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[2019/01/15] Unveiling the Mystery of Migraine: NYMU Discovered an Important Link between Chronic Migraine and Neuronal Activity

NYMU held a press conference to explain the importance of the research results


Why do some patients have headaches that evolve into chronic migraine? Scientists still don't fully understand the mechanism. For the first time, "the Taipei Veterans General Hospital-National Yang-Ming University (TVGH-NYMU) Headache Medicine Team", which consist of the Brain Research Center of NYMU and the Department of Neurology of TVGH, have found that the answer may lie in a decrease in the brain of the concentration of a neuronal activity index chemical, N-acetyl-aspartate or NAA. The research has revealed the mystery behind the chronic migraine, and the result has been published in the internationally renowned journal “Brain”.


According to the TVGH-NYMU Headache Medicine Team’s previous research, about 1.5 million people in Taiwan suffer from migraine, including more than 100,000 with chronic migraine. Most of these patients were originally patients with paroxysmal attacks. Their headaches have gradually evolved into chronic migraine due to unknown mechanisms, with attacks occurring at least 15 days per month with more than eight days of these being migraine attacks. The disease duration can last more than three months. Thus chronic migraines would seem to be of great burden for individuals and society as a whole. Recent studies have shown that chronic migraine is associated with abnormal signal transduction in the thalamus, but the detailed mechanism has not yet become clear.


Brain Research Center and Taipei Veterans General Hospital Neurological Institute Director Shuu-Jiun Wang and a Danish associate researcher at the Brain Science Research Center Dr. David M. Niddam, collected 74 subjects, made up of 25 chronic migraine patients and 24 paroxysmal migraine patients, as well as 25 healthy adults, which formed the control group. Magnetic resonance spectroscopic imaging (MRSI) of the bilateral medial walls of the brain was used to measure N-acetyl-aspartate (NAA) concentrations in the regions related to migraine and pain, namely the bilateral thalami, the occipital cingulate cortices and the anterior cingulate cortices (ACC). This process was carried out on patients with chronic migraine (CM) as well as the healthy controls (HC) and the patients with episodic migraine (EM). Interregional NAA correlations among the regions of interest were also examined between the three study groups. These were then compared using a correlation matrix that included each pair of groups, the aim being to test if there were differences in the interregional connectivity.



  Research members starting from the left: Director of the Brain Research Center Wang, associate researcher Dr. Niddam, and Dr. Lai from the TVGH Neurology Center


The thalamus plays a pivotal role in sensory transmission. The vast majority of sensory input passes through the thalamus before entering into the cortex. Previous studies have demonstrated that the process of migraine becoming chronic seems to involve dysfunction affecting the thalamus and also the thalamocortical pathway. This study aimed to decipher whether the concentration of a neurochemical, such as NAA, is altered in CM, by applying MRSI. It was found that CM was associated with a reduced NAA level in the bilateral thalami and in the right ACC. The degree of reduction of NAA in the right thalamus negatively correlated with disease duration. Compared with HC patients, CM patients were found to have altered interregional NAA correlations for the right thalamus-ACC, the thalamus-occipital cortex, and the left and right ACC. NAA concentrations and interregional correlations in EM patients were found to be intermediate between the HC patient values and the control values. These results, namely a reduced NAA concentration linked to altered interregional NAA correlations, provide evidence supporting the notion that thalamus and the thalamocortical pathway play important roles in migraines becoming chronic. Such findings should lead to a new avenues for further migraine research and help with drug development in the future.


Director Wang remarked that patients with chronic migraine often see headache as a symptom that only requires control. As a result, they take painkillers without receiving preventive treatment. However, according to the results of this study, long term chronic migraine may lead to and be a result of dysfunction in the central nervous system. If a patient develops an increased frequency of headaches, or there is progression of headaches into chronic ones, they need to seek early professional help in order to prevent the development of chronic headaches.


Dr. Niddam stated that previous studies using MRS in migraine research have mainly focused on a single brain region such as the visual cortex due to technical limitations. In addition, most previous studies were done using EM subjects, rather than CM subjects. In the present study, the medial wall MRSI technique was applied, which is newly developed approach and involved cooperation between National Yang-Ming University and National Taipei University of Technology. This approach allows the imagining of different brain regions, such as the medial wall of bilateral cerebral hemisphere, at the same time, thus allowing an analysis of interregional connectivity to be carried out later. Moreover, this is the first large-scale study to evaluate differences in regional metabolism in CM patients and in matched groups of EM and HC patients. The study has revealed that chronic migraine not only exert its influences on the well-known node associated with migraine pathogenesis, namely the thalamus, but also affects the functional connectome of the thalamus, and hence in turn results in a greater detrimental impact on the brain. Much more attention needs to be paid to this important issue in the future.


In addition to the TVGH-NYMU Headache Medicine Team, this study also involves Taipei Guan Du Hospital, Taipei University of Science and Technology, and National Cheng Chi University. Finally, the research results have been published in the internationally renowned neuromedical journal “Brain.”