Fiabilidad intra e interevaluador de un sensor inercial para el rango de movimiento de la rodilla en sujetos asintomáticos / Intra- and inter-reliability of an inertial sensor for knee range of motion in asymptomatic subjects

Introducción: La cuantificación del rango de movimiento de la rodilla es una medida clínicamente relevante en el ámbito sanitario, ya que su disminución puede alterar las actividades de la vida diaria. La obtención de una medida fiable del rango de movimiento nos permite valorar la eficacia de las intervenciones, así como la gravedad de la enfermedad. Por esto, el objetivo de este estudio fue conocer la fiabilidad intra e interevaluador de un protocolo para el rango de movimiento articular de la rodilla llevado a cabo con un sensor inercial en sujetos asintomáticos. Métodos: Se midió el rango de movimiento de 32 rodillas en sujetos asintomáticos, se realizaron 2 sesiones de medición, una por evaluador, en el mismo día. En cada sesión se hicieron un total de 8 mediciones (2 medidas para flexión en decúbito supino, 2 medidas para extensión en decúbito supino, 2 medidas para flexión en bipedestación y 2 para la extensión en bipedestación). Resultados: Para la fiabilidad interevaluador se consiguieron buenos resultados con un ICC superior a 0,79 para todos los movimientos. Los datos obtenidos para la fiabilidad intraevaluador en todos los movimientos fueron excelentes (ICC > 0,88). Conclusión: Este estudio obtuvo una excelente fiabilidad interevaluador e intraevaluador para los sujetos sanos midiendo con sensores inerciales

Introduction: The quantification of knee range of motion is a clinically relevant measurement in the healthcare setting, as its decrease can alter activities of daily living. Collecting reliable measurements of the range of motion allows us to evaluate the reliability of interventions, or the severity of the pathology. The objective of this study was to obtain the intra- and inter- rater reliability of a protocol for the knee the range of joint motion, measured with an inertial sensor in asymptomatic subjects. Methods: The range of motion of 32 asymptomatic knees was measured. Two measurement sessions were performed by two different evaluators. A total of 8 measurements were made in each session: 2 measurements for flexion in supine decubitus position, 2 measurements for extension in supine decubitus, 2 measurements for flexion in standing position and 2 measurements for extension in standing position. Results: For inter-rater reliability, good results were achieved, with an ICC > 0.79 for all movements. The obtained data for intra-rater reliability in all the movements was excellent, with an ICC > 0.88. Conclusion: This study obtained excellent inter-rater and intra-rater reliability for healthy subjects

Review of the novelties from the 2014 ECTRIMS-ACTRIMS Joint Congress, presented at the 7th Post-ECTRIMS Meeting (II).

For the seventh year in a row the Post-ECTRIMS Meeting has been held in Madrid (Spain). Renowned specialists in multiple sclerosis and national leaders in this area have gathered once again to discuss the novelties presented at the 2014 ECTRIM-ACTRIMS World Congress. That meeting gave rise to this review, which is published in two parts. This second part shows that immunological phenomena are increasingly more present in the pathogenesis of the disease, and that the interaction between inflammation and neurodegeneration is becoming more apparent. Metabolic, mitochondrial dysfunction and oxidative stress phenomena are also involved in axonal degeneration and the experimental models open up the way to promising new therapeutic approaches for regenerative strategies. Although ambitious, inducible neural progenitor cells have become a promising alternative to the conventional treatments with stem cells, and the identification of new genetic variants of susceptibility to multiple sclerosis opens up the way to the discovery of new drugs. Reconsidering the value of old drugs and procedures would be another alternative therapeutic development.

TITLE: Revision de las novedades del congreso conjunto ECTRIMS-ACTRIMS 2014, presentadas en la VII Reunion Post-ECTRIMS (II).Por septimo año consecutivo se ha celebrado en Madrid (España) la Reunion Post-ECTRIMS. Reconocidos especialistas en esclerosis multiple y lideres de opinion nacionales se han reunido un año mas para exponer las novedades presentadas en el Congreso Mundial ECTRIMS-ACTRIMS 2014, y fruto de esa reunion se genera esta revision que se publica en dos partes. En esta segunda parte se pone de manifiesto que los fenomenos inmunologicos cada vez estan mas presentes en la patogenia de la enfermedad, y que la interaccion entre inflamacion y neurodegeneracion es mas evidente. Fenomenos metabolicos, de disfuncion mitocondrial y de estres oxidativo tambien se implican en la degeneracion axonal, y los modelos experimentales abren paso a nuevos enfoques terapeuticos con esperanza para las estrategias regenerativas. Aunque resulte ambicioso, los progenitores neurales inducibles se convierten en una prometedora alternativa a los tratamientos convencionales con celulas madre, y la identificacion de nuevas variantes geneticas de susceptibilidad a la esclerosis multiple abre camino al descubrimiento de nuevos farmacos. Replantear el valor de antiguos farmacos y procedimientos seria otra alternativa de desarrollo terapeutico.

[Review of the novelties from the 2014 ECTRIMS-ACTRIMS Joint Congress, presented at the 7th Post-ECTRIMS meeting (I)]. / Revision de las novedades del congreso conjunto ECTRIMS-ACTRIMS 2014, presentadas en la VII Reunion Post-ECTRIMS (I).

For the seventh year in a row the Post-ECTRIMS Meeting has been held in Madrid (Spain). Renowned specialists in multiple sclerosis and national leaders in this area have gathered once again to discuss the novelties presented at the 2014 ECTRIM-ACTRIMS World Congress. That meeting gave rise to this review, which will be published in two parts. One of the main conclusions in this first part is the deeper understanding of the genetic component of multiple sclerosis that we are acquiring, although it is still insufficient unless we bear in mind its interaction with the environmental risk factors of the disease or the impact of comorbidity and healthy habits on the patients' susceptibility and prognosis. In this respect, the authors insist on the fact that, in clinical practice, the cognitive and psychiatric disorders remain under-diagnosed and are rarely taken into account in clinical research. Yet, although scarce, the evidence we have points to the possible benefits of disease-modifying drugs and alternatives to treatment with selective serotonin reuptake inhibitors. Addressing the sub-populations in multiple sclerosis and variants of the disease enhances the importance of an early accurate diagnosis in order to offer patients a safer and more personalised prognosis and treatment. Paediatric multiple sclerosis is ideal for studying the risk factors of the disease but, given its low prevalence, the use of prospective studies raises a number of doubts and there is a preference for conducting collaborative studies.

TITLE: Revision de las novedades del congreso conjunto ECTRIMS-ACTRIMS 2014, presentadas en la VII Reunion Post-ECTRIMS (I).Por septimo año consecutivo se ha celebrado en Madrid (España) la Reunion Post-ECTRIMS. Reconocidos especialistas en esclerosis multiple y lideres de opinion nacionales se han reunido un año mas para exponer las novedades presentadas en el Congreso Mundial ECTRIMS-ACTRIMS 2014, y fruto de esa reunion se genera esta revision que sale publicada en dos partes. Como principales conclusiones de esta primera parte se destaca el mayor entendimiento del componente genetico de la esclerosis multiple al que estamos asistiendo, el cual no resulta suficiente si no se considera su interaccion con los factores ambientales de riesgo de la enfermedad, ni el impacto de la comorbilidad y de las conductas saludables en la susceptibilidad y pronostico de los pacientes. Al respecto, los autores insisten en que, en la practica clinica, las alteraciones cognitivas y psiquiatricas estan infradiagnosticadas y son poco consideradas en la investigacion clinica; no obstante, la evidencia, aunque escasa, apunta hacia posibles beneficios de los farmacos modificadores de la enfermedad y alternativas al tratamiento inhibidor selectivo de la recaptacion de serotonina. El abordaje de las subpoblaciones en esclerosis multiple y variantes de la enfermedad refuerza la importancia del diagnostico precoz y preciso para ofrecer a los pacientes un pronostico y un tratamiento mas seguros y personalizados. La esclerosis multiple pediatrica es idonea para estudiar factores de riesgo de la enfermedad, pero dada su baja prevalencia, se cuestionan los estudios prospectivos y se aboga por los estudios colaborativos.

Associated Inosine to interferon: results of a clinical trial in multiple sclerosis.

BACKGROUND: Uric acid (UA) could act as a natural peroxynitrite scavenger with antioxidant properties. It has been proposed that hyperuricemia might protect against multiple sclerosis (MS). METHODS: Patients with relapsing-remitting MS starting treatment with interferon beta-1a 44 µg sc 3/week were randomly assigned to receive either inosine 3 g/day or placebo in a double-blind manner. Follow-up was 12 months. Outcome measures were adverse events and UA laboratory results. Secondary end point was clinical and radiological activity of MS. Relapse rates, percentage of patients without relapses, and progression to secondary MS (SPMS) were assessed. RESULTS: Thirty six patients were included. Two patients in the inosine group showed UA serum level above 10 mg/ml, and symptoms derived from renal colic not leading to hospital admission. Ten additional patients had asymptomatic hyperuricemia (>7 mg). Efficacy parameters (clinical and radiological) were similar between groups. No patient progressed to SPMS CONCLUSIONS: Inosine administration was associated with hyperuricemia and renal colic with no additional effect on MS. We cannot conclude inosine is a safe and well-tolerated drug. Doses of around 2 g/day may be more appropriate for future trials.

Review of the novelties presented at the 29th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) (I).

The most relevant data presented at the 29th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS), held in October 2013 in Denmark, were summarised at the sixth edition of the Post-ECTRIMS Expert Meeting, held in Madrid in October 2013, resulting in this review, to be published in three parts. This first part of the Post-ECTRIMS review presents an update on gender differences in multiple sclerosis (MS) as well as new evidence on the impact of sex hormones on the disease. We should consider that there is still much to discover with regard to the genetic components of the disease. Similarly, possible infections and lifestyle habits are added as triggers of the known environmental risk factors for MS. The interaction between genetics and the environment has been increasingly implicated as a cause of susceptibility to MS. With regard to the mechanisms of inflammation, axo-glial proteins, instead of myelin proteins, may be the early antigenic targets, and B cells have been implicated in the production of cytokines toxic to oligodendrocytes. Chitinase 3-like 1 (CHI3L1) is validated as a prognostic marker of conversion to MS, and immunoglobulin M oligoclonal bands and L-selectin could be incorporated as possible measures of the risk stratification strategy in patients treated with natalizumab.

TITLE: Revision de las novedades presentadas en el XXIX Congreso del Comite Europeo para el Tratamiento e Investigacion en Esclerosis Multiple (ECTRIMS) (I).Los datos mas relevantes presentados en la XXIX edicion del Congreso del Comite Europeo para el Tratamiento e Investigacion en Esclerosis Multiple (ECTRIMS), celebrado en octubre de 2013 en Dinamarca, se han resumido en la sexta edicion de la Reunion de Expertos Post-ECTRIMS celebrada en Madrid en octubre de 2013, fruto de la cual nace esta revision, que se publica en tres partes. Esta primera parte de la revision Post-ECTRIMS presenta una vision actualizada de las diferencias de genero en la esclerosis multiple (EM), asi como las nuevas evidencias sobre el impacto de las hormonas sexuales en la enfermedad. Podemos asumir que aun queda mucho por descubrir con relacion al componente genetico de la enfermedad. De la misma manera, a los ya conocidos factores ambientales de riesgo para la EM se unen posibles infecciones y habitos de vida como desencadenantes. La interaccion entre la genetica y el ambiente cada vez cobra mas fuerza como causa de susceptibilidad a la EM. En cuanto a los mecanismos de inflamacion, las proteinas del complejo axoglial pueden ser las dianas antigenicas iniciales en lugar de las proteinas de mielina, y las celulas B se han visto implicadas en la produccion de citocinas toxicas para los oligodendrocitos. La quitinasa 3-like 1 se valida como marcador pronostico de conversion a EM, y las bandas oligoclonales de inmunoglobulina M y la L-selectina podrian incorporarse como posibles medidas dentro de la estrategia de estratificacion del riesgo en pacientes tratados con natalizumab.

Buscando una herramienta para la detección precoz de deterioro cognitivo en esclerosis múltiple / Looking for a tool for early detection of cognitive impairment in multiple sclerosis

Introducción: el deterioro cognitivo tiene una elevada prevalencia en Esclerosis Múltiple (EM). Sin embargo su detección continúa siendo difícil y tardía. Los tests neuropsicológicos continúan siendo las herramientas de screening más utilizadas. Recientemente, se ha sugerido, que variables objetivas y cuantificables, como potenciales evocados cognitivos (onda P300) y la tomografía de coherencia óptica (OCT), podrían ser útiles en la evaluación cognitiva. Objetivos: realizar un estudio comparativo entre Paced-Auditory-Serial-Addition-Test (PASAT) y Faces-Symbol-Test (FST); posteriormente aplicar OCT y P300 y valorar el grado de concordancia existente entre estas pruebas y los tests neuropsicológicos. Material y métodos: se seleccionaron pacientes con EM, pertenecientes a la consulta de Neurología del Hospital Xeral de Vigo, que cumplieran con los criterios de inclusión del estudio. Se aplicaron el FST y PASAT, registrándose el tiempo empleado para su realización. Se entregó una Escala Subjetiva de Valoración de ambos tests. Finalmente, se completó el estudio con la aplicación de OCT y P300. Resultados: se incluyeron 25 pacientes. El análisis estadísitico observó un alto grado de concordancia entre el PASAT y el FST en cuanto a capacidad diagnóstica. Sin embargo el PASAT precisó más tiempo para su realización y fue considerado un test incómodo. A su vez se objetivó un grado aceptable de concordancia entre el FST, la OCT y la P300. El PASAT no demostró dicha correlación. Conclusiones: el FST ofrece resultados superponibles a los del PASAT en cuanto a la detección del deterioro cognitivo en pacientes con EM. A su vez, presenta un elevado grado de concordancia con marcadores objetivos como la OCT y la onda P300 (AU)

Background. Cognitive impairment is highly prevalent in multiple sclerosis (MS). But detection remains difficult and late. Neuropsychological tests remain being the best screening tools used. Recently, it has been suggested that objective and quantifiable variables, such as cognitive evoked potentials (P300) and optical coherence tomography (OCT), may be useful in cognitive assessment. Objectives: to conduct a comparative study between Paced Auditory Serial- Addition -Test (PASAT) and Faces- Symbol- Test (FST) and then apply OCT and P300, and assess the degree of agreement between these tests and neuropsychological tests. Methods: MS patients were selected, belonging to the Neurology Xeral Hospital of Vigo, who met the study inclusion criteria The FST and PASAT were applied and the time taken to complete them was recorded. One Subjective Rating Scale was given to patients to asses both tests. Finally, the study was completed with the applicationof OCT and P300. Results: 25 patients were included in the study. The statistical analysis observed a high degree of concordance between the PASAT and FST in terms of diagnostic capability. However PASAT required more time to be completed and was considered an uncomfortable test. In turn, an acceptable level of agreement between the FST, the OCT and the P300 was observed. The PASAT showed no such correlation. Conclusions: FST provides results that overlap those of PASAT regarding detection of cognitive impairment in MS patients. Turn, has a high degree of concordance with objective markers such as OCT and P300 (AU)

Review of the novelties presented at the 28th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) (II).

The most relevant data presented at the 28th edition of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) held in October 2012 in France have been summarised in the fifth edition of the Post-ECTRIMS Expert Meeting held in Madrid in October 2012. This review is the result of the meeting, which is being published in three parts. This second part of the Post-ECTRIMS review discusses the biology of recovery and remyelination in multiple sclerosis (MS) as well as the different repair and endogenous and exogenous remyelination strategies currently being evaluated based on the fact that resident microglia and oligodendroglial progenitor cells have been implicated in the remyelination process. This review also discusses the current state and future use of biomarkers in MS and proposes as markers of neurodegeneration the following: T2 lesion volume and brain atrophy using MRI and the loss of the ganglion cell layer as assessed by optical coherence tomography. A greater future utility for double inversion recovery (DIR) sequences is proposed to correlate cognitive impairment with MS impairment, given its higher diagnostic yield in locating and defining cortical lesions. The availability of novel biomarkers in the future requires strict validation. In this context, this paper proposes possible areas of action to improve the current situation and also presents the latest research results in identifying potential candidates with useful diagnostic characteristics, prognostic characteristics, treatment responses, and safety procedures.

TITLE: Revision de las novedades presentadas en el XXVIII Congreso del Comite Europeo para el Tratamiento e Investigacion en Esclerosis Multiple (ECTRIMS) (II).Los datos mas relevantes presentados en la XXVIII edicion del Congreso del Comite Europeo para el Tratamiento e Investigacion en Esclerosis Multiple (ECTRIMS), celebrado en octubre de 2012 en Francia, han sido resumidos en la quinta edicion de la Reunion de Expertos Post-ECTRIMS celebrada en Madrid en octubre de 2012, fruto de la cual nace esta revision que se publica en tres partes. En esta segunda parte de la revision Post-ECTRIMS se analiza la biologia de la recuperacion y remielinizacion en la esclerosis multiple (EM), y se discuten las diferentes estrategias de reparacion y remielinizacion endogena y exogena que actualmente estan siendo evaluadas, sobre la base de que la microglia residente y las celulas precursoras de oligodendrocitos se han visto implicadas en el proceso de remielinizacion. Asimismo, se expone el estado actual y uso futuro de los biomarcadores en EM, y se proponen como marcadores de neurodegeneracion el volumen lesional en T2 y la atrofia cerebral mediante resonancia magnetica, asi como la perdida de capa de celulas ganglionares mediante tomografia de coherencia optica. Se plantea una mayor utilidad futura de las secuencias DIR para correlacionar las alteraciones cognitivas con las alteraciones de la EM, dado su mayor rendimiento diagnostico en localizar y definir lesiones corticales. La disponibilidad de nuevos biomarcadores en un futuro requiere una validacion estricta. En este sentido, se plantean posibles areas de actuacion dirigidas a mejorar la situacion actual, y ademas se presentan los resultados de las investigaciones mas recientes en la identificacion de posibles candidatos con utilidad diagnostica, pronostica, de respuesta al tratamiento y de seguridad.

Severe haematological complications during treatment with natalizumab.

The safety profile of natalizumab has been widely discussed due to several cases of progressive multifocal leukoencephalopathy, reported worldwide. Since the launch of natalizumab, 32 patients have been treated at our centre. In this context, we describe two cases (6.25%), one of immune-mediated acute haemolytic anaemia (IAHA) and another of immune thrombocytopenic purpura during treatment with natalizumab. The temporal relationship between drug administration and the nature of the haematological complications, confirmed with the serological findings in the case of the IAHA, suggests that natalizumab is the most probable cause for these adverse events. Although very uncommon, the haematological complications are severe enough to justify a close and careful monitoring for all patients with multiple sclerosis treated with an immunosuppressant treatment.

[Review of the novelties presented at the 26th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) (II)]. / Revision de las novedades presentadas en el XXVI Congreso del Comite Europeo para el Tratamiento e Investigacion en Esclerosis Multiple (ECTRIMS) (II).

The new insights presented at European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS), held in the city of Gothenburg, Sweden, in October 2010, have been summarized at the third edition of Post-ECTRIMS meeting held in Madrid in November 2010. Encouraging findings from the 5-years follow up extension from PreCISe study confirm the benefit of early treatment with glatiramer acetate in patients with clinically isolated syndromes (CIS) against the conversion to clinically definitive multiple sclerosis and cerebral atrophy with an adequate safety and tolerability. Regarding treatment decision with escalation or induction therapy, different strategies have been proposed depending on to the characteristics of the individual patient with CIS. Findings from several of the reported studies have revealed the favorable role of combined therapy on relapse rate but not on magnetic resonance parameters in patients with recurrent-remittent multiple sclerosis. Novel therapies such as alemtuzumab, daclizumab ofatutumab or ocrelizumab have shown promising findings regarding efficacy. Nevertheless, safety findings for these emerging therapies have detected some severe adverse events, the main ones being potentially fatal opportunistic infections such as progressive multifocal leukoencephalopathy (PML) caused by JC virus, mainly linked to natalizumab treatment. In this regard, clinicians will face the assessment of he benefit-risk ratio when deciding on the adequate treatment for each patient in the clinical setting. In this regard, determination of antibodies to JC virus by a novel two-step enzyme-linked immunosorbent assay (ELISA) could provide clinicians with a useful tool to stratify PML risk in patients. Regarding non pharmacologic therapies, behavioral intervention has emerged as an effective therapy in the treatment of depression in multiple sclerosis, showing additional benefits on fatigue, disability and adherence to treatment.

[Behavioural disorders in Alzheimer's disease. Data from a populational study]. / Alteraciones del comportamiento en la enfermedad de Alzheimer. Datos de un estudio poblacional.

AIMS: The purpose of this work was to study the characteristics of the behavioural disorders (non-cognitive or neuropsychiatric symptoms) presented by subjects with Alzheimer's disease from a sample of the population together with their relation to the cognitive and functional impairment suffered by these patients. PATIENTS AND METHODS: NEDICES is a longitudinal populational study based on the census of neurological diseases in subjects above the age of 64. In 2001, a study was conducted of the situation of 83 subjects who had started suffering from Alzheimer's disease between 1994 and 1997. Due to death and a number of other reasons, only 32 of them could be examined. Patients were administered a structured interview with scales referring to the cognitive state, functional capacity, severity of the dementia and the presence and severity of neuropsychiatric disorders. RESULTS: All the patients studied presented some non-cognitive symptom. Apathy was the most frequent (93.8%), followed by irritability (81.1%), anxiety (75.0%), dysphoria (71.8%) and agitation-aggressiveness (56.2%). The least frequent were deliria (50.2%), altered nocturnal behaviour and aberrant motor activity (37.6%), altered appetite and eating, and hallucinations (24.9%), disinhibition (21.8%) and euphoria (21.6%). The degree of cognitive impairment and the presence of non-cognitive symptoms exerted a similar and independent effect on functional capacity. Only 56.3% of the patients were treated with some kind of anticholinesterase or psychotropic medication. CONCLUSIONS: Our census-based populational study confirmed the high prevalence rate of non-cognitive symptoms in patients with Alzheimer's disease. These data confirm the notion that these symptoms are intrinsic manifestations of the disease.

Alteraciones del comportamiento en la enfermedad de Alzheimer. Datos de un estudio poblacional / Behavioural disorders in Alzheimer's disease. Data from a populational study

Objetivo. Investigar las características de las alteraciones del comportamiento (síntomas no cognitivos o neuropsiquiátricos) que presentan los sujetos con enfermedad de Alzheimer procedentes de una muestra poblacional y su relación con el deterioro cognitivo y funcional que muestran estos pacientes. Pacientes y métodos. El NEDICES es un estudio poblacional longitudinal basado en el censo sobre enfermedades neurológicas en sujetos mayores de 64 años. En 2001 se estudió la situación de 83 sujetos que habían iniciado una enfermedad de Alzheimer entre 1994 y 1997. Sólo pudieron examinarse 32, debido a fallecimientos y a otras causas. Se realizó una entrevista estructurada con escalas referentes a la situación cognitiva, la capacidad funcional, la gravedad de la demencia y la presencia y gravedad de alteraciones neuropsiquiátricas. Resultados. Todos los pacientes estudiados presentaban algún síntoma no cognitivo. La apatía fue el más frecuente (93,8 por ciento), seguido por la irritabilidad (81,1 por ciento), la ansiedad (75,0 por ciento), la disforia (71,8 por ciento) y la agitación-agresión (56,2 por ciento). Los menos frecuentes fueron los delirios (50,2 por ciento), las alteraciones del comportamiento nocturno y la actividad motora aberrante (37,6 por ciento), las alteraciones del apetito y la alimentación y las alucinaciones (24,9 por ciento), la desinhibición (21,8 por ciento) y la euforia (21,6 por ciento). El grado del deterioro cognitivo y la presencia de síntomas no cognitivos tuvieron una influencia similar e independiente sobre la capacidad funcional. Sólo el 56,3 por ciento de los pacientes se trataban con algún tipo de medicación anticolinesterásica o psicotrópica. Conclusiones. Confirmamos en un estudio poblacional con base en el censo la alta prevalencia de síntomas no cognitivos en los pacientes con enfermedad de Alzheimer; este dato reafirma que estos síntomas son manifestaciones intrínsecas de la enfermedad. (AU)

Aims. The purpose of this work was to study the characteristics of the behavioural disorders (non-cognitive or neuropsychiatric symptoms) presented by subjects with Alzheimer’s disease from a sample of the population together with their relation to the cognitive and functional impairment suffered by these patients. Patients and methods. NEDICES is a longitudinal populational study based on the census of neurological diseases in subjects above the age of 64. In 2001, a study was conducted of the situation of 83 subjects who had started suffering from Alzheimer’s disease between 1994 and 1997. Due to death and a number of other reasons, only 32 of them could be examined. Patients were administered a structured interview with scales referring to the cognitive state, functional capacity, severity of the dementia and the presence and severity of neuropsychiatric disorders. Results. All the patients studied presented some non-cognitive symptom. Apathy was the most frequent (93.8%), followed by irritability (81.1%), anxiety (75.0%), dysphoria (71.8%) and agitation-aggressiveness (56.2%). The least frequent were deliria (50.2%), altered nocturnal behaviour and aberrant motor activity (37.6%), altered appetite and eating, and hallucinations (24.9%), disinhibition (21.8%) and euphoria (21.6%). The degree of cognitive impairment and the presence of non-cognitive symptoms exerted a similar and independent effect on functional capacity. Only 56.3% of the patients were treated with some kind of anticholinesterase or psychotropic medication. Conclusions. Our census-based populational study confirmed the high prevalence rate of non-cognitive symptoms in patients with Alzheimer’s disease. These data confirm the notion that these symptoms are intrinsic manifestations of the disease (AU)

[Experience in the treatment of multiple sclerosis with interferon beta in Galicia]. / Experiencia del tratamiento con interferón beta en la esclerosis múltiple en Galicia.

OBJECTIVE: To analyze the experience in daily clinical practice of interferon-beta (IFN-beta) treatment in relapsing-remitting (RR) and secondary progressive (SP) multiple sclerosis (MS) in Galicia (Spain). PATIENTS AND METHODS: Patients with RR-MS and SP-MS treated with IFN-beta1a and 1b between 1995 and December/2000, analyzing demographic and clinical data. RESULTS: 313 patients were included, with a mean age of 38.2 years. A total of 296 patients (94.6%) were clinically defined MS and 17 (5.4%) were laboratory supported (Poser criteria); 84.6% of the patients were RR and 15.4% were SP. The mean duration of the disease prior to treatment was 7.06 years. Betaferon was used in 52.4% patients (115 RR-MS and 47 SP-MS), Avonex in 26% and Rebif in 21.6%. Relapse rate was reduced in 68.8% for the RR-MS for Betaferon-treated patients, 73.3% for Avonex treated and 35.7% for Rebif-treated patients. Betaferon reduced relapse rate in 50% for SP-MS. The global EDSS remained stable during IFN-beta treatment. During treatment, 33% of Betaferon, 60.5% of Avonex and 54.5% of Rebif-treated patients remained relapse-free. Treatment was suspended in 12.9% of Betaferon, 6.2% of Avonex, and 3% Rebif-treated patients. The most frequent causes of treatment suspension were increase in disability and in relapse count. CONCLUSIONS: The present study supports the benefits of IFN-beta treatment in RR MS and SP MS in daily clinical practice, with reduction in relapses count and incapacity, good over-all tolerance and low incidence of serious adverse side-effects.

Experiencia del tratamiento con interferón B en la esclerosis múltiple en Galicia / Experience in the treatment of multiple of multiple sclerosis with interferón beta in Galicia

Objetivo. Analizar la experiencia en la práctica clínica diaria del tratamiento con interferón b (IFN b) en la esclerosis múltiple (EM) remitenterecidivante (RR) y secundaria progresiva (SP) en Galicia. Pacientes y métodos. Se analizaron los datos clínicos y demográficos de pacientes con EM RR y EM SP tratados con IFN b 1a y 1b entre 1995 y diciembre de 2000. Resultados. Se incluyeron 313 pacientes, con una media de edad de 38,2 años. Un total de 296 caso (94,6%) fueron EM clínicamente definidos y 17 (5,4%) fueron EM apoyados por laboratorio (criterios Poser); el 84,6% de los pacientes padecían EM RR y el 15,4%, EM SP. La duración media de la enfermedad antes del tratamiento fue 7,06 años. Se empleó Betaferón â en el 52,4% de los pacientes (115 EM RR y 47 EM SP), Avonex â en el 26% y Rebif â en el 21,6%. La tasa de brotes se redujo en un 68,8% para la EM RR en los pacientes tratados con Betaferón, en un 73,3% en los tratados con Avonex y en un 35,7% en los tratados con Rebif. El Betaferón redujo la tasa de brotes en un 50% para la EM SP. Durante el tratamiento, el EDSS global permaneció estable, y el 33% de los pacientes tratados con Betaferón, el 60,5% de los tratados con Avonex y el 54,5% de los tratados con Rebif permanecieron libres de brotes. El tratamiento se suspendió en el 12,9% de los pacientes tratados con Betaferón, el 6,2% de los tratados con Avonex, y el 3% de los tratados con Rebif, y las causas más frecuentes fueron el incremento de la discapacidad y el aumento de brotes. Conclusiones. Este estudio apoya el beneficio del tratamiento con IFN b en la EM RR y la EM SP en la práctica clínica diaria, pues promueve la reducción de los brotes, la tasa de brotes y la discapacidad, con una buena tolerancia global y una baja incidencia de efectos secundarios graves (AU)

Objective. To analyze the experience in daily clinical practice of interferonbeta (IFN b) treatment in relapsing remitting (RR) and secondary progressive (SP) multiple sclerosis (MS) in Galicia (Spain). Patients and methods. Patients with RRMS and SPMS treated with IFN b 1a and 1b between 1995 and December/2000, analyzing demographic and clinical data. Results. 313 patients were included, with a mean age of 38,2 years. A total of 296 patients (94,6%) were clinically defined MS and 17 (5,4%) were laboratory supported (Poser criteria); 84,6% of the patients were RR and 15,4% were SP. The mean duration of the disease prior to treatment was 7,06 years. Betaferon â was used in 52,4% patients (115 RRMS and 47 SPMS), Avonex â in 26% and Rebif â in 21,6%. Relapse rate was reduced in 68,8% for the RRMS for Betaferontreated patients, 73,3% for Avonex treated and 35,7% for ebiftreated patients. Betaferon reduced relapse rate in 50% for SPMS. The global EDSS remained stable during IFN b treatment. During treatment, 33% of Betaferon, 60,5% of Avonex and 54,5% of Rebiftreated patients remained relapsefree. Treatment was suspended in 12,9% of Betaferon, 6,2% of Avonex, and 3% Rebiftreated patients. The most frequent causes of treatment suspension were increase in disability and in relapse count. Conclusions. The present study supports the benefits of IFN b treatment in RR MS and SP MS in daily clinical practice, with reduction in relapses count and discapacity, good overall tolerance and low incidence of serious adverse sideeffects (AU)

Clinicopathological studies of some non-Alzheimer dementing diseases.

The brains of most demented patients show at autopsy the lesions of Alzheimer's disease (AD). However, the brains of other demented patients show either no morphological changes or lesions distinct from those of AD. We report clinicopathological studies on two diseases in this latter group. The study of these diseases can improve our understanding of AD. Pick's disease is characterized by dementia, lobar cerebral atrophy, and neuronal cytoplasmic inclusions. Most cases, which we have called "classical", show inclusions made up of straight fibrils that are immunologically cross-reactive with the paired helical filaments of AD. In other "generalized" cases, similar fibrils are coated by granular material and are less reactive with anticytoskeletal antibodies. In contrast to the cytoplasmic localization of the lesions in Pick's disease, it is the cell nucleus that shows abnormalities in neuronal intranuclear hyaline inclusion disease. This disease can present clinically as dementia of adult onset. Thus, either nuclear or cytoplasmic lesions can produce a pattern of neuronal dysfunction resulting in dementia.

Gliogenesis in organotypic tissue culture of the spinal cord of the embryonic mouse. I. Immunocytochemical and ultrastructural studies.

The technique of organotypic tissue culture offers an opportunity to observe in vitro complex interactions among glial cells and neurons, leading to the formation of myelin. In the present and accompanying work a combined ultrastructural, immunocytochemical and autoradiographic approach was used in a detailed study of the process of gliogenesis. Using immunocytochemical and ultrastructural criteria, differentiation along the oligodendroglia cell line is seen to be initiated a few days later than along the astroglial line. The sequence and timing of oligodendroglial differentiation both ultrastructurally and chemically follow those described in vivo. Formation of myelin has been demonstrated only by oligodendrocytes in which there is continuity between the perikaryal plasmalemma and myelin membranes. Oligodendroglial maturation culminated with the formation of light, medium and dark oligodendrocytes. The periodic acid Schiff-positive, glial fibrillary acidic protein (GFAP)-negative process of radial glial cells at explantation become GFAP-positive within 3 days, as described in vivo. Many of the astrocytes appear to have been derived from radial glial cells. Large numbers of dark glial cells, similar to the so-called 'intermediate glial cells', were seen. These were found to be astrocytes whose appearance probably reflected reaction to explantation-induced injury.

Adult-onset neuronal intranuclear hyaline inclusion disease.

We studied the clinical and pathologic features of two cases of neuronal intranuclear hyaline inclusion disease. The cases were unique in late onset, presentation with dementia, possible autosomal dominant pattern of inheritance (in one patient), predominance of inclusions in glial cells, and mineral deposits within some inclusions. Differences from other reported cases indicate that this is probably not a homogeneous entity.