Headache in Children and Adolescents.

OBJECTIVE: This article reviews the assessment of children and adolescents presenting with headache, provides an overview of primary headache disorders, and reviews evidence-based management of headache in this age group. LATEST DEVELOPMENTS: In the last few years, new epidemiological data have shed light on less common pediatric headache disorders (eg, pediatric trigeminal autonomic cephalalgias) and psychosocial risk factors associated with primary headache disorders in children and adolescents. There has also recently been a substantial increase in interventions that target the calcitonin gene-related peptide pathway and that treat primary headache disorders using noninvasive neuromodulation. Although these interventions have primarily been studied in adults, there is emerging evidence of their use in the pediatric population. ESSENTIAL POINTS: Primary headache disorders are very common in youth, and the most commonly encountered headache diagnosis in neurology practice is migraine, which affects approximately 10% of children and adolescents. Diagnosing and effectively treating primary headache disorders before adulthood may have a sustained impact on the patient by improving long-term headache and mental health outcomes, thereby significantly reducing the burden of disability over time. There are several available and emerging acute and preventive interventions for youth with primary headache disorders, and treatment decisions should be made in the context of available evidence using a shared decision-making approach.

Cluster Headache, SUNCT, and SUNA.

OBJECTIVE: This article reviews the epidemiology, clinical features, differential diagnosis, pathophysiology, and management of three types of trigeminal autonomic cephalalgias: cluster headache (the most common), short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing (SUNCT), and short-lasting unilateral neuralgiform headache attacks with cranial autonomic symptoms (SUNA). LATEST DEVELOPMENTS: The first-line treatments for trigeminal autonomic cephalalgias have not changed in recent years: cluster headache is managed with oxygen, triptans, and verapamil, and SUNCT and SUNA are managed with lamotrigine. However, new successful clinical trials of high-dose prednisone, high-dose galcanezumab, and occipital nerve stimulation provide additional options for patients with cluster headache. Furthermore, new genetic and imaging tests in patients with cluster headache hold promise for a better understanding of its pathophysiology. ESSENTIAL POINTS: The trigeminal autonomic cephalalgias are a group of diseases that appear similar to each other and other headache disorders but have important differences. Proper diagnosis is crucial for proper treatment.

Melatonin in hemicrania continua and paroxysmal hemicrania.

BACKGROUND: Hemicrania continua (HC) and paroxysmal hemicrania (PH) belong to a group of primary headache disorders called trigeminal autonomic cephalalgias. One of the diagnostic criteria for both HC and PH is the absolute response to the therapeutic dose of indomethacin. However, indomethacin is discontinued in many patients as a result of intolerance to its side effects. Melatonin, a pineal hormone, which shares similar chemical structure to indomethacin, has been reported to have some efficacy for HC in previous case reports and series. To our knowledge, there is no literature regarding the use of melatonin in PH. We aimed to describe the clinical use of melatonin in the preventive management of HC and PH. METHODS: Patient level data were extracted as an audit from routinely collected clinical records in consecutive patients seen in outpatient neurology clinic at King's College Hospital, London, UK, from September 2014 to April 2023. Our cohort of patients were identified through a search using the keywords: hemicrania continua, paroxysmal hemicrania, melatonin and indomethacin. Descriptive statistics including absolute and relative frequencies, mean ± SD, median and interquartile range (IQR) were used. RESULTS: Fifty-six HC patients were included with a mean ± SD age of 52 ± 16 years; 43 of 56 (77%) patients were female. Melatonin was taken by 23 (41%) patients. Of these 23 patients, 19 (83%) stopped indomethacin because of different side effects. The doses of melatonin used ranged from 0.5 mg to 21 mg, with a median dose of 10 mg (IQR = 6-13 mg). Fourteen (61%) patients reported positive relief for headache, whereas the remaining nine (39%) patients reported no headache preventive effect. None of the patients reported that they were completely pain free. Two patients continued indomethacin and melatonin concurrently for better symptom relief. Eight patients continued melatonin as the single preventive treatment. Side effects from melatonin were rare. Twenty-two PH patients were included with mean ± SD age of 50 ± 17 years; 17 of 22 (77%) patients were female. Melatonin was given to six (27%) patients. The median dose of melatonin used was 8 mg (IQR = 6-10 mg). Three (50%) patients responded to melatonin treatment. One of them used melatonin as adjunctive treatment with indomethacin. CONCLUSIONS: Melatonin showed some efficacy in the treatment of HC and PH with a well-tolerated side effect profile. It does not have the same absolute responsiveness as indomethacin, at the doses used, although it does offer a well-tolerated option that can have significant ameliorating effects in a substantial cohort of patients.

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

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: Recent advances in the understanding of SUNHA have improved the recognition and treatment approaches for this unique condition.

Complementary and Integrative Medicine for the Treatment of Trigeminal Neuralgia and Trigeminal Autonomic Cephalalgia.

PURPOSE OF REVIEW: Trigeminal neuralgia (TN) and trigeminal autonomic cephalalgias (TACs) are both painful diseases which directly impact the branches of the trigeminal nerve, which supply the face. Patients who have experienced adverse effects, have not responded to mainstream treatments, or have a personal preference for nonmedication options, often turn to complementary and integrative medicine (CIM). The aim of this review is to discuss the efficacy and safety of CIM therapies available for the treatment of TN and TACs. RECENT FINDINGS: Not only are there limited therapeutic options for TN and TAC patients, but also is there a proportion of patients who are intolerant to standard medical treatments. Recent findings have illustrated that 86% of patients with headache disorders utilize CIM modalities in combination with mainstream medical therapy. CIM modalities can be helpful for these diseases and have primarily been studied in combination with standard medical therapy. There is limited evidence for CIM and behavioral therapies in managing these conditions, and more research is needed to confirm which therapies are safe and effective.

SUNCT/SUNA: ¿frecuentemente mal diagnosticada como neuralgia del trigémino? / SUNCT/SUNA: frequently misdiagnosed as trigeminal neuralgia?

Objetivo: Identificar el número de casos con posible diagnóstico de cefalea neuralgiforme unilateral de corta duración con inyección conjuntival y lagrimeo (SUNCT) o cefalea neuralgiforme unilateral de corta duración con síntomas autonómicos craneales (SUNA) en pacientes con un previo diagnóstico de neuralgia del trigémino (NT) en el servicio de neurología del Centro Médico Nacional 20 de Noviembre, comprobando así que estas cefaleas trigeminoautonómicas deben ser descartadas y consideradas como diagnósticos diferenciales de la NT. Pacientes y métodos: Estudio transversal y retrospectivo. Se evaluaron los expedientes clínicos electrónicos completos de 100 pacientes con diagnóstico de NT durante el período de abril de 2010 a mayo de 2020. Intencionalmente se buscaron síntomas autonómicos en éstos y se compararon con los criterios diagnósticos de SUNCT y SUNA de la Clasificación Internacional de las Cefaleas, tercera edición. Se realizaron pruebas de chi cuadrado y posteriormente de regresión bivariada para determinar la asociación entre las variables. Resultados: Se incluyó a 100 pacientes con diagnóstico de NT. Tras la revisión de las manifestaciones clínicas, se encontró a 12 pacientes con síntomas autonómicos y se compararon con los criterios diagnósticos de SUNCT y SUNA. Estos no cumplieron los criterios absolutos para ser diagnosticados con las enfermedades previamente mencionadas; sin embargo, cumplieron las características del espectro de cefaleas trigeminoautonómicas. Conclusión: La NT es una entidad dolorosa y frecuente que puede presentar síntomas autonómicos, y es importante pensar en diagnósticos diferenciales, como la SUNCT y la SUNA, para la identificación y el tratamiento correctos.(AU)

Objective: 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. Patients and methods: 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. Results: 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. Conclusions: 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.(AU)

Paroxysmal hemicrania and hemicrania continua: Review on pathophysiology, clinical features and treatment.

BACKGROUND: Paroxysmal hemicrania and hemicrania continua are indometacin-sensitive trigeminal autonomic cephalalgias, a terminology which reflects the predominant distribution of the pain, observable cranial autonomic features and shared pathophysiology. Understanding the latter is limited, both by low prevalence and the intricacies of studying brain function, requiring multimodal techniques to glean insights into such disorders. Similarly obscure is the curious response to indometacin. This review will address what is currently known about pathophysiology, the rationale for the current classification and, features which may confound the diagnosis, such as lack of cranial autonomic symptoms and those which are typically associated with migraine such as nausea, photophobia, phonophobia and aura. Despite these characteristics, a dramatic response to indometacin, which is not seen in migraine nor the other trigeminal autonomic cephalalgias , provides the hallmark of the diagnosis. The main clinical differential for paroxysmal hemicrania is based on temporal pattern and lies between cluster headache and short-lasting-neuralgiform headache attacks with tearing or additional cranial autonomic symptoms. For hemicrania continua it is more challenging as the main differential for which the disorder is often treated is migraine. A prior episodic pattern, often days at a time, and the tendency to exacerbation with analgesics will further deflect from the diagnosis. The relevance of this is that there is little overlap in therapeutics between paroxysmal hemicrania and hemicrania continua and other headache disorders and there are limited effective alternatives to indometacin. The most effective are other non-steroidal anti-inflammatory drugs including the newer COX-II inhibitors. Even though early reports suggest that a higher indometacin dose-requirement may herald a secondary precipitating pathology, this does not seem to be the case, with syndrome and response to treatment being similar with the primary disorder. In this context imaging of new onset paroxysmal hemicrania or hemicrania continua and implication of the results will be discussed as will alternative treatment options.

Cigarette smoking history (personal and secondary childhood exposure) in non-cluster headache trigeminal autonomic cephalalgias: A clinic based study.

OBJECTIVE: To look at cigarette smoking history (personal and secondary exposure as a child) in non-cluster headache trigeminal autonomic cephalalgias seen at a headache clinic and to determine smoking exposure prevalence utilizing previously published data. METHODS: Retrospective chart review and PubMed/Google Scholar search. RESULTS: Forty-eight clinic patients met ICHD-3 criteria for non-cluster headache trigeminal autonomic cephalalgias. Four had paroxysmal hemicrania, 75% were smokers and secondary exposure was noted in all. 16 patients had short lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing (SUNCT) or short lasting unilateral neuralgiform headache attacks with autonomic symptoms (SUNA), 12.5% were smokers and secondary exposure was noted in 91%. Twenty-eight patients had hemicrania continua, 21% were smokers and secondary exposure was found in 62.5%.Since 1974 there have been 88 paroxysmal hemicrania, 50 SUNCT or SUNA and 89 hemicrania continua patients with a documented smoking exposure history. From current data and previous studies, a smoking history was noted in 60% paroxysmal hemicrania, 18% SUNCT and SUNA and 21% hemicrania continua patients. CONCLUSION: A cigarette smoking history appears to be connected to paroxysmal hemicrania (personal and secondary exposure) and possibly to SUNCT/SUNA (secondary) and hemicrania continua (secondary).

Efficacy of Occipital Nerve Stimulation in Trigeminal Autonomic Cephalalgias: A Systematic Review.

BACKGROUND: Trigeminal autonomic cephalalgias (TACs) are a group of highly disabling primary headache disorders. Although pharmacological treatments exist, they are not always effective or well tolerated. Occipital nerve stimulation (ONS) is a potentially effective surgical treatment. OBJECTIVE: To perform a systematic review of the efficacy of ONS in treating TACs. METHODS: A systematic review was performed using Medline, Embase, and Cochrane databases. Primary outcomes were reduction in headache intensity, duration, and frequency. Secondary outcomes included adverse event rate and reduction in medication use. Because of large differences in outcome measures, data for patients suffering from short-lasting, unilateral, and neuralgiform headache attacks with conjunctival injection and tearing (SUNCT) and cranial autonomic symptoms (SUNA) were reported separately. Risk of bias was assessed using the NIH Quality Assessment Tools. RESULTS: A total of 417 patients from 14 published papers were included in the analysis, of which 15 patients were in the SUNCT/SUNA cohort. The mean reduction in headache intensity and duration was 26.2% and 31.4%, respectively. There was a mean reduction in headache frequency of 50%, as well as a 61.2% reduction in the use of abortive medications and a 31.1% reduction in the use of prophylactic medications. In the SUNCT/SUNA cohort, the mean decrease in headache intensity and duration was 56.8% and 42.8%. The overall responder rate, defined as a >50% reduction in attack frequency, was 60.8% for the non-SUNCT/non-SUNA cohort and 66.7% for the SUNCT/SUNA cohort. Adverse events requiring repeat surgery were reported in 33% of cases. Risk of bias assessment suggests that articles included in this review had reasonable internal validity. CONCLUSION: ONS may be an effective surgical treatment for approximately two thirds of patients with medically refractory TACs.

Epidemiology, burden and clinical spectrum of cluster headache: a global update.

BACKGROUND: This narrative review aims to broaden our understanding of the epidemiology, burden and clinical spectrum of cluster headache based on updated findings with a global perspective. METHODS: We conducted a literature search on the following topics: (a) epidemiology; (b) burden: quality of life, disability, economic burden, job-related burden and suicidality; and (c) clinical spectrum: male predominance and its changes, age, pre-cluster and pre-attack symptoms, aura, post-drome, attack characteristics (location, severity, duration and associated symptoms), bout characteristics (attack frequency, bout duration and bout frequency), circadian and seasonal rhythmicity and disease course. RESULTS: New large-scale population-based reports have suggested a lower prevalence than previous estimations. The impact of cluster headache creates a significant burden in terms of the quality of life, disability, economic and job-related burdens and suicidality. Several studies have reported decreasing male-to-female ratios and a wide age range at disease onset. The non-headache phases of cluster headache, including pre-cluster, pre-attack and postictal symptoms, have recently been revisited. The latest data regarding attack characteristics, bout characteristics, and circadian and seasonal rhythmicity from different countries have shown variability among bouts, attacks, individuals and ethnicities. Studies on the disease course of cluster headache have shown typical characteristics of attacks or bouts that decrease with time. CONCLUSIONS: Cluster headache may be more than a "trigeminal autonomic headache" because it involves complex central nervous system phenomena. The spectrum of attacks and bouts is wider than previously recognised. Cluster headache is a dynamic disorder that evolves or regresses over time.

Status of diagnosis and preventative treatment for primary headache disorders: real-world data of unmet needs in China.

BACKGROUND: Headache disorders are widely prevalent and pose a considerable economic burden on individuals and society. Globally, misdiagnosis and inadequate treatment of primary headache disorders remain significant challenges, impeding the effective management of such conditions. Despite advancements in headache management over the last decade, a need for comprehensive evaluations of the status of primary headache disorders in China regarding diagnosis and preventative treatments persists. METHODS: In the present study, we analyzed the established queries in the Survey of Fibromyalgia Comorbidity with Headache (SEARCH), focusing on previous diagnoses and preventative treatment regimens for primary headache disorders. This cross-sectional study encompassed adults diagnosed with primary headache disorders who sought treatment at 23 hospitals across China between September 2020 to May 2021. RESULTS: The study comprised 2,868 participants who were systematically examined. Migraine and tension-type headaches (TTH) constituted a majority of the primary headache disorders, accounting for 74.1% (2,124/2,868) and 23.3% (668/2,868) of the participants, respectively. Medication overuse headache (MOH) affected 8.1% (231/2,868) of individuals with primary headache disorders. Over half of the individuals with primary headache disorders (56.6%, 1,624/2,868) remained undiagnosed. The previously correct diagnosis rates for migraine, TTH, TACs, and MOH were 27.3% (580/2,124), 8.1% (54/668), 23.2% (13/56), and 3.5% (8/231), respectively. The misdiagnosis of "Nervous headache" was found to be the most prevalent among individuals with migraine (9.9%, 211/2,124), TTH (10.0%, 67/668), trigeminal autonomic cephalalgias (TACs) (17.9%, 10/56), and other primary headache disorders (10.0%, 2/20) respectively. Only a minor proportion of individuals with migraine (16.5%, 77/468) and TTH (4.7%, 2/43) had received preventive medication before participating in the study. CONCLUSIONS: While there has been progress made in the rate of correct diagnosis of primary headache disorders in China compared to a decade ago, the prevalence of misdiagnosis and inadequate treatment of primary headaches remains a veritable issue. As such, focused efforts are essential to augment the diagnosis and preventive treatment measures related to primary headache disorders in the future.

Trigeminal Autonomic Cephalalgias and Neuralgias in Children and Adolescents: a Narrative Review.

PURPOSE OF REVIEW: To summarize the available literature as well as the authors' experience on trigeminal autonomic cephalalgias (TACs) and cranial neuralgias in children and adolescents. RECENT FINDINGS: While TACs and cranial neuralgias are rare in children, several recent case series have been published. TACs in children share most of the clinical features of TACs in adults. However, there are many reported cases with clinical features which overlap more than one diagnosis, suggesting that TACs may be less differentiated in youth. Indomethacin-responsive cases of cluster headache and SUNCT/SUNA have been reported in children, whereas in adults indomethacin is usually reserved for paroxysmal hemicrania and hemicrania continua. Neuralgias appear to be rare in children. Clinical features are often similar to adult cases, though clinicians should maintain a high index of suspicion for underlying causes.

Hemicrania Continua: An Update.

PURPOSE OF REVIEW: Hemicrania Continua (HC) is a rare and disabling primary headache disorder that is characterized by persistent, unilateral headache with ipsilateral, cranial autonomic symptoms and restlessness or agitation. The diagnosis requires patients to experience an absolute response to therapeutic doses of indomethacin. RECENT FINDINGS: HC is diagnosed in in about 1.8% of adult patients who were evaluated for headache in tertiary care services, albeit this estimate should be interpreted with caution. The most prevalent accompanying symptoms appear to be lacrimation, conjunctival injection and restlessness or agitation. However, the available literature is limited by methodologic issues, and the current diagnostic criteria lack clarity on what defines absolute response to indomethacin. More rigorous studies are thus needed to improve our understanding of HC which, in turn, will facilitate better disease management in clinical practice. Here, we provide a comprehensive overview of HC, including its epidemiology, clinical presentation, diagnostic evaluation, and management.

[SUNCT/SUNA: frequently misdiagnosed as trigeminal neuralgia?] / SUNCT/SUNA: ¿frecuentemente mal diagnosticada como neuralgia del trigémino?

OBJECTIVE: 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. PATIENTS AND METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

TITLE: SUNCT/SUNA: ¿frecuentemente mal diagnosticada como neuralgia del trigémino?Objetivo. Identificar el número de casos con posible diagnóstico de cefalea neuralgiforme unilateral de corta duración con inyección conjuntival y lagrimeo (SUNCT) o cefalea neuralgiforme unilateral de corta duración con síntomas autonómicos craneales (SUNA) en pacientes con un previo diagnóstico de neuralgia del trigémino (NT) en el servicio de neurología del Centro Médico Nacional 20 de Noviembre, comprobando así que estas cefaleas trigeminoautonómicas deben ser descartadas y consideradas como diagnósticos diferenciales de la NT. Pacientes y métodos. Estudio transversal y retrospectivo. Se evaluaron los expedientes clínicos electrónicos completos de 100 pacientes con diagnóstico de NT durante el período de abril de 2010 a mayo de 2020. Intencionalmente se buscaron síntomas autonómicos en éstos y se compararon con los criterios diagnósticos de SUNCT y SUNA de la Clasificación Internacional de las Cefaleas, tercera edición. Se realizaron pruebas de chi cuadrado y posteriormente de regresión bivariada para determinar la asociación entre las variables. Resultados. Se incluyó a 100 pacientes con diagnóstico de NT. Tras la revisión de las manifestaciones clínicas, se encontró a 12 pacientes con síntomas autonómicos y se compararon con los criterios diagnósticos de SUNCT y SUNA. Estos no cumplieron los criterios absolutos para ser diagnosticados con las enfermedades previamente mencionadas; sin embargo, cumplieron las características del espectro de cefaleas trigeminoautonómicas. Conclusión. La NT es una entidad dolorosa y frecuente que puede presentar síntomas autonómicos, y es importante pensar en diagnósticos diferenciales, como la SUNCT y la SUNA, para la identificación y el tratamiento correctos.

Central generators of migraine and autonomic cephalalgias as targets for personalized pain management: Translational links.

BACKGROUND AND OBJECTIVE: Migraine oscillates between different states in association with internal homeostatic functions and biological rhythms that become more easily dysregulated in genetically susceptible individuals. Clinical and pre-clinical data on migraine pathophysiology support a primary role of the central nervous system (CNS) through 'dysexcitability' of certain brain networks, and a critical contribution of the peripheral sensory and autonomic signalling from the intracranial meningeal innervation. This review focuses on the most relevant back and forward translational studies devoted to the assessment of CNS dysfunctions involved in primary headaches and discusses the role they play in rendering the brain susceptible to headache states. METHODS AND RESULTS: We collected a body of scientific literature from human and animal investigations that provide a compelling perspective on the anatomical and functional underpinnings of the CNS in migraine and trigeminal autonomic cephalalgias. We focus on medullary, hypothalamic and corticofugal modulation mechanisms that represent strategic neural substrates for elucidating the links between trigeminovascular maladaptive states, migraine triggering and the temporal phenotype of the disease. CONCLUSION: It is argued that a better understanding of homeostatic dysfunctional states appears fundamental and may benefit the development of personalized therapeutic approaches for improving clinical outcomes in primary headache disorders. SIGNIFICANCE: This review focuses on the most relevant back and forward translational studies showing the crucial role of top-down brain modulation in triggering and maintaining primary headache states and how these central dysfunctions may interact with personalized pain management strategies.

Symptomatic trigeminal autonomic cephalalgias in neuromyelitis optica spectrum disorders.

BACKGROUND: The pathophysiology of trigeminal autonomic cephalalgias (TACs) is poorly understood at present. Symptomatic TACs are rarely reported in neuromyelitis optica spectrum disorders (NMOSD). To better clarify this distinct clinical manifestation in NMOSD and to investigate its possible pathophysiology, we reviewed articles describing such cases including our own case. METHODS: We performed a search of all clinical studies of TACs in NMOSD published up to September 1st, 2022. We put no restrictions on the year of English publication in our search. The following keywords were searched: trigeminal autonomic cephalalgias, cluster headache, short-lasting unilateral neuralgiform headache with conjunctival injection and tearing (SUNCT), short-lasting unilateral neuralgiform headache with autonomic symptoms (SUNA), hemicrania continua, paroxysmal hemicrania, neuromyelitis optica, neuromyelitis optica spectrum disorder, Devic's disease. RESULT: We reviewed six cases (five published reports and our own case study) that fulfilled the diagnosis of NMOSD and TACs. Four of them were SUNCT, one was SUNA, and one was paroxysmal hemicrania. In three of these cases, headache was the initial sole manifestation. Only one case had a good response to routine TACs' treatment. All these patients had lesions in the medulla oblongata and cervical cord. Three cases' TACs were side-locked, and two of them had a left dorsolateral medulla oblongata lesion that corresponded with the left side TACs, while three cases' headaches happened on either side of the head. The phenomenon could be explained by the activation of trigeminal-autonomic reflex and ephaptic coupling. CONCLUSION: TACs could be the initial sole brainstem manifestation of NMOSD. An underlying cause for SUNCT/SUNA should be considered, especially if there is a limited response to anti-epileptic medication. The activation of trigeminal-autonomic reflex and ephaptic coupling might be the underlying mechanism of symptomatic TACs in NMOSD.

Clínica y fisiopatología de la cefalea en racimos. Acercamiento a la indicación de neuroestimulación combinada occipital y supraorbitaria / Symptoms and pathophysiology of cluster headache. Approach to combined occipital and supraorbital neurostimulation

La cefalea en racimos (CR) se encuadra dentro del apartado 3 de la clasificación de la Sociedad Internacional de Cefaleas (IHS), que es el reservado para las llamadas cefaleas trigémino autonómicas (CTA). Se trata de uno de los procesos de cefalea primaria más frecuentes, dolorosos e incapacitantes. Los tratamientos farmacológicos agudos y preventivos son, en muchos casos, mal tolerados y de efectividad limitada. Debido a la mejora en la comprensión de su fisiopatología de la CR, los dispositivos de neuromodulación se han posicionado como opciones seguras y eficaces de tratamiento preventivo y el tratamiento agudo de la CR. Haremos un recorrido sobre la información disponible hasta el momento y además, exponemos el caso de un paciente con CR incapacitante, muy resistente al tratamiento médico, tratado en nuestra Unidad del Dolor con el implante de un sistema de neuroestimulación de nervio periférico de nervios supraorbitario (SON) y nervio occipital mayor (GON). A continuación revisaremos los criterios diagnósticos que la definen la CR, lo datos que conocemos, a día de hoy, sobre su fisiopatología y la posición que ocupa actualmente la neuromodulación en el abordaje terapéutico de la misma. Con la descripción del caso clínico de un paciente tratado en nuestra Unidad del Dolor con una cefalea especialmente severa y resistente al tratamiento farmacológico.(AU)

Cluster headache (CH) is included under section 3 - Trigeminal autonomic cephalalgias (TAC) of the International Headache Society (IHS) classification. It is one of the most frequent, painful and disabling primary headaches. Acute and preventive pharmacological treatments are often poorly tolerated and of limited effectiveness. Due to improved understanding of the pathophysiology of CH, neuromodulation devices are now considered safe and effective options for preventive and acute treatment of CH. In this paper, we review the information available to date, and present the case of a patient with disabling cluster headache highly resistant to medical treatment who underwent implantation of a peripheral nerve neurostimulation system to stimulate the supraorbital nerves (SON) and greater occipital nerve (GON) in our Pain Unit. We also review the diagnostic criteria for CH, the state of the knowledge on the pathophysiology of CH, and the role played by neuromodulation in treating this condition.(AU)

Management of Trigeminal Autonomic Cephalalgias Including Chronic Cluster: A Review.

Importance: Trigeminal autonomic cephalalgias (TACs) comprise a unique collection of primary headache disorders characterized by moderate or severe unilateral pain, localized in in the area of distribution of the first branch of the trigeminal nerve, accompanied by cranial autonomic symptoms and signs. Most TACs are rare diseases, which hampers the possibility of performing randomized clinical trials and large studies. Therefore, knowledge of treatment efficacy must be based only on observational studies, rare disease registries, and case reports, where real-world data and evidence play an important role in health care decisions. Observations: Chronic cluster headache is the most common of these disorders, and the literature offers some evidence from randomized clinical trials to support the use of pharmacologic and neurostimulation treatments. Galcanezumab, a monoclonal antibody targeting the calcitonin gene-related peptide, was not effective at 3 months in a randomized clinical trial but showed efficacy at 12 months in a large case series. For the other TACs (ie, paroxysmal hemicrania, hemicrania continua, short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing, and short-lasting unilateral neuralgiform headache attacks with cranial autonomic symptoms), only case reports and case series are available to guide physicians in everyday management. Conclusions and Relevance: The accumulation of epidemiologic, pathophysiologic, natural history knowledge, and data from case series and small controlled trials, especially over the past 20 years from investigators around the world, has added to the previously limited evidence and has helped advance and inform the treatment approach to rare TACs, which can be extremely challenging for clinicians.

Clinical Reasoning: A Teenager With Right-Sided Headache and Periorbital Changes.

While migraine is the most common headache disorder in children and adolescents presenting to a neurologist, other primary headache disorders are important to recognize. Trigeminal autonomic cephalalgias represent a rare group of primary headache disorders with different characteristics, workup, and management. In this study, we present an adolescent with 1 common and 1 unique headache phenotype, followed by a guided discussion of the differential diagnoses, workup, treatments, and a brief summary of further management considerations.