Short-lasting Unilateral Neuralgiform Headache Research Articles

Long-term Observation of Therapeutic Effect of Onabotulinumtoxin A on Short-lasting Unilateral Neuralgiform Headache Attacks with Conjunctival Injection and Tearing

Short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing (SUNCT) is a rare primary headache disorder characterized by severe intractable stabbing headache and accompanying tearing and conjunctival injections. In this report, we present a case of a patient with SUNCT who achieved sustained remarkable improvement more than 6 months following successful treatment with a single session of botulinum toxin A, after being refractory or intolerant to several preventives for 4 months.

Sex and gender differences in the epidemiology, clinical features, and pathophysiology of trigeminal autonomic cephalalgias

Emerging evidence suggests that primary headaches, classified as trigeminal autonomic cephalalgias (TACs), may exhibit sex and gender differences in clinical features, mechanisms, and treatment responses. While epidemiological and clinical gender-specific differences have been widely reported for cluster headache, limited evidence is available for other TACs. In this narrative review, we have analyzed the existing data on the influence of sex and gender on cluster headache, paroxysmal hemicrania, short-lasting unilateral neuralgiform headache attacks, and hemicrania continua. Given the role of calcitonin gene-related peptide (CGRP) in migraine and cluster headache, sex and gender differences in the levels and function of CGRP in preclinical models and patients are reported. Future studies are warranted to elucidate the role of sex and gender in the complex interplay of genetic and neurochemical factors in TACs.

Plain Language Summary Publication: Low-dose psilocybin in short-lasting unilateral neuralgiform headache attacks: Results from an open-label phase Ib ascending dose study.

Plain Language Summary Publication: Low-dose psilocybin in short-lasting unilateral neuralgiform headache attacks: Results from an open-label phase Ib ascending dose study.

Low-dose psilocybin in short-lasting unilateral neuralgiform headache attacks: results from an open-label phase Ib ascending dose study.

Short-lasting unilateral neuralgiform headache attacks (SUNHA) are trigeminal autonomic cephalalgiasthat feature intense and recurrent paroxysms of pain and autonomic symptoms. Many patients are left with debilitating symptoms despite best-available treatment. Psychedelics, such as the serotonin 2A partial agonist psilocybin, have shown promise in related disorders such as migraine and cluster headache. In this open-label phase Ib ascending dose study, we aimed to assess the effects of low-dose oral psilocybin with psychological support in six to 12 patients with chronic SUNHA. Study objectives were to determine effects on cognition, as well as safety, tolerability, and effects on headache severity and frequency. Oral psilocybin in ascending doses of 5, 7.5, and 10 mg (one dose per session; three dosing sessions in total) were administered. Cognition was assessed via the Cambridge Neuropsychological Tests Automated Battery. Headache attacks were assessed via headache diaries and the six-item Headache Impact Test (HIT-6). Subjective dose intensity was assessed via the five-Dimensional Altered States of Consciousness Questionnaire (5D-ASC). The study was terminated early due to recruitment difficulties; four patients were enrolled, three of whom were study completers. Post hoc, we undertook a thematic analysis of the applicable free-text clinical trial notes from the dosing and subsequent visits (n = 22). An inductive method was employed to establish emergent themes. No significant adverse events were recorded. We were unable to collect data as planned on cognitive function during the acute experience due to high ratings of subjective dose intensity (mean 5D-ASC scores 37.8-45.7). The impact of the headaches remained severe throughout the duration of the trial (HIT-6 mean scores 64.3-65.7). There were limited effects on headache duration and severity based on the diaries; however, mean daily attack frequency decreased by >50% in two participants at final follow-up (22.9 to 11.0 and 56.4 to 28.0, respectively). Completing participants and their clinicians recorded "much" (two participants) or "minimal" improvements (one participant) at final follow-up via the Clinical Global Impression rating scale. Thematic analysis indicated that psychological insights were key features of participants' experience; these insights included re-configured relationships to their headache pain. The study met with recruitment difficulties and cognition could not be assessed during the acute experience due to subjective dose intensity, likely mediated in part by expectancy effects. The clinical results provide no conclusive evidence for the use of psilocybin in SUNHA. We suggest that accounting for psychological factors in chronic SUNHA may be an important facet of treatment.

Excellent Response to Repeated Greater Occipital Nerve Blocks in a Patient with Short-Lasting Unilateral Neuralgiform Headache with Conjunctival Tearing.

Excellent Response to Repeated Greater Occipital Nerve Blocks in a Patient with Short-Lasting Unilateral Neuralgiform Headache with Conjunctival Tearing.

One-year prevalence of cluster headache, hemicrania continua, paroxysmal hemicrania and SUNCT in Norway: a population-based nationwide registry study

BackgroundThere is lack of population-based studies evaluating the prevalence of paroxysmal hemicrania, hemicrania continua and short-lasting unilateral neuralgiform headache attacks.ObjectivesThe aim of this study was to investigate the gender-specific 1-year prevalence of cluster headache, paroxysmal hemicrania, hemicrania continua, and short-lasting unilateral neuralgiform headache attacks.MethodsA nationwide study was conducted from January 1 2022 and December 31 2022 by linking diagnostic codes from Norwegian Patient Registry and prescription of relevant drugs from Norwegian Prescription Database on an individual basis. The 1-year prevalence with 95% confidence intervals (CI) of cluster headache, paroxysmal hemicrania, hemicrania continua and short-lasting unilateral neuralgiform headache attacks are estimated based on the combination of diagnostic codes, prescription of drugs and corresponding reimbursement codes.ResultsAmong 4,316,747 individuals aged ≥ 18 years, the 1-year prevalence per 100,000 was 14.6 (95% CI 13.5–15.8) for cluster headache, 2.2 (95% CI 1.8–2.7) for hemicrania continua, 1.4 (95% CI 1.0–1.8) for paroxysmal hemicrania, and 1.2 (95% CI 0.8–1.4) for short-lasting unilateral neuralgiform headache attacks. For all the trigeminal autonomic cephalalgies, cluster headache included, the prevalence was higher for women than men.ConclusionsIn this nationwide register-based study, we found a 1-year prevalence per 100,100 of 14.6 for cluster headache, 2.2 for hemicranias continua, 1.4 for paroxysmal hemicranias, and 1.2 for short-lasting unilateral neuralgiform headache attacks. This is the first study reporting higher prevalence of cluster headache for women than men.

SUNCT, SUNA and short-lasting unilateral neuralgiform headache attacks: Debates and an update.

Short-lasting unilateral neuralgiform headache attacks (SUNHA) have the features of both short-lasting unilateral neuralgiform pain, such as trigeminal neuralgia or stabbing headache, and associated trigeminal autonomic symptoms, such as paroxysmal hemicrania or cluster headache. Recognizing and adequately treating SUNHA is essential but current treatment methods are ineffective in treating SUNHA. We reviewed the changes in the concept of short-lasting unilateral neuralgiform headache attacks and provide a narrative review of the current medical and surgical treatment options, from the first choice of treatment for patients to treatments for selective intractable cases. Unlike the initial impression of an intractable primary headache disorder affecting older men, SUNHA affects both sexes throughout their lifespan. One striking feature of SUNHA is that the attacks are triggered by cutaneous or intraoral stimulation. The efficacy of conventional treatments is disappointing and challenging, and preventive therapy is the mainstay of treatment because of highly frequent attacks of a very brief duration. Amongst them, lamotrigine is effective in approximately two-third of the patients with SUNHA, and intravenous lidocaine is essential for the management of acute exacerbation of intractable pain. Topiramate, oxcarbazepine and gabapentin are considered good secondary options for SUNHA, and botulinum toxin can be used in selective cases. Neurovascular compression is commonly observed in SUNHA, and surgical approaches, such as neurovascular compression, have been reported to be effective for intractable cases. Recent advances in the understanding of SUNHA have improved the recognition and treatment approaches for this unique condition.

Missed pituitary microadenoma during endoscopic transsphenoidal surgery for short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing with symptom relief: illustrative case.

Short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing (SUNCT) is a rare headache disorder that has been associated with pituitary adenomas. Resection has been posited to be curative. A 60-year-old female presented with a 10-year history of SUNCT, which had been medically refractory. Sellar magnetic resonance imaging (MRI) showed a 2 × 2 mm nodule in the right anterolateral aspect of the pituitary. Endoscopic endonasal transsphenoidal resection of the pituitary microadenoma with neuronavigation was performed. The patient felt immediate relief from the headaches. Postoperative MRI showed persistence of the pituitary microadenoma and the resection tract to be inferomedial to the lesion. The right middle and partial superior turbinectomy site was close to the sphenopalatine foramen (SPF). The patient was discharged on postoperative day 1 and remained headache-free without any medications at the 4-month follow-up. Resection of pituitary lesions associated with SUNCT may not necessarily be the cause of SUNCT resolution. Manipulation of the middle and superior turbinate close to the SPF may lead to a pterygopalatine ganglion block. This may be the mechanism of cure for SUNCT in patients with related pituitary lesions who undergo endonasal resection.

A transformation of trigeminal neuralgia into SUNCT/SUNA: A case report and literature review

IntroductionTrigeminal neuralgia and Short-lasting Unilateral Neuralgiform Headache with Conjunctival injection and Tearing (SUNCT)/Short-lasting Unilateral Neuralgiform Headache Attacks with Cranial Autonomic Symptoms (SUNA) are characterized by similar clinical manifestations, which may lead to diagnostic confusion. However, the transformation of trigeminal neuralgia into SUNCT/SUNA is a rare phenomenon. This report describes a case of trigeminal neuralgia transformation into SUNCT/SUNA due to neurovascular compression and reviews all previously published cases of trigeminal neuralgia to SUNCT/SUNA transformation in the literature.Case presentationA 49-year-old Thai male patient presented with progressive right facial pain for a period of three months. One year prior, he developed trigeminal neuralgia along the maxillary branch of the trigeminal nerve, characterized by electrical shock-like pain in the right upper molar, exacerbated by eating. His symptoms were effectively managed with carbamazepine. Nine months later, he began experiencing recurrent electrical shock-like pain along the ophthalmic division of the right trigeminal nerve, accompanied by lacrimation, which failed to respond to continued treatment with carbamazepine. Three months prior to presentation, his symptoms evolved into SUNCT/SUNA, characterized by electrical shock-like pain in the right periorbital area and conjunctival injection, lacrimation. Neuroimaging revealed high-grade neurovascular compression of the right trigeminal nerve by the right superior cerebellar artery. The patient's symptoms resolved following microvascular decompression.ConclusionClinicians should be aware that patients with longer disease duration of trigeminal neuralgia who develop new neuralgic pain in the ophthalmic branch division with mild autonomic symptoms may be at risk for transformation into SUNCT/SUNA.

Percutaneous balloon compression of the trigeminal ganglion for refractory short-lasting unilateral neuralgiform headache with conjunctival redness and tearing syndrome

Percutaneous balloon compression of the trigeminal ganglion for refractory short-lasting unilateral neuralgiform headache with conjunctival redness and tearing syndrome

SUNCT/SUNA: frequently misdiagnosed as trigeminal neuralgia?

Identify the number of cases with a possible diagnosis of short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing (SUNCT) or short-lasting unilateral neuralgiform headache attacks with cranial autonomic symptoms (SUNA) in patients with a previous diagnosis of Trigeminal Neuralgia (TN) at the Neurology Service of the National Medical Center 20 de Noviembre. This will confirm that these trigeminal-autonomic cephalalgias should be ruled out and considered as differential diagnoses of trigeminal neuralgia. Cross-sectional and retrospective study. The complete electronic medical records of 100 patients with a diagnosis of TN were evaluated during the period from April 2010 to May 2020. Autonomic symptoms were intentionally searched for in these patients and compared with the diagnostic criteria of SUNCT and SUNA of the 3rd edition of the International Classification of Headache Disorders. Chi-square tests and subsequent bivariate regression were performed to determine the association between variables. One hundred patients with a diagnosis of TN were included. After reviewing the clinical manifestations, 12 patients with autonomic symptoms were found and compared with the diagnostic criteria of SUNCT and SUNA. However, they did not meet the absolute criteria to be diagnosed with the previously mentioned diseases, nor to be ruled out. TN is a painful and frequent entity that can present with autonomic symptoms, therefore making it important to identify SUNCT and SUNA as differential diagnoses, to recognize them and treat them appropriately.

Gray Zones in the Trigeminal Autonomic Cephalalgias

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.

A Retrospective Comparative Study in Patients with SUNA and SUNCT.

Short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing (SUNCT) and short-lasting unilateral neuralgiform headache attacks with cranial autonomic symptoms (SUNA) are rare primary headache disorders. The aim of the study is to describe and compare the clinical characteristics of patients with SUNA and SUNCT. Patients with SUNCT or SUNA observed in a neurology clinic of a tertiary hospital in India between January 2017 and December 2022 were evaluated. Thirteen patients with SUNA (seven female, 54%) and 16 patients with SUNCT (nine female, 56%) were identified for the evaluation. The mean ages at the onset of SUNA and SUNCT were 36.8.5 ± 8.1 years and 37.2 ± 8.4 years, respectively. The age of onset in our patients was somewhat younger than that of other large series. The demographic and clinical features of SUNA patients were comparable to those of SUNCT patients. Orbital/retro-orbital area was the most common site of pain in both types of headaches. The pattern of pain was noted as single stab (in all patients), repetitive stabs (SUNA vs. SUNCT: 77% vs. 75%), and sawtooth patterns (SUNA vs. SUNCT: 23% vs. 25%). The majority of attacks in both groups lasted less than two minutes. Conjunctival injection and tearing were present in all SUNCT patients (as a part of the diagnostic criteria). The prevalence of conjunctival injection and tearing in SUNA was 46% and 31%, respectively. All patients reported spontaneous attacks. Triggers were reported in seven (54%) patients with SUNA and nine (56%) with SUNCT. Only one patient in each group had a refractory period following a trigger-induced episode. Two patients in the SUNCT group had compression of the trigeminal nerve by a vascular loop. This is the largest case series from India. There were no significant differences between patients with SUNA and SUNCT.

Trigeminal autonomic cephalalgias and intranasal lidocaine: a symptomatic management option

Introduction Trigeminal Autonomic Cephalalgias (TAC) are excruciating headaches with limited treatment options. In addition to drug therapy, there are some studies regarding nerve blocking and nerve stimulation with acceptable results. We had a sequence of three difficult to treat patients because of the disease or some associated condition that made us try something not so usual. Lidocaine, by blocking voltage-gated Na+ channels can reduce the excitability of neurons and thus prevent or reduce the sensation of pain, which can relieve neuropathic pain, hyperalgesia, and complex regional pain syndrome. Objective Observe if intranasal lidocaine could be effective and safe for patients with TAC. Methods and Results The three patients signed a consent permission form. (1) 29-year-old pregnant woman with a history of headaches for about 3 years. Pain was localized in the right periorbital region with the severity of about 7 out of 10. Attacks of excruciating pain associated with ipsilateral tearing 5–8 times a day - Paroxistic Hemicrania. She was diagnosed with prolactinoma two years ago. The management of the tumor had resolved the pain. With the pregnancy, Bromocriptine has been stopped. So, 1 month later, the pain returned. As indomethacin could not be used in this situation, we opted to prescribe intranasal lidocaine. After the first dose, the patient had control of the pain. It was prescribed lidocaine 2%, 2mL intranasal (IN) until four times a day. (2) 56-year-old man with a history of headaches for about 4 months. Pain was localized in the right periorbital region with the severity of about 10 out of 10. Attacks of excruciating pain associated with ipsilateral tearing and conjunctival injection lasting for 30-90 seconds and occurring as single stabs 30-50 times a day - Short-lasting unilateral neuralgiform headache attacks with conjunctival... (Too see the complet abstract, please, check out the PDF,)

Similarities and differences between SUNCT and SUNA: a cross-sectional, multicentre study of 76 patients in China

BackgroundShort-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing (SUNCT) and short-lasting unilateral neuralgiform headache attacks with cranial autonomic symptoms (SUNA) have not been evaluated sufficiently due to limited data, particularly in China.MethodsPatients with SUNCT or SUNA treated in a tertiary headache centre or seven other headache clinics of China between April 2009 and July 2022 were studied; we compared their demographics and clinical phenotypes.ResultsThe 45 patients with SUNCT and 31 patients with SUNA had mean ages at onset of 37.22 ± 14.54 years and 42.45 ± 14.72 years, respectively. The mean ages at diagnosis of SUNCT and SUNA were 41.62 ± 12.70 years and 48.68 ± 13.80 years, respectively (p = 0.024). The correct diagnosis of SUNCT or SUNA was made after an average of 2.5 (0–20.5) years or 3.0 (0–20.7) years, respectively. Both diseases had a female predominance (SUNCT: 1.14:1; SUNA: 2.10:1). The two diseases differed in the most common attack site (temporal area in SUNCT, p = 0.017; parietal area in SUNA, p = 0.002). Qualitative descriptions of the attacks included stabbing pain (44.7%), electric-shock-like pain (36.8%), shooting pain (25.0%), and slashing pain (18.4%). Lacrimation was the most common autonomic symptom in both SUNCT and SUNA patients, while eyelid oedema, ptosis, and miosis were less frequent. Triggers such as cold air and face washing were shared by the two diseases, and they were consistently ipsilateral to the attack site.ConclusionsIn contrast to Western countries, SUNCT and SUNA in China have a greater female predominance and an earlier onset. The shared core phenotype of SUNCT and SUNA, despite their partial differences, suggests that they are the same clinical entity.

Paroxysmal hemicrania or short-lasting unilateral neuralgiform headache attacks with trigeminal neuralgia - functional neuroimaging findings.

Paroxysmal hemicrania or short-lasting unilateral neuralgiform headache attacks with trigeminal neuralgia - functional neuroimaging findings.

Short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing (SUNCT) responsive to intranasal lidocaine and nerve blockage: a case report

Abstract Background: Trigeminal autonomic cephalalgias comprehend a myriad of headaches with different symptoms, with comprehend short-lasting unilateral neuralgiform headache attacks with cranial autonomic symptoms (SUNA) or with conjunctival injection and tearing (SUNCT). Current treatment options are limited, and they are based mostly on case reports and small studies. Case Report: We report here the case of a 75 years old man suffering from acutetrigeminal autonomic headache with a satisfying response to intranasal lidocaine and nerve blockage. Conclusion: Intranasal lidocaine and nerve blockage may represent a useful and costeffective treatment for patients with SUNCT/SUNA.

Trigeminal microvascular decompression for short-lasting unilateral neuralgiform headache attacks.

A significant proportion of patients with short-lasting unilateral neuralgiform headache attacks are refractory to medical treatments. Neuroimaging studies have suggested a role for ipsilateral trigeminal neurovascular conflict with morphological changes in the pathophysiology of this disorder. We present the outcome of an uncontrolled open-label prospective single-centre study conducted between 2012 and 2020, to evaluate the efficacy and safety of trigeminal microvascular decompression in refractory chronic short-lasting unilateral neuralgiform headache attacks with MRI evidence of trigeminal neurovascular conflict ipsilateral to the pain side. Primary endpoint was the proportion of patients who achieved an ‘excellent response’, defined as 90–100% weekly reduction in attack frequency, or ‘good response’, defined as a reduction in weekly headache attack frequency between 75% and 89% at final follow-up, compared to baseline. These patients were defined as responders. The study group consisted of 47 patients, of whom 31 had short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing, and 16 had short-lasting unilateral neuralgiform headache attacks with cranial autonomic symptoms (25 females, mean age ± SD 55.2 years ± 14.8). Participants failed to respond or tolerate a mean of 8.1 (±2.7) preventive treatments pre-surgery. MRI of the trigeminal nerves (n = 47 patients, n = 50 symptomatic trigeminal nerves) demonstrated ipsilateral neurovascular conflict with morphological changes in 39/50 (78.0%) symptomatic nerves and without morphological changes in 11/50 (22.0%) symptomatic nerves. Postoperatively, 37/47 (78.7%) patients obtained either an excellent or a good response. Ten patients (21.3%, short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing = 7 and short-lasting unilateral neuralgiform headache attacks with cranial autonomic symptoms = 3) reported no postoperative improvement. The mean post-surgery follow-up was 57.4 ± 24.3 months (range 11–96 months). At final follow-up, 31 patients (66.0%) were excellent/good responders. Six patients experienced a recurrence of headache symptoms. There was no statistically significant difference between short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing and short-lasting unilateral neuralgiform headache attacks in the response to surgery (P = 0.463). Responders at the last follow-up were, however, more likely to not have interictal pain (77.42% versus 22.58%, P = 0.021) and to show morphological changes on the MRI (78.38% versus 21.62%, P = 0.001). The latter outcome was confirmed in the Kaplan–Meyer analysis, where patients with no morphological changes were more likely to relapse overtime compared to those with morphological changes (P = 0.0001). All but one patient, who obtained an excellent response without relapse, discontinued their preventive medications. Twenty-two post-surgery adverse events occurred in 18 patients (46.8%) but no mortality or severe neurological deficit was seen. Trigeminal microvascular decompression may be a safe and effective long-term treatment for patients suffering short-lasting unilateral neuralgiform headache attacks with MRI evidence of neurovascular conflict with morphological changes.

The spectrum of indomethacin-responsive headaches in children and adolescents.

BackgroundHeadaches with marked, specific response to indomethacin occur in children, but the phenotypic spectrum of this phenomenon has not been well-studied.MethodsWe reviewed pediatric patients with headache showing ≥80% improvement with indomethacin, from seven academic medical centers.ResultsWe included 32 pediatric patients (16 females). Mean headache onset age was 10.9 y (range 2–16 y). Headache syndromes included hemicrania continua (n = 13), paroxysmal hemicrania (n = 10), primary stabbing headache (n = 2), short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing (n = 1), primary exercise headache (n = 1) and primary cough headache (n = 1). Adverse events were reported in 13, most commonly gastrointestinal symptoms, which often improved with co-administration of gastro-protective agents.ConclusionIndomethacin-responsive headaches occur in children and adolescents, and include headache syndromes, such as primary cough headache, previously thought to present only in adulthood. The incidence of adverse events is high, and patients must be co-treated with a gastroprotective agent.

Autonomic Disorders in Trigeminal Autonomic Cephalalgias: An Update

The term trigeminal autonomic cephalalgias (TACs) was introduced in the 2nd edition of the International Classification of Headache Disorders, and has been retained in the 3rd edition. TACs include cluster headache, paroxysmal hemicrania, short-lasting unilateral neuralgiform headache attacks, hemicrania continua, and probable trigeminal autonomic cephalalgia. Headaches classified as TACs share clinical features with unilateral headache and usually present with prominent lateralized and ipsilateral cranial parasympathetic autonomic features, including the following: (1) conjunctival injection and/or lacrimation, (2) nasal congestion and/or rhinorrhea, (3) eyelid edema, (4) forehead and facial sweating, (5) miosis and/or ptosis. "Clinical Practice Guideline for Headache 2021 (Japanese version)" will serve as a useful aid for diagnosis and treatment of TACs. Currently, hypothalamic activation, activation of the trigeminal-autonomic nerve reflex, internal carotid artery dilatation, and the action of some neuropeptides are implicated as pathophysiological mechanisms underlying TACs; however, it is not unequivocal. Further studies are warranted to gain deeper insight into several unclear aspects associated with TACs.