Original article
Experience with botulinum toxin in chronic migraine
Experiencia con toxina botulínica en la migraña crónica
A. Castrillo Sanz
, N. Morollón Sánchez-Mateos, C. Simonet Hernández, B. Fernández Rodríguez, D. Cerdán Santacruz, A. Mendoza Rodríguez, M.F. Rodríguez Sanz, C. Tabernero García, P. Guerrero Becerra, M. Ferrero Ros, J. Duate García-Luis
Corresponding author
Sección de Neurología, Complejo Hospitalario de Segovia, Segovia, Spain
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Castrillo Sanz, N. Morollón Sánchez-Mateos, C. Simonet Hernández, B. Fernández Rodríguez, D. Cerdán Santacruz, A. Mendoza Rodríguez, M.F. Rodríguez Sanz, C. Tabernero García, P. Guerrero Becerra, M. Ferrero Ros, J. Duate García-Luis" "autores" => array:11 [ 0 => array:4 [ "nombre" => "A." "apellidos" => "Castrillo Sanz" "email" => array:1 [ 0 => "anacastrillosanz@yahoo.es" ] "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cor0005" ] ] ] 1 => array:2 [ "nombre" => "N." "apellidos" => "Morollón Sánchez-Mateos" ] 2 => array:2 [ "nombre" => "C." "apellidos" => "Simonet Hernández" ] 3 => array:2 [ "nombre" => "B." "apellidos" => "Fernández Rodríguez" ] 4 => array:2 [ "nombre" => "D." "apellidos" => "Cerdán Santacruz" ] 5 => array:2 [ "nombre" => "A." "apellidos" => "Mendoza Rodríguez" ] 6 => array:2 [ "nombre" => "M.F." "apellidos" => "Rodríguez Sanz" ] 7 => array:2 [ "nombre" => "C." "apellidos" => "Tabernero García" ] 8 => array:2 [ "nombre" => "P." "apellidos" => "Guerrero Becerra" ] 9 => array:2 [ "nombre" => "M." "apellidos" => "Ferrero Ros" ] 10 => array:2 [ "nombre" => "J." "apellidos" => "Duate García-Luis" ] ] "afiliaciones" => array:1 [ 0 => array:2 [ "entidad" => "Sección de Neurología, Complejo Hospitalario de Segovia, Segovia, Spain" "identificador" => "aff0005" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Experiencia con toxina botulínica en la migraña crónica" ] ] "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Chronic migraine is an extremely complex and severely disabling neurological disorder which causes a profound impact on patients’ quality of life.<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">1</span></a> The third edition of the International Classification of Headache Disorders (ICHD-3) defines chronic migraine as migraine occurring on at least 15 days per month for more than 3 months, which has the features of migraine headache with or without aura on at least 8 days per month or responds to migraine treatment. The complex pathogenic mechanisms of chronic migraine affect multiple sensory pathways, emotional networks, autonomic systems, and cortical functions. The condition has a prevalence of 1.4-2.2%.<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">3</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">The use of botulinum toxin type A (OnabotA) for prophylaxis has considerably changed the management of chronic migraine. The efficacy of this treatment for chronic migraine was confirmed by the results of the PREEMPT programme. The programme demonstrated the efficacy of OnabotA in decreasing the frequency of headache days per month, reducing medication use, and improving quality of life. The PREEMPT trials also showed the treatment's safety and tolerability and the low incidence of associated adverse reactions.<a class="elsevierStyleCrossRefs" href="#bib0140"><span class="elsevierStyleSup">4–6</span></a> Subsequent studies have confirmed the efficacy, safety, and long-term effect of the drug, as well as its positive impact on quality of life and healthcare cost savings.<a class="elsevierStyleCrossRefs" href="#bib0155"><span class="elsevierStyleSup">7,8</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">Although the analgesic effect of OnabotA is not fully understood, the drug is thought to act not only by inhibiting acetylcholine release at the presynaptic level, relaxing the pericranial muscles, but also through an effect on other pathways. OnabotA inhibits the release of nociceptive mediators such as calcitonin gene-related peptide, glutamate, and substance P from afferent peripheral nerve fibres. This, in turn, inhibits neurogenic inflammation and consequently peripheral nociceptive fibre sensitivity, reducing the transmission of peripheral pain signals to the central nervous system. This decreases central sensitisation, which is responsible for progression to chronic migraine.<a class="elsevierStyleCrossRefs" href="#bib0165"><span class="elsevierStyleSup">9,10</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">In this study, we describe our experience with OnabotA for the treatment of chronic migraine at Complejo Asistencial de Segovia over a period of 16 months. We evaluate the treatment's capacity to reduce pain intensity and frequency and attempt to identify possible clinical markers of good response to treatment.</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Patients and methods</span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Study design</span><p id="par0025" class="elsevierStylePara elsevierViewall">We conducted a prospective study with a sample of patients aged 18 years and older who visited our hospital's neurology department between 1 October 2013 and 1 April 2015; all participants met ICHD-3 diagnostic criteria for chronic migraine.<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">2</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">All patients received OnabotA injections according to the PREEMPT injection paradigm (155<span class="elsevierStyleHsp" style=""></span>U in 31 sites) every 3-4 months for 16 months. We gathered patients’ demographic and clinical data, including age, sex, history of psychiatric disorders, previous preventive treatments, number of headache days per month, and pain intensity. Patients were asked to complete a headache diary, in which they recorded the number of headache days and rated pain intensity using the visual analogue scale (VAS). We also recorded the number of injections each patient received and any adverse reactions to OnabotA (type of reaction, duration, and outcome).</p><p id="par0035" class="elsevierStylePara elsevierViewall">The effect of OnabotA was evaluated by comparing the response after each cycle with the patients’ baseline status (status before first injection), and based on the following parameters: change in the number of headache days, subjective improvement (VAS scores), and adverse reactions to OnabotA.</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Statistical analysis</span><p id="par0040" class="elsevierStylePara elsevierViewall">Statistical analysis was performed using SPSS statistics software, version 15.0.</p><p id="par0045" class="elsevierStylePara elsevierViewall">We used a two-way analysis of variance (ANOVA) to evaluate the effect of the treatment, comparing values at baseline and after each treatment period. Statistical significance was set at <span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>.006. We used linear regression to analyse the correlation between the effect of the treatment and the remaining variables in order to determine which clinical markers may help predict good treatment response in clinical practice.</p></span></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Results</span><p id="par0050" class="elsevierStylePara elsevierViewall">The study included 69 patients meeting the diagnostic criteria for chronic migraine. The mean age was 43.2<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>15.2 years (range, 18-80); 88.4% were women. History of psychiatric disorders (including anxiety and depression) was present in 20.3% of participants; 82.6% had previously received treatment for chronic migraine. <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a> summarises the treatments received previously to OnabotA injection; 12 patients (17.4%) had never received preventive treatment, 24 (34.8%) had received one, 21 (30.4%) had received two, 8 (11.6%) had received three, and 4 (5.8%) had received four treatments. Furthermore, eight patients (11.6%) had previously received botulinum toxin at a mean dose of 94.4<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>21.5<span class="elsevierStyleHsp" style=""></span>U (95% CI, 76.4-112.3).</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0055" class="elsevierStylePara elsevierViewall">Patients in our sample received a mean of two OnabotA injections (range, 1-5). During the study period, 50 patients received at least two injections, with 28 receiving three and 14 receiving four. One patient who received 5 injections was not included in our study, since the last follow-up visit to assess the results of the fifth injection took place after the study period had concluded.</p><p id="par0060" class="elsevierStylePara elsevierViewall">Our patients experienced 20.6<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>8.5 headache days per month at baseline. Frequency decreased to 8.6<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>8.1 headache days per month after the first injection, 7.5<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>7.5 after the second injection, 7.8<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>6.6 after the third injection, and to 5.5<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>4.8 after the fourth. At baseline, patients reported a pain intensity of 8.1<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>1.3 points on the VAS. Intensity decreased to 6.1<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>1.8 points after the first injection, 5.8<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>2.2 after the second, 6.1<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>1.6 after the third, and to 6.1<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>1.7 after the fourth. Changes in pain frequency and intensity are summarised in <a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>. The number of headache days per month decreased by 48.5%, and pain intensity by 20.7%.</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><p id="par0065" class="elsevierStylePara elsevierViewall">To evaluate the effect of the treatment in relation with time, we analysed the changes observed over the study period in the variables “number of headache days per month” and “pain intensity.” Both variables were observed to decrease significantly after treatment; decreases were uniform throughout the study period, with no significant differences between injections. These results are summarised in <a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>.</p><elsevierMultimedia ident="tbl0015"></elsevierMultimedia><p id="par0070" class="elsevierStylePara elsevierViewall">The 28 patients who received three injections were analysed separately. In these patients, pain intensity and the number of headache days per month were observed to decrease significantly after treatment (sustained decrease over time, with no differences between the 3 injections; <span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>.005).</p><p id="par0075" class="elsevierStylePara elsevierViewall">To evaluate the presence of markers of good treatment response, we analysed the correlation between the variable “decrease in the number of headache days per month” and the remaining variables using a linear regression model; we analysed the slope of the regression line. <span class="elsevierStyleItalic">P</span> values <.05 were considered statistically significant. We observed no association between the decrease in the number of headache days per month and any other variable (<a class="elsevierStyleCrossRef" href="#tbl0020">Table 4</a>). However, we did find a negative correlation between the decrease in pain intensity and the number of treatments received previously (slope –0.20; 95% CI –0.37 to –0.02; <span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>.0278): the fewer treatments the patient had received before OnabotA injection, the greater the decrease in pain intensity (<a class="elsevierStyleCrossRef" href="#tbl0025">Table 5</a>).</p><elsevierMultimedia ident="tbl0020"></elsevierMultimedia><elsevierMultimedia ident="tbl0025"></elsevierMultimedia><p id="par0080" class="elsevierStylePara elsevierViewall">Over the study period, 26 patients were excluded for a number of reasons: 17 patients (24.63%) due to lack of improvement (after a mean of 2 injections), one due to pregnancy (after the second injection), 2 patients wishing to conceive (one after the second injection and the other after the third), 4 due to psychiatric disorders or cognitive impairment under evaluation (after the first injection), and 2 patients who were lost to follow up after the first injection.</p><p id="par0085" class="elsevierStylePara elsevierViewall">Regarding adverse events, 3 patients experienced mild ptosis, resolving in less than a week in all cases.</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Discussion</span><p id="par0090" class="elsevierStylePara elsevierViewall">The World Health Organization regards chronic migraine as one of the most disabling conditions.<a class="elsevierStyleCrossRefs" href="#bib0175"><span class="elsevierStyleSup">11,12</span></a></p><p id="par0095" class="elsevierStylePara elsevierViewall">This complex disorder is characterised by persistent pain and resistance to preventive treatment, making it a severely disabling condition with a negative impact on patients’ quality of life.<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">12</span></a> It is therefore essential to share clinical practice experiences with effective treatments. Studies into chronic migraine treatment should be designed with similar inclusion and treatment response criteria to avoid biases or non-conclusive data. Correct patient selection is key to ensure the success of botulinum toxin in treating chronic migraine.</p><p id="par0100" class="elsevierStylePara elsevierViewall">OnabotA was approved in 2010 as a preventive treatment for chronic migraine in view of the results of the PREEMPT programme. The programme included 1354 patients, who received botulinum toxin injections every 12 weeks for 24 weeks, followed by a 32-week open-label phase. The PREEMPT programme, a multicentre, double-blind, placebo-controlled clinical trial, was conducted in 2 phases and demonstrated the efficacy, safety, and tolerability of OnabotA for preventing chronic migraine in adults.<a class="elsevierStyleCrossRefs" href="#bib0140"><span class="elsevierStyleSup">4–8,13</span></a></p><p id="par0105" class="elsevierStylePara elsevierViewall">The present study is prospective and evaluates the effectiveness and tolerability of OnabotA in real-life conditions: in patients with chronic migraine visiting our neurology department. Following the PREEMPT injection paradigm, we injected patients with 155<span class="elsevierStyleHsp" style=""></span>U of OnabotA at 31 sites distributed over the head and neck.<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">13</span></a> We observed significant, sustained improvements: the number of headache days per month decreased by 48.5%, whereas pain intensity decreased by 20.7%. We measured pain intensity using the VAS, whereas the PREEMPT programme measured the number of days with severe headache pain and the condition's impact on the activities of daily living.</p><p id="par0110" class="elsevierStylePara elsevierViewall">The demographic characteristics of our sample are similar, and therefore comparable, to those of the PREEMPT cohort<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">6</span></a>: our patients had a mean age of 43.2 years and were predominantly women (88.4%), vs a mean age of 41.1 years and 87.6% women in the PREEMPT cohort. In our study, and in line with the literature,<a class="elsevierStyleCrossRefs" href="#bib0185"><span class="elsevierStyleSup">13,14</span></a> chronic migraine was observed to be considerably more frequent among women.</p><p id="par0115" class="elsevierStylePara elsevierViewall">The PREEMPT study included patients experiencing at least 20 headache days per month.<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">6</span></a> Similarly, our patients experienced a mean of 20.6 headache days per month before starting treatment with OnabotA. In our study, the number of headache days decreased by 48.5%. The PREEMPT study evaluated treatment effectiveness differently, reporting a decrease of at least 50% in the number of headache days in 47.1% of patients.<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">6</span></a></p><p id="par0120" class="elsevierStylePara elsevierViewall">In line with the results of studies published in the last 2 years, which provide extensive data on clinical practice experience with this treatment, we not only achieved a significant decrease in the number of headache days per month after treatment with OnabotA, but also confirmed that treatment effect is maintained over time.<a class="elsevierStyleCrossRefs" href="#bib0170"><span class="elsevierStyleSup">10,14–18</span></a></p><p id="par0125" class="elsevierStylePara elsevierViewall">A novel aspect of the present study is the correlation between clinical improvement due to OnabotA treatment and the number of previous treatments, whereby the sooner OnabotA is administered, the greater the benefits. Other recent studies have not identified clinical predictors of good response to OnabotA.<a class="elsevierStyleCrossRef" href="#bib0215"><span class="elsevierStyleSup">19</span></a> Our results support early treatment with OnabotA for patients with refractory chronic migraine.</p><p id="par0130" class="elsevierStylePara elsevierViewall">According to our findings and those of other studies,<a class="elsevierStyleCrossRefs" href="#bib0190"><span class="elsevierStyleSup">14,20,21</span></a> OnabotA has an excellent safety and tolerability profile. Only 3 patients in our sample developed mild ptosis (4.3%). This rate is similar to those reported by other studies, including the PREEMPT programme (3.3%).<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">6</span></a> Furthermore, all of our cases resolved within a week. Our results also show that the benefits observed are maintained over time: successive injections increase the benefits achieved after the first session.<a class="elsevierStyleCrossRef" href="#bib0230"><span class="elsevierStyleSup">22</span></a></p><p id="par0135" class="elsevierStylePara elsevierViewall">OnabotA has been shown to be cost-effective and constitutes a promising preventive treatment option for chronic migraine.<a class="elsevierStyleCrossRefs" href="#bib0235"><span class="elsevierStyleSup">23,24</span></a></p><p id="par0140" class="elsevierStylePara elsevierViewall">Our study does have certain limitations, including the small sample size and the lack of a control group, given that it includes a series of patients seen in clinical practice. The novel contribution of this study is the recommendation to administer OnabotA as early as possible, as its benefits for refractory chronic migraine may be greater with earlier administration.</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Conclusion</span><p id="par0145" class="elsevierStylePara elsevierViewall">Correct patient selection is key to ensuring the success of botulinum toxin for chronic migraine. The benefits of OnabotA for chronic migraine are maintained over time. This treatment shows a good safety and tolerability profile. For the greatest benefits, it should be administered as early as possible in cases of refractory chronic migraine.</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Funding</span><p id="par0150" class="elsevierStylePara elsevierViewall">This study was funded by the Foundation of the College of Physicians of Segovia.</p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Conflicts of interest</span><p id="par0155" class="elsevierStylePara elsevierViewall">The authors have no conflicts of interest to declare.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:12 [ 0 => array:3 [ "identificador" => "xres1091976" "titulo" => "Abstract" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Objective" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Patients and methods" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Conclusion" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec1034970" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres1091975" "titulo" => "Resumen" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0025" "titulo" => "Objetivo" ] 1 => array:2 [ "identificador" => "abst0030" "titulo" => "Pacientes y métodos" ] 2 => array:2 [ "identificador" => "abst0035" "titulo" => "Resultados" ] 3 => array:2 [ "identificador" => "abst0040" "titulo" => "Conclusión" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec1034969" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:3 [ "identificador" => "sec0010" "titulo" => "Patients and methods" "secciones" => array:2 [ 0 => array:2 [ "identificador" => "sec0015" "titulo" => "Study design" ] 1 => array:2 [ "identificador" => "sec0020" "titulo" => "Statistical analysis" ] ] ] 6 => array:2 [ "identificador" => "sec0025" "titulo" => "Results" ] 7 => array:2 [ "identificador" => "sec0030" "titulo" => "Discussion" ] 8 => array:2 [ "identificador" => "sec0035" "titulo" => "Conclusion" ] 9 => array:2 [ "identificador" => "sec0040" "titulo" => "Funding" ] 10 => array:2 [ "identificador" => "sec0045" "titulo" => "Conflicts of interest" ] 11 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2016-06-22" "fechaAceptado" => "2016-09-08" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec1034970" "palabras" => array:3 [ 0 => "Chronic migraine" 1 => "OnabotulinumtoxinA" 2 => "Prospective study" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec1034969" "palabras" => array:3 [ 0 => "Migraña crónica" 1 => "Toxina botulínica A" 2 => "Estudio prospectivo" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:3 [ "titulo" => "Abstract" "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Objective</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">The purposes of this study were to describe our 16-month experience with onabotulinumtoxinA (OnabotA) for the treatment of chronic migraine (CM) in the Spanish province of Segovia, evaluate its benefits, and determine clinical markers of good response to treatment.</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Patients and methods</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Prospective study of patients with CM who received OnabotA for 16 months. The effectiveness of OnabotA was evaluated based on the reduction in the number of headache days, pain intensity, and side effects. We used two-way analysis of variance to assess the effects of treatment according to the time factor. We studied the correlation between treatment effects and other variables using a linear regression model to establish the clinical markers of good response to treatment.</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Results</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">We included 69 patients who met the diagnostic criteria for CM. Patients underwent an average of two infiltrations. Mean age was 43 years; 88.4% were women. The number of headache days and pain intensity decreased significantly (<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>.005); improvements remained over time. We found a negative correlation between the reduction in pain intensity and the number of treatments before OnabotA.</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusion</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">The beneficial effects of OnabotA for CM continue over time. OnabotA is a safe and well-tolerated treatment whose use for refractory CM should not be delayed since early treatment provides greater benefits.</p></span>" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Objective" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Patients and methods" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Conclusion" ] ] ] "es" => array:3 [ "titulo" => "Resumen" "resumen" => "<span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Objetivo</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Describir la experiencia con la administración de toxina botulínica tipo A (OnabotA) en el tratamiento de la migraña crónica (MC) en Segovia durante 16 meses, evaluar su beneficio y buscar marcadores clínicos que sirvan para predecir una mejor respuesta al tratamiento.</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Pacientes y métodos</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Estudio prospectivo de pacientes con MC que recibieron infiltraciones con OnabotA durante 16 meses. Se evaluó la eficacia de OnabotA comparando la reducción en el número de días de cefalea, en la intensidad y efectos adversos. Se comparó el efecto del tratamiento con el factor tiempo mediante un análisis de la varianza de dos vías (ANOVA). Se estudió la correlación del efecto del tratamiento con el resto de las variables mediante un modelo de regresión lineal para buscar marcadores clínicos que sirvan para predecir una mejor respuesta.</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Resultados</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Se incluyó a 69 pacientes que cumplían criterios de MC. Se les realizó una media de 2 infiltraciones. La edad media fue de 43 años, el 88,4% fueron mujeres. La frecuencia de los días de cefalea y su intensidad se redujeron de forma significativa (p<span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0,005) y esta mejoría se mantuvo a lo largo del tiempo. Se encontró una correlación negativa entre la reducción de la intensidad y el número de tratamientos previos a la administración de la toxina.</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Conclusión</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">El efecto beneficioso de la OnabotA en la MC se mantiene en el tiempo, siendo un tratamiento seguro y bien tolerado. No debe retrasarse su uso en MC refractaria, ya que su beneficio podría ser mayor cuanto antes se administre.</p></span>" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0025" "titulo" => "Objetivo" ] 1 => array:2 [ "identificador" => "abst0030" "titulo" => "Pacientes y métodos" ] 2 => array:2 [ "identificador" => "abst0035" "titulo" => "Resultados" ] 3 => array:2 [ "identificador" => "abst0040" "titulo" => "Conclusión" ] ] ] ] "NotaPie" => array:2 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0015">Please cite this article as: Castrillo Sanz A, Morollón Sánchez-Mateos N, Simonet Hernández C, Fernández Rodríguez B, Cerdán Santacruz D, Mendoza Rodríguez A, et al. Experiencia con toxina botulínica en la migraña crónica. Neurología. 2018;33:499–504.</p>" ] 1 => array:2 [ "etiqueta" => "☆☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0020">This study was presented as an oral communication at the 67th Annual Meeting of the Spanish Society of Neurology, 2015.</p>" ] ] "multimedia" => array:5 [ 0 => array:8 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at1" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Treatment \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Patients, no. (%)<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a> \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Beta blockers \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">17 (29.8) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Calcium channel blockers \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">15 (26.3) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Antiepileptics \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">30 (52.6) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Antidepressants \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">44 (77.2) \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1867232.png" ] ] ] "notaPie" => array:1 [ 0 => array:3 [ "identificador" => "tblfn0005" "etiqueta" => "a" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Some patients received more than one treatment.</p>" ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Distribution of preventive treatments received before OnabotA injection.</p>" ] ] 1 => array:8 [ "identificador" => "tbl0010" "etiqueta" => "Table 2" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at2" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:1 [ "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head " align="" valign="top" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">No. of days (mean<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>SD) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">95% CI \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Pain intensity (VAS score) (mean<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>SD) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">95% CI \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Baseline \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">20.6<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>8.5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">18.5-22.6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">8.1<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>1.3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">7.8-8.4 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">First injection \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">8.6<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>8.1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">6.6-10.5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">6.1<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>1.8 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">5.7-6.6 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Second injection \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">7.5<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>7.5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">5.4-9.6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">5.8<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>2.2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">5.2-6.4 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Third injection \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">7.8<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>6.6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">5.2-10.3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">6.1<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>1.6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">5.5-6.8 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Fourth injection \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">5.5<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>4.8 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2.7-8.3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">6.1<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>1.7 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">5.2-7.1 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1867235.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Number of headache days per month and pain intensity after each injection.</p>" ] ] 2 => array:8 [ "identificador" => "tbl0015" "etiqueta" => "Table 3" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at3" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head " align="" valign="top" scope="col"> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " colspan="2" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Treatment 1<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">a</span></a> (<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>69)</th><th class="td" title="table-head " colspan="2" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Treatment 2<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">a</span></a> (<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>50)</th><th class="td" title="table-head " colspan="2" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Treatment 3<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">a</span></a> (<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>28)</th></tr><tr title="table-row"><th class="td" title="table-head " align="" valign="top" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Difference between means (95% CI) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black"><span class="elsevierStyleItalic">P</span> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Difference between means (95% CI) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black"><span class="elsevierStyleItalic">P</span> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Difference between means (95% CI) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black"><span class="elsevierStyleItalic">P</span> \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">No. of days \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">–11.96 (–14.77 to –9.15) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top"><.006 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">–13.07 (–16.05 to –10.08) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top"><.006 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">–12.87 (–16.38 to –9.22) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top"><.006 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Pain intensity (VAS score) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">–1.98 (–2.52 to –1.45) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top"><.006 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">–2.33 (–3.01 to –1.64) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top"><.0060 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">–1.98 (–2.60 to –1.37) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top"><.006 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1867234.png" ] ] ] "notaPie" => array:1 [ 0 => array:3 [ "identificador" => "tblfn0010" "etiqueta" => "a" "nota" => "<p class="elsevierStyleNotepara" id="npar0010">Treatment 1: difference between baseline and first injection; Treatment 2: difference between baseline and second injection; Treatment 3: difference between baseline and third injection.</p>" ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Effect of treatment with OnabotA over time.</p>" ] ] 3 => array:8 [ "identificador" => "tbl0020" "etiqueta" => "Table 4" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at4" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:1 [ "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td-with-role" title="table-head ; entry_with_role_rowhead " align="left" valign="top" scope="col">Variable \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " colspan="3" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Decrease in the number of headache days per month</th></tr><tr title="table-row"><th class="td" title="table-head " align="" valign="top" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Slope \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">95% CI \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black"><span class="elsevierStyleItalic">P</span> \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Age \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">–0.01 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">–0.02 to 0.00 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">.1527 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">No. of previous treatments \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">–0.21 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">–0.58 to 0.14 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">.2305 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">No. of treatments with botulinum toxin \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.04 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">–0.09 to 0.17 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">.5868 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1867231.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">Correlation between the decrease in the number of headache days per month and the remaining variables.</p>" ] ] 4 => array:8 [ "identificador" => "tbl0025" "etiqueta" => "Table 5" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at5" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:1 [ "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td-with-role" title="table-head ; entry_with_role_rowhead " align="left" valign="top" scope="col">Variable \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " colspan="3" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Decrease in pain intensity</th></tr><tr title="table-row"><th class="td" title="table-head " align="" valign="top" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Slope \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">95% CI \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black"><span class="elsevierStyleItalic">P</span> \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Age \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.00 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">–0.01 to 0.00 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">.1531 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">No. of previous treatments \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">–0.20 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">–0.37 to –0.02 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">.0278 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">No. of treatments with botulinum toxin \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">–0.01 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">–0.08 to 0.05 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">.7460 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1867233.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">Correlation between the decrease in pain intensity and the remaining variables.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0015" "bibliografiaReferencia" => array:24 [ 0 => array:3 [ "identificador" => "bib0125" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Disability, HRQoL and resource use among chronic and episodic migraineurs: results from the International Burden of Migraine Study (IBMS)" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "A. Blumenfeld" 1 => "S. Varon" 2 => "T.K. Wilcox" 3 => "D.C. Buse" 4 => "A.K. Kawata" 5 => "A. Manack" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1177/0333102410381145" "Revista" => array:6 [ "tituloSerie" => "Cephalalgia" "fecha" => "2011" "volumen" => "31" "paginaInicial" => "301" "paginaFinal" => "315" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20813784" "web" => "Medline" ] ] ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib0130" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Headache Classification Committee of the International Headache Society (IHS). The international classification of headache disorders, 3rd edn (beta version)" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "J. Olesen" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1177/0333102413485658" "Revista" => array:6 [ "tituloSerie" => "Cephalalgia" "fecha" => "2013" "volumen" => "33" "paginaInicial" => "629" "paginaFinal" => "808" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23771276" "web" => "Medline" ] ] ] ] ] ] ] ] 2 => array:3 [ "identificador" => "bib0135" "etiqueta" => "3" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Chronic migraine prevalence, disability, and sociodemographic factors: results from the American Migraine Prevalence and Prevention Study" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "D.C. Buse" 1 => "A.N. Manack" 2 => "K.M. Fanning" 3 => "D. Serrano" 4 => "M.L. Reed" 5 => "C.C. 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| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 October | 17 | 5 | 22 |
| 2024 September | 38 | 15 | 53 |
| 2024 August | 38 | 5 | 43 |
| 2024 July | 25 | 6 | 31 |
| 2024 June | 32 | 7 | 39 |
| 2024 May | 35 | 14 | 49 |
| 2024 April | 30 | 14 | 44 |
| 2024 March | 46 | 15 | 61 |
| 2024 February | 33 | 11 | 44 |
| 2024 January | 44 | 10 | 54 |
| 2023 December | 52 | 28 | 80 |
| 2023 November | 52 | 15 | 67 |
| 2023 October | 80 | 40 | 120 |
| 2023 September | 58 | 20 | 78 |
| 2023 August | 41 | 10 | 51 |
| 2023 July | 38 | 14 | 52 |
| 2023 June | 49 | 19 | 68 |
| 2023 May | 62 | 9 | 71 |
| 2023 April | 44 | 13 | 57 |
| 2023 March | 48 | 21 | 69 |
| 2023 February | 41 | 35 | 76 |
| 2023 January | 36 | 24 | 60 |
| 2022 December | 27 | 7 | 34 |
| 2022 November | 27 | 12 | 39 |
| 2022 October | 36 | 8 | 44 |
| 2022 September | 29 | 24 | 53 |
| 2022 August | 52 | 12 | 64 |
| 2022 July | 73 | 8 | 81 |
| 2022 June | 24 | 11 | 35 |
| 2022 May | 34 | 11 | 45 |
| 2022 April | 43 | 11 | 54 |
| 2022 March | 41 | 5 | 46 |
| 2022 February | 23 | 6 | 29 |
| 2022 January | 40 | 10 | 50 |
| 2021 December | 33 | 12 | 45 |
| 2021 November | 42 | 10 | 52 |
| 2021 October | 58 | 14 | 72 |
| 2021 September | 42 | 11 | 53 |
| 2021 August | 25 | 12 | 37 |
| 2021 July | 15 | 13 | 28 |
| 2021 June | 15 | 9 | 24 |
| 2021 May | 27 | 12 | 39 |
| 2021 April | 95 | 48 | 143 |
| 2021 March | 65 | 20 | 85 |
| 2021 February | 55 | 17 | 72 |
| 2021 January | 39 | 12 | 51 |
| 2020 December | 31 | 16 | 47 |
| 2020 November | 25 | 18 | 43 |
| 2020 October | 41 | 19 | 60 |
| 2020 September | 19 | 15 | 34 |
| 2020 August | 34 | 6 | 40 |
| 2020 July | 27 | 12 | 39 |
| 2020 June | 23 | 21 | 44 |
| 2020 May | 37 | 31 | 68 |
| 2020 April | 26 | 9 | 35 |
| 2020 March | 42 | 9 | 51 |
| 2020 February | 23 | 13 | 36 |
| 2020 January | 27 | 9 | 36 |
| 2019 December | 22 | 5 | 27 |
| 2019 November | 34 | 9 | 43 |
| 2019 October | 14 | 9 | 23 |
| 2019 September | 25 | 11 | 36 |
| 2019 August | 12 | 5 | 17 |
| 2019 July | 23 | 10 | 33 |
| 2019 June | 106 | 14 | 120 |
| 2019 May | 84 | 9 | 93 |
| 2019 April | 59 | 14 | 73 |
| 2019 March | 13 | 5 | 18 |
| 2019 February | 26 | 15 | 41 |
| 2019 January | 17 | 13 | 30 |
| 2018 December | 20 | 14 | 34 |
| 2018 November | 28 | 19 | 47 |
| 2018 October | 30 | 10 | 40 |
| 2018 September | 6 | 3 | 9 |
| 2018 August | 2 | 1 | 3 |
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