Cluster headache (CH) is a common primary headache that severely impacts patients\' quality of life, characterized by recurrent, severe, unilateral headaches often centered around the eyes, temples, or forehead. Distinguishing CH from other headache disorders is challenging, and its pathogenesis remains unclear. Notably, patients with CH often experience high levels of depression and suicidal tendencies, necessitating increased clinical attention. This comprehensive assessment combines various reports and the latest scientific literature to evaluate the current state of CH research. It covers epidemiology, population characteristics, predisposing factors, and treatment strategies. Additionally, we provide strategic insights into the holistic management of CH, which involves continuous, individualized care throughout the prevention, treatment, and rehabilitation stages. Recent advances in the field have revealed new insights into the pathophysiology of CH. While these findings are still evolving, they offer a more detailed understanding of the neurobiological mechanisms underlying this disorder. This growing body of knowledge, alongside ongoing research efforts, promises to lead to the development of more targeted and effective treatments in the future.

UNASSIGNED: Current literature extensively covers the use of sphenopalatine ganglion stimulation (SPGs) in treating a broad spectrum of medical conditions, such as allergic rhinitis, cluster headaches, and strokes. Nevertheless, a discernible gap in the systematic organization and analysis of these studies is evident. This paper aims to bridge this gap by conducting a comprehensive review and analysis of existing literature on SPGs across various medical conditions.
UNASSIGNED: This study meticulously constructed a comprehensive database through systematic computerized searches conducted on PubMed, Embase, CNKI, Wanfang, VIP, and CBM up to May 2022. The inclusion criteria encompassed randomized controlled trials (RCTs) published in either Chinese or English, focusing on the therapeutic applications of SPGs for various medical conditions. Both qualitative and quantitative outcome indicators were considered eligible for inclusion.
UNASSIGNED: This comprehensive study reviewed 36 publications, comprising 10 high-quality, 23 medium-quality, and three low-quality articles. The study investigated various diseases, including allergic rhinitis (AR), ischemic strokes (IS), cluster headache (CH), primary trigeminal neuralgia (PTN), pediatric chronic secretory otitis (PCSO), refractory facial paralysis (RFP), chronic tension-type headache (CTTH), as well as the analysis of low-frequency sphenopalatine ganglion stimulation (LF-SPGs) in chronic cluster headache (CCH) and the impact of SPGs on Normal nasal cavity function (NNCF). SPGs demonstrate efficacy in the treatment of AR. Regarding the improvement of rhinoconjunctivitis quality of life questionnaire (RQLQ) scores, SPGs are considered the optimal intervention according to the SUCRA ranking. Concerning the improvement in Total Nasal Symptom Score (TNSS), Conventional Acupuncture Combined with Tradiational Chinese Medicine (CA-TCM) holds a significant advantage in the SUCRA ranking and is deemed the best intervention. In terms of increasing Effective Rate (ER), SPGs outperformed both conventional acupuncture (CA) and Western Medicine (WM; P < 0.05). In the context of SPGs treatment for IS, the results indicate a significant improvement in the 3-month outcomes, as evaluated by the modified Rankin Scale (mRS) in the context of Cerebral Cortical Infarction (CCI; P < 0.05). In the treatment of CH with SPGs, the treatment has been shown to have a statistically significant effect on the relief and disappearance of headaches (P < 0.05). The impact of SPGs on NNCF reveals statistically significant improvements (P < 0.05) in nasal airway resistance (NAR), nasal cavity volume (NCV), exhaled nitric oxide (eNO), substance P (SP), vasoactive intestinal peptide (VIP) and neuropeptide Y (NPY). SPGs treatments for PCSO, RFP, and CTTH, when compared to control groups, yielded statistically significant results (P < 0.05).
UNASSIGNED: SPGs demonstrate significant effectiveness in the treatment of AR, IS, and CH. Effective management of CCH may require addressing both autonomic dysregulation and deeper neural pathways. However, additional high-quality research is essential to clarify its effects on NNCF, PTN, PCSO, RFP, and CTTH.
UNASSIGNED: PROSPERO, identifier CRD42021252073, https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=312429.

UNASSIGNED: Extensive research on cluster headaches (CHs) has been conducted worldwide; however, there is currently no bibliometric research on CHs. Therefore, this study aimed to analyze the current research hotspots and frontiers of CHs over the past decade.
UNASSIGNED: Raw data on CHs was obtained from the Web of Science Core Collection database from 2014 to 2023. CiteSpace V6.2 R7 (64 bit) and Microsoft Excel were used to assess the annual publication volume, authors, countries, and references. VOSviewer 1.6.19 software was used to assess the institutions, cited authors, and keywords, and co-occurrence and clustering functions were applied to draw a visual knowledge map.
UNASSIGNED: In the past decade, the overall annual publication volume of articles related to CHs has increased year by year, showing promising development prospects. The total 1909 articles contained six types of literature, among which the proportion of original research articles was the highest (1,270 articles, 66.53%), published in 201 journals. Cephalalgia (439 articles, 23.00%) had the highest publication volume, and the Lancet was the journal with the highest impact factor (IF = 168.9). Furthermore, the United States of America was the country with the most published papers (584 articles, 30.60%), University of London was the research institution with the most published papers (142 articles, 7.44%), and Goodsby, Peter J was found to be the most prolific author (38 articles, 1.99%).
UNASSIGNED: This study may provide some direction for subsequent researcher on CHs. The hotspots and frontiers of future research on CHs are suggested as follows: in basic medicine, more attention should be paid to pathophysiology, especially on increasing research on the pathogenesis mediated by CGRP; in clinical medicine, more attention should be paid to the design of evidence-based medicine methodology, especially the strict design, including double-blind, questionnaire, and follow-up, in randomized controlled trials, using high-quality articles for meta-analyses, and recommending high-level evidence; therapeutic techniques need to be further explored, suggesting the implementation of transcranial magnetic stimulation of the cortex, and stimulation of the sphinopalatine ganglia and occipital nerve to achieve peripheral neuromodulation. Furthermore, chronic migraine and insomnia are inextricably linked to CHs.

BACKGROUND: The clinical profile of cluster headache may differ among different regions of the world, warranting interest in the data obtained from the initial Chinese Cluster Headache Register Individual Study (CHRIS) for better understanding.
METHODS: We conducted a multicenter, prospective, longitudinal cohort study on cluster headache across all 31 provinces of China, aiming to gather clinical characteristics, treatment approaches, imaging, electrophysiological and biological samples.
RESULTS: In total 816 patients were enrolled with a male-to-female ratio of 4.33:1. The mean age at consultation was 34.98 ± 9.91 years, and 24.89 ± 9.77 years at onset. Only 2.33% were diagnosed with chronic cluster headache, and 6.99% had a family history of the condition. The most common bout was one to two times per year (45.96%), lasting two weeks to one month (44.00%), and occurring frequently in spring (76.23%) and winter (73.04%). Of these, 68.50% experienced one to two attacks per day, with the majority lasting one to two hours (45.59%). The most common time for attacks was between 9 am and 12 pm (75.86%), followed by 1 am and 3 am (43.48%). Lacrimation (78.80%) was the most predominant autonomic symptom reported. Furthermore, 39.22% of patients experienced a delay of 10 years or more in receiving a correct diagnosis. Only 35.67% and 24.26% of patients received common acute and preventive treatments, respectively.
CONCLUSIONS: Due to differences in ethnicity, genetics and lifestyle conditions, CHRIS has provided valuable baseline data from China. By establishing a dynamic cohort with comprehensive multidimensional data, it aims to advance the management system for cluster headache in China.

BACKGROUND: Despite hypothalamus has long being considered to be involved in the pathophysiology of cluster headache, the inconsistencies of previous neuroimaging studies and a limited understanding of the hypothalamic areas involved, impede a comprehensive interpretation of its involvement in this condition.
METHODS: We used an automated algorithm to extract hypothalamic subunit volumes from 105 cluster headache patients (57 chronic and 48 episodic) and 59 healthy individuals; after correcting the measures for the respective intracranial volumes, we performed the relevant comparisons employing logist regression models. Only for subunits that emerged as abnormal, we calculated their correlation with the years of illness and the number of headache attacks per day, and the effects of lithium treatment. As a post-hoc approach, using the 7 T resting-state fMRI dataset from the Human Connectome Project, we investigated whether the observed abnormal subunit, comprising the paraventricular nucleus and preoptic area, shows robust functional connectivity with the mesocorticolimbic system, which is known to be modulated by oxytocin neurons in the paraventricular nucleus and that is is abnormal in chronic cluster headache patients.
RESULTS: Patients with chronic (but not episodic) cluster headache, compared to control participants, present an increased volume of the anterior-superior hypothalamic subunit ipsilateral to the pain, which, remarkably, also correlates significantly with the number of daily attacks. The post-hoc approach showed that this hypothalamic area presents robust functional connectivity with the mesocorticolimbic system under physiological conditions. No evidence of the effects of lithium treatment on this abnormal subunit was found.
CONCLUSIONS: We identified the ipsilateral-to-the-pain antero-superior subunit, where the paraventricular nucleus and preoptic area are located, as the key hypothalamic region of the pathophysiology of chronic cluster headache. The significant correlation between the volume of this area and the number of daily attacks crucially reinforces this interpretation. The well-known roles of the paraventricular nucleus in coordinating autonomic and neuroendocrine flow in stress adaptation and modulation of trigeminovascular mechanisms offer important insights into the understanding of the pathophysiology of cluster headache.

Primary headache disorder is the main cause of headache attacks, leading to significant disability and impaired quality of life. This disorder is increasingly recognized as a heterogeneous condition with a complex network of genetic, environmental, and lifestyle factors. However, the timely diagnosis and effective treatment of these headaches remain challenging. Precision medicine is a potential strategy based on P4 (predictive, preventive, personalized, and participatory) medicine that may bring new insights for headache care. Recent machine learning advances and widely available molecular biology and imaging data have increased the usefulness of this medical strategy. Precision medicine emphasizes classifying headaches according to their risk factors, clinical presentation, and therapy responsiveness to provide individualized headache management. Furthermore, early preventive strategies, mainly utilizing predictive tools, are critical in reducing headache attacks and improving the quality of life of individuals with headaches. The current review comprehensively discusses the potential application value of P4 medicine in headache management.

OBJECTIVE: Previous studies have shown that the salience network (SN) and the thalamus are involved in cluster headache (CH) attacks. However, very little is known regarding the altered thalamus-SN functional connectivity in CH. The aim of this study was to explore alterations of functional connectivity between the thalamus and the SN in patients with CH to further gain insight into the pathophysiology of CH.
METHODS: The resting-state functional MRI (rs-fMRI) data of 21 patients with CH in the headache attack remission state during in-bout periods and 21 age- and sex-matched normal controls were obtained. The rs-fMRI data were analyzed by the independent component analysis (ICA) method, and the thalamus-SN functional connectivity in patients with right-sided and left-sided CH was compared with that in normal controls.
RESULTS: Decreased functional connectivity was found between the thalamus, both ipsilateral and contralateral to the headache side, and the SN during headache remission state in both right-sided CH patients and left-sided CH patients.
CONCLUSIONS: The findings suggest that the decreased functional connectivity between the thalamus and SN might be one of the pathologies underpinning the CH. This helps us to understand better the nature of the brain dysfunction in CH and the basic pathologies of CH, which implies that this deserves further investigation.

BACKGROUND: Although headache disorders are common, the current diagnostic approach is unsatisfactory. Previously, we designed a guideline-based clinical decision support system (CDSS 1.0) for diagnosing headache disorders. However, the system requires doctors to enter electronic information, which may limit widespread use.
METHODS: In this study, we developed the updated CDSS 2.0, which handles clinical information acquisition via human-computer conversations conducted on personal mobile devices in an outpatient setting. We tested CDSS 2.0 at headache clinics in 16 hospitals in 14 provinces of China.
RESULTS: Of the 653 patients recruited, 18.68% (122/652) were suspected by specialists to have secondary headaches. According to \"red-flag\" responses, all these participants were warned of potential secondary risks by CDSS 2.0. For the remaining 531 patients, we compared the diagnostic accuracy of assessments made using only electronic data firstly. In Comparison A, the system correctly recognized 115/129 (89.15%) cases of migraine without aura (MO), 32/32 (100%) cases of migraine with aura (MA), 10/10 (100%) cases of chronic migraine (CM), 77/95 (81.05%) cases of probable migraine (PM), 11/11 (100%) cases of infrequent episodic tension-type headache (iETTH), 36/45 (80.00%) cases of frequent episodic tension-type headache (fETTH), 23/25 (92.00%) cases of chronic tension-type headache (CTTH), 53/60 (88.33%) cases of probable tension-type headache (PTTH), 8/9 (88.89%) cases of cluster headache (CH), 5/5 (100%) cases of new daily persistent headache (NDPH), and 28/29 (96.55%) cases of medication overuse headache (MOH). In Comparison B, after combining outpatient medical records, the correct recognition rates of MO (76.03%), MA (96.15%), CM (90%), PM (75.29%), iETTH (88.89%), fETTH (72.73%), CTTH (95.65%), PTTH (79.66%), CH (77.78%), NDPH (80%), and MOH (84.85%) were still satisfactory. A patient satisfaction survey indicated that the conversational questionnaire was very well accepted, with high levels of satisfaction reported by 852 patients.
CONCLUSIONS: The CDSS 2.0 achieved high diagnostic accuracy for most primary and some secondary headaches. Human-computer conversation data were well integrated into the diagnostic process, and the system was well accepted by patients. The follow-up process and doctor-client interactions will be future areas of research for the development of CDSS for headaches.

Primary headache disorders including migraine, cluster headache, and tension-type headache are among the most common disabling diseases worldwide. The unclear pathogenesis of primary headache disorders has led to high rates of misdiagnosis and limited available treatment options. In this review, we have summarized the pathophysiological factors for a better understanding of primary headache disorders. Advances in functional neuroimaging, genetics, neurophysiology have indicated that cortical hyperexcitability, regional brain dysfunction, central sensitization and neuroplasticity changes play vital roles in the development of primary headache disorders. Moreover, we have also discussed a series of neurostimulation approaches with their stimulation mechanism, safety and efficacy for prevention and treatment of primary headache disorders. Noninvasive or implantable neurostimulation techniques show great promise for treating refractory primary headache disorders.

UNASSIGNED: To explore changes of depression, anxiety and sleep disturbance in patients with episodic cluster headache inside and outside the attack period and assess the therapy to improve the treatment.
UNASSIGNED: We prospectively recruited 396 patients from 11 specialized headache outpatients and analyzed their headache characteristics, Hospital Anxiety Depression Scale scores, Pittsburgh sleep quality index scores, and the usage of psychiatric medications during as well as 1 month after the attack period.
UNASSIGNED: A total of 220 patients completed the follow-up, 52.73% of whom had anxiety, 47.27% had depression and 49.09% had sleep disturbance inside the attack period. At follow-up, the percentage of these patients significantly decreased to 16.36%, 21.82% and 14.55% in the remission period, respectively (p < 0.05). Antidepressants and mood stabilizers were prescribed to 58.18% of the patients. However, both of the changes of Hospital Anxiety Depression Scale scores after the end of the attack period for anxiety (3.52±2.91 vs 3.32±3.09, p =0.61) and depression (3.41±3.33 vs 2.90±3.58, P =0.28) were comparable in patients with and without taking these medications. Nocturnal onset of headache was positively correlated with Pittsburgh score (OR=8.71), anxiety (OR=2.33) and depression scores (OR=3.56) (p < 0.05).
UNASSIGNED: Depression, anxiety and sleep disturbance were significantly alleviated after the attack period. However, psychiatric medications showed limited effect on depression and anxiety. Additionally, the nocturnal attack may cause anxiety and depression in episodic cluster headache.