| 摘要: | 頭痛是全世界最常見的疾患。依據國際頭痛疾病分類第二版(ICHD-2)，頭痛疾病可分為原發性與次發性頭痛兩大類。偏頭痛，是原發性頭痛中的主要疾患，全世界成人中的9-15%受其影響，並造成全球疾病負擔中的30%。偏頭痛有許多不同的共病症。其中，不寧腿症候群與偏頭痛的相關性也在近年受到注意。但是，不寧腿症候群對偏頭痛病患的臨床影響仍未清楚。
我們於一個頭痛門診連續收錄偏頭痛病患，以了解偏頭痛病患中合併有不寧腿症候群的比例，並與其他原發性頭痛病患比較。結果顯示偏頭痛病患合併不寧腿症候群的比例遠高於叢發性頭痛與張力性頭痛病患。此外，合併有不寧腿症候群的若偏頭痛病患，也較容易合併有頭暈、耳鳴，頸部疼痛、怕光、怕吵等症狀。而合併有不寧腿症候群的偏頭痛病患的睡眠品質較一般偏頭痛病患更差。
偏頭痛與不寧腿症候群均曾被報導與中樞鐵的代謝有關，但在研究中顯示，偏頭痛病患在腦中鐵的沉積增加，而不寧腿症候群卻是減少，在我們的研究中發現，偏頭痛病患會造成紅核鐵的沉積增加而不寧腿症候群會使鐵在紅核與黑質的鐵濃度減少。在偏頭痛合併不寧腿症候群的病患，因為兩者均為陣發性發作，兩者之間發作是否有其時間相關性仍未清楚，本研究中收錄偏頭痛合併不寧腿症候群的病患，並依其日記記錄研究其相關性，發現偏頭痛發作與不寧腿之發作有正相關性，且偏頭痛可能為不寧腿發作的誘發因子。
在基因研究中，不寧腿有19個已知的基因變異，而在偏頭痛合併不寧腿症候群的病患卻仍未知，我們經由檢測這些已知的基因變異位置，在1024位病患中發現MEIS1基因與偏頭痛合併不寧腿症候群相關。
偏頭痛與不寧腿症候群之間的相關性，經由一系列的研究，逐漸了解其可能的共病原因，基因的變異合併偏頭痛發作時造成的神經傳導物質改變，可能進一步加強不寧腿發作的機會。
此外，我們也試著了解晨間頭痛這個與睡眠呼吸中止症與偏頭痛相關的臨床常見疾患。在偏頭痛病患中，晨間頭痛相當常見且常以偏頭痛的形式發生，而且其他失眠等問題也是造成晨間頭痛的重要因素。因此，晨間頭痛並非專屬於呼吸中止症的特異症狀，臨床上應了解病患是否有偏頭痛與其他相關睡眠疾患，才能給予適當的治療。
Headache is the most prevalent disorder in the world.(1) On the basis of The International Classification of Headache Disorder, 2nd edition (ICHD-2), the headache disorders were separated into primary and secondary headache groups.(2) Migraine, the major primary headache disease, affects approximately 9-15% of the adult population in the world and accounts 30% global burden.(1) Migraine have many different comorbidities. An association between restless legs syndrome and migraine has been reported recently. However, the clinical correlates and impact of comorbidity of restless legs syndrome (RLS) are not fully described in patients with migraine.
Our research investigated the frequency of RLS in patients with migraine in a headache clinic, and the clinical impact on sleep in migraine patients comorbid with RLS, Our results demonstrated that the frequencies of RLS in patients with migraine (11.4%) was higher than in those with TTH (4.6%) or CH (2.0%) (p=0.002). In migraine patients, comorbidity with RLS was associated with higher frequencies of photophobia, phonophobia, exacerbation due to physical activities, vertigo, dizziness, tinnitus and neck pain. Migraine patients with RLS had a poorer sleep quality.
Magnetic resonance imaging studies ever showed decreased levels of brain iron in RLS but increased iron deposition in migraine. This study assessed regional brain iron levels in migraine with RLS by magnetic resonance relaxometry. Four groups patients: migraine with RLS. Migraine without RLS, idiopathic RLS and normal control were included. All of them received a multislice T2*-weighted gradient echo sequence for T2* relaxometry and serum ferritin level measurement. T2* relaxation time (T2*-RT) was measured in the substantia nigra, red nucleus, periaqueductal gray matter, putamen, caudate and globus pallidus. Longer T2*-RTs denote lower iron levels. Among these four groups, T2*-RT was significantly different in the red nucleus (migraine without RLS<migraine with RLS≒control< primary RLS: 79.0±8.6, 86.4±10.0, 84.0±7.5, 92.1±11.2ms, p<0.0001) and substantia nigra (migraine without RLS≒control<migraine with RLS< primary RLS: 75.9±8.2, 77.6±7.0, 84.3±10.2, 88.7±11.9ms p=0.0001). Migraine was associated with higher iron levels in the red nucleus; whereas, RLS was associated with lower iron levels in both the red nucleus and substantia nigra.
We also tried to clarify the temporal association between migraine and RLS attacks based on the daily diary records of migraine patients comorbid with RLS. 30 migraine patients with RLS were recruited from a headache clinic. Based on the 420 days diary without any medication use, we noted a positive temporal and severity correlation between migraine and RLS attacks in migraine patients with RLS. It is postulated that migraine and RLS may share some common mechanisms or migraine attacks might trigger the RLS symptoms.
Genetic studies have identified the 19 variants in 7 genomic region associated with idiopathic RLS. However, the genetic importance in migraine patients comorbid with RLS remains to be explored. The current study was performed to assess the role of these genetic variants in migraine patients. Migraine patients were investigated from a headache clinic. RLS was diagnosed based on essential criteria of International RLS Study Group (IRLSSG). Night-teen single nucleotide polymorphisms (SNPs) within the 7 genomic regions were selected for analysis according to the results of previous genetic reports in idiopathic RLS. All genotypes were determined blinded to the clinical characteristics. We investigated 188 migraine patients with RLS and 1024 migraine patients without RLS (262M/950F, mean age 39.4±12.6). Two SNPs encompassing the genes MEIS1 were identified associated with the RLS in migraine patients. (rs2300478, p=0.037, OR:1.31; rs12469063, p=0.024, OR:1.34 )
In addition, obstructive sleep apnea syndrome related morning headache and stroke related headache were common secondary headaches encountered by neurologists in day to day practice. The morning headache was suspected to be one of the symptoms of obstructive sleep apnea syndrome (OSAS). Our study showed that morning headache was common in habitual snorers and associated with a pervasive impairment of health related quality of life. Migrainous features were not uncommon. Not only OSAS, but migraine, insomnia and psychological distress were also important predictors for morning headache, even in snoring patients. |
