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The COVID-19 pandemic has affected millions of people worldwide. While coronaviruses typically have low rates of neurotropic effects, the massive transmission of SARS-CoV-2 suggests that a substantial population will suffer from potential SARS-CoV-2-related neurological disorders. The rapid and recent emergence of SARS-CoV-2 means little research exists on its potential neurological effects. Here we analyze the effects of similar viruses to provide insight into the potential effects of SARS-CoV-2 on the nervous system and beyond. Seven coronavirus strains (HCoV-OC43, HCoV-HKU1, HCoV-229E, HCoV-NL63, SARS-CoV, MERS-CoV, SARS-CoV-2) can infect humans. Many of these strains cause neurological effects, such as headaches, dizziness, strokes, seizures, and critical illness polyneuropathy/myopathy. Certain studies have also linked coronaviruses with multiple sclerosis and extensive central nervous system injuries. Reviewing these studies provides insight into the anticipated effects for patients with SARS-CoV-2. This review will first describe the effects of other coronaviruses that have caused severe disease (SARS-CoV, MERS-CoV) on the nervous system, as well as their proposed origins, non-neurological effects, and neurological infection mechanisms. It will then discuss what is known about SARS-CoV-2 in these areas with reference to the aforementioned viruses, with the goal of providing a holistic picture of SARS-CoV-2.

Systemic lupus erythematosus (SLE) is a chronic disease of connective tissue with multi-organ invol­vement. Manifestation in the nervous system is one of the most difficult symptoms to assess and interpret. The aim of the study is to indicate diagnostic problems in patients with SLE in whom neurological symptoms are present at the time of diagnosis of SLE but also with complications that occurred after diagnosis. In the presented case, the appearance of flaccid tetraparesis with areflexia suggested peripheral damage to the nervous system. In the electromyography performed in this patient, acute axonal polyneuropathy was mainly suspected. Further differential diagnosis should consider other acute and subacute developing polyneuropathies. Guillain-Barré polyneuropathy deserves special attention. To our knowledge, this is the first case documented in the literature of the coexistence of critical illness polyneuropathy and SLE.

Critical illness-associated weakness (CIAW) is an umbrella term used to describe a group of neuromuscular disorders caused by severe illness. It can be subdivided into three major classifications based on the component of the neuromuscular system (i.e. peripheral nerves or skeletal muscle or both) that are affected. This includes critical illness polyneuropathy (CIP), critical illness myopathy (CIM), and an overlap syndrome, critical illness polyneuromyopathy (CIPNM). It is a common complication observed in people with critical illness requiring intensive care unit (ICU) admission. Given CIAW is found in individuals experiencing grave illness, it can be challenging to study from a practical standpoint. However, over the past 2 decades, many insights into the pathophysiology of this condition have been made. Results from studies in both humans and animal models have found that a profound systemic inflammatory response and factors related to bioenergetic failure as well as microvascular, metabolic, and electrophysiological alterations underlie the development of CIAW. Current management strategies focus on early mobilization, achieving euglycemia, and nutritional optimization. Other interventions lack sufficient evidence, mainly due to a dearth of large trials. The goal of this Physiology in Medicine article is to highlight important aspects of the pathophysiology of these enigmatic conditions. It is hoped that improved understanding of the mechanisms underlying these disorders will lead to further study and new investigations for novel pharmacologic, nutritional, and exercise-based interventions to optimize patient outcomes.

Background Critical illness polyneuropathy and myopathy (CIPNM) is a frequent neurological manifestation in patients with acute respiratory distress syndrome (ARDS) from coronavirus disease 2019 (COVID‐19) infection. CIPNM diagnosis is usually limited to clinical evaluation. We compared patients with ARDS from COVID‐19 and other aetiologies, in whom a neurophysiological evaluation for the detection of CIPNM was performed. The aim was to determine if there were any differences between these two groups in frequency of CINPM and outcome at discharge from the intensive care unit (ICU). Materials and Methods This was a single‐centre retrospective study performed on mechanically ventilated patients consecutively admitted (January 2016‐June 2020) to the ICU of Careggi Hospital, Florence, Italy, with ARDS of different aetiologies. Neurophysiological evaluation was performed on patients with stable ventilation parameters, but marked widespread hyposthenia (Medical Research Council score

INTRODUCTION Data are consistent on the benefits of inpatient rehabilitation for intensive care unit-acquired weaknesses (ICUAW), including critical illness myopathy, critical illness polyneuropathy, critical illness polyneuromyopathy, and disuse atrophy. This study focuses on the effects of inpatient rehabilitation on patients with ICUAW, specifically those with a clinical pattern of proximal muscle weakness and sensory sparing. OBJECTIVES To evaluate the impact of inpatient rehabilitation on patients with ICUAW versus other medically complex patients, and to identify comorbidities associated with poor rehabilitation outcomes. DESIGN Retrospective cohort study. SETTING Institutional, inpatient rehabilitation hospital. PATIENTS Two hundred seventy adult patients (≥18 years) divided into two groups: diagnosis of ICUAW (N = 55) or otherwise medically complex (N = 215), and admitted under the care of one physiatrist. INTERVENTIONS Not applicable. MAIN OUTCOME MEASURES For all patients we compared functional independence measure (FIM) gain, FIM efficiency, rehabilitation length of stay (RLOS), discharge disposition, and major medical comorbidities. RESULTS Patients with ICUAW had significantly greater FIM gain (P = .015) and RLOS (P = .02). There was no significant difference in FIM efficiency (P = .15). Patients with ICUAW had a significantly lower odds of acute hospital transfer (odds ratio [OR] = 0.52, with 95% confidence interval [CI] 0.47, 0.58) and skilled nursing facility discharge (OR = 0.19, with 95% CI 0.038, 0.95). However, patients with ICUAW did have a higher percent of acute hospital transfers than other medically complex patients (P = .017). In addition, patients with ICUAW were more medically complex, as evidenced by a significantly higher Charlson Comorbidity Index (P

Objective To report clinical and electroneuromyographic (ENMG) characteristics of patients affected by severe COVID-19 infection, evaluated for muscular weakness. Materials and methods ENMGs performed for evaluation of diffuse weakness in patients who could not be discharged from semi-intensive care COVID unit because of difficulties in ventilation weaning were reviewed. Patients with severe COVID-19 infection who had undergone endotracheal intubation and able to co-operate were considered. ENMG protocol was focused on neurophysiological items that excluded or confirmed critical illness polyneuropathy (CIP), myopathy (CIM), or polyneuromyopathy (CIPM). Standardized clinical evaluation was performed using Medical Research Council (MRC) sum score. Results Eight patients were included in the study. All presented known risk factors for intensive care unit-acquired weakness (ICU-AW), and none of them had history of underlying neuromuscular disorders. ENMG findings were normal in two patients, while only two patients had an altered MRC sum score (< 48). Neuromuscular involvement was diagnosed in 6/8 patients (75%): 2 had CIP, 1 had possible CIM, 1 had CIPM, while 1 patient, with clinically evident weakness but equivocal ENMG findings, was classified as ICU-AW. Finally, 1 patient was diagnosed with acute demyelinating neuropathy. Patients with neuromuscular involvement were those with longer intubation duration and higher levels of IL-6 at admission. Conclusion Neuromuscular complications are frequent in severe COVID-19 and cannot be excluded by MRC sum scores above 48. Standardized ENMG is helpful in guiding diagnosis when clinical evaluation is not reliable or possible. Elevated IL-6 at admission may be a predictor biomarker of ICU-AW in COVID-19.

Background Around 20% of patients hospitalized for COVID-19 need mechanical ventilation (MV). MV may be prolonged, thus warranting tracheostomy. Methods Observational cohort study enrolling patients admitted due to COVID-19. Demographic and clinical data at hospital and ICU admission were collected. The primary endpoint was to identify parameters associated with a need for tracheostomy; secondary endpoints were to analyze the clinical course of patients who needed tracheostomy. Results 118 patients were enrolled; 37 patients (31.5%) were transferred to ICU, of which 11 (29.72%) needed a tracheostomy due to prolonged MV. Sequential Organ Failure Assessment (SOFA) score at ICU admission (OR 0.65, 95% CI 0.47–0.92, p 0.015) was the only variable found to be associated with increased risk of the need for tracheostomy, with a cut-off point of 4.5 (sensitivity 0.72, specificity 0.73, positive predictive value 0.57 and negative predictive value 0.85). The main complications were nosocomial infection (100%), supraventricular cardiac arrhythmia (45.5%), agitation (54.5%), pulmonary thromboembolism (9.1%) and depression (9.1%). All patients presented with hypoalbuminemia and significant critical illness polyneuropathy. Conclusion SOFA at ICU admission is associated with an increased risk of tracheostomy in patients with COVID-19. Moreover, they present clinical features similar to those with chronic critical illness and suffer SARS-CoV-2-related complications.

Introduction:The aim of this study was to determine the frequency of patients with critical illness polyneuropathy/myopathy followed by mechanical ventilator in the intensive care unit, and to determine the risk factors associated with this condition and discuss them with the literature.Methods:This study was performed retrospectively (August 2012 to August 2017), at a tertiary university hospital in Turkey. A total of 31 patients who were on mechanical ventilation and diagnosed with polyneuropathy/myopathy by electroneuromyography (ENMG) during pediatric intensive care unit follow-up were included in the study. Data were collected from patient files and computer system. Demographic characteristics of the patients, causes of hospitalization, underlying disease, length of the pediatric intensive care unit and hospital stay, length of mechanical ventilation, and treatment modalities were recorded. Patients without respiratory support and patients on mechanical ventilation without ENMG procedures were excluded.Results:A total of 31 patients were included in the study. Myopathy was present in 5/31 (16.1%) and polyneuropathy in 26/31 (83.9%) patients. Respiratory distress/failure was the most common cause of respiratory support (n=10, 32.3%) and the second most common cause was post cardiac surgery (n=9, 29%). The diagnosis of 18 (58%) patients were sepsis and 2 (6.4%) patients had multiple organ failure. The mean duration of mechanical ventilation was 27.4±14.1 days, length of pediatric intensive care unit stay was 41.5±24 days, length of hospital stay was 57.5±27.5 days. Mortality was observed in 5 (16.1%) of 31 patients.Conclusion:Critical illness polyneuropathy and myopathy in intensive care practice is a condition with increasing frequency and importance. Increased attention to this matter allows to take the necessary preventions, early recognition and to make the appropriate approach.

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

Neurological manifestations are increasingly reported in a subset of COVID-19 patients. Previous infections related to coronaviruses, namely Severe Acute Respiratory Syndrome (SARS) and Middle Eastern Respiratory Syndrome (MERS) also appeared to have neurological effects on some patients. The viruses associated with COVID-19 like that of SARS enters the body via the ACE-2 receptors in the central nervous system, which causes the body to balance an immune response against potential damage to nonrenewable cells. A few rare cases of neurological sequelae of SARS and MERS have been reported. A growing body of evidence is accumulating that COVID-19, particularly in severe cases, may have neurological consequences although respiratory symptoms nearly always develop prior to neurological ones. Patients with preexisting neurological conditions may be at elevated risk for COVID-19-associated neurological symptoms. Neurological reports in COVID-19 patients have described encephalopathy, Guillain-Barré syndrome, myopathy, neuromuscular disorders, encephalitis, cephalgia, delirium, critical illness polyneuropathy, and others. Treating neurological symptoms can pose clinical challenges as drugs that suppress immune response may be contraindicated in COVID-19 patients. It is possible that in some COVID-19 patients, neurological symptoms are being overlooked or misinterpreted. To date, neurological manifestations of COVID-19 have been described largely within the disease trajectory and the long-term effects of such manifestations remain unknown.

Highlights • Critical illness myopathy/neuropathy often go under-diagnosed. • Over 70% of patients hospitalized for SARS-CoV-2 were ≥50 years old. • Older populations are at higher risk of suffering from ICU acquired weakness. • Early mobilization is a mainstay of treatment for ICU acquired weakness., One of the major concerns of the health care community and the public surrounding the SARS-CoV-2 pandemic is the availability and use of ventilators. Unprecedented surges of patients presented to intensive care units across the country, with older adults making up a large proportion of the patient population. This paper illustrates contemporary approaches to critical illness myopathy (CIM), critical illness polyneuropathy (CIP), and critical illness polyneuromyopathy (CIPNM) in older patients, including incidence, risk factors, mechanisms for pathology, diagnosis, contemporary treatment approaches, and outcomes. We hope that the following analysis may help educate clinicians and ultimately decrease the duration of the mechanical ventilation required by these patients, resulting in improved clinical outcomes and an increase in ventilator availability for other patients in need.

The new COVID-19 coronavirus infection, which has become a pandemic, is a very dangerous disease, the clinical picture of which can vary from mild to extremely severe forms of the course. Currently, there are no complete data on the pathogenetic mechanism of SARS-CoV-2, but there are extensive data on the probable risk factors for the development of extremely severe forms of COVID-19. The study of such factors becomes most suitable in terms of preventing their development and influence on the course of the disease in individuals with compromised immune systems and patients with impaired neuromuscular transmission. The article describes two clinical cases of extremely severe COVID-19 in patients with impaired neuromuscular transmission. Based on the analysis of the course of diseases, the conclusions are made about the possible aggravation and mutual activation of the immunopathological process with the launch of the cascade mechanism of the “cytokine storm”. An assumption has been made about the influence of human leukocyte antigen (HLA) on the severity of COVID-19, which is confirmed by a positive dynamics against the background of administration of IVIG, glucocorticosteroids (GCS), virusinactivated plasma and extracorporeal detoxification methods.

The spectrum of neuromuscular diseases encountered in the ICUs today has rapidly evolved over the last decades. Multiple predisposing factors are involved in the development of neuromuscular complications in intensive care patients. Those complications broadly classified into weakness from the preexisting neuromuscular disease exacerbated by critical illness or the complication of the critical illness itself. Patients, when unresponsive, confused, or sedated precludes careful clinical examination. A careful schematic approach that involves acquiring extensive history, any underlying infections, use of any offending medications, and the course of presenting illness will help in delineating the underlying etiology. Here in this review, we describe many causes and the pathophysiology that contribute to the development of neuromuscular weakness in the ICU. A comprehensive investigation protocol must strictly be adhered to all the cases in the ICU settings to reduce the mortality and morbidity.

Although the exact pathophysiology of critical illness polyneuropathy (CIP) is still unknown, there are several hypotheses, some of which are increased inflammation and oxidative stress. We used rodent sepsis model in which we induced sepsis through cecal ligation followed by cecal puncture. We then administered ascorbic acid (AA) and evaluated outcomes. The levels of malondialdehyde (MDA), tumor necrosis factor α (TNF-α), interleukins (IL)-6 in the plasma, and heat shock protein-70 (HSP-70) levels in the sciatic nerve were measured, and also electromyography analyses were performed. While plasma MDA, TNF-α, and IL-6 levels were decreased significantly with AA treatment, sciatic nerve levels of HSP-70 were significantly elevated in the AA group. A significant increase in compound muscle action potential (CMAP) amplitude and a significant decrease in CMAP latency were detected in the AA group. We observed healing effects of AA on a rat model of CIP and these effects seem to be related to its anti-inflammatory and antioxidant properties.

Background: Critical illness polyneuropathy and myopathy (CIPNM) is a disabling neuropathy that occurs in intensive care unit (ICU) subjects. It was hypothesized that a low serum level or deficiency of 25(OH)D might be associated with CIPNM. The aim of the present study was to ascertain the 25(OH)D serum level in subjects with CIPNM. Method: Consecutive ICU patients admitted to neuro-rehabilitation were prospectively enrolled. At admission, vitamin D serum levels were measured and EMG examination was performed to ascertain those with CIPNM. 25(OH)D was stratified as sufficient (≥30 ng/mL) insufficient (20-29.9 ng/mL), and deficient (

A variety of neuropsychiatric complications has been described in association with Covid-19 infection. Large scale studies presenting a wider picture of these complications and their relative frequency are lacking. The objective of our study was to describe the spectrum of neurological and psychiatric complications in patients with Covid-19 seen in a multidisciplinary hospital center over six months. We conducted a retrospective, observational study on all patients showing neurological or psychiatric symptoms in the context of Covid-19 seen in the medical and university neuroscience department of Assistance Publique Hopitaux de Paris -Sorbonne University. We collected demographic data, comorbidities, symptoms and severity of Covid-19 infection, neurological and psychiatric symptoms, neurological and psychiatric examination data and, when available, results from CSF analysis, MRI, EEG and EMG. A total of 249 Covid-19 patients with a de novo neurological or psychiatric manifestation were included in the database and 245 were included in the final analyses. One-hundred fourteen patients (47%) were admitted to the intensive care unit and 10 (4%) died. The most frequent neuropsychiatric complications diagnosed were encephalopathy (43%), critical illness polyneuropathy and myopathy (26%), isolated psychiatric disturbance (18%), and cerebrovascular disorders (16%). No patients showed CSF evidence of SARS-CoV-2. Encephalopathy was associated with older age and higher risk of death. Critical illness neuromyopathy was associated with an extended stay in the intensive care unit. The majority of these neuropsychiatric complications could be imputed to critical illness, intensive care and systemic inflammation, which contrasts with the paucity of more direct SARS-CoV-2-related complications or post-infection disorders., Graphical Abstract Graphical Abstract