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3. Extreme phenotypic heterogeneity in non-expansion spinocerebellar ataxias.

Author

Cunha, P., Petit, E., Coutelier, M., Coarelli, G., Mariotti, C., Faber, J., Gaalen, J. van, Damasio, J., Fleszar, Z., Tosi, M., Rocca, C., Michele, G. de, Minnerop, M., Ewenczyk, C., Santorelli, F.M., Heinzmann, A., Bird, T., Amprosi, M., Indelicato, E., Benussi, A., Charles, P., Stendel, C., Romano, S, Scarlato, M., Ber, I. Le, Bassi, M.T., Serrano, M., Schmitz-Hübsch, T., Doss, S., Velzen, G.A.J. Van, Thomas, Q., Trabacca, A., Ortigoza-Escobar, J.D., D'Arrigo, S., Timmann, D., Pantaleoni, C., Martinuzzi, A., Besse-Pinot, E., Marsili, L., Cioffi, E., Nicita, F., Giorgetti, A., Moroni, I., Romaniello, R., Casali, C., Ponger, P., Casari, G., Bot, S.T. de, Ristori, G., Blumkin, L., Borroni, B., Goizet, C., Marelli, C., Boesch, S., Anheim, M., Filla, A., Houlden, H., Bertini, E., Klopstock, T., Synofzik, M., Riant, F., Zanni, G., Magri, S., Bella, D. Di, Nanetti, L., Sequeiros, J., Oliveira, J., Warrenburg, B. Van de, Schöls, L., Taroni, F., Brice, A., Durr, A., Cunha, P., Petit, E., Coutelier, M., Coarelli, G., Mariotti, C., Faber, J., Gaalen, J. van, Damasio, J., Fleszar, Z., Tosi, M., Rocca, C., Michele, G. de, Minnerop, M., Ewenczyk, C., Santorelli, F.M., Heinzmann, A., Bird, T., Amprosi, M., Indelicato, E., Benussi, A., Charles, P., Stendel, C., Romano, S, Scarlato, M., Ber, I. Le, Bassi, M.T., Serrano, M., Schmitz-Hübsch, T., Doss, S., Velzen, G.A.J. Van, Thomas, Q., Trabacca, A., Ortigoza-Escobar, J.D., D'Arrigo, S., Timmann, D., Pantaleoni, C., Martinuzzi, A., Besse-Pinot, E., Marsili, L., Cioffi, E., Nicita, F., Giorgetti, A., Moroni, I., Romaniello, R., Casali, C., Ponger, P., Casari, G., Bot, S.T. de, Ristori, G., Blumkin, L., Borroni, B., Goizet, C., Marelli, C., Boesch, S., Anheim, M., Filla, A., Houlden, H., Bertini, E., Klopstock, T., Synofzik, M., Riant, F., Zanni, G., Magri, S., Bella, D. Di, Nanetti, L., Sequeiros, J., Oliveira, J., Warrenburg, B. Van de, Schöls, L., Taroni, F., Brice, A., and Durr, A.

Abstract

Contains fulltext : 294768.pdf (Publisher’s version ) (Closed access), Although the best-known spinocerebellar ataxias (SCAs) are triplet repeat diseases, many SCAs are not caused by repeat expansions. The rarity of individual non-expansion SCAs, however, has made it difficult to discern genotype-phenotype correlations. We therefore screened individuals who had been found to bear variants in a non-expansion SCA-associated gene through genetic testing, and after we eliminated genetic groups that had fewer than 30 subjects, there were 756 subjects bearing single-nucleotide variants or deletions in one of seven genes: CACNA1A (239 subjects), PRKCG (175), AFG3L2 (101), ITPR1 (91), STUB1 (77), SPTBN2 (39), or KCNC3 (34). We compared age at onset, disease features, and progression by gene and variant. There were no features that reliably distinguished one of these SCAs from another, and several genes-CACNA1A, ITPR1, SPTBN2, and KCNC3-were associated with both adult-onset and infantile-onset forms of disease, which also differed in presentation. Nevertheless, progression was overall very slow, and STUB1-associated disease was the fastest. Several variants in CACNA1A showed particularly wide ranges in age at onset: one variant produced anything from infantile developmental delay to ataxia onset at 64 years of age within the same family. For CACNA1A, ITPR1, and SPTBN2, the type of variant and charge change on the protein greatly affected the phenotype, defying pathogenicity prediction algorithms. Even with next-generation sequencing, accurate diagnosis requires dialogue between the clinician and the geneticist.

Published
2023

4. Neuro-telehealth for fragile patients in a tertiary referral neurological institute during the COVID-19 pandemic in Milan, Lombardy

Author

Pareyson, D, Pantaleoni, C, Eleopra, R, De Filippis, G, Moroni, I, Freri, E, Zibordi, F, Bulgheroni, S, Pagliano, E, Sarti, D, Silvani, A, Grazzi, L, Tiraboschi, P, Didato, G, Anghileri, E, Bersano, A, Valentini, L, Piacentini, S, Muscio, C, Leonardi, M, Mariotti, C, Eoli, M, Nuzzo, S, Tagliavini, F, Confalonieri, P, De Giorgi, F, Antozzi, C, Ardissone, A, Bersano, E, Boncoraglio, G, Bonvegna, S, Botturi, A, Brambilla, L, Canafoglia, L, Caputi, L, Caroppo, P, Carriero, M, Casali, C, Casazza, M, Catania, A, Ciaccio, C, Cilia, R, Dallabella, E, D'Amico, D, Danti, F, D'Arrigo, S, Decurtis, M, Deleo, F, Devigili, G, Difede, G, Digiacomo, R, Elia, A, Esposito, S, Estienne, M, Fenu, S, Fichera, M, Finocchiaro, G, Frangiamore, R, Gatti, M, Gaviani, P, Giaccone, G, Giani, L, Giovagnoli, A, Andreasi, N, Granata, T, Granocchio, E, Lamperti, C, Lamperti, E, Leone, M, Masson, R, Nanetti, L, Nardocci, N, Pastori, C, Pisciotta, C, Cecchini, A, Ragona, F, Redaelli, V, Saletti, V, Salsano, E, Scelzo, E, Solazzi, R, Tozzo, A, Usai, S, Zorzi, G, Arnoldi, M, Foscan, M, Marchi, A, Pedrinelli, I, Zanin, R, Gazzola, S, Magazu, S, Scopelliti, M, Casalino, T, Desalvatore, M, Mazzanti, S, Taddei, M, Fedeli, A, Sattin, D, Galimberti, L, Zagari, R, Bombonato, M, Fonte, L, Floridia, S, Pareyson D., Pantaleoni C., Eleopra R., De Filippis G., Moroni I., Freri E., Zibordi F., Bulgheroni S., Pagliano E., Sarti D., Silvani A., Grazzi L., Tiraboschi P., Didato G., Anghileri E., Bersano A., Valentini L., Piacentini S., Muscio C., Leonardi M., Mariotti C., Eoli M., Nuzzo S., Tagliavini F., Confalonieri P., De Giorgi F., Antozzi C., Ardissone A., Bersano E., Boncoraglio G., Bonvegna S., Botturi A., Brambilla L., Canafoglia L., Caputi L., Caroppo P., Carriero M. R., Casali C., Casazza M., Catania A., Ciaccio C., Cilia R., DallaBella E., D'Amico D., Danti F. R., D'Arrigo S., DeCurtis M., Deleo F., Devigili G., DiFede G., DiGiacomo R., Elia A., Esposito S., Estienne M., Fenu S., Fichera M., Finocchiaro G., Frangiamore R., Gatti M., Gaviani P., Giaccone G., Giani L., Giovagnoli A. R., Andreasi N. G., Granata T., Granocchio E., Lamperti C., Lamperti E., Leone M., Masson R., Nanetti L., Nardocci N., Pastori C., Pisciotta C., Cecchini A. P., Ragona F., Redaelli V., Saletti V., Salsano E., Scelzo E., Solazzi R., Tozzo A., Usai S., Zorzi G., Arnoldi M. T., Foscan M., Marchi A., Pedrinelli I., Zanin R., Gazzola S., Magazu S., Scopelliti M. R., Casalino T., DeSalvatore M., Mazzanti S., Taddei M., Fedeli A., Sattin D., Galimberti L., Zagari R., Bombonato M., Fonte L., Floridia S., Pareyson, D, Pantaleoni, C, Eleopra, R, De Filippis, G, Moroni, I, Freri, E, Zibordi, F, Bulgheroni, S, Pagliano, E, Sarti, D, Silvani, A, Grazzi, L, Tiraboschi, P, Didato, G, Anghileri, E, Bersano, A, Valentini, L, Piacentini, S, Muscio, C, Leonardi, M, Mariotti, C, Eoli, M, Nuzzo, S, Tagliavini, F, Confalonieri, P, De Giorgi, F, Antozzi, C, Ardissone, A, Bersano, E, Boncoraglio, G, Bonvegna, S, Botturi, A, Brambilla, L, Canafoglia, L, Caputi, L, Caroppo, P, Carriero, M, Casali, C, Casazza, M, Catania, A, Ciaccio, C, Cilia, R, Dallabella, E, D'Amico, D, Danti, F, D'Arrigo, S, Decurtis, M, Deleo, F, Devigili, G, Difede, G, Digiacomo, R, Elia, A, Esposito, S, Estienne, M, Fenu, S, Fichera, M, Finocchiaro, G, Frangiamore, R, Gatti, M, Gaviani, P, Giaccone, G, Giani, L, Giovagnoli, A, Andreasi, N, Granata, T, Granocchio, E, Lamperti, C, Lamperti, E, Leone, M, Masson, R, Nanetti, L, Nardocci, N, Pastori, C, Pisciotta, C, Cecchini, A, Ragona, F, Redaelli, V, Saletti, V, Salsano, E, Scelzo, E, Solazzi, R, Tozzo, A, Usai, S, Zorzi, G, Arnoldi, M, Foscan, M, Marchi, A, Pedrinelli, I, Zanin, R, Gazzola, S, Magazu, S, Scopelliti, M, Casalino, T, Desalvatore, M, Mazzanti, S, Taddei, M, Fedeli, A, Sattin, D, Galimberti, L, Zagari, R, Bombonato, M, Fonte, L, Floridia, S, Pareyson D., Pantaleoni C., Eleopra R., De Filippis G., Moroni I., Freri E., Zibordi F., Bulgheroni S., Pagliano E., Sarti D., Silvani A., Grazzi L., Tiraboschi P., Didato G., Anghileri E., Bersano A., Valentini L., Piacentini S., Muscio C., Leonardi M., Mariotti C., Eoli M., Nuzzo S., Tagliavini F., Confalonieri P., De Giorgi F., Antozzi C., Ardissone A., Bersano E., Boncoraglio G., Bonvegna S., Botturi A., Brambilla L., Canafoglia L., Caputi L., Caroppo P., Carriero M. R., Casali C., Casazza M., Catania A., Ciaccio C., Cilia R., DallaBella E., D'Amico D., Danti F. R., D'Arrigo S., DeCurtis M., Deleo F., Devigili G., DiFede G., DiGiacomo R., Elia A., Esposito S., Estienne M., Fenu S., Fichera M., Finocchiaro G., Frangiamore R., Gatti M., Gaviani P., Giaccone G., Giani L., Giovagnoli A. R., Andreasi N. G., Granata T., Granocchio E., Lamperti C., Lamperti E., Leone M., Masson R., Nanetti L., Nardocci N., Pastori C., Pisciotta C., Cecchini A. P., Ragona F., Redaelli V., Saletti V., Salsano E., Scelzo E., Solazzi R., Tozzo A., Usai S., Zorzi G., Arnoldi M. T., Foscan M., Marchi A., Pedrinelli I., Zanin R., Gazzola S., Magazu S., Scopelliti M. R., Casalino T., DeSalvatore M., Mazzanti S., Taddei M., Fedeli A., Sattin D., Galimberti L., Zagari R., Bombonato M., Fonte L., and Floridia S.

Abstract

Background: Lombardy was severely hit by the COVID-19 pandemic since February 2020 and the Health System underwent rapid reorganization. Outpatient clinics were stopped for non-urgent patients: it became a priority to manage hundreds of fragile neurological patients who suddenly had less reference points. In Italy, before the pandemic, Televisits were neither recognized nor priced. Methods: At the Fondazione IRCCS Istituto Neurologico C. Besta, we reorganized outpatient clinics to deliver Neuro-telemedicine services, including Televisits and Teleneurorehabilitation, since March 2020. A dedicated Working Group prepared the procedure, tested the system, and designed satisfaction questionnaires for adults and children. Results: After a pilot phase, we prepared a procedure for Telemedicine outpatient clinics which was approved by hospital directions. It included prescription, booking, consenting, privacy and data protection, secure connection with patients (Teams Microsoft 365), electronic report preparation and delivery, reporting, and accountability of the services. During the March–September 2020 period, we delivered 3167 Telemedicine services, including 1618 Televisits, to 1694 patients (972 adults, 722 children) with a wide range of chronic neurological disorders. We successfully administered different clinical assessment and scales. Satisfaction among patients and caregivers was very high. Conclusions: During the dramatic emergency, we were able to take care of more than 1600 patients by organizing Neuro-telehealth in a few weeks, lessening the impact of the pandemic on fragile patients with chronic neurological disorders; this strategy is now stably embedded in our care pathways. In Italy, Telehealth is at present recognized and priced and is becoming a stable pillar of the health system.

Published
2021

5. Progression characteristics of the European Friedreich's Ataxia Consortium for Translational Studies (EFACTS): a 4-year cohort study

Author

Reetz, K, Dogan, I, Hilgers, R, Giunti, P, Parkinson, M, Mariotti, C, Nanetti, L, Durr, A, Ewenczyk, C, Boesch, S, Nachbauer, W, Klopstock, T, Stendel, C, Rodriguez de Rivera Garrido, F, Rummey, C, Schols, L, Hayer, S, Klockgether, T, Giordano, I, Didszun, C, Rai, M, Pandolfo, M, Schulz, J, Labrum, R, Thomas-Black, G, Manso, K, Solanky, N, Gellera, C, Mongelli, A, Castaldo, A, Fichera, M, Palau, F, O'Callaghan, M, Biet, M, Monin, M, Eigentler, A, Indelicato, E, Amprosi, M, Radelfahr, F, Bischoff, A, Holtbernd, F, Brcina, N, Hohenfeld, C, Koutsis, G, Breza, M, Bertini, E, Vasco, G, Reetz K., Dogan I., Hilgers R. -D., Giunti P., Parkinson M. H., Mariotti C., Nanetti L., Durr A., Ewenczyk C., Boesch S., Nachbauer W., Klopstock T., Stendel C., Rodriguez de Rivera Garrido F. J., Rummey C., Schols L., Hayer S. N., Klockgether T., Giordano I., Didszun C., Rai M., Pandolfo M., Schulz J. B., Labrum R., Thomas-Black G., Manso K., Solanky N., Gellera C., Mongelli A., Castaldo A., Fichera M., Palau F., O'Callaghan M., Biet M., Monin M. L., Eigentler A., Indelicato E., Amprosi M., Radelfahr F., Bischoff A. T., Holtbernd F., Brcina N., Hohenfeld C., Koutsis G., Breza M., Bertini E., Vasco G., Reetz, K, Dogan, I, Hilgers, R, Giunti, P, Parkinson, M, Mariotti, C, Nanetti, L, Durr, A, Ewenczyk, C, Boesch, S, Nachbauer, W, Klopstock, T, Stendel, C, Rodriguez de Rivera Garrido, F, Rummey, C, Schols, L, Hayer, S, Klockgether, T, Giordano, I, Didszun, C, Rai, M, Pandolfo, M, Schulz, J, Labrum, R, Thomas-Black, G, Manso, K, Solanky, N, Gellera, C, Mongelli, A, Castaldo, A, Fichera, M, Palau, F, O'Callaghan, M, Biet, M, Monin, M, Eigentler, A, Indelicato, E, Amprosi, M, Radelfahr, F, Bischoff, A, Holtbernd, F, Brcina, N, Hohenfeld, C, Koutsis, G, Breza, M, Bertini, E, Vasco, G, Reetz K., Dogan I., Hilgers R. -D., Giunti P., Parkinson M. H., Mariotti C., Nanetti L., Durr A., Ewenczyk C., Boesch S., Nachbauer W., Klopstock T., Stendel C., Rodriguez de Rivera Garrido F. J., Rummey C., Schols L., Hayer S. N., Klockgether T., Giordano I., Didszun C., Rai M., Pandolfo M., Schulz J. B., Labrum R., Thomas-Black G., Manso K., Solanky N., Gellera C., Mongelli A., Castaldo A., Fichera M., Palau F., O'Callaghan M., Biet M., Monin M. L., Eigentler A., Indelicato E., Amprosi M., Radelfahr F., Bischoff A. T., Holtbernd F., Brcina N., Hohenfeld C., Koutsis G., Breza M., Bertini E., and Vasco G.

Abstract

Background: The European Friedreich's Ataxia Consortium for Translational Studies (EFACTS) investigates the natural history of Friedreich's ataxia. We aimed to assess progression characteristics and to identify patient groups with differential progression rates based on longitudinal 4-year data to inform upcoming clinical trials in Friedreich's ataxia. Methods: EFACTS is a prospective, observational cohort study based on an ongoing and open-ended registry. Patients with genetically confirmed Friedreich's ataxia were seen annually at 11 clinical centres in seven European countries (Austria, Belgium, France, Germany, Italy, Spain, and the UK). Data from baseline to 4-year follow-up were included in the current analysis. Our primary endpoints were the Scale for the Assessment and Rating of Ataxia (SARA) and the activities of daily living (ADL). Linear mixed-effect models were used to analyse annual disease progression for the entire cohort and subgroups defined by age of onset and ambulatory abilities. Power calculations were done for potential trial designs. This study is registered with ClinicalTrials.gov, NCT02069509. Findings: Between Sept 15, 2010, and Nov 20, 2018, of 914 individuals assessed for eligibility, 602 patients were included. Of these, 552 (92%) patients contributed data with at least one follow-up visit. Annual progression rate for SARA was 0·82 points (SE 0·05) in the overall cohort, and higher in patients who were ambulatory (1·12 [0·07]) than non-ambulatory (0·50 [0·07]). ADL worsened by 0·93 (SE 0·05) points per year in the entire cohort, with similar progression rates in patients who were ambulatory (0·94 [0·07]) and non-ambulatory (0·91 [0·08]). Although both SARA and ADL showed slightly greater worsening in patients with typical onset (symptom onset at ≤24 years) than those with late onset (symptom onset ≥25 years), differences in progression slopes were not significant. For a 2-year parallel-group trial, 230 (115 per group) patients would be r

Published
2021

6. Predictors of malnutrition risk in neurodegenerative diseases: The role of swallowing function

Author

Pizzorni, N, Ciammola, A, Casazza, G, Ginocchio, D, Bianchi, F, Feroldi, S, Poletti, B, Nanetti, L, Mariotti, C, Mora, G, Schindler, A, Pizzorni, Nicole, Ciammola, Andrea, Casazza, Giovanni, Ginocchio, Daniela, Bianchi, Federica, Feroldi, Sarah, Poletti, Barbara, Nanetti, Lorenzo, Mariotti, Caterina, Mora, Gabriele, Schindler, Antonio, Pizzorni, N, Ciammola, A, Casazza, G, Ginocchio, D, Bianchi, F, Feroldi, S, Poletti, B, Nanetti, L, Mariotti, C, Mora, G, Schindler, A, Pizzorni, Nicole, Ciammola, Andrea, Casazza, Giovanni, Ginocchio, Daniela, Bianchi, Federica, Feroldi, Sarah, Poletti, Barbara, Nanetti, Lorenzo, Mariotti, Caterina, Mora, Gabriele, and Schindler, Antonio

Abstract

Background and purpose: Oropharyngeal dysphagia is generally recognized to increase the risk of malnutrition; however, its role in patients with neurodegenerative disease has yet to be determined. This cross-sectional study aimed to investigate the impact of swallowing function on malnutrition risk in patients with neurodegenerative diseases. Methods: Patients with oral nutrition and diagnosis of Huntington disease (HD), Parkinson disease (PD), or amyotrophic lateral sclerosis (ALS) were recruited. Demographic and clinical data were collected. The swallowing assessment included a fiberoptic endoscopic evaluation of swallowing, an oral phase assessment, and a meal observation scored with the Mealtime Assessment Scale (MAS). Malnutrition risk was assessed with the Mini Nutritional Assessment. Results: Overall, 148 patients were recruited (54 HD, 33 PD, and 61 ALS). One hundred (67.6%) patients were considered at risk of malnutrition. In the multivariate analysis, age ≥ 65 years (odds ratio [OR] = 3.16, p = 0.014), disease severity (moderate vs mild OR = 3.89, severe vs mild OR = 9.71, p = 0.003), number of masticatory cycles (OR = 1.03, p = 0.044), and MAS safety (OR = 1.44, p = 0.016) were significantly associated with malnutrition risk. Conclusions: Prolonged oral phase and signs of impaired swallowing safety during meals, together with older age and disease severity, are independent predictors of malnutrition risk in neurodegenerative diseases. This study broadens the focus on dysphagia, stressing the importance of early detection not only of pharyngeal signs, but also of oral phase impairment and meal difficulties through a multidimensional swallowing assessment.

Published
2022

7. Multifaceted and Age-Dependent Phenotypes Associated With Biallelic PNPLA6 Gene Variants: Eight Novel Cases and Review of the Literature

Author

Nanetti, L, Di Bella, D, Magri, S, Fichera, M, Sarto, E, Castaldo, A, Mongelli, A, Baratta, S, Fenu, S, Moscatelli, M, Bonati, M, Martinuzzi, A, Mariotti, C, Taroni, F, Nanetti, Lorenzo, Di Bella, Daniela, Magri, Stefania, Fichera, Mario, Sarto, Elisa, Castaldo, Anna, Mongelli, Alessia, Baratta, Silvia, Fenu, Silvia, Moscatelli, Marco, Bonati, Maria Teresa, Martinuzzi, Andrea, Mariotti, Caterina, Taroni, Franco, Nanetti, L, Di Bella, D, Magri, S, Fichera, M, Sarto, E, Castaldo, A, Mongelli, A, Baratta, S, Fenu, S, Moscatelli, M, Bonati, M, Martinuzzi, A, Mariotti, C, Taroni, F, Nanetti, Lorenzo, Di Bella, Daniela, Magri, Stefania, Fichera, Mario, Sarto, Elisa, Castaldo, Anna, Mongelli, Alessia, Baratta, Silvia, Fenu, Silvia, Moscatelli, Marco, Bonati, Maria Teresa, Martinuzzi, Andrea, Mariotti, Caterina, and Taroni, Franco

Abstract

A wide spectrum of neurodegenerative diseases has been associated with pathogenic variants in the PNPLA6 (patatin-like phospholipase domain-containing protein 6) gene, including spastic paraplegia type 39, Gordon—Holmes, Boucher—Neuhauser, Oliver—Mc Farlane, and Laurence—Moon syndromes. These syndromes present variable and overlapping clinical symptoms, encompassing cerebellar ataxia, hypogonadotropic hypogonadism, chorioretinal dystrophy, spastic paraplegia, muscle wasting, peripheral neuropathy, and cognitive impairment. In the present study, we performed a wide genetic screening in 292 patients presenting with ataxia or spastic paraplegia using a probe-based customized gene panel, covering >200 genes associated with spinocerebellar diseases. We identified six novel and four recurrent PNPLA6 gene variants in eight patients (2.7%). Six patients presented an infantile or juvenile onset (age <18), and two patients had an adult onset. Cerebellar ataxia was observed in seven patients and spastic paraplegia in one patient. Progression of cerebellar symptoms was slow in all patients, who retained ambulation even after a mean disease duration of 15 years. Brain MRI showed cerebellar atrophy in 6/8 patients, more pronounced in superior and dorsal vermis lobules (I to VII). Additional clinical features included hypogonadotropic hypogonadism (5/8), growth hormone deficiency (2/8), peripheral axonal neuropathy (4/8), cognitive impairment (3/8), chorioretinal dystrophy (2/8), and bilateral vestibular areflexia with a reduced visual vestibule-ocular reflex (1/8). In accordance with previous studies, chorioretinal dystrophy was the most frequent presenting symptom in early onset patients, hypogonadotropic hypogonadism in juvenile onset cases, and cerebellar ataxia in adult patients. One patient had an initial clinical presentation compatible with Cerebellar Ataxia with Neuropathy and Vestibular Areflexia Syndrome (CANVAS), but no pathological expansions in the RFC1 gene. I

Published
2022

8. Comorbidities in Friedreich ataxia: incidence and manifestations from early to advanced disease stages

Author

Fichera, M, Castaldo, A, Mongelli, A, Marchini, G, Gellera, C, Nanetti, L, Mariotti, C, Fichera, Mario, Castaldo, Anna, Mongelli, Alessia, Marchini, Gloria, Gellera, Cinzia, Nanetti, Lorenzo, Mariotti, Caterina, Fichera, M, Castaldo, A, Mongelli, A, Marchini, G, Gellera, C, Nanetti, L, Mariotti, C, Fichera, Mario, Castaldo, Anna, Mongelli, Alessia, Marchini, Gloria, Gellera, Cinzia, Nanetti, Lorenzo, and Mariotti, Caterina

Abstract

Objectives: Friedreich’s ataxia (FA) is the most common hereditary ataxia, characterized by multisystemic manifestations including neurological, cardiological, and skeletal abnormalities. In this study, we aimed to analyze the incidences of disease-related and unrelated comorbidities occurring in different stages of the disease progression. Methods: We analyzed longitudinal data from a 10-year prospective observational study in a cohort of 175 FA patients with disease onset < 25 years. We analyzed the time of diagnosis for the most frequently reported medical conditions, with respect to age and disease duration of each patient. Results: In the early stage of the disease, scoliosis (53.3%), hypertrophic cardiomyopathy (46.7%), and pes cavus (33.3%) were the most frequently diagnosed conditions, sometimes occurring even before the onset of ataxia. Diabetes, bone fractures, and depression have the same incidence at all disease stages. In patients with > 20 years of disease duration, the most frequent complications were hearing and visual loss (20% and 26%), arrhythmias (16%), and psychosis (18%). Thirteen patients presented hallucinations/delusions in the absence of neurological acute events or mental illness predisposing to psychotic manifestations. Six of these patients fulfill the diagnostic criteria for Charles Bonnet syndrome. Conclusions: Incidence of FA-related medical conditions varies according to disease duration. In patients with very long disease duration, we observed an unexpectedly high incidence of visual and auditory pseudo-hallucinations that were not previously reported in FA patients. We hypothesized that these late complications may be possibly related to the severe sensory deafferentation syndrome observed in the advanced stages of FA disease.

Published
2022

11. Is overwork weakness relevant in Charcot–Marie–Tooth disease?

Author

Piscosquito, G, Reilly, M M, Schenone, A, Fabrizi, G M, Cavallaro, T, Santoro, L, Vita, G, Quattrone, A, Padua, L, Gemignani, F, Visioli, F, Laurà, M, Calabrese, D, Hughes, R A C, Radice, D, Solari, A, Pareyson, D, Marchesi, C, Salsano, E, Nanetti, L, Marelli, C, Scaioli, V, Ciano, C, Rimoldi, M, Lauria, G, Rizzetto, E, Camozzi, F, Narciso, E, Grandis, M, Monti-Bragadin, M, Nobbio, L, Casano, A, Bertolasi, L, Cabrini, I, Corrà, K, Rizzuto, N, Manganelli, F, Pisciotta, C, Nolano, M, Mazzeo, A, Di Leo, R, Majorana, G, Russo, M, Valentino, P, Nisticò, R, Pirritano, D, Lucisano, A, Canino, M, Pazzaglia, C, Granata, G, Foschini, M, Brindani, F, Vitetta, F, Allegri, I, Bogani, P, Blake, J, Koltzenburg, M, Hutton, E, and Lunn, M

Published
2014
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12. PMP22 messenger RNA levels in skin biopsies: testing the effectiveness of a Charcot–Marie–Tooth 1A biomarker

Author

Nobbio, Lucilla, Visigalli, Davide, Radice, Davide, Fiorina, Elisabetta, Solari, Alessandra, Lauria, Giuseppe, Reilly, Mary M., Santoro, Lucio, Schenone, Angelo, Pareyson, Davide, Pareyson, D., Marchesi, C., Salsano, E., Nanetti, L., Marelli, C., Scaioli, V., Ciano, C., Rimoldi, M., Lauria, G., Rizzetto, E., Camozzi, F., Schenone, A., Narciso, E., Grandis, M., Monti-Bragadin, M., Nobbio, L., Fabrizi, G. M., Cavallaro, T., Casano, A., Bertolasi, L., Cabrini, I., Corrà, K., Rizzuto, N., Santoro, L., Manganelli, F., Pisciotta, C., Nolano, M., Vita, G., Mazzeo, A., Aguennouz, M., Di Leo, R., Majorana, G., Lanzano, N., Valenti, F., Quattrone, A., Valentino, P., Nisticò, R., Pirritano, D., Lucisano, A., Canino, M., Padua, L., Pazzaglia, C., Granata, G., Foschini, M., Gemignani, F., Brindani, F., Vitetta, F., Allegri, I., Visioli, F., Bogani, P., and Visioli, F.

Published
2014
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27. Prediction of Survival With Long-Term Disease Progression in Most Common Spinocerebellar Ataxia

Author

Diallo, A., Jacobi, H., Cook, A., Giunti, P., Parkinson, M.H., Labrum, R., Durr, A., Brice, A., Charles, P., Marelli, C., Mariotti, C., Nanetti, L., Panzeri, M., Castaldo, A., Rakowicz, M., Rola, R., Sulek, A., Schmitz-Hubsch, T., Schols, L., Hengel, H., Baliko, L., Melegh, B., Filla, A., Antenora, A., Infante, J., Berciano, J., Warrenburg, B.P.C. van de, Timmann, D., Boesch, S., Nachbauer, W., Pandolfo, M., Schulz, J.B., Bauer, P., Jun-Suk, K., Klockgether, T., Tezenas du Montcel, S., Diallo, A., Jacobi, H., Cook, A., Giunti, P., Parkinson, M.H., Labrum, R., Durr, A., Brice, A., Charles, P., Marelli, C., Mariotti, C., Nanetti, L., Panzeri, M., Castaldo, A., Rakowicz, M., Rola, R., Sulek, A., Schmitz-Hubsch, T., Schols, L., Hengel, H., Baliko, L., Melegh, B., Filla, A., Antenora, A., Infante, J., Berciano, J., Warrenburg, B.P.C. van de, Timmann, D., Boesch, S., Nachbauer, W., Pandolfo, M., Schulz, J.B., Bauer, P., Jun-Suk, K., Klockgether, T., and Tezenas du Montcel, S.

Abstract

Item does not contain fulltext, BACKGROUND: Spinocerebellar ataxias are rare dominantly inherited neurodegenerative diseases that lead to severe disability and premature death. OBJECTIVE: To quantify the impact of disease progression measured by the Scale for the Assessment and Rating of Ataxia on survival, and to identify different profiles of disease progression and survival. METHODS: Four hundred sixty-two spinocerebellar ataxia patients from the EUROSCA prospective cohort study, suffering from spinocerebellar ataxia type 1, spinocerebellar ataxia type 2, spinocerebellar ataxia type 3, and spinocerebellar ataxia type 6, and who had at least two measurements of Scale for the Assessment and Rating of Ataxia score, were analyzed. Outcomes were change over time in Scale for the Assessment and Rating of Ataxia score and time to death. Joint model was used to analyze disease progression and survival. RESULTS: Disease progression was the strongest predictor for death in all genotypes: An increase of 1 standard deviation in total Scale for the Assessment and Rating of Ataxia score increased the risk of death by 1.28 times (95% confidence interval: 1.18-1.38) for patients with spinocerebellar ataxia type 1; 1.19 times (1.12-1.26) for spinocerebellar ataxia type 2; 1.30 times (1.19-1.42) for spinocerebellar ataxia type 3; and 1.26 times (1.11-1.43) for spinocerebellar ataxia type 6. Three subgroups of disease progression and survival were identified for patients with spinocerebellar ataxia type 1: "severe" (n = 13; 12%), "intermediate" (n = 31; 29%), and "moderate" (n = 62; 58%). Patients in the severe group were more severely affected at baseline with higher Scale for the Assessment and Rating of Ataxia scores and frequency of nonataxia signs compared to those in the other groups. CONCLUSION: Rapid ataxia progression is associated with poor survival of the most common spinocerebellar ataxia. Theses current results have implications for the design of future interventional studies of spinocerebellar ataxi

Published
2019

33. Suicidal ideation in a European Huntington's disease population

Author

Hubers, Aa, van Duijn, E, Roos, Ra, Craufurd, D, Rickards, H, Bernhard Landwehrmeyer, G, van der Mast RC, Giltay, Ej, Bachoud Lévi AC, Bentivoglio, Ar, Biunno, I, Bonelli, Rm, Burgunder, Jm, Dunnett, Sb, Ferreira, Jj, Handley, Oj, Heiberg, A, Llmann, Ti, Landwehrmeyer, Gb, Levey, J, Ramos Arroyo MA, Nielsen, Je, Prokoivisto, S, Päivärinta, M, Rojo Sebastián, A, Tabrizi, Sj, Vandenberghe, W, Verellen Dumoulin, C, Zaremba, J, Uhrova, T, Wahlström, J, Barth, K, Correia Guedes, L, Finisterra, Am, Garde, Mb, Bos, R, Betz, S, Callaghan, J, Fullam, R, Ecker, D, Nielsen, Mg, Hvalstedt, C, Held, C, Koppers, K, Laurà, M, Horta, Sm, Descals, Am, Mestre, T, Minster, S, Monza, D, Mütze, L, Oehmen, M, Townhill, J, Orth, M, Padieu, H, Paterski, L, Peppa, N, Pro Koivisto, S, Roedig, V, Rialland, A, Røren, N, Šašinková, P, Seliverstov, Y, Cubillo, Pt, Walsem, Mr, Wright, A, da Silva WV, Witjes Ané MN, Yudina, E, Zielonka, D, Zielonka, E, Zinzi, P, Herranhof, B, Holl, A, Kapfhammer, Hp, Koppitz, M, Magnet, M, Otti, D, Painold, A, Reisinger, K, Scheibl, M, Hecht, K, Lilek, S, Müller, N, Schöggl, H, Ullah, J, Brugger, F, Hepperger, C, Hotter, A, Seppi, K, Wenning, G, Buratti, L, Hametner, Em, Holas, C, Hussl, A, Poewe, W, Braunwarth, Em, Sprenger, F, Müller, C, Sinadinosa, D, Walleczek, Am, Ladurner, G, Staffen, W, Flamez, A, Morez, V, de Raedt, S, Boogaerts, A, van Reijen, D, Klempíř, J, Majerová, V, Roth, J, Hartikainen, P, Hiivola, H, Martikainen, K, Tuuha, K, Ignatius, J, Kärppä, M, Åman, J, Mustonen, A, Kajula, O, Santala, M, Allain, P, Guérid, Ma, Gohier, B, Olivier, A, Prundean, A, Scherer Gagou, C, Verny, C, Bost, M, Babiloni, B, Debruxelles, S, Duché, C, Goizet, C, Lafoucrière, D, Jameau, L, Spampinato, U, De Bruycker, C, Cabaret, M, Carette, As, Defebvre, L, Decorte, E, Delval, A, Delliaux, M, Destee, A, Dujardin, K, Peter, M, Plomhouse, L, Sablonnière, B, Simonin, C, Lemaire, Mh, Manouvrier, S, Thibault Tanchou, S, Vuillaume, I, Krystkowiak, P, Duru, C, Roussel, M, Wannepain, S, Berrissoul, H, Bellonet, M, Courtin, F, Mantaux, B, Fasquel, V, Godefroy, O, Azulay, Jp, Fluchère, F, Delfini, M, Eusebio, A, Mundler, L, Longato, N, Rudolf, G, Steinmetz, G, Tranchant, C, Wagner, C, Zimmermann, M, Marcel, C, Calvas, F, Pariente, J, Démonet, Jf, Cheriet, S, Kosinski, Cm, Milkereit, E, Probst, D, Reetz, K, Sass, C, Schiefer, J, Schlangen, C, Werner, Cj, Gelderblom, H, Priller, J, Prüß, H, Spruth, Ej, Andrich, J, Ellrichmann, G, Hoffmann, R, Kaminski, B, Saft, C, Stamm, C, Lange, H, Bosredon, C, Maass, A, Schmidt, S, Storch, A, Wolz, M, Kohl, Z, Winkler, J, Capetian, P, Lambeck, J, Zucker, B, Boelmans, K, Ganos, C, Goerendt, I, Hidding, U, Lewerenz, J, Münchau, A, Schmalfeld, J, Stubbe, L, Zittel, S, Diercks, G, Dressler, D, Gorzolla, H, Schrader, C, Tacik, P, Heinicke, W, Longinus, B, Bürk, K, Möller, Jc, Rissling, I, Mühlau, M, Peinemann, A, Städtler, M, Weindl, A, Winkelmann, J, Ziegler, C, Bohlen, S, Hölzner, E, Reilmann, R, Dose, M, Leythaeuser, G, Marquard, R, Raab, T, Schrenk, C, Schuierer, M, Buck, A, Connemann, J, Eschenbach, C, Landwehrmeyer, B, Lezius, F, Nepper, S, Niess, A, Schwenk, D, Süßmuth, S, Trautmann, S, Weydt, P, Cormio, C, Sciruicchio, V, Serpino, C, Tommaso, M, Capellari, S, Cortelli, P, Gallassi, R, Poda, R, Rizzo, G, Scaglione, C, Bertini, E, Ghelli, E, Ginestroni, A, Massaro, F, Mechi, C, Paganini, M, Piacentini, S, Pradella, S, Romoli, Am, Sorbi, S, Abbruzzese, G, di Poggio MB, Di Maria, E, Ferrandes, G, Mandich, P, Marchese, R, Albanese, A, Di Bella, D, Di Donato, S, Gellera, C, Genitrini, S, Mariotti, C, Nanetti, L, Paridi, D, Soliveri, P, Tomasello, C, De Michele, G, Di Maio, L, Salvatore, E, Rinaldi, C, Rossi, F, Massarelli, M, Roca, A, Ammendola, S, Russo, Cv, Squitieri, F, Elifani, F, Maglione, V, Di Pardo, A, Alberti, S, Griguoli, A, Amico, E, Martino, T, Petrollini, M, Catalli, C, Di Giacopo, R, Fasano, A, Frontali, M, Guidubaldi, A, Ialongo, T, Jacopini, G, Loria, G, Piano, C, Chiara, P, Quaranta, D, Romano, Silvia, Soleti, F, Spadaro, M, Romano, S, van Hout MS, van Vugt JP, Weert, A, Bolwijn, J, Dekker, M, Leenders, K, Kremer, Hp, Dumas, Em, van den Bogaard SJ, 't Hart EP, Økland, E, Hauge, E, Tyvoll, H, Frich, J, Aaserud, O, Wehus, R, Bjørgo, K, Fannemel, M, Gørvell, P, Lorentzen, E, Koivisto, Sp, Retterstøl, L, Overland, T, Stokke, B, Sando, B, Dziadkiewicz, A, Nowak, M, Robowski, P, Sitek, E, Slawek, J, Soltan, W, Szinwelski, M, Blaszcyk, M, Boczarska Jedynak, M, Ciach Wysocka, E, Gorzkowska, A, Jasinska Myga, B, Opala, G, Kłodowska Duda, G, Stompel, D, Banaszkiewicz, K, Boćwińska, D, Szczudlik, A, Rudzińska, M, Wójcik, M, Dec, M, Krawczyk, M, Jaremek, Kb, Szczygieł, E, Stenwak, A, Ielewska, Aw, Bryl, A, Ciesielska, A, Klimberg, A, Marcinkowski, J, Sempołowicz, J, Samara, H, Wiśniewski, B, Janik, P, Gogol, A, Kwiecinski, H, Jamrozik, Z, Kaminska, A, Antczak, J, Jachinska, K, Rakowicz, M, Richter, P, Rola, R, Ryglewicz, D, Sienkiewicz Jarosz, H, Stępniak, I, Witkowski, G, Zdzienicka, E, Sułek, A, Krysa, W, Zieora Jakutowicz, K, Júlio, F, Januário, C, Coelho, M, Mendes, T, Valadas, A, Timóteo, Â, Costa, C, Cavaco, S, Damásio, J, Loureiro, R, Magalhães, M, Andrade, C, Gago, M, Garrett, C, Guerra, Mr, Lima, J, Massano, J, Meireles, J, Herrera, Cd, Garcia, Pm, Barrero, F, Morales, B, Cubo, E, Mariscal, N, Sánchez, J, Alonso Frech, F, Perez, Mr, Fenollar, M, García, Rg, Quiroga, Pp, Rivera, Sv, Villanueva, C, Alegre, J, Bascuñana, M, Caldentey, Jg, Ventura, Mf, Ribas, Gg, Yébenes, Jg, López Sendón Moreno JL, García Ruíz PJ, Martínez Descals, A, Artiga, Mj, Sánchez, V, Guerrero, R, Bárcenas, Ah, Noguera Perea MF, Fortuna, L, Martirio, M, Torres, A, Reinante, G, Moreau, Lv, Barbera, Ma, Guia, Db, Hernanz, Lc, Catena, Jl, Sebastián, Ar, Ferrer, Pq, Carruesco, Gt, Bas, J, Busquets, N, Calopa, M, Elorza, Md, Díez AjaLópez, C, Terol, Sd, Robert, Mf, Ruíz, Bg, Casado, Ag, Martínez, Ih, Viladrich, Cm, Càrdenas, Rp, Roca, E, Llesoy, Jr, Idiago, Jm, Vergara, Mr, García, Ss, Riballo, Av, González, Sg, Guisasola, Lm, Salvador, C, San Martín ES, González, M, Gorospe, A, Legarda, I, Arques, Pn, Torres Rodríguez MJ, Vives, B, Gaston, I, Martinez Jaurrieta MD, Manuel, J, Moreno, G, Peña, Jc, Avarvarei, Ld, Bastida, Am, Recio, Mf, Vergé, Lr, Sánchez, Vs, Carrillo, F, Cáceres, Mt, Mir, P, Suarez, Mj, Bosca, M, Burguera, Ja, Garcia, Ac, Brugada, Fc, Martínez, Lm, Val, Jl, Loutfi, G, Olofsson, C, Stattin, El, Westman, L, Wikström, B, Lhagen, Se, Paucar, M, Svenningsson, P, Reza Soltani TW, Höglund, A, Sandström, B, Høsterey Ugander, U, Fredlund, G, Constantinescu, R, Neleborn Lingefjärd, L, Tedr off, J, Esmaeilzadeh, M, Winnberg, E, Pålhagen, S, Svennigsson, P, Riza Soltani TW, Sundblom, J, Johansson, A, Wiklund, L, Ekwall, C, Göller, Ml, Petersén, A, Reimer, J, Widner, H, Stebler, Y, Kaelin, A, Romero, I, Schüpbach, M, Weber, S, Miedzybrodzka, Z, Rae, D, Downie, L, Simpson, S, Summers, F, Ure, A, Jack, R, Matheson, K, Akhtar, S, Crooks, J, Curtis, A, Souza, J, Wright, J, Hayward, B, Sieradzan, K, Barker, Ra, O'Keefe, D, Di Pietro, A, Fisher, K, Hill, S, Mason, S, Swain, R, Valle, N, Guzman, Bisson, J, Busse, M, Butcher, C, Clenaghan, C, Dunnett, S, Handley, O, Hunt, S, Hughes, A, Johnstone, C, Jones, L, Jones, U, Khalil, H, Owen, M, Price, K, Rose, Le, Rosser, A, Porteous, M, Edwards, M, Ho, C, Mcgill, M, Pearson, P, Brockie, P, Foster, J, Johns, N, Mckenzie, S, Rothery, J, Thomas, G, Yates, S, Miller, J, Ritchie, S, Burrows, L, Fletcher, A, Harding, A, Laver, F, Silva, M, Thomson, A, Rowett, L, Gallantrae, D, Longthorpe, M, Markova, I, Raman, A, Hamer, S, Wild, S, Yarduiman, P, Chu, C, Kraus, A, Yardumian, P, Musgrave, H, Toscano, J, Jamieson, S, Hobson, E, Clayton, C, Dipple, H, Middleton, J, Freire Patino, D, Andrews, T, Dougherty, A, Kavalier, F, Golding, C, Laing, H, Lashwood, A, Robertson, D, Ruddy, D, Whaite, A, Santhouse, A, Patton, M, Peterson, M, Rose, S, Bruno, S, Chu, E, Doherty, K, Haider, S, Hensman, D, Lahiri, N, Lewis, M, Novak, M, Patel, A, Robertson, N, Rosser, E, Tabrizi, S, Taylor, R, Warner, T, Wild, E, Howard, L, Sollom, A, Snowden, J, Thompson, J, Jones, M, Murphy, H, Trender Gerhard, I, Rogers, D, Bek, J, Oughton, E, Johnson, L, Hare, M, Arran, N, Verstraelen, N, Partington Jones, L, Huson, S, Stopford, C, Westmoreland, L, Davidson, J, Morgan, K, Savage, L, Singh, B, Komati, S, Nemeth, Ah, Armstrong, R, Valentine, R, Siuda, G, Harrison, D, Hughes, M, Parkinson, A, Soltysiak, B, Burn, J, Coleman, C, Bandmann, O, Bradbury, A, Gill, P, Fairtlough, H, Fillingham, K, Foustanos, I, Kazoka, M, O'Donovan, K, Taylor, C, Tidswell, K, Quarrell, O., Laboratoire de Psychologie des Pays de la Loire (LPPL), Université d'Angers (UA)-Université de Nantes - UFR Lettres et Langages (UFRLL), Université de Nantes (UN)-Université de Nantes (UN), A. A., M, E. v., Duijn, R. A., C, D., Craufurd, H., Rickard, G. B., Landwehrmeyer, R. C., Van, E. J., Giltay, R. E., G., Rinaldi, Carlo, Anna A.M. Huber, Erik van Duijn, Raymund A.C. Roo, David Craufurd, Hugh Rickard, G. Bernhard Landwehrmeyer, Rose C. van der Mast, Erik J. Giltay REGISTRY investigators of the European Huntington's Disease Network. Collaborators: Bachoud-Lévi AC, Bentivoglio AR, Biunno I, Bonelli RM, Burgunder JM, Dunnett SB, Ferreira JJ, Handley OJ, Heiberg A, llmann TI, Landwehrmeyer GB, Levey J, Ramos-Arroyo MA, Nielsen JE, ProKoivisto S, Päivärinta M, Roos RA, Rojo Sebastián A, Tabrizi SJ, Vandenberghe W, Verellen- Dumoulin C, Zaremba J, Uhrova T, Wahlström J, Barth K, Correia-Guedes L, Finisterra AM, Garde MB, Bos R, Betz S, Callaghan J, Fullam R, Ecker D, Nielsen MG, Hvalstedt C, Held C, Koppers K, Laurà M, Horta SM, Descals AM, Mestre T, Minster S, Monza D, Mütze L, Oehmen M, Townhill J, Orth M, Padieu H, Paterski L, Peppa N, Pro Koivisto S, Roedig V, Rialland A, Røren N, Šašinková P, Seliverstov Y, Cubillo PT, Walsem MR, Wright A, da Silva WV, Witjes-Ané MN, Yudina E, Zielonka D, Zielonka E, Zinzi P, Herranhof B, Holl A, Kapfhammer HP, Koppitz M, Magnet M, Otti D, Painold A, Reisinger K, Scheibl M, Hecht K, Lilek S, Müller N, Schöggl H, Ullah J, Brugger F, Hepperger C, Hotter A, Seppi K, Wenning G, Buratti L, Hametner EM, Holas C, Hussl A, Poewe W, Braunwarth EM, Sprenger F, Müller C, Sinadinosa D, Walleczek AM, Ladurner G, Staffen W, Flamez A, Morez V, de Raedt S, Boogaerts A, van Reijen D, Klempíř J, Majerová V, Roth J, Hartikainen P, Hiivola H, Martikainen K, Tuuha K, Ignatius J, Kärppä M, Åman J, Mustonen A, Kajula O, Santala M, Allain P, Guérid MA, Gohier B, Olivier A, Prundean A, Scherer- Gagou C, Verny C, Bost M, Babiloni B, Debruxelles S, Duché C, Goizet C, Lafoucrière D, Jameau L, Spampinato U, De Bruycker C, Cabaret M, Carette AS, Defebvre L, Decorte E, Delval A, Delliaux M, Destee A, Dujardin K, Peter M, Plomhouse L, Sablonnière B, Simonin C, Lemaire MH, Manouvrier S, Thibault-Tanchou S, Vuillaume I, Krystkowiak P, Duru C, Roussel M, Wannepain S, Berrissoul H, Bellonet M, Courtin F, Mantaux B, Fasquel V, Godefroy O, Azulay JP, Fluchère F, Delfini M, Eusebio A, Mundler L, Longato N, Rudolf G, Steinmetz G, Tranchant C, Wagner C, Zimmermann M, Marcel C, Calvas F, Pariente J, Démonet JF, Cheriet S, Kosinski CM, Milkereit E, Probst D, Reetz K, Sass C, Schiefer J, Schlangen C, Werner CJ, Gelderblom H, Priller J, Prüß H, Spruth EJ, Andrich J, Ellrichmann G, Hoffmann R, Kaminski B, Saft C, Stamm C, Lange H, Bosredon C, Maass A, Schmidt S, Storch A, Wolz M, Kohl Z, Winkler J, Capetian P, Lambeck J, Zucker B, Boelmans K, Ganos C, Goerendt I, Hidding U, Lewerenz J, Münchau A, Schmalfeld J, Stubbe L, Zittel S, Diercks G, Dressler D, Gorzolla H, Schrader C, Tacik P, Heinicke W, Longinus B, Bürk K, Möller JC, Rissling I, Mühlau M, Peinemann A, Städtler M, Weindl A, Winkelmann J, Ziegler C, Bohlen S, Hölzner E, Reilmann R, Dose M, Leythaeuser G, Marquard R, Raab T, Schrenk C, Schuierer M, Buck A, Connemann J, Eschenbach C, Landwehrmeyer B, Lezius F, Nepper S, Niess A, Schwenk D, Süßmuth S, Trautmann S, Weydt P, Cormio C, Sciruicchio V, Serpino C, Tommaso M, Capellari S, Cortelli P, Gallassi R, Poda R, Rizzo G, Scaglione C, Bertini E, Ghelli E, Ginestroni A, Massaro F, Mechi C, Paganini M, Piacentini S, Pradella S, Romoli AM, Sorbi S, Abbruzzese G, di Poggio MB, Di Maria E, Ferrandes G, Mandich P, Marchese R, Albanese A, Di Bella D, Di Donato S, Gellera C, Genitrini S, Mariotti C, Nanetti L, Paridi D, Soliveri P, Tomasello C, De Michele G, Di Maio L, Salvatore E, Rinaldi C, Rossi F, Massarelli M, Roca A, Ammendola S, Russo CV, Squitieri F, Elifani F, Maglione V, Di Pardo A, Alberti S, Griguoli A, Amico E, Martino T, Petrollini M, Catalli C, Di Giacopo R, Fasano A, Frontali M, Guidubaldi A, Ialongo T, Jacopini G, Loria G, Piano C, Chiara P, Quaranta D, Romano S, Soleti F, Spadaro M, van Hout MS, van Vugt JP, Weert A, Bolwijn J, Dekker M, Leenders K, Kremer HP, Dumas EM, van den Bogaard SJ, 't Hart EP, van Duijn E, Økland E, Hauge E, Tyvoll H, Frich J, Aaserud O, Wehus R, Bjørgo K, Fannemel M, Gørvell P, Lorentzen E, Koivisto SP, Retterstøl L, Overland T, Stokke B, Sando B, Dziadkiewicz A, Nowak M, Robowski P, Sitek E, Slawek J, Soltan W, Szinwelski M, Blaszcyk M, Boczarska-Jedynak M, Ciach-Wysocka E, Gorzkowska A, Jasinska-Myga B, Opala G, Kłodowska-Duda G, Stompel D, Banaszkiewicz K, Boćwińska D, Szczudlik A, Rudzińska M, Wójcik M, Dec M, Krawczyk M, Jaremek KB, Szczygieł E, Stenwak A, ielewska AW, Bryl A, Ciesielska A, Klimberg A, Marcinkowski J, Sempołowicz J, Samara H, Wiśniewski B, Janik P, Gogol A, Kwiecinski H, Jamrozik Z, Kaminska A, Antczak J, Jachinska K, Rakowicz M, Richter P, Rola R, Ryglewicz D, Sienkiewicz-Jarosz H, Stępniak I, Witkowski G, Zdzienicka E, Sułek A, Krysa W, Zieora-Jakutowicz K, Júlio F, Januário C, Coelho M, Mendes T, Valadas A, Timóteo Â, Costa C, Cavaco S, Damásio J, Loureiro R, Magalhães M, Andrade C, Gago M, Garrett C, Guerra MR, Lima J, Massano J, Meireles J, Herrera CD, Garcia PM, Barrero F, Morales B, Cubo E, Mariscal N, Sánchez J, Alonso-Frech F, Perez MR, Fenollar M, García RG, Quiroga PP, Rivera SV, Villanueva C, Alegre J, Bascuñana M, Caldentey JG, Ventura MF, Ribas GG, Yébenes JG, López-Sendón Moreno JL, García Ruíz PJ, Martínez-Descals A, Artiga MJ, Sánchez V, Guerrero R, Bárcenas AH, Noguera Perea MF, Fortuna L, Martirio M, Torres A, Reinante G, Moreau LV, Barbera MA, Guia DB, Hernanz LC, Catena JL, Sebastián AR, Ferrer PQ, Carruesco GT, Bas J, Busquets N, Calopa M, Elorza MD, Díez-AjaLópez C, Terol SD, Robert MF, Ruíz BG, Casado AG, Martínez IH, Viladrich CM, Càrdenas RP, Roca E, Llesoy JR, Idiago JM, Vergara MR, García SS, Riballo AV, González SG, Guisasola LM, Salvador C, San Martín ES, González M, Gorospe A, Legarda I, Arques PN, Torres Rodríguez MJ, Vives B, Gaston I, Martinez-Jaurrieta MD, Manuel J, Moreno G, Peña JC, Avarvarei LD, Bastida AM, Recio MF, Vergé LR, Sánchez VS, Carrillo F, Cáceres MT, Mir P, Suarez MJ, Bosca M, Burguera JA, Garcia AC, Brugada FC, Martínez LM, Val JL, Loutfi G, Olofsson C, Stattin EL, Westman L, Wikström B, lhagen SE, Paucar M, Svenningsson P, Reza- Soltani TW, Höglund A, Sandström B, Høsterey-Ugander U, Fredlund G, Constantinescu R, Neleborn-Lingefjärd L, Tedr- off J, Esmaeilzadeh M, Winnberg E, Pålhagen S, Svennigsson P, Riza-Soltani TW, Sundblom J, Johansson A, Wiklund L, Ekwall C, Göller ML, Petersén A, Reimer J, Widner H, Stebler Y, Kaelin A, Romero I, Schüpbach M, Weber S, Miedzybrodzka Z, Rae D, Downie L, Simpson S, Summers F, Ure A, Jack R, Matheson K, Akhtar S, Crooks J, Curtis A, Souza J, Rickards H, Wright J, Hayward B, Sieradzan K, Barker RA, O'Keefe D, Di Pietro A, Fisher K, Hill S, Mason S, Swain R, Valle N, Guzman, Bisson J, Busse M, Butcher C, Clenaghan C, Dunnett S, Handley O, Hunt S, Hughes A, Johnstone C, Jones L, Jones U, Khalil H, Owen M, Price K, Rose LE, Rosser A, Porteous M, Edwards M, Ho C, McGill M, Pearson P, Brockie P, Foster J, Johns N, McKenzie S, Rothery J, Thomas G, Yates S, Miller J, Ritchie S, Burrows L, Fletcher A, Harding A, Laver F, Silva M, Thomson A, Rowett L, Gallantrae D, Longthorpe M, Markova I, Raman A, Hamer S, Wild S, Yarduiman P, Chu C, Kraus A, Yardumian P, Musgrave H, Toscano J, Jamieson S, Hobson E, Clayton C, Dipple H, Middleton J, Freire-Patino D, Andrews T, Dougherty A, Kavalier F, Golding C, Laing H, Lashwood A, Robertson D, Ruddy D, Whaite A, Santhouse A, Patton M, Peterson M, Rose S, Bruno S, Chu E, Doherty K, Haider S, Hensman D, Lahiri N, Lewis M, Novak M, Patel A, Robertson N, Rosser E, Tabrizi S, Taylor R, Warner T, Wild E, Craufurd D, Howard L, Sollom A, Snowden J, Thompson J, Jones M, Murphy H, Trender-Gerhard I, Rogers D, Bek J, Oughton E, Johnson L, Hare M, Arran N, Verstraelen N, Partington-Jones L, Huson S, Stopford C, Westmoreland L, Davidson J, Morgan K, Savage L, Singh B, Komati S, Nemeth AH, Armstrong R, Valentine R, Siuda G, Harrison D, Hughes M, Parkinson A, Soltysiak B, Burn J, Coleman C, Bandmann O, Bradbury A, Gill P, Fairtlough H, Fillingham K, Foustanos I, Kazoka M, O'Donovan K, Taylor C, Tidswell K, Quarrell O., Molecular Neuroscience and Ageing Research (MOLAR), Hubers, Aa, van Duijn, E, Roos, Ra, Craufurd, D, Rickards, H, Bernhard Landwehrmeyer, G, van der Mast, Rc, Giltay, Ej, CollaboratorsBachoud Lévi AC, REGISTRY investigators of the European Huntington's Disease N. e. t. w. o. r. k., Bentivoglio, Ar, Biunno, I, Bonelli, Rm, Burgunder, Jm, Dunnett, Sb, Ferreira, Jj, Handley, Oj, Heiberg, A, Llmann, Ti, Landwehrmeyer, Gb, Levey, J, Ramos Arroyo, Ma, Nielsen, Je, Prokoivisto, S, Päivärinta, M, Rojo Sebastián, A, Tabrizi, Sj, Vandenberghe, W, Verellen Dumoulin, C, Zaremba, J, Uhrova, T, Wahlström, J, Barth, K, Correia Guedes, L, Finisterra, Am, Garde, Mb, Bos, R, Betz, S, Callaghan, J, Fullam, R, Ecker, D, Nielsen, Mg, Hvalstedt, C, Held, C, Koppers, K, Laurà, M, Horta, Sm, Descals, Am, Mestre, T, Minster, S, Monza, D, Mütze, L, Oehmen, M, Townhill, J, Orth, M, Padieu, H, Paterski, L, Peppa, N, Pro Koivisto, S, Roedig, V, Rialland, A, Røren, N, a??inková, P, Seliverstov, Y, Cubillo, Pt, Walsem, Mr, Wright, A, da Silva, Wv, Witjes Ané, Mn, Yudina, E, Zielonka, D, Zielonka, E, Zinzi, P, Herranhof, B, Holl, A, Kapfhammer, Hp, Koppitz, M, Magnet, M, Otti, D, Painold, A, Reisinger, K, Scheibl, M, Hecht, K, Lilek, S, Müller, N, Schöggl, H, Ullah, J, Brugger, F, Hepperger, C, Hotter, A, Seppi, K, Wenning, G, Buratti, L, Hametner, Em, Holas, C, Hussl, A, Poewe, W, Braunwarth, Em, Sprenger, F, Müller, C, Sinadinosa, D, Walleczek, Am, Ladurner, G, Staffen, W, Flamez, A, Morez, V, de Raedt, S, Boogaerts, A, van Reijen, D, Klempí??, J, Majerová, V, Roth, J, Hartikainen, P, Hiivola, H, Martikainen, K, Tuuha, K, Ignatius, J, Kärppä, M, Åman, J, Mustonen, A, Kajula, O, Santala, M, Allain, P, Guérid, Ma, Gohier, B, Olivier, A, Prundean, A, Scherer Gagou, C, Verny, C, Bost, M, Babiloni, B, Debruxelles, S, Duché, C, Goizet, C, Lafoucrière, D, Jameau, L, Spampinato, U, De Bruycker, C, Cabaret, M, Carette, A, Defebvre, L, Decorte, E, Delval, A, Delliaux, M, Destee, A, Dujardin, K, Peter, M, Plomhouse, L, Sablonnière, B, Simonin, C, Lemaire, Mh, Manouvrier, S, Thibault Tanchou, S, Vuillaume, I, Krystkowiak, P, Duru, C, Roussel, M, Wannepain, S, Berrissoul, H, Bellonet, M, Courtin, F, Mantaux, B, Fasquel, V, Godefroy, O, Azulay, Jp, Fluchère, F, Delfini, M, Eusebio, A, Mundler, L, Longato, N, Rudolf, G, Steinmetz, G, Tranchant, C, Wagner, C, Zimmermann, M, Marcel, C, Calvas, F, Pariente, J, Démonet, Jf, Cheriet, S, Kosinski, Cm, Milkereit, E, Probst, D, Reetz, K, Sass, C, Schiefer, J, Schlangen, C, Werner, Cj, Gelderblom, H, Priller, J, Prüß, H, Spruth, Ej, Andrich, J, Ellrichmann, G, Hoffmann, R, Kaminski, B, Saft, C, Stamm, C, Lange, H, Bosredon, C, Maass, A, Schmidt, S, Storch, A, Wolz, M, Kohl, Z, Winkler, J, Capetian, P, Lambeck, J, Zucker, B, Boelmans, K, Ganos, C, Goerendt, I, Hidding, U, Lewerenz, J, Münchau, A, Schmalfeld, J, Stubbe, L, Zittel, S, Diercks, G, Dressler, D, Gorzolla, H, Schrader, C, Tacik, P, Heinicke, W, Longinus, B, Bürk, K, Möller, Jc, Rissling, I, Mühlau, M, Peinemann, A, Städtler, M, Weindl, A, Winkelmann, J, Ziegler, C, Bohlen, S, Hölzner, E, Reilmann, R, Dose, M, Leythaeuser, G, Marquard, R, Raab, T, Schrenk, C, Schuierer, M, Buck, A, Connemann, J, Eschenbach, C, Landwehrmeyer, B, Lezius, F, Nepper, S, Niess, A, Schwenk, D, Süßmuth, S, Trautmann, S, Weydt, P, Cormio, C, Sciruicchio, V, Serpino, C, Tommaso, M, Capellari, S, Cortelli, P, Gallassi, R, Poda, R, Rizzo, G, Scaglione, C, Bertini, E, Ghelli, E, Ginestroni, A, Massaro, F, Mechi, C, Paganini, M, Piacentini, S, Pradella, S, Romoli, Am, Sorbi, S, Abbruzzese, G, di Poggio, Mb, Di Maria, E, Ferrandes, G, Mandich, P, Marchese, R, Albanese, A, Di Bella, D, Di Donato, S, Gellera, C, Genitrini, S, Mariotti, C, Nanetti, L, Paridi, D, Soliveri, P, Tomasello, C, DE MICHELE, Giuseppe, Di Maio, L, Salvatore, Elena, Rossi, F, Massarelli, Marco, Roca, Alessandro, Ammendola, S, Russo, Cinzia, Squitieri, F, Elifani, F, Maglione, V, Di Pardo, A, Alberti, S, Griguoli, A, Amico, E, Martino, T, Petrollini, M, Catalli, C, Di Giacopo, R, Fasano, A, Frontali, M, Guidubaldi, A, Ialongo, T, Jacopini, G, Loria, G, Piano, C, Chiara, P, Quaranta, D, Romano, S, Soleti, F, Spadaro, M, Rinaldi, C, Massarelli, M, Roca, A, Russo, Cv, van Hout, M, van Vugt, Jp, Weert, A, Bolwijn, J, Dekker, M, Leenders, K, Kremer, Hp, Dumas, Em, van den Bogaard, Sj, 't Hart, Ep, Økland, E, Hauge, E, Tyvoll, H, Frich, J, Aaserud, O, Wehus, R, Bjørgo, K, Fannemel, M, Gørvell, P, Lorentzen, E, Koivisto, Sp, Retterstøl, L, Overland, T, Stokke, B, Sando, B, Dziadkiewicz, A, Nowak, M, Robowski, P, Sitek, E, Slawek, J, Soltan, W, Szinwelski, M, Blaszcyk, M, Boczarska Jedynak, M, Ciach Wysocka, E, Gorzkowska, A, Jasinska Myga, B, Opala, G, K??odowska Duda, G, Stompel, D, Banaszkiewicz, K, Bo??wi??ska, D, Szczudlik, A, Rudzi??ska, M, Wójcik, M, Dec, M, Krawczyk, M, Jaremek, Kb, Szczygie??, E, Stenwak, A, Ielewska, Aw, Bryl, A, Ciesielska, A, Klimberg, A, Marcinkowski, J, Sempo??owicz, J, Samara, H, Wi??niewski, B, Janik, P, Gogol, A, Kwiecinski, H, Jamrozik, Z, Kaminska, A, Antczak, J, Jachinska, K, Rakowicz, M, Richter, P, Rola, R, Ryglewicz, D, Sienkiewicz Jarosz, H, St??pniak, I, Witkowski, G, Zdzienicka, E, Su??ek, A, Krysa, W, Zieora Jakutowicz, K, Júlio, F, Januário, C, Coelho, M, Mendes, T, Valadas, A, Timóteo, Â, Costa, C, Cavaco, S, Damásio, J, Loureiro, R, Magalhães, M, Andrade, C, Gago, M, Garrett, C, Guerra, Mr, Lima, J, Massano, J, Meireles, J, Herrera, Cd, Garcia, Pm, Barrero, F, Morales, B, Cubo, E, Mariscal, N, Sánchez, J, Alonso Frech, F, Perez, Mr, Fenollar, M, García, Rg, Quiroga, Pp, Rivera, Sv, Villanueva, C, Alegre, J, Bascuñana, M, Caldentey, Jg, Ventura, Mf, Ribas, Gg, Yébenes, Jg, López Sendón Moreno, Jl, García Ruíz, Pj, Martínez Descals, A, Artiga, Mj, Sánchez, V, Guerrero, R, Bárcenas, Ah, Noguera Perea, Mf, Fortuna, L, Martirio, M, Torres, A, Reinante, G, Moreau, Lv, Barbera, Ma, Guia, Db, Hernanz, Lc, Catena, Jl, Sebastián, Ar, Ferrer, Pq, Carruesco, Gt, Bas, J, Busquets, N, Calopa, M, Elorza, Md, Díez AjaLópez, C, Terol, Sd, Robert, Mf, Ruíz, Bg, Casado, Ag, Martínez, Ih, Viladrich, Cm, Càrdenas, Rp, Roca, E, Llesoy, Jr, Idiago, Jm, Vergara, Mr, García, S, Riballo, Av, González, Sg, Guisasola, Lm, Salvador, C, San Martín, E, González, M, Gorospe, A, Legarda, I, Arques, Pn, Torres Rodríguez, Mj, Vives, B, Gaston, I, Martinez Jaurrieta, Md, Manuel, J, Moreno, G, Peña, Jc, Avarvarei, Ld, Bastida, Am, Recio, Mf, Vergé, Lr, Carrillo, F, Cáceres, Mt, Mir, P, Suarez, Mj, Bosca, M, Burguera, Ja, Garcia, Ac, Brugada, Fc, Martínez, Lm, Val, Jl, Loutfi, G, Olofsson, C, Stattin, El, Westman, L, Wikström, B, Lhagen, Se, Paucar, M, Svenningsson, P, Reza Soltani, Tw, Höglund, A, Sandström, B, Høsterey Ugander, U, Fredlund, G, Constantinescu, R, Neleborn Lingefjärd, L, Tedr off, J, Esmaeilzadeh, M, Winnberg, E, Pålhagen, S, Svennigsson, P, Riza Soltani, Tw, Sundblom, J, Johansson, A, Wiklund, L, Ekwall, C, Göller, Ml, Petersén, A, Reimer, J, Widner, H, Stebler, Y, Kaelin, A, Romero, I, Schüpbach, M, Weber, S, Miedzybrodzka, Z, Rae, D, Downie, L, Simpson, S, Summers, F, Ure, A, Jack, R, Matheson, K, Akhtar, S, Crooks, J, Curtis, A, Souza, J, Wright, J, Hayward, B, Sieradzan, K, Barker, Ra, O'Keefe, D, Di Pietro, A, Fisher, K, Hill, S, Mason, S, Swain, R, Valle, N, Bisson, J, Busse, M, Butcher, C, Clenaghan, C, Dunnett, S, Handley, O, Hunt, S, Hughes, A, Johnstone, C, Jones, L, Jones, U, Khalil, H, Owen, M, Price, K, Rose, Le, Rosser, A, Porteous, M, Edwards, M, Ho, C, Mcgill, M, Pearson, P, Brockie, P, Foster, J, Johns, N, Mckenzie, S, Rothery, J, Thomas, G, Yates, S, Miller, J, Ritchie, S, Burrows, L, Fletcher, A, Harding, A, Laver, F, Silva, M, Thomson, A, Rowett, L, Gallantrae, D, Longthorpe, M, Markova, I, Raman, A, Hamer, S, Wild, S, Yarduiman, P, Chu, C, Kraus, A, Yardumian, P, Musgrave, H, Toscano, J, Jamieson, S, Hobson, E, Clayton, C, Dipple, H, Middleton, J, Freire Patino, D, Andrews, T, Dougherty, A, Kavalier, F, Golding, C, Laing, H, Lashwood, A, Robertson, D, Ruddy, D, Whaite, A, Santhouse, A, Patton, M, Peterson, M, Rose, S, Bruno, S, Chu, E, Doherty, K, Haider, S, Hensman, D, Lahiri, N, Lewis, M, Novak, M, Patel, A, Robertson, N, Rosser, E, Tabrizi, S, Taylor, R, Warner, T, Wild, E, Howard, L, Sollom, A, Snowden, J, Thompson, J, Jones, M, Murphy, H, Trender Gerhard, I, Rogers, D, Bek, J, Oughton, E, Johnson, L, Hare, M, Arran, N, Verstraelen, N, Partington Jones, L, Huson, S, Stopford, C, Westmoreland, L, Davidson, J, Morgan, K, Savage, L, Singh, B, Komati, S, Nemeth, Ah, Armstrong, R, Valentine, R, Siuda, G, Harrison, D, Hughes, M, Parkinson, A, Soltysiak, B, Burn, J, Coleman, C, Bandmann, O, Bradbury, A, Gill, P, Fairtlough, H, Fillingham, K, Foustanos, I, Kazoka, M, O'Donovan, K, Taylor, C, Tidswell, K, and Quarrell, O.

Subjects
Male, medicine.medical_specialty, Heterozygote, Psychopharmacology, Population, Poison control, psychology/statistics /&/ numerical data, Suicide, Attempted, Suicide prevention, Suicidal Ideation, [SHS]Humanities and Social Sciences, 03 medical and health sciences, 0302 clinical medicine, medicine, Prevalence, Humans, epidemiology, Europe, Psychiatry, education, Suicidal ideation, ComputingMilieux_MISCELLANEOUS, Proportional Hazards Models, Attempted, Psychiatric Status Rating Scales, education.field_of_study, Psychological Tests, Suicide attempt, Psychopathology, Depression, Hazard ratio, Huntington's disease, Odds ratio, Middle Aged, 3. Good health, 030227 psychiatry, Europe, psychology, Male, Middle Aged, Prevalence, Proportional Hazards Models, Psychiatric Status Rating Scales, Psychological Tests, Suicidal Ideation, Suicide, Clinical Psychology, Psychiatry and Mental health, Suicide, Huntington Disease, epidemiology, Female, Heterozygote, Humans, Huntington Disease, Cohort studies, Female, medicine.symptom, Psychology, 030217 neurology & neurosurgery, Clinical psychology
Abstract

BACKGROUND: Previous studies indicate increased prevalences of suicidal ideation, suicide attempts, and completed suicide in Huntington's disease (HD) compared with the general population. This study investigates correlates and predictors of suicidal ideation in HD.METHODS: The study cohort consisted of 2106 HD mutation carriers, all participating in the REGISTRY study of the European Huntington's Disease Network. Of the 1937 participants without suicidal ideation at baseline, 945 had one or more follow-up measurements. Participants were assessed for suicidal ideation by the behavioural subscale of the Unified Huntington's Disease Rating Scale (UHDRS). Correlates of suicidal ideation were analyzed using logistic regression analysis and predictors were analyzed using Cox regression analysis.RESULTS: At baseline, 169 (8.0%) mutation carriers endorsed suicidal ideation. Disease duration (odds ratio [OR]=0.96; 95% confidence interval [CI]: 0.9-1.0), anxiety (OR=2.14; 95%CI: 1.4-3.3), aggression (OR=2.41; 95%CI: 1.5-3.8), a previous suicide attempt (OR=3.95; 95%CI: 2.4-6.6), and a depressed mood (OR=13.71; 95%CI: 6.7-28.0) were independently correlated to suicidal ideation at baseline. The 4-year cumulative incidence of suicidal ideation was 9.9%. Longitudinally, the presence of a depressed mood (hazard ratio [HR]=2.05; 95%CI: 1.1-4.0) and use of benzodiazepines (HR=2.44; 95%CI: 1.2-5.0) at baseline were independent predictors of incident suicidal ideation, whereas a previous suicide attempt was not predictive.LIMITATIONS: As suicidal ideation was assessed by only one item, and participants were a selection of all HD mutation carriers, the prevalence of suicidal ideation was likely underestimated.CONCLUSIONS: Suicidal ideation in HD frequently occurs. Assessment of suicidal ideation is a priority in mutation carriers with a depressed mood and in those using benzodiazepines.

Published
2013
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34. Safety and tolerability of carbamylated erythropoietin in Friedreich's ataxia

Author

Boesch S, Nachbauer W, Mariotti C, Klockgether T, Klopstock T, Sch?ls L, Jacobi H, B?chner B, Vom Hagen JM, Nanetti L, Manicom K., SACCA', FRANCESCO, FILLA, ALESSANDRO, Boesch, S, Nachbauer, W, Mariotti, C, Sacca', Francesco, Filla, Alessandro, Klockgether, T, Klopstock, T, Sch?ls, L, Jacobi, H, B?chner, B, Vom Hagen, Jm, Nanetti, L, and Manicom, K.

Abstract

BACKGROUND: Erythropoietin (EPO) derivatives have been found to increase frataxin levels in Friedreich's ataxia (FRDA) in vitro. This multicenter, double-blind, placebo-controlled, phase II clinical trial aimed to evaluate the safety and tolerability of Lu AA24493 (carbamylated EPO; CEPO). METHODS: Thirty-six ambulatory FRDA patients harboring >400 GAA repeats were 2:1 randomly assigned to either CEPO in a fixed dose (325 µg thrice-weekly) or placebo. Safety and tolerability were assessed up to 103 days after baseline. Secondary outcome measures of efficacy (exploration of biomarkers and ataxia ratings) were performed up to 43 days after baseline. RESULTS: All patients received six doses of study medication. Adverse events were equally distributed between CEPO and placebo. There was no evidence for immunogenicity of CEPO after multiple dosing. Biomarkers, such as frataxin, or measures for oxidative stress and ataxia ratings did not differ between CEPO and placebo. CONCLUSION: CEPO was safe and well tolerated in a 2-week treatment phase. Secondary outcome measures remained without apparent difference between CEPO and placebo.

Published
2014

35. The V471A polymorphism in autophagy-related gene ATG7 modifies age at onset specifically in Italian Huntington disease patients

Author

Metzger S, Walter C, Riess O, Roos RA, Nielsen JE, Craufurd D, Nguyen HP, REGISTRY Investigators of the European Huntington’s Disease Network:Bachoud Lévi AC, Bentivoglio AR, Biunno I, Bonelli RM, Burgunder JM, Dunnett SB, Ferreira JJ, Handley OJ, Heiberg A, Illmann T, Landwehrmeyer G, Levey J, Ramos Arroyo MA, Nielsen J, Koivisto SP, Päivärinta M, Sebastián AR, Tabrizi S, Vandenberghe W, Verellen Dumoulin C, Zaremba J, Uhrová T, Wahlström J, Barth K, Correia Guedes L, Finisterra AM, Garde MB, Bos R, Betz S, Callaghan J, Fullam R, Ecker D, Nielsen MG, Hvalstedt C, Held C, Koppers K, Laurà M, Horta SM, Descals AM, Díaz MF, Mestre T, Minster S, Monza D, Mütze L, Oehmen M, Townhill J, Orth M, Padieu H, Paterski L, Peppa N, Roedig V, Rialland A, Røren N, Šašinková P, Seliverstov Y, Cubillo PT, van Walsem MR, Wright A, Silva WV, Witjes Anné MN, Yudina E, Zielonka D, Zielonka E, Zinzi P, Herranhof B, Holl A, Kapfhammer HP, Koppitz M, Magnet M, Otti D, Painold A, Reisinger K, Scheibl M, Hecht K, Lilek S, Müller N, Schöggl H, Ullah J, Ribaï P, Boogaerts A, van Reijen D, Klempíř J, Majerová V, Roth J, Hjermind L, Jacobsen O, Vinthev Jensen T, Larsen IU, Stockholm J, Hiivola H, Martikainen K, Tuuha K, Ignatius J, Kärppä M, Åman J, Mustonen A, Kajula O, Santala M, Allain P, Guérid MA, Gohier B, Olivier A, Prundean A, Scherer Gagou C, Verny C, Bost M, Babiloni B, Debruxelles S, Duché C, Goizet C, Lafoucrière D, Jameau L, Spampinato U, De Bruycker C, Cabaret M, Carette AS, Defebvre L, Decorte E, Delval A, Delliaux M, Destee A, Dujardin K, Peter M, Plomhouse L, Sablonnière B, Simonin C, Lemaire MH, Manouvrier S, Thibault Tanchou S, Vuillaume I, Krystkowiak P, Duru C, Roussel M, Wannepain S, Berrissoul H, Bellonet M, Courtin F, Mantaux B, Fasquel V, Godefroy O, Azulay JP, Fluchère F, Delfini M, Eusebio A, Mundler L, Longato N, Rudolf G, Steinmetz G, Tranchant C, Wagner C, Zimmermann MA, Marcel C, Andrich J, Ellrichmann G, Hoffmann R, Kaminski B, Saft C, Stamm C, Boelmans K, Ganos C, Goerendt I, Hidding U, Lewerenz J, Münchau A, Schmalfeld J, Stubbe L, Zittel S, Bürk K, Möller JC, Rissling I, Cormio C, Sciruicchio V, Serpino C, de Tommaso M, CAPELLARI, SABINA, CORTELLI, PIETRO, Gallassi R, PODA, ROBERTO, RIZZO, GIOVANNI, Scaglione C, Abbruzzese G, di Poggio MB, Di Maria E, Ferrandes G, Mandich P, Marchese R, Albanese A, Di Bella D, Di Donato S, Gellera C, Genitrini S, Mariotti C, Nanetti L, Paridi D, Soliveri P, Tomasello C, Squitieri F, Elifani F, Maglione V, Di Pardo A, Alberti S, Griguoli A, Amico E, Martino T, Petrollini M, Catalli C, Di Giacopo R, Fasano A, Frontali M, Guidubaldi A, Ialongo T, Jacopini G, Loria G, Piano C, Chiara P, Quaranta D, Romano S, Soleti F, Spadaro M, van Hout MS, van Vugt JP, de Weert A, Bolwijn JJ, Dekker M, Leenders KL, Dumas EM, van den Bogaard SJ, 't Hart EP, van Duijn E, Kremer B, Verstappen CC, Blinkenberg EØ, Hauge E, Tyvoll H, Frich J, Aaserud O, Wehus R, Bjørgo K, Fannemel M, Gørvell P, Lorentzen E, Retterstøl L, Overland T, Stokke B, Bjørnevoll I, Sando SB, Dziadkiewicz A, Nowak M, Robowski P, Sitek E, Slawek J, Soltan W, Szinwelski M, Blaszcyk M, Boczarska Jedynak M, Ciach Wysocka E, Gorzkowska A, Jasinska Myga B, Opala G, Kłodowska Duda G, Stompel D, Banaszkiewicz K, Boćwińska D, Szczudlik A, Rudzinska M, Wójcik M, Dec M, Krawczyk M, Bojakowska Jaremek K, Szczygieł E, Stenwak A, Wasielewska A, Bryl A, Ciesielska A, Klimberg A, Marcinkowski J, Sempołowicz J, Samara H, Wiśniewski B, Janik P, Gogol A, Kwiecinski H, Jamrozik Z, Kaminska A, Antczak J, Jachinska K, Rakowicz M, Richter P, Rola R, Ryglewicz D, Sienkiewicz Jarosz H, Stępniak I, Witkowski G, Zdzienicka E, Sułek A, Krysa W, Stepniak I, Zieora Jakutowicz K, Júlio F, Januário C, Coelho M, Mendes T, Valadas A, Andrade C, Gago M, Garrett C, Guerra MR, Lima J, Massano J, Meireles J, Herrera CD, Garcia PM, Barrero F, Morales B, Cubo E, Mariscal N, Sánchez J, Alonso Frech F, Perez MR, Fenollar M, García RG, Pin Quiroga P, Vázquez Rivera S, Villanueva C, Alegre J, Bascuñana M, Caldentey JG, Ventura MF, Ribas GG, de Yébenes JG, Moreno JL, Ruíz PJ, Martínez Descals A, Artiga MJ, Sánchez V, Guerrero R, Bárcenas AH, Perea MF, Fortuna L, Torres MM, Reinante G, Moreau LV, Barbera MA, Guia DB, Hernanz LC, Catena JL, Ferrer PQ, Carruesco GT, Bas J, Busquets N, Calopa M, Elorza MD, López CD, Durán Sindreu Terol S, Robert MF, Ruíz BG, Casado AG, Martínez IH, Viladrich CM, Cárdenas RP, Roca E, Llesoy JR, Idiago JM, Vergara MR, García SS, Riballo AV, González SG, Guisasola LM, Salvador C, Martín ES, González M, Gorospe A, Legarda I, Arques PN, Rodríguez MJ, Vives B, Gaston I, Martinez Jaurrieta MD, Moreno JM, Peña JC, Avarvarei LD, Bastida AM, Recio MF, Vergé LR, Sánchez VS, Carrillo F, Cáceres MT, Mir P, Suarez MJ, Loutfi G, Olofsson C, Stattin EL, Westman L, Wikström B, Pålhagen SE, Paucar M, Svenningsson P, Reza Soltani TW, Höglund A, Sandström B, Høsterey Ugander U, Fredlund G, Constantinescu R, Neleborn Lingefjärd L, Stebler Y, Kaelin A, Romero I, Schüpbach M, Zaugg SW, Miedzybrodzka Z, Rae D, Downie L, Simpson S, Summers F, Ure A, Jack R, Matheson K, Akhtar S, Crooks J, Curtis A, de Souza J, Rickards H, Wright J, Barker RA, O' Keefe D, Di Pietro A, Fisher K, Goodman A, Hill S, Mason S, Swain R, Guzman NV, Bisson J, Busse M, Butcher C, Clenaghan C, Dunnett S, Handley O, Hunt S, Hughes A, Johnstone C, Jones L, Jones U, Khalil H, Owen M, Price K, Rose LE, Rosser A, Porteous M, Edwards M, Ho C, McGill M, Pearson P, Brockie P, Foster J, Johns N, McKenzie S, Rothery J, Thomas G, Yates S, Burrows L, Fletcher A, Harding A, Laver F, Silva M, Thomson A, Rowett L, Gallantrae D, Longthorpe M, Markova I, Raman A, Hamer S, Yarduiman P, Chu C, Kraus A, Wild S, Musgrave H, Toscano J, Jamieson S, Hobson E, Clayton C, Dipple H, Middleton J, Freire Patino D, Andrews T, Dougherty A, Kavalier F, Golding C, Laing H, Lashwood A, Robertson D, Ruddy D, Whaite A, Santhouse A, Patton M, Peterson M, Rose S, Bruno S, Chu E, Doherty K, Haider S, Hensman D, Lahiri N, Lewis M, Novak M, Patel A, Robertson N, Rosser E, Taylor R, Warner T, Wild E, Howard L, Sollom A, Snowden J, Thompson J, Jones M, Murphy H, Trender Gerhard I, Rogers D, Bek J, Oughton E, Johnson L, Hare M, Arran N, Verstraelen N, Partington Jones L, Huson S, Stopford C, Westmoreland L, Davidson J, Morgan K, Savage L, Singh B, Komati S, Nemeth AH, Armstrong R, Valentine R, Siuda G, Harrison D, Hughes M, Parkinson A, Soltysiak B, Bandmann O, Bradbury A, Gill P, Fairtlough H, Fillingham K, Foustanos I, Kazoka M, O' Donovan K, Taylor C, Tidswell K, Quarrell O, Metzger S, Walter C, Riess O, Roos RA, Nielsen JE, Craufurd D, Nguyen HP, REGISTRY Investigators of the European Huntington’s Disease Network:Bachoud-Lévi AC, Bentivoglio AR, Biunno I, Bonelli RM, Burgunder JM, Dunnett SB, Ferreira JJ, Handley OJ, Heiberg A, Illmann T, Landwehrmeyer G, Levey J, Ramos-Arroyo MA, Nielsen J, Koivisto SP, Päivärinta M, Sebastián AR, Tabrizi S, Vandenberghe W, Verellen-Dumoulin C, Zaremba J, Uhrová T, Wahlström J, Barth K, Correia-Guedes L, Finisterra AM, Garde MB, Bos R, Betz S, Callaghan J, Fullam R, Ecker D, Nielsen MG, Hvalstedt C, Held C, Koppers K, Laurà M, Horta SM, Descals AM, Díaz MF, Mestre T, Minster S, Monza D, Mütze L, Oehmen M, Townhill J, Orth M, Padieu H, Paterski L, Peppa N, Roedig V, Rialland A, Røren N, Šašinková P, Seliverstov Y, Cubillo PT, van Walsem MR, Wright A, Silva WV, Witjes-Anné MN, Yudina E, Zielonka D, Zielonka E, Zinzi P, Herranhof B, Holl A, Kapfhammer HP, Koppitz M, Magnet M, Otti D, Painold A, Reisinger K, Scheibl M, Hecht K, Lilek S, Müller N, Schöggl H, Ullah J, Ribaï P, Boogaerts A, van Reijen D, Klempíř J, Majerová V, Roth J, Hjermind L, Jacobsen O, Vinthev-Jensen T, Larsen IU, Stockholm J, Hiivola H, Martikainen K, Tuuha K, Ignatius J, Kärppä M, Åman J, Mustonen A, Kajula O, Santala M, Allain P, Guérid MA, Gohier B, Olivier A, Prundean A, Scherer-Gagou C, Verny C, Bost M, Babiloni B, Debruxelles S, Duché C, Goizet C, Lafoucrière D, Jameau L, Spampinato U, De Bruycker C, Cabaret M, Carette AS, Defebvre L, Decorte E, Delval A, Delliaux M, Destee A, Dujardin K, Peter M, Plomhouse L, Sablonnière B, Simonin C, Lemaire MH, Manouvrier S, Thibault-Tanchou S, Vuillaume I, Krystkowiak P, Duru C, Roussel M, Wannepain S, Berrissoul H, Bellonet M, Courtin F, Mantaux B, Fasquel V, Godefroy O, Azulay JP, Fluchère F, Delfini M, Eusebio A, Mundler L, Longato N, Rudolf G, Steinmetz G, Tranchant C, Wagner C, Zimmermann MA, Marcel C, Andrich J, Ellrichmann G, Hoffmann R, Kaminski B, Saft C, Stamm C, Boelmans K, Ganos C, Goerendt I, Hidding U, Lewerenz J, Münchau A, Schmalfeld J, Stubbe L, Zittel S, Bürk K, Möller JC, Rissling I, Cormio C, Sciruicchio V, Serpino C, de Tommaso M, Capellari S, Cortelli P, Gallassi R, Poda R, Rizzo G, Scaglione C, Abbruzzese G, di Poggio MB, Di Maria E, Ferrandes G, Mandich P, Marchese R, Albanese A, Di Bella D, Di Donato S, Gellera C, Genitrini S, Mariotti C, Nanetti L, Paridi D, Soliveri P, Tomasello C, Squitieri F, Elifani F, Maglione V, Di Pardo A, Alberti S, Griguoli A, Amico E, Martino T, Petrollini M, Catalli C, Di Giacopo R, Fasano A, Frontali M, Guidubaldi A, Ialongo T, Jacopini G, Loria G, Piano C, Chiara P, Quaranta D, Romano S, Soleti F, Spadaro M, van Hout MS, van Vugt JP, de Weert A, Bolwijn JJ, Dekker M, Leenders KL, Dumas EM, van den Bogaard SJ, 't Hart EP, van Duijn E, Kremer B, Verstappen CC, Blinkenberg EØ, Hauge E, Tyvoll H, Frich J, Aaserud O, Wehus R, Bjørgo K, Fannemel M, Gørvell P, Lorentzen E, Retterstøl L, Overland T, Stokke B, Bjørnevoll I, Sando SB, Dziadkiewicz A, Nowak M, Robowski P, Sitek E, Slawek J, Soltan W, Szinwelski M, Blaszcyk M, Boczarska-Jedynak M, Ciach-Wysocka E, Gorzkowska A, Jasinska-Myga B, Opala G, Kłodowska-Duda G, Stompel D, Banaszkiewicz K, Boćwińska D, Szczudlik A, Rudzinska M, Wójcik M, Dec M, Krawczyk M, Bojakowska-Jaremek K, Szczygieł E, Stenwak A, Wasielewska A, Bryl A, Ciesielska A, Klimberg A, Marcinkowski J, Sempołowicz J, Samara H, Wiśniewski B, Janik P, Gogol A, Kwiecinski H, Jamrozik Z, Kaminska A, Antczak J, Jachinska K, Rakowicz M, Richter P, Rola R, Ryglewicz D, Sienkiewicz-Jarosz H, Stępniak I, Witkowski G, Zdzienicka E, Sułek A, Krysa W, Stepniak I, Zieora-Jakutowicz K, Júlio F, Januário C, Coelho M, Mendes T, Valadas A, Andrade C, Gago M, Garrett C, Guerra MR, Lima J, Massano J, Meireles J, Herrera CD, Garcia PM, Barrero F, Morales B, Cubo E, Mariscal N, Sánchez J, Alonso-Frech F, Perez MR, Fenollar M, García RG, Pin Quiroga P, Vázquez Rivera S, Villanueva C, Alegre J, Bascuñana M, Caldentey JG, Ventura MF, Ribas GG, de Yébenes JG, Moreno JL, Ruíz PJ, Martínez-Descals A, Artiga MJ, Sánchez V, Guerrero R, Bárcenas AH, Perea MF, Fortuna L, Torres MM, Reinante G, Moreau LV, Barbera MA, Guia DB, Hernanz LC, Catena JL, Ferrer PQ, Carruesco GT, Bas J, Busquets N, Calopa M, Elorza MD, López CD, Durán-Sindreu Terol S, Robert MF, Ruíz BG, Casado AG, Martínez IH, Viladrich CM, Cárdenas RP, Roca E, Llesoy JR, Idiago JM, Vergara MR, García SS, Riballo AV, González SG, Guisasola LM, Salvador C, Martín ES, González M, Gorospe A, Legarda I, Arques PN, Rodríguez MJ, Vives B, Gaston I, Martinez-Jaurrieta MD, Moreno JM, Peña JC, Avarvarei LD, Bastida AM, Recio MF, Vergé LR, Sánchez VS, Carrillo F, Cáceres MT, Mir P, Suarez MJ, Loutfi G, Olofsson C, Stattin EL, Westman L, Wikström B, Pålhagen SE, Paucar M, Svenningsson P, Reza-Soltani TW, Höglund A, Sandström B, Høsterey-Ugander U, Fredlund G, Constantinescu R, Neleborn-Lingefjärd L, Stebler Y, Kaelin A, Romero I, Schüpbach M, Zaugg SW, Miedzybrodzka Z, Rae D, Downie L, Simpson S, Summers F, Ure A, Jack R, Matheson K, Akhtar S, Crooks J, Curtis A, de Souza J, Rickards H, Wright J, Barker RA, O' Keefe D, Di Pietro A, Fisher K, Goodman A, Hill S, Mason S, Swain R, Guzman NV, Bisson J, Busse M, Butcher C, Clenaghan C, Dunnett S, Handley O, Hunt S, Hughes A, Johnstone C, Jones L, Jones U, Khalil H, Owen M, Price K, Rose LE, Rosser A, Porteous M, Edwards M, Ho C, McGill M, Pearson P, Brockie P, Foster J, Johns N, McKenzie S, Rothery J, Thomas G, Yates S, Burrows L, Fletcher A, Harding A, Laver F, Silva M, Thomson A, Rowett L, Gallantrae D, Longthorpe M, Markova I, Raman A, Hamer S, Yarduiman P, Chu C, Kraus A, Wild S, Musgrave H, Toscano J, Jamieson S, Hobson E, Clayton C, Dipple H, Middleton J, Freire-Patino D, Andrews T, Dougherty A, Kavalier F, Golding C, Laing H, Lashwood A, Robertson D, Ruddy D, Whaite A, Santhouse A, Patton M, Peterson M, Rose S, Bruno S, Chu E, Doherty K, Haider S, Hensman D, Lahiri N, Lewis M, Novak M, Patel A, Robertson N, Rosser E, Taylor R, Warner T, Wild E, Howard L, Sollom A, Snowden J, Thompson J, Jones M, Murphy H, Trender-Gerhard I, Rogers D, Bek J, Oughton E, Johnson L, Hare M, Arran N, Verstraelen N, Partington-Jones L, Huson S, Stopford C, Westmoreland L, Davidson J, Morgan K, Savage L, Singh B, Komati S, Nemeth AH, Armstrong R, Valentine R, Siuda G, Harrison D, Hughes M, Parkinson A, Soltysiak B, Bandmann O, Bradbury A, Gill P, Fairtlough H, Fillingham K, Foustanos I, Kazoka M, O' Donovan K, Taylor C, Tidswell K, and Quarrell O

Subjects
Adult, Adolescent, Genotype, Huntington, Ubiquitin-Activating Enzymes, Autophagy-Related Protein 7, Polymorphism, Single Nucleotide, Cohort Studies, Young Adult, Gene Frequency, V471A polymorphism, Genetics, Autophagy, Humans, Age of Onset, Child, Biology, Genetic Association Studies, Aged, Clinical Genetics, Evolutionary Biology, Computational Biology, Human Genetics, Middle Aged, Huntington Disease, Neurology, Italy, Autosomal Dominant, Child, Preschool, Genetic Polymorphism, Medicine, Population Genetics, gene ATG7, Research Article
Abstract

The cause of Huntington disease (HD) is a polyglutamine repeat expansion of more than 36 units in the huntingtin protein, which is inversely correlated with the age at onset of the disease. However, additional genetic factors are believed to modify the course and the age at onset of HD. Recently, we identified the V471A polymorphism in the autophagy-related gene ATG7, a key component of the autophagy pathway that plays an important role in HD pathogenesis, to be associated with the age at onset in a large group of European Huntington disease patients. To confirm this association in a second independent patient cohort, we analysed the ATG7 V471A polymorphism in additional 1,464 European HD patients of the "REGISTRY" cohort from the European Huntington Disease Network (EHDN). In the entire REGISTRY cohort we could not confirm a modifying effect of the ATG7 V471A polymorphism. However, analysing a modifying effect of ATG7 in these REGISTRY patients and in patients of our previous HD cohort according to their ethnic origin, we identified a significant effect of the ATG7 V471A polymorphism on the HD age at onset only in the Italian population (327 patients). In these Italian patients, the polymorphism is associated with a 6-years earlier disease onset and thus seems to have an aggravating effect. We could specify the role of ATG7 as a genetic modifier for HD particularly in the Italian population. This result affirms the modifying influence of the autophagic pathway on the course of HD, but also suggests population-specific modifying mechanisms in HD pathogenesis.

Published
2013

36. Responsiveness of clinical outcome measures in Charcot-Marie-Tooth disease

Author

Piscosquito, G., Reilly, M. M., Schenone, A., Fabrizi, G. M., Cavallaro, T., Santoro, L., Manganelli, F., Vita, G., Quattrone, A., Padua, L., Gemignani, F., Visioli, F., Laurà, M., Calabrese, D., Hughes, R. A. C., Radice, D., Solari, A., Pareyson, D, Marchesi, C, Salsano, E, Nanetti, L, Marelli, C, Scaioli, V, Ciano, C, Rimoldi, M, Lauria, G, Ferrari, G, Rizzetto, E, Camozzi, F, Narciso, E, Grandis, M, Monti-Bragadin, M, Nobbio, L, Casano, A, Bertolasi, L, Cabrini, I, Corrà, K, Rizzuto, N, Pisciotta, C, Nolano, M, Mazzeo, A, R Di Leo, Majorana, G, Russo, M, Valentino, P, Nisticò, R, Pirritano, D, Lucisano, A, Canino, M, Pazzaglia, C, Granata, G, Foschini, M, Brindani, F, Vitetta, F, Allegri, I, Bogani, P, Blake, J, Koltzenburg, M, Hutton, E, Lunn, M, Piscosquito, G, Reilly, M. M, Schenone, A, Fabrizi, G. M, Cavallaro, T, Santoro, Lucio, Manganelli, Fiore, Vita, G, Quattrone, A, Padua, L, Gemignani, F, Visioli, F, Laurà, M, Calabrese, D, Hughes, R. A. C, Radice, D, Solari, A, Pareyson, D., and Nolano, Maria

Subjects
Adult, Male, Change over time, medicine.medical_specialty, responsiveness, Charcot−Marie−Tooth disease, Disease, Placebo, hereditary motor sensory neuropathy, Tooth disease, Charcot-Marie-Tooth Disease, Outcome Assessment, Health Care, Humans, Medicine, Charcot-Marie-Tooth disease, Clinical trials, Evaluative outcome measures, Hereditary motor sensory neuropathy, Responsiveness, Clinical Trials as Topic, Exercise Test, Female, Middle Aged, Outcome Assessment (Health Care), Neurology, Neurology (clinical), clinical trials, evaluative outcome measures, evaluative outcome measure, business.industry, Outcome measures, clinical trial, Charcot−Marie−Tooth disease,clinical trials,evaluative outcome measures,hereditary motor sensory neuropathy,responsiveness, Ascorbic acid, Clinical trial, Settore MED/26 - NEUROLOGIA, medicine.anatomical_structure, Physical therapy, Upper limb, business, Settore MED/34 - MEDICINA FISICA E RIABILITATIVA
Abstract

Background and purpose Charcot−Marie−Tooth disease (CMT) is a very slowly progressive neuropathy which makes it difficult to detect disease progression over time and to assess intervention efficacy. Experience from completed clinical trials with ascorbic acid and natural history studies confirm difficulties in detecting such changes. Consequently, sensitive-to-change outcome measures (OMs) are urgently needed. Methods The relative responsiveness of clinical scales of the Italian−UK ascorbic acid trial (placebo arm) were assessed by using the standardized response mean (SRM), which is the ratio of the paired scores mean change over time to the standard deviation of the score change (0 is worst responsiveness). Results Little worsening of OM scores was found over 2 years. In detail, the primary OM of the trial, the CMT Neuropathy Score version 1 (CMTNSv1), showed low responsiveness (SRM 0.13). Some CMTNS items showed slightly greater responsiveness (CMT Examination Score 0.17; CMTNS Signs 0.19). Myometric assessments of handgrip and foot dorsiflexion strength were the most responsive (SRM −0.31 and −0.38, respectively). Amongst the other measures, the nine-hole peg test, which assesses upper limb functioning, showed the best sensitivity to change (SRM 0.28). Conclusions Overall these OMs showed low or negligible responsiveness, confirming the need to improve current OMs and to develop novel ones for prognostic and interventional studies. However, handgrip and foot dorsiflexion myometry are worth retaining for future trials as they were the most responsive and are likely to be clinically relevant for patients.

Published
2015

37. Whole body cholesterol metabolism is impaired in Huntington's disease

Author

Leoni, V, Mariotti, C, Nanetti, L, Salvatore, E, Squitieri, F, Bentivoglio, A, Bandettini Del Poggio, M, Piacentini, S, Monza, D, Valenza, M, Cattaneo, E, Di Donato, S, Leoni V, Mariotti C, Nanetti L, Salvatore E, Squitieri F, Bentivoglio AR, Bandettini Del Poggio M, Piacentini S, Monza D, Valenza M, Cattaneo E, Di Donato S, Leoni, V, Mariotti, C, Nanetti, L, Salvatore, E, Squitieri, F, Bentivoglio, A, Bandettini Del Poggio, M, Piacentini, S, Monza, D, Valenza, M, Cattaneo, E, Di Donato, S, Leoni V, Mariotti C, Nanetti L, Salvatore E, Squitieri F, Bentivoglio AR, Bandettini Del Poggio M, Piacentini S, Monza D, Valenza M, Cattaneo E, and Di Donato S

Abstract

We previously reported impaired cholesterol biosynthesis in rodent Huntington Disease (HD) models and HD patients' fibroblasts and post mortem brains. We also found that plasma levels of 24S-hydroxycholesterol (24OHC), the brain specific elimination product of cholesterol considered a marker of brain cholesterol turnover, were significantly reduced in HD patients at any disease stage. In the present study we analysed by mass spectrometry the fasting plasma levels of cholesterol, its biosynthetic precursors lanosterol and lathosterol, of the whole-body elimination products 27-hydroxycholesterol and of brain 24OHC in a cohort of premanifest and HD patients at different disease stages. We found that the cholesterol precursors lanosterol and lathosterol (both index of whole body cholesterol synthesis), the levels of the bile acid precursor 27-hydroxycholesterol, and of the brain specific 24OHC, were all significantly reduced in manifest HD patients, suggesting that whole-body and brain cholesterol homeostasis are both impaired in HD

Published
2011

38. Observing Huntington's disease: the European Huntington's Disease Network's REGISTRY

Author

Orth, M, Handley, Oj, Schwenke, C, Dunnett, S, Wild, Ej, Tabrizi, Sj, Landwehrmeyer, Gb, Bachoud Lévi AC, Bentivoglio, Ar, Biunno, I, Bonelli, R, Burgunder, Jm, Dunnett, Sb, Ferreira, Jj, Giuliano, J, Heiberg, A, Illmann, T, van Kammen, D, Landwehrmeye, Gb, Levey, J, Nielsen, Je, Päivärinta, M, Roos, Ra, Sebastián, Ar, Vandenberghe, W, Verellen Dumoulin, C, Zaremba, J, Uhrova, T, Wahlström, J, Wallner, M, Barth, K, Guedes, Lc, Finisterra, Am, Garde, Mb, Bos, R, Burg, S, Ecker, D, Held, C, Koppers, K, Laurà, M, Descals, Am, Mclean, T, Mestre, T, Minster, S, Monza, D, Townhill, J, Padieu, H, Paterski, L, Peppa, N, Koivisto, Sp, Rialland, A, Røren, N, Sasinková, P, Cubillo, Pt, Tritsch, C, van Walsem MR, Witjes Ané MN, Yudina, E, Zielonka, D, Zielonka, E, Zinzi, P, Bonelli, Rm, Herranhof, B, Holl, A, Kapfhammer, Hp, Koppitz, M, Magnet, M, Otti, D, Painold, A, Reisinger, K, Scheibl, M, Hecht, K, Lilek, S, Müller, N, Schöggl, H, Ullah, J, Brugger, F, Hepperger, C, Hotter, A, Mahlknecht, P, Nocker, M, Seppi, K, Wenning, G, Buratti, L, Hametner, Em, Holas, C, Hussl, A, Mair, K, Poewe, W, Wolf, E, Zangerl, A, Braunwarth, Em, Sinadinosa, D, Walleczek, Am, Ladurner, G, Staffen, W, Ribaï, P, Flamez, A, Morez, V, de Raedt, S, Boogaerts, A, van Reijen, D, Klempíř, J, Kucharík, M, Roth, J, Šenkárová, Z, Hasholt, L, Hjermind, Le, Jakobsen, O, Nørremølle, A, Sørensen, Sa, Stokholm, J, Nielsen, J, Hiivola, H, Martikainen, K, Tuuha, K, Peippo, M, Sipponen, M, Ignatius, J, Kärppä, M, Åman, J, Santala, M, Allain, P, Guérid, Ma, Gohier, B, Olivier, A, Prundean, A, Scherer Gagou, C, Verny, C, Babiloni, B, Debruxelles, S, Goizet, C, Lafoucrière, D, De Bruycker, C, Carette, As, Decorte, E, Delval, A, Delliaux, M, Dujardin, K, Peter, M, Plomhouse, L, Simonin, C, Thibault Tanchou, S, Bellonet, M, Duru, C, Krystkowiak, P, Roussel, M, Wannepain, S, Azulay, Jp, Chabot, C, Delphini, M, Eusebio, A, Grosjean, H, Mundler, L, Nowak, M, Rudolf, G, Steinmetz, G, Tranchant, C, Wagner, C, Zimmermann, Ma, Calvas, F, Cheriet, S, Démonet, Jf, Galitzky, M, Kosinski, Cm, Milkereit, E, Probst, D, Sass, C, Schiefer, J, Schlangen, C, Werner, Cj, Gelderblom, H, Priller, J, Prüss, H, Spruth, Ej, Andrich, J, Hoffmann, R, Kraus, Ph, Muth, S, Prehn, C, Saft, C, Salmen, S, Stamm, C, Steiner, T, Strassburger, K, Lange, H, Friedrich, A, Hunger, U, Löhle, M, Schmidt, S, Storch, A, Wolz, A, Wolz, M, Lambeck, J, Zucker, B, Boelmans, K, Ganos, C, Hidding, U, Lewerenz, J, Münchau, A, Schmalfeld, J, Stubbe, L, Zittel, S, Diercks, G, Gorzolla, H, Schrader, C, Heinicke, W, Ribbat, M, Longinus, B, Bürk, K, Möller, Jc, Rissling, I, Peinemann, A, Städtler, M, Weindl, A, Bechtel, N, Beckmann, H, Bohlen, S, Hölzner, E, Reilmann, R, Rohm, S, Rumpf, S, Schepers, S, Beister, A, Dose, M, Hammer, K, Kieni, J, Leythaeuser, G, Marquard, R, Raab, T, Richter, S, Selimbegovic Turkovic, A, Schrenk, C, Schuierer, M, Wiedemann, A, Buck, A, Connemann, J, Eschenbach, C, Landwehrmeyer, B, Lezius, F, Nepper, S, Niess, A, Süssmuth, S, Trautmann, S, Weydt, P, Cormio, C, Difruscolo, O, Sciruicchio, V, Serpino, C, de Tommaso, M, Capellari, S, Cortelli, P, Gallassi, R, Poda, R, Rizzo, G, Scaglione, C, Bertini, E, Ghelli, E, Ginestroni, A, Massaro, F, Mechi, C, Paganini, M, Piacentini, S, Pradella, S, Romoli, Am, Sorbi, S, Abbruzzese, G, di Poggio MB, Di Maria, E, Ferrandes, G, Mandich, P, Marchese, R, Albanese, A, Di Bella, D, Di Donato, S, Gellera, C, Genitrini, S, Mariotti, C, Nanetti, L, Paridi, D, Soliveri, P, Tomasello, C, De Michele, G, Di Maio, L, Rinaldi, C, Russo, Cv, Salvatore, E, Tucci, T, Cannella, M, Codella, V, De Gregorio, F, De Nicola, N, Martino, T, Simonelli, M, Squitieri, F, Catalli, C, Di Giacopo, R, Fasano, A, Frontali, M, Guidubaldi, A, Ialongo, T, Jacopini, G, Loria, G, Modoni, A, Piano, C, Chiara, P, Quaranta, D, Romano, Silvia, Soleti, F, Spadaro, M, van Hout MS, van Vugt JP, de Weert AM, Bolwijn, Jj, Dekker, M, Leenders, Kl, van Oostrom JC, Dumas, Em, Jurgens, Ck, van den Bogaard SJ, 't Hart EP, Kremer, B, Verstappen, Cc, Frich, J, Wehus, R, Aaserud, O, Borgerød, N, Bjørgo, K, Fannemel, M, Gørvell, P, Pro Koivisto, S, Retterstøl, L, Overland, T, Stokke, B, Bjørnevoll, I, Sando, Sb, Blinkenberg, Eø, Hauge, E, Tyvoll, H, Sitek, E, Slawek, J, Soltan, W, Boczarska Jedynak, M, Jasinska Myga, B, Opala, G, Kłodowska Duda, G, Banaszkiewicz, K, Szczudlik, A, Rudzińska, M, Wójcik, M, Dec, M, Krawczyk, M, Bryl, A, Ciesielska, A, Klimberg, A, Marcinkowski, J, Sempołowicz, J, Samara, H, Janik, P, Kalbarczyk, A, Kwiecinski, H, Jamrozik, Z, Antczak, J, Jachinska, K, Rakowicz, M, Richter, P, Ryglewicz, D, Witkowski, G, Zdzienicka, E, Sułek, A, Krysa, W, Júlio, F, Januário, C, Guedes, L, Coelho, M, Mendes, T, Valadas, A, Timóteo, Â, Costa, C, Vale, J, Cavaco, S, Damásio, J, Magalhães, M, Gago, M, Garrett, C, Guerra, Mr, Solis, P, Herrera, Cd, Garcia, Pm, Barrero, F, Morales, B, Cubo, E, Mariscal, N, Alonso Frech, F, Perez, Mr, Fenollar, M, García, Rg, Quiroga, Pp, Rivera, Sv, Villanueva, C, Bascuñana, M, Ventura, Mf, Ribas, Gg, de Yébenes JG, Moreno, Jl, Ruíz, Pj, Martínez Descals, A, Artiga, Mj, Sánchez, V, Perea, Mf, Lorenza, F, Torres, Mm, Reinante, G, Moreau, Lv, Barbera, Ma, Guia, Db, Hernanz, Lc, Catena, Jl, Ferrer, Pq, Carruesco, Gt, Bas, J, Busquets, N, Calopa, M, Buongiorno, Mt, Muñoz, E, Elorza, Md, López, Cd, Terol, Sd, Robert, Mf, Ruíz, Bg, Casado, Ag, Martínez, Ih, Viladrich, Cm, Càrdenas R, Pons i., Roca, E, Llesoy, Jr, Idiago, Jm, Vergara, Mr, García, Ss, Villa Riballo, A, González, Sg, Guisasola, Lm, Salvador, C, San Martín ES, Gorospe, A, Legarda, I, Arques, Pn, Rodríguez, Mj, Vives, B, Gaston, I, Ramos Arroyo MA, Moreno, Jm, Peña, Jc, Avarvarei, Ld, Bastida, Am, Recio, Mf, Vergé, Lr, Sánchez, Vs, Carrillo, F, Cáceres, Mt, Mir, P, Suarez, Mj, Bosca, M, Burguera, Ja, Garcia, Ac, Martínez, Lm, del Val JL, Loutfi, G, Olofsson, C, Stattin, El, Westman, L, Wikström, B, Höglund, A, Pålhagen, Se, Paucar, M, Sandström, B, Soltani, R, Svenningsson, P, Reza Soltani TW, Constantinescu, R, Fredlund, G, Høsterey Ugander, U, Neleborn Lingefjärd, L, Esmaeilzadeh, M, Tedroff, J, Winnberg, E, Björn, Y, Ekwall, C, Gøller, Ml, Johansson, A, Wiklund, L, Petersen, Å, Reimer, J, Widner, H, Burgunder, Y, Stebler, Y, Kaelin, A, Romero, I, Schüpbach, M, Zaugg, Sw, Jack, R, Matheson, K, Miedzybrodzka, Z, Rae, D, Simpson, S, Summers, F, Ure, A, Crooks, J, Curtis, A, de Souza Keylock, J, Rickards, H, Wright, J, Hayward, B, Sieradzan, K, Wright, A, Barker, Ra, Di Pietro, A, Fisher, K, Goodman, A, Hill, S, Kershaw, A, Mason, S, Paterson, N, Raymond, L, Bisson, J, Busse, M, Clenaghan, C, Ellison Rose, L, Handley, O, Hunt, S, Price, K, Rosser, A, Edwards, M, Hughes, T, Mcgill, M, Pearson, P, Porteous, M, Smith, P, Zeman, A, Causley, A, Harrower, T, Howcroft, D, Lambord, N, Rankin, J, Brockie, P, Foster, J, Johns, N, Mckenzie, S, Rothery, J, Thomas, G, Yates, S, Miller, J, Ritchie, S, Burrows, L, Fletcher, A, Harding, A, Laver, F, Silva, M, Thomson, A, Burns, P, Chu, C, Evans, C, Hamer, S, Markova, I, Raman, A, Barnes, K, Hobson, E, Jamieson, S, Thomson, J, Toscano, J, Wild, S, Yardumian, P, Bourne, C, Clayton, C, Dipple, H, Clapton, J, Grant, D, Hallam, C, Middleton, J, Murch, A, Patino, D, Bate, L, Pate, L, Andrews, T, Dougherty, A, Kavalier, F, Golding, C, Lashwood, A, Robertson, D, Ruddy, D, Whaite, A, Patton, M, Peterson, M, Rose, S, Bruno, S, Chu, E, Doherty, K, Henley, S, Lahiri, N, Novak, M, Patel, A, Read, J, Rosser, E, Say, M, Tabrizi, S, Taylor, R, Warner, T, Wild, E, Arran, N, Callaghan, J, Craufurd, D, Fullam, R, Howard, L, Huson, S, Oughton, E, Partington Jones, L, Snowden, J, Sollom, A, Stopford, C, Thompson, J, Trender Gerhad, I, Verstraelen, N, Westmoreland, L, Nemeth, Ah, Siuda, G, Harrison, D, Hughes, M, Parkinson, A, Soltysiak, B, Burn, J, Coleman, C, Majeed, T, Verstraelen Ritchie, N, Bandmann, O, Bradbury, A, Gill, P, Fairtlough, H, Fillingham, K, Foustanos, I, O'Donovan, K, Tidswell, K, Quarrell, O., Orth, M, European Huntington's Disease, Network, Handley, Oj, Schwenke, C, Dunnett, S, Wild, Ej, Tabrizi, Sj, Bachoud Lévi AC, Landwehrmeyer G. B., Bentivoglio, Ar, Biunno, I, Bonelli, R, Burgunder, Jm, Dunnett, Sb, Ferreira, Jj, Giuliano, J, Heiberg, A, Illmann, T, van Kammen, D, Landwehrmeye, Gb, Levey, J, Nielsen, Je, Päivärinta, M, Roos, Ra, Sebastián, Ar, Vandenberghe, W, Verellen Dumoulin, C, Zaremba, J, Uhrova, T, Wahlström, J, Wallner, M, Barth, K, Guedes, Lc, Finisterra, Am, Garde, Mb, Bos, R, Burg, S, Ecker, D, Held, C, Koppers, K, Laurà, M, Descals, Am, Mclean, T, Mestre, T, Minster, S, Monza, D, Townhill, J, Padieu, H, Paterski, L, Peppa, N, Koivisto, Sp, Rialland, A, Røren, N, Sasinková, P, Cubillo, Pt, Tritsch, C, van Walsem, Mr, Witjes Ané, Mn, Yudina, E, Zielonka, D, Zielonka, E, Zinzi, P, Bonelli, Rm, Herranhof, B, Holl, A, Kapfhammer, Hp, Koppitz, M, Magnet, M, Otti, D, Painold, A, Reisinger, K, Scheibl, M, Hecht, K, Lilek, S, Müller, N, Schöggl, H, Ullah, J, Brugger, F, Hepperger, C, Hotter, A, Mahlknecht, P, Nocker, M, Seppi, K, Wenning, G, Buratti, L, Hametner, Em, Holas, C, Hussl, A, Mair, K, Poewe, W, Wolf, E, Zangerl, A, Braunwarth, Em, Sinadinosa, D, Walleczek, Am, Ladurner, G, Staffen, W, Ribaï, P, Flamez, A, Morez, V, de Raedt, S, Boogaerts, A, van Reijen, D, Klempíř, J, Kucharík, M, Roth, J, Šenkárová, Z, Hasholt, L, Hjermind, Le, Jakobsen, O, Nørremølle, A, Sørensen, Sa, Stokholm, J, Nielsen, J, Hiivola, H, Martikainen, K, Tuuha, K, Peippo, M, Sipponen, M, Ignatius, J, Kärppä, M, Åman, J, Santala, M, Allain, P, Guérid, Ma, Gohier, B, Olivier, A, Prundean, A, Scherer Gagou, C, Verny, C, Babiloni, B, Debruxelles, S, Goizet, C, Lafoucrière, D, De Bruycker, C, Carette, A, Decorte, E, Delval, A, Delliaux, M, Dujardin, K, Peter, M, Plomhouse, L, Simonin, C, Thibault Tanchou, S, Bellonet, M, Duru, C, Krystkowiak, P, Roussel, M, Wannepain, S, Azulay, Jp, Chabot, C, Delphini, M, Eusebio, A, Grosjean, H, Mundler, L, Nowak, M, Rudolf, G, Steinmetz, G, Tranchant, C, Wagner, C, Zimmermann, Ma, Calvas, F, Cheriet, S, Démonet, Jf, Galitzky, M, Kosinski, Cm, Milkereit, E, Probst, D, Sass, C, Schiefer, J, Schlangen, C, Werner, Cj, Gelderblom, H, Priller, J, Prüss, H, Spruth, Ej, Andrich, J, Hoffmann, R, Kraus, Ph, Muth, S, Prehn, C, Saft, C, Salmen, S, Stamm, C, Steiner, T, Strassburger, K, Lange, H, Friedrich, A, Hunger, U, Löhle, M, Schmidt, S, Storch, A, Wolz, A, Wolz, M, Lambeck, J, Zucker, B, Boelmans, K, Ganos, C, Hidding, U, Lewerenz, J, Münchau, A, Schmalfeld, J, Stubbe, L, Zittel, S, Diercks, G, Gorzolla, H, Schrader, C, Heinicke, W, Ribbat, M, Longinus, B, Bürk, K, Möller, Jc, Rissling, I, Peinemann, A, Städtler, M, Weindl, A, Bechtel, N, Beckmann, H, Bohlen, S, Hölzner, E, Reilmann, R, Rohm, S, Rumpf, S, Schepers, S, Beister, A, Dose, M, Hammer, K, Kieni, J, Leythaeuser, G, Marquard, R, Raab, T, Richter, S, Selimbegovic Turkovic, A, Schrenk, C, Schuierer, M, Wiedemann, A, Buck, A, Connemann, J, Eschenbach, C, Landwehrmeyer, B, Lezius, F, Nepper, S, Niess, A, Süssmuth, S, Trautmann, S, Weydt, P, Cormio, C, Difruscolo, O, Sciruicchio, V, Serpino, C, de Tommaso, M, Capellari, S, Cortelli, P, Gallassi, R, Poda, R, Rizzo, G, Scaglione, C, Bertini, E, Ghelli, E, Ginestroni, A, Massaro, F, Mechi, C, Paganini, M, Piacentini, S, Pradella, S, Romoli, Am, Sorbi, S, Abbruzzese, G, di Poggio, Mb, Di Maria, E, Ferrandes, G, Mandich, P, Marchese, R, Albanese, A, Di Bella, D, Di Donato, S, Gellera, C, Genitrini, S, Mariotti, C, Nanetti, L, Paridi, D, Soliveri, P, Tomasello, C, DE MICHELE, Giuseppe, Di Maio, L, Rinaldi, Carlo, Russo, Cv, Salvatore, Elena, Tucci, T, Cannella, M, Codella, V, De Gregorio, F, De Nicola, N, Martino, T, Simonelli, M, Squitieri, F, Catalli, C, Di Giacopo, R, Fasano, A, Frontali, M, Guidubaldi, A, Ialongo, T, Jacopini, G, Loria, G, Modoni, A, Piano, C, Chiara, P, Quaranta, D, Romano, S, Soleti, F, Spadaro, M, van Hout, M, van Vugt, Jp, de Weert, Am, Bolwijn, Jj, Dekker, M, Leenders, Kl, van Oostrom, Jc, Dumas, Em, Jurgens, Ck, van den Bogaard, Sj, 't Hart, Ep, Kremer, B, Verstappen, Cc, Frich, J, Wehus, R, Aaserud, O, Borgerød, N, Bjørgo, K, Fannemel, M, Gørvell, P, Pro Koivisto, S, Retterstøl, L, Overland, T, Stokke, B, Bjørnevoll, I, Sando, Sb, Blinkenberg, Eø, Hauge, E, Tyvoll, H, Sitek, E, Slawek, J, Soltan, W, Boczarska Jedynak, M, Jasinska Myga, B, Opala, G, Kłodowska Duda, G, Banaszkiewicz, K, Szczudlik, A, Rudzińska, M, Wójcik, M, Dec, M, Krawczyk, M, Bryl, A, Ciesielska, A, Klimberg, A, Marcinkowski, J, Sempołowicz, J, Samara, H, Janik, P, Kalbarczyk, A, Kwiecinski, H, Jamrozik, Z, Antczak, J, Jachinska, K, Rakowicz, M, Richter, P, Ryglewicz, D, Witkowski, G, Zdzienicka, E, Sułek, A, Krysa, W, Júlio, F, Januário, C, Guedes, L, Coelho, M, Mendes, T, Valadas, A, Timóteo, Â, Costa, C, Vale, J, Cavaco, S, Damásio, J, Magalhães, M, Gago, M, Garrett, C, Guerra, Mr, Solis, P, Herrera, Cd, Garcia, Pm, Barrero, F, Morales, B, Cubo, E, Mariscal, N, Alonso Frech, F, Perez, Mr, Fenollar, M, García, Rg, Quiroga, Pp, Rivera, Sv, Villanueva, C, Bascuñana, M, Ventura, Mf, Ribas, Gg, de Yébenes, Jg, Moreno, Jl, Ruíz, Pj, Martínez Descals, A, Artiga, Mj, Sánchez, V, Perea, Mf, Lorenza, F, Torres, Mm, Reinante, G, Moreau, Lv, Barbera, Ma, Guia, Db, Hernanz, Lc, Catena, Jl, Ferrer, Pq, Carruesco, Gt, Bas, J, Busquets, N, Calopa, M, Buongiorno, Mt, Muñoz, E, Elorza, Md, López, Cd, Terol, Sd, Robert, Mf, Ruíz, Bg, Casado, Ag, Martínez, Ih, Viladrich, Cm, Pons i., Càrdenas R, Roca, E, Llesoy, Jr, Idiago, Jm, Vergara, Mr, García, S, Villa Riballo, A, González, Sg, Guisasola, Lm, Salvador, C, San Martín, E, Gorospe, A, Legarda, I, Arques, Pn, Rodríguez, Mj, Vives, B, Gaston, I, Ramos Arroyo, Ma, Moreno, Jm, Peña, Jc, Avarvarei, Ld, Bastida, Am, Recio, Mf, Vergé, Lr, Carrillo, F, Cáceres, Mt, Mir, P, Suarez, Mj, Bosca, M, Burguera, Ja, Garcia, Ac, Martínez, Lm, del Val, Jl, Loutfi, G, Olofsson, C, Stattin, El, Westman, L, Wikström, B, Höglund, A, Pålhagen, Se, Paucar, M, Sandström, B, Soltani, R, Svenningsson, P, Reza Soltani, Tw, Constantinescu, R, Fredlund, G, Høsterey Ugander, U, Neleborn Lingefjärd, L, Esmaeilzadeh, M, Tedroff, J, Winnberg, E, Björn, Y, Ekwall, C, Gøller, Ml, Johansson, A, Wiklund, L, Petersen, Å, Reimer, J, Widner, H, Burgunder, Y, Stebler, Y, Kaelin, A, Romero, I, Schüpbach, M, Zaugg, Sw, Jack, R, Matheson, K, Miedzybrodzka, Z, Rae, D, Simpson, S, Summers, F, Ure, A, Crooks, J, Curtis, A, de Souza Keylock, J, Rickards, H, Wright, J, Hayward, B, Sieradzan, K, Wright, A, Barker, Ra, Di Pietro, A, Fisher, K, Goodman, A, Hill, S, Kershaw, A, Mason, S, Paterson, N, Raymond, L, Bisson, J, Busse, M, Clenaghan, C, Ellison Rose, L, Handley, O, Hunt, S, Price, K, Rosser, A, Edwards, M, Hughes, T, Mcgill, M, Pearson, P, Porteous, M, Smith, P, Zeman, A, Causley, A, Harrower, T, Howcroft, D, Lambord, N, Rankin, J, Brockie, P, Foster, J, Johns, N, Mckenzie, S, Rothery, J, Thomas, G, Yates, S, Miller, J, Ritchie, S, Burrows, L, Fletcher, A, Harding, A, Laver, F, Silva, M, Thomson, A, Burns, P, Chu, C, Evans, C, Hamer, S, Markova, I, Raman, A, Barnes, K, Hobson, E, Jamieson, S, Thomson, J, Toscano, J, Wild, S, Yardumian, P, Bourne, C, Clayton, C, Dipple, H, Clapton, J, Grant, D, Hallam, C, Middleton, J, Murch, A, Patino, D, Bate, L, Pate, L, Andrews, T, Dougherty, A, Kavalier, F, Golding, C, Lashwood, A, Robertson, D, Ruddy, D, Whaite, A, Patton, M, Peterson, M, Rose, S, Bruno, S, Chu, E, Doherty, K, Henley, S, Lahiri, N, Novak, M, Patel, A, Read, J, Rosser, E, Say, M, Tabrizi, S, Taylor, R, Warner, T, Wild, E, Arran, N, Callaghan, J, Craufurd, D, Fullam, R, Howard, L, Huson, S, Oughton, E, Partington Jones, L, Snowden, J, Sollom, A, Stopford, C, Thompson, J, Trender Gerhad, I, Verstraelen, N, Westmoreland, L, Nemeth, Ah, Siuda, G, Harrison, D, Hughes, M, Parkinson, A, Soltysiak, B, Burn, J, Coleman, C, Majeed, T, Verstraelen Ritchie, N, Bandmann, O, Bradbury, A, Gill, P, Fairtlough, H, Fillingham, K, Foustanos, I, O'Donovan, K, Tidswell, K, Quarrell, O., Faculty of Economic and Social Sciences and Solvay Business School, Neurology, Clinical sciences, Neuroprotection & Neuromodulation, Orth M., European Huntington's Disease Network, Handley O.J., Schwenke C., Dunnet S., Wild E.J., Tabrizi S.J., Landwehrmeyer G.B., Capellari S., Cortelli P., Gallassi R., Poda R., Rizzo G., and Scaglione C.

Subjects
Gerontology, medicine.medical_specialty, Neurology, International Cooperation, Disease, Irritability, Data Collection/methods, Huntington's disease, medicine, Humans, Registries, Psychiatry, Suicidal ideation, Disease burden, business.industry, Data Collection, medicine.disease, Europe, Huntington Disease, Psychiatry and Mental health, European Huntington's Disease Network, Surgery, Observational study, Neurology (clinical), medicine.symptom, business
Abstract

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.

Published
2011

39. NMDA receptor gene variations as modifiers in Huntington disease: a replication study

Author

Saft C, Epplen JT, Wieczorek S, Landwehrmeyer GB, Roos RA, de Yebenes JG, Dose M, Tabrizi SJ, Craufurd D, REGISTRY Investigators of the European Huntington's Disease Network, Arning L. CollaboratorsBarth K, Bascuñana Garde M, Bos R, Ecker D, Handley O, Heinonen N, Held C, Laurà M, Martínez Descals A, Mestre T, Monza D, Naji J, Orth M, Padieu H, Pro Koivisto S, Rialland A, Sasinková P, Trigo Cubillo P, van Walsem M, Witjes Ané MN, Zielonka D, Bonelli R, Herranhof B, Hödl A, Kapfhammer HP, Koppitz M, Magnet M, Otti D, Painold A, Reisinge K, Brugger F, Hepperger C, Hotter A, Mahlknecht P, Nocker M, Seppi K, Wenning G, Ribaï P, Verellen Dumoulin C, Klempí?? J, Kucharik M, Roth J, Hasholt L, Hjermind L, Jakobsen O, Nielsen J, Nørremølle A, Sørensen S, Stokholm J, Hiivola H, Martikainen K, Tuuha K, Kosinski C, Probst D, Sass C, Schiefer J, Schlangen C, Werner C, Lange H, Löhle M, Storch A, Wolz A, Wolz M, Lambeck J, Zucker B, Münchau A, Stubbe L, Zittel S, Heinicke W, Longinus B, Peinemann A, Städtler M, Weindl A, Bohlen S, Reilmann R, Beister A, Hammer K, Leythaeuser G, Marquard R, Raab T, Schrenk C, Schuierer M, Wiedemann A, Eschenbach C, Landwehrmeyer B, Lezius F, Trautmann S, Cormio C, Difruscolo O, de Tommaso M, Sciruicchio V, Serpino C, Bertini E, Mechi C, Paganini M, Piacentini S, Romoli M, Sorbi S, Abbruzzese G, Di Maria E, Bandettini di Poggio Giovanna Ferrandes M, Mandich P, Marchese R, Albanese A, Di Donato S, Mariotti C, Soliveri P, Gellera C, Tomasello C, Nanetti L, Luigi D, Squitieri F, Martino T, Orobello S, Alberti S, De Gregorio F, Codella V, De Nicola N, Maglione V, Bentivoglio A, Fasano A, Frontali M, Guidubaldi A, Ialongo T, Jacopini G, Loria G, Piano C, Romano S, Soleti F, Spadaro M, Zinzi P, Heiberg A, Bjørgo K, Fannemel M, Gørvell P, Retterstøl L, Bjørnevoll I, Botne Sando S, Slawek J, Soltan W, Sitek E, Boczarska Jedynak M, Jasinska Myga B, Opala G, Szczudlik A, Rudzi??ska M, Wójcik M, Banaszkiewicz K, Krawczyk M, Marcinkowski J, Ciesielska A, Sempo??owicz J, Bryl A, Klimberg A, Janik P, Kalbarczyk A, Kwiecinski H, Jamrozik Z, Witkowski G, Ryglewicz D, Antczak J, Rakowicz M, Jachinska K, Zdzienicka E, Richter P, Zaremba J, Coelho M, Ferreira J, Rosa M, Valadas A, Gago M, Garrett C, Guerra M, Barrero F, Morales B, López Sendón Moreno J, Cubo E, Mariscal N, Sánchez J, García R, Villanueva C, Pin Quiroga P, Bascuñana M, Fatàas M, Luis López Moreno J, García Ribas G, Schwarz C, de Yébenes JG, José Saiz Artiga M, García Ruíz P, Sánchez V, Fortuna Alcaraz L, Fuensanta Noguera Perea M, Martirio Antequera Torres M, Vivancos Moreau L, Rojo Sebastian A, Aguilar Barbera M, Badenes Guia D, Casas Hernanz L, Tome Carruesco G, Suarez San Martin E, López Catena J, Bas J, Calopa M, Busquets N, Navas Arques P, Gorospe A, Legarda I, José Torres Rodríguez M, Vives B, Carrillo F, Mir P, José Lama Suarez M, Loutfi G, Stattin EL, Westman L, Wikström B, Pålhagen S, Björnsson E, Burgunder JM, Romero I, Schüpbach M, Weber Zaugg S, van Hout M, van Vugt J, Marit de Weert A, Bolwijn JJ, Dekker M, Leenders KL, van Oostrom JC, Dumas E, Jurgens C, van den Bogaard SA, Roos R, Kremer B, Verstappen CC, de Souza J, Rickards H, Wright J, Barker R, Fisher K, Goyder Goodman A, Hill S, Kershaw A, Mason S, Paterson N, Raymond L, Bisson J, Busse M, Ellison Rose L, Hunt S, Price K, Rosser A, Dunnett S, Edwards M, De Sousa P, Hughes T, McGill M, Pearson P, Porteous M, Smith P, Zeman A, Lambord N, Rankin J, Burrows L, Fletcher A, Laver F, Silva M, Thomson A, Andrews T, Dougherty A, Kavalier F, Golding C, Lashwood A, Robertson D, Ruddy D, Whaite A, Patton M, Patterson M, Bourne C, Clayton C, Dipple H, Clapton J, Grant J, Gross D, Hallam C, Middleton J, Murch A, Patino D, Bruno S, Chu E, Doherty K, Lahiri N, Novak M, Patel A, Tabrizi S, Taylor R, Warner T, Wild E, Arran N, Fullam R, Howard L, Huson S, Partington Jones L, Verstraelen N, Snowden J, Sollom A, Stopford C, Thompson J, Westmoreland L, Nemeth A, Siuda G, Bandmann O, Bradbury A, Fillingham K, Foustanos I, Tidswell K, Quarrell O., DE MICHELE, GIUSEPPE, RINALDI, CARLO, RUSSO, CINZIA, SALVATORE, ELENA, TUCCI, TECLA, Saft C, Epplen JT, Wieczorek S, Landwehrmeyer GB, Roos RA, de Yebenes JG, Dose M, Tabrizi SJ, Craufurd D, REGISTRY Investigators of the European Huntington's Disease Network, Arning L. Collaborators (348), Saft, C, Epplen, Jt, Wieczorek, S, Landwehrmeyer, Gb, Roos, Ra, de Yebenes, Jg, Dose, M, Tabrizi, Sj, Craufurd, D, Russo, CINZIA VALERIA, Arning L., CollaboratorsBarth K, Bascuñana Garde, M, Bos, R, Ecker, D, Handley, O, Heinonen, N, Held, C, Laurà, M, Martínez Descals, A, Mestre, T, Monza, D, Naji, J, Orth, M, Padieu, H, Pro Koivisto, S, Rialland, A, Sasinková, P, Trigo Cubillo, P, van Walsem, M, Witjes Ané, Mn, Zielonka, D, Bonelli, R, Herranhof, B, Hödl, A, Kapfhammer, Hp, Koppitz, M, Magnet, M, Otti, D, Painold, A, Reisinge, K, Brugger, F, Hepperger, C, Hotter, A, Mahlknecht, P, Nocker, M, Seppi, K, Wenning, G, Ribaï, P, Verellen Dumoulin, C, Klempí??, J, Kucharik, M, Roth, J, Hasholt, L, Hjermind, L, Jakobsen, O, Nielsen, J, Nørremølle, A, Sørensen, S, Stokholm, J, Hiivola, H, Martikainen, K, Tuuha, K, Kosinski, C, Probst, D, Sass, C, Schiefer, J, Schlangen, C, Werner, C, Lange, H, Löhle, M, Storch, A, Wolz, A, Wolz, M, Lambeck, J, Zucker, B, Münchau, A, Stubbe, L, Zittel, S, Heinicke, W, Longinus, B, Peinemann, A, Städtler, M, Weindl, A, Bohlen, S, Reilmann, R, Beister, A, Hammer, K, Leythaeuser, G, Marquard, R, Raab, T, Schrenk, C, Schuierer, M, Wiedemann, A, Eschenbach, C, Landwehrmeyer, B, Lezius, F, Trautmann, S, Cormio, C, Difruscolo, O, de Tommaso, M, Sciruicchio, V, Serpino, C, Bertini, E, Mechi, C, Paganini, M, Piacentini, S, Romoli, M, Sorbi, S, Abbruzzese, G, Di Maria, E, Bandettini di Poggio Giovanna Ferrandes, M, Mandich, P, Marchese, R, Albanese, A, Di Donato, S, Mariotti, C, Soliveri, P, Gellera, C, Tomasello, C, Nanetti, L, Luigi, D, DE MICHELE, Giuseppe, Rinaldi, Carlo, Russo, Cinzia, Salvatore, Elena, Tucci, Tecla, Squitieri, F, Martino, T, Orobello, S, Alberti, S, De Gregorio, F, Codella, V, De Nicola, N, Maglione, V, Bentivoglio, A, Fasano, A, Frontali, M, Guidubaldi, A, Ialongo, T, Jacopini, G, Loria, G, Piano, C, Romano, S, Soleti, F, Spadaro, M, Zinzi, P, Heiberg, A, Bjørgo, K, Fannemel, M, Gørvell, P, Retterstøl, L, Bjørnevoll, I, Botne Sando, S, Slawek, J, Soltan, W, Sitek, E, Boczarska Jedynak, M, Jasinska Myga, B, Opala, G, Szczudlik, A, Rudzi??ska, M, Wójcik, M, Banaszkiewicz, K, Krawczyk, M, Marcinkowski, J, Ciesielska, A, Sempo??owicz, J, Bryl, A, Klimberg, A, Janik, P, Kalbarczyk, A, Kwiecinski, H, Jamrozik, Z, Witkowski, G, Ryglewicz, D, Antczak, J, Rakowicz, M, Jachinska, K, Zdzienicka, E, Richter, P, Zaremba, J, Coelho, M, Ferreira, J, Rosa, M, Valadas, A, Gago, M, Garrett, C, Guerra, M, Barrero, F, Morales, B, López Sendón Moreno, J, Cubo, E, Mariscal, N, Sánchez, J, García, R, Villanueva, C, Pin Quiroga, P, Bascuñana, M, Fatàas, M, Luis López Moreno, J, García Ribas, G, Schwarz, C, de Yébenes, Jg, José Saiz Artiga, M, García Ruíz, P, Sánchez, V, Fortuna Alcaraz, L, Fuensanta Noguera Perea, M, Martirio Antequera Torres, M, Vivancos Moreau, L, Rojo Sebastian, A, Aguilar Barbera, M, Badenes Guia, D, Casas Hernanz, L, Tome Carruesco, G, Suarez San Martin, E, López Catena, J, Bas, J, Calopa, M, Busquets, N, Navas Arques, P, Gorospe, A, Legarda, I, José Torres Rodríguez, M, Vives, B, Carrillo, F, Mir, P, José Lama Suarez, M, Loutfi, G, Stattin, El, Westman, L, Wikström, B, Pålhagen, S, Björnsson, E, Burgunder, Jm, Romero, I, Schüpbach, M, Weber Zaugg, S, van Hout, M, van Vugt, J, Marit de Weert, A, Bolwijn, Jj, Dekker, M, Leenders, Kl, van Oostrom, Jc, Dumas, E, Jurgens, C, van den Bogaard, Sa, Roos, R, Kremer, B, Verstappen, Cc, de Souza, J, Rickards, H, Wright, J, Barker, R, Fisher, K, Goyder Goodman, A, Hill, S, Kershaw, A, Mason, S, Paterson, N, Raymond, L, Bisson, J, Busse, M, Ellison Rose, L, Hunt, S, Price, K, Rosser, A, Dunnett, S, Edwards, M, De Sousa, P, Hughes, T, Mcgill, M, Pearson, P, Porteous, M, Smith, P, Zeman, A, Lambord, N, Rankin, J, Burrows, L, Fletcher, A, Laver, F, Silva, M, Thomson, A, Andrews, T, Dougherty, A, Kavalier, F, Golding, C, Lashwood, A, Robertson, D, Ruddy, D, Whaite, A, Patton, M, Patterson, M, Bourne, C, Clayton, C, Dipple, H, Clapton, J, Grant, J, Gross, D, Hallam, C, Middleton, J, Murch, A, Patino, D, Bruno, S, Chu, E, Doherty, K, Lahiri, N, Novak, M, Patel, A, Tabrizi, S, Taylor, R, Warner, T, Wild, E, Arran, N, Fullam, R, Howard, L, Huson, S, Partington Jones, L, Verstraelen, N, Snowden, J, Sollom, A, Stopford, C, Thompson, J, Westmoreland, L, Nemeth, A, Siuda, G, Bandmann, O, Bradbury, A, Fillingham, K, Foustanos, I, Tidswell, K, and Quarrell, O.

Abstract

Several candidate modifier genes which, in addition to the pathogenic CAG repeat expansion, influence the age at onset (AO) in Huntington disease (HD) have already been described. The aim of this study was to replicate association of variations in the N-methyl D-aspartate receptor subtype genes GRIN2A and GRIN2B in the "REGISTRY" cohort from the European Huntington Disease Network (EHDN). The analyses did replicate the association reported between the GRIN2A rs2650427 variation and AO in the entire cohort. Yet, when subjects were stratified by AO subtypes, we found nominally significant evidence for an association of the GRIN2A rs1969060 variation and the GRIN2B rs1806201 variation. These findings further implicate the N-methyl D-aspartate receptor subtype genes as loci containing variation associated with AO in HD.

Published
2011

40. Ascorbic acid in Charcot-Marie-Tooth disease type 1A (CMT-TRIAAL and CMT-TRAUK): a double-blind randomised trial

Author

Pareyson, D, Reilly, Mm, Schenone, A, Fabrizi, Gm, Cavallaro, T, Vita, G, Quattrone, A, Padua, L, Gemignani, F, Visioli, F, Laurà, M, Radice, D, Calabrese, D, Hughes, Ra, Solari, A, Marchesi, C, Salsano, E, Nanetti, L, Marelli, C, Scaioli, V, Ciano, C, Rimoldi, M, Lauria, G, Rizzetto, E, Camozzi, F, Narciso, E, Grandis, M, Monti Bragadin, M, Nobbio, L, Casano, A, Bertolasi, L, Cabrini, I, Corrà, K, Rizzuto, N, Santoro, L, Nolano, M, Mazzeo, A, Aguennouz, M, Di Leo, R, Majorana, G, Lanzano, N, Valenti, F, Valentino, P, Nisticò, R, Pirritano, D, Lucisano, A, Canino, M, Pazzaglia, C, Granata, G, Foschini, M, Brindani, F, Vitetta, F, Allegri, I, Bogani, P, Blake, J, Koltzenburg, M, Hutton, E, Lunn, M, Mancardi, Gl, Cavaletti, G, Galimberti, S, Ferrari, G, Sereda, M., NOLANO, MARIA, SANTORO, LUCIO, MANGANELLI, FIORE, PISCIOTTA, CHIARA, Pareyson, D, Reilly, Mm, Schenone, A, Fabrizi, Gm, Cavallaro, T, Santoro, Lucio, Vita, G, Quattrone, A, Padua, L, Gemignani, F, Visioli, F, Laurà, M, Radice, D, Calabrese, D, Hughes, Ra, Solari, A, Marchesi, C, Salsano, E, Nanetti, L, Marelli, C, Scaioli, V, Ciano, C, Rimoldi, M, Lauria, G, Rizzetto, E, Camozzi, F, Narciso, E, Grandis, M, Monti Bragadin, M, Nobbio, L, Casano, A, Bertolasi, L, Cabrini, I, Corrà, K, Rizzuto, N, Santoro, L, Manganelli, Fiore, Pisciotta, Chiara, Nolano, M, Mazzeo, A, Aguennouz, M, Di Leo, R, Majorana, G, Lanzano, N, Valenti, F, Valentino, P, Nisticò, R, Pirritano, D, Lucisano, A, Canino, M, Pazzaglia, C, Granata, G, Foschini, M, Brindani, F, Vitetta, F, Allegri, I, Bogani, P, Blake, J, Koltzenburg, M, Hutton, E, Lunn, M, Mancardi, Gl, Cavaletti, G, Galimberti, S, Ferrari, G, Sereda, M., Nolano, Maria, Reilly, M, Fabrizi, G, Hughes, R, for the CMT, T, CMT TRAUK, G, and CMT TRAUK, g. r. o. u. p. s.

Subjects
Male, patients, Antioxidants, law.invention, 0302 clinical medicine, Randomized controlled trial, law, Charcot-Marie-Tooth Disease, Charcot-Marie-Tooth disease type 1A, 0303 health sciences, CMT1A, ascorbic acid, neuropathy, trial, Middle Aged, Charcot-Marie-Tooth Disease Type 1A, drug therapy, 3. Good health, Settore MED/26 - NEUROLOGIA, Treatment Outcome, Tolerability, Female, Antioxidant, Human, Adult, medicine.medical_specialty, SF-36, Adolescent, Clinical Neurology, double-blind controlled trial, Placebo, Double blind, 03 medical and health sciences, Acido ascorbico, Double-Blind Method, Internal medicine, medicine, Fast track — Articles, Humans, Adverse effect, 030304 developmental biology, Aged, business.industry, Ascorbic acid, Adolescent, Adult, Aged, Antioxidants, therapeutic use, Ascorbic Acid, therapeutic use, Charcot-Marie-Tooth Disease, drug therapy, Double-Blind Method, Female, Humans, Male, Middle Aged, Treatment Outcome, Surgery, therapeutic use, Charcot Marie Tooth, Neurology (clinical), business, 030217 neurology & neurosurgery
Abstract

Summary Background Ascorbic acid reduced the severity of neuropathy in transgenic mice overexpressing peripheral myelin protein 22 ( PMP22 ), a model of Charcot–Marie–Tooth disease type 1A (CMT1A) associated with the PMP22 duplication. However, in three 1-year trials, ascorbic acid had no benefit in human beings. We did a multicentre 2-year trial to test the efficacy and tolerability of ascorbic acid in patients with CMT1A. Methods Adult patients (aged 18–70 years) with symptomatic CMT1A were enrolled from nine centres in Italy and the UK, and were randomly assigned (1:1 ratio) to receive 1·5 g/day oral ascorbic acid or matching placebo for 24 months. The randomisation sequence was computer generated by block randomisation, stratified by centre and disease severity, and patients were allocated to treatment by telephone. The primary outcome was change in the CMT neuropathy score (CMTNS) at 24 months. Secondary outcomes were timed 10 m walk test, nine-hole peg test, overall neuropathy limitations scale, distal maximal voluntary isometric contraction, visual analogue scales for pain and fatigue, 36-item short-form questionnaire, and electrophysiological measurements. Patients, treating physicians, and physicians assessing outcome measures were masked to treatment allocation. Analysis of the primary outcome was done on all randomised patients who received at least one dose of study drug. This study is registered, numbers ISRCTN61074476 (CMT-TRAUK) and EudraCT 2006-000032-27 (CMT-TRIAAL). Findings We enrolled and randomly assigned 277 patients, of whom six (four assigned to receive ascorbic acid) withdrew consent before receiving treatment; 138 receiving ascorbic acid and 133 receiving placebo were eligible for analysis. Treatment was well tolerated: 241 of 271 patients (89% in each group) completed the study; 20 patients (nine receiving ascorbic acid) dropped out because of adverse events. Mean CMTNS at baseline with missing data imputed was 14·7 (SD 4·8) in the ascorbic acid group and 13·9 (4·2) in the placebo group. Mean worsening of CMTNS was 0·2 (SD 2·8, 95% CI −0·3 to 0·7) in the ascorbic acid group and 0·2 (2·7, −0·2 to 0·7) in the placebo group (mean difference 0·0, 95% CI −0·6 to 0·7; p=0·93). We recorded no differences between the groups for the secondary outcomes at 24 months. 21 serious adverse events occurred in 20 patients, eight in the ascorbic acid group and 13 in the placebo group. Interpretation Ascorbic acid supplementation had no significant effect on neuropathy compared with placebo after 2 years, suggesting that no evidence is available to support treatment with ascorbic acid in adults with CMT1A. Funding Telethon-UILDM and AIFA (Italian Medicines Agency) for CMT-TRI AA L, and Muscular Dystrophy Campaign for CMT-TRAUK.

Published
2011

41. Cerebral and extracerebral cholesterol biosynthesis is impaired in HD patients

Author

Leoni, V, Mariotti, C, Nanetti, L, Tomasello, C, Salvatore, E, Di Michele, G, Soletti, F, Bentivoglio, AR, Bandettini del Poggio, M, Abbruzzese, G, Piacentini, S, Squitieri, F, Valenza, M, Cattaneo, E, Di Donato, S, Leoni, V, Mariotti, C, Nanetti, L, Tomasello, C, Salvatore, E, Di Michele, G, Soletti, F, Bentivoglio, A, Bandettini del Poggio, M, Abbruzzese, G, Piacentini, S, Squitieri, F, Valenza, M, Cattaneo, E, and Di Donato, S

Subjects
mass spectrometry, oxysterols, organic acids, fatty acids, metabolomics, cholesterol, neurodegenerative diseases
Published
2010

42. Is overwork weakness relevant in Charcot-Marie-Tooth disease?

Author

Piscosquito, G., Reilly, M. M., Schenone, A., Fabrizi, G. M., Cavallaro, T., Santoro, L., Vita, G., Quattrone, A., Padua, L., Gemignani, F., Visioli, F., Laura, M., Calabrese, D., Hughes, R. A. C., Radice, D., Solari, A., Pareyson, D., Marchesi, C., Salsano, E., Nanetti, L., Marelli, C., Scaioli, V., Ciano, C., Rimoldi, M., Lauria, G., Rizzetto, E., Camozzi, F., Narciso, E., Grandis, M., Monti Bragadin, M., Nobbio, L., Casano, A., Bertolasi, L., Cabrini, I., Corra, K., Rizzuto, N., Manganelli, F., Pisciotta, C., Nolano, M., Mazzeo, A., Di Leo, R., Majorana, G., Russo, M., Valentino, P., Nistico, R., Pirritano, D., Lucisano, A., Canino, M., Pazzaglia, C., Granata, G., Foschini, M., Brindani, F., Vitetta, F., Allegri, I., Bogani, P., Blake, J., Koltzenburg, M., Hutton, E., Lunn, M., G., Piscosquito, M. M., Reilly, A., Schenone, G. M., Fabrizi, T., Cavallaro, Santoro, Lucio, G., Vita, A., Quattrone, L., Padua, F., Gemignani, F., Visioli, M., Laura, D., Calabrese, R. A. C., Hughe, D., Radice, A., Solari, D., Pareyson, C., Marchesi, E., Salsano, L., Nanetti, C., Marelli, V., Scaioli, C., Ciano, M., Rimoldi, G., Lauria, E., Rizzetto, F., Camozzi, E., Narciso, M., Grandi, M., Monti Bragadin, L., Nobbio, A., Casano, L., Bertolasi, I., Cabrini, K., Corra, N., Rizzuto, Manganelli, Fiore, Pisciotta, Chiara, M., Nolano, A., Mazzeo, R., Di Leo, G., Majorana, M., Russo, P., Valentino, R., Nistico, D., Pirritano, A., Lucisano, M., Canino, C., Pazzaglia, G., Granata, M., Foschini, F., Brindani, F., Vitetta, I., Allegri, P., Bogani, J., Blake, M., Koltzenburg, E., Hutton, and M., Lunn

Subjects
Adult, Male, REHABILITATION, congenital, hereditary, and neonatal diseases and abnormalities, Weakness, medicine.medical_specialty, Neuromuscular disease, Adolescent, Cumulative Trauma Disorders, medicine.medical_treatment, physical activity, Neurogenetics, CLINICAL NEUROLOGY, overwork weakness, Functional Laterality, Young Adult, Charcot-Marie-Tooth Disease, Hand strength, medicine, Humans, Muscle Strength, Young adult, Muscle, Skeletal, Aged, Charcot-Marie-Tooth disease, lower limb, muscles, rehabilitation, Rehabilitation, Muscle Weakness, NEUROGENETICS, Hand Strength, business.industry, NEUROPATHY, Muscle weakness, Middle Aged, medicine.disease, Gait, Psychiatry and Mental health, Settore MED/26 - NEUROLOGIA, Physical therapy, Surgery, Female, HMSN (CHARCOT-MARIE-TOOTH), Neurology (clinical), medicine.symptom, business
Abstract

BACKGROUND: In overwork weakness (OW), muscles are increasingly weakened by exercise, work or daily activities. Although it is a well-established phenomenon in several neuromuscular disorders, it is debated whether it occurs in Charcot-Marie-Tooth disease (CMT). Dominant limb muscles undergo a heavier overload than non-dominant and therefore if OW occurs we would expect them to become weaker. Four previous studies, comparing dominant and non-dominant hand strength in CMT series employing manual testing or myometry, gave contradictory results. Moreover, none of them examined the behaviour of lower limb muscles. METHODS: We tested the OW hypothesis in 271 CMT1A adult patients by comparing bilateral intrinsic hand and leg muscle strength with manual testing as well as manual dexterity. RESULTS: We found no significant difference between sides for the strength of first dorsal interosseous, abductor pollicis brevis, anterior tibialis and triceps surae. Dominant side muscles did not become weaker than non-dominant with increasing age and disease severity (assessed with the CMT Neuropathy Score); in fact, the dominant triceps surae was slightly stronger than the non-dominant with increasing age and disease severity. DISCUSSION: Our data does not support the OW hypothesis and the consequent harmful effect of exercise in patients with CMT1A. Physical activity should be encouraged, and rehabilitation remains the most effective treatment for CMT patients. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Published
2014
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43. PMP22 messenger RNA levels in skin biopsies: testing the effectiveness of a Charcot-Marie-Tooth 1A biomarker

Author

Nobbio, L, Visigalli, D, Radice, D, Fiorina, E, Solari, A, Lauria, G, Reilly, Mm, Santoro, L, Schenone, A, Pareyson, D, Marchesi, C, Salsano, E, Nanetti, L, Marelli, C, Scaioli, V, Ciano, C, Rimoldi, M, Rizzetto, E, Camozzi, F, Narciso, E, Grandis, M, Monti, M, Fabrizi, G, Cavallaro, T, Casano, A, Bertolasi, L, Cabrini, I, Corra, K, Rizzuto, N, Manganelli, F, Pisciotta, C, Nolano, M, Vita, Giuseppe, Mazzeo, Anna, Aguennouz, M'Hammed, DI LEO, Rita, Majorana, G, Lanzano, N, Valenti, F, Quattrone, A, Valentino, P, Nistico, R, Pirritano, D, Lucisano, A, Canino, M, Padua, L, Pazzaglia, C, Granata, G, Foschini, M, Gemignani, F, Brindani, F, Vitetta, F, Allegri, I, Visioli, F, Bogani, P, and Visioli, F.

Published
2014

44. Selected items from the Charcot-Marie-Tooth (CMT) Neuropathy Score and secondary clinical outcome measures serve as sensitive clinical markers of disease severity in CMT1A patients

Author

Mannil, M., Solari, A., Leha, A., Pelayo-Negro, A. L., Berciano, J., Schlotter-Weigel, B., Walter, M. C., Rautenstrauss, B., Schnizer, T. J., Schenone, A., Seeman, P., Kadian, C., Schreiber, O., Angarita, N. G., Fabrizi, G. M., Gemignani, F., Padua, L., Santoro, L., Quattrone, A., Vita, G., Calabrese, D., Marchesi, C., Salsano, E., Nanetti, L., Marelli, C., Scaioli, V., Ciano, C., Rimoldi, M., Lauria, G., Rizzetto, E., Camozzi, F., Narciso, E., Grandis, M., Monti-Bragadin, M., Nobbio, L., Cavallaro, T., Casano, A., Bertolasi, L., Cabrini, I., Corra, K., Manganelli, F., Pisciotta, C., Nolano, M., Mazzeo, A., Aguennouz, M., Di Leo, R., Majorana, G., Lanzano, N., Valenti, F., Valentino, P., Nistico, R., Pirritano, D., Lucisano, A., Canino, M., Pazzaglia, C., Granata, G., Foschini, M., Brindani, F., Vitetta, F., Allegri, I., Visioli, F., Bogani, P., Blake, J., Koltzenburg, M., Hutton, E., Lunn, M., Young, P., Laura, M., Haberlova, J., Mazanec, R., Paulus, W., Beissbarth, T., Shy, M. E., Reilly, M. M., Pareyson, D., Sereda, M. W., Manoj, Mannil, Alessandra, Solari, Andreas, Leha, Ana L., Pelayo Negro, Josè, Berciano, Beate Schlotter, Weigel, Maggie C., Walter, Bernd, Rautenstrau, Tuuli J., Schnizer, Angelo, Schenone, Pavel, Seeman, Chandini, Kadian, Olivia, Schreiber, Natalia G., Angarita, Gian Maria, Fabrizi, Franco, Gemignani, Luca, Padua, Santoro, Lucio, Aldo, Quattrone, Giuseppe, Vita, Daniela, Calabrese, Cmt, Trial, Manganelli, Fiore, CMT TRIAL Chiara, Pisciotta, CMT TRAUK, Group, Peter, Young, Matilde, Laurà, Jana, Haberlova, Radim, Mazanec, Walter, Paulu, Tim, Beissbarth, Michael E., Shy, Mary M., Reilly, Davide, Pareyson, and Michael W., Sereda

Subjects
Male, Outcome Assessment, CMTNS, Disease, Ascorbic Acid, Walking, Severity of Illness Index, Antioxidants, Cohort Studies, Charcot-Marie-Tooth Disease, Outcome Assessment, Health Care, Charcot-Marie-Tooth, CMT1A, HMSN, secondary clinical outcome measures, score generation, Cluster Analysis, Age Factor, Genetics (clinical), Score generation, Secondary clinical outcome measures, Adolescent, Adult, Age Factors, Disease Progression, Double-Blind Method, Female, Humans, Middle Aged, Muscle Strength, Pain Measurement, Psychomotor Performance, Young Adult, Snap, Outcome measures, Dorsal flexion, Compound muscle action potential, Settore MED/26 - NEUROLOGIA, Secondary clinical outcome measure, Neurology, Antioxidant, Human, medicine.medical_specialty, Outcome Assessment (Health Care), Physical medicine and rehabilitation, Disease severity, medicine, Sensory symptoms, Cluster Analysi, business.industry, Health Care, Pediatrics, Perinatology and Child Health, Sensory nerve action potential, Neurology (clinical), Cohort Studie, business
Abstract

This study evaluates primary and secondary clinical outcome measures in Charcot-Marie-Tooth disease type 1A (CMT1A) with regard to their contribution towards discrimination of disease severity. The nine components of the composite Charcot-Marie-Tooth disease Neuropathy Score and six additional secondary clinical outcome measures were assessed in 479 adult patients with genetically proven CMT1A and 126 healthy controls. Using hierarchical clustering, we identified four significant clusters of patients according to clinical severity. We then tested the impact of each of the CMTNS components and of the secondary clinical parameters with regard to their power to differentiate these four clusters. The CMTNS components ulnar sensory nerve action potential (SNAP), pin sensibility, vibration and strength of arms did not increase the discriminant value of the remaining five CMTNS components (Ulnar compound motor action potential [CMAP], leg motor symptoms, arm motor symptoms, leg strength and sensory symptoms). However, three of the six additional clinical outcome measures the 10 m-timed walking test (T10MW), 9 hole-peg test (9HPT), and foot dorsal flexion dynamometry further improved discrimination between severely and mildly affected patients. From these findings, we identified three different composite measures as score hypotheses and compared their discriminant power with that of the CMTNS. A composite of eight components CMAP, Motor symptoms legs, Motor symptoms arms, Strength of Legs, Sensory symptoms), displayed the strongest power to discriminate between the clusters. As a conclusion, five items from the CMTNS and three secondary clinical outcome measures improve the clinical assessment of patients with CMT1A significantly and are beneficial for upcoming clinical and therapeutic trials. (C) 2014 Elsevier B.V. All rights reserved.

Published
2014
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46. Long-term disease progression in spinocerebellar ataxia types 1, 2, 3, and 6: a longitudinal cohort study

Author

Jacobi, H., Montcel, S.T. du, Bauer, P., Giunti, P., Cook, A., Labrum, R., Parkinson, M.H., Durr, A., Brice, A., Charles, P., Marelli, C., Mariotti, C., Nanetti, L., Panzeri, M., Rakowicz, M., Sulek, A., Sobanska, A., Schmitz-Hubsch, T., Schols, L., Hengel, H., Baliko, L., Melegh, B., Filla, A., Antenora, A., Infante, J., Berciano, J., Warrenburg, B.P.C. van de, Timmann, D., Szymanski, S., Boesch, S., Kang, J.S., Pandolfo, M., Schulz, J.B., Molho, S., Diallo, A., Klockgether, T., Jacobi, H., Montcel, S.T. du, Bauer, P., Giunti, P., Cook, A., Labrum, R., Parkinson, M.H., Durr, A., Brice, A., Charles, P., Marelli, C., Mariotti, C., Nanetti, L., Panzeri, M., Rakowicz, M., Sulek, A., Sobanska, A., Schmitz-Hubsch, T., Schols, L., Hengel, H., Baliko, L., Melegh, B., Filla, A., Antenora, A., Infante, J., Berciano, J., Warrenburg, B.P.C. van de, Timmann, D., Szymanski, S., Boesch, S., Kang, J.S., Pandolfo, M., Schulz, J.B., Molho, S., Diallo, A., and Klockgether, T.

Abstract

Item does not contain fulltext, BACKGROUND: Spinocerebellar ataxias are dominantly inherited neurodegenerative diseases. As potential treatments for these diseases are being developed, precise knowledge of their natural history is needed. We aimed to study the long-term disease progression of the most common spinocerebellar ataxias: SCA1, SCA2, SCA3, and SCA6. Furthermore, we aimed to establish the order and occurrence of non-ataxia symptoms, and identify predictors of disease progression. METHODS: In this longitudinal cohort study (EUROSCA), we enrolled men and women with positive genetic testing for SCA1, SCA2, SCA3, or SCA6 and with progressive, otherwise unexplained ataxia who were aged 18 years or older from 17 ataxia referral centres in ten European countries. Patients were seen every year for 3 years, and at irregular intervals thereafter. The primary outcome was the scale for the assessment and rating of ataxia (SARA), and the inventory of non-ataxia signs (INAS). We used linear mixed models to analyse progression. To account for dropouts, we applied a pattern-mixture model. This study is registered with ClinicalTrials.gov, number NCT02440763. FINDINGS: Between July 1, 2005, and Aug 31, 2006, 526 patients with SCA1, SCA2, SCA3, or SCA6 were enrolled. We analysed data for 462 patients with at least one follow-up visit. Median observation time was 49 months (IQR 35-72). SARA progression data were best fitted with a linear model in all genotypes. Annual SARA score increase was 2.11 (SE 0.12) in patients with SCA1, 1.49 (0.07) in patients with SCA2, 1.56 (0.08) in patients with SCA3, and 0.80 (0.09) in patients with SCA6. The increase of the number of non-ataxia signs reached a plateau in SCA1, SCA2, and SCA3. In patients with SCA6, the number of non-ataxia symptoms increased linearly, but more slowly than in patients with SCA1, SCA2, and SCA3 (p<0.0001). Factors that were associated with faster progression of the SARA score were short duration of follow-up (p=0.0179), older age at inclusion (

Published
2015

48. β-Defensin Genomic Copy Number Does Not Influence the Age of Onset in Huntington's Disease

Author

Vittori, A, Orth, M, Roos, Ra, Outeiro, Tf, Giorgini, F, Hollox, Ej, Bachoud-Levi, Ac, Bentivoglio, Ar, Biunno, I, Bonelli, Rm, Burgunder, Jm, Dunnett, Sb, Ferreira, Jj, Handley, Oj, Heiberg, A, Illmann, T, Landwehrmeyer, Gb, Levey, J, Martinez-Jaurrieta, Md, Nielsen, Je, Pro Koivisto, S, Piiiviirinta, M, Sebastian, Ar, Tabrizi, Sj, Vandenberghe, W, Verellen-Dumoulin, C, Zaremba, J, Uhrova, T, Wahlstrom, J, Barth, K, Correia-Guedes, L, Finisterra, Am, Bascuiiana Garde, M, Betz, S, Bos, R, Ecker, D, Held, C, Koppers, K, Laura, M, Descals, Am, Mestre, T, Monza, D, Townhill, J, Padieu, H, Paterski, L, Peppa, N, Rialland, A, Røren, N, Sasinkova, P, Trigo Cubillo, P, van Walsem, M, Witjes-Ane, Mn, Yudina, E, Zielonka, D, Zielonka, E, Zinzi, P, Herranhof, B, Hod, A, Kapfhammer, Hp, Koppitz, M, Magnet, M, Otti, D, Painold, A, Reisinge, K, Scheib, M, Hecht, K, Lilek, S, Muller, N, Schoggl, H, Ullah, J, Ribal, P, Klempff, J, Majerova, V, Roth, J, Hjermind, Le, Jakobsen, O, Vinthev-Jensen, T, Larsen, Iu, Stokholm, J, Hiivola, H, Martikainen, K, Tuuha, K, Santala, M, Milkereit, E, Kosinski, Cm, Probst, D, Reetz, K, Sass, C, Schiefer, J, Schlangen, C, Werner, Cj, Andrich, J, Ellrichmann, G, Hoffmann, R, Kaminski, B, Saft, C, Stamm, C, Lange, H, Lohle, M, Schmidt, S, Storch, A, Wolz, A, Wolz, M, Capetian, P, Lambeck, J, Zucker, B, Boelmans, K, Ganos, C, Hidding, U, Lewerenz, J, Miinchau, A, Schmalfeld, J, Stubbe, L, Zittel, S, Heinicke, W, Ribbat, M, Longinus, B, Miihlau, M, Peinemann, A, Stiidtler, M, Weindl, A, Winkelmann, J, Ziegler, C, Bechtel, N, Beckmann, H, Bohlen, S, Holzner, E, Reilmann, R, Rohm, S, Rumpf, S, Schepers, S, Dose, M, Leythaeuser, G, Marquard, R, Raab, T, Schrenk, C, Schuierer, M, Buck, A, Eschenbach, C, Landwehrmeyer, B, Lezius, F, Nepper, S, Niess, A, Schwenk, D, Siissmuth, S, Trautmann, S, Weydt, P, Cormio, C, de Tommaso, M, Sciruicchio, V, Serpino, C, Ghelli, E, Ginestroni, A, Bertini, E, Massaro, F, Mechi, C, Paganini, M, Piacentini, S, Pradella, S, Romoli, Am, Sorbi, S, Abbruzzese, G, Ferrandes, Mb, Di Maria, E, Ferrandes, G, Mandich, P, Marchese, R, Di Donato, S, Gellera, C, Genitrini, S, Mariotti, C, Nanetti, L, Soliveri, P, Tomasello, C, De Michele, G, Dimaio, L, Massarelli, M, Rinaldi, C, Roca, A, Rossi, F, Russo, Cv, Salvatore, E, Sorrentino, P, Tucci, T, De Nicola, A, Elifani, F, Petrollini, M, Martino, T, Lovo, F, Squitieri, F, Catalli, C, Di Giacopo, R, Fasano, A, Frontali, M, Guidubaldi, A, Ialongo, T, Jacopini, G, Loria, G, Piano, C, Piccininni, C, Quaranta, D, Romano, S, Soleti, F, Spadaro, M, van Hout MS, van Vugt JP, de Weert, A, Bolwijn, Jj, Neurologie, P, Dekker, M, Leenders, Kl, van Oostrom JC, Dumas, Em, Jurgens, Ck, van den Bogaard SJ, 't Hart EP, Kremer, B, Verstappen, Cc, van Walsem MR, Frich, J, Aaserud, O, Wehus, R, Bjørgo, K, Fannemel, M, Gørvell, P, Lorentzen, E, Koivisto, Sp, Retterstøl, L, Stokke, B, Bjørnevoll, I, Sando, Sb, Dziadkiewicz, A, Nowak, M, Robowski, P, Sitek, E, Slawek, J, Soltan, W, Szinwelski, M, Blaszczyk, M, Boczarska-Jedynak, M, Ciach-Wysocka, E, Gorzkowska, A, Jasinska-Myga, B, Opala, G, Klodowska, G, Stompel, D, Banaszkiewicz, K, Boewiriska, D, Bojakowska-Jaremek, K, Neurologii, A, Dec, M, Krawczyk, M, Rudziriska, M, Szczudlik, A, Szczygiel, E, Wasielewska, A, Wojcik, M, Bryl, A, Ciesielska, A, Klimberg, A, Marcinkowski, J, Samara, H, Sempolowicz, J, Janik, P, Kalbarczyk, A, Kwiecinski, H, Jamrozik, Z, Antczak, J, Jachinska, K, Krysa, W, Rakowicz, M, Richter, P, Rola, R, Ryglewicz, D, Sienkiewicz-Jarosz, H, Sulek, A, Witkowski, G, Zdzienicka, E, Zieora-Jakutowicz, K, Coelho, M, Mendes, T, Valadas, A, Andrade, C, Joao, Ps, Gago, M, Garrett, C, Guerra, Mr, Solis, P, Herrera, Cd, Garcia, Pm, Cubo, E, Mariscal, N, Sanchez, J, Barrero, Fj, Alonso-Frech, F, Perez, Mr, Fenollar, M, Garda, R, Rivera, Sv, Villanueva, C, Alegre, J, Bascuiiana, M, Ventura, Mf, Ribas, Gg, Moreno, Jl, Cubillo, Pt, Rufz, Pj, Frech, Fa, Dfaz, J, Guerrero, R, Artiga, Mj, Sanchez, V, Alcaraz, Lf, de Ia Arrixaca, V, Manzanares, S, Perea, Mf, Reinante, G, Arrixaca, Ia, Torres, Mm, Moreau, Lv, Barbera, Ma, Guia, Db, Hernanz, Lc, Catena, Jl, Sebastian, R, Ferrer, Pq, Carruesco, Gt, Bas, J, Busquets, N, Calopa, M, Buongiorno, Mt, Munoz, E, Elorza, Md, Lopez, Cd, Terol, Ds, Robert, Mf, Rufz, Bg, Casado, Ag, Martinez, Ih, Viladrich, Cm, Pons, R, Roca, E, Llesoy, Jr, Idiago, Jm, Vergara, Mr, Garcia, Ss, Riballo, Av, Hoglund, A, Palhagen, Se, Paucar, M, Sandstrom, B, Svenningsson, P, Reza-Soltani, Tw, Kaelin, A, Romero, I, Schupbach, M, Stebler, Y, Zaugg, Sw, Akhtar, S, Crooks, J, Curtis, A, de Souza, J, Rickards, H, Wright, J, Barker, Ra, Di Pietro, A, Fisher, K, Goodman, Ao, Hill, S, Kershaw, A, Mason, S, O'Keefe, D, Swain, R, Guzman, Nv, Busse, M, Butcher, C, Clenaghan, C, Dunnett, S, Fullam, R, Jones, L, Jones, U, Khalil, H, Minster, S, Owen, M, Hunt, S, Price, K, Rosser, A, Edwards, M, Ho, C, Mcgill, M, Pearson, P, Porteous, M, Brockie, P, Foster, J, Johns, N, Mckenzie, S, Rothery, J, Thomas, G, Yates, S, Burrows, L, Chu, C, Fletcher, A, Gallantrae, D, Harding, A, Hamer, S, Kraus, A, Laver, F, Longthorpe, M, Markova, I, Raman, A, Silva, M, Thomson, A, Wild, S, Yardumian, P, Hobson, E, Jamieson, S, Musgrave, H, Rowett, L, Toscano, J, Clayton, C, Dipple, H, Middleton, J, Patino, D, Andrews, T, Dougherty, A, Kavalier, F, Golding, C, Laing, H, Lashwood, A, Robertson, D, Ruddy, D, Whaite, A, Santhouse, A, Bruno, S, Doherty, K, Lahiri, N, Novak, M, Patel, A, Rosser, E, Tabrizi, S, Taylor, R, Warner, T, Wild, E, Arran, N, Bek, J, Callaghan, J, Craufurd, D, Howard, L, Hare, M, Huson, S, Johnson, L, Jones, M, Murphy, H, Oughton, E, Partington-Janes, L, Rogers, D, Snowden, J, Sollom, A, Stopford, C, Thompson, J, Trender-Gerhard, I., Vittori, Angelica, Orth, Michael, Roos, Raymund A C, Outeiro, Tiago F, Giorgini, F, Russo, Cinzia Valeria, Flaviano, and Hollox, Edward J

Subjects
Adult, Male, Age of Onset, DNA Copy Number Variations, Female, Genotype, Humans, Huntington Disease, Middle Aged, beta-Defensins, Disease, Biology, Genetic modifier, Article, Pathogenesis, 03 medical and health sciences, Cellular and Molecular Neuroscience, 0302 clinical medicine, Huntington's disease, medicine, Copy-number variation, Defensin, 030304 developmental biology, Genetics, 0303 health sciences, copy number variation, inflammation, Acquired immune system, medicine.disease, 3. Good health, Beta defensin, Neurology (clinical), Age of onset, 030217 neurology & neurosurgery
Abstract

Background: Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder caused by the abnormal expansion of a CAG triplet repeat tract in the huntingtin gene. While the length of this CAG expansion is the major determinant of the age of onset (AO), other genetic factors have also been shown to play a modulatory role. Recent evidence suggests that neuroinflammations is a pivotal factor in the pathogenesis of HD, and that targeting this process may have important therapeutic ramifications. The human β-defensin 2 (hBD2)- encoded by DEFB4- is an antimicrobial peptide that exhibits inducible expression in astrocytes during inflammation and is an important regulator of innate and adaptive immune response. Therefore, DEFB4 may contribute to the neuroinflammatory processes observed in HD. Objective: In this study we tested the hypothesis that copy number variation (CNV) of the β-defensin region, including DEFB4, modifies the AO in HD. Methods and results: We genotyped β-defensin CNV in 490 HD individuals using the paralogue ratio test and found no association between β-defensin CNV and onset of HD. Conclusions: We conclude that it is unlikely that DEFB4 plays a role in HD pathogenesis.

Published
2013

49. Vitamin C and Charcot-Marie-Tooth 1A: Pharmacokinetic considerations

Author

Visioli, F, Reilly, Mm, Rimoldi, M, Solari, A, Pareyson, D, Marchesi, C, Salsano, E, Nanetti, L, Marelli, C, Scaioli, V, Ciano, C, Lauria, G, Rizzetto, E, Camozzi, F, Schenone, Angelo, Narciso, E, Grandis, Marina, Monti Bragadin, M, Nobbio, Lucilla, Fabrizi, Gm, Cavallaro, T, Casano, A, Bertolasi, L, Cabrini, I, Corrà, K, Rizzuto, N, Santoro, L, Manganelli, F, Pisciotta, C, Nolano, M, Vita, G, Mazzeo A, ., Aguennouz, M, Di Leo, R, Majorana, G, Lanzano N, ., Valenti, F, Quattrone, A, Valentino, P, Nisticò, R, Pirritano, D, Lucisano, A, Canino, M, Padua, L, Pazzaglia, C, Granata, G, Foschini, M, Gemignani, F, Brindani, F, Vitetta, F, Allegri, I, Bogani, P. ., Visioli, F, Reilly, Mm, Rimoldi, M, Solari, A, Pareyson, D, Manganelli, Fiore, Cmt, Triaal2, CMT TRAUK, Group, Pisciotta, Chiara, Santoro, Lucio, and for the CMT, Triaal

Subjects
Drug, congenital, hereditary, and neonatal diseases and abnormalities, Ascorbic acid, Charcot-Marie-Tooth disease, Myelin, Neuromuscular disorders, Pharmacology, Pharmacology (medical), Food Science, media_common.quotation_subject, Disease, Charcot–Marie–Tooth disease, Article, law.invention, Randomized controlled trial, Pharmacokinetics, law, Medicine, media_common, Vitamin C, business.industry, Clinical trial, Tolerability, business
Abstract

Highlights ► Charcot-Marie-Tooth 1A cannot rely on effective pharmacological treatment. ► Several human trials failed to provide evidence of a therapeutic role of vitamin C. ► Human vitamin C's pharmacokinetics are tightly regulated. ► Ascorbic acid should not be given in excess of its transport system capacity., Charcot–Marie–Tooth 1A disease (CMT1A) is a disease for which no drug treatments are available. In 2004, it was reported that ascorbic acid reduced the severity of neuropathy in transgenic mice overexpressing PMP22, an animal model of human CMT1A, compared with untreated mice. Based on those results, clinical trials were undertaken at different centers worldwide and four of them have been completed, but none of them resulted in significant improvements. Based on the pharmacokinetics of ascorbic acid, we propose that the randomized clinical trial carried out thus far confirmed the tight control of ascorbic acid's absorption and proved its tolerability at one and two years. The pharmacokinetic considerations discussed in this article might largely explain the disappointing results of the recent CMT1A trials.

Published
2013

50. Discrepancies in reporting the CAG repeat lengths for Huntington's disease

Author

Quarrell, Ow, Handley, O, O'Donovan, K, Dumoulin, C, Ramos Arroyo, M, Biunno, I, Bauer, P, Kline, M, Landwehrmeyer, Gb, Barth, K, Correia Guedes, L, Maria Finisterra, A, Bascuñana Garde, M, Bos, R, Ecker, D, Held, C, Koppers, K, Laurà, M, Martínez Descals, A, Mclean, T, Mestre, T, Minster, S, Monza, D, Townhill, J, Orth, M, Padieu, H, Paterski, L, Peppa, N, Koivisto, Sp, Rialland, A, Røren, N, Šašinková, P, Cubillo, Pt, van Walsem MR, Witjes Ané MN, Yudina, E, Zielonka, D, Zielonka, E, Zinzi, P, Bachoud Lévi AC, Bentivoglio, Ar, Bonelli, R, Burgunder, Jm, Dunnett, Sb, Ferreira, Jj, Handley, Oj, Heiberg, A, Illmann, T, Levey, J, Nielsen, Je, Päivärinta, M, Roos, Ra, Rojo Sebastián, A, Tabrizi, Sj, Vandenberghe, W, Verellen Dumoulin, C, Zaremba, J, Uhrova, T, Wahlström, J, Bonelli, Rm, Herranhof, B, Holl, A, Kapfhammer, Hp, Koppitz, M, Magnet, M, Otti, D, Painold, A, Reisinger, K, Scheibl, M, Hecht, K, Lilek, S, Müller, N, Schöggl, H, Ullah, J, Brugger, F, Hepperger, C, Hotter, A, Mahlknecht, P, Nocker, M, Seppi, K, Wenning, G, Buratti, L, Hametner, Em, Holas, C, Hussl, A, Mair, K, Poewe, W, Wolf, E, Zangerl, A, Braunwarth, Em, Ribaï, P, Flamez, A, Morez, V, de Raedt, S, Boogaerts, A, van Reijen, D, Klempíř, J, Kucharík, M, Roth, J, Hjermind, Le, Jakobsen, O, Stokholm, J, Hasholt, L, Nørremølle, A, Sørensen, Sa, Hiivola, H, Martikainen, K, Tuuha, K, Peippo, M, Sipponen, M, Kosinski, Cm, Milkereit, E, Probst, D, Sass, C, Schiefer, J, Schlangen, C, Werner, Cj, Gelderblom, H, Priller, J, Prüss, H, Spruth, Ej, Andrich, J, Hoffmann, R, Kraus, Ph, Muth, S, Prehn, C, Saft, C, Salmen, S, Stamm, C, Steiner, T, Strassburger, K, Lange, H, Friedrich, A, Hunger, U, Löhle, M, Schmidt, S, Storch, A, Wolz, A, Wolz, M, Lambeck, J, Zucker, B, Boelmans, K, Ganos, C, Hidding, U, Lewerenz, J, Münchau, A, Schmalfeld, J, Stubbe, L, Zittel, S, Heinicke, W, Longinus, B, Uni, M, Bürk, K, Möller, Jc, Rissling, I, Peinemann, A, Städtler, M, Weindl, A, Bechtel, N, Beckmann, H, Bohlen, S, Hölzner, E, Reilmann, R, Rohm, S, Rumpf, S, Schepers, S, Beister, A, Dose, M, Hammer, K, Kieni, J, Leythaeuser, G, Marquard, R, Raab, T, Richter, S, Selimbegovic Turkovic, A, Schrenk, C, Schuierer, M, Wiedemann, A, Buck, A, Connemann, J, Eschenbach, C, Landwehrmeyer, B, Lezius, F, Nepper, S, Niess, A, Süssmuth, S, Trautmann, S, Weydt, P, Cormio, C, Difruscolo, O, Sciruicchio, V, Serpino, C, de Tommaso, M, Capellari, S, Cortelli, P, Gallassi, R, Poda, R, Rizzo, G, Scaglione, C, Bertini, E, Ghelli, E, Ginestroni, A, Massaro, F, Mechi, C, Paganini, M, Piacentini, S, Pradella, S, Romoli, Am, Sorbi, S, Abbruzzese, G, Bandettini di Poggio, M, Di Maria, E, Ferrandes, G, Mandich, P, Marchese, R, Albanese, A, Di Bella, D, Di Donato, S, Gellera, C, Genitrini, S, Mariotti, C, Nanetti, L, Paridi, D, Soliveri, P, Tomasello, C, De Michele, G, Di Maio, L, Rinaldi, C, Valeria Russo, C, Salvatore, E, Tucci, T, Cannella, M, Codella, V, De Gregorio, F, De Nicola, N, Martino, T, Simonelli, M, Squitieri, F, Catalli, C, Di Giacopo, R, Fasano, A, Frontali, M, Guidubaldi, A, Ialongo, T, Jacopini, G, Loria, G, Modoni, A, Piano, C, Piccininni, C, Quaranta, D, Romano, Silvia, Soleti, F, Spadaro, M, van Hout MS, van Vugt JP, Marit de Weert, A, Bolwijn, Jj, Dekker, M, Leenders, Kl, van Oostrom JC, Dumas, Em, Jurgens, Ck, van den Bogaard SJ, 't Hart EP, Kremer, B, Verstappen, Cc, Aaserud, O, Wehus, R, Bjørgo, K, Fannemel, M, Gørvell, P, Retterstøl, L, Overland, T, Stokke, B, Bjørnevoll, I, Sando, Sb, Sitek, E, Slawek, J, Soltan, W, Boczarska Jedynak, M, Jasinska Myga, B, Opala, G, Kodowska Duda, G, Banaszkiewicz, K, Szczudlik, A, Rudziñska, M, Wójcik, M, Dec, M, Krawczyk, M, Bryl, A, Ciesielska, A, Klimberg, A, Marcinkowski, J, Sempoowicz, J, Samara, H, Janik, P, Kalbarczyk, A, Kwiecinski, H, Jamrozik, Z, Antczak, J, Jachinska, K, Rakowicz, M, Richter, P, Ryglewicz, D, Witkowski, G, Zdzienicka, E, Suek, A, Krysa, W, Guedes, L, Coelho, M, Mendes, T, Valadas, A, Cavaco, S, Damásio, J, Magalhães, M, Gago, M, Garrett, C, Guerra, Mr, Barrero, F, Morales, B, Cubo, E, Mariscal, N, Sánchez, J, Alonso Frech, F, Rabasa Perez, M, Fenollar, M, García, R, Quiroga, Pp, Vázquez Rivera, S, Villanueva, C, Bascuñana, M, Fatás Ventura, M, García Ribas, G, García de Yébenes, J, López Sendón Moreno JL, García Ruíz PJ, José Saiz Artiga, M, Sánchez, V, Noguera Perea, F, Lorenza, F, Torres, Mm, Reinante, G, Vivancos Moreau, L, Barbera, Ma, Badenes Guia, D, Hernanz, Lc, Catena, Jl, Ferrer, Pq, Tome Carruesco, G, Bas, J, Busquets, N, Calopa, M, Dalmau Elorza, M, Díez, C, López, A, Durán, S, Terol, S, Floriach Robert, M, Garzón Ruíz, B, González Casado, A, Haro Martínez, I, Viladrich, Cm, Càrdenas R, Pons i., Roca, E, Llesoy, Jr, Ruiz Idiago JM, Ruíz Vergara, M, Soriano García, S, Villa Riballo, A, Gorospe, A, Legarda, I, Arques, Pn, Torres Rodríguez MJ, Vives, B, Gaston, I, Bosca, M, Burguera, Ja, Garcia, Ac, Pålhagen, Se, Paucar, M, Svenningsson, P, Walldén Reza Soltani, T, Höglund, A, Sandström, B, Høsterey Ugander, U, Fredlund, G, Constantinescu, R, Neleborn Lingefjärd, L, Tedroff, J, Esmaeilzadeh, M, Winnberg, E, Burgunder, Y, Stebler, Y, Kaelin, A, Romero, I, Schüpbach, M, Zaugg, Sw, Jack, R, Matheson, K, Miedzybrodzka, Z, Rae, D, Simpson, S, Summers, F, Ure, A, Crooks, J, Curtis, A, de Souza, J, Rickards, H, Wright, J, Barker, Ra, Di Pietro, A, Fisher, K, Goodman, A, Hill, S, Kershaw, A, Mason, S, Paterson, N, Raymond, L, Bisson, J, Busse, M, Clenaghan, C, Ellison Rose, L, Hunt, S, Price, K, Rosser, A, Edwards, M, Hughes, T, Mcgill, M, Pearson, P, Porteous, M, Smith, P, Zeman, A, Causley, A, Harrower, T, Howcroft, D, Lambord, N, Rankin, J, Brockie, P, Foster, J, Johns, N, Mckenzie, S, Rothery, J, Thomas, G, Yates, S, Miller, J, Ritchie, S, Burrows, L, Fletcher, A, Harding, A, Laver, F, Silva, M, Thomson, A, Barnes, K, Chu, C, Hobson, E, Jamieson, S, Markova, I, Thomson, J, Toscano, J, Wild, S, Yardumian, P, Bourne, C, Clayton, C, Dipple, H, Clapton, J, Grant, J, Gross, D, Hallam, C, Middleton, J, Murch, A, Patino, D, Andrews, T, Dougherty, A, Kavalier, F, Golding, C, Lashwood, A, Robertson, D, Ruddy, D, Whaite, A, Patton, M, Peterson, M, Rose, S, Bruno, S, Chu, E, Doherty, K, Henley, S, Lahiri, N, Novak, M, Patel, A, Read, J, Rosser, E, Say, M, Tabrizi, S, Taylor, R, Warner, T, Wild, E, Arran, N, Callaghan, J, Craufurd, D, Fullam, R, Howard, L, Huson, S, Oughton, E, Partington Jones, L, Snowden, J, Sollom, A, Stopford, C, Thompson, J, Trender Gerhad, I, Verstraelen, N, Westmoreland, L, Nemeth, Ah, Suida, G, Harrison, D, Hughes, M, Parkinson, A, Soltysiak, B, Bandmann, O, Bradbury, A, Gill, P, Fairtlough, H, Fillingham, K, Foustanos, I, Tidswell, K., Kaelin, André, Quarrel O.W., Handley O., O'Donovan K., Dumoulin C., Ramos-Arroyo M., Biunno I., Bauer P., Kline M., Capellari S., Cortelli P., Gallassi R., Landwehrmeyer G.B., European Huntington's Disease Network., Neurology, Clinical sciences, Neuroprotection & Neuromodulation, Quarrell, Ow, Handley, O, O'Donovan, K, Dumoulin, C, Ramos Arroyo, M, Biunno, I, Bauer, P, Kline, M, Landwehrmeyer, Gb, European Huntington's Disease, Network, European Huntington's Disease, N. e. t. w. o. r. k., Rinaldi, Carlo, Salvatore, Elena, and DE MICHELE, Giuseppe

Subjects
medicine.medical_specialty, Concordance, International Cooperation, Diagnostic Errors/statistics & numerical data, Nerve Tissue Proteins, Guidelines as Topic, Bioinformatics, Sensitivity and Specificity, Article, Huntingtin Gene, Huntington's disease, Trinucleotide Repeats, Internal medicine, External quality assessment, Genetics, medicine, Humans, Nerve Tissue Proteins/genetics, Diagnostic laboratory, Genetic Testing, Genetic Testing/methods/standards, Allele, Diagnostic Errors, standard reference material, Genetics (clinical), Alleles, Huntingtin Protein, ddc:618, business.industry, international cooperation, Nuclear Proteins, Reproducibility of Results, Reference Standards, medicine.disease, CAG repeat length, Nuclear Proteins/genetics, Huntington Disease, Huntington Disease/diagnosis, Mutation, Medical genetics, reproducibility of results, mutation, business, Trinucleotide repeat expansion, Huntington Disease/diagnosis/genetics, Genetic Testing/methods
Abstract

Huntington's disease results from a CAG repeat expansion within the Huntingtin gene; this is measured routinely in diagnostic laboratories. The European Huntington's Disease Network REGISTRY project centrally measures CAG repeat lengths on fresh samples; these were compared with the original results from 121 laboratories across 15 countries. We report on 1326 duplicate results; a discrepancy in reporting the upper allele occurred in 51% of cases, this reduced to 13.3% and 9.7% when we applied acceptable measurement errors proposed by the American College of Medical Genetics and the Draft European Best Practice Guidelines, respectively. Duplicate results were available for 1250 lower alleles; discrepancies occurred in 40% of cases. Clinically significant discrepancies occurred in 4.0% of cases with a potential unexplained misdiagnosis rate of 0.3%. There was considerable variation in the discrepancy rate among 10 of the countries participating in this study. Out of 1326 samples, 348 were re-analysed by an accredited diagnostic laboratory, based in Germany, with concordance rates of 93% and 94% for the upper and lower alleles, respectively. This became 100% if the acceptable measurement errors were applied. The central laboratory correctly reported allele sizes for six standard reference samples, blind to the known result. Our study differs from external quality assessment (EQA) schemes in that these are duplicate results obtained from a large sample of patients across the whole diagnostic range. We strongly recommend that laboratories state an error rate for their measurement on the report, participate in EQA schemes and use reference materials regularly to adjust their own internal standards.

Published
2012

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