[Frequent involvement of the amyloid pathway in prodromal dementia with Lewy bodies]. / Frecuente alteracion de la via amiloide en la demencia con cuerpos de Lewy prodromica.

INTRODUCTION: Lewy body dementia (LBD) is the most frequent of the degenerative dementias, after Alzheimer's disease. AIM: To analyse the core biomarkers of Alzheimer's disease in the cerebrospinal fluid of exclusively Hispanic patients with prodromal LBD, in order to determine whether there is involvement of the amyloid pathway or the tau pathway. PATIENTS AND METHODS: Between 2008 and 2017 we included 430 patients with mild cognitive impairment according to Petersen criteria, from three hospitals in the province of Alicante. They underwent clinical check-ups every 6-12 months to evaluate their clinical stability or their progression to dementia using current clinical criteria. Among other complementary tests, biomarkers for Alzheimer's disease in the cerebrospinal fluid were analysed. RESULTS: Of all the patients included, 26 developed LBD and 29 remained stable for at least five years, and were thus considered as a reference. In this group only five (17%) had Abeta(1-42) protein values below normal, whereas 16 (55%) of the patients with LBD had altered levels. No differences were found in the levels of tau protein. On comparing the LBD groups with and without amyloidosis, differences were only found in the levels of Abeta(1-42) protein. CONCLUSIONS: We highlight the frequent presence of amyloid pathology in prodromal LBD in our population, and the probable involvement of different metabolic pathways in the same clinically defined dementia.

TITLE: Frecuente alteracion de la via amiloide en la demencia con cuerpos de Lewy prodromica.Introduccion. La demencia con cuerpos de Lewy (DCLW) es la mas frecuente de las degenerativas, despues de la enfermedad de Alzheimer. Objetivo. Analizar los biomarcadores core de la enfermedad de Alzheimer en el liquido cefalorraquideo de pacientes exclusivamente hispanos con DCLW prodromica, para conocer si existe alteracion de la via amiloide o de la via tau. Pacientes y metodos. Entre 2008-2017 incluimos a 430 pacientes con deterioro cognitivo leve segun los criterios de Petersen, procedentes de tres hospitales de la provincia de Alicante. Se les realizaron revisiones clinicas cada 6-12 meses para evaluar su estabilidad clinica o la progresion a demencia utilizando los criterios clinicos vigentes. Entre otras pruebas complementarias se analizaron los biomarcadores de enfermedad de Alzheimer en el liquido cefalorraquideo. Resultados. Entre todos los pacientes incluidos, 26 desarrollaron DCLW y 29 se mantuvieron estables durante al menos cinco años, por lo que los consideramos como referencia. En este grupo solamente cinco (17%) tenian valores de proteina Abeta(1-42) inferiores a la normalidad, mientras que 16 (55%) de los pacientes con DCLW tenian niveles alterados. No se encontraron diferencias en los niveles de las proteinas tau. Al comparar los grupos con DCLW con y sin amiloidosis solamente encontramos diferencias en los niveles de proteina Abeta(1-42). Conclusiones. Destacamos la frecuente presencia de patologia amiloidea en la DCLW prodromica en nuestra poblacion y la probable alteracion de diferentes vias metabolicas en una misma demencia clinicamente definida.

Transorbital ultrasonography for measuring optic nerve atrophy in multiple sclerosis.

OBJECTIVE: we aimed to evaluate the utility of transorbital ultrasonography (TOS) in optic nerve assessment and quantification of ON atrophy in MS patients, and to determine whether ON atrophy correlates with the disease duration and disability measured on the Kurtzke Expanded Disability Status Scale (EDSS). MATERIALS AND METHODS: Prospective, multicentre, blinded cohort study of 59 patients diagnosed with relapsing-remitting MS and 36 controls. RESULTS: When measured with TOS, the diameter of both the right (2.69 ± 0.30 mm in cases; 3.20 ± 0.19 mm in controls, P < .0001) and left (2.71 ± 0.26 mm in cases; 3.24 ± 0.15 mm controls, P < .0001) ON of study patients was smaller than controls. We observed a negative correlation between EDSS and both right (ρ = .524) and left (ρ = .469) ON diameter. We also observed a negative correlation between disease duration and both right (r = .602) and left (r = .538) ON diameter. No difference was observed in the diameter of both ON among patients with a history of optic neuritis (right OND 2.68 ± 0.29 mm; left OND 2.69 ± 0.25 mm) and patients with no history of optic neuritis (right OND 2.70 ± 0.30 mm; left OND 2.73 ± 0.27 mm) (P = .805; P = .651). CONCLUSIONS: The thickness of ON measured with TOS is correlated with EDSS and the duration of the disease without being interfered by the previous history of optic neuritis. TOS could be a reliable technique for measuring ON atrophy in MS.

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

INTRODUCTION: Post-authorisation studies are important to confirm whether the outcomes of clinical trials are reproduced in usual clinical practice. AIMS: To evaluate the effectiveness and safety of fingolimod in clinical practice in the province of Alicante. PATIENTS AND METHODS: A retrospective multi-centre study was conducted with remitting multiple sclerosis patients treated with fingolimod. Demographic, clinical and pharmacological data were collected. We report on the effectiveness of the drug -annualised relapse rate (ARR) and percentage of patients free from attacks- at one and at two years after treatment in relation to the previous year, and data concerning side effects are also provided. RESULTS: The sample consisted of 89 patients. Previous treatment was with immunomodulators (interferon beta or glatiramer acetate) in 54 patients and natalizumab in 32. Fifty patients changed due to failure with the immunomodulator and 31 owing to positive serology for JC virus (JCV+). Overall ARR decreased by 67.3% the first year (p < 0.0001) and by 84.1% the second (p = 0.0078). It diminished in patients with immunomodulator failure (85.6% the first year, p < 0.0001; 88.9% the second year, p = 0.0039) and increased in a non-significant manner in JCV+ patients in the first year. The percentage of patients free from relapses in the overall population increased from 32.6% to 68.1% in the first year (p < 0.0019) and to 82.6% in the second (p = 0.0215). This increase was not observed in JCV+ patients. Side effects were reported by 13 patients, which led to the drug being withdrawn in two of them. CONCLUSION: In clinical practice in the province of Alicante, levels of effectiveness and safety of fingolimod proved to be slightly higher than those found in clinical trials.

TITLE: Fingolimod: efectividad y seguridad en la practica clinica habitual. Estudio observacional, retrospectivo y multicentrico en la provincia de Alicante.Introduccion. Los estudios postautorizacion son importantes para confirmar si los resultados de los ensayos clinicos se reproducen en la practica clinica habitual. Objetivo. Evaluar la efectividad y seguridad del fingolimod en la practica clinica en la provincia de Alicante. Pacientes y metodos. Estudio multicentrico retrospectivo de pacientes con esclerosis multiple remitente tratados con fingolimod. Se recogen las caracteristicas demograficas, clinicas y farmacologicas. Se describe la efectividad del farmaco ­tasa anualizada de brotes (TAB) y porcentaje de pacientes libres de brotes­ al año y a los dos años de tratamiento en relacion con el año previo y datos de efectos secundarios. Resultados. Se incluyo a 89 pacientes. El tratamiento previo fue inmunomodulador (interferon beta o acetato de glatiramero) en 54 pacientes y natalizumab en 32. Cincuenta pacientes cambiaron por fracaso con el inmunomodulador y 31 por serologia positiva del virus JC (VJC+). La TAB global disminuyo el 67,3% el primer año (p < 0,0001) y el 84,1% el segundo (p = 0,0078). Disminuyo en los pacientes con fracaso del inmunomodulador (el 85,6% el primer año, p < 0,0001; el 88,9% el segundo año, p = 0,0039) y aumento de forma no significativa en los pacientes VJC+ en el primer año. El porcentaje de pacientes libres de brotes en la poblacion global aumento del 32,6 al 68,1% en el primer año (p < 0,0019) y al 82,6% en el segundo (p = 0,0215). Este aumento no se observo en los pacientes VJC+. Trece pacientes tuvieron efectos secundarios, que obligaron a la retirada del farmaco en dos de ellos. Conclusion. En la practica clinica de la provincia de Alicante, el fingolimod mostro una efectividad y una seguridad ligeramente superiores a las de los ensayos clinicos.

Polirradiculoneuritis aguda sensitivo-motora axonal autoinmune en el seno de una enfermedad inflamatoria intestinal / Autoimmune acute motor sensory axonal polyradiculoneuritis in a case of inflammatory bowel disease

No disponible

Papel del estudio neurofisiológico en el síndrome de Miller-Fisher / Role of neurophysiological studies in Miller-Fisher syndrome

No disponible

Acetato de glatiramero en pacientes con esclerosis múltiple remitente-recurrente no respondedores al interferón beta / Glatiramer acetate in interferon beta non respondent relapsing-remitting multiple selerosis

Introducción y objetivo. Existen cuatro tratamientos inmunomoduladores eficaces (3 interferones beta [IFNß] y el acetato de glatiramero [AG]) aprobados como primera línea de tratamiento para los pacientes con esclerosis múltiple remitente-recurrente. El objetivo de este estudio es analizar si el acetato de glatiramero es útil en aquellos pacientes en los que han suspendido el IFNß por presentar una respuesta subóptima o efectos adversos. Métodos. Se trata de un estudio observacional y retrospectivo en pacientes diagnosticados de EM remitente recurrente que habían sustituido IFN (2,9±2,4 años de tratamiento) por AG (duración media de 1,9±1,4 años). Se clasificaron en dos grupos dependiendo del motivo del cambio: respuesta subóptima o efectos secundarios. Se analizó la duración de los tratamientos, el número de brotes y las causas de abandono de ambos fármacos. Resultados. Se incluyeron 58 pacientes, de los que 20 pacientes suspendieron el IFNß por falta de eficacia, mientras que 38 lo hicieron por efectos adversos. En el primer grupo la tasa de brotes se redujo desde 1,38±0,95 brotes anuales con IFNß a 0,52±0,86 con AG. En el segundo grupo, la tasa anual de brotes fue similar: 0,33±0,64 brotes anuales con IFNß y 0,37±0,79 tasa de brotes con AG. Conclusiones. El AG puede ser considerado una buena alternativa para los pacientes con EM remitente recurrente activa que no respondan al IFNß y para aquellos que muestren efectos adversos, ya que ambos fármacos tienen mecanismos de acción diferentes (AU)

Introduction and objective. There are 4 immunomodulator treatments approved as first line therapy for patients with re-lapsing-remitting multiple sclerosis (RRMS). The objective of this study is to assess if glatiramer acetate (GA) is useful or not in patients who have discontinued interferon beta due to a suboptimal response or adverse events. Methods. This is an observational and retrospective study in RRMS patients who discontinued IFN-beta therapy (2.9±2.4 years of treatment) and switched to GA (1.9±1.4 years). They were classified in 2 groups depending on the reason for discontinuation: suboptimal response or side effects. In both treatments we analysed number of relapses, treatment duration and causes of discontinuation. Results. We included 58 patients of which 20 discontinued IFN-beta for lack of effectiveness whereas 38 were due to adverse events. Patients who discontinued for suboptimal response changed from 1.38 ± 0.95 relapses per year with IFN-beta to 0.52±0.86 with GA. Patients who discontinued for adverse events changed from 0.33 ± 0.64 relapses per year with IFN-beta to 0.37±0.79 with GA. Conclusions. GA can be considered a good alternative treatment for MS patients with a suboptimal response or adverse events with IFN-beta which confirms the existence of different mechanisms of action in both drugs (AU)

[Restless legs syndrome. Features and impact on sleep]. / Síndrome de piernas inquietas. Características e impacto sobre el sueño.

INTRODUCTION: Restless legs syndrome (RLS) is a chronic neurological disorder that has a negtive influence on sleep. We describe clinical spectrum, polysomnogram and impact on sleep of patients' series with RLS. METHODS: We studied 49 patients with RLS. We analyse socio- demographic information, clinical features, therapy and impact on sleep. We realized differents questionnaire: Index of Severity of Sleep, Epworth Scale, Index-RLS, Questionnaire Quality of Life-RLS and Questionnaire from limitation of laboral productivity. RESULTS: Mean age is 60.33+/-14.27 with similar distribution enter gender. They presented a positive family history in 36,73% with predominant in early onset of symptoms. Secondary causes more frequent associated were rheumatoid arthritis, iron-deficiency, uremia, pregnancy and polineuropathy. Significative prevalence of insomnia (73,43%) and periodic limb movement disorder (51,02%), obstructive sleep apnea syndrome (22,45%) and hipersomnia (22,45 %). Pharmacological treatment more used were dopaminergic drugs. We didn't find significant stadistic differences enter clinical feature and therapy, so tendency to better quality of life with dopaminergic drugs. CONCLUSIONS: It's an neurological disorder with important delay in diagnosis. Early detection is needed because important impact on sleep efficiency and quality of life, and improvement with therapy, solely dopaminergic drugs.

[Opsoclonus-myoclonus-ataxia syndrome: two anatomo-clinical case reports]. / Sindrome opsoclono-mioclono-ataxia: dos casos anatomoclinicos.

INTRODUCTION: Opsoclonus-myoclonus-ataxia syndrome (OMAS) is characterised by the acute or subacute development of chaotic eye movements and diffuse myoclonus. On some occasions it is associated with ataxia and encephalopathy. In adults there are multiple causations and a possible paraneoplastic origin must always be taken into account. CASE REPORTS: We report two cases of OMAS of a paraneoplastic origin with a post mortem study. In the first case, the syndrome was associated to a small-cell carcinoma in the lungs, and in the second patient it was associated to a digestive lymphoma. Neuroimaging studies did not reveal any kind of alterations in either of the two cases. In our cases, none of the antibodies that are relatively frequently associated to this syndrome were found. In both of them, an immunomodulator treatment regimen was established; only the patient with the lymphoma showed an initial improvement with antineoplastic therapy. In the pathological study, alterations were observed in the brain stem, and in the second patient alterations were also found in the cerebellum. CONCLUSIONS: This is a rare condition that obliges the specialist to think in order to reach a correct diagnosis, and to search for the primary tumour and establish early treatment in order to bring about an improvement and even the remission of the neurological signs and symptoms. The pathological findings are not pathognomonic, but they are typical of this syndrome.

Síndrome opsoclono-mioclono-ataxia: dos casos anatomoclínicos / Opspclonus. Myoclonuz-ataxia syndrome: Two anatomo-clinical case reports

Introducción. El síndrome opsoclono-mioclono-ataxia (SOMA) se caracteriza por el desarrollo agudo o subagudode movimientos oculares caóticos y mioclono difuso. En algunas ocasiones, asocia ataxia y encefalopatía. En el adulto existen múltiples etiologías, y hay que tener siempre en cuenta el posible origen paraneoplásico. Casos clínicos. Presentamos dos casos de SOMA de origen paraneoplásico con estudio post mortem. En el primer caso, el síndrome se asoció a un carcinomade células pequeñas de pulmón, y en el segundo paciente a un linfoma digestivo. Los estudios de neuroimagen no mostraron alteraciones en ninguno de los dos casos. No se descubrió en nuestros casos ninguno de los anticuerpos asociados con relativa frecuencia a este síndrome. En ambos se pautó tratamiento inmunomodulador; únicamente el paciente con linfoma mejoró inicialmente con el tratamiento antineoplásico. En el estudio anatomopatológico se observaron alteraciones en el tronco del encéfalo, y en el segundo paciente también en el cerebelo. Conclusión. Se trata de una entidad rara, en la que hay que pensar para lograr un diagnóstico correcto, búsqueda del tumor primario y su tratamiento precoz, con el fin de producir mejoría e inclusoremisión del cuadro neurológico. Los hallazgos anatomopatológicos no son patognomónicos, pero sí típicos de este síndrome

Introduction. Opsoclonus-myoclonus-ataxia syndrome (OMAS) is characterised by the acute or subacute development of chaotic eye movements and diffuse myoclonus. On some occasions it is associated with ataxia and encephalopathy. In adults there are multiple causations and a possible paraneoplastic origin must always be taken into account. Case reports. Wereport two cases of OMAS of a paraneoplastic origin with a post mortem study. In the first case, the syndrome was associated to a small-cell carcinoma in the lungs, and in the second patient it was associated to a digestive lymphoma. Neuroimaging studies did not reveal any kind of alterations in either of the two cases. In our cases, none of the antibodies that are relativelyfrequently associated to this syndrome were found. In both of them, an immunomodulator treatment regimen was established; only the patient with the lymphoma showed an initial improvement with antineoplastic therapy. In the pathological study, alterations were observed in the brain stem, and in the second patient alterations were also found in the cerebellum. Conclusions. This is a rare condition that obliges the specialist to think in order to reach a correct diagnosis, and to search forthe primary tumour and establish early treatment in order to bring about an improvement and even the remission of the neurological signs and symptoms. The pathological findings are not pathognomonic, but they are typical of this syndrome

Síndrome de piernas inquietas. Características e impacto sobre el sueño / Restless legs síndrome. Features and impacto on sleep

Introducción. El síndrome de piernas inquietas (SPI) es un trastorno neurológico crónico que afecta de forma negativa al sueño. El objetivo principal es determinar las características clínicas, polisomnográficas, la eficacia de los tratamientos empleados y el impacto sobre el sueño de una serie de pacientes. Métodos. Estudiamos 49 pacientes con SPI. Se recoge información sociodemográfica, datos clínicos y polisomnográficos, tratamientos empleados y el impacto sobre el sueño. Se realizaron diferentes encuestas: índice de severidad de sueño (ISS), escala de Epworth, cuestionario de evaluación sobre el SPI (IRLS), cuestionario de calidad de vida del SPI (QoL-RLS) y cuestionario sobre la limitación de la productividad laboral (LPL). Resultados. La edad media es de 60,33±14,27 años, con distribución por sexos similar. Presentan una historia familiar positiva el 36,73 %, con predominio en el grupo de inicio precoz de los síntomas. Las causas secundarias más frecuentemente asociadas son la artritis reumatoide, ferropenia, uremia, embarazo y polineuropatía. Prevalencia significativa del insomnio (73,47%) y de los movimientos periódicos de extremidades (MMPE) (51,02%), y también síndrome de apnea obstructiva del sueño (22,45%) e hipersomnia (22,45%). El tratamiento farmacológico más empleado son los agonistas dopaminérgicos. No encontramos diferencias estadísticamente significativas entre la evolución clínica y el tratamiento empleado, aunque una tendencia a mejor calidad de vida con agonistas dopaminérgicos. Conclusiones. Se trata de una enfermedad con un tiempo de demora en el diagnóstico nada desdeñable. Tiene gran importancia su detección precoz dado el impacto que produce sobre la eficiencia del sueño y la calidad de vida, y la eficacia que demuestran los tratamientos empleados, fundamentalmente los agonistas dopaminérgicos (AU)

Introduction: Restless legs syndrome (RLS) is a chronic neurological disorder that has a negtive influence on sleep. We describe clinical spectrum, polysomnogram and impact on sleep of patients' series with RLS. Methods: We studied 49 patients with RLS. We analyse socio- demographic information, clinical features, therapy and impact on sleep. We realized differents questionnaire: Index of Severity of Sleep, Epworth Scale, Index-RLS, Questionnaire Quality of Life-RLS and Questionnaire from limitation of laboral productivity. Results: Mean age is 60.33+/-14.27 with similar distribution enter gender. They presented a positive family history in 36,73% with predominant in early onset of symptoms. Secondary causes more frequent associated were rheumatoid arthritis, iron-deficiency, uremia, pregnancy and polineuropathy. Significative prevalence of insomnia (73,43%) and periodic limb movement disorder (51,02%), obstructive sleep apnea syndrome (22,45%) and hipersomnia (22,45 %). Pharmacological treatment more used were dopaminergic drugs. We didn't find significant stadistic differences enter clinical feature and therapy, so tendency to better quality of life with dopaminergic drugs. Conclusions: It's an neurological disorder with important delay in diagnosis. Early detection is needed because important impact on sleep efficiency and quality of life, and improvement with therapy, solely dopaminergic drugs (AU)