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Saroj K Pradhan,1– 3 Felix Angst,2 Jie Xu,1,3 Andreas R Gantenbein,4 Susanne Lehmann,2 Peter S Sandor,4 Yiming Li,1– 3 Michael Furian1 1Research Department, Swiss University of Traditional Chinese Medicine, Bad Zurzach, Switzerland; 2Research Department, Rehaklinik Bad Zurzach, Bad Zurzach, Switzerland; 3TCM Ming Dao, Bad Zurzach, Switzerland; 4Neurorehabilitation & Research Department, Rehaklinik Bad Zurzach, Bad Zurzach, SwitzerlandCorrespondence: Michael Furian, Swiss University of Traditional Chinese Medicine, Langwiesstrasse 7, Bad Zurzach, 5330, Switzerland, Tel +41 79 403 75 86, Email michael.furian@tcmuni.chIntroduction: Chronic low back pain (CLBP) cannot sufficiently be treated by pharmacological therapy and generates substantial health-care costs worldwide. Acupuncture, a cost-effective, safe and non-pharmacological therapy, has shown promising results in relieving acute low back pain; however, the optimal acupuncture therapy for CLBP remains controversial. This study will compare two acupuncture methods for pain relief in CLBP.Methods and Analysis: This randomized, controlled, single-blind, parallel trial will be conducted in patients with clinically diagnosed CLBP with a disease duration ≥ 3 months and an average pain intensity of ≥ 4 points on an 11-point Pain Intensity Numerical Rating Scale (pain-NRS) on the previous 7 days. Patients will be randomized to 9-week acupuncture therapy using Jiu Gong Points (termed Swiss low back acupuncture, SLBA) or standard acupuncture (SA) therapy (weeks 1– 6: two sessions/week, weeks 7– 9: one session/week, 15 sessions/patient in total). Measurements will be conducted before the first session (T1), at the end of the 9-week therapy (T2) and after 3- and 6-month follow-up (T3 and T4). The primary hypothesis is that 9 weeks of SLBA will be superior in reducing the pain severity assessed by the pain-NRS compared to SA therapy for CLBP. Secondary outcomes will be derived from the Short-Form 36, Oswestry Disability Index, Multidimensional Pain Inventory questionnaire, Symptom Checklist-90 – Revised questionnaire and a daily pain diary. Assuming a minimal clinically important difference in the pain-NRS of 0.39 and an effect size of ≥ 0.6 between SLBA and SA, 80% power, 0.05 alpha level and 20% dropouts, a total of 55 patients/arm will be required. The primary outcome will be analyzed in the intention-to-treat population using chained linear regression models. Patients, outcome assessors and data analysts will be blinded to the treatment arm.Trial Registration: Clinicaltrials.gov Identifier: NCT05232487.Keywords: Chinese medicine, chronic disease, pain, Pain Intensity Numerical Rating Scale, Multidimensional Pain Inventory, Oswestry Disability Index, Randomized clinical trial

Because the “intensity dependence” of cortical auditory evoked potentials (IDAP) is under serotonergic control, it can be used to assess central antimigraine effects of 5HT1B/1D agonists. We measured IDAP before and 2 h after naratriptan (5 mg, n = 19) and zolmitriptan (5 mg, n =19) in healthy volunteers, IDAP was expressed as the amplitude-stimulus intensity function (“ASP slope”). Naratriptan tended to increase ASF slope (mean difference 0.23±0.62 μV/10 dB, p =0.06) while zolmitriptan (08±0.95 μV/10 dB, p =0.35) did not. We assessed the suitability of IDAP for measuring central antimigraine drug effects using repeatability data (see companion paper). We calculated the trade-off between the size of the expected drug effects (ASF slope difference) and the necessary sample size. Because of poor repeatability 36 to 80 subjects are required to detect ASF slope changes in the 0.25–0.5 μV/10 dB range. These data can he used to design trials using IDAP. [ABSTRACT FROM AUTHOR]

Background: Medication-overuse headache (MOH) has been related to the spectrum of dependence behavior and impaired orbitofrontal cortex function. Alexithymia is a trait comprising deficits in identifying self-emotions and perception. It was the aim of the study to investigate impulsivity and alexithymia, in patients with MOH and perform correlations with cerebral grey matter., Material and Methods: Patients with chronic migraine and MOH according to ICHD criteria from a tertiary headache clinic and healthy controls were investigated by a single psychiatrist, using clinical scales for self-control (BIS-11) and alexithymia (TAS-20) and screened for dependence based on DSM-IV criteria. Correlations of BIS-11 and TAS-20 with cerebral grey matter were analysed with the SPM based toolbox CAT12, using high resolution T1weighted MRI-Sequences acquired on a 3 T scanner., Results: MRI data were available from 30 MOH patients (24 women) and 47 healthy controls (26 women). MOH patients had increased impulsivity (62.2 ± 11.1 vs. 55.7 ± 7.2; p  = 0.007) and alexithymia (49.8 ± 14.8 vs. 38.0 ± 6.5; p  < 0.001). Analyzing only women, the results remained significant. Ninety percent of patients fulfilled DSM-IV criteria for substance dependence. There was a positive correlation between impulsivity and grey matter in the left middle orbital gyrus in healthy controls but not in patients ( p  < 0.05, corrected). No correlations with alexithymia and cerebral grey matter were found., Conclusions: The present study suggests a neurobehavioral basis for MOH, consisting of impaired impulse control, and self-perception along with features of substance dependence. Although decreased orbitofrontal cortex volume was confirmed in this MOH cohort, impulsivity and alexithymia were not correlated with this structural abnormality., Competing Interests: None of the authors has conflicts of interest with regard to this work, (© 2024 The Authors. Published by Elsevier B.V.)

Objectives: To examine whether somatisation, depression, anxiety, fatigue, coping dimensions, pain, physical and social function, or sociodemographic characteristics can differentiate fibromyalgia from low back pain in a cross-sectional cohort setting of our Zurzach Interdisciplinary Pain Programme., Methods: Fibromyalgia and low back pain (not fulfilling the diagnostic criteria for fibromyalgia) were compared using the Symptom Checklist-90R (SCL-90R) Somatisation scale, the Quantification Inventory for Somatoform Syndromes (QUISS) Number of somatoform symptoms, and other standardised instruments. Standardised mean differences (SMDs) quantified the score differences, and binomial logistic regression modelling with various co-variates differentiated fibromyalgia from low back pain., Results: The largest differences indicating worse health in fibromyalgia (n = 131) were in somatisation (SCL-90R: SMD=-0.971, QUISS: SMD=-0.960), followed by affective health, pain and coping (SMDs between -0.632 and -0.280). Physical and social functioning were comparable in the two conditions (n = 262 low back pain). The two somatisation scales both with odds ratios (OR)=0.966 (p≤ 0.002) plus female sex (OR = 3.396, p< 0.001) predicted 74.3% of the cases correctly (accuracy) with a positive predictive value of 65.3% and a specificity of 87.0% for fibromyalgia. In the female subsample (n = 280), the model remained stable with an accuracy of 71.9%., Conclusion: Somatisation stood out from all other somatic, psychosocial, and coping dimensions and sociodemographics as the one significant specific predictor distinguishing fibromyalgia from low back pain. The fibromyalgia phenotype is characterised by the generalisation of painful loci but equally prominently by generalised somatoform symptoms. Assessment of somatisation is recommended to ensure accurate identification and understanding of the multifaceted syndrome of fibromyalgia., (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: The Fascial Distortion Model (FDM) is a relatively new manual therapy approach in the field of musculoskeletal physical therapy, and its potential effectiveness in treating chronic ankle instability (CAI) remains unexplored., Methods: A randomized controlled trial with 23 participants was conducted. Patients were randomly assigned to either the FDM + balance-strength training (BST) group ( n = 8), receiving extra FDM sessions weekly in addition to two sessions of BST, or the BST group ( n = 7). Healthy controls ( n = 8) did not receive any treatment and participated only in pre- and post-test measurements. Objective measurements including Y-Balance Test Lower Quarter (YBT-LQ), Flamingo Balance Test (FBT), Weight-Bearing Lunge Test (WBLT), ankle joint range of motion (ROM), and Cumberland Ankle Instability Tool (CAIT) were recorded at baseline and the end of the intervention. The results demonstrated significant differences between the FDM + BST and BST groups for supination ROM ( p = 0.008) and similarly for WBLT ( p = 0.041), FBT ( p = 0.40), YBT-LQ ( p = 0.023), and CAIT score ( p = 0.008). Moreover, while both groups demonstrated significant improvement at the post-test compared with their pre-test for plantarflexion and pronation ROM, WBLT, and CAIT score, the FDM + BST group demonstrated significant improvements in supination ROM, FBT, and YBT-LQ., Conclusion: Our study suggests that the addition of FDM concepts to a BST may lead to enhanced improvements in ankle ROM, static and dynamic balance, and self-reported outcomes in individuals with CAI compared to BST.

Objective: To quantify therapy-attributable effects of a comprehensive inpatient rehabilitation program for lower limb lymphedema (LLL) and to compare the levels of health-related quality of life (HRQL) to population-based norms., Design: Naturalistic prospective cohort study with intra-individual control of effects., Setting: Rehabilitation hospital., Participants: Patients with LLL (N=67; 46 women)., Interventions: Comprehensive, multidisciplinary inpatient rehabilitation with 45-60 hours of therapy., Main Outcome Measures: Short Form 36 (SF-36) for HRQL, lymphedema-specific Freiburg Quality of Life Assessment for lymphatic disorders, Short Version (FLQA-lk), knee-specific Knee Outcome Survey Activities of Daily Living Scale (KOS-ADL), and Symptom Checklist-90Standard (SCL-90S). Observed pre/post rehabilitation effects were individually corrected by subtracting the home waiting-time effects and expressed as standardized effect sizes (ESs) and standardized response means (SRMs). Score differences to norms were quantified by standardized mean differences (SMDs)., Results: Participants were on average aged 60.5 years, not yet obese, and had 3 comorbidities (n=67). The greatest improvement was in HRQL on the FLQA-lk with ES=0.767/SRM=0.718, followed by improvements in pain and function with ES/SRM=0.430-0.495 on the SF-36, FLQA-lk, and KOS-ADL (all P<.001). Vitality, mental health, emotional well-being, and interpersonal sensitivity improved most by ES/SRM=0.341-0.456 on all 4 measures (all P≤.003). Post rehabilitation scores were significantly higher than population norms on SF-36 bodily pain (SMD=1.140), vitality (SMD=0.886), mental health (SMD=0.815), and general health (SMD=0.444) (all P<.001), and comparable on the other scales., Conclusions: Those affected by LLL stages II and III benefited substantially from the intervention, attaining equal or higher levels of HRQL than expected compared with the general population norms. Multidisciplinary, inpatient rehabilitation should be recommended for LLL management., (Copyright © 2023 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.)

Objectives: To develop a clinical model to predict the risk of an individual patient developing delirium during inpatient rehabilitation, based on patient characteristics and clinical data available on admission., Design: Retrospective observational study based on electronic health record data., Setting and Participants: We studied a previously validated data set of inpatients including incident delirium episodes during rehabilitation. These patients were admitted to ZURZACH Care, Rehaklinik Bad Zurzach, a Swiss inpatient rehabilitation clinic, between January 1, 2015, and December 31, 2018., Methods: We performed logistic regression analysis using backward and forward selection with alpha = 0.01 to remove any noninformative potential predictor. We subsequentially used the Akaike information criterion (AIC) to select the final model among the resulting "intermediate" models. Discrimination of the final prediction model was evaluated using the C-statistic., Results: Of the 20 candidate predictor variables, 6 were included in the final prediction model: a linear spline of age with 1 knot at 60 years and a linear spline of the functional independence measure (FIM), a measure of the functional degree of patients independency, with 1 knot at 64 points, diagnosis of disorders of fluid, electrolyte, and acid-base balance (E87), use of other analgesic and antipyretics (N02B), use of anti-parkinson drugs (N04B), and an anticholinergic burden score (ACB) of ≥3 points., Conclusions and Implications: Our clinical prediction model could, upon validation, identify patients at risk of incident delirium at admission to inpatient rehabilitation, and thus enable targeted prevention strategies., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Objectives: To investigate the association between a wide set of baseline characteristics (age, sex, rehabilitation discipline), functional scores [Functional Independence Measure (FIM), cumulative Illness Rating Scale (CIRS)], diseases, and administered drugs and incident delirium in rehabilitation inpatients and, furthermore, to assess clinical implications of developing delirium during rehabilitation., Design: Matched case-control study based on electronic health record data., Setting and Participants: We studied rehabilitation stays of inpatients admitted between January 1, 2015, and December 31, 2018, to ZURZACH Care, Rehaklinik Bad Zurzach, an inpatient rehabilitation clinic in Switzerland., Methods: We conducted unconditional logistic regression analyses to estimate adjusted odds ratios (AORs) with 95% CIs of exposures that were recorded in ≥5 cases and controls., Results: Among a total of 10,503 rehabilitation stays, we identified 125 validated cases. Older age, undergoing neurologic rehabilitation, a low FIM, and a high CIRS were associated with an increased risk of incident delirium. Being diagnosed with a bacterial infection (AOR 2.62, 95% CI 1.06-6.49), a disorder of fluid, electrolyte, or acid-base balance (AOR 2.76, 95% CI 1.19-6.38), Parkinson's disease (AOR 5.68, 95% CI 2.54-12.68), and administration of antipsychotic drugs (AOR 8.06, 95% CI 4.26-15.22), antiparkinson drugs (AOR 2.86, 95% CI 1.42-5.77), drugs for constipation (AOR 2.11, 95% CI 1.25-3.58), heparins (AOR 2.04, 95% CI 1.29-3.24), or antidepressant drugs (AOR 1.88, 95% CI 1.14-3.10) during rehabilitation, or an increased anticholinergic burden (ACB ≥ 3) (AOR 2.59, 95% CI 1.41-4.73) were also associated with an increased risk of incident delirium., Conclusions and Implications: We identified a set of factors associated with an increased risk of incident delirium during inpatient rehabilitation. Our findings contribute to detect patients at risk of delirium during inpatient rehabilitation., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Delirium is a brain condition associated with poor outcomes in rehabilitation. It is therefore important to assess delirium incidence in rehabilitation., Purpose: To develop and validate a chart-based method to identify incident delirium episodes within the electronic database of a Swiss rehabilitation clinic, and to identify a study population of validated incident delirium episodes for further research purposes., Design: Retrospective validation study., Settings: Routinely collected inpatient clinical data from ZURZACH Care., Participants: All patients undergoing rehabilitation at ZURZACH Care, Rehaklinik Bad Zurzach between 2015 and 2018 were included., Methods: Within the study population, we identified all rehabilitation stays for which ≥2 delirium-predictive key words (common terms used to describe delirious patients) were recorded in the medical charts. We excluded all prevalent delirium episodes and defined the remaining episodes to be potentially incident. At least two physicians independently confirmed or refuted each potential incident delirium episode by reviewing the patient charts. We calculated the positive predictive value (PPV) with 95% confidence interval (95% CI) for all potential incident delirium episodes and for specific subgroups., Results: Within 10,515 rehabilitation stays we identified 554 potential incident delirium episodes. Overall, 125 potential incident delirium episodes were confirmed by expert review. The PPV of the chart-based method varied from 0.23 (95% CI 0.19-0.26) overall to 0.69 (95% CI 0.56-0.79) in specific subgroups., Conclusions: Our chart-based method was able to capture incident delirium episodes with low to moderate accuracy. By conducting an additional expert review of the medical charts, we identified a study population of validated incident delirium episodes. Our chart-based method contributes towards an automated detection of potential incident delirium episodes that, supplemented with expert review, efficiently yields a validated population of incident delirium episodes for research purposes.

Migraine can be regarded as a conserved, adaptive response that occurs in genetically predisposed individuals with a mismatch between the brain's energy reserve and workload. Given the high prevalence of migraine, genotypes associated with the condition seem likely to have conferred an evolutionary advantage. Technological advances have enabled the examination of different aspects of cerebral metabolism in patients with migraine, and complementary animal research has highlighted possible metabolic mechanisms in migraine pathophysiology. An increasing amount of evidence - much of it clinical - suggests that migraine is a response to cerebral energy deficiency or oxidative stress levels that exceed antioxidant capacity and that the attack itself helps to restore brain energy homeostasis and reduces harmful oxidative stress levels. Greater understanding of metabolism in migraine offers novel therapeutic opportunities. In this Review, we describe the evidence for abnormalities in energy metabolism and mitochondrial function in migraine, with a focus on clinical data (including neuroimaging, biochemical, genetic and therapeutic studies), and consider the relationship of these abnormalities with the abnormal sensory processing and cerebral hyper-responsivity observed in migraine. We discuss experimental data to consider potential mechanisms by which metabolic abnormalities could generate attacks. Finally, we highlight potential treatments that target cerebral metabolism, such as nutraceuticals, ketone bodies and dietary interventions.

Background: In the emergency setting, non-traumatic headache is a benign symptom in 80% of cases, but serious underlying conditions need to be ruled out. Copeptin improves risk stratification in several acute diseases. Herein, we investigated the value of copeptin to discriminate between serious secondary headache and benign headache forms in the emergency setting., Methods: Patients presenting with acute non-traumatic headache were prospectively enrolled into an observational cohort study. Copeptin was measured upon presentation to the emergency department. Primary endpoint was serious secondary headache defined by a neurologic cause requiring immediate treatment of the underlying disease. Secondary endpoint was the combination of mortality and hospitalization within 3 months. Two board-certified neurologist blinded to copeptin levels verified the endpoints after a structured 3-month-telephone interview., Results: Of the 391 patients included, 75 (19%) had a serious secondary headache. Copeptin was associated with serious secondary headache (OR 2.03, 95%CI 1.52-2.70, p < 0.0001). Area under the curve (AUC) for copeptin to identify the primary endpoint was 0.70 (0.63-0.76). After adjusting for age > 50, focal-neurological abnormalities, and thunderclap onset of symptoms, copeptin remained an independent predictive factor for serious secondary headache (OR 1.74, 95%CI 1.26-2.39, p = 0.001). Moreover, copeptin improved the AUC of the multivariate logistic clinical model (p-LR-test < 0.001). Even though copeptin values were higher in patients reaching the secondary endpoint, this association was not significant in multivariate logistic regression., Conclusions: Copeptin was independently associated with serious secondary headache as compared to benign headaches forms. Copeptin may be a promising novel blood biomarker that should be further validated to rule out serious secondary headache in the emergency department., Trial Registration: Study Registration on 08/02/2010 as NCT01174901 at clinicaltrials.gov.

The aim of this pilot study was to determine health-related quality of life (HRQoL) in patients with history of medication overuse headache (MOH) after detoxification and a headache-specific inpatient rehabilitation program and to receive necessary information for future prospective studies.HRQoL and headache-related disability were cross-sectionally measured by Short Form 36 (SF-36), Hospital Anxiety and Depression Scale (HADS), Migraine Disability Score (MIDAS), Coping Strategies Questionnaire (CSQ), and Symptom Checklist 90 revised (SCL-90-R). SF-36, HADS, and SCL-90-R data were compared to German population norms, stratified by age, sex, and comorbidities.Fifty-one patients (72.5% females, mean age 47.3 years) were included with an average headache duration of 25.3 years. Moderate to high levels of headache were reported on the MIDAS VAS at 6.51 (range 0-10); SF-36 bodily pain was 40.3 (norm = 59.0, P < .001, 100 = best). Impaired functioning averaged at 78.4 (100 = no impairment) on the MIDAS. In contrast, SF-36 physical functioning was comparable to the norm (mean: 78.4, norm = 81.8, P = .63). All other SF-36 scales were significantly lower than expected from the norm (all P < .001). The scales depression, anxiety, obsessive-compulsive, and interpersonal sensitivity were significantly affected, whereas the levels of SCL-90-R schizophrenia nuclear and schizotypia were not lower than the norm. Coping with pain was moderate.This pilot study is the first that presents a comprehensive and simultaneously specific assessment of health and quality of life of MOH patients after detoxification and inpatient rehabilitation. Moderate to high levels of pain and self-reported disability owing to headache were observed, whereas physical function on the SF-36 was not different from the expected level of the norm. Mental health was substantially affected in several dimensions, which had been described to reduce the ability to cope with pain. MOH patients seem to have high expectations of functionality, low symptomatology, and intact well-being., (Copyright © 2017 The Authors. Published by Wolters Kluwer Health, Inc. All rights reserved.)

Objectives: Widespread sensory deficits resembling hemihypoesthesia occur in 20% to 40% of chronic pain patients on the side of pain, independent of pain etiology, and have been termed nondermatomal sensory deficits (NDSDs). Sensory profiles have rarely been investigated in NDSDs., Materials and Methods: Quantitative sensory testing according to the protocol of the German Research Network on Neuropathic Pain (DFNS) was performed in the face, hand, and foot of the painful body side and in contralateral regions in chronic pain patients. Twenty-five patients with NDSDs and 23 without NDSDs (termed the pain-only group) were included after exclusion of neuropathic pain. Comprehensive clinical and psychiatric evaluations were carried out., Results: NDSD in chronic pain was associated with high burden of disease and more widespread pain. Only in the NDSD group were significantly higher thresholds for mechanical and painful stimuli found in at least 2 of 3 regions ipsilateral to pain. In addition, we found a bilateral loss of function for temperature and vibration detection, and a gain of function for pressure pain in certain regions in patients with NDSD. Sensory loss and gain of function for pressure pain correlated with pain intensity in several regions., Discussion: This may indicate a distinct sensory profile in chronic non-neuropathic pain and NDSD, probably attributable to altered central pain processing and sensitization. The presence of NDSD in chronic non-neuropathic pain may be regarded as a marker for higher burden of pain disease.

Background Neuroimaging studies revealed structural and functional changes in medication-overuse headache (MOH), but it remains unclear whether similar changes could be observed in other chronic pain disorders. Methods In this cross-sectional study, we investigated functional connectivity (FC) with resting-state functional magnetic resonance imaging (fMRI) and white matter integrity using diffusion tensor imaging (DTI) to measure fractional anisotropy (FA) and mean diffusivity (MD) in patients with MOH ( N = 12) relative to two control groups: patients with chronic myofascial pain (MYO; N = 11) and healthy controls (CN; N = 16). Results In a data-driven approach we found hypoconnectivity in the fronto-parietal attention network in both pain groups relative to CN (i.e. MOH < CN and MYO < CN). In contrast, hyperconnectivity in the saliency network (SN) was detected only in MOH, which correlated with FA in the insula. In a seed-based analysis we investigated FC between the periaqueductal grey (PAG) and all other brain regions. In addition to overlapping hyperconnectivity seen in patient groups (relative to CN), MOH had a distinct connectivity pattern with lower FC to parieto-occipital regions and higher FC to orbitofrontal regions compared to controls. FA and MD abnormalities were mostly observed in MOH, involving the insula. Conclusions Hyperconnectivity within the SN along with associated white matter changes therein suggest a particular role of this network in MOH. In addition, abnormal connectivity between the PAG and other pain modulatory (frontal) regions in MOH are consistent with dysfunctional central pain control.

Objectives: Widespread sensory deficits occur in 20-40% of chronic pain patients on the side of pain, independent of pain aetiology, and are known as nondermatomal sensory deficits (NDSDs). NDSDs can occur in absence of central or peripheral nervous system lesions. We hypothesised that NDSDs were associated with cerebral grey matter changes in the sensory system and in pain processing regions, detectable with voxel-based morphometry., Methods: Twenty-five patients with NDSDs, 23 patients without NDSDs ("pain-only"), and 29 healthy controls were studied with high resolution structural MRI of the brain. A comprehensive clinical and psychiatric evaluation based on Diagnostic and Statistical Manual was performed in all patients., Results: Patients with NDSDs and "pain-only" did not differ concerning demographic data and psychiatric diagnoses, although anxiety scores (HADS-A) were higher in patients with NDSDs. In patients with NDSDs, grey matter increases were found in the right primary sensory cortex, thalamus, and bilaterally in lateral temporal regions and the hippocampus/fusiform gyrus. "Pain-only" patients showed a bilateral grey matter increase in the posterior insula and less pronounced changes in sensorimotor cortex., Conclusions: Dysfunctional sensory processing in patients with NDSDs is associated with complex changes in grey matter volume, involving the somatosensory system and temporal regions.

Migraine is a disabling headache disorder, which affects up to 17% of the female population. Oestrogen withdrawal during the menstrual cycle or the hormone-free interval in users of combined hormonal contraceptives (CHC) plays a pivotal role. Two diary-based studies demonstrated a positive impact of the progestin-only pill (POP) desogestrel 75 μg on the frequency of the migraine attacks and pain intensity. In both studies, CHC users as well as nonusers were included, which makes it difficult to distinguish between the effect of taking women off the CHC and the benefit of the POP itself. With the present study, we compared the therapeutic effect of the POP desogestrel 75 μg on migraine in current CHC users and nonusers. We found a positive influence of desogestrel on migraine not only in women who switched from CHCs to desogestrel, but also in those who had not used hormones over 6 months before starting it. Our findings need to be confirmed in prospectively conducted studies with larger sample size.

Objective: Using surface-based morphometry we aimed to provide a detailed examination of cortical alterations in medication-overuse headache (MOH), by disentangling between altered cortical thickness and gyrification (folding)., Background: In MOH, pain modulation is probably dysfunctional at the cortical and subcortical level, resulting in a disequilibrium between pain inhibition and facilitation. Both increased and decreased cortical volumes have been reported in individuals with MOH. There is however no detailed examination to date that distinguishes between altered cortical thickness and gyrification. Such distinction would help to identify the nature and timing of neurodevelopmental mechanisms at play in affected individuals., Methods: We investigated cortical thickness and gyrification in 29 patients with MOH according to International Headache Society criteria and 29 age- and gender-matched controls, using high-resolution structural MRIs of the brain analyzed with FreeSurfer. This is a secondary analysis of data from a previously published voxel-based morphometry study., Results: In patients with MOH compared to controls, reduced cortical thickness was observed in the left prefrontal cortex. We also observed higher local gyrification in one cluster extending from the fusiform cortex to adjacent medial temporal regions, and in another cluster in the right occipital pole. Higher gyrification in the right occipital pole predicted poor response after detoxification., Conclusions: Corroborating previous volumetric results, our study adds information on the putative neurobiological mechanisms involved in MOH, suggesting neurodevelopmental changes in MOH., (© 2016 American Headache Society.)

Headaches are amongst the most common reasons for visiting a general practitioner in Switzerland. The key features in differentiating migraine from other types of headache are the pulsating pain, interfering with daily activities, and the hypersensitivity to stimuli such as light or sound. Around 15 % of the patients report a preceeding aura, consisting of transient neurological symptoms. An effective migraine management is based on non-pharmacological treatment as well as acute and preventive medication. Non-pharmacological options include the management of the trigger factors stress, sleep deprivation, musculoskeletal tension. Acute treatment should be stratified and include non-opioid analgesics for milder attacks, triptans or combinations for more severe attacks. The spectrum of preventive medication is broad. Therefore it is essential to find a suitable and well tolerable drug for the individual patient.

We report the case of a 60-year-old man suffering from episodic cluster headache treated successfully with sodium oxybate. Sodium oxybate may be a therapeutic option in attacks of episodic cluster headache., (© 2013 American Headache Society.)

Patients with chronic daily headache and overuse of analgesics, triptans, or other acute headache compounds, are considered to suffer from medication-overuse headache (MOH). This implies that medication overuse is the cause of headache chronification. It remains a key question why only two-thirds of patients with chronic migraine-like headache and overuse of pain medication improve after detoxification, whereas the remainder continue to have chronic headache. In the present longitudinal MRI study, we used voxel-based morphometry to investigate gray matter changes related to medication withdrawal in a group of humans with MOH. As a main result, we found that only patients with significant clinical improvement showed a significant decrease of previously increased gray matter in the midbrain including periaqueductal gray matter and nucleus cuneiformis, whereas patients without improvement did not. Patients without treatment response had less gray matter in the orbitofrontal cortex. Another striking result is the correlation of treatment response with the amount of orbitofrontal gray matter. Thus, we demonstrate adaptive gray matter changes within the pain modulatory system in patients with MOH who responded to detoxification, probably reflecting neuronal plasticity. Decreased gray matter in the orbitofrontal cortex at baseline may be predictive of poor response to treatment.

Introduction: Pharmacotherapy in patients with neuropathic pain syndromes (NPS) can be associated with long periods of trial and error before reaching satisfactory analgesia. The aim of this study was to investigate whether a short intravenous (i.v.) infusion of lidocaine may have a predictive value for the efficacy of oxcarbazepine., Methods: In total, 16 consecutive patients with NPS were studied in a prospective, uncontrolled, open-label study design. Each patient received i.v. lidocaine (5 mg/kg) within 30 min followed by a long-term oral oxcarbazepine treatment (900-1,500 mg/day). During an observation period of 28 days, treatment response was documented by a questionnaire including the average daily pain score documented on a numeric rating scale (NRS)., Results: A total of 6 out of 16 patients (38%) were lidocaine responders (defined as pain reduction >50% during the infusion), and 4 of 16 (25%) were oxcarbazepine responders. In total, 6 out of 16 participants (38%) discontinued oxcarbazepine treatment due to side effects. In an interim analysis predictive value of the lidocaine infusion was low with a Kendall's tau correlation coefficient of 0.29 and coefficient of determination R(2) of 0.119 (95% confidence interval -0.29 to 0.72). As a consequence of this low correlation, the study was discontinued for ethical reasons., Conclusion: In conclusion, lidocaine infusion has a low predictive value for effectiveness of oxcarbazepine-if at all.

Background: Migraine seems to be substantially related to hormonal changes. However, migraine, but also the use of combined oral contraceptives (COC), is associated with an increased risk for vascular events. Therefore progestagen-only contraception is an important alternative to combined preparations. Clinical observations and one pilot study demonstrate that the use of desogestrel 75 µg may have a positive impact on migraine., Aim: The aim of this retrospective analysis of prospectively collected headache diaries was to study the effect of desogestrel 75 µg on headache frequency, intensity and use of acute medication in premenopausal women with migraine in a clinical setting., Methods: Patients' charts were included from women who wanted to use desogestrel 75 µg as a contraceptive and had kept headache diaries over six months (three months pretreatment and three months during treatment). Out of 58 women, 38 women had completed headache diaries for this period. Incomplete diaries ( N  = 12), side effects ( N  = 5) and loss to follow-up ( N  = 3) were the reasons for the exclusion of 20 women. The three months (total of 90 days) before and after initiation of the progestin were compared., Results: Days with migraine (5.2 vs. 3.7), days with all kind of headache (8.3 vs. 6.5) and days with use of any headache medication (5.7 vs. 3.5) were significantly reduced at follow-up after three months. In addition there was a reduction in headache intensity ( P  < 0.0001). The reduction in number of days with use of triptans was not significant ( P  < 0.14)., Conclusion: In the 38/58 migraineurs with complete diaries there was a statistically significant decrease in migraine days, headache intensity and medication use. Tension-type headache days decreased but were not significant. Our preliminary data are promising, but should be interpreted cautiously because they were obtained in a small population of women visiting a specialty hormone and migraine clinic. Randomised controlled trials need to be conducted to substantiate our results.

Background: The objectives of this cross-sectional, observational study were to determine the prevalence of self-reported headache among the employees of the large Swiss university hospital, to measure the impact of headache using the MIDAS questionnaire, to assess current treatment and to estimate economic burden of headache considering indirect costs., Methods: A self-administered questionnaire was distributed internally to 2000 randomly selected employees of the University Hospital Zurich., Results: 1210 employees (60.5%) responded. Of the 1192 (98.5%) employees who provided sufficiently complete information, 723 (61%) reported at least one headache type in the last three months. The prevalence of migraine, and tension-type headache was 20% and 50%, respectively. Regarding the occupational groups, there was a trend that healthcare staff, administration employees, and medical technicians suffered more from headaches than physicians, correcting for age and sex. The economic consequences of lost productivity were calculated to amount to approximately 14 million Swiss Francs (9.5 million EUR), representing 3.2% of the overall annual expenditure of the hospital for personnel., Conclusion: Headache is highly prevalent among university hospital employees, with significant economic impact.

Background: Headache is one of the most common symptoms in primary care. To improve the quality of headache diagnosis and management with the largest possible benefit for the general population, headache and pain societies around the world have recently been devoting more attention to headache in primary care.The aim of the study was to investigate the potential contribution that national societies can make toward raising the awareness of primary headaches in general practice., Findings: In a qualitative telephone survey, targeting primary care practices (PCP), we asked about the frequency of headache patients in their practices and inquired about their treatment and referral strategies.A total of 1000 telephone interviews with PCP have been conducted. Three-hundred and fifty physicians have been directly interviewed, 95% of them see headache patients every week, 23% daily. Direct MRI referral is done by 84%. Sixty-two per cent of the physicians knew the Swiss headache society, 73% were interested in further education about headaches., Conclusion: The survey yielded information about the physicians' awareness of the Swiss Headache Society and its activities, and about their desire for continuing education in the area of headache. National headache societies should work to improve the cooperation between headache specialists and PCP, aiming for a better care for our patients with headache.

Chronic migraine (CM) was first defined in the second edition of the International Headache Society (IHS) classification in 2004. The definition currently used (IHS 2006) requires the patient to have headache on more than 15 days/month for longer than 3 months and a migraine headache on at least 8 of these monthly headache days and that there is no medication overuse. In daily practice the majority of the patients with CM also report medication overuse but it is difficult to determine whether the use is the cause or the consequence of CM. Most the patients also have other comorbidities, such as depression, anxiety and chronic pain at other locations. Therapy has to take this complexity into consideration and is generally multimodal with behavioral therapy, aerobic training and pharmacotherapy. The use of analgesics should be limited to fewer than 15 days per month and use of triptans to fewer than 10 days per month. Drug treatment should be started with topiramate, the drug with the best scientific evidence. If there is no benefit, onabotulinum toxin A (155-195 Units) should be used. There is also some limited evidence that valproic acid and amitriptyline might be beneficial. Neuromodulation by stimulation of the greater occipital nerve or vagal nerve is being tested in studies and is so far an experimental procedure only.

Objectives: Medication-overuse headache (MOH) is associated with psychiatric comorbidities. Neurobiological similarities to substance dependence have been suggested. This study investigated grey matter changes, focussing on pain and reward systems., Methods: Using voxel-based morphometry, structural MRIs were compared between 29 patients with both, MOH and migraine, according to International Headache Society criteria, and healthy controls. The Migraine Disability Assessment (MIDAS) score was used. Anxiety and depression were screened for with the Hospital Anxiety and Depression Scale (HADS) and confirmed by a psychiatrist, using the Mini International Neuropsychiatric Interview., Results: Nineteen patients (66%) had a present or past psychiatric disorder, mainly affective (N = 11) and anxiety disorders (N = 8). In all patients a significant increase of grey matter volume (GMV) was found in the periaqueductal grey matter of the midbrain, which correlated positively with the MIDAS and the HADS-anxiety subscale. A GMV increase was found bilaterally in the thalamus, and the ventral striatum. A significant GMV decrease was detected in frontal regions including orbitofrontal cortex, anterior cingulate cortex, the left and right insula, and the precuneus., Conclusion: These findings are consistent with dysfunction of antinociceptive systems in MOH, which is influenced by anxiety. Dysfunction of the reward system may be a neurobiological basis for dependence in a subgroup of MOH patients.

Introduction: Infiltration of the greater occipital nerve (GON) with local anaesthetics and corticosteroids is a treatment option for cluster headache., Methods: We retrospectively analysed the efficacy and safety of 121 GON injections in 60 patients with episodic or chronic cluster headache over a period of 4 years., Results: Almost 80% of the infiltrations were at least partially effective (reduction of attack frequency, duration or severity) and 45% resulted in a complete response (no further attacks). The effect was maintained for 3.5 weeks on average in chronic cluster headache. In episodic cluster headache, the effect lasted for most of the bout. In 18 infiltrations, transient side effects were reported, such as local pain, steroid effects (facial oedema, sleeping disorders, acne), bradycardia or syncope., Conclusion: Our data show that GON infiltration is a valuable and safe option in the clinical setting to treat patients suffering from cluster headache, especially for the episodic form of the disorder.

Acute confusional migraine (ACM) is a rare migraine variant, affecting children and adolescents, as well as adults. Between 0.45 and 7.8% of children with migraine present with ACM, but the disorder may well be underdiagnosed. ACM is an exclusion diagnosis and some dangerous causes of confusion (e.g., epilepsy, ischemia, hemorrhagia, neoplasm, intoxication and encephalitis) should be ruled out. The confusional state often manifests with a wide diversity of cortical dysfunctions, such as speech difficulties, increased alertness, agitation and amnesia. Exact history taking, clinical examination, and laboratory, radiological and electroencephalographical findings lead the practitioner towards the diagnosis. Approximately half of the cases may be triggered by mild head trauma. Transient global amnesia is an important differential diagnosis, possibly caused by similar pathophysiological mechanisms. The exact pathomechanism remains unclear, with the common hypothesis comprising of the confusional state as a complex aura phenomenon, in which the cortical spreading depression wave reaches not only the occipital, but also the temporal, parietal and frontal cortex, as well as the brainstem and the hippocampi, leading to transient hypoperfusion and dysfunction of these brain areas.

We report the case of a 49-year-old lady with cluster headache, who had received sumatriptan s.c. treatment for 15 years with daily dosages between 12 and 222 mg (average of 150 mg during the last year). The therapy was successful in aborting CH attacks. Long-term overdosage of sumatriptan was well tolerated, without adverse events., (© 2011 American Headache Society.)

In contrast to patent foramen ovale that is highly prevalent in the general population, atrial septal defect (ASD) is a rare congenital heart defect. The effect of ASD closure on headache and migraine remains a matter of controversy. The objectives of our study were (1) to determine headache prevalence in consecutive patients with ASD scheduled for percutaneous closure for cardiologic indications, using the International Classification of Headache Disorders and (2) to compare headache characteristics before and after closure of ASD. In this observational case series no a priori power analysis was performed. Twenty-five consecutive patients were prospectively included over 27 months. Median duration of follow-up was 12 months [interquartile range 0]. Prevalence of active headache seemed to be higher compared with the general population: any headaches 88% (95% confidence interval 70-96), migraine without aura 28% (14-48), migraine with aura 16% (6-35). After ASD closure, we observed a slightly lower headache frequency (median frequency 1.0 [2.6] vs. 0.3 [1.5] headaches per month; P = .067). In patients with ongoing headaches, a significant decrease in headache intensity (median VAS 7 [3] vs. 5 [4]; P = .036) was reported. Three patients reporting migraine with aura before the intervention noted no migraine with aura attacks at follow-up, 2 of them reported ongoing tension-type headache, 1 migraine without aura. In summary, this prospective observational study confirms the high prevalence of headache, particularly migraine, in ASD patients and suggests a possible small beneficial effect of ASD closure., (© 2011 American Headache Society.)

We developed a 103-item self-reporting questionnaire to assess the burden of primary headache disorders on those affected by them, including headache characteristics, associated disability, co-morbidities, disease-management and quality of life. We validated the questionnaire in five languages with 426 participants (131 in UK, 60 in Italy, 107 in Spain, 83 in Germany/Austria, and 45 in France). After a linguistic and a face-content validation, we tested the questionnaire for comprehensibility, internal consistency and test-retest reliability at an interval of one month. In the different countries, response rates were between 73% and 100%. Test-retest reliability varied between -0.27 to 1.0 depending of the nature of the expected agreement. The internal consistency was between 0.69 and 0.91. The EUROLIGHT questionnaire is suitable for evaluating the burden of primary headache disorders, and can be used in English, German, French, Italian and Spanish.

Familial trigeminal neuralgia has been reported in 1-2% of cases consistent with an autosomal dominant inheritance. We present a Swiss family with several members suffering from occipital and nervus intermedius neuralgia alone or in combination. We suggest that peripheral sensory anastomoses or central convergence of afferent pathways could explain neuralgia affecting two cranial nerves. The pedigree has two main characteristics: (1) affected individuals in two generations and (2) in the first generation the father is affected, in the second generation all women are affected, and none of the men. This is suggestive of an X-linked dominant or an autosomal dominant mode of inheritance.