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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.

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OBJECTIVE: To test the hypothesis that the effect of video consultations is noninferior to traditional consultations in managing patients with overuse headache (MOH). MATERIALS AND METHODS: Patients were recruited from referrals to a neurological clinic. In a randomized controlled trial (RCT), headache burden measured by headache impact test (HIT-6) and frequency of headache days <15 per month and visual analogue pain scale (VAS) at baseline, 3 months and 1 year were compared between groups consulted by video- (n = 51) and traditional consultations (n = 51) in a post hoc analysis. RESULTS: The overall response rate was 74.5%. HIT-6 changed from 66.3 (SD = 4.7) to 60.0 (SD = 9.1) from baseline to 12 months in participants randomized to video consultations and from 65.8 (SD = 3.7) to 58.4 (SD = 8.3) in the group consulted traditionally (95% CI -2.3 to 6.5, p = 0.44). Frequency of headache days <15 per month at 1-year follow-up were 9 (23.1%) respectively 10 (27.0%), p = 0.60. In the video group, VAS improved by 2.3 points compared to 2.4 in the traditional group from baseline to 12 months (95% CI -1.2 to 1.2, p = 0.76). Analyses of repeated measurements comparing HIT-6 and VAS over two points of time in the two groups were insignificant. CONCLUSION: The effect of video consultations is noninferior to traditional consultations in managing MOH patients. Using video may be a good alternative in consulting patients with MOH.

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We investigated the association between serum creatine kinase (CK) and body fat mass in an overweight and obese population. In this cross-sectional study, 454 Caucasian overweight and obese individuals recruited from a medical outpatient clinic and via newspaper advertising underwent dual-energy X-ray absorptiometry (DEXA). Serum CK was obtained along with supplementary blood samples. This report is based on a secondary analysis from a previous randomized controlled trial treating obesity with vitamin D3. Serum CK correlated negatively with body fat mass in men (r = -.18, p = .025) but not in women (r = -.11, p = .069). An insignificant negative trend for logCK across quartiles of fat mass in men was found (p = .098). CK did not associate significantly with lean mass, but lean mass correlated positively with fat mass in both groups (p < .0001). In a multivariate model, serum CK was inversely and independently related to fat mass in men. Fat mass decreased with 7.83 kg per unit logCK increase when adjusted for age and lean mass (95% CI -12.3 to -3.3, p = .001). These data support the view that circulating CK interacts with obesity in a favourable way independent of its muscular connection in men. CK was not associated with fat mass in women.

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BACKGROUND: Obesity is associated with inflammation, but the role of lean mass and creatine kinase (CK) on the inflammatory process is less known. We investigated the associations between lean mass, CK and fat mass upon inflammatory parameters in an overweight and obese adult population. MATERIAL AND METHODS: Body composition examined by dual-energy X-ray absorptiometry, high-sensitivity C-reactive protein (hs-CRP), erythrocyte sedimentation rate (ESR), CK and supplementary clinical parameters were measured in 454 overweight and obese individuals. This is a secondary analysis from a cohort of obese individuals treated with Vitamin D. RESULTS: Mean age was 47·6 ± 11·4 years and mean body mass index 34·6 ± 3·9 kg/m2 . Lean mass correlated negatively with hs-CRP (r = -0·127, P = 0·042) and ESR (r = -0·381, P < 0·001). Median lean mass in the lower ESR quartile was significantly higher than in the upper quartile (P < 0·001) but not between lower and upper hs-CRP quartiles (P = 0·114). CK was negatively correlated with hs-CRP (r = -0·151, P < 0·001) and ESR (r = -0·240, P < 0·001). Median CK in the lower hs-CRP and ESR quartiles were significantly higher than in the upper quartiles (P < 0·001 for both). Conversely, fat mass was positively associated with hs-CRP and ESR. CONCLUSIONS: Inflammatory parameters were related to reduced lean mass and CK in an overweight and obese population. Hypothetically, lean mass has a favourable effect on obesity-related inflammation, and CK may play a role as an inhibitor of inflammation in obesity.

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OBJECTIVE: To evaluate long-term treatment efficacy and safety of one-time telemedicine consultations for nonacute headaches. METHODS: We randomized, allocated, and consulted nonacute headache patients via telemedicine (n = 200) or in a traditional manner (n = 202) in a noninferiority trial. Efficacy endpoints, assessed by questionnaires at 3 and 12 months, included change from baseline in Headache Impact Test-6 (HIT-6) (primary endpoint) and pain intensity (visual analogue scale [VAS]) (secondary endpoint). The primary safety endpoint, assessed via patient records, was presence of secondary headache within 12 months after consultation. RESULTS: We found no differences between telemedicine and traditional consultations in HIT-6 (p = 0.84) or VAS (p = 0.64) over 3 periods. The absolute difference in HIT-6 from baseline was 0.3 (95% confidence interval [CI] -1.26 to 1.82, p = 0.72) at 3 months and 0.2 (95% CI -1.98 to 1.58, p = 0.83) at 12 months. The absolute change in VAS was 0.4 (95% CI -0.93 to 0.22, p = 0.23) after 3 months and 0.3 (95% CI -0.94 to 0.29, p = 0.30) at 12 months. We found one secondary headache in each group at 12 months. The estimated number of consultations needed to miss one secondary headache with the use of telemedicine was 20,200. CONCLUSION: Telemedicine consultation for nonacute headache is as efficient and safe as a traditional consultation. CLINICALTRIALSGOV IDENTIFIER: NCT02270177. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that a one-time telemedicine consultation for nonacute headache is noninferior to a one-time traditional consultation regarding long-term treatment outcome and safety.

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OBJECTIVE: To investigate associations between photophobia and seasonal variation of migraine. METHODS: In this cross-sectional study, migraineurs consecutively recruited were referred to a specialist center located above the Arctic Circle at 68-71 degrees North during a 2.5-year period. Data were obtained through a structured interview. RESULTS: In total, 302 migraineurs with a mean (±SD) age of 35.5 (±12.6) years were included. Patients who reported seasonal variation of migraine (n = 90; 29.8%) also reported more often interictal photophobia than the others (61/90, 67.8% vs 92/212, 43.4%, P < .0001). Patients reported sunlight or other bright light to trigger migraine attacks in 74.4% with seasonal migraine (SM) compared with 40.6% in patients with non-seasonal migraine (NSM) (P < .0001), but there were similar frequencies of attacks reported to be triggered by sleep, menstruation, and other precipitating factors. After adjusting for migraine with aura, migraine disability, chronic migraine, interictal photophobia, and insomnia, sunlight or other bright light, photophobia was still associated with SM (OR; 3.47, CI [95%]; 1.83-6.59, P < .0001). CONCLUSIONS: Migraineurs in a subarctic area reporting seasonal variation of attack frequency also report increased interictal photophobia independent of other clinical factors. Chronobiological mechanisms and/or increased activity in the visual system may be responsible for this phenomenon.

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Objectives We determined headache patients' satisfaction with telemedicine and assessed how telemedicine influenced headache burden, compliance with diagnosis and treatment, and need for follow-up consultations. Methods During 2.5 years, patients from Northern Norway referred with non-acute headaches for a specialist consultation at Tromsø University Hospital were consecutively randomised to either telemedicine or traditional visits. Baseline data were recorded and compared to data from a three-month follow-up questionnaire (see Supplementary material). The following were evaluated: (1) satisfaction with the consultation; (2) headache status; subjective improvement, average pain intensity, treatment, headache days per month, and Headache Impact Test (HIT-6); and (3) treatment compliance and follow-up visits. Results Out of 402 consultations, 348 (86.6%) answered the questionnaire. Satisfaction was similar in the telemedicine and the traditional group (88.8% vs. 92.3%; p = 0.35). Subgroup analyses were not prespecified, but there were no differences in satisfaction among females, migraineurs, rural patients and urban patients. Improvement from baseline after three months was reported equally in the telemedicine and the traditional groups. There were also no differences in treatment compliance, but rural telemedicine patients had less-frequent headache visits at three months' follow-up (28.9% vs. 48.7%, p = 0.002). Conclusion Telemedicine is non-inferior to traditional consultations in patient satisfaction, specialist evaluation, and treatment of non-acute headaches. ClinicalTrials.gov ID: NCT02270177.

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The correlation between creatine kinase (CK) and blood pressure (BP) was examined prospectively in 120 patients with persistent high CK and 130 individuals with normal CK. Hypertension was defined as systolic BP (SBP) ≥ 140 mm Hg or diastolic BP (DBP) ≥ 90 mm Hg or current use of antihypertensive medication. Baseline CK was weakly correlated with SBP (r = 0.11, P = .07) and DBP (r = 0.16, P = .01) at follow-up. Persons with persistent high CK had higher SBP (140.8 mm Hg vs 138.2 mm Hg) and DBP (83.2 mm Hg vs 81.0 mm Hg, P = .06) values and were more likely to have hypertension (66.7% vs 55.5%, P = .05) than individuals with normal CK. In age- and sex-adjusted analysis, a 1-unit change in logCK was associated with a 4.9-mm Hg higher SBP, a 3.3-mm Hg higher DBP, and a 2.2-higher odds for having hypertension at follow-up (P = .1, .07, and .06, respectively). When including body mass index (BMI) to the model, BMI was a strong and independent predictor for SBP, DBP, and hypertension at follow-up and the CK effect on blood pressure was substantially attenuated. This study showed that the CK effect on blood pressure is clearly modified by BMI.

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OBJECTIVE: Cluster headache (CH) may cause excruciating pain and not all patients get satisfactory help. Patient dissatisfaction with general practitioners (GPs) and neurologists, and use of complementary and alternative treatment (CAM) may reflect this. The authors studied patient satisfaction with doctors' treatment and use of CAM in a Norwegian CH cohort. SUBJECTS: A total of 196 subjects with a cluster headache diagnosis were identified in the registers of two neurological departments in North Norway. DESIGN: Of these, 70 with a confirmed diagnosis according to the second edition of the International Classification of Headache Disorders (ICHD-2) completed a comprehensive questionnaire with questions concerning satisfaction with doctors' treatment, use of CAM, and effect of both treatment regimes. RESULTS: Satisfaction with doctors' treatment was reported in 44/70 (63%) (GPs) and 50/70 (71%) (neurologists) while 39/70 (56%) were satisfied with both. Too long a time to diagnosis, median four years, was the most commonly reported claim regarding doctors' treatment. Use of CAM was reported in 27/70 (39%), and 14/70 (20%) reported experience with ≥ 2 CAM. Ten patients reported benefit from CAM (37% of "CAM users"). The average cluster period was longer in CAM-users than others (p = 0.02), but CAM use was not associated with age, education, use of medication, effect of conventional treatment, duration of cluster attacks, or time to diagnosis. CONCLUSION: About two-thirds of CH patients were satisfied with treatment from either GPs or neurologists, and about one-third had used CAM. Despite experiencing diagnostic delay and severe pain, cluster patients seem in general to be satisfied with doctors' conventional treatment.

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OBJECTIVE: To assess the prevalence of chronic insomnia and the periodicity of headache attacks in an Arctic cluster headache population. BACKGROUND: Cluster headache is a sleep-related disorder, and attacks have both circadian and circannual rhythmicity. METHODS: Through a retrospective hospital chart review, we identified all subjects diagnosed with episodic cluster headache (ICD-10 G 44.0) at the Neurological Departments in Northern Norway (located north of 66°33'N) between January 1, 2000 and December 31, 2010. Patients with a confirmed diagnosis (ICHD-2) received a comprehensive questionnaire covering demographic data, clinical characteristics, sleep, and periodicity of attacks. RESULTS: A total of 196 subjects were registered, and 178 received the questionnaire. The response rate was 88/178 (49%). Fifty-eight men (aged 49.2 ± 13.6) and 12 women (aged 49.7 ± 15.5) were included. Forty percent of the responders suffered from chronic insomnia (Diagnostic and Statistical Manual of Mental Disorders 4th edition). Forty-nine percent of the responders and 42% of the non-responders were shift workers, which is much higher than compared with the general population (24%). Insomnia was significantly associated with shift work and experiencing longer-lasting cluster bouts. One third attributed their insomnia to the cluster headache. Thirty-seven percent reported a seasonal predilection of the cluster periods, and 58% a diurnal periodicity of attacks. Eighty percent often or always had headache attacks during sleep, the most frequent time interval being at 12:00-4:00 am. Shift workers were significantly more likely to see lack of sleep as a cluster attack trigger than daytime workers. CONCLUSIONS: Chronic insomnia and shift work seem to be common among Arctic cluster headache patients. The small number of subjects included in this study implies that conclusions should be drawn with caution, but the findings support the idea of cluster headache as a circadian rhythm disorder.

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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.

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INTRODUCTION: The development of preventive treatments for migraine has lagged behind, in part because of limited knowledge about the primum movens of attacks. AREAS COVERED: We aimed to make a status report about newer preventive drugs for migraine, mainly by reviewing ongoing studies and their potential mechanism of action. An overview of published and unpublished trials was obtained from electronic databases focusing on randomized controlled trials (RCTs) published or initiated during the last 3 years. Drugs inhibiting cortical spreading depression and calcitonin gene-related peptide antagonist, which mainly acts vasoconstrictive, seem promising, but need further exploration. The use of nitric oxide blockers and drugs modifying excitatory brain activity such as glutamate antagonists and newer antiepileptics have so far not been successful. Drugs such as melatonin, vitamin E and botulinum toxins aiming for other targets seem to have no or marginal effect. EXPERT OPINION: The results from Phase II studies with newer prophylactic drugs for migraine targeting binding sites in the brain are conflicting, but they may have potential for clinical use. No major breakthrough in migraine prevention can be expected from the ongoing trials, but further insight into the effect on migraine subtypes is anticipated.

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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.

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OBJECTIVES: In the vast majority of cases the cause for hypertension is not known. On the basis of observations from black and multiethnic populations, it has been hypothesized that a genetically high tissue creatine kinase activity may be an independent factor responsible for primary hypertension. If the relation between creatine kinase and blood pressure is causal, it is reasonable to believe that it will be independent of ethnicity and present in different populations. In this cross-sectional study, we examined whether creatine kinase was associated with blood pressure in a large Caucasian normal population. METHODS AND RESULTS: Data on creatine kinase and blood pressure were analyzed in a random sample of 12 776 men and women (65% of those eligible), aged 30-87 years from a normal population in the municipality of Tromsø, Norway. We used linear regression to model the association between creatine kinase and blood pressure. Creatine kinase was independently associated with blood pressure. A one unit increase in log CK was associated with a 3.3 (95% CI 1.4-5.2) mmHg increase in systolic blood pressure and a 1.3 (95% CI 0.3-2.3) mmHg increase in diastolic blood pressure, after adjustment for age, sex, body mass index, s-glucose, s-creatinine, physical activity and alcohol consumption. The creatine kinase effect on blood pressure was independent of antihypertensive medication, and no difference in creatine kinase level was found between those with controlled and uncontrolled hypertension (geometric mean 101 vs. 104 IU/l, P = 0.1). CONCLUSION: Creatine kinase was associated with blood pressure in this population.

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BACKGROUND: A previous open-label study of melatonin, a key substance in the circadian system, has shown effects on migraine that warrant a placebo-controlled study. METHOD: A randomized, double-blind, placebo-controlled crossover study was carried out in 2 centers. Men and women, aged 18-65 years, with migraine but otherwise healthy, experiencing 2-7 attacks per month, were recruited from the general population. After a 4-week run-in phase, 48 subjects were randomized to receive either placebo or extended-release melatonin (Circadin®, Neurim Pharmaceuticals Ltd., Tel Aviv, Israel) at a dose of 2 mg 1 hour before bedtime for 8 weeks. After a 6-week washout treatment was switched. The primary outcome was migraine attack frequency (AF). A secondary endpoint was sleep quality assessed by the Pittsburgh Sleep Quality Index (PSQI). RESULTS: Forty-six subjects completed the study (96%). During the run-in phase, the average AF was 4.2 (±1.2) per month and during melatonin treatment the AF was 2.8 (±1.6). However, the reduction in AF during placebo was almost equal (p = 0.497). Absolute risk reduction was 3% (95% confidence interval -15 to 21, number needed to treat = 33). A highly significant time effect was found. The mean global PSQI score did not improve during treatment (p = 0.09). CONCLUSION: This study provides Class I evidence that prolonged-release melatonin (2 mg 1 hour before bedtime) does not provide any significant effect over placebo as migraine prophylaxis. CLASSIFICATION OF EVIDENCE: This study provides Class I evidence that 2 mg of prolonged release melatonin given 1 hour before bedtime for a duration of 8 weeks did not result in a reduction in migraine frequency compared with placebo (p = 0.497).

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BACKGROUND: A system of giving all patients referred to hospital a guaranteed priority has been introduced in Norway. We wished to investigate whether the frequency of first- time referrals from general practioners to neurological out-clinics varied between the two northernmost counties and between selected municipalities in that region of Norway. MATERIAL AND METHODS: We studied referrals for specialist consultations at the neurological out-clinic in Tromsø during 12 months. Inclusion criteria were: 1) referral from a general practitioner and 2) referral for diagnosis. RESULTS: Of totally 2260 referred patients, 1265 were referred without a specific diagnosis (56 %). The mean age for patients referred from Finnmark county (45.5 years) was somewhat lower than for Troms county (48.0 years). The frequency of referral varied from 0.5 % in Troms and 0.6 % in Finnmark to 1 % in the small municipality of Lyngen. Neurological examination showed abnormal findings in about a third of the patients. Information about patients' ability to work was reported for 23 % of those referred. Locums were less likely to include this information. INTERPRETATION: In spite of a lower age and a greater distance to the out-clinic, there were slightly more referrals from Finnmark than from Troms. This may indicate that ambulatory organization of neurologists visiting patients in their home area involves no great change in referral practice.

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