Clara Domínguez1, Ana López1, Pedro Ramos-Cabrer1, Alba Vieites-Prado1, Maria Pérez-Mato1, Carmen Villalba1, Tomás Sobrino1, Xiana Rodriguez-Osorio1, Francisco Campos1, José Castillo1, Rogelio Leira2. 1. From the Departments of Neurology (C.D., A.L., X.R.-O., R.L.) and Radiology (C.V.), Hospital Clinico Universitario, Universidade de Santiago de Compostela; Clinical Neurosciences Research Laboratory (A.V.-P., M.P.-M., T.S., F.C., J.C., R.L.), Health Research Institute of Santiago de Compostela; Magnetic Resonance Imaging (P.R.-C.), Molecular Imaging Unit, CIC biomaGUNE, Donostia-San Sebastian; and Ikerbasque (P.R.-C.), The Basque Foundation for Science, Bilbao, Spain. 2. From the Departments of Neurology (C.D., A.L., X.R.-O., R.L.) and Radiology (C.V.), Hospital Clinico Universitario, Universidade de Santiago de Compostela; Clinical Neurosciences Research Laboratory (A.V.-P., M.P.-M., T.S., F.C., J.C., R.L.), Health Research Institute of Santiago de Compostela; Magnetic Resonance Imaging (P.R.-C.), Molecular Imaging Unit, CIC biomaGUNE, Donostia-San Sebastian; and Ikerbasque (P.R.-C.), The Basque Foundation for Science, Bilbao, Spain. rogelio.leira.muino@sergas.es.
Abstract
OBJECTIVE: To study iron deposition in red nucleus (RN), globus pallidus (GP), and periaqueductal gray matter (PAG) as a potential biomarker of chronic migraine (CM) and its association with levels of biomarkers related to migraine pathophysiology. METHODS: This case-control study included 112 patients with migraine (55 CM, 57 episodic migraine [EM]) and 25 headache-free controls. We analyzed iron deposition using 3T MRI and the NIH software platform ImageJ; we analyzed serum levels of markers of inflammation, endothelial dysfunction, and blood-brain barrier (BBB) disruption by ELISA in peripheral blood during interictal periods. RESULTS: Patients with CM showed larger iron grounds volume in RN compared to patients with EM (70.2 ± 6.8 vs 25.5 ± 7.3 μL, p < 0.001) and controls (70.2 ± 6.8 vs 15.1 ± 10.8 μL, p < 0.001), as well as larger iron deposits in PAG compared to patients with EM (360.3 ± 6.5 vs 249.7 ± 6.9 μL, p < 0.001) and controls (360.3 ± 6.5 vs 168.6 ± 10.3 μL, p < 0.001). In PAG, differences were also significant between patients with EM and controls. No significant differences were obtained for GP. Receiver operating characteristic curves showed that the optimal threshold for iron volume was 15 μL in RN (80% sensitivity, 71% specificity) and 240 μL in PAG (93% sensitivity, 97% specificity). Iron grounds volume in PAG was correlated with higher plasma levels of soluble tumor necrosis factor-like WEAK (r = 0.395, p = 0.005) and cellular fibronectin (r = 0.294, p = 0.040). CONCLUSIONS: Patients with CM showed increased iron deposition in RN and PAG compared to patients with EM and controls. Iron grounds volume in PAG identified correctly patients with CM and was associated with elevated biomarkers of endothelial dysfunction and BBB disruption.
OBJECTIVE: To study iron deposition in red nucleus (RN), globus pallidus (GP), and periaqueductal gray matter (PAG) as a potential biomarker of chronic migraine (CM) and its association with levels of biomarkers related to migraine pathophysiology. METHODS: This case-control study included 112 patients with migraine (55 CM, 57 episodic migraine [EM]) and 25 headache-free controls. We analyzed iron deposition using 3T MRI and the NIH software platform ImageJ; we analyzed serum levels of markers of inflammation, endothelial dysfunction, and blood-brain barrier (BBB) disruption by ELISA in peripheral blood during interictal periods. RESULTS:Patients with CM showed larger iron grounds volume in RN compared to patients with EM (70.2 ± 6.8 vs 25.5 ± 7.3 μL, p < 0.001) and controls (70.2 ± 6.8 vs 15.1 ± 10.8 μL, p < 0.001), as well as larger iron deposits in PAG compared to patients with EM (360.3 ± 6.5 vs 249.7 ± 6.9 μL, p < 0.001) and controls (360.3 ± 6.5 vs 168.6 ± 10.3 μL, p < 0.001). In PAG, differences were also significant between patients with EM and controls. No significant differences were obtained for GP. Receiver operating characteristic curves showed that the optimal threshold for iron volume was 15 μL in RN (80% sensitivity, 71% specificity) and 240 μL in PAG (93% sensitivity, 97% specificity). Iron grounds volume in PAG was correlated with higher plasma levels of soluble tumor necrosis factor-like WEAK (r = 0.395, p = 0.005) and cellular fibronectin (r = 0.294, p = 0.040). CONCLUSIONS:Patients with CM showed increased iron deposition in RN and PAG compared to patients with EM and controls. Iron grounds volume in PAG identified correctly patients with CM and was associated with elevated biomarkers of endothelial dysfunction and BBB disruption.
Authors: M Torres-Ferrús; F Ursitti; A Alpuente; F Brunello; D Chiappino; T de Vries; S Di Marco; S Ferlisi; L Guerritore; N Gonzalez-Garcia; A Gonzalez-Martinez; D Khutorov; M Kritsilis; A Kyrou; T Makeeva; A Minguez-Olaondo; L Pilati; A Serrien; O Tsurkalenko; D Van den Abbeele; W S van Hoogstraten; C Lampl Journal: J Headache Pain Date: 2020-04-29 Impact factor: 7.277