Cephalalgia最新文献

Background: Orthostatic headache (OH) is a common feature of various conditions, including spontaneous intracranial hypotension (SIH), but no precise definition currently exists outlining the typical OH characteristics. This ambiguity risks misdiagnosis with unnecessary investigations and delay in institution of treatment. The present study aimed to carry out structured phenotyping of OH in patients with SIH with the aim of outlining its typical characteristics.

Methods: Eligible patients with clinico-radiological confirmed SIH underwent a structured interview, after which a specialist interest group utilised the modified Delphi process to analyse the data and achieve consensus on defining the typical characteristics of OH in SIH.

Results: In total, 137 patients were recruited. OH was present in 75.9%. Typical OH characteristics in SIH were defined as having a baseline severity (lying flat) on waking up of ≤3 (0-10, verbal response scale), headache onset-time of ≤4.5 h on becoming upright, time to peak severity of ≤7.5 h and an offset to baseline severity within 1.5 h of recumbency. Intra-individual consistency in the onset and offset-time was deemed a necessary characteristic.

Conclusions: Defining typical OH characteristics has the potential of enhancing SIH diagnostics and management, at the same time as minimising unwarranted invasive procedures.

Background: Individuals with autism spectrum disorder (ASD) experience a wide array of neurological, psychiatric and medical comorbidities, yet little attention has been given to the potential link between ASD and migraine, one of the most prevalent neurological disorders worldwide. This study aimed to investigate whether a genetic predisposition for ASD is linked to migraine and its major subtypes, with and without aura. Additionally, potential moderator and mediators of the association between ASD and migraine were explored.

Methods: Polygenic scores (PGS) for ASD were constructed based on the genome-wide association study by the Psychiatric Genomics Consortium, on the UK Biobank cohort dataset comprising 337,386 participants using PRSice-2. Regression analyses were performed to investigate the association of ASD PGS with migraine and its major subtypes, with and without aura. Sex was explored as a potential moderating factor. The mediation analyses took into consideration variables such as education, personality trait neuroticism, body mass index (BMI) and four categories of comorbidities (psychiatric, vascular, neurologic and others).

Results: ASD PGS were significantly and positively associated with migraine (odds ratio (OR) = 1.04, 95% confidence interval (CI) = 1.02-1.05, p < 0.002), migraine without aura (OR = 1.05, 95% CI = 1.02-1.07, p < 0.002) and migraine with aura (OR = 1.05, 95% CI = 1.02-1.07, p < 0.002). No moderating effect of sex on the association between ASD PGS and migraine was observed. As for potential mediators, only the personality trait neuroticism significantly mediated the association between ASD PGS and migraine, with the proportion of effect mediated 8.75% (95% CI = 4-18%).

Conclusions: Our study suggests that individuals genetically predisposed to autism are at higher risk of experiencing migraine, including the two major subtypes, with and without aura. While emphasizing the complex shared genetic and pathophysiological interactions of these conditions, the role of personality trait neuroticism as a mediator of this relationship is highlighted.

Background: Familial hemiplegic migraine (FHM) types 1-3 are associated with protein-altering genetic variants in CACNA1A, ATP1A2 and SCN1A, respectively. These genes have also been linked to epilepsy. Previous studies primarily focused on phenotypes, examining genetic variants in individuals with characteristic FHM symptoms. This study aimed to investigate the association of FHM genetic variation with migraine and epilepsy, utilizing a genotype-first approach.

Methods: Whole-exome sequence data from 454,706 individuals from the UK Biobank were examined for self-reported and inpatient-diagnosed migraine and epilepsy. Carriers were compared with non-carriers in a burden analysis using logistic regression while accounting for age, biological sex and UK Biobank assessment center. A machine learning-based approach was employed to predict whether variants resulted in gain-of-function (GoF), loss-of-function (LoF) or neutral effects.

Results: Heterozygous carriers of GoF CACNA1A variants, LoF ATP1A2 variants or neutral SCN1A variants were at increased risk of migraine. Homozygous carriers of neutral SCN1A variants were also associated with migraine but these carriers showed a reduced disease risk of epilepsy.

Conclusions: Heterozygous genotypes in all three FHM genes were associated with migraine but not epilepsy in this genotype-focused study. Homozygous SCN1A genotypes also showed increased disease risk of migraine, yet these carriers were protected against epilepsy.

Purpose: Photophobia is a common and debilitating symptom associated with migraine. Women are disproportionately affected by migraines, with a higher prevalence and more severe symptoms compared to men. This study investigated the effects of cortical spreading depression on light-aversive and dark-seeking behaviors in a rat model, with an emphasis on sex differences.

Method: Experiments were conducted on seven to eight-week-old male and female Sprague Dawley rats. cortical spreading depression was modeled by injections of potassium chloride or artificial cerebrospinal fluid into the occipital cortex through a guide cannula. Key behavioral assessments included light-aversive and dark-seeking behaviors measured using a three-chamber box, pupil to iris ratio, periorbital tightening, periorbital allodynia and facial withdrawal thresholds.

Results: Our results demonstrated that cortical potassium chloride injections significantly increased photophobic behaviors, particularly in female rats. Specifically, potassium chloride-injected females demonstrated a significant reduction in the time spent in the light chamber (p = 0.001) and increased time in the dark chamber compared to control rats (p = 0.01), indicating heightened light-aversion. Females exhibited more substantial pupil constriction and eyelid closure at 180 min after potassium chloride injection compared to artificial cerebrospinal fluid injection, suggesting a stronger physiological response to light. Similarly, a greater percent of female rats displayed periorbital allodynia (withdrawal threshold <6 g) over a post injection time course compared to male rats. Among rats that exhibited periorbital allodynia at least two consecutive time points, females had significantly lower facial withdrawal thresholds than males at 60-, 90-, 120-, and 180-min post injection (p < 0.05), suggesting a difference in magnitude and duration. Furthermore, the area under the curve for the time course experiment indicated development of tactile allodynia in periorbital region among female rats (p < 0.0001).

Conclusion: Altogether these findings highlight the importance of considering sex-specific differences in developing therapeutic strategies for the treatment of migraine. We report for the first time a complete time course analysis of migraine-related responses, providing a comprehensive overview of the dynamics involved. The results suggest that potassium chloride-induced cortical spreading depression may offer a valuable model for studying the underlying mechanisms and sex differences of photophobia in migraine, aiding in the development of targeted treatments.

Background: Women with endometriosis are more likely to have migraine. The mechanisms underlying this co-morbidity are unknown. Prolactin, a neurohormone secreted and released into circulation from the anterior pituitary, can sensitize sensory neurons from female, but not male, rodents, monkeys and human donors.

Methods: We used a syngeneic model of endometriosis to determine whether elevated prolactin levels can sensitize trigeminal ganglion neurons and increase vulnerability to migraine pain.

Results: Mice with endometriotic lesions showed increased serum prolactin levels and developed persistent abdominal, but not cephalic, allodynia. However, inhalation of a transient receptor potential ankyrin 1 agonist, umbellulone, a known environmental trigger of headache in some patients, elicited cephalic allodynia in mice with endometriosis but not sham controls, suggesting that endometriosis can promote sensitization of trigeminal neurons and migraine attacks. Endometriosis dysregulated the expression of prolactin receptor isoforms in trigeminal neurons and increased their excitability measured by in vitro patch clamp electrophysiology. Inhibition of pituitary prolactin following a 2-week treatment with a dopamine receptor agonist, cabergoline, prevented cephalic allodynia elicited by activation of trigeminal afferents with umbellulone. Cabergoline treatment also normalized the expression of prolactin receptor isoforms in trigeminal ganglia and the hyperexcitability of trigeminal neurons.

Conclusions: These data demonstrate that circulating prolactin in endometriosis promotes vulnerability to migraine through sensitization of trigeminal afferents. Clinically available dopamine receptor agonists or novel monoclonal antibodies targeting prolactin signaling may be effective for migraine prevention in women with endometriosis.

There is a multitude of scientific papers and guideline papers on the methodology of drug trials in migraine. Here, we try to condense this into a single paper and to make proposals for future consideration. Literature known by the authors and from reference lists of relevant publications was used for the history. Relevant literature for our proposals was searched on PubMed. The main headings in published guidelines, namely, Patient selection, Trial design, Evaluation of results and Statistics, have remained unchanged over the years. Most of the methodology has remained unchanged but the changes that have taken place are important. Chronic migraine has been studied separately from episodic migraine, children and adolescents distinguished from adults, and migraine without aura from migraine with aura. In trial design, the group comparison design has taken priority over the cross-over design, but the latter is suggested for investigator driven, comparative, dose finding and aura trials because of its superior power. There is a confusing number of possible primary end points: number of migraine attacks, number of migraine days, number of headache days and number of 50% responders in prophylactic trials, whereas two-hour pain free is agreed in acute trials. However, also 24- and 48-hour pain free have been suggested and headache relief is sometimes still used against recommendations. Most bothersome symptom has been requested as a co-primary end point by Food and Drug Administration (FDA). Our future suggestions are meant to provide food for thought for future committee work. We suggest that most bothersome symptom needs to be discussed with FDA as a co-primary end point in acute trials. It could also be discussed whether episodic- and chronic migraine need separate study. Migraine with- and without aura should be studied separately. Furthermore, two-hour pain free should be maintained as the primary end point but the use of stricter outcome parameters should be explored. In prophylactic trials, migraine days are recommended over migraine attacks and over 50% responders. For investigator-initiated trials, comparative trials and proof of concept trials by small companies, the cross-over design with its superior power is still recommended. Finally, the need to lump various guidelines into one major document should be considered. The methodology of drug trials in migraine has been worked out in detail. It is important that these guidelines be followed in all clinical trials. We highlight several issues that merit attention in the future.