Brain MR patterns in inherited disorders of monoamine neurotransmitters: An analysis of 70 patients
Por:
Hübschmann OK, Mohr A, Friedman J, Manti F, Horvath G, Cortés-Saladelafont E, Mercimek-Andrews S, Yildiz Y, Pons R, Kulhánek J, Oppebøen M, Koht JA, Podzamczer-Valls I, Domingo-Jimenez R, Ibáñez S, Alcoverro-Fortuny O, Gómez-Alemany T, de Castro P, Alfonsi C, Zafeiriou DI, López-Laso E, Guder P, Santer R, Honzík T, Hoffmann GF, Garbade SF, Sivri HS, Leuzzi V, Jeltsch K, Garcia-Cazorla A, Opladen T, Harting I and International Working Group on Neurotransmitter Related Disorders
Publicada:
1 jul 2021
Ahead of Print:
1 ene 2021
Resumen:
Inherited monoamine neurotransmitter disorders (iMNDs) are rare disorders with clinical manifestations ranging from mild infantile hypotonia, movement disorders to early infantile severe encephalopathy. Neuroimaging has been reported as non-specific. We systematically analyzed brain MRIs in order to characterize and better understand neuroimaging changes and to re-evaluate the diagnostic role of brain MRI in iMNDs. 81 MRIs of 70 patients (0.1-52.9 years, 39 patients with tetrahydrobiopterin deficiencies, 31 with primary disorders of monoamine metabolism) were retrospectively analyzed and clinical records reviewed. 33/70 patients had MRI changes, most commonly atrophy (n = 24). Eight patients, six with dihydropteridine reductase deficiency (DHPR), had a common pattern of bilateral parieto-occipital and to a lesser extent frontal and/or cerebellar changes in arterial watershed zones. Two patients imaged after acute severe encephalopathy had signs of profound hypoxic-ischemic injury and a combination of deep gray matter and watershed injury (aromatic l-amino acid decarboxylase (AADCD), tyrosine hydroxylase deficiency (THD)). Four patients had myelination delay (AADCD; THD); two had changes characteristic of post-infantile onset neuronal disease (AADCD, monoamine oxidase A deficiency), and nine T2-hyperintensity of central tegmental tracts. iMNDs are associated with MRI patterns consistent with chronic effects of a neuronal disorder and signs of repetitive injury to cerebral and cerebellar watershed areas, in particular in DHPRD. These will be helpful in the (neuroradiological) differential diagnosis of children with unknown disorders and monitoring of iMNDs. We hypothesize that deficiency of catecholamines and/or tetrahydrobiopterin increase the incidence of and the CNS susceptibility to vascular dysfunction.
Filiaciones:
Hübschmann OK:
Oya Kuseyri Hübschmann, Department of Child Neurology and Metabolic Disorders, University Children's Hospital, Heidelberg, Germany
Mohr A:
Alexander Mohr, Department of Neuroradiology, University Hospital Heidelberg, Germany
Friedman J:
Jennifer Friedman, UCSD Departments of Neuroscience and Pediatrics
Rady Children's Hospital Division of Neurology, Rady Children's Institute for Genomic Medicine, San Diego, USA
Manti F:
Filippo Manti, Unit of Child Neurology and Psychiatry, Department of Human Neuroscience, Sapienza, University of Rome, Italy
Horvath G:
Gabriella Horvath, University of British Columbia, Department of Pediatrics, Division of Biochemical Genetics, BC Children's Hospital, Vancouver, British Columbia, Canada
Cortés-Saladelafont E:
Elisenda Cortès-Saladelafont, Inborn errors of metabolism Unit, Institut de Recerca Sant Joan de Déu and CIBERER-ISCIII, Barcelona, Spain and Unit of Pediatric Neurology and Metabolic Disorders, Department of Pediatrics, Hospital Germans Trias i Pujol, and Faculty of Medicine, Universitat Autònoma de Barcelona, Barcelona, Spain
Mercimek-Andrews S:
Saadet Mercimek-Andrews, Division of Clinical and Metabolic Genetics Department of Pediatrics, University of Toronto, The Hospital for Sick Children 555 University Avenue Toronto, Ontario
Yildiz Y:
Yilmaz Yildiz, Hacettepe University, Faculty of Medicine, Department of Pediatrics, Section of Metabolism, Ankara, Turkey
Pons R:
Roser Pons, First Department of Pediatrics of the University of Athens, Aghia Sofia Hospital
Kulhánek J:
Jan Kulhánek, Department of Pediatrics and Inherited Metabolic Disorders, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czech Republic
Oppebøen M:
Mari Oppebøen, Childrens Department Division of Child Neurology Oslo University Hospital Rikshospitalet, Oslo, Norway
Koht JA:
Jeanette Aimee Koht, Department of Neurology, Oslo University Hospital, Oslo, Norway
Podzamczer-Valls I:
Inés Podzamczer-Valls, Department of Neurology. Neurometabolic Unit, and Synaptic Metabolism Laboratory. Hospital Sant Joan de Déu, Esplugues de Llobregat, Barcelona, Spain and Universitat de Barcelona, Barcelona, Spain
Domingo-Jimenez R:
Rosario Domingo-Jiménez, Department of Pediatric Neurology, Hospital Virgen de la Arrixaca and IMIB-Arrixaca, Murcia, CIBERER-ISCIII, Madrid, Spain
Ibáñez S:
Salvador Ibáñez-Micó, Department of Pediatric Neurology, Hospital Virgen de la Arrixaca, Murcia, Spain
Alcoverro-Fortuny O:
Oscar Alcoverro-Fortuny, Service of Psychiatry, Hospital Benito Menni - Hospital General de Granollers, Barcelona, Spain
Gómez-Alemany T:
Teresa Gómez-Alemany, Service of Psychiatry, Hospital Benito Menni - Hospital General de Granollers, Barcelona, Spain
de Castro P:
Pedro de Castro, Department of Pediatric Neurology, Hospital Gregorio Marañón, Madrid, Spain
Alfonsi C:
Elisenda Cortès-Saladelafont, Inborn errors of metabolism Unit, Institut de Recerca Sant Joan de Déu and CIBERER-ISCIII, Barcelona, Spain and Unit of Pediatric Neurology and Metabolic Disorders, Department of Pediatrics, Hospital Germans Trias i Pujol, and Faculty of Medicine, Universitat Autònoma de Barcelona, Barcelona, Spain
Chiara Alfonsi, Department of Human Neuroscience, Sapienza, University of Rome, Inborn errors of metabolism Unit. Institut de Recerca Sant Joan de Déu and CIBERER-ISCIII, Barcelona, Spain
Zafeiriou DI:
Dimitrios I Zafeiriou, Child Neurology and Developmental Pediatrics1st Department of Pediatrics Aristotle University of Thessaloniki, Thessaloniki, Greece
López-Laso E:
Eduardo López-Laso, Pediatric Neurology Unit, Department of Pediatrics, University Hospital Reina Sofía, IMIBIC and CIBERER, Córdoba, Spain
Guder P:
Philipp Guder, Department of Pediatrics, UKE, Hamburg
Santer R:
René Santer, Department of Pediatrics, UKE, Hamburg
Honzík T:
Tomáš Honzík, Department of Pediatrics and Inherited Metabolic Disorders, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czech Republic
Hoffmann GF:
Georg F. Hoffmann, Department of Child Neurology and Metabolic Disorders, University Children's Hospital, Heidelberg, Germany
Garbade SF:
Sven. F. Garbade, Department of Child Neurology and Metabolic Disorders, University Children's Hospital, Heidelberg, Germany
Sivri HS:
H. Serap Sivri, Hacettepe University, Faculty of Medicine, Department of Pediatrics, Section of Metabolism, Ankara, Turkey
Leuzzi V:
Vincenzo Leuzzi, Department of Human Neuroscience, Unit of Child Neurology and Psychiatry, Università degli Studi di Roma La Sapienza, Italy
Jeltsch K:
Kathrin Jeltsch, Department of Child Neurology and Metabolic Disorders, University Children's Hospital, Heidelberg, Germany
Garcia-Cazorla A:
Angeles García-Cazorla, Inborn errors of metabolism Unit, Department of Neurology. Institut de Recerca Sant Joan de Déu, CIBERER-ISCIII and MetabERN, Barcelona, Spain
Opladen T:
Thomas Opladen, Department of Child Neurology and Metabolic Disorders, University Children's Hospital, Heidelberg, Germany
Harting I:
Inga Harting, Department of Neuroradiology, University Hospital Heidelberg, IH, Germany
Green Published, hybrid
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