Cranial autonomic symptoms: prevalence, phenotype and laterality in migraine and two potentially new symptoms

Abstract

BackgroundWhilst cranial autonomic symptoms (CAS) are typically associated with the trigeminal autonomic cephalalgias (TAC’s), they have also been reported in migraine. Identification and understanding of these symptoms in migraine is important to ensure timely diagnosis and effective management. MethodsMigraineurs seen within our tertiary headache service between 2014-2018 ( n =340): cohort one, and a separate cohort of headache patients seen between 2014-May 2021 reporting voice change and/or throat swelling as CAS were selected ( n =64); cohort two. We examined, as a service evaluation, our records regarding age, sex, diagnosis, headache and CAS frequency and laterality as acquired from the first consultation, during which a detailed headache history is taken by a trained physician. ResultsCohort 1: Mean age 43 (range 14-94, SD 15). The most common diagnosis was chronic migraine (78%). Median monthly headache frequency was 26 days (IQR 15-75). At least one CAS was reported in 74%, with a median of two (IQR 0-3). The most common were nasal congestion (32%), lacrimation (31%) and aural fullness (25%). Most patients reported unilateral headache (80%) and strictly unilateral CAS (64%). There was a positive association between headache and CAS laterality (ꭓ 2 1 = 20.7, P < 0.001), with a positive correlation between baseline headache frequency and number of CAS reported ( r = 0.11, P = 0.047). Cohort two: mean age 49 (range 23-83, SD 14). Diagnoses were chronic migraine (50%), chronic cluster headache (11%), undifferentiated continuous lateralised headache (9%), SUNCT/SUNA (8%), hemicrania continua (8%), episodic migraine (8%), episodic cluster headache (3%) and trigeminal neuropathies (3%). Most (89%) described trigeminal distribution pain; 25% involving all three divisions. Throat swelling was reported by 54, voice change by 17, and both by 7. The most common CAS reported were lacrimation ( n = 47), facial swelling ( n = 45) and rhinorrhoea ( n = 37). There was significant agreement between the co-reporting of throat swelling (ꭓ 2 1 = 7.59, P = 0.013) and voice change (ꭓ 2 1 = 6.49, P = 0.02) with aural fullness. ConclusionsCAS are common in migraine, are associated with increasing headache frequency and tend to co-lateralise with headache. Voice change and throat swelling should be recognized as possible parasympathetically-mediated CAS. They may be co-associated and associated with aural fullness, suggesting a broadly somatotopic 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.…”

“…The prevalence in women is confirmed and chronic migraine has often a higher prevalence of CAS than episodic migraine. In Table 2 [4,6,8,11,15,17,18] and [22][23][24][25][26], the clinical series of adult migraineurs are summarized.…”

“…The diagnostic criteria of the IHS classification [2], used in the TACs, identify the following signs/symptoms as an expression of the autonomic trigeminal reflex: lacrimation, eyelid edema, conjunctival injection, nasal congestion, rhinorrhea, face and forehead sweating, eyelid miosis and ptosis. These CAS are those usually searched in studies on migraines, however several authors have researched and proposed other symptoms in consideration of the parasympathetic/sympathetic innervation involved in the head, which are frequently present and often associated with others [12][13][14]26]. Those reported are red ear, facial flushing, foreign body sensation in the eye, aura fullness, and most recently throat swelling and voice change.…”

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

“…We have included the symptom eyelid oedema in the proposed diagnostic criteria based on the literature, since eyelid oedema is a well described autonomic symptom among patients with migraine (Supplementary Table 3) (3 –5,7,10,15 –23), although, we did not have data on this symptom in our cohort. We believe that the diagnostic criteria suggested here are valid and useful.…”

“…To identify dominant patterns of clusters, we performed the clustering analysis 50 times. We identified 15 studies on migraine with CAS, which included a population prevalence of migraine with CAS (3 –7,10,15 –23). Data on the population prevalence of having one or more CAS and the population prevalence of individual CAS items were extracted from the articles and reported in this study for comparison with the population prevalences in this study.…”