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OBJECTIVE: To confirm a previously reported association of TRPV1 rs8065080 with the risk of transformation from episodic (EM) to chronic migraine (CM) and to extend knowledge about the role of other TRPV1 single nucleotide polymorphisms (SNPs), we first investigated the impact of three TRPV1 SNPs (rs8065080, rs222747 and rs222749) on the risk of migraine chronification in a case-control study. A systematic review and meta-analysis were then conducted to summarize the accumulated findings. METHODS: Genotyping of the selected TRPV1 SNPs was performed using TaqMan real-time PCR in 167 EM and 182 CM participants. Crude and adjusted odds ratios with associated 95% confidence intervals were calculated in the log-additive, dominant, and recessive genetic models. A comprehensive literature search was performed in PubMed, Web of Knowledge, Cochrane Library, and OpenGrey until February 2024. RESULTS: In our case-control study, no association was found between TRPV1 SNPs and the risk of migraine chronification, both in the unadjusted logistic regression models and after adjustment for confounding clinical variables. The results of the meta-analysis with a total of 241 participants with EM and 223 with CM confirmed no association between TRPV1 SNPs and the risk of migraine chronification in any of the genetic models tested. CONCLUSION: The results of the present case-control study and meta-analysis exclude a major role of TRPV1 rs8065080, rs222747, and rs222749 as risk factors for migraine chronification. However, further research is needed to investigate the gene-gene and gene-environment interactions of TRPV1 SNPs on the risk of transformation from episodic to chronic migraine.
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BACKGROUND: miR-155 is involved in the generation and maintenance of inflammation and pain, endothelial function and immune system homeostasis, all functions that are relevant for migraine. The present study aims to assess the levels of miR-155 in migraine subtypes (episodic and chronic) in comparison to age- and sex-matched healthy controls. METHODS: This is a cross-sectional, controlled, study involving three study groups: I) episodic migraine (n = 52, EM), II) chronic migraine with medication overuse (n = 44, CM-MO), and III) healthy controls (n = 32, HCs). We assessed the interictal gene expression levels of miR-155, IL-1ß, TNF-α, and IL-10 in peripheral blood monocytes using rtPCR. The monocytic differentiation toward the M1 (pro-inflammatory) or M2 (anti-inflammatory) phenotypes was assessed in circulating monocytes with flow cytometry analysis and cell sorting. RESULTS: miR-155 gene expression was higher in CM-MO group (2.68 ± 2.47 Relative Quantification - RQ) when compared to EM group (1.46 ± 0.85 RQ, p = 0.006) and HCs (0.44 ± 0.18 RQ, p = 0.001). In addition, miR-155 gene expression was higher in EM group when compared to HCs (p = 0.001). A multivariate analysis confirmed the difference between EM and CM-MO groups after correction for age, sex, smoking habit, preventive treatment, aura, presence of psychiatric or other pain conditions. We found higher gene expression of IL-1ß, TNF-α, and lower gene expression of IL-10 in migraine participants when compared to HCs (p = 0.001 for all comparisons). TNF-α and IL-10 genes alterations were more prominent in CM-MO when compared to EM participants (p = 0.001). miR-155 positively correlated with IL-1ß (p = 0.001) and TNF-α (p = 0.001) expression levels. Finally, in people with CM-MO, we described an up-regulated percentage of events in both M1 and M2 monocytic profiles. CONCLUSIONS: Our study shows for the first time a specific profile of activation of miR-155 gene expression levels in monocytes of selected migraine subpopulations, more pronounced in subjects with CM-MO. Interestingly, mir-155 expression correlated with markers of activation of the inflammatory and immune systems. The CM-MO subpopulation showed a peculiar increase of both pro-inflammatory and anti-inflammatory monocytes which worths further investigation. TRIAL REGISTRATION: www. CLINICALTRIALS: gov . (NCT05891808).
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Inflamación , MicroARNs , Trastornos Migrañosos , Monocitos , Fenotipo , Humanos , MicroARNs/sangre , MicroARNs/genética , Monocitos/metabolismo , Femenino , Masculino , Adulto , Trastornos Migrañosos/sangre , Trastornos Migrañosos/genética , Estudios Transversales , Persona de Mediana Edad , Inflamación/sangre , Inflamación/genética , Índice de Severidad de la Enfermedad , Expresión GénicaRESUMEN
BACKGROUND: The Cluster Headache Impact Questionnaire (CHIQ) is a specific and easy-to-use questionnaire to assess the current impact of cluster headache (CH). The aim of this study was to validate the Italian version of the CHIQ. METHODS: We included patients diagnosed with episodic CH (eCH) or chronic CH (cCH) according to the ICHD-3 criteria and included in the "Italian Headache Registry" (RICe). The questionnaire was administered to patients through an electronic form in two sessions: at first visit for validation, and after 7 days for test-retest reliability. For internal consistency, Cronbach's alpha was calculated. Convergent validity of the CHIQ with CH features and the results of questionnaires assessing anxiety, depression, stress, and quality of life was evaluated using Spearman's correlation coefficient. RESULTS: We included 181 patients subdivided in 96 patients with active eCH, 14 with cCH, and 71 with eCH in remission. The 110 patients with either active eCH or cCH were included in the validation cohort; only 24 patients with CH were characterized by a stable attack frequency after 7 days, and were included in the test-retest cohort. Internal consistency of the CHIQ was good with a Cronbach alpha value of 0.891. The CHIQ score showed a significant positive correlation with anxiety, depression, and stress scores, while showing a significant negative correlation with quality-of-life scale scores. CONCLUSION: Our data show the validity of the Italian version of the CHIQ, which represents a suitable tool for evaluating the social and psychological impact of CH in clinical practice and research.
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Cefalalgia Histamínica , Humanos , Cefalalgia Histamínica/diagnóstico , Cefalalgia Histamínica/psicología , Calidad de Vida/psicología , Reproducibilidad de los Resultados , Encuestas y Cuestionarios , Italia , PsicometríaRESUMEN
In recent years, numerous efforts have been made to identify reliable biomarkers useful in migraine diagnosis and progression or associated with the response to a specific treatment. The purpose of this review is to summarize the alleged diagnostic and therapeutic migraine biomarkers found in biofluids and to discuss their role in the pathogenesis of the disease. We included the most informative data from clinical or preclinical studies, with a particular emphasis on calcitonin gene-related peptide (CGRP), cytokines, endocannabinoids, and other biomolecules, the majority of which are related to the inflammatory aspects and mechanisms of migraine, as well as other actors that play a role in the disease. The potential issues affecting biomarker analysis are also discussed, such as how to deal with bias and confounding data. CGRP and other biological factors associated with the trigeminovascular system may offer intriguing and novel precision medicine opportunities, although the biological stability of the samples used, as well as the effects of the confounding role of age, gender, diet, and metabolic factors should be considered.
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Péptido Relacionado con Gen de Calcitonina , Trastornos Migrañosos , Humanos , Péptido Relacionado con Gen de Calcitonina/metabolismo , Trastornos Migrañosos/tratamiento farmacológico , Biomarcadores , Citocinas/uso terapéutico , Medicina de PrecisiónRESUMEN
BACKGROUND: Social cognition refers to all mental operations to decipher information needed in social interactions. Here we aimed to outline the socio-cognitive profile of Chronic Migraine with Medication Overuse (CM + MO), given they are recognized to be at risk of socio-cognitive difficulties. Given the multidimensionality of this construct, we considered: (1) socio-cognitive abilities, (2) socio-cognitive beliefs, (3) alexithymia and autism traits, and (4) social relationships. METHODS: Seventy-one patients suffering from CM + MO, 61 from episodic migraine (EM), and 80 healthy controls (HC) were assessed with a comprehensive battery: (1) the Faux Pas test (FP), the Strange Stories task (SS), the Reading Mind in the Eyes test (RMET), (2) the Tromsø Social Intelligence Scale, (3) the Toronto Alexithymia Scale, the Autism Spectrum Quotient, (4) the Lubben Social Network Scale, the Friendship Scale. RESULTS: CM + MO: (1) performed similar to EM but worse than HC in the FP and SS, while they were worse than EM and HC in the RMET; (2) were similar to EM and HC in social intelligence; (3) had more alexithymic/autistic traits than EM and HC; (4) reported higher levels of contact with their family members but felt little support from the people around them than HC. CONCLUSIONS: CM + MO results characterized by a profile of compromised socio-cognitive abilities that affects different dimensions. These findings may have a relevant role in multiple fields related to chronic headache: from the assessment to the management.
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Mentalización , Trastornos Migrañosos , Humanos , Estudios Transversales , Cognición Social , Uso Excesivo de Medicamentos Recetados , Cognición , Trastornos Migrañosos/tratamiento farmacológico , Relaciones InterpersonalesRESUMEN
AIMS: In this study, we tested the validity of the Severity of Dependence Scale in detecting dependence behaviours in patients with chronic migraine and medication overuse (CM + MO) using the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) and the Leeds Dependence Questionnaire as gold standard measures. METHODS: Four hundred and fifty-four patients with CM + MO filled in the Severity of Dependence Scale and the Leeds Dependence Questionnaire and underwent a psychological evaluation for the diagnosis of substance dependence according to the DSM-IV criteria. RESULTS: Sixty-nine percent of subjects (n = 313) presented substance dependence according to the DSM-IV criteria. These patients scored significantly higher than those without substance dependence in Severity of Dependence Scale total score (Z = -3.29, p = 0.001), and in items 1 (Z = -2.44, p = 0.015), 2 (Z = -2.50, p = 0.012), 4 (Z = -2.05, p = 0.04), and 5 (Z = -3.39, p = 0.001). Severity of Dependence Scale total score (ß = 0.13, SE = 0.04, z = 3.49, p < 0.001) was a significant predictor for substance dependence. Receiver Operating Characteristic (ROC) curves showed that Severity of Dependence Scale discriminated patients with or without substance dependence. CONCLUSION: Severity of Dependence Scale could represent an interesting screening tool for dependency-like behaviors in CM + MO patients.
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Cefaleas Secundarias , Trastornos Migrañosos , Trastornos Relacionados con Sustancias , Manual Diagnóstico y Estadístico de los Trastornos Mentales , Cefaleas Secundarias/psicología , Humanos , Trastornos Migrañosos/tratamiento farmacológico , Uso Excesivo de Medicamentos Recetados , Trastornos Relacionados con Sustancias/diagnóstico , Trastornos Relacionados con Sustancias/psicologíaRESUMEN
INTRODUCTION: In this open label, single-arm trial we evaluated the efficacy of onabotulinum toxin-A in the prevention of high-frequency episodic migraine (8-14 migraine days/month). METHODS: We enrolled 32 high-frequency episodic migraine subjects (age 44.8 ± 11.9 years, 11.0 ± 2.2 migraine days, 11.5 ± 2.1 headache days, 7 females). After a 28-day baseline period, subjects underwent 4 subsequent onabotulinum toxin-A treatments according to the phase III research evaluating migraine prophylaxis therapy (PREEMPT) paradigm, 12-weeks apart. The primary outcome was the reduction of monthly migraine days from baseline in the 12-week period following the last onabotulinum toxin-A treatment. RESULTS: Onabotulinum toxin-A reduced monthly migraine days by 3.68 days (-33.1%, p < 0.01). Thirty-nine percent of the patients experienced a ≥50% reduction in monthly migraine days. Onabotulinum toxin-A also reduced the number of headache days (-33.9%, p < 0.01) and the intake of acute medications (-22.9%, p = 0.03). Disability and quality of life (QoL) scores improved markedly (migraine disability assessment (MIDAS) -41.7%; migraine specific questionnaire (MSQ) -31.7%, p < 0.01). CONCLUSIONS: The findings suggest that, when administered according to the PREEMPT paradigm, onabotulinum toxin-A is effective in the prevention of high-frequency episodic migraine.Trial Registration: NCT04578782.
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Toxinas Botulínicas Tipo A , Trastornos Migrañosos , Adulto , Toxinas Botulínicas Tipo A/uso terapéutico , Femenino , Cefalea/tratamiento farmacológico , Humanos , Masculino , Persona de Mediana Edad , Trastornos Migrañosos/tratamiento farmacológico , Trastornos Migrañosos/prevención & control , Compuestos Orgánicos , Calidad de Vida , Resultado del TratamientoRESUMEN
AIM: First, we investigated whether the exposure to different visual feedback conditions may modulate pain perception by means of visual induced analgesia in patients with chronic migraine. Second, to comprehend the way emotional face expressions could induce visual analgesia, we evaluated the degree of identification with the four experimental conditions. METHODS: In a 1 × 4 within-subject study design, 38 female chronic migraine patients were exposed to different visual stimuli - positive face, neutral face, negative face, and control (white screen) - during a migraine attack. Visual stimuli were presented 3 times in a randomized order (each condition lasted 40 seconds). Migraine pain ratings and identification scores were assessed immediately after the observation of each visual condition. RESULTS: We observed a significant difference in pain ratings between the positive (median: 30, 95% CI 26.69 to 38.20) and the negative (median: 30, 95% CI 33.09 to 44.13) (z = -4.46, p < 0.0001) facial expressions or the neutral facial expression (median: 30, 95% CI 31.89 to 42.41) (z = 3.41, p < 0.001). Participants identified more with the neutral face condition than with the other conditions. CONCLUSIONS: Observation of a positive emotional face resulted sufficient to modulate pain perception possibly via the mediation of emotion regulation for positive emotions. This study paves the way for the integration of new cognitive behavioural interventions based on the adoption of visual induced analgesia to further control pain perception in chronic migraine patients.
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Expresión Facial , Trastornos Migrañosos , Emociones/fisiología , Femenino , Humanos , Dolor/psicología , Percepción del DolorRESUMEN
Vestibular symptoms accompanying headache are quite common in migraine patients. Based on the association of vertigo with migraine, vestibular migraine was included in the appendix of the 3rd edition of the International Classification of Headache Disorders as a possible migraine subtype worthy of further investigation. In this post hoc, exploratory analysis, we investigated the occurrence of oculo-vestibular signs (OVSs) during experimentally induced migraine attacks in 24 episodic migraine patients and 19 healthy controls exposed to sublingual nitroglycerin (NTG - 0.9 mg). A comprehensive clinical examination was performed at baseline, at the onset of the migraine-like attack, and immediately before hospital discharge (180 minutes after NTG administration). Three of the 13 migraine patients who developed a spontaneous-like migraine attack during the hospital observation period (23.1%) also developed OVSs during the induction test. Noteworthy, none of the patients with a negative induction test developed OVSs and no OVSs were reported in healthy subjects at any time point. The exploratory nature of our study does not allow to draw definite conclusions on the possible implications of a vestibular dysfunction in migraine pathophysiology. Our results however suggest that NTG administration may lend itself to investigate vestibular dysfunction in migraine, at least in a subset of patients. The present findings represent a starting point for designing future ad hoc and well-powered studies.
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Trastornos de Cefalalgia , Trastornos Migrañosos , Vestíbulo del Laberinto , Humanos , Vértigo/diagnóstico , Trastornos Migrañosos/diagnóstico , Cefalea/complicaciones , Trastornos de Cefalalgia/complicacionesRESUMEN
BACKGROUND: In Italy, monoclonal antibodies targeting the CGRP pathway are subsidized for the preventive treatment of high frequency and chronic migraine (CM) in patients with a MIgraine Disability ASsessment (MIDAS) score ≥ 11. Eligibility to treatment continuation requires a ≥ 50% MIDAS score reduction at three months (T3). In this study, we evaluate whether a ≥ 50% MIDAS score reduction at T3 is a reliable predictor of response to one-year erenumab treatment. METHODS: In this prospective, open-label, real-world study, 77 CM patients were treated with erenumab 70-140 mg s.c. every 28 days for one year (T13). We collected the following variables: monthly migraine days (MMDs), monthly headache days (MHDs), days of acute medication intake, MIDAS, HIT-6, anxiety, depression, quality of life and allodynia. Response to erenumab was evaluated as: i) average reduction in MMDs during the 1-year treatment period; and ii) percentage of patients with ≥ 50% reduction in MMDs during the last 4 weeks after the 13th injection (RespondersT13). RESULTS: Erenumab induced a sustained reduction in MMDs, MHDs and intake of acute medications across the 12-month treatment period, with 64.9% of patients qualifying as RespondersT13. At T3, 55.8% of patients reported a ≥ 50% reduction in MIDAS score (MIDASRes) and 55.4% of patients reported a ≥ 50% reduction in MMDs (MMDRes). MIDASRes and MMDRes patients showed a more pronounced reduction in MMDs during the 1-year treatment as compared to NON-MIDASRes (MIDASRes: T0: 23.5 ± 4.9 vs. T13: 7.7 ± 6.2; NON- MIDASRes: T0: 21.6 ± 5.4 vs. T13: 11.3 ± 8.8, p = 0.045) and NON-MMDRes (MMDRes: T0: 23.0 ± 4.5 vs. T13: 6.6 ± 4.8; NON-MMDRes: T0: 22.3 ± 6.0 vs. T13: 12.7 ± 9.2, p < 0.001) groups. The percentage of RespondersT13 did not differ between MIDASRes (74.4%) and NON-MIDASRes (52.9%) patients (p = 0.058), while the percentage of RespondersT13 was higher in the MMDRes group (83.3%) when compared to NON-MMDRes (42.9%) (p = 0.001). MMDRes predicted the long-term outcome according to a multivariate analysis (Exp(B) = 7.128; p = 0.001), while MIDASRes did not. Treatment discontinuation based on MIDASRes would have early excluded 36.0% of RespondersT13. Discontinuation based on "either MIDASRes or MMDRes" would have excluded a lower percentage (16%) of RespondersT13. CONCLUSION: MIDASRes only partly reflects the 12-month outcome of erenumab treatment in CM, as it excludes more than one third of responders. A criterion based on the alternative consideration of ≥ 50% reduction in MIDAS score or MMDs in the first three months of treatment represents a more precise and inclusive option. TRIAL REGISTRATION: The trial was retrospectively registered at www. CLINICALTRIALS: gov (NCT05442008). CGRP: Calcitonin Gene Related Peptide. MIDAS: MIgraine Disability Assessment. MMDs: monthly migraine days. MIDASRes: Patients with a MIDAS score reduction of at least 50% at T3. MMDRes: Patients with a MMDs reduction of at least 50% at T3. ResponderT13: Patients with a MMDs reduction from baseline of at least 50% in the last 4 weeks of observation period (after 13 erenumab administrations). T0: First erenumab administration. T3, T6, T9, T12: Follow-up visits at three, six, nine, and twelve months after first erenumab administration. T13: Last visit of the protocol.
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Péptido Relacionado con Gen de Calcitonina , Trastornos Migrañosos , Anticuerpos Monoclonales/uso terapéutico , Anticuerpos Monoclonales Humanizados , Péptido Relacionado con Gen de Calcitonina/uso terapéutico , Evaluación de la Discapacidad , Humanos , Trastornos Migrañosos/prevención & control , Estudios Prospectivos , Calidad de VidaRESUMEN
BACKGROUND: Psychosocial variables are key factors influencing psycho-physical equilibrium in migraine patients. Social isolation and vulnerability to stressors may prevent efficient psychological adjustment negatively affecting adaptation to life changes, as that imposed during Covid-19 lockdown. Here, we explored psychosocial dimensions and changes in clinical condition during Covid-19 lockdown in migraine patients, with regard to migraine type and headache impact. METHODS: Sixty-four migraine patients (32 episodic and 32 chronic) and 64 healthy control subjects were included in a case-control cross-sectional study. A two-step clustering procedure split patients into two clusters, based on the Headache Impact Test. Perceived global distress, loneliness, empathy, and coping levels were compared in groups, as well as changes in clinical condition. RESULTS: Migraine patients reported higher general loneliness and lower social support compared to healthy control subjects. Emotional loneliness was more marked in patients with higher headache impact. This subgroup of patients more frequently reported changes in the therapeutic and care paths as the perceived cause of the occurrence of motor or extra-motor symptomatology. CONCLUSIONS: Migraine patients, especially those more severely affected, proved more vulnerable than healthy control subjects to Covid-19 lockdown. Long-lasting interruption of social interactions may be detrimental in fragile patients that are in need of structured support interventions to maintain psycho-physical wellbeing.
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COVID-19/complicaciones , COVID-19/psicología , Cefalea/etiología , Trastornos Migrañosos/etiología , Cuarentena/psicología , Aislamiento Social , Apoyo Social , Adulto , Ansiedad/psicología , COVID-19/epidemiología , Estudios de Casos y Controles , Control de Enfermedades Transmisibles , Estudios Transversales , Brotes de Enfermedades , Femenino , Cefalea/epidemiología , Humanos , Soledad , Masculino , Persona de Mediana Edad , Trastornos Migrañosos/epidemiología , SARS-CoV-2RESUMEN
BACKGROUND: Preclinical and clinical evidence suggests a role for the dysregulation of the endocannabinoid system in migraine pain, particularly in subjects with chronic migraine. METHODS: The gene expression of endocannabinoid system components was assayed in peripheral blood mononuclear cells of 25 subjects with episodic migraine, 26 subjects with chronic migraine with medication overuse (CM-MO) and 24 age-matched healthy controls. We also evaluated the protein expression of cannabinoid receptors 1 and 2 as well as DNA methylation changes in genes involved in endocannabinoid system components. RESULTS: Both episodic migraine and CM-MO subjects showed higher cannabinoid receptor 1 and cannabinoid receptor 2 gene and protein expression compared to controls. Fatty acid amide hydrolase gene expression, involved in anandamide degradation, was lower in migraine groups compared to healthy control subjects. N-arachidonoyl phosphatidylethanolamine phospholipase D gene expression was significantly higher in all migraineurs, as were monoacylglycerol lipase and diacylglycerol lipase gene expressions. The above markers significantly correlated with the number of migraine days and with the days of acute drug intake. CONCLUSION: The findings point to transcriptional changes in endocannabinoid system components occurring in migraineurs. These changes were detected peripherally, which make them amenable for a wider adoption to further investigate their role and applicability in the clinical field.clinicaltrials.gov NTC04324710.
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Trastornos Migrañosos , Enfermedad Crónica , Endocannabinoides , Humanos , Leucocitos Mononucleares , Trastornos Migrañosos/genética , Proyectos Piloto , Receptores de Cannabinoides/genéticaRESUMEN
BACKGROUND: Monoclonal antibodies (mABs) targeting the calcitonin gene-related peptide (CGRP) pathway represent the first disease-specific preventive migraine therapy. Growing evidence suggests that they are effective in the preventive treatment of difficult-to-treat patients. In this study, we evaluated the psychological predictors of the outcome of treatment with the anti-CGRP monoclonal antibody erenumab in patients with chronic migraine (CM). METHODS: Seventy-five patients with CM who had already failed at least 3 preventive therapies received erenumab every 28 days for a period of 12 months. Before the first administration, patients received a full psychological evaluation using The Structured Clinical Interview for DSM-5 Clinician Version (SCID-5-CV) to assess personality disturbances (primary outcome), mood and anxiety disorders, and as well specific questionnaires to evaluate alexithymia traits, childhood traumas, and current stressors (secondary outcomes). RESULTS: After 12 months of treatment, 53 patients reported a reduction of at least 50% in headache days/per month (Responders), whereas 22 did not (Non Responders). When compared to Responders, Non Responders were characterized by a higher prevalence of personality disorders belonging to Cluster C (avoidant, dependent, and obsessive-compulsive) (77% vs 37%, p = .001). Non Responders were also characterized by a higher prevalence of anxiety disorders (90% vs 60%, p = 0.007), showed more alexithymic traits (51.7 ± 13.7 vs 42.9 ± 14.3, p = 0.017), and reported a higher number of 'at least serious' current stressors (3.2 ± 4.0 vs 0.8 ± 1.4, p < .0001) than Responders. At the multivariate analysis, higher prevalence of Cluster C personality disorders (OR 3.697; p = 0.05) and higher number of 'at least serious' life events (OR 1.382; p = 0.017) arose as prognostic factors of erenumab failure. CONCLUSIONS: Erenumab confirmed its effectiveness in a population of difficult-to-treat migraine. The presence of "anxious-fearful" personality together with current stressors and anxiety represent negative predictors of treatment outcome. TRIAL REGISTRATION: The study protocol was registered at clinicaltrials.gov ( NCT04361721 ).
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Antagonistas del Receptor Peptídico Relacionado con el Gen de la Calcitonina , Trastornos Migrañosos , Anticuerpos Monoclonales Humanizados , Humanos , Trastornos Migrañosos/tratamiento farmacológico , Estudios Prospectivos , Resultado del TratamientoRESUMEN
INTRODUCTION: Anti-calcitonin gene-related peptide antibodies proved effective in the preventive treatment of chronic migraine. In this open label study, we aim to assess the effects of erenumab administration on neurophysiological and biomolecular profiles in a representative cohort of chronic migraine patients. METHODS: Forty patients with a history of chronic migraine for at least 12 months prior to enrollment, and previous failure of at least two different preventive therapies, were enrolled. After a 1-month observation period (T0), patients were treated with erenumab 70 mg s.c. (every 28 days) for a total of three administrations. At week 12, they returned for the end-of-protocol visit (T3). At T0 and T3, patients underwent recording of clinical features, recording of single stimulus (RTh), temporal summation (TST) thresholds of the nociceptive withdrawal reflex, venous blood sampling for miR-382-5p, and miR-34a-5p quantification. RESULTS: At T3, 31 patients (77.5%) qualified as 30% Responders (reduction in monthly migraine days by at least 30% in the last 4-week observation period). RTh (T0: 15.4 ± 8.1 mA, T3: 19.7 ± 8.2 mA) as well as TST (T0: 11.2 ± 5.8 mA, T3: 13.4 ± 5.0 mA) significantly increased at T3 in 30% Responders (p = 0.001 for both), while we did not observe significant changes in NON-responder patients. MiR-382-5p and miR-34a-5p levels were significantly lower after erenumab administration in the overall study population (p = 0.015, and p = 0.001, respectively), without significant differences between 30% Responder and NON-responder groups. CONCLUSIONS: Different migraine phenotypes, characterized by different treatment susceptibility, may exist as suggested by the divergent behavior between neurophysiological and biomolecular findings in 30% Responder vs. NON-responder patients.The study protocol was registered at clinicaltrials.gov (NCT04361721).
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Anticuerpos Monoclonales Humanizados/uso terapéutico , Antagonistas del Receptor Peptídico Relacionado con el Gen de la Calcitonina/uso terapéutico , Trastornos Migrañosos/tratamiento farmacológico , Umbral del Dolor/efectos de los fármacos , Adulto , Enfermedad Crónica , Femenino , Humanos , Masculino , MicroARNs/efectos de los fármacos , Persona de Mediana Edad , Resultado del TratamientoRESUMEN
BACKGROUND: Migraine can manifest with an episodic or a chronic pattern in a continuum of disease severity. Multiple factors are associated with the progression of the pattern from episodic to chronic. One of the most consistently reported factors is the overuse of medications (MO) for the acute treatment of migraine attacks. The mechanisms through which MO facilitates the transformation of episodic migraine (EM) into chronic migraine (CM) are elusive. In order to provide insights into these mechanisms, the present study aims to identify possible peripheral biomarkers associated with the two forms of migraine, and with the presence of MO. METHODS: We evaluated the plasma levels of calcitonin gene-related peptide (CGRP) and the expression of miR-34a-5p and miR-382-5p in peripheral blood mononuclear cells of subjects with EM (n = 27) or CM-MO (n = 28). Subjects in the CM-MO group were also tested 2 months after an in-hospital detoxification protocol. RESULTS: CGRP, miR-382-5p, and miR-34a-5p levels were significantly higher in CM-MO subjects when compared to EM patients (p = 0.003 for all comparisons). After correcting for age, sex, and disease duration, miRNAs expression was still significantly associated with migraine phenotype (EM vs. CM-MO: p = 0.014 for miR-382-5p, p = 0.038 for miR-34a-5p), while CGRP levels were not (p = 0.115). CGRP plasma levels significantly and positively correlated with miR-382-5p (Spearman's rho: 0.491, p = 0.001) and miR-34a-5p (Spearman's rho: 0.303, p =0.025) in the overall population. In the CM-MO group, detoxification significantly decreased CGRP levels and miRNAs expression (p = 0.001). When comparing responders and non-responders to the detoxification, the former group (n = 23) showed significantly higher levels of CGRP at baseline, and significantly lower expression of miR-382-5p after the detoxification. CONCLUSIONS: Our findings identify a potential panel of peripheral markers associated with migraine subtypes and disease severity. CGRP levels as well as miRNAs expression were influenced by MO, and modulated by detoxification in subjects with CM-MO. TRIAL REGISTRATION: The study protocol was registered at www.clinicaltrials.gov ( NCT04473976 ).
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MicroARNs , Trastornos Migrañosos , Biomarcadores , Calcitonina , Péptido Relacionado con Gen de Calcitonina , Humanos , Leucocitos Mononucleares , Trastornos Migrañosos/genética , PlasmaRESUMEN
AIM: To identify factors that may be predictors of the outcome of a detoxification treatment in medication-overuse headache. METHODS: Consecutive patients entering a detoxification program in six centres in Europe and Latin America were evaluated and followed up for 6 months. We evaluated anxious and depressive symptomatology (though patients with severe psychiatric comorbidity were excluded), quality of life, headache-related disability, headache characteristics, and prophylaxis upon discharge. RESULTS: Of the 492 patients who completed the six-month follow up, 407 ceased overuse following the detoxification (non overusers), another 23 ceased overuse following detoxification but relapsed during the follow-up. In the 407 non-overusers, headache acquired an episodic pattern in 287 subjects (responders). At the multivariate analyses, lower depression scores (odds ratio = 0.891; p = 0.001) predicted ceasing overuse. The primary headache diagnosis - migraine with respect to tension-type headache (odds ratio = 0.224; p = 0.001) or migraine plus tension-type headache (odds ratio = 0.467; p = 0.002) - and the preventive treatment with flunarizine (compared to no such treatment) (odds ratio = 0.891; p = 0.001) predicted being a responder. A longer duration of chronic headache (odds ratio = 1.053; p = 0.032) predicted relapse into overuse. Quality of life and disability were not associated with any of the outcomes. CONCLUSIONS: Though exploratory in nature, these findings point to specific factors that are associated with a positive outcome of medication-overuse headache management, while identifying others that may be associated with a negative outcome. Evaluation of the presence/absence of these factors may help to optimize the management of this challenging groups of chronic headache sufferers.
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Cefaleas Secundarias/psicología , Cefaleas Secundarias/rehabilitación , Trastornos Relacionados con Sustancias/psicología , Trastornos Relacionados con Sustancias/rehabilitación , Ansiedad/complicaciones , Depresión/complicaciones , Estudios de Seguimiento , Humanos , Factores de Riesgo , Resultado del TratamientoRESUMEN
BACKGROUND: The International Classification of Headache Disorders lists different subtypes of medication overuse headache (MOH), according to the medication overused. The aim of this study is to evaluate whether the different subtypes correspond to clinically distinguishable phenotypes in a large population. METHOD: This descriptive cross-sectional observational study included 660 patients with MOH referred to headache centers in Europe and Latin America as a part of the COMOESTAS project. Information about clinical features was collected with structured patient interviews and with self-administered questionnaires for measuring disability, anxiety, and depression. RESULTS: Female/male ratio, body mass index, marital status, and level of education were similar among in subjects enrolled in the 5 centers. The mean age was higher among subjects overusing triptans (T-MOH) with respect to subjects overusing simple analgesic (A-MOH). Duration of headache before chronification was longer in T-MOH (19.2 ± 11.9 years) and in subjects overusing ergotamines (E-MOH, 17.8 ± 11.7 years) with respect to the A-MOH group (13.1 ± 10.9; P < .001 and P = .017, respectively) and in T-MOH with respect multiple drug classes (M-MOH, 14.9 ± 11.7; P = .030). Migraine Disability Assessment (MIDAS) score was significantly lower in E-MOH group (33.6 ± 41.6), while T-MOH group (56.8 ± 40.6) had a significant lower MIDAS score with respect to M-MOH (67.2 ± 62.5; P = .016 and P = .037, respectively). Prevalence of depression and anxiety was lower in patients overusing T with respect to other groups of patients (χ2 = 10.953, P = .027 and χ2 = 25.725, P < .001, respectively). CONCLUSION: In this study on a large and very well characterized population of MOH, we describe the distinctive clinical characteristics of MOH subtypes. These findings contribute to more clearly define the clinical picture of a poorly delineated headache disorder. They also provide some insights in the possible trajectories leading to this highly disabling chronic headache, that is classified as a secondary form, but whose occurrence is entirely dependent on an underlying primary headache.
Asunto(s)
Cefaleas Secundarias/psicología , Adulto , Anciano , Ansiedad/etiología , Ansiedad/psicología , Índice de Masa Corporal , Estudios de Cohortes , Estudios Transversales , Depresión/etiología , Depresión/psicología , Evaluación de la Discapacidad , Escolaridad , Europa (Continente)/epidemiología , Femenino , Cefaleas Secundarias/complicaciones , Cefaleas Secundarias/epidemiología , Humanos , América Latina/epidemiología , Masculino , Estado Civil , Persona de Mediana Edad , Prevalencia , Factores Sexuales , Encuestas y Cuestionarios , Triptaminas/efectos adversos , Triptaminas/uso terapéutico , Adulto JovenRESUMEN
BACKGROUND AND AIM: Factors implicated in the evolution of episodic migraine into chronic migraine are largely elusive. Medication overuse is considered to be one of the main determinants, but other possible clinical and psychological factors can play a role. The aim of this study is to identify factors that are associated with chronic migraine with medication overuse. METHOD: We enrolled consecutive migraine patients, subdividing them in two groups: Subjects with a long history of episodic migraine and subjects with chronic migraine and medication overuse. We then compared their clinical and psychological variables in a cross-sectional study. RESULTS: Three hundred and eighteen patients were enrolled, of which 156 were episodic migraine and 162 were chronic migraine and medication overuse patients. The mean age was 42.1 ± 10.3, 80.8% were female. The duration of migraine was 24.6 years in episodic migraine and 24.0 years in chronic migraine and medication overuse ( p = 0.57). After the multivariate analysis, the factors associated to chronic migraine and medication overuse were: Marital status (married vs. unmarried, OR 3.65, 95% CI 1.63-8.19, p = 0.002; separated/divorced/widowed vs. unmarried, OR 4.19, 95% CI 1.13-15.47, p = 0.031), physical activity (OR 0.42, 95% CI 0.19-0.91, p = 0.029), age at onset of migraine (OR 0.94, 95% CI 0.89-0.98, p = 0.016), use of at least one migraine preventive medication (OR 2.36, 95% CI 1.18-4.71, p = 0.014), history of depression (OR 2.91, 95% CI 1.25-6.73, p = 0.012), insomnia associated with the use of hypnotics (OR 5.59, 95% CI 1.65-18.93, p = 0.006), traumatic head injuries (OR 3.54, 95% CI 1.57-7.99, p = 0.002), snoring (OR 2.24, 95% CI 1.05-4.79, p = 0.036), previous and/or actual use of combined oral contraceptives (OR 3.38, 95% CI 1.10-10.3, p = 0.031) and higher scores in the Childhood Trauma questionnaire (OR 1.48, 95% CI 1.09-2.02, p = 0.012). CONCLUSION: We considered several aspects that may be involved in the development of chronic migraine and medication overuse. A multivariate analysis identified 10 factors belonging to five different areas, to suggest that chronic migraine and medication overuse onset is likely influenced by a complex mixture of factors. This information is useful when planning strategies to prevent and manage chronic migraine and medication overuse.
Asunto(s)
Cefaleas Secundarias , Trastornos de Cefalalgia , Trastornos Migrañosos , Adulto , Estudios Transversales , Progresión de la Enfermedad , Femenino , Trastornos de Cefalalgia/etiología , Trastornos de Cefalalgia/psicología , Cefaleas Secundarias/etiología , Cefaleas Secundarias/psicología , Humanos , Masculino , Persona de Mediana Edad , Trastornos Migrañosos/etiología , Trastornos Migrañosos/psicología , Factores de RiesgoRESUMEN
Aims To evaluate the impact of treatment success on depression and anxiety symptoms in medication-overuse headache (MOH) and whether depression and anxiety can be predictors of treatment outcome. Methods All consecutive patients entering the detoxification program were analysed in a prospective, non-randomised fashion over a six-month period. Depression and anxiety were assessed using the Hospital Anxiety and Depression Scale. Results A total of 663 MOH patients were evaluated, and 492 completed the entire protocol. Of these, 287 ceased overuse and reverted to an episodic pattern (responders) and 23 relapsed into overuse. At the final evaluation, the number of patients with depressive symptoms was reduced by 63.2% among responders ( p < 0.001) and did not change in relapsers ( p = 0.13). Anxious symptomatology was reduced by 43.1% in responders ( ps < 0.001) and did not change in relapsers ( p = 0.69). At the multivariate analysis, intake of a prophylactic drug and absence of symptoms of depression at six months emerged as prognostic factors for being a responder (OR 2.406; p = 0.002 and OR 1.989; p = 0.019 respectively), while lack of antidepressant drugs and presence of symptoms of depression at six months were prognostic factors for relapse into overuse (OR 3.745; p = 0.004 and OR 3.439; p = 0.031 respectively). Conclusions Symptomatology referred to affective state and anxiety can be significantly reduced by the treatment of MOH. Baseline levels of depression and anxiety do not generally predict the outcome at six months. Their persistence may represent a trait of patients with a negative outcome, rather than the consequence of a treatment failure.
Asunto(s)
Ansiedad/epidemiología , Depresión/epidemiología , Cefaleas Secundarias/psicología , Cefaleas Secundarias/terapia , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Recurrencia , Resultado del TratamientoRESUMEN
Background Medication-overuse headache (MOH) is a chronic disabling condition associated with a high rate of relapse. Methods We evaluated whether the adoption of electronic-assisted monitoring, advice and communication would improve the outcome over a follow-up of 6 months in a controlled, multicentre, multinational study conducted in six headache centres located in Europe and Latin America. A total of 663 MOH subjects were enrolled and divided into two groups: the Comoestas group was monitored with an electronic diary associated with an alert system and a facilitated communication option, and the Classic group with a paper headache diary. Results We observed a significantly higher percentage of overuse-free subjects in the Comoestas group compared with the Classic group: 73.1 vs 64.1% (odds ratio 1.45, 95% confidence interval 1.07-2.09, p = 0.046). The Comoestas group performed better also regarding the number of days/month with intake of acute drugs and the level of disability [Migraine Disability Assessment Score: Comoestas group - 42.5 ± 53.6 (35.5-49.3) and Classic group - 27.5 ± 56.1 (20.6-34.3) ( p < 0.003)]. Conclusion The adoption of the electronic tool improved the outcome of patients suffering from MOH after withdrawal from overused drugs. Information and communication technology represents a valid aid for optimizing the management of chronic conditions at risk of worsening or of relapsing. Trial registration The trial was registered at ClinicalTrials.gov (no. NCT02435056).