Restless legs syndrome (RLS) är ett vanligt sensorimotoriskt tillstånd som kännetecknas av obehagliga förnimmelser i benen i vila, ett starkt rörelsebehov samt ofta uttalad sömnstörning. Tillståndet är associerat med dysreglering i monoaminerga och glutamaterga system, förändrad järnmetabolism i centrala nervsystemet samt ökad spinal och central excitabilitet. Trots etablerad farmakologisk behandling kvarstår en grupp patienter med otillräcklig effekt eller behandlingsbegränsningar, vilket motiverar undersökning av alternativa eller kompletterande strategier.

Denna rapport sammanfattar och analyserar det aktuella kunskapsläget kring två icke-invasiva neuromodulatoriska metoder: transkutan elektrisk nervstimulering (TENS) och transkutan aurikulär vagusnervstimulering (taVNS). TENS verkar huvudsakligen genom perifer afferent aktivering och modulering av spinal excitabilitet, medan taVNS påverkar centrala neuromodulatoriska system via afferenta vagusbanor. Studier av transkutan spinal direktströmsstimulering (tsDCS) diskuteras som en neurofysiologisk referensram för elektrisk modulering av spinala och centrala nätverk.

För TENS föreligger preliminärt stöd från mindre kliniska studier, inklusive randomiserade prövningar, med rapporterad symtomlindring och förbättrad sömnkvalitet. För taVNS är evidensläget mer begränsat och huvudsakligen baserat på pilotstudier hos patienter med svår farmakorefraktär RLS. För samtliga metoder överstiger den mekanistiska plausibiliteten den kliniska evidensstyrkan.

Sammantaget framstår icke-invasiv elektrisk neuromodulation som ett biologiskt rimligt och forskningsmässigt motiverat angreppssätt vid RLS. Väl designade, sham-kontrollerade studier med objektiva utfallsmått och systematisk dosoptimering är dock nödvändiga för att fastställa metodernas kliniska roll.

Restless legs syndrome (RLS) is a common sensorimotor disorder characterized by uncomfortable sensations in the legs at rest, an urge to move, and frequently significant sleep disturbance. The condition is associated with dysregulation of monoaminergic and glutamatergic systems, altered central iron metabolism, and increased spinal and central excitability. Despite established pharmacological treatments, a subgroup of patients experiences insufficient symptom control or treatment-related limitations, highlighting the need to explore complementary or alternative therapeutic strategies.

This report summarizes and analyzes the current state of knowledge regarding two non-invasive neuromodulatory approaches: transcutaneous electrical nerve stimulation (TENS) and transcutaneous auricular vagus nerve stimulation (taVNS). TENS primarily acts through peripheral afferent activation and modulation of spinal excitability, whereas taVNS influences central neuromodulatory systems via afferent vagal pathways. Studies of transcutaneous spinal direct current stimulation (tsDCS) are discussed as a neurophysiological reference framework for electrical modulation of spinal and central networks.

For TENS, preliminary support exists from smaller clinical studies, including randomized trials, reporting symptom reduction and improved sleep quality. For taVNS, the evidence base remains more limited and is largely derived from pilot studies in patients with severe, pharmacoresistant RLS. For all methods, mechanistic plausibility currently exceeds the strength of clinical evidence.

Overall, non-invasive electrical neuromodulation appears to represent a biologically plausible and scientifically motivated approach in RLS. However, well-designed, sham-controlled trials with objective outcome measures and systematic dose optimization are required to clarify the clinical role of these interventions.

Denna skrift ger en översikt över transkutan aurikulär vagusnervstimulering (taVNS) som ett potentiellt behandlingsalternativ vid post COVID-19 och flera associerade symtom. Vagusnerven spelar en central roll i regleringen av autonoma funktioner, inflammation, kognition och emotion, och vagal hypoaktivitet har föreslagits bidra till patofysiologin vid långvariga postvirala tillstånd. taVNS, som stimulerar vagusgrenarna i ytterörat, erbjuder ett icke-invasivt sätt att modulera dessa system.

För kliniker är det centrala budskapet att taVNS inte riktar sig mot endast ett enskilt post-COVID-19-symtom, utan mot flera samverkande patofysiologiska processer.Metoden kan därför vara särskilt relevant hos patienter med kombinerad fatigue, hjärndimma, autonom dysfunktion och sömnstörning, där traditionell symtomfokuserad behandling ofta ger begränsad effekt. taVNS bör i nuläget betraktas som en biologiskt plausibel, låg-risk adjuvant behandling inom ramen för rehabilitering.

Artikeln lyfter fram två huvudsakliga mekanismer av särskild relevans vid post COVID-19: aktivering av den kolinerga antiinflammatoriska reflexen (CAP), vilket kan dämpa proinflammatoriska cytokiner såsom IL-1β, IL-6 och TNF-α, samt återställning av autonom balans genom ökad vagustonus och minskat sympatikuspåslag. Mindre kliniska pilotstudier indikerar förbättring av trötthet, ångest, kognitiv påverkan, sömn och andfåddhet efter taVNS, med god säkerhetsprofil, men resultaten är ännu inte bekräftade i större randomiserade kontrollerade studier.

Ett särskilt fokus ägnas fatiguesyndromet, där tre mekanistiska nivåer integreras: perifer inflammation och ”sickness behavior”, autonom dysreglering med låg HRV och sympatikusdominans, samt central neurobiologisk påverkan i locus coeruleus och frontala nätverk. taVNS kan teoretiskt modulera samtliga dessa nivåer och därigenom bidra till att bryta mekanismer som upprätthåller kronisk fatigue. Liknande resonemang förs för hjärndimma och sömnstörningar, där taVNS genom påverkan på centrala nätverk, autonom balans och neuroinflammation kan ha potentiell klinisk relevans.

Artikeln sammanfattar att taVNS är en biologiskt plausibel och lovande, men ännu bara en preliminärt evidensbaserad behandlingsmetod och betonar behovet av större randomiserade studier med objektiva biomarkörer för att fastställa effekt och optimala behandlingsparametrar.

This article provides an overview of transcutaneous auricular vagus nerve stimulation (taVNS) as a potential treatment option for post COVID-19 and several associated symptoms. The vagus nerve plays a central role in regulating autonomic function, inflammation, cognition, and emotion, and vagal hypoactivity has been proposed to contribute to the pathophysiology of prolonged post-viral conditions. taVNS, which stimulates vagal branches in the external ear, offers a non-invasive means of modulating these systems.

For clinicians, the key message is that taVNS does not target a single post COVID-19 symptom, but rather multiple interacting pathophysiological processes. The method may therefore be particularly relevant for patients presenting with combined fatigue, cognitive impairment (“brain fog”), autonomic dysfunction, and sleep disturbance, where traditional symptom-focused treatments often provide limited benefit. At present, taVNS should be regarded as a biologically plausible, low-risk adjuvant treatment within rehabilitation.

The article highlights two main mechanisms of relevance to post COVID-19: activation of the cholinergic anti-inflammatory pathway (CAP), which may attenuate pro-inflammatory cytokines such as IL-1β, IL-6, and TNF-α, and restoration of autonomic balance through increased vagal tone and reduced sympathetic activation. Small clinical pilot studies indicate improvements in fatigue, anxiety, cognitive impairment, sleep, and dyspnea following taVNS, with a favorable safety profile; however, these findings have not yet been confirmed in larger randomized controlled trials.

A particular focus is placed on fatigue syndromes, integrating three mechanistic levels: peripheral inflammation and “sickness behavior”, autonomic dysregulation characterized by low heart rate variability (HRV) and sympathetic dominance, and central neurobiological effects involving the locus coeruleus and frontal networks. taVNS may theoretically modulate all of these levels and help disrupt mechanisms that sustain chronic fatigue. Similar reasoning is applied to cognitive impairment and sleep disturbances, where taVNS, through effects on central networks, autonomic balance, and neuroinflammation, may have potential clinical relevance.

The article concludes that taVNS represents a biologically plausible and promising, but still preliminarily evidence-based, therapeutic approach and emphasizes the need for larger randomized studies incorporating objective biomarkers to establish efficacy and determine optimal treatment parameters.

Denna skrift beskriver nya potentiella möjligheter att använda neuromodulering i form av transkutan vagusstimulering (tVNS) som adjuvant behandling av såväl akut stroke, som mer kroniska resttillstånd efter stroke. Detta bygger främst på att använda sig av vagusstimuleringens (VNS) väldokumenterade effekter att ändra den autonoma balansen mot en minskad sympatisk tonus med framförallt olika antiinflammatoriska mekanismer som följd. VNS kan också neuromodulatoriskt öka plasticiteten i, och påverka de funktionella kopplingarna mellan olika delar av centrala nervsystemet.

Vad gäller den akuta fasen av stroke så beskriver rapporten det prekliniska underlaget för hur olika former av tVNS vid ischemisk stroke (”propp”) skulle kunna minska storleken på infarktens utbredning, volym och förekomst av reperfusionsskador, minska neuroinflammation, oxidativ stress, och programmerad celldöd, skydda blodhjärnbarriären och mitrokondriefunktionen med minskad grad av depolarisering och excitotoxitet som följd, men sist men inte minst också kunna ge en förbättrad funktionsförmåga. tVNS möjlighet att minska reperfusionsskador i samband med trombektomi och trombolys diskuteras.

Den i preklinisk och klinisk vetenskaplig litteratur hittills rapporterade användningen av VNS i samband med akut ischemisk stroke, men också i samband ischemi och reperfusion vid andra tillstånd utöver cerebral stroke redovisas. Även beskrivningar av effekterna av VNS i samband med hemorragisk stroke (”blödning”) framgår av rapporten.

Vad gäller den mer kroniska fasen av strokesjukdom beskriver rapporten hur man med transkutan aurikulär vagusstimulering (taVNS) via stimulering av ytterörat kan förbättra kroppens autonoma reglering, modulera inflammatoriska processer, men också förbättra strokepatienternas motoriska och sensoriska funktioner samt positivt påverka den kognitiva och emotionella återhämtningen. Metoder och resultat av olika kliniska studier av motorisk och sensorisk rehabiliteringsträning med komplement av VNS redovisas tillsammans med en översikt kring pågående eller planerade framtida kliniska studier av taVNS och kronisk cerebral stroke. Rapporten innehåller för behandling av akut respektive kronisk stroke också lite av en framtidsspaning över planerade framtida kliniska studier av tVNS och olika former av cerebral stroke, men också vilka medicintekniska lösningar som redan idag finns tillgängliga på prototypstadiet för klinisk prövning.

This text describes new potential opportunities for using neuromodulation in the form of transcutaneous vagus nerve stimulation (tVNS) as an adjunctive treatment for both acute stroke and more chronic residual conditions following stroke. This approach is primarily based on utilizing the well-documented effects of vagus nerve stimulation (VNS) in altering the autonomic balance toward a reduced sympathetic tone, primarily resulting in various anti-inflammatory mechanisms. Additionally, VNS can act as a neuromodulatory tool to enhance plasticity and influence the functional connections between different parts of the central nervous system.

Regarding the acute phase of stroke, the report outlines preclinical evidence showing how different forms of tVNS could impact ischemic stroke ("blockage") by reducing the extent, volume, and occurrence of reperfusion injuries, decreasing neuroinflammation, oxidative stress, apoptosis, and pyroptosis, and protecting the blood-brain barrier and mitochondrial function. This would result in reduced depolarization and excitotoxicity, and most importantly, improved functional outcomes. The potential of tVNS to mitigate reperfusion injuries during thrombectomy and thrombolysis is also discussed.

The use of VNS in connection with acute ischemic stroke, as reported in preclinical and clinical scientific literature, as well as in cases of ischemia and reperfusion in conditions beyond cerebral stroke, is presented. The report also includes descriptions of the effects of VNS in connection with hemorrhagic stroke ("bleeding").

Regarding the more chronic phase of stroke, the report describes how transcutaneous auricular vagus nerve stimulation (taVNS), applied via stimulation of the outer ear, can improve the body's autonomic regulation, modulate inflammatory processes, enhance motor and sensory functions in stroke patients, and positively affect cognitive and emotional recovery. Methods and results from various clinical studies on motor and sensory rehabilitation training complemented by VNS are presented, along with an overview of ongoing or planned future clinical studies on taVNS and chronic cerebral stroke. The report includes a forward-looking perspective on planned future clinical studies of taVNS for treating both acute and chronic stroke, as well as a discussion of the medical device solutions currently available for clinical trials.

Introduction: The COVID-19 pandemic flooded intensive care units with patients needing supportive care. In Scandinavia, the greater Stockholm area was among the most affected. This study aimed to capture healthcare workers’ conditions and challenges during this prolonged crisis, including perspectives from the intensive care team.

Methods: The data consist of 22 semistructured individual interviews with regular and temporary healthcare workers involved in the intensive care of COVID-19 patients, including nurse assistants, registered nurses, critical care nurses and consultant and junior physicians. Thematic analysis was used to analyse the data.

Results: The overarching theme that emerged was trying to create order in chaos . The theme encompassed four categories: adaptation with consequences, learning and growing while sacrificing my health, supporting and balancing staff resources without having enough, and challenging ICU values and standards . Each category comprised multiple subcategories.

Conclusion: Our study demonstrates challenges and identifies workarounds, support strategies and personnel learning experienced by COVID-19 intensive care teams in delivering patient care, ensuring patient safety and managing staff resilience. The findings can be used to better prepare for future crises.

Den här rapporten ger en översikt av den vetenskapliga litteraturen om användningen av elektrisk neuromodulering av det autonoma nervsystemet genom icke-invasiv transkutan aurikulär vagusnervstimulering, taVNS. Vagusnerven kan på ett icke-invasivt och säkert sätt stimuleras elektriskt via öronen med hjälp av vanligt förekommande apparatur för transkutan elektrisk nervstimulering, TENS. Ett stort antal prekliniska och kliniska studier har publicerats de senaste åren som beskriver mekanismerna för hur taVNS fungerar och dess potentiella kliniska användning, särskilt som en kompletterande behandling för olika medicinska tillstånd. De huvudsakliga verkningsmekanismerna verkar vara att taVNS kan minska sympatisk tonus, ha antiinflammatoriska effekter, öka plasticiteten i centrala nervsystemet samt ändra neurotransmission och funktionella kopplingar mellan olika delar av hjärnan. Stimulering av vagusnerven genom öronen erbjuder god patientsäkerhet och kan enkelt och skonsamt utföras till låg ekonomisk kostnad.

This report provides an overview of the scientific literature on the use of electrical neuromodulation of the autonomic nervous system through non-invasive transcutaneous auricular vagus nerve stimulation (taVNS). The vagus nerve can be electrically stimulated in a non-invasive and safe manner via the ears using commonly available transcutaneous electrical nerve stimulation (TENS) equipment. A large number of preclinical and clinical studies have been published in recent years describing the mechanisms of how taVNS works and its potential clinical applications, particularly as an adjunctive treatment for various medical conditions. The main mechanisms of action seem to be that taVNS can reduce sympathetic tone, have anti-inflammatory effects, increase plasticity in the central nervous system, and alter neurotransmission and functional connectivity between different parts of the brain. Stimulation of the vagus nerve through the ears offers good patient safety and can be performed easily and gently at a low economic cost.

Background: The COVID‐19 pandemic stretched Swedish intensive care unit (ICU) resources to an extent never experienced before, but even before the pandemic staffing was difficult and the number of staffed ICU beds was low. Studies have revealed high levels of COVID‐19 ICU staff burn‐out and fatigue, and as similar situations with high demands are likely to occur in the future a better understanding of resources that improve staff resilience is important. Using the job‐demand resource theory as a framework, we explored ICU professionals’ views on demands and resources when working in COVID‐19 ICUs with the aim to highlight factors that increased the job resources.

Methods: Data were collected via a web survey distributed to COVID‐19 ICU professionals, including both regular and temporary roles, working in 13 COVID‐19 ICU wards in Stockholm and Sörmland counties during the spring 2021. A total of 251 written responses to the question “What would have made work in the COVID‐19 ICU less demanding?” were analyzed using thematic analysis. One year later a member‐checking focus group interview was conducted to validate and further explore staff experiences.

Results: The main themes were work strategy, fairness and support, continuity, accessible leadership, introduction/information, and crisis preparedness. The analysis of the focus group conducted confirmed the main results and the extreme demands on ICU staff during the initial stages of the pandemic.

Conclusion: To increase staff health and performance in a long‐term crisis our results suggest; maintaining workplace leadership, scheduling work in advance and, when possible, schedule for recovery.

IntroductionThe COVID-19 pandemic has had a profound effect on many domains of healthcare. Even in high-income countries such as Sweden, the number of patients has vastly outnumbered the resources in affected areas, in particular during the first wave. Staff caring for patients with COVID-19 in intensive care units (ICUs) faced a very challenging situation that continued for months. This study aimed to describe burnout, safety climate and causes of stress among staff working in COVID-19 ICUs.MethodA survey was distributed to all staff working in ICUs treating patients with COVID-19 in five Swedish hospitals during 2020 and 2021. The numbers of respondents were 104 and 603, respectively. Prepandemic data including 172 respondents from 2018 served as baseline.ResultsStaff exhaustion increased during the pandemic, but disengagement decreased compared with prepandemic levels (p<0.001). Background factors such as profession and work experience had no significant impact, but women scored higher in exhaustion. Total workload and working during both the first and second waves correlated positively to exhaustion, as did being regular ICU staff compared with temporary staff. Teamwork and safety climate remained unchanged compared with prepandemic levels.Respondents reported 'making a mistake' as the most stressful of the predefined stressors. Qualitative analysis of open-ended questions identified 'lack of knowledge and large responsibility', 'workload and work environment', 'uncertainty', 'ethical stress' and 'organization and teamwork' as major causes of stress.ConclusionDespite large workloads, disengagement at work was low in our sample, even compared with prepandemic levels. High levels of exhaustion were reported by the ICU staff who carried the largest workload. Multiple significant causes of stress were identified, with fear of making a mistake the most significant stressor.

Sleep loss and psychosocial stress often co-occur in today's society, but there is limited knowledge on the combined effects. Therefore, this experimental study investigated whether one night of sleep deprivation affects the response to a psychosocial challenge. A second aim was to examine if older adults, who may be less affected by both sleep deprivation and stress, react differently than young adults. 124 young (18-30 years) and 94 older (60-72 years) healthy adults participated in one of four conditions: i. normal night sleep & Placebo-Trier Social Stress Test (TSST), ii. normal night sleep & Trier Social Stress Test, iii. sleep deprivation & Placebo-TSST, iv. sleep deprivation & TSST. Subjective stress ratings, heart rate variability (HRV), salivary alpha amylase (sAA) and cortisol were measured throughout the protocol. At the baseline pre-stress measurement, salivary cortisol and subjective stress values were higher in sleep deprived than in rested participants. However, the reactivity to and recovery from the TSST was not significantly different after sleep deprivation for any of the outcome measures. Older adults showed higher subjective stress, higher sAA and lower HRV at baseline, indicating increased basal autonomic activity. Cortisol trajectories and HRV slightly differed in older adults compared with younger adults (regardless of the TSST). Moreover, age did not moderate the effect of sleep deprivation. Taken together, the results show increased stress levels after sleep deprivation, but do not confirm the assumption that one night of sleep deprivation increases the responsivity to an acute psychosocial challenge.