[15th Post-ECTRIMS Meeting: a review of the latest developments presented at the 2022 ECTRIMS Congress (Part II)]. / XV Reunión Post-ECTRIMS: revisión de las novedades presentadas en el Congreso ECTRIMS 2022 (II).

INTRODUCTION: On 4 and 5 November 2022, Madrid hosted the 15th edition of the Post-ECTRIMS Meeting, where neurologists specialised in multiple sclerosis outlined the latest developments presented at the 2022 ECTRIMS Congress, held in Amsterdam from 26 to 28 October. AIM: To synthesise the content presented at the 15th edition of the Post-ECTRIMS Meeting, in an article broken down into two parts. DEVELOPMENT: This second part describes the new developments in terms of therapeutic strategies for escalation and de-escalation of disease-modifying therapies (DMT), when and in whom to initiate or switch to highly effective DMT, the definition of therapeutic failure, the possibility of treating radiologically isolated syndrome and the future of personalised treatment and precision medicine. It also considers the efficacy and safety of autologous haematopoietic stem cell transplantation, different approaches in clinical trial design and outcome measures to assess DMT in progressive stages, challenges in the diagnosis and treatment of cognitive impairment, and treatment in special situations (pregnancy, comorbidity and the elderly). In addition, results from some of the latest studies with oral cladribine and evobrutinib presented at ECTRIMS 2022 are shown.

TITLE: XV Reunión Post-ECTRIMS: revisión de las novedades presentadas en el Congreso ECTRIMS 2022 (II).Introducción. El 4 y el 5 de noviembre se celebró en Madrid la Reunión Post-ECTRIMS, en la que neurólogos expertos en esclerosis múltiple resumieron las principales novedades presentadas en el congreso de ECTRIMS 2022, celebrado entre el 26 y el 28 de octubre en Ámsterdam. Objetivo. Sintetizar las ponencias que tuvieron lugar en la Reunión Post-ECTRIMS, en un artículo desglosado en dos partes. Desarrollo. En esta segunda parte, se presentan las novedades sobre las estrategias terapéuticas de escalado y desescalado de los tratamientos modificadores de la enfermedad (TME), cuándo y a quién iniciar o cambiar a TME de alta eficacia, la definición de fracaso terapéutico, la posibilidad de tratar el síndrome radiológico asilado, el futuro del tratamiento personalizado y la medicina de precisión, la eficacia y seguridad del autotrasplante de células madre hematopoyéticas, diferentes aproximaciones en el diseño de ensayos clínicos y en las medidas de resultados para evaluar TME en fases progresivas, retos en el diagnóstico y tratamiento del deterioro cognitivo, y tratamiento en situaciones especiales (embarazo, comorbilidad y personas mayores). Además, se muestran los resultados de algunos de los últimos estudios realizados con cladribina oral y evobrutinib presentados en el ECTRIMS 2022.

Photoprotection beyond ultraviolet radiation--effective sun protection has to include protection against infrared A radiation-induced skin damage.

Solar radiation is well known to damage human skin, for example by causing premature skin ageing (i.e. photoageing). We have recently learned that this damage does not result from ultraviolet (UV) radiation alone, but also from longer wavelengths, in particular near-infrared radiation (IRA radiation, 760-1,440 nm). IRA radiation accounts for more than one third of the solar energy that reaches human skin. While infrared radiation of longer wavelengths (IRB and IRC) does not penetrate deeply into the skin, more than 65% of the shorter wavelength (IRA) reaches the dermis. IRA radiation has been demonstrated to alter the collagen equilibrium of the dermal extracellular matrix in at least two ways: (a) by leading to an increased expression of the collagen-degrading enzyme matrix metalloproteinase 1, and (b) by decreasing the de novo synthesis of the collagen itself. IRA radiation exposure therefore induces similar biological effects to UV radiation, but the underlying mechanisms are substantially different, specifically, the cellular response to IRA irradiation involves the mitochondrial electron transport chain. Effective sun protection requires specific strategies to prevent IRA radiation-induced skin damage.

Prevention of infrared-A radiation mediated detrimental effects in human skin.

Photoaging and skin damage that is caused by solar radiation is well known. We have recently learned that within the solar spectrum this damage not only results from ultraviolet (UV) radiation, but also from longer wavelengths, in particular near infrared radiation. Accordingly, infrared radiation (IR) has been shown to alter the collagen equilibrium of the dermal extracellular matrix in at least 2 ways: (1) by leading to an increased expression of the collagen degrading enzyme matrixmetalloproteinase-1 while (2) decreasing the de novo synthesis of the collagen itself. Infrared-A (IRA) radiation exposure, therefore, induces similar biological effects to UV, but the underlying mechanisms are substantially different. IRA acts via the mitochondria and therefore protection from IR requires alternative strategies.

[Photocoagulation guided by fundus camera (new photocoagulation method of the retina with a non-contact and wide field system)]. / Fotocoagulación guiada por retinografía (nuevo método de fotocoagulación de la retina mediante un sistema de no contacto y de campo amplio).

PURPOSE: To design a device that integrates a laser photocoagulator in a fundus camera so that the functions of both are incorporated for their simultaneous use. This system would allow the visualizacion of the fundus during photocoagulation, with a no-contact, no hand-helped lens technique. MATERIAL AND METHODS: To test the device we used a fundus camera Fx500 (Kowa) and a diode laser Oculight SLx (Iris Medical). We analysed the physical and power laser parameters, performing a comprehensive control of the device's safety. In order to measure the error in the precision of the laser, we designed a micrometric test to evaluate the directionality of the beam and the focusing system. Finally, we test the size, time of exposure and intensity necessary to obtain an effective impact. RESULTS: With our system, transpupilar photocoagulation fullfils the main safety requirements on laser radiation and illumination in retinoscopy. After diverse adjustments, the laser impacts were placed in the desired retinal areas. The lesions generated in the pig eyes were quite similar to those obtained by conventional techniques and they were time and intensity dependent. CONCLUSIONS: Photocoagulation with our sytem is very simple and potentially safe and effective. It may facilitate the photocoagulation process inasmuch as it is more comfortable and user-friendly.

Microchip vagal pacing reduces food intake and body mass.

BACKGROUND/AIMS: Morbid obesity is an increasing problem worldwide. In many patients pharmacotherapy is ineffective and these cases are treated by surgery. Different types of gastroplasty and gastric bypasses have been described. However, all of these ablative surgical methods are irreversible and often replace obesity by other disorders. Neuromodulation of vagal activity is a method of inducing significant changes in stomach motility. We developed a pre-programmed microchip able to pace vagal afferent activity by changing current parameters. The aim of our study was to evaluate long-term effects of vagal neuromodulation on food intake and body mass in rabbits. METHODOLOGY: Twenty-seven healthy male adult New Zealand white rabbits were included into the study and divided into three groups: A, B and C, 9 animals each. Microchips were implanted by laparotomy access. Anesthesia was obtained by continuous intravenous infusion of propofol. Microchips were fixed in the preperitoneal pocket and two electrodes were positioned on the posterior vagus in group A by forward, and in group B by backward pacing. Control group C was sham operated by laparotomy and only vagal nerves preparation was performed. The following parameters were estimated: daily solid food and liquids intake, amount of feces, body mass and heart rate. RESULTS: Within four weeks after operation body mass in group B had decreased up to 12% (P = 0.029), whereas in group A and C changed to -3% and +2%, respectively. An 87% solid food intake was observed in group A, 60% in group B (P < 0.01), and 143% in group C, compared to preoperative period. No significant differences were observed between groups A, B and C for liquids intake. Total feces weight changes corresponded to solid food intake. Heart rate decreased intraoperatively to 78% and 74% in groups A and B, respectively. CONCLUSIONS: Microchip mediated functional gastroplasty significantly reduces food intake and body mass. Obtained results encourage using similar treatment in morbid obesity human patients. However, further studies are required.

A simplified arteriovenous malformation model in sheep: feasibility study.

BACKGROUND AND PURPOSE: Recently, a swine model of a cerebral arteriovenous malformation (AVM) has been developed that closely resembles a human AVM of the brain. The creation of such a model requires sophisticated neurointerventional techniques. The purpose of this study was to develop a simple and cost-effective AVM animal model that does not require additional endovascular techniques. METHODS: A surgical anastomosis was created in seven sheep between the common carotid artery and the ipsilateral jugular vein, followed by ligation of the jugular vein above the anastomosis and of the proximal common carotid artery below the anastomosis. The anastomosis was created on the left side in four animals and on the right side in three. Cerebral angiography from the contralateral carotid artery was performed before and immediately after surgery to delineate the relevant cerebral vascular anatomy and to determine the direction of blood flow. RESULTS: An angiographic appearance simulating an AVM was found in all the animals. The ramus anastomoticus and arteria anastomotica functioned as the feeding vessels to the rete mirabile, which represented the nidus in our model, and to the jugular vein, which represented the draining vein from the malformation. Extensive collateral flow through the rete mirabile into the distal segment of the external carotid artery above the ligature was observed angiographically, with retrograde flow through the surgical anastomosis into the jugular vein. CONCLUSION: A simple surgically created experimental model for cerebral AVMs was developed in sheep without the need for additional complex endovascular catheter manipulations of intracranial branches. Such an animal model can substantially reduce the cost of research and training in the neurointerventional or radiosurgical management of AVMs.