Consenso de expertos españoles sobre el uso de la safinamida en la enfermedad de Parkinson / Spanish expert consensus on the use of safinamide in Parkinson's disease

La safinamida es un nuevo fármaco para el tratamiento de pacientes con enfermedad de Parkinson (EP) con fluctuaciones como tratamiento complementario a levodopa. Dado que por el momento aún no existen estudios de fase IV postautorización debido a la reciente incorporación de la safinamida a la práctica clínica habitual, el interés de este proyecto radica en el desarrollo de una guía de manejo clínico de la safinamida basada en las opiniones de expertos de trastornos del movimiento. Este proyecto se desarrolló en 2 fases: una primera fase que constó de 16 reuniones locales y una segunda fase que consistió en una reunión nacional. Dichas reuniones siguieron un guion de trabajo preestablecido. Tras la reunión nacional se recopilaron las principales conclusiones de los expertos, que han supuesto la base para redactar la presente guía clínica. Se concluyó que la safinamida es eficaz en la reducción de las fluctuaciones motoras y no motoras. Los pacientes con EP con fluctuaciones leves-moderadas son los que más se benefician del tratamiento, si bien el fármaco puede contribuir a mejorar diversos problemas clínicos en pacientes con EP avanzada. Se ha destacado la posibilidad de reducir la dosis de otros fármacos dopaminérgicos tras la introducción de la safinamida, lo cual contribuiría a reducir efectos adversos como el trastorno de control de impulsos. Se hipotetizó sobre el posible efecto de la safinamida sobre la mejoría de las discinesias a dosis más altas de las habitualmente utilizadas. Se ha consensuado que la safinamida es bien tolerada y presenta un perfil de efectos adversos favorable frente a placebo. (AU)

Safinamide is a new add-on drug to levodopa for the treatment of Parkinson's disease (PD) with motor fluctuations. Due to the recent incorporation of safinamide into routine clinical practice, no post-authorisation phase IV studies on the safety of safinamide have been conducted to date. This study provides clinical management guidelines for safinamide based on the opinion of a group of experts in movement disorders. This project was developed in 2 phases: 16 local meetings in phase 1 and a national meeting in phase 2. The meetings followed a pre-established agenda. The present clinical practice guidelines are based on the main conclusions reached during the national meeting. The group concluded that safinamide is effective in reducing motor and non-motor fluctuations. PD patients with mild-to-moderate fluctuations benefit most from treatment, although the drug may also improve the clinical status of patients with advanced PD. The dose of other dopaminergic drugs may be reduced after introducing safinamide, which would contribute to reducing such adverse reactions as impulse control disorder. At doses higher than those usually prescribed, safinamide may also improve dyskinesia. The experts agreed that safinamide is well tolerated and causes few adverse reactions when compared with placebo. (AU)

Spanish expert consensus on the use of safinamide in Parkinson's disease.

Safinamide is a new add-on drug to levodopa for the treatment of Parkinson's disease (PD) with motor fluctuations. Due to the recent incorporation of safinamide into routine clinical practice, no post-authorisation phase IV studies on the safety of safinamide have been conducted to date. This study provides clinical management guidelines for safinamide based on the opinion of a group of experts in movement disorders. This project was developed in 2 phases: 16 local meetings in phase 1 and a national meeting in phase 2. The meetings followed a pre-established agenda. The present clinical practice guidelines are based on the main conclusions reached during the national meeting. The group concluded that safinamide is effective in reducing motor and non-motor fluctuations. PD patients with mild-to-moderate fluctuations benefit most from treatment, although the drug may also improve the clinical status of patients with advanced PD. The dose of other dopaminergic drugs may be reduced after introducing safinamide, which would contribute to reducing such adverse reactions as impulse control disorder. At doses higher than those usually prescribed, safinamide may also improve dyskinesia. The experts agreed that safinamide is well tolerated and causes few adverse reactions when compared with placebo.

[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.

Spanish expert consensus on the use of safinamide in Parkinson's disease. / Consenso de expertos españoles sobre el uso de la safinamida en la enfermedad de Parkinson.

Safinamide is a new add-on drug to levodopa for the treatment of Parkinson's disease (PD) with motor fluctuations. Due to the recent incorporation of safinamide into routine clinical practice, no post-authorisation phase IV studies on the safety of safinamide have been conducted to date. This study provides clinical management guidelines for safinamide based on the opinion of a group of experts in movement disorders. This project was developed in 2 phases: 16 local meetings in phase 1 and a national meeting in phase 2. The meetings followed a pre-established agenda. The present clinical practice guidelines are based on the main conclusions reached during the national meeting. The group concluded that safinamide is effective in reducing motor and non-motor fluctuations. PD patients with mild-to-moderate fluctuations benefit most from treatment, although the drug may also improve the clinical status of patients with advanced PD. The dose of other dopaminergic drugs may be reduced after introducing safinamide, which would contribute to reducing such adverse reactions as impulse control disorder. At doses higher than those usually prescribed, safinamide may also improve dyskinesia. The experts agreed that safinamide is well tolerated and causes few adverse reactions when compared with placebo.

Diagnostic Validity Comparison Between Criteria Based on CSF Alzheimer's Disease Biomarkers.

AIM: To compare the diagnostic validity of NIA-AA criteria, for AD CSF biomarkers, with our own new criteria. MATERIALS AND METHODS: Between 2008 and 2011, 170 patients with Mild Cognitive Impairment (MCI) were included. CSF levels of Aß1-42, T-tau, P-tau181, and ratios of T-tau/Aß1-42 and P-tau181/Aß1-42 were analyzed. In our criteria, we considered 3 or more abnormal variables indicative of a high likelihood of MCI due to AD. RESULTS: After a clinical follow-up of 4.5 ± 1.2 years, 44 patients remained stable, 95 developed AD, 15 other forms of dementia, 7 died and 9 received other diagnoses. Using the NIA-AA criteria and our own criteria, the diagnostic validity of the CSF biomarkers was 58% versus 85%, specificity 84% versus 72%, PPV 82% versus 79% and NPV 61% versus 79%. CONCLUSION: The inclusion of the ratios in diagnostic criteria increases sensitivity and NPV for the diagnosis of MCI due to AD.

Influence of APOE Genotype on Alzheimer's Disease CSF Biomarkers in a Spanish Population.

OBJECTIVES: To evaluate the association between apolipoprotein E (APOE) genotype and cerebrospinal fluid (CSF) levels of Alzheimer's disease (AD) biomarkers and to study the influence of APOE genotype on the development of AD in a Spanish population. MATERIAL AND METHODS: The study comprised 29 amnestic mild cognitive impairment (MCI) patients and 27 control subjects. Using ELISA methodology, CSF biomarkers and tau/Aß ratios were obtained. ANOVA and adjusted odds ratios were calculated. RESULTS: We observed the effect of APOE genotype and age on CSF AD variables. The progression to AD was more clearly influenced by CSF AD variables than by age or APOE status. CONCLUSIONS: APOE status influences CSF AD variables. However, the presence of APOE ε4 does not appear to be a deterministic factor for the development of AD, because CSF variables have a greater influence on progression to the disease. These results confirm previous observations and, to our knowledge, are the first published in a Spanish population.

Comparación de la capacidad diagnóstica precoz de los biomarcadores de la enfermedad de Alzheimer en resonancia magnética cerebral y líquido cefalorraquídeo / A comparison of early diagnostic utility of Alzheimer disease biomarkers in brain magnetic resonance and cerebrospinal fluid

Introducción: Nuestros objetivos fueron comparar la capacidad de diagnóstico precoz de los biomarcadores (BMC) de enfermedad de Alzheimer (EA) en LCR y RM cerebral, en condiciones posibles de nuestra práctica clínica y, además, conocer la precisión diagnóstica de la combinación de ambas técnicas. Métodos: Entre 2008 y 2009, estudiamos a 30 pacientes con deterioro cognitivo leve (DCL) mediante RM cerebral de 1,5 teslas y análisis de BMC de EA en el LCR. Las RM fueron valoradas por 2 neurorradiólogos, atendiendo a la escala visual de Korf (2004). Los BMC de EA en LCR se analizaron mediante reactivos INNOTEST para proteínas A 1-42, total-tau y fosfo-tau. Se evaluó la evolución clínica (según criterios NINCDS-ADRDA) a los 2 a˜nos tras la inclusión. Resultados: Entre los 30 pacientes iniciales, 15 evolucionaron a EA (criterios NINCDS-ADRDA) a los 2 a˜nos de la inclusión. La capacidad predictiva de los BMC en LCR (RR 2,7; IC del 95%, 1,1-6,7; p < 0,01) es superior a los de RM (RR 1,5; IC del 95%, 0,7-3,4; p < 0,2), y la combinación de ambas técnicas alcanza una sensibilidad y valor predictivo negativo del 100%. La normalidad de ambas pruebas complementarias descartó al 100% el desarrollo de EA, en los 2 a˜nos siguientes a la realización de las mismas. Conclusiones: Siguiendo nuestra metodología, la precisión diagnóstica de los BMC en LCR es superior a los de la RM para el diagnóstico precoz de EA. La combinación de ambas técnicasconsigue una precisión diagnóstica muy alta, tanto para diagnosticar como para excluir precozmente EA, en pacientes con DCL

Introduction: The goals of this study were to compare the early diagnostic utility of Alzheimer disease biomarkers in the CSF with those in brain MRI in conditions found in our clinical practice, and to ascertain the diagnostic accuracy of both techniques used together. Methods: Between 2008 and 2009, we included 30 patients with mild cognitive impairment (MCI) who were examined using 1.5 Tesla brain MRI and AD biomarker analysis in CSF. MRI studies were evaluated by 2 radiologists according to the Korf s visual scale. CSF biomarkers were analysed using INNOTEST reagents for A 1-42, total-tau and phospho-tau181p. We evaluated clinical changes 2 years after inclusion. Results: By 2 years after inclusion, 15 of the original 30 patients (50%) had developed AD (NINCDS-ADRA criteria). The predictive utility of AD biomarkers in CSF (RR 2.7; 95% CI, 1.1-6.7; P < .01) was greater than that of MRI (RR 1.5; 95% CI 95%, 0.7-3.4; P < .2); using both techniques together yielded a sensitivity and a negative predictive value of 100%. Normal results on both complementary tests ruled out progression to AD (100%) within 2 years of inclusion. Conclusions: Our results show that the diagnostic accuracy of biomarkers in CSF is higher than that of biomarkers in MRI. Combined use of both techniques is highly accurate for either early diagnosis or exclusion of AD in patients with MCI

A comparison of early diagnostic utility of Alzheimer disease biomarkers in brain magnetic resonance and cerebrospinal fluid.

INTRODUCTION: The goals of this study were to compare the early diagnostic utility of Alzheimer disease biomarkers in the CSF with those in brain MRI in conditions found in our clinical practice, and to ascertain the diagnostic accuracy of both techniques used together. METHODS: Between 2008 and 2009, we included 30 patients with mild cognitive impairment (MCI) who were examined using 1.5 Tesla brain MRI and AD biomarker analysis in CSF. MRI studies were evaluated by 2 radiologists according to the Korf́s visual scale. CSF biomarkers were analysed using INNOTEST reagents for Aß1-42, total-tau and phospho-tau181p. We evaluated clinical changes 2 years after inclusion. RESULTS: By 2 years after inclusion, 15 of the original 30 patients (50%) had developed AD (NINCDS-ADRA criteria). The predictive utility of AD biomarkers in CSF (RR 2.7; 95% CI, 1.1-6.7; P<.01) was greater than that of MRI (RR 1.5; 95% CI 95%, 0.7-3.4; P<.2); using both techniques together yielded a sensitivity and a negative predictive value of 100%. Normal results on both complementary tests ruled out progression to AD (100%) within 2 years of inclusion. CONCLUSIONS: Our results show that the diagnostic accuracy of biomarkers in CSF is higher than that of biomarkers in MRI. Combined use of both techniques is highly accurate for either early diagnosis or exclusion of AD in patients with MCI.

Pacientes con deterioro cognitivo leve y reducción de la proteína Aβ 1-42 en LCR evolucionan rápidamente a enfermedad de Alzheimer / Patients with mild cognitive impairment and a reduced CSF A_1-42 protein progress rapidly to Alzheimer’s disease

Introducción: En muchos artículos recientes, el análisis de las proteínas Aβ 1-42, tau total (T-tau) y tau fostorilada (P-tau) en LCR puede discriminar entre los pacientes con deterioro cognitivo leve (DCL) estables y aquellos otros que van a progresar a enfermedad de Alzheimer (EA). Nuestro objetivo fue comprobar la capacidad de estas proteínas del LCR para discriminar, entre nuestros pacientes DCL, según la evolución clínica en el año siguiente a la punción lumbar. Material y métodos: Se incluyó a 36 pacientes DCL amnésico (criterios de Petersen 2006) procedentes de la consulta de deterioro cognitivo del Hospital General de Alicante. Usando los reactivos INNO-BIA Alzbio-3 (Innogenetics), cuantificamos las proteínas Aβ1-42, T-tau, P-tau181p en LCR, y calculamos los cocientes T-tau/Aβ1-42 y P-tau181p/Aβ1-42. El estudio fue aprobado por el comité ético de investigación del Hospital General de Alicante. Resultados: En los 12 meses posteriores a la punción lumbar, 14 pacientes DCL (38%) evolucionaron a EA. Estos pacientes, presentaron menores niveles de Aβ1-42 (285,3 vs. 377,7 ng/ml, p<0,02), y un aumento en el valor del cociente P-tau181p/Aβ1-42 (0,25 vs. 0,16, p<0,02) que los pacientes que se mantuvieron estables. No hubo diferencias significativas en el resto de las variables estudiadas. Conclusiones: Nuestros pacientes DCL que presentaron niveles reducidos de la proteína Aβ1-42 y elevación del cociente P-tau181p/Aβ1-42 en LCR, evolucionaron rápidamente a EA. Estos resultados pueden ayudar a conseguir el objetivo de identificar de forma precoz a los pacientes DCL con peor pronóstico (AU)

Introduction: Some studies have shown that CSF amyloid-beta 1-42 (A_1-42), total tau (T-tau) and tau phosphorylated at threonine 181 (P-tau181p) proteins are useful diagnostic markers for distinguishing between clinically stable mild cognitive impairment (MCI) patients and those who will develop Alzheimer's disease (AD). Our objective was to test the ability of this technique to discriminate in our cohort of MCI patients, according to the clinical outcome, one year after the lumbar puncture. Material and methods: A total of 36 MCI patients were included from the local hospital memory clinic. Using INNO-BIA Alzbio-3 reagents from Innogenetics, we measured CSF A_1-42, T-tau and P-tau181p proteins, and calculated the T-tau/A_1-42 y P-tau181p/A_1-42 ratios. Thisproject was approved by the local ethics committee. Results: One year after the lumbar puncture, 14 MCI patients (38%) developed AD. These patients had lower A_ 1-42 protein levels (285.3 vs 377 ng/ml, P < .02) and higher P-tau181p/A_1-42 ratio (0,25 vs 0,16, p < .02) than the clinically stable patients. Conclusions: Our MCI patients with lower A_1-42 protein levels and an increased P-tau181p /A_1-42 ratio progressed quickly to AD. These results may help to identify those MCI patients with a poorer prognosis (AU)

[Patients with mild cognitive impairment and a reduced CSF Aß1₋42 protein progress rapidly to Alzheimer's disease]. / Pacientes con deterioro cognitivo leve y reducción de la proteína Aß(1-42) en LCR evolucionan rápidamente a enfermedad de Alzheimer.

INTRODUCTION: Some studies have shown that CSF amyloid-beta 1-42 (Aß1₋42), total tau (T-tau) and tau phosphorylated at threonine 181 (P-tau(181p)) proteins are useful diagnostic markers for distinguishing between clinically stable mild cognitive impairment (MCI) patients and those who will develop Alzheimers disease (AD). Our objective was to test the ability of this technique to discriminate in our cohort of MCI patients, according to the clinical outcome, one year after the lumbar puncture. MATERIAL AND METHODS: A total of 36 MCI patients were included from the local hospital memory clinic. Using INNO-BIA Alzbio-3 reagents from Innogenetics, we measured CSF Aß1₋42, T-tau and P-tau(181p) proteins, and calculated the T-tau/Aß1₋42 y P-tau(181p)/Aß1₋42 ratios. This project was approved by the local ethics committee. RESULTS: One year after the lumbar puncture, 14 MCI patients (38%) developed AD. These patients had lower Aß1₋42 protein levels (285.3 vs 377 ng/ml, P<.02) and higher P-tau(181p)/Aß1₋42 ratio (0,25 vs 0,16, p<.02) than the clinically stable patients. CONCLUSIONS: Our MCI patients with lower Aß1₋42 protein levels and an increased P-tau(181p) /Aß1₋42 ratio progressed quickly to AD. These results may help to identify those MCI patients with a poorer prognosis.

Biomarkers of Alzheimer's disease in the cerebrospinal fluid of Spanish patients with mild cognitive impairment.

The study of biomarkers in the cerebrospinal fluid (CSF) of patients with mild cognitive impairment (MCI) is a technique used with increasing frequency in the early diagnosis of Alzheimers disease (AD). Our objectiv was to gain an own experience while evaluating the reliability, sensitivity, and reproducibility of this technique in Spanish patients. Thirty-seven patients with MCI and twenty-four control subjects were studied by means of AD biomarker analysis in CSF. xMAP Luminex and INNO-BIA Alzbio3 reagents of Innogenetics were used. The study variables assessed were levels of Aß(1-42), T-tau and P-tau(181p) proteins as well as the ratios of T-tau/Aß(1-42) and P-tau(181p)/Aß(1-42). Samples from nineteen patients were examined twice. Intra-class correlation coefficients for the three biomarkers used showed values higher than 0.95. We observed significant differences between the control group and the MCI groups. In the 6 months following lumbar puncture (LP), eleven (29%) patients with MCI developed AD. These patients showed significant lower levels in Aß(1-42) protein (276.35 ± 78 vs. 367.13 ± 123.49, P < 0.03) and higher ratios (T-tau/Aß(1-42) [0.38 ± 0.2 vs. 0.22 ± 0.14, P < 0.01] and P-tau(181p)/Aß(1-42) [0.27 ± 0.13 vs. 0.16 ± 0.1, P < 0.008]) to those in the same group who remained stable. We obtained similar results to those in the most recent reliable literature with our ROC curves, especially with our P-tau(181p) values and T-tau/Aß(1-42) ratio in order to differentiate between control and AD groups. Our experience showed that the analysis of CSF-AD biomarkers in patients with MCI is reliable, sensitive and reproducible. In our knowledge, this is the first experience in Spanish patients.

Biomarcadores en el líquido cefalorraquídeo de pacientes con deterioro cognitivo leve: metaanálisis de su capacidad predictiva para el diagnóstico de la enfermedad de Alzheimer / Biomarkers in the cerebrospinal fluid of patients with mild cognitive impairment: a meta-analysis of their predictive capacity for the diagnosis of Alzheimer’s disease

Introducción. Varios estudios han descrito alteraciones en los biomarcadores del líquido cefalorraquídeo (proteínas Abeta- 42, T-tau y P-tau), tanto en la enfermedad de Alzheimer (EA) como en el deterioro cognitivo leve (DCL). Objetivo. Realizar un metaanálisis sobre la rentabilidad diagnóstica de esta técnica para la predicción de los pacientes con DCL que van a progresar a EA. Materiales y métodos. Tras una búsqueda en PubMed y Embase de los artículos publicados entre 1999 y septiembre de 2008, se incluyeron sólo estudios prospectivos para la revisión sistemática. Se estudió la sensibilidad y especificidad para cada biomarcador por separado y también de forma conjunta.Resultados. De los 12 estudios incluidos, 6 cuantificaron la proteína Abeta-42, 11 la proteína T-tau y 7 la proteína P-tau. En tres estudios se pudieron obtener los datos de los tres biomarcadores de forma combinada. La sensibilidad de la cuantificación de las proteínas T-tau y P-tau es del 82%, con una odds ratio diagnóstica de 12,09 (intervalo de confianza al 95%, C 95% = 7,71-18,99; p = 0,1) y 16,29 (IC 95% = 9,69-27,4; p = 0,9), respectivamente. La alteración de alguno de los tres biomarcadores tiene una especificidad del 87%, con una odds ratio diagnóstica de 35,97 (IC 95% = 7,8-164,6; p = 0,04). Conclusiones. La alteración aislada de los niveles de T-tau o P-tau en el líquido cefalorraquídeo es muy sensible para diferenciar entre los pacientes con DCL que van a desarrollar EA de los que van a permanecer estables. La normalidad de los tres biomarcadores es muy fiable para descartar la evolución a EA en pacientes con DCL (AU)

Introduction. Several studies have reported alterations in the cerebrospinal fluid biomarkers (Abeta-42, T-tau and P-tau proteins), both in Alzheimer’s disease (AD) and in mild cognitive impairment (MCI). Aim. To perform a meta-analysis of the diagnostic yield of this technique for the prediction of patients with MCI who are going to progress to AD. Materials and methods. A search was conducted in PubMed and Embase of papers published between 1999 and September 2008, and as a result only prospective studies were included for the systematic review. The sensitivity and specificity for each biomarker were studied separately and also jointly. Results. Of the 12 studies that were included, 6 quantified the Abeta-42 protein, 11 the T-tau protein and seven the P-tau protein. In three of the studies data was obtained from the three biomarkers in combination. The sensitivity of the quantification of the T-tau and P-tau proteins is 82%, with a diagnostic odds ratio of 12.09 (confidence interval 95%, CI 95% = 7.71-18.99; p = 0.1) and 16.29 (CI 95% = 9.69-27.4; p = 0.9), respectively. Alteration of any of the three biomarkers has a specificity of 87%, with a diagnostic odds ratio of 35.97 (CI 95% = 7.8-164.6; p = 0.04). Conclusions. The isolated alteration of T-tau or P-tau levels in cerebrospinal fluid is very sensitive for differentiating between patients with MCI who are going to develop AD and those who are going to remain stable. Normality of the three biomarkers is a very reliable way of ruling out the progression of AD in patients with MCI (AU)

Versión española del test perfil de síntomas autonómicos / Spanish version of the autonomic symptom profile test

Resumen. Introducción. El perfil de síntomas autonómicos (PSA) es un cuestionario autorrellenable, que ha sido validado en lengua inglesa para valorar los síntomas autonómicos y diferenciar entre pacientes y sujetos sanos según dicha sintomatología. Nuestro grupo ha estudiado su aplicación en lengua castellana. Sujetos y métodos. Después de traducir al castellano la versión inglesa y retrotraducirla, se evaluó la fiabilidad y la validez de criterio de la versión española del test PSA en una muestra de 50 sujetos (27 controles y 23 enfermos). A todos los pacientes con síntomas de disfunción autonómica se les estudió mediante la batería de Ewing y Clarke. Resultados. La fiabilidad de la versión española del PSA fue alta, y se obtuvo un coeficiente de correlación intraclase de 0,93. Con una puntuación en el test de 47 o superior, se obtiene una sensibilidad del 73,9% y una especificidad del 100% para detectar disfunción autonómica. Además, la puntuación de la versión española del test PSA mostró diferencias estadísticamente significativas entre el grupo de pacientes y el grupo control. Conclusiones. La versión española del PSA es fiable y permite distinguir entre pacientes con disfunción autonómica y sujetos control. En nuestro conocimiento, se trata del primer test que valora la sintomatología del sistema nervioso autónomo de forma global y en castellano (AU)

Summary. Introduction. The Autonomic Symptom Profile (ASP) is a self-administered questionnaire that has been validated in English to assess autonomic symptoms and to differentiate between patients and healthy subjects according to said symptoms. Our group has studied its application in Spanish. Subjects and methods. After translating the English version into Spanish and then back-translating it, the reliability and validity of criteria in the Spanish version of the ASP test were evaluated in a sample of 50 subjects (27 controls and 23 patients). All the patients with symptoms of autonomic dysfunction were studied by means of the Ewing and Clarke battery. Results. The reliability of the Spanish version of the ASP was high and an interclass correlation coefficient of 0.93 was obtained. A score of 47 or over in the test yields a sensitivity of 73.9% and a specificity of 100% for the detection of autonomic dysfunction. Furthermore, the score in the Spanish version of the ASP test showed statistically significant differences between the group of patients and the control group. Conclusions. The Spanish version of the ASP is reliable and makes it possible to distinguish between patients with autonomic dysfunction and control subjects. As far as we are aware, this is the first test to evaluate the symptoms of the autonomic nervous system in a global manner and in Spanish (AU)

[Spanish version of the Autonomic Symptom Profile test]. / Versión española del test perfil de síntomas autonómicos.

INTRODUCTION: The Autonomic Symptom Profile (ASP) is a self-administered questionnaire that has been validated in English to assess autonomic symptoms and to differentiate between patients and healthy subjects according to said symptoms. Our group has studied its application in Spanish. SUBJECTS AND METHODS: After translating the English version into Spanish and then back-translating it, the reliability and validity of criteria in the Spanish version of the ASP test were evaluated in a sample of 50 subjects (27 controls and 23 patients). All the patients with symptoms of autonomic dysfunction were studied by means of the Ewing and Clarke battery. RESULTS: The reliability of the Spanish version of the ASP was high and an interclass correlation coefficient of 0.93 was obtained. A score of 47 or over in the test yields a sensitivity of 73.9% and a specificity of 100% for the detection of autonomic dysfunction. Furthermore, the score in the Spanish version of the ASP test showed statistically significant differences between the group of patients and the control group. CONCLUSIONS: The Spanish version of the ASP is reliable and makes it possible to distinguish between patients with autonomic dysfunction and control subjects. As far as we are aware, this is the first test to evaluate the symptoms of the autonomic nervous system in a global manner and in Spanish.

[Two years' experience in a specific autonomic nervous system service]. / Experiencia de dos años en una consulta específica de sistema nervioso autónomo.

INTRODUCTION: Despite the high incidence and prevalence of pathologies affecting the autonomic nervous system (ANS), this part of neurology has received very little specific attention in clinical care in our country. AIM: To present the experience we have gained over a two-year period in an ANS-specific service. PATIENTS AND METHODS: Our patients were referred to the ANS service by other colleagues, most of whom were neurologists, between April 2006 and April 2008, after proposing a set of eligibility and exclusion criteria. Clinical history, examination and general analysis were performed for all patients. The following tests were also carried out on an individualised basis: Ewing-Clarke test, the Spanish version of the autonomic symptom profile test, tilt table test, holter heart monitor, urodynamic study and reflex sympathetic test, among other complementary studies. RESULTS: Thirty-four first visits and 62 successive visits were registered. The most frequent diagnoses were neurologically mediated syncopes and diabetic autonomic neuropathies, but other less prevalent conditions were also diagnosed. The most cost-effective complementary tests were the Ewing-Clarke test and the autonomic symptom profile test. Apart from benzodiazepines, the most commonly prescribed pharmacological treatments were paroxetine and pyridostigmine. CONCLUSIONS: As expected, neurologically mediated syncopes and diabetic neuropathies with an autonomic component are the most frequent pathologies in an ANS service. Nevertheless, their diagnosis and individualised treatment, together with that of other less prevalent autonomic pathologies, may require specific attention. To our knowledge, this is the first service of its kind in our country.

Experiencia de dos años en una consulta específica de sistema nervioso autónomo / Two years'experience in a specific autonomic nervous system service

Introducción. A pesar de la alta incidencia y prevalencia de la patología del sistema nervioso autónomo (SNA), esta parte de la neurología apenas ha merecido una atención específica en la asistencia clínica de nuestro país. Objetivo. Presentar nuestra experiencia de dos años en una consulta específica de SNA. Pacientes y métodos. Pacientes enviados a la consulta de SNA por otros compañeros, en su mayoría neurólogos, entre abril de 2006 y abril de 2008, tras proponer unos criterios de inclusión y exclusión. A todos los pacientes se les realizó anamnesis, exploración y analítica general. De forma individualizada, se realizaron test de Ewing-Clarke, versión española del test perfil de síntomas autonómicos, test de la mesa basculante, holter cardíaco, estudio urodinámico y test simpático reflejo, entre otros estudios complementarios. Resultados. Se realizaron 34 primeras consultas y 62 sucesivas. Los diagnósticos más frecuentes fueron los síncopes neurológicamente mediados y las neuropatías diabéticas autonómicas, pero se han diagnosticado otras entidades menos prevalentes. Las pruebas complementarias más rentables fueron el test de Ewing-Clarke y el test perfil de síntomas autonómicos. Los tratamientos farmacológicos más prescritos han sido, aparte de las benzodiacepinas, la paroxetina y la piridostigmina. Conclusiones. Como cabía esperar, los síncopes neurológicamente mediados y las neuropatías diabéticas con componente autonómico son las patologías más frecuentes en una consulta de SNA. Sin embargo, su diagnóstico y tratamiento individualizado, así como el de otras patologías autonómicas menos prevalentes, pueden requerir una atención específica. En nuestro conocimiento, se trata de la primera consulta de estas características en nuestro país (AU)

Introduction. Despite the high incidence and prevalence of pathologies affecting the autonomic nervous system (ANS), this part of neurology has received very little specific attention in clinical care in our country. Aim. To present the experience we have gained over a two-year period in an ANS-specific service. Patients and methods. Our patients were referred to the ANS service by other colleagues, most of whom were neurologists, between April 2006 and April 2008, after proposing a set of eligibility and exclusion criteria. Clinical history, examination and general analysis were performed for all patients. The following tests were also carried out on an individualised basis: Ewing-Clarke test, the Spanish version of the autonomic symptom profile test, tilt table test, holter heart monitor, urodynamic study and reflex sympathetic test, among other complementary studies. Results. Thirty-four first visits and 62 successive visits were registered. The most frequent diagnoses were neurologically mediated syncopes and diabetic autonomic neuropathies, but other less prevalent conditions were also diagnosed. The most cost-effective complementary tests were the Ewing-Clarke test and the autonomic symptom profile test. Apart from benzodiazepines, the most commonly prescribed pharmacological treatments were paroxetine and pyridostigmine. Conclusions. As expected, neurologically mediated syncopes and diabetic neuropathies with an autonomic component are the most frequent pathologies in an ANS service. Nevertheless, their diagnosis and individualised treatment, together with that of other less prevalent autonomic pathologies, may require specific attention. To our knowledge, this is the first service of its kind in our country (AU)

Síndrome de taquicardia postural / No disponible

No disponible

Métodos de evaluación de trastornos cognitivos en modelos animales / Methods to evaluate cognitive disorders in animal models

Introducción. El aumento de la prevalencia de la disfunción cognitiva y la demencia, asociado, entre otros factores, al envejecimiento de la población en los países desarrollados, ha despertado un gran interés por el estudio de la etiopatogénesis del déficit cognitivo y de las posibles dianas farmacológicas para mejorar la función intelectual o frenar la neurodegeneraciónsubyacente en estos síntomas. Desarrollo y conclusiones. Un instrumento esencial a tal fin es la utilización de modelos animales de las enfermedades humanas que cursan clínicamente con deterioro cognitivo y demencia. En esta revisión analizamos los modelos animales de estos trastornos y las principales pruebas que, mediante la observación de la evolución de la conducta del animal de experimen-tación, permiten valorar sus funciones cognitivas y su modificación por los tratamientos experimentales que se quieran ensayar, de cara a su posible aplicación a los pacientes

Introduction. The increasing prevalence of cognitive dysfunction and dementia associated, among others, topopulation aging in developed countries has grown a great interest in the study of the etiopathogenesis of cognitive deficit and the likely pharmacological targets which improve intellectual function or alter the neurodegeneration underlying these symptoms. Development and conclusions. An essential tool for that purpose is the use of animal models of human-relatedpathologies which clinically develop with cognitive impairment and dementia. In this review we will analyse the animal models of these disorders and, specially, the main tests that, by means of the observational evolution of the experimental animal, allow assessing its cognitive functions and its modification by experimental treatments that are wanted to investigate for its eventual introduction into clinics

[Methods to evaluate cognitive disorders in animal models]. / Métodos de evaluación de trastornos cognitivos en modelos animales.

INTRODUCTION: The increasing prevalence of cognitive dysfunction and dementia associated, among others, to population aging in developed countries has grown a great interest in the study of the etiopathogenesis of cognitive deficit and the likely pharmacological targets which improve intellectual function or alter the neurodegeneration underlying these symptoms. DEVELOPMENT AND CONCLUSIONS: An essential tool for that purpose is the use of animal models of human-related pathologies which clinically develop with cognitive impairment and dementia. In this review we will analyse the animal models of these disorders and, specially, the main tests that, by means of the observational evolution of the experimental animal, allow assessing its cognitive functions and its modification by experimental treatments that are wanted to investigate for its eventual introduction into clinics.