Relationship between migraine and non-celiac gluten sensitivity in Korea : the necessity of further evaluation of gluten sensitivity in Eastern countries

Jiyun Park 고려대학교 의학전문대학원 2018 국내석사

Objective: The paper aims to investigate whether there is a positive relevance between migraine and NCGS (non-celiac gluten sensitivity) in Korea. Also, the effect of GFD (gluten free diet) on migraineurs will be assessed. Background: The correlation between the migraine and NCGS is raising its reasonability because of the following reasons: 1) The migraine brain is genetically hyperactive. 2) On the concept of the brain-gut axis, indigestible gluten causes chronic inflammation and activates the neuronal signaling of ENS. 3) Migraineurs commonly suffer from gastrointestinal symptoms, and most gluten sensitive patients have headache. Therefore, it had been reported in Western countries that GFD improved patients who had both migraine and NCGS. Methods: Migraineurs were recruited from neurology outpatient clinics in Korea University Hospital between April 2016 and August 2016. Patients answered the questionnaire about their headache characteristics (frequency, average intensity, triggering factor), gastrointestinal symptoms (using ROME Ⅲ criteria of IBS (irritable bowel syndrome)), and wheat diet pattern. 36 migraineurs who ingests wheat and have IBS were educated to avoid gluten for 1 month. The follow-up 16 patients answered the second questionnaire. The authors classified the patients into the SRWIH (self-reported wheat induced headache) group and IBS group. The analysis was done on their headache characteristics and if the symptoms improved after GFD. Results: Among the 36 patients, 6 (17%) patients had SRWIH, 20 (56%) patients had IBS, and 14 patients (14%) had both SRWIH and IBS. The SRWIH group had more frequent headache (p=0.094) and higher frequency plus intensity score (p=0.086). The SRWIH/IBS group had more frequent headache (p=0.012) and higher frequency plus intensity score (p=0.008). Among the 16 follow-up patients, 4 patients succeeded in avoiding. 2 patients were SRWIH, and the other 2 patients were non-SRWIH but had IBS. All 4 patients who succeeded in GFD were improved, and among the 12 failed patients only 1 patient improved. Discussion: More frequent and intense headache happens if the patient has SRWIH and IBS. GFD will be effective to those patients. This study supports the established hypothesis of the positive relevance between migraine and NCGS. On the other hand, it raises a question on the conventional belief of GRD (gluten related disorders) as a Western genetic disease. Undiagnosed gluten sensitivity might exist in Korea and further evaluation is required. 목 표: 본 연구의 목표는 한국에서 편두통과 비-셀리악 글루텐 민감성 간 상호관련성이 존재하는지 알아보기 위함이다. 또한 글루텐 제한식이 편두통 환자에게 미치는 영향에 대해 논한다. 배 경: 서양 국가에서 편두통과 비-셀리악 글루텐 민감성은 다음의 근거들을 토대로 상호관련성이 있다고 알려져 있다: 1) 편두통성 뇌는 유전적으로 항진되어 있다. 2) 뇌-장축 이론에 따르면 소화되지 않은 글루텐은 장내 만성 염증을 일으키고 장신경계의 신경전달을 활성화시킨다. 3) 편두통 환자들은 대부분 위장증상을 동반하며, 비-셀리악 글루텐 민감성의 대표적인 증상 중 하나가 두통이다. 따라서 비-셀리악 글루텐 민감성을 동반한 편두통 환자에서 글루텐 제한식이 증상을 호전 시킬 수 있다고 알려져 있다. 방 법: 2016년 4월 ~ 8월에 구로병원 신경과 외래로 내원한 편두통 환자를 대상으로 두통의 양상 (빈도, 평균 강도, 유발 인자), 소화기 증상 (과민성 대장증후군의 여부), 그리고 밀 섭취 양상을 설문하였다. 밀을 섭취하며, 과민성 대장증후군의 기준에 맞는 36명의 편두통 환자들을 대상으로 1개월 간 글루텐 제한식을 진행하였다. 글루텐 제한식 후 16명의 환자를 추적할 수 있었다. 환자들을 ‘자가보고 밀 유발 두통 환자군’과 ‘과민대장증후군 군’으로 나누어 그들의 두통 양상과 글루텐 제한식 후 호전 여부를 분석하였다. 결 과: 36명의 환자 중 6명 (17%) 이 ‘자가보고 밀 유발 두통 환자군’에, 20명 (56%) 이 ‘과민대장증후군 군’에, 14명 (14%) 이 ‘자가보고 밀 유발 두통 환자군/ 과민대장증후군 군’에 동시에 해당되었다. ‘자가보고 밀 유발 두통 환자군’은 두통 빈도가 더 높았고 (p=0.094), 두통 빈도와 강도를 더한 값도 더 높았다 (p=0.086). 16명의 추적 환자들 중 4명만이 글루텐 제한식에 성공하였는데, 이들 중 2명은 ‘자가보고 밀 유발 두통 환자군’이었고, 2명은 ‘과민대장증후군 군’이었다. 글루텐 제한식에 성공한 4명은 모두 호전되었고, 실패한 12명 중 1명이 호전되었다. 토 론: 편두통 환자 중 ‘자가보고 밀 유발 두통 환자군’ 이나 ‘과민대장증후군 군’에 속할 경우 더 빈번하고 강한 두통을 겪으며, 이들에게 글루텐 제한식은 효과적이다. 본 연구 결과는 기존의 편두통 – NCGS 간 관련성을 지지한다. 반면 글루텐 관련질환은 서양 국가의 유전질환이라는 통념에 이의를 제기하며, 국내에 진단되지 않은 NCGS 환자들이 있을 가능성을 제시한다.

Hypomagnesemia as a Prognostic Marker of Ischemic Stroke

김한준 Graduate School, Korea University 2022 국내석사

Background and Purpose: Hypomagnesemia is related to initial stroke severity and increased in-hospital mortality of acute ischemic stroke. Our aim is to assess whether serum magnesium concentration could predict the functional outcome in acute ischemic stroke. Methods: From January 1, 2014, to July 31, 2017, a total of 1006 patients with acute ischemic stroke were analyzed. Serum magnesium level < 1.6 mEq/L was defined as hypomagnesemia. The poor functional outcome was defined as a 3-month modified Rankin scale (mRS) ≥ 4. To determine the effect of hypomagnesemia in the prognosis of ischemic stroke, we used multivariate logistic regression models. Furthermore, patients were grouped according to the severity and the type of stroke. Within each group, subgroup analyses and interaction analyses were done to describe whether the effect of hypomagnesemia on functional outcome is still valid among different clinical conditions. Results: After adjustment with potential confounding factors, the odds ratio (OR) of poor 3-month mRS in patients with hypomagnesemia was 2.15 [95% Confidence Interval (CI) 1.16–3.98; p=0.015]. Hypomagnesemia was significantly associated with poor 3-month functional outcome in patients with minor stroke [Initial National Institutes of Health Stroke Scale (NIHSS) < 5] (adjusted OR 3.11; 95% CI 1.17–8.25; p=0.022). A significant interaction between hypomagnesemia and severity of Initial NIHSS was observed (p=0.047) as well. Although without significant interaction (p=0.053), in the cardioembolic stroke group, hypomagnesemia was significantly associated with poor functional outcomes. (adjusted OR 9.81; 95% CI 2.27–42.51; p=0.002) Conclusions: Hypomagnesemia was associated with a higher risk of poor 3-month mRS among patients with acute ischemic stroke suggesting the role of magnesium as a prognostic marker in ischemic stroke. Hypomagnesemia was a stronger prognostic marker of poor functional outcome in certain subgroups, especially in mild severity stroke and in cardioembolic stroke.

편두통 환자에서 광공포증 설문지의 유용성

최정윤 고려대학교 대학원 2009 국내석사

Photophobia is an important criterion for the diagnosis of migraine. However, several Asian epidemiologic surveys about migraine showed lower prevalence of photophobia than that of Western studies. This discrepancy is probably caused by underestimation of photophobia due to inappropriate questioning of patients by physicians. To investigate this issue, we developed a questionnaire about photophobia and evaluated its usefulness in 103 patients with migraine. In phase 1 of the study, we found good repeatability of the questionnaire with a 0.826 kappa coefficient. In phase 2 of the study, the prevalence of photophobia from interviews and that from the questionnaire were compared. The prevalence of interview-documented photophobia was 51.5% and questionnaire-documented photophobia was 82.5% (p<0.001). In phase 3, we attempted to make a short-form questionnaire with the same detection power of the whole questionnaire. Two short-form questionnaires were identified as a useful method for detecting photophobia. The prevalence of photophobia could be underreported via interview, especially in Asian migraineurs. Using this questionnaire to test for photophobia, the diagnostic rate of photophobia and migraine could be improved. 광공포증은 편두통 진단에 있어 중요한 인자이다. 그러나 아시아인을 대상으로 하는 많은 편두 역학조사에서는 서양인을 대상으로 하는 연구에서 보다 상대적으로 낮은 빈도의 광공포증이 관찰되고 있다. 이와 같은 광공포증의 저 평가는 환자에 대한 올바르지 못한 질문에 기인한 것으로 추정된다. 저자는 이에 대한 적절한 평가를 위하여 8개의 질문으로 구성된 광공포증 설문지를 작성하였으며, 이를 103명의 편두통 환자를 대상으로 하여 유용성을 평가하였다. 첫 번째 분석에서 광공포증 설문지의 적절한 재현성을 확인할 수 있었다. 두 번째 분석에서는 인터뷰와 설문지에 의한 광공포증의 양성률을 비교하였고 인터뷰에 의한 양성률 (51.5%) 에 비하여 설문지의 양성률 (82.5%) 이 유의하게 높은 것을 확인하였다. 또한 세 번째 분석에서는 전체 광공포증 설문지와 동일한 양성률을 가지는 축소된 설문지 또는 질문의 조합을 확인하고자 하였으며, 각각 3개의 질문으로 구성된 2개의 축소된 설문지가 도출되었다. 본 연구는 아시아의 편두통 환자에서 짧은 인터뷰를 통해서는 광공포증의 존재가 저평가될 수 있음을 확인하였다. 또한 설문지를 이용하면 광공포증의 양성률 및 편두통의 진단률을 향상시킬 수 있을 것이다.