Trigeminal Autonomic Cephalalgias Research Articles

Cephalgic syndrome in patients with acromegaly

The aim of this review is to summarize the data available in the literature on the causes of headache in patients with acromegaly, as well as on the effect of various methods of acromegaly treatment on headache. Publications were searched in the PubMed database using the keywords «Headache in patients with acromegaly», «Headache in patients with pituitary adenomas», «Tension-type headache», «Migraine». Headache in patients with pituitary adenomas secreting somatotropic hormone (STH) is not uncommon: according to various authors, cephalgic syndrome occurs in 30-70% of patients with acromegaly and can worsen their quality of life, along with other factors, up to disability. By the nature of development, headache with acromegaly is classified into primary (migraine, tension headache, trigeminal autonomic cephalgia, for example, SUNCT syndrome and cluster headaches), and can also be caused by various causes directly related to the tumor. All this requires differential diagnosis. The factors causing headaches in somatotropinomas have not yet been well studied and require further research. These include the mass effect of the tumor, hormonal hypersecretion, pathology of the temporomandibular joint, sodium and fluid retention in the body, psychological factors, etc. The authors evaluated the effect on headache of various methods of acromegaly treatment: transnasal transsphenoidal adenomectomy, radiation therapy and drug therapy with somatostatin analogues, dopamine agonists and growth hormone receptor antagonist. However, even when normal levels of STH and insulin-like growth factor 1 (IGF-1) are reached, cephalgic syndrome may persist, therefore patients should be warned about this in advance and referred to a cephalgologist to select adequate headache therapy.

Neurological and Systemic Pitfalls in the Diagnosis of Cluster Headaches: A Case-Based Review.

To describe different pitfalls in the diagnosis of primary cluster headaches (CHs) with the guidance of seven case vignettes. The question of whether primary CHs and migraines are totally different entities has been long debated. Autonomic features can be detected in as many as 60% of migraine patients. Although some genetic similarities have been found, CACNA1A mutations have not been detected among CH patients with hemimotor aura in contrast to hemiplegic migraine. Recently, functional MRI studies have shown that the left thalamic network was the most discriminative MRI feature in distinguishing migraine from CH patients. Compared to migraine, CH patients showed decreased functional interaction between the left thalamus and cortical areas mediating interception and sensory integration. However, clinically the most significant feature had been the restlessness and agitation seen during headache attacks patients with CHs. This feature is also important in distinguishing cluster patients from other patients having other trigeminal autonomic cephalalgias except for a subset of patients with hemicrania continua. CH is an important member of the group of headache disorders characterized by their association with one or more autonomic features in the trigeminal nerve distribution and termed Trigeminal Autonomic Cephalalgias (TACs). Although CH is a relatively rare condition, judged by the distress it generally causes to the affected individual, early diagnosis and institution of appropriate therapy seem mandatory. Correct diagnosis of CHs needs avoidance of pitfalls. Such pitfalls generally include differentiation from migraine, differentiation from other side locked headache disorders, from other trigeminal autonomic cephalalgias (TACs), and lastly, recognition of rare presentations of cluster-like manifestations with hemiplegic aura and simulating trigeminal and glossopharyngeal neuralgias. Differentiation between primary and symptomatic CHs related to sellar pathologies and systemic medical conditions is of equal importance. In the present review such issues are discussed with the assistance of seven case vignettes.

Clinical characteristics of 2378 patients presenting with headache disorders to headache clinics in Japan: A clinic-based multicenter study

BackgroundThere are reports from single-center studies on patients visiting headache clinics; however, few multicenter studies have been conducted in Japan. This study aims to address this gap by conducting a multicenter analysis of the clinical characteristics, headache types, severity, and psychiatric comorbidities of patients attending headache clinics. MethodsWe prospectively evaluated the clinical characteristics of 2378 patients with headache disorders visiting three headache clinics. Baseline demographics, such as the visual analog scale (VAS), and psychiatric assessments, such as the Generalized Anxiety Disorder-7 (GAD-7) and the Patient Health Questionnaire-9 (PHQ-9), were evaluated. Headache types were classified as migraine, tension-type headache (TTH), trigeminal autonomic cephalalgias (TACs), other primary headache disorders (OPHDs), and secondary headache. Parameters were compared between headache types using the Kruskal–Wallis test or analysis of covariance, as appropriate. ResultsThe most common headache type was migraine (78.8 %), followed by TTH (12.2 %), secondary headache (5.5 %), OPHDs (2.1 %), and TACs (1.6 %). Patients with migraine were significantly younger at first consultation (median age 32.0) than those with other headache types (TTH; 47.0, TACs; 39.0, OPHDs; 49.5, and secondary headache; 47.0). Patients with TACs exhibited the highest severity and psychiatric symptoms, with VAS (median 90.0), GAD-7 (7.0), and PHQ-9 (7.5) scores significantly higher than those of other headache type (migraine; 70.0, 5.0, 5.0, TTH; 50.0, 4.0, 4.0, OPHDs; 65.0, 4.0, 3.5, and secondary headache; 60.0, 3.0, 3.5: p<0.001, p=0.019, p<0.001). ConclusionMost patients visiting headache clinics had migraine; patients with TACs showed significantly higher headache severity and psychiatric symptoms than those with other headache types.

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

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

Pharmacological Dissociation in Hemicrania Continua With Persistent Visual Aura Evolved From Episodic Migraine: A Case Report.

To report a case of hemicrania continua (HC) and persistent visual aura without infarction in a patient with previous episodic migraine with visual aura, whose persistent aura symptoms improved only after treatment with divalproex sodium. Once regarded as highly specific for migraine, visual aura has been associated with trigeminal autonomic cephalalgias, including HC. In previous descriptions of HC and episodes of typical visual aura, the aura occurred exclusively with severe headache exacerbations and, like the pain, resolved with indomethacin. Case report and literature review. A 54-year-old man with a history of episodic migraine with visual aura reported a gradual onset of HC with persistent visual aura of 15 months duration. General medical and neurological examinations were normal, including imaging studies. HC's headache responded to indomethacin, while the visual aura was recalcitrant, only improving with oral divalproex sodium treatment. As our patient experienced HC, which evolved from episodic migraine, we hypothesize that migraine and HC may share a common pathophysiology. However, the persistence of the visual aura, despite the abolition of pain and autonomic features with a therapeutic dose of indomethacin, and the subsequent successful treatment of the aura with divalproex sodium, suggest that aura and HC headache arise from distinct and dissociable mechanisms.

Primary Headaches and Their Most Important Imagistic Features in Clinical Practice

Background. Primary headaches are comprised of three big categories: migraines (with or without aura), the third most common and the 6th most disabling disease worldwide, tension-headaches, and trigeminal autonomic cephalalgias, each with different, complex, and not completely understood pathophysiological, clinical, and neuroimagistic characteristics. Structures like the brain stem, hippocampus, or hypothalamus have been depicted as being the main triggers of these types of headaches, which have a significant impact on the quality of life. Methods. We performed a broad literature review on primary headaches from January 2016 to June 2023, analyzing the latest scientific updates and emphasizing the pathophysiological and neuroimagistic characteristics. Results. We provide a concise review of the main neuroimaging studies that help in differential diagnosis between several types of primary headaches. Conclusions. It is difficult to approach the pathophysiology of these three primary headache categories. Keeping in mind that neuroimagistic methods are rapidly developing (especially in the MRI sphere), the most important endpoint of future studies will be to establish a reliable distinction system for all these types of cephalalgias, thus updating the protocols and guidelines. Currently, imaging studies are indicated only in certain circumstances.

Evaluating the Phenotypic Patterns of Post-Traumatic Headache: A Systematic Review of Military Personnel.

Mild traumatic brain injury (TBI) affects a significant number of military personnel, primarily because of physical impact, vehicle incidents, and blast exposure. Post-traumatic headache (PTH) is the most common symptom reported following mild TBI and can persist for several years. However, the current International Classification of Headache Disorders lacks phenotypic characterization for this specific headache disorder. It is important to appropriately classify the headache sub-phenotypes as it may enable more targeted management approaches. This systematic review seeks to identify the most common sub-phenotype of headaches in military personnel with PTH attributed to mild TBI. We conducted a systematic search following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses reporting guidelines, focusing on the military population. PubMed, Web of Science, Cochrane, and Clinicaltrials.gov databases were searched. Abstracts and full texts were independently reviewed by two authors using predefined inclusion and exclusion criteria. Data extraction was performed using a standardized form. The risk of bias was assessed using the Newcastle-Ottawa Scale. Eight papers related to the military population were included in this review. Migraine was the most commonly reported headache sub-phenotype, with a prevalence ranging from 33 to 92%. Additionally, one military study identified tension-type headaches as the most prevalent headache phenotype. Although not the primary phenotype, one military cohort reported that approximately one-third of their cohort experienced trigeminal autonomic cephalalgias, which were associated with exposure to blast injuries and prior concussions. This systematic review demonstrated that PTH in the military population frequently exhibit migraine-like features. Tension-type headache and trigeminal autonomic cephalalgias also occur, although less commonly reported. Sub-phenotyping PTH may be important for initiating effective treatment since different phenotypes may respond differently to medications. The study populations analyzed in this systematic review display heterogeneity, underscoring the necessity for additional research features, more stringent criteria and comprehensive recording of baseline characteristics. Characterizing headaches following injury is crucial for an accurate diagnosis to enable effective management and rehabilitation planning for our armed forces.

Preliminary External Validation Results of the Artificial Intelligence-Based Headache Diagnostic Model: A Multicenter Prospective Observational Study.

The misdiagnosis of headache disorders is a serious issue, and AI-based headache model diagnoses with external validation are scarce. We previously developed an artificial intelligence (AI)-based headache diagnosis model using a database of 4000 patients' questionnaires in a headache-specializing clinic and herein performed external validation prospectively. The validation cohort of 59 headache patients was prospectively collected from August 2023 to February 2024 at our or collaborating multicenter institutions. The ground truth was specialists' diagnoses based on the initial questionnaire and at least a one-month headache diary after the initial consultation. The diagnostic performance of the AI model was evaluated. The mean age was 42.55 ± 12.74 years, and 51/59 (86.67%) of the patients were female. No missing values were reported. Of the 59 patients, 56 (89.83%) had migraines or medication-overuse headaches, and 3 (5.08%) had tension-type headaches. No one had trigeminal autonomic cephalalgias or other headaches. The models' overall accuracy and kappa for the ground truth were 94.92% and 0.65 (95%CI 0.21-1.00), respectively. The sensitivity, specificity, precision, and F values for migraines were 98.21%, 66.67%, 98.21%, and 98.21%, respectively. There was disagreement between the AI diagnosis and the ground truth by headache specialists in two patients. This is the first external validation of the AI headache diagnosis model. Further data collection and external validation are required to strengthen and improve its performance in real-world settings.

Prevalence of cranial autonomic symptoms in frequent episodic tension-type headache: A post hoc analysis of the cross-sectional Migraine in Poland study.

Cranial autonomic symptoms (CASs) include lacrimation, conjunctival injection, rhinorrhea, nasal congestion, facial flushing or sweating, ptosis, and myosis. These symptoms may be associated with trigeminal autonomic cephalalgias (TACs) and migraine. The aim of the study was to assess whether CASs are also reported by patients with frequent episodic tension-type headache (eTTH). A cross-sectional online survey of a large Polish population was conducted between August 2021 and June 2022. The analysis assessed diagnostic criteria for migraine and eTTH, as well as the presence of allodynia, headache-related disability and symptoms of depression. The survey involved 3,225 respondents (age: 13-80 years, mean (M) = 38.9 years; 87.1% female). A total of 166 individuals met the diagnostic criteria for isolated frequent eTTH without migraine or probable migraine with or without aura. Allodynia was present during the majority of attacks in 40 (24.1%) eTTH subjects, while 86 (51.8%) eTTH respondents reported at least 1 CAS during their headache attacks. The presence of at least 1 CAS was more prevalent in migraine than in eTTH (p = 0.001). The respondents with at least 1 CAS during eTTH attacks reported a higher burden associated with pain (p = 0.024) and higher Patient Health Questionnaire-9 (PHQ-9) scores (p = 0.016). The prevalence of retrospectively reported CASs was high among individuals with eTTH, which may potentially contribute to diagnostic errors. Cranial autonomic symptoms in eTTH do not appear to be caused by severe pain or central sensitization.

Melatonin in hemicrania continua and paroxysmal hemicrania.

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. 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. 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. 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.

Primary Headache Is Related to Reduced Health-Related Quality of Life in Children with Epilepsy.

Headache is a frequent comorbidity in patients with epilepsy. Data are sparse regarding the distribution of headache types in children with epilepsy (CWE). We aimed to assess the prevalence of primary headache types and their influence on health-related quality of life (QoL) in CWE. CWE filled out a validated headache questionnaire to assess migraine (MIG), tension-type headache (TTH), trigeminal-autonomic cephalalgia (TAC), or, if the criteria were not fulfilled, non-classifiable headache (NCH). QoL was measured using both patient and parent versions of a validated questionnaire. Of 119 CWE (59 female; 11.5 ± 3.1 y), headache was found in 46 (38.7%). Sixteen (34.8%) patients showed MIG, 9 (19.6%) patients TTH, and 21 (45.7%) patients described NCH. More girls reported headache (χ2 = 5.4, p = 0.02) when compared to boys. Overall, QoL was reduced in patients with headache from both the patients' and parents' points of view (70.8% [39.6; 87.5] vs. 77.0% [46.9; 95.8], p = 0.002; 71,9% [33.3; 87.5] vs. 78,1% [54.2; 95.8], p = 0.003). Headache is common among CWE with MIG as the most prevalent primary headache type and higher rates in female patients. Importantly, patients and their parents perceive a reduced overall QoL when suffering from headache.

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

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. 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.

Headache providers' perspectives of headache diaries in the era of increasing technology use: a qualitative study.

No matter what type of headache is being considered across various populations, one of the mainstays of headache medicine is headache tracking. This self-management tool enables patients and their providers to understand patients' underlying symptoms and the effects of treatments they have tried. This is important to determining whether headaches are related to menses for women's health, to determining the time of headache occurrence, e.g., hypnic headache, and the location and duration of symptoms, e.g., trigeminal autonomic cephalgia. Prior research has investigated what people with headaches perceive about headache diary use and how people with headaches utilize electronic headache diaries. However, headache providers' perspectives on the important factors related to headache diaries are less known. Previously, using the Modified Delphi Process, a panel of four experts opined what they perceived as the most important factors for a headache diary. We sought to better understand headache providers' perspectives about headache diary/app usage from providers working in various institutions nationwide. We conducted 20 semi-structured qualitative interviews of headache providers across the US from various institutions and asked them their perspectives on headache diary use. We transcribed the interviews, which two independent coders then coded. Themes and subthemes were developed using grounded theory qualitative analysis. Six themes emerged: (1) Providers were generally agnostic regarding the headache tracking method, but nearly all recommend the use of smartphones for tracking; (2) Providers had concerns regarding the accessibility of headache trackers; (3) Providers noted benefits to integrating headache tracking data into the EMR but had mixed opinions on how this integration might be done; (4) Providers had mixed opinions regarding the utility and interpretation of the data, specifically regarding data accuracy and efficiency; (5) Providers generally felt that headache tracking lends itself to more collaborative plan management; (6) Providers recommend behavioral health apps for patients but stated that there are few digital behavioral health interventions for headache specifically. Interviews of headache providers, recommenders, and users of headache data are vital informants who can provide a robust amount of information about headache diary development, use in different populations, integration, and more.

Hemicrania paroxística com representação na face e associação com disfunção temporomandibular: relato de caso

ABSTRACT Paroxysmal Hemicrania is a trigeminal autonomic cephalalgia described as a severe and strictly unilateral pain, which occurs in paroxysms at orbital, supraorbital and/ or temporal region. A 45-year-old woman presented to an orofacial pain specialist reporting severe, burning, throbbing, strictly right-sided headache associated to ipsilateral autonomic symptoms and orofacial pain. The pain was perceived on the maxillary region followed by pain spread to the head. Interdisciplinary evaluation, along with absolute responsiveness to indomethacin and normal Brain Magnetic Resonance imaging, led to the diagnosis of primary Episodic paroxysmal hemicrania with facial representation and myofascial pain of masticatory muscles. Dentists should be aware of paroxysmal hemicrania with facial representation and the possibility of temporomandibular disorder coexistence, in order to avoid misdiagnosis and inadequate management. Paroxysmal hemicrania may be first perceived on the face and may be associated with interparoxysmal pain. In these cases, efficient anamnesis and clinical evaluation followed by interdisciplinary approach is needed.

Other primary headache disorders: Data from the HEAD-MENA-A study in Africa, Asia, and the Middle East

ObjectiveOther primary headache disorders (OPHD) are under-investigated compared to frequent primary headache types like migraine, tension-type headache, and trigeminal autonomic cephalalgias. Knowledge of the distribution and characteristics of OPHD subtypes is crucial for their recognition. We aimed to determine the prevalence at the hospital and headache clinics and clinical characteristics of OPHDs in patients from 13 countries. MethodsWe analyzed a large dataset from the cross-sectional study Head-MENA-A (Middle East, North Africa, Asia). Consecutive patients over 10 years of age presenting with headaches were included from outpatient, inpatient, and emergency settings. A structured questionnaire addressing demographics, headache characteristics, accompanying symptoms, and triggers was administered. Headache subtypes were diagnosed according to the ICHD-3 criteria. ResultsAmong patients complaining of headaches (n = 3722), 106 (2.9%) were diagnosed with OPHD. Fifty-two patients (1.4% of all headache patients) had only OPHD, while 54 (1.5%) had both OPHD and a co-existing primary headache (mostly migraine). All OPHDs were more common in females. The most frequent subtypes were new daily persistent headache and primary stabbing headache (0.2% each among all admitted patients). Photophobia and phonophobia were the most frequent accompanying symptoms, while physical activity (28.8%), stress (15.4%), and the Valsalva maneuver (15.4%) were the most common triggering factors. The majority of triggering factors were more pronounced in patients with both migraine and OPHD. ConclusionsOther primary headaches are rare and heterogeneous. Their high co-existence with migraine suggests shared predisposing factors, hinting at a "headache continuum" concept for primary headaches.

The Ability of Injections Versus Needle Insertion to Decrease the Severity and Frequency of Symptoms for Patients With Chronic Headaches: A Critically Appraised Topic

Clinical Scenario: Headaches can be categorized as tension-type headaches, migraine, trigeminal autonomic cephalgia, and other primary headache disorders according to the Third International Classification of Headache Disorders. Headaches are one of the most common disorders within the nervous system and have a prevalence of &gt;48% within the general population. Nerve blocks are a type of nerve stimulation that is believed to help reduce the frequency and severity of headaches. The physiological effect of the greater occipital nerve block on headaches is thought to be due to the central nervous system connections of the greater occipital nerve and trigeminal and cervical afferent fibers, which is believed to be the prime origin of migraine headaches. Nerve blocks can contain a variety of drug regimens including steroids, local anesthetics, or a mixture of both. Trigger point injections (TPIs) are an invasive therapy where a needle is guided directly into a trigger point that has been previously identified upon examination. Botulinum toxin A is an alternative treatment modality that can be injected with TPIs. Botulinum toxin A is a potent naturally occurring toxin that causes dose-dependent muscular relaxation by inhibiting the release of acetylcholine at the neuromuscular junction. Summary of Key Findings: (1) Both greater occipital nerve blocks and TPIs have been shown to reduce headache frequency and severity in the short term; however, it appears to be due to the needle injected into the soft tissue structures and not due to the type of solution injected. (2) Ultrasound guidance allows for a more accurate and effective technique than a blind injection as it allows for accurate injection into the targeted muscles, thereby minimizing complications and increasing the chance of success. (3) Once symptoms have been alleviated, clinicians should evaluate the patient’s mechanics in the upper trunk to determine whether there are any mechanical abnormalities leading to the formation of myofascial pain and/or trigger points causing the headache symptoms. If identified and treated appropriately, this can allow for a long-term solution in correcting the cause rather than the symptoms alone. (4) Participants receiving a greater occipital nerve block or TPI, despite the drug regimen or dosage, experienced similar benefits with no statistical significance. In deciding which treatment approach to take, the clinician should speak with the patient to educate them on the available options and allow the patient to be part of the decision-making process to best meet their needs and include a rehabilitation plan with all the treatment approaches. Clinical Question: In patients who experience chronic headaches, was there a greater decrease in headache frequency and severity with a greater occipital nerve block or TPI? Clinical Bottom Line: Needles into the supraclavicular region for headaches lead to decreased severity and frequency of headaches in the short term but will not lead to headache resolution. Strength of Recommendation: B.

Epidemiology and clinical features of paroxysmal hemicrania: Asystematic review and meta-analysis.

To assess the prevalence or relative frequency of paroxysmal hemicrania and its clinical features in the adult general population and among adult patients evaluated for headache in tertiary care. Paroxysmal hemicrania is a rare trigeminal autonomic cephalalgia with characteristic attacks of headache, associated cranial autonomic symptoms and signs, and an absolute response to indomethacin. Its epidemiological burden remains unknown in both the adult general population and among adult patients evaluated for headache in a tertiary care setting. Moreover, the frequencies of the clinical features associated with paroxysmal hemicrania have not been well established. A literature search of PubMed and Embase was conducted from January 1, 1988, to January 20, 2023. Eligible for inclusion were observational studies reporting the point prevalence or relative frequency of paroxysmal hemicrania or its clinical features in the adult general population or among adult patients evaluated for headache in tertiary care. Two independent investigators (M.J.H. and J.G.L.) performed the title, abstract, and full-text article screening. Each included study's risk of bias was critically appraised using the Joanna Briggs Institute Critical Appraisal Checklist for Studies Reporting Prevalence Data. Estimates of prevalence or relative frequency were calculated using a random-effects meta-analysis. The between-study heterogeneity was assessed using the I2 statistic and further explored with meta-regression. This study was pre-registered on PROSPERO (identifier: CRD42023391127). A total of 17 clinic-based studies and one population-based study met the eligibility criteria. Importantly, an overall high risk of bias was observed across the eligible studies. The relative frequency of paroxysmal hemicrania was estimated to be 0.3% (95% CI, 0.2%-0.5%) among adult patients evaluated for headache in tertiary care with considerable heterogeneity (I2 = 76.4%). No cases with paroxysmal hemicrania were identified among 1,838 participants in a population-based sample. Moreover, the most prevalent cranial autonomic symptoms were lacrimation (77.3% [95% Cl, 62.7%-87.3%]), conjunctival injection (75.0% [95% Cl, 60.3%-85.6%]), and nasal congestion (47.7% [95% Cl, 33.6%-62.3%]). Our findings suggest that paroxysmal hemicrania is a rare disorder among adults evaluated for headache in tertiary care, while its prevalence in the general population remains unknown. Further studies focusing on the clinical features of paroxysmal hemicrania are warranted.

Evidence for converging pathophysiology in complex regional pain-syndrome and primary headache disorders: results from a case–control study

BackgroundNeuroinflammation and maladaptive neuroplasticity play pivotal roles in migraine (MIG), trigeminal autonomic cephalalgias (TAC), and complex regional pain syndrome (CRPS). Notably, CRPS shares connections with calcitonin gene-related peptide (CGRP) in its pathophysiology. This study aims to assess if the documented links between CRPS and MIG/TAC in literature align with clinical phenotypes and disease progressions. This assessment may bolster the hypothesis of shared pathophysiological mechanisms.MethodsPatients with CRPS (n = 184) and an age-/gender-matched control group with trauma but without CRPS (n = 148) participated in this case–control study. Participant answered well-established questionnaires for the definition of CRPS symptoms, any headache complaints, headache entity, and clinical management.ResultsPatients with CRPS were significantly more likely to suffer from migraine (OR: 3.23, 95% CI 1.82–5.85), TAC (OR: 8.07, 95% CI 1.33–154.79), or non-classified headaches (OR: 3.68, 95% CI 1.88–7.49) compared to the control group. Patients with MIG/TAC developed CRPS earlier in life (37.2 ± 11.1 vs 46.8 ± 13.5 years), had more often a central CRPS phenotype (60.6% vs. 37.0% overall) and were three times more likely to report allodynia compared to CRPS patients with other types of headaches. Additionally, these patients experienced higher pain levels and more severe CRPS, which intensified with an increasing number of headache days. Patients receiving monoclonal antibody treatment targeting the CGRP pathway for headaches reported positive effects on CRPS symptoms.ConclusionThis study identified clinically relevant associations of MIG/TAC and CRPS not explained by chance. Further longitudinal investigations exploring potentially mutual pathomechanisms may improve the clinical management of both CRPS and primary headache disorders.Trial registrationGerman Clinical Trials Register (DRKS00022961).

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

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.

Use of spinal cord stimulation in treatment of intractable headache diseases.

Headache diseases remain one of the leading causes of disability in the world. With the development of neuromodulation strategies, high cervical spinal cord stimulation (hcSCS) targeting the trigeminocervical complex has been deployed to treat refractory headache diseases. In this article, we review the proposed mechanism behind hcSCS stimulation, and the various studies that have been described for the successful use of this treatment strategy in patients with chronic migraine, cluster headache, and other trigeminal autonomic cephalalgias.