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The Journal of Headache and Pain Jun 2024The development of several experimental migraine provocation models has significantly contributed to an understanding of the signaling mechanisms of migraine. The early... (Review)
Review
INTRODUCTION
The development of several experimental migraine provocation models has significantly contributed to an understanding of the signaling mechanisms of migraine. The early history of this development and a view to the future are presented as viewed by the inventor of the models.
METHODS
Extensive knowledge of the literature was supplemented by scrutiny of reference lists.
RESULTS
Early studies used methodologies that were not blinded. They suggested that histamine and nitroglycerin (Glyceryl trinitrate, GTN) could induce headache and perhaps migraine. The development of a double blind, placebo-controlled model, and the use of explicit diagnostic criteria for induced migraine was a major step forward. GTN, donor of nitric oxide (NO), induced headache in people with- and without migraine as well as delayed migraine attacks in those with migraine. Calcitonin gene-related peptide (CGRP) did the same, supporting the development of CGRP antagonists now widely used in patients. Likewise, pituitary adenylate cyclase activating peptide (PACAP) provoked headache and migraine. Recently a PACAP antibody has shown anti migraine activity in a phase 2 trial. Increase of second messengers activated by NO, CGRP and PACAP effectively induced migraine. The experimental models have also been used in other types of headaches and have been combined with imaging and biochemical studies. They have also been used for drug testing and in genetic studies.
CONCLUSION
Conclusion. Human migraine provocation models have informed about signaling mechanisms of migraine leading to new drugs and drug targets. Future use of these models in imaging-, biochemistry- and genetic studies as well as in the further study of animal models is promising.
Topics: Migraine Disorders; Humans; Animals; Signal Transduction; Calcitonin Gene-Related Peptide; Nitroglycerin; Disease Models, Animal
PubMed: 38902612
DOI: 10.1186/s10194-024-01796-1 -
The Journal of Headache and Pain Jun 2024Non-steroidal anti-inflammatory drugs (NSAIDs) are considered first-line medications for acute migraine attacks. However, the response exhibits considerable variability...
BACKGROUND
Non-steroidal anti-inflammatory drugs (NSAIDs) are considered first-line medications for acute migraine attacks. However, the response exhibits considerable variability among individuals. Thus, this study aimed to explore a machine learning model based on the percentage of amplitude oscillations (PerAF) and gray matter volume (GMV) to predict the response to NSAIDs in migraine treatment.
METHODS
Propensity score matching was adopted to match patients having migraine with response and nonresponse to NSAIDs, ensuring consistency in clinical characteristics and migraine-related features. Multimodal magnetic resonance imaging was employed to extract PerAF and GMV, followed by feature selection using the least absolute shrinkage and selection operator regression and recursive feature elimination algorithms. Multiple predictive models were constructed and the final model with the smallest predictive residuals was chosen. The model performance was evaluated using the area under the receiver operating characteristic (ROCAUC) curve, area under the precision-recall curve (PRAUC), balance accuracy (BACC), sensitivity, F1 score, positive predictive value (PPV), and negative predictive value (NPV). External validation was performed using a public database. Then, correlation analysis was performed between the neuroimaging predictors and clinical features in migraine.
RESULTS
One hundred eighteen patients with migraine (59 responders and 59 non-responders) were enrolled. Six features (PerAF of left insula and left transverse temporal gyrus; and GMV of right superior frontal gyrus, left postcentral gyrus, right postcentral gyrus, and left precuneus) were observed. The random forest model with the lowest predictive residuals was selected and model metrics (ROCAUC, PRAUC, BACC, sensitivity, F1 score, PPV, and NPV) in the training and testing groups were 0.982, 0.983, 0.927, 0.976, 0.930, 0.889, and 0.973; and 0.711, 0.648, 0.639, 0.667,0.649, 0.632, and 0.647, respectively. The model metrics of external validation were 0.631, 0.651, 0.611, 0.808, 0.656, 0.553, and 0.706. Additionally, a significant positive correlation was found between the GMV of the left precuneus and attack time in non-responders.
CONCLUSIONS
Our findings suggest the potential of multimodal neuroimaging features in predicting the efficacy of NSAIDs in migraine treatment and provide novel insights into the neural mechanisms underlying migraine and its optimized treatment strategy.
Topics: Humans; Migraine Disorders; Anti-Inflammatory Agents, Non-Steroidal; Female; Adult; Male; Magnetic Resonance Imaging; Gray Matter; Neuroimaging; Machine Learning; Middle Aged; Biomarkers
PubMed: 38902598
DOI: 10.1186/s10194-024-01812-4 -
World Journal of Clinical Cases Jun 2024Granulomatosis with polyangiitis (GPA) is one of the most prevalent forms of the antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis. GPA is characterized...
BACKGROUND
Granulomatosis with polyangiitis (GPA) is one of the most prevalent forms of the antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis. GPA is characterized histologically by necrotizing granulomatous inflammation in addition to vasculitis. The diagnosis of GPA depends on clinical presentation, serological evidence of a positive ANCA, and/or histological evidence of necrotizing vasculitis or granulomatous destructive parenchymal inflammation. Cytoplasmic ANCA (c-ANCA) is positive in 65%-75% of GPA patients, accompanied by proteinase 3 (PR3), the main target antigen of c-ANCA, another 5% of GPA patients had negative ANCA.
CASE SUMMARY
The patient, a 52-year-old male, presented with unexplained nasal congestion, tinnitus, and hearing loss. After a duration of 4 months experiencing these symptoms, the patient subsequently developed fever and headache. The imaging examination revealed the presence of bilateral auricular mastoiditis and partial paranasal sinusitis, and the ANCA results were negative. The anti-infective therapy proved to be ineffective, but the patient's symptoms and fever were quickly relieved after 1 wk of treatment with methylprednisolone 40 mg once a day. However, after continuous use of methylprednisolone tablets for 3 months, the patient experienced a recurrence of fever accompanied by right-sided migraine, positive c-ANCA and PR3, and increased total protein in cerebrospinal fluid. The patient was diagnosed with GPA. After receiving a treatment regimen of intravenous methylprednisolone 40 mg/d and cyclophosphamide 0.8 g monthly, the patient experienced alleviation of fever and headache. Additionally, the ANCA levels became negative and there has been no recurrence.
CONCLUSION
For GPA patients with negative ANCA, there is a potential for early missed diagnosis. The integration of histopathological results and multidisciplinary communication plays a crucial role in facilitating ANCA-negative GPA.
PubMed: 38899312
DOI: 10.12998/wjcc.v12.i16.2881 -
Vascular Medicine (London, England) Jun 2024Spontaneous coronary artery dissection (SCAD) is a nonatherosclerotic cause of myocardial infarction. Migraine headache has been reported to be common among patients...
INTRODUCTION
Spontaneous coronary artery dissection (SCAD) is a nonatherosclerotic cause of myocardial infarction. Migraine headache has been reported to be common among patients with SCAD, but the degree of migraine-related disability has not been quantified.
METHODS
Clinical data and headache variables were obtained from the baseline assessment of the prospective, multicenter iSCAD Registry. Migraine-related disability was quantified using the self-reported Migraine Disability Assessment (MIDAS). Demographic, clinical, psychosocial, and medical characteristics from data entry forms were compared between patients with and without migraine.
RESULTS
Of the 773 patients with available data, 46% reported previous or current migraines. Those with migraines were more likely to be women (96.9% vs 90.3%, = 0.0003). The presence of underlying carotid fibromuscular dysplasia was associated with migraine (35% vs 27%, = 0.0175). There was not a significant association with carotid artery dissection and migraine. Current migraine frequency was less than monthly (58%), monthly (24%), weekly (16%), and daily (3%). Triptan use was reported in 32.5% of patients, and 17.5% used daily migraine prophylactic medications. Using the MIDAS to quantify disability related to migraine, 60.2% reported little or no disability, 14.4% mild, 12.7% moderate, and 12.7% severe. The mean MIDAS score was 9.9 (mild to moderate disability). Patients with SCAD had higher rates of depression and anxiety (28.2% vs 17.7% [ = 0.0004] and 35.3% vs 26.7% [ = 0.0099], respectively).
CONCLUSIONS
Migraines are common, frequent, and a source of disability in patients with SCAD. The association between female sex, anxiety, and depression may provide some insight for potential treatment modalities.
Topics: Humans; Female; Registries; Male; Migraine Disorders; Middle Aged; Vascular Diseases; Coronary Vessel Anomalies; Adult; Prospective Studies; Risk Factors; Disability Evaluation; Aged; Fibromuscular Dysplasia; Depression
PubMed: 38898631
DOI: 10.1177/1358863X241252444 -
CNS Neuroscience & Therapeutics Jun 2024Proteome-wide Mendelian randomization studies have been increasingly utilized to identify potential drug targets for diseases. We aimed to identify potential therapeutic...
BACKGROUND
Proteome-wide Mendelian randomization studies have been increasingly utilized to identify potential drug targets for diseases. We aimed to identify potential therapeutic targets for migraine and its subtypes through the application of Mendelian randomization and co-localization analysis methods.
METHODS
We utilized cis-protein quantitative trait loci data for 1378 plasma proteins available from two studies with 7213 individuals and 35,559 individuals, respectively. Summary data for migraine and its subtypes were obtained from a genetic study involving up to 1,339,303 individuals. Proteins that passed both the discovery and validation Mendelian randomization analysis, sensitivity analysis, heterogeneity test, and pleiotropy test, were associated with ≥2 outcomes, and received strong support from co-localization analysis (PP.H4.abf ≥0.80) and were classified as tier 1 proteins.
RESULTS
We identified three tier 1 proteins (LRP11, ITIH1, and ADGRF5), whose genes have not been previously identified as causal genes for migraine in genetic studies. LRP11 was significantly associated with the risk of any migraine (OR [odds ratio] = 0.968, 95% CI [confidence interval] = 0.955-0.981, p = 1.27 × 10) and significantly/suggestively associated with three migraine subtypes. ITIH1 was significantly associated with the risk of any migraine (OR = 1.044, 95% CI = 1.024-1.065, p = 1.08 × 10) and migraine with visual disturbances. ADGRF5 was significantly associated with the risk of any migraine (OR = 0.964, 95% CI = 0.946-0.982, p = 8.74 × 10) and suggestively associated with migraine with aura. The effects of LRP11 and ADGRF5 were further replicated using cerebrospinal fluid protein data. Apart from ADGRF5, there was no evidence of potential adverse consequences when modulating the plasma levels. We also identified another four proteins (PLCG1, ARHGAP25, CHGA, and MANBA) with no potential adverse consequences when modulating the plasma levels, and their genes were not reported by previous genetic studies.
CONCLUSIONS
We found compelling evidence for two proteins and suggestive evidence for four proteins that could be promising targets for migraine treatment without significant adverse consequences. The corresponding genes were not reported in previous genetic studies. Future studies are needed to confirm the causal role of these proteins and explore the underlying mechanisms.
Topics: Humans; Genome-Wide Association Study; Migraine Disorders; Proteome; Mendelian Randomization Analysis; Quantitative Trait Loci; Female; Male; Genetic Predisposition to Disease; Polymorphism, Single Nucleotide
PubMed: 38898596
DOI: 10.1111/cns.14817 -
Scientific Reports Jun 2024This study aims to investigate auditory hypersensitivity and cortical function in migraine patients using the Hyperacusis Questionnaire and the Event-Related Potential...
This study aims to investigate auditory hypersensitivity and cortical function in migraine patients using the Hyperacusis Questionnaire and the Event-Related Potential (ERP) technique. The study analyzes alterations in the latency and amplitude of the event-related potentials MMN and P300 components. The findings contribute to a better understanding of the physiological relationship between migraine and auditory hypersensitivity. Seventeen migraine patients were admitted to the outpatient clinic of the Department of Otorhinolaryngology-Head and Neck Surgery at Peking University People's Hospital from June 2023 to September 2023. Nineteen matched healthy subjects were also selected. All participants underwent the pure tone audiometry and the auditory brainstem response test to determine hearing thresholds, the Hyperacusis Questionnaire, the Tinnitus Handicap Inventory, and an ERP examination. The Oddball classical paradigm was used as the stimulation task, and electroencephalography signals were recorded synchronously. The scores of the Hyperacusis Questionnaire, latency and amplitude of MMN and P300 component were compared between the migraine group and the control group, and their correlation was analyzed. The latency of MMN at the Fz and Cz sites in migraine patients was significantly shorter than that in the control group (P < 0.05), and the amplitudes were significantly higher than those in the control group (P < 0.05). The variances in latency and amplitude of P300 at Cz and Pz sites in migraine patients were not statistically significant when compared with the control group. (P > 0.05). The Hyperacusis Questionnaire was negatively correlated with MMN latency, with a correlation coefficient of - 0.374 (P = 0.025), and positively correlated with MMN amplitude, with a correlation coefficient of 0.378 (P = 0.023). There was no significant similarity between the Hyperacusis Questionnaire and P300 latency and amplitude (P > 0.05). Overall, auditory hypersensitivity was enhanced in individuals with migraines compared to healthy individuals, leading to faster information processing, while there may be less impairment in cognitive function.
Topics: Humans; Female; Migraine Disorders; Male; Hyperacusis; Adult; Surveys and Questionnaires; Middle Aged; Electroencephalography; Event-Related Potentials, P300; Evoked Potentials; Case-Control Studies; Young Adult; Audiometry, Pure-Tone
PubMed: 38898084
DOI: 10.1038/s41598-024-65014-3 -
Journal of Nippon Medical School =... Jun 2024A 56-year-old right-handed man was referred to our hospital for evaluation of sudden-onset transient quadrantanopia, which was followed by throbbing headache consistent...
A 56-year-old right-handed man was referred to our hospital for evaluation of sudden-onset transient quadrantanopia, which was followed by throbbing headache consistent with migraine with aura (MA). Magnetic resonance imaging (MRI) of the right parieto-occipital cortex on admission showed a hyperintense region on diffusion-weighted imaging, which disappeared 7 days later. A small cortical infarct in the parieto-occipital cortex can cause MA-like headache, and the present infarct lesion was only detectable on MRI during the acute phase. Performing MRI for patients with suspected acute MA might help identify the cause of MA-like headache and ensure appropriate management of patients.
PubMed: 38897949
DOI: 10.1272/jnms.JNMS.2025_92-103 -
Diagnostics (Basel, Switzerland) May 2024To compare white matter hyperintensities (WMHs) on T2-weighted magnetic resonance imaging (MRI) of patients with sudden sensorineural hearing loss (SSNHL) and analyze...
OBJECTIVE
To compare white matter hyperintensities (WMHs) on T2-weighted magnetic resonance imaging (MRI) of patients with sudden sensorineural hearing loss (SSNHL) and analyze subpopulations with age-matched controls.
METHODS
T2-weighted MRI scans of 150 patients with SSNHL were assessed for WMHs and compared with the data of 148 healthy age-matched adults. Assessments of WMHs included independent grading of deep white matter hyperintensities (DWMHs) and periventricular hyperintensities (PVHs). WMH severity was visually rated using the Fazekas and Mirsen scales by two independent observers.
RESULTS
Fazekas grades for PVHs ( < 0.001) and DWMHs ( < 0.001) of SSNHL patients were found to be significantly greater than those of healthy participants. The average Mirsen grades for DWMHs of healthy and SSNHL patients were evaluated to be 0.373 ± 0.550 and 2.140 ± 0.859, respectively. Mirsen grades for DWMHs of SSNHL patients were found to be significantly greater ( < 0.001) than those of healthy participants. The Mirsen scale was found to have higher sensitivity ( < 0.001) than the Fazekas scale in grading PVHs and DWMHs. No significant difference ( = 0.24) was found in specificities between the two scales.
CONCLUSIONS
Patients with sudden hearing loss have a much higher likelihood of having periventricular and deep white matter hyperintensities compared to age-matched controls. These findings indicate that sudden hearing loss patients are more likely to have microvascular changes in the brain, which may indicate a vascular and/or migraine origin to sudden sensorineural hearing loss.
PubMed: 38893635
DOI: 10.3390/diagnostics14111109 -
Journal of Clinical Medicine Jun 2024At present, the patent foramen ovale (PFO) does not receive the deserved medical attention. The PFO poses a serious threat to health and even the life of mankind. The... (Review)
Review
At present, the patent foramen ovale (PFO) does not receive the deserved medical attention. The PFO poses a serious threat to health and even the life of mankind. The first respective case report in the medical literature dates back to the 19th century. It led to death. The fact that a PFO is present in roughly 25% of people underscores its overall potential to cause harm. Yet at the same time, the sheer number discourages the medical community from screening for it and from treating it. About 5% of the population have particularly dangerous forms of PFOs. Such PFOs portray a high enough risk for clinical events, the likes of death, stroke, myocardial infarction, or ocular, visceral, and peripheral embolism, to justify screening for them. Highly significant health incidents being at stake, it appears obvious that PFO closure should be used for primary prevention. This is supported by the fact that closing a PFO is the simplest intervention in cardiology, with presumably the highest clinical yield. Being mainly a preventive measure, PFO closure represents a mechanical vaccination. When closing PFOs for one of the rarer therapeutic indications (migraine, platypnea orthodeoxia, etc.), patients automatically profit from the collateral benefit of getting, at the same time, mechanically vaccinated for life against paradoxical embolism. Vice versa, closing a PFO for the prevention of paradoxical embolism betters or cures migraine or exercise dyspnea not infrequently, thereby improving quality of life as a collateral benefit.
PubMed: 38893065
DOI: 10.3390/jcm13113355 -
Journal of Clinical Medicine May 2024: Compare the effects of greater occipital nerve (GON) and sphenopalatine ganglion (SPG) blocks on headache intensity and duration, number of headache days, and...
: Compare the effects of greater occipital nerve (GON) and sphenopalatine ganglion (SPG) blocks on headache intensity and duration, number of headache days, and disability in patients with episodic migraine. : In this prospective single-blind randomized study, patients with episodic migraine were randomly divided into two groups: GON and SPG block groups. Patients received blocks once a week for 4 weeks, and once a month for 2 months. The number of headache days, the headache duration, numeric rating scale (NRS) scores, and number of acute medical treatments were assessed before the procedures and 1 month, 2 months, and 3 months after the procedures. Disability was evaluated using the migraine disability assessment (MIDAS) questionnaire at baseline and 3 months after treatment. This study protocol is registered at ClinicalTrials.gov (NCT06243874.). 19 patients in the GON block group and 18 patients in the SPG block group were evaluated. Significant improvements in pain severity, headache duration, number of headache days, and the need for acute medical treatment were observed in the 1st, 2nd, and 3rd months compared to baseline in the two groups ( < 0.001). There were significant improvements in the MIDAS scores in the third month ( < 0.001). The GON block group showed a greater reduction in headache intensity, duration, number of headache days, and MIDAS scores compared to the SPG block group in the 3rd month ( < 0.001). : GON block reduces headache duration, intensity, the number of headache days, and the need for acute medical treatment much more than SPG block in patients with episodic migraine.
PubMed: 38892738
DOI: 10.3390/jcm13113027