c/em\u003e\u003cstrong\u003e6\u003c/strong\u003e, 233\u0026ndash;246 (2019).\u003c/li\u003e\n \u003cli\u003eOshima, T. \u0026amp; Hatakeyama, J. Nutritional therapy for the prevention of post-intensive care syndrome. \u003cem\u003eJ. Intensive Care\u003c/em\u003e\u003cstrong\u003e12\u003c/strong\u003e, 1\u0026ndash;8 (2024).\u003c/li\u003e\n \u003cli\u003eStevens, R. D. \u003cem\u003eet al.\u003c/em\u003e Neuromuscular dysfunction acquired in critical illness: a systematic review. \u003cem\u003eIntensive Care Med.\u003c/em\u003e\u003cstrong\u003e33\u003c/strong\u003e, 1876\u0026ndash;1891 (2007).\u003c/li\u003e\n \u003cli\u003eFan, E. \u003cem\u003eet al.\u003c/em\u003e An official american thoracic society clinical practice guideline: The diagnosis of intensive care unit-acquired weakness in adults. \u003cem\u003eAm. J. Respir. Crit. Care Med.\u003c/em\u003e\u003cstrong\u003e190\u003c/strong\u003e, 1437\u0026ndash;1446 (2014).\u003c/li\u003e\n \u003cli\u003eAppleton, R. T. D., Kinsella, J. \u0026amp; Quasim, T. The incidence of intensive care unit-acquired weakness syndromes: A systematic review. \u003cem\u003eJ. Intensive Care Soc.\u003c/em\u003e\u003cstrong\u003e16\u003c/strong\u003e, 126\u0026ndash;136 (2015).\u003c/li\u003e\n \u003cli\u003eVan Aerde, N. \u003cem\u003eet al.\u003c/em\u003e Five-year impact of ICU-acquired neuromuscular complications: a prospective, observational study. \u003cem\u003eIntensive Care Med.\u003c/em\u003e\u003cstrong\u003e46\u003c/strong\u003e, 1184\u0026ndash;1193 (2020).\u003c/li\u003e\n \u003cli\u003ede S\u0026egrave;ze, M. \u003cem\u003eet al.\u003c/em\u003e Critical illness polyneuropathy. A 2-year follow-up study in 19 severe cases. \u003cem\u003eEur. Neurol.\u003c/em\u003e\u003cstrong\u003e43\u003c/strong\u003e, 61\u0026ndash;69 (2000).\u003c/li\u003e\n \u003cli\u003eLiu, M., Luo, J., Zhou, J. \u0026amp; Zhu, X. Intervention effect of neuromuscular electrical stimulation on ICU acquired weakness: A meta-analysis. \u003cem\u003eInt. J. Nurs. Sci.\u003c/em\u003e\u003cstrong\u003e7\u003c/strong\u003e, 228\u0026ndash;237 (2020).\u003c/li\u003e\n \u003cli\u003eSilva, P. E. \u003cem\u003eet al.\u003c/em\u003e Neuromuscular electrical stimulation in critically ill traumatic brain injury patients attenuates muscle atrophy, neurophysiological disorders, and weakness: A randomized controlled trial. \u003cem\u003eJ. Intensive Care\u003c/em\u003e\u003cstrong\u003e7\u003c/strong\u003e, 1\u0026ndash;13 (2019).\u003c/li\u003e\n \u003cli\u003eKelmenson, D. A., Quan, D. \u0026amp; Moss, M. What is the diagnostic accuracy of single nerve conduction studies and muscle ultrasound to identify critical illness polyneuromyopathy: a prospective cohort study. \u003cem\u003eCrit. CARE\u003c/em\u003e\u003cstrong\u003e22\u003c/strong\u003e, (2018).\u003c/li\u003e\n \u003cli\u003eHermans, G. \u003cem\u003eet al.\u003c/em\u003e Predictive value for weakness and 1-year mortality of screening electrophysiology tests in the ICU. \u003cem\u003eIntensive Care Med.\u003c/em\u003e\u003cstrong\u003e41\u003c/strong\u003e, 2138\u0026ndash;2148 (2015).\u003c/li\u003e\n \u003cli\u003eSilva, P. E. \u003cem\u003eet al.\u003c/em\u003e Towards innovative electrodiagnosis tests to investigate neuromuscular excitability dysfunction in critically ill patients: an agreement study. \u003cem\u003eRes. Biomed. Eng.\u003c/em\u003e (2023).\u003c/li\u003e\n \u003cli\u003eSilva, P. E. \u003cem\u003eet al.\u003c/em\u003e Neuromuscular electrophysiological disorders and muscle atrophy in mechanically-ventilated traumatic brain injury patients: New insights from a prospective observational study. \u003cem\u003eJ. Crit. Care\u003c/em\u003e\u003cstrong\u003e44\u003c/strong\u003e, 87\u0026ndash;94 (2018).\u003c/li\u003e\n \u003cli\u003eMoss, M. \u003cem\u003eet al.\u003c/em\u003e Screening for critical illness polyneuromyopathy with single nerve conduction studies. \u003cem\u003eIntensive Care Med.\u003c/em\u003e\u003cstrong\u003e40\u003c/strong\u003e, 683\u0026ndash;690 (2014).\u003c/li\u003e\n \u003cli\u003eLubben, N., Ensink, E., Coetzee, G. A. \u0026amp; Labrie, V. The enigma and implications of brain hemispheric asymmetry in neurodegenerative diseases. \u003cem\u003eBrain Commun.\u003c/em\u003e\u003cstrong\u003e3\u003c/strong\u003e, fcab211 (2021).\u003c/li\u003e\n \u003cli\u003eVandenbroucke, J. P. \u003cem\u003eet al.\u003c/em\u003e Strengthening the Reporting of Observational Studies in Epidemiology (STROBE): explanation and elaboration. \u003cem\u003ePLoS Med.\u003c/em\u003e\u003cstrong\u003e4\u003c/strong\u003e, e297 (2007).\u003c/li\u003e\n \u003cli\u003eLatronico, N. \u003cem\u003eet al.\u003c/em\u003e Validation of the peroneal nerve test to diagnose critical illness polyneuropathy and myopathy in the intensive care unit: The multicentre Italian CRIMYNE-2 diagnostic accuracy study. \u003cem\u003eF1000Research\u003c/em\u003e\u003cstrong\u003e3\u003c/strong\u003e, (2022).\u003c/li\u003e\n \u003cli\u003eKatirji, B. \u003cem\u003eElectromyography in Clinical Practice: A Case Study Approach.\u003c/em\u003e 40, 244 (Mosby, 2007).\u003c/li\u003e\n \u003cli\u003eTan, F. C. \u003cem\u003eEMG Secrets\u003c/em\u003e. 178 (Hanley \u0026amp; Belfus, 2002).\u003c/li\u003e\n \u003cli\u003ePreston, D. C. \u0026amp; Shapiro, B. E. \u003cem\u003eElectromyography and Neuromuscular Disorders\u003c/em\u003e. 466, 476 (Elsevier, 2005).\u003c/li\u003e\n \u003cli\u003eSharma, H. Statistical significance or clinical significance? A researcher\u0026rsquo;s dilemma for appropriate interpretation of research results. \u003cem\u003eSaudi J. Anaesth.\u003c/em\u003e\u003cstrong\u003e15\u003c/strong\u003e, 431\u0026ndash;434 (2021).\u003c/li\u003e\n \u003cli\u003eMaday, S., Twelvetrees, A. E., Moughamian, A. J. \u0026amp; Holzbaur, E. L. F. Axonal transport: cargo-specific mechanisms of motility and regulation. \u003cem\u003eNeuron\u003c/em\u003e\u003cstrong\u003e84\u003c/strong\u003e, 292\u0026ndash;309 (2014).\u003c/li\u003e\n \u003cli\u003eNagappan, P. G., Chen, H. \u0026amp; Wang, D. Y. Neuroregeneration and plasticity: A review of the physiological mechanisms for achieving functional recovery postinjury. \u003cem\u003eMil. Med. Res.\u003c/em\u003e\u003cstrong\u003e7\u003c/strong\u003e, 1\u0026ndash;16 (2020).\u003c/li\u003e\n \u003cli\u003eSchweickert, W. D. \u003cem\u003eet al.\u003c/em\u003e Early physical and occupational therapy in mechanically ventilated, critically ill patients: a randomised controlled trial. \u003cem\u003eLancet\u003c/em\u003e\u003cstrong\u003e373\u003c/strong\u003e, 1874\u0026ndash;1882 (2009).\u003c/li\u003e\n \u003cli\u003eBolton, C. F., Young, G. B. \u0026amp; Zochodne, D. W. The neurological complications of sepsis. \u003cem\u003eAnn. Neurol.\u003c/em\u003e\u003cstrong\u003e33\u003c/strong\u003e, 94\u0026ndash;100 (1993).\u003c/li\u003e\n \u003cli\u003eLatronico, N. \u0026amp; Friedrich, O. Electrophysiological investigations of peripheral nerves and muscles: a method for looking at cell dysfunction in the critically ill patients. \u003cem\u003eCrit. CARE\u003c/em\u003e\u003cstrong\u003e23\u003c/strong\u003e, 33 (2019).\u003c/li\u003e\n \u003cli\u003eSouron, R. \u003cem\u003eet al.\u003c/em\u003e Relationship between intensive care unit-acquired weakness, fatigability and fatigue: What role for the central nervous system? \u003cem\u003eJ. Crit. Care\u003c/em\u003e\u003cstrong\u003e62\u003c/strong\u003e, 101\u0026ndash;110 (2021).\u003c/li\u003e\n \u003cli\u003eWitt, N. J. \u003cem\u003eet al.\u003c/em\u003e Peripheral nerve function in sepsis and multiple organ failure. \u003cem\u003eChest\u003c/em\u003e\u003cstrong\u003e99\u003c/strong\u003e, 176\u0026ndash;184 (1991).\u003c/li\u003e\n \u003cli\u003eBerek, K. \u003cem\u003eet al.\u003c/em\u003e Polyneuropathies in critically ill patients: a prospective evaluation. \u003cem\u003eIntensive Care Med.\u003c/em\u003e\u003cstrong\u003e22\u003c/strong\u003e, 849\u0026ndash;855 (1996).\u003c/li\u003e\n \u003cli\u003eKelmenson, D. A. \u003cem\u003eet al.\u003c/em\u003e Electrophysiological abnormalities can differentiate pre-hospital discharge functional status in critically ill patients with normal strength. \u003cem\u003eIntensive care medicine\u003c/em\u003e vol. 42 1504\u0026ndash;1505 (2016).\u003c/li\u003e\n \u003cli\u003eKamble, N., Shukla, D. \u0026amp; Bhat, D. Peripheral Nerve Injuries: Electrophysiology for the Neurosurgeon. \u003cem\u003eNeurol. India\u003c/em\u003e\u003cstrong\u003e67\u003c/strong\u003e, 1419\u0026ndash;1422 (2019).\u003c/li\u003e\n \u003cli\u003eTankisi, H., de Carvalho, M. \u0026amp; Z\u0026rsquo;Graggen, W. J. Critical Illness Neuropathy. \u003cem\u003eJ. Clin. Neurophysiol. Off. Publ. Am. Electroencephalogr. Soc.\u003c/em\u003e\u003cstrong\u003e37\u003c/strong\u003e, 205\u0026ndash;207 (2020).\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"scientific-reports","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"scirep","sideBox":"Learn more about [Scientific Reports](http://www.nature.com/srep/)","snPcode":"","submissionUrl":"","title":"Scientific Reports","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Scientific Reports","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Bilateral Evaluation, Asymmetry, Compound Muscle Action Potential, Neuromuscular Electrophysiological Disorders, Clinical Diagnosis, Critical Illness Polyneuropathy, Critically Ill Patients","lastPublishedDoi":"10.21203/rs.3.rs-6619019/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6619019/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground: \u003c/strong\u003eIn search of simplified nerve conduction studies as screening electrophysiological tests in Intensive Care Unit (ICU), previous studies have suggested that unilateral electrophysiological evaluations may be sufficient for screening probable critical illness polyneuro and/or myopathy (CIP/CIM) in ICU - also called as neuromuscular electrophysiological disorder (NED) - since quantitative statistical analyses did not detect significant bilateral differences, at first reinforcing its symmetrical manifestation as established.\u003cstrong\u003e \u003c/strong\u003eThis study aimed to investigate the presence of asymmetry in the onset of NED and the relevance of bilateral electrophysiological assessments for correct screening to avoid diagnostic and analysis errors. We also investigated possible effects of laterality and focal lesions of the central nervous system on NED.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods\u003c/strong\u003e: From Abril to October 2024, a cross-sectional observational study of critically ill patients admitted in ICU was conducted. All participants underwent bilateral nerve conduction study for the motor peroneal nerve to investigate asymmetry. Different from previous studies, bilateral Compound Muscle Action Potential (CMAP) records were analyzed based on the electrodiagnostic criterion for asymmetry.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults:\u003c/strong\u003e 41 patients were enrolled, in which 82 assessments were carried out. NED was identified in 34 (83%) participants. Based on electrodiagnostic criterion, asymmetries were observed in 12 (29%) participants, with diagnostic divergence in 5 (12%), in which NED could be overlooked if the evaluation were unilateral. Patients with NED had a two-fold odds ratio of asymmetry between bilateral electrodiagnostic assessments compared to patients without NED. We also identified a possible match between brain anatomical landmarks and the worst CMAP on the contralateral side, with an attributable risk of 17% in patients with NED.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion: \u003c/strong\u003eThis study suggests that electrodiagnostic screening tests for neuromuscular electrophysiological disorders in critically illness participants in ICU should be performed bilaterally to avoid diagnostic error and analysis bias, due to the clinical relevance of asymmetry in the development of this dysfunction. The impact of cerebral laterality and focal brain lesions on electrodiagnostic asymmetry in the early phase of NED needs to be further studied.\u003c/p\u003e","manuscriptTitle":"Clinical Significance of Asymmetry on Electrodiagnostic Testing to detect Polyneuromyopathy in Critically Ill Patients: a cross-sectional study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-02-02 05:58:13","doi":"10.21203/rs.3.rs-6619019/v1","editorialEvents":[{"type":"communityComments","content":6},{"type":"decision","content":"Revision requested","date":"2026-02-23T12:50:49+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-02-22T18:35:45+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-02-21T22:15:33+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-02-18T09:46:56+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-02-11T13:02:01+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-02-05T13:41:27+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-02-03T10:47:42+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"286423268892957215724815341373388099309","date":"2026-02-03T10:00:29+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"331364654079882762935410432822363672910","date":"2026-01-30T09:54:37+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"123386857567222860956238181841611481589","date":"2026-01-30T05:16:09+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"61143322754974191106799250026740322342","date":"2026-01-30T00:53:11+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"310304466956632191602201411436233884633","date":"2026-01-29T13:45:46+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"87780578320455745607813732529017025763","date":"2026-01-29T10:54:15+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2026-01-29T09:26:44+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-08-11T07:29:26+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2025-05-22T15:41:08+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-05-22T03:33:26+00:00","index":"","fulltext":""},{"type":"submitted","content":"Scientific Reports","date":"2025-05-08T09:21:47+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"scientific-reports","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"scirep","sideBox":"Learn more about [Scientific Reports](http://www.nature.com/srep/)","snPcode":"","submissionUrl":"","title":"Scientific Reports","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Scientific Reports","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"d449623b-f27b-4480-9bea-ed3b4ac853ed","owner":[],"postedDate":"February 2nd, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[{"id":62059533,"name":"Biological sciences/Neuroscience"},{"id":62059534,"name":"Health sciences/Diseases"},{"id":62059535,"name":"Health sciences/Medical research"},{"id":62059536,"name":"Health sciences/Neurology"}],"tags":[],"updatedAt":"2026-04-28T20:23:37+00:00","versionOfRecord":[],"versionCreatedAt":"2026-02-02 05:58:13","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-6619019","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6619019","identity":"rs-6619019","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}