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Clinical and biobehavioral perspectives: Is medication overuse headache a behavior of dependence?

Medication overuse headache (MOH), previously known as analgesic abuse headache or medication misuse headaches, is a common form of chronic headache disorder that has a detrimental impact on health and society. Although it has been widely accepted that overusing abortive medications is paradoxically the cause of MOH and drug discontinuation is the treatment of choice, ongoing debates exist as to whether drug consumption per se is the cause or consequence of headache chronification. Certain features in MOH such as their compulsive drug-seeking behavior, withdrawal headaches and high relapse rates share similarities with drug dependence, suggesting that there might be common underlying biological and psychobehavioral mechanisms. In this regard, this article will discuss the updated evidence and current debates on the possible biobehavioral overlap between MOH and drug dependence. To begin with, we will discuss whether MOH has characteristics of substance dependence based on standard psychiatry diagnostic criteria and other widely used dependence scales. Recent epidemiological studies underscoring common psychiatric comorbidities between the two disorders will also be presented. Although both demonstrate seemingly distinct personality traits, recent studies revealed similar decision-making impairment from a cognitive perspective, indicating the presence of a maladaptive reward system in both disorders. In addition, emerging imaging studies also support this notion by showing reversible morphological and functional brain changes related to the mesocorticolimbic reward circuitry in MOH, with a strong resemblance to those in addiction. Finally, an increased familial risk for drug dependence and genetic association with dopaminergic and drug dependence molecular pathways in MOH also support a possible link between MOH and addiction. Understanding the role of dependence in MOH will have a great impact on disease management as this will provide the missing piece of the puzzle in current therapeutic strategies.

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Galcanezumab in migraine prevention: a systematic review and meta-analysis of randomized controlled trials.

Galcanezumab, along with three other monoclonal antibodies targeting the calcitonin gene-related peptide (CGRP) pathway, represents the latest disease-specific and mechanism-based treatment for the prophylaxis of migraine. Galcanezumab shares data also for the prophylaxis of cluster headache.

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Two-step deep neural network for segmentation of deep white matter hyperintensities in migraineurs.

Patients with migraine show an increased presence of white matter hyperintensities (WMHs), especially deep WMHs. Segmentation of small, deep WMHs is a critical issue in managing migraine care. Here, we aim to develop a novel approach to segmenting deep WMHs using deep neural networks based on the U-Net.

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Associations between migraine occurrence and the effect of aura, age at onset, family history, and sex: A cross-sectional study.

The relationships between family history, sex, age at onset, and migraine occurrence have been documented. However, the associations between these factors across different sexes and subgroups of patients have yet to be elucidated. This study evaluated the association between family history and migraine in male and female patients experiencing episodic and chronic migraine with and without aura.

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The Spontaneous Activity Pattern of the Middle Occipital Gyrus Predicts the Clinical Efficacy of Acupuncture Treatment for Migraine Without Aura.

The purpose of the present study was to explore whether and to what extent the neuroimaging markers could predict the relief of the symptoms of patients with migraine without aura (MWoA) following a 4-week acupuncture treatment period. In study 1, the advanced multivariate pattern analysis was applied to perform a classification analysis between 40 patients with MWoA and 40 healthy subjects (HS) based on the z-transformed amplitude of low-frequency fluctuation (zALFF) maps. In study 2, the meaningful classifying features were selected as predicting features and the support vector regression models were constructed to predict the clinical efficacy of acupuncture in reducing the frequency of migraine attacks and headache intensity in 40 patients with MWoA. In study 3, a region of interest-based comparison between the pre- and post-treatment zALFF maps was conducted in 33 patients with MwoA to assess the changes in predicting features after acupuncture intervention. The zALFF value of the foci in the bilateral middle occipital gyrus, right fusiform gyrus, left insula, and left superior cerebellum could discriminate patients with MWoA from HS with higher than 70% accuracy. The zALFF value of the clusters in the right and left middle occipital gyrus could effectively predict the relief of headache intensity ( = 0.38 ± 0.059, mean squared error = 2.626 ± 0.325) and frequency of migraine attacks ( = 0.284 ± 0.072, mean squared error = 20.535 ± 2.701) after the 4-week acupuncture treatment period. Moreover, the zALFF values of these two clusters were both significantly reduced after treatment. The present study demonstrated the feasibility and validity of applying machine learning technologies and individual cerebral spontaneous activity patterns to predict acupuncture treatment outcomes in patients with MWoA. The data provided a quantitative benchmark for selecting acupuncture for MWoA.

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Therapeutic role of melatonin in migraine prophylaxis: Is there a link between sleep and migraine?

Melatonin is a ubiquitously distributed molecule that possesses diverse functions. Melatonin plays a key role in the endogenous circadian rhythms of humans via light stimulation in the hypothalamus. In addition, melatonin has roles in the opioid system, the nitric oxide pathway, free radical scavenging, inflammation, and antinociception. Melatonin is nontoxic and relatively safe. Recently, exogenous melatonin has been shown to have significant effects in the treatment of migraine. Further, it has demonstrated efficacy in the treatment of sleep disorders, including insomnia, circadian rhythm sleep-wake disorders, parasomnias, and sleep breathing disorders. Sleep disorders are commonly reported by those who experience migraine, and migraine and sleep disorders have been reported to be closely associated in cross-sectional studies. Longitudinal studies have shown that some sleep disorders and migraine show bidirectional comorbidities. Therefore, the identification and treatment of sleep disorders is important when treating migraine. Melatonin represents a promising treatment strategy for both disorders, especially when these conditions are combined.

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Cathodal tDCS Guided by Thermography as Adjunctive Therapy in Chronic Migraine Patients: A Sham-Controlled Pilot Study.

To explore the efficacy of cathodal tDCS applied ipsilateral to the cold patch, as determined by thermographic evaluation, in the treatment of chronic migraine. Transcranial direct current stimulation (tDCS) is a non-invasive and safe technique that modulates the activity of the underlying cerebral cortex. tDCS has been extensively tested as a possible treatment for chronic pain and migraine with controversial results mainly due to the different setting procedure and location of electrodes. Since the presence of a hypothermic patch region detected through thermography has been suggested as a possible support for headache diagnosis, this "cold patch" could considered as possible effective location for tDCS application. Forty-five patients with chronic migraine were randomized to receive either cathodal (25 patients) or sham tDCS, for 5 consecutive daily sessions plus a recall session after 1 month. Cathodal tDCS was delivered at 1.5 mA for 15 min in each session. Subjects were evaluated before treatment (baseline, T0), and after 10 (T10), 60 (T60), and 120 (T120) days after treatment. The number of attacks, duration of attacks, pain intensity, number of days with headache, and number of analgesics were collected at each time evaluation. Patients in the tDCS group showed a significant improvement compared to the sham group, during the whole study period in the frequency of migraine attacks (tDCS vs. sham: -47.8 ± 50.1% vs. -14.2 ± 16.5%, = 0.004), number of days with headache (tDCS vs. sham: -42.7 ± 65.4% vs. -11.3 ± 18.0%, = 0.015), duration of attacks (tDCS vs. sham: -29.1 ± 43.4% vs. -7.5 ± 17.6%, = 0.016), intensity of the pain during an attack (tDCS vs. sham -31.1 ± 36.9% vs. 8.3 ± 13.5%, = 0.004), and number of analgesics (tDCS vs. sham -54.3 ± 37.4% vs. -16.0 ± 19.6%, < 0.0001). Our results suggest that cathodal tDCS is an effective adjuvant technique in migraine provided that an individual correct montage of the electrodes is applied, according to thermographic investigation.

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Cannabinoids induce latent sensitization in a preclinical model of medication overuse headache.

Evaluation of cannabinoid receptor agonists in a preclinical model of medication overuse headache.

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Guideline update: Pharmacologic prevention of pediatric migraine.

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Cortical Thickness in Migraine: A Coordinate-Based Meta-Analysis.

Cortical thickness (CTh) via surface-based morphometry analysis is a popular method to characterize brain morphometry. Many studies have been performed to investigate CTh abnormalities in migraine. However, the results from these studies were not consistent and even conflicting. These divergent results hinder us to obtain a clear picture of brain morphometry regarding CTh alterations in migraine. Coordinate-based meta-analysis (CBMA) is a promising technique to quantitatively pool individual neuroimaging studies to identify consistent brain areas involved. Electronic databases (PubMed, EMBASE, Web of Science, China National Knowledge Infrastructure, WanFang, and SinoMed) and other sources (bioRxiv and reference lists of relevant articles and reviews) were systematically searched for studies that compared regional CTh differences between patients with migraine and healthy controls (HCs) up to May 15, 2020. A CBMA was performed using the Seed-based d Mapping with Permutation of Subject Images approach. In total, we identified 16 studies with 17 datasets reported that were eligible for the CBMA. The 17 datasets included 872 patients with migraine (average sample size 51.3, mean age 39.6 years, 721 females) and 949 HCs (average sample size 59.3, mean age 44.2 years, 680 females). The CBMA detected no statistically significant consistency of CTh alterations in patients with migraine relative to HCs. Sensitivity analysis and subgroup analysis verified this result to be robust. Metaregression analyses revealed that this CBMA result was not confounded by age, gender, aura, attack frequency per month, and illness duration. Our CBMA adds to the evidence of the replication crisis in neuroimaging research that is increasingly recognized. Many potential confounders, such as underpowered sample size, heterogeneous patient selection criteria, and differences in imaging collection and methodology, may contribute to the inconsistencies of CTh alterations in migraine, which merit attention before planning future research on this topic.

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