A case control study of the relationship between persistent serum creatine kinase elevation and polyneuropathy.

Creatine kinase (CK) has been associated with neuropathy, but the mechanisms are uncertain. We hypothesized that peripheral nerve function is impaired in subjects with persistent CK elevation (hyperCKemia) compared to age- and sex matched controls in a general population. The participants were recruited from the population based Tromsø study in Norway. Neuropathy impairment score (NIS), nerve conduction studies (NCS) and electromyography (EMG) in subjects with persistent hyperCKemia (n = 113; 51 men, 62 women) and controls (n = 128; 61 men, 67 women) were performed. The hyperCKemia group had higher NIS score than the controls (p = 0.050). NCS of the tibial nerve showed decreased compound motor action potential amplitude (p < 0.001), decreased motor conduction velocity (p < 0.001) and increased F-wave latency (p = 0.044). Also, reduced sensory amplitudes of the median, ulnar, and sural nerves were found. EMG showed significantly increased average motor unit potential amplitude in all examined muscles. CK correlated positively with glycated hemoglobin and non-fasting glucose in the hyperCKemia group, although not when controlled for covariates. The length dependent polyneuropathy demonstrated in the hyperCKemia group is unexplained, but CK leakage and involvement of glucose metabolism are speculated on.

Insomnia and sleep-disordered breathing in FKRP-related limb-girdle muscular dystrophy R9. The Norwegian LGMDR9 cohort study (2020).

Limb-girdle muscular dystrophy R9 (LGMDR9) is a progressive and disabling genetic muscle disease. Sleep is relevant in the patient care as it impacts on health, functioning, and well-being. LGMDR9 may potentially affect sleep by physical or emotional symptoms, myalgia, or sleep-disordered breathing (SDB) through cardiorespiratory involvement. The objective was to investigate the occurrence of insomnia and unrecognized or untreated SDB in LGMDR9, associated factors, and relationships with fatigue and health-related quality of life (HRQoL). All 90 adults in a Norwegian LGMDR9 cohort received questionnaires on sleep, fatigue, and HRQoL. Forty-nine of them underwent clinical assessments and 26 without mask-based therapy for respiration disorders additionally underwent polysomnography (PSG) and capnometry. Among 77 questionnaire respondents, 31% received mask-based therapy. The prevalence of insomnia was 32% of both those with and without such therapy but was significantly increased in fatigued respondents (54% vs 21%). Insomnia levels correlated inversely with mental HRQoL. Among 26 PSG candidates, an apnea-hypopnea index (AHI) ≥ 5/h was observed in 16/26 subjects (≥ 15/h in 8/26) with median 6.8 obstructive apneas and 0.2 central apneas per hour of sleep. The AHI was related to advancing age and an ejection fraction < 50%. Sleep-related hypoventilation was detected in one subject. Fatigue severity did not correlate with motor function or nocturnal metrics of respiration or sleep but with Maximal Inspiratory Pressure (r = - 0.46). The results indicate that insomnia and SDB are underrecognized comorbidities in LGMDR9 and associated with HRQoL impairment and heart failure, respectively. We propose an increased attention to insomnia and SDB in the interdisciplinary care of LGMDR9. Insomnia and pulmonary function should be examined in fatigued patients.

Obstructive sleep apnea is common in patients with high-impact chronic pain - an exploratory study from an interdisciplinary pain center.

OBJECTIVES: Sleep disturbances are increasingly recognized as a major part of chronic pain pathology. Obstructive sleep apnea (OSA) is a common occurrence in patients with chronic pain attending specialized pain clinics, yet its prevalence remains unclear. Using screening tools such as the Berlin and STOP-BANG questionnaires may aid in early identification of OSA and improve clinical care. This study i) examined the frequency of OSA based on objective sleep monitoring in patients with high-impact chronic pain, ii) explored potential differences in self-reported pain and sleep characteristics between patients with and without OSA, and iii) tested the agreement between OSA classification based on objective assessment and two OSA screening questionnaires. METHODS: A consecutive cohort of 90 patients (71 women and 19 men; mean age: 47.1 ± 11.0 years) referred for interdisciplinary pain treatment, underwent one night of sleep monitoring using portable respiratory polygraphy (RP), and suspected OSA was confirmed with polysomnography (PSG). Self-reported data on clinical pain (severity, pain drawings and health-related quality of life), sleep characteristics (sleep quality insomnia, sleepiness), and risk of OSA (Berlin and STOP-BANG questionnaires) were collected the day before RP assessment. RESULTS: Forty-six (51.1%) patients were classified with OSA according to RP and verified with PSG. Twenty-eight patients (31.1%) had moderate or severe OSA (apnea-hypopnea index [AHI] >15). Patients with OSA reported lower sleep quality compared with patients without OSA. Scores on pain severity, disability, quality of life, insomnia and sleepiness were comparable between patients with and without OSA. Sensitivity and specificity were 78.6 and 45.2% respectively for the Berlin questionnaire, and 71.4 and 58.1% respectively for the STOP-BANG questionnaire. The agreement for both questionnaires with objective assessment was poor-to-fair. Both questionnaires had acceptable negative predictive values but low positive predictive values reducing the clinical utility to identify patients with low OSA-risk in this sample. CONCLUSIONS: The current study demonstrates a high prevalence of OSA in patients with high-impact chronic pain referred to specialized pain treatment, however the clinical pain profiles were similar in patients with and without OSA. The Berlin and STOP-BANG questionnaires have poor specificity and low-to-fair agreement with RP/PSG questioning their clinical utility in identifying OSA in this sample.

Daily associations between sleep and pain in patients with chronic musculoskeletal pain.

Patients with chronic pain commonly report sleep problems, and the evidence for a relationship between sleep disturbance and pain seems robust. The day-to-day associations between these constructs are less well studied, particularly with objective sleep measures such as actigraphy. Moreover, the concurrent presence of negative affective symptoms, as well as seasonality effects at extreme latitudes may complicate it further. Here, we studied 56 patients with chronic primary musculoskeletal pain conditions, contributing data in two separate 7-day data-collection periods during the summer and winter, respectively. The effect of self-reported sleep quality, and actigraphy measured sleep duration, efficiency and timing on next-day pain, as well as the effect of pain on the same sleep indices were estimated by generalised linear mixed regression models. The models were additionally adjusted for age, sex, education, data collection period, weekend, season and mental distress, with the latter two also specified as moderators. We observed a significant effect of pain as a predictor of next-night sleep quality (p = .003) and marginally of next-night sleep duration (p = .079). Conversely, sleep quality tentatively predicted next-day pain (p = .063). No other day-to-day associations were present. Mental distress was the strongest predictor of pain, but it did not modify the sleep-pain associations, nor did season. In conclusion pain, sleep quality and mental distress are closely related, underscoring the importance of encompassing this complexity in assessment and treatment of patients with chronic pain.

Sleep Characteristics in Adults With and Without Chronic Musculoskeletal Pain: The Role of Mental Distress and Pain Catastrophizing.

OBJECTIVES: Sleep disturbance is associated with persistence and exacerbation of chronic pain. As this relationship seems to be bidirectional, factors underpinning sleep disturbance may prove important in multimodal rehabilitation approaches. The aim of this cross-sectional study was to examine the impact of psychological symptoms on subjective and objective sleep measures in patients with chronic musculoskeletal pain (CMP), as compared with pain-free controls. MATERIALS AND METHODS: Sleep was assessed by self-report questionnaires, actigraphy, and polysomnography recordings in 56 patients (75.0% female; M age=41.7 y, SD=10.8 y) with CMP and compared with 53 matched pain-free controls (71.7% female; M age=41.8 y, SD=10.7). Mental distress (Hopkins Symptoms Checklist [HSCL]) and Pain Catastrophizing Scale (PCS) were tested as predictors of objective and subjective sleep measures in multiple regression models, and their indirect effects were tested in bootstrapped mediation models. RESULTS: The sleep data revealed substantially more subjective sleep disturbance (Hedge g: 1.32 to 1.47, P<0.001), moderately worse sleep efficiency in the actigraphy measures (Hedges g: 0.5 to 0.6, P<0.01), and less polysomnography measured slow wave sleep (Hedges g: 0.43, P<0.05) in patients, as compared with controls. HSCL was strongly associated with the self-reported measures Insomnia Severity Index (ISI) and Pittsburgh Sleep Quality Index (PSQI). HSCL also partially explained the association between pain and sleep, but HSCL was not associated with any of the objective sleep measures. More pain catastrophizing was related to less slow wave sleep. DISCUSSION: The differences in subjective and objective sleep measures indicate that they probe different aspects of sleep functioning in patients with musculoskeletal pain, and their combined application may be valuable in clinical practice. Self-reported sleep disturbance seems to overlap with affective dimensions reflected by the HSCL questionnaire.

Seasonality in pain, sleep and mental distress in patients with chronic musculoskeletal pain at latitude 69° N.

Seasonality is evident in several aspects of human health and behavior, whereas seasonality in chronic pain is less well studied. We examined seasonal variation in pain severity and pain dissemination, as well as in pain-associated conditions, such as sleep impairment, sleep timing, mental distress, fatigue and physical activity. We also examined if any of these associated conditions moderated the seasonality in pain. This prospective study was conducted in the subarctic municipality of Tromsø, Norway (69º North), on a sample of patients with chronic musculoskeletal pain (N = 56). Data were collected with self-report questionnaires and objective actigraphy measures (7 days) twice: winter and summer. Mixed linear regression models were fitted. A modest seasonality effect was observed in pain severity (highest in summer), but not in pain dissemination. Seasonality with increased physical activity and delayed sleep timing in the summer was also present. The remaining pain-associated self-report or objective measures indicated no seasonality. The season-pain association was not significantly moderated by any of the pain-associated conditions. Previous studies on healthy individuals residing in polar areas have suggested an opposite seasonal effect with delay of the sleep-wake rhythm in winter. Our results based on a clinical sample thus represent a novel finding that needs to be examined further with regard to seasonal circadian entrainment and alignment in pain populations. These results may have clinical value for the treatment of patients with musculoskeletal pain as seasonality may require seasonal adjustments of pain treatment strategies.

Clinical impact of persistent hyperCKemia in a Norwegian general population: a case-control study.

In this case-control study we assessed the clinical impact of persistent hyperCKemia in a Norwegian general population. HyperCKemia was defined according to the NORIP- references (women 35-210 U/L, men <50 years 50-400 U/L, and men ≥50 years 40-280 U/L). We compared the frequency of muscular symptoms and function, neuromuscular diseases and risk factors between 120 cases with persistent hyperCKemia and 130 age- and sex-matched controls with normal CK values, all recruited from the single-centre, population-based prospective Tromsø Study. The participants underwent a standardized interview assessing muscle symptoms, physical activity, use of statins and presence of other CK risk factors, prior to clinical neurological and neurophysiological examination. Knee extensor muscle strength (Cybex NORM dynamometer) and dominant hand grip strength (Martin Vigorimeter) was assessed. A total of 85 cases (71%) reported either muscle pain, muscle stiffness or cramps, compared to 70 controls (54%) (p=0.017) There were no differences in muscle strength between the groups. In men, weight, Body Mass Index and muscle symptoms were significantly higher in the group with persistent hyperCKemia. In women, no differences between the groups were detected. Use of statins was similar in cases and controls. We diagnosed 3 women with previously unknown myopathy, all in the group with persistent hyperCKemia. This study support that CK may be used as a marker of muscular symptoms in the general population.

Variation of serum creatine kinase (CK) levels and prevalence of persistent hyperCKemia in a Norwegian normal population. The Tromsø Study.

In this cross-sectional study we assessed the prevalence of hyperCKemia, defined as persistent CK values ≥210 U/L in women, ≥400 U/L in men <50 years and ≥280 U/L in men ≥50 years (reference values according to the Nordic Reference Interval Project). Blood samples were obtained from 12,828 participants in the 6th survey of The Tromsø Study. We identified 686 (5.3%) individuals with incidentally elevated CK. After a standardized control test, 169 persons (1.3%) had persistent hyperCKemia, i.e. 69.9% normalization. Use of statins or other causes of hyperCKemia were detected in 78 individuals (46.2%), giving a prevalence of "idiopathic hyperCKemia" of 0.71%. CK variation was highest in younger men and in females between 60 and 69 years. This study has identified persistent hyperCKemia in 1.3% of the normal population, and demonstrates the importance of performing controlled CK analyses, also in those with identified risk factors.