Clinical practice patterns in multiple sclerosis management: Mexican consensus recommendations.

BACKGROUND: Multiple sclerosis affects more than 2 million people. Clinical decisions are performed under evidence-based medicine. The appearance of new disease-modifying therapies and changes in diagnostic criteria complicates the decision-making process in clinical practice. OBJECTIVES: To characterize the criteria for radiologically isolated syndrome (RIS), clinically isolated syndrome (CIS), and relapsing-remitting multiple sclerosis (RRMS) by Mexican neurologists in a real-world setting. METHODS: A two-round modified Delphi method (RAND/UCLA) was applied. RESULTS: In RIS, LP, spinal cord MRI and VEP should be included in diagnostic testing; DMT initiation is not necessary. A follow-up MRI within 3 months are recommended. In CIS, corticosteroid therapy should be initiated at first relapse; both simple and Gd-enhanced MRI is mandatory. LP, selective blood tests, and NMO-IgG/AQP4 antibodies should be performed as complementary. IFN beta or GA were the most suitable DMTs for treating high-risk CIS. Patients with RRMS should begin with DMT at diagnosis, include a follow-up MRI if a patient had 2 relapses within 6 months. GA and oral DMTs are the most eligible DMTs for mild RRMS. Monoclonal antibodies-based therapy is chosen when disability is present. Radiological criteria for switching DMT included >1 Gd+ lesion and >2 new T2 lesions. CONCLUSIONS: Although many coincidences, there are still many hollows in the medical attention of MS in Mexico. This consensus recommendation could be helpful to implement better evidence-based recommendations and guidelines in a real-world setting.

Native American ancestry significantly contributes to neuromyelitis optica susceptibility in the admixed Mexican population.

Neuromyelitis Optica (NMO) is an autoimmune disease with a higher prevalence in non-European populations. Because the Mexican population resulted from the admixture between mainly Native American and European populations, we used genome-wide microarray, HLA high-resolution typing and AQP4 gene sequencing data to analyze genetic ancestry and to seek genetic variants conferring NMO susceptibility in admixed Mexican patients. A total of 164 Mexican NMO patients and 1,208 controls were included. On average, NMO patients had a higher proportion of Native American ancestry than controls (68.1% vs 58.6%; p = 5 × 10-6). GWAS identified a HLA region associated with NMO, led by rs9272219 (OR = 2.48, P = 8 × 10-10). Class II HLA alleles HLA-DQB1*03:01, -DRB1*08:02, -DRB1*16:02, -DRB1*14:06 and -DQB1*04:02 showed the most significant associations with NMO risk. Local ancestry estimates suggest that all the NMO-associated alleles within the HLA region are of Native American origin. No novel or missense variants in the AQP4 gene were found in Mexican patients with NMO or multiple sclerosis. To our knowledge, this is the first study supporting the notion that Native American ancestry significantly contributes to NMO susceptibility in an admixed population, and is consistent with differences in NMO epidemiology in Mexico and Latin America.

Comparación de los espectros de neuromielitis óptica según el seroestado del anticuerpo AQP4 en un centro de referencia mexicano / Comparison of neuromyelitis optica spectra according to AQP4 antibody serostatus in a Mexican referral centre

Introducción. Estudios recientes describen que los pacientes con neuromielitis óptica (NMO) o trastornos del espectro de NMO seronegativos exhiben características clínicas diferentes a los pacientes seropositivos al anticuerpo acuaporina-4 (AQP4). Objetivo. Analizar las características clínicas y paraclínicas de pacientes con NMO según el estado sérico del anticuerpo AQP4. Pacientes y métodos. Estudio retrospectivo de 100 pacientes con NMO que cumplían los criterios de Wingerchuk: 70 presentaron positividad al anticuerpo AQP4 y 30 fueron seronegativos. Resultados. Un 70% de los sujetos cumplió los criterios para la NMO, y un 30%, para los trastornos del espectro de NMO. Los pacientes seropositivos presentaron mayor discapacidad en las puntuaciones de la escala de la Asociación Americana de Lesión de la Medula Espinal (ASIA) y la escala ampliada del estado de discapacidad (p = 0,034 y 0,004, respectivamente) comparados con los seronegativos durante el seguimiento; en este mismo grupo hubo mayor afectación visual (p = 0,02), mayor número de recaídas (p = 0,008) y mayor número de segmentos medulares afectados (p = 0,003). Conclusión. Este estudio proporciona una visión general de las características clínicas y paraclínicas de los pacientes con NMO según el seroestado del anticuerpo AQP4. Los pacientes seropositivos al anticuerpo AQP4 presentan mayor afectación clínica e imaginológica (AU)

Introduction. Recent studies report that patients with neuromyelitis optica (NMO) or seropositive NMO spectra disorders display clinical characteristics that are different from those of patients who are seropositive for the aquaporin-4 (AQP4) antibody. Aim. To analyse the clinical and paraclinical characteristics of patients with NMO according to their serum AQP4 status. Patients and methods. We conducted a retrospective study of 100 patients with NMO who fulfilled the Wingerchuk criteria: 70 were positive for the AQP4 antibody and 30 were seronegative. Results. 70% of the subjects met the criteria for NMO, and 30% met criteria for NMO spectra disorders. The seropositive patients presented greater disability in the scores on the American Spinal Injury Association scale (ASIA) and the Expanded Disability Status Scale (p = 0.034 and 0.004, respectively) compared to seronegatives during the follow-up; in this same group there was greater visual involvement (p = 0.02), a higher number of relapses (p = 0.008) and a greater number of spinal segments involved (p = 0.003). Conclusion. This study provides an overview of the clinical and paraclinical characteristics of patients with NMO according to the AQP4 antibody serostatus. Patients who are seropositive for the AQP4 antibody present greater clinical and imaging Involvement (AU)

Síntomas depresivos inducidos por el retiro de benzodiacepinas en el trastorno esquizoafectivo. Reporte de un caso / Depressive symptoms induced by benzodiazepine withdrawal in schizoaffective disorder. Case report

Resumen Introducción: Dentro del espectro de las enfermedades psiquiátricas, una de las más complejas es el trastorno esquizoafectivo debido al reto diagnóstico y al manejo psicofarmacológico. Esta enfermedad combina síntomas cardinales de la esquizofrenia con síntomas de trastornos del afecto. El tratamiento se enfoca entonces a mejorar los síntomas psicóticos y regular el estado de ánimo. Dentro de los fármacos que se utilizan se encuentran las benzodiacepinas, que deben retirarse gradualmente para evitar recaídas o síntomas de abstinencia. En este reporte comentamos el caso de una paciente que después del retiro gradual hasta la suspensión de clonazepam presentó síntomas depresivos que remitieron tras la reinstalación del fármaco. Reporte del caso: Mujer de 31 años de edad sin antecedentes de importancia para su padecimiento actual. Inició con síntomas psicóticos que requirieron hospitalización, donde se agregaron síntomas maniatiformes y se integró el diagnostico de episodio maniaco con síntomas psicóticos. Se manejó con un antipsicótico, estabilizador del estado de ánimo y benzodiacepinas, con lo que sus síntomas remitieron. A los dos años presentó un cuadro psicótico sin síntomas afectivos y se diagnosticó como trastorno esquizoafectivo según el DSM V. Por su mejoría se disminuyeron los fármacos de forma gradual. Tras la suspensión del clonazepam, la paciente presentó síntomas depresivos que remitieron al reinstalar el fármaco. Discusión: La aparición súbita de síntomas depresivos se consideró como una posible recaída dada la patología de base. Estrictamente hablando, la paciente no cumplía criterios para diagnosticar un síndrome de abstinencia a benzodiacepinas. En la literatura se reporta que en algunos casos los síntomas depresivos pueden ser parte de este espectro, sin embargo no se especifica ni temporalidad ni alguna otra característica relevante. Tras el reinicio del fármaco a la dosis mínima que utilizaba la paciente, en menos de dos semanas se logró la remisión total de un episodio que cumplía los criterios diagnósticos para un trastorno depresivo mayor. Esto nos permitió establecer una relación directa entre la suspensión del clonazepam y la aparición de dichos síntomas. Conclusiones: A pesar de que el manejo dependerá de las características de cada paciente y las preferencias de su médico, vale la pena tener en mente la aparición de síntomas poco usuales asociados con el uso de los fármacos aun a pesar de seguir los lineamientos establecidos para el cambio y suspensión, en este caso, de las benzodiacepinas.

Abstract Introduction: Within the spectrum of psychiatric illnesses one of the most complex is the schizoaffective disorder due to the fact that both, its diagnosis and pharmacological management are challenging. This disease combines cardinal symptoms of schizophrenia and mood disorders symptoms. The aim of the treatment focuses on improving both psychotic symptoms and mood stabilization. Benzodiazepines are frequently used, and should be gradually reduced in order to prevent either a relapse or withdrawal symptoms. Here, we report the case of a 31-year-old female patient that after a gradual reduction of benzodiazepines and the suspension of clonazepam developed depressive symptoms, which subsided after the drug reinstatement. Case report: A 31-year-old female with no relevant past medical history developed psychotic symptoms that required hospitalization. Maniac symptoms appeared and therefore, the diagnosis was a manic episode with psychotic symptoms. Antipsychotic drugs, a mood stabilizer and benzodiazepines were the treatment used and the patient showed clinical improvement. She was free of clinical manifestations for two years, until the patient presented a psychotic episode without mood symptoms; therefore she was diagnosed with schizoaffective disorder according to the DSM V criteria. After clinical improvement drugs were decreased gradually. Following the suspension of clonazepam the patient had depressive symptoms that disappeared after the reinstatement of the drug. Discussion: The sudden appearance of depressive symptoms was considered as a possible relapse linked to the underlying disease. Strictly speaking, the patient did not meet the criteria for benzodiazepine withdrawal syndrome. The literature reports that in some cases depressive symptoms may be part of this spectrum, however neither a temporality nor any other relevant characteristics were specified. After restarting the drug at the lowest dose that the patient used, total remission of the major depressive disorder was achieved in less than two weeks. This allowed us to establish, at our discretion, a direct link between the suspension of clonazepam and the appearance of these symptoms. Conclusion: Although the management depends on the characteristics of each patient and the physician preferences, it is worth keeping in mind the possibility of unusual symptoms that may appear even by following the correct guidelines established for a correct decrease doses and the suspension of benzodiazepines.