[Show abstract][Hide abstract] ABSTRACT: At present, no consensus exists among clinical and academic experts regarding an appropriate placebo for randomized controlled trials (RCTs) of spinal manipulative therapy (SMT). Therefore, we investigated whether it was possible to conduct a chiropractic manual-therapy RCT with placebo. Seventy migraineurs were randomized to a single-blinded placebo-controlled clinical trial that consisted of 12 treatment sessions over 3 months. The participants were randomized to chiropractic SMT or placebo (sham manipulation). After each session, the participants were surveyed on whether they thought they had undergone active treatment (“yes” or “no”) and how strongly they believed that active treatment was received (numeric rating scale 0–10). The outcome measures included the rate of successful blinding and the certitude of the participants’ beliefs in both treatment groups. At each treatment session, more than 80% of the participants believed that they had undergone active treatment, regardless of group allocation. The odds ratio for believing that active treatment was received was >10 for all treatment sessions in both groups (all p < 0.001). The blinding was maintained throughout the RCT. Our results strongly demonstrate that it is possible to conduct a single-blinded manual-therapy RCT with placebo and to maintain the blinding throughout 12 treatment sessions given over 3 months.
[Show abstract][Hide abstract] ABSTRACT: Copy number variations (CNVs) are important in relation to diversity and evolution but can sometimes cause disease. The most common genetic cause of the inherited peripheral neuropathy Charcot-Marie-Tooth disease is the PMP22 duplication; otherwise, CNVs have been considered rare. We investigated CNVs in a population-based sample of Charcot-Marie-Tooth (CMT) families. The 81 CMT families had previously been screened for the PMP22 duplication and point mutations in 51 peripheral neuropathy genes, and a genetic cause was identified in 37 CMT families (46%). Index patients from the 44 CMT families with an unknown genetic diagnosis were analysed by whole-genome array comparative genomic hybridization to investigate the entire genome for larger CNVs and multiplex ligation-dependent probe amplification to detect smaller intragenomic CNVs in MFN2 and MPZ. One patient had the pathogenic PMP22 duplication not detected by previous methods. Three patients had potentially pathogenic CNVs in the CNTNAP2, LAMA2, or SEMA5A, that is, genes related to neuromuscular or neurodevelopmental disease. Genotype and phenotype correlation indicated likely pathogenicity for the LAMA2 CNV, whereas the CNTNAP2 and SEMA5A CNVs remained potentially pathogenic. Except the PMP22 duplication, disease causing CNVs are rare but may cause CMT in about 1% (95% CI 0–7%) of the Norwegian CMT families.
BioMed Research International 01/2015; 2015(960404). DOI:10.1155/2015/960404 · 2.71 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The debate on the clinical definition of refractory Chronic Migraine (rCM) is still far to be concluded. The importance to create a clinical framing of these rCM patients resides in the complete disability they show, in the high risk of serious adverse events from acute and preventative drugs and in the uncontrolled application of therapeutic techniques not yet validated.
The European Headache Federation Expert Group on rCM presents hereby the updated definition criteria for this harmful subset of headache disorders. This attempt wants to be the first impulse towards the correct identification of these patients, the correct application of innovative therapeutic techniques and lastly aim to be acknowledged as clinical entity in the next definitive version of the International Classification of Headache Disorders 3 (ICHD-3 beta).
The Journal of Headache and Pain 11/2014; 15(1):47. DOI:10.1186/1129-2377-15-47 · 2.80 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: This is to our knowledge the first systematic review regarding the efficacy of manual therapy randomized clinical trials (RCT) for primary chronic headaches. A comprehensive English literature search on CINHAL, Cochrane, Medline, Ovid and PubMed identified 6 RCTs all investigating chronic tension-type headache (CTTH). One study applied massage therapy and five studies applied physiotherapy. Four studies were considered to be of good methodological quality by the PEDro scale. All studies were pragmatic or used no treatment as a control group, and only two studies avoided co-intervention, which may lead to possible bias and makes interpretation of the results more difficult. The RCTs suggest that massage and physiotherapy are effective treatment options in the management of CTTH. One of the RCTs showed that physiotherapy reduced headache frequency and intensity statistical significant better than usual care by the general practitioner. The efficacy of physiotherapy at post-treatment and at 6 months follow-up equals the efficacy of tricyclic antidepressants. Effect size of physiotherapy was up to 0.62. Future manual therapy RCTs are requested addressing the efficacy in chronic migraine with and without medication overuse. Future RCTs on headache should adhere to the International Headache Society's guidelines for clinical trials, i.e. frequency as primary end-point, while duration and intensity should be secondary end-point, avoid co-intervention, includes sufficient sample size and follow-up period for at least 6 months.
The Journal of Headache and Pain 10/2014; 15(1):67. DOI:10.1186/1129-2377-15-67 · 2.80 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Most knowledge on chronic tension-type headache (CTTH) is based on data from selected clinic populations, while data from the general population is sparse. Since pericranial tenderness is found to be the most prominent finding in CTTH, we wanted to explore the relationship between CTTH and pericranial muscle tenderness in a population-based sample.
An age- and gender-stratified random sample of 30,000 persons aged 30-44 years from the general population received a mailed questionnaire. Those with a self-reported chronic headache were interviewed and examined by neurological residents. The questionnaire response rate was 71% and the interview participation rate was 74%. The International Classification of Headache Disorders II was used. Pericranial muscle tenderness was assessed by a total tenderness score (TTS) involving 8 pairs of muscles and tendon insertions. Cross-sectional data from the Danish general population using the same scoring system were used for comparison.
The tenderness scores were significantly higher in women than men in all muscle groups. The TTS was significantly higher in those with co-occurrence of migraine compared with those without; 19.3 vs. 16.8, p = 0.02. Those with bilateral CTTH had a significantly higher TTS than those with unilateral CTTH. The TTS decreased significantly with age. People with CTTH had a significantly higher TTS compared to the general population.
People with CTTH have increased pericranial tenderness. Elevated tenderness scores are associated with co-occurrence of migraine, bilateral headache and low age.
Whether the increased muscle tenderness is primary or secondary to the headache should be addressed by future studies.
The Journal of Headache and Pain 09/2014; 15(1):58. DOI:10.1186/1129-2377-15-58 · 2.80 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Objectives:
The objective of this article is to compare the diagnosis of menstrual migraine without aura (MM) from a clinical interview with prospective headache diaries in a population-based study.
Material and methods:
A total of 237 women with self-reported migraine in at least half of menstruations were interviewed by a neurologist about headache and diagnosed according to the International Classification of Headache Disorders II (ICHD II). Additionally, the MM criteria were expanded to include other types of migraine related to menstruation. Subsequently, all women were asked to complete three month prospective headache diaries.
A total of 123 (52%) women completed both clinical interview and diaries. Thirty-eight women were excluded from the analyses: Two had incomplete diaries and 36 women recorded ≤1 menstruation, leaving 85 diaries eligible for analysis. Sensitivity, specificity, positive and negative predictive value and Kappa for the diagnosis of MM in clinical interview vs. headache diary were 82%, 83%, 90%, 71% and 0.62 (95% CI 0.45-0.79). Using a broader definition of MM, Kappa was 0.64 (95% CI 0.47-0.83).
A thorough clinical interview is valid for the diagnosis of MM. When this is undertaken, prospective headache diaries should not be mandatory to diagnose MM but may be necessary to exclude a chance association.
The Journal of Headache and Pain 08/2014; 35(5). DOI:10.1177/0333102414545891 · 2.80 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background Medication-overuse headache (MOH) is common in the general population. We investigated effectiveness of brief intervention (BI) for achieving drug withdrawal in primary care patients with MOH.
Methods The study was double-blind, pragmatic and cluster-randomised controlled. A total of 25 486 patients (age 18–50) from 50 general practitioners (GPs) were screened for MOH. GPs defined clusters and were randomised to receive BI training (23 GPs) or to continue business as usual (BAU; 27 GPs). The Severity of Dependence Scale was applied as a part of the BI. BI involved feedback about individual risk of MOH and how to reduce overuse. Primary outcome measures were reduction in medication and headache days/month 3 months after the intervention and were assessed by a blinded clinical investigator.
Results 42% responded to the postal screening questionnaire, and 2.4% screened positive for MOH. A random selection of up to three patients with MOH from each GP were invited (104 patients), 75 patients were randomised and 60 patients included into the study. BI was significantly better than BAU for the primary outcomes (p<0.001). Headache and medication days were reduced by 7.3 and 7.9 (95% CI 3.2 to 11.3 and 3.2 to 12.5) days/month in the BI compared with the BAU group. Chronic headache resolved in 50% of the BI and 6% of the BAU group.
Conclusions The BI method provides GPs with a simple and effective instrument that reduces medication-overuse and headache frequency in patients with MOH.
Trial registration number NCT01314768.
[Show abstract][Hide abstract] ABSTRACT: Charcot-Marie-Tooth (CMT) disease is the most prevalent inherited neuropathy. Today more than 40 CMT genes have been identified. Diagnosing heterogeneous diseases by conventional Sanger sequencing is time consuming and expensive. Thus, more efficient and less costly methods are needed in clinical diagnostics. We included a population based sample of 81 CMT families. Gene mutations had previously been identified in 22 families; the remaining 59 families were analysed by next-generation sequencing. Thirty-two CMT genes and 19 genes causing other inherited neuropathies were included in a custom panel. Variants were classified into five pathogenicity classes by genotype-phenotype correlations and bioinformatics tools. Gene mutations, classified certainly or likely pathogenic, were identified in 37 (46%) of the 81 families. Point mutations in known CMT genes were identified in 21 families (26%), whereas four families (5%) had point mutations in other neuropathy genes, ARHGEF10, POLG, SETX, and SOD1. Eleven families (14%) carried the PMP22 duplication and one family carried a MPZ duplication (1%). Most mutations were identified not only in known CMT genes but also in other neuropathy genes, emphasising that genetic analysis should not be restricted to CMT genes only. Next-generation sequencing is a cost-effective tool in diagnosis of CMT improving diagnostic precision and time efficiency.
BioMed Research International 06/2014; 2014:13. DOI:10.1155/2014/210401 · 3.17 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: This review investigates the relation between obstructive sleep apnea and sleep apnea headache, migraine and tension-type headache. Focus is made on studies from the general population with interviews conducted by a physician and obstructive sleep apnea confirmed by polysomnography. Obstructive sleep apnea syndrome is observed in 3% of the middle-aged population. The prevalence of sleep apnea headache in this population is 12%-18%, while morning headache with similar symptomatology as sleep apnea headache occur in 5%-8% of the general population. People with sleep apnea headache did have significantly more minutes below 90% oxygen saturation (23.1 min vs. 1.9 min, p = 0.002), higher level of average oxygen desaturation (5.9% vs. 4.5%, p < 0.001) and lower average of the lowest oxygen saturation (80.9% vs. 88.5%, p < 0.001) than people with morning headache. A comparison of those with obstructive sleep apnea with or without sleep apnea headache showed no significant differences. Thus, oxygen desaturation alone cannot explain the pathophysiology of sleep apnea headache. Obstructive sleep apnea and migraine, and obstructive sleep apnea and tension-type headache are not related in the general population. The cause of sleep apnea headache remains to be elucidated.
[Show abstract][Hide abstract] ABSTRACT: Background
Menstrual migraine without aura (MM) affects approximately 20% of female migraineurs in the general population. The aim of the present study was to investigate the influence of contraception on the attacks of migraine without aura (MO) in women with MM.
141 women from the general population with a history of MM according to the International Classification of Headache Disorders II (ICHD II) were interviewed by a headache specialist. Of 49 women with a history of MM currently using hormonal contraception, 23 reported amenorrhoea. Significantly more women with amenorrhoea reported no MO- days during the preceding month compared to women without amenorrhoea (OR 16.1; 95% confidence interval (CI) 1.8-140.4; P = 0.003). A reduction of MO-frequency was more often reported in women with than without amenorrhoea (OR 3.5; 95% CI 1.1-11.4; P = 0.04).
Amenorrhoea leads to a reduction of MO-frequency in women with MM using hormonal contraceptives. Future prospective studies on MM should focus on contraceptive methods that achieve amenorrhoea.
The Journal of Headache and Pain 05/2014; 15(1):30. DOI:10.1186/1129-2377-15-30 · 2.80 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Medication-overuse headache (MOH) is a common problem in primary care. Brief intervention (BI) has successfully been used for detoxification from overuse of alcohol and drugs. The aim of this pilot study was to develop and test methodology, acceptability and logistics for a BI for MOH in primary care.
Observational feasibility study of an intervention in a Norwegian general practice population.Six general practitioners (GPs) were recruited. A screening questionnaire for MOH was sent to all 18-50 year old patients on these GPs` list. GPs were taught BI, which was applied to MOH patients as follows: Severity of dependence scale (SDS) scores were collected and individual feedback was given of the relationship between the SDS, medication overuse and headache. Finally, advice to reduce medication was given. Patients were invited to a headache interview three months after the BI. Main outcomes were feedback from GPs/patients about the feasibility and logistics of the study design, screening/recruitment process, BI and headache interviews. Efficacy and patient-related outcomes were not focused. The patients reported a high degree of acceptability of the methodology. The GPs reported the BI to be feasible to implement within a busy practice and to represent a new and improved instrument for communication with MOH patients. The BI requires further testing in a randomised controlled trial (RCT) in order to provide evidence of efficacy.
This feasibility study will be used to improve the BI for MOH and the design of a cluster-RCT.Trial registration: ClinicalTrials.gov: NCT01078012 (Initially registered as controlled efficacy trial but changed to observational study).
BMC Research Notes 03/2014; 7(1):165. DOI:10.1186/1756-0500-7-165
[Show abstract][Hide abstract] ABSTRACT: Bakground: The objectives of this study were; (1) to assess the prevalence and frequency of headache in patients referred to polysomnography (PSG) due to a clinical suspicion of obstructive sleep apnea (OSA) or another sleep disturbance and compare with a reference population, and (2) to assess the association of OSA severity with headache and headache frequency.
A total of 784 participants filled in a headache questionnaire between 2003 and 2009 at the Department of Clinical Neurophysiology, Akershus University Hospital. Of these patients 477 were suspected to have OSA, and 307 had other sleep complaints. We assessed the prevalence of headache and monthly headache frequencies, as well as sleep apnea severity using an apnea-hypopnea index (AHI). The association of headache and monthly headache frequencies with PSG subgroups was assessed using multivariate logistic and ordered logistic regression analysis.
The frequency of headache was not associated with the severity of OSA. Patients referred to a sleep study for any reason had higher odds ratio (OR) for having experienced headache during the past year than population controls after adjustment for age, gender and education, i.e. patients with normal AHI had OR of 3.56, patients with OSA had OR of 3.51, and patients with other sleep disturbances had OR of 3.33. Similarly, the adjusted OR of being in a higher category of monthly headache frequency compared to controls was higher in those with normal AHI (OR 3.42), OSA (OR 3.29), and other sleep disturbances (OR 3.00).
The odds of headache and headache frequency were higher in subjects referred to a PSG for any sleep disturbance independently of OSA, compared to general population controls. However, there was no association between experiencing headache during the past year or headache frequency with OSA severity.
The Journal of Headache and Pain 11/2013; 14(1):90. DOI:10.1186/1129-2377-14-90 · 2.80 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To present data from a population-based epidemiological study on menstrual migraine.
Altogether, 5000 women aged 30-34 years were screened for menstrual migraine. Women with self-reported menstrual migraine in at least half of their menstrual cycles were invited to an interview and examination. We expanded the International Classification of Headache Disorders III beta appendix criteria on menstrual migraine to include both migraine without aura and migraine with aura, as well as probable menstrual migraine with aura and migraine without aura.
A total of 237 women were included in the study. The prevalence among all women was as follows: any type of menstrual migraine 7.6%; menstrual migraine without aura 6.1%; menstrual migraine with aura 0.6%; probable menstrual migraine without aura 0.6%; probable menstrual migraine with aura 0.3%. The corresponding figures among female migraineurs were: any type of menstrual migraine 22.0%, menstrual migraine without aura 17.6%, menstrual migraine with aura 1.7%, probable menstrual migraine without aura 1.6% and probable menstrual migraine with aura 1.0%.
More than one of every five female migraineurs aged 30-34 years have migraine in ≥50% of menstruations. The majority has menstrual migraine without aura and one of eight women had migraine with aura in relation to their menstruation. Our results indicate that the ICHD III beta appendix criteria of menstrual migraine are not exhaustive.
[Show abstract][Hide abstract] ABSTRACT: Sleep apnea headache is a recurrent universal pressing headache without accompanying symptoms at awakening that resolves within 4 h. The diagnosis requires polysomnography-verified apnea hypopnea index ≥5, that is, obstructive sleep apnea (OSA). Morning headache has similar symptomatology without OSA. The prevalence of sleep apnea headache is 10-15% in people with OSA, whereas morning headache occurs in 5%. The severity of OSA only slightly affects the prevalence of sleep apnea headache. The pathophysiology of sleep apnea headache remains an enigma, since average oxygen desaturation and lowest oxygen saturation are similar in OSA people without sleep apnea headache. Migraine and tension-type headache are unrelated to OSA. Thus, growing concern of sleep apnea headache in an increasingly obese population is unfounded with our current knowledge.
[Show abstract][Hide abstract] ABSTRACT: Background
Chronic headache is associated with disability and high utilisation of health care including complementary and alternative medicine (CAM).
We investigated self-reported efficacy of CAM in people with chronic headache from the general population. Respondents with possible self-reported chronic headache were interviewed by physicians experienced in headache diagnostics. CAM queried included acupuncture, chiropractic, homeopathy, naprapathy, physiotherapy, psychological treatment, and psychomotor physiotherapy. Sixty-two % and 73% of those with primary and secondary chronic headache had used CAM.
Self-reported efficacy of CAM ranged from 0-43% without significant differences between gender, headache diagnoses, co-occurrence of migraine, medication use or physician contact.
CAM is widely used, despite self-reported efficacy of different CAM modalities is modest in the management of chronic headache.
The Journal of Headache and Pain 04/2013; 14(1):36. DOI:10.1186/1129-2377-14-36 · 2.80 Impact Factor