Ipsilateral Cranial Autonomic Symptoms Research Articles

Cephalalgia heterotopica: a case series of extratrigeminal cluster headache

Introduction Cluster headache is a very disabling neurological disorder that usually presents with unilateral severe headache associated with ipsilateral cranial autonomic symptoms. Even among the typical cases, there is a considerable diagnostic delay and most patients will have seen three general practitioners before being referred to neurology services, some having been to colleagues in dentistry or otorhinolaryngology. The extratrigeminal presentation of this condition poses a great obstacle to a proper diagnostic workup. Objective This consecutive case series study aimed to report clinical features, treatment, and outcome of 3 patients with extratrigeminal Cluster Headache. Materials and Methods Case series of our Headache Clinic. Data disclosure was authorized by the patients through an informed consent form. Results Two males and one female were evaluated. The ages were 53, 64, and 71 years. The mean age of symptoms onset was 50, 60, and 66 years, respectively. Two patients described excruciating shoulder pain and one presents severe pain in the malar area. All patients reported prominent autonomic ipsilateral symptoms such as lacrimation, conjunctival injection, nasal symptoms, and restlessness accompanying pain attacks. Preventive treatment with verapamil and occipital nerve block was useful. Conclusion Extratrigeminal cluster presentation is a diagnostic challenge. Proper recognition of these cases prevents unnecessary examination and treatment trials and directly benefits the patients since effective treatment is already available. A proper case definition of this rare clinical presentation may provide new insight into our understanding of the cluster headache mechanisms. Keywords: Cluster headache, Extratrigeminal headache, Shoulder pain.

202 Placebo-controlled intravenous nitroglycerin phenotyping of acute attacks of cluster headache

IntroductionCluster headache (CH) is characterised by attacks of excruciating unilateral headache, ipsilateral cranial autonomic symptoms (CAS) and/or agitation. Nitroglycerin (NTG) is known to induce CH. This study is the first single-blind placebo-controlled study using intravenous NTG in CH to characterise comprehensively NTG induced CH attacks.MethodsCH patients attended three study visits in total, first visit CH patients were unblinded and received intravenous NTG 0.5mcg/kg/min over 20 minutes, if successful they were asked to return for blinded visits either receiving NTG or placebo. The clinical phenotype was recorded. The study was approved by the NHS Research Ethics Committee.ResultsThirty-three patients participated, 24 completed all study visits. Nineteen episodic cluster headache (58%) and 14 chronic cluster headache (42%). NTG brought on CH attacks (n= 26, 79%), agitation (n= 24, 73%) and CAS (n= 31, 94%) in the unblinded NTG visit. NTG brought on CH attacks (n= 19, 76%), agitation (n= 20, 80%) and CAS (n= 21, 84%) in the blinded NTG visit. Only one participant had a spontaneous CH attack (4%) in the placebo visits, four participants reported unilateral CAS symptoms, and none had agitation.ConclusionWe demonstrate that intravenous NTG effectively triggers CH attacks.diana.wei@kcl.ac.uk

Diagnostic Delay and Its Predictors in Cluster Headache.

ObjectiveCluster headache (CH) is a rare, primary headache disorder, characterized of excruciating, strictly one-sided pain attacks and ipsilateral cranial autonomic symptoms. Given the debilitating nature of CH, delayed diagnosis can increase the disease burden. Thus, we aimed to investigate the diagnostic delay, its predictors, and clinical influence among patients with CH.MethodsData from a prospective multicenter CH registry over a 4-year period were analyzed. CH was diagnosed according to the International Classification of Headache Disorders (ICHD)-3 criteria, and diagnostic delay of CH was assessed as the time interval between the year of the first onset and the year of CH diagnosis. Patients were classified into three groups according to the tertiles of diagnostic delay (1st tertile, <1 year; 2nd tertile, 1–6 years; and 3rd tertile, ≥7 years).ResultsOverall, 445 patients were evaluated. The mean duration of diagnosis delay was 5.7 ± 6.7 years, (range, 0–36 years). Regarding the age of onset, majority of young patients (age <20 years) belonged to the third tertile (60%), whereas minority of old patients (>40 years) belonged to the third tertile (9.0%). For year of onset, the proportion of patients in the 3rd tertile was the highest for the groups before the publication year of the ICHD-2 (74.7%) and the lowest for the groups after the publication year of the ICHD-3 beta version (0.5%). Compared with the first CH, episodic CH [multivariable-adjusted odds ratio (aOR) = 5.91, 95% CI = 2.42–14.48], chronic CH (aOR = 8.87, 95% CI = 2.66–29.51), and probable CH (aOR = 4.12, 95% CI = 1.48–11.43) were associated with the tertiles of diagnostic delay. Age of onset (aOR = 0.97, 95% CI = 0.95–0.99) and PHQ-9 score (aOR = 0.96, 95% CI = 0.93–0.99) were inversely associated with the tertile of diagnostic delay. The prevalence of suicidal ideation was highest in the patients of the third tertile. The mean HIT-6 score increased significantly with the diagnostic delay (p = 0.041).ConclusionsPatients with a younger onset of CH have a higher risk of diagnostic delay. Nevertheless, the rate of delayed diagnosis gradually improved over time and with the publication of the ICHD criteria, supporting the clinical significance of diagnostic clinical criteria and headache education to reduce the disease burden of CH.

Update on Treatment of Cluster Headache

Cluster headache (CH) is characterized by severe unilateral short-lasting headache attacks, accompanying ipsilateral cranial autonomic symptoms or the sense of restlessness and agitation, or both. CH is a highly disabling primary headache disorder but often not optimally treated. High-flow oxygen and parenteral triptans are the most effective treatment to treat an acute CH attack. Transitional treatments include systemic steroid therapy and sub-occipital steroid injection. For preventive therapy, verapamil and lithium are recommended as first-line treatments. Novel treatments have appeared, such as neuromodulation and medication targeting calcitonin gene-related peptide (CGRP) or its receptor. Galcanezumab, the only anti-CGRP receptor monoclonal antibody with proven efficacy for the preventive treatment of episodic CH, represents an important advance for pharmacological treatment of CH. Neuromodulation strategies, such as the non-invasive vagus nerve stimulation and the sphenopalatine ganglion stimulation, have been proven effective in reducing the intensity and frequency of attacks, and also to be safe and well tolerated.

Cluster Headache: What's New?

Cluster headache is a highly disabling primary headache disorder which is widely described as the most painful condition a human can experience. To provide an overview of the clinical characteristics, epidemiology, risk factors, differential diagnosis, pathophysiology and treatment options of cluster headache, with a focus on recent developments in the field. Structured review of the literature on cluster headache. Cluster headache affects approximately one in 1000 of the population. It is characterised by attacks of severe unilateral head pain associated with ipsilateral cranial autonomic symptoms, and the tendency for attacks to occur with circadian and circannual periodicity. The pathophysiology of cluster headache and other primary headache disorders has recently become better understood and is thought to involve the hypothalamus and trigeminovascular system. There is good quality evidence for acute treatment of attacks with parenteral triptans and high flow oxygen; preventive treatment with verapamil; and transitional treatment with oral corticosteroids or greater occipital nerve injection. New pharmacological and neuromodulation therapies have recently been developed. Cluster headache causes distinctive symptoms, which once they are recognised can usually be managed with a variety of established treatments. Recent pathophysiological understanding has led to the development of newer pharmacological and neuromodulation therapies, which may soon become established in clinical practice.

SUNCT and SUNA: An Update.

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

Machine phenotyping of cluster headache and its response to verapamil.

Cluster headache is characterized by recurrent, unilateral attacks of excruciating pain associated with ipsilateral cranial autonomic symptoms. Although a wide array of clinical, anatomical, physiological, and genetic data have informed multiple theories about the underlying pathophysiology, the lack of a comprehensive mechanistic understanding has inhibited, on the one hand, the development of new treatments and, on the other, the identification of features predictive of response to established ones. The first-line drug, verapamil, is found to be effective in only half of all patients, and after several weeks of dose escalation, rendering therapeutic selection both uncertain and slow. Here we use high-dimensional modelling of routinely acquired phenotypic and MRI data to quantify the predictability of verapamil responsiveness and to illuminate its neural dependants, across a cohort of 708 patients evaluated for cluster headache at the National Hospital for Neurology and Neurosurgery between 2007 and 2017. We derive a succinct latent representation of cluster headache from non-linear dimensionality reduction of structured clinical features, revealing novel phenotypic clusters. In a subset of patients, we show that individually predictive models based on gradient boosting machines can predict verapamil responsiveness from clinical (410 patients) and imaging (194 patients) features. Models combining clinical and imaging data establish the first benchmark for predicting verapamil responsiveness, with an area under the receiver operating characteristic curve of 0.689 on cross-validation (95% confidence interval: 0.651 to 0.710) and 0.621 on held-out data. In the imaged patients, voxel-based morphometry revealed a grey matter cluster in lobule VI of the cerebellum (−4, −66, −20) exhibiting enhanced grey matter concentrations in verapamil non-responders compared with responders (familywise error-corrected P = 0.008, 29 voxels). We propose a mechanism for the therapeutic effect of verapamil that draws on the neuroanatomy and neurochemistry of the identified region. Our results reveal previously unrecognized high-dimensional structure within the phenotypic landscape of cluster headache that enables prediction of treatment response with modest fidelity. An analogous approach applied to larger, globally representative datasets could facilitate data-driven redefinition of diagnostic criteria and stronger, more generalizable predictive models of treatment responsiveness.

Understanding Cluster Headache Using Magnetic Resonance Imaging.

Cluster headache is an excruciating pain syndrome characterized by unilateral head pain attacks, lasting between 15 and 180 min, accompanied by marked ipsilateral cranial autonomic symptoms, such as lacrimation and conjunctival injection. Despite important insights provided by neuroimaging studies and deep brain stimulation findings, the pathophysiology of cluster headache and its pathways of chronicization are still elusive. In this mini-review, we will provide an overview of the functional and structural neuroimaging studies in episodic and chronic cluster headache conditions conducted to clarify the underlying pathophysiology.

Managing cluster headache

Cluster headache is a neurological disorder that presents with unilateral severe headache associated with ipsilateral cranial autonomic symptoms. Cluster headache attacks often occur more than once a day, and typically...

Trigeminal autonomic cephalalgias: The impersonators

Orofacial pain disorders are highly prevalent and debilitating conditions involving the head, face, and neck. Headache is the most common complaint reported to dental and medical practitioners, which manifests as a myriad of neuro-ophthalmologic symptoms, including orbital pain, disturbances of vision, aura, photophobia, lacrimation, conjunctival injection, ptosis, and other manifestations. The differential diagnosis is extensive and includes both primary and secondary headache disorders. The similarity in clinical presentation and diagnostic features is a challenge to the clinicians because of two facts: (a) the orofacial region is complex and (b) pain can arise from many sources. The term “trigeminal autonomic cephalalgias (TACs)” includes a group of headache disorders characterized by moderate-to-severe, short-lived head pain in the trigeminal distribution, with accompanying unilateral cranial parasympathetic autonomic features, such as lacrimation, rhinorrhea, conjunctival injection, eyelid edema, and ptosis. TACs include cluster headache (CH), paroxysmal hemicrania (PH), short-lasting unilateral neuralgiform headache attacks, and hemicrania continua. They are grouped on the basis of their shared clinical features of unilateral headache of varying durations and ipsilateral cranial autonomic symptoms. TACs are rare with the prevalence rate of <1%. The peculiarity of these conditions is their similar clinical presentation and overlapping features. A sound knowledge of TACs is essential for proper diagnosis. Moreover, multidisciplinary approaches for the management of these conditions are strongly recommended. Hence, the aim of this article is to provide an overview of trigeminal autonomic cephalalgias.

THUR 084 Cranial autonomic symptoms in cluster headache induced by nitroglycerin

IntroductionCluster headache (CH) is characterised by attacks of unilateral excruciating headache, ipsilateral cranial autonomic symptoms (CAS) and/or agitation. Studying of CAS can further our understanding of CH pathophysiology, but is limited by the episodic nature of the disease. Nitroglycerin (NTG) is known to induce CH. The aim of this study is to characterise CAS induced by NTG.MethodsCH patients received intravenous NTG 0.5 mcg/kg/min over 20 min. CAS and headache phenotype were recorded. The study was approved by the NHS Research Ethics Committee.ResultsTwenty-three patients participated: 83% male and 61% episodic cluster headache. The most common spontaneous CAS reported were lacrimation, nasal congestion and conjunctival injection. Agitation was reported in 96%. Nitroglycerin induced ipsilateral CAS in 91% of the patients, with 74% with ipsilateral pain. Most commonly induced CAS were nasal congestion, lacrimation and periorbital swelling. Agitation was reported in 61%. The majority of the CAS (80%) induced by NTG presented before the onset of severe pain.ConclusionWe demonstrate that NTG effectively triggers ipsilateral cranial autonomic symptoms in CH patients and that they often present in a phase before the onset of pain reflecting the underlying pathways during a cluster headache attack.

Trigeminal autonomic cephalalgias

Trigeminal autonomic cephalalgias is the group of primary headaches that include cluster headache, paroxysmal hemicranias, hemicranias continua and short-lasting unilateral neuralgic-like headache attacks. The common manifestations of these headache types are spontaneous attack of unilateral severe pain of orbital, supraorbital and/or temporal localization which are accompanied with ipsilateral cranial autonomic symptoms including conjunctival injection, lacrimation, nasal blockage, rhinorrhea, eyelid edema, facial sweating, feeling of ear fullness, miosis or ptosis. Agitation and restlessness during attacks are typical for all trigeminal autonomic cephalalgias. Pathophysiology has centered on the activation of the posterior hypothalamus and trigeminal autonomic reflex. But these trigeminal autonomic cephalalgias are differentiated by the duration, daily frequency of attacks, diurnal rhythms and reaction to different treatment and preventive medication.

Cluster headache.

Cluster headache is an excruciating, strictly one-sided pain syndrome with attacks that last between 15 minutes and 180 minutes and that are accompanied by marked ipsilateral cranial autonomic symptoms, such as lacrimation and conjunctival injection. The pain is so severe that female patients describe each attack as worse than childbirth. The past decade has seen remarkable progress in the understanding of the pathophysiological background of cluster headache and has implicated the brain, particularly the hypothalamus, as the generator of both the pain and the autonomic symptoms. Anatomical connections between the hypothalamus and the trigeminovascular system, as well as the parasympathetic nervous system, have also been implicated in cluster headache pathophysiology. The diagnosis of cluster headache involves excluding other primary headaches and secondary headaches and is based primarily on the patient's symptoms. Remarkable progress has been achieved in developing effective treatment options for single cluster attacks and in developing preventive measures, which include pharmacological therapies and neuromodulation.

Overview of Trigeminal Autonomic Cephalalgias: Nosologic Evolution, Diagnosis, and Management.

The term trigeminal autonomic cephalalgias (TACs) encompasses four primary headache disorders – cluster headache, paroxysmal hemicrania (PH), hemicrania continua (HC), short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing (SUNCT)/short-lasting unilateral neuralgiform headache attacks with cranial autonomic symptoms (SUNA). All of these except HC are characterized by short-lasting headaches. HC is characterized by a continuous unilateral headache that waxes and wanes in its intensity without complete resolution. It is included in the TACs group given the overlap in the activation of the posterior hypothalamic grey, and the shared clinical feature of unilateral head pain with ipsilateral cranial autonomic symptoms. The present review gives an overview of the nosologic evolution, diagnosis, and management of TACs.

Cluster Headache: Epidemiology, Pathophysiology, Clinical Features, and Diagnosis.

Cluster headache is a primary headache disorder affecting up to 0.1% of the population. Patients suffer from cluster headache attacks lasting from 15 to 180 min up to 8 times a day. The attacks are characterized by the severe unilateral pain mainly in the first division of the trigeminal nerve, with associated prominent unilateral cranial autonomic symptoms and a sense of agitation and restlessness during the attacks. The male-to-female ratio is approximately 2.5:1. Experimental, clinical, and neuroimaging studies have advanced our understanding of the pathogenesis of cluster headache. The pathophysiology involves activation of the trigeminovascular complex and the trigeminal-autonomic reflex and accounts for the unilateral severe headache, the prominent ipsilateral cranial autonomic symptoms. In addition, the circadian and circannual rhythmicity unique to this condition is postulated to involve the hypothalamus and suprachiasmatic nucleus. Although the clinical features are distinct, it may be misdiagnosed, with patients often presenting to the otolaryngologist or dentist with symptoms. The prognosis of cluster headache remains difficult to predict. Patients with episodic cluster headache can shift to chronic cluster headache and vice versa. Longitudinally, cluster headache tends to remit with age with less frequent bouts and more prolonged periods of remission in between bouts.

SUN: Short-Lasting Unilateral Neuralgiform Headache Attacks.

Short-lasting unilateral neuralgiform headache attacks (SUN) are part of the group of primary headaches called trigeminal autonomic cephalalgias (TACs). They are characterized by unilateral attacks of pain with associated ipsilateral cranial autonomic symptoms. Recently the classification of these attacks has changed, to incorporate the different types of autonomic symptoms such as conjunctival injection and tearing (or lack thereof). Previously considered to be rare and rather refractory to treatment, there is an increasing awareness of this syndrome and the therapeutic possibilities. This article discusses the clinical aspects of the syndrome, pathophysiology, current, and future treatments.

Trigeminal autonomic cephalalgias: a review

Trigeminal autonomic cephalalgias are a group of primary headache disorders presenting as unilateral pain in the somatic distribution of the trigeminal nerve, associated with ipsilateral cranial autonomic symptoms. This clinicopathologic group includes cluster headache, paroxysmal hemicrania, hemicrania continua and short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing/cranial autonomic features, which differ mainly as regards the duration and frequency of pain as well as response to treatment. These disorders are not as rare as they were thought to be and due to the severity of the pain can substantially affect the patients’ quality of life. Many other forms of primary headaches, such as migraine, trigeminal neuralgia and primary stabbing headache, as well as secondary headaches, particularly those caused by pituitary, posterior fossa, orbital, paranasal sinus and vascular pathology, need to be carefully considered in the diagnosis of trigeminal autonomic cephalalgias. Research in this field, particularly using functional neuroimaging, has resulted in a much better understanding of these disorders. Dysfunction in the nociceptive modulatory pathways in brain’s pain matrix is currently thought to produce a permissive state for the occurrence of a trigeminal autonomic cephalalgia attack, with posterior hypothalamus serving as a terminator rather than the generator of the attack. The current treatment strategies include medical and surgical approaches; of the latter, neuromodulation techniques, particularly deep brain stimulation of posterior hypothalamus, have proven to be particularly effective and promising.

Trigeminal Autonomic Cephalalgias.

This article reviews the clinical features of and treatment options for the trigeminal autonomic cephalalgias (TACs). The TACs are a group of primary headache disorders characterized by short-lasting episodes of severe unilateral headaches that are associated with ipsilateral cranial autonomic symptoms. The best known and most commonly seen TAC in clinical practice is cluster headache. The other syndromes within this group include paroxysmal hemicrania, hemicrania continua, and short-lasting unilateral neuralgiform headache attacks. Although these disorders share a similar phenotype, they are distinguished by differences in attack frequency and duration. Recognition of these clinical differences is paramount because treatment options vary; paroxysmal hemicrania and hemicrania continua demonstrate an absolute response to treatment with indomethacin, while the other syndromes respond to other agents. Although much less common than other headache disorders seen in clinical practice, recognition of the TACs is especially important as they are among the most severe and disabling syndromes in headache medicine.

Therapy of trigeminal autonomic headaches

Trigeminal autonomic cephalgias (TAC) are characterized by severe and strictly unilateral headaches with a frontotemporal and periorbital preponderance in combination with ipsilateral cranial autonomic symptoms, such as lacrimation, conjunctival injection, rhinorrhea, nasal congestion, and restlessness or agitation. One main differentiating factor is the duration of painful attacks. While attacks typically last 5s to 10min in SUNCT syndrome (short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing), paroxysmal hemicrania lasts 2-30min and cluster headaches 15-180min. Hemicrania continua represents a continuous TAC variant. From a therapeutic view, TACs differ substantially. Lamotrigine is used as first-choice prevention in SUNCT syndrome and indometacin in paroxysmal hemicrania. For cluster headaches, acute therapy with inhaled pure oxygen and fast-acting triptans (sumatriptan s.c. and intranasal zolmitriptan) is equally important to short-term preventive therapy with methysergide and cortisone and long-term prophylactic treatment comprising verapamil as drug of first choice and lithium carbonate and topiramate as drugs of second choice. In refractory cases of chronic cluster headache, neuromodulatory approaches such as occipital nerve stimulation and sphenopalatine ganglion stimulation are increasingly applied.

Diagnosis and Clinical Features of Trigemino‐Autonomic Headaches

Although severe short-lasting headaches are rare, they can be considered disabling conditions with a major impact on the quality of life of patients. These headaches can divided broadly in to those associated with autonomic symptoms, so called trigeminal autonomic cephalgias (TACs), and those with few or no autonomic symptoms. The TACs include cluster headache, paroxysmal hemicranias, hemicrania continua, and short-lasting unilateral neuralgiform headache attacks with cranial autonomic symptoms as well as short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing syndrome. In all of these syndromes, half-sided head pain and ipsilateral cranial autonomic symptoms such as lacrimation or rhinorrhea are prominent. The paroxysmal hemicranias have, unlike cluster headaches, a very robust response to indomethacin, leading to a notion of indomethacin-sensitive headaches. The diagnosis of TACs is exclusively a clinical task. Because of the fact that cluster headache is strictly half-sided, typically involves the region around the eye and temple and often starts in the upper jaw, most patients first consult a dentist or ophthalmologist. No single instrumental examination has yet been able to define, or ensure, the correct diagnosis, or differentiate idiopathic headache syndromes. It is crucial that a trained neurologist sees these patients early so that management can be optimized and unnecessary procedures can be avoided. Although TACS are, in comparison to migraine, quite rare, they are nevertheless clinically very important for the neurologist to consider as they are easy to diagnose and the treatment is very effective in most patients.