[Neurointensive care medicine and COVID-19]. / Neurointensivmedizin und COVID-19.

This review article summarizes important findings on the interfaces between the coronavirus disease 2019 (COVID-19) pandemic and neurology with an emphasis of the implications for neurointensive care medicine. More specifically, the prevalence, pathomechanisms and impact of neurological manifestations are reported. The most common neurological manifestations of critically ill COVID-19 patients are cerebrovascular complications, encephalopathies and intensive care unit-acquired weakness (ICUAW). A relevant direct pathophysiological effect by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) itself has not yet been established with certainty. In fact, indirect systemic inflammatory processes triggered by the viral infection and side effects of intensive care treatment are much more likely to cause the reported sequelae. The impact of the pandemic on patients with neurological disorders and neurointensive care medicine is far-reaching but not yet sufficiently studied.

Muscle strength/intensive care unit acquired weakness in COVID-19 and non-COVID-19 patients.

BACKGROUND: Intensive care unit acquired weakness (ICU-AW) affects both coronavirus disease 19 (COVID-19) and non-COVID-19 patients. ICU-AW can result in a variety of consequences, including increased patient mortality. AIMS: The current study aimed to compare muscle strength and ICU-AW in COVID-19 and non-COVID-19 patients. STUDY DESIGN: This was a cross-sectional, descriptive-analytical pilot study. METHODS: Fifteen conscious COVID-19 patients and 15 conscious non-COVID-19 patients admitted to the ICUs of a public hospital were selected by convenience sampling. Muscle strength in arms and legs was assessed by a hand-held dynamometer (HHD), and ICU-AW was measured with the medical research council sum score (MRC-SS) scale on the first, fourth, and seventh days of admission to ICUs. RESULTS: The results showed that muscle strength in the arms and legs of the COVID-19 patients assessed by a HHD and MRC was significantly lower than that of non-COVID-19 patients. On the fourth day of ICU admission, 80% of the COVID-19 patients and 40% of the non-COVID-19 patients had ICU-AW. All COVID-19 patients and 86.8% of the non-COVID-19 patients had ICU-AW on the seventh day of ICU admission. CONCLUSIONS: Decreased muscle strength and ICU-AW are more likely in COVID-19 patients who must stay in the ICU compared with non-COVID-19 patients. RELEVANCE TO CLINICAL PRACTICE: Health systems should plan to provide rehabilitation facilities for COVID-19 patients and prevent prolonged complications of COVID-19.

Acute Neurological Manifestations of COVID-19 Patients From Three Tertiary Care Hospitals in Qatar.

Introduction Worldwide, there are more than 424 million confirmed cases of COVID-19. Most of the hospitalized critical COVID-19 patients manifested neurological signs and symptoms and higher mortality. The majority of COVID-19 fatalities occurred mostly in patients with advanced age and underlying medical comorbidities. This is the first local retrospective study in Qatar, which reported neurologic manifestations (48.5%) of hospitalized COVID-19 patients. The primary objective of this study is to evaluate acute neurological manifestations in COVID-19 hospitalized patients in the country. Methods This is a retrospective, observational study of 413 hospitalized COVID-19 patients. They were admitted to three different COVID-19 designated hospitals (Hazm Mebaireek, Ras Laffan, and Cuban tertiary care Hospitals) under the Hamad Medical Corporation, Qatar from 1st January 2020, to 31 January 2021. We evaluated electronic medical records of these patients and data were collected while their neurological manifestations were confirmed by two trained neurologists. These neurologic manifestations were categorized into three major groups: central nervous system (CNS), peripheral nervous system (PNS), and neuromuscular system. Results Of 413 patients, 94% (389) were male and 6% (24) were female; the mean age was 52 years. Among all different nationalities of COVID-19 patients, 20.3% (84) were Indian, 12.5% (52) were Bangladeshi, 10.1% (42) were Qatari and 9.2% (38) were Nepali. The most common symptoms at the onset of COVID-19 illness were as follows: 77.5% (321) had a fever, 67.4% (279) experienced cough, 58.7% (243) experienced shortness of breath and 26.1% (108) developed a sore throat. Overall 48.5% (201) patients developed different neurologic manifestations. The most common neurologic symptoms were myalgia (28%; 116), headache (10.4%; 43), dizziness (5.8%; 24) and hemiparesis due to strokes (5.3%; 22). In this study, the most common risk factors were hypertension (47.6%), diabetes (46.9%), obesity (21%), chronic kidney disease (10%), ischemic heart disease (9.7%), and smoking (6.8%). About 45.2% (187) patients were admitted to MICU and 8.5% (35) died due to COVID-19 complications. Significant other extrapulmonary multiorgan system involvement were skeletal muscle injury (39.4%), kidney injury (36.7%), liver injury (27.5%), myocardial injury (23.9%), rhabdomyolysis (15.7%) heart failure (11.4%) and acute pancreatitis (11.1%). Discussion The most common neurologic signs and symptoms were myalgia, headache, dizziness, and strokes, mainly due to large vessel thrombosis, lacunar, and posterior circulation strokes. Conclusions Patients with COVID-19 are at high risk of developing neurological manifestations. The most common COVID-19-related acute neurological manifestations were myalgia, headache, dizziness, and acute ischemic stroke. Prompt recognition, early diagnosis, and appropriate management of these manifestations could potentially lead to better patient outcomes in COVID-19 patients.

Relation between nutrition therapy in the acute phase and outcomes of ventilated patients with COVID-19 infection: a multicenter prospective observational study.

BACKGROUND: Optimal nutrition therapy has not yet been established for the acute phase of severe coronavirus disease 2019 (COVID-19) infection. OBJECTIVES: We aimed to examine the effects of nutrition delivery in the acute phase on mortality and the long-term outcomes of post-intensive care syndrome (PICS). METHODS: A multicenter prospective study was conducted on adult patients with COVID-19 infection requiring mechanical ventilation during an intensive care unit (ICU) stay. Daily total energy (kcal/kg) and protein (g/kg) deliveries in the first week of the ICU stay were calculated. The questionnaire for PICS evaluation was mailed within a median of 6 mo after hospital discharge. The primary outcome was in-hospital mortality, and secondary outcomes were the PICS components of physical impairment, cognitive dysfunction, and mental illness. RESULTS: Among 414 eligible patients, 297 who received mechanical ventilation for 7 d or longer were examined. PICS was evaluated in 175 patients among them. High protein delivery on days 4-7 correlated with a low in-hospital mortality rate. In contrast, high protein delivery on days 1-3 correlated with physical impairment. A multivariate logistic regression analysis adjusted for age, sex, BMI, and severity revealed that average energy and protein deliveries on days 4-7 correlated with decreased in-hospital mortality (OR: 0.94; 95% CI: 0.89, 0.99; P = 0.013 and OR: 0.40; 95% CI: 0.17, 0.93; P = 0.031, respectively). Nutrition delivery did not correlate with PICS outcomes after adjustments. In the multivariate regression using a restricted cubic spline model, in-hospital mortality monotonically decreased with increases in average nutrition delivery on days 4-7. CONCLUSIONS: In patents with COVID-19 on mechanical ventilation for ≥7 d, nutrition delivery in the late period of the acute phase was monotonically associated with a decrease in in-hospital mortality. Adequate protein delivery is needed on days 4-7.This trial was registered at https://www.umin.ac.jp as UMIN000041276.

Sex-Specific Aspects of Skeletal Muscle Metabolism in the Clinical Context of Intensive Care Unit-Acquired Weakness.

(1) Background: Female sex is considered a risk factor for Intensive Care Unit-Acquired Weakness (ICUAW). The aim is to investigate sex-specific aspects of skeletal muscle metabolism in the context of ICUAW. (2) Methods: This is a sex-specific sub-analysis from two prospectively conducted trials examining skeletal muscle metabolism and advanced muscle activating measures in critical illness. Muscle strength was assessed by Medical Research Council Score. The insulin sensitivity index was analyzed by hyperinsulinemic-euglycemic (HE) clamp. Muscular metabolites were studied by microdialysis. M. vastus lateralis biopsies were taken. The molecular analysis included protein degradation pathways. Morphology was assessed by myocyte cross-sectional area (MCSA). Multivariable linear regression models for the effect of sex on outcome parameters were performed. (3) Results: n = 83 (♂n = 57, 68.7%; ♀n = 26, 31.3%) ICU patients were included. ICUAW was present in 81.1%♂ and in 82.4%♀ at first awakening (p = 0.911) and in 59.5%♂ and in 70.6%♀ at ICU discharge (p = 0.432). Insulin sensitivity index was reduced more in women than in men (p = 0.026). Sex was significantly associated with insulin sensitivity index and MCSA of Type IIa fibers in the adjusted regression models. (4) Conclusion: This hypothesis-generating analysis suggests that more pronounced impairments in insulin sensitivity and lower MCSA of Type IIa fibers in critically ill women may be relevant for sex differences in ICUAW.

Bilateral phrenic nerve block as an effective means of controlling inspiratory efforts in a COVID-19 patient.

Bilateral continuous phrenic nerve block effectively regulates refractory persistent, strong inspiratory effort in a patient with coronavirus disease (COVID-19). A 73-year-old man with acute respiratory distress syndrome (ARDS) due to COVID-19 was admitted to the intensive care unit (ICU). Use of neuromuscular blocking agents (NMBAs) was stopped due to uncontrollable strong inspiratory efforts and worsened lung injury. We performed bilateral continuous phrenic nerve block, which suppressed inspiratory efforts, resulting in lung injury improvement. A bilateral continuous phrenic nerve block is a viable alternative to control refractory strong inspiratory effort leading to lung injury in cases with prolonged NMBA use.

Role of rehabilitation in a COVID-19 survivor with intensive care unit-acquired weakness: A case report.

Intensive care unit-acquired weakness (ICU-AW) is a catastrophic and debilitating clinical condition that causes generalized weakness and predisposes to adverse short- and long-term outcomes. Novel coronavirus disease-2019 (COVID-19) has been a global pandemic since November 2019. Each additional ICU admission for COVID-19 stresses intensive care unit (ICU) and hospital capacity. Accurately designed, timely rehabilitation procedures may reduce the patient burden of ICUs and hospitals. In this article, we describe a COVID-19 survivor who developed acute respiratory distress syndrome (ARDS) and ICU-AW. Early pulmonary rehabilitation in the ICU and long-term rehabilitation maintenance after the ICU and hospital discharge resulted in a positive outcome.

Clinical and neurophysiological characterization of muscular weakness in severe COVID-19.

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.

"Neurological manifestations of COVID-19" - guideline of the German society of neurology.

Infection with the new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) leads to a previously unknown clinical picture, which is known as COVID-19 (COrona VIrus Disease-2019) and was first described in the Hubei region of China. The SARS-CoV-2 pandemic has implications for all areas of medicine. It directly and indirectly affects the care of neurological diseases. SARS-CoV-2 infection may be associated with an increased incidence of neurological manifestations such as encephalopathy and encephalomyelitis, ischemic stroke and intracerebral hemorrhage, anosmia and neuromuscular diseases. In October 2020, the German Society of Neurology (DGN, Deutsche Gesellschaft für Neurologie) published the first guideline on the neurological manifestations of the new infection. This S1 guideline provides guidance for the care of patients with SARS-CoV-2 infection regarding neurological manifestations, patients with neurological disease with and without SARS-CoV-2 infection, and for the protection of healthcare workers. This is an abbreviated version of the guideline issued by the German Neurological society and published in the Guideline repository of the AWMF (Working Group of Scientific Medical Societies; Arbeitsgemeinschaft wissenschaftlicher Medizinischer Fachgesellschaften).

Intensive Care Unit-Acquired Weakness: Not just Another Muscle Atrophying Condition.

Intensive care unit-acquired weakness (ICUAW) occurs in critically ill patients stemming from the critical illness itself, and results in sustained disability long after the ICU stay. Weakness can be attributed to muscle wasting, impaired contractility, neuropathy, and major pathways associated with muscle protein degradation such as the ubiquitin proteasome system and dysregulated autophagy. Furthermore, it is characterized by the preferential loss of myosin, a distinct feature of the condition. While many risk factors for ICUAW have been identified, effective interventions to offset these changes remain elusive. In addition, our understanding of the mechanisms underlying the long-term, sustained weakness observed in a subset of patients after discharge is minimal. Herein, we discuss the various proposed pathways involved in the pathophysiology of ICUAW, with a focus on the mechanisms underpinning skeletal muscle wasting and impaired contractility, and the animal models used to study them. Furthermore, we will explore the contributions of inflammation, steroid use, and paralysis to the development of ICUAW and how it pertains to those with the corona virus disease of 2019 (COVID-19). We then elaborate on interventions tested as a means to offset these decrements in muscle function that occur as a result of critical illness, and we propose new strategies to explore the molecular mechanisms of ICUAW, including serum-related biomarkers and 3D human skeletal muscle culture models.

Approach to critical illness myopathy and polyneuropathy in the older SARS-CoV-2 patients.

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.