OBJECTIVE:To investigate early alterations in motor nerve membrane properties during critical illness using nerve excitability testing. METHODS:Adult critically ill patients admitted to the intensive care unit were examined within 24 h of intubation (day 1) and on days 2, 5 and 10. Examinations included neurological examination, nerve excitability testing, laboratory analyses and review of medication records; and on day 10 conventional nerve conduction studies, electromyography and a fine needle muscle biopsy. RESULTS:All critically ill patients (N = 26) showed nerve hypoexcitability within 24 h compared to healthy subjects, which persisted up to day 10. Additional nerve membrane depolarisation was only observed in critically ill patients with acute kidney injury (AKI) (n = 13). Four patients fulfilled the diagnostic criteria for critical illness polyneuropathy (CIP) at day 10 (15.4%), and six (23.1%) had a reduced myosin:actin ratio indicative of myosin loss consistent with critical illness myopathy. CONCLUSIONS:Nerve hypoexcitability appears to be a key feature of the early phase of critical illness, whereas additional nerve membrane depolarisation is associated with AKI, which may be linked to changes in serum potassium levels. SIGNIFICANCE:The findings do not support CIP as predominant explanation for nerve membrane depolarisation and muscle weakness seems to be associated with myosin loss.

Objective:To establish normative data for muscle excitability testing in the tibialis anterior muscle of a healthy population, and to determine their dependence on age and sex. Methods:Parameters of muscle velocity recovery cycle recordings with 1, 2 and 5 conditioning stimuli of 197 healthy subjects and frequency ramp recordings of 151 healthy subjects were retrospectively analysed for age and sex differences. Results:There were no differences by sex and only small age differences were found in healthy subjects older than 60 years for the muscle excitability parameters muscle relative refractory period, early supernormality and latency to the first response in a train at 15 Hz and 30 Hz. Conclusions:In this study, based on a large sample of muscle velocity recovery cycle and frequency ramp recordings, we have provided normative data and shown that muscle excitability testing is not influenced by sex, and that age only has an influence from the age of 60 years onwards on parameters reflecting muscle membrane potential. Significance:Our results suggest that future studies no longer need to control for sex when using a healthy control group.

Objectives: Intensive care unit acquired weakness (ICUAW) is a clinical diagnosis and an umbrella term for acquired weakness due to neuromuscular disorders such as critical illness myopathy (CIM) but also muscular inactivity/atrophy. Without a clear understanding of the distinct aetiology, it seems difficult to predict outcomes of ICUAW and to test and apply effective future treatments. The present study contrasts ICUAW with CIM and assesses the diagnostic and clinical relevance for affected patients. Methods: Data from a previous prospective cohort study investigating critically ill COVID-19 patients was analysed in a retrospective fashion. Patients were examined ten days after intubation with clinical assessment, nerve conduction studies, electromyography and muscle biopsy. Mortality was assessed during critical illness and at three months after hospital discharge. ICUAW and CIM were diagnosed according to the current diagnostic guidelines. Results: In this patient sample (n = 22), 92 % developed ICUAW, 55 % developed ICUAW and CIM, and 36 % had ICUAW but did not develop CIM. Overall, 27 % patients died during their stay in the intensive care unit. At three months after discharge, there were no further deaths, but in 14% of patients the outcome was unknown. The diagnosis of CIM was more strongly associated with death during critical illness than ICUAW. No patient with ICUAW who did not fulfil the criteria for CIM died. Both clinical and electrophysiological criteria showed excellent sensitivity for CIM diagnosis, but only electrophysiological criteria had a high specificity. Determination of the myosin:actin ratio showed neither high sensitivity nor specificity for the diagnosis of CIM. Conclusions: The results of the present study support that ICUAW is a non-specific clinical diagnosis of low predictive power with regard to mortality. Further, diagnosing "ICUAW" seems also of little research value for both exploring the aetiology and pathophysiology of muscle weakness in critically ill patients and for evaluating potential treatment effects. Thus, more specific diagnoses such as CIM are more appropriate. Within the different diagnostic criteria for CIM, electrophysiological studies are the most sensitive and specific examinations compared to clinical and muscle tissue assessment. Significance: Avoiding an overarching diagnosis of "ICUAW" and instead focusing on specific diagnoses appears to have several relevant consequences: more precise diagnosis making, more accurate referral to aetiology and pathophysiology, improved outcome prediction, and development of more appropriate treatments. (c) 2024 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

BACKGROUND AND PURPOSE:Patients with postural tachycardia syndrome report position-dependent visual symptoms. Despite their impact on daily life, these symptoms have remained largely unexplored in research. The aim of this study was to investigate the nature of visual symptoms in postural tachycardia syndrome and possible underlying pathophysiological mechanisms. METHODS:Fifteen patients with postural tachycardia syndrome and 15 healthy controls were included in the study. Through a comprehensive array of measurements, including haemodynamics, subjective symptom assessments, eye movement tracking and pupil diameter analysis, participants were assessed during free image exploration in both supine and 60° head-up tilt positions. RESULTS:During head-up tilt, patients showed a decreased number and duration of fixations, as well as a decreased number, peak velocity and amplitude of saccades compared to the supine position and the control group. This reduction in visual exploration occurred primarily in the peripheral field of view and coincided with the occurrence of subjective visual symptoms. No significant differences in the saccade main sequence were observed between the two groups in either body position. CONCLUSIONS:Patients with postural tachycardia syndrome have a reduced exploration of the peripheral field of view when in an upright body position, potentially leading to tunnel vision. Since the normality of the saccade main sequence in patients combined with the focus on the centre of the field of view and the lower saccade amplitudes points to an intact brainstem function, the decrease in peripheral visual exploration may be attributed to a position-dependent dysfunction of the frontal eye field.

BACKGROUND:The COVID-19 pandemic has greatly increased the incidence and clinical importance of critical illness myopathy (CIM), because it is one of the most common complications of modern intensive care medicine. Current diagnostic criteria only allow diagnosis of CIM at an advanced stage, so that patients are at risk of being overlooked, especially in early stages. To determine the frequency of CIM and to assess a recently proposed tool for early diagnosis, we have followed a cohort of COVID-19 patients with acute respiratory distress syndrome and compared the time course of muscle excitability measurements with the definite diagnosis of CIM.METHODS:Adult COVID-19 patients admitted to the Intensive Care Unit of the University Hospital Bern, Switzerland requiring mechanical ventilation were recruited and examined on Days 1, 2, 5, and 10 post-intubation. Clinical examination, muscle excitability measurements, medication record, and laboratory analyses were performed on all study visits, and additionally nerve conduction studies, electromyography and muscle biopsy on Day 10. Muscle excitability data were compared with a cohort of 31 age-matched healthy subjects. Diagnosis of definite CIM was made according to the current guidelines and was based on patient history, results of clinical and electrophysiological examinations as well as muscle biopsy.RESULTS:Complete data were available in 31 out of 44 recruited patients (mean [SD] age, 62.4 [9.8] years). Of these, 17 (55%) developed CIM. Muscle excitability measurements on Day 10 discriminated between patients who developed CIM and those who did not, with a diagnostic precision of 90% (AUC 0.908; 95% CI 0.799-1.000; sensitivity 1.000; specificity 0.714). On Days 1 and 2, muscle excitability parameters also discriminated between the two groups with 73% (AUC 0.734; 95% CI 0.550-0.919; sensitivity 0.562; specificity 0.857) and 82% (AUC 0.820; CI 0.652-0.903; sensitivity 0.750; specificity 0.923) diagnostic precision, respectively. All critically ill COVID-19 patients showed signs of muscle membrane depolarization compared with healthy subjects, but in patients who developed CIM muscle membrane depolarization on Days 1, 2 and 10 was more pronounced than in patients who did not develop CIM.CONCLUSIONS:This study reports a 55% prevalence of definite CIM in critically ill COVID-19 patients. Furthermore, the results confirm that muscle excitability measurements may serve as an alternative method for CIM diagnosis and support its use as a tool for early diagnosis and monitoring the development of CIM.

Background:Brain fog is a common and highly disturbing symptom for patients with neuropathic postural tachycardia syndrome (POTS). Cognitive deficits have been measured exclusively in the upright body position and mainly comprised impairments of higher cognitive functions. The cause of brain fog is still unclear today. This study aimed to investigate whether increased autonomic activation might be an underlying mechanism for the occurrence of brain fog in neuropathic POTS. We therefore investigated cognitive function in patients with neuropathic POTS and a healthy control group depending on body position and in relation to catecholamine release as a sensitive indicator of acute stress. The second aim was to test the effect of water intake on cardiovascular regulation, orthostatic symptoms, cognitive function and catecholamine release.Methods:Thirteen patients with neuropathic POTS and 15 healthy control subjects were included. All participants completed a total of four rounds of cognitive testing: two before and two after the intake of 500 ml still water, each first in the supine position and then during head-up tilt. At the end of each cognitive test, a blood sample was collected for determination of plasma catecholamines. After each head-up tilt phase participants were asked to rate their current symptoms on a visual analogue scale.Results:Working memory performance in the upright body position was impaired in patients, which was associated with self-reported symptom severity. Patients had elevated plasma norepinephrine independent of body position and water intake that increased excessively in the upright body position. The excessive increase of plasma norepinephrine was related to heart rate and symptom severity. Water intake in patients decreased norepinephrine concentrations and heart rate, and improved symptoms as well as cognitive performance.Conclusion:Brain fog and symptom severity in neuropathic POTS are paralleled by an excessive norepinephrine secretion. Bolus water drinking down-regulates norepinephrine secretion and improves general symptom severity including brain fog.

Background: Postural tachycardia syndrome (POTS) is a form of autonomic dysregulation. There is increasing evidence that the etiology may be immune-mediated in a subgroup of patients. Patients with POTS often experience an exacerbation of their symptoms associated with (viral) infections and often fear the same symptom aggravation after vaccination. In this report we describe the tolerability of messenger ribonucleic acid (mRNA) vaccines against coronavirus disease 19 (COVID-19) and the consequences of a COVID-19 infection on POTS symptoms in our cohort of patients with neuropathic POTS. Methods: We conducted a standardized, checklist-based interview with 23 patients and recorded the acute side effects of mRNA vaccination, acute symptoms of COVID-19 infection as well as the effects of vaccination and COVID-19 infection on POTS symptoms. Results: Of all included patients, 20 patients received two mRNA vaccines without having had a previous COVID-19 infection, and five patients in total had suffered a COVID-19 infection. Of these, three had COVID-19 without and two after being vaccinated. No increased frequency of side effects after both doses of mRNA vaccines was observed. Six patients reported a mild and short-term aggravation of their POTS symptoms beyond the duration of acute vaccine side effects. All five patients who suffered a COVID-19 infection subsequently reported a pronounced and persistent exacerbation of POTS symptoms. Conclusions: Our observations suggest that mRNA vaccines are not associated with a higher frequency of acute side effects in patients with POTS. Symptom exacerbation as a consequence of mRNA vaccination seems to be less frequent and of shorter duration compared to patients who suffered a COVID-19 infection.

Purpose of review Critical illness myopathy (CIM) is a common neuro-muscular complication of intensive care treatment associated with increased morbidity and mortality. The current guidelines for diagnosis include clinical and electrophysiological criteria as well as a muscle biopsy, and allow diagnosis only at an advanced stage of the disease. To date, there is no treatment for CIM available, apart from symptomatic and rehabilitative interventions. In this review, we discuss different diagnostic approaches and describe new treatment possibilities for CIM. Recent findings Of the diagnostic approaches evaluated, a new electrophysiological technique for measuring muscle excitability has the greatest potential to allow earlier diagnosis of CIM than the current guidelines do and thereby may facilitate the conduction of future pathophysiological and therapeutic studies. Although clinical trials are still lacking, in animal models, BGP-15, vamorolone, and ruxolitinib have been shown to have anti-inflammatory effects, to reduce muscle wasting and to improve muscle function and survival. Summary In recent years, promising methods for early and confirmatory diagnosis of CIM have been developed, but still need validation. Experimental studies on novel pharmacological interventions show promising results in terms of preventive CIM treatments, but future clinical studies will be needed to study the effectiveness and safety of these drugs.

Background: Postural tachycardia syndrome (POTS) is a form of autonomic dysregulation. There is increasing evidence that the etiology may be immune-mediated in a subgroup of patients. Patients with POTS often experience an exacerbation of their symptoms associated with (viral) infections and often fear the same symptom aggravation after vaccination. In this report we describe the tolerability of messenger ribonucleic acid (mRNA) vaccines against coronavirus disease 19 (COVID-19) and the consequences of a COVID-19 infection on POTS symptoms in our cohort of patients with neuropathic POTS. Methods: We conducted a standardized, checklist-based interview with 23 patients and recorded the acute side effects of mRNA vaccination, acute symptoms of COVID-19 infection as well as the effects of vaccination and COVID-19 infection on POTS symptoms. Results: Of all included patients, 20 patients received two mRNA vaccines without having had a previous COVID-19 infection, and five patients in total had suffered a COVID-19 infection. Of these, three had COVID-19 without and two after being vaccinated. No increased frequency of side effects after both doses of mRNA vaccines was observed. Six patients reported a mild and short-term aggravation of their POTS symptoms beyond the duration of acute vaccine side effects. All five patients who suffered a COVID-19 infection subsequently reported a pronounced and persistent exacerbation of POTS symptoms. Conclusions: Our observations suggest that mRNA vaccines are not associated with a higher frequency of acute side effects in patients with POTS. Symptom exacerbation as a consequence of mRNA vaccination seems to be less frequent and of shorter duration compared to patients who suffered a COVID-19 infection.

PURPOSE:In neuropathic postural tachycardia syndrome, peripheral sympathetic dysfunction leads to excessive venous blood pooling during orthostasis. Up to 84% of patients report leg pain and weakness in the upright position. To explore possible pathophysiological processes underlying these symptoms, the present study examined muscle excitability depending on body position in patients with neuropathic postural tachycardia syndrome and healthy subjects.METHODS:In ten patients with neuropathic postural tachycardia syndrome and ten healthy subjects, muscle excitability measurements were performed repeatedly: in the supine position, during 10 min of head-up tilt and during 6 min thereafter. Additionally, lower leg circumference was measured and subjective leg pain levels were assessed.RESULTS:In patients with neuropathic postural tachycardia syndrome, muscle excitability was increased in the supine position, decreased progressively during tilt, continued to decrease after being returned to the supine position, and did not completely recover to baseline values after 6 min of supine rest. The reduction in muscle excitability during tilt was paralleled by an increase in lower leg circumference as well as leg pain levels. No such changes were observed in healthy subjects.CONCLUSIONS:This study provides evidence for the occurrence of orthostatic changes in muscle excitability in patients with neuropathic postural tachycardia syndrome and that these may be associated with inadequate perfusion of the lower extremities. Insufficient perfusion as a consequence of blood stasis may cause misery perfusion of the muscles, which could explain the occurrence of orthostatic leg pain in neuropathic postural tachycardia syndrome.

Introduccion: la COVID-19 es unaenfermedad respiratoria producida por el nuevo coronavirus SARS-CoV-2, constituye una pandemia a nivel mundial, por lo que representa una epidemia que ninguno de los profesionales de la salud puede ignorar. Objetivo: caracterizar la epidemiologia y terapeutica de la COVID-19 en el Hospital General «Vladimir Ilich Lenin» de Holguin. Metodos: se realizo un estudio descriptivo y observacional en pacientes del Hospital General «Vladimir Ilich Lenin» en Holguin, de enero a junio de 2020. De un universo de 546 pacientes ingresados por la COVID 19 de las areas de salud en estudio, se seleccionaron como muestra 30 pacientes. Se emplearon metodos teoricos y empiricos; se realizo analisis estadistico de los datos obtenidos y se reflejaron en tablas. Resultados: las edades entre 76 y 100 anos representan la mayor parte del total. Sobresalio el sexo masculino (57%). Prevalecieron los sintomas de: fiebre, cefalea ymialgia. Existio un predominio de pacientes con enfermedades cronicas no transmisibles (67%). La mejoria fue asociada al tratamiento combinado (30%). Conclusiones: En la investigacion existio un predominio de las edades extremas de la vida; se destacoel sexo masculino. La sintomatologia mas presentada fue: fiebre, cefalea y mialgia. Existio un predominio de pacientes con enfermedades cronicas no transmisibles. La mejoria con el tratamiento combinado con Interferon y Kaletra resulto superior al tratamiento simple.

The technique of multifiber muscle velocity recovery cycle recordings was developed as a diagnostic tool to assess muscle membrane potential changes and ion channel function in vivo. This study was undertaken to assess the impact of intermittent high-frequency stimulation on muscle velocity recovery cycle components and to study whether the changes can be modified by endurance training. We recorded muscle velocity recovery cycles with 1 and 2 conditioning stimuli in the left tibialis anterior muscle in 15 healthy subjects during intermittent 37-Hz stimulation and analyzed its effects on the different phases of supernormality. Recordings were conducted before and after 2-wk endurance training. Training effect was assessed by measuring the difference in endurance time, peak force, and limb circumference. Muscle velocity recovery cycle recordings during intermittent high-frequency stimulation were successfully recorded in 12 subjects. Supernormality for interstimulus intervals shorter than 15 ms (early supernormality) was maximally reduced at the beginning of repetitive stimulation and recovered during stimulation. Supernormality for interstimulus intervals between 50 and 150 ms (late supernormality) showed a delayed decrease and stayed significantly reduced after high-frequency stimulation. Training had no significant effect on any of the measured parameters, but we found that training induced changes in peak force correlated positively with baseline changes of early supernormality. Our results support the hypothesis that early supernormality represents membrane potential, which depolarizes in the beginning of high-frequency stimulation. Late supernormality probably reflects transverse tubular function and shows progressive changes during high-frequency stimulation with delayed normalization.NEW & NOTEWORTHY A conditioning impulse in human muscle fibers induces a prolonged phase of increased velocity (also called supernormality) with two phases related to an early and late afterpotential. We investigated the effects of intermittent 37-Hz stimulation on muscle fiber supernormality and found that the early and late phases of supernormality changed differently, and that the late phase may reflect the ionic interactions responsible for the counter-regulation of muscle fatigue.

Background: Delayed cerebral ischemia and cerebral vasospasm remain the leading causes of poor outcome in survivors of aneurysmal subarachnoid hemorrhage. Refractory cerebral vasospasms can be treated with endovascular vasodilator therapy, which can either be performed in conscious sedation or general anesthesia. The aim of this study is to compare the effect of the anesthesia modality on long-term clinical outcomes in patients undergoing endovascular vasodilator therapy due to cerebral vasospasm and hypoperfusion. Methods: Modified Rankin Scale (mRS) scores were retrospectively analyzed at time of discharge from the hospital and six months after aneurysmal subarachnoid hemorrhage. Additionally, National Institutes of Health Stroke Scale (NIHSS) was assessed 24 hours before, immediately before, immediately after, and 24 hours after endovascular vasodilator therapy, and at discharge and six months. Interventional parameters such as duration of intervention, choice and dosage of vasodilator and number of arteries treated were also recorded. Results: A total of 98 patients were included in this analysis and separated into patients who had interventions in conscious sedation, general anesthesia and a mix of both. Neither mRS at discharge nor at six months showed a significant difference for functionally independent outcomes (mRS 0-2) between groups. NIHSS before endovascular vasodilator therapy was significantly higher in patients receiving interventions in general anesthesia but did not differ anymore between groups six months after the initial bleed. Conclusion: This study did not observe a difference in outcome whether patients underwent endovascular vasodilator therapy in general anesthesia or conscious sedation for refractory cerebral vasospasms. Hence, the choice should be made for each patient individually.

BACKGROUND AND PURPOSE:Postural tachycardia syndrome (POTS) is a form of autonomic dysfunction characterized by symptoms of orthostatic intolerance, often accompanied by sudomotor dysfunction and gastrointestinal dysmotility. Recently, evidence has accumulated that in a subset of patients, the pathogenesis of dysautonomia may be immune-mediated. The aim of the current report was to evaluate the use of intravenous immunoglobulin (IVIG) treatment in patients with progressive and/or refractory immune-mediated POTS.METHODS:We retroactively assessed the effect and tolerance of monthly administered IVIG in six patients using autonomic function testing, standardized symptom questionnaires, and patients' symptom diaries both before and 6 months into IVIG treatment. Objective outcome measures included heart rate increase after 10 min of head-up tilt as well as duration and anhidrotic area in a thermoregulatory sweat test. Subjective outcome measures were patient reports and symptom ratings from the symptom questionnaire.RESULTS:All patients responded to immunomodulatory treatment, regardless of disease duration. After 6 months of IVIG, symptom severity was reduced by nearly 40%. Autonomic function testing showed improved cardiovascular functioning by 50% and a reduction of anhidrotic areas by one third. Overall, tolerance of IVIG treatment was poor, but could be improved by a reduction in infusion rate, premedication with steroids, and additional intravenous hydration.CONCLUSIONS:Using subjective but also standardized objective measures, the case series describes promising effects of IVIG treatment in POTS patients with immune-mediated dysautonomia. By reducing the infusion rate, pretreatment with steroids, and intravenous hydration, tolerance could be improved, and no patient had to discontinue the treatment.

Background Postural orthostatic tachycardia syndrome is a disorder of the autonomic nervous system. Approximately 30% of patients experience orthostatic headaches. Orthostatic headaches also are a hallmark symptom in spontaneous intracranial hypotension. While the cause of orthostatic headaches in spontaneous intracranial hypotension can be linked to the cerebrospinal fluid loss at the spinal level and consecutively reduced intracranial pressure in the upright position, the cause of orthostatic headaches in postural orthostatic tachycardia syndrome still remains unknown. The present study examined orthostatic changes of intracranial pressure using dynamic ultrasound of the optic nerve and optic nerve sheath diameter in postural orthostatic tachycardia syndrome, spontaneous intracranial hypotension and healthy subjects. Methods Data was obtained from postural orthostatic tachycardia syndrome patients with (n = 7) and without orthostatic headaches (n = 7), spontaneous intracranial hypotension patients (n = 5) and healthy subjects (n = 8). All participants underwent high-resolution transorbital ultrasound in the supine and upright position to assess optic nerve and optic nerve sheath diameter. Results Group differences were found in percentage deviations when changing position of optic nerve sheath diameter (p < 0.01), but not regarding the optic nerve diameter. Pairwise comparisons indicated differences in optic nerve sheath diameter only between spontaneous intracranial hypotension and the other groups. No differences were found between postural orthostatic tachycardia syndrome patients with and without orthostatic headaches. Conclusion This study shows that the size of the optic nerve sheath diameter dynamically decreases during orthostatic stress in spontaneous intracranial hypotension, but not in postural orthostatic tachycardia syndrome with or without orthostatic headaches, which indicates different underlying causes.

Background: Postural tachycardia syndrome (POTS) is a form of autonomic dysregulation and is characterized by an excessive heart rate (HR) increment upon the upright body position while blood pressure is maintained. Patients experience typical symptoms of orthostatic intolerance such as dizziness, nausea and cognitive impairments. The present study assessed position-dependent attentional and cognitive functioning in POTS patients compared to healthy subjects and tested the response of cognitive performance to acute water intake. Methods: Data was obtained from eight patients with neuropathic POTS and eight healthy subjects of similar age and gender. All participants completed questionnaires that assessed health-related quality of life and depression and underwent four rounds of neuropsychological testing overall, each before and after the intake of 500 ml still mineral water and both in the supine and in the upright posture. Results: Postural tachycardia syndrome patients showed deficits in working memory (WM) exclusively in the upright position compared to healthy subjects, but no position-dependent impairments in alertness or divided attention. Rapid water ingestion had a beneficial effect on WM in the upright posture, lead to a decrease in HR increment and to an improvement of subjective symptom experience. Conclusion: The results provide support for the occurrence of purely orthostatic cognitive deficits in POTS, especially when increased executive control and cognitive resources are required and document a favorable effect of water intake on cognitive performance. These findings have important implications for the management of cognitive symptoms in POTS as high water intake is an easy and accessible strategy.