MRI-ASL-based CBF changesduring the interictal period after anti-CGRP therapy in migraine patients

doi:10.21203/rs.3.rs-5069054/v1

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MRI-ASL-based CBF changesduring the interictal period after anti-CGRP therapy in migraine patients

https://doi.org/10.21203/rs.3.rs-5069054/v1

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Objective: Migraine and insomnia often accompany migraine are not steady-state conditions because cerebral blood flow (CBF) autoregulation and the glymphatic system are impaired. Anti-endogenous anti-calcitonin gene-related peptide (CGRP) therapy may thus reduce the interictal CBF.

Methods: Interictal magnetic resonance arterial spin labeling (ASL) was performed on 73 migraineurs before and after anti-CGRP therapy, including antibody switching, to investigate changes in CBF and predictors of treatment response.

Results: Multivariate analysis revealed that the significant positive neuroradiological predictors were no migraine with cortical hyperperfusion (CHP) findings despite insomnia and no insomnia with white matter hyperintensities. Patients in this study were divided into four clinical groups according to CBF changes after anti-CGRP therapy: Group A, CHP findings before treatment and decreased CBF after treatment (27 patients); Group B, no CHP before treatment and decreased CBF after treatment (19 patients); Group C, no CHP before treatment and increased CBF after treatment (18 patients); and Group D, no change in CBF before or after treatment. Changes in CBF after therapy were appropriate in Groups A and C; in particular, Group C had the highest percentage of ³ 50% of the responders, reaching 94%. Approximately 90% of patients in Group B showed an inappropriate reduction in CBF below normal after treatment. All but 1 patient in Group D did not respond to treatment.

Conclusion: Interictal CBF measurements by ASL before and after anti-CGRP therapy are clinically useful biomarkers for predicting and evaluating treatment efficacy.

Neurology

arterial spin labeling MRI

migraineur

cerebral blood flow

cortical hyperperfusion

anti-calcitonin gene-related peptide therapy

insomnia

Calcitonin gene-related peptide (CGRP) is a potent endogenous vasodilator and an important neurotransmitter within the migraine headache-generating trigeminovascular system [1]. CGRP induces endothelium-independent vasodilation via direct actions on vascular smooth muscle cells in the cerebral and coronary vascular beds, and cerebral blood flow (CBF) autoregulation is partially mediated by CGRP [2].

CGRP is not considered to be involved in the regulation of steady-state vascular tone [3]. Anti-CGRP monoclonal antibody (anti-CGRP) therapy is therefore widely used for preventing migraine. However, migraine and insomnia often occur with a common pathophysiology of glymphatic system (GS) impairment and can aggravate each other and lead to impaired autoregulation and white matter hyperintensity (WMH) [4-6]. Migraine patients are thus not in a steady state. Given these findings, we speculated that CGRP suppression by anti-CGRP therapy in migraine patients would result in changes in CBF.

Compared with those in normal individuals, concentrations of CGRP in plasma, tears, and saliva are reportedly higher not only during migraine attacks but also during the interictal period in migraine patients [7-10]. The trigeminovascular system thus shows ongoing activation both during and between migraine attacks. In this prospective study, we measured interictal CBF using magnetic resonance imaging (MRI) and arterial spin labeling (ASL) in migraine patients before and after anti-CGRP therapy to identify predictors of therapeutic efficacy and whether CBF changes after therapy.

Subjects

This was a prospective, longitudinal, single-center study performed at our institution. All migraine patients included in this study met the diagnostic criteria of the International Headache Classification, third edition, of the International Headache Society [11]. With that in mind, all the migraine patients included had no abnormalities according to neurological examination, MRI, or magnetic resonance angiography.

Among 77 patients who underwent anti-CGRP therapy during the study period, 3 patients who were unable to undergo MRI due to claustrophobia and 1 patient for whom satisfactory images could not be obtained due to image artifacts caused by a metal orthodontic appliance were excluded. Ultimately, this prospective cross-sectional study enrolled 73 outpatients who received anti-CGRP therapy from October 2022 to July 2023 at our hospital.

Treatment protocols

We prospectively analyzed all outpatients treated with one of two anti-CGRP monoclonal antibodies (mAbs), either of which were generated from yolumab or galcanezumab, at our institution and who underwent ASL before and after treatment. The indications for anti-CGRP therapy were as follows in accordance with the Japanese guidelines for promoting appropriate use: i) mean monthly headache days (MHD) ³ 4 days for ³ 3 months before starting treatment; ii) life impaired even with appropriate acute treatment daily; and iii) treatment with migraine preventive drugs (valproate sodium, etc.) approved in Japan, which cannot be used due to low efficacy and tolerability.

All patients started anti-CGRP therapy after providing written informed consent and received another anti-CGRP mAb if the first proven ineffective. If the first treatment was an anti-CGRP ligand mAb (galcanezumab), the second was an anti-CGRP receptor mAb (erenumab), and vice versa. Switching between erenumab and galcanezumab was not performed if the initial treatment was effective. In general, the effectiveness of anti-CGRP therapy was determined 2–3 months after administration in accordance with the consensus statement from the American Headache Society [12]. Efficacy was considered only if one of the following was achieved: i) the average MHD decreased by ³ 50% compared to the pretreatment baseline or ii) the headache impact test (HIT-6) [13] score decreased by ³ 5. When the plants were switched, a 28-day washout period was provided between the first and second treatments.

In this study, 70 mg/month of erenumab or 240 mg of galcanezumab was subcutaneously injected initially, followed by 120 mg/month.

MRI perfusion protocols

CBF studies with ASL were performed for all migraine patients during the interictal period ³ 48 hours after both the last attack and migraine treatment, such as for triptans.

We performed all MRI studies at our hospital on a 1.5-T MR scanner (Signa Explorer; GE Healthcare, Milwaukee, WI) with an Express head–neck array coil.

A routine MRI scan takes 16–18 min to complete. Of the total MRI examination time, ASL can quantitatively measure CBF in a short time frame of approximately 2 min 30 s.

WMH was defined as hyperintensity on fluid-attenuated inversion recovery without hypointensity on T1-weighted imaging.

Background-suppressed three-dimensional pulse-continuous ASL (also known as pseudocontinuous ASL) images were acquired using the parameters used in our previous paper [14]. Because this study did not include patients with severe cerebrovascular stenosis, a postlabeling delay of 1525 ms was used for the CBF analysis.

For the quantitative region of interest (ROI) analysis of the ASL map, we used fully automated ROI-based analysis software (3DSRT NEURO; FUJIFILM Toyama Chemical Co., Tokyo, Japan) for the positioning or selection of an ROI, which was objective and provided excellent reproducibility [15, 16]. Quantitative CBF images obtained from the study subjects were anatomically registered to the standard brain atlas. The 3DSRT software has predefined ROIs on the standard brain atlas and provides regional CBF (rCBF) values for each of the right and left sides of the following nine regions: the callosomarginal, precentral, central, parietal, angular, temporal, posterior cerebral, pericallosal, and thalamic regions (Online Resource 1; Supplementary Figure 1). Referring to a paper by Inoue et al. [17], we determined the following: rCBF in the territory of the anterior cerebral artery (ACA) through the use of callosomarginal and pericallosal ROIs; rCBF in the anterior part of the territory of the middle cerebral artery (AM) through the use of precentral and central ROIs; rCBF in the posterior part of the territory of the middle cerebral artery (PM) through the use of parietal, angular, and temporal ROIs; and rCBF in the territory of the posterior cerebral artery (PCA) through the use of a posterior cerebral ROI (Online Resource 1; Supplementary Figure 1). These ROI settings for cortical regions were performed as described in our previous report [14].

Like in our previous report [14], as with the diagnostic criteria for hyperperfusion immediately after an epileptic seizure or postoperative moyamoya disease, an ROI was defined as exhibiting hyperperfusion if the CBF in the ROI was at least two standard deviations greater than the mean reference value for CBF in control subjects [18, 19]. Based on the results of a previous paper, cortical hyperperfusion (CHP) in this study was defined as hyperperfusion of ³ 60 ml/100 g/min in two or more ROIs in each cortical area (ACA, AM, PM, and PCA) [14].

We defined an increase rate of -5% or more as a decrease and an increase rate of +5% or more as an increase when evaluating the change in CBF before and after anti-CGRP therapy.

Variables, Data Extraction, and Endpoints

MHDs were extracted from patient-written headache diaries. We also extracted the following patient characteristics: sex; age; age range; episodic migraine (EM); chronic migraine (CM); aura; HIT-6 [13]; morning migraine; Athens Insomnia Scale (AIS) [20]; Beck Depression Inventory, second edition (BDI-II) [21]; menstrual migraine; weather-related migraine; medication overuse headache (MOH); and combination preventive treatment of ³ 3 types. “Morning migraine” was defined as waking up in the morning due to migraine pain. Insomnia was defined as an AIS score ³ 4, and depression was defined as a BDI-II score ³ 11. We evaluated the degree of interference with daily life during the interictal period before and after anti-CGRP therapy using the Migraine Interictal Burden Scale (MIBS-4) [22].

Institutional Review Board Approval

All study protocols were approved by the Clinical Research Review Board (approval no. 22R-078) and the Conflict of Interest Management Committee (approval no. 22-168) at our university. The study protocol was conducted in accordance with the Declaration of Helsinki, and all migraine patients included in the study provided written informed consent before participating in the study. Our report complies with the "Strengthening the Reporting of Observational Studies in Epidemiology" (STROBE) statement for cohort studies.

Endpoints and analysis

The primary endpoint was the change in CBF during the interictal period on ASL before and after anti-CGRP therapy. The secondary endpoint was CBF measured by ASL as a pretreatment predictor of the therapeutic effect of anti-CGRP therapy.

Statistical analysis

All the statistical analyses were performed using commercially available software (IBM SPSS Statistics for Windows, version 27.0; IBM Corp., Armonk, NY).

The distributions of each variable were checked for normality using the Shapiro–Wilk test. The significance of clinical factors potentially associated with the effectiveness of anti-CGRP therapy was determined using Fisher's exact test. Continuous variables were tested using an independent sample Student's t test. The homogeneity of variance was analyzed using the Levene test. Values of p<0.05 were considered to indicate statistical significance. All the data are presented as the mean ± standard deviation, unless otherwise specified.

Overall Results of Switching Anti-CGRP Therapy

The treatment flow of anti-CGRP therapy, including the switch of drugs, is shown in Fig. 1. Treatment outcomes resulting from anti-CGRP therapy with or without switching of CGRP antibodies and treatment outcomes resulting from treatment with erenumab and galcanezumab are shown in Supplementary Table 1 of Online Resource 1. Among the 73 patients treated with anti-CGRP therapy, 46 were treated with two different anti-CGRP mAbs. Overall treatment results for anti-CGRP therapy with and without switching of CGRP antibodies (≥ 50%, ≥ 75%, and 100% reductions in MHD) were obtained for 54 (74%), 47 (64%), and 23 patients (32%), respectively (Online Resource 1; Supplementary Table 1).

Predictors of Response to Anti-CGRP Therapy

In this study, similar to a previous report [14], we calculated the asymmetry index (AI) in migraine patients and confirmed a lack of significant laterality in the rCBF before and after anti-CGRP therapy with asymmetric perfusion and an absolute AI > 10 [23, 24]. We then averaged the left and right rCBFs based on the ROIs of the migraine patients, calculated the mean and standard deviation for each clinical group, and diagnosed CHP patients.

The clinical factor data before anti-CGRP therapy are presented in Supplementary Table 2 of Online Resource 1. Among the 73 patients treated with anti-CGRP therapy, 66 were women (90%), 54 (74%) had CM, and 19 (26%) had EM. Thirty patients (41%) had aura, and 46 patients (63%) had MOH. Fifty-nine patients (81%) had insomnia with an AIS score ≥ 4, and 43 patients (59%) had depression with a BDI-II score ≥ 11. Thirty-three patients (45%) had CHP findings on ASL, 24 of whom had CHP despite insomnia. Among the 28 patients (38%) with WMH findings on MRI, 25 patients had insomnia with WMH. All patients with WMHs had a Fazekas scale [25] grade 1, except for one 75-year-old patient.

Clinical features associated with response (≥ 50% reductions in MHD) in migraine patients are shown in Supplementary Table 2 of Online Resource 1.

Multivariate logistic regression analysis revealed that significant positive clinical and neuroradiological factors associated with a ≥ 50% response in migraine patients were BDI-II < 11 (p = 0.007), no failure of preventive drugs (≥ 3 types) (p = 0.008), no migraine with CHP findings despite insomnia (p = 0.006) and no insomnia with WMH (p = 0.010) (Table 1).

Table 1

Multivariate analysis of the associations between clinical factors before anti-CGRP therapy and response rate after therapy (≥ 50% reduction in monthly headache days) in migraine patients
Clinical factors	Odds ratio	95%CI	p value
Clinical factors BDI-II < 11 No failure of preventive drugs (≥ 3 types) Neuroradiological factors No migraine with CHP findings despite insomnia No insomnia with WMH	8.500 8.846 9.502 6.187	1.788–40.420 1.771–44.187 1.897–47.600 1.533–24.971	0.007 0.008 0.006 0.010
CI, confidence interval; BDI-II, Beck Depression Inventory, second edition; CHP, cortical hyperperfusion on MRI-arterial spin labeling; WMH, white matter hyperintensity.

Changes in CBF after Anti-CGRP Therapy

The 73 migraine patients in this study were classified into four clinical groups according to changes in CBF after anti-CGRP therapy. Group A (27 patients) exhibited CHP before anti-CGRP therapy and decreased CBF after anti-CGRP therapy. Group B (19 patients) had no CHP before anti-CGRP therapy but had a decreased CBF after anti-CGRP therapy. Group C (18 patients) had no CHP before anti-CGRP therapy but had increased CBF after anti-CGRP therapy. Finally, Group D (9 patients) showed no change in CBF before or after anti-CGRP therapy (6 patients displayed CHP before anti-CGRP therapy). Typical imaging findings for each group are shown in Fig. 2A-D.

Differences in Clinical Features between Groups

Clinical features associated with clinical groups according to CBF changes are shown in Supplementary Table 3 of Online Resource 1.

Clinical factors before treatment

The frequencies of failure of preventive drugs (≥ of 3 types) (14 of 19 patients, 74%), WMH (16 of 19 patients, 84%) and insomnia with WMH (15 of 19 patients, 79%) were significantly greater in Group B than in the other three groups (p > 0.001). The frequency of AIS ≥ 4 before therapy was significantly lower in Group A than in Groups B, C, and D (p < 0.001). The frequency of BDI-II scores > 11 before therapy was significantly greater in Group D than in Groups A, B, and C (p = 0.028). No significant differences in the frequency of MIBS-4 > 1 or mean MIBS-4 score before anti-CGRP therapy were observed between the groups.

The frequencies of migraine patients with CHP findings despite insomnia were significantly greater in Groups A and D than in Groups B and C (p > 0.001).

Clinical factors after treatment

Responder rates, as the frequencies of ≥ 50% and ≥ 75% responses, were significantly greater in Groups A–C than in Group D. Similarly, the frequency of 100% response was significantly lower in Groups A and D than in Groups B and C (p = 0.046). ≥ of 50% (94%), ≥ of 75% (89%), and 100% (50%) of the responses were all highest in Group C, but the differences were not significant.

In addition, the reduction in the HIT-6 score was significantly greater in Groups A (p = 0.027), B (p = 0.023), and C (p = 0.002) than in Group D.

The frequency of AIS improvement after anti-CGRP therapy was significantly lower in Groups B and D than in Groups A and C (p < 0.001). The frequency of BDI-II ≥ 11 after anti-CGRP therapy was significantly greater in Group D than in Groups A–C (p = 0.003). The frequency of improvement in the MIBS-4 score after anti-CGRP therapy was significantly greater in Groups A and C (p = 0.001).

Changes in CBF before and after anti-CGRP therapy in each group

Since our CBF data were normally distributed, we used one-way analysis of variance (ANOVA) for multiple comparisons to test for significant differences in CBF data between the four clinical groups. The homogeneity of variance was analyzed using the Levene test. Equal variance in CBF data from each of the four clinical groups was confirmed, so the significance of ANOVA was determined using Tukey's honestly significant difference test.

Changes in CBF in each group according to ROI after anti-CGRP therapy are shown in Fig. 3. Compared with those of the other groups, the pretreatment CBF of Group A was significantly greater in all ROIs (ACA, AM, PM, PCA and thalamus) (Online Resource 1; Supplementary Table 4). Compared with those in the other groups, post-CGRP therapy CBF was significantly lower in Group B in all ROIs (ACA, AM, PM, PCA, and thalamus) and below normal values in all regions (Online Resource 1; Supplementary Table 4). Only Group C showed a positive increase after treatment, and the increase rate was significantly greater for all ROIs (Online Resource 1; Supplementary Table 4). Conversely, after anti-CGRP therapy, the CBF in Group A decreased, and the CBF in Group C increased; thus, the CBF in both groups became approximately equivalent across all ROIs (Online Resource 1; Supplementary Table 4).

Predictors of Anti-CGRP therapeutic efficacy

In this study, multivariate analysis revealed that the significant negative clinical predictors of a 50% response to anti-CGRP therapy were a BDI-II score ≥ 11 and the failure of ≥ 3 types of prophylactic drugs. These results are consistent with previous reports [26, 27], suggesting that treating migraine patients early after disease onset with effective preventive treatment is important in clinical practice [8].

The GS is a potential brain waste removal system that includes the perivascular space. This system and the neurovascular unit (NVU), which play important roles in regulating CBF and neurovascular coupling, form a structural and functional continuum to maintain CBF and cerebrospinal fluid homeostasis [6]. The GS and NVU are involved in the pathophysiology of cerebral small vessel disease (CSVD) [6]. As GSs function primarily during sleep, insomnia leads to impairment of GSs and, consequently, reduced CBF. Impaired GS also leads to the accumulation of neuroexcitatory and proinflammatory chemicals, such as CGRP, which are involved in the pathogenesis of migraine [4]. This may predispose individuals to the development of MOH and CM, and migraine itself may directly or indirectly (through GS dysfunction) exacerbate sleep disorders [4]. Furthermore, WMHs in migraine patients are thought to be the result of GS dysfunction [4]. All three factors, migraine, insomnia, and WMH (reflecting CSVD), are thus related to each other via GS impairment [4]. Given the above findings, insomnia accompanied by WMH was a significant negative predictive factor in this study, suggesting that anti-CGRP therapy cannot be expected to be successful for patients with migraine who suffer from the triple overlap of migraine, insomnia, and WMH (reflecting CSVD) associated with GS impairment.

On the other hand, we reported that CHP was observed in 92% of the interictal ASL images from migraine patients without insomnia [14]. In contrast, the incidence of CHP was extremely low in migraine patients with insomnia, at 18%, probably due to the decrease in CBF caused by GS impairment [14]. In this study, the CHP in migraine patients, despite insomnia, was a negative predictor of the efficacy of anti-CGRP therapy. This may be because vasodilator peptides other than CGRP (e.g., vasoactive intestinal polypeptide, adrenal cortical medullary protein, and amylin) [28] markedly increase CBF, offsetting the decrease in CBF caused by insomnia. In other words, these migraine patients who exhibited CHP despite insomnia are presumed to have had CGRP-independent migraine, similar to Group D patients, who showed no change in CBF before or after treatment.

This is the first study to identify factors predicting the effectiveness of anti-CGRP therapy via MRI.

Changes in CBF After Anti-CGRP Therapy

In Group A, because CHP is a finding that reflects a state of high endogenous CGRP levels caused by ongoing activation of the trigeminovascular system, including during the interictal period, the disappearance of CHP and normalization of CBF during the interictal period reflect appropriate CBF changes following initiation of anti-CGRP therapy.

Group C had no CHP findings because all patients had insomnia, but the CBF after anti-CGRP therapy increased to an extent that did not reach the CHP. Insomnia improved in approximately 80% of patients after treatment, and the increase in CBF among Group C patients was attributed to improved insomnia due to reductions in MHD. The change in CBF after treatment in Group C was also appropriate, and the frequency of ≥ 50% response was 94%, the best among all the groups. We speculate that changes in the appropriate CBF in Groups A and C contributed to the improvement in the MIBS-4 score after anti-CGRP therapy.

Changes in Inappropriate CBF After Anti-CGRP Therapy

CGRP mediates CBF autoregulation in part by acting on cerebral vascular smooth muscle cells and inducing endothelium-independent vasodilation [2]; thus, it can rescue vasoconstriction and hypoperfusion of the cerebral vascular bed in cerebral ischemia [2, 29–31]. Normally, endogenous CGRP does not change CBF in the steady state, but migraine and insomnia are not steady states due to the presence of CBF autoregulation disorders. Anti-CGRP therapy for migraine patients may thus result in reduced interictal CBF. In the present study, approximately 90% of patients in Group B displayed ROIs in which CBF decreased by > 5% from normal values after anti-CGRP therapy, and this change in CBF was considered inappropriate.

Regarding the differences between Groups B and C, the rate of improvement in insomnia was significantly greater in Group C (79%) than in Group B (26%), suggesting that the insomnia in Group C was reversible and caused by migraine itself. That is, we speculated that in Group C, the reduction in MHD improved insomnia, leading to increased CBF because the resolution of GS impairment exceeded the decrease in CBF due to anti-CGRP therapy. On the other hand, the frequency of CM, failure of preventive medication, and insomnia with WMH were significantly greater in Group B than in Group C, and the improvement rate for insomnia was also significantly lower. This means that the migraines in Group B became chronic and complicated, and the comorbid GS impairment became severe enough to cause WMH (CSVD), making insomnia irreversible. As a result, in Group B, even among 50% of the responders, the decrease in CBF due to insomnia persisted after treatment. We speculated that this was combined with the decrease in CBF due to anti-CGRP therapy itself, resulting in a decrease in CBF after treatment. A decrease in CBF to below normal in Group B represented an inappropriate change. As a result, the improvement in the MIBS-4 score was also significantly lower than that in Groups A and C. Many patients in Group B exhibited subnormal CBF, which may lead to cerebral ischemia. Regular follow-up of ASL is therefore warranted.

Limitations

This study has several limitations that need to be kept in mind when interpreting the results. First, we did not measure CGRP levels before and after anti-CGRP therapy; therefore, consideration of CGRP-dependent or CGRP-independent migraine relies on speculative evidence. Second, this study did not provide a sufficient washout period when switching between CGRP mAbs was required for a crossover study. This study was therefore unable to conduct precise comparisons of treatment efficacy between galcanezumab and erenumab. Finally, if a migraine attack occurred on the day of the follow-up visit, ASL was postponed until the following month, so the period during which the treatment response was evaluated varied and could not be standardized.

CBF measurements by ASL before and after anti-CGRP therapy were clinically useful for predicting treatment response and evaluating treatment efficacy. Some patients exhibit an inappropriate decrease in CBF after treatment and should be followed with care.

Acknowledgments

The authors are grateful to the radiological technologists and nursing staff at our institute for their assistance in this work.

Funding

The authors received no financial support for the research, authorship or publication of this article.

Ethics Approval and Consent to Participate

All study protocols were approved by the Institutional Review Board for Clinical Research (approval no. 22R-078) and the Conflict of Interest Management Committee (approval no. 22-168) at our university. The study protocol was implemented in accordance with the 1964 Declaration of Helsinki and its later amendments, and all patients provided written informed consent before participating in the study. For all migraine patients, written informed consent for participation was obtained for the prospective study of data acquired during routine medical treatments based on national legislation and institutional requirements. Our report complies with the "Strengthening the Reporting of Observational Studies in Epidemiology" (STROBE) statement for cohort studies.

Consent for Publication

All participants in the study consented to the publication of the data obtained in relation to the present study.

Availability of Data and Materials

All the data generated or analyzed during this study are included in this published article.

Authors' Contributions

All the authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by Masami Shimoda, Kaori Hoshikawa, Shinri Oda, Masaaki Imai, Rie Aoki and Chiaki Shinohara. The first draft of the manuscript was written by Masami Shimoda, and all the authors commented on previous versions of the manuscript. All the authors read and approved the final manuscript.

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The authors declare no competing interests.

SupplementaryFigure1.docx
Supplementary Figure 1. ROI settings for cortical regions
SupplementaryTable1.docx
Supplementary Table 1. Response rate (> 50%, > 75%, and 100% reduction in monthly headache days) after anti-CGRP therapy in migraine patients
SupplementaryTable2..docx
Supplementary Table 2. Relationship between clinical factors before anti-CGRP therapy and response rate after therapy (> 50% reduction in monthly headache days) in migraine patients
SupplementaryTable3.docx
Supplementary Table 3. Clinical features of each CBF group
SupplementaryTable4.docx
Supplementary Table 4. Changes in CBF before and after anti-CGRP therapy using MRI-ASL in each group

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MRI-ASL-based CBF changesduring the interictal period after anti-CGRP therapy in migraine patients

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Abstract

Figures

INTRODUCTION

METHODS

RESULTS

Overall Results of Switching Anti-CGRP Therapy

Predictors of Response to Anti-CGRP Therapy

Changes in CBF after Anti-CGRP Therapy

Differences in Clinical Features between Groups

Clinical factors before treatment

Clinical factors after treatment

Changes in CBF before and after anti-CGRP therapy in each group

DISCUSSION

Predictors of Anti-CGRP therapeutic efficacy

Changes in CBF After Anti-CGRP Therapy

Limitations

CONCLUSIONS

STATEMENTS AND DECLARATION

References

Additional Declarations

Supplementary Files

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