This study showed that migraine is frequently co-morbid with RLS. However, we did not find any effect of potential factors like sleep disturbance, severity of RLS, family history and depression.
Earlier studies conducted in headache patients reported that RLS is more frequent in migraineurs as compared with population prevalence.[5
] Similarly, in the present study, the prevalence of migraine, and particularly migraine without aura, was higher in RLS patients as compared with the general population. This result could be a spurious finding as in previous studies as well as in the present study, as the samples were taken from the clinic. Earlier studies have shown that prevalence of headache is definitely higher in the clinical sample as compared with a population-based sample.[18
] Hence, a population-based study assessing migraine and RLS will throw more light on this issue.
Earlier studies had suggested that migraine and RLS might have a common neurobiological factor.[10
] Migraineurs with dopaminergic premonitory symptoms, e.g. yawning, somnolence, food craving, etc., were found to have higher chances of harboring RLS.[3
] d’Onafrio et al
] also supported the dopaminergic hypothesis as an underlying factor. Dopamine deficiency has been implicated in the pathogenesis of RLS, and dopamine agonists have been found to be effective in the treatment of RLS.[21
] On the other hand, migraineurs were thought to have an increased activation of dopaminergic neurotransmission, and dopamine antagonists were found to be an effective antimigraine therapy.[23
] These views are actually antagonistic and refute the dopaminergic link between the two disorders in question. However, recent literature suggests that the role of dopamine is not as straight-forward as always thought in migraine. Direct application of dopamine had been found to block firing of the trigemino-vascular system and to show antinociceptive effect.[24
] Further, the sites implicated in the dopamine hypothesis of both disorders are dissimilar – nigro-striatal tract in RLS while ventral tegmental area and hypothalamus in migraine.[21
] In short, multiple dopaminergic receptors in the brain at different levels and in different areas of the brain were implicated in RLS and migraine. Hence, further studies at the molecular level are required before we confirm a direct dopaminergic link between migraine and RLS.
Secondly, if not the dopamine, then sleep disturbance might be another causative link between RLS and migraine.[10
] Sleep disturbance is inherent to RLS, and depends upon the severity, duration and frequency of symptoms.[26
] Migraine was also known to be associated with sleep disturbance.[27
] In addition, recent studies had shown that sleep disturbances lead to chronification of headache, and chronic headache patients often show co-morbid sleep disorders.[28
] Earlier studies in migraine-RLS plus subjects had reported a higher prevalence of sleep disturbances in these subjects.[5
] On the other hand, at least one other study conducted in migraineurs did not find any difference in the sleep quality between migraine-RLS plus and migraine without RLS subjects.[3
] We think that the difference could be attributed to sample selection. Earlier studies included patients from headache clinics; thus, they reduced the chances of finding disturbance in sleep, except in cases of frequent or chronic headache. On the contrary, we recruited subjects primarily presenting with sleep disturbance and hence, all of them had difficulties with sleep initiation or maintenance; hence, the effect of sleep disturbance was minimized on the causation of headache. Also, this could be one reason why we did not find a significant difference in sleep disturbance between “RLS with migraine” and “RLS without migraine” groups.
Thirdly, an association has been reported between migraine, depression and RLS. RLS is commonly associated with depressive disorder.[15
] Migraine and depression had been reported to co-occur in a number of patients, and psychiatric morbidity was considered to worsen the course of migraine through various mechanisms.[7
] However, Cologne et al
] did not find any difference in the prevalence of depression between “migraine with RLS” subjects and RLS subjects without headache. Depression, migraine and RLS, all three, had shown an association with the dopaminergic neurotransmission; however, the exact molecular pathway is yet to be found.[21
Lastly, we hypothesized that a positive family history of RLS would be associated with increased chances of having migraine, as reported in a previous study.[7
] However, we failed to find any difference in the family history of RLS in subjects with and without migraine. This finding needs to be replicated as we cannot exclude the potential recall bias despite our best efforts to establish a family history of RLS. Or, it is also possible that there is no genetic or biological link between RLS and migraine. As already discussed earlier, a well-planned population-based study will be able throw more light on this issue.
Like any other scientific study, the present study also had some methodological limitations: First, the sample was taken from a clinic and was not population based. Secondly, RLS, migraine, sleep disturbance and depression, are all functional disorders. Hence, we did not have any laboratory evidence of the problem. Thirdly, we could not reliably gather the data regarding total duration of headache, time since worsening, etc. as most of the subjects reported onset of headache during adolescence, and they were not able to provide the exact details regarding temporal change in symptoms of headaches, which could help us in categorization of the headache. Fourth, a recall bias cannot be excluded, especially regarding the family history of RLS. Fifth, we could not reliably establish the family history of headache in these subjects; hence, this was not included in the analysis. Still, this is the first study to examine the relationship between headache and RLS in RLS subjects. Strict exclusion criteria assured inclusion of idiopathic RLS only.
In conclusion, migraine is frequently associated with RLS in the clinical population. However, the potential underlying mechanisms in a population-based sample need to be explored for providing better care to these patients.