Clinical Survey On Cranial Autonomic Symptoms In Patients With Migraine

Objective:To investigate the incidence of cranial autonomic symptoms(CAS)in patients with migraine,and to compare the clinical characteristics between migraine with cranial autonomic symptoms(MwCAS)and migraine without cranial autonomic symptoms(MwoCAS),and analyze its pathophysiological mechanism.Background:CAS is not only a hallmark feature of trigeminal autonomic cephalalgias(TACs),but also a common manifestation of migraine.Some studies have confirmed that there were certain clinical differences between MwCAS and MwoCAS,and infer that the former may be related to the peripheral and central neural sensitization.At present,researches on related aspects in China’s mainland are still blank,and the mechanism of CAS in migraine needs to be further verified.Methods:This study is a single-center cross-sectional study based on a tertiary headache clinical center.We investigated 158 patients with migraine who visited the headache clinic in the Department of Neurology of Shandong Provincial Hospital from July 24,2020 to February 3,2021,collected the general information,clinical features of migraine,auxiliary examination results,scores of headache-related scales,and scores of depression and anxiety scales,and performed corresponding statistical analysis.Results:Eighty(50.6%)patients with migraine had at least one CAS.The most common CAS was forehead and facial sweating(47/158,29.7%),followed by lacrimation(32/158,20.3%),with more than 1/2(44/80,55.0%)patients having only one CAS,and some patients having a maximum of six CAS(2/80,2.5%).Compared with MwoCAS cases,there were more patients with strictly unilateral headache in MwCAS cases(38.8%vs 23.1%,P=0.033).In the comparison of pain sites,MwCAS patients had more temporal headaches(83.8%vs 70.5%,P=0.047)and parietal headaches(51.2%vs 33.3%,P=0.023).MwCAS patients had more severe headaches than MwoCAS subjects,which was indicated by the maximum value of visual analogue scale(VAS-max:8.0 vs 7.0,P=0.003).Among the common headache-accompanying symptoms,phonophobia was more common in MwCAS patients than that in MwoCAS subjects(72.5%vs 55.1%,P=0.023).Among the 16 migraine triggers investigated in this research,triggers of alcohol(27.5%vs 14.1%,P=0.03 8),strenuous exercise(17.5%vs 5.1%,P=0.014),and common cold/influenza(42.5%vs 19.2%,P=0.002)were more common in MwCAS patients than those in MwoCAS subjects,and menstrual trigger was more common in women with MwCAS than women with MwoCAS(51.0%vs 32.2%,P=0.048).The Headache Impact Test-6(HIT-6)score of MwCAS patients was higher than that of MwoCAS patients(65.0 vs 61.5,P=0.010).MwCAS patients had higher Patient Health Questionnaire-9(PHQ-9)scores than MwoCAS patients(7.0 vs 4.0,P<0.001),and those with depression(PHQ-9 score>5,70.0%vs 39.7%)or moderate to severe depression(PHQ-9 score ≥ 10,36.3%vs 15.4%)were more common(P<0.001).The Generalized Anxiety Disorder-7(GAD-7)score of MwCAS patients was higher than that of MwoCAS patients(5.0 vs 3.0,P<0.001),and those with anxiety(GAD-7 score>5,58.7%vs 32.1%)or those with moderate to severe anxiety(GAD-7 score ≥10.25.0%vs 7.7%)were also more common(P<0.001).Pulsating headache(52.5%vs 48.7%,P=0.635),motion sensitivity(52.5%vs 48.7%,P=0.635)and other indicators reflecting peripheral nerve sensitization had no statistically significant differences between the two groups.And as for cutaneous allodynia,which is used as an indicator of central nervous system sensitization,there was no statistically significant difference between the two groups(16.3%vs 10.3%,P=0.267).Conclusion:CAS is a kind of symptom very common in patients with migraine.MwCAS may be a unique subtype between migraine and cluster headache.Compared with MwoCAS patients,"side locked" headaches are more common in patients with MwCAS.Temporal and parietal headaches are more common than those with MwoCAS.The severity of headaches is more severe,and the incidence of phonophobia one of the most common headache-accompanying symptoms,is higher.Alcohol,strenuous exercise,common cold,menstruation triggers are more common among patients with MwCAS,HIT-6 score is higher,and anxiety and depression are more common and more serious.The evidence of neural sensitization in MwCAS,including peripheral and central sensitization,is not sufficient in the results of this study.It is speculated that neural sensitization may be just a concomitant phenomenon of CAS in patients with migraine,not a pathogenesis.Hypothalamus is closely related to headache,CAS,anxiety and depression,and is a key brain function area in the pathophysiology of MwCAS.This study found for the first time the relationship between CAS and anxiety and depression comorbidities in patients with migraine,which reminded clinicians to pay attention to the screening of anxiety and depression comorbidities in MwCAS patients.