Trigeminal autonomic cephalalgias: current and future treatments

The trigeminal autonomic cephalgias include cluster headache, paroxysmal hemicrania, and short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing (SUNCT). The evidence for the current treatment options for each of these syndromes is considered, including oxygen, sumatriptan, and verapamil in cluster headache, indomethacin in paroxysmal hemicrania, and intravenous lidocaine and lamotrigine in SUNCT. Some treatments such as topiramate have an effect in all of these, as well as in migraine and other pain syndromes. The involvement of the hypothalamus in functional imaging studies implies that this may be a substrate for targeting treatment options in the future.     

少见的三叉神经自主神经性头痛临床特点

目的:探讨伴有结膜充血及流泪的单侧短暂持续性神经痛样头痛(SUNCT)和阵发性偏侧头痛(PH)的临床特点.方法:回顾性分析2例SUNCT患者和3例PH患者的临床表现及治疗方法.结果:5例患者均表现为单侧眼眶、颞部的剧烈疼痛,并伴有同侧的颅内副交感神经激活症状,持续时间从20秒到30分钟,每天发作频率从8次到100次;S...     

Chronic cluster-like headache secondary to prolactinoma: uncommon cephalalgia in association with brain tumors

Headache is a common and disabling aspect of pituitary disease. Chronic and episodic migraine are the most common clinical syndromes of headaches related to pituitary tumors, although other types of headache, such as trigeminal autonomic cephalalgias (TACs), can also be present. TACs include short-lasting, unilateral neuralgiform headache attacks with conjunctival injection and tearing; paroxysmal hemicrania; and cluster headache. We report on a patient with a chronic cluster-like headache associated with a macroprolactinoma. Although cabergoline, pregabalin, and corticosteroids were not effective as preventive treatments, high-dose verapamil showed good efficacy. Morphine and octreotide were efficacious as abortive treatments for attacks, but pain was only partially responsive to oxygen and refractory to subcutaneous sumatriptan.     

Pathophysiology and treatment of trigeminal autonomic cephalalgias

Trigeminal autonomic cephalalgias (TACs) are a group of primary headache disorders, which are characterized by strictly unilateral pain, together with ipsilateral cranial autonomic symptoms. TACs include cluster headache (CH), paroxysmal hemicrania (PH) and short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing (SUNCT syndrome). These diseases all have one thing in common: an activation of trigeminal nociceptive afferentia with a reflex-like activation of cranial autonomic efferentia via the facial nerve. TACs show differences not only in the length and frequency of attacks but also in the response to drug treatment. It is important to recognize and differentiate between these syndromes because they react very well, but very selectively to therapy.     

Different forms of trigeminal autonomic cephalalgias in the same patient: description of a case

The trigeminal autonomic cephalalgias (TACs), including cluster headache, paroxysmal hemicrania and SUNCT, are characterized by the cardinal combination of short-lasting unilateral pain and autonomic phenomena affecting the head. Hemicrania continua (HC) shares many clinical characteristics with TACs, including unilateral pain and ipsilateral autonomic features. Nevertheless, HC is separately classified in the revised International Classification of Headache Disorders (ICHD-II). Here, we describe the case of a 45-year-old man presenting an unusual concurrence of different forms of primary headaches associated with autonomic signs, including subsequently ipsilateral cluster headache, SUNCT and HC. This report supports the theory that common mechanisms could be involved in pathophysiology of different primary headache syndromes.     

Neues zur Pathophysiologie und Therapie der trigeminoautonomen Kopfschmerzsyndrome

Trigeminal autonomic cephalalgias (TACs) are a group of primary headache disorders, which are characterized by strictly unilateral pain, together with ipsilateral cranial autonomic symptoms. TACs include cluster headache (CH), paroxysmal hemicrania (PH) and short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing (SUNCT syndrome). These diseases all have one thing in common: an activation of trigeminal nociceptive afferentia with a reflex-like activation of cranial autonomic efferentia via the facial nerve. TACs show differences not only in the length and frequency of attacks but also in the response to drug treatment. It is important to recognize and differentiate between these syndromes because they react very well, but very selectively to therapy.     

Hemicrania Continua. Unquestionably a Trigeminal Autonomic Cephalalgia

Hemicrania continua (HC) is a well‐known primary headache. The present version of the International Classification of Headache Disorders lists HC in the “other primary headaches” group. However, evidence has emerged demonstrating that HC is a phenotype that belongs to the trigeminal autonomic cephalalgias together with cluster headache, paroxysmal hemicrania (PH), and short‐lasting, unilateral neuralgiform headache attacks with conjunctival injection and tearing. This is supported by a common general clinical picture – paroxysmal, fluctuating, unilateral, side‐locked headaches located to the ocular, frontal, and/or temporal regions, accompanied by ipsilateral autonomic dysfunctions including for example, tearing and conjunctival injection. Apart from the remarkable clinical similarities, the absolute and incomparable effect of indomethacin in HC parallels the effect of this drug in PH, suggesting a shared core pathogenesis. Finally, neuroimage findings demonstrate a posterior hypothalamic activation in HC similarly to cluster headache, PH, and short‐lasting, unilateral neuralgiform headache attacks with conjunctival injection and tearing. Taken together, data indicate that HC is certainly a type of trigeminal autonomic cephalalgia that should no longer be placed in a group of miscellaneous primary headache disorders.     

Unilateral photophobia or phonophobia in migraine compared with trigeminal autonomic cephalalgias

Our objective was to compare the presence of self-reported unilateral photophobia or phonophobia, or both, during headache attacks comparing patients with trigeminal autonomic cephalalgias (TACs)—including cluster headache, short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing (SUNCT) and paroxysmal hemicrania—or hemicrania continua, and other headache types. We conducted a prospective study in patients attending a referral out-patient clinic over 5 months and those admitted for an intramuscular indomethacin test. Two hundred and six patients were included. In episodic migraine patients, two of 54 (4%) reported unilateral photophobia or phonophobia, or both. In chronic migraine patients, six of 48 (13%) complained of unilateral photophobia or phonophobia, or both, whereas none of the 24 patients with medication-overuse headache reported these unilateral symptoms, although these patients all had clinical symptoms suggesting the diagnosis of migraine. Only three of 22 patients (14%) suffering from new daily persistent headache (NDPH) experienced unilateral photophobia or phonophobia. In chronic cluster headache 10 of 21 patients (48%) had unilateral photophobia or phonophobia, or both, and this symptom appeared in four of five patients (80%) with episodic cluster headache. Unilateral photophobia or phonophobia, or both, were reported by six of 11 patients (55%) with hemicrania continua, five of nine (56%) with SUNCT, and four of six (67%) with chronic paroxysmal hemicrania. Unilateral phonophobia or photophobia, or both, are more frequent in TACs and hemicrania continua than in migraine and NDPH. The presence of these unilateral symptoms may be clinically useful in the differential diagnosis of primary headaches.     

An unusual form of TAC-TAC sine autonomic phenomena

The trigeminal autonomic cephalalgias (TACs) are characterized by the cardinal combination of short-lasting unilateral pain and autonomic phenomena affecting the head, including cluster headache, paroxysmal hemicrania and SUNCT. Infrequently reported have been cases with dissociation of these two cardinal features- usually with autonomic phenomena without pain, rather than the reverse. Herein is described the case of a 56-year-old man presenting with an unusual form of TAC resembling chronic paroxysmal hemicrania but with a lower frequency of occurrence, with temporal features not typical of previously described TACs, and consisting of severe unilateral head pain without any autonomic symptoms or signs, absolutely responsive to indomethacin.     

Hypothalamic activation in trigeminal autonomic cephalgia: functional imaging of an atypical case

We report headache induced BOLD changes in an atypical case of trigeminal autonomic cephalgia (TAC). A 68-year-old patient was imaged using fMRI during three attacks of a periorbital head-pain with a average duration of 3 min. During the attacks, left sided conjunctival injection, rhinorrhea, lacrimation, facial sweating and hypersalivation were apparent. These attacks were usually partly responsive to oxygen administration but otherwise refractory to any drug. The patient described either attacks with a duration of one minute or less or longer attacks persisting for maximum of 20 min with headaches occurring up to 100 times a day. When considering the symptoms, frequency, duration and therapeutic response of the patient's headache, no clear-cut classification to one of the subtypes of trigeminal autonomic cephalgias (cluster headache, paroxysmal hemicrania, SUNCT) or trigeminal neuralgia was possible. The cerebral activation pattern was similar but not identical to those previously observed in cluster headache and SUNCT with a prominent activation in the hypothalamic grey matter. This case study underlines the conceptual value of the term TAC for the group of headaches focusing around the trigeminal-autonomic reflex. Our results emphasize the importance of the hypothalamus as key region in the pathophysiology of this entity.     

Chronic paroxysmal hemicrania, hemicrania continua and SUNCT syndrome in association with other pathologies: a review

We present a review of 22 cases of headache mimicking chronic paroxysmal hemicrania (CPH) (17 female and five male; F : M ratio 3.4), nine cases mimicking hemicrania continua (HC) (seven female and two male) and seven cases mimicking SUNCT syndrome (five male and two female) found in association with other pathologies published from 1980 up to the present. All case reports were discussed with respect to diagnostic criteria proposed by International Headache Society (IHS) for CPH, by Goadsby and Lipton for HC and SUNCT, and evaluated to identify a possible causal relationship between the pathology and the onset of headache. The aim of the present review was to evaluate if the presence of associated lesions and their location could help elucidate the pathogenesis of trigeminal autonomic cephalalgias (TACs).     

Simultaneous occurrence of ipsilateral cluster headache and chronic paroxysmal hemicrania: a case report

A 42-year-old man came to our headache unit in October 1995 complaining of recurrent attacks of headache, which had begun in February 1991. Chronic cluster headache was diagnosed, and he was given verapamil, 360 mg per day. The attacks ceased in the following months and verapamil was stopped in March 1996. In May 1997, a recurrence of the attacks required the readministration of verapamil, 360 mg per day. The attacks decreased (one to three per week), but after 2 months the patient reported a worsening in his condition due to the appearance of shorter attacks, which were diagnosed as chronic paroxysmal hemicrania. The administration of indomethacin, 225 mg per day, resulted in the disappearance of the short attacks. The concomitant occurrence of attacks of cluster headache and chronic paroxysmal hemicrania suggests the presence of shared factors in the pathophysiology of the two forms of headache. This hypothesis is supported by previous reports in the literature.     

Ipsilateral cluster headache and chronic paroxysmal hemicrania: two case reports

We report two patients with ipsilateral attacks of cluster headache and chronic paroxysmal hemicrania. The first patient, a 33-year-old man, started having attacks of chronic cluster headache at the age of 27. At 33, they were replaced by typical attacks of ipsilateral chronic paroxysmal hemicrania which showed a dramatic improvement with indomethacin 150 mg daily. After two days of complete remission, cluster headache attacks reappeared and persisted until verapamil, 360 mg a day, was added to indomethacin. The second patient, a 45-year-old man, first developed attacks of episodic cluster headache at the age of 35. At 44, he experienced ipsilateral typical attacks of chronic paroxysmal hemicrania, and two months later attacks of cluster headache. Under verapamil 240 mg daily, attacks of cluster headache disappeared, but those of chronic paroxysmal hemicrania increased in frequency until indomethacin 150 mg daily was added. These observations suggest a close relationship but not a similarity between cluster headache and chronic paraoxysmal hemicrania, and show the practical therapeutic interest of maintaining this distinction.     

Chronic paroxysmal hemicrania in paediatric age: report of two cases

Chronic paroxysmal hemicrania (CPH) is a rare primary headache syndrome, which is classified along with hemicrania continua and short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing (SUNCT) as trigeminal autonomic cephalalgia (TACs). CPH is characterised by short-lasting (2-30 min), severe and multiple (more than 5/day) pain attacks. Headache is unilateral, and fronto-orbital-temporal pain is combined with cranial autonomic symptoms. According to the International Classification of Headache Disorders, 2nd edition, the attacks are absolutely responsive to indomethacin. CPH has been only rarely and incompletely described in the developmental age. Here, we describe two cases concerning a 7-year-old boy and a 11-year-old boy with short-lasting, recurrent headache combined with cranial autonomic features. Pain was described as excruciating, and was non-responsive to most traditional analgesic drugs. The clinical features of our children's headache and the positive response to indomethacin led us to propose the diagnosis of CPH. Therefore, our children can be included amongst the very few cases of this trigeminal autonomic cephalgia described in the paediatric age.     

Post-traumatic short-lasting unilateral headache with cranial autonomic symptoms (SUNA)

Short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing (SUNCT) syndrome is a rare headache syndrome classified among the trigeminal autonomic cephalalgias. It is usually idiopathic, although infrequent secondary forms have been described. Recently the term short-lasting unilateral headache with cranial autonomic symptoms (SUNA) has been defined by the International Headache Society (ICHD-2) as similar to SUNCT with less prominent or absent conjunctival injection and lacrimation. We report two patients with paroxysmal orbito-fronto-temporal pains, phenotypically suggesting SUNA, occurring after traumatic head injury.     

The differential diagnosis of chronic daily headaches: an algorithm-based approach

Chronic daily headaches (CDHs) refers to primary headaches that happen on at least 15 days per month, for 4 or more hours per day, for at least three consecutive months. The differential diagnosis of CDHs is challenging and should proceed in an orderly fashion. The approach begins with a search for "red flags" that suggest the possibility of a secondary headache. If secondary headaches that mimic CDHs are excluded, either on clinical grounds or through investigation, the next step is to classify the headaches based on the duration of attacks. If the attacks last less than 4 hours per day, a trigeminal autonomic cephalalgia (TAC) is likely. TACs include episodic and chronic cluster headache, episodic and chronic paroxysmal hemicrania, SUNCT, and hypnic headache. If the duration is > or =4 h, a CDH is likely and the differential diagnosis encompasses chronic migraine, chronic tension-type headache, new daily persistent headache and hemicrania continua. The clinical approach to diagnosing CDH is the scope of this review.     

Kopfschmerzattacken und autonome Symptome

Following the new IHS-classification, cluster headache, paroxysmal hemicrania and SUNCT syndrome are included into the classification as trigemino-autonomic cephalgias (TAC's). Clinically, they share strictly halfsided head pain with autonomic symptoms. The headaches often occur during particular sleep stages and are associated with other chronobiologic factors. Broadly the management of TAC's comprises acute and prophylactic treatment. Paroxysmal hemicrania and hemicrana continua have a very robust response to indomethacin. Acute cluster headache attacks can be treated with inhalation of oxygen or serotonin agonists, whereas verapamil is the drug of choice in the prophylactic treatment. This review covers the clinical picture and therapeutic options. Allthough studies following the criteria of evidence based medicine (EBM) are rare, most patients can be treated sufficiently.     

SUNCT syndrome: forehead sweating pattern

The forehead sweating function has been assessed in SUNCT syndrome-a short-lasting, unilateral, neuralgifonn headache syndrome with autonomic phenomena on the symptomatic side (conjunctival injection, lacrimation, etc.). In the three patients (of a total of six) who could be studied during paroxysms, increased evaporation was present on the symptomatic side of the forehead compared to the non-symptomatic side during attacks or to the symptomatic side between attacks. Basal sweating was generally within control limits, so long as the attack frequency was not so high as to influence the interictal level. During attacks precipitated by eating chocolate or sour apple (in the case of one of the patients), forehead sweating was also increased on the symptomatic side. The forehead sweating responses to heating and pilocarpine were without any notable or systematic asymmetries. The forehead sweating pattern in SUNCT syndrome may differ from the patterns in unilateral headaches like cluster headache, on the one hand (in which there is generally an asymmetry during heating and pilocarpine tests), and chronic paroxysmal hemicrania (CPH) and cervicogenic headache, on the other (where there is no systematic increase during attacks).     

Therapie und Prophylaxe von Cluster-Kopfschmerzen und anderen trigemino-autonomen Kopfschmerzen

Following the new IHS classification, cluster headache, paroxysmal hemicrania, and short-lasting unilateral neuralgiform headache with conjunctival injection and tearing (SUNCT syndrome) are included in the classification as trigeminal autonomic cephalgias (TAC). The similarities of these syndromes suggest a considerable shared pathophysiology. These syndromes have in common that they involve activation of trigeminovascular nociceptive pathways with reflex cranial autonomic activation. Clinically, this physiology predicts pain with some combination of lacrimation, conjunctival injection, nasal congestion, or eyelid edema. Broadly the management of TAC comprises acute and prophylactic treatment. Some types of trigeminal autonomic headaches such as paroxysmal hemicrania and hemicrania continua have, unlike cluster headaches, a very robust response to indomethacin, leading to a consideration of indomethacin-sensitive headaches. This review covers the clinical picture and therapeutic options. Although studies following the criteria of evidence-based medicine (EBM) are rare, most patients can be treated sufficiently.     

Clomiphene citrate for treatment refractory chronic cluster headache

A treatment refractory chronic cluster headache patient is presented who became cluster-free on clomiphene citrate. The author has previously reported a SUNCT patient responding to clomiphene citrate. Hypothalamic hormonal modulation therapy with clomiphene citrate may become a new preventive choice for trigeminal autonomic cephalalgias. The possible mechanism of action of clomiphene citrate for cluster headache prevention will be discussed.