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Year : 2023  |  Volume : 40  |  Issue : 1  |  Page : 15-19

Gray zones in the trigeminal autonomic cephalalgias

Department of Neurology, Mersin University School of Medicine, Mersin, Turkey

Date of Submission08-Jun-2022
Date of Decision07-Dec-2022
Date of Acceptance07-Dec-2022
Date of Web Publication29-Mar-2023

Correspondence Address:
Nevra Oksuz
Mersin Üniversite Hastanesi, Çiftlik Köy Kampüsü, Kat: 1 Yetişkin Nöroloji Polikliniği Yenişehir, Mersin
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/nsn.nsn_108_22

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Background: Limited data are available about the importance of migrainous features of the trigeminal autonomic cephalalgias (TACs). Methods: We enrolled 99 patients with TACs including 71 cluster headaches, 11 with short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing, 10 with paroxysmal hemicrania, and seven with hemicrania continua. The presence of diagnostic migraine criteria such as throbbing headache, nausea and/or vomiting, photophobia, phonophobia, and aggravation by physical activity was questioned in these patients as well as autonomic features. Furthermore, supportive features of migraine including motion sickness, atopy and allergy, exacerbation during menstrual periods, irregular sleep, dizziness, and family history of any primary headache were noted. Results: The most common cranial autonomic symptom was lacrimation (87.9%) and the most common migrainous features were throbbing headache (51.5%), phonophobia (41.4%), nausea (39.4%), and photophobia (34.3%). Family history of any primary headache (25.3%) and atopy and allergy (13.1%) was the most common supportive features. Conclusion: We found higher percentages of migrainous features in patients with TACs; phonophobia, throbbing headache, and nausea frequently accompanied TACs. Aggravation by physical activity, which is one of the diagnostic migraine criteria, and motion sickness, which is one of the supportive features of migraine, were much lower in patients with TAC compared with migraineurs.

Keywords: Autonomic symptoms, migraine, migrainous features, trigeminal autonomic cephalalgias

How to cite this article:
Oksuz N, Özge A. Gray zones in the trigeminal autonomic cephalalgias. Neurol Sci Neurophysiol 2023;40:15-9

How to cite this URL:
Oksuz N, Özge A. Gray zones in the trigeminal autonomic cephalalgias. Neurol Sci Neurophysiol [serial online] 2023 [cited 2023 Jun 10];40:15-9. Available from: http://www.nsnjournal.org/text.asp?2023/40/1/15/372779

  Introduction Top

Trigeminal autonomic cephalalgias (TACs) are a group of five primary headache disorders, characterized by unilateral trigeminal distribution pain and prominent ipsilateral autonomic features. TACs include cluster headaches (CHs), paroxysmal hemicrania (PH), hemicrania continua (HC), short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing (SUNCT), and short-lasting unilateral neuralgiform headache attacks with cranial autonomic symptoms (CASs).[1] The exact prevalence of TACs cannot be determined clearly due to difficulties in diagnosing and their rarity. The prevalence of even CH, which is the most common TAC, has been reported as 0.1% in studies, and it is quite rare.[2] According to the International Classification of Headache Disorders 3 (ICHD-3), the diagnostic criteria of these rare syndromes are clear but gray zones are frequently encountered in our clinical practice.[3] Similar to TACs, autonomic symptoms have been reported in some patients with migraine, and some migrainous features have been reported in TACs.[4],[5] The ICHD-3 makes a clear distinction between these two entities, but the common features shared with migraine can cause difficulties in the diagnosis of TACs. Data obtained from studies and the patients we examined also suggest that they exhibit common features. Therefore, it is important to determine the migrainous features, especially in cases with subtle autonomic features and in patients with fewer attacks. For this purpose, we investigated the prevalence of these features in patients with TACs evaluated in our clinic. It is important to identify these entities in practice because treatment differs based on the right diagnosis.

  Methods Top

Study population and data collection

The data set was composed using the Turkish headache database, Mersin Branch. All our patients' information was in this database in detail.[6] The study was approved by the local Ethics Committee of Mersin University (MEU., October 20, 2008). Informed consent was obtained from all participants. Within the scope of the Headache Outpatient Clinic of Mersin University Neurology Department, 312 patients with TACs were enrolled in the study. Thirty-five patients with underlying secondary causes and 16 patients aged under 18 years were excluded from the study. Patients with regular follow-ups and complete contact information were included in our study. In this context, 152 patients were called by phone, and 99 patients who agreed to come to the outpatient clinic for a new examination were included in the study. A total of 71 patients with CH, 11 with SUNCT, 10 with PH, and seven with HC were enrolled in our study. Headache diagnosis was based on the ICHD-3 (Headache Classification Committee, 2018). The participants completed a questionnaire about their headache characteristics and possible supportive features of migraine. Age at onset, headache duration (how long the patient has had a headache, not attack duration), headache frequency, localization of pain, visual analog scale (VAS), and medical and family history was noted for all patients in face-to-face interviews. Subjects aged younger than 18 years were not included in the study.

Statistical analysis

The IBM SPSS 21 (IBM) program was used for data entry and analysis. Results are given as 95% confidence intervals and P < 0.05 was accepted as significant. The Shapiro–Wilk test was used to assess the normality of continuous variables. One-way analysis of variance was used for variables that conformed to a normal distribution, and the Kruskal–Wallis test was used for those that did not. The Chi-square test was used in the analysis of categorical data.

  Results Top

Demographic and headache characteristics of patients and autonomic features are summarized below [Table 1]. A total of 99 patients, 55 men (55.6%) and 44 women (44.4%), were included in the study, with a mean (standard deviation) age of 43.74 years. Because the majority of the patients had CH, there was a male predominance (P = 0.047). Group I (CH) consisted of 71 patients, group II (SUNCT) comprised 11 patients, group III (PH) consisted of 10 patients, and group IV (HC) was constituted of seven patients. The proportion of patients reporting at least one ipsilateral CAS was 92.9%. Lacrimation (87.9%) and eye redness (64.6%) were the most common autonomic features among the patients. VAS scores did not differ between the groups and the mean score was 8.46 (P = 0.552). Throbbing headache was the most common, followed by piercing and shock-like headaches, respectively (P = 0.001). Smoking, among the triggers, showed a statistically significant difference between the groups (P = 0.001), and the others did not. However, the most common triggers were alcohol, stress, and irregular sleep.
Table 1: Clinical and demographic characteristics of the study patients

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Migrainous features and possible supporters in TACs are summarized below [Table 2]. The proportion of patients reporting at least one diagnostic criterion of migraine (aggravation by physical activity, nausea, vomiting, photophobia, and phonophobia) was 70.7%. The most common were phonophobia (41.4%), nausea (39.4%), and photophobia (34.3%). The presence of a family history of any primary headache disorder (25.3%) and atopy and allergy (13.1%) were also frequent. In our study group, the number of patients with phonophobia or photophobia was 50 (50.5%), and the number of patients with both phonophobia and photophobia was 16 (22.5%). There were also 13 (18.3%) patients with both nausea and vomiting. Although allodynia did not differ between the groups, the rate was high in all groups with an average of 42.4%.
Table 2: Migrainous features and supporters in patients with trigeminal autonomic cephalalgias

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  Discussion Top

Although there are many studies in the literature on the presence of autonomic symptoms in migraine, there are insufficient studies on migrainous features in TACs. We know that migrainous features are also seen in TACs because autonomic symptoms can be seen in migraine.[4],[5],[7] In our study, we found that migrainous features accompanied TACs to a substantial extent. Concerning migrainous features in TACs, phonophobia or photophobia was 50.5% and both nausea and vomiting were 18.3%. Similarly, in the study of Schürks et al., these rates were found as 61.2% and 27.8%, respectively.[8] In some studies, the presence of photophobia or phonophobia was found to be quite high (73.2%).[9] In our study, it was remarkable that 70.7% of the patients reported at least one diagnostic criterion of migraine. Similarly, high rates (varying from 17% to 90% with a mean prevalence of 60%) were reported in studies conducted on HC.[10]

In addition to migrainous features, features such as the presence of a family history of any primary headache (25.3%) and atopy and allergy (13.1%) that would support migraine were also found frequently in these patients. Motion sickness is another common symptom reported by patients with migraine (occurring in approximately 50% of migraineurs), but in our study group, only 11.1% of the patients reported motion sickness. Although it is the most common vestibular symptom, the pathophysiologic basis is not yet understood, and it is thought to be related to interactions between pain and vestibular pathways.[11] The pain was mostly throbbing (51.5%), followed by piercing or stabbing (21.2%) and shock-like (14.1%) pain in patients with TACs. Blunt (7.1%) and pressing (5.1%) type headaches were less common. As is known, the rate of throbbing character in migraine is much higher (over 80%) and is associated with the activation of meningeal nociceptors at the origin of the trigeminovascular system.[4],[12] There are bidirectional connections between the posterior hypothalamus, the primary affected area in TACs, and brainstem nuclei, and these descending connections are thought to regulate brainstem pain processing.[13]

Previous studies showed that CH pain, in particular, is made better with movement in most cases. In our study, in line with the literature, exacerbation with physical activity was described in only 21 (21.2%) patients. In migraineurs, this rate is much higher (85%).[9],[14],[15] In previous studies, allodynia has been reported in up to 62% of patients with migraine, but it was also found to be considerably higher (42.4%) in our study group.[16] This is thought to be a clinical feature of peripheral or central sensitization.[17] The rate of current smokers in our study group was also high (49.5%), in line with the literature.[8] On the other hand, this rate was reported to be lower in patients with migraine (35.7%).[18]

In our study, patients reporting at least one CAS was 92.9% and patients reporting more than one CAS was 88.9%. This rate (more than one CAS) was 15% in migraine.[19] A high proportion of patients with TAC (64.6%) reported at least one accompanying symptom (phonophobia, photophobia, nausea, or vomiting) typically described in patients with migraine attacks, but migrainous features in TACs were not so common. Similarly, in the study of Gaul et al., this rate was found to be high, but only episodic and chronic CH were included in that study. Furthermore, in the same study, 99.5% of patients reported a minimum of one CAS, but the study did not include TACs other than CH.[9]

Migraine and TACs are considered two different entities with different pathophysiologies. However, in our clinical practice, it may not be possible to clearly distinguish these headaches due to overlapping headache characteristics. Although hypothalamic involvement has been shown as the main underlying mechanism in TACs, other brain regions such as cingulate areas, the temporal and frontal cortex, insula, basal ganglia, and thalamus may also be affected. Brainstem and dorsal pontine activity often indicate migraine attacks but these commonly shared features suggest that there may be a common pathway in the development of autonomic symptoms and functional alterations in hypothalamic or brainstem circuits.[20] Considering that the pain matrix is a wide network, it was thought that many peripheral and central structures might play a role in the pathophysiology of migraine-like features in TACs. Until now, the studies in the literature are mostly on CH; there are no studies on migrainous features in all trigeminal autonomic headaches. Accordingly, we investigated the frequency of migrainous features in TACs including patients with SUNCT, PH, and HC, as well as patients with CH increases the importance of our study. In addition to the migraine diagnostic criteria, investigating the frequency of symptoms such as motion sickness, atopy, and allergy accompanying migraine also makes our study important. The main limitation of our study was the rarity of other types of TACs except for CH and the majority of the patients being in the CH group. Symptoms such as exacerbation during menstrual periods could not be evaluated due to the predominance of CH. Another limitation of our study was the fact osmophobia, which we know frequently accompanies migraine, was not evaluated.

  Conclusion Top

In our study, we found that accompanying migraine features are common in TACs and may lead to misdiagnosis. TACs and migraine may share some common pathophysiologic processes as reflected in the clinical features that are not yet clearly understood. Identification of these features is essential for physicians to make an accurate diagnosis and obtain accurate prevalence rates. In this respect, future studies that are conducted by expanding the number of patients may provide new contributions.


We thank the Global Migraine and Pain Society for providing access to the information on www. globalmigraine-paindataset.com.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

  References Top

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Togha M, Jafari E, Moosavian A, Farbod A, Ariyanfar S, Farham F. Cranial autonomic symptoms in episodic and chronic migraine: A cross sectional study in Iran. BMC Neurol 2021;21:493.  Back to cited text no. 5
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  [Table 1], [Table 2]


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