Kristian Bernhard Nilsen

• Arora, Tarun; Almokdad, Mohammed; Sorensen, Daniel M.; Abrahao, Agessandro; Alaamel, Abir & Alaydin, Halil C [Show all 28 contributors for this article] (2026). Reliability and Agreement of CMAP Scan-Derived MUNE Algorithms in Healthy Individuals. IEEE Transactions on Biomedical Engineering. ISSN 0018-9294. p. 10–10. doi: 10.1109/tbme.2026.3728251. Full text in Research Archive
• Szczepanski, Tomasz Szymon; Nilsen, Kristian Bernhard; Dunker, Øystein; Reiner, Andrew Henry; Sand, Trond Halfdan & Tannemaat, Martijn [Show all 11 contributors for this article] (2026). Improving Indirect Methods for Calculating Reference Limits for Nerve Conduction Studies From Historical Data. Muscle and Nerve. ISSN 0148-639X. 74(2), p. 328–338. doi: 10.1002/mus.70281. Full text in Research Archive Show summary

  Introduction/Aims: High quality reference limits for nerve conduction studies (NCS) are essential for diagnosis of neuromuscular disorders. Examining healthy controls to calculate reference limits directly is expensive and time consuming. Indirect methods, including extrapolated norms (E-norms), extrapolated reference values (E-Ref), and multivariate extrapolated reference values (MeRef), use historical hospital data instead. These methods sort the historical measurements in increasing order, creating so called S-curves, and select normal measurements based on the shape of these S-curves. Current versions of these methods have several limitations, and we aimed to improve them by modifying how they select normal measurements. Methods: E-norms, E-Ref and MeRef were modified with new S-curve selection algorithms. The modified versions of the methods were used to calculate reference limits for common NCS measurements from a large historical database. The results were compared to reference limits calculated from 680 healthy subjects using Youden’s J statistic and z-score deviation. Results: The modified methods provided reference limits with Youden’s J > 0.8 and z-score deviation < 0.9 for most types of NCS measurements and similar or higher Youden’s J than the unmodified methods. In most cases, the methods required at least 500 measurements and fewer than 20% abnormal measurements for good performance. Discussion: Changing the S-curve selection algorithms improves E-norms, E-Ref, and MeRef. The modifications require a sufficient number and proportion of normal measurements in the historical database. When these prerequisites are met, a combination of indirect methods can be used when developing reference limits from historical patient data.

• Holme, Andreas Næss; Moen, Line Victoria; Sallinen, Mikael; Nilsen, Kristian Bernhard; Boccara, Charlotte & Phillips, Andrew JK [Show all 8 contributors for this article] (2026). Adaptation across consecutive night shifts at 71°N under Arctic summer daylight and winter darkness. Effects on alertness, sleepiness, and fatigue. Scandinavian Journal of Work, Environment and Health. ISSN 0355-3140. 52(4), p. 403–414. doi: 10.5271/sjweh.4295. Full text in Research Archive Show summary

  Objectives: This study aimed to investigate how alertness, sleepiness, and fatigue change across consecutive night compared to morning shifts among Arctic shift workers and whether these effects differ between seasons of midnight sun and polar night. Methods: We conducted an observational crossover study of 118 shift workers from an industrial plant at a high latitude (71°N) in northern Norway. Eighty-one individuals participated in both the light (near 24-hour daylight) and dark (minimal natural light) seasons. Work schedules included blocks of seven consecutive morning shifts and seven consecutive night shifts, separated by four rest days. Alertness (psychomotor vigilance test), subjective sleepiness (Karolinska Sleepiness Scale), and subjective fatigue were measured at the end of shifts on days 1, 3, and 6 of each shift block. We analyzed data using multilevel mixed-effects regression models with season, shift type (morning/night), and consecutive workday number as fixed effects. Results: Night shifts were linked to lower alertness and higher sleepiness and fatigue in both seasons, with the largest impairments on the first night. Across six consecutive night shifts, alertness improved and sleepiness and fatigue decreased, with similar trajectories in both seasons. There was no evidence that season significantly affected alertness, sleepiness, or fatigue. Conclusions: Night shifts generally impair alertness and increase sleepiness and fatigue, yet outcomes improved across consecutive nights. Despite the well-established effects of natural light on circadian rhythms, the seasonal photoperiod altered neither the shift-related impairments in alertness, sleepiness or fatigue nor the subsequent improvements across consecutive nights; workers showed similar adaptation in both seasons.

• Dunker, Øystein; Bergsjø, Leonora Onarheim; Severinsen, Gro-Hilde; Glette, Henrik & Nilsen, Kristian Bernhard (2026). Is accuracy enough? trust and barriers to AI-based clinical decision support in clinical neurophysiology. Clinical Neurophysiology Practice (CNP). 11, p. 262–270. doi: 10.1016/j.cnp.2026.04.003. Full text in Research Archive Show summary

  Objective To investigate attitudes, trust, expectations and concerns among patients and healthcare personnel regarding the use of AI-based clinical decision support systems (AI-CDSS) in clinical neurophysiology. Methods We iteratively designed a questionnaire and conducted a national survey of patients and healthcare personnel in Norway. Patients were recruited from a quality registry, while healthcare personnel and technicians were recruited from hospital laboratories. Items included binary and Likert-scale questions addressing attitudes, expectations, concerns and trust, as well as a scenario-based trust assessment. Between-group comparisons were performed using non-parametric and categorical statistical tests. Results Both groups reported positive attitudes toward AI-CDSS. Patients more often expected AI-CDSS to improve diagnostic accuracy (p = 0.005), while healthcare personnel anticipated improved equity of services across regions (p = 0.017). Key concerns in both groups were related to responsibility, doctor-patient relationships, AI literacy, overreliance on AI, and potential deskilling. The scenario-based question revealed lower trust when AI-CDSS directly influenced decision-making without physician involvement. Trust in public institutions was high, whereas trust in commercial or industry use of health data was consistently low. Conclusions Attitudes toward AI-CDSS in clinical neurophysiology are positive, but diagnostic accuracy isn’t enough: Acceptance is conditional on human oversight, delineated responsibilities, and steps taken to improve transparency and minimize deskilling. Patients want to share health data for AI purposes, but the commercial sector needs to build trust. Significance AI-CDSS in clinical neurophysiology is promising, but design and implementation need to address key concerns shared by both patients and health care personnel.

• Tronstad, Christian; Kleggetveit, Inge Petter; Arora, Tarun; Bakken, André; Nilsen, Kristian Bernhard & Pettersen, Fred-Johan (2025). Advancing possibilities in noninvasive nerve function testing with miniature sensory and motor nerve conduction instrumentation. IEEE Engineering in Medicine and Biology Society. Conference Proceedings. ISSN 1557-170X. doi: 10.1109/EMBC58623.2025.11253218. Full text in Research Archive
• Arora, Tarun; Thorgersen, Jørn Klepp; Jones, Kelvin Edward; Allen, Sara Maria; Schulze, Daniel Gregor & Dunker, Øystein [Show all 8 contributors for this article] (2025). Test-retest measurement properties of the MScanFit method for motor unit number estimation in individuals with Amyotrophic Lateral Sclerosis. Clinical Neurophysiology. ISSN 1388-2457. 178, p. 2110940–2110940. doi: 10.1016/j.clinph.2025.2110940. Full text in Research Archive
• Spildrejorde, Mari Roberts; Dunker, Øystein; Allen, Sara Maria; Kvaløy, Marie Bu; Uglem, Martin & Hjelland, Ina Elen [Show all 13 contributors for this article] (2025). Genome-wide association study of neuropathic pain. Pain. ISSN 0304-3959. doi: 10.1097/j.pain.0000000000003848. Full text in Research Archive Show summary

  Neuropathic pain is a complex chronic condition with a multifactorial etiology that includes genetic susceptibility. However, the genetic basis of neuropathic pain remains poorly understood. We aimed to investigate genetic variants associated with the presence and intensity of neuropathic pain using genome-wide association analyses in the GeNeuP cohort, comprised of 1146 deeply phenotyped individuals with peripheral neuropathy from Norway. Genotyping was performed using the Illumina Global Screening Array, and analyses were conducted to test associations with the presence and intensity of neuropathic pain. No significant associations were detected at the genome-wide significance level (P < 5 × 10−8) for either the presence or intensity of neuropathic pain. However, at the subthreshold level (P < 10−6), 3 single nucleotide polymorphisms (annotated to the CHRDL1 and MCF2L gene and a long non-coding RNA) were associated with intensity of neuropathic pain. A targeted candidate gene analysis of 163 genes previously implicated in neuropathic pain and neuropathy did not yield significant associations. These results highlight the complexity of the genetic architecture underlying neuropathic pain and the challenges in identifying common variants with detectable effects. The identification of subthreshold associations of genes involved in synaptic plasticity is intriguing and merits further investigation. Larger studies with refined phenotyping will be essential to validate these signals and to advance understanding of the genetic contributors to neuropathic pain.

• Szczepanski, Tomasz Szymon; Omland, Petter Moe; Dunker, Øystein; Sand, Trond Halfdan; Tannemaat, Martijn & Reijntjes, Robert [Show all 11 contributors for this article] (2025). Deriving reference limits from historical data – A comparison of four novel methods. Clinical Neurophysiology. ISSN 1388-2457. 182. doi: 10.1016/j.clinph.2025.2111451. Full text in Research Archive Show summary

  Objective To compare four novel methods – extrapolated norms (E-norms), extrapolated reference values (E-Ref), multivariable extrapolated reference values (MeRef) and mixture model clustering (MMC) – for obtaining reference limits for nerve conduction studies (NCS) from historical data containing both normal and abnormal studies. Methods Reference limits for 29 commonly clinically used NCS measurements were calculated from a historical database containing measurements from 24 618 patients using E-norms, E-ref, MeRef and MMC. The resulting reference limits were compared to reference limits for NCS calculated from 680 healthy subjects using Youden’s J statistics. Results Except for distal latencies, E-norms produced reference limits with the highest Youden’s J statistics with higher sensitivity, but lower specificity. E-Ref, MeRef and MMC produced reference limits with high specificity, but lower sensitivity than E-norms. Conclusions There are substantial differences in the performance of E-norms, E-Ref, MeRef and MMC. A dynamic approach, where the methods used are changed based on the type of NCS measurement and the amount of historical data available, may yield the highest accuracy. Significance When combining the different novel methods, it is possible to create clinically useful reference limits using historical data.

• Matre, Dagfinn; Haugen, Fred; Moe, Anne-Mari Gjestvang; Schjølberg, Tiril; Knardahl, Stein & Holm, Kathrine [Show all 7 contributors for this article] (2025). Experimental partial-night sleep restriction increases pain sensitivity, but does not alter inflammatory plasma biomarkers. Scandinavian Journal of Pain. ISSN 1877-8860. 25(1). doi: 10.1515/sjpain-2024-0081. Full text in Research Archive Show summary

  Objectives: Disturbed sleep and chronic pain are public health concerns. Sleep disturbances seem to influence inflammation and may contribute to the increased pain sensitivity after sleep restriction (SR), such as after night work. The primary objective of this study was to determine the effects of SR on pain sensitivity and on relevant markers of inflammation. A secondary objective was to determine if SR affected pain sensitivity and inflammatory responses differently in men and women. Methods: A paired crossover design with block randomization was applied. Subjects were instructed to follow their habitual sleep (HS) rhythm for two nights (HS condition) and to delay their bedtime to shorten their sleep with 50% for two nights (SR condition). Thirty-nine healthy volunteers between 19 and 44 years old participated (21 women). Experimental pain sensitivity was tested with heat-, electrical-, and pressure pain thresholds (PPTs); electrical temporal summation threshold; pinprick pain; suprathreshold heat pain tolerance; and rating of suprathreshold heat and cold pain. The following markers of inflammation were measured in plasma from a blood sample taken between 10:00 and 12:00: C-reactive protein, fractalkine, tumor necrosis factor, interleukin -8, and monocyte chemoattractant protein-1. Results: Most subjects did not comply with the SR instructions. Total sleep time during SR was on average 2.6 h shorter than during HS. Therefore, the SR condition was re-defined to be “at least 40% reduction in the time in bed (TIB) the last night.” The HS condition was re-defined to “at least 85% of normally reported TIB.” SR produced higher suprathreshold heat pain sensitivity and cold pressor pain, compared to HS, but no significant change in electrical pain threshold, electrical temporal summation threshold, PPT, or any of the measured immune parameters. Sex-stratified analyses indicated that the effect on heat pain only occurred in women and that the effect on cold pressor pain was significant only in men. Conclusions: The present findings indicate that heat and cold pressor pain were rated higher following SR, whereas pain thresholds remained unchanged. We did not find an effect of SR on biomarkers of inflammation. The findings should be cautiously interpreted given the poor adherence to the SR condition.

• Brock, Christina; Andersen, Henning; Alibegovic, Amra Ciric; Andersen, Signe Toft; Andreasen, Laura Jul & Charles, Morten Haaning [Show all 35 contributors for this article] (2025). Barriers and new opportunities in developing effective therapies for diabetic neuropathy: International expert consensus recommendations. Diabetes Research and Clinical Practice. ISSN 0168-8227. 221. doi: 10.1016/j.diabres.2025.112010. Full text in Research Archive Show summary

  Background Diabetic neuropathy (DN) affects up to half of individuals with type 1 and type 2 diabetes. Despite evidence that improving metabolic and cardiovascular health can slow its progression, DN remains a significant clinical challenge due to the lack of disease-modifying therapies and effective pain management strategies. This consensus aimed to identify gaps and recommend strategies to address these challenges. Method A workshop, initiated by Steno Diabetes Centre Copenhagen and the Danish Diabetes and Endocrinology Academy, conducted a gap analysis based on insights from clinical studies, observational cohorts, and clinical practice. Online invitations targeted experienced clinicians, researchers, and drug developers committed to improving DN treatment through innovative clinical trials. Thirty-five participants from six countries reached consensus via a Delphi process on key steps to advance DN therapy. Result Four critical barriers and needs were addressed: (1) Translating bench research to clinical practice, (2) Enhancing clinical trial design, (3) Improving outcome measures, and (4) Identifying effective treatments for painful DN. Conclusion Successful interventional trials require robust outcome measures to capture clinically meaningful changes in DN phenotypes, providing the basis for developing effective, disease-modifying treatments.

• Sand, Trond Halfdan; Uglem, Martin; Johnsen, Gjermund; Grøtting, Arnstein; Dunker, Øystein & Sandvik, Jorunn [Show all 7 contributors for this article] (2025). Sensory Nerve Conduction Amplitudes and Z-Compounds Depend on Body Mass Index in Overweight and Obese Individuals. Muscle and Nerve. ISSN 0148-639X. 71(6), p. 1052–1062. doi: 10.1002/mus.28403. Full text in Research Archive Show summary

  Introduction/Aims: The association between body mass index (BMI) and nerve conduction study (NCS) amplitudes has not been adequately studied in overweight and obese subjects. Our aim was to estimate the impact of high BMI on NCS amplitudes and NCS summary measures. Methods: One hundred and seventy-five patients with previous gastric bypass surgery and 86 subjects from the general population had clinical evaluations and NCS of upper and lower limbs. Subjects with diabetes, mononeuropathy, or polyneuropathy (PNP) were excluded. Eighty-three former patients with a mean age of 48years (SD 8), BMI mean=34.3kg/m2 (range 22–60) and 62 control subjects from the general population with a mean age of 55 years (SD 11), BMI mean=26.6kg/m2 (range 19–40), were analyzed. Several Z-compounds were calculated from NCS parameters. Multiple linear regression models compared the impact of BMI on NCS amplitude measurements, corrected for height and age, and NCS-based Z-compounds. Results: Most sensory amplitudes and tibial nerve motor amplitude decreased significantly with increasing BMI. The magnitudes of association were comparable for BMI and age. A new Z-compound for sensory amplitudes correlated moderately strongly with BMI for subjects with BMI<30kg/m2 and BMI ≥30kg/m2 (standardized beta 0.55 and 0.47 respectively, p<0.0005). Discussion: Sensory NCS amplitudes depend on BMI in obese and non-obese subjects. Lower reference limits for several sensory amplitudes should probably be adjusted for BMI. Reference limits for amplitude-dependent Z-compounds should be corrected for BMI. The findings have relevance for all patients investigated with nerve conduction studies, in particular, patients with suspected axonal polyneuropathies.

• Bondjers, Kristina; Hyland, Philip; Atar, Dan; Christensen, Jan Olav; Nilsen, Kristian Bernhard & Reitan, Solveig Klæbo [Show all 12 contributors for this article] (2025). Burnout trajectories among healthcare workers during a pandemic, and predictors of change. BMC Health Services Research. 25(1). doi: 10.1186/s12913-025-12802-w. Full text in Research Archive Show summary

  Background: While several cross-sectional studies have suggested high burnout levels among health-care workers (HCW) during the Covid-19 pandemic, fewer studies have examined longitudinal trajectories of burnout. Objectives: To examine (1) trajectories of change in levels of burnout among Norwegian HCW during a one-year period in the mid-phase of the Covid-19 pandemic (second, third, and fourth incidence rate peaks), and (2) how demographic and occupational variables, and pandemic-related experiences (e.g., own infection, severe infection in family, friend, or colleague, caring for deceased patient with Covid-19) were associated with such change. Methods: Burnout was measured by the Copenhagen Burnout Inventory. Latent growth curve modeling was used to estimate trajectories of burnout symptoms, and predictors of starting point and rate of change in burnout levels. Results: Starting points of burnout scores were, on average, low-to-moderate. Women, younger HCW, those living alone, and nurses had higher initial scores. Overall, burnout scores remained mostly unchanged across the study period. However, lower burnout scores at the initial assessment were associated with increasing scores over time. Being exposed to patients with Covid-19 and having a Covid-19 infection were associated with increased burnout over time. Conclusions: While burnout symptoms among frontline health workers remained stable across the peaks of the Covid-19 pandemic overall, the study identified higher risk of worsening symptoms over time among certain demographic (younger personnel, females, and nurses) and highly exposed individuals and groups. These findings may be helpful for identifying frontline workers at particular risk of burnout during future public health emergencies.

• Akerlund, Mikael; Baskozos, Georgios; Li, Wenqianglong; Themistocleous, Andreas C.; Pascal, Mathilde M.V. & Rayner, N. William [Show all 40 contributors for this article] (2024). Genetic associations of neuropathic pain and sensory profile in a deeply phenotyped neuropathy cohort. Pain. ISSN 0304-3959. doi: 10.1097/j.pain.0000000000003463. Full text in Research Archive Show summary

  We aimed to investigate the genetic associations of neuropathic pain in a deeply phenotyped cohort. Participants with neuropathic pain were cases and compared with those exposed to injury or disease but without neuropathic pain as control subjects. Diabetic polyneuropathy was the most common aetiology of neuropathic pain. A standardised quantitative sensory testing protocol was used to categorize participants based on sensory profile. We performed genome-wide association study, and in a subset of participants, we undertook whole-exome sequencing targeting analyses of 45 known pain-related genes. In the genome-wide association study of diabetic neuropathy (N = 1541), a top significant association was found at the KCNT2 locus linked with pain intensity (rs114159097, P = 3.55 × 10−8). Gene-based analysis revealed significant associations between LHX8 and TCF7L2 and neuropathic pain. Polygenic risk score for depression was associated with neuropathic pain in all participants. Polygenic risk score for C-reactive protein showed a positive association, while that for fasting insulin showed a negative association with neuropathic pain, in individuals with diabetic polyneuropathy. Gene burden analysis of candidate pain genes supported significant associations between rare variants in SCN9A and OPRM1 and neuropathic pain. Comparison of individuals with the “irritable” nociceptor profile to those with a “nonirritable” nociceptor profile identified a significantly associated variant (rs72669682, P = 4.39 × 10−8) within the ANK2 gene. Our study on a deeply phenotyped cohort with neuropathic pain has confirmed genetic associations with the known pain-related genes KCNT2, OPRM1, and SCN9A and identified novel associations with LHX8 and ANK2, genes not previously linked to pain and sensory profiles, respectively.

• Turella, S.; Dankiewicz, J.; Ben-Hamouda, N.; Nilsen, Kristian Bernhard; Düring, J. & Endisch, C. [Show all 30 contributors for this article] (2024). EEG for good outcome prediction after cardiac arrest: A multicentre cohort study. Resuscitation. ISSN 0300-9572. 202. doi: 10.1016/j.resuscitation.2024.110319. Full text in Research Archive
• Dunker, Øystein; Szczepanski, Tomasz Szymon; Do, Hoang Oanh Pauline; Omland, Petter Moe; Lie, Marie Udnesseter & Sand, Trond Halfdan [Show all 8 contributors for this article] (2024). Harnessing historical data to derive reference limits – A comparison of e-norms to traditionally derived reference limits. Clinical Neurophysiology Practice (CNP). 9, p. 168–175. doi: 10.1016/j.cnp.2024.04.001. Full text in Research Archive Show summary

  Objective Nerve conduction studies (NCS) require valid reference limits for meaningful interpretation. We aimed to further develop the extrapolated norms (e-norms) method for obtaining NCS reference limits from historical laboratory datasets for children and adults, and to validate it against traditionally derived reference limits. Methods We compared reference limits obtained by applying a further developed e-norms with reference limits from healthy controls for the age strata’s 9–18, 20–44 and 45–60 years old. The control data consisted of 65 healthy children and 578 healthy adults, matched with 1294 and 5628 patients respectively. Five commonly investigated nerves were chosen: The tibial and peroneal motor nerves (amplitudes, conduction velocities, F-waves), and the sural, superficial peroneal and medial plantar sensory nerves (amplitudes, conduction velocities). The datasets were matched by hospital to ensure identical equipment and protocols. The e-norms method was adapted, and reference limit calculatio

• Stavås, Jon Are; Nilsen, Kristian Bernhard & Matre, Dagfinn (2024). The association between proportion of night shifts and musculoskeletal pain and headaches in nurses: a cross-sectional study. BMC Musculoskeletal Disorders. 25(1). doi: 10.1186/s12891-024-07196-5. Full text in Research Archive Show summary

  Background and purpose Shift work is associated with musculoskeletal pain and headaches, but little is known about how the intensity of shift work exposure is related to musculoskeletal pain and headaches. This study aimed to investigate whether a higher proportion of night shifts is associated with a higher occurrence of musculoskeletal pain and headaches. Furthermore, to investigate whether sleep duration can mediate this potential association. Method The study included 684 nurses in rotating shift work who responded to a daily questionnaire about working hours, sleep, and pain for 28 consecutive days. The data were treated cross-sectionally. Results A negative binomial regression analysis adjusted for age and BMI revealed that working a higher proportion of night shifts is not associated with a higher occurrence of musculoskeletal pain and headaches. On the contrary, those working ≥ 50% night shifts had a significantly lower occurrence of pain in the lower extremities than those who worked < 25% night shifts (IRR 0.69 95% CI 0.51, 0.94). There was no indication of a mediation effect with total sleep time (TST). Conclusion The results of this study indicate that working a higher proportion of night shifts is not associated with a higher occurrence of musculoskeletal pain and headaches.

• Ulvin, Line Maria Bedos; Nilsen, Kristian Bernhard; Taubøll, Erik; Etholm, Lars & Heuser, Kjell (2024). Sensitivity and specificity of the Salzburg EEG criteria for nonconvulsive status epilepticus. Annals of clinical and translational neurology. doi: 10.1002/acn3.52184. Full text in Research Archive Show summary

  Objective The Salzburg EEG criteria for nonconvulsive status epilepticus (NCSE) have been proposed as consensus criteria for NCSE. We aimed to perform an independent study of their diagnostic accuracy. Methods A prospective study was carried out at Oslo University Hospital, including all consecutive patients ≥15 years old who were referred for an EEG with an explicit or implicit question of NCSE from February 2020 to February 2022. Two independent EEG readers scored the included EEGs according to the Salzburg criteria and blinded to the clinical data. The reference standard was defined as the clinical diagnosis the patient received based on all available clinical and paraclinical data. Diagnostic accuracy in identifying “certain/possible NCSE” was assessed by calculating sensitivity, specificity, positive predictive value, and negative predictive value with their 95% confidence intervals. Results In total, 469 patients/EEGs were included in the study. The prevalence of NCSE according to the reference standard was 11% (n = 53). The criteria showed a sensitivity of 94% (95% CI: 92–96%), a specificity of 77% (95% CI: 73–81%), a positive predictive value of 34% (95% CI: 30–39%), and a negative predictive value of 99% (95% CI: 98–100%). False positives for “certain NCSE” (n = 16) included many serial seizures and stimulus-induced rhythmic and periodic discharges (SIRPIDs), as well as a focal cortical dysplasia. False positives for “possible NCSE” (n = 79) were mainly represented by different encephalopathies and postictality. Interpretation The low specificity of the Salzburg criteria calls for refinement before implementation into daily clinical practice.

• Porcheret, Kate Louise; Hopstock, Laila Arnesdatter & Nilsen, Kristian Bernhard (2024). Prevalence of insomnia in a general adult population cohort using different diagnostic criteria: The seventh survey of the Tromsø study 2015–2016. Sleep Medicine. ISSN 1389-9457. 119, p. 289–295. doi: 10.1016/j.sleep.2024.05.002. Full text in Research Archive Show summary

  Insomnia disorder is a subjective complaint of sleep dissatisfaction including both night-time and daytime symptoms. Currently there are three commonly used diagnostic manuals each with their own set of criteria, which is often credited for the wide range in insomnia prevalence reported by population-based studies, especially those with self-reported insomnia. However, there are limited studies directly comparing different criteria and little is known about associations with health outcomes. Thus, the aim of this study was to compare the most commonly used diagnostic criteria for insomnia from the literature and to explore the associations with a range of physical and mental health outcomes. We used data from 21,083 women and men from the seventh survey of the population-based Tromsø Study which included adults aged 40–99 years. A revised version of the Bergen Insomnia Scale was used to define insomnia based on the 4th (revised) and 5th edition of Diagnostic and Statistical Manual of Mental Disorders (DSM-IV-TR and DSM5), the 10th edition of the International Classification of Diseases (ICD-10), and the 3rd edition of the International Classification of Sleep Disorders (ICSD-3). We found the following prevalence of insomnia: DSM-IV-TR 23.6 %, DSM5 8.5 %, ICD-10 9.9 % and ICSD-3 20.0 %. When looking at each symptom, we found over half the participants classified as having insomnia using the DSM-IV-TR and ICSD-3 criteria did not report having impaired daytime functioning at least three days per week. Overall, participants with DSM5 and ICD-10 insomnia appeared to have worse health profiles, based on a higher percentage meeting the cut-off for possible anxiety or depression, reporting a psychological problem or chronic pain, and using antidepressants, painkillers or sleeping pills. However logistic regression models showed largely the same health factors had the same association with the odds for being classified as having insomnia disorder from each set of criteria. Overall, this study suggests that insomnia prevalence may be overestimated if daytime symptoms are not adequately included in accordance with current guidelines.

• Neverdahl, Jan Petter; Uglem, Martin; Matre, Dagfinn; Nilsen, Kristian Bernhard; Hagen, Knut & Gravdahl, Gøril Bruvik [Show all 8 contributors for this article] (2024). Endogenous pain modulation after sleep restriction in migraine: a blinded crossover study. The Journal of Headache and Pain. ISSN 1129-2369. 25(1). doi: 10.1186/s10194-024-01879-z. Full text in Research Archive Show summary

  Background: Patients with migraine are vulnerable to insufficient sleep, but the impact of sleep restriction is largely unknown. In addition, the importance of sleep may be different in patients with migraine who mostly have attack onsets during sleep, so called sleep-related migraine, compared to patients with non-sleep-related migraine. In this study we investigate the effect of sleep restriction on endogenous pain modulation in patients with migraine and healthy controls. We also compared the effect of sleep restriction in sleep-related and in non-sleep-related migraine. Methods: Measurements were conducted in 39 patients with migraine between attacks and 31 controls, once after habitual sleep and once after two consecutive nights of partial sleep restriction. There were 29 and 10 patients with non-sleep-related and sleep-related migraine respectively. Test stimulus was 2-min tonic noxious heat to the left volar forearm. Temporal summation was calculated as the regression coefficient for rated pain in the

• Sørensen, DM; Bostock, Hugh; Abrahao, A; Alaamel, A; Alaydin, HC & Ballegaard, M [Show all 32 contributors for this article] (2023). Estimating motor unit numbers from a CMAP scan: Repeatability study on three muscles at 15 centres. Clinical Neurophysiology. ISSN 1388-2457. 151, p. 92–99. doi: 10.1016/j.clinph.2023.04.008. Full text in Research Archive
• Dunker, Øystein; Uglem, Martin; Kvaløy, Marie Bu; Løseth, Sissel; Hjelland, Ina Elen & Allen, Sara Maria [Show all 10 contributors for this article] (2023). Diagnostic accuracy of the 5.07 monofilament test for diabetes polyneuropathy: influence of age, sex, neuropathic pain and neuropathy severity. BMJ Open Diabetes Research & Care. 11(6). doi: 10.1136/bmjdrc-2023-003545. Full text in Research Archive Show summary

  Introduction There is a need for simple and cheap diagnostic tools for diabetic polyneuropathy (DPN). We aimed to assess the diagnostic accuracy of the 5.07/10 g monofilament test in patients referred to polyneuropathy assessments, as well as to examine how disease severity, age, sex and neuropathic pain (NP) impact diagnostic accuracy. Research design and methods Five Norwegian university hospitals recruited patients with diabetes aged 18–70 referred to neurological outpatient clinics for polyneuropathy assessments. The 5.07/10 g Semmes-Weinstein monofilament examination (SWME) was validated against the Toronto consensus for diagnosing diabetic neuropathies; the results were stratified by age, sex and NP. Disease severity was graded by a combined nerve conduction study (NCS) Z-score, and logistic regression was applied to assess whether disease severity was a predictor of diagnostic accuracy. Results In total, 506 patients were included in the study. Global sensitivity was 0.60 (95% CI 0.55, 0.66), specificity 0.82 (95% CI 0.75, 0.87), positive and negative predictive values were 0.86 (95% CI 0.81, 0.90) and 0.52 (95% CI 0.46, 0.58), respectively, positive and negative likelihood ratios were 3.28 (95% CI 2.37, 4.53) and 0.49 (95% CI 0.42, 0.57), respectively. The SWME was less sensitive in females (0.43), had lower specificity in patients with NP (0.56), and performed worse in patients ≥50 years. NCS-based disease severity did not affect diagnostic accuracy (OR 1.15, 95% CI 0.95, 1.40). Conclusions This multicenter study demonstrates poor diagnostic performance for the 5.07/10 g SWME in patients with diabetes referred to polyneuropathy assessments; it is particularly unsuited for female patients and those with NP. The diagnostic accuracy of the SWME was not influenced by NCS-based disease severity, demonstrating that it does not perform better in patients with later stages of DPN. We do not recommend the use of the 5.07/10 g monofilament in the evaluation of patients with diabetes referred to polyneuropathy assessments.

• Jacobsen, Kaya Kvarme; Børte, Sigrid; Laborie, Lene Bjerke; Kristiansen, Hege; Schäfer, Annette & Martinsen, Amy [Show all 30 contributors for this article] (2023). COL11A1 is associated with developmental dysplasia of the hip and secondary osteoarthritis in the HUNT study. Osteoarthritis and Cartilage Open. 6(1), p. 1–7. doi: 10.1016/j.ocarto.2023.100424. Full text in Research Archive Show summary

  Objective: Developmental dysplasia of the hip (DDH) is a congenital condition affecting 2-3% of all infants. DDH increases the risk of osteoarthritis, is the cause of 30% of all total hip arthroplasties (THAs) in adults <40 years of age and can result in loss of life quality. Our aim was to explore the genetic background of DDH in order to improve diagnosis, management and longterm outcome. Design: We used the large, ongoing, longitudinal Trøndelag Health Study (HUNT) database. Case definition was based on ICD-9/-10 diagnoses of DDH, or osteoarthritis secondary to DDH. Analyses were performed using SAIGE software, with covariates including sex, batch, birth year and principal components. We included only single nucleotide polymorphisms (SNPs) with minor allele frequency (MAF) 0.01, R2 0.8 and Hardy-Weinberg equilibrium (HWE) P-value 0.0001. Significance level was set at p < 5x10-8. Meta-analysis using data from DDH and primary osteoarthritis genome-wide association studies (GWASs) was done using METAL software. The study was approved by the regional ethical committee. Results: Analysis included 69,500 individuals, of which 408 cases, and 8,531,386 SNPs. Two SNPs near COL11A1 were significantly associated with DDH; rs713162 ( = -0.43, SE = 0.07, p = 8.4x10-9) and rs6577334 ( = -0.43, SE = 0.08, p = 8.9x10-9). COL11A1 has previously been associated with acetabular dysplasia and osteoarthritis. Meta-analysis supported previous GWAS findings of both DDH and primary osteoarthritis. Conclusions: This large, genome-wide case-control study indicates an association between COL11A1 and DDH and is an important contribution to investigating the etiology of DDH, with further research needed.

• Andries, Aristomo; Ørstavik, Kristin; Rueegg, Corina Silvia; Eng, Sindre Rike; Edvardsen, Elisabeth & Allen, Sara Maria [Show all 10 contributors for this article] (2022). Polyneuropathy in Adolescent Childhood Cancer Survivors: The PACCS Study. Pediatric Neurology. ISSN 0887-8994. 140. doi: 10.1016/j.pediatrneurol.2022.11.012. Full text in Research Archive Show summary

  Background: Childhood cancer survivors (CCS) are at risk of polyneuropathy due to chemotherapy, but studies in young survivors are scarce and diagnosis is challenging. We aimed to study the presence of polyneuropathy and the possible effect of cumulative doses of chemotherapeutic agents in a representative group of adolescent survivors. Methods: CCS aged nine to 18 years and age- and sex-matched controls were recruited from the cross-sectional Physical Activity and Fitness among Childhood Cancer Survivors (PACCS) study. CCS with various cancer diagnoses who had ended cancer treatment one year or more before study were included. Polyneuropathy was evaluated clinically and with nerve conduction studies (NCSs) in three motor and five sensory nerves. We used mixed-effects linear regression models to compare CCS and controls, and investigate possible associations between cumulative chemotherapy doses and NCS amplitudes. Results: A total of 127 CCS and 87 controls were included, with 14% CCS having probable or confirmed polyneuropathy. NCS amplitudes were lower in survivors compared with controls in all nerves. The largest mean difference was 3.47 μV (95% confidence interval [CI], 2.18 to 4.75) in the tibial plantar medial sensory and 1.91 mV (95% CI, 0.78 to 3.04) in the tibial motor nerve. The cumulative dose of platinum derivatives was associated with lower tibial motor nerve amplitude (−0.20; 95% CI, −0.35 to −0.04 mV for 100 mg/m2 dose increase) but not in other nerves. We found no significant associations between vinca alkaloids cumulative dose and amplitudes. Conclusions: CCS without clinical signs or symptoms of polyneuropathy may have subtle nerve affection. The clinical long-term impact of this novel observation should be evaluated in larger, longitudinal studies.

• Bahrami, Shahram; Hindley, Guy Frederick Lanyon; Winsvold, Bendik K S; O'Connell, Kevin Sean; Frei, Oleksandr & Shadrin, Alexey [Show all 39 contributors for this article] (2022). Dissecting the shared genetic basis of migraine and mental disorders using novel statistical tools. Brain. ISSN 0006-8950. 145(1), p. 142–153. doi: 10.1093/brain/awab267. Full text in Research Archive Show summary

  Migraine is three times more prevalent in people with bipolar disorder or depression. The relationship between schizophrenia and migraine is less certain although glutamatergic and serotonergic neurotransmission are implicated in both. A shared genetic basis to migraine and mental disorders has been suggested but previous studies have reported weak or non-significant genetic correlations and five shared risk loci. Using the largest samples to date and novel statistical tools, we aimed to determine the extent to which migraine’s polygenic architecture overlaps with bipolar disorder, depression and schizophrenia beyond genetic correlation, and to identify shared genetic loci. Summary statistics from genome-wide association studies were acquired from large-scale consortia for migraine (n cases = 59 674; n controls = 316 078), bipolar disorder (n cases = 20 352; n controls = 31 358), depression (n cases = 170 756; n controls = 328 443) and schizophrenia (n cases = 40 675, n controls = 64 643). We applied the bivariate causal mixture model to estimate the number of disorder-influencing variants shared between migraine and each mental disorder, and the conditional/conjunctional false discovery rate method to identify shared loci. Loci were functionally characterized to provide biological insights. Univariate MiXeR analysis revealed that migraine was substantially less polygenic (2.8 K disorder-influencing variants) compared to mental disorders (8100–12 300 disorder-influencing variants). Bivariate analysis estimated that 800 (SD = 300), 2100 (SD = 100) and 2300 (SD = 300) variants were shared between bipolar disorder, depression and schizophrenia, respectively. There was also extensive overlap with intelligence (1800, SD = 300) and educational attainment (2100, SD = 300) but not height (1000, SD = 100). We next identified 14 loci jointly associated with migraine and depression and 36 loci jointly associated with migraine and schizophrenia, with evidence of consistent genetic effects in independent samples. No loci were associated with migraine and bipolar disorder. Functional annotation mapped 37 and 298 genes to migraine and each of depression and schizophrenia, respectively, including several novel putative migraine genes such as L3MBTL2, CACNB2 and SLC9B1. Gene-set analysis identified several putative gene sets enriched with mapped genes including transmembrane transport in migraine and schizophrenia. Most migraine-influencing variants were predicted to influence depression and schizophrenia, although a minority of mental disorder-influencing variants were shared with migraine due to the difference in polygenicity. Similar overlap with other brain-related phenotypes suggests this represents a pool of ‘pleiotropic’ variants that influence vulnerability to diverse brain-related disorders and traits. We also identified specific loci shared between migraine and each of depression and schizophrenia, implicating shared molecular mechanisms and highlighting candidate migraine genes for experimental validation.

• Nilsen, Kristian Bernhard; Kleggetveit, Inge Petter & Hoven, Stian (2022). Kan vi skille mellom arvelige og inflammatoriske nevropatier? Tidsskrift for Den norske legeforening (Tidsskriftet). ISSN 0029-2001. 142(13). doi: 10.4045/tidsskr.22.0559. Full text in Research Archive
• Schulze, Daniel Gregor; Nilsen, Kristian Bernhard; Clemm, Thomas; Grotle, Margreth; Zwart, John Anker Henrik & Ulvestad, Bente [Show all 7 contributors for this article] (2022). Influence of ergonomic factors on peripheral neuropathy under HAV exposure. Occupational Medicine. ISSN 0962-7480. 73(1), p. 13–18. doi: 10.1093/occmed/kqac118. Full text in Research Archive Show summary

  Background: Hand-arm vibration (HAV) is a risk factor for carpal tunnel syndrome (CTS) and ulnar neuropathy at the elbow (UNE). It is unclear how ergonomic factors influence the relationship between HAV exposure and CTS and UNE. Aims: We aimed to assess the relationship between cumulative HAV exposure and CTS and UNE in workers exposed to HAV from two tools with different ergonomic profiles. Methods: We performed nerve conduction studies (NCSs) of the sensory and motor median and ulnar nerves and recorded symptoms indicating CTS and UNE in workers exposed to HAV from impact wrenches or from rock drills. Exposure was measured as cumulative lifetime exposure. We used linear regression adjusted for age and body mass index to assess linear relationships. Results: Sixty-five workers participated (33 rock drill and 32 impact wrench operators). We found inverse linear associations between cumulative HAV exposure and median nerve sensory conduction velocity in impact wrench operators and ulnar nerve motor conduction velocity in rock drill operators (beta of 0.63 and 0.75). Based on NCS findings and symptoms, seven impact wrench operators had CTS and one UNE, and four rock drill operators had CTS and six UNE. Conclusions: Our findings indicate that ergonomic factors influence the development of CTS and UNE under HAV exposure. The ergonomic profile seems to influence which type of neuropathy workers exposed to HAV will develop. Design of occupational exposure guidelines and future studies should be based on ergonomic profile and exposure characteristics for different tools and not merely HAV.

• Lie, Marie; Pedersen, Linda Margareth; Heuch, Ingrid; Winsvold, Bendik K S; Gjerstad, Johannes & Hasvik, Eivind Olay [Show all 11 contributors for this article] (2022). Low Back Pain With Persistent Radiculopathy; the Clinical Role of Genetic Variants in the Genes SOX5, CCDC26/GSDMC and DCC. Frontiers in Genetics. 12(12). doi: 10.3389/fgene.2021.757632. Full text in Research Archive Show summary

  In a recently published genome-wide association study (GWAS) chronic back pain was associated with three loci; SOX5, CCDC26/GSDMC and DCC. This GWAS was based on a heterogeneous sample of back pain disorders, and it is unknown whether these loci are of clinical relevance for low back pain (LBP) with persistent radiculopathy. Thus, we examine if LBP with radiculopathy 12 months after an acute episode of LBP with radiculopathy is associated with the selected single nucleotide polymorphisms (SNPs); SOX5 rs34616559, CCDC26/GSDMC rs7833174 and DCC rs4384683. In this prospective cohort study, subjects admitted to a secondary health care institution due to an acute episode of LBP with radiculopathy, reported back pain, leg pain, and Oswestry Disability Index (ODI), were genotyped and followed up at 12 months (n = 338). Kruskal-Wallis H test showed no association between the SNPs and back pain, leg pain or ODI. In conclusion, LBP with radiculopathy 12 months after an acute episode of LBP with radiculopathy, is not associated with the selected SNPs; SOX5 rs34616559, CCDC26/GSDMC rs7833174 and DCC rs4384683. This absent or weak association suggests that the SNPs previously associated with chronic back pain are not useful as prognostic biomarkers for LBP with persistent radiculopathy.

• Dunker, Øystein; Grotle, Margreth; Kvaløy, Marie Bu; Uglem, Martin; Løseth, Sissel & Hjelland, Ina Elen [Show all 12 contributors for this article] (2022). Accuracy of neuropathic pain measurements in patients with symptoms of polyneuropathy: validation of painDETECT, Self-Completed Leeds Assessment of Neuropathic Symptoms and Signs, and Douleur Neuropathique 4. Pain. ISSN 0304-3959. 164(5), p. 991–1001. doi: 10.1097/j.pain.0000000000002793. Full text in Research Archive Show summary

  Pain is a common symptom in patients referred to polyneuropathy assessment. Diagnostic evaluation and choice of treatment may depend on whether the pain is likely to be neuropathic or not. This study aimed to investigate the diagnostic accuracy of 3 tools commonly used to differentiate between neuropathic and nonneuropathic pain. To accomplish this, we included patients with bilateral distal lower extremity pain, referred to neurological outpatient clinics at 5 Norwegian University hospitals for polyneuropathy assessment. The patients filled in Norwegian versions of painDETECT, the Self-Completed Leeds Assessment of Neuropathic Symptoms and Signs (S-LANSS), and the clinician-rated Douleur Neuropathique 4 (DN4). All patients underwent a clinical examination and nerve conduction measurements and were classified according to the NeuPSIG neuropathic pain criteria (reference standard). In total, 729 patients were included, of which 63% had neuropathic pain by the reference standard. Only DN4 demonstrated high sensitivity (0.87), whereas all 3 tools had low specificity (≤0.65). Importantly, the tools' predictive ability was unsatisfactory; The probability of getting a correct test result was 3 quarters at best, and at worst, no better than two fifths. Consequently, we show that neither DN4, painDETECT, nor S-LANSS can be confidently used to assess neuropathic pain in a neurological outpatient population with symptoms of polyneuropathy.

• Ho, Kevin Kwan Ngai; Skarpsno, Eivind S.; Nilsen, Kristian Bernhard; Ferreira, Paulo Herrique; Pinheiro, Marina & Hopstock, Laila Arnesdatter [Show all 11 contributors for this article] (2022). A bidirectional study of the association between insomnia, high-sensitivity C-reactive protein, and comorbid low back pain and lower limb pain. Scandinavian Journal of Pain. ISSN 1877-8860. 23(1), p. 110–125. doi: 10.1515/sjpain-2021-0197. Full text in Research Archive Show summary

  Objectives - To examine the possible bidirectional association between insomnia and comorbid chronic low back pain (LBP) and lower limb pain and to explore whether high-sensitivity C-reactive protein (hsCRP) amplifies these associations. Methods - We calculated adjusted risk ratios (RR) with 95% confidence intervals (CI) for the development of insomnia and mild-to-severe chronic LBP and lower limb pain at 11 years follow-up in participants aged ≥32 years and with hsCRP ≤10 mg/L at baseline in 2007–2008: 3,714 without chronic LBP or lower limb pain (sample 1) and 7,892 without insomnia (sample 2). Results - Compared to participants without chronic pain, participants with comorbid chronic LBP and lower limb pain had a RR of insomnia of 1.37 (95% CI 1.12–1.66). Compared with participants without insomnia, participants with insomnia did not have an increased risk of comorbid chronic LBP and lower limb pain (RR: 1.06, 95% CI 0.76–1.46); however, participants with insomnia had a RR of chronic LBP of 1.20 (95% CI 1.02–1.42). There was no strong amplifying effect of elevated hsCRP (3.00–10.0 mg/L) on these associations. Conclusions - These findings suggest that elevated hsCRP does not amplify the associations between insomnia and mild-to-severe chronic LBP and lower limb pain. Further research using data on the temporal relation between insomnia, chronic pain, and inflammatory responses are required to fully understand the causal pathways.

• Verdugo, Renato J.; Matamala, José M.; Inui, Koji; Kakigi, Ryusuke; Valls-Solé, Josep & Hansson, Per [Show all 15 contributors for this article] (2022). Review of techniques useful for the assessment of sensory small fiber neuropathies: Report from an IFCN expert group. Clinical Neurophysiology. ISSN 1388-2457. 136, p. 13–38. doi: 10.1016/j.clinph.2022.01.002. Full text in Research Archive
• Aamodt, Anne Hege; Taubøll, Erik; Ele, Tom Eich; Romundstad, Luis Georg; Sorteberg, Angelika & Wallace, Sean Ciaran [Show all 24 contributors for this article] (2021). Brain monitoring in hospitals needs to be strengthened. Tidsskrift for Den norske legeforening (Tidsskriftet). ISSN 0029-2001. 141(15), p. 1–8. doi: 10.4045/tidsskr.21.0412. Full text in Research Archive
• Rahman, Shafiqur; Winsvold, Bendik K S; Chavez, Sergio; Børte, Sigrid; Tsepilov, Vakov & Sharapov, Sodbo Zh [Show all 32 contributors for this article] (2021). Genome-wide association study identifies RNF123 locus as associated with chronic widespread musculoskeletal pain. Annals of the Rheumatic Diseases. ISSN 0003-4967. 80(9), p. 1227–1235. doi: 10.1136/annrheumdis-2020-219624. Full text in Research Archive Show summary

  Background and objectives Chronic widespread musculoskeletal pain (CWP) is a symptom of fibromyalgia and a complex trait with poorly understood pathogenesis. CWP is heritable (48%–54%), but its genetic architecture is unknown and candidate gene studies have produced inconsistent results. We conducted a genome-wide association study to get insight into the genetic background of CWP. Methods Northern Europeans from UK Biobank comprising 6914 cases reporting pain all over the body lasting >3 months and 242 929 controls were studied. Replication of three independent genome-wide significant single nucleotide polymorphisms was attempted in six independent European cohorts (n=43 080; cases=14 177). Genetic correlations with risk factors, tissue specificity and colocalisation were examined. Results Three genome-wide significant loci were identified (rs1491985, rs10490825, rs165599) residing within the genes Ring Finger Protein 123 (RNF123), ATPase secretory pathway Ca 2+ transporting 1 (ATP2C1) and catechol-O-methyltransferase (COMT). The RNF123 locus was replicated (meta-analysis p=0.0002), the ATP2C1 locus showed suggestive association (p=0.0227) and the COMT locus was not replicated. Partial genetic correlation between CWP and depressive symptoms, body mass index, age of first birth and years of schooling were identified. Tissue specificity and colocalisation analysis highlight the relevance of skeletal muscle in CWP. Conclusions We report a novel association of RNF123 locus and a suggestive association of ATP2C1 locus with CWP. Both loci are consistent with a role of calcium regulation in CWP. The association with COMT, one of the most studied genes in chronic pain field, was not confirmed in the replication analysis.

• Ragnum, Harald Bull; Bortoli, Alessandro De; Elsais, Ahmed; Nilsen, Kristian Bernhard; Hammarström, Clara Louise & Nyakas, Marta Sølvi (2021). En mann i 6o-årene med dyspné etter immunterapi. Tidsskrift for Den norske legeforening (Tidsskriftet). ISSN 0029-2001. 141(12), p. 1–8. doi: 10.4045/tidsskr.21.0139. Full text in Research Archive
• Matre, Dagfinn; Christensen, Jan Olav; Mork, Paul Jarle; Ferreira, Paulo; Sand, Trond & Nilsen, Kristian Bernhard (2021). Shift work, inflammation and musculoskeletal pain. The HUNT Study. Occupational Medicine. ISSN 0962-7480. 71(9), p. 422–427. doi: 10.1093/occmed/kqab133. Full text in Research Archive Show summary

  Background: Studies have indicated that shift work, in particular night work, is associated with chronic musculoskeletal pain but the mechanisms are unclear. It has been suggested that sleep disturbance, a common complaint among shift and night workers, may induce low-grade inflammation as well as heightened pain sensitivity. Aims: Firstly, this study was aimed to examine the cross-sectional associations between shift work, C-reactive protein (CRP) level and chronic musculoskeletal pain, and secondly, to analyse CRP as a mediator between shift work and chronic musculoskeletal pain. Methods: The study included 23 223 vocationally active women and men who participated in the HUNT4 Survey of the Trøndelag Health Study (HUNT). Information was collected by questionnaires, interviews, biological samples and clinical examination. Results: Regression analyses adjusted for sex, age and education revealed significant associations between shift work and odds of any chronic musculoskeletal pain (odd ratio [OR] 1.11, 95% confidence interval [CI] 1.04-1.19), between shift work and CRP level (OR 1.09, 95% CI 1.03-1.16) and between CRP level 3.00-10 mg/L and any chronic musculoskeletal pain (OR 1.38, 95% CI 1.27-1.51). Shift work and CRP were also associated with number of chronic pain sites. Mediation analysis indicated that shift work was indirectly associated with any chronic musculoskeletal pain through CRP (OR 1.03, 95% CI 1.01-1.06). Conclusions: The results support the hypothesis that shift work is associated with chronic musculoskeletal pain, and that systemic inflammation may be a biological mechanism linking shift work to chronic pain.

• Dunker, Øystein; Lie, Marie & Nilsen, Kristian Bernhard (2021). Can within-subject comparisons of thermal thresholds be used for diagnostic purposes? Clinical Neurophysiology Practice (CNP). 6, p. 63–71. doi: 10.1016/j.cnp.2021.01.002. Full text in Research Archive Show summary

  Objective: Quantitative thermal testing (QTT) is a psychophysical assessment method of small nerve fibers that relies on reference material to assess function. Normal limits for within-subject comparisons of thermal thresholds are scarce, and their association with age, height and sex is not fully elucidated. The aim of this study was to investigate the normal limits for distal-proximal– and contralateral homologous comparisons of thermal thresholds with QTT, and their association with age, sex or height. Methods: Fifty healthy volunteers ages 20–79 participated in the experiment. Cold detection thresholds (CDT), warm detection thresholds (WDT), heat pain thresholds (HPT), and cold pain thresholds (CPT) were measured bilaterally at the thenar eminence, anterior thigh, distal medial leg and foot dorsum. Sample normal limits were calculated as (mean) ± 2 SD. Results: Forty-eight subjects were included in the analysis. CPT was excluded from all analyses due to a large floor-effect. Sample normal limits for side-differences ranged from 1.8 to 7.2 °C for CDT, 2.4–6.8 °C for WDT and 3.2–4.0 °C for HPT, depending on anatomical site. For distal-proximal comparisons, sample normal limits ranged from 4.0 to 8.7 °C for CDT, 6.0–14.0 °C for WDT and 4.2–9.0 °C for HPT, depending on the pairs compared. Age was associated with side-differences for CDT in the thenar eminences (p < 0.001) and distal medial legs (p < 0.002), and with 11 of 18 distal-proximal comparisons (p < 0.01). Conclusions: The normal limits for distal-proximal- and contralateral homologous thermal thresholds were wide, and thus of limited use in a clinical setting, although the reported values may be somewhat inflated by low sample-size and consequent age-pooling. Age, but not sex or height, was associated with contralateral differences in CDT in the thenar eminences and distal medial legs, and with most distal-proximal differences. Significance: Due to wide normal limits, we advise caution when utilizing relative comparisons of thermal thresholds for diagnostic purposes.

• Dunker, Øystein; Nilsen, Kristian Bernhard; Olsen, Sandra Elise; Åsvold, Bjørn Olav; Bjørgaas, Marit Ragnhild Rokne & Sand, Trond (2021). Which combined nerve conduction study scores are best suited for polyneuropathy in diabetic patients? Muscle and Nerve. ISSN 0148-639X. 65(2), p. 1–9. doi: 10.1002/mus.27445. Full text in Research Archive Show summary

  Introduction/Aims Nerve conduction studies (NCS) are widely used in diagnosing diabetic polyneuropathy. Combining the Z scores of several measures (Z-compounds) may improve diagnostics by grading abnormality. We aimed to determine which combination of nerves and measures is best suited for studies of diabetic polyneuropathy. Methods Sixty-eight patients with type 1 diabetes and 35 controls were included in this study. NCS measurements were taken from commonly investigated nerves in one arm and both legs. Different Z-compounds were calculated and compared with reference material to assess abnormality. A sensitivity proxy, the accuracy index (AI), and Cohen's d were calculated. Results Z-compounds with the highest AI consisted of the tibial and peroneal motor, and the sural, superficial peroneal, and tibial medial plantar sensory nerves in one or two legs. All Z-compounds were able to discriminate between diabetic subjects and nondiabetic controls (mean Cohen's d = 1.42 [range, 1.03-1.63]). The association between AI and number of measures was best explained logarithmically (R2 = 0.401), with diminishing returns above approximately 14 or 15 measures. F-wave inclusion may increase the AI of the Z compounds. Although often clinically useful among the non-elderly, the additional inclusion of medial plantar NCS into Z-compounds in general did not improve AI. Discussion Performing unilateral NCS in several motor and sensory lower extremity nerves is suited for the evaluation of polyneuropathy in diabetic patients. The use of Z-compounds may improve diagnostic accuracy in diabetic polyneuropathy and may be particularly useful for follow-up research studies as single summary measures of NCS abnormality development over time.

• Hansen, Johannes Orvin; Omland, Petter Moe; Nilsen, Kristian Bernhard; Sand, Trond & Matre, Dagfinn (2021). Experimental sleep restriction increases latency jitter in pain elicited cortical responses. Heliyon. 7(2). doi: 10.1016/j.heliyon.2021.e06188. Full text in Research Archive Show summary

  Objective Previous studies have shown increased pain scores to painful stimulation after experimental sleep restriction, but reduced or unchanged magnitude of the event related potentials (ERPs) when averaged in the time-domain. However, some studies found increased response magnitude when averaging in the time-frequency domain. The aim of this study was to determine whether ERP-latency jitter may contribute to this discrepancy. Methods Ninety painful electrical stimuli were given to 21 volunteers after two nights of 50% sleep restriction and after two nights of habitual sleep. ERPs were analyzed in the time-domain (N2-and P2-peaks) and time-frequency domain (power spectral density). We quantified latency jitter by the mean consecutive difference (MCD) between single-trial peak latencies and by phase locking value (PLV) across trials. Results P2-MCD increased from 20.4 ± 2.1 ms after habitual sleep to 24.3 ± 2.2 ms after sleep restriction (19%, p = 0.038) and PLV decreased from 0.582 ± 0.015 after habitual sleep to 0.536 ± 0.015 after sleep restriction (7.9%, p = 0.009). We found no difference for N2-MCD. Conclusions Our results indicate that partial sleep restriction increase latency jitter in cortical responses to experimental pain.

• Sørensen, Daniel Mosgaard; Bostock, Hugh; Ballegaard, Martin; Fuglsang-Frederiksen, Anders; Graffe, Carolina Canillo & Grøtting, Arnstein [Show all 20 contributors for this article] (2021). Assessing inter-rater reproducibility in MScanFit MUNE in a 6-subject, 12-rater “Round Robin” setup. Neurophysiologie clinique. ISSN 0987-7053. doi: 10.1016/j.neucli.2021.11.002. Full text in Research Archive Show summary

  Objective To assess the inter-rater reliability of MScanFit MUNE using a “Round Robin” research design. Methods Twelve raters from different centres examined six healthy study participants over two days. Median, ulnar and common peroneal nerves were stimulated, and compound muscle action potential (CMAP)-scans were recorded from abductor pollicis brevis (APB), abductor digiti minimi (ADM) and anterior tibial (TA) muscles respectively. From this we calculated the Motor Unit Number Estimation (MUNE) and “A50”, a motor unit size parameter. As statistical analysis we used the measures Limits of Agreement (LOA) and Coefficient of Variation (COV). Study participants scored their perception of pain from the examinations on a rating scale from 0 (no pain) to 10 (unbearable pain). Results Before this study, 41.6% of the raters had performed MScanFit less than five times. The mean MUNE-values were: 99.6 (APB), 131.4 (ADM) and 126.2 (TA), with LOA: 19.5 (APB), 29.8 (ADM) and 20.7 (TA), and COV: 13.4 (APB), 6.3 (ADM) and 5.6 (TA). MUNE-values correlated to CMAP max amplitudes (R2-values were: 0.463 (APB) (p<0.001), 0.421 (ADM) (p<0.001) and 0.645 (TA) (p<0.001)). The average perception of pain was 4. Discussion MScanFit indicates a high level of inter-rater reliability, even with only limited rater experience and is overall reasonably well tolerated by patients. These results may indicate MScanFit as a reliable MUNE method with potential as a biomarker in drug trials.

• Freidin, Maxim B.; Tsepilov, Yakov A.; Stanaway, Ian B.; Meng, Weihua; Hayward, Caroline & Smith, Blair H. [Show all 36 contributors for this article] (2021). Sex- and age-specific genetic analysis of chronic back pain. Pain. ISSN 0304-3959. 162(4), p. 1176–1187. doi: 10.1097/j.pain.0000000000002100. Full text in Research Archive Show summary

  Sex differences for chronic back pain (cBP) have been reported, with females usually exhibiting greater morbidity, severity, and poorer response to treatment. Genetic factors acting in an age-specific manner have been implicated but never comprehensively explored. We performed sex- and age-stratified genome-wide association study and single nucleotide polymorphism-by-sex interaction analysis for cBP defined as “Back pain for 3+ months” in 202,077 males and 237,754 females of European ancestry from UK Biobank. Two and 7 nonoverlapping genome-wide significant loci were identified for males and females, respectively. A male-specific locus on chromosome 10 near SPOCK2 gene was replicated in 4 independent cohorts. Four loci demonstrated single nucleotide polymorphism-by-sex interaction, although none of them were formally replicated. Single nucleotide polymorphism-explained heritability was higher in females (0.079 vs 0.067, P = 0.006). There was a high, although not complete, genetic correlation between the sexes (r = 0.838 ± 0.041, different from 1 with P = 7.8E-05). Genetic correlation between the sexes for cBP decreased with age (0.858 ± 0.049 in younger people vs 0.544 ± 0.157 in older people; P = 4.3E-05). There was a stronger genetic correlation of cBP with self-reported diagnosis of intervertebral disk degeneration in males than in females (0.889 vs 0.638; P = 3.7E-06). Thus, the genetic component of cBP in the UK Biobank exhibits a mild sex- and age-dependency. This provides an insight into the possible causes of sex- and age-specificity in epidemiology and pathophysiology of cBP and chronic pain at other anatomical sites.

• Khoury, Samar; Parisien, Marc; Thompson, Scott J.; Vachon-Presseau, Etienne; Roy, Mathieu & Mitchell, Amy [Show all 32 contributors for this article] (2021). Genome-wide analysis identifies impaired axonogenesis in chronic overlapping pain conditions. Brain. ISSN 0006-8950. 145(3), p. 1111–1123. doi: 10.1093/brain/awab359. Full text in Research Archive Show summary

  Chronic pain is often present at more than one anatomical location, leading to chronic overlapping pain conditions (COPC). Whether COPC represents a distinct pathophysiology from the occurrence of pain at only one site is unknown. Using genome-wide approaches, we compared genetic determinants of chronic single-site vs. multisite pain in the UK Biobank. We found that different genetic signals underlie chronic single-site and multisite pain with much stronger genetic contributions for the latter. Among 23 loci associated with multisite pain, 9 loci replicated in the HUNT cohort, with the DCC netrin-1 receptor (DCC) as the top gene. Functional genomics identified axonogenesis in brain tissues as the major contributing pathway to chronic multisite pain. Finally, multimodal structural brain imaging analysis showed that DCC is most strongly expressed in subcortical limbic regions and is associated with alterations in the uncinate fasciculus microstructure, suggesting that DCC-dependent axonogenesis may contribute to COPC via cortico-limbic circuits. Keywords: chronic overlapping pain conditions, netrin, uncinate fasciculus

• Christensen, Jan Olav; Nilsen, Kristian Bernhard; Hopstock, Laila Arnesdatter; Steingrimsdottir, Olöf Anna; Nielsen, Christopher Sivert & Zwart, John-Anker [Show all 7 contributors for this article] (2021). Shift work, low-grade inflammation, and chronic pain: a 7-year prospective study. International Archives of Occupational and Environmental Health. ISSN 0340-0131. 94, p. 1013–1022. doi: 10.1007/s00420-020-01626-2. Full text in Research Archive Show summary

  Objectives We investigated prospective associations of shift work with chronic pain and C‐reactive protein (CRP), an indicator of inflammation. Furthermore, we elucidated CRP as a possible mediator and/or moderator of effects of shift work on pain. Methods Data from a 7 years follow‐up study were analyzed (N = 2323). Shift work and chronic pain of “neck/shoulder”, “arm/hand”, “upper back”, “low back”, “hip/leg/feet”, and “other regions” were measured by questionnaires. “Chronic widespread pain”, “number of chronic pain sites”, and “any chronic pain” were computed. CRP was measured in serum samples. Logistic and Poisson regressions were conducted. Mediation was assessed by casual mediation analyses and moderation by the Relative Excess Risk due to Interaction (RERI). Results Shift work was not associated with any chronic pain variable and no mediation was detected. CRP was associated with low back pain, hip/leg pain, and “number of pain sites”, and also with the combination of shift work and CRP of 1–2.99 mg/L (compared to: no shiftwork and CRP < 1). Additionally, shiftwork and CRP 1–2.99 mg/L was associated with risk of “any chronic pain” (OR: 1.76, 95% CI: 1.12, 2.85), which was not associated with CRP alone. Moderation analyses suggested the risks for “any chronic pain” and “number of pain regions” increased when individuals with elevated CRP worked shifts—beyond what the separate effects of CRP and shift would suggest. Conclusions We found no evidence of shift work in general affecting CRP or chronic pain. However, shift work and elevated CRP combined may influence chronic pain.

• Schulze, Daniel Gregor; Nilsen, Kristian Bernhard; Killingmo, Rikke Munk; Zwart, John Anker & Grotle, Margreth (2021). Clinical Utility of the 6-Item CTS, Boston-CTS, and Hand-Diagram for Carpal Tunnel Syndrome. Frontiers in Neurology. 12, p. 1–10. doi: 10.3389/fneur.2021.683807. Full text in Research Archive Show summary

  Background: Self-reported measures are often used in research and clinical practice to diagnose carpal tunnel syndrome (CTS) and guide therapeutic choices. We aimed to assess the clinical utility of the Norwegian versions of two self-reported outcome measures for symptom severity assessment, the 6-item CTS (CTS-6), and Boston-CTS (BCTQ), and of one diagnostic measure, the hand-diagram, by evaluating measurement properties including discriminative ability for severity assessment (CTS-6, BCTQ), and diagnosis of CTS (hand-diagram). Methods: We performed forward and backward translation and cultural adaptation of the Norwegian CTS-6 and BCTQ. Following COSMIN guidelines, we investigated internal consistency, reliability, construct validity, and discriminative ability for distinguishing between severity levels of CTS in patients with confirmed CTS for the CTS-6 and BCTQ and reliability and discriminative ability for diagnosing CTS for the hand-diagram. Results: Two hundred and fifty-one patients referred for diagnostic work-up for CTS with nerve conduction studies (NCS) participated. The CTS-6 and BCTQ had acceptable internal consistency (Crohnbach’s α = 0.82 and 0.86, respectively), reliability (ICC = 0.86 and 0.90; SEM = 0.24 and 0.20; SDC95% = 0.68 and 0.55, respectively), construct validity (all eight pre-defined hypotheses confirmed) and discriminative ability to distinguish between severity levels of CTS [Area under the curve (AUC) = 0.75, 95% CI 0.64–0.85]. The hand-diagram had acceptable reliability (Cohen’s kappa = 0.69) and discriminative ability to diagnose CTS (sensitivity = 0.72, specificity = 0.90). Conclusion: Our findings support the clinical utility of the CTS-6 and BCTQ for symptom severity assessment and of the hand-diagram for diagnostic screening.

• Winsvold, Bendik K S; Kitsos, Ioannis; Thomas, Laurent; Skogholt, Anne Heidi; Gabrielsen, Maiken Elvestad & Zwart, John Anker Henrik [Show all 7 contributors for this article] (2021). Genome-Wide Association Study of 2,093 Cases With Idiopathic Polyneuropathy and 445,256 Controls Identifies First Susceptibility Loci. Frontiers in Neurology. 12, p. 1–11. doi: 10.3389/fneur.2021.789093. Full text in Research Archive Show summary

  Background: About one third of patients with chronic polyneuropathy have no obvious underlying etiology and are classified as having idiopathic polyneuropathy. The lack of knowledge about pathomechanisms and predisposing factors limits the development of effective prevention and treatment for these patients. We report the first genome-wide association study (GWAS) of idiopathic polyneuropathy. Methods: Cases with idiopathic polyneuropathy and healthy controls were identified by linkage to hospital records. We performed genome-wide association studies using genetic data from two large population-based health studies, the Trøndelag Health Study (HUNT, 1,147 cases and 62,204 controls) and UK Biobank (UKB, 946 cases and 383,052 controls). In a two-stage analysis design, we first treated HUNT as a discovery cohort and UK Biobank as a replication cohort. Secondly, we combined the two studies in a meta-analysis. Downstream analyses included genetic correlation to other traits and diseases. We specifically examined previously reported risk loci, and genes known to cause hereditary polyneuropathy. Results: No replicable risk loci were identified in the discovery-replication stage, in line with the limited predicted power of this approach. When combined in a meta-analysis, two independent loci reached statistical significance (rs7294354 in B4GALNT3, P-value 4.51 × 10−8) and (rs147738081 near NR5A2, P-value 4.75 × 10−8). Idiopathic polyneuropathy genetically correlated with several anthropometric measures, most pronounced for height, and with several pain-related traits. Conclusions: In this first GWAS of idiopathic polyneuropathy we identify two risk-loci that indicate possible pathogenetic mechanisms. Future collaborative efforts are needed to replicate and expand on these findings.

• Katsifaraki, Maria; Nilsen, Kristian Bernhard; Christensen, Jan Olav; Wærsted, Morten; Knardahl, Stein & Bjorvatn, Bjørn [Show all 8 contributors for this article] (2020). Pain complaints after consecutive nights and quick returns in Norwegian nurses working three-shift rotation: an observational study. BMJ Open. 10(9). doi: 10.1136/bmjopen-2019-035533. Full text in Research Archive Show summary

  Objectives To determine whether nurses working consecutive night shifts, or short transitions between shifts (quick returns (QRs)), yielded higher risk for pain complaints when compared with regular morning shifts. Sleep duration was tested as a potential mediator. Design Observational diary study. Setting Random hospitals. Participants Nurses with three-shift rotation (morning, evening and night), n=679, 22–63 years old. Outcomes measures Daily ratings of working hours, sleep and subjective pain complaints in six anatomical regions (head, neck/shoulder/upper back, upper extremity, low back, lower extremity and abdomen) for 28 days. In addition, we assessed demographics, habitual sleep and pain complaints, work and lifestyle factors. It was tested (1) whether the risk for pain complaints was higher after workday 3 versus after workday 2, and whether the difference was larger for consecutive night shifts versus consecutive morning shifts, and (2) whether the risk for pain complaints was higher after QRs versus after two morning shifts. Risk for pain complaints refers to combined increased risk for any pain and risk for increased intensity. Results Adjusted analyses showed no shift type by workday interaction for pain complaints in the neck/shoulder/upper back, upper extremities, low back, lower extremities or abdomen. For headache, a strong trend indicated that the risk was higher on workday 3 compared with workday 2 for night shifts (OR 1.13, 95% CI 0.99 to 1.28). The risk was lowered if sleep duration was taken into account (OR 0.37, 95% CI 0.17 to 0.81). No conclusive support was found for the risk for pain complaints being higher after QRs, compared with after morning shifts. Conclusions For five of six pain complaints, the hypotheses were not supported by the current data. For headache, we found potential support for a sleep-relieving effect on headache after working several nights in a row. Pain complaints were not instigated or exacerbated by an evening-to-morning transition between shifts.

• Nordstrand, Sebjørg Elizabeth Hesla; Juvodden, Hilde Therese; Viste, Rannveig; Rootwelt-Revheim, Terje; Karlsen, Tor-Ivar & Thorsby, Per Medbøe [Show all 10 contributors for this article] (2020). Obesity and other medical comorbidities among NT1 patients after the Norwegian H1N1 influenza epidemic and vaccination campaign. Sleep. ISSN 0161-8105. 43(5). doi: 10.1093/sleep/zsz277. Full text in Research Archive
• Barzenje, Aros Dlawer; Gjesdal, Knut; Winsvold, Bendik K S; Småstuen, Milada Cvancarova; Stovner, Lars Jacob & Gravdahl, Gøril Bruvik [Show all 7 contributors for this article] (2020). Clinical and vascular responses to propranolol and candesartan in migraine patients: A randomized controlled clinical trial. Cephalalgia Reports. 3, p. 1–8. doi: 10.1177/2515816320946491. Full text in Research Archive Show summary

  Background: Both propranolol and candesartan are prophylactic drugs for migraine, but with unknown mechanisms of action. The objectives of the present study were to investigate these drugs’ effects on arterial wall dynamics and the potential relation between their vascular and clinical effect. Methods: The study was based on data from a previously published randomized, placebo-controlled, triple-blinded, double crossover clinical trial comparing the prophylactic effects of candesartan and propranolol in 72 patients. Finapres noninvasive blood pressure curves were analyzed. On the descending limb of the pulse curve, a notch is produced by pulse wave reflection, and its relative height compared to the top of the curve (the notch ratio) was used as a marker of arterial wall stiffness. Results: Candesartan decreased the notch ratio from baseline (p ¼ 0.005), reflecting more compliant arteries and vasodilation, whereas propranolol increased the notch ratio (p ¼ 0.005), reflecting less compliant arteries and vasoconstriction. There was no difference in baseline notch ratio between clinical responders and nonresponders. Conclusion: The drugs are both efficient prophylactic medications, yet they have opposite effects on arterial wall dynamics. This suggests that drug effects other than those on arterial compliance must be responsible for their prophylactic effect in migraine.

• Hansen, Berit M Hjelde; Juvodden, Hilde Therese; Nordstrand, Sebjørg Elizabeth Hesla; Viste, Rannveig; Thorsby, Per Medbøe & Swanson, David [Show all 9 contributors for this article] (2020). High prevalence of ADHD symptoms in unmedicated youths with post-H1N1 narcolepsy type 1. Sleep Medicine. ISSN 1389-9457. 75, p. 171–180. doi: 10.1016/j.sleep.2020.06.014. Full text in Research Archive Show summary

  Objectives To characterize attention deficit-hyperactivity disorder (ADHD) symptoms in unmedicated post-H1N1 narcolepsy type 1 (NT1) youths, and explore associations between ADHD symptoms and the narcolepsy phenotype. Methods A total of 50 consecutively enrolled post-H1N1 NT1 youths (7–20 years, 62% females, 98% HLA-DQB1∗06:02-positive, 98% CSF hypocretin-1 deficient, 88% vaccinated) were assessed after two weeks off medication for ADHD (ADHD diagnosis pre/post-narcolepsy, parent-rated ADHD symptoms) and narcolepsy-phenotyped (semi-structured interview, Stanford Sleep Questionnaire, Epworth Sleepiness Scale, polysomnography (PSG), Multiple Sleep Latency Test (MSLT)). Results In sum, 26 (52%) and 15 (30%) of participants had ADHD symptoms above and below the clinical significant cut-off, respectively, while 9 (18%) had no ADHD symptoms. High values were found for ADHD total score (mean (SD), 17.9 (9.5)) and ADHD subscores (inattentive score, 11.0 (6.3); hyperactive/impulsivity score, 6.9 (4.7)). These were significantly higher than previously reported in a mainly medicated narcolepsy cohort (p < 0.0001). Age, gender and disease duration did not influence scores. Two participants (4%) had ADHD diagnosis prior to narcolepsy onset. ADHD symptoms were correlated with parent-rated, but not with patient rated ESS scores, objective sleepiness (mean sleep latency), sleep fragmentation (sleep stage shift index, awakening index), or CSF hypocretin-1 level. Conclusion Comorbid ADHD symptoms were more prevalent in unmedicated post-H1N1 NT1 youths than previously reported in mainly medicated pediatric narcolepsy cohorts. The high prevalence was not due to pre-existing ADHD and generally not correlated with core narcolepsy sleep/wake phenotype characteristics, indicating that the ADHD symptoms were not a direct consequence of disturbed sleep or daytime sleepiness.

• Lie, Marie; Winsvold, Bendik; Gjerstad, Johannes; Matre, Dagfinn; Pedersen, Linda Margareth & Heuch, Ingrid [Show all 8 contributors for this article] (2020). The association between selected genetic variants and individual differences in experimental pain. Scandinavian Journal of Pain. ISSN 1877-8860. 21(1), p. 163–173. doi: 10.1515/sjpain-2020-0091. Full text in Research Archive Show summary

  Objectives The underlying mechanisms for individual differences in experimental pain are not fully understood, but genetic susceptibility is hypothesized to explain some of these differences. In the present study we focus on three genetic variants important for modulating experimental pain related to serotonin (SLC6A4 5-HTTLPR/rs25531 A>G), catecholamine (COMT rs4680 Val158Met) and opioid (OPRM1 rs1799971 A118G) signaling. We aimed to investigate associations between each of the selected genetic variants and individual differences in experimental pain. Methods In total 356 subjects (232 low back pain patients and 124 healthy volunteers) were genotyped and assessed with tests of heat pain threshold, pressure pain thresholds, heat pain tolerance, conditioned pain modulation (CPM), offset analgesia, temporal summation and secondary hyperalgesia. Low back pain patients and healthy volunteers did not differ in regards to experimental test results or allelic frequencies, and were therefore analyzed as one group. The associations were tested using analysis of variance and the Kruskal-Wallis test. Results No significant associations were observed between the genetic variants (SLC6A4 5-HTTLPR/rs25531 A>G, COMT rs4680 Val158Met and OPRM1 rs1799971 A118G) and individual differences in experimental pain (heat pain threshold, pressure pain threshold, heat pain tolerance, CPM, offset analgesia, temporal summation and secondary hyperalgesia). Conclusions The selected pain-associated genetic variants were not associated with individual differences in experimental pain. Genetic variants well known for playing central roles in pain perception failed to explain individual differences in experimental pain in 356 subjects. The finding is an important contribution to the literature, which often consists of studies with lower sample size and one or few experimental pain assessments.

• Sivertsen, Børge; Pallesen, Ståle; Friborg, Oddgeir; Nilsen, Kristian Bernhard; Bakke, Øystein & Goll, Jonas Bjørnskov [Show all 7 contributors for this article] (2020). Sleep patterns and insomnia in a large population-based study of middle-aged and older adults: The Tromsø study 2015–2016. Journal of Sleep Research. ISSN 0962-1105. 30(1). doi: 10.1111/jsr.13095. Full text in Research Archive Show summary

  Epidemiological studies assessing adult sleep duration have yielded inconsistent findings and there are still large variations in estimation of insomnia prevalence according to the most recent diagnostic criteria. Our objective was to describe sleep patterns in a large population of middle‐aged and older adults, by employing accurate measures of both sleep duration and insomnia. Data stem from the Tromsø Study (2015–2016), an ongoing population‐based study in northern Norway comprising citizens aged 40 years and older (n = 21,083, attendance = 64.7%). Sleep parameters were reported separately for weekdays and weekends and included bedtime, rise time, sleep latency and total sleep time. Insomnia was defined according to recent diagnostic criteria (International Classification of Sleep Disorders; ICSD‐3). The results show that 20% (95% confidence interval,19.4–20.6) fulfilled the inclusion criteria for insomnia. The prevalence was especially high among women (25%), for whom the prevalence also increased with age. For men, the prevalence was around 15% across all age groups. In all, 42% of the women reported sleeping <7 hr (mean sleep duration of 7:07 hr), whereas the corresponding proportion among males was 52% (mean sleep duration of 6:55 hr). We conclude that the proportion of middle‐aged and older adults not getting the recommended amount of sleep is worryingly high, as is also the observed prevalence of insomnia. This warrants attention as a public health problem in this population.

• Ree, Anbjørn; Nilsen, Kristian Bernhard; Knardahl, Stein; Sand, Trond & Matre, Dagfinn (2019). Sleep restriction does not potentiate nocebo‐induced changes in pain and cortical potentials. European Journal of Pain. ISSN 1090-3801. 24(1), p. 110–121. doi: 10.1002/ejp.1466. Full text in Research Archive Show summary

  Background: The increased pain sensitivity following reduced sleep may be related to changes in cortical processing of nociceptive stimuli. Expectations shape pain perception and can inhibit (placebo) or enhance (nocebo) pain. Sleep restriction appears to enhance placebo responses; however, whether sleep restriction also affects nocebo responses remains unknown. The aim of the present study was to determine whether sleep restriction facilitates nocebo‐induced changes in pain and pain‐evoked cortical potentials. Methods: In an experimental study with a crossover design, the sensitivity to electrically induced pain was determined in 53 nurses under two sleep conditions, after habitual sleep and after two consecutive nights at work. Nocebo was induced by conditioning one‐third of the pain stimuli. Pain‐elicited cortical event‐related potentials were recorded by electroencephalography (EEG). Data were analysed both in the time‐domain (N2P2 amplitude) and in the time‐frequency domain (ERP magnitude). Sleepiness and vigilance were also assessed. Results: Both nocebo alone and sleep restriction alone increased the sensitivity to electrically induced pain. However, no interaction effect was found. Moreover, the magnitude of the pain‐elicited responses increased after sleep restriction and decreased after nocebo expectation, suggesting that nocebo is probably not an underlying mechanism for the commonly observed hyperalgesia induced by sleep restriction. Conclusions: The present work addresses whether sleep restriction, known to increase the sensitivity of the pain system, facilitates nocebo‐induced hyperalgesia. Our findings suggest that this is not the case, indicating that the increased sensitivity of the pain system following nocebo and sleep restriction are mediated by different cortical mechanisms.

• Hagen, Knut; Hopstock, Laila Arnesdatter; Eggen, Anne Elise; Mathiesen, Ellisiv B. & Nilsen, Kristian Bernhard (2019). Does insomnia modify the association between C-reactive protein and migraine? The Tromsø Study 2015-2016. Cephalalgia. ISSN 0333-1024. 39(8), p. 1022–1029. doi: 10.1177/0333102418825370. Full text in Research Archive Show summary

  Background The relationship between high sensitivity C-reactive protein and migraine is unclear. The aim of this cross-sectional population-based study was to investigate the association between high sensitivity C-reactive protein and types of headache, and to evaluate the impact of insomnia on this association. Methods A total of 20,486 (63%) out of 32,591 invited, aged ≥40 years or older, participated in the seventh wave of the Tromsø study conducted in 2015–2016 and had valid information on headache, insomnia and high sensitivity C-reactive protein. The influence of insomnia on the association between questionnaire-based diagnoses of headache and elevated high sensitivity C-reactive protein defined as >3.0 mg/L was assessed using multiple logistic regression, estimating prevalence odds ratio with 95% confidence intervals. Results A total of 6290 participants (30.7%) suffered from headache during the last year. Among these, 1736 (8.5%) fulfilled the criteria of migraine, 991 (4.8%) had migraine with aura, 746 (3.6%) migraine without aura (3.8%), and 4554 (22.2%) had non-migrainous headache. In the final multi-adjusted analysis, elevated high sensitivity C-reactive protein was associated with headache (odds ratio 1.10, 95% confidence interval 1.01–1.20), migraine (odds ratio 1.17, 95% confidence interval 1.01–1.35), and migraine with aura (odds ratio 1.23, 95% confidence interval 1.01–1.53). No association was found between elevated high sensitivity C-reactive protein and migraine without aura or non-migrainous headache. The association between high sensitivity C-reactive protein and migraine was strongly dependent on insomnia status. Among individuals with insomnia, elevated high sensitivity C-reactive protein was associated with migraine (odds ratio 1.49, 95% confidence interval 1.02–2.17), and migraine with aura (odds ratio 1.59, 95% confidence interval 1.03–2.45), whereas no such relationship was found among those without insomnia. Conclusions In this cross-sectional study, participants with migraine, in particular migraine with aura, were more likely to have elevated high sensitivity C-reactive protein, evident only among those with insomnia.

• Skarpsno, Eivind S.; Mork, Paul Jarle; Nilsen, Tom Ivar Lund; Steingrímsdóttir, Ólöf Anna; Zwart, John-Anker & Nilsen, Kristian Bernhard (2019). The interplay between sleeplessness and high-sensitivity C-reactive protein on risk of chronic musculoskeletal pain: longitudinal data from the Tromsø Study. Sleep. ISSN 0161-8105. 42(9). doi: 10.1093/sleep/zsz127. Full text in Research Archive Show summary

  Study Objectives To examine independent associations of sleeplessness and high-sensitivity C-reactive protein (hsCRP) with risk of chronic musculoskeletal pain, and to explore the joint effect of sleeplessness and hsCRP on risk of chronic musculoskeletal pain. Methods A population-based prospective study of 3214 women and 3142 men (mean age: 55.4, range: 32–87) without severe chronic musculoskeletal pain and with hsCRP ≤ 10 mg/L at baseline in 2007–2008. Modified Poisson regression was used to calculate adjusted risk ratios (RRs) with 95% confidence intervals (CIs) for any chronic musculoskeletal pain and chronic widespread pain (CWP) at follow-up in 2015–2016 associated with self-reported sleeplessness and hsCRP at baseline. Results Compared with persons without sleeplessness, women and men reporting often/or always sleeplessness had RRs of CWP of 2.53 (95% CI: 1.94–3.29) and 2.48 (95% CI: 1.63–3.77), respectively. There was no clear association between hsCRP and risk of any chronic musculoskeletal pain or CWP. Joint effect analyses using persons without sleeplessness and with a hsCRP < 1.00 mg/L as the reference gave RRs for chronic musculoskeletal pain of 1.73 (95% CI: 1.26–2.37) for those with often/always sleeplessness and hsCRP < 1.00 mg/L; 1.01 (95% CI: 0.78–1.32) for those without sleeplessness and hsCRP ≥3.00 mg/L; and 2.47 (95% CI: 1.79–3.40) if they had both often/always sleeplessness and hsCRP ≥ 3.00 mg/L. The corresponding RRs for CWP were 1.89 (95% CI: 1.27–2.83), 0.96 (95% CI: 0.68–1.37), and 2.83 (95% CI: 1.91–4.20), respectively. Conclusions These results suggest that there is an interplay between sleeplessness and hsCRP on risk of any chronic musculoskeletal pain and CWP.

• Schulze, Daniel Gregor; Nordby, Karl-Christian; Småstuen, Milada Cvancarova; Clemm, Thomas; Grotle, Margreth & Zwart, John-Anker [Show all 7 contributors for this article] (2019). Impact of technical variations on the ring-finger test for carpal tunnelsyndrome. Clinical Neurophysiology Practice (CNP). 5, p. 23–29. doi: 10.1016/j.cnp.2019.11.005. Full text in Research Archive Show summary

  Objective To assess if recording the sensory latencies of the median and ulnar nerves one-by-one (consecutive) or at the same time (simultaneous) in the ring-finger test for carpal tunnel syndrome (CTS) will show equivalent results or if it will lead to a different clinical classification of patients. Methods We assessed the limits of agreement between the simultaneous and the consecutive method based on the median- ulnar sensory latency difference derived by both methods in 80 subjects and compared the number of minimal CTS cases identified by the two methods. Results Limits of agreement ranged from −0.23 to 0.29 ms. A significantly higher proportion of subjects with minimal CTS (only detectable by using the comparison test) was found using the simultaneous method (n = 8 and 2, respectively; p = 0.03). Conclusion The two methods have a poor to moderate agreement as indicated by the range of the limits of agreement (0.5 ms).

• Benavent, Sigrid Aune de Rodez; Nygaard, Gro Owren; Nilsen, Kristian Bernhard; Etholm, Lars; Sowa, Piotr & Gustavsen, Marte Wendel [Show all 11 contributors for this article] (2019). Neurodegenerative interplay of cardiovascular autonomic dysregulation and the retina in early multiple sclerosis. Frontiers in Neurology. 10, p. 1–9. doi: 10.3389/fneur.2019.00507. Full text in Research Archive Show summary

  Introduction: Autonomic nervous system (ANS) symptoms are prevalent in multiple sclerosis (MS) as is neurodegeneration. Our aim was to explore the occurrence of ANS symptoms and retinal neurodegeneration in a newly diagnosed MS population with tools available in a clinical setting. Methods: Forty-three MS patients and 44 healthy controls took part in the study. We employed a bedside cardiovascular ANS test battery together with classical pupillometry, optical coherence tomography (OCT) evaluation of retinal neurodegeneration in eyes without previous optic neuritis (MSNON) and patients' self-report forms on fatigue, orthostatic and ANS symptoms. Results: Half of the patients presented with ANS symptoms and a high level of fatigue. There was a significant difference in ganglion cell layer thickness (mean GCIPL) evaluated by OCT in MSNON compared to healthy control eyes. We found a negative linearity of mean GCIPL on group level with increasing disease duration. Three patients fulfilled the criteria of postural orthostatic tachycardia syndrome (POTS). Conclusion: Our results demonstrate retinal neurodegeneration in MSNON, a high frequency of fatigue and a high prevalence of ANS symptoms in newly diagnosed patients. Whether neurodegeneration precedes ANS dysfunction or vice versa is still open to debate, but as unveiled by the presence of POTS in this MS population, differences in stress-response regulation add to the understanding of variation in onset-time of ANS dysfunction in early MS.

• Lie, Marie; Petriu, Elena; Matre, Dagfinn; Hansson, Per; Andersen, Ole Kæseler & Zwart, John-Anker [Show all 7 contributors for this article] (2019). Psychophysical or spinal reflex measures when assessing conditioned pain modulation? European Journal of Pain. ISSN 1090-3801. 23(10), p. 1879–1889. doi: 10.1002/ejp.1462. Full text in Research Archive Show summary

  Background Assessing conditioning pain modulation (CPM) with spinal reflex measures may produce more objective and stable CPM effects than using psychophysical measures. The aim of the study was to compare the CPM effect and test‐retest reliability between a psychophysical protocol with thermal test‐stimulus and a spinal reflex protocol with electrical test‐stimulus. Methods Twenty‐five healthy volunteers participated in two identical experiments separated by minimum 1 week. The thermal test‐stimulus was a constant heat stimulation of 120 seconds on the subjects' forearm with continuous ratings of pain intensity on a 10 cm visual analogue scale. The electrical test‐stimulus was repeated electrical stimulation on the arch of the foot for 120 seconds, which elicited a nociceptive withdrawal reflex recorded from the anterior tibial muscle. Conditioning stimulus was a 7°C water bath. Differences in the magnitude and test–retest reliability were investigated with repeated‐measures analysis of variance and by relative and absolute reliability indices. Results The CPM effect was 46% and 4.5% during the thermal and electrical test‐stimulus (p<0.001), respectively. Intraclass correlation coefficient of 0.5 and 0.4 was found with the electrical and thermal test‐stimulus, respectively. Wide limits of agreement were found for both the electrical (‐3.4 to 3.8 mA) and the thermal test‐stimulus (‐3.2 to 3.6 cm). Conclusions More pronounced CPM effect was demonstrated when using a psychophysical protocol with thermal test‐stimulus compared to a spinal reflex protocol with electrical test‐stimulus. Fair relative reliability and poor absolute reliability (due to high intra‐individual variability) was found in both protocols.

• Lane, Jacqueline M.; Jones, Samuel E.; Dashti, Hassan S.; Wood, Andrew R.; Aragam, Krishna G & Hees, Vincent T. van [Show all 59 contributors for this article] (2019). Biological and clinical insights from genetics of insomnia symptoms. Nature Genetics. ISSN 1061-4036. 51(3), p. 387–393. doi: 10.1038/s41588-019-0361-7. Full text in Research Archive Show summary

  Insomnia is a common disorder linked with adverse long-term medical and psychiatric outcomes. The underlying pathophysiological processes and causal relationships of insomnia with disease are poorly understood. Here we identified 57 loci for self-reported insomnia symptoms in the UK Biobank (n = 453,379) and confirmed their effects on self-reported insomnia symptoms in the HUNT Study (n = 14,923 cases and 47,610 controls), physician-diagnosed insomnia in the Partners Biobank (n = 2,217 cases and 14,240 controls), and accelerometer-derived measures of sleep efficiency and sleep duration in the UK Biobank (n = 83,726). Our results suggest enrichment of genes involved in ubiquitin-mediated proteolysis and of genes expressed in multiple brain regions, skeletal muscle, and adrenal glands. Evidence of shared genetic factors was found between frequent insomnia symptoms and restless legs syndrome, aging, and cardiometabolic, behavioral, psychiatric, and reproductive traits. Evidence was found for a possible causal link between insomnia symptoms and coronary artery disease, depressive symptoms, and subjective well-being.

• Fjeld, Olaf Randall; Grotle, Margreth; Matre, Dagfinn; Pedersen, Linda Margareth; Lie, Marie & Småstuen, Milada Cvancarova [Show all 11 contributors for this article] (2019). Predicting the outcome of persistent sciatica using conditioned pain modulation: 1-year results from a prospective cohort study. Scandinavian Journal of Pain. ISSN 1877-8860. 20(1), p. 69–75. doi: 10.1515/sjpain-2019-0112. Full text in Research Archive Show summary

  Background and aims Recovery in patients hospitalised with severe sciatica is unpredictable. Prognostic tools to aid clinicians in the early identification of patients at risk of developing chronic sciatic pain are warranted. Conditioned pain modulation (CPM) is a psychophysical measure of the endogenous pain modulatory pathways. Several studies have suggested CPM as a potentially important predictive biomarker for the development of chronic pain. The aim of the study was to determine whether CPM effect in patients still suffering from leg pain 6 weeks after hospital discharge for severe sciatica is associated with persistent leg pain at 12 months. A potential association would suggest that measuring CPM effect could be a valuable prognostic tool in the hospital management of sciatica. Methods A prospective cohort study in which CPM effect was measured 6 weeks after hospital discharge following an acute admission with sciatica as the main complaint. The impact of CPM effect on the outcome was analysed using logistic regression. The outcome measured was self-reported leg pain score of ≥1 in the past week on a 0-10 numeric rating scale (NRS) at 12 months post discharge. Results A total of 111 patients completed the entire study, 51 of whom received non-randomised surgical treatment. Crude and confounder adjusted analyses showed no significant association between CPM effect and leg-pain measured at 12 months, crude Odds Ratio 0.87, 95% CI 0.7-1.1, p = 0.23. Conclusions Our results suggest that CPM assessment has limited prognostic value for the long-term outcome in severe sciatica when measured 6 weeks after hospital discharge. Implications The present study adds important knowledge concerning the limited clinical use of late CPM testing in sciatica patients. The heterogeneity in patients, the wide range of treatments received and a generally favourable outcome are factors that may affect CPM's clinical value as a prognostic factor for severe sciatica.

• Matre, Dagfinn; Nilsen, Kristian Bernhard; Katsifaraki, Maria; Waage, Siri; Pallesen, Ståle & Bjorvatn, Bjørn (2019). Pain complaints are associated with quick returns and insomnia among Norwegian nurses, but do not difer between shift workers and day only workers. International Archives of Occupational and Environmental Health. ISSN 0340-0131. 93, p. 1–9. doi: 10.1007/s00420-019-01481-w. Full text in Research Archive Show summary

  Purpose To determine whether common work schedule characteristics among Norwegian nurses were associated with subjective pain complaints. Methods A cross-sectional study in a sample of 1585 nurses, part of the longitudinal questionnaire-based cohort project ‘Survey of Shift work, Sleep and Health’ (SUSSH). Pain from six regions were assessed: ‘headache’, ‘neck/shoulder/upper back’, ‘upper extremities’, ‘lower back’, ‘lower extremities’, and ‘abdomen’. Logistic and negative binomial regression (adjusted for age, sex, percentage of full-time equivalent, marital status and children living at home) were conducted where work schedule, number of night shifts last year, number of quick returns (QR) last year (< 11 h between shifts) and insomnia were predictors of localized pain, widespread pain and number of pain sites. Results Localized pain, widespread pain and number of pain sites were associated with insomnia (OR 2.06, 95% CI 1.66–2.55, OR 2.14, 95% CI 1.47–3.09, IRR 1.70, 95% CI 1.51–1.91, respectively). Work schedule and number of night shifts worked last year were not associated with any of the three pain measures. Number of QRs worked last year tended to be associated with number of pain sites. Conclusion The study did not support the hypothesis that non-daytime work schedules are associated with pain complaints. Neither was there support for the hypothesis linking number of night shifts, or the number of QRs, to pain complaints. Future studies should aim to determine the association between QRs and pain in more detail. Pain complaints were associated with insomnia.

• Hagen, Knut; Stovner, Lars Jacob; Nilsen, Kristian Bernhard; Kristoffersen, Espen Saxhaug & Winsvold, Bendik K S (2019). The impact of C-reactive protein levels on headache frequency in the HUNT study 2006-2008. BMC Neurology. 19(229), p. 1–8. doi: 10.1186/s12883-019-1462-8. Full text in Research Archive Show summary

  Background: Increased high sensitivity C- reactive protein (hs-CRP) levels have been found in many earlier studies on migraine, and recently also in persons with migraine and insomnia. The aim of this study was to see whether these findings could be reproduced in a large-scale population-based study. Methods: A total of 50,807 (54%) out of 94,194 invited aged ≥20 years or older participated in the third wave of the Nord-Trøndelag Health Study study performed in 2006–2008. Among these, 38,807 (41%) had valid measures of hs-CRP and answered questions on headache and insomnia. Elevated hs-CRP was defined as > 3.0 mg/L. The crosssectional association with headache was estimated by multivariate analyses using multiple logistic regression. The precision of the odds ratio (OR) was assessed with 95% confidence interval (CI). Results: In the fully adjusted model, elevated hs-CRP was associated with migraine (OR 1.14, 95% CI 1.04–1.25) and migraine with aura (OR 1.15, 95% CI 1.03–1.29). The association was strongest among individuals with headache ≥15 days/month for any headache (OR 1.26, 95% CI 1.08–1.48), migraine (OR 1.62, 95% CI 1.21–2.17), and migraine with aura (OR 1.84, 95% CI 1.27–2.67). No clear relationship was found between elevated hs-CRP and headache less than 7 days/month or with insomnia. Conclusions: Cross-sectional data from this large-scale population-based study showed that elevated hs-CRP was associated with headache ≥7 days/month, especially evident for migraine with aura.

• Ho, Kevin Kwan Ngai; Simic, Milena; Småstuen, Milada Cvancarova; Pinheiro, Marina de Barros; Ferreira, Paulo Herrique & Johnsen, Marianne Bakke [Show all 10 contributors for this article] (2019). The association between insomnia, c-reactive protein, and chronic low back pain: Cross-sectional analysis of the HUNT study, Norway. Scandinavian Journal of Pain. ISSN 1877-8860. 19(4), p. 765–777. doi: 10.1515/sjpain-2019-0033. Full text in Research Archive Show summary

  Chronic low back pain (chronic LBP) is the number one cause for years lived with disability among 301 diseases and injuries analyzed by The Global Burden of Disease study 2013. Insomnia is highly prevalent among people with chronic LBP. To explain the sleep-pain relationship, theoretical models propose that insomnia symptoms may be associated with increased basal inflammation, operationalized as c-reactive protein (CRP) and lead to further pain and disrupted sleep. We aimed to determine the associations between insomnia, chronic LBP, and inflammation (operationalized as CRP), whilst controlling for age, body mass index, smoking, physical activity, depression, anxiety and osteoarthritis.

• Nordstrand, Sebjørg Elizabeth Hesla; Hansen, Berit M Hjelde; Rootwelt-Revheim, Terje; Karlsen, Tor-Ivar; Swanson, David & Nilsen, Kristian Bernhard [Show all 7 contributors for this article] (2019). Psychiatric symptoms in patients with post-H1N1 narcolepsy type 1 in Norway. Sleep. ISSN 0161-8105. 42(4), p. 1–9. doi: 10.1093/sleep/zsz008. Full text in Research Archive Show summary

  Study Objectives Several studies have reported psychiatric comorbidity in patients with narcolepsy type 1 (NC1). The primary aim of this study was to explore the extent of psychiatric symptoms in a cohort of Norwegian NC1 patients, most of whom were H1N1-vaccinated. We also wanted to explore possible causes of the psychiatric symptoms seen in NC1. Methods Cross-sectional study. Psychiatric symptoms were assessed by the Achenbach System of Empirically Based Assessment (ASEBA) Child Behavior Check List (CBCL) in children and by Adult Self Report (ASR) in adults. Results The mean (SD) total T-scores were 58.6 (9.2) for children and 57.0 (9.8) for adults, these being mainly driven by internalizing problems. Internalizing symptom T-scores showed that 37.5% of the children and 33.3% of the adults were in the clinical range of concern. T-scores were lower when the questionnaire’s sleep-related items were excluded. However, 27.5% of children and 22.2% of adults still remained within the total psychiatric symptoms clinical range. Psychiatric symptoms and excessive daytime sleepiness were not associated. However, in children fragmented sleep, measured by sleep-stage shift index was significantly negatively associated with all the psychiatric summary scores (all p ≤ 0.020), and awakening index was negatively associated with externalizing (p = 0.042) and total summary scores (p = 0.042). In adults, awakening index, but not sleep-stage shift index, was positively associated with internalizing score (p = 0.015). Hypocretin-1 levels showed no association with psychiatric symptoms. Conclusions We found a high prevalence of psychiatric symptoms in NC1 patients. Fragmented sleep was significantly associated with psychiatric symptoms. Keywords: narcolepsy type 1, narcolepsy with cataplexy, psychiatric symptoms, Pandemrix, H1N1

• Nordstrand, Sebjørg Elizabeth Hesla; Hansen, Berit M Hjelde; Kamaleri, Yusman; Nilsen, Kristian Bernhard; Rootwelt-Revheim, Terje & Karlsen, Tor-Ivar [Show all 7 contributors for this article] (2018). Changes in quality of life in individuals with narcolepsy type 1 after the H1N1-influenza epidemic and vaccination campaign in Norway: a two-year prospective cohort study. Sleep Medicine. ISSN 1389-9457. 50, p. 175–180. doi: 10.1016/j.sleep.2018.05.037. Full text in Research Archive Show summary

  Objective Cross-sectional studies show a lower health-related quality of life (HRQoL) in individuals with narcolepsy. We aimed to describe changes in HRQoL after two years of multidisciplinary follow-up in a cohort of mainly post-H1N1 vaccination narcolepsy type-1 (NT1) patients in Norway. Methods Prospective-cohort study. Narcolepsy diagnosis was based on the International Classification of Sleep Disorders (third edition). Psychiatric comorbidity was assessed using the Achenbach System of Empirically Based Assessment (ASEBA). HRQoL was evaluated with the Pediatric Quality of Life Inventory (PedsQL™ Generic Core Scales 4.0) at baseline and follow-up. Mean follow-up time was 20.7 (2.7) months. Results Thirty one patients (18 females) with NT1, mean age 14.6 (SD = 4.8) years answered questionnaires at baseline and follow-up. On a group level, the PedsQL Total Health Summary score significantly improved by a mean of 5.9 (95%CI = 0.4, 11.9), p = 0.038; this was mainly driven by improvements in the Physical Health Summary score by 9.8 (3.0, 16.5) points, p = 0.006 and the School Functioning Scale score by 7.5 (1.0, 13.9) points p = 0.025. The Total ASEBA score was correlated with PedsQL Total Health Summary score at baseline, but not with changes in HRQoL. Sodium oxybate (Xyrem®) treatment at follow up was positively associated with changes in PedsQL Total Health Summary score, after adjusting for age and gender, p = 0.027. Conclusion HRQoL in NT1 patients improved after two years of follow-up. The use of sodium oxybate (Xyrem®) at follow-up was associated with increases in HRQoL. Psychiatric comorbidity was correlated with HRQoL at baseline but did not predict changes in HRQoL at follow-up.

• Iversen, Johanne Marie; Uglem, Martin; Indredavik, Marit Sæbø; Romundstad, Pål Richard; Nilsen, Kristian Bernhard & Sand, Trond [Show all 7 contributors for this article] (2018). Pain sensitivity and thermal detection thresholds in young adults born preterm with very low birth weight or small for gestational age at term compared with controls. Journal of Pain. ISSN 1526-5900. 19(8), p. 873–884. doi: 10.1016/j.jpain.2018.03.001. Full text in Research Archive Show summary

  The objective of this prospective long-term follow-up study was to investigate whether somatosensory function is altered among young adults born preterm with very low birth weight (VLBW; ≤1,500 g) or small for gestational age (SGA; <10th percentile) at term. In a blinded quantitative sensory testing protocol, we determined thermal detection, thermal pain, and pressure pain thresholds and the response to prolonged supra-threshold heat among 51 VLBW, 66 term SGA, and 86 term-born controls (birth weight ≥10th percentile) at 28 years. Self-reported chronic pain was also investigated. Except for increased sensitivity to cool in the term SGA group versus controls, we found no significant group differences regarding thermal or pain thresholds. Overall, male participants had higher pain thresholds, and no significant interactions of group and sex were observed (P > .14). Within the VLBW group, neonatal mechanical ventilation was associated with reduced sensitivity to cool, and length of mechanical ventilation correlated with lower pressure pain thresholds. The response to prolonged supra-threshold heat was similar between the groups, and the prevalence of self-reported chronic pain was not reliably different. In conclusion, low birth weight young adults were as sensitive to thermal and pain stimuli as term-born, normal birth weight controls, with the same sex differences.

• Katsifaraki, Maria; Nilsen, Kristian Bernhard; Christensen, Jan Olav; Wærsted, Morten; Knardahl, Stein & Bjorvatn, Bjørn [Show all 8 contributors for this article] (2018). Sleep duration mediates abdominal and lower-extremity pain after night work in nurses. International Archives of Occupational and Environmental Health. ISSN 0340-0131. p. 1–8. doi: 10.1007/s00420-018-1373-9. Full text in Research Archive Show summary

  Objectives: The aim of this study was to investigate the association between different working shifts (i.e. morning, evening, night shifts) and headache, musculoskeletal and abdominal pain, and the extent to which reduced sleep duration could account for these associations. Methods: Nurses (N = 679, 649 female, aged 22–53 years) were followed up for a period of 28 consecutive days, responding to a diary about sleep, shift type and pain complaints (measured on a Likert-type scale ranging from 0 to 3). Generalised structural equation modelling mediation analysis (GSEM) was performed to test whether shift type was associated with higher incidence or higher intensity of pain (headache, pain in neck/shoulders/upper back, upper extremity, low back, lower extremity and abdominal pain), and if this effect was mediated by sleep duration (continuous variable), after controlling for age, work and lifestyle factors. Results: Pain scores in lower extremities were decreased following night shifts in general. However, when night shifts were followed by short sleep duration, the risk of pain in the lower extremities and abdominal pain were increased. Headache and pain in the upper extremity were increased after night shifts, but were not associated with sleep duration. Pain in the neck/shoulder/upper back and lower back was not related to shift work. Conclusions: Among nurses in a three-shift rotating schedule, night shifts increased the risk of pain in several regions, but only pain in the lower extremities and abdomen was related to reduced sleep duration.

• Fjeld, Olaf Randall; Grotle, Margreth; Siewers, Vibeke; Pedersen, Linda Margareth; Nilsen, Kristian Bernhard & Zwart, John-Anker (2017). Prognostic Factors for Persistent Leg-Pain in Patients Hospitalized with Acute Sciatica. Spine. ISSN 0362-2436. 42(5), p. E272–E279. doi: 10.1097/BRS.0000000000001773. Full text in Research Archive Show summary

  Study Design: Prospective cohort study. Objective. To identify potential prognostic factors for persistent leg-pain at 12 months among patients hospitalized with acute severe sciatica. Summary of Background Data. The long-term outcome for patients admitted to hospital with sciatica is generally unfavorable. Results concerning prognostic factors for persistent sciatica are limited and conflicting. Methods: A total of 210 patients acutely admitted to hospital for either surgical or nonsurgical treatment of sciatica were consecutively recruited and received a thorough clinical and radiographic examination in addition to responding to a comprehensive questionnaire. Follow-up assessments were done at 6 weeks, 6 months, and 12 months. Potential prognostic factors were measured at baseline and at 6 weeks. The impact of these factors on leg-pain was analyzed by multiple linear regression modeling. Results: A total of 151 patients completed the entire study, 93 receiving nonrandomized surgical treatment. The final multivariate models showed that the following factors were significantly associated with leg-pain at 12 months: high psychosocial risk according to the Örebro Musculosceletal Pain Questionnaire (unstandardized beta coefficient 1.55, 95% confidence interval [CI] 0.72–2.38, P < 0.001), not receiving surgical treatment (1.11, 95% CI 0.29–1.93, P = 0.01), not actively employed upon admission (1.47, 95% CI 0.63–2.31, P < 0.01), and self-reported leg-pain recorded 6 weeks posthospital admission (0.49, 95% CI 0.34–0.63, P < 0.001). Interaction analysis showed that the Örebro Musculosceletal Pain Questionnaire had significant prognostic value only on the nonsurgically treated patients (3.26, 95% CI 1.89–4.63, P < 0.001). Conclusion: The results suggest that a psychosocial screening tool and the implementation of a 6-week postadmission follow-up has prognostic value in the hospital management of severe sciatica.

• Benavent, Sigrid Aune de Rodez; Nygaard, Gro Owren; Harbo, Hanne Flinstad; Tønnesen, Siren; Sowa, Piotr & Landrø, Nils Inge [Show all 13 contributors for this article] (2017). Fatigue and cognition: Pupillary responses to problem-solving in early multiple sclerosis patients. Brain and Behavior. 7(7). doi: 10.1002/brb3.717. Full text in Research Archive Show summary

  Introduction In early multiple sclerosis (MS) patients, cognitive changes and fatigue are frequent and troublesome symptoms, probably related to both structural and functional brain changes. Whether there is a common cause of these symptoms in MS is unknown. In theory, an altered regulation of central neuropeptides can lead to changes in regulation of autonomic function, cognitive difficulties, and fatigue. Direct measurements of central neuropeptides are difficult to perform, but measurements of the eye pupil can be used as a reliable proxy of function. Methods This study assesses pupil size during problem-solving in early MS patients versus controls. A difference in pupil size to a cognitive challenge could signal altered activity within the autonomic system because of early functional brain changes associated with cognitive load. We recruited MS patients (mean disease duration: 2.6 years, N = 41) and age-matched healthy controls (N = 43) without eye pathology. Neurological impairment, magnetic resonance imaging, visual evoked potentials, depression, and fatigue were assessed in all of the patients. In both groups, we assessed processing speed and retinal imaging. Pupil size was recorded with an eye-tracker during playback of multiplication tasks. Results Both groups performed well on the cognitive test. The groups showed similar pupillary responses with a mean of 0.55 mm dilation in patients and 0.54 mm dilation in controls for all the tasks collapsed together. However, controls (N = 9) with low cognitive scores (LCS) had an increased pupillary response to cognitive tasks, whereas LCS MS patients (N = 6) did not (p < .05). There was a tendency toward a smaller pupillary response in patients with fatigue. Conclusions This is the first study to investigate pupillary responses to cognitive tasks in MS patients. Our results suggest that MS-related changes in cognition and fatigue may be associated with changes in arousal and the autonomic regulation of task-related pupillary responses. This supports the theory of a link between cognition and fatigue in MS.

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• Holme, Andreas Næss; Moen, Line Victoria; Sallinen, Mikael; Nilsen, Kristian Bernhard; Boccara, Charlotte & Haugen, Fred [Show all 7 contributors for this article] (2026). Night Shift Work as an Arctic Hazard: Do Seasonal Light Extremes Affect Alertness, Sleepiness, and Fatigue? Full text in Research Archive Show summary

  Introduction: Light is the primary entrainment mechanism (‘zeitgeber’) of the circadian clock. Its sensitivity to light means that seasonal changes in photoperiod can affect circadian entrainment in shift workers, potentially influencing their adaptation to night work. At high latitudes, such as the Arctic, extreme daylight variations across seasons provide a unique context for studying consequences of such light sensitivity. Polar nights and midnight sun may further challenge circadian entrainment mechanisms. Whether shift work and seasonal variations cumulate or combine their effect in the photoperiodic zeitgeber remains unclear. This study investigates how seasonal variations may interact with consecutive morning and night shifts to impact alertness, sleepiness and fatigue in shift workers. Methods: We recruited 112 three-shift process operators at 71°N, among which 81 participated during both the dark and light seasons. The work schedule included seven consecutive morning shifts and seven consecutive night shifts, separated by four rest days. Objective alertness was measured by the 3-minute Psychomotor Vigilance Task (PVT-B), using lapses (omissions ≥355ms) and response speed (inverse response time) as outcome variables. Subjective sleepiness and fatigue were assessed by the Karolinska Sleepiness Scale (KSS) and a separate question to assess mental fatigue, respectively. Tests were conducted at the end of shift on days 1, 3, and 6 of each 7-day shift block. Data were analysed using multilevel linear mixed-effects regression models with season, shift type (morning/night) and consecutive workday number as fixed effects. Results: Night shifts were associated with lower alertness and higher levels of sleepiness and fatigue, especially on the first night shift, compared to morning shifts. Furthermore, the results indicated significant improvements in alertness and reduced sleepiness and fatigue over the consecutive six night shifts. There was no effect of season on any of the outcome variables. Conclusion: These findings suggest that while night shifts generally impair alertness, as well as increase sleepiness and fatigue, workers may gradually adapt over consecutive shifts, as evidenced by improvements by the sixth night. The lack of significant seasonal effects on sleepiness and fatigue suggests that workers might adapt equally well to night shifts regardless of the photoperiod.

• Arora, Tarun; Fossmo, Hanne Ludt; Raastad, Truls; Fjermestad, Krister Westlye; Ramberg, Cathrine & Nilsen, Kristian Bernhard [Show all 12 contributors for this article] (2025). 314P Personalized training for people with rare neuromuscular disorders (PETRA-NMD): a multi-center randomized controlled clinical trial. Neuromuscular Disorders. ISSN 0960-8966. 53(Supplement, September), p. 75–75. doi: 10.1016/j.nmd.2025.105738. Full text in Research Archive
• Halford, J.J.; Brinkmann, B.A.; Rampp, S.; Rémi, J.; Poznikoff, S. & Nilsen, Kristian Bernhard [Show all 8 contributors for this article] (2025). DICOM encoding of annotation and montage data for waveform recordings. Clinical Neurophysiology. ISSN 1388-2457. 174, p. 190–190. doi: 10.1016/j.clinph.2025.04.002. Full text in Research Archive
• Holme, Andreas Næss; Moen, Line Victoria; Sallinen, Mikael; Nilsen, Kristian Bernhard; Boccara, Charlotte & Haugen, Fred [Show all 7 contributors for this article] (2025). Night Work During Midnight Sun and Polar Nights: Impact on Alertness, Sleepiness and Fatigue. doi: 10.1055/s-0045-1812737. Full text in Research Archive Show summary

  Introduction: The circadian clock's sensitivity to light means that seasonal changes in photoperiod can affect circadian entrainment in shift workers, thus influencing their adaptation to night work. At high latitudes, such as the Arctic, extreme daylight variations across seasons, provide a unique context for studying such circadian disruption. Polar nights and midnight sun may further challenge circadian entrainment mechanisms. Whether shift work and seasonal variations cumulate or combine their effect in the photoperiodic zeitgeber remains unclear. This study investigates how seasonal variations may interact with consecutive morning and night shifts to impact alertness, sleepiness and fatigue. Methods: We recruited 112 three-shift process operators at 71°N, among which 84 participated during both the dark and light seasons. Their work schedule included blocks of seven consecutive morning shifts and seven consecutive night shifts, separated by four rest days. Alertness was measured by the 3-minute Psychomotor Vigilance Task (PVT-B), using lapses (omissions ≥355ms) and response speed (inverse response time) as outcome variables. Sleepiness was assessed by the Karolinska Sleepiness Scale (KSS). A separate question was used to assess mental fatigue. Tests were conducted at the end of the operators’ shift on days 1, 3, and 6 of each shift block. KSS was also assessed at the start and end of all shifts. Data were analyzed using multilevel mixed-effects regression models with season, shift type (morning/night) and consecutive workday number as fixed effects. Results: Night shifts were linked to lower alertness, as well as higher sleepiness and fatigue, especially on the first night shift. Interaction effects indicated improved response speed, fewer lapses, and reduced sleepiness and fatigue over six-night shifts, with significant differences between night 1 and night 6. These patterns were similar for both seasons across all variables. However, PVT-tests showed that the overall contrast between morning and night shifts was only significant during the dark season (response speed: p < 0.0001, lapses: p≈0.005), but not during the light season. Neither sleepiness, nor fatigue, were significantly affected by seasons. Conclusion: These findings suggest that while night shifts generally impair alertness, as well as increase sleepiness and fatigue, workers may gradually adapt over consecutive shifts, as evidenced by improvements by the sixth night. The lack of significant seasonal effects on sleepiness and fatigue suggests that workers might adapt equally well to night shifts regardless of the photoperiod. However, the more pronounced differences in alertness between morning and night shifts during the dark season highlight the potential interplay between reduced daylight’s influence on circadian rhythms and adaptability to work night shifts.

• Arora, Tarun; Thorgersen, Jørn Klepp; Jones, Kelvin Edward; Allen, Sara Maria; Schulze, Daniel Gregor & Dunker, Øystein [Show all 8 contributors for this article] (2025). Utility of MScanFit for Motor Unit Number Estimation in three muscles affected by Amyotrophic Lateral Sclerosis - Test-retest measurement properties. Full text in Research Archive
• Do, Hoang Oanh Pauline; Thomas, Anub Mathew; Omland, Petter Moe; Szczepanski, Tomasz Szymon; Dunker, Øystein & Schulze, Daniel Gregor [Show all 7 contributors for this article] (2025). A comparative Evaluation of Carpal Tunnel Syndrome Diagnosis Based on Historical Nerve Conduction Study Reference Limits. Full text in Research Archive
• Szczepanski, Tomasz Szymon; Omland, Petter Moe; Dunker, Øystein; Sand, Trond Halfdan; Tannemaat, Martijn & Reijntjes, Robert [Show all 11 contributors for this article] (2025). Deriving reference limits from historical data - A comparison of four novel methods. Full text in Research Archive
• Moen, Line Victoria; Holme, Andreas Næss; Sallinen, Mikael; Phillips, Andrew J.K.; Nilsen, Kristian Bernhard & Lie, Jenny-Anne Sigstad [Show all 8 contributors for this article] (2024). Impacts of night work and season on sleepiness and vigilance in Arctic industrial workers. Full text in Research Archive
• Omland, Petter Moe; Li, Ruiyi; Szczepanski, Tomasz Szymon; Engstrøm, Morten; Uglem, Martin & Sand, Trond Halfdan [Show all 7 contributors for this article] (2024). Beregning av referansegrenser for visuelt fremkalt respons fra historiske data: En enkelt og effektiv måte for utvikling og vedlikehold av referansegrenser. Full text in Research Archive
• Halford, J.J.; Campobello, G.; Brinkmann, B.H.; Stead, M.; Rampp, S. & Rémi, J. [Show all 14 contributors for this article] (2024). Letter to the Editor: Announcement of a Call for Proposals for biomedical waveform coding. Clinical Neurophysiology. ISSN 1388-2457. 165, p. 88–89. doi: 10.1016/j.clinph.2024.06.010. Full text in Research Archive
• Szczepanski, Tomasz Szymon; Omland, Petter Moe & Nilsen, Kristian Bernhard (2024). New national reference limits for nerve conduction studies. Full text in Research Archive
• Omland, Petter Moe; Szczepanski, Tomasz Szymon; Engstrøm, Morten; Uglem, Martin; Sand, Trond Halfdan & Nilsen, Kristian Bernhard (2024). Deriving reference limits for visual evoked potentials from historical data. Full text in Research Archive
• Dunker, Øystein & Nilsen, Kristian Bernhard (2023). Vanskelig å diagnostisere nervesmerter i føtter. Ekspertsykehuset OUS. Full text in Research Archive
• Nilsen, Kristian Bernhard (2023). Digital gold mining in historical neurophysiological data. Full text in Research Archive
• Dunker, Øystein; Grotle, Margreth & Nilsen, Kristian Bernhard (2023). Validating clinical tools for neuropathic pain: Should negative studies be thrown out? Reply to Attal and Bouhassira. Pain. ISSN 0304-3959. 164(5). doi: 10.1097/j.pain.0000000000002908. Full text in Research Archive
• Matre, Dagfinn; Sallinen, Mikael; Phillips, Andrew J K; Moen, Line Victoria; Nilsen, Kristian Bernhard & Haugen, Fred (2023). Night work, season and alertness as occupational safety hazards in the Arctic: Protocol for the Noralert observational crossover study among Norwegian process operators. Occupational and Environmental Medicine. ISSN 1351-0711. 13(10). doi: 10.1136/bmjopen-2023-075107. Full text in Research Archive Show summary

  Introduction The objective of this study is to determine the effects of night work, Arctic seasonal factors and cold working environments on human functions relevant to safety. The study aims to quantify the contribution of (1) several consecutive night shifts, (2) seasonal variation on sleepiness, alertness and circadian rhythm and (3) whether a computational model of sleep, circadian rhythms and cognitive performance can accurately predict the observed sleepiness and alertness. Methods and analysis In an observational crossover study of outdoor and indoor workers (n=120) on a three-shift schedule from an industrial plant in Norway (70 °N), measurements will be conducted during the summer and winter. Sleep duration and quality will be measured daily by smartphone questionnaire, aided by actigraphy and heart rate measurements. Sleepiness and alertness will be assessed at regular intervals by the Karolinska Sleepiness Scale and the psychomotor vigilance test, respectively. Saliva samples will assess melatonin levels, and a blood sample will measure circadian time. Thermal exposures and responses will be measured by sensors and by thermography. Ethics and dissemination All participants will give written informed consent to participate in the study, which will be conducted in accordance with the Declaration of Helsinki. The Norwegian Regional Committee for Medical Research Ethics South-East D waivered the need for ethics approval (reference 495816). Dissemination plans include academic and lay publications, and partnerships with national and regional policymakers.

• Nilsen, Kristian Bernhard (2023). Et første skritt mot bedre behandling av smertefull diabetesnevropati. Ekspertsykehuset OUS. Full text in Research Archive
• Nilsen, Kristian Bernhard & Dunker, Øystein (2023). Hvorfor trenger vi bedre metoder for å diagnostisere diabetisk perifer nevropati? Ekspertsykehuset OUS. Full text in Research Archive
• Kerkhof, Fabian; Reijntjes, Robert; Dunker, Øystein; Lie, Marie Udnesseter; Nilsen, Kristian Bernhard & Tannemaat, Martijn (2023). Deriving reference values for nerve conduction studies and ultrasound measurements of the median nerve using mixture model clustering. Clinical Neurophysiology. ISSN 1388-2457. doi: 10.1016/j.clinph.2023.03.114. Full text in Research Archive
• Schulze, Daniel Gregor; Nilsen, Kristian Bernhard; Clemm, Thomas; Grotle, Margreth; Ulvestad, Bente & Nordby, Karl-Christian (2023). Peripheral neuropathy among workers with Hand-arm vibration exposure. Clinical Neurophysiology. ISSN 1388-2457. 150. doi: 10.1016/j.clinph.2023.03.028. Full text in Research Archive Show summary

  Objectives Identify associations between peripheral neuropathy and Hand-arm vibration exposure. Content Background: Carpal tunnel syndrome (CTS) and ulnar neuropathy (UNE) are common among workers exposed to hand-arm vibration (HAV). The role of ergonomic factors is unclear. We aimed to investigate the relationship between CTS and UNE and HAV-exposure in workers using vibrating tools with different ergonomic profile. Methods: We tested two groups of workers with exposure to hand-arm vibration from different tools. All workers were tested with nerve conduction studies (NCS) of sensory and motor

• Nilsen, Kristian Bernhard; Lie, Marie Udnesseter; Andries, Aristomo Ibnu Chalid; Dunker, Øystein; Do, Hoang Oanh Pauline & Reiner, Andrew Henry [Show all 10 contributors for this article] (2023). The DIGMINE project – Improved diagnostics by digital gold mining in historical neurophysiological data. Clinical Neurophysiology. ISSN 1388-2457. doi: 10.1016/j.clinph.2023.03.090. Full text in Research Archive
• Dunker, Øystein; Nilsen, Kristian Bernhard; Olsen, Sandra Elise & Sand, Trond (2022). WHICH AGGREGATE COMBINATION OF NERVE CONDUCTION STUDY MEASURES IS BEST SUITED TO EVALUATE DIABETIC POLYNEUROPATHY? Clinical Neurophysiology. ISSN 1388-2457. doi: 10.1016/j.clinph.2022.07.302. Full text in Research Archive
• Dunker, Øystein; Grotle, Margreth; Kvaløy, Marie Bu; Uglem, Martin; Løseth, Sissel & Hjelland, Ina Elen [Show all 12 contributors for this article] (2022). SCREENING FOR NEUROPATHIC PAIN IN PATIENTS WITH POSSIBLE POLYNEUROPATHY – A VALIDATION STUDY OF THREE DIFFERENT QUESTIONNAIRES. Full text in Research Archive
• Dunker, Øystein; Kvaløy, Marie Bu; Uglem, Martin; Løseth, Sissel; Hjelland, Ina Elen & Kleggetveit, Inge Petter [Show all 10 contributors for this article] (2022). Assessing diabetes polyneuropathy using a 5.07/10g Semmes-Weinstein monofilament. Full text in Research Archive
• Dunker, Øystein; Nilsen, Kristian Bernhard; Olsen, Sandra Elise; Åsvold, Bjørn Olav; Bjørgaas, Marit Ragnhild Rokne & Sand, Trond (2022). WHICH AGGREGATE COMBINATION OF NERVE CONDUCTION STUDY MEASURES IS BEST SUITED TO EVALUATE DIABETIC POLYNEUROPATHY? Full text in Research Archive
• Andries, Aristomo; Ørstavik, Kristin; Rueegg, Corina Silvia; Eng, Sindre; Edvardsen, Elisabeth & Allen, Sara-Maria [Show all 10 contributors for this article] (2022). Polynevropati hos barnekreftoverlevere. Full text in Research Archive
• Nilsen, Kristian Bernhard (2021). Motor unit estimation in ALS. Full text in Research Archive
• Nilsen, Kristian Bernhard (2021). Utredning og diagnostikk av nevropatisk smerte. Full text in Research Archive
• Nilsen, Kristian Bernhard (2021). Diagnostikk av nevropatisk smerte. Full text in Research Archive
• Nilsen, Kristian Bernhard (2021). Polynevropati hos barnekreftoverlevere. [Journal]. Våre Barn. Full text in Research Archive
• Bajwa, Simranjit Kaur; Nilsen, Kristian Bernhard; Erichsen, Erik Aksel Spendrup; Berg-Hansen, Pål & Harbo, Hanne Flinstad (2018). En mann i 50-årene med svimmelhet, dobbeltsyn og gangvansker. Tidsskrift for Den norske legeforening (Tidsskriftet). ISSN 0029-2001. 138(3). doi: 10.4045/tidsskr.16.1109. Full text in Research Archive
• Iversen, Johanne Marie; Uglem, Martin; Indredavik, Marit Sæbø; Evensen, Kari Anne Indredavik; Romundstad, Pål Richard & Nilsen, Kristian Bernhard [Show all 8 contributors for this article] (2018). Thermal detection and pain sensitivity in young adults born preterm with very low birth weight. Full text in Research Archive
• Engstrøm, Morten; Aarrestad, Sigurd; Eldøen, Guttorm; Alme, Anders; Bjørge, Trond & Miljeteig, Harald [Show all 10 contributors for this article] (2018). Nye anbefalinger for objektiv undersøkelse av søvn og søvnforstyrrelser. Tidsskrift for Den norske legeforening (Tidsskriftet). ISSN 0029-2001. 138(19), p. 1805–1806. doi: 10.4045/tidsskr.18.0741. Full text in Research Archive
• Nordstrand, Sebjørg Elizabeth Hesla; Hansen, Berit M Hjelde; Kamaleri, Yusman; Nilsen, Kristian Bernhard; Karlsen, Tor-Ivar & Knudsen, Stine (2017). Changes in Quality of Life in individuals with narcolepsy in Norway after H1N1-influensa epidemic in 2009- a 2-year prospective cohort study. Full text in Research Archive

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