PMC:4536239 / 17474-26274 JSONTXT

{"project":"TEST0","denotations":[{"id":"26272681-145-151-1506049","span":{"begin":622,"end":624},"obj":"[\"17381554\"]"},{"id":"26272681-145-150-1506050","span":{"begin":772,"end":773},"obj":"[\"23091530\"]"},{"id":"26272681-148-154-1506051","span":{"begin":775,"end":777},"obj":"[\"24666014\"]"},{"id":"26272681-193-199-1506052","span":{"begin":973,"end":975},"obj":"[\"24666014\"]"},{"id":"26272681-156-161-1506053","span":{"begin":1134,"end":1135},"obj":"[\"19289218\"]"},{"id":"26272681-159-164-1506054","span":{"begin":1137,"end":1138},"obj":"[\"23091530\"]"},{"id":"26272681-162-167-1506055","span":{"begin":1140,"end":1141},"obj":"[\"11554952\", \"9051330\", \"11075840\"]"},{"id":"26272681-75-81-1506056","span":{"begin":1221,"end":1223},"obj":"[\"21631472\"]"},{"id":"26272681-150-156-1506057","span":{"begin":1376,"end":1378},"obj":"[\"21795081\", \"19725258\", \"18274269\"]"},{"id":"26272681-157-163-1506058","span":{"begin":1383,"end":1385},"obj":"[\"21826739\"]"},{"id":"26272681-161-167-1506059","span":{"begin":1387,"end":1389},"obj":"[\"18973260\"]"},{"id":"26272681-128-134-1506060","span":{"begin":1520,"end":1522},"obj":"[\"21795081\"]"},{"id":"26272681-125-131-1506061","span":{"begin":2136,"end":2138},"obj":"[\"22395798\"]"},{"id":"26272681-136-142-1506062","span":{"begin":2147,"end":2149},"obj":"[\"24840006\"]"},{"id":"26272681-95-101-1506063","span":{"begin":2998,"end":3000},"obj":"[\"15222997\"]"},{"id":"26272681-99-105-1506064","span":{"begin":3002,"end":3004},"obj":"[\"20164768\"]"},{"id":"26272681-155-161-1506065","span":{"begin":3270,"end":3272},"obj":"[\"19025553\"]"},{"id":"26272681-108-114-1506066","span":{"begin":3383,"end":3385},"obj":"[\"8489403\"]"},{"id":"26272681-112-118-1506067","span":{"begin":3387,"end":3389},"obj":"[\"19467991\"]"},{"id":"26272681-145-151-1506068","span":{"begin":3537,"end":3539},"obj":"[\"10733616\"]"},{"id":"26272681-149-155-1506069","span":{"begin":3541,"end":3543},"obj":"[\"16740411\"]"},{"id":"26272681-234-240-1506070","span":{"begin":3904,"end":3906},"obj":"[\"17566118\"]"},{"id":"26272681-170-176-1506071","span":{"begin":4739,"end":4741},"obj":"[\"20191944\"]"},{"id":"26272681-174-180-1506072","span":{"begin":4743,"end":4745},"obj":"[\"22671714\"]"},{"id":"26272681-129-135-1506073","span":{"begin":5273,"end":5275},"obj":"[\"18612765\", \"21255910\", \"22077141\", \"12858135\"]"},{"id":"26272681-102-108-1506074","span":{"begin":5677,"end":5679},"obj":"[\"24700622\"]"},{"id":"26272681-173-179-1506075","span":{"begin":6801,"end":6803},"obj":"[\"17566118\"]"},{"id":"26272681-112-118-1506076","span":{"begin":6918,"end":6920},"obj":"[\"19195928\"]"},{"id":"26272681-89-95-1506077","span":{"begin":7096,"end":7098},"obj":"[\"14592342\"]"},{"id":"26272681-227-233-1506078","span":{"begin":8059,"end":8061},"obj":"[\"1941010\"]"},{"id":"26272681-123-128-1506079","span":{"begin":8187,"end":8188},"obj":"[\"23091530\"]"},{"id":"26272681-126-131-1506080","span":{"begin":8190,"end":8191},"obj":"[\"9051330\"]"},{"id":"26272681-129-134-1506081","span":{"begin":8193,"end":8194},"obj":"[\"11075840\"]"},{"id":"26272681-132-138-1506082","span":{"begin":8196,"end":8198},"obj":"[\"17381554\"]"},{"id":"26272681-136-142-1506083","span":{"begin":8200,"end":8202},"obj":"[\"12583837\"]"}],"text":"Discussion\nThe key findings of the present study are as follows: 1) the prevalence of migraine and RLS in the Korean population were both 5.3 %; 2) RLS was more prevalent in migraineurs and subjects with non-migraine headaches when compared to non-headache control subjects in the 19–49 age groups but not in the 50–69 age groups; 3) the RLS prevalence was higher among migraineurs with \u003e1 headache attacks per month compared to migraineurs with ≤1 headache attacks per month.\nThe 1-year migraine prevalence rate (5.3 %) in the present study was somewhat lower than that previously observed in Western countries (9–25 %) [34]. However, the migraine prevalence rate in the present study was similar to those observed in previous studies in Korea and other Asian countries [3, 35]. The 1-year prevalence of migraine ranges from 4.7 % to 9.1 % in most studies of Asian countries, which is somewhat lower than that recorded in studies of European and North American countries [35]. As in most migraine epidemiological studies, migraine prevalence peaked in the 30–49 age groups and decreased in the 50–69 age groups in the present study [1, 3, 5–7]. These findings may be attributed to hormonal effects on migraine in women [36].\nRLS prevalence (5.3 %) in the present study was similar to those in previous studies in Korea and other Asian countries, ranging from 1.8 % to 8.3 % [15–17, 19, 22]. Like migraine, RLS prevalence in Asian populations was reported to be somewhat lower than that observed in Western populations [15, 24]. The wide range of RLS prevalence values reported in previous studies may be explained by differences in ethnicity, cultural background, survey methods, and assessment tools. Similar to previous epidemiological studies for RLS, the prevalence increased with age in the present study. The similarities in the prevalence of migraine and RLS between previous studies and the present study suggest that our study properly reflects the actual prevalence of each in the Korean population.\nOver the past years, a number of epidemiological and clinical studies have reported an association between migraine and RLS [23–25, 27, 28]. In the present study, a similar association between migraine and RLS was found in the form of a higher RLS prevalence among migraineurs compared to non-headache controls. We further investigated the association between migraine and RLS in the different age groups and found that migraine and RLS showed a significant association in adults aged 19–29 and aged 40–49, but not in those aged 50–69 (Table 2). Among aged 30–39, a trend towards an association was observed.\nThe different associations observed between migraine and RLS according to age could be explained by several factors. First, difference in pathophysiological mechanisms according to age in migraine and RLS may explain this lack of a significant association in the elderly population. Dopamine and iron dysregulation have been proposed to be mechanisms both for migraine and RLS [37, 38]. There were some evidences of different dopamine or iron dysregulation in migraine and RLS according to age. Iron deposition in deep brain nuclei was significant among migraineurs aged \u003c50 years than age-matched controls, but not among migraineurs aged ≥50 years [39]. Striatal D2 dopamine receptor, which was reported to be reduced in RLS, decreased with the increase of age [40, 41]. Late-onset RLS patients showed stronger association with serum iron status and less decrease in brain iron compared to early-onset RLS patients [42, 43]. Complex action of pathogenic mechanisms according to age might influence on the association between 2 disorders in elderly.\nSecond, RLS is positively associated with many medical conditions such as neuropathy, radiculopathy, renal failure, iron-deficiency anaemia, cardiac diseases, genitourinary diseases, gastrointestinal diseases, and pulmonary diseases [44]. If associated with 1 of these known contributors, RLS is considered to be secondary to the condition. Considering that the prevalence of diseases that are related to RLS could be elevated in the elderly population, it may be the case that the secondary RLS prevalence is also increased. A general increase in secondary RLS and decrease in the migraine prevalence within the elderly population could induce the observed lack of an association between migraine and RLS. We did not attempt to evaluate other medical conditions which were related to secondary RLS in the present study. As such, the results of this study have a limitation regarding secondary RLS.\nThird, some medications such as neuroleptic agents, antidepressants, opioid antagonists, and antiemetic agents can cause or exacerbate RLS and cease or relieve migraine [45, 46]. Elderly populations are more likely to take these medications and that could result in a higher RLS prevalence within the elderly group without altering the migraine prevalence. This medication-induced increase in the RLS prevalence and decrease in the migraine prevalence in the elderly group may also result in the observed lack of an association between migraine and RLS in the elderly group.\nPrevious studies regarding the association between non-migraine headaches and RLS has been reported in clinic-based setting [23, 47–51]. Some studies reported positive results regarding the association between non-migraine headaches and RLS but other studies reported negative results. Our study firstly investigated the association between non-migraine headaches and RLS in a population-based setting and found a positive result. A recent population-based study reported a positive association between RLS and multi-site body pain [52]. Further population-based studies regarding the association between non-migraine headaches and RLS would be needed to verify the association between non-migraine headaches and RLS.\nPrior to the current work, RLS prevalence data among migraineurs according to migraine/headache status were not available in a population-based study. Our study showed that RLS was more prevalent among migraineurs with 1–10 attacks per month than among migraineurs with \u003c1 attack per month (Table 3). The HIT-6 score of migraineurs with RLS was greater than that of migraineurs without RLS (59.1 ± 9.4 vs. 53.7 ± 9.2, p = 0.047). Considering headache frequency and HIT-6 score are important markers for migraine severity, these findings may corroborate the association between migraine and RLS.\nOur study has several limitations. First, we diagnosed RLS based on participants’ reports according to IRLSSG criteria and some conditions similar to RLS may be included. It is known that these criteria can mimic other conditions including nocturnal leg cramps, anxiety disorders, akathisia, meralgia paresthetica, and peripheral neuropathies [44]. To minimise the accidental inclusion of these conditions, a new diagnostic questionnaire was recently proposed [53]. It showed a high specificity but has not yet been used in an epidemiological study. Second, we did not assess the severity of RLS due to limits on the questionnaire length [54]. An attempt to model a quantitative correlation between migraine and RLS may add better insights to the association between these 2 disorders. As such, further study including the RLS severity scale would be needed to better understanding this association. Third, although this is a population-based study with a low sampling error, its statistical power for examining subgroups was limited. Thus, some results might have not reached statistical significance merely because of the limited sample numbers, especially for small groups based upon the age-band. Fourth, we did not thoroughly investigate the secondary causes of headache because this is difficult to document with the questionnaire method used in this population study. Although most of recurrent headache sufferers in general population were considered to have primary headaches rather than secondary headaches, some secondary headaches sufferers might be classified as having primary headaches [55]. The 1-year prevalences of all headaches and migraine were similar to previous studies in Korean and other Asian countries [3, 6, 7, 34, 56].\nOur study has several strengths. First, we used clustered random sampling proportional to the Korean population and the estimated sampling error was low. Second, we used the ICHD-2 and IRLSSG criteria for the diagnosis of migraine and RLS, respectively. Third, we analysed RLS prevalence according to headache frequency among migraineurs. Fourth, we assessed the association between non-migraine headaches and RLS in a population-based setting. Balancing the limitations and the strengths, we think that this study successfully assessed the association between migraine and RLS according to age."}

{"project":"2_test","denotations":[{"id":"26272681-17381554-60560342","span":{"begin":622,"end":624},"obj":"17381554"},{"id":"26272681-23091530-60560343","span":{"begin":772,"end":773},"obj":"23091530"},{"id":"26272681-24666014-60560344","span":{"begin":775,"end":777},"obj":"24666014"},{"id":"26272681-24666014-60560345","span":{"begin":973,"end":975},"obj":"24666014"},{"id":"26272681-19289218-60560346","span":{"begin":1134,"end":1135},"obj":"19289218"},{"id":"26272681-23091530-60560347","span":{"begin":1137,"end":1138},"obj":"23091530"},{"id":"26272681-11554952-60560348","span":{"begin":1140,"end":1141},"obj":"11554952"},{"id":"26272681-9051330-60560348","span":{"begin":1140,"end":1141},"obj":"9051330"},{"id":"26272681-11075840-60560348","span":{"begin":1140,"end":1141},"obj":"11075840"},{"id":"26272681-21631472-60560349","span":{"begin":1221,"end":1223},"obj":"21631472"},{"id":"26272681-21795081-60560350","span":{"begin":1376,"end":1378},"obj":"21795081"},{"id":"26272681-19725258-60560350","span":{"begin":1376,"end":1378},"obj":"19725258"},{"id":"26272681-18274269-60560350","span":{"begin":1376,"end":1378},"obj":"18274269"},{"id":"26272681-21826739-60560351","span":{"begin":1383,"end":1385},"obj":"21826739"},{"id":"26272681-18973260-60560352","span":{"begin":1387,"end":1389},"obj":"18973260"},{"id":"26272681-21795081-60560353","span":{"begin":1520,"end":1522},"obj":"21795081"},{"id":"26272681-22395798-60560354","span":{"begin":2136,"end":2138},"obj":"22395798"},{"id":"26272681-24840006-60560355","span":{"begin":2147,"end":2149},"obj":"24840006"},{"id":"26272681-15222997-60560356","span":{"begin":2998,"end":3000},"obj":"15222997"},{"id":"26272681-20164768-60560357","span":{"begin":3002,"end":3004},"obj":"20164768"},{"id":"26272681-19025553-60560358","span":{"begin":3270,"end":3272},"obj":"19025553"},{"id":"26272681-8489403-60560359","span":{"begin":3383,"end":3385},"obj":"8489403"},{"id":"26272681-19467991-60560360","span":{"begin":3387,"end":3389},"obj":"19467991"},{"id":"26272681-10733616-60560361","span":{"begin":3537,"end":3539},"obj":"10733616"},{"id":"26272681-16740411-60560362","span":{"begin":3541,"end":3543},"obj":"16740411"},{"id":"26272681-17566118-60560363","span":{"begin":3904,"end":3906},"obj":"17566118"},{"id":"26272681-20191944-60560364","span":{"begin":4739,"end":4741},"obj":"20191944"},{"id":"26272681-22671714-60560365","span":{"begin":4743,"end":4745},"obj":"22671714"},{"id":"26272681-18612765-60560366","span":{"begin":5273,"end":5275},"obj":"18612765"},{"id":"26272681-21255910-60560366","span":{"begin":5273,"end":5275},"obj":"21255910"},{"id":"26272681-22077141-60560366","span":{"begin":5273,"end":5275},"obj":"22077141"},{"id":"26272681-12858135-60560366","span":{"begin":5273,"end":5275},"obj":"12858135"},{"id":"26272681-24700622-60560367","span":{"begin":5677,"end":5679},"obj":"24700622"},{"id":"26272681-17566118-60560368","span":{"begin":6801,"end":6803},"obj":"17566118"},{"id":"26272681-19195928-60560369","span":{"begin":6918,"end":6920},"obj":"19195928"},{"id":"26272681-14592342-60560370","span":{"begin":7096,"end":7098},"obj":"14592342"},{"id":"26272681-1941010-60560371","span":{"begin":8059,"end":8061},"obj":"1941010"},{"id":"26272681-23091530-60560372","span":{"begin":8187,"end":8188},"obj":"23091530"},{"id":"26272681-9051330-60560373","span":{"begin":8190,"end":8191},"obj":"9051330"},{"id":"26272681-11075840-60560374","span":{"begin":8193,"end":8194},"obj":"11075840"},{"id":"26272681-17381554-60560375","span":{"begin":8196,"end":8198},"obj":"17381554"},{"id":"26272681-12583837-60560376","span":{"begin":8200,"end":8202},"obj":"12583837"}],"text":"Discussion\nThe key findings of the present study are as follows: 1) the prevalence of migraine and RLS in the Korean population were both 5.3 %; 2) RLS was more prevalent in migraineurs and subjects with non-migraine headaches when compared to non-headache control subjects in the 19–49 age groups but not in the 50–69 age groups; 3) the RLS prevalence was higher among migraineurs with \u003e1 headache attacks per month compared to migraineurs with ≤1 headache attacks per month.\nThe 1-year migraine prevalence rate (5.3 %) in the present study was somewhat lower than that previously observed in Western countries (9–25 %) [34]. However, the migraine prevalence rate in the present study was similar to those observed in previous studies in Korea and other Asian countries [3, 35]. The 1-year prevalence of migraine ranges from 4.7 % to 9.1 % in most studies of Asian countries, which is somewhat lower than that recorded in studies of European and North American countries [35]. As in most migraine epidemiological studies, migraine prevalence peaked in the 30–49 age groups and decreased in the 50–69 age groups in the present study [1, 3, 5–7]. These findings may be attributed to hormonal effects on migraine in women [36].\nRLS prevalence (5.3 %) in the present study was similar to those in previous studies in Korea and other Asian countries, ranging from 1.8 % to 8.3 % [15–17, 19, 22]. Like migraine, RLS prevalence in Asian populations was reported to be somewhat lower than that observed in Western populations [15, 24]. The wide range of RLS prevalence values reported in previous studies may be explained by differences in ethnicity, cultural background, survey methods, and assessment tools. Similar to previous epidemiological studies for RLS, the prevalence increased with age in the present study. The similarities in the prevalence of migraine and RLS between previous studies and the present study suggest that our study properly reflects the actual prevalence of each in the Korean population.\nOver the past years, a number of epidemiological and clinical studies have reported an association between migraine and RLS [23–25, 27, 28]. In the present study, a similar association between migraine and RLS was found in the form of a higher RLS prevalence among migraineurs compared to non-headache controls. We further investigated the association between migraine and RLS in the different age groups and found that migraine and RLS showed a significant association in adults aged 19–29 and aged 40–49, but not in those aged 50–69 (Table 2). Among aged 30–39, a trend towards an association was observed.\nThe different associations observed between migraine and RLS according to age could be explained by several factors. First, difference in pathophysiological mechanisms according to age in migraine and RLS may explain this lack of a significant association in the elderly population. Dopamine and iron dysregulation have been proposed to be mechanisms both for migraine and RLS [37, 38]. There were some evidences of different dopamine or iron dysregulation in migraine and RLS according to age. Iron deposition in deep brain nuclei was significant among migraineurs aged \u003c50 years than age-matched controls, but not among migraineurs aged ≥50 years [39]. Striatal D2 dopamine receptor, which was reported to be reduced in RLS, decreased with the increase of age [40, 41]. Late-onset RLS patients showed stronger association with serum iron status and less decrease in brain iron compared to early-onset RLS patients [42, 43]. Complex action of pathogenic mechanisms according to age might influence on the association between 2 disorders in elderly.\nSecond, RLS is positively associated with many medical conditions such as neuropathy, radiculopathy, renal failure, iron-deficiency anaemia, cardiac diseases, genitourinary diseases, gastrointestinal diseases, and pulmonary diseases [44]. If associated with 1 of these known contributors, RLS is considered to be secondary to the condition. Considering that the prevalence of diseases that are related to RLS could be elevated in the elderly population, it may be the case that the secondary RLS prevalence is also increased. A general increase in secondary RLS and decrease in the migraine prevalence within the elderly population could induce the observed lack of an association between migraine and RLS. We did not attempt to evaluate other medical conditions which were related to secondary RLS in the present study. As such, the results of this study have a limitation regarding secondary RLS.\nThird, some medications such as neuroleptic agents, antidepressants, opioid antagonists, and antiemetic agents can cause or exacerbate RLS and cease or relieve migraine [45, 46]. Elderly populations are more likely to take these medications and that could result in a higher RLS prevalence within the elderly group without altering the migraine prevalence. This medication-induced increase in the RLS prevalence and decrease in the migraine prevalence in the elderly group may also result in the observed lack of an association between migraine and RLS in the elderly group.\nPrevious studies regarding the association between non-migraine headaches and RLS has been reported in clinic-based setting [23, 47–51]. Some studies reported positive results regarding the association between non-migraine headaches and RLS but other studies reported negative results. Our study firstly investigated the association between non-migraine headaches and RLS in a population-based setting and found a positive result. A recent population-based study reported a positive association between RLS and multi-site body pain [52]. Further population-based studies regarding the association between non-migraine headaches and RLS would be needed to verify the association between non-migraine headaches and RLS.\nPrior to the current work, RLS prevalence data among migraineurs according to migraine/headache status were not available in a population-based study. Our study showed that RLS was more prevalent among migraineurs with 1–10 attacks per month than among migraineurs with \u003c1 attack per month (Table 3). The HIT-6 score of migraineurs with RLS was greater than that of migraineurs without RLS (59.1 ± 9.4 vs. 53.7 ± 9.2, p = 0.047). Considering headache frequency and HIT-6 score are important markers for migraine severity, these findings may corroborate the association between migraine and RLS.\nOur study has several limitations. First, we diagnosed RLS based on participants’ reports according to IRLSSG criteria and some conditions similar to RLS may be included. It is known that these criteria can mimic other conditions including nocturnal leg cramps, anxiety disorders, akathisia, meralgia paresthetica, and peripheral neuropathies [44]. To minimise the accidental inclusion of these conditions, a new diagnostic questionnaire was recently proposed [53]. It showed a high specificity but has not yet been used in an epidemiological study. Second, we did not assess the severity of RLS due to limits on the questionnaire length [54]. An attempt to model a quantitative correlation between migraine and RLS may add better insights to the association between these 2 disorders. As such, further study including the RLS severity scale would be needed to better understanding this association. Third, although this is a population-based study with a low sampling error, its statistical power for examining subgroups was limited. Thus, some results might have not reached statistical significance merely because of the limited sample numbers, especially for small groups based upon the age-band. Fourth, we did not thoroughly investigate the secondary causes of headache because this is difficult to document with the questionnaire method used in this population study. Although most of recurrent headache sufferers in general population were considered to have primary headaches rather than secondary headaches, some secondary headaches sufferers might be classified as having primary headaches [55]. The 1-year prevalences of all headaches and migraine were similar to previous studies in Korean and other Asian countries [3, 6, 7, 34, 56].\nOur study has several strengths. First, we used clustered random sampling proportional to the Korean population and the estimated sampling error was low. Second, we used the ICHD-2 and IRLSSG criteria for the diagnosis of migraine and RLS, respectively. Third, we analysed RLS prevalence according to headache frequency among migraineurs. Fourth, we assessed the association between non-migraine headaches and RLS in a population-based setting. Balancing the limitations and the strengths, we think that this study successfully assessed the association between migraine and RLS according to age."}