Cranial Autonomic Symptoms in Migraine Patient Presenting in the Department of Neurology of a Tertiary Care Center: A Descriptive Cross-sectional Study.

INTRODUCTION: Cranial autonomic symptoms (CAS) are typically associated with trigeminal autonomic cephalagias (TACs) and are also a part of TACs' diagnostic criteria. However, they have also been commonly reported in migraine patients. This study aimed to find the prevalence of CAS in Migraine patients who presented to the Department of Neurology in a tertiary care center. METHODS: This descriptive cross-sectional study was conducted among migraine patients who visited the Department of Neurology of a tertiary care center from September 2023 to December 2023 after obtaining ethical approval from the Institutional Review Committee. Neurologists used ICHD-3 beta criteria to diagnose migraine and the presence of cranial autonomic symptoms in patients with migraine through face-to-face interviews using a structured questionnaire. A convenience sampling method was used. The point estimate was calculated at a 95% Confidence Interval. RESULTS: Among 119 migraine patients, at least one cranial autonomic symptom was seen in 76 (63.86%) (55.23-72.51, at 95% Confidence Interval). Lacrimation 34 (44.73%) and conjunctival injection 27 (35.52%) were the two most commonly reported symptoms. Bilateral CAS was present in 60 (78.94%) patients. CONCLUSIONS: The prevalence of at least one CAS in migraine patients was found to be similar to other studies done in similar settings.

The Role of the Autonomic Nervous System in Epilepsy and Migraine: A Narrative Review.

Autonomic symptoms may be local and general clinical manifestations of both epilepsy and migraine caused by the dysfunction of brain areas best known as the central autonomic network. Despite their prevalence, autonomic signs are often misdiagnosed and their treatment is undervalued. This review aims to describe the autonomic manifestations reported during seizures and migraineur attacks according to their presentation, focusing on the role of the central autonomic network (CAN) and on the parasympathetic outflow that often-induced cranial autonomic symptoms (CAS) during migraineur attacks. Further, our purpose is to analyze the pathophysiological meanings and whether their presence influences the prognosis and therapy of these disorders.

Extended Phenotyping of Migraine in Children: A Cross-Sectional Study in a Specialist Children's Headache Clinic.

BACKGROUND: The pediatric migraine phenotype may exhibit differences to adults, leading to diagnostic challenges. We aimed to perform a cross-sectional systematic study to characterize the extended phenotype of pediatric migraine. METHODS: New migraine patients presenting to the Children's Headache Clinic were included (n = 105). Data were collected via a detailed symptom questionnaire at the first clinical encounter and were analyzed using descriptive statistics, Cohen kappa (k), Spearman correlation (ρ), and Poisson and binomial logistic regression models within SPSS. RESULTS: Patients were 65% female and aged five to 17 years (median 14, interquartile range [IQR] 11 to 15), with a mean disease duration of 4.7 years (S.D. 2.8). Monthly headache frequency was 1 to 30 days (median 30, IQR 12 to 30). Attack duration varied between 2 and 168 hours (median 12, IQR 5 to 72). The majority (81%) experienced bilateral headache. Premonitory symptoms (PS) were reported by 93% (range 0 to 7; mood change and tiredness most commonly), cranial autonomic symptoms (CAS) by 58% (range 0 to 6; pallor and lacrimation most commonly), and premonitory CAS by 23%. Vertigo (53%) and allodynia (16%) were present. The laterality of headache and CAS showed agreement (k = 0.5, P < 0.001). For every year of disease duration, 1.07 times more PS were reported (95% confidence interval [CI] 1.03 to 1.12, P < 0.001). The number of CAS (odds ratio 2.13, 95% CI 1.2 to 3.8, P = 0.01) significantly predicted allodynia. CONCLUSIONS: Children display a more enriched PS phenotype with disease chronicity. CAS and allodynia may be markers of central sensitization with shared neurobiological mechanisms in the absence of peripheral nociceptor activation.

The Prevalence and Clinical Phenotypes of Cluster Headache in Relation with Latitude.

PURPOSE OF REVIEW: Previous studies have indicated a possible link between the prevalence of cluster headache (CH) and sunlight exposure. However, this theory has yet to be tested systemically. In this article, we aim to examine how latitude affects the prevalence and phenotypes of CH. RECENT FINDINGS: To our knowledge, there is by far no article describing the effect of latitude on disease phenotype; thus, we performed a literature review. We noted positive effects of latitude on 1-year prevalence, the proportion of chronic CH, and the proportion of miosis and/or ptosis. Latitude may affect the phenotypic presentations of cluster headache, probably partially mediated via temperature and sunlight variations. Still, other factors, such as environmental exposure to smoking and the genetic difference between the Eastern and Western populations, may participate in the pathogenesis and clinical manifestations of CH.

Cranial Autonomic Symptoms and Neck Pain in Differential Diagnosis of Migraine.

Cranial autonomic symptoms and neck pain have been reported to be highly prevalent in migraine, although they are rarely considered in clinical evaluation. The aim of this review is to focus on the prevalence, pathophysiology, and clinical characteristics of these two symptoms, and their importance in the differential diagnosis between migraines and other headaches. The most common cranial autonomic symptoms are aural fullness, lacrimation, facial/forehead sweating, and conjunctival injection. Migraineurs experiencing cranial autonomic symptoms are more likely to have more severe, frequent, and longer attacks, as well as higher rates of photophobia, phonophobia, osmophobia, and allodynia. Cranial autonomic symptoms occur due to the activation of the trigeminal autonomic reflex, and the differential diagnosis with cluster headaches can be challenging. Neck pain can be part of the migraine prodromal symptoms or act as a trigger for a migraine attack. The prevalence of neck pain correlates with headache frequency and is associated with treatment resistance and greater disability. The convergence between upper cervical and trigeminal nociception via the trigeminal nucleus caudalis is the likely mechanism for neck pain in migraine. The recognition of cranial autonomic symptoms and neck pain as potential migraine features is important because they often contribute to the misdiagnosis of cervicogenic problems, tension-type headache, cluster headache, and rhinosinusitis in migraine patients, delaying appropriate attack and disease management.

Comorbidity or combination - more evidence for cluster-migraine?

BACKGROUND: While migraine and cluster headache share some clinical features and therapies, they differ considerably in the frequency and duration of the headache, as well as the inter-attack, or inter-bout, pathophysiology. Neither is fully understood, with their shared pathways being of interest. FINDINGS: Five patients for whom it was difficult to distinguish migraine from cluster headache are presented. They had aspects of their phenotypes, which could be attributed to both disorders. Each patient was thoroughly examined, excluding secondary causes of headache, and had been treated with a number of medicines. CONCLUSION: A correct diagnosis is key to the appropriate treatment approach. Especially, if treatment is not successful for the suspected headache type, and enlargement of the diagnostic and therapeutic range, respectively, should be evaluated. Whether in such settings there is shared or different pathophysiology can only be speculated upon.

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

Cranial autonomic symptoms (CAS) have been usually associated with trigeminal autonomic cephalalgias (TAC's), however in the last few years several reports in adult and pediatric population have reported important presence of the CAS in migraine. Also several evidences experimentally show that the increased parasympathetic outflow can enhance the sensitization of nociceptive receptors involved in migraine. The presence of CAS suggests an activation of the trigeminal-autonomic reflex, probably related to an over-activation of the trigeminal afferent arm. For these reasons identifing and understanding of these symptoms in migraine may be important to help in the diagnosis and effective management. The purpose of this review is, analyzing the literature data, to discuss the prevalence of these CAS in migraine, the pathophysiological meaning in the pathogenesis of migraine and whether their presence influences the prognosis and therapy of migraine in adult and pediatric age.

Debate: Are cluster headache and migraine distinct headache disorders?

Cluster headache and migraine are regarded as distinct primary headaches. While cluster headache and migraine differ in multiple aspects such as gender-related and headache specific features (e.g., attack duration and frequency), both show clinical similarities in trigger factors (e.g., alcohol) and treatment response (e.g., triptans). Here, we review the similarities and differences in anatomy and pathophysiology that underlie cluster headache and migraine, discuss whether cluster headache and migraine should indeed be considered as two distinct primary headaches, and propose recommendations for future studies. Video recording of the debate held at the 1st International Conference on Advances in Migraine Sciences (ICAMS 2022, Copenhagen, Denmark) is available at https://www.youtube.com/watch?v=uUimmnDVTTE .

Predictors of response to anti-CGRP monoclonal antibodies: a 24-week, multicenter, prospective study on 864 migraine patients.

BACKGROUND AND OBJECTIVES: The identification of predictors of response to antiCGRP mAbs could favor tailored therapies and personalized treatment plans. This study is aimed at investigating predictors of ≥ 50%, ≥ 75% and 100% response at 24 weeks in patients with high-frequency episodic (HFEM: 8-14 days/month) or chronic migraine (CM). METHODS: This is a large, multicenter, cohort, real-life study. We considered all consecutive adult patients affected by HFEM or CM who were prescribed antiCGRP mAbs for ≥ 24 weeks in 20 headache centers. Patients were interviewed face-to-face using a shared semi-structured questionnaire carefully exploring socio-demographic and clinical characteristics. Patients received subcutaneous erenumab (70 mg or140 mg, monthly), galcanezumab (120 mg monthly, following a 240 mg loading dose), or fremanezumab (225 mg, monthly or 675 mg, quarterly) according to drug market availability, physician's choice, or patient's preference. The primary endpoint of the study was the assessment of ≥ 50% response predictors at 24 weeks. Secondary endpoints included ≥ 75% and 100% response predictors at 24 weeks. RESULTS: Eight hundred sixty-four migraine patients had been treated with antiCGRP mAbs for ≥ 24 weeks (erenumab: 639 pts; galcanezumab: 173 pts; fremanezumab: 55 pts). The ≥50% response (primary endpoint) in HFEM was positively associated with unilateral pain (UP) + unilateral cranial autonomic symptoms (UAs) (OR:4.23, 95%CI:1.57-11.4; p = 0.004), while in CM was positively associated with UAs (OR:1.49, 95%CI:1.05-2.11; p = 0.026), UP + UAs (OR:1.90, 95%CI:1.15-3.16; p = 0.012), UP + allodynia (OR:1.71, 95%CI:1.04-2.83; p = 0.034), and negatively associated with obesity (OR:0.21, 95%CI:0.07-0.64; p = 0.006). The 75% response (secondary endpoint) was positively associated with UP + UAs in HFEM (OR:3.44, 95%CI:1.42-8.31; p = 0.006) and with UP + UAs (OR:1.78, 95%CI:1.14-2.80; p = 0.012) and UP + allodynia (OR:1.92, 95%CI:1.22-3.06; p = 0.005) in CM. No predictor of 100% response emerged in patients with HFEM or CM. CONCLUSIONS: A critical evaluation of headache characteristics indicating peripheral or central sensitization may help in predicting responsiveness to antiCGRP mAbs in HFEM and CM. A more precise pain profiling may represent a steppingstone for a mechanism-based approach and personalized treatment of migraine with compounds targeting specific molecular mechanisms.

Cranial Autonomic Symptoms in Migraine: An Observational Study.

Objective: Our aim was to observe frequency of cranial autonomic symptoms (CAS) in migraineurs (primary) and its relation with laterality of headache or other factors, if any. Background: Migraine episodes have headaches with or without aura, and sometimes associated with systemic autonomic nervous system symptoms. Primarily presence of cranial autonomic symptoms suggests diagnosis of TACs. But many studies reported cranial autonomic symptoms (CAS) ranging from 26% to 80% in migraine patients. Material and Methods: Consecutive patients of migraine attending our headache clinic were included in our study. Presence of CAS was recorded with respect to ocular, nasal, facial and aural symptoms along with headache characteristics and laterality information. Detailed clinical examination was performed. We used ICHD 3 (beta version) criteria. Results: Our study cohort comprised of 200 patients having mean (± SD) age 31.12 (± 10.67) years. There were 157 (78.5%), females. Out of 200 patients, 148 (74%) were having at least one CAS, of which 70% were having 2 or more CAS. Frequency of CAS was lacrimation (45.5%), conjunctival injection (34.5%), eyelid edema (34%), aural fullness (27.5%), facial sweating (25%), facial flushing (17.5%), nasal congestion (9%), rhinorrhea (5%) and ptosis (4%). Bilateral CAS was present in 129 (87%) and unilateral CAS in 19 (13%) (OR 35.31; 95% CI 9.19 to 135.7), (P < 0.0001). Sunlight as a trigger was present in all 148 (100%) patients. Conclusion: Our study showed that CASs in migraine is common and bilateral. Sunlight triggers headache in almost all CAS positive patients.

Cranial autonomic symptoms and response to monoclonal antibodies targeting the Calcitonin gene-related peptide pathway: A real-world study.

Objective: Cranial autonomic symptoms (CAS), including conjunctival injection, tearing, nasal congestion or rhinorrhea, eyelid edema, miosis or ptosis, and forehead or facial sweating ipsilateral to headache, are often reported by patients with migraine during headache attacks. CAS is a consequence of the activation of the trigeminovascular system, which is the target of monoclonal antibodies acting on the CGRP pathway. Therefore, we hypothesized that patients with CAS might have higher trigeminovascular activation than those without CAS leading to a better response to anti-CGRP treatments. Methods: We performed a prospective analysis including patients with episodic or chronic migraine treated with anti-CGRP monoclonal antibodies (i.e., erenumab, fremanezumab, and galcanezumab) between 2019 and 2021. The observation period included a 12-week baseline before treatment with anti-CGRP antibodies and a 12-week treatment follow-up. We evaluated the prevalence of CAS in our cohort and compared disease characteristics and treatment response (i.e., 12-week monthly headache days and 0-29, 30-49, 50-74, 75-99, and 100% monthly headache days reduction from baseline) among patients with and without CAS using the χ2 test, Kruskal-Wallis test, and Mann-Whitney U-test. Results: Out of 136 patients, 88 (65%) had CAS. Both patients with and without CAS reported a significant decrease in monthly headache days from baseline. During the 12-week follow-up, the median difference in monthly headache days from baseline was higher in patients with CAS (-10, IQR-15 to-6) than in those without CAS (6, IQR 12 to 3; P = 0.009). However, the proportions of patients with 0 to 29, 30 to 49, 50 to 74, 75 to 99, and 100% response rates did not differ between the two groups. Conclusions: In our cohort, the presence of CAS was associated with a greater response to monoclonal antibodies targeting the CGRP pathway. CAS could be a clinical marker of trigeminovascular activation and thus be related to a better response to CGRP treatments.

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

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.

The prevalence and characteristics of visceral autonomic symptoms among migraineurs: A population-based study.

BACKGROUND: There is limited evidence about visceral autonomic symptoms in the different phases of migraine attack. We evaluated the prevalence of these symptoms in migraineurs before, during, and after headache attacks. In addition, the association between migraine characteristics and visceral autonomic symptoms was investigated. METHODS: A total of 605 participants who met the entry criteria were enrolled prospectively in this cross-sectional study. Participants were 18-60 years old and met the ICHD-3 criteria for migraine with or without aura. Information on the migraine symptoms was gathered from all participants in face-to-face interviews. A structured questionnaire was used to evaluate the related symptoms before, during, and after attacks. Migraine features of frequency, duration, and severity were also assessed. RESULTS: Considering all phases, the most commonly present visceral symptom was nausea (52.9%). About half of participants reported at least one visceral symptom before the onset of attacks. While, during and after attacks, 71% and 36% of participants reported such characteristics, respectively. Notably, the migraine headache in participants with visceral symptoms was longer during attacks compared to participants without them (24.4 ± 29.6 vs. 16.8 ± 19.8; P = 0.008). Additionally, subjects with positive visceral symptoms experienced more severe migraine attacks than participants without symptoms for both the premonitory (8 ± 1.7 vs. 7.6 ± 1.8; P = 0.02) and during-attack (8.01 ± 1.7 vs. 7.09 ± 1.9; P = 0.001) phases. CONCLUSION: This study demonstrated that visceral symptoms were common in migraine sufferers not only during attacks but also in the premonitory and postdrome phases. Positive visceral symptoms were also associated with more burdensome headache attacks. Therefore, recognizing the phenotypic presentation of associated symptoms of migraine, especially during the pre-attack phase, could aid in early implementation of optimal management.

Cranial autonomic symptoms in episodic and chronic migraine: a cross sectional study in Iran.

BACKGROUND: Cranial autonomic symptoms are common in migraine, with eye redness and tearing being the most common ones. Their identification can help to avoid misdiagnosis, predict the disease course, and select the appropriate treatment. METHODS: This was a cross-sectional study of 904 patients who presented with migraine to a headache referral clinic. The participants filled out a questionnaire about their headache characteristics, as well as the presence of cranial autonomic symptoms. A total of 904 patients, 698 women (77.2%) and 206 men (22.8%), were included in the study, with a mean (SD) age of 38.05 (11.76) years. RESULTS: About 70% of subjects with chronic migraine and 56.2% of those with episodic migraine reported one or more cranial autonomic symptoms. The two most commonly reported autonomic symptoms were eye redness (36.06%) and tearing (21.02%). Chronic migraine (43.4% vs. 29.5%), unilateral headache (56.8% vs. 48.7%), and blurred vision (20% vs. 14.7%) were significantly more frequent in migraineurs with cranial autonomic symptoms. Headache intensity and frequency in subjects with cranial autonomic symptoms were significantly higher than in those without cranial autonomic symptoms. CONCLUSION: We found higher percentages of cranial autonomic symptoms in patients with unilateral headaches, frequent and severe attacks and blurred vision. A diagnosis of cranial autonomic symptoms accompanying migraine may predict more severe disease and the possibility of evolution into chronic migraine.

SUNCT and SUNA: An Update.

BACKGROUND: Short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing (SUNCT) and short-lasting unilateral neuralgiform headache with autonomic symptoms (SUNA) are rare and disabling primary headache disorders that are subtypes of Short-lasting unilateral neuralgiform headache attacks (SUNHA). AIM: The aim of this narrative review was to provide a comprehensive update on headache phenotype, pathophysiology, and various treatment options available for SUNCT and SUNA. METHODS: References for this review were identified by searches of articles published in the English language in PubMed between 1978 and October 2020 using "short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing (SUNCT)", "short-lasting unilateral neuralgiform headache with autonomic symptoms (SUNA)", "short-lasting unilateral neuralgiform headache attacks (SUNHA)", "trigeminal autonomic cephalalgias" as keywords in various combinations. RESULTS: Of a potential 1103 articles, seven case series describing clinical characteristics of SUNCT/SUNA patients were identified for this review. For symptomatic/secondary SUNCT/SUNA, 53 individual case reports, and one case series were reviewed. One placebo-controlled trial and 11 open-label case series that evaluated various medical and surgical treatments in SUNCT/SUNA were also reviewed. Available literature suggests that SUNCT and SUNA are subtypes of the same disorder characterized by severe side locked short duration headache with ipsilateral prominent cranial autonomic symptoms and signs. Pathophysiology may involve both peripheral and central mechanisms. Lamotrigine is the most effective preventive therapy while intravenous lidocaine is the most efficacious drug as transitional therapy for severe disabling attacks. Surgical options including microvascular decompression in those having neurovascular conflict, occipital nerve stimulation, and hypothalamic deep brain stimulation can be alternative treatment options for medically refractory patients.

Comprehensive clinical phenotyping of nitroglycerin infusion induced cluster headache attacks.

BACKGROUND: Nitroglycerin administration allows the study of cluster headache attacks in their entirety in a standardised way. METHODS: A single-blind, placebo-controlled, cross-over study using weight-calculated intravenous nitroglycerin administration at 0.5 µg/kg/min over 20 minutes to study cluster headache attacks, including accompanying non-headache symptoms and cranial autonomic symptoms. RESULTS: Thirty-three subjects with cluster headache were included in the study; 24 completed all three study visits. Nitroglycerin-induced attacks developed in 26 out of 33 subjects (79%) receiving unblinded nitroglycerin infusion, and in 19 out of 25 subjects (76%) receiving single-blinded nitroglycerin infusion, compared with one out of 24 subjects (4%) receiving single-blinded placebo infusion. Episodic cluster headache subjects had a shorter latency period to a nitroglycerin-induced attack compared to the chronic cluster headache (CCH) subjects (U = 15, z = -2.399, p = 0.016). Sixteen of nineteen episodic cluster headache (mean, 84%; 95% confidence interval, 66-100%) and 11 of 14 chronic cluster headache subjects developed a nitroglycerin-induced attack (79%, 54-100%) following the unblinded nitroglycerin infusion. Following the single-blinded nitroglycerin infusion, eight out of 13 episodic cluster headache (62%, 31-92%) and 11 out of 12 chronic cluster headache (92%, 73-100%) subjects developed nitroglycerin-induced attacks. Nitroglycerin induced non-headache symptoms in the majority of subjects receiving it: 91% in the open unblinded nitroglycerin visit and 84% in the single-blinded nitroglycerin visits, compared with 33% in the single-blinded placebo visit. Cranial autonomic symptoms were induced by nitroglycerin infusion, 94% in the open unblinded nitroglycerin visit and 84% in the single-blinded nitroglycerin visit, compared with 17% in the single-blinded placebo visit. CONCLUSION: Intravenous weight-adjusted nitroglycerin administration in both episodic cluster headache in bout and chronic cluster headache is effective and reliable in inducing cluster headache attacks, cranial autonomic symptoms and non-headache symptoms.

SUNCT/SUNA: Case series presenting in an orofacial pain clinic.

AIM: Little is known about short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing (SUNCT) and short-lasting unilateral neuralgiform headache attacks with cranial autonomic symptoms (SUNA). We present our experience with SUNCT/SUNA patients to aid identification and management of these disorders. METHODS: A retrospective review of patient records of one orofacial pain clinic was performed. Inclusion criteria was a diagnosis of SUNCT/SUNA confirmed with at least one follow-up visit. RESULTS: Six of the 2464 new patients seen between 2015-2018 met the selection criteria (SUNCT n = 2, SUNA n = 4). Gender distribution was one male to one female and average age of diagnosis was 52 years (range 26-62). Attacks were located in the V1/V2 trigeminal distributions, and five patients reported associated intraoral pain. Pain quality was sharp, shooting, and burning with two patients reporting "numbness". Pain was moderate-severe in intensity, with daily episodes that typically lasted for seconds. Common autonomic features were lacrimation, conjunctival injection, rhinorrhea, and flushing. Frequent triggers were touching the nose or a specific intraoral area. Lamotrigine and gabapentin were commonly used as initial therapy. CONCLUSIONS: Differentiating between SUNCT/SUNA does not appear to be clinically relevant. Presenting symptoms were consistent with those published, except 5/6 patients describing intraoral pain and two patients describing paresthesia.

Cranial Autonomic Symptoms of Migraine in Japan: Prospective Study of 373 Migraine Patients at a Tertiary Headache Center.

OBJECTIVE: To clarify the detailed clinical characteristics of cranial autonomic symptoms (CAS) of Japanese patients with migraine and to get insight into the pathophysiological implications. BACKGROUND: Recent studies reported that CAS in migraine is causing diagnostic confusion with cluster headache or sinus headache; however, most reports have concerned Caucasians, and Asian data are scarce. The regional differences in the clinical characteristics of primary headaches between Caucasians and Asians have also been revealed recently. METHOD: This was a cross-sectional study. We investigated 373 patients with migraine in a tertiary headache center with face-to-face interviews. RESULTS: According to our findings, 158/373 (42.4%) patients with migraine had CAS and were characterized by more frequent cutaneous allodynia than those without CAS, suggesting the contribution of central sensitization; however, there were no statistically significant differences in pulsating pain or motion sensitivity as signs of peripheral sensitization. In contrast to the previous study, osmophobia was found to be significantly related to CAS. CONCLUSION: CAS in patients with migraine is common not only in Caucasians but also in Asians. Central sensitization seems to contribute more than peripheral sensitization to CAS manifestation, and osmophobia might be noteworthy among Asian patients with migraine. To avoid a misdiagnosis, we emphasize the need for comments on CAS in the international classification of headache disorders migraine criteria.

Migraine in children under 6 years of age: A long-term follow-up study.

BACKGROUND: Early starting of migraine seems predictive for less favorable outcome in later ages, however follow-up investigations are very few and all with short-term prospective period. We report here the longest follow-up study in a population of children presenting with migraine under the age of 6. METHODS: We followed-up 74 children under 6 years of age, referred for headache to our department between 1997 and 2003. The study was carried out between October 2016 and March 2018. Headache diagnoses were made according to the IHS criteria. RESULTS: 23/74 patients, 31% of the original cohort, were found at follow-up in a period ranging between 15 to 21 years after the first visit. Seven of them were headache free. The remaining 16 patients had migraine. In the migraine group, the localization of pain changed in 75% of the subjects, 11/16 (68.7%) had allodynia and 9/16 (56.25%) had cranial autonomic symptoms. CONCLUSIONS: Our results suggest that the onset of migraine at very young age represents unfavorable prognostic factor for persistence of the disease at later ages. Some clinical features may change during clinical course, and the active persistence of the disorder may lead to an increase in allodynia.

Cranial Autonomic Symptoms, Neck Pain: Challenges in Pediatric Migraine.

OBJECTIVES: More than just a headache, migraine attack is a severe, prolonged head pain preceded and/or followed by a constellation of symptoms. Getting a proper diagnosis will be the most challenging step of migraine care. When cranial autonomic symptoms (CASs), and/or neck pain are observed, children are often exposed to advanced tests for additional diseases. The aim of this study was to investigate the frequency of these symptoms in migraine and to compare the clinical characteristics of patients with and without these symptoms. Frequency of the patients that exposed to the additional investigations was searched. MATERIALS AND METHODS: In this prospective study between February 2016 and March 2017, 170 pediatric patients who were referred to our tertiary teaching hospital with migraine were enrolled. RESULTS: A total of 170 children, 61 male (35.9%) and 109 female (64.1%) were included in the study. CASs were present in 68 patients (40%), single symptom in 31 (45.6%), and multiple symptoms in 37 (54.4%) patients. Of 68 patients with CAS, 24 (35%) patients were referred to allergists and all were tested for inhaler specific IgE and skin tests. Seventy (32.9%) patients had neck pain/stiffness in which 28 (40%) were exposed to radiation. CAS and neck pain were more frequent in patients with frequent attacks (P = 0.04 and P = 0.032, respectively). Neck pain was more frequent in patients with CAS (P = 0.029). CONCLUSIONS: It is important for pediatricians and primary care physicians to be aware of the common nature of CASs and neck pain/stiffness in children with migraine to prevent unnecessary procedures. High frequency of migrain attacks was associated with high frequency of CAS and neck pain.