[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.

Validation of a New Semiautomated Segmentation Pipeline Based on the Spinal Cord Toolbox DeepSeg Algorithm to Estimate the Cervical Canal Area.

BACKGROUND AND PURPOSE: As in the brain reserve concept, a larger cervical canal area may also protect against disability. In this context, a semiautomated pipeline has been developed to obtain quantitative estimations of the cervical canal area. The aim of the study was to validate the pipeline, to evaluate the consistency of the cervical canal area measurements during a 1-year period, and to compare cervical canal area estimations obtained from brain and cervical MRI acquisitions. MATERIALS AND METHODS: Eight healthy controls and 18 patients with MS underwent baseline and follow-up 3T brain and cervical spine sagittal 3D MPRAGE. The cervical canal area was measured in all acquisitions, and estimations obtained with the proposed pipeline were compared with manual segmentations performed by 1 evaluator using the Dice similarity coefficient. The cervical canal area estimations obtained on baseline and follow-up T1WI were compared; brain and cervical cord acquisitions were also compared using the individual and average intraclass correlation coefficients. RESULTS: The agreement between the manual cervical canal area masks and the masks provided by the proposed pipeline was excellent, with a mean Dice similarity coefficient mean of 0.90 (range, 0.73-0.97). The cervical canal area estimations obtained from baseline and follow-up scans showed a good level of concordance (intraclass correlation coefficient = 0.76; 95% CI, 0.44-0.88); estimations obtained from brain and cervical MRIs also had good agreement (intraclass correlation coefficient = 0.77; 95% CI, 0.45-0.90). CONCLUSIONS: The proposed pipeline is a reliable tool to estimate the cervical canal area. The cervical canal area is a stable measure across time; moreover, when cervical sequences are not available, the cervical canal area could be estimated using brain T1WI.

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

INTRODUCTION: On 4 and 5 November 2022, Madrid hosted the 15th edition of the Post-ECTRIMS Meeting, where neurologists specialised in multiple sclerosis (MS) outlined the most relevant novelties 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: In this first part, the initial events involved in the onset of MS, the role played by lymphocytes and the migration of immune system cells into the central nervous system are presented. It describes emerging biomarkers in body fluids and imaging findings that are predictive of disease progression and useful in the differential diagnosis of MS. It also discusses advances in imaging techniques which, together with a better understanding of the agents involved in demyelination and remyelination processes, provide a basis for dealing with remyelination in the clinical setting. Finally, the mechanisms triggering the inflammatory reaction and neurodegeneration involved in MS pathology are reviewed.

TITLE: XV Reunión Post-ECTRIMS: revisión de las novedades presentadas en el Congreso ECTRIMS 2022 (I).Introducción. El 4 y el 5 de noviembre se celebró en Madrid la XV edición de la Reunión Post-ECTRIMS, donde neurólogos expertos en esclerosis múltiple (EM) resumieron las principales novedades presentadas en el congreso de ECTRIMS 2022, celebrado en Ámsterdam entre el 26 y el 28 de octubre. Objetivo. Sintetizar las ponencias que tuvieron lugar en la Reunión Post-ECTRIMS, en un artículo desglosado en dos partes. Desarrollo. En esta primera parte se presentan los primeros eventos involucrados en el inicio de la EM, la implicación de los linfocitos y la migración de células del sistema inmunitario hacia el sistema nervioso central. Se describen los biomarcadores emergentes en fluidos corporales y los hallazgos de imagen que permiten predecir la evolución de la enfermedad, y que resultan útiles en el diagnóstico diferencial de la EM. También se exponen los avances en las técnicas de imagen que, junto con un mayor conocimiento de los agentes involucrados en los procesos de desmielinización y remielinización, proporcionan una base para abordar la remielinización en el entorno clínico. Por último, se repasan los mecanismos desencadenantes de la reacción inflamatoria y la neurodegeneración implicados en la patología de la EM.

Clinical improvement after intraarticular and intraosseous injections of platelet rich plasma combined with hyaluronic acid for knee osteoarthritis. Case series.

INTRODUCTION: knee osteoarthritis (KOA) is known as the most common form of osteoarthrosis with a 6% prevalence in people over 30 years old, and more than 40% in the population over 70 years old. The use of PRP led to diverse results and this disparity can be attributed to the dissimilar methods of PRP preparation. This study aims to assess the functional effects of intraosseous (IO) and intraarticular (IA) injections of platelet rich plasma (PRP) followed by IA injections of hyaluronic acid (HA). OBJECTIVES: this study aimed to assess the functional effects of intraosseous (IO) and intraarticular (IA) injections of platelet rich plasma (PRP) followed by IA injections of hyaluronic acid (HA), administered 3 and 4 weeks after the initiation of treatment in 33 patients with grade II-III (Ahlback scale) knee osteoarthritis (KOA). MATERIAL AND METHODS: retrospectively, 33 patients were assessed using the Western Ontario and McMaster Universities (WOMAC) osteoarthritis index and visual analogue scale (VAS) score. They were followed-up for 12.92 months on average. Patients were divided into three groups based on age and four groups based on the follow-up period. RESULTS: the pre-operative mean of the WOMAC index was 44.35 ± 20.20 and the post-operative mean was 22.81 ± 17.25 (p < 0.001). The pre-operative and post-operative mean of the VAS scores were 5.79 ± 2.01 and 2.41 ± 1.43 (p < 0.001), respectively. The largest improvement in WOMAC (from 42.86 to 13.69) was observed in the youngest patients (44 to 55 years old) and the largest reduction in VAS (from 6.89 to 2.22) was seen in patients aged 56 to 70 years. CONCLUSION: the combination of IO and IA plasma rich in growth factor (PRGF) treatment with the IA-HA treatment yielded excellent results, diminishing pain and improving motor functionality in patients with KOA.

INTRODUCCIÓN: la artrosis de rodilla (OA) es conocida como la forma más común de osteoartrosis con una prevalencia de 6% en personas mayores de 30 años y más de 40% en la población mayor de 70 años. El uso de plasma rico en plaquetas (PRP) condujo a resultados diversos y esta disparidad puede atribuirse a los diferentes métodos de preparación del PRP. Este estudio tiene como objetivo evaluar los efectos funcionales de las inyecciones intraóseas (IO) e intraarticulares (IA) de plasma rico en plaquetas (PRP) seguidas de inyecciones IA de ácido hialurónico (AH). OBJETIVOS: este estudio tuvo como objetivo evaluar los efectos funcionales de las inyecciones intraóseas (IO) e intraarticulares (IA) de plasma rico en plaquetas (PRP) seguidas de inyecciones IA de ácido hialurónico (AH), administrada 3 y 4 semanas después del inicio del tratamiento en 33 pacientes con osteoartrosis de rodilla (OR) grado II-III (escala de Ahlbäck). MATERIAL Y MÉTODOS: retrospectivamente, se evaluó a 33 pacientes utilizando el índice de osteoartritis de las Universidades Western Ontario y McMaster (WOMAC) y la puntuación de la escala visual analógica (EVA). Se les realizó un seguimiento medio de 12.92 meses. Los pacientes se dividieron en tres grupos según la edad y cuatro grupos según el período de seguimiento. RESULTADOS: la media preoperatoria del índice WOMAC fue de 44.35 ± 20.20 y la media postoperatoria fue de 22.81 ± 17.25 (p < 0.001). La media preoperatoria y postoperatoria de las puntuaciones de la EVA fue de 5.79 ± 2.01 y 2.41 ± 1.43 (p < 0.001), respectivamente. La mayor mejoría en WOMAC (de 42.86 a 13.69) se observó en los pacientes más jóvenes (44 a 55 años) y la mayor reducción de la EVA (de 6.89 a 2.22) se observó en pacientes de 56 a 70 años. CONCLUSIÓN: la combinación del tratamiento de plasma rico en factores de crecimiento (PRGF) IO e IA con el tratamiento IA-AH produjo excelentes resultados, disminuyendo el dolor y mejorando la funcionalidad motora de los pacientes con OR.

Simultaneous improvement in solvent permeability and deacidification of soybean oil by nanofiltration.

In this paper, soybean oil deacidification and hexane removal using laboratory scale solvent resistance nanofiltration membranes based technique is presented. Composite nanofiltration membranes made of different polymers poly(vinylideneflouride) (PVDF), polydimethylsiloxane (SI), polycarbonate (PC), and glycerol were tested to remove the hexane and free fatty acid (FFA) from soybean oil/hexane miscella (oil feed solution 10, 25, and 35% w/w) at 20 bar of transmembrane pressure and 30 °C, in a dead-end filtration set up. All membranes tested showed low fouling phenomena and high stability in the presence of hexane throughout the membrane pre-treatment and permeation procedure. The PVDF-10SI-1PC membrane showed the best performance achieving a miscella permeability of Lm = 6.8 × 10-6 L (h m bar)-1, oil and FFA sieving efficiency of ß(oil) = 0.21(80% of oil rejection) and ßFFA = 2.43 (27% of FFA removal), respectively, at oil feed concentration of 25%. Apart from these specific properties, the PVDF-10SI-1PC membrane presented excellent mechanical and chemical resistances and low reversible fouling. The results demonstrate that membrane technology can attain a high efficiency in the simultaneous solvent recovery and deacidification of oil/hexane miscella commonly processed in the soybean oil industry.

Influence of Pectin as a green polymer electrolyte on the transport properties of Chitosan-Pectin membranes.

Novel blend membranes have been prepared from Chitosan (CH), Pectin (PEC) and their mixtures. The obtained samples were cross-linked and sulfonated before characterization. The results show that CH/PEC membranes display structural changes on the chemical and physical properties as a function of composition. DSC analysis reveals an endothermic peak due to the scission of the ionic pairs between carboxylic groups and ammonium groups, which produces a strong change on physical properties such as methanol permeability and proton conductivity. The methanol permeability decreases with the amount of Pectin from (4.24±0.04)×10-6cm2/s for pure Chitosan membrane to (1.51±0.03)×10-6cm2/s for blend CH/PEC membranes when the amount of Pectin is 50% (v/v). The proton conductivities of the blend membranes follow a similar behavior. For a pure CH membrane the conductivity is 2.44×10-3S/cm, decreasing with pectin content until the composition 50/50 (v/v), in which the conductivity drops almost one order of magnitude.

Spinocerebellar ataxia type 2: Measures of saccade changes improve power for clinical trials

BACKGROUND:Saccadic eye movement abnormalities are common in patients with spinocerebellar ataxia type 2, but it is unclear how these alterations progress over time. The aim of this study was to assess the progression of saccade involvement in spinocerebellar ataxia type 2 patients, identify its main determinants, and evaluate its usefulness as outcome measures in clinical trials.METHODS:A prospective 5-year follow-up study was performed with 30 spinocerebellar ataxia type 2 patients and their matched healthy controls, who were evaluated a total of four times by clinical and electrooculographical assessments of horizontal saccades and by the scoring of ataxia.RESULTS:Patients showed significant decreases in saccade peak velocity and saccade accuracy as well as increases of saccadic latency during the follow-up period. Annual progression rates were significantly higher in patients compared to controls. Faster progression rates of saccade slowing were associated with higher trinucleotide cytosine-adenine-guanine repeat expansions. Sample-size estimates for two-arm trials would require 19 patients per group to detect a 50 percent reduction in disease progression using saccade peak velocity as outcome variable, but 44 and 124 patients using saccade latency and accuracy, respectively (power, 80 percent; alpha = 0.05).CONCLUSIONS:Electrooculographical measures of saccade changes are useful for the objective quantification of disease course in spinocerebellar ataxia type 2. The progression rate of saccade slowing is influenced by the expansion size, providing novel insight into the cumulative polyglutamine neurotoxicity, and supporting the usefulness of saccade peak velocity as a sensitive biomarker during the natural history of the disease, and as suitable outcome measure for therapeutic trials (AU)

NaOH treatment of chitosan films: Impact on macromolecular structure and film properties.

In this paper, we examine the significance of treatment with NaOH on chitosan (CH) film structure to obtain biodegradable materials for several applications. In order to determine the structure of the films, an analysis based on SEM, FTIR spectroscopy and X-ray diffraction data was performed. In addition, the consequences of this treatment were evaluated by swelling index measurements and mechanical testing. As result of FTIR and X-ray analysis, three effects were identified: the deprotonation and phosphate extraction, which allowed new hydrogen bonds to form, and a higher CH deacetylation. These studies also revealed that two hydrated and anhydrous polymorphs were present in the CH-NaOH films. Moreover, the new hydrogen bond and the reduction of N-acetyl groups produced films with a more compact and disordered structure, reducing their swelling characteristics and increasing their brittleness. The introduction of a mild NaOH treatment is a versatile tool to obtain chitosan films with interesting and tunable properties.

Fractional statistical theory of adsorption applied to protein adsorption.

Experimental adsorption isotherms of bovine serum albumin (BSA) adsorbed on sulfonated microspheres were described by means of two analytical models: the first is the well-known Langmuir-Freundlich model (LF), and the second, called fractional statistical theory of adsorption (FSTA), is a statistical thermodynamics model developed recently by Ramirez-Pastor et al. [Phys. Rev. Lett. 93 (2004) 186101]. The experimental data, obtained by Hu et al. [Biochem. Eng. J. 23 (2005) 259] for different concentrations of sulfonate group on the surface of the microspheres, were correlated by using a fitting algorithm based on least-squares statistics. The combination of LF and FSTA models, along with the choice of an adequate fitting procedure, allowed us to obtain several conclusions: (i) as previously reported in the literature, the maximum amount adsorbed increases as the amount of sulfonate group increases; (ii) the equilibrium constant does not appear as a sensitive parameter to the amount of sulfonate group on the surface of the microspheres; and (iii) the values of the fitting parameters obtained from FSTA may be indicative of a mismatch between the equilibrium separation of the intermolecular interaction and the distance between the adsorption sites. The exhaustive study presented here has shown that FSTA model is a good one considering the complexity of the physical situation, which is intended to be described and could be more useful in interpreting experimental data of adsorption of molecules with different sizes and shapes.

Electroneurografía de nervios craneales en ataxia espinocerebelosa tipo 2 / Electroneurography of the cranial nerves in spinocerebellar ataxia type 2

No disponible

No disponible

Patrón electromiográfico en enfermos y portadores asintomáticos de la mutación SCA2 / Electromyographic pattern in patients and asymptomatic carriers of the SCA2 mutation

No disponible

No disponible

Electroneurografía de nervios craneales en ataxia espinocerebelosa tipo 2

Las ataxias cerebelosas autosómicas dominantes–autosomal dominant cerebellar ataxias(ADCA)constituyen un grupo heterogéneode enfermedades, caracterizadas clínicamentepor Harding en 1983, quien las dividióen los tipos I, II, III y IV. En la tipo I, laataxia de la marcha es el signo clínico primario,relacionado con oftalmoplejía supranuclear,signos piramidales, extrapiramidales, demenciamoderada y neuropatía periférica. Estegrupo incluye la ataxia espinocerebelosa tipo2 (SCA 2) [1,2], que es una de las 29 formasmoleculares descritas actualmente, en laque se ha comprobado una mutación dinámica[3,4] caracterizada por una expansión intergeneracionaldel triplete CAG (cromosoma 12),que explica el incremento en la gravedad delcuadro clínico y el inicio del cuadro a edadesmás tempranas en generaciones sucesivas...(AU)

Saccade velocity is reduced in presymptomatic spinocerebellar ataxia type 2.

OBJECTIVE: A characteristic feature of spinocerebellar ataxia type 2 (SCA2) is saccadic slowing at early disease stages. We sought to determine whether this sign is detectable before clinical manifestation and quantifies the disease progression throughout life in linear fashion. METHODS: In a specialized ataxia clinic, 54 presymptomatic carriers of SCA2 polyglutamine expansions and 56 relatives without mutation were documented with regard to their maximal saccade velocity (MSV). RESULTS: Among the control individuals, a significant effect of aging on MSV was observed. After elimination of this age influence through a matched-pair approach, a presymptomatic decrease of MSV could be shown. The MSV reduction was stronger in carriers of large expansions. In the years before calculated disease manifestation, the MSV impairment advanced insidiously. CONCLUSION: Saccade velocity is a sensitive SCA2 endophenotype that reflects early pontine degeneration and may be a useful diagnostic parameter before the onset of ataxia. SIGNIFICANCE: Future neuroprotective therapies of polyglutamine neurodegeneration may be assessed by MSV from earliest to prefinal disease stages.

Saccade velocity is reduced in presymptomatic spinocerebellar ataxia type 2

A characteristic feature of spinocerebellar ataxia type 2 (SCA2) is saccadic slowing at early disease stages. We sought to determine whether this sign is detectable before clinical manifestation and quantifies the disease progression throughout life in linear fashion. In a specialized ataxia clinic, 54 presymptomatic carriers of SCA2 polyglutamine expansions and 56 relatives without mutation were documented with regard to their maximal saccade velocit Spinocerebellar ataxia type 2 Among the control individuals, a significant effect of aging on MSV was observed. After elimination of this age influence through a matched-pair approach, a presymptomatic decrease of MSV could be shown. The MSV reduction was stronger in carriers of large expansions. In the years before calculated disease manifestation, the MSV impairment advanced insidiously.Saccade velocity is a sensitive SCA2 endophenotype that reflects early pontine degenerationPolyglutamine expansion and may be a useful diagnostic parameter before the onset of ataxia. Significance: Future neuroprotective therapies of polyglutamine neurodegeneration may be assessed by MSV from earliest to prefinal disease stages...(AU)

A rapid and efficient inoculation method for Tomato spotted wilt tospovirus.

A rapid and efficient method of inoculation for Tomato spotted wilt tospovirus (TSWV) was achieved by applying the inoculum with a device consisting of a spray gun, an atomizer and a CO2-powered sprayer. The inoculum contained infected leaf sap prepared in 0.1M phosphate buffer, pH 7.0, 0.2% sodium sulfite and 0.01 M 2-mercaptoethanol (1g: 10 ml) and 1% each of Celite 545 and Carborundum 320 grit. The spray application of chilled inoculum at the rate of 1.1 ml/plant and at an air pressure of 4.1 bar resulted in systemic infection nearly to a 100% of the tobacco (Nicotiana tabacum) plants inoculated. The inoculation procedure was successfully applied to two other important host species of TSWV, peanut (Arachis hypogaea) and tomato (Lycopersicon esculentum), where 75.0-100% and 72.2-91.6% plants developed systemic infection, respectively. The approach facilitated a much faster inoculation of test plants with TSWV as it was estimated to be about 50 times quicker (depending on the plant species) than the hand inoculation. The procedure is suitable for rapid and simultaneous inoculation of a large number of test plants with TSWV and should facilitate screening of germplasm and breeding lines for virus resistance.

Self-healing property of a caustic optical beam.

It is well known that Bessel beams and the other families of propagation-invariant optical fields have the property of self-healing when obstructed by an opaque object. Here it is shown that there exists another kind of field distribution that can have an analog property. In particular, we demonstrate that a class of caustic wave fields, whose transverse intensity patterns change on propagation, when perturbed by an opaque object can reappear at a further plane as if they had not been obstructed. The physics of the phenomenon is fully explained and shown to be related to that of self-healing propagation invariant optical fields.