Treatment of migraine with aura with osteopathic manipulative treatment: a case report with renewed perspectives.

Migraines make up a significant number of office visits every year, yet their pathophysiology and etiology remain largely elusive. This case report presents a 33-year-old patient who originally presented to the emergency department (ED) as a stroke alert and was later determined to have migraine with aura. The patient experienced an acute onset of headache, dizziness, and new-onset expressive aphasia. Before administration of a migraine cocktail, osteopathic manipulative treatment (OMT) was performed and was able to fully resolve all of her symptoms. In an effort to explain the outcomes in this case, a review of the current literature was performed, which provides an interesting perspective on the interplay of the musculoskeletal system and neuroanatomy. The literature establishes that somatic dysfunctions in the cervical vertebrae and trapezius may play a role in migraines and provide rationale for the use of OMT.

Higher sodium in older individuals or after stroke/reperfusion, but not in migraine or Alzheimer's disease - a study in different preclinical models.

Sodium serves as one of the primary cations in the central nervous system, playing a crucial role in maintaining normal brain function. In this study, we investigated alterations in sodium concentrations in the brain and/or cerebrospinal fluid across multiple models, including an aging model, a stroke model, a nitroglycerin (NTG)-induced rat migraine model, a familial hemiplegic migraine type 2 (FHM2) mouse model, and a transgenic mouse model of Alzheimer's disease (AD). Our results reveal that older rats exhibited higher sodium concentrations in cerebrospinal fluid (CSF), plasma, and various brain regions compared to their younger counterparts. Additionally, findings from the stroke model demonstrated a significant increase in sodium in the ischemic/reperfused region, accompanied by a decrease in potassium and an elevated sodium/potassium ratio. However, we did not detect significant changes in sodium in the NTG-induced rat migraine model or the FHM2 mouse model. Furthermore, AD transgenic mice showed no significant differences in sodium levels compared to wild-type mice in CSF, plasma, or the hippocampus. These results underscore the nuanced regulation of sodium homeostasis in various neurological conditions and aging, providing valuable insights into potential mechanisms underlying these alterations.

Misdiagnosed case of acute angle closure caused severe visual field defects.

In this case report, a 33-year-old pregnant woman with migraine and visual aura complained of headache, nausea, and blurred vision. Clinically, she presented with bilateral dilated and fixed pupils, ptosis, and tearing. She was erroneously diagnosed as having a migraine attack, but after referral to an ophthalmological department she was diagnosed with bilateral acute angle closure. At one-year follow-up her visual acuity was normalized but the severe visual field defects affected her daily activities and prevented her from having a driving licence.

Proteome-wide Mendelian randomization identified potential drug targets for migraine.

BACKGROUND: Migraine is a highly prevalent and complex neurovascular disease. However, the currently available therapeutic drugs often fall to adequately meet clinical needs due to limited effectiveness and numerous undesirable side effects. This study aims to identify putative novel targets for migraine treatment through proteome-wide Mendelian randomization (MR). METHODS: We utilized MR to estimate the causal effects of plasma proteins on migraine and its two subtypes, migraine with aura (MA) and without aura (MO). This analysis integrated plasma protein quantitative trait loci (pQTL) data with genome-wide association studies (GWAS) findings for these migraine phenotypes. Moreover, we conducted a phenome-wide MR assessment, enrichment analysis, protein-protein interaction networks construction, and mediation MR analysis to further validate the pharmaceutical potential of the identified protein targets. RESULTS: We identified 35 protein targets for migraine and its subtypes (p < 8.04 × 10-6), with prioritized targets showing minimal side effects. Phenome-wide MR identified novel protein targets-FCAR, UBE2L6, LATS1, PDCD1LG2, and MMP3-that have no major disease side effects and interacted with current acute migraine medication targets. Additionally, MMP3, PDCD1LG2, and HBQ1 interacted with current preventive migraine medication targets. The causal effects of plasma protein on migraine were partly mediated by plasma metabolites (proportion of mediation from 3.8% to 21.0%). CONCLUSIONS: A set of potential protein targets for migraine and its subtypes were identified. These proteins showed rare side effects and were responsible for biological mechanisms involved in migraine pathogenesis, indicating priority for the development of migraine treatments.

Migraine versus tension-type headache in automatic emotional processing: A visual mismatch negativity study.

OBJECTIVE: It is important to discriminate different headaches in clinical practice, and neurocognitive biomarkers may serve as objective tools. Several reports have suggested potential cognitive impairment for primary headaches, whereas cognitions within specific domains remain elusive, e.g., emotional processing. In this study, we aimed to characterize processing of facial expressions in migraine and tension-type headache (TTH) by analyzing expression-related visual mismatch negativity (EMMN) and explored whether their processing patterns were distinct. METHODS: Altogether, 73 headache patients (20 migraine with aura (MA), 28 migraine without aura (MwoA), 25 TTH) and 27 age-matched healthy controls were recruited. After a battery of mood/neuropsychological evaluations, an expression-related oddball paradigm containing multiple models of neutral, happy and sad faces was used to investigate automatic emotional processing. RESULTS: We observed cognitive impairment in all headache patients, especially in attention/execution subdomains, but no discrepancy existed among different headaches. Although analyses of P1/N170 did not reach significant levels, amplitude of early and late EMMN was markedly diminished in MA and MwoA compared with controls and TTH, regardless of happy or sad expression. Moreover, sad EMMN was larger (more negative) than happy EMMN only in controls, while not in all headache groups. CONCLUSIONS: Our findings implied that migraine, rather than TTH, might lead to more severe impairment of automatic emotional processing, which was manifested as no observable EMMN elicitation and disappearance of negative bias effect. The EMMN component could assist in discrimination of migraine from TTH and diagnosis of undefined headaches, and its availability needed further validations.

Familial hemiplegic migraine.

Hemiplegic migraine consists of attacks of migraine with aura that includes reversible motor weakness. It is classified as familial or sporadic depending on the involvement or not of a first or second degree relative. The most described subtypes of familial hemiplegic migraine include FHM1, FHM2, and FHM3. These have been demonstrated to have a mutation in either CACNA1A, ATP1A2 or SCN1A, which encode different subunits of channels, involving P/Q-type calcium channel, Na/K pump and Na channel, respectively, located in neurons and glial cells. Mutations localized in different genes are defined as "other loci." Patients with a known mutation can have different genetic penetrance, and may present a more complex and disabling phenotype that develops earlier in life. The clinical manifestations can be similar in the three mutations, including neurologic comorbidities other than muscular weakness, such as episodes of loss of consciousness, epilepsy, gait or limb ataxia or movement disorders, among others. Treatment includes antiepileptics such as lamotrigine, valproate or topiramate, calcium blockers such as flunarizine or verapamil and acetazolamide.

Effects of levcromakalim in patients with migraine aura without headache: An experimental study.

BACKGROUND/HYPOTHESIS: Levcromakalim has previously been shown to induce attacks of migraine with aura in certain individuals. In this study, we tested the migraine-inducing effect of levcromakalim in a cohort of participants with migraine aura without headache. METHODS: In a double-blind, randomized, placebo-controlled cross-over study, eight adult participants with migraine with aura received intravenous infusions of levcromakalim and saline. Headache, aura and associated symptoms were evaluated for 24 h following administration of the study drug. The primary endpoint was occurrence of migraine-like attacks with or without aura in the 24-h observation period. RESULTS: Five participants (62.5%) developed migraine of any type following levcromakalim compared with three participants (37.5%) following placebo. No participants developed aura following levcromakalim. CONCLUSION/INTERPRETATION: Our findings suggest that the aura-inducing effect of levcromakalim is likely not based on direct induction of cortical spreading depression but may involve activation of the trigeminovascular system. This hypothesis should be further explored in future studies. CLINICALTRIALS.GOV IDENTIFIER: NCT04905654.

Headache-related disability as a function of migraine aura: A daily diary study.

OBJECTIVE: To examine the unique role of migraine aura in predicting day-to-day levels of headache-related disability. BACKGROUND: Migraine symptoms and psychological variables contribute to headache-related disability. Migraine aura may be associated with more severe symptom profiles and increased risk of psychiatric comorbidities, but the impact of aura on daily functioning is unknown. The present study sought to evaluate the role of migraine aura in predicting same-day and subsequent-day migraine-related disability while accounting for demographic, headache, and psychological variables. METHODS: This was an observational prospective cohort study among 554 adults with migraine. For each participant, data on migraine symptoms and psychological variables were collected daily for 90 days using the N-1 Headache™ digital app (N = 11,156 total migraine days). Analyses assessed whether the presence of aura predicted daily ratings of migraine-related disability independently of other headache and psychological variables. Given the number of predictors examined, statistical significance was set at p < 0.01. RESULTS: The mean (standard deviation, range) patient-level Migraine Disability Assessment questionnaire score across days of the migraine episode was 1.18 (1.03, 0-3). Aura was significantly associated with higher disability ratings on all days of the migraine episode (odds ratio [OR] 1.40, 99% confidence interval [CI] 1.13-1.74; p < 0.001). This relationship remained unchanged after adjusting for patient-level variables (OR 1.40, 99% CI 1.13-1.73; p < 0.001) and day-level psychological variables (OR 1.39, 99% CI 1.12-1.73; p < 0.001) but was fully negated after controlling for day-level headache variables (OR 1.19, 99% CI 0.95-1.49; p = 0.039). Aura on the first day of the episode was associated with increased odds of allodynia (OR 1.87, 99% CI 1.22-2.86; p < 0.001), phonophobia (OR 1.62, 99% CI 1.17-2.25; p < 0.001), photophobia (OR 1.89, 99% CI 1.37-2.59; p < 0.001), and nausea/vomiting (OR 1.54, 99% CI 1.17-2.02; p < 0.001) on all days of the episode, but not episode duration (p = 0.171), peak severity (p = 0.098), or any examined psychological variables (sleep duration [p = 0.733], sleep quality [p = 0.186], stress [p = 0.110], anxiety [p = 0.102], or sadness [p = 0.743]). CONCLUSION: The presence of aura is predictive of increased headache-related disability during migraine episodes, but this effect is attributable to associated non-pain symptoms of migraine.

Association between patients with migraine and sarcopenia: A retrospective study.

Recently, interest in sarcopenia has been increasing in patients with various neurological diseases. Thus, we investigated the presence of sarcopenia in patients with episodic migraine (EM) based on temporal muscle thickness (TMT). This was a retrospectively observational study following STROBE guidelines. We enrolled patients with EM and healthy controls. Both groups underwent brain magnetic resonance imaging, including three-dimensional T1-weighted imaging. We calculated the TMT using T1-weighted imaging, which is a marker for sarcopenia. We compared TMT between patients with EM and healthy controls, and analyzed it according to presence of migraine aura. We retrospectively enrolled 82 patients with EM and 53 healthy controls. TMT was not different between patients with EM and healthy controls (10.804 ±â€…2.045 mm in patients with EM vs 10.721 ±â€…1.547 mm in healthy controls, P = .801). Furthermore, TMT was not different according to presence of migraine aura in patients with EM (10.994 ±â€…2.016 mm in patients with migraine aura vs 10.716 ±â€…2.071 mm in those without, P = .569). There were no correlations between TMT and clinical characteristics in patients with EM, including age, age of onset, duration of migraine, headache intensity, and headache frequency. This study found no statistical difference in TMT between patients with EM and healthy controls or between patients with EM with and without aura. These findings suggest that there is no evidence of sarcopenia in patients with EM.

Evaluation of retinal perfusion density and foveal avascular zone in migraine subjects with and without aura.

Migraine, classified as a neurovascular disease, has been identified as a potential risk factor for ocular vascular complications. Our study aimed to compare retinal vessel density and perfusion density between subjects with migraine and healthy subjects using optical coherence tomography angiography (OCTA). In this cross-sectional case-control study, we enrolled 30 migraine subjects with aura (MWA), 30 migraine subjects without aura (MWOA) and 30 age and gender-matched healthy controls (HC). The foveal avascular zone (FAZ) in superficial capillary plexus (SCP), Vessel density (VD) and perfusion density (PD) in SCP and deep capillary plexus (DCP) were assessed in a 3 × 3 mm scan of the macula with the swept source OCT. Results indicated that the FAZ of MWA and MWOA subjects was significantly larger from HC. Also, FAZ of MWA was larger from MWOA. VD and PD in both SCP and DCP were significantly reduced in both MWA and MWOA groups compared to HC. However, VD and PD did not show significant differences among MWA and MWOA. Additionally, the duration of disease was the main determinant of the FAZ. In conclusion, the FAZ in the SCP, VD and PD in the SCP and DCP of the macula were affected in both MWA and MWOA. FAZ, specifically, was increased with the evolution of the disease. These findings might contribute to an increased risk of ocular vascular complications among subjects with migraine and could potentially use OCTA as a biomarker for this population.

Investigation of the relationship between thrombophilic disorders and brain white matter lesions in migraine with aura.

BACKGROUND: Migraine is associated with several genetic or acquired comorbidities. Studies conducted in recent years emphasize that the frequency of thrombophilia is high in migraine, especially migraine with aura (MA). Similarly, the presence of white matter lesions (WMLs) on brain magnetic resonance imaging (MRI) scans has been associated with migraine for many years. OBJECTIVE: Based on the knowledge that both WMLs and thrombophilia variants are frequently observed in MA, we aimed to investigate whether there is a relationship between genetic thrombophilia and the presence of WMLs in these patients. METHODS: The levels of proteins S and C, antithrombin III activities, activated protein C (APC) resistance, antiphospholipid immunoglobulin G/immunoglobulin M (IgG/IgM) and anticardiolipin IgG/IgM antibodies were investigated in 66 MA patients between the ages of 18 and 49 years who presented no cardiovascular risk factors. The presence of WMLs and the Fazekas grade was determined from the brain magnetic resonance imaging (MRI) scans' T2-weighted and fluid-attenuated inversion recovery (FLAIR) sequence taken from the patients. The rates of WMLs were compared in patients with and without thrombophilia. RESULTS: Thrombophilia was detected in 34.8% of the patients, and 27.3% were determined to have WMLs in brain MRI scans. The WMLs were detected in 23.3% of the patients without thrombophilia, in 34.8% of those with thrombophilia, and in 50% of the subjects with multiple thrombophilia disorders. Among the thrombophilia disorders, only APC resistance was significantly more common in patients with WMLs. CONCLUSION: The results of the present study showed that thrombophilia may be a mechanism that should be investigated in the etiology of increased WMLs in MA.

ANTECEDENTES: La migraña se asocia con una serie de comorbilidades genéticas o adquiridas. Los estudios realizados en los últimos años destacan que la frecuencia de trombofilia es elevada en la migraña, especialmente en la migraña con aura (MA). De manera similar, la presencia de lesiones de la sustancia blanca (LSB) en las imágenes por resonancia magnética (RM) del cerebro se ha asociado con la migraña hace muchos años. OBJETIVO: Con base en la información de que se suelen observar tanto LSB como variantes de la trombofilia en MA, nuestro objetivo fue investigar si existe una relación entre la trombofilia genética y la presencia de LSB en estos pacientes. MéTODOS: Se investigaron los niveles de proteína S y de proteína C, actividades de antitrombina III, resistencia a la proteína C activada (PCA), anticuerpos antifosfolípidos inmunoglobulina G/inmunoglobulina M (IgG/IgM) y anticuerpos anticardiolipina IgG/IgM en 66 pacientes con MA entre 18 y 49 años que no presentaban factores de riesgo cardiovascular. Se determinaron la presencia de LSB y el grado de Fazekas a partir de imágenes por RM del cerebro en la secuencia ponderada en T2 y recuperación de la inversión atenuada de fluido (fluid-attenuated inversion recovery, FLAIR, en inglés) obtenidas de los pacientes. Se compararon las tasas de LSB en pacientes con y sin trombofilia. RESULTADOS: Se detectó trombofilia en el 34,8% de los pacientes y LSB en el 27,3%. Las LSB estuvieron presentes en el 23,3% de los pacientes sin trombofilia, en el 34,8% de los que tenían trombofilia, y en el 50% de los que tenían múltiples trastornos trombofílicos. La resistencia a la PCA fue significativamente más común en aquellos pacientes con LSB. CONCLUSIóN: Los resultados del presente estudio mostraron que la trombofilia puede ser un mecanismo que debe investigarse en la etiología del aumento de LSB en MA.

Generation of iPSC line (FMCPGHi003-A) from human PBMCs of a patient with Familial hemiplegic migraine type 3.

Peripheral blood mononuclear cells (PBMCs) were obtained from a patient diagnosed with Familial Hemiplegic Migraine Type 3, who carried a heterozygous A > C mutation in the SCN1A gene and reprogrammed using CytoTuneTM-iPS 2.0 Sendai Reprogramming Kit. The iPSC line maintained the mutation while expressing markers of pluripotency. Additionally, it exhibited a normal karyotype and demonstrated potential for in vitro differentiation into cells representing all three embryonic germ layers.

The imaging findings of migraine with visual aura in a CADASIL patient.

Head MRI images of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) patients during migraine attacks are rare.

Unravelling the Genetic Landscape of Hemiplegic Migraine: Exploring Innovative Strategies and Emerging Approaches.

Migraine is a severe, debilitating neurovascular disorder. Hemiplegic migraine (HM) is a rare and debilitating neurological condition with a strong genetic basis. Sequencing technologies have improved the diagnosis and our understanding of the molecular pathophysiology of HM. Linkage analysis and sequencing studies in HM families have identified pathogenic variants in ion channels and related genes, including CACNA1A, ATP1A2, and SCN1A, that cause HM. However, approximately 75% of HM patients are negative for these mutations, indicating there are other genes involved in disease causation. In this review, we explored our current understanding of the genetics of HM. The evidence presented herein summarises the current knowledge of the genetics of HM, which can be expanded further to explain the remaining heritability of this debilitating condition. Innovative bioinformatics and computational strategies to cover the entire genetic spectrum of HM are also discussed in this review.

Alteration in the expression of long non-coding RNAs in the circulation of migraineurs.

BACKGROUND: Current studies have shown emerging roles of lncRNAs in the pathobiology of neuropathic pain and migraine. METHODS: We have chosen five lncRNAs, namely, PVT1, DSCAM-AS, MEG3, LINC-ROR, and SPRY4-IT1 for assessment of their expression in the circulation of migraineurs. RESULTS: Expressions of PVT1 and MEG3 were higher in total migraineurs and both subgroups compared with controls (P < 0.0001). Meanwhile, expression of both lncRNA was higher in migraineurs with aura versus migraineurs without aura (P value < 0.0001 and = 0.01, respectively). Expression of DSCAM-AS1 was not different between any groups of patients compared with controls. Expression of LINC-ROR was elevated in total patients and patients with aura compared with controls (P value = 0.0002 and < 0.0001, respectively). It was also over-expressed in migraineurs with aura vs. migraineurs without aura (P = 0.01). Finally, expression of SPRY4-IT1 was higher in total patients and patients without aura compared with migraine-free persons (P values < 0.0001). Expressions of five mentioned lncRNAs were correlated in almost all study groups. In patients without aura, correlations were significant only for two pairs (SPRY4-IT1/PVT1 and SPRY4-IT1/DSCAM-AS1). PVT1 and MEG3 had the appropriate AUC, sensitivity and specificity values for separation of total migraineurs and both groups of patients from controls. The highest AUC value was reported for PVT1 in separation of migraineurs with aura from healthy controls (AUC = 0.98). CONCLUSION: Cumulatively, our study shows evidence for deregulation of lncRNAs in migraineurs.

Investigating the causal association between systemic lupus erythematosus and migraine using Mendelian randomization analysis.

OBJECTIVE: To assess whether systemic lupus erythematosus (SLE) may be genetically causally associated with migraine, including the two primary subtypes: migraine with aura (MWA) and migraine without aura (MWoA). BACKGROUND: The association between SLE and migraine has been investigated extensively. Previous studies have shown a higher prevalence of migraine in patients with SLE, although the exact relationship remains unclear. This study investigated the potential causal association between SLE and migraine using the powerful analytical tool of Mendelian randomization (MR). METHODS: We performed two-sample MR analysis of publicly available summary statistic datasets using inverse variance-weighted (IVW), weighted median, and MR-Egger methods based on an SLE genome-wide association study (GWAS; 5201 cases; 9066 controls; the exposure frequency is 36.5%) as an exposure and migraine GWAS (15,905 cases; 264,662 controls) in individuals with European ancestry as outcomes, focusing on the two migraine subtypes MWA (6780 cases; 264,662 controls) and MWoA (5787 cases; 264,662 controls). Thepleiotropy and heterogeneity were performed. RESULTS: We selected 42 single-nucleotide polymorphisms from SLE GWAS as instrumental variables (IVs) for SLE on migraine, and 41 SNP IVs for SLE on MWA or MWoA. The IVW (odds ratio [OR] = 1.01, 95% confidence interval [CI] = [0.99, 1.03], p = 0.271), weighted median (OR = 1.00, 95% CI = [0.97, 1.03], p = 0.914), and MR-Egger (OR = 1.04, 95% CI = [0.99, 1.09], p = 0.153) methods showed no causal effect of SLE on migraine. A causal effect of SLE was observed on MWA (IVW: OR = 1.05, 95% CI = [1.02, 1.08], p = 0.001; weighted median: OR = 1.05, 95% CI = [1.01, 1.10], p = 0.018; MR-Egger: OR = 1.07, 95% CI = [1.01, 1.14], p = 0.035 and pIVW < 0.017 [Bonferroni correction]) but not MWoA (IVW: OR = 0.99, 95% CI = [0.96, 1.02], p = 0.331; weighted median: OR = 0.98, 95% CI = [0.94, 1.03], p = 0.496; MR-Egger: OR = 1.02, 95% CI = [0.95, 1.09], p = 0.652). The results showed no significant pleiotropy or heterogeneity. CONCLUSION: Our MR analysis demonstrated the complex relationship between SLE and migraine, suggesting a potential effect of SLE on the risk of MWA but not MWoA. These findings can aid in the development of improved subtype-specific management of migraine in patients with SLE.