Recomendaciones de la Asociación Colombiana de Neurología para el uso de anticuerpos monoclonales antiCGRP en la profilaxis de migraña / Recommendations on the use of the antiCGRP monoclonal antibodies for migraine prophylaxis on behalf of the Colombian Association of Neurology

RESUMEN INTRODUCCIÓN: El desarrollo de anticuerpos monoclonales (mAbs) contra el péptido relacionado con el gen de la calcitonina (CGRP) ha determinado una nueva era terapéutica en la profilaxis de migraña, demostrando su efectividad en pacientes con migraña episódica (ME) y migraña crónica (MC), con respuesta desde pacientes naïve hasta refractarios a múltiples medicamentos. La disminución del 50% de los ataques de migraña al mes (DMM) durante los primeros 3 meses de uso es el desenlace aproximado en el 50% de los pacientes que reciben esta terapia. OBJETIVO: Este consenso de la Asociación Colombiana de Neurología (ACN) tiene el objetivo de guiar la selección y uso racional de los mAbs antiCGRP en pacientes con ME y MC. MATERIALES Y MÉTODOS: El comité de cefalea de la ACN mediante la aplicación de la metodología Delphi y discusiones en reuniones posteriores desarrolló un documento en formato de consenso soportado en literatura y recomendaciones de expertos. RESULTADOS: Se obtuvieron respuestas de 14 expertos en cefalea sobre moléculas utilizadas en profilaxis de migraña, analizando su aplicabilidad en situaciones clínicas frecuentes. DISCUSIÓN: Los mAbs antiCGRP han demostrado efectividad con adecuado soporte fisiopatológico, considerando que son moléculas de alto precio en una enfermedad de alta prevalencia, existe la necesidad de guíar la selección del paciente que mejor puede beneficiarse de su administración CONCLUSIONES: Los mAbs antiCGRP están recomendados en pacientes con ME y MC que presentan falla terapéutica a otras moléculas profilácticas.

ABSTRACT INTRODUCTION: The development of monoclonal antibodies (mAbs) against Calcitonin Gene Related Peptide (CGRP) has determined a new therapeutic era in migraine prophylaxis, demonstrating its effectiveness in patients with episodic migraine (EM) and chronic migraine (CM), obtaining a response in naive patients and in those who are refractory to multiple medications. A 50% decrease in migraine attacks per month during the first 3 months of use is the approximate outcome in 50% of patients receiving this therapy. OBJECTIVE: This consensus from the Colombian Association of Neurology (ACN) has the objective of serving as a guide for the rational use of antiCGRP mAbs in patients with EM and CM. METHODS AND MATERIALS: The headache committee through the application of the Delphi methodology and discussions in subsequent meetings, develops this consensus, supported in the published literature and expert recommendations. RESULTS: Fourteen answers from headache experts were received regarding the use of drugs for migraine prophylaxis, analyzing their applicability in frequent clinical situations. DISCUSSION: AntiCGRP mAbs have proved their effectiveness with adequate pathophysiological support, but with a high price in a highly prevalent disease, there is then a need to select the patient who best benefits from this therapy. CONCLUSIONS: AntiCGRP mAbs are recommended in patients with EM and CM that have previously failed to other prophylactic drugs.

Guideline on the preventive treatment of chronic migraine, chronic tension type headache, hemicrania continua and new daily persistent headache on behalf of the Colombian Association of Neurology / Guía de la Asociación Colombiana de Neurología para el tratamiento preventivo de la migraña crónica, cefalea tipo tensión crónica, hemicránea continua y cefalea diaria persistente de novo

SUMMARY INTRODUCTION: Chronic daily headache is a high impact entity in the general population. Although chronic migraine and tension-type headache are the most frequent conditions, it is necessary to consider hemicrania continua and new daily persistent headache as part of the differential diagnoses to perform a correct therapeutic approach. OBJECTIVE: To make recommendations for the treatment of chronic daily headache of primary origin METHODOLOGY: The Colombian Association of Neurology, by consensus and Grade methodology (Grading of recommendations, assessment, development and evaluation), presents the recommendations for the preventive treatment of each of the entities of the daily chronic headache of primary origin group. RESULTS: For the treatment of chronic migraine, the Colombian Association of Neurology recommends onabotulinum toxin A, erenumab, topiramate, flunarizine, amitriptyline, and naratriptan. In chronic tension-type headache the recommended therapeutic options are amitriptyline, imipramine, venlafaxine and mirtazapine. Topiramate, melatonin, and celecoxib for the treatment of hemicrania continua. Options for new daily persistent headache include gabapentin and doxycycline. The recommendations for inpatient treatment of patients with chronic daily headache and the justifications for performing neural blockades as a therapeutic complement are also presented. CONCLUSION: The therapeutic recommendations for the treatment of chronic daily headache based on consensus methodology and Grade System are presented.

RESUMEN INTRODUCCIÓN: La cefalea crónica diaria es una entidad de alto impacto en la población general. Aunque la migraña crónica y la cefalea tipo tensión son las condiciones más frecuentes, es necesario considerar la hemicránea continua y la cefalea diaria persistente de novo como parte de los diagnósticos diferenciales para realizar un enfoque terapéutico correcto. OBJETIVO: Hacer recomendaciones para el tratamiento de la cefalea crónica diaria de origen primario METODOLOGÍA: La Asociación Colombiana de Neurología, mediante consenso y metodología GRADE (Grading of Reccomendations, Assesment, Development and Evaluation), presenta las recomendaciones para el tratamiento preventivo de cada una de las entidades del grupo de la cefalea crónica diaria de origen primario. RESULTADOS: Para el tratamiento de la migraña crónica, la Asociación Colombiana de Neurología recomienda onabotulinum toxina A, erenumab, galcanezumab, fremanezumab, topiramato, flunarizina, amitriptilina y naratriptan. En cefalea tipo tensional crónica las opciones terapéuticas recomendadas son amitriptilina, imipramina, venlafaxina y mirtazapina. Para el tratamiento de la hemicránea continua topiramato, melatonina y celecoxib. Las opciones para cefalea diaria persistente de novo incluyen gabapentin y doxiciclina. Se presentan adicionalmente las recomendaciones para el tratamiento intrahospitalario de los pacientes con cefalea crónica diaria y las justificaciones para la realización de bloqueos neurales como complemento terapéutico. CONCLUSIÓN: se presentan las recomendaciones terapéuticas para el tratamiento de la cefalea crónica diaria basado en metodología de consenso y sistema GRADE.

Enfoque del paciente con cefalea en tiempos de covid-19 / Approach to the patient with headache in times of COVID-19

RESUMEN Ante el número cada vez mayor de pacientes con covid-19 y los rápidos cambios que ha traído consigo la pandemia en los estilos de vida, se redactó el presente documento, con el objetivo de proveer una recomendación a los neurológos y médicos en general para el abordaje del paciente con cefalea. Inicialmente, se realiza el abordaje de la cefalea como uno de los síntomas del covid-19, revisando las series de casos y proponiendo posibles clasificaciones diagnósticas para explicar su presencia en estos pacientes. Posteriormente, se evaluará la cefalea secundaria a otros trastornos neurológicos también reportados en pacientes con covid-19 y los signos de alarma para realizar estudios complementarios. Por último se revisará como ha cambiado el seguimiento de los pacientes con cefalea primaria en medio de la pandemia, recomendaciones sobre ajustes que se deben hacer durante este tiempo en su manejo y formulación, y finalmente recomendaciones sobre interacciones en sus medicamentos en caso de enfermar por covid-19.

SUMMARY Given the increasing number of patients with COVID-19 and the rapid changes that the pandemic has brought about in lifestyles, this document was developed with the aim of providing a recommendation to neurologists and doctors in general for the approach of the patient with headache. Initially, the headache was treated as one of the symptoms of COVID-19, reviewing the case series and proposing possible diagnostic classifications to explain its presence in these patients. Subsequently, headache secondary to other neurological disorders also reported in patients with COVID-19 and the warning signs will be evaluated to carry out complementary studies. Finally, it will be reviewed how the follow-up of patients with primary headache in the midst of the pandemic has changed, recommendations on adjustments to be made during this time in its management and formulation, and finally recommendations on drug interactions in case of illness due to COVID-19.

Consenso de expertos de la Asociación Colombiana de Neurología parael tratamiento preventivo y agudo de la migraña / Expert consensus on the preventive and acute treatment of migraine on behalf of the Colombian Association of Neurology

La migraña es la cefalea primaria de mayor impacto en la población general; de acuerdo conla información local se calcula que al menos 3 millones de personas en Colombia padecen esta condición,conduciendo esta entidad a alta carga y discapacidad.Objetivo: Determinar información unificada respecto al tratamiento preventivo y agudo de los pacientescon migraña. Se incluye información del tratamiento de la migraña crónica y su asociación al uso excesivo deanalgésicos.Materiales y métodos: Consenso de expertos mediante metodología virtual Delphi en dos rondas con el grupototal y una con el grupo desarrollador. Se hizo una revisión de la literatura para obtener información destinadaal diseño de preguntas con relevancia clínica. Se incluyeron neurólogos de las principales regiones del país.Resultados: Se debe ofrecer tratamiento preventivo a los pacientes que sufren por lo menos 6 días al mes dedolor de cabeza por migraña durante 6 a 12 meses de acuerdo con las condiciones clínicas de cada paciente.Topiramato, ácido valproico/divalproato de sodio, metoprolol, propranolol, amitriptilina, y flunarizina sonsugeridos como medicamentos de primera línea.Conclusiones: Se obtienen recomendaciones y sugerencias del tratamiento agudo y preventivo de los pacientescon migraña. Se presentan recomendaciones para el tratamiento de casos refractarios y del uso excesivode analgésicos...

Migraine is the primary headache with the highest impact in the general population. Accordingto local information, about 3 million people in Colombia suffer from this neurological condition leading tohigh burden and disability.Objective: To provide uniform information regarding the acute and preventive treatment of patients withmigraine. Information about chronic migraine, medication overuse was considered.Materials and methods: Expert consensus by using online Delphi methodology. Three rounds were carriedout, the whole group participated in two of them and the developer group in the total number of rounds. Areview of the literature was conducted to obtain academic support to design questions with clinical relevance.Neurologists from the main Colombian regions were included...

Fisiopatología de la migraña / Pathophysiology of migraine

(AU)La migraña es una enfermedad neurobiológica. Diversas estructuras cerebrales participan en el procesamiento deldolor, con la presencia de fenómenos neuronales y bioquímicos que modulan la respuesta del sistema nervioso.A través de los estudios realizados se puede observar la presencia de diferentes elementos que participan en lageneración de la migraña; estos pueden ser estructurales (alteración de sustancia gris periacueductal y núcleos delrafé), genéticos, neuronales como la depresión cortical diseminada y la liberación de múltiples neurotransmisoresentre los que predominan el péptido relacionado con el gen de la calcitonina y la serotonina, que median diferentestipos de alteraciones durante el proceso de inflamación neurogénica, y cambios en funcionamiento de múltiplesáreas como sistema nervioso autónomo entre otras

Interpretation of mycobacterial antibodies in the cerebrospinal fluid of adults with tuberculous meningitis.

OBJECTIVE: Microbiological identification of Mycobacterium tuberculosis is insensitive and slow, and clinical distinction of tuberculous meningitis (TBM) from other subacute or chronic meningoenchephalitides (SACM) is difficult. Successful use of highly specific M. tuberculosis serological assays on cerebrospinal fluid has been reported, but their performance for diagnosis in a tuberculosis endemic country where they would be of most value is unclear. We sought to determine the biological basis for the uncertainty in interpretation of antibody detection in the CSF of TBM patients. METHODS: We identified prospectively 46 adults with SACM and explored the concordance between TBM diagnosis and detection of highly specific M. tuberculosis antibodies in CSF. The source of antibodies in CSF was explored by evaluating the correlation between antibody titres in CSF with those in serum, or with the albumin quotient. Intrathecal IgG synthesis was assessed by the IgG index. RESULTS: Positive antibody titres were more frequent among TBM patients (76%), but were also present in individuals with other SACM (59%). A positive correlation between antibody titres in CSF with those in serum, or with the albumin quotient, supported the leakage of antibodies from plasma to CSF through an increased blood-brain barrier permeability. Intrathecal IgG synthesis was only detected in 35% of the TBM cases. CONCLUSION: Plasma antibodies likely synthesized in response to previous tuberculosis infections were a major source of mycobacterial antibodies in CSF due to leakage through an impaired blood-brain barrier. Interpretation of mycobacterial antibodies in CSF of adults for TBM, however specific, must take into account the contribution of antibodies from plasma, and hence, has questionable use for diagnosis.

Tinnitus in migraine: an allodynic symptom secondary to abnormal cortical functioning?

Tinnitus is not a common auditory symptom in migraine. Recent research suggests that central sensitization (CS) develops in most migraneurs during the course of a migraine attack. Herein we describe 3 patients with primary headache disorders and tinnitus as their chief complaint, in whom the tinnitus intensity consistently increased during headache attacks. In headache patients, tinnitus may be related to spontaneous and aberrant neural activity at any level along the auditory axis, with abnormal reorganization processes in the auditory cortex following hearing receptor damage. We hypothesize that the tinnitus intensity increase could be an allodynic symptom related to CS, or alternatively could be associated with cortical hyperexcitability.

Patterns of use of triptans and reasons for switching them in a tertiary care migraine population.

OBJECTIVE: To assess the reasons for switching triptans within migraine patients presenting to a specialty clinic. DESIGN AND METHODS: We reviewed data of migraineurs who (1) were currently using a triptan as acute treatment medication for migraine, and (2) had previously used at least one other triptan, or a different triptan formulation. All subjects were followed for at least 1 year. For every triptan/formulation used, the reasons for discontinuation were obtained. RESULTS: Our sample consisted of 386 patients, 339 of whom (87.8%) were females. Sumatriptan was first used by 349 (90.4%); zolmitriptan, by 238 (61.5%); rizatriptan, by 195 (50.5%); naratriptan, by 137 (35.4%); and almotriptan, by 31 (8.0%). Almotriptan was excluded from this analysis because of our small sample. We found significant differences among those who wanted to try another triptan to see if it would be better in those who first used sumatriptan 25 mg, compared to those first using sumatriptan 50 mg (P = .01), sumatriptan 100 mg (P < .001), sumatriptan nasal spray (NS) (P < .001), sumatriptan subcutaneous (SC) (P < .001), zolmitriptan 5 mg (P < .001), rizatriptan 10 mg (P < .001), and naratriptan (P = .001). Patients using rizatriptan, sumatriptan NS, and sumatriptan SC had significantly lower rates of reporting this answer. Subjects first using naratriptan were less likely to report recurrence than those using sumatriptan 25 mg (P = .004), sumatriptan 50 mg (P = .0005), sumatriptan 100 mg (P = .003), zolmitriptan (P = .02), and rizatriptan (P = .006). Incomplete relief was more frequently reported by those first using sumatriptan 25 mg and naratriptan. Inconsistency was a reason for switching in those initially using sumatriptan NS, sumatriptan 25 mg, and naratriptan and less frequently reported in those using zolmitriptan and sumatriptan SC. Side effects were major factors for those first using sumatriptan 100 mg, NS, and SC, and less for those using naratriptan and sumatriptan 25 mg. From those subjects that initially used sumatriptan SC and were switched to a different triptan or formulation, 19.5% returned to sumatriptan SC; for the other triptans/formulations, the percentages were: sumatriptan 25 mg, 7.8%; sumatriptan 50 mg or 100 mg, 42.3%; sumatriptan NS, 17.7%; zolmitriptan, 17.6%; rizatriptan, 16.5%; naratriptan, 9.4%. For those who used more than three triptans/formulations, the last triptan used was: sumatriptan, 29.5%; zolmitriptan, 31.8%; rizatriptan, 25.0%; naratriptan, 12.5%. CONCLUSIONS: A variety of treatment attributes are important in determining the reasons involved in switching a triptan. To assess this attributes can provide additional information to supplement the traditional tests of efficacy provided by randomized clinical trials.

Naratriptan in the preventive treatment of refractory chronic migraine: a review of 27 cases.

OBJECTIVE: To review the efficacy of naratriptan as preventive treatment in 27 patients with chronic migraine refractory to other commonly used preventive therapies. BACKGROUND: The treatment of chronic migraine often poses a major challenge to the clinician. Even when given expert care, patients with chronic migraine may continue to have daily or near-daily headaches. METHODS: Clinical records and headache calendars were reviewed of 27 patients fulfilling the following inclusion criteria: (1) aged 18 to 65 years; (2) diagnosis of chronic migraine (formerly transformed migraine), according to the criteria proposed by Silberstein et al; (3) previous failure of at least 4 preventive medications prescribed as part of a management program that included nonpharmacological measures, preventive medication, acute care medication, and detoxification from overused medication; and (4) have used daily naratriptan for no less than 2 consecutive months. The dose of naratriptan prescribed was 2.5 mg twice daily. We considered the following outcomes: (1) frequency of headache, (2) intensity of pain, (3) number of days per month with severe headache, (4) headache index (frequency times intensity), and (5) proportion of patients who reverted to an episodic pattern of pain after 6 months of treatment. RESULTS: There was a statistically significant reduction in the frequency of headache days 2 months (15.3 days versus 24.1 days at baseline, P<.001), 6 months (9.1 days, P<.001), and 1 year (7.3 days, P<.001) after daily treatment with naratriptan was initiated. There was also a statistically significant reduction in the number of days per month of severe pain at 1 month (5.6 days versus 12.5 days at baseline, P<.01), 2 months (5.7 days, P<.01), 6 months (2.8 days, P<.01), and 1 year (2.6 days, P<.01). Similarly, there was a statistically significant reduction in the headache index at 2 months (33 versus 56.4 at baseline, P<.001), 6 months (19.5, P<.001), and 1 year (17.2, P<.001). Of the 20 patients who continued to use naratriptan daily for at least 6 months, 13 (65%) reverted to an episodic pattern of pain (migraine). At 1 year, 11 (55%) still continued to experience episodic headache, 1 (5%) relapsed to chronic migraine, and 2 (10%) were lost to follow-up. No patients had intolerability to naratriptan during the treatment period, and no one stopped treatment due to adverse events. CONCLUSIONS: Naratriptan may have a role in the preventive treatment of intractable chronic migraine. Prospective, controlled studies should be considered.

Similar diagnostic performance for neurocysticercosis of three glycoprotein preparations from Taenia solium metacestodes.

The detection of antibodies to Taenia solium metacestodes is very important in the differential diagnosis of neurocysticercosis (NCC). In this study, an electroimmunotransfer blot (EITB) assay that uses an elaborate protocol with metacestode glycoproteins as antigens was compared with two other Western blots that use glycoproteins obtained using simpler methods, including an eluate from a lectin column, or the vesicular fluid (VF) of the parasite. The concordance between the three assays was 91% in patients with active NCC and 100% in patients with suspected NCC and previous documentation of negative serology. The specificities for the Western blots and the EITB assay were 98% and 100%, respectively (98% concordance). These data suggest that the simplest of these immunoassays, the one that uses the VF of T. solium metacestodes in a Western blot format, can be reliably used for the serologic diagnosis of NCC in developing countries where access to the EITB assay is difficult.

Neurosífilis en el Hospital San Vicente de Paul de Medellin: nuevos aspectos clínicos / Neurosyphilis in San Vicente de Paul Hospital (Medellin, Colombia): new clinical features

El objetivo del trabajo fue presentar las características clínicas de la neurosifilis en nuestros días. El método fue la revisión de historias clínicas de los pacientes con diagnóstico de neurosifilis. Se obtuvieron 25 pacientes, 21 hombres y 4 mujeres, con una edad promedio de 40 años. La forma clínica más frecuente fue meningovascular 28/100, seguida de parálisis general progresiva y neurosífilis aséptica 16/100, meningomielitis 12/100, meningitis aguda 8/100, atrofia óptica 8/100, meningovascular espinal 8/100, amitrófia sifilítica 8/100, neuropatía craneana 8/100, síndrome convulsivo 8/100 y tabes dorsal en 4/100. La forma meningovascular continua predominando en la presentación clínica de la sífilis. La presencia de alteraciones del LCR en pacientes con VIH, hace necesaria la realización de pruebas treponémicas para confirmar el diagnóstico

Malaria cerebral y vasculomielinopatía diseminada: presentación de un caso / Cerebral malaria: presentation of one case

Se presenta una paciente con malaria por Plasmodium falciparum, con un episodio de encefalopatía; se analizan los hallazgos clínicos y radiológicos y se discute, recuperando lo postulado por G. Toro y G. Roman, que la fisiopatología de las manifestaciones encefalopáticas pueda corresponder a una alteración de la unión vasculomielínica