IntroductionGabapentin (GBP) is commonly used for chronic neuropathic pain, yet its therapeutic response varies widely across individuals. As a substrate of the organic cation transporter 2 (OCT2), encoded by the SLC22A2 gene, GBP’s penetration into the central nervous system (CNS) may be influenced by genetic variability. This study aimed to characterize the impact of SLC22A2 c.808G>T polymorphism on GBP pharmacokinetics (PK) and pharmacodynamics (PD) and inform genotype-guided dosing strategies.MethodsData from two clinical studies (n = 94) were pooled, including single and multiple oral dose regimens of GBP. Population PK/PD modeling was performed using nonlinear mixed-effects modeling.ResultsA two-compartment PK model with first-order absorption and linear elimination best described GBP disposition, with estimated apparent clearance (CL/F) significantly influenced by renal function (eGFR). Pain scores revealed delayed pain relief relative to peak plasma levels, requiring an effect compartment to link PK to an Imax model. The SLC22A2 c.808G>T (OCT2) variant was associated with a 10-fold reduction in the influx rate constant (ke1) to the effect site, suggesting impaired CNS drug delivery. Simulations demonstrated that GT carriers experienced markedly reduced pain relief, even at the maximum approved doses, compared to GG homozygotes. Renal impairment increased systemic exposure but did not alter CNS penetration.ConclusionThese findings highlight the importance of the OCT2 genotype in modulating GBP’s analgesic efficacy. Incorporating transporter pharmacogenetics into PK/PD models may enhance individualized therapy for neuropathic pain, particularly in identifying poor responders who may benefit from alternative dosing or adjunct treatments.

ObjectiveTo develop a position statement based on expert opinions for the management of medication overuse headache (MOH) in Brazil.MethodThis was an observational, prospective, descriptive, and opinion-based study. The experts were in several Brazilian states. Twelve experts who fulfilled the inclusion criteria completed a questionnaire that explored their experiences and approaches to managing MOH in both the private and public sectors.ResultsAccording to most experts, more than 50% of migraine patients have MOH and psychiatric comorbidities. Experts abruptly stop pain medications, prescribing a bridge treatment for more than 50% of patients. Acute treatment is administered for up to two days per week. Prophylaxis was initiated immediately, and topiramate and monoclonal antibodies were the first choices, respectively, for 36.3% and 54% of professionals. The first follow-up appointment should occur within 4 weeks.ConclusionsFurther guidelines based on evidence as well as expert opinions should be developed for the Brazilian reality, and future prospective studies can be conducted to compare the effects of different treatment regimens for MOH.

Background Chronic migraine (CM) is a disabling neurological condition with high burden, common comorbidities, and a frequent profile of treatment resistance. Although there is progress in mechanism-based therapeutic approaches, such as anti-calcitonin gene-related peptide (CGRP) monoclonal antibodies (mAbs), real-world data on their clinical use and positioning in Latin America remain limited. Methods A cross-sectional, expert-opinion survey of 21 Brazilian headache specialists was carried out to inform a position statement of the Brazilian Academy of Headache and Orofacial Pain. The electronic survey consisted of 49 structured questions that addressed clinical experience with CM, the prevalence of comorbid medication-overuse headache (MOH), the use of anti-CGRP mAbs fremanezumab and galcanezumab as treatment options, comparative assessment, therapeutic positioning, and consensus statements. Descriptive statistics were employed, and consensus was considered as 80% agreement. Results Twenty-one specialists participated; 14 (66.7%) had >20 years' experience. Misdiagnosis was common (16 (81.0%)), and 12 (57.1%) had a diagnostic delay of one year or more. The rate of treatment resistance was high (13 (61.9%) reported that over half of patients were non-responders to two or more prior preventives), and the prevalence of MOH was also high (17 (81.0%) estimated 80% coexistence or higher). The anti-CGRP mAbs were the most used therapies (fremanezumab 17 (81.0%), galcanezumab 18 (85.7%)) and were perceived by respondents as effective in reducing migraine days and improving quality of life. Safety and tolerability ratings reported by clinicians were favorable, with the most common reactions being injection-site reactions. Most clinicians did not indicate notable differences among agents, although no statistical comparison was performed. Early use was prescribed in CM with MOH sufferers (17 (85.0%)). The primary barrier was cost (19 (90.5%)), followed by a strong agreement with earlier use and region-specific guidance. Conclusions Diagnostic delays, high treatment resistance, and significant comorbidity burden characterize CM management in Brazil. In the opinion of the surveyed specialists, anti-CGRP mAbs are perceived as effective and well tolerated, particularly in patients with MOH, and most respondents favored their earlier positioning in the treatment algorithm.

INTRODUCTION:The Brazilian Unified Health System (SUS) is one of the largest publicly funded health systems worldwide, yet persistent regional inequalities and structural constraints challenge equitable access to care. Understanding referral patterns for paediatric neurological conditions at tertiary centres may help inform evolving health system demands. METHODS:We conducted a retrospective longitudinal study of paediatric neurology outpatient visits from 2014 to 2024 at a single tertiary referral centre within the SUS, using first visits per patient within each specialised clinic. Primary diagnoses grouped by ICD-10 code and populational-level data were extracted from medical records. Temporal trends, diagnostic overlap, and sociodemographic associations were analysed. RESULTS:We analysed 9,000 outpatient visits. Epilepsy was the most frequent diagnosis (32.7%), followed by cerebral palsy (CP; 15.8%) and autism spectrum disorder (ASD; 11.0%). ASD increased from 3.9% in 2014 to 21.6% in 2024, whereas epilepsy declined from 39.3% to 25.2%. Over time, ASD showed the strongest increase in odds of diagnosis (OR 1.18 [1.16-1.21]; p < 0.001), along with genetic counselling, sleep disorders, and headaches, while epilepsy, CP, intellectual disability, neonatal seizures, and rare diseases showed lower odds. Male sex was associated with higher odds of ASD (1.59 [1.37-1.85]; p < 0.001) and attention-deficit hyperactivity disorder (2.13 [1.73-2.61]; p < 0.001). Diagnostic overlap was identified in 27.1% of patients. CONCLUSION:These findings suggest a change in the referral case-mix at a single tertiary paediatric neurology centre within the Brazilian SUS, characterised by a marked pre-pandemic rise in ASD referrals that stabilised at an elevated level, alongside shifts in the distribution of other neurological diagnoses.

Introduction: The pathophysiology of migraine is strongly associated with central sensitization, the presence of which is related to cutaneous allodynia and cervical musculoskeletal dysfunction. However, these aspects remain understudied in children and adolescents. Thus, this study aimed to evaluate differences in clinical variables, sensitization, and musculoskeletal alterations between children (CR) and adolescents (AD) with migraine, considering the presence or absence of cutaneous allodynia. Methods: One hundred and one participants aged 6 to 16 years with a clinical diagnosis of migraine were evaluated. Outcomes included cervical range of motion (ROM), pressure pain threshold (PPT) of cranio-cervical muscles, and presence of cutaneous allodynia. Results: Significant differences were observed between CR and AD for age (p<0.001) and PPTs of the sternocleidomastoid (p=0.002), levator scapulae (p=0.006), suboccipital (p=0.006), trapezius (p<0.001), and anterior scalene (p<0.001) muscles. The subgroups CR and AD with and without allodynia showed significant differences in the PPTs of the sternocleidomastoid (p=0.020), levator scapulae (p=0.016), suboccipital (p=0.038), trapezius (p<0.001), anterior scalene (p<0.001) muscles, and in cervical ROM in the sagittal plane (p=0.016). The main differences were observed between adolescents and children with and without allodynia. No differences were found within the children and adolescents’ subgroups. Conclusion: The presence of cutaneous allodynia is associated with increased muscle sensitivity and reduced cervical sagittal mobility. These findings highlight the importance of early assessment of allodynia and musculoskeletal sensitivity in children and adolescents with migraine.

BackgroundWhile the association between migraine, neck pain, and cervical musculoskeletal dysfunctions is well established in adults, such a relationship remains unclear in the pediatric population. This gap limits our understanding of early pathophysiological mechanisms and hinders the development of targeted interventions.ObjectiveTo assess self-reported neck pain, pressure pain threshold (PPT), global cervical range of motion (ROM), and upper cervical mobility in children and adolescents with and without migraine.MethodsA cross-sectional study was conducted with 102 participants in total (51 with migraine - MG - and 51 controls - CG), aged six to 16 years. Neck pain characteristics (presence, frequency, intensity, and duration) were recorded. Cervical ROM was measured in flexion, extension, lateral flexion, and rotation. Upper cervical mobility was evaluated using the Flexion Rotation Test (FRT), and PPT was bilaterally assessed in the sternocleidomastoid, levator scapulae, suboccipital, upper trapezius, and anterior scalene muscles. Comparisons between groups were made using Student's t-test, Mann-Whitney U test, or Chi-square test, with a significance level set at 5%.ResultsCompared to the control group, the MG showed a higher prevalence of neck pain (39.2% vs. 5.9%; p < 0.001) and longer average duration (19 ± 8.6 vs. 8 ± 3.4 h; p = 0.046). Reduced lateral flexion (p < 0.001) and reduced upper cervical mobility (p < 0.001) were observed in the MG. Additionally, all evaluated muscles exhibited significantly lower PPT values in the MG (p < 0.001) than controls, indicating increased pain sensitivity.ConclusionSimilar to adults, children and adolescents with migraine demonstrate cervical musculoskeletal impairments, including neck pain, reduced cervical mobility-especially in lateral flexion and upper cervical rotation-and heightened sensitivity in craniocervical muscles. These findings support the routine inclusion of cervical musculoskeletal assessments in the clinical management of pediatric migraine.

The comorbidity between headache and epilepsy is well known; however, some clinical aspects need to be explored. Aim and methods: It's a transversal study designed to compare clinical features between patients with epilepsy with and without headache. Two questionnaires were developed to collect data, such as age, age at the first seizure, seizure type, and temporal relation between headache and epilepsy. The WHOQOL-bref was applied for the quality-of-life evaluation. In total, 100 patients, between 18 and 65 years old, were selected from a drug-resistant epilepsy (DRE) clinic, and equally divided into two groups: G1—patients with DRE and at least 1 headache attack per month, and G2—patients with DRE without headaches in the last 6 months. Data were analyzed by SPSS software. Ethical board approval 01482918.5.0000.5440. Results and conclusion: In G1 (n = 50), the seizures began before headache attacks (mean age: 13 × 19 years), preictal headache occurred in 9 patients, postictal in 24, and interictal in 48. The majority of those with interictal headaches (31) also experience preictal or postictal headaches. Chronic headaches are observed in 25.8% of patients with interictal plus headache and in 29.4% of those with exclusively interictal headaches. The comparison between groups showed that there are no differences in the mean age (39.1 × 40.9; p = 0.416) and the mean age at the first seizure (13.7 × 10.2; p = 0.93); however, there are more women in G1 (28 × 14; p = 0.005). With respect to the seizure type (n = 100), 86% (90% × 82%) is classified as focal onset, 9% (6% × 12%) as generalized, 1% (0% × 2%) as focal and generalized, and 4% (4% × 4%) as unclassified, with no difference between groups. Regarding general quality of life, no significant differences were observed between groups; however, G1 showed less satisfaction in relation to the general health aspect (p = 0.014). This study showed that in patients with DRE and headache, chronic headaches are frequent and negatively impact the quality of health.