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    Neurobiology of migraine progression
    (2022-08-01) ;
    Rapoport, Alan
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    Chronic migraine is one of the most devastating headache disorders. The estimated prevalence is 1.4–2.2% in the population. The factors which may predispose to the process of migraine progression include high frequency of migraine attacks, medication overuse, comorbid pain syndromes, and obesity. Several studies showed that chronic migraine results in the substantial anatomical and physiological changes in the brain. Despite no clear explanation regarding the pathophysiologic process leading to the progression, certain features such as increased sensory sensitivity, cutaneous allodynia, impaired habituation, identify the neuronal hyperexcitability as the plausible mechanism. In this review, we describe two main mechanisms which can lead to this hyperexcitability. The first is persistent sensitization caused by repetitive and prolonged trigeminal nociceptive activation. This process results in changes in several brain networks related to both pain and non-pain behaviours. The second mechanism is the decrease in endogenous brainstem inhibitory control, hence increasing the excitability of neurons in the trigeminal noceptive system and cerebral cortex. The combination of increased pain matrix connectivity, including hypothalamic hyperactivity and a weak serotonergic system, may contribute to migraine chronification.
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    The Evolution of Medication Overuse Headache: History, Pathophysiology and Clinical Update
    (2021-05-01)
    Sun-Edelstein, Christina
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    Rapoport, Alan M.
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    Medication overuse headache (MOH), the development or worsening of chronic headache resulting from frequent and excessive intake of medications used for acute treatment of headache, is a common secondary headache disorder and is associated with significant personal and societal burdens. The plausible physiologic mechanism is that chronic exposure to acute care migraine treatment leads to suppression of endogenous antinociceptive systems, consequently facilitating the trigeminal nociceptive process via up-regulation of the calcitonin gene-related peptide (CGRP) system. Recognizing and preventing its development is an integral aspect of migraine management, as medication overuse is a modifiable risk factor in the progression from episodic to chronic migraine. Over the years, MOH has been difficult to treat and has generated much controversy. Ongoing debates exist over the diagnostic criteria and treatment strategies, particularly regarding the roles of formal detoxification and preventive treatment. The arrival of the anti-CGRP monoclonal antibodies has also challenged our views of MOH and its treatment. This review outlines the evolution of MOH diagnostic criteria, presents the current understanding of MOH pathogenesis and discusses the debates over its development and treatment. Data on the efficacy of anti-CGRP monoclonal antibodies in the setting of medication overuse is also presented. These results indicate that patients with medication overuse, who are treated with these new medications, may not need to be detoxified in order to treat MOH. In light of these developments, it is likely that in the future MOH will be more readily diagnosed and treatment will result in better outcomes.
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    The current state of artificial intelligence-augmented digitized neurocognitive screening test
    (2023-01-01)
    Sirilertmekasakul, Chananchida
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    Gongvatana, Assawin
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    The cognitive screening test is a brief cognitive examination that could be easily performed in a clinical setting. However, one of the main drawbacks of this test was that only a paper-based version was available, which restricts the test to be manually administered and graded by medical personnel at the health centers. The main solution to these problems was to develop a potential remote assessment for screening individuals with cognitive impairment. Currently, multiple studies have been adopting artificial intelligence (AI) technology into these tests, evolving the conventional paper-based neurocognitive test into a digitized AI-assisted neurocognitive test. These studies provided credible evidence of the potential of AI-augmented cognitive screening tests to be better and provided the framework for future studies to further improve the implementation of AI technology in the cognitive screening test. The objective of this review article is to discuss different types of AI used in digitized cognitive screening tests and their advantages and disadvantages.
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    Understanding the genetics and neurology: an overview of adult neurogenetics
    (2025-08-01)
    Hemachudha, Pasin
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    Anukoolwittaya, Prakit
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    Pongpitakmetha, Thanakit
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    Joyjinda, Yutthana
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    Ruchisrisarod, Chanida
    Neurogenetics investigates the genetic basis of neurological disorders. It encompasses conditions ranging from neurodegenerative diseases with predominantly polygenic risk genes, such as Alzheimer's and Parkinson's, to monogenic diseases and repeated expansion disorders within movement and neuromuscular disorders, such as Friedreich ataxia and muscular dystrophies. Significant advances in recent years that have revolutionized our understanding of disease mechanisms and paved the way for personalized medicine approaches are due to the field of neurogenetics, with its intricate relationship both with clinical and genetic research. Therefore, all neurologists, even in resource-limited settings, are aware of the critical genetic basis; standard molecular diagnostic techniques such as next-generation sequencing, whole exome, and whole genome sequencing; and possible therapeutic modalities of their field. This review will also touch on elements of the neurogenetic clinic in tertiary care, ethical considerations, and insight into ongoing research that would help improve patient care and enhance clinical outcomes.
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    Medication “underuse” headache
    (2024-04-01) ;
    Rapoport, Alan
    ;
    Background: Many risk factors have been associated with migraine progression, including insufficient and ineffective utilization of migraine medications; however, they have been inadequately explored. This has resulted in suboptimal usage of medications without effective altering of prescribing recommendations for patients, posing a risk for migraine chronification. Methods: Our aim is to conduct a comprehensive review of the available evidence regarding the underuse of migraine medications, both acute and preventive. The term “underuse” includes, but is not limited to: (1) ineffective use of appropriate and inappropriate medication; (2) underutilization; (3) inappropriate timing of usage; and (4) patient dissatisfaction with medication. Results: The underuse of both acute and preventive medications has been shown to contribute to the progression of migraine. In terms of acute medication, chronification occurs as a result of insufficient drug use, including failure of the prescriber to select the appropriate type based on pain intensity and disability, patients taking medication too late (more than 60 minutes after the onset or after central sensitization has occurred as evidenced by allodynia), and discontinuation because of lack of effect or intolerable side effects. The underlying cause of inadequate effectiveness of acute medication lies in its inability to halt the propagation of peripheral activation to central sensitization in a timely manner. For oral and injectable preventive migraine medications, insufficient efficacy and intolerable side effects have led to poor adherence and discontinuation with subsequent progression of migraine. The underlying pathophysiology here is rooted in the repetitive stimulation of afferent sensory pain fibers, followed by ascending brainstem pain pathways plus dysfunction of the endogenous descending brainstem pain inhibitory pathway. Although anti-calcitonin gene-related peptide (CGRP) medications partially address pain caused by the above factors, including decreased efficacy and tolerability from conventional therapy, some patients do not respond well to this treatment. Research suggests that initiating preventive anti-CGRP treatment at an early stage (during low frequency episodic migraine attacks) is more beneficial than commencing it during high frequency episodic attacks or when chronic migraine has begun. Conclusions: The term “medication underuse” is underrecognized, but it holds significant importance. Optimal usage of acute care and preventive migraine medications could potentially prevent migraine chronification and improve the treatment of migraine attacks.
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    Transcultural headache medicine: A framework for integrating cultural contexts into headache science and care – a call to action from the International Headache Society
    (2026-04-01)
    Peres, Mario F.P.
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    Lucchetti, Giancarlo
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    Vallada, Homero
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    Riso, Ivy L.
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    Westenhofen, Georgia K.
    Headache disorders are among the most disabling neurological conditions, affecting over 1.5 billion people globally. Despite advances in pharmacological therapies, major inequities persist due to underdiagnosis, undertreatment and limited access to effective care, particularly in low- and middle-income countries. Social determinants of health, including cultural meanings, language and health beliefs, are increasingly recognized as key drivers of disparities in burden, diagnosis and treatment outcomes. Traditional medicine, used by more than 80% of the global population, remains first-line care in many regions and continues to influence therapeutic choices in high-income settings. Major systems such as Ayurveda, Traditional Chinese Medicine, Unani and Tibetan medicine, as well as diverse indigenous traditions, emphasize holistic approaches that integrate mental and physical symptoms into diagnosis and management. Additionally, religious and spiritual practices are commonly used to relieve suffering and pain. These culturally grounded explanatory models not only strongly shape health-seeking behavior, treatment adherence and patient narratives, but also may delay biomedical care when misconceptions or unsafe practices predominate. This paper introduces Transcultural Headache Medicine as an emerging framework that integrates cultural contexts, linguistic diversity and traditional practices into headache research, clinical care and policy. We review global traditions and therapeutic modalities including herbal, physical, mental and spiritual approaches, and propose a research agenda combining ethnography, culturally adapted diagnostic tools, experimental studies and clinical trials to evaluate benefits, risks, and contextual effects. We conclude with a call to action from the International Headache Society, aiming to map and evaluate culturally embedded practices, strengthen rigorous evidence and build a global learning network that supports culturally safe integration of effective, affordable and safe headache care.