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August 21, 2018; 91 (8) Article

An observational study of functional abilities in infants, children, and adults with type 1 SMA

Marika Pane, Concetta Palermo, Sonia Messina, Valeria A. Sansone, Claudio Bruno, Michela Catteruccia, Maria Sframeli, Emilio Albamonte, Marina Pedemonte, Adele D'Amico, Giorgia Brigati, Roberto de Sanctis, Giorgia Coratti, Simona Lucibello, Enrico Bertini, Giuseppe Vita, Francesco Danilo Tiziano, Eugenio Mercuri, on behalf of the Italian EAP Working Group
First published July 25, 2018, DOI: https://doi.org/10.1212/WNL.0000000000006050
Marika Pane
From Paediatric Neurology and Centro Clinico Nemo (M. Pane, C.P., R.d.S., G.C., S.L.), Catholic University and Fondazione Policlinico Gemelli IRCCS, Rome; Department of Clinical and Experimental Medicine (S.M., M.S., G.V., E.M.), University of Messina and Centro Clinico Nemo, Messina; Neurorehabilitation Unit (V.S., E.A.), University of Milan, Centro Clinico Nemo, Niguarda Hospital, Milan; Center of Myology and Neurodegenerative Disorders (C.B., M. Pedemonte, G.B.), Istituto Giannina Gaslini, Genoa; Unit of Neuromuscular and Neurodegenerative Disorders (M.C., A.D., E.B.), Bambino Gesù Children's Hospital, Rome; and Institute of Genomic Medicine (F.D.T.), Catholic University, Rome, Italy.
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Concetta Palermo
From Paediatric Neurology and Centro Clinico Nemo (M. Pane, C.P., R.d.S., G.C., S.L.), Catholic University and Fondazione Policlinico Gemelli IRCCS, Rome; Department of Clinical and Experimental Medicine (S.M., M.S., G.V., E.M.), University of Messina and Centro Clinico Nemo, Messina; Neurorehabilitation Unit (V.S., E.A.), University of Milan, Centro Clinico Nemo, Niguarda Hospital, Milan; Center of Myology and Neurodegenerative Disorders (C.B., M. Pedemonte, G.B.), Istituto Giannina Gaslini, Genoa; Unit of Neuromuscular and Neurodegenerative Disorders (M.C., A.D., E.B.), Bambino Gesù Children's Hospital, Rome; and Institute of Genomic Medicine (F.D.T.), Catholic University, Rome, Italy.
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Sonia Messina
From Paediatric Neurology and Centro Clinico Nemo (M. Pane, C.P., R.d.S., G.C., S.L.), Catholic University and Fondazione Policlinico Gemelli IRCCS, Rome; Department of Clinical and Experimental Medicine (S.M., M.S., G.V., E.M.), University of Messina and Centro Clinico Nemo, Messina; Neurorehabilitation Unit (V.S., E.A.), University of Milan, Centro Clinico Nemo, Niguarda Hospital, Milan; Center of Myology and Neurodegenerative Disorders (C.B., M. Pedemonte, G.B.), Istituto Giannina Gaslini, Genoa; Unit of Neuromuscular and Neurodegenerative Disorders (M.C., A.D., E.B.), Bambino Gesù Children's Hospital, Rome; and Institute of Genomic Medicine (F.D.T.), Catholic University, Rome, Italy.
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Valeria A. Sansone
From Paediatric Neurology and Centro Clinico Nemo (M. Pane, C.P., R.d.S., G.C., S.L.), Catholic University and Fondazione Policlinico Gemelli IRCCS, Rome; Department of Clinical and Experimental Medicine (S.M., M.S., G.V., E.M.), University of Messina and Centro Clinico Nemo, Messina; Neurorehabilitation Unit (V.S., E.A.), University of Milan, Centro Clinico Nemo, Niguarda Hospital, Milan; Center of Myology and Neurodegenerative Disorders (C.B., M. Pedemonte, G.B.), Istituto Giannina Gaslini, Genoa; Unit of Neuromuscular and Neurodegenerative Disorders (M.C., A.D., E.B.), Bambino Gesù Children's Hospital, Rome; and Institute of Genomic Medicine (F.D.T.), Catholic University, Rome, Italy.
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Claudio Bruno
From Paediatric Neurology and Centro Clinico Nemo (M. Pane, C.P., R.d.S., G.C., S.L.), Catholic University and Fondazione Policlinico Gemelli IRCCS, Rome; Department of Clinical and Experimental Medicine (S.M., M.S., G.V., E.M.), University of Messina and Centro Clinico Nemo, Messina; Neurorehabilitation Unit (V.S., E.A.), University of Milan, Centro Clinico Nemo, Niguarda Hospital, Milan; Center of Myology and Neurodegenerative Disorders (C.B., M. Pedemonte, G.B.), Istituto Giannina Gaslini, Genoa; Unit of Neuromuscular and Neurodegenerative Disorders (M.C., A.D., E.B.), Bambino Gesù Children's Hospital, Rome; and Institute of Genomic Medicine (F.D.T.), Catholic University, Rome, Italy.
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Michela Catteruccia
From Paediatric Neurology and Centro Clinico Nemo (M. Pane, C.P., R.d.S., G.C., S.L.), Catholic University and Fondazione Policlinico Gemelli IRCCS, Rome; Department of Clinical and Experimental Medicine (S.M., M.S., G.V., E.M.), University of Messina and Centro Clinico Nemo, Messina; Neurorehabilitation Unit (V.S., E.A.), University of Milan, Centro Clinico Nemo, Niguarda Hospital, Milan; Center of Myology and Neurodegenerative Disorders (C.B., M. Pedemonte, G.B.), Istituto Giannina Gaslini, Genoa; Unit of Neuromuscular and Neurodegenerative Disorders (M.C., A.D., E.B.), Bambino Gesù Children's Hospital, Rome; and Institute of Genomic Medicine (F.D.T.), Catholic University, Rome, Italy.
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Maria Sframeli
From Paediatric Neurology and Centro Clinico Nemo (M. Pane, C.P., R.d.S., G.C., S.L.), Catholic University and Fondazione Policlinico Gemelli IRCCS, Rome; Department of Clinical and Experimental Medicine (S.M., M.S., G.V., E.M.), University of Messina and Centro Clinico Nemo, Messina; Neurorehabilitation Unit (V.S., E.A.), University of Milan, Centro Clinico Nemo, Niguarda Hospital, Milan; Center of Myology and Neurodegenerative Disorders (C.B., M. Pedemonte, G.B.), Istituto Giannina Gaslini, Genoa; Unit of Neuromuscular and Neurodegenerative Disorders (M.C., A.D., E.B.), Bambino Gesù Children's Hospital, Rome; and Institute of Genomic Medicine (F.D.T.), Catholic University, Rome, Italy.
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Emilio Albamonte
From Paediatric Neurology and Centro Clinico Nemo (M. Pane, C.P., R.d.S., G.C., S.L.), Catholic University and Fondazione Policlinico Gemelli IRCCS, Rome; Department of Clinical and Experimental Medicine (S.M., M.S., G.V., E.M.), University of Messina and Centro Clinico Nemo, Messina; Neurorehabilitation Unit (V.S., E.A.), University of Milan, Centro Clinico Nemo, Niguarda Hospital, Milan; Center of Myology and Neurodegenerative Disorders (C.B., M. Pedemonte, G.B.), Istituto Giannina Gaslini, Genoa; Unit of Neuromuscular and Neurodegenerative Disorders (M.C., A.D., E.B.), Bambino Gesù Children's Hospital, Rome; and Institute of Genomic Medicine (F.D.T.), Catholic University, Rome, Italy.
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Marina Pedemonte
From Paediatric Neurology and Centro Clinico Nemo (M. Pane, C.P., R.d.S., G.C., S.L.), Catholic University and Fondazione Policlinico Gemelli IRCCS, Rome; Department of Clinical and Experimental Medicine (S.M., M.S., G.V., E.M.), University of Messina and Centro Clinico Nemo, Messina; Neurorehabilitation Unit (V.S., E.A.), University of Milan, Centro Clinico Nemo, Niguarda Hospital, Milan; Center of Myology and Neurodegenerative Disorders (C.B., M. Pedemonte, G.B.), Istituto Giannina Gaslini, Genoa; Unit of Neuromuscular and Neurodegenerative Disorders (M.C., A.D., E.B.), Bambino Gesù Children's Hospital, Rome; and Institute of Genomic Medicine (F.D.T.), Catholic University, Rome, Italy.
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Adele D'Amico
From Paediatric Neurology and Centro Clinico Nemo (M. Pane, C.P., R.d.S., G.C., S.L.), Catholic University and Fondazione Policlinico Gemelli IRCCS, Rome; Department of Clinical and Experimental Medicine (S.M., M.S., G.V., E.M.), University of Messina and Centro Clinico Nemo, Messina; Neurorehabilitation Unit (V.S., E.A.), University of Milan, Centro Clinico Nemo, Niguarda Hospital, Milan; Center of Myology and Neurodegenerative Disorders (C.B., M. Pedemonte, G.B.), Istituto Giannina Gaslini, Genoa; Unit of Neuromuscular and Neurodegenerative Disorders (M.C., A.D., E.B.), Bambino Gesù Children's Hospital, Rome; and Institute of Genomic Medicine (F.D.T.), Catholic University, Rome, Italy.
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Giorgia Brigati
From Paediatric Neurology and Centro Clinico Nemo (M. Pane, C.P., R.d.S., G.C., S.L.), Catholic University and Fondazione Policlinico Gemelli IRCCS, Rome; Department of Clinical and Experimental Medicine (S.M., M.S., G.V., E.M.), University of Messina and Centro Clinico Nemo, Messina; Neurorehabilitation Unit (V.S., E.A.), University of Milan, Centro Clinico Nemo, Niguarda Hospital, Milan; Center of Myology and Neurodegenerative Disorders (C.B., M. Pedemonte, G.B.), Istituto Giannina Gaslini, Genoa; Unit of Neuromuscular and Neurodegenerative Disorders (M.C., A.D., E.B.), Bambino Gesù Children's Hospital, Rome; and Institute of Genomic Medicine (F.D.T.), Catholic University, Rome, Italy.
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Roberto de Sanctis
From Paediatric Neurology and Centro Clinico Nemo (M. Pane, C.P., R.d.S., G.C., S.L.), Catholic University and Fondazione Policlinico Gemelli IRCCS, Rome; Department of Clinical and Experimental Medicine (S.M., M.S., G.V., E.M.), University of Messina and Centro Clinico Nemo, Messina; Neurorehabilitation Unit (V.S., E.A.), University of Milan, Centro Clinico Nemo, Niguarda Hospital, Milan; Center of Myology and Neurodegenerative Disorders (C.B., M. Pedemonte, G.B.), Istituto Giannina Gaslini, Genoa; Unit of Neuromuscular and Neurodegenerative Disorders (M.C., A.D., E.B.), Bambino Gesù Children's Hospital, Rome; and Institute of Genomic Medicine (F.D.T.), Catholic University, Rome, Italy.
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Giorgia Coratti
From Paediatric Neurology and Centro Clinico Nemo (M. Pane, C.P., R.d.S., G.C., S.L.), Catholic University and Fondazione Policlinico Gemelli IRCCS, Rome; Department of Clinical and Experimental Medicine (S.M., M.S., G.V., E.M.), University of Messina and Centro Clinico Nemo, Messina; Neurorehabilitation Unit (V.S., E.A.), University of Milan, Centro Clinico Nemo, Niguarda Hospital, Milan; Center of Myology and Neurodegenerative Disorders (C.B., M. Pedemonte, G.B.), Istituto Giannina Gaslini, Genoa; Unit of Neuromuscular and Neurodegenerative Disorders (M.C., A.D., E.B.), Bambino Gesù Children's Hospital, Rome; and Institute of Genomic Medicine (F.D.T.), Catholic University, Rome, Italy.
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Simona Lucibello
From Paediatric Neurology and Centro Clinico Nemo (M. Pane, C.P., R.d.S., G.C., S.L.), Catholic University and Fondazione Policlinico Gemelli IRCCS, Rome; Department of Clinical and Experimental Medicine (S.M., M.S., G.V., E.M.), University of Messina and Centro Clinico Nemo, Messina; Neurorehabilitation Unit (V.S., E.A.), University of Milan, Centro Clinico Nemo, Niguarda Hospital, Milan; Center of Myology and Neurodegenerative Disorders (C.B., M. Pedemonte, G.B.), Istituto Giannina Gaslini, Genoa; Unit of Neuromuscular and Neurodegenerative Disorders (M.C., A.D., E.B.), Bambino Gesù Children's Hospital, Rome; and Institute of Genomic Medicine (F.D.T.), Catholic University, Rome, Italy.
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Enrico Bertini
From Paediatric Neurology and Centro Clinico Nemo (M. Pane, C.P., R.d.S., G.C., S.L.), Catholic University and Fondazione Policlinico Gemelli IRCCS, Rome; Department of Clinical and Experimental Medicine (S.M., M.S., G.V., E.M.), University of Messina and Centro Clinico Nemo, Messina; Neurorehabilitation Unit (V.S., E.A.), University of Milan, Centro Clinico Nemo, Niguarda Hospital, Milan; Center of Myology and Neurodegenerative Disorders (C.B., M. Pedemonte, G.B.), Istituto Giannina Gaslini, Genoa; Unit of Neuromuscular and Neurodegenerative Disorders (M.C., A.D., E.B.), Bambino Gesù Children's Hospital, Rome; and Institute of Genomic Medicine (F.D.T.), Catholic University, Rome, Italy.
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Giuseppe Vita
From Paediatric Neurology and Centro Clinico Nemo (M. Pane, C.P., R.d.S., G.C., S.L.), Catholic University and Fondazione Policlinico Gemelli IRCCS, Rome; Department of Clinical and Experimental Medicine (S.M., M.S., G.V., E.M.), University of Messina and Centro Clinico Nemo, Messina; Neurorehabilitation Unit (V.S., E.A.), University of Milan, Centro Clinico Nemo, Niguarda Hospital, Milan; Center of Myology and Neurodegenerative Disorders (C.B., M. Pedemonte, G.B.), Istituto Giannina Gaslini, Genoa; Unit of Neuromuscular and Neurodegenerative Disorders (M.C., A.D., E.B.), Bambino Gesù Children's Hospital, Rome; and Institute of Genomic Medicine (F.D.T.), Catholic University, Rome, Italy.
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Francesco Danilo Tiziano
From Paediatric Neurology and Centro Clinico Nemo (M. Pane, C.P., R.d.S., G.C., S.L.), Catholic University and Fondazione Policlinico Gemelli IRCCS, Rome; Department of Clinical and Experimental Medicine (S.M., M.S., G.V., E.M.), University of Messina and Centro Clinico Nemo, Messina; Neurorehabilitation Unit (V.S., E.A.), University of Milan, Centro Clinico Nemo, Niguarda Hospital, Milan; Center of Myology and Neurodegenerative Disorders (C.B., M. Pedemonte, G.B.), Istituto Giannina Gaslini, Genoa; Unit of Neuromuscular and Neurodegenerative Disorders (M.C., A.D., E.B.), Bambino Gesù Children's Hospital, Rome; and Institute of Genomic Medicine (F.D.T.), Catholic University, Rome, Italy.
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Eugenio Mercuri
From Paediatric Neurology and Centro Clinico Nemo (M. Pane, C.P., R.d.S., G.C., S.L.), Catholic University and Fondazione Policlinico Gemelli IRCCS, Rome; Department of Clinical and Experimental Medicine (S.M., M.S., G.V., E.M.), University of Messina and Centro Clinico Nemo, Messina; Neurorehabilitation Unit (V.S., E.A.), University of Milan, Centro Clinico Nemo, Niguarda Hospital, Milan; Center of Myology and Neurodegenerative Disorders (C.B., M. Pedemonte, G.B.), Istituto Giannina Gaslini, Genoa; Unit of Neuromuscular and Neurodegenerative Disorders (M.C., A.D., E.B.), Bambino Gesù Children's Hospital, Rome; and Institute of Genomic Medicine (F.D.T.), Catholic University, Rome, Italy.
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From Paediatric Neurology and Centro Clinico Nemo (M. Pane, C.P., R.d.S., G.C., S.L.), Catholic University and Fondazione Policlinico Gemelli IRCCS, Rome; Department of Clinical and Experimental Medicine (S.M., M.S., G.V., E.M.), University of Messina and Centro Clinico Nemo, Messina; Neurorehabilitation Unit (V.S., E.A.), University of Milan, Centro Clinico Nemo, Niguarda Hospital, Milan; Center of Myology and Neurodegenerative Disorders (C.B., M. Pedemonte, G.B.), Istituto Giannina Gaslini, Genoa; Unit of Neuromuscular and Neurodegenerative Disorders (M.C., A.D., E.B.), Bambino Gesù Children's Hospital, Rome; and Institute of Genomic Medicine (F.D.T.), Catholic University, Rome, Italy.
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An observational study of functional abilities in infants, children, and adults with type 1 SMA
Marika Pane, Concetta Palermo, Sonia Messina, Valeria A. Sansone, Claudio Bruno, Michela Catteruccia, Maria Sframeli, Emilio Albamonte, Marina Pedemonte, Adele D'Amico, Giorgia Brigati, Roberto de Sanctis, Giorgia Coratti, Simona Lucibello, Enrico Bertini, Giuseppe Vita, Francesco Danilo Tiziano, Eugenio Mercuri, on behalf of the Italian EAP Working Group
Neurology Aug 2018, 91 (8) e696-e703; DOI: 10.1212/WNL.0000000000006050

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Abstract

Objective To report cross-sectional clinical findings in a large cohort of patients affected by type 1 spinal muscular atrophy.

Methods We included 122 patients, of age ranging between 3 months and 22 years, 1 month. More than 70% (85/122) were older than 2 years and 25% (31/122) older than 10 years. Patients were classified according to the severity of phenotype and to the number of SMN2 copies.

Results Patients with the more common and the most severe phenotype older than 2 years were, with few exceptions, on noninvasive ventilation and, with increasing age, more often had tracheostomy or >16-hour ventilation and a gastrostomy inserted. In contrast, 25 of the 28 patients with the mildest phenotype older than 2 years had no need for tracheostomy or other ventilatory or nutritional support. In patients older than 2 years, the Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders scores were generally lower compared to those found in younger patients and showed distinct levels of functional abilities according to the severity of the phenotype. Similar findings were also observed on the Hammersmith Infant Neurological Examination.

Conclusions Our findings confirm that, after the age of 2 years, patients with type 1 spinal muscular atrophy generally survive only if they have gastrostomy and tracheostomy or noninvasive ventilation >16 hours and have low scores on the functional scales. More variability, however, can be expected in those with the mildest phenotype, who achieve head control. These data provide important baseline information at the time treatments are becoming available.

Glossary

CHOP INTEND=
Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders;
EAP=
early access program;
HINE=
Hammersmith Infant Neurological Examination;
PEG=
percutaneous endoscopic gastrostomy;
SMA=
spinal muscular atrophy

Footnotes

  • ↵* These authors contributed equally to this work as first authors.

  • Go to Neurology.org/N for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.

  • Italian EAP Working Group coinvestigators are listed at links.lww.com/WNL/A633.

  • Editorial, page 337

  • Received March 15, 2018.
  • Accepted in final form May 29, 2018.
  • © 2018 American Academy of Neurology
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