Population-based prevalence of cranial autonomic symptoms in migraine and proposed diagnostic appendix criteria

Abstract

Background Migraine with cranial autonomic symptoms is well described in the literature, but its prevalence in previous studies varies enormously. A precise estimate of the prevalence in a population-based material is important because migraine with cranial autonomic symptoms might represent an endophenotype, in which genetic and pathophysiological features differ from those without cranial autonomic features. The aim of the present study, therefore, was to estimate the prevalence in a big population-based sample using both questionnaire-based diagnosis (N = 12,620) and interview-based diagnosis (N = 302). We validate questionnaire-based diagnosis of migraine with cranial autonomic symptoms and develop the first diagnostic criteria for future research of this possible endophenotype. Methods The Danish Blood Donor Study included 127,802 persons who all received a migraine diagnostic questionnaire. Participants who had answered the diagnostic questionnaire constituted the Danish Migraine Population Cohort (N = 62,677) of whom 12,620 had migraine. The diagnostic migraine questionnaire included questions about the following cranial autonomic symptoms: Facial/forehead sweating, lacrimation, ptosis, conjunctival injection, rhinorrhea, nasal congestion, and miosis. Validation was performed by a follow-up semi-structured, purpose-built interview of 302 participants with migraine, where detailed questions were asked to ascertain the validity of the symptoms. Results The questionnaire-based prevalences of one, respectively two cranial autonomic symptoms were 57% and 31%. The semi-structured interview-based prevalences of one, respectively two symptoms were 44% and 22%. The most common symptoms were facial/forehead sweating (39%) and lacrimation (24%). The specificity of the questionnaire was 80% and the sensitivity was 68%. Correlation analysis showed a weak correlation between symptoms ranging from 0.07 – 0.41, and no clear clustering of symptoms was detected. We suggest the first diagnostic appendix criteria for genetic and epidemiological studies and tighter criteria for clinical and pathophysiological studies. We encourage further studies of severity and consistency of symptoms. Conclusion Migraine with cranial autonomic symptoms is prevalent in the general population. Suggested diagnostic appendix criteria are important for future studies of this possible migraine endophenotype.

Cranial Autonomic Symptoms and Migraine: What Relationship and What Meaning? A Review

“…These data [7,28] confirmes those coming from the clinical series [4][5][6][8][9][10][11][12][13][14][15][17][18][19][20][21][22][23][24][25][26][27]. Further the prevalence may be sometimes undervalued because some researches only look for the unilateral CAS while in clinical series they may be also present bilaterally as well as migraine pain may have bilateral lateralization.…”

“…and functional areas of the autonomic control of the head (secretory, vasodilatory, sympathetic, etc. ), the studies carried out fail to highlight a mode of association between them or a tendency to form specific clusters even if some authors favor these hypotheses [13,20] while the most recent Danish study [28] does not support these conclusions. "-", not reported; CAS, unilateral Cranial Autonomic Symptoms; "*" percentage value referred to the total of cases; "°" percentage value referred to set Migraine CAS+.…”

“…In addition, CAS were more frequently associated with unilateral headache and more severe pain attack, than those who didin't have these symptoms. Very recently the Danish group's study [28], conducted on population, reported prevalence of 57% of CAS (at least one CAS) and 31% with two or more CAS by a questionnaire while the prevalence reduced to 44% of one CAS and 22% with two or more CAS by semi-structured interview. The facial/forehead sweating was the most common symptom (39%) followed by lacrimation (24%).…”

“…Further the prevalence may be sometimes undervalued because some researches only look for the unilateral CAS while in clinical series they may be also present bilaterally as well as migraine pain may have bilateral lateralization. In Table 1 the studies [7,16,28] on population are summarized.…”

“…In these studies that report the intensity of CAS in the course of a migraine attack, it is usually referred to as milder than that found in individuals with cluster headaches [8,28], however this is a fact that must be confirmed because it may be due to several reasons, see the retrospective nature of the studies.…”