To investigate the whole-brain resting-state functional connectivity in patients with chronic migraine (CM) using a data-driven method. We prospectively recruited patients with either episodic migraine (EM) or CM aged 18–60 years who visited the headache clinic of the Samsung Medical Center from July 2016 to December 2017. All patients underwent 3 T MRI using an identical scanner. Patients were considered interictal if they did not have a migraine headache at the day and ± 1 days of functional MRI acquisition. Using the group-independent component analysis (ICA), connectivity analysis with a weighted and undirected network model was performed. The between-group differences in degree centrality (DC) values were assessed using 5000 permutation tests corrected with false discovery rate (FDR). A total of 62 patients (44 EM and 18 CM) were enrolled in this study. Among the seven functionally interpretable spatially independent components (ICs) identified, only one IC, interpreted as the pain matrix, showed a significant between-group difference in DC (CM > EM, p = 0.046). This association remained significant after adjustment for age, sex, migraine with aura (MWA), allodynia, depression, and anxiety (p = 0.038). The pain matrix was functionally correlated with the hypothalamus (p = 0.040, EM > CM) and dorsal raphe nucleus (p = 0.039, CM > EM) with different levels of strength in EM and CM. CM patients have a stronger connectivity in the pain matrix than do EM patients. Functional alteration of the pain network might play a role in migraine chronification.

Calcitonin gene-related peptide (CGRP) has been reported as elevated in chronic migraine. We aimed to validate the role of interictal serum CGRP concentration in peripheral blood samples as a biomarker of chronic migraine. We prospectively recruited patients with episodic and chronic migraine and normal controls (NCs) in the Samsung Medical Center between August 2015 and May 2016. Blood samples were collected interictally from antecubital veins per prespecified protocol. Serum CGRP measurement was performed in the central laboratory by a single experienced technician blinded to clinical information. Migraine subtype, headache days in the previous month, and the presence and characteristics of headache at ±2 days of measurement were evaluated at every visit. A total of 156 migraineurs (106 episodic and 50 chronic) and 27 NCs were recruited in this study. Compared to NCs (75.7 ± 20.07 pg/mL) and patients with episodic migraine (67.0 ± 20.70 pg/mL), patients with chronic migraine did not show an interictal elevation of serum CGRP levels (64.9 ± 15.32 pg/mL). Serum CGRP concentration was not associated with headache status (ictal vs. interictal), migraine subtype (migraine with vs. without aura), use of preventive or acute medications, and comorbid medication overuse. Higher serum CGRP concentration did not predict treatment response in patients with chronic migraine. Serum CGRP concentration may not be a feasible biomarker for chronic migraine. Further validation is necessary before CGRP can be used in the clinical practice.

To investigate suicidality related to cluster headache and factors associated with increased suicidality in cluster headache patients. In this multicenter study, 193 cluster headache patients were recruited between September 2016 and August 2018. Patients were asked about their suicidality during and between attacks, specifically about passive suicidal ideation, active suicidal ideation, suicide plan, and suicide attempt. Univariable and multivariable logistic regression analyses were performed to evaluate the factors associated with high ictal suicidality (sum of positive response ≥ 2). Patients were followed up when they were in the between-bouts period. A total of 175 cluster headache patients in the in-bout period were included in this study. Passive suicidal ideation, active suicidal ideation, suicidal planning, and suicidal attempt were reported by 111 (64.2%), 62 (35.8%), 10 (5.8%), and four (2.3%) patients during attacks; seven (4.0%), six (3.5%), five (2.9%) and two (1.2%) patients interictally; and none (0%), one (1.9%), one (1.9%), and none (0%) among patients in the between-bouts period. Factors associated with high ictal suicidality were longer disease duration, the Headache Impact Test score, and the Patient Health Question-9 score (multivariable OR = 1.90 per 10-year increase in disease duration, 95% CI = 1.18–3.05, p = 0.008; multivariable OR = 3.19 per 10-point increase in HIT-6, 95% CI = 1.73–5.87, p < 0.001; multivariable OR = 2.11 per 10-point increase in PHQ-9, 95% CI = 1.13–3.95, p = 0.020, respectively). Cluster headache attack carries a high suicidality compared to the interictal or between-bouts state. An intensive treatment to reduce cluster headache burden may be helpful to alleviate suicide risk in cluster headache patients.

Cho S, et al. J Clin Neurol. 2020 Apr;16(2):237-244. https://doi.org/10.3988/jcn.2020.16.2.237

Background: Spontaneous intracranial hypotension is diagnosed by an abnormal finding in brain MRI, spinal imaging, or lumbar puncture. However, the sensitivity of each test is low. We investigated whether patients with suspected spontaneous intracranial hypotension and negative imaging findings would respond to epidural blood patch. Methods: We prospectively recruited patients with new-onset orthostatic headache admitted at the Samsung Medical Center from January 2017 to July 2021. In patients without abnormal imaging findings and no history of prior epidural blood patch, treatment outcome—defined as both 50% response in maximal headache intensity and improvement of orthostatic component—was collected at discharge and three months after epidural blood patch. Results: We included 21 treatment-naïve patients with orthostatic headache and negative brain and spinal imaging results who received epidural blood patch. After epidural blood patch (mean 1.3 times, range 1–3), 14 (66.7%) and 19 (90.5%) patients achieved both 50% response and improvement of orthostatic component at discharge and three months post-treatment, respectively. Additionally, complete remission was reported in 11 (52.4%) patients at three-month follow-up, while most of the remaining patients had only mild headaches. Among nine (42.9%) patients who underwent lumbar puncture, none had an abnormally low opening pressure (median 13.8 cm H₂O, range 9.2–21.5). Conclusion: Given the high responder rates of epidural blood patch in our study, empirical epidural blood patch should be considered to treat new-onset orthostatic headache, even when brain and spinal imaging are negative. The necessity of lumbar puncture is questionable considering the high response rate of epidural blood patch and low rate of “low pressure.”