The journal of headache and pain
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The migraine premonitory phase is characterized in part by increased thirst, urination and yawning. Imaging studies show that the hypothalamus is activated in the premonitory phase. Stress is a well know migraine initiation factor which was demonstrated to engage dynorphin/kappa opioid receptors (KOR) signaling in several brain regions, including the hypothalamus. This study proposes the exploration of the possible link between hypothalamic KOR and migraine premonitory symptoms in rodent models. ⋯ Our studies in rodents identified the KOR in a hypothalamic region as a mechanism that promotes behaviors consistent with clinically-observed premonitory symptoms of migraine, including increased thirst and urination but not yawning. Importantly, these behaviors occurred in the absence of pain responses, consistent with the emergence of the premonitory phase before the headache phase. Early intervention for preventive treatment even before the headache phase may be achievable by targeting the hypothalamic KOR.
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Migraine affects a significant fraction of the world population, yet its etiology is not completely understood. In vitro results highlighted thalamocortical and intra-cortical glutamatergic synaptic gain-of-function associated with a monogenic form of migraine (familial-hemiplegic-migraine-type-1: FHM1). However, how these alterations reverberate on cortical activity remains unclear. As altered responsivity to visual stimuli and abnormal processing of visual sensory information are common hallmarks of migraine, herein we investigated the effects of FHM1-driven synaptic alterations in the visual cortex of awake mice. ⋯ Contrast-driven ɣ modulation in V1 activity occurs at a much higher frequency in FHM1. This is likely to play a role in the altered processing of visual information. Computational studies suggest that this shift is specifically due to enhanced cortical excitatory transmission. Our network model can help to shed light on the relationship between cellular and network levels of migraine neural alterations.
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In disease areas with 'soft' outcomes (i.e., the subjective aspects of a medical condition or its management) such as migraine or depression, extraction and validation of real-world evidence (RWE) from electronic health records (EHRs) and other routinely collected data can be challenging due to how the data are collected and recorded. In this study, we aimed to define and validate a scalable framework model to measure outcomes of migraine treatment and prevention by use of artificial intelligence (AI) algorithms within EHR data. ⋯ Our findings indicate the feasibility of technology-enabled models for validated determination of soft outcomes such as migraine progression using the data elements typically captured in the real-world clinical setting, providing a scalable approach to credible EHR-based clinical studies.
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Clinical Trial
Does MIDAS reduction at 3 months predict the outcome of erenumab treatment? A real-world, open-label trial.
In Italy, monoclonal antibodies targeting the CGRP pathway are subsidized for the preventive treatment of high frequency and chronic migraine (CM) in patients with a MIgraine Disability ASsessment (MIDAS) score ≥ 11. Eligibility to treatment continuation requires a ≥ 50% MIDAS score reduction at three months (T3). In this study, we evaluate whether a ≥ 50% MIDAS score reduction at T3 is a reliable predictor of response to one-year erenumab treatment. ⋯ MIDASRes only partly reflects the 12-month outcome of erenumab treatment in CM, as it excludes more than one third of responders. A criterion based on the alternative consideration of ≥ 50% reduction in MIDAS score or MMDs in the first three months of treatment represents a more precise and inclusive option.
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Chronic migraine is a common neurovascular brain disorder with substantial economic costs. We performed a systematic review to identify economic evaluations of pharmacological treatments for adults with chronic migraine. ⋯ Evidence to support the cost-effectiveness of pharmacological treatments of chronic migraine in the adult population using Botox and Erenumab were identified. Our findings suggest that both Botox and Erenumab, are cost-effective compared to placebo; although Erenumab had more incremental economic benefits compared to Botox, the ICERs were above the most common willingness-to-pay thresholds. Hence, Erenumab might be an acceptable treatment for chronic migraine for patients whom other treatments such as Botox do not work. Further research is needed to help characterise the data to adequately structure and parameterise an economic model to support decision-making for chronic migraine therapies.