Indomethacin-responsive trigeminal autonomic cephalgias: a review of key characteristics and pathophysiology.

Trigeminal autonomic cephalgias (TACs) are a well-defined subset of uncommon primary headaches that share comparable onset, pathophysiology and symptom patterns. TACs are characterised by the presentation of one-sided and high-intensity trigeminal pain together with unilateral cranial autonomic signs, which can include lacrimation, rhinorrhea, and miosis. The International Classification of Headache Disorders 3rd Edition recognises four different headache entities in this group, with cluster headache as the most recognised among them. Hemicrania continua (HC) and paroxysmal hemicrania (PH) are both distinctive cephalgias of which the diagnostic criteria include an absolute response to indomethacin. Consequently, for this reason they are often referred to as 'indomethacin-responsive' TACs. The main focus of this review was to discuss the state of knowledge regarding the pathophysiology and key characteristics of PH and HC. Given the limited understanding of these conditions, and their exceptionally uncommon prevalence, a correct diagnosis can pose a clinical challenge and the search for an effective treatment may be prolonged, which frequently has a serious impact upon patients' quality of life. The information provided in this review is meant to help physicians to differentiate indomethacin-sensitive cephalgias from other distinct headache disorders with a relatively similar clinical presentation, such as cluster headache, trigeminal neuralgia, and various migraine conditions.

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.

Imaging in headache disorders.

Patients with a suspected change in intracranial pressure or a trigeminal autonomic cephalgia require MRI. The need for investigation for other headache disorders is guided by the clinical evaluation of the patient. Particular care should be taken to identify any 'red flags'. Incidental findings on MRI occur in approximately 2% of patients. Patients with migraine have an increased rate of white matter lesions, but these are of uncertain clinical significance.

Clinical Presentation and Management of Headache in Pituitary Tumors.

PURPOSE OF REVIEW: This article provides an overview of headache in the setting of pituitary adenoma. The purpose of this article is to educate providers on the association, possible pathophysiology, and the clinical presentation of headache in pituitary tumor. RECENT FINDINGS: Recent prospective evaluations indicate that risk factors for development of headache in the setting of pituitary adenoma include highly proliferative tumors, cavernous sinus invasion, and personal or family history of headache. Migraine-like headaches are the predominant presentation. Unilateral headaches are often ipsilateral to the side of cavernous sinus invasion. In summary, this paper describes how the size and type of pituitary tumors play an important role in causation of headaches. Pituitary adenoma-associated headache can also mimic primary headache disorders making recognition of a secondary process difficult. Therefore, this paper highlights the association of between trigeminal autonomic cephalgias and pituitary adenomas and urges practitioners to maintain a high index of suspicion when evaluating patients with these uncommon headache presentations. However, on balance, given the prevalence of both primary headache disorders and pituitary adenomas, determining causality can be challenging. A thoughtful and multidisciplinary approach is often the best management strategy, and treatment may require the expertise of multiple specialties including neurology, neurosurgery, and endocrinology.

Novel Interventional Nonopioid Therapies in Headache Management.

PURPOSE OF REVIEW: Headaches encompass a broad-based category of a symptom of pain in the region of the head or neck. For those patients who unfortunately do not obtain relief from conservative treatment, interventional techniques have been developed and are continuing to be refined in an attempt to treat this subset of patients with the goal of return of daily activities. This investigation reviews various categories of headaches, their pathophysiology, and types of interventional treatments currently available. RECENT FINDINGS: Injection of botulinum toxin has been shown to increase the number of headache free days for patients suffering from chronic tension-type headaches. Suboccipital steroid injection has been demonstrated as a successful treatment option for patients suffering from cluster headache. Occipital nerve stimulation (ONS) has been described as a treatment for all types of trigeminal autonomic cephalgias. Percutaneous ONS is a minimally invasive and reversible approach to manage occipital neuralgia performed utilizing subcutaneous electrodes placed superficial to the cervical muscular fascia in the suboccipital area. Radiofrequency lesioning is another commonly used treatment in the management of chronic pain syndromes of the head and neck. If a diagnostic sphenopalatine ganglion block successfully resolves the patient's symptoms, neurolysis can be employed as a more permanent solution. Although many patients who suffer from headaches can be treated with conservative, less-invasive treatments, there still remains at present an ever-increasing need for those patients who are refractory to conservative measures and thus require interventional treatments. These procedures are continually evolving to become safer, more precise, and more readily available for clinicians to provide to their patients.

Red Ear Syndrome.

The Red Ear syndrome (RES) is an intriguing syndrome originally described for the first time nearly 20 years ago. RES is characterized by unilateral/bilateral episodes of pain and burning sensation of the ear, associated with ipsilateral erythema. RES episodes are indeed isolated in some patients, but they can occur in association with primary headaches, including in particular migraine in the developmental age. Although the underlying pathophysiological mechanisms are still uncertain, in the recent years the described comorbidities have aroused increasing interest because of possible clinical implications. Moreover, RES seems to be more often associated with clinical features of migraine partially provoked by the involvement of the parasympathetic system. This clinical association has shed new light on the pathophysiology of RES, supporting the hypothesis of a shared pathophysiological background, for example, through the activation of the trigeminal autonomic reflex. Current therapies of RES will be also discussed. Finally, we will resume the more controversial aspects of this relatively new and probably underestimated neurological syndrome.

[Trigeminal autonomic cephalgias: features of diagnosis and treatment]. / Trigeminal'nye avtonomnye tsefalgii: osobennosti diagnostiki i lecheniya.

Trigeminal autonomic cephalgias is a group of primary headaches, including cluster headache, paroxysmal hemicrania and hemicrania continua, as well as two forms of short- lasting unilateral neuralgiform headache attacks, the complexity of diagnosis of which is determined by the low prevalence and some similarity of clinical manifestations both among themselves and with other diseases in particular with migraine and trigeminal neuralgia. Despite the rather short duration of headache attacks, the intensity of the pain syndrome reaches a severe and very severe degree, and the high frequency of paroxysms per day significantly complicates abortion treatment and leads to a pronounced professional and social maladjustment. At the same time, the possibility of using effective specific prophylactic therapy determines the importance of accurate diagnosis and, therefore, the knowledge of neurologists on this issue.

Insights on the terminology and on some pathophysiological aspects of cluster headache and related conditions / Insights sobre a terminologia e alguns aspectos fisiopatológicos da cefaléia em salvas e condições relacionadas

Introduction: Cluster headache and the more recently reported "related conditions",namely Chronic Paroxysmal Hemicrania, Short lasting, unilateral, Neuralgiform Headache with Conjunctival Injection and Tearing (SUNCT) Syndrome and (possibly also) Hemicrania Continua, are one of the fascinating groups of conditions in Neurology whose cardinal features are the almost absolute unilaterality of pain, its excruciating severity, besides the prominent mainly facial autonomic disturbances and overall the intriguing biorhythmicity. Beyond any doubt, the progress of our knowledge about the mechanisms of these conditions has been considerable, but there is always room for reflection on where we are and where we can go. Objective: The objectives of the present study are to analyze the metrics of publications on the pathophysiology of these conditions, to explore in detail how proper the term "Trigeminal Autonomic Cephalgia" is, and to comment on their numerous synonyms. Comment: Much is needed to know the exact structures and circuitry involved in the pathophysiology of these conditions; accordingly, a non-compromising and just descriptive term might be useful. Along this line of reasoning and bearing in mind the cardinal points of such conditions, namely, pain in the trigeminal territory, prominent autonomic symptoms, prominent chronobiological features, and the excruciating character of the pain, a terminological possibility would be: Unilateral with Prominent Rhythmicity and Autonomic Symptoms Excrutiating Cephalgia (UPRASEC).

Introdução: Cefaleia em salvas e as "condições relacionadas" relatadas mais recentemente, nomeadamente Hemicrania Paroxística Crónica, Cefaleia Neuralgiforme unilateral de curta duração com Síndrome de Injecção e Lacrimejamento Conjuntival (SUNCT) e (possivelmente também) Hemicrania Continua, são um dos grupos fascinantes de condições em Neurologia cujas características cardinais são a unilateralidade quase absoluta da dor, sua gravidade excruciante, além dos proeminentes distúrbios autonômicos principalmente faciais e, em geral, da intrigante biorritmicidade. Sem dúvida, o progresso do nosso conhecimento sobre os mecanismos destas condições tem sido considerável, mas há sempre espaço para reflexão sobre onde estamos e para onde podemos ir. Objetivo: Os objetivos do presente estudo são analisar as métricas das publicações sobre a fisiopatologia dessas condições, explorar detalhadamente o quão adequado é o termo "Cefalgia Autonômica Trigeminal" e comentar seus numerosos sinônimos. Comentário: É necessário muito conhecimento das estruturas e circuitos exatos envolvidos na fisiopatologia dessas condições; consequentemente, um termo não comprometedor e apenas descritivo pode ser útil. Nessa linha de raciocínio e tendo em mente os pontos cardeais de tais condições, a saber, dor no território trigêmeo, sintomas autonômicos proeminentes, características cronobiológicas proeminentes e o caráter excruciante da dor, uma possibilidade terminológica seria: Unilateral com Ritmicidade Proeminente e sintomas autonômicos excruciantes da cefalgia (UPRASEC).

Hypothalamic deep brain stimulation in the treatment of chronic cluster headache.

Cluster headache (CH) is a short-lasting unilateral headache associated with ipsilateral craniofacial autonomic manifestations. A positron emission tomography (PET) study has shown that the posterior hypothalamus is activated during CH attacks, suggesting that hypothalamic hyperactivity plays a key role in CH pathophysiology. On this basis, stimulation of the ipsilateral posterior hypothalamus was hypothesized to counteract such hyperactivity to prevent intractable CH. Ten years after its introduction, hypothalamic stimulation has been proved to successfully prevent attacks in more than 60% of 58 hypothalamic implanted drug-resistant chronic CH patients. The implantation procedure has generally been proved to be safe, although it carries a small risk of brain haemorrhage. Long-term stimulation is safe, and nonsymptomatic impairment of orthostatic adaptation is the only noteworthy change. Microrecording studies will make it possible to better identify the target site. Neuroimaging investigations have shown that hypothalamic stimulation activates ipsilateral trigeminal complex, but with no immediate perceived sensation within the trigeminal distribution. Other studies on the pain threshold in chronically stimulated patients showed increased threshold for cold pain in the distribution of the first trigeminal branch ipsilateral to stimulation. These studies suggest that activation of the hypothalamus and of the trigeminal system are both necessary, but not sufficient to generate CH attacks. In addition to the hypothalamus, other unknown brain areas are likely to play a role in the pathophysiology of this illness. Hypothalamus implantation is associated with a small risk of intracerebral haemorrhage and must be performed by an expert neurosurgical team, in selected patients.