Use of the ID migraine questionnaire for migraine in TMJ and orofacial pain clinic

김성택 연세대학교 대학원 2005 국내석사

As migraine pain represents a substantial personal and social burden worldwide, there has been a great deal of effort in developing a screening instrument for migraine. Lipton et al(2003) developed and validated the ID Migraine questionnaire, which is a self-administered screener for migraine in primary care, and it is brief and easy to use for a primary care provider. The aim of this study was to determine if the ID Migraine questionnaire could be applied successfully to assess the headache patients with temporomandibular disorders(TMD) and orofacial pain. This study found that nausea, photophobia and headache-related disability had the highest individual sensitivities and specificities, and the performance of the three-item screener was equivalent to that reported in a previous study. Although the sensitivity of the three-item screener in this study (0.58) was lower than in a previous study (0.81), the specificity (0.98) was higher and the positive predictive value was 93.9%. This suggest that the ID Migraine questionnaire is very efficient in this setting. In conclusion, the ID Migraine questionnaire, which is a three-item screener consisting of nausea, photophobia and headache-related disability, is effective as a self-administered report for detecting migraine headaches in patients with temporomandibular disorders(TMD) and orofacial pain. 최근 Lipton 등(2003)은 자가적으로 시행할 수 있는 편두통 진단용 설문지인 ID Migraine을 개발하여 일차 진료실에서 편두통을 간단하고 쉽게 진단할 수 있도록 하였는데, 이 항목에는 오심(nausea), 빛 공포증(photophobia), 그리고 두통과 연관된 기능장애(disability) 등이 포함된다. 본 연구의 주된 목적은 이전 연구에 사용된 자가 설문지가 턱관절 및 안면통증클리닉에서 편두통을 평가하는데 효과적으로 적용될 수 있는지 여부에 대하여 알아보는 것이었다. 각 개인에서 오심(nausea), 빛 공포증(photophobia), 그리고 두통과 연관된 기능장애(disability)가 가장 높은 민감도(sensitivity)와 특이도(specificity)를 보였으며 그 결과는 이전의 연구와 거의 대등한 것으로 나타났다. 3개 항목 설문지(ID Migraine)의 민감도가(0.58) 이전 연구의 민감도(0.81)보다 낮았으나, 특이도는(0.98) 이전 연구의 특이도(0.75)보다 더 높은 것으로 나타났고 93.9%의 높은 양성 예측도는 이 설문지가 이러한 환경에서 매우 유용하다는 것을 나타낸다. 결론적으로, 3개 항목으로 이루어진 ID Migraine 설문지는 턱관절 및 안면통증클리닉에서 편두통을 진단하는데 유용하다고 할 수 있다.

Targeting Nociceptors and Transient Receptor Potential Channels for the Treatment of Migraine

Cohen, Cinder F University of Cincinnati ProQuest Dissertations & 2022 해외박사(DDOD)

Migraine is a highly prevalent neurovascular disorder that is a leading cause of disability and consequent economic losses. The underlying mechanisms giving rise to this complex disorder remain elusive. Identification of CGRP as a key neuropeptide implicated in migraine has led to the development of several pharmacotherapies that target CGRP signaling. While these treatments represent a significant advance in this often-intractable disorder, there is still an unmet need for efficacious and safe therapies. Activation and sensitization of afferent nociceptive neurons innervating the meninges and its associated vasculature is postulated to play a central role in migraine. These nociceptors are rich in TRP channels, some of which have been implicated in migraine, thus making them promising migraine therapeutic targets. Recent studies in our lab identified a novel role for the TRPC4 channel in psoriasiform itch via regulation of CGRP release. In a separate study we found that a lipid mediator, RvD3, attenuated itch and pain as well as CGRP release via a TRPV1 mediated mechanism. Results of this research prompted the studies undertaken and described in this thesis including: 1) Elucidating the role of TRPC4 in migraine related pain, and 2) Investigation of resolvins as a potential novel class of migraine therapeutics. To probe these questions, we utilized a common, validated mouse model of migraine involving administration of nitroglycerin (NTG), a potent vasodilator and known migraine trigger. We characterized two experimental paradigms of this model: single injection of NTG to model acute episodic migraine, and repeated intermittent NTG injections to mimic development of chronic migraine. Next, we performed various behavioral assays to assess the effects of NTG in both experimental paradigms and concluded that mechanical hypersensitivity was the most robust behavioral endpoint. Both the TRPC4 and resolvin studies sought to uncover alternate targets for migraine therapy. In our TRPC4 study we showed that ML-204, a TRPC4 selective antagonist, prevented NTG-evoked mechanical hypersensitivity in our NTG model, and notably these effects were observed in male and female mice. To probe the mechanisms behind the analgesic effect of TRPC4 inhibition, we analyzed expression of migraine associated genes in DRG and found decreased CGRP transcripts in ML-204 treated male and female mice. We further revealed that TRPC4 is highly expressed in trigeminal ganglia (TG), specifically in CGRP-positive neurons, suggesting a functional role in TG related pain. Using cultured primary sensory neurons, we showed that ML-204 inhibited CGRP release in neurons treated with Englerin A, a TRPC4/5 agonist, thus demonstrating that TRPC4 inhibition has direct effects on sensory neurons. We next sought to determine if resolvins, which act as TRP channel modulators, would prevent migraine associated pain. The analgesic effects of several resolvins were tested in our acute NTG migraine model. Our results indicate that resolvin D3 (RvD3) prevented NTG evoked mechanical hypersensitivity in female mice. Altogether, our studies provide evidence for two novel approaches for treating migraine related pain: 1) Targeting TRPC4, a TRP channel not associated with thermoregulation, and 2) Using resolvins to indirectly target TRP channels.

Characterizing a Novel Metabolic Pathogenic Mechanism in Familial Hemiplegic Migraine

Smith, Sarah Elizabeth Washington University in St. Louis ProQuest Disser 2021 해외박사(DDOD)

Migraine, an episodic neurological disorder, afflicts about 1 in 10 people at least monthly, yet the underlying pathophysiological mechanisms remain poorly understood. The prototypical monogenic migraine disorder, Familial Hemiplegic Migraine, theoretically presents an excellent opportunity for preclinical modeling, but thus far animal models of migraine have failed to recapitulate the severe migraine aura symptoms of episodic paralysis and ataxia. Mutations that cause Familial Hemiplegic Migraine occur in one of three genes, two neuronal ion channels, and interestingly, the astrocytic α2-Na/K ATPase. In the case of α2-Na/K ATPase, mutations primarily result in loss of protein function. As migraine is thought to be a disease of primarily neuronal hyperexcitability, it is unclear how a loss of α2-Na/K ATPase in astrocytes can confer hyperexcitability non-cell autonomously.To better characterize the sequelae stemming from loss of α2-Na/K ATPase in the brain, we generated α2-Na/K ATPase conditional knockout mice using an astrocyte-selective Cre driver. To our surprise, conditional knockout mice developed episodic paralysis and ataxia not unlike that seen in Familial Hemiplegic Migraine patients. Familial Hemiplegic Migraine motor symptoms present as part of the migraine aura, a set of neurological symptoms associated with a slow wave of synchronized neuronal activity followed by silence known as cortical spreading depression. Using widefield imaging of hemodynamics and neuronal activity via intrinsic optical signal and genetically encoded calcium indicators respectively, we discovered that unanaesthetized conditional knockout mice exhibit cortical spreading depression spontaneously at a similar frequency as paralysis bouts. Moreover, EEG abnormalities known as low voltage activity reliably accompanied cortical spreading depression. By recording continuous bilateral EEG activity in awake and behaving mice, we showed that low voltage activity is coincident with episodes of paralysis and ataxia. In sum, this data suggests that α2-Na/K ATPase conditional knockout mice model Familial Hemiplegic Migraine in an entirely novel way because they develop spontaneous migraine aura and associated motor symptoms.Next, we probed the pathogenic mechanisms of migraine in the conditional knockout mice by performing bulk and astrocyte-enriched RNA-Sequencing on cortex from mice prior to the onset of paralysis symptoms. From these studies, we discovered dysregulated metabolic pathways in the astrocytes, particularly in pathways related to amino acid metabolism. We next performed metabolomics and intersected the bioinformatics data with the metabolite levels. The metabolism network analysis revealed that serine, an uncharged, polar amino acid, is highly upregulated, as are the enzymes and other metabolites closely related to it in the network. Furthermore, HPLC verified that the levels of both enantiomers of serine, D- and L-, are significantly increased. D-serine is a particularly relevant amino acid to neurons because it serves as a co-agonist to the NMDA glutamate receptor, meaning that excess D-serine could theoretically confer neuronal hyperexcitability. We tested the hypothesis that excess serine contributes to the development of migraine aura motor symptoms in conditional knockout mice by implementing a diet with no serine or metabolically related amino acid glycine. Mass spectrometry verified that the serine/glycine free diet substantially lowered the levels of serine in the brain. Strikingly, conditional knockout mice on the serine/glycine free diet take nearly twice as long to develop paralysis symptoms, and symptoms are significantly less severe. Moreover, their motor function is significantly better for the duration of their lives that conditional knockout mice on the control diet. In sum, these studies suggest a novel metabolic pathogenic mechanism in Familial Hemiplegic Migraine. We anticipate that future studies will clarify mechanistic details driving serine buildup after astrocytic α2-Na/K ATPase loss and investigate the therapeutic potential of serine-lowering diets.

Association between cerebrovascular reactivity and deep white matter hyperintensities using blood oxygenation level-dependent magnetic resonance imaging: comparison between patients with migraine and normal subjects

조수현 성균관대학교 일반대학원 2022 국내박사

편두통에서 백질고신호강도(white matter hyperintensities)의 유병률이 증가되나 그 기전에 대해서는 아직 밝혀져 있지 않다. 따라서 편두통에서 백질고신호강도의 발병 기전을 밝히기 위하여 편두통 환자의 심부백질고신호강도에 대한 뇌혈관반응성의 영향을 조사하였다. 혈관 위험인자가 없는 총 40명의 간헐성 편두통(20명의 무조짐편두통 및 20명의 조짐편두통) 환자와 20명의 연령 및 성별이 일치하는 정상군에게 3T 자기공명영상을 시행하였다. 피험자의 호기말 이산화탄소에 맞춰진 혈중 산소 농도 신호의 변화로 뇌혈관반응성을 측정하였으며 자동화된 세분화 방법을 사용하여 심부백질고신호강도를 정량화 하였다. 심부백질고신호강도와 뇌혈관반응성을 편두통 환자와 정상 환자 사이에서 비교하였다. 심부백질고신호강도에서 뇌혈관반응성과 관련된 요인을 평가하기 위해 Pearson의 상관 관계 및 선형 회귀 분석을 수행하였다. 또한 일반화 선형 혼합 모델을 통해 각 복셀에서의 뇌혈관반응성이 심부백질고신호강도에 영향을 미치는지 분석하였다. 편두통 환자는 정상 대상자보다 심부백질고신호강도의 전체 수와 부피가 더 많았다. 편두통 환자 및 정상군에서의 심부백질고신호강도 영역의 뇌혈관반응성은 정상백질 영역의 뇌혈관반응성보다 낮았다. 그러나 심부백질고신호강도와 정상백질영역의 뇌혈관반응성은 각 그룹 간에 차이가 없었다. 선형 회귀 분석에서 남성의 성별 및 월별 두통 일수가 높을수록 낮은 심부백질고신호강도의 뇌혈관반응성과 관련이 있었다. 일반화 선형 혼합 모델 분석에서 감소된 뇌혈관반응성과 편두통은 심부백질고신호강도 존재와 유의하게 연관되었다. 또한 감소한 뇌혈관반응성의한 심부백질고신호강도 존재에 대한 영향은 편두통 환자에서 정상군에 비해 컸다. 심부백질고신호강도 정도는 편두통 환자에서 정상인보다 높았으나 조짐편두통 및 무조짐편두통 환자간에는 차이가 없었다. 그룹 간 뇌혈관반응성의 유의미한 차이가 없음에도 불구하고 감소된 뇌혈관반응성과 편두통은 심부백질고신호강도의 가능성과 연관되었다. 특히 편두통 환자에서 뇌혈관반응성의 심부백질고신호강도에 대한 보호 효과가 정상군에 비해 작았다. 본 연구의 결과를 바탕으로, 편두통 뇌의 특징, 특히 과흥분성과 겉질확산성억제가 심부백질고신호강도의 발병 기전에 영향을 주었을 것으로 생각된다. Background: The mechanisms underlying the increased prevalence of white matter hyperintensities (WMHs) in migraine are not properly understood. To unveil the mechanism of WMH in migraine, I aimed to investigate the effect of cerebrovascular reactivity (CVR) on deep WMHs in patients with migraine. Methods: A total of 40 patients with episodic migraine (20 with migraine without aura [MO] and 20 with migraine with aura [MA]) who had no vascular risk factors and 20 age- and sex-matched headache-free patients underwent 3T magnetic resonance imaging with prospective end-tidal carbon dioxide targeting. Deep WMHs were quantified using an automated segmentation method. The CVR was measured by changes in blood oxygen level-dependent signals fitted to subjects’ end-tidal carbon dioxide. The characteristics of deep WMH and CVR were compared among patients with MO, those with MA and normal subjects. Pearson’s correlation and linear regression analyses were performed to assess the factors associated with CVR in deep WMHs. The association of migraine and CVR with the presence of WMH in each voxel and interaction of migraine and CVR on deep WMH were analyzed. Results: Patients with migraine had a greater number and volume of deep WMHs than normal subjects (p=0.009 and p=0.005, respectively). In patients with MO, those with MA and normal subjects, the CVR of the deep WMH region was lower than that of the normal-appearing white matter (WM) region. However, the CVR of the deep WMH and normal-appearing WM regions was not different among groups (MO vs. MA vs. normal subjects). In univariable and multivariable linear regression analyses, the male sex and higher headache days per months were associated with lower deep WMH CVR (beta = -0.088, 95% CI = -0.170 – -0.006, p = 0.037 and beta = -0.017, 95% CI = -0.028 – -0.007, p = 0.002, respectively). In univariable and multivariable generalized linear mixed model analyses, reduced CVR and presence of migraine were associated with increased probability of having deep WMHs in a given voxel (adjusted OR = 0.766, 95% CI = 0.518 – 1.134, p = 0.045; adjusted OR = 3.064, 95% CI = 1.556 – 6.031, p = 0.001, respectively). CVR was less protective for WMH in patients with migraine than in normal subjects (p for interaction <0.001). Conclusions: The burden of deep WMHs was higher in patients with migraine than in normal subjects, while burden of deep WMH were similar between patients with MO and those with MA. Reduced CVR and presence of migraine were associated with having deep WMHs, however the protective effect of CVR was less in the presence of migraine. Migraine-WMH association can be explained by the effect modification on the CVR.

편두통 환자에서 대뇌피질 과흥분성에 대한 divalproex sodium의 효과

오형근 중앙대학교 대학원 2001 국내석사

Purpose : Cortical hyperexcitability is proposed to be the putative basis for the physiological disturbances in migraine. Recent studies have demonstrated that divalproex sodium effectively prevents migraine. The cortical silent period (CSP) elicited by transcranial magnetic stimulation (TMS) reflects the cortical inhibition of the central motor pathway. So the purpose of this study is to observe that divalproex sodium may play a role in prophylaxis of migraine by decreasing cortical neuronal hyperexcitability through the changes of CSP. Methods : We studied the CSP of bilateral first dorsal interossei muscles evoked by TMS in 15 patients with migraine and 15 normal subjects. As a prophylactic therapy, 15 patients with migraine were treated with divalproex sodium 500-750 mg/day. After 3 months, we studied the CSP in patients with migraine for the purpose of comparing with results before medication. Results : The CSP was shorter in migraine patients than in controls (135.8±27.8 msec vs 203.7±32.2 msec, p<0.001). After treatment with divalproex sodium, the CSP was significantly prolonged in migraine patients (196.9±31.0 msec, p=0.001). Conclusions : The shortened CSP in migraine patients suggests increased excitability of the cortical neurons in migraine. The prolonged CSP after medication in patients with migraine suggests that the divalproex sodium may play a role in prophylaxis of migraine by decreasing cortical neuronal hyperexcitability.

Concussion, Migraine, and the Athletic Trainer

Burns, Karlee Nicole ProQuest Dissertations & Theses Temple University 2023 해외박사(DDOD)

PURPOSE: Sport-related concussions and migraine are both national healthcare concerns that cost billions of dollars in economic burden annually in the United States as well as cause hardship on the individual. More than 539,600 student-athletes in the United States will be directly affected by both comorbidities each year, and the health care providers that care for them will have to make decisions based on both conditions. How healthcare providers are educated on these two conditions, their attitudes in diagnosing and managing these conditions, and beliefs about their role has not been established (aim 1). Due to a common pathophysiology, pre-morbid migraine has been identified as a risk factor for worse outcomes after an individual sustains concussion. However, the impact of these conditions and prescribed medications on commonly used baseline assessments has not been identified (aims 2 and 3). This may have implications in student-athlete referral to other healthcare professionals, in interpretation of test results, and in management of post-injury cases. Many individuals diagnosed with migraine take daily preventative medication (e.g., topiramate); however, these medications have been identified to cause cognitive impairment but the deficit in the collegiate student athlete and on the baseline concussion assessment is unknown (aim 3). Since cognitive exams make up a large portion of the concussion baseline assessment, identifying any real or perceived deficits in these tests may also allow healthcare providers to make decisions for test interpretation for these individuals. PARTICIPANTS: For aim 1, certified athletic trainers from the National Athletic Trainers’ Association and targeted social media groups were recruited to take a novel electronic survey. A total of 576 individuals that completed more than 90% of the survey iii were included in the final analysis. Student-athletes participating in club and varsity sports at Temple University undergoing routine baseline concussion assessments were recruited to have their data included for aims 2 and 3 (non-migraine = 387, migraine = 33, missing migraine status = 137). METHODS: The survey for aim 1 consisted of 7 subgroups of questions: demographics, concussion, migraine, and comorbid knowledge and atttitudes and beliefs. Questions mainly consisted of true/false and likert-style questions. For aims 2 and 3, student-atheltes completed their routine annual concussion baseline assessment. This consisted of a health history questionnaire, symptom checklist, Hospital Anxiety and Depression Scale, cognitive assessments, postural control test, and vestibular/oculomotor exams. Indiviudals that self-reported a history of migraine were included in aim 3 for analysis of medication use. RESULTS: For aim 1, 61% of respondents had a masters degree and 40% worked in middle or high school athletics. Over 94% of respondents previously reported receiving concussion education, compared to only 40.5% for migraine education. Respondents were able to correctly identify an average of 74% of concussion signs and symptoms and 66% of migraine signs and symptoms. Collegiate and split positions were associated with more negative concussion attitudes and beliefs. A lack of previous concussion or migraine education was associated with more negative attitudes and beliefs. For each year clinically practicing, attitude and belief scores were slightly more positive (β = 0.03 – 0.70, p < 0.001). Females also generally had more positive attitudes and beliefs across outcomes (β = 1.09 – 2.61, p < 0.001). A total of 577 student-athletes were included in aims 2 and 3. Having migraine was associated with 2.36 more symptoms (p = 0.008) and a 5.20 higher severity score (p = 0.005). Migraine was also associated with a 5.58 higher odds of a slower reading time iv on the King-Devick (p < 0.01). From ImPACT, having migraine decreased visual memory composite by 9.97-points (p = 0.02) and visual motor composite score by 3.89- points (p = 0.07). Of the 33 student-athletes with migraine, 15 were taking a prescription medication, 3 were taking an over-the-counter medication or supplement, and 7 were taking both. None of the athletes were taking a daily preventative medicaton for migraine. The median Migraine Disability Assessment score was 4.5, indicating only little or no disability. The Brief Disability Questionniare showed no significant difference between those with and without migraine (Kruskall-Wallis (1) = 0.4, p = 0.50). Finally, there was high provider trust as measured with the modified Patient-Doctor Relationship Questionniare, and no significant difference between those with and without migraine (Kruskall-Wallis (1) = 1.59, p = 0.21). CONCLUSION: This was one of the first studies to identify athletic trainer knowledge, attitudes and beliefs surrounding concussion and migraine. Idenitfying groups with decreased atttitudes and beliefs can be used for targeted programming and ensuring these athletic trainers have support to increase knowledge and attitudes and beliefs for more positive patient outcomes. This study also determined that migraine affects some aspects of baseline concussion assesments. This can be used by clinicians during test interpretation for patient care. These student-athletes had low measures of disability and high levels of provider trust, key components for individuals with migraine to receive appropriate care. Concussion and migraine are significant healthcare concerns present in populations seen by athletic trainers. Future studies exploring post-concussion migraine effects and medication over the course of collegiate career should be considered. Adequate knowledge and positive attitudes and beliefs would be beneficial in ensuring appropriate medical care given to individuals experiencing these conditions.

편두통에 대한 인지행동 치료의 체계적 문헌고찰 및 메타 분석

배지용 경희대학교 대학원 2023 국내박사

배경 및 목적 : 편두통은 중등도 이상 통증의 두통과 안면홍조, 코 막힘, 발한과 같은 자율신경계 기능 장애를 일으켜 삶의 질을 떨어뜨리는 만성 신경질환이다. 편두통의 주요 치료 방법에는 약물 치료와 인지행동치료를 포함한다. 인지행동치료는 정신질환 증상으로 인한 통증, 장애, 정서 장애를 줄이고 정신건강에 대한 이해를 높여, 통증 치료와 다양한 심인성 신경질환에 활용되고 있다. 이 연구는 편두통 치료에서 인지 행동 치료의 효과와 안전성을 평가하는 것을 목표로 하였다. 방법 : 2023년 4월까지 7개의 국내외 데이터베이스를 통해 검색을 진행하였고, 편두통에 대한 치료 방법으로 인지행동치료를 사용한 무작위 대조군 연구가 포함되었다. 이 연구의 일차 결과 지표는 편두통 빈도, 시각적 상사 척도(Visual Analog Scale : VAS)로 표현된 편두통 강도, 약물 사용 빈도와 편두통 장애 평가 설문(Migraine Disability Assessment : MIDAS) 및 두통 영향 평가(Headache Impact Test : HIT-6 index)였다. 선정된 무작위 대조군 연구의 데이터 추출 및 품질 평가를 수행하였으며, RevMan V.5.4를 사용하여 메타 분석을 수행했다. 결과 : 분석에 포함된 14개의 무작위 대조군 연구 중 7개는 미국에서, 3개는 독일에서, 2개는 이란에서, 2개는 영국과 이탈리아에서 각각 실시되었다. 하위 그룹 분석에서, 편두통에 대한 교육만 실시한 군에 비해 인지 행동치료 군에서는 편두통 빈도, MIDAS에서 통계적으로 유의한 결과를 보였다. 또 편두통에 대해 특별한 치료를 하지 않은 대조군에 비해 인지 행동 치료 군에서는 두통 빈도, 통증 강도, MIDAS 와 HIT-6 Index가 통계적으로 유의미한 감소를 보였다. 포함된 연구들 중 세 개의 연구에서는 편두통의 강도와 빈도의 악화, 호흡기 증상, 그리고 충격적인 사건에 대한 생생한 기억을 포함한 부작용을 보고했다. 결론 : 편두통에 대한 인지행동치료는 메타 분석 및 두통 강도 하위 그룹 분석에서 부작용이 적으며, 두통 빈도, 편두통 장애 평가 설문(Migraine Disability Assessment : MIDAS)와, 두통 영향 평가(Headache Impact Test : HIT-6 index)를 효과적으로 감소시켰다. Background and Objectives: Migraine is chronic neurological diseases that reduce the quality of life by causing severe headaches and autonomic nervous system dysfunction, such as facial flushing, nasal stuffiness, and sweating and etc. Their major treatment methods include medication and cognitive behavioral therapy (CBT). CBT has been used for pain treatment and various psychogenic neurological diseases by reducing pain, disability, and emotional disorders caused by symptoms of mental illness and improving the understanding of mental health. This study aimed to evaluate the effectiveness and safety of CBT in treating migraines. Materials and Methods: Seven electronic databases were searched up to april 2023. Randomized controlled studies(RCTs) and Quasi randomized controlled studies(Quasi-RCTs) using CBT as an intervention for migraine were included. The primary outcome of this study was to determine the frequency of migraines and the intensity of migraines on visual analog scale (VAS), migraine disability assessment (MIDAS), and headache impact test (HIT-6) index. The author conducted the data extraction and quality assessment of the included RCTs, and conducted meta-analysis with RevMan V.5.4. Results: Among the 501 studies, 14 RCTs were included in this systematic review. Seven out of the 14 RCTs were conducted in the USA, and three were conducted in Germany, two were conducted in Iran, one was conducted in the UK and one was conducted in the Italy. Headache frequency and MIDAS scores were statistically significant reduced. In the subgroup analysis, headache CBT group showed statistically significant reduce in MIDAS score, HIT-6 score compared with WL/TALU/SMC group, showed statistically significant reduce in headache frequency, headache intensity, MIDAS score compared with education group. Three of the included studies reported adverse effects, including worsening of migraine intensity and frequency, respiratory symptoms, and vivid memory of a traumatic event. Conclusions: CBT for migraine effectively reduced headache frequency and MIDAS score in meta-analysis with few adverse events. Through this study, it was found that cognitive behavioral therapy can be a complementary treatment for migraine.

The Efficacy of Shinbaro for the preventive treatment of migraine : A pilot study

정예솔 서울대학교 대학원 2019 국내석사

본 연구는 생약 성분에 대한 건조 추출물로 소염, 진통, 및 골관절염 치료제로 사용되고 있는 신바로의 편두통 예방 효과를 알아보기 위해 진행되었다. 전향적, 중재적 연구로 대조군 없이 대상자의 전과 후의 데이터가 비교 분석되었으며, 총 37명의 대상자가 12주간 600mg의 신바로정을 하루에 두 번 매일 복용하였다. 평가 변수로 대상자 평균 편두통 빈도, 구제약 사용 빈도가 두통일기를 통해 4주 간격으로 조사되었고, 이때 수정된 버전의 편두통 장애 평가 설문지인 MIDAS가 시행되었다. 또 다른 평가 변수인 serum CGRP 레벨은 12주간의 신바로 복용 전과 후에 측정되어 비교 분석되었다. 대상자의 월평균 편두통 빈도는 baseline 20.5일에서 12주째 16.4일로 현저히 감소하였으며 (p =0.003), 대상자의 22%가 50% 이상의 편두통 빈도 감소율을 보였다. 이때 4주째부터 편두통 빈도가 감소하기 시작하였으며 (p =0.035), 8주째와 12주째 점차 감소하는 것을 확인할 수 있었다. 구제약 사용 빈도 역시 baseline 17.4일에서 12주째 13.2일로 유의하게 감소하였다 (p =0.035). MIDAS 점수의 변화는 유의하지 않았다. 마지막으로, serum CGRP 레벨은 신바로 복용 전 (baseline) 434.6 pg/mL에서 12주째 371.4 pg/mL로 통계적으로 유의하게 감소하였다 (p <0.001). 본 연구에서 12주간 신바로 복용 후 대상자 평균 편두통 빈도, 구제약 사용 빈도, 그리고 serum CGRP 레벨이 유의하게 감소하였다. 이는 신바로가 CGRP 감소를 통한 편두통 기전을 막는 예방적 치료 효과를 보인다고 사료되며, 또한 최근 편두통 예방치료제로 미국 FDA 승인을 받은 CGRP antibody 치료제에 대한 고찰을 할 수 있다. 향후 임상연구에서의 본 파일럿 연구에 대한 보완과 응용이 중요할 것으로 생각된다. Objective: To investigate the therapeutic potential and efficacy of Shinbaro, an herbal medication for inflammatory diseases and bone disorders, as a preventive treatment of migraine. Methods: In this prospective, interventional, single-arm, pre-post study, 37 migraine patients took 600mg bid of Shinbaro for 12 weeks. At 4-week intervals, the migraine frequency and the rescue medications frequency were measured from each patient’s headache diary. The modified Migraine Disability Assessment (MIDAS) questionnaires to assess migraine associated disabilities were also completed at each visit. The serum calcitonin gene-related peptide (CGRP) concentrations before and after 12 weeks of Shinbaro administration were compared. Results: The monthly migraine frequency was significantly reduced from 20.5 days at baseline to 16.4 days at week 12 (P =0.003), and 22% of the participants showed ≥ 50% reduction. The frequency reduction was observed by week 4 (P =0.035) and continuously occurred through week 8 (P =0.001) and week 12 (P =0.003). The rescue medications frequency also decreased significantly from 17.4 days at baseline to 13.2 days at week 12 (P =0.035). Lastly, the serum CGRP concentration dropped from 434.6 pg/mL at baseline to 371.4 pg/mL at week 12, which was statistically significant (P <0.001). Conclusions: Shinbaro demonstrated prophylactic effects in migraine patients, significantly reducing their mean migraine frequency, rescue medications frequency, and the serum CGRP concentration after 12 weeks of treatment.

Quantitative Assessment of Vascular Permeability in Migraine on Dynamic Contrast-Enhanced Magnetic Resonance Imaging

김연수 서울대학교 대학원 2019 국내석사

배경 및 목적: 본 연구에서는 동적 조영 증강 자기 공명 영상을 이용하여 편두통과 관련된 뇌 영역의 정량적 혈액 뇌 장벽 투과성을 측정하고, 편두통의 병태생리학적 위치를 결정하고자 한다. 재료 및 방법: 실제 임상 결과를 분석하기 위해 2016년 9월부터 2017년 12월에 걸쳐 가도뷰트롤 투여 후 얻은 동적 조영 증강 자기 공명 영상을 촬영한 56명의 피험자를 편두통군 (총 35명) 과 대조군 (총 21명) 으로 분류하여 분석하였다. 프리서퍼를 사용하여 조영증강 전 T1 강조 영상에서 전체 뇌 영역에 대하여 자동 영역 분할을 수행하였다. 이후, 노르딕아이스를 사용하여 자동 영역 분할이 끝난 전체 뇌영역으로부터 편두통과 관련된 뇌 영역 마스크를 추출하였다. 동적 조영 증강 자기 공명 영상으로부터 혈관 내 영역에서 혈관외 세포외 공간 영역으로 이동되는 조영제의 분율을 표현한 체적전달상수 (Ktrans) 지도와 혈관내 혈장 부피를 표현한 혈장체적지도 (Vp)를 추출하였다. 앞서 추출한 편두통과 관련된 뇌 영역 마스크마다 관류 관련 인자인 체적전달상수 (Ktrans) 및 혈장체적 (Vp) 을 모두 구하고 그 영역 마스크에서 각 관류 관련 인자의 평균값을 구하였다. 편두통군과 대조군간에 각 관심 영역 마스크의 관류 관련 인자의 평균값을 비교하기 위해 독립표본티검정과 맨-휘트니 검정을 사용하였다. 수신자 조작 특성 곡선 분석과 로지스틱 회귀 분석을 이용하여 편두통 환자의 임상적 특성과 이전 비교 분석시 의미가 있었던 관류 관련 인자 간의 상관 관계를 확인하였다. 결과: 편두통군의 평균 연령은 57.23 세 (범위: 26 – 79세)로 대조군의 평균 연령 71.33 세 (범위: 58 – 87세)보다 유의하게 낮았다 (P<0.0001). 좌측 편도체에서 측정된 혈장체적 (Vp) 의 평균은 편두통군에서 4.45x10-1±4.64x10-1 ml/100g 이었고, 대조군에서 7.17x10-1±9.22x10-1 ml/100g 로 편두통군에서 유의하게 낮았다 (P=0.0382). 편두통 환자의 임상적 특성 중 두통 발작의 강도만이 좌측 편도체에서 측정된 혈장체적 (Vp) 의 평균값과 유의미한 상관관계가 있었다 (P=0.0350). 결론: 본 연구에서 좌측 편도체에서 혈장체적 (Vp) 평균의 감소는 편두통과 관련이 있었다. 해당 관류 관련 인자는 편두통과 연관된 위치에서 혈액 뇌 장벽의 증가된 투가도를 반영하는 영상 생체표지자로서 사용될 수 있을 것으로 생각된다. Introduction: To determine the pathophysiologic loci of migraine, we analyzed the quantitative blood-brain-barrier (BBB) permeability in migraine-associated brain regions using dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI). Materials and methods: From September 2016 to December 2017, 56 subjects underwent DCE MRI after gadobutrol administration and were classified into migraine (n=35) and control groups (n=21). Automatic volumetric segmentation was performed on the precontrast T1-weighted image using FreeSurfer, and migraine-associated brain region masks were extracted using NordicICE. The corresponding pharmacokinetic parameters of Ktrans, the volume transfer constant, and Vp, the fractional plasma volume, maps were coregistered with the region of interest masks, and their statistics were calculated. For comparison between the two groups, the unpaired t-test or Mann-Whitney test was used. Receiver operating characteristic curve analysis and logistic regression analysis were used to identify correlations between clinical characteristics and the aforementioned perfusion parameters. Results: Age in the migraine group was significantly younger than that in the control group (p<0.0001). In the migraine group, the mean value of Vp in the left amygdala was lower than those in the control group (p=0.0382). Only the mean value of Vp in the left amygdala had a correlation with the intensity of headache attack in migraine patients (p=0.0350). Conclusion: The decreased Vp in the left amygdala is related to migraine, which can be used as a migraine-associated imaging biomarker.

전정 편두통 환자에서 보툴리눔 독소 A형 치료의 효과: 휴지기 기능적 연결성 변화에 대한 기능적 자기공명영상 종단 연구

강진주 전북대학교 일반대학원 2022 국내박사

Background: Vestibular migraine (VM) has been recognized as a distinct clinical entity with recently published diagnostic criteria. Although migraine prophylactic medications can improve headache profiles and dizziness symptoms, treatment trials that focus on VM are scarce. Botulinum toxin type A (BTX-A) has been approved for prophylactic treatment of chronic and episodic migraine; however, its efficacy for migraine-related dizziness or VM has not been validated. The purpose of this study was to investigate the efficacy of BTX-A in prophylactic treatment of VM and to determine whether this treatment modulates intrinsic functional brain network connectivity. Methods: Twenty patients (mean age 45.4 years, range 20–69 years) who satisfied the Bárány Society and International Headache Society diagnostic criteria for VM and who were refractory to conventional prophylactic therapies for more than five months had BTX-A injection and resting-state functional MRI (rs-fMRI) before and 2 months after the injection. We measured the changes in the frequency of vertigo and migraine attacks, symptomatic functional disability scores, and neuropsychiatric inventories before and after the treatments. Results: After BTX-A injection, the mean monthly frequencies of migraine and vertigo episodes decreased significantly compared to baseline (p<0.01, Wilcoxon signed rank test). The headache impact, as measured by the Headache Impact Test-6 score and the Migraine Disability Assessment, was improved (p<0.001). The vertigo parameters, measured by the Dizziness Handicap Inventory and the Vertigo Symptom Scale, showed an improvement (p<0.001), as did the anxiety and depression scores (p<0.001) 2 months after BTX-A treatment. The low-frequency fluctuation analysis of the rs-fMRI data found significant changes in functional connectivity of the right superior temporal gyrus (STG). Adoption of the right STG cluster as the seed region, increased functional connectivity with the left post-central gyrus, right supramarginal gyrus, and right middle temporal gyrus was seen after BTX-A treatment. Conclusion: This prospective study shows that BTX-A treatment is effective at ameliorating migraine headache and vertigo symptoms in VM patients who were refractory to conventional medical therapies. Along with symptomatic improvements, changes in the functional connectivity within the multisensory vestibular and pain networks in the right temporal regions suggest that abnormal brain activity leads to dysmodulation of multimodal sensory integration and abnormal cortical processing of the vestibular and pain signals in VM patients.