Spontaneous convexity subarachnoid haemorrhage: Clinical series of 3 patients with associated cerebral amyloid angiopathy. / Hemorragia subaracnoidea espontánea de la convexidad cerebral: una serie clínica de 3 pacientes asociada con angiopatía amiloide cerebral.

INTRODUCTION: Convexity subarachnoid haemorrhage (cSAH) is a rare type of spontaneous, non-traumatic, and nonaneurysmal SAH characterised by blood collections in one or more cortical sulci in the convexity of the brain; the aetiology varies. We report a clinical case series of 3 patients with cSAH associated with probable cerebral amyloid angiopathy (CAA) who presented with focal sensory seizures and responded well to corticosteroid treatment. PATIENTS: Case 1 was a 67-year-old man reporting right-sided paroxysmal sensory episodes with Jacksonian progression, cheiro-oral symptoms, and motor dysphasia. Case 2 was a 79-year-old man reporting left-sided paroxysmal episodes with cheiro-oral signs and dysarthria. Case 3 was a 71-year-old woman also reporting recurrent left cheiro-oral signs and dysarthria. None of the patients had headache or clinical dementia. Aneurysms were ruled out using MR angiography. RESULTS: Brain CT scan detected an isolated hyperintensity in a sulcus of the frontal convexity; brain gradient echo T2-weighted MRI sequences showed meningeal haemosiderosis and microbleeds. However, no atrophy was identified in medial temporal lobes including the hippocampal formation. All patients had low levels of beta-amyloid in CSF, low values on the Hulstaert index and high levels of phosphorylated tau protein. Patients were initially treated with prednisone and levetiracetam, but symptoms recurred in 2 patients after prednisone was discontinued. CONCLUSIONS: We present a series of 3 patients with cSAH associated with CAA, characterised by a stereotypical syndrome responding well to corticoid treatment; there were no cases of headache or clinical dementia.

[Epidemiology of myasthenia gravis in the Iberian Peninsula and Latin America]. / Epidemiología de la miastenia grave en la península ibérica y Latinoamérica.

INTRODUCTION: Although today we live in a globalised world, the ties established between the Iberian Peninsula and the countries of Latin America are particularly strong, with important migratory flows. This connection may condition the development of diseases that involve a genetic influence, which may in turn be modulated by various environmental factors. The aim of this review is to determine the descriptive epidemiology of myasthenia gravis in the Iberian Peninsula and in Latin America. DEVELOPMENT: A literature search was conducted in Medline, LILACS and Google Scholar for the different countries of interest using the terms 'prevalence', 'incidence', 'epidemiology' and 'myasthenia gravis'. The methodology and quality were reviewed, and descriptive data about the study population as well as data on prevalence were extracted. CONCLUSIONS: Many countries lack epidemiological studies on myasthenia gravis and in others the data reported focus on one referral hospital, making it difficult to compare prevalence between countries. In the Iberian Peninsula, the prevalence is consistently above 100 cases x 106 inhabitants, the highest figures being found in the area of Osona (Barcelona) and in the province of Ourense. In Latin America, much lower prevalence figures are reported, generally below 100 x 106 inhabitants. There is a predominance of females in the early-onset forms (<50 years) and a clear increase in prevalence in the elderly population, especially in the very late onset forms (>65 years), where it is more frequent in men.

TITLE: Epidemiología de la miastenia grave en la península ibérica y Latinoamérica.Introducción. Aunque hoy en día vivimos en un mundo globalizado, los vínculos establecidos entre la península ibérica y los países de Latinoamérica son especialmente fuertes y con importantes flujos migratorios. Esta conexión puede condicionar la presentación de enfermedades que reconozcan una influencia genética, la cual puede ser modulada por diversos factores medioambientales. El objetivo de esta revisión es conocer la epidemiología descriptiva de la miastenia grave en la península ibérica y en Latinoamérica. Desarrollo. Se realizó una búsqueda bibliográfica en Medline, en LILACS y en Google Scholar para los diferentes países de interés con los términos 'prevalence', 'incidence', 'epidemiology' y 'myasthenia gravis'. Se revisó la metodología y la calidad, y se extrajeron datos descriptivos de la población estudiada, así como los datos de prevalencia. Conclusiones. Muchos países carecen de estudios epidemiológicos sobre la miastenia grave, y en otros, los datos comunicados se centran en un hospital de referencia, lo que hace difícil la comparación de la prevalencia entre los diferentes países. En la península ibérica, la prevalencia es constantemente superior a 100 casos × 106 habitantes, con las cifras más altas correspondientes a la comarca de Osona (Barcelona) y a la provincia de Ourense. En Latinoamérica se registran cifras mucho menores de prevalencia, generalmente inferiores a 100 × 106 habitantes. Se constata un predominio femenino en las formas de inicio precoz (<50 años) y un claro aumento de la prevalencia en la población anciana, sobre todo en las formas de inicio muy tardío (>65 años), en las que es más frecuente en los varones.

Alemtuzumab treatment in real clinical practice: Experience in a multicenter cohort.

BACKGROUND: Alemtuzumab is a highly effective treatment for relapsing remitting multiple sclerosis (RRMS), but in recent years safety-related concerns had emerged due to description of novel serious side effects not registered in CARE-MS I and CARE-MS II phase 3 studies, nor in TOPAZ extension study. Data about alemtuzumab use in real clinical practice are limited and based mainly on retrospective studies with small sample sizes. Therefore, more information about effectiveness and safety of alemtuzumab in this context is needed. METHODS: A multicenter observational prospective study to investigate effectivity and safety of alemtuzumab in a real-world setting was performed. Primary endpoints were the change in annualized relapse rate (ARR), and in disability measured by EDSS score. Secondary endpoints were the cumulative probability of confirmed 6-month disability improvement and worsening. Disability worsening and disability improvement were considered when the EDSS score was increased or decreased, respectively, in 1 point if baseline EDSS score was <5.0, or in 0.5 point if baseline EDSS score was ≥5.5, confirmed over 6 months. Other secondary endpoint was the proportion of patients who achieved NEDA-3 status (absence of clinical relapses, disability EDSS progression, and MRI disease activity as depicted by new/enlarging T2 lesions or Gadolinium enhancing T1 lesions). Adverse events also were recorded. RESULTS: A total of 195 RRMS patients (70% female) who started alemtuzumab treatment were included. Mean of follow-up was 2.38 years. Alemtuzumab significantly reduced the annualized relapse rate from baseline with risk reductions of 86%, 83.5%, and 84%, at 12, 24, and 36 months of follow-up respectively (Friedman test, p-value < 0.05 for all comparisons). Alemtuzumab also significantly reduced EDSS score over one and two years after starting alemtuzumab treatment (Friedman test, p-value<0.001 for both comparisons). A high proportion of patients presented confirmed 6-month stability or disability improvement (92%, 82%, and 79%, over 1, 2 and 3 years of follow-up respectively). The proportion of patients who retained NEDA-3 status at 12, 24 and 36 months were 61%, 49%, and 42%, respectively. Baseline characteristics associated with a lower probability of achieving NEDA-3 were younger age, sex female, high ARR, elevated number of previous treatments, and switch from a second line therapy. Infusion related reactions were the most frequent adverse event observed. The most common infections were urinary tract infections (50%), and upper respiratory tract infections (19%) over the 3 years of follow- up. Secondary thyroid autoimmunity was developed in 18.5% of patients. CONCLUSION: Alemtuzumab has demonstrated in real clinical practice high effectiveness in controlling multiple sclerosis activity, and no unexpected adverse events were observed.

Epidemiology of myasthenia gravis in the province of Ourense (Galicia, Spain).

INTRODUCTION: Myasthenia gravis (MG) is an autoimmune disease affecting nerve transmission at the level of the neuromuscular junction, and typically causes fluctuating muscle weakness. Epidemiological studies show an increase in MG prevalence, particularly among the older population. OBJECTIVE: We performed a retrospective epidemiological study to determine the incidence and prevalence of MG in the province of Ourense (Galicia, Spain), characterised by population ageing. MATERIAL AND METHODS: Patients were selected from our clinical neuromuscular diseases database by searching for patients with an active prescription for pyridostigmine bromide. Incidence was estimated for the period 2009-2018. We calculated prevalence at 31/12/2018. According to census data for the province of Ourense, the population on 1/1/2019 was 307 651, of whom 96 544 (31.4%) were aged ≥ 65 years. RESULTS: We identified 80 cases of MG, with a prevalence rate of 260 cases/1 000 000 population (95% CI, 202.7-316.4), rising to 517.9/1 000 000 population in those aged ≥ 65 (95% CI, 363.2-672.9). Cumulative incidence in the study period was 15.4 cases per 1 000 000 person-years. Early onset (≤ 50 years) was recorded in 29.1% of cases. CONCLUSION: The prevalence of MG in our health district is one of the highest published figures, and the disease is highly prevalent in the older population.

[Clinical and radiological effectiveness of natalizumab extended dosage interval in patients with relapsing multiple sclerosis]. / Efectividad clínica y radiológica del intervalo extendido de dosis con natalizumab en pacientes con esclerosis múltiple recurrente.

INTRODUCTION: Natalizumab (NTZ) is a very effective treatment approved for highly active multiple sclerosis. The main risk of treatment with NTZ is the possibility of developing progressive multifocal leukoencephalopathy, which is related to JC virus positivity and the number of NTZ infusions. This risk decreases with the extended dosage interval (EDI), which involves 9 or fewer infusions/year. However, it is a matter of controversy as to whether EDI remains effective in reducing recurrences and the presence of new lesions in magnetic resonance imaging (MRI). PATIENTS AND METHODS: A prospective observational study was conducted from 1 April 2019 to 30 June 2021, following up patients on NTZ treatment who switched to EDI. Patients should have at least one MRI six months after the start of EDI. The presence of attacks or MRI activity (new lesions in T2) during the EDI was recorded. RESULTS: Twenty-three patients with a mean age of 43.5 ± 9.4 years were included. The median number of NTZ infusions was 68 (minimum, 25; maximum, 127). The median interval between the start of the EDI and the last MRI was 14 months (minimum, 6; maximum, 25), and 23 months from the last medical follow-up visit (minimum, 7; maximum, 28). Two patients (8.7%) presented with attacks and two others (8.7%) showed MRI activity. CONCLUSIONS: EDI with NTZ maintains high clinical and activity effectiveness in MRI.

TITLE: Efectividad clínica y radiológica del intervalo extendido de dosis con natalizumab en pacientes con esclerosis múltiple recurrente.Introducción. El natalizumab (NTZ) es un tratamiento de alta eficacia aprobado para la esclerosis múltiple de alta actividad. El principal riesgo del tratamiento con NTZ es la posibilidad de desarrollar una leucoencefalopatía multifocal progresiva, que está en relación con la positividad al virus JC y el número de infusiones del NTZ. Este riesgo disminuye con el intervalo extendido de dosis (IED), lo que supone 9 infusiones/año o menos. Sin embargo, es materia de controversia si el IED mantiene la efectividad sobre la reducción de las recurrencias y la presencia de nuevas lesiones en la resonancia magnética (RM). Pacientes y métodos. Se ha realizado un estudio observacional prospectivo desde el 1 de abril de 2019 hasta el 30 de junio de 2021, siguiendo a los pacientes en tratamiento con NTZ que se pasaron al IED. Los pacientes deberían tener al menos una RM a los seis meses del inicio del IED. Se registró la presencia de brotes o de actividad en la RM (nuevas lesiones en T2) durante el IED. Resultados. Se incluyó a 23 pacientes con una media de edad de 43,5 ± 9,4 años. La mediana de infusiones de NTZ fue de 68 (mínimo, 25; máximo, 127). La mediana del intervalo entre el inicio del IED y la última RM fue de 14 meses (mínimo, 6; máximo, 25), y de 23 meses respecto a la última visita de seguimiento médico (mínimo, 7; máximo, 28). Dos pacientes (8,7%) presentaron brotes y otros dos pacientes (8,7%) presentaron actividad en la RM. Conclusiones. El IED de NTZ mantiene una alta efectividad clínica y de actividad en la RM.

[The prevalence of multiple sclerosis in the city of Ourense, Galicia, in the north-west of the Iberian Peninsula]. / Prevalencia de la esclerosis múltiple en la ciudad de Ourense, Galicia, noroeste de la Península Ibérica.

INTRODUCTION: Multiple sclerosis is an inflammatory neurodegenerative disease of the central nervous system, which mainly affects young people of working and reproductive age, and represents the first cause of non-traumatic disability in this age group of the population. A north-south latitude gradient is recognised, with prevalence rates increasing as we move away from the equator. This gradient probably represents the genetic predisposition transmitted from the Scandinavian regions through the Viking invasions and could presuppose an influence of the vitamin D deficit related to a lower number of hours of sunshine per year. AIMS: To determine the prevalence and incidence of multiple sclerosis in the city of Ourense, Galicia. PATIENTS AND METHODS: The latitude coordinate of the city of Ourense is 42° 34' N. A retrospective epidemiological study covering the period from 2002 to 2016 was conducted. The prevalence date was 31 December 2016. According to the latest census, the population of the city of Ourense was 105,892 on 1 January 2016. RESULTS: Altogether, 195 cases were recorded, representing a prevalence of 184.1 cases/100,000 inhabitants. In the period 2002-2016, 127 cases of multiple sclerosis were diagnosed, representing an average incidence of 7.86 cases/100,000 inhabitants/year. CONCLUSION: The city of Ourense has the highest prevalence rate of multiple sclerosis of those studied to date in the Iberian Peninsula, with a figure that brings it closer to the data reported in more northern areas under Nordic and Anglo-American influence.

TITLE: Prevalencia de la esclerosis múltiple en la ciudad de Ourense, Galicia, noroeste de la Península Ibérica.Introducción. La esclerosis múltiple es una enfermedad inflamatoria y neurodegenerativa del sistema nervioso central, que afecta fundamentalmente a personas jóvenes en edad laboral y reproductiva, y que representa la primera causa de discapacidad no traumática en este rango etario de la población. Se reconoce un gradiente de latitud norte-sur, con un aumento de las tasas de prevalencia a medida que nos alejamos del ecuador. Este gradiente probablemente representa la predisposición genética transmitida desde las regiones escandinavas a través de las invasiones vikingas y podría presuponer una influencia del déficit de vitamina D en relación con un menor número de horas de sol anuales. Objetivo. Determinar la prevalencia e incidencia de la esclerosis múltiple en la ciudad de Ourense, Galicia. Pacientes y métodos. La ciudad de Ourense tiene una coordenada de latitud de 42° 34' N. Se ha realizado un estudio epidemiológico retrospectivo que abarca desde 2002 a 2016. La fecha de prevalencia fue el 31 de diciembre de 2016. El censo de la población de la ciudad de Ourense a 1 de enero de 2016 era de 105.892 habitantes. Resultados. Se registraron 195 casos, lo que representa una prevalencia de 184,1 casos/100.000 habitantes. En el período 2002-2016 se diagnosticaron 127 casos de esclerosis múltiple, lo que supone una incidencia media de 7,86 casos/ 100.000 habitantes/año. Conclusión. La ciudad de Ourense presenta la tasa de prevalencia de esclerosis múltiple más alta de las estudiadas hasta la actualidad en la Península Ibérica, con una cifra que la aproxima a los datos comunicados en áreas más septentrionales de influencia nórdica y anglosajona.

Epidemiology of myasthenia gravis in the province of Ourense (Galicia, Spain). / Epidemiología de la miastenia gravis en la provincia de Ourense (Galicia, noroeste de España).

INTRODUCTION: Myasthenia gravis (MG) is an autoimmune disease affecting nerve transmission at the level of the neuromuscular junction, and typically causes fluctuating muscle weakness. Epidemiological studies show an increase in MG prevalence, particularly among the older population. OBJECTIVE: We performed a retrospective epidemiological study to determine the incidence and prevalence of MG in the province of Ourense (Galicia, Spain), characterised by population ageing. MATERIAL AND METHODS: Patients were selected from our clinical neuromuscular diseases database by searching for patients with an active prescription for pyridostigmine bromide. Incidence was estimated for the period 2009-2018. We calculated prevalence at 31/12/2018. According to census data for the province of Ourense, the population on 1/1/2019 was 307,651, of whom 96,544 (31.4%) were aged ≥ 65 years. RESULTS: We identified 80 cases of MG, with a prevalence rate of 260 cases/1 000 000 population (95% CI, 202.7-316.4), rising to 517.9/1 000 000 population in those aged ≥ 65 (95% CI, 363.2-672.9). Cumulative incidence in the study period was 15.4 cases per 1 000 000 person-years. Early onset (≤ 50 years) was recorded in 29.1% of cases. CONCLUSION: The prevalence of MG in our health district is one of the highest published figures, and the disease is highly prevalent in the older population.

Reduction of plasma CGRP levels in migraine patients treated with erenumab or galcanezumab. / Reducción de los niveles plasmáticos de CGRP en pacientes con migraña tratados con erenumab o galcanezumab.

TITLE: Reducción de los niveles plasmáticos de CGRP en pacientes con migraña tratados con erenumab o galcanezumab.

[Prevalence of myasthenia gravis in Colombia. Reply]. / Prevalencia de la miastenia grave en Colombia. Réplica.

TITLE: Prevalencia de la miastenia grave en Colombia. Réplica.

Epidemiología de la miastenia grave en la península ibérica y Latinoamérica / Epidemiology of myasthenia gravis in the Iberian Peninsula and Latin America

Introducción: Aunque hoy en día vivimos en un mundo globalizado, los vínculos establecidos entre la península ibérica y los países de Latinoamérica son especialmente fuertes y con importantes flujos migratorios. Esta conexión puede condicionar la presentación de enfermedades que reconozcan una influencia genética, la cual puede ser modulada por diversos factores medioambientales. El objetivo de esta revisión es conocer la epidemiología descriptiva de la miastenia grave en la península ibérica y en Latinoamérica. Desarrollo: Se realizó una búsqueda bibliográfica en Medline, en LILACS y en Google Scholar para los diferentes países de interés con los términos ‘prevalence’, ‘incidence’, ‘epidemiology’ y ‘myasthenia gravis’. Se revisó la metodología y la calidad, y se extrajeron datos descriptivos de la población estudiada, así como los datos de prevalencia. Conclusiones: Muchos países carecen de estudios epidemiológicos sobre la miastenia grave, y en otros, los datos comunicados se centran en un hospital de referencia, lo que hace difícil la comparación de la prevalencia entre los diferentes países. En la península ibérica, la prevalencia es constantemente superior a 100 casos × 106 habitantes, con las cifras más altas correspondientes a la comarca de Osona (Barcelona) y a la provincia de Ourense. En Latinoamérica se registran cifras mucho menores de prevalencia, generalmente inferiores a 100 × 106 habitantes. Se constata un predominio femenino en las formas de inicio precoz (<50 años) y un claro aumento de la prevalencia en la población anciana, sobre todo en las formas de inicio muy tardío (>65 años), en las que es más frecuente en los varones.(AU)

Introduction: Although today we live in a globalised world, the ties established between the Iberian Peninsula and the countries of Latin America are particularly strong, with important migratory flows. This connection may condition the development of diseases that involve a genetic influence, which may in turn be modulated by various environmental factors. The aim of this review is to determine the descriptive epidemiology of myasthenia gravis in the Iberian Peninsula and in Latin America. Development: A literature search was conducted in Medline, LILACS and Google Scholar for the different countries of interest using the terms ‘prevalence’, ‘incidence’, ‘epidemiology’ and ‘myasthenia gravis’. The methodology and quality were reviewed, and descriptive data about the study population as well as data on prevalence were extracted. Conclusions: Many countries lack epidemiological studies on myasthenia gravis and in others the data reported focus on one referral hospital, making it difficult to compare prevalence between countries. In the Iberian Peninsula, the prevalence is consistently above 100 cases × 106 inhabitants, the highest figures being found in the area of Osona (Barcelona) and in the province of Ourense. In Latin America, much lower prevalence figures are reported, generally below 100 × 106 inhabitants. There is a predominance of females in the early-onset forms (<50 years) and a clear increase in prevalence in the elderly population, especially in the very late onset forms (>65 years), where it is more frequent in men.(AU)

Epidemiología de la miastenia gravis en la provincia de Ourense (Galicia, noroeste de España) / Epidemiology of myasthenia gravis in the province of Ourense (Galicia, Spain)

Introducción: La miastenia gravis (MG) es un enfermedad autoinmune que afecta a la transmisión nerviosa a nivel de la unión neuromuscular causando debilidad muscular típicamente fluctuante. Los estudios epidemiológicos constatan un aumento de las tasas de prevalencia de la MG y es especialmente evidente en la población anciana.ObjetivoRealizar un estudio epidemiológico retrospectivo para conocer las tasas de incidencia y prevalencia en la provincia de Ourense (Galicia) caracterizada por el envejecimiento poblacional.Material y métodosLos pacientes fueron reclutados de nuestra base de datos clínica de enfermedades neuromusculares y a través de la búsqueda de pacientes con prescripción activa de bromuro de piridostigmina. La tasa de incidencia se estimó entre los años 2009-2018. Se estableció la fecha de prevalencia al 31/12/2018. El censo de la provincia de Ourense al 1/1/2019 era de 307.651 habitantes, de los que 96.544 (31,4%) tenían una edad ≥ de 65 años.ResultadosSe identificaron 80 casos de MG. La prevalencia fue de 260 casos/1.000.000 habitantes (IC95%: 202,7-316,4), y en la población ≥ 65 años de 517,9/1.000.000 habitantes (IC95%: 363,2-672,9). La incidencia acumulada en el periodo de estudio fue de 15,4 casos/1.000.000 habitantes-año. El inicio precoz (≤ 50 años) ocurrió en el 29,1% de los casos.ConclusiónLa prevalencia de la MG en nuestra área sanitaria es de las más altas entre las cifras previamente reportadas, y es una enfermedad muy prevalente en la población anciana. (AU)

Introduction: Myasthenia gravis (MG) is an autoimmune disease affecting nerve transmission at the level of the neuromuscular junction, and typically causes fluctuating muscle weakness. Epidemiological studies show an increase in MG prevalence, particularly among the older population.ObjectiveWe performed a retrospective epidemiological study to determine the incidence and prevalence of MG in the province of Ourense (Galicia, Spain), characterised by population ageing.Material and methodsPatients were selected from our clinical neuromuscular diseases database by searching for patients with an active prescription for pyridostigmine bromide. Incidence was estimated for the period 2009-2018. We calculated prevalence at 31/12/2018. According to census data for the province of Ourense, the population on 1/1/2019 was 307,651, of whom 96,544 (31.4%) were aged ≥ 65 years.ResultsWe identified 80 cases of MG, with a prevalence rate of 260 cases/1 000 000 population (95% CI, 202.7-316.4), rising to 517.9/1 000 000 population in those aged ≥ 65 (95% CI, 363.2-672.9). Cumulative incidence in the study period was 15.4 cases per 1 000 000 person-years. Early onset (≤ 50 years) was recorded in 29.1% of cases.ConclusionThe prevalence of MG in our health district is one of the highest published figures, and the disease is highly prevalent in the older population. (AU)

[Frequent episodic migraine and calcitonin gene-related peptide. Influence of treatment with topiramate and zonisamide on levels of the peptide]. / Migraña episodica frecuente y peptido relacionado con el gen de la calcitonina. Influencia del tratamiento con topiramato y zonisamida en los niveles del peptido.

INTRODUCTION: The pathophysiology of pain in migraine is related to the activation of the trigeminovascular system by releasing vasoactive neuropeptides, the most important of which is calcitonin gene-related peptide (CGRP), which causes a neurogenic inflammation in the leptomeningeal vessels. AIM: To study whether CGRP is increased in frequent episodic migraine and whether preventive treatment with topiramate or zonisamide modifies its levels. SUBJECTS AND METHODS: We studied 28 patients with episodic migraine with or without aura, in accordance with the International Headache Society criteria, with a frequency of 4-14 days/month. Plasma levels of CGRP were determined in all the patients during an interictal period (> 72 hours without pain). Patients were divided at random into two treatment groups, one with 50 mg/day of topiramate and the other with 50 mg/day of zonisamide, for three months. At the end of the active period the CGRP level was analysed again. The control group consisted of nine healthy subjects. RESULTS: CGRP was significantly higher in the episodic migraine group than in the control group (50.61 ± 22.5 pg/mL versus 34.96 ± 17.03 pg/mL; p = 0.037). After treatment with neuromodulators no significant differences were found in the level of CGRP (46.11 ± 24.2 pg/mL basal versus 47.5 ± 24.88 pg/mL post-treatment). Neither were any differences found on analysing the topiramate and zonisamide groups individually. CONCLUSIONS: The plasma level of CGRP is increased in episodic migraine, and its levels are not modified by treatment with low doses of topiramate or zonisamide.

TITLE: Migraña episodica frecuente y peptido relacionado con el gen de la calcitonina. Influencia del tratamiento con topiramato y zonisamida en los niveles del peptido.Introduccion. La fisiopatologia del dolor en la migraña se relaciona con la activacion del sistema trigeminovascular por medio de la liberacion de neuropeptidos vasoactivos, y el mas importante es el peptido relacionado con el gen de la calcitonina (CGRP), que causa una inflamacion neurogena en los vasos leptomeningeos. Objetivo. Investigar si el CGRP esta incrementado en la migraña episodica frecuente y si el tratamiento preventivo con topiramato o zonisamida modifica sus niveles. Sujetos y metodos. Se estudiaron 28 pacientes con migraña episodica con o sin aura, cumpliendo los criterios de la Sociedad Internacional de Cefaleas, con una frecuencia de 4-14 dias/mes. En todos los pacientes se determinaron los niveles plasmaticos del CGRP durante un periodo intercritico (> 72 h sin dolor). Los pacientes se aleatorizaron en dos grupos de tratamiento, uno con 50 mg/dia de topiramato y otro con 50 mg/dia de zonisamida, durante tres meses. Al finalizar el periodo activo se analizo nuevamente el nivel del CGRP. El grupo control lo constituyeron nueve sujetos sanos. Resultados. El CGRP fue significativamente superior en el grupo de migraña episodica comparado con el grupo control (50,61 ± 22,5 pg/mL frente a 34,96 ± 17,03 pg/mL; p = 0,037). Despues del tratamiento con neuromoduladores no se hallaron diferencias significativas en el nivel de CGRP (46,11 ± 24,2 pg/mL basal frente a 47,5 ± 24,88 pg/mL postratamiento). Tampoco se hallaron diferencias al analizar los grupos de topiramato y zonisamida de forma individualizada. Conclusiones. El nivel plasmatico del CGRP esta incrementado en la migraña episodica y sus niveles no son modificados por el tratamiento con dosis bajas de topiramato o zonisamida.

Efectividad clínica y radiológica del intervalo extendido de dosis con natalizumab en pacientes con esclerosis múltiple recurrente / Clinical and radiological effectiveness of natalizumab extended dosage interval in patients with relapsing multiple sclerosis

Introducción: El natalizumab (NTZ) es un tratamiento de alta eficacia aprobado para la esclerosis múltiple de alta actividad. El principal riesgo del tratamiento con NTZ es la posibilidad de desarrollar una leucoencefalopatía multifocal progresiva, que está en relación con la positividad al virus JC y el número de infusiones del NTZ. Este riesgo disminuye con el intervalo extendido de dosis (IED), lo que supone 9 infusiones/año o menos. Sin embargo, es materia de controversia si el IED mantiene la efectividad sobre la reducción de las recurrencias y la presencia de nuevas lesiones en la resonancia magnética (RM). Pacientes y métodos: Se ha realizado un estudio observacional prospectivo desde el 1 de abril de 2019 hasta el 30 de junio de 2021, siguiendo a los pacientes en tratamiento con NTZ que se pasaron al IED. Los pacientes deberían tener al menos una RM a los seis meses del inicio del IED. Se registró la presencia de brotes o de actividad en la RM (nuevas lesiones en T2) durante el IED. Resultados: Se incluyó a 23 pacientes con una media de edad de 43,5 ± 9,4 años. La mediana de infusiones de NTZ fue de 68 (mínimo, 25; máximo, 127). La mediana del intervalo entre el inicio del IED y la última RM fue de 14 meses (mínimo, 6; máximo, 25), y de 23 meses respecto a la última visita de seguimiento médico (mínimo, 7; máximo, 28). Dos pacientes (8,7%) presentaron brotes y otros dos pacientes (8,7%) presentaron actividad en la RM. Conclusiones: El IED de NTZ mantiene una alta efectividad clínica y de actividad en la RM.(AU)

Introduction: Natalizumab (NTZ) is a very effective treatment approved for highly active multiple sclerosis. The main risk of treatment with NTZ is the possibility of developing progressive multifocal leukoencephalopathy, which is related to JC virus positivity and the number of NTZ infusions. This risk decreases with the extended dosage interval (EDI), which involves 9 or fewer infusions/year. However, it is a matter of controversy as to whether EDI remains effective in reducing recurrences and the presence of new lesions in magnetic resonance imaging (MRI). Patients and methods: A prospective observational study was conducted from 1 April 2019 to 30 June 2021, following up patients on NTZ treatment who switched to EDI. Patients should have at least one MRI six months after the start of EDI. The presence of attacks or MRI activity (new lesions in T2) during the EDI was recorded. Results: Twenty-three patients with a mean age of 43.5 ± 9.4 years were included. The median number of NTZ infusions was 68 (minimum, 25; maximum, 127). The median interval between the start of the EDI and the last MRI was 14 months (minimum, 6; maximum, 25), and 23 months from the last medical follow-up visit (minimum, 7; maximum, 28). Two patients (8.7%) presented with attacks and two others (8.7%) showed MRI activity. Conclusions: EDI with NTZ maintains high clinical and activity effectiveness in MRI.(AU)

[Fingolimod: effectiveness and safety in routine clinical practice. An observational, retrospective, multi-centre study in Galicia]. / Fingolimod: efectividad y seguridad en la practica clinica habitual. Estudio observacional, retrospectivo y multicentrico en Galicia.

INTRODUCTION: The effectiveness and safety of fingolimod in patients with relapsing-remitting multiple sclerosis (RRMS) have been proven in clinical trials. Yet, due to their limitations, it is important to know how it behaves under everyday clinical practice conditions. Hence, the aim of this study is to evaluate the effectiveness and safety of fingolimod after 12 months' usage in clinical practice in Galicia. PATIENTS AND METHODS: We conducted a retrospective, multi-centre study (n = 8) of patients with RRMS who were treated with one or more doses of fingolimod, 0.5 mg/day. Effectiveness was assessed -annualised relapse rate (ARR), changes in the score on the Expanded Disability Status Scale (EDSS), percentage of patients free from relapses, free from progression of disability and free from activity in resonance- for the total number of patients and according to previous treatment. Safety was assessed based on the percentage of patients who withdrew and presented adverse side effects. RESULTS: After 12 months' use, fingolimod reduced the ARR by 87% (1.7 to 0.23; p < 0.0001) and, consequently, 81% of patients were free from relapses. The score was reduced by 9%. In all, 91% of patients were free from progression of disability and 72% were free from resonance activity. No signs of disease activity were found in 43% of the patients. Most of the benefits of fingolimod differed depending on previous treatment. About a third of the patients reported adverse side effects, but only 2% of them withdrew for this reason. CONCLUSIONS: In clinical practice, most of the results on the effectiveness of the clinical trials conducted with fingolimod were observed during the first 12 months of treatment. A better safety profile was observed than that reported in the clinical trials.

TITLE: Fingolimod: efectividad y seguridad en la practica clinica habitual. Estudio observacional, retrospectivo y multicentrico en Galicia.Introduccion. La efectividad y seguridad del fingolimod en pacientes con esclerosis multiple remitente recurrente (EMRR) se demostro en ensayos clinicos. Sin embargo, por las limitaciones de estos, es importante saber como se comporta en condiciones de practica clinica habitual. Asi, el objetivo de este estudio es evaluar la efectividad y seguridad del fingolimod despues de 12 meses de uso en la practica clinica en Galicia. Pacientes y metodos. Estudio retrospectivo y multicentrico (n = 8) de pacientes con EMRR y tratados con una o mas dosis de fingolimod, 0,5 mg/dia. Se evaluo la efectividad ­tasa anualizada de brotes (TAB), cambio en la puntuacion de la escala expandida del estado de discapacidad (EDSS), porcentaje de pacientes libres de brotes, libres de progresion de discapacidad y libres de actividad en resonancia­ para el total de pacientes y segun tratamiento previo. Se evaluo la seguridad a partir del porcentaje de pacientes que discontinuaron y que presentaron efectos adversos. Resultados. Despues de 12 meses de uso, el fingolimod redujo un 87% la TAB (de 1,7 a 0,23; p < 0,0001) y, en consecuencia, un 81% de pacientes estuvo libre de brotes. La puntuacion de la EDSS disminuyo un 9%. Un 91% de pacientes estuvo libre de progresion de discapacidad y un 72%, libre de actividad en resonancia. En el 43% de los pacientes no se evidenciaron signos de la actividad de la enfermedad. La mayoria de los beneficios del fingolimod difirieron segun el tratamiento previo. Alrededor de un tercio de los pacientes comunicaron efectos adversos, pero solo el 2% discontinuo debido a ellos. Conclusiones. La mayoria de los resultados de efectividad de los ensayos clinicos del fingolimod se observa durante los 12 primeros meses de tratamiento en la practica clinica. Se observo un mejor perfil de seguridad al comunicado en los ensayos clinicos.

Insulin sensitivity, glucose effectiveness, and beta-cell function in obese males with essential hypertension: investigation of the effects of treatment with a calcium channel blocker (diltiazem) or an angiotensin-converting enzyme inhibitor (quinapril).

It has been suggested that hyperinsulinemia secondary to insulin resistance may be a pathogenetic factor common to obesity, non-insulin-dependent diabetes mellitus (NIDDM), and hypertension. Furthermore, beta-blockers and thiazide diuretics have been shown to be capable of increasing insulin resistance and thus of inducing NIDDM in predisposed individuals. We used the minimal model approach (MMA) to glucose metabolism and insulin kinetics to compare peripheral insulin sensitivity and beta-cell function in hypertensive and normotensive obese men. The hypertensive group consisted of 37 obese men with mild to moderate hypertension; following a drug-free period of 4 weeks, 20 of these subjects received diltiazem and 17 quinapril over the 12-week study period. The normotensive (control) group contained 17 obese men without microalbuminuria, dyslipidemia, or a family history of essential hypertension or NIDDM. Before and at the end of the 12-week study period, subjects underwent frequently sampled intravenous glucose tolerance (FSIGT) tests. The results were used to estimate an insulin sensitivity index (S(I)), a glucose effectiveness index (S(G)), and beta-cell sensitivity to glucose indices during first- and second-phase insulin secretion (phi1 and phi2) using the minimal models of glucose metabolism and insulin kinetics. No significant differences in S(I) or S(G) were detected between the hypertensive and control groups. Twelve weeks' treatment with diltiazem led to a slight but significant increase in phi1; however, neither diltiazem nor quinapril had significant effects on S(I) or S(G). We conclude that men with obesity and hypertension have no greater insulin resistance than those with obesity alone, suggesting that hypertension is not generally associated with any significant increase in insulin resistance. Treatment with diltiazem or quinapril does not have undesirable effects on glucose metabolism. However, treatment with diltiazem led to a significant increase in beta-cell sensitivity to glucose; this is of particular interest, given the importance of phi1 for peripheral glucose uptake.

Insulin sensitivity, glucose effectiveness, and insulin secretion in nondiabetic offspring of patients with non-insulin-dependent diabetes mellitus: a cross-sectional study.

To evaluate the factors that determine the worsening of intravenous glucose tolerance in subjects at high risk for developing non-insulin-dependent diabetes mellitus (NIDDM), 15 glucose-tolerant offspring of NIDDM patients and 21 control subjects were studied. Each subject underwent a frequently sampled intravenous glucose tolerance (FSIGT) test. The intravenous glucose tolerance index (K(G) index) was calculated between minutes 10 and 40 of a FSIGT test. Insulin sensitivity (S(I)), glucose effectiveness at zero insulin (GEZI), and first- and second-phase insulin responsiveness (phi1 and phi2) were estimated using glucose and insulin kinetic minimal models. The acute insulin response to glucose (AIRg) was calculated as the area under the insulin curve above the basal level between 0 and 10 minutes, and the suprabasal insulin effect was determined by the product of S(I) times AIRg. Offspring had a lower S(I) than control subjects (14.1 +/- 7.5 v 9.25 +/- 4.20 x 10(-5) x min(-1)(pmol x L(-1))(-1), P < .01), and their AIRg was similar (3,284 +/- 2,280 v 3,105 +/- 1,499 pmol x L(-1), NS). Sample division according to the median K(G) value showed that control subjects with low tolerance had a lower AIRg (4,417 +/- 2,531 v 2,043 +/- 1,068 pmol x L(-1), P < .05) and a lower suprabasal insulin effect (0.057 +/- 0.03 v 0.023 +/- 0.009 min(-1), P < .05) than control subjects with high tolerance. Offspring with low tolerance had a lower AIRg (2,574 +/- 1,197 v 3,707 +/- 1,656 pmol x L(-1), P < .05) and a lower GEZI (0.101 +/- 0.05 v 0.212 +/- 0.08 x 10(-1) x min(-1), P < .05) than offspring with high tolerance. Offspring with high and low tolerance showed lower phi1 (375 +/- 155 v 272 +/- 181 v 698 +/- 336 (pmol x L(-1))min(mmol x L(-1)), NS) than control subjects with high tolerance. In conclusion, our data suggest that decreases in GEZI and AIRg are the main factors responsible for the worsening of intravenous glucose tolerance in the offspring of NIDDM patients.