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Anti-NMDA receptor (NMDAR) encephalitis is associated with a post-acute stage that is not well known. We aimed to describe the clinical features of this stage, similarities with schizophrenia spectrum disorders, and the factors that predict cognitive-psychiatric outcomes and could serve as prognostic biomarkers.In this prospective cohort study, participants (aged 12-60 years) with anti-NMDAR encephalitis during the post-acute stage visited Hospital Clínic de Barcelona (Barcelona, Spain) on three occasions (at study entry [V1], at 6 months [V2], and at 12 months [V3]) and underwent comprehensive neuropsychiatric evaluations. Similar evaluations were done in a group of age-matched participants with schizophrenia spectrum disorders and a group of age-matched and sex-matched healthy participants also recruited from Hospital Clínic de Barcelona. We analysed differences between and within groups in the longitudinal follow-up using multilevel linear mixed-effect models, adjusting for group, age, sex, and socioeconomic status to control for possible confounding.Between Jan 1, 2017, and Sept 30, 2020, 82 participants were recruited, 28 (34%) with anti-NMDAR encephalitis, 27 (33%) with schizophrenia spectrum disorders, and 27 (33%) healthy participants. Although, by V1 (median 4 months [IQR 3-7] from disease onset), many acute-stage symptoms in participants with anti-NMDAR encephalitis had resolved (acute stage median modified Rankin Scale [mRS] score 5 [IQR 4-5] vs V1 mRS score 2 [1-2]; p0·0001), 25 (89%) participants showed deficits in at least one cognitive domain. In this group, 15 (68%) of 22 cognitive domain variables were impaired at V1, whereas only eight (36%) were altered at V3 (p=0·016). In participants with schizophrenia spectrum disorders, 11 (50%) of 22 variables (all shared with participants with anti-NMDAR encephalitis) were impaired at V1, without changes at V3. Two acute-stage features of anti-NMDAR encephalitis (ie, decreased consciousness and no improvement within the first 4 weeks of treatment) predicted cognitive domain outcomes, and a visuospatial task (ie, serial biases) at V1 showed potential in predicting learning and memory outcomes. At V1, all psychiatric symptom clusters were similarly altered in participants with anti-NMDAR encephalitis and in those with schizophrenia spectrum disorders, but only those in individuals with anti-NMDAR encephalitis subsequently improved (p=0·031). The greatest cognitive-psychiatric improvement in participants with anti-NMDAR encephalitis occurred between V1 and V2. During this interval, four (14%) participants with anti-NMDAR encephalitis would have met the diagnostic criteria of schizophrenia if CSF antibody findings had not been investigated.The cognitive-psychiatric symptoms of anti-NMDAR encephalitis in the post-acute stage resembled those of stabilised schizophrenia, but only those in participants with anti-NMDAR encephalitis progressively improved, predominantly during V1-V2. These findings are important for clinical trials on anti-NMDAR encephalitis and suggest that prompt cognitive-psychosocial rehabilitation might be a valuable intervention.Instituto Salud Carlos III, NEURON Network of European Funding for Neuroscience Research, National Alliance for Research in Schizophrenia and Affective Disorders, and la Caixa Health-Research Foundation.

First-line therapy with interferon beta (IFN-β), involved in gene expression modulation in immune response, is widely used for multiple sclerosis. However, 30-50% of patients do not respond optimally. Variants in CBLB, CTSS, GRIA3, OAS1 and TNFRSF10A genes have been proposed to contribute to the variation in the individual response. The purpose of this study was to evaluate the influence of gene polymorphisms on the IFN-β response in relapsing-remitting multiple sclerosis (RRMS) patients. CBLB (rs12487066), GRIA3 (rs12557782), CTSS (rs1136774), OAS1 (rs10774671) and TNFRSF10A (rs20576) polymorphisms were analysed by Taqman in 137 RRMS patients. Response to IFN-β and change in the Expanded Disability Status Scale (EDSS) after 24 months were evaluated using multivariable logistic regression analysis. Carriers of at least one copy of the C allele of CTSS-rs1136774 had a better response to IFN-β (p = 0.0423; OR = 2.94; CI95% = 1.03, 8.40). Carriers of TT genotype of TNFRSF10A-rs20576 had a higher probability of maintaining their EDSS stable after 24 months of IFN-β treatment (p = 0.0251; OR = 5.71; CI95% = 1.39, 31.75). No influence of CBLB (rs12487066), OAS1 (rs10774671) and GRIA3 (rs12557782) gene polymorphisms in the variation of the individual response to IFN-β was shown. Our results suggest that the TNFRSF10A-rs20576 and CTSS-rs1136774 gene polymorphisms influence the response to IFN-β after 24 months, while the CBLB (rs12487066), OAS1 (rs10774671) or GRIA3 (rs12557782) gene polymorphisms had no effect on the variation of the individual response to IFN-β.

To analyze the effectiveness of a home-based restorative and compensatory upper limb apraxia (ULA) rehabilitation program.Randomized controlled trial.Neurology Unit of San Cecilio Hospital and 2 private and specialized health care centers.Community dwelling participants (N=38) between the ages of 25 and 95 years old (sex ratio, 1:1) with unilateral mild-to-moderate poststroke lesions (time of evolution since stroke, 12.03±8.98mo) and secondary ULA.Participants were randomly assigned to an 8-week combined ULA functional rehabilitation group (n=19) 3 days per week for 30 minutes or to a traditional health care education protocol group (n=19) once a month for 8 weeks. Both interventions were conducted at home.Sociodemographic and clinical data, Barthel Index (primary outcome), Lawton and Brody Scale, observation and scoring activities of daily living, the De Renzi tests for ideational and ideomotor apraxia and imitating gestures test, recognition of gestures, test for upper limb apraxia , and stroke-specific quality of life scale were assessed at 3 time points: baseline, posttreatment (8wk), and follow-up (8wk).There were statistically significant differences among the groups regarding ideomotor apraxia, imitating gestures, global recognition of gestures, intransitive gestures, and comprehension of gesture production (P.05) in favor of the experimental group. However, no statistically significant differences were found between the groups regarding functionality or quality of life (P.05). Regarding the within-group effect, statistically significant differences were found in all neuropsychological outcomes at posttreatment and follow-up (P.05).A functional rehabilitation program was found to be superior to a traditional health care education program and resulted in improvements in neuropsychological functioning in ULA poststroke. Conventional education showed an insufficient effect on apraxia recovery. Further studies with larger sample sizes are needed to determine the effect of rehabilitation strategies on functionality and quality of life of poststroke ULA patients.

Resumen Los anticuerpos antiSOX-1 positivos se relacionan con una elevada prevalencia de neoplasia oculta, especialmente por carcinoma microcitico de pulmon. Ademas, nuestro caso anade un nuevo cuadro clinico como sindrome paraneoplasico neurologico asociado a su presencia: la corea. No se conoce el mecanismo exacto de los anticuerpos antiSOX-1, pero se han descrito con variedad de cuadros clinicos, incluyendo ahora el nuestro, por lo que su presencia parece apoyar la hipotesis de que podrian poseer un papel directo en su patogenia.

Background PD is a complex polygenic disorder. In recent years, several genes from the endocytic membrane-trafficking pathway have been suggested to contribute to disease etiology. However, a systematic analysis of pathway-specific genetic risk factors is yet to be performed. Objectives To comprehensively study the role of the endocytic membrane-trafficking pathway in the risk of PD. Methods Linkage disequilibrium score regression was used to estimate PD heritability explained by 252 genes involved in the endocytic membrane-trafficking pathway including genome-wide association studies data from 18,869 cases and 22,452 controls. We used pathway-specific single-nucleotide polymorphisms to construct a polygenic risk score reflecting the cumulative risk of common variants. To prioritize genes for follow-up functional studies, summary-data based Mendelian randomization analyses were applied to explore possible functional genomic associations with expression or methylation quantitative trait loci. Results The heritability estimate attributed to endocytic membrane-trafficking pathway was 3.58% (standard error = 1.17). Excluding previously nominated PD endocytic membrane-trafficking pathway genes, the missing heritability was 2.21% (standard error = 0.42). Random heritability simulations were estimated to be 1.44% (standard deviation = 0.54), indicating that the unbiased total heritability explained by the endocytic membrane-trafficking pathway was 2.14%. Polygenic risk score based on endocytic membrane-trafficking pathway showed a 1.25 times increase of PD risk per standard deviation of genetic risk. Finally, Mendelian randomization identified 11 endocytic membrane-trafficking pathway genes showing functional consequence associated to PD risk. Conclusions We provide compelling genetic evidence that the endocytic membrane-trafficking pathway plays a relevant role in disease etiology. Further research on this pathway is warranted given that critical effort should be made to identify potential avenues within this biological process suitable for therapeutic interventions. © 2019 International Parkinson and Movement Disorder Society.

Resumen: Introducción: La enfermedad de Parkinson (EP) carece de escalas neuropsicológicas específicas para valorar las alteraciones cognitivas más relevantes en la EP, lo que ha condicionado la utilización de criterios subjetivos o de instrumentos diseñados para otras patologías, dificultando la comparación entre estudios o el seguimiento de los pacientes. Recientemente se ha validado un test de cribado para la demencia en la EP (Parkinson's Disease Dementia-Short Screen [PDD-SS]). Evaluar el grado de satisfacción de los pacientes e investigadores con el uso del PDD-SS en la práctica clínica habitual. Pacientes y métodos: Estudio observacional, transversal, multicéntrico y nacional en 471 pacientes con EP. El grado de satisfacción de los pacientes se midió mediante un cuestionario cuyos ítems puntuaban según una escala analógica-visual de 0-10 puntos (0 = totalmente en desacuerdo, 10 = completamente de acuerdo), mientras que en los investigadores se determinó según una escala Likert de 1-5 puntos (1 = totalmente en desacuerdo, 5 = completamente de acuerdo). Resultados: El 36,3% (n = 171) de los pacientes presentó demencia asociada a EP según el PDD-SS, considerándose un 77,3% satisfechos con su uso. La satisfacción medida total de los investigadores fue de 3,6 ± 0,6 puntos. El 90% (n = 45) de ellos reportó una puntuación global > 3 puntos en el cuestionario de satisfacción. La valoración media de la percepción de aplicabilidad, manejabilidad y fiabilidad del PDD-SS entre los investigadores fue de 3,5 ± 0,7; 3,7 ± 0,6 y 3,1 ± 0,5 puntos, respectivamente. Conclusión: Los pacientes con EP, así como la mayoría de los investigadores se mostraron satisfechos con el uso del PDD-SS en la práctica clínica habitual. Abstract: Introduction: Parkinson disease (PD) has no specific neuropsychological scales for assessing the most significant cognitive impairment in PD, which has determined the use of subjective criteria or instruments designed for other diseases, making difficult the comparison between studies or the follow-up of patients. A screening test for dementia in PD (Parkinson's Disease Dementia-Short Screen [PDD-SS]) has recently been validated. To assess the degree of satisfaction of patients and researchers through the use of PDD-SS in clinical practice. Patients and methods: An observational, cross-over, multicentre and national study was conducted on 471 patients with PD. The degree of patient satisfaction was measured using a questionnaire in which the items scored from 0 to 10 on a visual analogue scale (0 = strongly disagree, 10 = completely agree), while the researchers were determined on a 1-5 point Likert scale (1 = strongly disagree, 5 = completely agree). Results: A total of 171 patients (36.3%) patients had dementia associated with PD according to the PDD-SS, of whom 77.3% said they were satisfied with its use. The overall measurement of researcher satisfaction was 3.6 ± 0.6 points. Ninety per cent (n = 45) of them reported an overall score >3 points in the satisfaction questionnaire. The mean values of perception of applicability, usability and reliability of PDD-SS among researchers was 3.5 ± 0.7, 3.7 ± 0.6 and 3.1 ± 0.5 points, respectively. Conclusions: PD patients, as well as most of the researchers, were satisfied with the use of PDD-SS in clinical practice. Palabras clave: Demencia, Enfermedad de Parkinson, Test de diagnóstico, Cribado, Satisfacción, Cuestionarios, Keywords: Dementia, Parkinson's disease, Diagnostic test, Screening, Satisfaction, Questionnaires

Background Upper limb apraxia is a common disorder associated with stroke that can reduce patients’ independence levels in activities of daily living and increase levels of disability. Traditional rehabilitation programs designed to promote the recovery of upper limb function have mainly focused on restorative or compensatory approaches. However, no previous studies have been completed that evaluate a combined intervention method approach, where patients concurrently receive cognitive training and learn compensatory strategies for enhancing daily living activities. Methods/Design This study will use a two-arm, assessor-blinded, parallel, randomized controlled trial design, involving 40 patients who present a left- or right-sided unilateral vascular lesion poststroke and a clinical diagnosis of upper limb apraxia. Participants will be randomized to either a combined functional rehabilitation or a traditional health education group. The experimental group will receive an 8-week combined functional program at home, including physical and occupational therapy focused on restorative and compensatory techniques for upper limb apraxia, 3 days per week in 30-min intervention periods. The control group will receive a conventional health education program once a month over 8 weeks, based on improving awareness of physical and functional limitations and facilitating the adaptation of patients to the home. Study outcomes will be assessed immediately postintervention and at the 2-month follow-up. The primary outcome measure will be basic activities of daily living skills as assessed with the Barthel Index. Secondary outcome measures will include the following: 1) the Lawton and Brody Instrumental Activities of Daily Living Scale, 2) the Observation and Scoring of ADL-Activities, 3) the De Renzi Test for Ideational Apraxia, 4) the De Renzi Test for Ideomotor Apraxia, 5) Recognition of Gestures, 6) the Test of Upper Limb Apraxia (TULIA), and 7) the Quality of Life Scale For Stroke (ECVI-38). Discussion This trial is expected to clarify the effectiveness of a combined functional rehabilitation approach compared to a conservative intervention for improving upper limb movement and function in poststroke patients. Trial registration Clinical Trial Gov number NCT02199093. The protocol registration was received 23 July 2014. Participant enrollment began on 1 May 2014. The trial is expected to be completed in March 2016. Electronic supplementary material The online version of this article (doi:10.1186/s13063-015-1034-1) contains supplementary material, which is available to authorized users.

The study was partially funded by the “Accion Transversal del Cancer”, approved on the Spanish Ministry Council on the 11th October 2007, by the Instituto de Salud Carlos III-FEDER (PI08/1770, PI08/0533, PI08/1359, PS09/00773, PS09/01286,PS09/01903, PS09/02078, PS09/01662, PI11/01403, PI11/01889,PI11/00226, PI11/01810, PI11/02213, PI12/00488, PI12/00265,PI12/01270, PI12/00715, PI12/00150), Castaño-Vinyals, G., Aragonés, N., Pérez-Gómez, B., Martín, V., Llorca, J., Moreno, V., Altzibar, J.M., Ardanaz, E., de Sanjosé, S., Jiménez-Moleón, J.J., Tardón, A., Alguacil, J., Peiró, R., Marcos-Gragera, R., Navarro, C., Pollán, M., Kogevinas, M., Alonso, M.T., Amiano, P., Arias, C., Azpiri, M., Benavente, Y., Boldo, E., Bueno, A., Bustamante, M., Caballero, F.J., Campo, E., Cantón, R., Capelo, R., Carmona, C., Casabonne, D., Chirlaque, M.D., Cirac, J., Clofent, J., Colado, E., Costas, L., Crous, M., Del Campo, R., Santos, M.D., Dierssen-Sotos, T., Ederra, M., Espinosa, A., Cabrera, M.F., Somoano, A.F., Villa, T.F., García-Esquinas, E.G., Martín, P.G., Gómez-Acebo, I., Puga, C.G., Gràcia, E., Eslava, M.G., Guinó, E., Huerta, J.M., Lope, V., López-Abente, G., Lopez-Otín, C., Argüelles, B.M., Salas, S.M., Pozo, B.M., de la Torre, A.J., Moreno, E., Iribas, C.M., Olea, N., Gelis, G.O., Paré, L., Porta, M., Puig, M., Del Fresno, M.R., Robles, C., Suarez, M.M., Romero, B., Castillo, A.I., Serra, M.S., Trejo, D.S., Santaballa, A., Santibáñez, M., Sierra, Á., Souto, A., Villanueva, C.M., Carrasco, E., Sabaté, Y., Persavento, C., García, M., Carrasco, G., Expósito, A., Andreu, M., Bessa, X., Piracés, M., Lorente, J.A., Tusquets, I., Collet, I., Bory, F., Pera, M., Abella, E., Garcia, F., Salar, A., Piñol, M., Fernandez-Llamazares, J., Martín, M.V., Garsot, E., Servio, L.I., Arzoz-Fabregas, M., Suarez, L., Ruiz, J.M., Castells, A., Serradesanferm, A., Bosch, A., Muñoz, M., Fontanillas, M., Alcaraz, A., Mengual, L., Duran, E., Izard, C., López, C., Benítez, J.M., Massanes, A.B., Ferrer, O.G., Almeda, J., Sarret, S., Rodriguez, M.A., Valmaseda, A.B., Liceran, M., Petitbó, D., Nolla, J.I., Pérez, S., Martínez, S., Vilaseca, J.M., Sebastián, L., Quesada, P., Sequera, G., Barca, E.G., Domingo-Domenech, E., Oliveira, A., Alonso, E., de la Banda, E., Sabater, Y., Vergara, M., Exposito, A., Alonso, T., Padrol, I., Klaustermeier, J., Florencia, Y., Camon, V., Esteban, A., Aymerich, M., Lopez-Otin, C., Muñoz, A., Torralba, Y., Dot, D., Mercadal, S., Sarra, J., Medina, P., Atienza, C., Biondo, S., de Oca, J., Ferran, L., Rodriguez-Moranta, F., Soriano, A., Guardiola, J., Urruticoechea, A., Galan, M., Banda, J.M., Zumel, Á., Saez, A., Garrido, J.A., Lacasaña, M., Ariza, J.L., García, T., García, M.Á., Hidalgo, M.Á., Asuero, M., Bayo, J., Vázquez, V.C., Franco, F., Gurucelain, J.L., Frías, M.J., Van de Haar, R., Viñas, J., Jiménez, H., Aguayo, M., Pereira, A., Gutiérrez, S.P., Rada, R., Candón, J., Domínguez, J., Ramos, M., Pedraza, G., Braulio, J., Salas, J., Labrero, D., Muñoz, D., Barrero, F., Delgado, S., Galisteo, L., Camacho, A., Elena, H., Caballero, J., Muñoz, M.J., Arredondo, F., Linares, R., Tejada, A., Tinto, H., Alés, J.D., Coronado, M.V., Bernal, M.L., Ortiz, J.L., Ocaña, M.N., Cavanillas, A.B., Miguel, Mejías, E.J., Abril, O.M., Requena, R.O., Morata, J.L., Echezarreta, E.G., López, L.M., Martínez, M.M., Sedano, P.P., de la Pedraja Pavón, A., López-Rojo, C., Mendiola, J., Pellicer, E., Caparrós, J.M., Oltra, E.G., Martínez, J.M., Molina, A., Villanueva, V., Miranda, M.J., Abril, C., Martinez, J., Salas, D., Ruiz, J.L., Ponce, M., Noos, P., Cervera, J., Del Val, A., Segura, A., Jiménez, N., Bellmunt, E., Aznar, I., Ramos, D., Montón, T., Solera, M.C., Mora, E.M., Estañ, N., Camarasa, N., Solanas, J.V., Ripoll, J., Cantero, J., Díaz, C.A., García, A.S., Avellón, S.M., Neumann, M., González, M.J., Suárez, M.M., Fernández, G., Fresno, M.R., Gómez, A., Garín, U., de Gros, A., Tamayo, E., Rua, M., Lasarte, C.S., Jauregi, M., Recio, J., Fernández, M., Múgica, M., Ciria, J.P., Guimón, E., Adúriz, C., Lacasta, A., Francisco, J.S., Alvarez, I., Enriquez-Navascués, J.M., Ruiz, I., Michelena, M., Alberro, J.A., Almansa, A.M., Goñi, L.M., Elizagaray, M.I., Técnico, M.O., Pérez, R.B., De Miguel Medina, M.C., Repáraz Romero, M., de Azúa Ciria, A.Y., Díaz, M.M., Lizárraga, M.S., Jiménez, Y.L., López, C.E., Legaz, S.O., Lezaun, R.A., Hurtado, H.O., De Miguel Velasco, M., Rubio, P.A., Cunchillos, F.D., de Liaño Arguelles, Á.D., Peñuela, J.M., Dorronsoro, M.L., Celaya, F.B., García, D.R., de la Higuera Carnicer, B.G., Tricas, J.M., Rivera, E.M., García, F.V., Noain, J.J., Erdozain, E.A., Ulibarrena, C.I., Lopeandía, J.G., Caden, M.A., Moraza, F.A., Domench, J.J., Arteaga, A.A., Navarro, K.A., Del Burgo Tajadura, M.A., Irastorza, F.C., Urrisarri, M.J., Zubicoa, B.F., Lorente, P.G., Sevilla, P.H., Echamendi, M.L., Díaz, Á.M., Salaverri, J.M., Gorricho, F.J., Del Valle, M.P., de Prado Marcilla, J., Garcésducar, M., Herce, P.A., Barasoain, J.E., Campos, I.A., Vergara, E.A., Beraza, B.C., Blasco, L.F., Díaz, L.G., Larrañeta, J.G., Ruiz, N.G., García, J.G., Orduna, M.S., Larena, D.I., Fernández, M.P., de Ciriza Pejenaute, F.J., Escuin, R., Puertas, I.R., Samper, I.A., Sesma, M.E., López, M.J., Apestegui, C.Z., Linares, C., Cervantes, M., Ferreras, E., García-Pérez, J., Fernández-Navarro, P., Pastor, R., Ramis, R., González, Á., Ruiz, T., Muñoz, V., Delgado, R., Lanza, M., Marín, M., Posada, M., Cosmen, J., Villanueva, A., Castaño, A., Jiménez, J.A., Rin, A., Díaz, G., Herreros, M., Pedraza, V., López, P., de la Fuente, M., de Castro, M.F., Sobrino, J., Calvo, R., Carrascal, I., Bernal, R., Mateo, A., García-Olmo, D., Zarazaga, A., Gombau, M.Á., Díaz, J., Gómez, T., Sánchez, T., de la Quintana, P., Ordás, J., Cuevas, P., Sánchez-Pastor, M., de la Peña, J.J., Tabernero, Á., Cámara, N., Hardisson, D., Suárez, A., Burgos, E., Alves, J., Miguel, M., Feliú, J., Belda, C., Zamora, P., Sánchez, A., Hernández, A., Beato, T., Arroba, A., Ballesteros, A., Canora, S., García, C., Romero, M., José, T.S., Espinel, M., Mañas, A., Sánchez, M., Ramón, H., Morillo, J.L., Cuchí, M., García, M.J., Ramos, J.M., Rojo, R., Sanjuanbenito, A., Villanueva, A.G., Gras, M., Cabañas, J.L., Collado, V., Arano, I., Capela, I., Mojarrieta, C., Peñas, B., Rodríguez, M., Ramos, A., Sancho, S., Hervás, A., Moreno, P., Sánchez, C., DoloresRubio, Montoya, L., Sancho, P., Rodríguez, L., Durán, E., Morel, S., Burgos, J., García, R., Del Cañizo, C.G., Díaz, A., González, F., Cristóbal, E., Barahona, C., Vázquez, S., Esteban, V., Pedrera, M., Martínez, J., Carrato, A., Ponce, C.G., Santos-Olmo, A., Barrientos, R.R., López, G., Fernández, A., García, A.B., Noriega, A., Campo, M., Varona, E., López, F., Montero, M., Gómez, M.T., Bartibas, P., Sanz, R., Montes, T., Salinero, M.Á., Herrero, M., Igea, M., Calvo, C., Pérez-Pellón, C., Maestre, M., Agora, M.A., Martín, M.G., Velázquez, D., Fernández, B., Castro, M., Ayuso, E., Masa, R., Antelo, C., García, S., Herrero, S., Delgado, A., Vilardell, L., Puig-Vives, M., Osca-Gelis, G., Buxo, M., Izquierdo, A., Carmona-Garcia, M.C., Romanos, R.R., Galindo, C.T., Bargalló, P.M., Sanchez, E.R., Saez, M., Roncero, J.M., Gallardo, D., Coll, R., Blanco, I., Ruano, L.M., Castaño, E.A., Rusiñol, J.M., Perez, R.J., Pujol, I.M., Tuero, G.C., de Barrio Lera, J.P., Carral, J.M., Pérez, C.A., Puente, M.E., Balbuena, S.P., Presa, J.M., Ramírez, J.A., Martínez, A.Á., de Francisco, T.G., Elosua, T.G., Teso, E.P., Fueyo, J.F., Guadarrama, O.A., Turienzo Frade Mdel, A., De la Hoz Riesco, M., Fernández, J.J., Fernández, V.S., Fernández, R.C., Santamaría, M.V., Simón, J.A., Ganso, A.M., Pacho, A.V., Alegre, S.V., Plaza, F.J., Cuenllas, B.Á., Franco, E.H., Martín, M.H., Ariño, M.T., Tascón, C.D., Palomo, J.A., Castañón López Mdel, C., Lorenzo, M.P., González, I.A., Rivero, F.G., Román, C.H., Fernández, E.Á., Bayón, T.R., Fernández, A.G., Municio, F., de Celis, M.G., Ingelmo, L.Á., Herrero, J.G., Carbajo, M.J., Esteras, T.R., Baz, B.V., Baticón, C.H., Baza, E.Á., Urdiales, A.U., Gil, J.I., López, M.A., Ule, E.C., Diez, C.B., Marín, A.I., Bernabeu, M.Á., de Abajo Olea, S., Rojo, C.V., Fernández, M.Á., González, F.G., Martínez, L.G., Del Huertotrancón Moratiel, M., Ramos, N.C., Fidalgo, S.P., Coque, P.R., González, Á.G., Díez, A.B.

Background: Huntington’s disease (HD) is a rare triplet repeat (CAG) disorder. Advanced, multi-centre, multi-national research frameworks are needed to study simultaneously multiple complementary aspects of HD. This includes the natural history of HD, its management and the collection of clinical information and biosamples for research. Methods: We report on cross-sectional data of the first 1766 participants in REGISTRY, the European Huntington’s Disease Network’s (EHDN), multi-lingual, multi-national prospective observational study of HD in Europe. Data collection (demographics, phenotype, genotype, medication, co-morbidities, biosamples) followed a standard protocol. Results: Phenotype, and the HD genotype, of manifest HD participants across different European regions was similar. Motor onset was most common (48%) with a non-motor onset in more than a third of participants. Motor signs increased, and cognitive abilities and functional capacity declined as the disease burden (CAGn-35.5) X age) increased. A life-time history of behavioural symptoms was common, but the behavioural score was not related to disease burden. One fifth of participants had severe psychiatric problems, e.g. suicidal ideation and attempts, and/or irritability/aggression, with psychosis being less common. Participants on anti-dyskinetic medication had a higher motor and lower cognitive score, were older, and more prone to physical trauma. A higher motor and a lower cognitive score predicted more advanced disease. Conclusions: The unparalleled collection of clinical data and biomaterials within the EHDN’s REGISTRY can expedite the search for disease modifiers (genetic and environmental) of age at onset and disease progression that could be harnessed for the development of novel treatments.