Imaging the Brainstem Raphe in Medication-Overuse Headache: Pathophysiological Insights and Implications for Personalized Care

<b>Background/Objectives</b>: Medication-overuse headache (MOH) is a disabling condition affecting patients with chronic migraine resulting from excessive use of acute headache medication. It is characterized by both pain modulation and addiction-like mechanisms involving the brainstem r...

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Main Authors: Annika Mall, Christine Klötzer, Luise Bartsch, Johanna Ruhnau, Sebastian Strauß, Robert Fleischmann
Format: Article
Language:English
Published: MDPI AG 2025-01-01
Series:Biomedicines
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Online Access:https://www.mdpi.com/2227-9059/13/1/131
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author Annika Mall
Christine Klötzer
Luise Bartsch
Johanna Ruhnau
Sebastian Strauß
Robert Fleischmann
author_facet Annika Mall
Christine Klötzer
Luise Bartsch
Johanna Ruhnau
Sebastian Strauß
Robert Fleischmann
author_sort Annika Mall
collection DOAJ
description <b>Background/Objectives</b>: Medication-overuse headache (MOH) is a disabling condition affecting patients with chronic migraine resulting from excessive use of acute headache medication. It is characterized by both pain modulation and addiction-like mechanisms involving the brainstem raphe, a region critical to serotonergic signaling. This study investigates whether alterations in the brainstem raphe, assessed via transcranial sonography (TCS), are associated with MOH and independent of depressive symptoms, aiming to explore their utility as a biomarker. <b>Methods</b>: This prospective case-control study included 60 migraine patients (15 with MOH) and 7 healthy controls. Comprehensive clinical and psychometric assessments were performed to evaluate headache burden, medication use, and depressive symptoms. TCS was used to assess brainstem raphe echogenicity, with findings analyzed using generalized linear models adjusted for depression. <b>Results</b>: Non-visibility of the brainstem raphe was significantly associated with MOH, with an unadjusted odds ratio (OR) of 6.88 (95% CI: 1.32–36.01, <i>p</i> = 0.02). After adjusting for depressive symptoms, this association remained significant, with an adjusted OR of 1.85 (95% CI: 1.02–3.34, <i>p</i> = 0.041). TCS demonstrated good intraclass correlation, highlighting its reproducibility and ability to detect changes relevant to MOH pathophysiology. <b>Conclusions</b>: Brainstem raphe alterations are associated with MOH and may serve as a potential biomarker for its diagnosis and management. TCS offers a non-invasive, cost-effective tool for identifying MOH-specific mechanisms, which could improve clinical decision-making and support personalized care in chronic headache disorders. Further studies are needed to validate these findings and refine the clinical applications of brainstem-focused diagnostics.
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spelling doaj-art-93a632526ca54143ae76b3d3ffdfe01b2025-01-24T13:24:07ZengMDPI AGBiomedicines2227-90592025-01-0113113110.3390/biomedicines13010131Imaging the Brainstem Raphe in Medication-Overuse Headache: Pathophysiological Insights and Implications for Personalized CareAnnika Mall0Christine Klötzer1Luise Bartsch2Johanna Ruhnau3Sebastian Strauß4Robert Fleischmann5Department of Neurology, University Medicine Greifswald, 17489 Greifswald, GermanyDepartment of Neurology, University Medicine Greifswald, 17489 Greifswald, GermanyDepartment of Neurology, University Medicine Greifswald, 17489 Greifswald, GermanyDepartment of Neurology, University Medicine Greifswald, 17489 Greifswald, GermanyDepartment of Neurology, University Medicine Greifswald, 17489 Greifswald, GermanyDepartment of Neurology, University Medicine Greifswald, 17489 Greifswald, Germany<b>Background/Objectives</b>: Medication-overuse headache (MOH) is a disabling condition affecting patients with chronic migraine resulting from excessive use of acute headache medication. It is characterized by both pain modulation and addiction-like mechanisms involving the brainstem raphe, a region critical to serotonergic signaling. This study investigates whether alterations in the brainstem raphe, assessed via transcranial sonography (TCS), are associated with MOH and independent of depressive symptoms, aiming to explore their utility as a biomarker. <b>Methods</b>: This prospective case-control study included 60 migraine patients (15 with MOH) and 7 healthy controls. Comprehensive clinical and psychometric assessments were performed to evaluate headache burden, medication use, and depressive symptoms. TCS was used to assess brainstem raphe echogenicity, with findings analyzed using generalized linear models adjusted for depression. <b>Results</b>: Non-visibility of the brainstem raphe was significantly associated with MOH, with an unadjusted odds ratio (OR) of 6.88 (95% CI: 1.32–36.01, <i>p</i> = 0.02). After adjusting for depressive symptoms, this association remained significant, with an adjusted OR of 1.85 (95% CI: 1.02–3.34, <i>p</i> = 0.041). TCS demonstrated good intraclass correlation, highlighting its reproducibility and ability to detect changes relevant to MOH pathophysiology. <b>Conclusions</b>: Brainstem raphe alterations are associated with MOH and may serve as a potential biomarker for its diagnosis and management. TCS offers a non-invasive, cost-effective tool for identifying MOH-specific mechanisms, which could improve clinical decision-making and support personalized care in chronic headache disorders. Further studies are needed to validate these findings and refine the clinical applications of brainstem-focused diagnostics.https://www.mdpi.com/2227-9059/13/1/131migrainemedication-overuse headachechronic migraineaddictionbrainstem raphetranscranial ultrasound
spellingShingle Annika Mall
Christine Klötzer
Luise Bartsch
Johanna Ruhnau
Sebastian Strauß
Robert Fleischmann
Imaging the Brainstem Raphe in Medication-Overuse Headache: Pathophysiological Insights and Implications for Personalized Care
Biomedicines
migraine
medication-overuse headache
chronic migraine
addiction
brainstem raphe
transcranial ultrasound
title Imaging the Brainstem Raphe in Medication-Overuse Headache: Pathophysiological Insights and Implications for Personalized Care
title_full Imaging the Brainstem Raphe in Medication-Overuse Headache: Pathophysiological Insights and Implications for Personalized Care
title_fullStr Imaging the Brainstem Raphe in Medication-Overuse Headache: Pathophysiological Insights and Implications for Personalized Care
title_full_unstemmed Imaging the Brainstem Raphe in Medication-Overuse Headache: Pathophysiological Insights and Implications for Personalized Care
title_short Imaging the Brainstem Raphe in Medication-Overuse Headache: Pathophysiological Insights and Implications for Personalized Care
title_sort imaging the brainstem raphe in medication overuse headache pathophysiological insights and implications for personalized care
topic migraine
medication-overuse headache
chronic migraine
addiction
brainstem raphe
transcranial ultrasound
url https://www.mdpi.com/2227-9059/13/1/131
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