Eric J Mallack1, Stephanie van de Stadt1, Paul A Caruso1, Patricia L Musolino1, Reza Sadjadi1, Marc Engelen1, Florian S Eichler2. 1. From the Department of Neurology (E.J.M., P.L.M., R.S., F.S.E.) and Department of Radiology (P.A.C.), Division of Neuroradiology, Harvard Medical School, Massachusetts General Hospital, Boston; Department of Pediatrics (E.J.M.), Division of Child Neurology, Weill Cornell Medical College, New York-Presbyterian Hospital, NY; and Department of Pediatric Neurology (S.v.d.S., M.E.), Emma Children's Hospital, Amsterdam University Medical Center, the Netherlands. 2. From the Department of Neurology (E.J.M., P.L.M., R.S., F.S.E.) and Department of Radiology (P.A.C.), Division of Neuroradiology, Harvard Medical School, Massachusetts General Hospital, Boston; Department of Pediatrics (E.J.M.), Division of Child Neurology, Weill Cornell Medical College, New York-Presbyterian Hospital, NY; and Department of Pediatric Neurology (S.v.d.S., M.E.), Emma Children's Hospital, Amsterdam University Medical Center, the Netherlands. feichler@partners.org.
Abstract
OBJECTIVE: To gain insight into the natural history of arrested cerebral adrenoleukodystrophy (CALD) by quantifying the change in Neurologic Function Score (NFS) and Loes Score (LS) over time in patients whose cerebral lesions spontaneously stopped progressing. METHODS: We retrospectively reviewed a series of 22 patients with arrested CALD followed longitudinally over a median time of 2.4 years (0.7-17.0 years). Primary outcomes were change in radiographic disease burden (measured by LS) and clinical symptoms (measured by NFS) between patients who never developed a contrast-enhancing lesion (gadolinium enhancement (GdE)- subgroup) and those who did (GdE+ subgroup). Secondary analyses comparing patterns of neuroanatomic involvement and lesion number, and prevalence estimates, were performed. RESULTS: Cerebral lesions were first detected at a median age of 23.3 years (8.0-67.6 years) with an initial LS of 4 (0.5-9). NFS was 0.5 (0-6). Overall change in NFS or LS per year did not differ between subgroups. No patients who remained GdE- converted to a progressive CALD phenotype. The presence of contrast enhancement was associated with disease progression (r s = 0.559, p < 0.001). Four patients (18.2%) underwent step-wise progression, followed by spontaneous resolution of contrast enhancement and rearrest of disease. Three patients (13.6%) converted to progressive CALD. Nineteen patients (86.4%) had arrested CALD at the most recent follow-up. The prevalence of arrested CALD is 12.4%. CONCLUSION: Arrested CALD lesions can begin in childhood, and patients are often asymptomatic early in disease. The majority of patients remain stable. However, clinical and MRI surveillance is recommended because a minority of patients undergo step-wise progression or conversion to progressive CALD.
OBJECTIVE: To gain insight into the natural history of arrested cerebral adrenoleukodystrophy (CALD) by quantifying the change in Neurologic Function Score (NFS) and Loes Score (LS) over time in patients whose cerebral lesions spontaneously stopped progressing. METHODS: We retrospectively reviewed a series of 22 patients with arrested CALD followed longitudinally over a median time of 2.4 years (0.7-17.0 years). Primary outcomes were change in radiographic disease burden (measured by LS) and clinical symptoms (measured by NFS) between patients who never developed a contrast-enhancing lesion (gadolinium enhancement (GdE)- subgroup) and those who did (GdE+ subgroup). Secondary analyses comparing patterns of neuroanatomic involvement and lesion number, and prevalence estimates, were performed. RESULTS: Cerebral lesions were first detected at a median age of 23.3 years (8.0-67.6 years) with an initial LS of 4 (0.5-9). NFS was 0.5 (0-6). Overall change in NFS or LS per year did not differ between subgroups. No patients who remained GdE- converted to a progressive CALD phenotype. The presence of contrast enhancement was associated with disease progression (r s = 0.559, p < 0.001). Four patients (18.2%) underwent step-wise progression, followed by spontaneous resolution of contrast enhancement and rearrest of disease. Three patients (13.6%) converted to progressive CALD. Nineteen patients (86.4%) had arrested CALD at the most recent follow-up. The prevalence of arrested CALD is 12.4%. CONCLUSION:Arrested CALD lesions can begin in childhood, and patients are often asymptomatic early in disease. The majority of patients remain stable. However, clinical and MRI surveillance is recommended because a minority of patients undergo step-wise progression or conversion to progressive CALD.
Authors: E J Mallack; G Askin; S van de Stadt; P A Caruso; P L Musolino; M Engelen; S N Niogi; F S Eichler Journal: AJNR Am J Neuroradiol Date: 2021-09-09 Impact factor: 4.966
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Authors: Eric J Mallack; Bela R Turk; Helena Yan; Carrie Price; Michelle Demetres; Ann B Moser; Catherine Becker; Kim Hollandsworth; Laura Adang; Adeline Vanderver; Keith Van Haren; Maura Ruzhnikov; Joanne Kurtzberg; Gustavo Maegawa; Paul J Orchard; Troy C Lund; Gerald V Raymond; Molly Regelmann; Joseph J Orsini; Elisa Seeger; Stephan Kemp; Florian Eichler; Ali Fatemi Journal: J Inherit Metab Dis Date: 2021-01-09 Impact factor: 4.982
Authors: Neha P Godbole; Reza Sadjadi; Madeline A DeBono; Natalie R Grant; Daniel C Kelly; Peter F James; Christopher D Stephen; M David Balkwill; Richard F Lewis; Florian S Eichler Journal: Front Neurol Date: 2021-06-17 Impact factor: 4.003