Search Results (128)

Background: Valproic acid (VPA) is a medication used to treat epilepsy, bipolar disorder, and migraine. If taken during pregnancy, it can cause neural tube defects (NTDs) and leads to offspring ASD behavioral phenotype. It has recently been found that early postnatal VPA exposure can also induce the ASD phenotype, but the details of model production and intervention still need further investigation. Dimethylmalonic acid (DMM), a competitive inhibitor of succinate dehydrogenase, blocks the key element succinate of OXPHOS, decreasing the secretion of anti-inflammatory cytokines and ROS production. However, it is still unclear whether DMM is involved in the repair of developmental brain injuries. Objectives: The aim of this study was to evaluate the intervention effect and optimal dosage of DMM on behavioral phenotypes using a neonatal mouse VPA autism model. Methods: This experiment consists of two parts. The first part observed the effects of different concentrations of VPA on the development and neurobehavioral phenotype of mice. The second part determined the intervention effect of DMM on a developmental VPA autism model and determined the optimal therapeutic dose. Results: We found that the 40 mg/mL concentration had a greater impact on the neural reflex damage in mice. Moreover, DMM treatment can partially improve the neurobehavioral damage in the VPA model, and 20 mg/kg has the best intervention effect. Conclusions: This study provides valuable model construction data for further exploring the mechanism of DMM treatment for an ASD phenotype induced by VPA exposure in neonates. Full article

Migraine is a neurovascular paroxysmal disorder characterized by neurogenic inflammation and has a remarkable impact on the quality of life. The Food and Drug Administration (FDA) approved onabotulinumtoxin A in 2010 for the prophylactic treatment of chronic migraine. Today, in its 4th decade, it is approved in 100 countries for 15 main indications. Its mechanism of action, based on the inhibition of neurotransmitter release from primary sensory neurons, is very complex: it affords antinociception, but it also has an analgesic effect on neuropathic pain conditions and reduces the need for rescue medications. Genetic variants have been investigated for their potential role in the pathogenesis and clinical expression of migraine and of the response to treatments. These studies primarily involved genes associated with vascular regulation and cardiovascular pathology, including those encoding angiotensin-converting enzyme (ACE) and methylenetetrahydrofolate reductase (MTHFR). However, epigenetics and, particularly, genetic and epigenetic modifications are still poorly studied in terms of understanding the mechanisms implicated in susceptibility to migraine, aura, chronification and response to symptomatic and preventive treatments. In particular, the aim of the present study is to gather evidence on the genetic variants and epigenetic modifications affecting the pathway of the calcitonin gene-related peptide (CGRP), the target of onabotulinumtoxin A and of all the novel monoclonal antibodies. Full article

Magnesium is an essential mineral involved in hundreds of biochemical reactions, with particular relevance to maintaining neural homeostasis, modulating neurotransmitter systems, and regulating inflammatory and oxidative stress mechanisms. This comprehensive review aims to evaluate the potential role of magnesium in the pathophysiology and treatment of three prevalent neurological and psychiatric disorders—depression, migraine, and Alzheimer’s disease—as well as its broader implications for cognitive health. Current research suggests that magnesium deficiency is associated with the development of depression, as magnesium influences glutamatergic and GABAergic neurotransmission, as well as the activity of the hypothalamic–pituitary–adrenal (HPA) axis, both of which play critical roles in stress responses and mood regulation. Additionally, magnesium’s anti-inflammatory properties may contribute to the alleviation of depressive symptoms. In the context of migraine’s pathophysiology, magnesium plays a role in regulating cerebral vascular tone, modulating the trigeminovascular system, and reducing neuronal hyperexcitability, which may explain the observed correlation between magnesium levels and the incidence of migraines. Regarding Alzheimer’s disease, preclinical and epidemiological studies suggest that magnesium may contribute to modulating neurodegenerative processes and preserving cognitive function; however, due to the heterogeneity of the current findings, further longitudinal and interventional studies are necessary to determine its precise clinical relevance. This review aims to enhance the understanding of the relationship between magnesium and these disorders through a narrative review of relevant clinical studies. The findings may provide insights into the potential therapeutic applications of magnesium and guide the future directions of the research into the prevention and treatment of depression, migraine, and Alzheimer’s disease and overall cognitive health. Full article

Background/Objectives: Propranolol HCl (PPH), a nonselective beta-adrenergic receptor blocker, is employed as an anti-hypertensive, anti-anginal, anti-arrhythmic, and anti-migraine agent. Given its utility in chronic conditions, developing a sustained-release dosage form becomes imperative to optimize therapeutic outcomes while enhancing patient adherence and minimizing side effects. In this study, we employed a widely adopted matrix-based system to develop PPH sustained-release (PPH-SR) matrix tablets, ensuring the uniform dispersion of the drug within the polymeric matrix to regulate its release rate. Methods: Utilizing cellulose-based polymers, specifically HPMC K100M and ethyl cellulose (EC), as matrix formers, nine different formulations were prepared at varying drug-to-polymer ratios. We employed a wet granulation method, followed by compression of the dried granules, to fabricate round-shaped biconvex PPH-SR tablets. Results: Among these different formulations, formulation 2 (F2), comprising 40 mg PPH and 50 mg HPMC K100M (along with other excipients), showed excellent flowability, as evidenced by Carr’s index and angle of repose values of 12.50 and 28.50, respectively. Additionally, the mechanical properties of F2 tablets showed a hardness of 12.34 ± 0.91 KP, an average weight of 200.45 ± 1.87 mg, with a friability of 0.20%, and a content uniformity of 98.36%. Moreover, in vitro release characteristics of F2 tablets demonstrated a sustained-release behavior, with 94.3 ± 10.2% drug release over 24 h. A comparative analysis with marketed tablets yielded similarity and dissimilarity factors of 64 and 8, respectively. Furthermore, the release profile of F2 exhibited a high degree of linearity with the Korsmeyer–Peppas model (R² of 0.977), showcasing its reliability and predictability. Conclusions: In essence, this in-house developed PPH sustained-release formulation can improve patient adherence, reduce side effects, and improve therapeutic outcomes. These results align with our objective of enhancing the therapeutic efficacy of PPH and affirm the broader relevance of innovative formulation strategies in addressing the challenges of chronic disease management. Full article

Aim: New disease-specific and mechanism-based treatments for migraine that share good evidence of efficacy have recently been introduced. However, due to reimbursement problems with insurance companies and high costs, classical anti-migraine drugs continue to be used. The objective of this study was to assess the clinical efficacy and tolerability of flunarizine for the preventive treatment of episodic migraine without aura in a Turkish cohort, concentrating on alterations in headache frequency, pain intensity, and migraine-related disability as measured by MIDAS scores within a practical clinical environment. Methods: Clinical and demographic data of 243 patients with episodic migraine without aura (175 females, 68 males; mean age 33.9 years) were evaluated. Headache frequency, side effects of flunarizine, pain intensity, and MIDAS scores were recorded during initial and 3-month follow-up periods. Results: After three months of flunarizine treatment, significant improvements were observed in headache parameters. The mean Numeric Pain Rating Scale (NPRS) score, the mean MIDAS score, and the monthly migraine attack frequency declined significantly (all p values < 0.001). Adverse events were reported in 21.8% of patients, most commonly weight gain and tiredness, followed by mood changes, gastrointestinal symptoms, and numbness or tingling. Patients experiencing side effects were significantly older (p = 0.023), though side effects did not impact treatment efficacy. Regression analysis identified no significant predictors of disability improvement. Conclusion: Our results demonstrated that flunarizine had considerable short-term efficacy in decreasing the frequency of migraine attacks, alleviating headache severity, and reducing migraine-related disability among patients experiencing episodic migraine without aura. Although mild to moderate side effects were fairly prevalent, especially in older individuals, they did not compromise the effectiveness of the treatment. Notably, early adverse events occurring within the first two weeks resulted in treatment discontinuation for some patients, highlighting the necessity for vigilant monitoring during the initial phase of treatment. Full article

Background/Objectives: Migraines contain neurological and gastrointestinal manifestations. The first specific migraine preventive drugs, CGRP monoclonal antibodies (mAbs), though efficacious and very well-tolerated in general, induce constipation as their main adverse event. Our goal was to analyze the role of the two isoforms of CGRP in the development of constipation in patients treated with mABs. Methods: We prospectively measured by ELISA circulating alpha- and beta-CGRP levels in 133 high-frequency episodic/chronic migraine patients before and three months after mAbs treatment and correlated these levels with a number of clinical variables, including the development of constipation during this treatment. Results: Twelve patients (9.0%) noticed de novo constipation with mAbs. Demographics, efficacy end-points, profile of preventive treatment, and comorbidities, with the exception of anxiety/depression, were superimposable between patients with or without emergent constipation. Basal alpha-CGRP levels (49.5 [29.2–73.8] pg/mL) significantly decreased at month three of treatment (40.5 [20.4–61.0] pg/mL; p < 0.0001), both in patients with and without emergent constipation. Pre-treatment circulating beta-CGRP levels (4.0 [2.1–6.2] pg/mL) remained unchanged after three months of treatment (4.3 [2.5–6.0] pg/mL; p = 0.574) in the whole series but were selectively reduced in patients with emergent constipation (p = 0.034). Conclusions: This is the first work exploring the role of the two isoforms of CGRP in the pathophysiology of constipation with mAbs. Our results suggest that the antagonism on the alpha-CGRP isoform plays a relevant role in the antimigraine action of mABs but not in the development of constipation. By contrast, the specific reduction in beta-CGRP levels in patients with emergent constipation supports the role of beta-CGRP antagonism in the development of this adverse event. Full article

Hypericum hircinum L., commonly known as goat St. John’s wort or stinking tutsan, is a medicinal plant native to the Mediterranean basin and widespread across Europe and parts of the Middle East. It has a long history of traditional uses in folk medicine to treat respiratory diseases, wounds, and burns and to relieve migraine, rheumatism, and muscular pains. Despite numerous scientific studies shading light on the phytochemical profile and on the beneficial properties of the plant extracts, a comprehensive overview of the current knowledge is missing. In this paper, we summarized the available information on botany, traditional uses, phytochemistry, and pharmacological properties of Hypericum hircinum from peer-reviewed articles published till March 2025 in PubMed, ScienceDirect, Wiley, Springer, ACS, Scielo, and Web of Science databases. The presence of numerous valuable compounds, including terpenes, phenolic acids, flavonoids, and phloroglucinols, is reported as well as the wide range of pharmacological properties, such as antimicrobial, antifungal, antiviral, antidepressant, anti-collagenase, anti-α-glucosidase, and antioxidant activities, together with non-pharmacological properties. The data reported in this review contribute to a deeper understanding of the biological properties of the species and pave the way for further investigation of its potential applications. Full article

Background: Migraine is associated with structural brain abnormalities, including cortical thickness changes. Anti-calcitonin gene-related peptide monoclonal antibodies (anti-CGRP mAbs) are a novel therapy for migraine prevention, but their effects on cortical structures are poorly understood. Methods: In this prospective age- and sex-matched controlled study, 30 migraine patients receiving either anti-CGRP mAbs (fremanezumab) (n = 15) or oral preventive medications (n = 15) underwent 3T MRI scans before and after treatment. Treatment response was defined as a ≥50% reduction in monthly headache days after 3 months. Cortical thickness was analyzed across 46 cortical regions, comparing patients treated with anti-CGRP mAbs to those receiving oral preventive treatment, as well as responders to non-responders within the anti-CGRP group. Results: Cortical thickness changes did not differ significantly between the anti-CGRP and oral treatment groups. However, among patients receiving anti-CGRP mAbs, responders showed significant decreases in cortical thickness compared to non-responders, particularly in the right caudal anterior cingulate (p = 0.026) and left rostral middle frontal cortex (p = 0.007). These cortical changes correlated with treatment response to anti-CGRP mAbs (β = −0.429, 95% CI [−0.777, −0.081], p = 0.016 in the right caudal anterior cingulate; β = −0.224, 95% CI [−0.390, −0.057], p = 0.008 in the left rostral middle frontal cortex). Conclusions: This exploratory study, based on a small sample size, suggests that cortical thickness changes may be associated with treatment response to anti-CGRP mAbs rather than with CGRP mAb treatment itself. Further studies with larger cohorts are needed to confirm these findings. Full article

Introduction: Migraine is a prevalent neurological disorder characterized by recurrent headaches with autonomic and neurological symptoms, significantly impacting quality of life globally. Its pathogenesis involves genetic, neurological, inflammatory, and metabolic factors, with insulin resistance and metabolic dysfunction increasingly recognized as important contributors. Historically, it has been known that certain foods can trigger migraine attacks, which led for many years to the recommendation of elimination diets—now understood to primarily target histamine-rich foods. Over the past two decades, attention has shifted toward underlying metabolic disturbances, leading to the development of dietary approaches specifically aimed at addressing these dysfunctions. Methods: A scoping literature review was conducted using PubMed and Embase to evaluate the relationships among migraine, insulin-related mechanisms, neurogenic inflammation, and dietary interventions. Initial searches focused on “MIGRAINE AND (neurogenic inflammation)” (2019–15 April 2025), followed by expanded searches from 1950 onward using terms such as “MIGRAINE AND (insulin, insulin resistance, hyperinsulinism)”, and “MIGRAINE AND (diet, dietary, nutrition, nutritional)”. A specific search also targeted “(INSULIN OR insulin resistance OR hyperinsulinism) AND (neurogenic inflammation)”. Abstracts were screened, full texts were retrieved, and duplicates or irrelevant publications were excluded. No filters were applied by article type or language. Systematic reviews and meta-analyses were prioritized when available. Results: Migraine pathogenesis involves trigeminovascular system activation, neurogenic inflammation mediated by CGRP and PACAP, immune dysregulation, mast cell activation, and cortical spreading depression (CSD). Emerging evidence highlights significant associations between migraine, insulin resistance, and hyperinsulinism. Hyperinsulinism contributes to migraine through TRPV1 sensitization, increased CGRP release, oxidative stress, mitochondrial dysfunction, and systemic inflammation. Metabolic dysfunction, including obesity and insulin resistance, exacerbates migraine severity and frequency. Dietary interventions, particularly anti-inflammatory, Mediterranean, and ketogenic diets, show promise in reducing migraine frequency and severity through mechanisms involving reduced inflammation, oxidative stress, improved mitochondrial function, and glucose metabolism stabilization. Conclusions: The interplay between insulin resistance, metabolic dysfunction, and neuroinflammation is crucial in migraine pathophysiology. Targeted dietary interventions, including ketogenic and Mediterranean diets, demonstrate significant potential in managing migraines, emphasizing the need for personalized nutritional strategies to optimize therapeutic outcomes. Full article

Background/Objectives: Complex regional pain syndrome (CRPS) is a primary pain condition that can develop in a limb after a trauma. Although the condition is rare, it may cause lifelong pain and disability. Evidence-based treatments are limited. Neurogenic inflammation induced by the release of neuropeptides, such as calcitonin gene-related peptide (CGRP), is thought to play an important role in the pathophysiology of CRPS. Recently, drugs targeting CGRP have proven to be effective and well tolerated in the treatment of migraine, but their efficacy in other pain conditions, including CRPS, is unclear. The aim of this study is to assess the efficacy of the anti-CGRP antibody fremanezumab on pain in CRPS. Methods: In this randomized, double-blind, placebo-controlled, proof-of-concept study, 60 adult patients with CRPS with a disease duration of 3–36 months are randomized to treatment for eight weeks with fremanezumab 225 mg or placebo administered subcutaneously at a 1:1 rate. The primary objective is to compare the change in pain intensity from baseline to the last week of treatment between fremanezumab and the placebo. Other objectives are to assess pain relief and differences in clinical signs between the groups and to examine if the effect can be predicted by CGRP biomarkers. Adverse events and blinding will also be assessed. Conclusions: If found effective, fremanezumab and other anti-CGRP antibodies may emerge as a mechanism-based treatment option for patients with CRPS, which could hopefully improve the overall care of patients with this devastating disease. Full article

Background: Anti-CGRP (receptor) antibodies are approved for the preventive treatment of migraines and are increasingly used due to their favorable safety profile and potent efficacy. However, as CGRP is one of the most potent vasodilators, concerns have been raised regarding the possible impact of these drugs on arterial blood pressure. Methods: We present a retrospective cohort study at a tertiary headache center including a total of 259 patients with episodic and chronic migraine who received anti-CGRP antibody treatment for migraine prevention. Blood pressure was measured in a hospital using a standardized setting at baseline and at least at two follow-up visits. Significant increase in blood pressure was defined as an increase in systolic blood pressure ≥ 20 mmHg and/or an increase in diastolic blood pressure ≥ 10 mmHg from the baseline value. Results: Mean age of our population was 39.9 years (±12.1), and 217 (83.8%) were female. Blood pressure measurements between T0 and T2, incorporating all CGRP-antibody groups, showed a significant reduction in systolic (−3.3 mmHg; p = 0.001) and diastolic blood pressure (−2.3 mmHg; p = 0.021), respectively. The repeated-measures generalized linear model analysis revealed no significant variations between the CGRP antibodies relative to blood pressure. The most robust factor predicting systolic hypertensive measurements in the course of anti-CGRP antibody treatment was pre-existing hypertension at baseline (sum of mean squares 7.4; p = 0.019). Conclusions: Our data indicate that treatment with anti-CGRP (receptor) antibodies does not significantly increase blood pressure. However, it seems to be important to monitor patients with pre-existing arterial hypertension. Full article

Background/Objectives: Lasmiditan is a newly developed drug for the acute treatment of migraine attacks, but factors associated with its efficacy remain unclear. This study aimed to confirm the efficacy of lasmiditan started at 50 mg under various dosing conditions and identify factors associated with its efficacy. Methods: There are four reasons for prescribing lasmiditan: as an add-on to triptan, if triptan is ineffective, if triptan produces side effects, and when triptan is contraindicated. Lasmiditan was administered at a dose of 50 mg. The efficacy of lasmiditan was defined as the disappearance of headache or a 50% or greater reduction in headache intensity within two hours after dosing. This study included 108 patients with migraines who took lasmiditan. Results: The results for efficacy and the side effects of lasmiditan were as follows: effective without side effects (22), effective with mild side effects (32), ineffective (14), and severe side effects (40). The efficacy rate of lasmiditan 50 mg was 50.0% (54/108). The following factors were found to be associated with lasmiditan’s efficacy: sex, migraine classification, calcium channel blockers, and anti-calcitonin gene-related peptide monoclonal antibody (CGRP-mAb) treatment. The overall incidence of side effects was 66.7%, and the dropout rate was 37.0%. Somnolence was more prevalent in the effective group, and other side effects were more prevalent in patients who dropped out due to the side effects of lasmiditan. Conclusions: Lasmiditan is likely to be effective in males with severe migraine classification and receiving CGRP-mAb treatment. If mild somnolence is a side effect, the drug can be continued and may be effective. Full article

Sturge–Weber Syndrome (SWS) is a rare neurocutaneous disorder caused by a somatic nonsynonymous mosaic mutation most commonly in the GNAQ gene (G protein guanine Nucleotide-binding protein Alpha subunit q). SWS is characterized by capillary-venous malformations in the brain and eyes and a characteristic facial port wine (PW) birthmark (previously called port wine stain/PWS) in the head/neck region. Clinical manifestations vary and include epilepsy, stroke-like episodes, migraine headaches, cognitive delays, glaucoma, ocular vascular anomalies, heterochromia of the iris, visual field defects, and endocrine disorders like growth hormone deficiency or central hypothyroidism. The pathognomonic findings seen in neuroimaging with magnetic resonance imaging (MRI) include the presence of unilateral intracranial leptomeningeal angiomatosis, typically ipsilateral to the facial birthmark. SWS does not currently have a definitive cure, and management strategies focus on symptomatic management such as anti-seizure medications, limited surgical resection of the epileptogenic tissue or hemispherectomy for cases of drug-resistant epilepsy (DRE), selective photo-thermolysis of the PWS using a pulsed dye laser, and the medical and/or surgical management of glaucoma. In addition to these symptomatic treatments, the use of preventive, modifying, or stabilizing treatments like low-dose aspirin in reducing the frequency and severity of seizures and stroke-like events and the use of newer therapies like cannabidiols and mTOR inhibitors are being reviewed and have shown promising early results. This comprehensive narrative review summarizes the current literature on clinical management strategies, ongoing research studies, and future directions in the diagnosis and management of SWS. Full article

Introduction: The International Classification of Orofacial Pain (ICOP) recognizes orofacial migraine (OFM) and neurovascular orofacial pain (NVOP) as migraine-related entities affecting the facial and oral regions. The diagnostic features of OFM and NVOP indicate that there are many similarities between the two. However, we recently demonstrated that NVOP and OFM are two distinct diagnostic entities, confirming the ICOP classification. It was the aim of the present study to examine whether OFM and NVOP differ in response to pharmacotherapy. Materials and Methods: The cohort was made up of 40 patients attending a tertiary orofacial pain clinic. When implementing ICOP criteria, an OFM diagnosis was made in 23 and an NVOP diagnosis in 17. Results: No statistically significant differences between NVOP versus OFM were observed in the global response to standard abortive therapy such as triptans, or NSAIDs. Similarly, no statistically significant differences were found following prophylactic therapy that included beta-blockers, anti-epileptic drugs, and tricyclic antidepressants. Up to 80% of patients responded favorably with ≥50% pain reduction. Conclusions: NVOP and OFM differ in diagnostic characteristics, demonstrating unique features, and were confirmed as two diagnostic entities. However, NVOP and OFM did not differ in their response to abortive or prophylactic treatments. Study limitations include the lack of starting data precluding a more precise pharmacological analysis. The small sample size limits any far reaching conclusions. This is particularly true regarding individual drug efficacy. We were unable to analyze drug and dose responses separately due to data constraints. Full article

Migraine, with a prevalence of 14–15% in the world population, is one of the diseases that markedly reduce patients’ quality of life. Despite extensive therapeutic tools, the search for substances that may have potential therapeutic properties in migraine patients is still ongoing. Coenzyme Q10 (CoQ10), as a natural and potent antioxidant, appears to be a valuable adjunct in treating and preventing many conditions, such as cardiovascular, metabolic, autoimmune, or neurodegenerative diseases. This review aims to evaluate if CoQ10 can be a potential therapeutic agent in the treatment of migraine. Based on the studies discussed, CoQ10 may have applications in migraine therapy due to its potent anti-inflammatory and oxidative stress-reducing properties. Furthermore, by improving mitochondrial function, CoQ10 can contribute to the energy supply to brain cells, which is particularly important in migraine. Supplementation with CoQ10 in a wide range of doses has resulted in many therapeutic benefits in subjects, including a decrease in the frequency and duration of migraine attacks, a reduction in nausea, a lower maximum pain during an attack, and fewer days with migraine. Therefore, it seems that CoQ10 may be a relevant therapeutic supplement for the treatment and prevention of migraine. Full article