Publications

Professor of Neurology, of Pediatrics (Genetics) and, by Courtesy, of Pathology at the Stanford University Medical Center

Publications

  • Author Correction: Humanizing the mdx mouse model of DMD: the long and the short of it. NPJ Regenerative medicine Yucel, N., Chang, A. C., Day, J. W., Rosenthal, N., Blau, H. M. 2020; 5 (1): 25

    View details for DOI 10.1038/s41536-020-00112-0

    View details for PubMedID 33349636

  • Deep phenotypic dissection and natural history of a large multicentre CMT2A cohort Pipis, M., Feely, S., Skorupinska, M., Polke, J., Quiros, L., Laura, M., Moroni, I., Pisciotta, C., Vujovic, D., Lloyd, T., Acsadi, G., Yum, S., Lewis, R., Finkel, R., Herrmann, D., Day, J., Li, J., Saporta, M., Sadjadi, R., Walk, D., Burns, J., Ramchandren, S., Horvath, R., Johnson, N., Zuchner, S., Pareyson, D., Scherer, S., Rossor, A., Shy, M., Reilly, M. WILEY. 2020: 559
  • Development and Validation of the Pediatric CMT Quality of Life Outcome Measure. Annals of neurology Ramchandren, S., Wu, T. T., Finkel, R. S., Siskind, C. E., Feely, S. M., Burns, J., Reilly, M. M., Estilow, T., Shy, M. E., Childhood CMT Study Group, Bacon, C. J., Shy, R. R., Cornett, K., Muntoni, F., Day, J. W., Lloyd, T., Sumner, C. J., Herrmann, D. N., Kirk, C., Yum, S. W. 2020

    Abstract

    OBJECTIVE: Charcot-Marie-Tooth disease (CMT) reduces health-related quality of life (QOL), especially in children. Defining QOL in pediatric CMT can help physicians monitor disease burden clinically and in trials. We identified items pertaining to QOL in children with CMT and conducted validation studies to develop a pediatric CMT-specific QOL outcome measure (pCMT-QOL).METHODS: Development and validation of the pCMT-QOL patient-reported outcome measure was iterative, involving identifying relevant domains, item pool generation, prospective pilot testing and clinical assessments, structured focus-group interviews, and psychometric testing. Testing was conducted in children with CMT seen at participating sites from the USA, United Kingdom, and Australia.RESULTS: We conducted systematic literature reviews and analysis of generic QOL measures to identify six domains relevant to QOL in children with CMT. 60 items corresponding to those domains were developed de novo, or identified from literature review and CMT-specific modification of items from the pediatric Neuro-QOL measures. The draft version underwent prospective feasibility and face content validity assessments to develop a working version of the pCMT-QOL measure. From 2010-2016, the pCMT-QOL working version was administered to 398 children ages 8-18 seen at the participating study sites of the Inherited Neuropathies Consortium. The resulting data underwent rigorous psychometric analysis, including factor analysis, test-retest reliability, internal consistency, convergent validity, IRT analysis, and longitudinal analysis, to develop the final pCMT-QOL patient-reported outcome measure.INTERPRETATION: The pCMT-QOL patient-reported outcome measure is a reliable, valid, and sensitive measure of health-related QOL for children with CMT. This article is protected by copyright. All rights reserved.

    View details for DOI 10.1002/ana.25966

    View details for PubMedID 33222249

  • Respiratory trajectories in type 2 and non-ambulant 3 Spinal muscular atrophy in the iSMAC cohort study. Neurology Trucco, F., Ridout, D., Scoto, M., Coratti, G., Main, M. L., Lofra, R. M., Mayhew, A. G., Montes, J., Pane, M., Sansone, V., Albamonte, E., D'Amico, A., Bertini, E., Messina, S., Bruno, C., Parasuraman, D., Childs, A., Gowda, V., Willis, T., Ong, M., Marini-Bettolo, C., De Vivo, D. C., Darras, B. T., Day, J., Kichula, E. A., Mayer, O. H., Navas Nazario, A. A., Finkel, R. S., Mercuri, E., Muntoni, F., international SMA consortium (iSMAc) 2020

    Abstract

    OBJECTIVE: To describe the respiratory trajectories and their correlation with motor function in an international paediatric cohort of patients with type 2 and non-ambulant type 3 spinal muscular atrophy (SMA).METHODS: Eight-year retrospective observational study of patients in the iSMAc natural history study. We retrieved anthropometrics, forced vital capacity (FVC) absolute, FVC% predicted (FVC%P.), Non-Invasive ventilation (NIV) requirement. Hammersmith functional motor scale (HFMS) and Revised performance of upper limb (RULM) were correlated with respiratory function. We excluded patients in interventional clinical trials and on Nusinersen commercial therapy.RESULTS: There were 437 patients with SMA: 348 type 2, 89 non-ambulant type 3. Mean age at first visit was 6.9(±4.4) and 11.1(±4) years. In SMA type 2 FVC%P declined by 4.2%/year from 5 to 13 years, followed by a slower decline (1.0%/year). In type 3 FVC%P declined by 6.3%/year between 8 and 13 years, followed by a slower decline (0.9%/year). 39% SMA type 2 and 9% type 3 required NIV at median age 5.0(1.8-16.6) and 15.1(13.8-16.3) years. 84% SMA type 2 and 80% type 3 had scoliosis, 54% and 46% required surgery, which did not significantly affect respiratory decline. FVC%P positively correlated with HFMS and RULM in both subtypes.CONCLUSIONS: In SMA type 2 and non-ambulant type 3 lung function declines differently, with a common levelling after age 13 years. Lung and motor function correlated in both subtypes. Our data further defines the milder SMA phenotypes and provides novel information to benchmark the long-term efficacy of new treatments for SMA.

    View details for DOI 10.1212/WNL.0000000000011051

    View details for PubMedID 33067401

  • Switching between disease-modifying therapies in patients with spinal muscular atrophy: real-world data collected from the RESTORE Registry Servais, L., Day, J., De Vivo, D., Kirschner, J., Mercuri, E., Muntoni, F., Shieh, P., Tizzano, E., Desguerre, I., Quijano-Roy, S., Saito, K., Droege, M., Dabbous, O., Shah, A., Anderson, F., Finkel, R. PERGAMON-ELSEVIER SCIENCE LTD. 2020: S97
  • One-time administration of AVXS-101 intrathecal (IT) for spinal muscular atrophy in the phase 1 study (STRONG): safety report Chand, D., Finkel, R., Day, J., Darris, B., Kuntz, N., Connolly, A., Zaidman, C., Crawford, T., Butterfield, R., Shieh, P., Tennekoon, G., Brandesma, J., Iannaccone, S., Meriggioli, M., Tauscher-Wisniewski, S., Shoffner, J., Ogrinc, F., Kavanagh, S., Feltner, D., Mendell, J. PERGAMON-ELSEVIER SCIENCE LTD. 2020: S120
  • Escalating dose and randomized, controlled study of high-dose nusinersen in SMA; study design and updated enrollment for the DEVOTE Study Finkel, R., Day, J., Ryan, M., Mercuri, E., De Vivo, D., Pascual, S., Montes, J., Gurgel-Giannetti, J., Mitchell-Sweeney, N., Foster, R., Sun, P., Ramirez-Schrempp, D., Kandinov, B., Farwell, W. PERGAMON-ELSEVIER SCIENCE LTD. 2020: S124
  • SUNFISH Part 1: 24-month safety and exploratory outcomes of risdiplam (RG7916) treatment in patients with Type 2 or 3 spinal muscular atrophy (SMA) Day, J., Baranello, G., Boespflug-Tanguy, O., Borell, S., Goemans, N., Kirschner, J., Masson, R., Pera, M., Servais, L., Fuhrer, S., Gerber, M., Gorni, K., Kletzl, H., Martin, C., Scalco, R., Staunton, H., Yeung, W., Mercuri, E. PERGAMON-ELSEVIER SCIENCE LTD. 2020: S123
  • FIREFISH Part 1: 24-month safety and exploratory outcomes of risdiplam (RG7916) in infants with Type 1 spinal muscular atrophy (SMA) Baranello, G., Bloespflug-Tanguy, O., Darras, B., Day, J., Deconinck, N., Klein, A., Masson, R., Mercuri, E., Dodman, A., El-Khairi, M., Gerber, M., Gorni, K., Kletzl, H., Scalco, R., Servais, L. PERGAMON-ELSEVIER SCIENCE LTD. 2020: S122
  • Nusinersen in adolescents and young adults with SMA: Longitudinal experience from an expanded cohort of CS2/CS12 and SHINE participants Darras, B., Day, J., Swoboda, K., Chiriboga, C., Iannaccone, S., De Vivo, D., Deconinck, N., Finkel, R., Tulinius, M., Saito, K., Montes, J., Foster, R., Ramirez-Schrempp, D., Kandinov, B., Wong, J., Farwell, W. PERGAMON-ELSEVIER SCIENCE LTD. 2020: S120
  • FIREFISH Parts 1 and 2: 12-month pooled safety and efficacy outcomes of risdiplam (RG7916) in infants with Type 1 spinal muscular atrophy (SMA) Servais, L., Bloespflug-Tanguy, O., Darras, B., Day, J., Deconinck, N., Klein, A., Masson, R., Mazurkiewicz-Beldzinska, M., Mercuri, E., Rose, K., Vlodavets, D., Xiong, H., Zanoteli, E., Dodman, A., El-Khairi, M., Gerber, M., Gorni, K., Kletzl, H., Scalco, R., Baranello, G. PERGAMON-ELSEVIER SCIENCE LTD. 2020: S126
  • Analysis of Cobb angle and clinical characteristics in children with spinal muscular atrophy who enrolled in CHERISH and SHINE Young, S., Montes, J., Glanzman, A., Gee, R., Day, J., Finkel, R., Darras, B., De Vivo, D., Gambino, G., Foster, R., Wong, J., Kandinov, B., Berger, Z. PERGAMON-ELSEVIER SCIENCE LTD. 2020: S70
  • Clinical variability in spinal muscular atrophy type III. Annals of neurology Coratti, G., Messina, S., Lucibello, S., Pera, M. C., Montes, J., Pasternak, A., Stat, F. B., Escudero, J. E., Mazzone, E. S., Mayhew, A., Glanzman, A. M., Young, S. D., Salazar, R., Duong, T., Lofra, R. M., de Sanctis, R., Carnicella, S., Milev, E., Civitello, M., Pane, M., Scoto, M., Bettolo, C. M., Antonaci, L., Frongia, A., Sframeli, M., Vita, G. L., D'Amico, A., van den Hauwe, M., Albamonte, E., Goemans, N., Darras, B. T., Bertini, E., Sansone, V., Day, J., Osorio, A. N., Bruno, C., Muntoni, F., De Vivo, D. C., Finkel, R. S., Mercuri, E. 2020

    Abstract

    OBJECTIVE: We report natural history data in a large cohort of 199 spinal muscular atrophy (SMA) type III patients assessed using the Hammersmith Functional Motor Scale Expanded (HFMSE). The aim of the study was to establish annual rate and possible patterns of progression according to a number of variables, such as age of onset, age at assessment, SMN2 copy number and functional status.METHODS: HFMSE longitudinal changes were assessed using piecewise linear mixed-effects models. The dependency in the data due to repeated measures was accounted for by a random intercept per individual and an unstructured covariance R matrix was used as correlation structure. An additional descriptive analysis was performed for 123 patients, for a total of 375 12-month assessments.RESULTS: A break point at age 7 was set for the whole cohort and for SMA IIIA and IIIB. Age, SMA type and ambulatory status were significantly associated with changes in mean HFMSE score while sex and SMN2 copy number were not. The increase in response before the break point of age 7 is significant only for SMA IIIA (beta=1.79, p<.0001). After the break point the change in the rate of HFMSE score significantly decrease for both SMA IIIA (beta=1.15, p<.0001) and IIIB (beta=0.69, p=0.002).INTERPRETATION: Our findings contribute to the understanding of the natural history of type III SMA and will be helpful in the interpretation of the real-world data of patients treated with commercially available drugs. This article is protected by copyright. All rights reserved.

    View details for DOI 10.1002/ana.25900

    View details for PubMedID 32926458

  • Cobblestone Malformation in LAMA2 Congenital Muscular Dystrophy (MDC1A). Journal of neuropathology and experimental neurology Jayakody, H., Zarei, S., Nguyen, H., Dalton, J., Chen, K., Hudgins, L., Day, J., Withrow, K., Pandya, A., Teasley, J., Dobyns, W. B., Mathews, K. D., Moore, S. A. 2020

    Abstract

    Congenital muscular dystrophy type 1A (MDC1A) is caused by recessive variants in laminin alpha2 (LAMA2). Patients have been found to have white matter signal abnormalities on magnetic resonance imaging (MRI) but rarely structural brain abnormalities. We describe the autopsy neuropathology in a 17-year-old with white matter signal abnormalities on brain MRI. Dystrophic pathology was observed in skeletal muscle, and the sural nerve manifested a mild degree of segmental demyelination and remyelination. A diffuse, bilateral cobblestone appearance, and numerous points of fusion between adjacent gyri were apparent on gross examination of the cerebrum. Brain histopathology included focal disruptions of the glia limitans associated with abnormal cerebral cortical lamination or arrested cerebellar granule cell migration. Subcortical nodular heterotopia was present within the cerebellar hemispheres. Sampling of the centrum semiovale revealed no light microscopic evidence of leukoencephalopathy. Three additional MDC1A patients were diagnosed with cobblestone malformation on brain MRI. Unlike the autopsied patient whose brain had a symmetric distribution of cobblestone pathology, the latter patients had asymmetric involvement, most severe in the occipital lobes. These cases demonstrate that cobblestone malformation may be an important manifestation of the brain pathology in MDC1A and can be present even when patients have a structurally normal brain MRI.

    View details for DOI 10.1093/jnen/nlaa062

    View details for PubMedID 32827036

  • Procedural Patterns and Safety of Atrial Fibrillation Ablation: Findings from Get with The Guidelines-Atrial Fibrillation. Circulation. Arrhythmia and electrophysiology Loring, Z., Holmes, D. N., Matsouaka, R. A., Curtis, A. B., Day, J. D., Desai, N., Ellenbogen, K. A., Feld, G. K., Fonarow, G. C., Frankel, D. S., Hurwitz, J. L., Knight, B. P., Joglar, J. A., Russo, A. M., Sidhu, M. S., Turakhia, M. P., Lewis, W. R., Piccini, J. P. 2020

    Abstract

    Background - Catheter ablation is an increasingly utilized treatment for symptomatic atrial fibrillation (AF). However, there are limited prospective, nationwide data on patient selection and procedural characteristics. This study describes patient characteristics, techniques, treatment patterns, and safety outcomes of patients undergoing AF ablation. Methods - A total of 3,139 patients undergoing AF ablation between 2016-2018 in the Get With The Guidelines-Atrial Fibrillation registry from 24 US centers were included. Patient demographics, medical history, procedural details and complications were abstracted. Differences between paroxysmal and persistent AF patients were compared using Pearson's Chi-square and Wilcoxon rank-sum tests. Results - Patients undergoing AF ablation were predominantly male (63.9%) and Caucasian (93.2%) with a median age of 65. Hypertension was the most common comorbidity (67.6%) and persistent AF patients had more comorbidities than paroxysmal AF patients. Drug refractory, paroxysmal AF was the most common ablation indication (Class I, 53.6%) followed by drug refractory, persistent AF (Class I, 41.8%). Radiofrequency (RF) ablation with contact force (CF) sensing was the most common ablation modality (70.5%); 23.7% of patients underwent cryoballoon ablation. Pulmonary vein isolation (PVI) was performed in 94.6% of de novo ablations; the most common adjunctive lesions included left atrial roof or posterior/inferior lines, and cavotricuspid isthmus ablation. Complications were uncommon (5.1%), and were life-threatening in 0.7% of cases. Conclusions - More than 98% of AF ablations among participating sites are performed for Class I or Class IIA indications. CF-guided RF ablation is the dominant technique and PVI the principal lesion set. In-hospital complications are uncommon and rarely life-threatening.

    View details for DOI 10.1161/CIRCEP.119.007944

    View details for PubMedID 32703018

  • Gain and loss of abilities in type II SMA: A 12-month natural history study. Neuromuscular disorders : NMD Coratti, G., Lucibello, S., Pera, M. C., Duong, T., Muni Lofra, R., Civitello, M., D'Amico, A., Goemans, N., Darras, B. T., Bruno, C., Sansone, V. A., Day, J., Nascimento Osorio, A., Muntoni, F., Montes, J., Sframeli, M., Finkel, R., Mercuri, E., ISMAC group 2020

    Abstract

    The advent of clinical trials in spinal muscular atrophy (SMA) has highlighted the need to define patterns of progression using functional scales. It has recently been suggested that the analysis of abilities gained or lost applied to functional scales better reflects meaningful changes. We defined as "gain" a positive change between scores from 0 to either 1 or 2 and as "loss" a negative change from either 2 or 1 to 0. The aim of this study was to describe, over 12 months, which abilities on the Hammersmith Functional Motor Scale Expanded (HFMSE) were more frequently lost or gained in patients with SMA II. The cohort included 614 12-month assessments from 243 patients (age range: 30 months - 63 years; mean 9.94, SD ±7.91). The peak of abilities gained occurred before the age of 5 years while the highest number of lost abilities was found in the group 5-13 years. A correlation between the HFMSE baseline score and the ordinal number of the items was found for both lost (p<0.001) or gained (p<0.001) activities. No correlation was found with SMN2 copy number. These findings will have implications for clinical trial design and for the interpretation of real-world data using new therapeutic approaches.

    View details for DOI 10.1016/j.nmd.2020.07.004

    View details for PubMedID 32893082

  • Diagnosis of Myotonic Dystrophy Based on Resting State fMRI Using Convolutional Neural Networks. Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Annual International Conference Kamali, T., Hagerman, K. A., Day, J. W., Sampson, J., Lim, K. O., Mueller, B. A., Wozniak, J. 2020; 2020: 1714–17

    Abstract

    Myotonic dystrophies (DM) are neuromuscular conditions that cause widespread effects throughout the body. There are brain white matter changes on MRI in patients with DM that correlate with neuropsychological functional changes. How these brain alterations causally relate to the presence and severity of cognitive symptoms remains largely unknown. Deep neural networks have significantly improved the performance of image classification of huge datasets. However, its application in brain imaging is limited and not well described, due to the scarcity of labeled training data. In this work, we propose an approach for the diagnosis of DM based on a spatio-temporal deep learning paradigm. The obtained accuracy (73.71%) and sensitivities and specificities showed that the implemented approach based on 4-D convolutional neural networks leads to a compact, discriminative, and fast computing DM-based clinical medical decision support system.Clinical relevance- Many adults with DM experience cognitive and neurological effects impacting their quality of life, and ability to maintain employment. A robust and reliable DM-based clinical decision support system may help reduce the long diagnostic delay common to DM. Furthermore, it can help neurologists better understand the pathophysiology of the disease and analyze effects of new drugs that aim to address the neurological symptoms of DM.

    View details for DOI 10.1109/EMBC44109.2020.9176455

    View details for PubMedID 33018327

  • Determining An Appropriate Cardiopulmonary Exercise Testing Protocol For Individuals With Neuromuscular Disease Duong, T., Day, J., Dunaway-Young, S., Stevens, V. LIPPINCOTT WILLIAMS & WILKINS. 2020: 640
  • Descriptive analysis of varying real-world treatment patterns and outcomes in patients with spinal muscular atrophy collected from the RESTORE registry Finkel, R. S., Day, J. W., De Vivo, D. C., Kirschner, J., Mercuri, E., Muntoni, F., Shieh, P. B., Tizzano, E., Desguerre, I., Quijano-Roy, S., Saito, K., Droege, M., Dabbous, C., Shah, A., Khan, F., Anderson, F. A., Servais, L. WILEY. 2020: 620–21
  • SUNFISH Part 2: Efficacy and safety of risdiplam (RG7916) in patients with Type 2 or non-ambulant Type 3 spinal muscular atrophy (SMA) Mercuri, E., Barisic, N., Boespflug-Tanguy, O., Day, J. W., Deconinck, N., Kostera-Pruszczyk, A., Masson, R., Mazzone, E., Nascimento, A., Saito, K., Vlodavets, D., Fuerst-Recktenwald, S., Fuhrer, S., Gerber, M., Gorni, K., Kletzl, H., Martin, C., Yeung, W. Y., Vuillerot, C. WILEY. 2020: 869
  • Real-World Treatment Patterns and Outcomes in Patients with Spinal Muscular Atrophy Collected from the RESTORE Registry Servais, L., Day, J. W., De Vivo, D. C., Kirschner, J., Mercuri, E., Muntoni, F., Shieh, P. B., Tizzano, E., Desguerre, I., Quijano-Roy, S., Saito, K., Droege, M., Dabbous, O., Shah, A., Khan, F., Anderson, F. A., Finkel, R. S. LIPPINCOTT WILLIAMS & WILKINS. 2020
  • SUNFISH Part 2: Efficacy and Safety of Risdiplam (RG7916) in Patients with Type 2 or Non-Ambulant Type 3 Spinal Muscular Atrophy (SMA) Mercuri, E., Barisic, N., Boespflug-Tanguy, O., Deconinck, N., Kostera-Pruszczyk, A., Masson, R., Mazzone, E., Nascimento, A., Saito, K., Vlodavets, D., Vuillerot, C., Fuerst-Recktenwald, S., Fuhrer, S., Gerber, M., Gorni, K., Kletzl, H., Martin, C., Yeung, W., Day, J. W., SUNFISH Study Grp LIPPINCOTT WILLIAMS & WILKINS. 2020
  • One-Time Intrathecal (IT) Administration of AVXS-101 IT Gene-Replacement Therapy for Spinal Muscular Atrophy: Phase 1 Study (STRONG) Finkel, R. S., Day, J. W., Darras, B. T., Kuntz, N. L., Connolly, A. M., Crawford, T., Butterfield, R. J., Shieh, P. B., Tennekoon, G., Iannaccone, S. T., Meriggioli, M., Tauscher-Wisniewski, S., Shoffner, J., Ogrinc, F. G., Kavanagh, S., Kernbauer, E., Whittle, J., Sproule, D. M., Feltner, D. E., Mendell, J. R. LIPPINCOTT WILLIAMS & WILKINS. 2020
  • JEWELFISH: Safety and Pharmacodynamic Data in Non-Naive Patients with Spinal Muscular Atrophy (SMA) Receiving Treatment with Risdiplam (RG7916) Chiriboga, C., Bruno, C., Day, J. W., Duong, T., Fischer, D., Kirschner, J., Muntoni, F., Fuerst-Recktenwald, S., Gerber, M., Gorni, K., Kletzl, H., Warren, F., Yeung, W., Mercuri, E., JEWELFISH Study Grp LIPPINCOTT WILLIAMS & WILKINS. 2020
  • Pooled Safety Data from the Risdiplam (RG7916) Clinical Trial Development Program Baranello, G., Bertini, E., Chiriboga, C., Darras, B. T., Day, J. W., Deconinck, N., Fischer, D., Goemans, N., Kirschner, J., Klein, A., Masson, R., Mazurkiewicz-Beldzinska, M., Servais, L., Wang, Y., Fuerst-Recktenwald, S., Gerber, M., Gorni, K., Jaber, B., McIver, T., Scalco, R., Eugenio Mercuri FIREFISH, SUNFISH, JEWELFISH Study Grp LIPPINCOTT WILLIAMS & WILKINS. 2020
  • Onasemnogene Abeparvovec-xioi Gene-Replacement Therapy for Spinal Muscular Atrophy Type 1 (SMA1): Phase 3 US Study (STR1VE) Update Day, J. W., Chiriboga, C. A., Crawford, T. O., Darras, B. T., Finkel, R. S., Connolly, A. M., Iannaccone, S. T., Kuntz, N. L., Pena, L. M., Shieh, P. B., Smith, E. C., Schultz, M., Feltner, D. E., Tauscher-Wisniewski, S., Ogrinc, F. G., Shah, A., Ouyang, H., Macek, T., Kernbauer, E., Sproule, D. M., Mendell, J. R. LIPPINCOTT WILLIAMS & WILKINS. 2020
  • Escalating Dose and Randomized, Controlled Study of Nusinersen in Participants with Spinal Muscular Atrophy; Study Design of the Phase 2/3 DEVOTE (232SM203) Study to Explore High Dose Nusinersen Finkel, R. S., Day, J. W., Mitchell-Sweeney, N., Foster, R., Sun, P., Bhan, I., Kandinov, B., Farwell, W. LIPPINCOTT WILLIAMS & WILKINS. 2020
  • Longer-term Experience with Nusinersen in Teenagers and Young Adults with Spinal Muscular Atrophy: Results from the CS2/CS12 and SHINE Studies Day, J. W., Swoboda, K. J., Darras, B. T., Chiriboga, C. A., Iannaccone, S. T., De Vivo, D. C., Deconinck, N., Finkel, R. S., Tulinius, M., Saito, K., Montes, J., Sun, P., Bhan, I., Kandinov, B., Wong, J., Farwell, W. LIPPINCOTT WILLIAMS & WILKINS. 2020
  • RESTORE: A Prospective Multinational Registry of Patients with Genetically Confirmed Spinal Muscular Atrophy - Rationale and Study Design. Journal of neuromuscular diseases Finkel, R. S., Day, J. W., De Vivo, D. C., Kirschner, J., Mercuri, E., Muntoni, F., Shieh, P. B., Tizzano, E., Desguerre, I., Quijano-Roy, S., Saito, K., Droege, M., Dabbous, O., Khan, F., Renault, L., Anderson, F. A., Servais, L. 2020

    Abstract

    BACKGROUND: Dramatic improvements in spinal muscular atrophy (SMA) treatment have changed the prognosis for patients with this disease, leading to important new questions. Gathering representative, real-world data about the long-term efficacy and safety of emerging SMA interventions is essential to document their impact on patients and caregivers.OBJECTIVES: This registry will assess outcomes in patients with genetically confirmed SMA and provide information on the effectiveness and long-term safety of approved and emerging treatments.DESIGN AND METHODS: RESTORE is a prospective, multicenter, multinational observational registry. Patients will be managed according to usual clinical practice. Both newly recruitedSMAtreatment centers and sites involved in existing SMA registries, including iSMAC, Treat-NMD, French SMA Assistance Publique- Hopitaux de Paris (AP-HP), Cure-SMA, SMArtCARE, will be eligible to participate; de novo; sites already participating in another registry may be included via consortium agreements. Data from patients enrolled in partnering registries will be shared with the RESTORE Registry and data for newly diagnosed patients will be added upon enrollment. Patients will be enrolled over a 5-year period and followed for 15 years or until death. Assessments will include SMA history and treatment, pulmonary, nutritional, and motor milestones, healthcare resource utilization, work productivity, activity impairment, adverse events, quality of life, caregiver burden, and survival.Status:Recruitment started in September 2018. As of January 3, 2020, 64 patients were enrolled at 25 participating sites.CONCLUSIONS: The RESTORE Registry has begun recruiting recently diagnosed patients with genetically confirmed SMA, enabling assessment of both short- and long-term patient outcomes.

    View details for DOI 10.3233/JND-190451

    View details for PubMedID 32039859

  • Revised Recommendations for the Treatment of Infants Diagnosed with Spinal Muscular Atrophy Via Newborn Screening Who Have 4 Copies of SMN2. Journal of neuromuscular diseases Glascock, J., Sampson, J., Connolly, A. M., Darras, B. T., Day, J. W., Finkel, R., Howell, R. R., Klinger, K. W., Kuntz, N., Prior, T., Shieh, P. B., Crawford, T. O., Kerr, D., Jarecki, J. 2020

    View details for DOI 10.3233/JND-190468

    View details for PubMedID 32007960

  • A longitudinal study of CMT1A using Rasch analysis based CMT neuropathy and examination scores. Neurology Fridman, V. n., Sillau, S. n., Acsadi, G. n., Bacon, C. n., Dooley, K. n., Burns, J. n., Day, J. n., Feely, S. n., Finkel, R. S., Grider, T. n., Gutmann, L. n., Herrmann, D. N., Kirk, C. A., Knause, S. A., Laurá, M. n., Lewis, R. A., Li, J. n., Lloyd, T. E., Moroni, I. n., Muntoni, F. n., Pagliano, E. n., Pisciotta, C. n., Piscosquito, G. n., Ramchandren, S. n., Saporta, M. n., Sadjadi, R. n., Shy, R. R., Siskind, C. E., Sumner, C. J., Walk, D. n., Wilcox, J. n., Yum, S. W., Züchner, S. n., Scherer, S. S., Pareyson, D. n., Reilly, M. M., Shy, M. E. 2020

    Abstract

    To evaluate the sensitivity of Rasch analysis-based, weighted Charcot-Marie-Tooth Neuropathy and Examination Scores (CMTNS-R and CMTES-R) to clinical progression in patients with Charcot-Marie-Tooth disease type 1A (CMT1A).Patients with CMT1A from 18 sites of the Inherited Neuropathies Consortium were evaluated between 2009 and 2018. Weighted CMTNS and CMTES modified category responses were developed with Rasch analysis of the standard scores. Change from baseline for CMTNS-R and CMTES-R was estimated with longitudinal regression models.Baseline CMTNS-R and CMTES-R scores were available for 517 and 1,177 participants, respectively. Mean ± SD age of participants with available CMTES-R scores was 41 ± 18 (range 4-87) years, and 56% were female. Follow-up CMTES-R assessments at 1, 2, and 3 years were available for 377, 321, and 244 patients. A mixed regression model showed significant change in CMTES-R score at years 2 through 6 compared to baseline (mean change from baseline 0.59 points at 2 years, p = 0.0004, n = 321). Compared to the original CMTES, the CMTES-R revealed a 55% improvement in the standardized response mean (mean change/SD change) at 2 years (0.17 vs 0.11). Change in CMTES-R at 2 years was greatest in mildly to moderately affected patients (1.48-point mean change, 95% confidence interval 0.99-1.97, p < 0.0001, for baseline CMTES-R score 0-9).The CMTES-R demonstrates change over time in patients with CMT1A and is more sensitive than the original CMTES. The CMTES-R was most sensitive to change in patients with mild to moderate baseline disease severity and failed to capture progression in patients with severe CMT1A.NCT01193075.

    View details for DOI 10.1212/WNL.0000000000009035

    View details for PubMedID 32047073

  • Intensive Teenage Activity Is Associated With Greater Muscle Hyperintensity on T1W Magnetic Resonance Imaging in Adults With Dysferlinopathy. Frontiers in neurology Moore, U. n., Jacobs, M. n., Fernandez-Torron, R. n., LLauger Rossello, J. n., Smith, F. E., James, M. n., Mayhew, A. n., Rufibach, L. n., Carlier, P. G., Blamire, A. M., Day, J. W., Jones, K. J., Bharucha-Goebel, D. X., Salort-Campana, E. n., Pestronk, A. n., Walter, M. C., Paradas, C. n., Stojkovic, T. n., Mori-Yoshimura, M. n., Bravver, E. n., Pegoraro, E. n., Mendell, J. R., Bushby, K. n., Straub, V. n., Diaz-Manera, J. n. 2020; 11: 613446

    Abstract

    Practice of sports during childhood or adolescence correlates with an earlier onset and more rapidly progressing phenotype in dysferlinopathies. To determine if this correlation relates to greater muscle pathology that persists into adulthood, we investigated the effect of exercise on the degree of muscle fatty replacement measured using muscle MRI. We reviewed pelvic, thigh and leg T1W MRI scans from 160 patients with genetically confirmed dysferlinopathy from the Jain Foundation International clinical outcomes study in dysferlinopathy. Two independent assessors used the Lamminen-Mercuri visual scale to score degree of fat replacement in each muscle. Exercise intensity for each individual was defined as no activity, minimal, moderate, or intensive activity by using metabolic equivalents and patient reported frequency of sports undertaken between the ages of 10 and 18. We used ANCOVA and linear modeling to compare the mean Lamminen-Mercuri score for the pelvis, thigh, and leg between exercise groups, controlling for age at assessment and symptom duration. Intensive exercisers showed greater fatty replacement in the muscles of the pelvis than moderate exercisers, but no significant differences of the thigh or leg. Within the pelvis, Psoas was the muscle most strongly associated with this exercise effect. In patients with a short symptom duration of <15 years there was a trend toward greater fatty replacement in the muscles of the thigh. These findings define key muscles involved in the exercise-phenotype effect that has previously been observed only clinically in dysferlinopathy and support recommendations that pre-symptomatic patients should avoid very intensive exercise.

    View details for DOI 10.3389/fneur.2020.613446

    View details for PubMedID 33391171

    View details for PubMedCentralID PMC7773023

  • Onasemnogene Abeparvovec-xioi Gene-Replacement Therapy for Spinal Muscular Atrophy Type 1: Pulmonary and Ventilatory Findings from the Pivotal Phase 3 US Study (STR1VE) Shell, R., Day, J. W., Chiriboga, C. A., Crawford, T. O., Darras, B. T., Finkel, R. S., Connolly, A. M., Iannaconne, S. T., Kuntz, N. L., Pena, L. M., Shieh, P. B., Smith, E. C., Kwon, J. M., Zaidman, C., Schultz, M., Feltner, D. E., Tauscher-Wisniewski, S., Ogrinc, F. G., Thomasma, P., Ouyang, H., Macek, T. A., Kernbauer, E., Sproule, D. M., Mendell, J. R. AMER THORACIC SOC. 2020
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  • ONASEMNOGENE ABEPARVOVEC GENE-REPLACEMENT THERAPY (GRT) FOR SPINAL MUSCULAR ATROPHY TYPE 1 (SMA1): PRELIMINARY PULMONARY AND VENTILATORY FINDINGS FROM THE PHASE 3 STUDY (STR1VE) Shell, R., Day, J. W., Chiriboga, C. A., Crawford, T. O., Darras, B. T., Finkel, R. S., Connolly, A. M., Iannaccone, S. T., Kuntz, N. L., Pena, L. M., Shieh, P. B., Smith, E. C., Kausar, I., Schultz, M., Feltner, D. E., Ogrinc, F. G., Macek, T. A., Kernbauer, E., L'Italien, J., Sproule, D. M., Kaspar, B. K., Mendell, J. R. BMJ PUBLISHING GROUP. 2019: A42
  • Clinical characteristics and genotypes in the ADVANCE baseline data set, a comprehensive cohort of US children and adolescents with Pompe disease GENETICS IN MEDICINE Kishnani, P. S., Gibson, J. B., Gambello, M. J., Hillman, R., Stockton, D. W., Kronn, D., Leslie, N. D., Pena, L. M., Tanpaiboon, P., Day, J. W., Wang, R. Y., Goldstein, J. L., Haack, K., Sparks, S. E., Zhao, Y., Hahn, S., Pompe ADVANCE Study Consortium 2019; 21 (11): 2543–51
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  • Intrathecal administration of AVXS-101 gene-replacement therapy (GRT) for spinal muscular atrophy type 2 (SMA2): Phase 1/2A study (strong) Finkel, R. S., Day, J. W., Darras, B. T., Kuntz, N. L., Connolly, A. M., Crawford, T. O., Butterfield, R. J., Shieh, P. B., Tennekoon, G., Iannaccone, S. T., Meriggioli, M., Ogrinc, F. G., Kavanagh, S., Kernbauer, E., Whittle, J., L'Italien, J., Kaspar, B., Sproule, D. M., Spector, S. A., Feltner, D. E., Mendell, J. R. ELSEVIER. 2019
  • Onasemnogene abeparvovec gene-replacement therapy (GRT) for spinal muscular atrophy type 1 (SMA1): Global pivotal phase 3 study program (STR1VE-US, STR1VE-EU, STR1VE-AP) Mercuri, E., Baranello, G., Day, J. W., Bruno, C., Corti, S., Chiriboga, C. A., Crawford, T. O., Darras, B. T., Finkel, R. S., Connolly, A. M., Iannaccone, S. T., Kuntz, N. L., Masson, R., Pena, L. M., Baldinetti, F., Schultz, M., Shieh, P. B., Smith, E. C., Saito, K., Scoto, M., Spector, S. A., Truncated, A., Sproule, D. M., Mendell, J. R., Muntoni, F. ELSEVIER. 2019
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  • Adeno-Associated Virus Serotype 9 (AAV9) Antibodies in Patients With Spinal Muscular Atrophy (SMA) Screened for Treatment With Gene-Replacement Therapy (GRT) Onasemnogene Abeparvovec Day, J., Finkel, R., Mercuri, E., Swoboda, K., Kernbauer, E., Ogrinc, F., Menier, M., Sproule, D., Feltner, D., Mendell, J. WILEY. 2019: S121
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