Creatine kinase is associated with glycated haemoglobin in a nondiabetic population. The Tromsø study.

BACKGROUND: Creatine kinase (CK) has been associated with insulin resistance and identified as a risk marker of cardiovascular disease largely by its relationship with hypertension and increased body mass index. This study determined whether CK is a predictor of glycated haemoglobin (HbA1C) in a nondiabetic general population. METHODS: Associations between CK and the outcome variable HbA1C (%) were performed by variance and multivariate analyses in 11662 nondiabetic subjects defined as HbA1C (%) <6.5 who participated in the population based Tromsø study (Tromsø 6) in Norway. RESULTS: Abnormal elevated CK was detected in 543/11662 participants (4.66%). Mean HbA1C (%) in the "high CK" group was 5.62 (SD = 0.33) compared to 5.52 (SD = 0.36) in the "normal CK" group, P <0.001. CK increased significantly and linearly with higher levels of HbA1C (%) quartiles in women (P <0.001) and non-linearly in men (P <0.001). In a multivariate analysis, CK was independently associated with HbA1C (%) after adjusting for age, sex, body mass index, blood pressure, glucose, lipids, C-reactive protein, creatinine, alanine transaminase and aspartate aminotransferase. A 1-unit increase in log CK was associated with a 0.17-unit increase in HbA1C (%). CONCLUSION: These data demonstrate a positive and independent association between CK and glycated haemoglobin in a nondiabetic general population.

One-Year Remission Rate of Chronic Headache Comparing Video and Face-to-Face Consultations by Neurologist: Randomized Controlled Trial.

BACKGROUND: Chronic headache causing severe headache-related disability for those affected by the disease is under- or misdiagnosed in many cases and therefore requires easy access to a specialist for optimal health care management. OBJECTIVE: The goal of the research is to determine whether video consultations are noninferior to face-to-face consultations in treating chronic headache patients referred to a specialist in Northern Norway. METHODS: Patients included in the study were recruited from general practice referrals to a specialist at a neurological department in Northern Norway (Tromsø) and diagnosed according to the International Headache Society classification system. In a randomized controlled design, the 1-year remission rate of chronic headache (change from ≥15 to <15 headache days per month during the last 3 months), patient satisfaction with a specialist consultation, and need for follow-up consultations by general practitioners were compared between groups consulted by video and face-to-face in a post hoc analysis. Data were collected by interview (baseline) and questionnaire (follow-up). RESULTS: From a baseline cohort of 402 headache patients consecutively referred from general practice to a specialist over 2.5 years, 58.0% (233/402) were classified as chronic headache and included in this study. Response rates were 71.7% (86/120) in the video group and 67.3% (76/113) in the face-to-face group. One-year remission from chronic headache was achieved in 43.0% (37/86) in the video group and 39.5% (30/76) in the face-to-face group (P=.38). Patient satisfaction with consultations were 86.5% (32/37; video) and 93.3% (28/30; face-to-face; P=.25). A total of 30% (11/37) in the video group and 53% (16/30) in the face-to-face group consulted general practitioners during the follow-up period (P=.03), and median number of consultations was 1 (IQR 0-13) and 1.5 (IQR 0-15), respectively (P=.19). CONCLUSIONS: One-year remission rate from chronic headache was about 40% regardless of consultation form. Likewise, patient satisfaction with consultation and need for follow-up visits in general practice post consultation was similar. Treating chronic headache patients by using video consultations is not inferior to face-to-face consultations and may be used in clinical neurological practice. TRIAL REGISTRATION: ClinicalTrials.gov NCT02270177; https://clinicaltrials.gov/ct2/show/NCT02270177.

Serum alanine aminotransferase activity and risk factors for cardiovascular disease in a Caucasian population: the Tromsø study.

BACKGROUND: High and low levels of serum alanine aminotransferase (ALT) are both associated with cardiovascular diseases (CVD) risks especially in elderly, but the mechanisms are less known. This study investigated associations between ALT and CVD risk factors including effects of sex and age in a Caucasian population. METHODS: Cross-sectional data were analysed sex-stratified in 2555 men (mean age 60.4 years) and 2858 women (mean age 60.0 years) from the population study Tromsø 6. Associations were assessed by variance analysis and multivariable logistic regression of odds to have abnormal ALT. Risk factors included body mass index (BMI), waist-to-hip-ratio, blood pressure, lipids, glucose, glycated haemoglobin and high-sensitive C-reactive protein (CRP). RESULTS: Abnormal elevated ALT was detected in 113 men (4.4%) and 188 women (6.6%). Most CVD risk factors associated positively with ALT in both sexes except systolic blood pressure and CRP (women only), while ALT was positively associated with age in men when adjusted for CVD risk factors, P < 0.001. BMI predicted ALT in men (OR 0.94; 95% CI 0.88-1.00, P = 0.047) and women (OR 0.90; 95% CI 0.86-0.95, P < 0.001). A linear inversed association between age and ALT in men and a non-linear inversed U-trend in women with maximum level between 60 and 64 years were found. CONCLUSION: This study confirms a positive relationship between ALT and CVD risk factors, particularly BMI. Age is not a major confounder in the ALT-CVD relationship, but separate sex-analyses is recommended in such studies.

Leisure physical exercise and creatine kinase activity. The Tromsø study.

Creatine kinase (CK) is an enzyme catalyzing energy reaction in muscle cells and has proven to modify cardiovascular risks. The influence of skeletal muscle activity on CK concentrations is a potential study confounder but is mainly reported in connection with sport activities. This study investigated the association between leisure physical exercise and CK and estimated the effect of physical exercise on the CK values. CK and leisure physical exercise defined as intensity, frequency, and duration subsets were measured in the population-based Tromsø study. Comparisons of CK at different exercise levels, multivariate analyses, and relative differences in CK between "never exercise" and "heavy exercise" (moderate or hard exercise ≥2 hours per week) subgroups were analyzed age- and sex-stratified in 12 796 men and women. CK increased significantly with higher levels of physical exercise intensity and frequency in both sexes analyzed by ANOVA. In a multivariate analysis, CK was independently associated with heavy exercise after adjusting for age, BMI, and blood pressure; OR 9.38 (95% CI 5.32-16.53), P < .0001 in men and OR 5.20 (95% CI 2.53-10.69), P < .0001 in women. The differences in CK between physically inactive and participants performing heavy exercise varied between 3.1% (women) and 6.4% (men) and was also larger in participants ≥50 years. In conclusion, CK was positively and independently associated with increasing leisure physical exercise in a general population. CK values associated with exercise were approximately twice as high in men than women, but exercise altered CK only modestly.

Alanine Aminotransferase and Body Composition in Obese Men and Women.

There is a known relationship between serum alanine aminotransferase (ALT) and obesity in humans, but the mechanism(s) are not clarified. This study investigated the associations between serum ALT and body composition in an overweight and obese population. The results are based on data from a previous randomized controlled trial treating obesity with vitamin D3. A sample of 448 overweight and obese individuals underwent dual-energy X-ray absorptiometry (DEXA) and measured serum ALT along with supplementary blood samples at study baseline. Body fat mass and lean mass indexes were calculated by dividing total body fat/lean weight (kg) by body height squared (kg/m2). ALT correlated with body mass index (BMI) in men but not women (r = 0.33, P < 0.0001 vs. r = 0.06, P = 0.29). In men, serum ALT correlated positively with fat mass index (r = 0.23, P = 0.004) and lean mass index (r = 0.32, P < 0.0001). In women, ALT correlated with lean mass index (r = 0.13, P = 0.031) but not fat mass index (r = 0.003, P = 0.96). In a multivariate model adjusted for age and fat mass index, a 1-unit increase in lean mass index associated with a 0.37 U/L higher ALT in the male subgroup (95% CI 0.024 to 0.040, P < 0.0001). In conclusion, serum ALT was associated with body fat mass index in men and with lean mass index in men and women in an overweight and obese population. The findings also demonstrate a gender difference in the role of fat.

Creatine kinase is associated with reduced inflammation in a general population: The Tromsø study.

BACKGROUND: Creatine kinase (CK) has been associated with reduced inflammation in obesity while inflammation is associated with obesity-related cardiovascular diseases. We investigated the relationship between CK and high sensitive C-reactive protein (hs-CRP) in a general population. METHODS: CK and hs-CRP were measured in the population-based Tromsø study that included entire birth cohorts and random samples of citizens between 30-87 years of age. The analyses were performed sex-stratified in 5969 men and 6827 women. RESULTS: CK correlated negatively with hs-CRP in men (r = -0.08, P <0.001) and women (r = -0.06, P <0.001). In univariable regression analyses, CK associated negatively with hs-CRP in men (ß = -0.14, 95% CI -0.19 to -0.10, P <0.001) and women (ß = -0.13, 95% CI -0.18 to -0.08, P <0.001). Mean CK declined from the 2. to the 4. quartiles of hs-CRP in both genders (P <0.001 for trends). There were positive correlations between CK and body mass index (BMI) in men (r = 0.10, P <0.001) and women (r = 0.07, P <0.001). Multiple regression analyses showed a 0.13 unit decrease in hs-CRP (mg/dl) per unit CK increase in men (95% CI -0.35 to -0.20) and 0.29 mg/dl in women (95% CI -0.36 to -0.21) when adjusted for age, BMI, lipids, s-glucose, s-creatinine, transaminases and coronary heart disease. CONCLUSION: CK were inversely and independently associated with hs-CRP in a general population. These data provide evidence that CK might have anti-inflammatory properties, but the mechanism and clinical implications are unclarified.

Detecting At-Risk Alzheimer's Disease Cases.

While APOEɛ4 is the major genetic risk factor for Alzheimer's disease (AD), amyloid dysmetabolism is an initial or early event predicting clinical disease and is an important focus for secondary intervention trials. To improve identification of cases with increased AD risk, we evaluated recruitment procedures using pathological CSF concentrations of Aß42 (pAß) and APOEɛ4 as risk markers in a multi-center study in Norway. In total, 490 subjects aged 40-80 y were included after response to advertisements and media coverage or memory clinics referrals. Controls (n = 164) were classified as normal controls without first-degree relatives with dementia (NC), normal controls with first-degree relatives with dementia (NCFD), or controls scoring below norms on cognitive screening. Patients (n = 301) were classified as subjective cognitive decline or mild cognitive impairment. Subjects underwent a clinical and cognitive examination and MRI according to standardized protocols. Core biomarkers in CSF from 411 and APOE genotype from 445 subjects were obtained. Cases (both self-referrals (n = 180) and memory clinics referrals (n = 87)) had increased fractions of pAß and APOEɛ4 frequency compared to NC. Also, NCFD had higher APOEɛ4 frequencies without increased fraction of pAß compared to NC, and cases recruited from memory clinics had higher fractions of pAß and APOEɛ4 frequency than self-referred. This study shows that memory clinic referrals are pAß enriched, whereas self-referred and NCFD cases more frequently are pAß negative but at risk (APOEɛ4 positive), suitable for primary intervention.

Acceptability, Feasibility, and Cost of Telemedicine for Nonacute Headaches: A Randomized Study Comparing Video and Traditional Consultations.

BACKGROUND: The feasibility of telemedicine in diagnosing and treating nonacute headaches, such as primary headaches (migraine and tension-type) and medication-overuse headaches has not been previously investigated. By eliminating the need of travel to specialists, telemedicine may offer significant time and money savings. OBJECTIVES: Our objective was to estimate the acceptance of telemedicine and investigate the feasibility and cost savings of telemedicine consultations in diagnosing and treating nonacute headaches. METHODS: From September 2012 to March 2015, nonacute headache patients from Northern Norway who were referred to neurologists through an electronic application system were consecutively screened and randomized to participate in either telemedicine or traditional specialist visits. All patients were consulted by two neurologists at the neurological department in Tromsø University Hospital. Feasibility outcomes were compared between telemedicine and traditional groups. Baseline characteristics and costs were then compared between rural and urban patients. Travel costs were calculated by using the probabilistic method of the Norwegian traveling agency: the cheapest means of public transport for each study participant. Loss of pay was calculated based on the Norwegian full-time employee's average salary: < 3.5 hours=a half day's salary, > 3.5 hours spent on travel and consultation=one day's salary. Distance and time spent on travel were estimated by using Google Maps. RESULTS: Of 557 headache patients screened, 479 were found eligible and 402 accepted telemedicine participation (83.9%, 402/479) and were included in the final analyses. Of these, 202 received traditional specialist consultations and 200 received telemedicine. All patients in the telemedicine group were satisfied with the video quality, and 198 (99%, 198/200) were satisfied with the sound quality. The baseline characteristics as well as headache diagnostics and follow-up appointments, and the investigation, advice, and prescription practices were not statistically different between the two randomized groups. In addition, telemedicine consultations were shorter than traditional visits (38.8 vs 43.7 min, P<.001). The travel cost per rural individual (292/402, 73%) was €249, and estimated lost income was €234 per visit. The travel cost in the urban area (110/402, 27%) was €6, and estimated lost income was €117 per visit. The median traveling distance for rural patients was 526 km (range 1892 km), and the median traveling time was 7.8 hours (range 27.3 hours). Rural patients had a longer waiting time than urban patients (64 vs 47 days, P=.001), and fewer women were referred from rural areas (P=.04). Rural women reported higher pain scores than urban women (P=.005). CONCLUSION: Our study shows that telemedicine is an accepted, feasible, time-saving, and cost-saving alternative to traditional specialist consultations for nonacute headaches. TRIAL REGISTRATION: Clinicaltrials.gov NCT02270177; http://clinicaltrials.gov/ct2/show/NCT02270177 (Archived by WebCite at http://www.webcitation.org/6hmoHGo9Q).

Visual impairment and posterior cortical atrophy preceding rapid progressive dementia.

Posterior cortical atrophy (PCA), also known as Benson's disease, has been previously reported as a variant of Alzheimer's disease (AD). We present a clinical picture and MRI findings of a patient with PCA who developed early right-sided homonymous haemianopia and marked atrophy of parieto-occipital regions of the brain before a cognitive decline appeared. This case demonstrates that PCA may appear with advanced brain atrophy at the onset of focal visual deficits before the development of progressive dementia, and adds to the knowledge of dementias with rapid progression.

Are the currently used reference intervals for creatine kinase (CK) reflecting the general population? The Tromsø Study.

BACKGROUND: Laboratory reference intervals are not necessarily reflecting the range in the background population. This study compared creatine kinase (CK) reference intervals calculated from a large sample from a Norwegian population with those elaborated by the Nordic Reference Interval Project (NORIP). It also assessed the pattern of CK-normalization after standardized control analyses. METHODS: New upper reference limits (URL) CK values were calculated after exclusion of individuals with risk of hyperCKemia and including individuals with incidentally detected hyperCKemia after they had completed a standardized control analysis. After exclusion of 5924 individuals with possible causes of hyperCKemia, CK samples were analyzed in 6904 individuals participating in the 6th survey of The Tromsø Study. URL was defined as the 97.5 percentile. RESULTS: New URL in women was 207 U/L. In men <50 years it was 395 U/L and in men ≥50 years 340 U/L. In individuals with elevated CK, normalization grade after control analysis was inversely correlated to the CK level (p<0.04). CONCLUSIONS: URL CK values in women and in men <50 years of age were in accordance with URL CK values given by the NORIP. In men ≥50 years, a higher URL was found and the findings suggest an upward adjustment of URL in this age group.

Sun-induced migraine attacks in an Arctic population.

AIMS: The main purpose of the study was to evaluate the impact of weather, and especially sun exposure, on migraine. METHODS: Data from a previous prospective 12-month diary study was compared with meteorological data. We retrospectively evaluated 1250 migraine attacks recorded by a group of 40 women with a mean age of 37.1 years who fulfilled the IHS criteria for migraine with and without aura. RESULTS: The patients reported more sun-induced migraine attacks on sunny days, but the total distribution of migraine attacks was constant throughout the year. Also, no seasonal variation of migraine, nor any relationships between weather parameters and onset of migraine attacks, were found. An analysis of a subgroup of patients with 'sun-induced' migraine showed a significant increase in frequency of migraine attacks in the summer compared to the winter (p = 0.04). CONCLUSION: This study confirms that sunlight might be a trigger for migraine, but a risk for increased impact of light on the total ailment of migraine headache should be searched for in a subgroup of sensitive migraineurs.

[A woman with unilateral headache]. / En kvinne med ensidig hodepine.

A woman in her fifties, with a long history of side-locked unilateral headache, was hospitalized for left-sided side-locked paroxysmal headache (attacks with 10-20 min duration). Clinical and neurological examinations, and brain MRI revealed normal findings. She responded well to indomethacin (50 mg three times daily). Due to non-compliance because of dyspepsia, which delayed the final diagnosis of chronic paroxysmal hemicrania (CPH) for 16, months indomethacin was administered both rectally and orally. A retrospective review of her medical history showed 15 years of unsuccessfully treated unilateral headache, until she responded completely to rofecoxib. Ipsilateral cranial autonomic symptoms also supported the diagnosis of hemicrania continua, although these symptoms presented before indomethacin was tried. Diagnostic delay and misdiagnoses of unilateral headaches, as illustrated by this case, shows the clinical controversies and difficulties in diagnosing and treating this condition.

Hemicrania continua changed to chronic paroxysmal hemicrania after treatment with cyclooxygenase-2 inhibitor.

Remission of hemicrania continua (HC) and transformation from HC to chronic paroxysmal hemicrania (CPH) are unusual. We report a patient with left-sided HC who, after a period of remission, presented as CPH. The continuous HC headache disappeared completely after initiating treatment with cyclooxygenase (COX)-2 inhibitor, but reappeared on the same side after 14 months remission with paroxysmal, frequent, intense and short-lasting headache attacks accompanied by ipsilateral cranial autonomic symptoms. This happened shortly after the treatment was discontinued because of withdrawal of the COX-2 inhibitor from the market. The response to indomethacin was prompt, and the patient became completely free from her paroxysmal headache with a dose of 50 mg 2 times daily. This case questions a possible modification effect on the course of HC by use of COX-2 inhibitor, as well as further supporting that some aspects of the pathophysiology of HC may resemble those of CPH, and may argue for common biological mechanisms in HC and CPH.

Epilepsy in a patient with ataxia caused by vitamin E deficiency.

Ataxia due to vitamin E deficiency is important because disease progression can be stopped by supplementary therapy. A limited number of studies and case series suggest that the disease is mainly confined to the cerebellum and spinal cord tract and seems to be more common in North African countries. We report a patient from North Norway with progressive ataxia from the age of 5, bilateral dropfoot, Babinski's sign, dysarthria and early epilepsy. Two mutations, 513insTT and p.Arg134x, were detected. When treatment was initiated 25 years after onset of symptoms, the patient was bound to the wheel chair. No further progression of pareses, ataxia or epileptic seizures has been observed in a 3-year follow-up period. This case indicates that cerebral involvement may be present in patients with a lack of vitamin E. If this observation is confirmed, a further exploration of clinical presentation, anatomic involvement and geographic distribution of the disease is warranted.

[Subacute worsening of rigidity in a patient with Parkinson disease]. / Subakutt forverring av rigiditet ved Parkinsons sykdom.

In this paper we report a patient with Parkinson's disease (PD) presenting with subacute motor symptoms, especially rigidity. The 75-year-old man had relatively moderate PD for 12 years, which was treated with levodopa until he developed marked rigidity. The rigidity became worse, with prolonged off-periods, despite treatment with increased doses of levodopa. At the time of hospitalization he was unable to walk independently, but the clinical neurological examination only revealed aggravation of parkinsonian signs. MRI of the brain showed an intracerebral lesion, which was later confirmed as glioblastoma multiforme. The main feature was onset of marked rigidity a few weeks before severe tumour-specific symptoms developed, but spasticity or hyperreflexia were neither reported at the time of symptom exacerbation nor during hospitalization. This case demonstrates the importance of considering other underlying neurological disease in parkinsonian patients presenting with rapid progression of parkinsonian symptoms.

[Motor symptoms in Parkinson disease]. / Motoriske symptomer ved Parkinsons sykdom.

BACKGROUND: Early Parkinson's disease is dominated by a motor syndrome called parkinsonism, but as the disease develops motor complications and non-motor problems may occur as well. This paper describes how to diagnose Parkinson's disease and the various motor complications and gives recommendations on how to treat the symptoms in these patients. MATERIAL AND METHODS: The paper builds on international evidence-based publications and the Norwegian guidelines for treatment of Parkinson's disease. RESULTS AND INTERPRETATION: Motor symptoms such as tremor at rest, akinesia, rigidity and postural instability are the cardinal signs in Parkinson's disease. After diagnosing a patient with the disease we recommend to start with selegiline as a disease-modifying treatment strategy. When symptoms lead to functional impairment, symptomatic treatment should be started in addition. Dopamine agonists are primarily recommended in younger patients and levodopa in the older ones. When the patients develop motor complications it is important to first thoroughly evaluate the problems to arrive at the best possible treatment strategy. If a sufficient response is not obtained both deep brain stimulation and treatment with continuous delivery of medication should be considered.

[Patient satisfaction with assessment of headache by specialist consultation]. / Pasienttilfredshet etter spesialistkonsultasjon for hodepine.

BACKGROUND: Headache is a common cause for referral of patients from a general practitioner to a neurologist. We have investigated patient satisfaction with neurological consultations for headache in Northern Norway. MATERIAL AND METHODS: We sent a postal questionnaire to all patients referred for headache from general practice to departments of neurology in Northern Norway from 1998 to 2000. RESULTS: Of 1403 patients, 942 (67%) responded to all relevant items in the questionnaire.160 of the patients were seen in Vefsn, 191 in Bodø and 591 in Tromsø. About 54% (510/942) of the patients were satisfied with the specialist consultation. Patients examined at the department in Bodø were significantly more satisfied (62 %) than patients examined in Tromsø (54%) or Vefsn (44%). Patients investigated in Tromsø reported improvement after treatment significantly more often than those seen in Vefsn. There was no difference in satisfaction between the three locations in the subgroup of patients with migraine. Patients who received a diagnosis or were given some kind of therapy were more content than others. INTERPRETATION: Almost half of the patients were not satisfied with the consultation. The degree of satisfaction varied between departments. More investigations are needed to clarify which patients with headache will benefit from a specialist consultation.