Search Results (44)

Background: Serotonin (5-HT) is a neurotransmitter and a hormone that regulates various functions. Serotonin receptors have been studied in animal experiments in the vestibular system, beginning from the inner ear and vestibular nuclei. However, the role of serotonin in the vestibular system and disorders remains to be clarified. Methods: A review of the literature was performed on different databases according to the PRISMA guidelines. Only publications published on humans and in English have been included. A total of 41 articles were included in this review. Results: There are many publications regarding the use of SSRI/SNRI in vestibular disorders. Regarding persistent postural perceptual dizziness (PPPD) and chronic subjective dizziness (CSD) the available evidence supports multimodality treatment incorporating vestibular rehabilitation, serotonergic medications, and cognitive behavior therapy, although most studies have not included a placebo control group. As for vestibular migraine (VM), SNRI and SSRIs were proposed as preventive therapy and demonstrated a reduction in vertigo attacks in patients with Menière’s Disease (MD), especially when symptoms of anxiety disorder were present. Conclusions: Although SSRIs/SNRIs are considered an off-label therapy for vertigo, several studies have assessed their efficacy in vestibular disorders, as indicated in the data published on PPPD, MD, and VM above all. As some studies report that serotonin receptors are also present in the inner ear and vestibular nuclei, it can be postulated that in cases where the natural levels of serotonin are altered, such as in depression and anxiety, the change in serotonin levels may affect vestibular function and play a role in vestibular disorders. Full article

Background: Hypothyroidism is defined as a deficiency of thyroid hormones and is further classified into primary, secondary, and tertiary types, based on the root cause of the deficiency. Migraine is a primary headache disorder, characterized by unilateral, pulsating pain, lasting from 4 to 72 h, accompanied by symptoms such as photophobia, phonophobia, nausea, and emesis and sometimes preceded by specific aura phenomena. Both diseases are more prevalent in women than in men. While the primary focus of this systematic review was on the relationship between hypothyroidism and migraine, we also included relevant data on headaches in general when they provided valuable context or mechanistic insight. Methods: This systematic review aimed to summarize the current knowledge about the relationship between migraine and hypothyroidism. The Preferred Reporting Items for Systematic Reviews (PRISMA) guidelines were applied. Screening of two databases led to including 29 relevant studies in the review. Results: Studies demonstrated that migraine and disturbed thyroid function may influence one another. The positive correlation between migraine and hypothyroidism, mainly Hashimoto’s disease, was presented in several studies. Moreover, some research identified this correlation in pediatric populations. Finally, the effects of levothyroxine use, a treatment applied in hypothyroidism, on migraine course were presented. Conclusions: A better understanding of the correlation between migraine and hypothyroidism may lead to an increase in the understanding of the pathogenesis of both disorders and positively impact clinical practice. Full article

Introduction: Migraines are a prevalent neurovascular disorder that affects more than a billion people worldwide. Even though both women and men are affected by this neurological disorder, migraines are primarily recognized as a women’s health disruption factor. Pregnancy leads to significant hormonal changes, including a rise in estrogen, progesterone, and endogeny opioid levels, and, therefore, it can affect the course of migraines. Women dealing with migraines often experience migraine symptom reduction during the course of pregnancy, but in the setting of increased maternal body mass index and obesity, this common pattern may be altered. Due to the complexity of the interplay between pregnancy, obesity, and migraines, all mediated by hormonal changes, the aim of our study is to try to unravel the impact of migraines and obesity on maternal health and pregnancy outcomes. Methods: This study included 350 subjects who have suffered at least one migraine attack three months preceding pregnancy, or at any point during the course of pregnancy. Initially, the study subjects were divided into two groups. The first group included women suffering from migraines before pregnancy, but not during the course of pregnancy, and the other group included all subjects who remained symptomatic during the course of pregnancy or had a first migraine attack during their pregnancy. Further comparisons were made based on the patients’ BMI values, and correlations were made between the obese and non-obese study subjects. Results: Higher parity (p = 0.005), obesity (p = 0.005), earlier age of migraine onset (p = 0.004), and gestational diabetes mellitus (p = 0.004) were statistically significant predictors for migraine symptom persistence during pregnancy. Obese pregnant women were more likely to experience migraine intensity and frequency persistence during pregnancy (p < 0.001 and p < 0.001, respectively). They sought magnesium treatment more often (p < 0.001), but this had a modest therapeutic effect compared to non-obese pregnant women (p < 0.001). A diagnosis of hypertensive disorder of pregnancy and gestational diabetes mellitus was also more frequently established in the group of obese pregnant women (p = 0.002 and p < 0.001, respectively). Conclusions: Pregnancy induces substantial physiological changes that can both alleviate and exacerbate migraine symptoms. Obesity is a modifiable risk factor that not only may increase the intensity and frequency of migraine symptoms, but may also compromise pregnancy course and outcome. The co-occurrence of migraines and obesity during pregnancy may amplify health risks for the mother and fetus, including heightened susceptibility to gestational diabetes mellitus. Future research should prioritize focusing on better understanding the causal relationships between pregnancy, migraines, and obesity and providing treatment strategies the home in on weight management and the control of migraine symptoms and associated comorbidities. 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

Background/Objectives: Migraines are a common neurological disorder that significantly impact women, especially during their reproductive years. Hormonal, neurological, and lifestyle factors shape migraine patterns, with fluctuations during menstruation, pregnancy, perimenopause, and menopause influencing migraine prevalence and severity. This expert opinion explores current challenges, therapeutic strategies, and future directions for personalized care, addressing the limited inclusion of women in clinical research across different life stages. Methods: In order to focus on hormonal influences, pharmacological and non-pharmacological therapies, including CGRP monoclonal antibodies, neuromodulation, and lifestyle interventions, a comprehensive analysis of literature, in particular on clinical trials, real-world studies, and guidelines on migraine management was performed. Emerging digital tools and AI-based approaches were also evaluated to improve personalized care for women with migraine. Results: Hormonal therapies, including contraceptives and HRTs, present both risks and benefits, particularly for women with migraines with aura, highlighting the need for individualized approaches. Advances in CGRP-targeted therapies have shown effectiveness in preventing refractory migraines. Non-pharmacological treatments, such as neuromodulation, acupuncture, and lifestyle adjustments, further expand the treatment landscape. However, research gaps remain, particularly regarding hormonal influences on migraines during pregnancy and menopause. Conclusions: Future research should prioritize female-specific clinical trials to better understand the impact of hormonal changes on migraines. Tailored therapies combining pharmacological, non-pharmacological, and digital solutions are essential for improving care. A multidisciplinary approach integrating personalized medicine, technological advancements, and patient education is crucial to optimizing outcomes and enhancing quality of life for women with migraine. Full article

Background/Objectives: Transient Receptor Potential Melastatin 8 (TRPM8) is a non-selective, Ca²⁺-permeable cation channel involved in thermoregulation and other physiological processes, such as basal tear secretion, cell differentiation, and insulin homeostasis. The activation and deactivation of TRPM8 occur through genetic modifications, channel interactions, and signaling cascades. Recent evidence suggests a significant role of TRPM8 in the hypothalamus and amygdala related to pain sensation and sexual behavior. Notably, TRPM8 has been implicated in neuropathic pain, migraines, and neurodegenerative diseases such as Parkinson’s disease. Our laboratory has identified testosterone as a high-affinity ligand of TRPM8. TRPM8 deficiency appears to influence behavioral traits in mice, like increased aggression and deficits in sexual satiety. Here, we aim to explore the pathways altered in brain tissues of TRPM8-deficient mice using the expression and methylation profiles of messenger RNA (mRNA) and long non-coding RNA (lncRNA). Specifically, we focused on brain regions integral to behavioral and hormonal control, including the olfactory bulb, hypothalamus, amygdala, and insula. Methods: RNA was isolated and purified for microarray analysis collected from male wild-type and TRPM8 knockout mice. Results: We identified various differentially expressed genes tied to multiple signaling pathways. Among them, the androgen–estrogen receptor (AR-ER) pathway, steroidogenesis pathway, sexual reward pathway, and cocaine reward pathway are particularly worth noting. Conclusions: These results should bridge the existing gaps in the knowledge regarding TRPM8 and inform potential targets for future studies to elucidate its role in the behavior changes and pathology of the diseases associated with TRPM8 activity. Full article

Background and Objectives: Migraine is a common neurological condition that significantly impacts quality of life, especially in women during their reproductive years. Pregnancy poses unique challenges for migraine management due to hormonal changes and the limited use of pharmacological treatments. Non-pharmacological interventions, such as physiotherapy, exercise, and relaxation techniques, offer promising alternatives for managing migraines during this critical period. This study aims to evaluate the effectiveness of physiotherapy, structured exercise, and relaxation techniques in reducing migraine frequency, severity, and duration while improving psychosocial outcomes such as quality of life, stress levels, and sleep quality in pregnant women. Materials and Methods: Sixty pregnant women diagnosed with acute migraine were randomly assigned into three intervention groups: physiotherapy, structured exercise, and relaxation techniques. Each intervention lasted 8 weeks. The primary outcomes included migraine frequency, severity (measured by VAS), and duration. The secondary outcomes included quality of life (SF-36), stress (PSS), and sleep quality (PSQI). Statistical analyses were conducted using one-way ANOVA and paired t-tests. Results: All interventions significantly reduced migraine frequency, severity, and duration (p < 0.05). Physiotherapy demonstrated the greatest reduction in migraine frequency (45%) and severity (36%), while exercise yielded the most significant improvement in duration (42%). Relaxation techniques were particularly effective in reducing stress and anxiety levels. Quality of life and sleep quality improved across all groups, with unique benefits observed for each intervention. Conclusions: Physiotherapy, structured exercise, and relaxation techniques are effective, safe, and non-invasive interventions for managing acute migraines during pregnancy. These findings provide evidence-based alternatives to pharmacological treatments, highlighting the importance of holistic approaches to migraine management during pregnancy. Further research is needed to confirm long-term efficacy and explore combined interventions. Full article

Background: Ophthalmoplegic migraine (OM) is an uncommon variant of migraine characterised by headache and cranial nerve palsy, posing significant diagnostic and therapeutic challenges. Objective: This study aimed to describe an extremely rare OM variant with a partial therapeutic response. Clinical Case: A 34-year-old pregnant woman in gestational week 19.1 (G6P2A3) with a history of three consecutive spontaneous abortions presented at the emergency services with insidious onset and mild-to-moderate-intensity pulsatile bifrontal headache for 15 days, and the positional changes exacerbated this. At peak intensity, she experienced nausea, vomiting, tinnitus, and photophobia without phonophobia or osmophobia, prompting multiple visits to the emergency department. Despite a broad range of treatments, including intravenous fluids, analgesia, pericranial blocks, and preventive management, there was a non-significative improvement in the symptomatology described above. However, spontaneous resolution of this clinical picture was observed during the postpartum period. Results: This case highlights the complexity of ophthalmoplegic migraine, especially in the context of pregnancy, and raises questions about the underlying pathophysiological mechanisms. The absence of structural lesions on neuroimaging and postpartum resolution suggests a potential association with the hormonal and physiological changes associated with pregnancy. Conclusions: Despite limited scientific evidence, this report contributes to expanding the knowledge of this rare entity and emphasises the importance of a multidisciplinary approach to its management. Full article

Dry eye disease is a multifactorial condition characterised by tear film instability, hyperosmolarity and ocular surface inflammation. Understanding the epidemiology of dry eye disease and recognising both modifiable and non-modifiable risk factors can assist eye care practitioners in assessing, treating, and managing patients with the condition. This review considers current knowledge surrounding its incidence and prevalence, as well as associated demographic, systemic, ocular, and iatrogenic, and lifestyle-related modifiable risk factors. Population-based prevalence estimates vary according to the diagnostic criteria used to define dry eye disease, as well as severity and demographic characteristics of the population. Considering recent data and variable population demographics, conservative prevalence estimates suggest that 10–20% of the population over 40 years of age report moderate to severe symptoms and/or seek treatment for dry eye disease. Individuals with specific non-modifiable demographic risk factors may be at increased risk of developing dry eye disease. Advanced age, female sex and East Asian ethnicity have been identified as key non-modifiable demographic features predisposing individuals to dry eye disease. Systemic conditions that have been associated with an increased risk of dry eye disease include migraine, Sjögren syndrome, connective tissue disorders, mental health disorders, diabetes mellitus and androgen deficiency. Medications that may contribute to this risk include antidepressants, antihistamines, and hormone replacement therapy. Ocular and iatrogenic risk factors of dry eye disease include blepharitis, Demodex infestation, ocular surgery, blink completeness, contact lens wear, and topical ophthalmic medications. A range of modifiable lifestyle factors that can increase the risk of dry eye disease have also been identified, including low humidity environments, digital screen use, quality of sleep, diet, and eye cosmetic wear. Dry eye is a common disease affecting millions globally. Increasing knowledge regarding its associated risk factors can better prepare the eye care practitioner to successfully manage patients with this ocular surface disease. Full article

Headache and visceral pain are common clinical painful conditions, which often co-exist in the same patients. Numbers relative to their co-occurrence suggest possible common pathophysiological mechanisms. The aim of the present narrative review is to describe the most frequent headache and visceral pain associations and to discuss the possible underlying mechanisms of the associations and their diagnostic and therapeutic implications based on the most recent evidence from the international literature. The conditions addressed are as follows: visceral pain from the cardiovascular, gastrointestinal, and urogenital areas and primary headache conditions such as migraine and tension-type headache. The most frequent comorbidities involve the following: cardiac ischemic pain and migraine (possible shared mechanism of endothelial dysfunction, oxidative stress, and genetic and hormonal factors), functional gastrointestinal disorders, particularly IBS and both migraine and tension-type headache, primary or secondary dysmenorrhea and migraine, and painful bladder syndrome and headache (possible shared mechanisms of peripheral and central sensitization processes). The data also show that the various visceral pain–headache associations are characterized by more than a simple sum of symptoms from each condition but often involve complex interactions with the frequent enhancement of symptoms from both, which is crucial for diagnostic and treatment purposes. Full article

Sexual dimorphism in temporomandibular disorders (TMDs) and their comorbidity with migraine are important phenomena observed in clinics. TMDs are the most prevalent orofacial pain conditions with jaw joint and masseter muscle dysfunction. Migraine is the predominant headache commonly associated with TMDs. Women much more often suffer from this orofacial pain than men. However, currently, there is no gender-specific therapy for such pain conditions. Understanding the pathophysiological mechanisms behind sex differences in TMDs as well as their comorbidity with migraines is essential for developing novel approaches for gender-specific treatment of TMDs and related orofacial pain comorbidity. In this review, we summarize recent research progress regarding sex differences in TMDs, focusing on the underlying mechanisms including craniofacial anatomy, hormonal regulation, and roles of opioids, transient receptor potential channels, and endocannabinoid systems. We also discuss the mechanisms of comorbid TMDs and migraine. The information covered in this review will provide mechanistic insights into sex differences in TMDs and their comorbidity with migraine, which could aid in developing effective treatment strategies for the overlapping orofacial pain condition. Full article

Sex hormones and migraine are closely interlinked. Women report higher levels of migraine symptoms during periods of sex hormone fluctuation, particularly during puberty, pregnancy, and perimenopause. Ovarian steroids, such as estrogen and progesterone, exert complex effects on the peripheral and central nervous systems, including pain, a variety of special sensory and autonomic functions, and affective processing. A panel of basic scientists, when challenged to explain what was known about how sex hormones affect the nervous system, focused on two hormones: estrogen and oxytocin. Notably, other hormones, such as progesterone, testosterone, and vasopressin, are less well studied but are also highlighted in this review. When discussing what new therapeutic agent might be an alternative to hormone therapy and menopause replacement therapy for migraine treatment, the panel pointed to oxytocin delivered as a nasal spray. Overall, the conclusion was that progress in the preclinical study of hormones on the nervous system has been challenging and slow, that there remain substantial gaps in our understanding of the complex roles sex hormones play in migraine, and that opportunities remain for improved or novel therapeutic agents. Manipulation of sex hormones, perhaps through biochemical modifications where its positive effects are selected for and side effects are minimized, remains a theoretical goal, one that might have an impact on migraine disease and other symptoms of menopause. This review is a call to action for increased interest and funding for preclinical research on sex hormones, their metabolites, and their receptors. Interdisciplinary research, perhaps facilitated by a collaborative communication network or panel, is a possible strategy to achieve this goal. Full article

There is evidence to suggest that hormonal migraine is associated with altered cerebrovascular function. We aimed to investigate whether the expression of genes related to endothelial function in venous blood (1) might influence cerebrovascular function, (2) differs between hormonal migraineur and non-migraineur women, and (3) changes following resveratrol supplementation. This study utilised data obtained from 87 women (59 hormonal migraineurs and 28 controls) where RNA from venous blood was used to quantify gene expression and transcranial Doppler ultrasound was used to evaluate cerebrovascular function. Spearman’s correlation analyses were performed between gene expression, cerebrovascular function, and migraine-related disability. We compared the expression of genes associated with endothelial function between migraineurs and non-migraineurs, and between resveratrol and placebo. The expression of several genes related to endothelial function was associated with alterations in cerebrovascular function. Notably, the expression of CALCA was associated with increased neurovascular coupling capacity (p = 0.013), and both CALCA (p = 0.035) and VEGF (p = 0.014) expression were associated with increased cerebral blood flow velocity in the overall study population. Additionally, VCAM1 expression correlated with decreased pulsatility index (a measure of cerebral arterial stiffness) (p = 0.009) and headache impact test-6 scores (p = 0.007) in the migraineurs. No significant differences in gene expression were observed between migraineurs and controls, or between placebo and resveratrol treatments in migraineurs. Thus, altering the expression of genes related to endothelial function may improve cerebrovascular function and decrease migraine-related disability. Full article

Migraine is a highly prevalent neurological disorder. Among the risk factors identified, psychiatric comorbidities, such as depression, seem to play an important role in its onset and clinical course. Patients with migraine are 2.5 times more likely to develop a depressive disorder; this risk becomes even higher in patients suffering from chronic migraine or migraine with aura. This relationship is bidirectional, since depression also predicts an earlier/worse onset of migraine, increasing the risk of migraine chronicity and, consequently, requiring a higher healthcare expenditure compared to migraine alone. All these data suggest that migraine and depression may share overlapping biological mechanisms. Herein, this review explores this topic in further detail: firstly, by introducing the common epidemiological and risk factors for this comorbidity; secondly, by focusing on providing the cumulative evidence of common biological aspects, with a particular emphasis on the serotoninergic system, neuropeptides such as calcitonin-gene-related peptide (CGRP), pituitary adenylate cyclase-activating polypeptide (PACAP), substance P, neuropeptide Y and orexins, sexual hormones, and the immune system; lastly, by remarking on the future challenges required to elucidate the etiopathological mechanisms of migraine and depression and providing updated information regarding new key targets for the pharmacological treatment of these clinical entities. Full article

The study of migraine is based on the complexity of the pathology, both at the pathophysiological and epidemiological levels. Although it affects more than a billion people worldwide, it is often underestimated and underreported by patients. Migraine must not be confused with a simple headache; it is a serious and disabling disease that causes considerable limitations in the daily life of afflicted people, including social, work, and emotional effects. Therefore, it causes a daily state of suffering and discomfort. It is important to point out that this pathology not only has a decisive impact on the quality of life of those who suffer from it but also on their families and, more generally, on society as a whole. The clinical picture of migraine is complex, with debilitating unilateral or bilateral head pain, and is often associated with characteristic symptoms such as nausea, vomiting, photophobia, and phonophobia. Hormonal, environmental, psychological, dietary, or other factors can trigger it. The present review focuses on the analysis of the physiopathological and pharmacological aspects of migraine, up to the correct dietary approach, with specific nutritional interventions aimed at modulating the symptoms. Based on the symptoms that the patient experiences, targeted and specific therapy is chosen to reduce the frequency and severity of migraine attacks. Specifically, the role of calcitonin gene-related peptide (CGRP) in the pathogenesis of migraine is analyzed, along with the drugs that effectively target the corresponding receptor. Particularly, CGRP receptor antagonists (gepants) are very effective drugs in the treatment of migraine, given their high diffusion in the brain. Moreover, following a ketogenic diet for only one or two months has been demonstrated to reduce migraine attacks. In this review, we highlight the diverse facets of migraine, from its physiopathological and pharmacological aspects to prevention and therapy. Full article