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Publications

Journal Article Ahead of print

PubMed: 42314609 DOI: 10.1016/j.ymgme.2026.110189

Neuroradiological patterns and prognostic implications in type I Alexander disease.

Mol Genet Metab 148(4):110189

Authors: Ylenia Vaia, Filippo Arrigoni, Liat Ben Sira, Geneviève Bernard, Enrico Bertini, Odile Boespflug-Tanguy, Fabio Bruschi, Cristina Cereda, Florian Eichler, Alessandra Erbetta, Simona Ferraro, Morteza Heidari, Luca Lalli, Gabrielle Lambert, Stephanie Libzon, Daniela Longo, Isabella Moroni, Amanda Nagy, Francesco Nicita, Florence Renaldo, Diana Rodriguez, Golazin Shahbodagh Khan, Ali Reza Tavasoli, Ellen Winter, Ayelet Zerem, Cecilia Parazzini, Davide Tonduti

Affiliations

  • C.O.A.L.A. (Center for Diagnosis and Treatment of Leukodystrophies), Unit of Pediatric Neurology, V. Buzzi Children's Hospital, Milan, Italy; Neuroscience Research Center, Department of Biomedical and Clinical Sciences, University of Milan, Milan, Italy.
  • Unit of Pediatric Radiology and Neuroradiology, V. Buzzi Children's Hospital, Milan, Italy.
  • Pediatric Radiology, Department of Radiology, Tel Aviv Sourasky Medical Center; Gray Faculty of Medical and Health Sciences, Tel Aviv University, Tel Aviv, Israel.
  • Departments of Neurology and Neurosurgery, Pediatrics, and Human Genetics, McGill University, Montreal, Quebec, Canada; Department of Specialized Medicine, Division of Medical Genetics, McGill University Health Centre, Montreal, Quebec, Canada; Child Health and Human Development Program, Research Institute of the McGill University Health Centre, Montreal, Canada.
  • Research Unit of Muscular and Neurodegenerative Disorders, IRCCS Bambino Gesù Children's Hospital, Rome, Italy.
  • AP-HP, Centre de reference maladies rares « LEUKOFRANCE », Neurologie Pédiatrique, Université Paris-Cité, INSERM-UMR1141, Hôpital Robert-Debré, Paris, France.
  • C.O.A.L.A. (Center for Diagnosis and Treatment of Leukodystrophies), Unit of Pediatric Neurology, V. Buzzi Children's Hospital, Milan, Italy; Neuroscience Research Center, Department of Biomedical and Clinical Sciences, University of Milan, Milan, Italy.
  • Center of Functional Genomics and Rare Diseases, Dept. of Pediatrics Buzzi Children's Hospital, Milan, Italy; Pediatric Department, Buzzi Children's Hospital, Milan, Italy.
  • Harvard Medical School, Boston, MA, USA; Department of Neurology, Massachusetts General Hospital, Boston, MA, USA.
  • Neuroradiology Unit, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy.
  • Pediatric Neurology Division, Department of Pediatrics, Children's Medical Center, Pediatric Center of Excellence, Tehran University of Medical Sciences, Tehran, Iran; Pediatric Neurology Division, Myelin Disorders Clinic, Children's Medical Center, Pediatric Center of Excellence, Tehran University of Medical Sciences, Tehran, Iran.
  • Unit of Translational Immunology, IRCCS Foundation National Cancer Institute, Milan, Italy.
  • Departments of Neurology and Neurosurgery, Pediatrics, and Human Genetics, McGill University, Montreal, Quebec, Canada.
  • Pediatric Neurology Institute, Dana-Dwek Children's Hospital, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel; Sackler Faulty of Medicine, Tel Aviv University, Tel Aviv, Israel.
  • Neuroradiology Unit, Department of Imaging, IRCCS Bambino Gesù Children's Hospital, Scientific Institute for Research and Health Care, Rome, Italy.
  • Department of Pediatric Neurosciences, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy.
  • Research Unit of Muscular and Neurodegenerative Disorders, IRCCS Bambino Gesù Children's Hospital, Rome, Italy; Unit of Muscular and Neurodegenerative Diseases, IRCCS Bambino Gesù Children's Hospital, Rome, Italy.
  • Department of Pediatric Neurology, Reference Center for Rare Neurogenetic Diseases, Armand-Trousseau Hospital, APHP, Sorbonne University, Paris, France.
  • Pediatric Neurology Division, Department of Pediatrics, Children's Medical Center, Pediatric Center of Excellence, Tehran University of Medical Sciences, Tehran, Iran.
  • Pediatric Neurology Division, Department of Pediatrics, Children's Medical Center, Pediatric Center of Excellence, Tehran University of Medical Sciences, Tehran, Iran; Department of Neurology, Barrow Neurological Institute, Phoenix Children's Hospital, Phoenix, AZ, USA.
  • Department of Neurology, Massachusetts General Hospital, Boston, MA, USA.
  • C.O.A.L.A. (Center for Diagnosis and Treatment of Leukodystrophies), Unit of Pediatric Neurology, V. Buzzi Children's Hospital, Milan, Italy; Neuroscience Research Center, Department of Biomedical and Clinical Sciences, University of Milan, Milan, Italy.

Abstract

INTRODUCTION

Type I Alexander Disease (AxD) is a rare leukodystrophy that can be subclassified into subtypes (Ia, Ib, Ic, and Id), in order of decreasing severity. To date, no study has correlated MRI findings with AxD type I clinical evolution. This study aims to identify MRI features that may predict disease progression.

METHODS

Patients with genetically confirmed type I AxD were recruited from multiple Leukodystrophy Centers worldwide. Clinical data were collected via RedCap, and patients were retrospectively classified by disease subtype. Leukodystrophy experts analyzed the first available MRI scans using an adapted AxD MRI scoring protocol, and imaging findings were correlated with disease subtypes.

RESULTS

47 subjects with type I AxD were enrolled. Subtype distribution included 3 Ia, 12 Ib, 8 Ic, 10 Id, 10 Ic/Id, and 4 undetermined. Risk of belonging to type Ib compared to other subtypes was significantly increased in case of involvement of parietal subcortical WM (OR = 16.1, p = 0.003), occipital deep WM (p = 0.008), temporal deep (p = 0.018), and periventricular WM (p = 0.013), body of corpus callosum (p = 0.018), genu of corpus callosum (p = 0.047) and hilar region of cerebellum (p = 0.008). Involvement of occipital periventricular WM was associated to a higher risk of being type Ic compared to type Id (p = 0.010).

CONCLUSIONS

Some distinct MRI patterns on initial MRI scans may predict disease outcomes in type I AxD. These findings may help clinicians in early prognostic stratification, with key brain regions needing careful evaluation. Further studies are required to validate these findings and improve prognostic accuracy in type I AxD.

MeSH

Alexander Disease, Metabolic Diseases, Molecular Biology, Corpus Callosum