BACKGROUND: Pediatric headache is an increasing medical problem that has adverse effects on children\'s quality of life, academic performance, and social functioning. Children with primary headaches exhibit enhanced sensory sensitivity compared to their healthy peers. However, comprehensive investigations including multimodal sensory sensitivity assessment are lacking. This study aimed to compare sensory sensitivity of children with primary headaches with their healthy peers across multiple sensory domains.
METHODS: The study included 172 participants aged 6 to 17 years (M = 13.09, SD = 3.02 years; 120 girls). Of these 80 participants were patients with migraine, 23 were patients with tension-type headache, and 69 were healthy controls. The following sensory measures were obtained: Mechanical Detection Threshold (MDT), Mechanical Pain Threshold (MPT), Mechanical Pain Sensitivity (MPS), detection and pain threshold for Transcutaneous Electrical Nerve Stimulation (TENS), olfactory and intranasal trigeminal detection threshold, and odor identification ability. Sensory sensitivity was compared between groups with a series of Kruskal-Wallis tests. Binomial regression models were used to compare the relative utility of sensory sensitivity measures in classifying participants into patients and healthy controls, as well as into patients with migraine and tension-type headache.
RESULTS: Patients with migraine had lower MPT measured at the forearm than patients with tension-type headaches and healthy controls. MPS was higher in patients with migraine than in healthy controls. All patients with headaches had lower detection threshold of TENS and higher olfactory sensitivity. Healthy controls showed increased intranasal trigeminal sensitivity. Scores in MPS, TENS, and olfactory and trigeminal thresholds were significantly predicting presence of primary headaches. Additionally, scores in MPT, olfactory and trigeminal threshold were positive predictors of type of headache.
CONCLUSIONS: Children with primary headaches exhibit different sensory profiles than healthy controls. The obtained results suggest presence of increased overall, multimodal sensitivity in children with primary headaches, what may negatively impact daily functioning and contribute to further pain chronification.
BACKGROUND: The study was registered in the German Registry of Clinical Trials (DRKS) DRKS00021062.

BACKGROUND: Reversible cerebral vasoconstriction syndrome is a clinicoradiological entity with a self-limiting course that manifests with recurrent episodes of thunderclap headache, and is associated with certain triggers. Recurrence is very rare, and the pathophysiology is thought to be related to altered autoregulation of the cerebrovascular tone. We present a clinical case that raises questions about possible recurrences and triggers.
METHODS: A 44-year-old woman with a history of multiple sclerosis treated with interferon beta-1b who had four episodes of thunderclap headache while resting, after completing a course of corticosteroids due to a flare-up of optic neuritis. Three years earlier, the patient had presented several episodes of explosive-onset headache during a self-limited period of one month, only occurring during sexual intercourse. In the year prior to our assessment, she had suffered three thunderclap headaches with similar characteristics, but they were triggered only by intense physical exercise. She had not consulted a physician about these events. A cranial computed tomography scan was performed after the administration of contrast media and a cerebral arteriography, which were consistent with cerebral vasoconstriction syndrome, and its reversibility was confirmed three months later.
CONCLUSIONS: Reversible cerebral vasoconstriction syndrome shares a phenotypic expression with primary exertion headaches. It is associated with drugs with vasoactive effects, including interferons, and corticosteroids are associated with a worse prognosis, and such their administration should be avoided.
BACKGROUND: Síndrome de vasoconstricción cerebral reversible. Recurrencia de cefaleas en trueno tras tratamiento con corticoides.
Introducción. El síndrome de vasoconstricción cerebral reversible es una entidad clinicorradiológica de curso autolimitado que se manifiesta con episodios de cefalea en trueno recurrentes y que se asocia a determinados desencadenantes. La recidiva es muy poco frecuente y la fisiopatología se cree que está en relación con la alteración de la autorregulación del tono vascular cerebral. Presentamos un caso clínico que plantea cuestiones sobre posibles recurrencias y desencadenantes. Caso clínico. Mujer de 44 años con antecedente de esclerosis múltiple en tratamiento con interferón beta-1b que consultó por cuatro episodios de cefalea en trueno en reposo, tras finalizar un ciclo de corticoides por un brote de neuritis óptica. Tres años antes, la paciente había presentado varios episodios de cefalea de inicio explosivo durante un período autolimitado de un mes, únicamente producidos en el contexto de relaciones sexuales. El año previo a nuestra valoración padeció en tres ocasiones cefalea en trueno de características similares, pero exclusivamente desencadenadas con el ejercicio físico intenso. No había consultado por estos eventos. Se realizó una tomografía computarizada craneal tras la administración de contraste y una arteriografía cerebral, que fueron compatibles con síndrome de vasoconstricción cerebral, y se confirmó su reversibilidad tres meses después. Conclusiones. El síndrome de vasoconstricción cerebral reversible comparte expresión fenotípica con el grupo de cefaleas primarias por esfuerzo físico. Se asocia a fármacos con efectos vasoactivos, entre los que se encuentran los interferones, y los corticoides se asocian a un peor pronóstico, por lo que es importante evitar su administración.

OBJECTIVE: Migraine is a complex and disabling neurological disorder. Recent years have witnessed the development and emergence of novel treatments for the condition, namely those targeting calcitonin gene-related peptide (CGRP). However, there remains a substantial need for further treatments for those unresponsive to current therapies. Targeting pituitary adenylate cyclase-activating polypeptide (PACAP) as a possible therapeutic strategy in the primary headache disorders has gained interest over recent years.
METHODS: This review will summarize what we know about PACAP to date: its expression, receptors, roles in migraine and cluster headache biology, insights gained from preclinical and clinical models of migraine, and therapeutic scope.
RESULTS: PACAP shares homology with vasoactive intestinal polypeptide (VIP) and is one of several vasoactive neuropeptides along with CGRP and VIP, which has been implicated in migraine neurobiology. PACAP is widely expressed in areas of interest in migraine pathophysiology, such as the thalamus, trigeminal nucleus caudalis, and sphenopalatine ganglion. Preclinical evidence suggests a role for PACAP in trigeminovascular sensitization, while clinical evidence shows ictal release of PACAP in migraine and intravenous infusion of PACAP triggering attacks in susceptible individuals. PACAP leads to dural vasodilatation and secondary central phenomena via its binding to different G-protein-coupled receptors, and intracellular downstream effects through cyclic adenosine monophosphate (cAMP) and phosphokinase C (PKC). Targeting PACAP as a therapeutic strategy in headache has been explored using monoclonal antibodies developed against PACAP and against the PAC1 receptor, with initial positive results.
CONCLUSIONS: Future clinical trials hold considerable promise for a new therapeutic approach using PACAP-targeted therapies in both migraine and cluster headache.

Reversible cerebral vasoconstriction syndrome (RCVS) is a complex and etiologically diverse neurovascular disorder that typically presents with severe thunderclap headaches (TCH) as the primary symptom, accompanied by reversible vasoconstriction of the cerebral arteries. The clinical course may include focal neurological deficits or epileptic seizures. There are two types: idiopathic RCVS and secondary RCVS, the latter triggered by various substances, medical interventions, or diseases. In clinical practice, various medical specialists may initially encounter this condition, underscoring the importance of accurate recognition and diagnosis of RCVS. The clinical course often appears monophasic and self-limiting, with recurrences reported in only 1.7% of cases annually. Complications such as cerebral hemorrhages and cerebral ischemia can lead to death in 5-10% of cases. This article utilizes a case study to explore RCVS, its complications, and the diagnostic procedures involved.
UNASSIGNED: Das reversible zerebrale Vasokonstriktionssyndrom (RCVS) ist eine komplexe und ätiologisch vielfältige neurovaskuläre Erkrankung, die typischerweise mit Donnerschlagkopfschmerz („thunderclap headache“, TCH) als Hauptkriterium sowie einer reversiblen sekundären Vasokonstriktion der Hirnarterien einhergeht. Das RCVS kann mit oder ohne fokal-neurologische Defizite oder epileptische Anfälle verlaufen. Man unterscheidet zwischen einem idiopathischen RCVS und einem sekundären RCVS, welches durch verschiedene Substanzen, medizinische Eingriffe oder Erkrankungen ausgelöst wird. Den ersten Kontakt mit dieser Erkrankung haben in der täglichen Praxis verschiedene Spezialisten; die richtige Erkennung und Diagnose von RCVS bleiben weiterhin eine Herausforderung. Der klinische Verlauf ist in der Regel monophasisch und selbstlimitierend, wobei Rezidive lediglich in 1,7 % der Fälle pro Jahr auftreten. Komplikationen wie Hirnblutungen und zerebrale Ischämien führen in 5–10 % der Fälle zum Tod. In dieser Arbeit wird ein Fallbeispiel verwendet, um das RCVS und seine Komplikationen vorzustellen sowie die diagnostischen Verfahren zu erläutern.

OBJECTIVE: To investigate the prevalence of neuroimaging in patients with primary headaches and the clinician-based rationale for requesting neuroimaging in China.
METHODS: This study included patients with primary headaches admitted to hospitals and clinicians in China. We identified whether neuroimaging was requested and the types of neuroimaging conducted.
METHODS: This was a cross-sectional study, and convenience sampling was used to recruit patients with primary headaches. Clinicians were interviewed using a combination of personal in-depth and topic-selection group interviews to explore why doctors requested neuroimaging.
METHODS: We searched for the diagnosis of primary headache in the outpatient and inpatient systems according to the International Classification of Diseases-10 code of patients admitted to six hospitals in three provincial capitals by 2022.We selected three public and three private hospitals with neurology specialties that treated a corresponding number of patients.
RESULTS: Among the 2263 patients recruited for this study, 1942 (89.75%) underwent neuroimaging. Of the patients, 1157 (51.13%) underwent magnetic resonance imaging (MRI), 246 (10.87%) underwent both head computed tomography (CT) and MRI, and 628 (27.75%) underwent CT. Fifteen of the 16 interviewed clinicians did not issue a neuroimaging request for patients with primary headaches. Furthermore, we found that doctors issued a neuroimaging request for patients with primary headaches mostly, to exclude the risk of misdiagnosis, reduce uncertainty, avoid medical disputes, meet patients\' medical needs, and complete hospital assessment indicators.
CONCLUSIONS: For primary headaches, the probability of clinicians requesting neuroimaging was higher in China than in other countries. There is considerable room for improvement in determining appropriate strategies to reduce the use of low-value care for doctors and patients.

Reversible cerebral vasoconstriction syndrome (RCVS) is a complex neurovascular disorder characterized by repetitive thunderclap headaches and reversible cerebral vasoconstriction. The pathophysiological mechanism of this mysterious syndrome remains underexplored and there is no clinically available molecular biomarker. To provide insight into the pathogenesis of RCVS, this study reported the first landscape of dysregulated proteome of cerebrospinal fluid (CSF) in patients with RCVS (n  =  21) compared to the age- and sex-matched controls (n  =  20) using data-independent acquisition mass spectrometry. Protein-protein interaction and functional enrichment analysis were employed to construct functional protein networks using the RCVS proteome. An RCVS-CSF proteome library resource of 1054 proteins was established, which illuminated large groups of upregulated proteins enriched in the brain and blood-brain barrier (BBB). Personalized RCVS-CSF proteomic profiles from 17 RCVS patients and 20 controls reveal proteomic changes involving the complement system, adhesion molecules, and extracellular matrix, which may contribute to the disruption of BBB and dysregulation of neurovascular units. Moreover, an additional validation cohort validated a panel of biomarker candidates and a two-protein signature predicted by machine learning model to discriminate RCVS patients from controls with an area under the curve of 0.997. This study reveals the first RCVS proteome and a potential pathogenetic mechanism of BBB and neurovascular unit dysfunction. It also nominates potential biomarker candidates that are mechanistically plausible for RCVS, which may offer potential diagnostic and therapeutic opportunities beyond the clinical manifestations.

BACKGROUND: We recently found headache disorders to be highly prevalent among children (aged 6-11 years) and adolescents (aged 12-17) in Iran (gender- and age-adjusted 1-year prevalences: migraine 25.2%, tension-type headache 12.7%, undifferentiated headache [UdH] 22.1%, probable medication-overuse headache [pMOH] 1.1%, other headache on ≥ 15 days/month [H15+] 3.0%). Here we report on the headache-attributed burden, taking evidence from the same study.
METHODS: In a cross-sectional survey, following the generic protocol for the global schools-based study led by the Global Campaign against Headache, we administered the child and adolescent versions of the Headache-Attributed Restriction, Disability, Social Handicap and Impaired Participation (HARDSHIP) structured questionnaire in 121 schools, purposively selected to reflect the country\'s diversities. Pupils self-completed these in class, under supervision. Headache diagnostic questions were based on ICHD-3 criteria but for the inclusion of UdH (defined as mild headache with usual duration < 1 h). Burden enquiry was across multiple domains.
RESULTS: The analysed sample (N = 3,244) included 1,308 (40.3%) children and 1,936 (59.7%) adolescents (1,531 [47.2%] male, 1,713 [52.8%] female). The non-participating proportion was 3.4%. Mean headache frequency was 3.9 days/4 weeks, and mean duration 1.8 h. Estimated mean proportion of time in ictal state was 1.1% (1.4% for migraine, 16.5% for pMOH). Symptomatic medication was consumed on a mean of 1.6 days/4 weeks. Lost school time averaged 0.4 days/4 weeks overall (2%, assuming a 5-day week), but was eleven-fold higher (4.3 days; 22%) for pMOH. For most headache types, days of reported limited activity were several-fold more than days lost from school (45% for pMOH, 25% for other H15+). Almost one in 12 parents (7.9%) missed work at least once in 4 weeks because of their son\'s or daughter\'s headache. Emotional impact and quality-of-life scores reflected these measures of burden.
CONCLUSIONS: Headache, common in children and adolescents in Iran, is associated with symptom burdens that may be onerous for some but not for most. However, there are substantial consequential burdens, particularly for the 1.1% with pMOH and the 3.0% with other H15+, who suffer educational disturbances and potentially major life impairments. These findings are of importance to educational and health policies in Iran.

Thunderclap headache is a sudden severe headache with onset to peak within one minute. Multiple excruciating, short-lived thunderclap headaches over a few days to weeks are highly suggestive of reversible cerebral vasoconstriction syndrome (RCVS). RCVS can be primary or secondary to several factors, but it is rarely described after neuro-endovascular procedures using onyx material. A 10-year-old child presented with RCVS heralded by recurrent thunderclap headache following endovascular embolization of pial arteriovenous malformation with onyx material (contains organic solvent dimethyl sulfoxide). Dimethyl sulfoxide is an angiotoxic material that can cause dysregulation of cerebral vascular tone triggering reversible cerebral vasoconstriction syndrome. Recurrent thunderclap headache after embolization procedures using onyx material should prompt for the diagnosis of reversible cerebral vasoconstriction syndrome.

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BACKGROUND: The Global Burden of Disease (GBD) study is increasingly well informed with regard to headache disorders, but sub-Saharan Africa (SSA) remains one of the large regions of the world with limited data directly derived from population-based studies. The Global Campaign against Headache has conducted three studies in this region: Ethiopia in the east, Zambia in the south and Cameroon in Central SSA. Here we report a similar study in Benin, the first from West SSA.
METHODS: We used the same methods and questionnaire, applying cluster-randomized sampling in three regions of the country, randomly selecting households in each region, visiting these unannounced and randomly selecting one adult member (aged 18-65 years) of each household. The HARDSHIP structured questionnaire, translated into Central African French, was administered face-to-face by trained interviewers. Demographic enquiry was followed by diagnostic questions based on ICHD-3 criteria.
RESULTS: From 2,550 households with eligible members, we recruited 2,400 participants (participating proportion 94.1%). Headache ever was reported by almost all (95.2%), this being the lifetime prevalence. Headache in the last year was reported by 74.9%. Age-, gender- and habitation-adjusted estimates of 1-year prevalence were 72.9% for all headache, 21.2% for migraine (including definite and probable), 43.1% for TTH (also including definite and probable), 4.5% for probable medication-overuse (pMOH) and 3.1% for other headache on ≥ 15 days/month. One-day (point) prevalence of headache was 14.8% according to reported headache on the day preceding interview.
CONCLUSIONS: Overall, these findings are evidence that headache disorders are very common in Benin, a low-income country. The prevalence of pMOH, well above the estimated global mean of 1-2%, is evidence that poverty is not a bar to medication overuse. The findings are very much the same as those in a similar study in its near neighbour, Cameroon. With regard to migraine, they are reasonably in accord with two of three earlier studies in selected Beninese populations, which did not take account of probable migraine. This study adds to the hitherto limited knowledge of headache in SSA.