Potential of focal cortical dysplasia in migraine pathogenesis.

Focal cortical dysplasias are abnormalities of the cerebral cortex associated with an elevated risk of neurological disturbances. Cortical spreading depolarization/depression is a correlate of migraine aura/headache and a trigger of migraine pain mechanisms. However, cortical spreading depolarization/depression is associated with cortical structural changes, which can be classified as transient focal cortical dysplasias. Migraine is reported to be associated with changes in various brain structures, including malformations and lesions in the cortex. Such malformations may be related to focal cortical dysplasias, which may play a role in migraine pathogenesis. Results obtained so far suggest that focal cortical dysplasias may belong to the causes and consequences of migraine. Certain focal cortical dysplasias may lower the threshold of cortical excitability and facilitate the action of migraine triggers. Migraine prevalence in epileptic patients is higher than in the general population, and focal cortical dysplasias are an established element of epilepsy pathogenesis. In this narrative/hypothesis review, we present mainly information on cortical structural changes in migraine, but studies on structural alterations in deep white matter and other brain regions are also presented. We develop the hypothesis that focal cortical dysplasias may be causally associated with migraine and link pathogeneses of migraine and epilepsy.

Posttraumatic Headache.

OBJECTIVE: This article provides an overview of the epidemiology, diagnosis, clinical presentation, pathophysiology, prognosis, and treatment of posttraumatic headache attributed to mild traumatic brain injury (mTBI). LATEST DEVELOPMENTS: The International Classification of Headache Disorders, Third Edition requires that posttraumatic headache begin within 7 days of the inciting trauma. Although posttraumatic headache characteristics and associated symptoms vary, most commonly there is substantial overlap with symptoms of migraine or tension-type headache. New insights into posttraumatic headache pathophysiology suggest roles for neuroinflammation, altered pain processing and modulation, and changes in brain structure and function. Although the majority of posttraumatic headache resolves during the acute phase, about one-third of individuals have posttraumatic headache that persists for at least several months. Additional work is needed to identify predictors and early markers of posttraumatic headache persistence, but several potential predictors have been identified such as having migraine prior to the mTBI, the total number of TBIs ever experienced, and the severity of initial symptoms following the mTBI. Few data are available regarding posttraumatic headache treatment; studies investigating different treatments and the optimal timing for initiating posttraumatic headache treatment are needed. ESSENTIAL POINTS: Posttraumatic headache begins within 7 days of the causative injury. The characteristics of posttraumatic headache most commonly resemble those of migraine or tension-type headache. Posttraumatic headache persists for 3 months or longer in about one-third of individuals. Additional studies investigating posttraumatic headache treatment are needed.

Rationale and design of the SPRING trail: effectivity and safety of Pfo closuRe vs medIcine in alleviatiNg migraine, a multicenter, randomized and open-label trail.

BACKGROUND: Migraine is a leading cause of disability worldwide. Several retrospective studies have suggested that the closure of the Patent Foramen Ovale (PFO) may provide relief from migraines. However, three randomized controlled trials did not meet their primary endpoints regarding migraine cessation, reduction in monthly migraine days, and responder rates. METHODS: The SPRING study is a multicenter, prospective, randomized, and open-label trial designed to compare the effectiveness and safety of PFO closure versus medication in the relief of migraines. The primary endpoint is the total cessation of migraines, as recorded in patient headache diaries during the follow-up period. Additional diagnostic tools include echocardiography with agitated saline contrast, transcranial Doppler, and routine laboratory measurements. CONCLUSION: The SPRING trial aims to assess the effectiveness and safety of PFO closure versus medication in mitigating migraines in real-world settings. (Clinical Trails ID: NCT04946734).

Headache in Multiple Sclerosis: A Narrative Review.

Background: Multiple sclerosis (MS) is a chronic inflammatory demyelinating disorder of the central nervous system characterized by autoimmune-mediated damage to oligodendrocytes and subsequent myelin destruction. Clinical implications: Clinically, the disease presents with many symptoms, often evolving over time. The insidious onset of MS often manifests with non-specific symptoms (prodromal phase), which may precede a clinical diagnosis by several years. Among them, headache is a prominent early indicator, affecting a significant number of MS patients (50-60%). Results: Headache manifests as migraine or tension-type headache with a clear female predilection (female-male ratio 2-3:1). Additionally, some disease-modifying therapies in MS can also induce headache. For instance, teriflunomide, interferons, ponesimod, alemtuzumab and cladribine are associated with an increased incidence of headache. Conclusions: The present review analyzed the literature data on the relationship between headache and MS to provide clinicians with valuable insights for optimized patient management and the therapeutic decision-making process.

Understanding the Biological Relationship between Migraine and Depression.

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.

The correlation between the frequent intake of dietary migraine triggers and increased clinical features of migraine (analytical cross-sectional study from Egypt).

Despite the high prevalence of primary headaches, the role of food in modifying clinical characteristics among migraine patients is often overlooked. The aim is to detect the correlation between adopting unhealthy dietary habits and migraine severity and identify foods that have a greater chance of triggering specific subtypes of migraine. The present study was a cross-sectional analytical study that was conducted at Kasralainy Hospital, Cairo University, headache clinic at Alexandria University Hospital, and Al-Azhar University Hospitals from January to June 2020. We included 124 patients fulfilling the ICHD-3 criteria for migraine. A full clinical profile for migraine headaches was reported using a headache sheet applied to the Al-Azhar University headache unit. A nutritionist obtained data collected about dietary habits using many reliable scales and questionnaires such as food frequently sheets questionnaire. Logistic regression and Pearson correlation coefficients have been used to identify foods that are more likely to be associated with increased clinical features of migraine. Our participants reported that the fried meat, fried chicken, processed meats, fava beans, falafel, aged cheese "Pottery salted cheese" and "Rummy cheese", salted-full fatty cheese "Damietta cheese", citrus fruits, tea, coffee, soft drinks, nuts, pickles, chocolate, canned foods, sauces, ice cream, smoked herring, in addition to the stored food in the refrigerator for many days were significantly associated with the diagnosis of chronic migraine CM compared to episodic migraine (EM). Margarine, pickles, and smoked herring were significantly associated with the diagnosis of migraine with aura (MA) compared to migraine without aura (MO). Adopting unhealthy eating habits was a more prevalent dietary consumption pattern among people with chronic migraines compared to those with episodic migraine.

Relationship between shift work, night work, and headache and migraine risk: A meta-analysis of observational studies.

BACKGROUND: To date, there is insufficient research on whether shift work and night work increase the risk of experiencing headaches and migraines. OBJECTIVES: This study aimed to evaluate the potential association between shift work, night shift work, and headache/migraine. METHODS: We conducted a thorough search of the PubMed, Embase, and Web of Science databases up until October 2023 to identify relevant studies. Our inclusion criteria focused on observational studies that investigated the association between shift work exposure and headache/migraine outcomes. We extracted adjusted risk estimates from each study and calculated pooled odds ratios using either fixed or random-effects models. Our methodology followed the Meta-Analysis Group guidelines for observational studies in epidemiology. To ensure accuracy and consistency, two investigators independently reviewed the retrieved records and extracted data based on the predefined inclusion criteria. RESULTS: This meta-analysis included a total of seven studies involving 422,869 participants. The pooled analysis revealed a significant association between shift work and an increased risk of headaches (HR = 1.32, 95% CI: 1.15-1.52, P < 0.001). Specifically, individuals working night shifts had a 44% higher risk of developing headaches (HR = 1.44, 95% CI: 1.09-1.90, P = 0.011). Furthermore, shift work was also found to be associated with a higher incidence of migraines (HR = 1.63, 95% CI: 1.27-2.08, P < 0.001). Interestingly, night shift work was associated with a decreased incidence of migraines (HR = 0.74, 95% CI: 0.57-0.96, P = 0.024). CONCLUSION: Our study found a noteworthy association between shift work/night work and the occurrence of headaches and migraines. However, it is important to note that our study does not establish a causal relationship. Future research should investigate potential common vulnerability factors, such as genetics or health behaviors. This knowledge can help inform the implementation of preventive measures and interventions to mitigate the health risks associated with shift work.

Whether Weather Matters with Migraine.

PURPOSE OF REVIEW: Many patients with migraine report their attacks are triggered by various weather anomalies. Studies have shown mixed results regarding the association of migraine to weather changes. The purpose of the current review is to compile the most up-to-date research studies on how weather may affect migraine. In addition, we explore the association between weather and other inflammatory disease states as well as neurotransmitters. RECENT FINDINGS: Migraine attacks can be related to weather variables such as barometric pressure, humidity, and wind. However, the results of recent studies are inconsistent; weathers' effect on migraine attacks is around 20%. However, very strong weather factors have a more significant effect on migraine attack variables. Many individuals identify weather as a migraine attack trigger, yet we see no causative relationship between weather and migraine patterns. The outcomes of studies indicate mixed results and reflect individual variation in how weather can impact migraine patterns. Similar relationships can be seen with other rheumatologic and pain conditions in general. Overall, the combination of weather plus other factors appears to be a more significant migraine trigger.

Role of TNF-α in the Pathogenesis of Migraine.

Background: Neurogenic neuroinflammation has a wide role in migraine pathogenesis including the transition from episodic migraine to chronic one. The seed molecule of neurogenic neuroinflammation, i.e., the TNF-α proinflammatory molecule, has gathered a lot of attention. This pleiotropic cytokine is a classical component of inflammatory soup, secreted by the microglial cell, and promotes a wide range of inflammatory reactions. Aim: In this review, we aimed to provide a culminating and comprehending glimpse into the TNF-α in association with the migraine. Method: A systematic literature survey method with a mixture of keywords was utilized to grasp the different elements that represent the association between TNF-α and migraine. Discussion. Highlighted the probable involvement of the TNF-α with migraine, the complexity of the matter such as activation of NF-KB signaling cascade, autoactivation, sensitization, and increased likelihood of transition cannot be neglected. Being TNF-α as a core node, it becomes the factor for linking diseases such as chronic inflammatory disorders, including COVID-19, and also interaction with other genes to develop severe conditions. Conclusion: To this end, TNF-α plays a critical role in chronification, and inhibiting its signaling would likely be a crucial strategy for migraine therapy.

Headache in patients with inflammatory bowel disease: Migraine prevalence according to the Migraine Screening-Questionnaire (MS-Q) and headache characteristics / Cefalea en pacientes con enfermedad inflamatoria intestinal: prevalencia de migraña de acuerdo al Migraine Screening-Questionnaire (MS-Q) y características de la cefalea

Background The gut-brain axis describes a complex bidirectional association between neurological and gastrointestinal (GI) disorders. In patients with migraine, GI comorbidities are common. We aimed to evaluate the presence of migraine among patients with inflammatory bowel disease (IBD) according to Migraine Screen-Questionnaire (MS-Q) and describe the headache characteristics compared to a control group. Additionally, we explored the relationship between migraine and IBD severities. Methods We performed a cross-sectional study through an online survey including patients from the IBD Unit at our tertiary hospital. Clinical and demographic variables were collected. MS-Q was used for migraine evaluation. Headache disability scale HIT-6, anxiety-depression scale HADS, sleep scale ISI, and activity scale Harvey–Bradshaw and Partial Mayo scores were also included. Results We evaluated 66 IBD patients and 47 controls. Among IBD patients, 28/66 (42%) were women, mean age 42 years and 23/66 (34.84%) had ulcerative colitis. MS-Q was positive in 13/49 (26.5%) of IBD patients and 4/31 (12.91%) controls (p=0.172). Among IBD patients, headache was unilateral in 5/13 (38%) and throbbing in 10/13 (77%). Migraine was associated with female sex (p=0.006), lower height (p=0.003) and weight (p=0.002), anti-TNF treatment (p=0.035). We did not find any association between HIT-6 and IBD activity scales scores. Conclusions Migraine presence according to MS-Q could be higher in patients with IBD than controls. We recommend migraine screening in these patients, especially in female patients with lower height and weight and anti-TNF treatment (AU)

Introducción El eje intestino-cerebro describe una asociación bidireccional compleja entre las enfermedades neurológicas y gastrointestinales (GI). Las comorbilidades GI son frecuentes en la migraña. Nuestro objetivo fue evaluar la presencia de migraña en pacientes con enfermedad inflamatoria intestinal (EII) y describir las características de la cefalea. Además, analizamos la relación entre la gravedad de la migraña y la EII. Métodos Estudio transversal a través de encuesta electrónica en pacientes con EII de un hospital terciario. Se recogieron variables clínicas y demográficas. Se usó MS-Q para presencia de migraña. Se incluyeron escala de discapacidad de cefalea HIT-6, ansiedad-depresión HADS, sueño ISI y actividad de EII Harvey-Bradshaw y Partial Mayo. Resultados Se incluyeron 66EII y 47controles. Entre los EII, 28/66 (42%) eran mujeres, con una edad media de 42años, y 23/66 (34,84%) tenían colitis ulcerosa. El MS-Q fue positivo en 13/49 (26,5%) de EII y en 4/31 (12,91%) controles (p=0,172). Entre los pacientes con EII, la cefalea fue unilateral en 5/13 (38%) y pulsátil en 10/13 (77%). El sexo femenino (p=0.006), la altura (p=0,003) y el peso más bajos (p=0,002) y el tratamiento con anti-TNF (p=0,035) se relacionaron con la probabilidad de migraña. No encontramos asociación entre el HIT-6 y las escalas de actividad de EII. Conclusiones La presencia de migraña de acuerdo al MS-Q podría ser más alta en los pacientes con EII que en controles. Recomendamos realizar un cribado de migraña en estos pacientes, especialmente en mujeres de menor peso y altura y tratamiento anti-TNF (AU)

Retinal arterial occlusion and patent foramen ovale: A case study-based review.

PURPOSE: To identify all reported cases of retinal artery occlusion (RAO) associated with patent foramen ovale (PFO) in the literature and present a similar case of CRAO from our clinic. METHODS: PubMed database was searched for studies reporting RAO in individuals with PFO. Relevant data were tabulated and reviewed. We estimated each case's Risk of Paradoxical Embolism (RoPE) score. RESULTS: 23 cases of CRAO (n=10; including ours), BRAO (n=10), and CILRAO (n=3) were reviewed. Most cases were under 50 years of age (78.3%). The reported predisposing factors were: hypertension (26.1%), migraine (17.3%), smoking (13.0%), recent immobilization (13.0%), strenuous exertion (8.7%), pregnancy (8.7%), and diabetes (4.3%). A high RoPE score (≥7; suggestive of paradoxical embolism via PFO) was estimated for 71.4% of patients. In most cases, the neurological and cardiovascular examinations, laboratory studies, and imaging were unremarkable, except for the PFO±atrial septal aneurysm (present in 21.7%). In only 28.6% of cases, transthoracic echocardiography (TTE) (± saline contrast) could visualize the PFO; transesophageal echocardiography (TEE) was necessary to detect the PFO in 71.4%. Approximately one-half of the patients underwent percutaneous closure of the PFO; no complications or subsequent acute ischemic events ensued. The visual prognosis was poorer for CRAO than for BRAO or CILRAO. CONCLUSION: Timely diagnosis, acute management, and ensuring urgent initiation of stroke workup in cases with RAO or transient monocular vision loss are crucial. Clues to a possible paradoxical embolism as the cause include the absence of known cardiovascular risk factors, young age, migraine, recent immobility, vigorous exercise, and pregnancy.

Resistant and refractory migraine: clinical presentation, pathophysiology, and management.

Migraine is a leading cause of disability worldwide. A minority of individuals with migraine develop resistant or refractory conditions characterised by ≥ 8 monthly days of debilitating headaches and inadequate response, intolerance, or contraindication to ≥3 or all preventive drug classes, respectively. Resistant and refractory migraine are emerging clinical definitions stemming from better knowledge of the pathophysiology of migraine and from the advent of migraine-specific preventive treatments. Resistant migraine mostly results from drug failures, while refractory migraine has complex and still unknown mechanisms that impair the efficacy of preventive treatments. Individuals with resistant migraine can be treated with migraine-specific preventive drugs. The management of refractory migraine is challenging and often unsuccessful, being based on combinations of different drugs and non-pharmacological treatment. Future research should aim to identify individuals at risk of developing treatment failures, prevent the condition, investigate the mechanisms of refractoriness to treatments, and find effective treatment strategies.

Is there a correlation between migraine and eating disorders? A systematic literature review.

INTRODUCTION: Migraine is a common primary headache disorder, which affects mainly young females, usually those with some specific personality traits including neuroticism and obsessive-compulsive disorder. Among many factors that may trigger headache are to be found those associated with eating patterns and behaviours. Eating disorders are psychiatric disorders of abnormal eating or weight-control behaviours. According to the most up-to-date classification, six main types are identified, including anorexia nervosa, bulimia nervosa, and binge eating disorder. Similar to migraine, eating disorders are mainly diagnosed in young adults and, moreover, personality pattern, in at least some of the eating disorders, is also suggested to be consistent. MATERIAL AND METHODS: This systematic review aimed to summarise the available literature related to this topic. We performed an electronic article search through the Embase, PubMed, and Cochrane databases and included 16 articles into analysis in accordance with PRISMA 2020 guidelines. RESULTS: Most of the studies revealed the presence of a putative correlation between migraine and eating disorders, and these encourage further investigations. Moreover, apart from the clinical aspect, also the pathogenesis underlying both disorders is suggested to be similar. More frequent co-occurrence of other psychiatric disorders in migraineurs, such as depression and anxiety, was reported and should be considered in future research. Furthermore, adverse interactions between pharmacotherapy and symptoms of comorbid conditions underline the importance of this problem. CONCLUSIONS: A correlation between migraine and eating disorders appears highly probable. However, further investigations are required focusing on diverse aspects such as clinical, psychological, and pathogenic.

Migraine worsening after COVID-19 and COVID-19 vaccination: Are we facing a nocebo effect?

BACKGROUND AND PURPOSE: In clinical practice patients may report migraine worsening as a consequence of COVID-19 (either infection or vaccines), however, data in this area are lacking. We aimed to investigate the link between COVID-19 and COVID-19 vaccination with migraine worsening and its associated factors. METHODS: An online survey was sent to migraine patients followed up in a Spanish Headache Clinic, collecting demographic data, and information regarding SARS-CoV-2 infection and vaccination. We asked patients if they had noticed worsening of their migraine after these events and assessed concerns about infection, vaccination and migraine worsening. We also extracted data from participants' own electronic diaries (e-diaries), including 1-month data before and after their reported infection and/or vaccination. We compared participants who self-reported migraine worsening since infection or vaccination with those who did not. RESULTS: Of 550 participants, 44.9% (247/550) reported having had COVID-19 at least once and 83.3% (458/550) had been vaccinated. Sixty-one patients reported migraine worsening since COVID-19 and 52 since the vaccination. Among the risk factors for perceived migraine worsening in the two settings (infection and vaccination) was concern about migraine worsening itself (infection: odds ratio [OR] 2.498 [95% CI: 1.02-6.273], p = 0.046; vaccination: OR 17.3 [95% CI: confidence interval 5.3-68], p < 0.001). e-diary information was available for 136 of the 550 patients, 38.2% (52/136) for COVID-19 and 39.7% (54/136) for vaccination. We observed no significant difference in headache frequency 1 month before and after infection or vaccination, even when comparing patients with and without self-reported migraine worsening. CONCLUSIONS: Our preliminary data point to a negligible role of the infection and vaccination on migraine worsening and to the possible presence of a nocebo effect in these settings, as a remarkable proportion of patients had a clear perception of migraine worsening.

Migraine in multiple sclerosis patients: potential links and treatment approach.

INTRODUCTION: Migraine has been reported to be twice as prevalent in patients with multiple sclerosis (MS) compared to the non-MS population. However, prospective, controlled studies that could lead to robust conclusions are still lacking. AREAS COVERED: Treatment of migraine in patients with MS can be challenging. Comorbidities need to be assessed and managed early, and preventive treatment should be initiated when indicated. Caution is warranted regarding the selection of the preventive medication since certain agents can magnify MS symptoms and particularly cognitive symptoms. This paper aims to discuss the association of MS and migraine, shed light on distinguishing points and red flags, as well as offer practical advice on the selection of treatment according to patients' characteristics. EXPERT OPINION: A holistic approach including pharmacological and non-pharmacological modifications is required to treat migraine in patients with MS effectively. Anti-CGRP monoclonal antibodies are a promising option due to limited drug-to-drug interactions; however, larger prospective studies are required to draw robust conclusions on the concomitant use of anti-CGRPs with MS disease modifying treatments. Early migraine preventive treatment might be needed to reduce the burden of disease in patients with MS.

24-year-old woman • large joint arthralgias • history of type 1 diabetes, seizures, migraines • Dx?

► large joint arthralgias ► history of type 1 diabetes, seizures, migraines.