Filippo Arrigoni1, Romina Romaniello2, Denis Peruzzo3, Andrea Poretti4, Maria Teresa Bassi5, Carlo Pierpaoli6, Enza Maria Valente7,8, Sara Nuovo8,9, Eugen Boltshauser10, Thierry André Gerard Marie Huisman4, Fabio Triulzi11, Renato Borgatti2. 1. Neuroimaging Lab, Scientific Institute, IRCCS E. Medea, Via Don Luigi Monza 20, 23842, Bosisio Parini, Lecco, Italy. filippo.arrigoni@lanostrafamiglia.it. 2. Neuropsychiatry and Neurorehabilitation Unit, Scientific Institute, IRCCS E. Medea, Bosisio Parini, Lecco, Italy. 3. Neuroimaging Lab, Scientific Institute, IRCCS E. Medea, Via Don Luigi Monza 20, 23842, Bosisio Parini, Lecco, Italy. 4. Section of Pediatric Neuroradiology, Division of Pediatric Radiology, Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, Baltimore, MD, USA. 5. Laboratory of Molecular Biology, Scientific Institute, IRCCS E. Medea, Bosisio Parini, Lecco, Italy. 6. Quantitative Medical Imaging Section, National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health, Bethesda, MD, USA. 7. Department of Molecular Medicine, University of Pavia, Pavia, Italy. 8. Neurogenetics Lab, IRCCS Santa Lucia Foundation, Rome, Italy. 9. Department of Medicine and Surgery, University of Salerno, Salerno, Italy. 10. Department of Paediatric Neurology, University Children's Hospital, Zurich, Switzerland. 11. Neuroradiology Department, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Milano, Italy.
Abstract
OBJECTIVES: To describe the spectrum of brainstem malformations associated to mutations in the tubulin genes taking advantage of magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI). METHODS: Fifteen patients (six males; median age, 1.25 years; range, 1 month to 31 years) with mutations in the tubulin genes (TUBA1A = 8, TUBB2B = 4, TUBB3 = 3) studied with MRI and DTI were included in the study. Brain MR exams were reviewed to describe the malformative aspects of the brainstem. Malformations of the supratentorial brain and cerebellum were also recorded. Tractography was performed in seven selected cases. RESULTS: Fourteen patients (93%) showed complex malformations of the brainstem. Most common findings, apparent on anatomical MR sequences, were brainstem asymmetry (12 cases, 5 of which with a crossed pattern characterised by a hypertrophic right medulla oblongata and hypertrophic left pons), short and small pons on midline (10 cases) and anterior brainstem clefting (6 cases). DTI revealed abnormal transverse pontine fibres (13 cases), fusion of corticospinal tracts and medial lemnisci (9 cases) and a small decussation of the superior cerebellar peduncles (7 cases). CONCLUSIONS: Conventional/anatomical MRI and DTI reveal a complex pattern of brainstem malformations associated with tubulin genes mutations. KEY POINTS: • Brainstem malformations affect 93% patients with mutated tubulin genes • MRI shows homolateral and crossed brainstem asymmetries, clefts and pons hypoplasia • DTI demonstrates irregular representation of transverse pontine fibres and fusion of corticospinal tracts.
OBJECTIVES: To describe the spectrum of brainstem malformations associated to mutations in the tubulin genes taking advantage of magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI). METHODS: Fifteen patients (six males; median age, 1.25 years; range, 1 month to 31 years) with mutations in the tubulin genes (TUBA1A = 8, TUBB2B = 4, TUBB3 = 3) studied with MRI and DTI were included in the study. Brain MR exams were reviewed to describe the malformative aspects of the brainstem. Malformations of the supratentorial brain and cerebellum were also recorded. Tractography was performed in seven selected cases. RESULTS: Fourteen patients (93%) showed complex malformations of the brainstem. Most common findings, apparent on anatomical MR sequences, were brainstem asymmetry (12 cases, 5 of which with a crossed pattern characterised by a hypertrophic right medulla oblongata and hypertrophic left pons), short and small pons on midline (10 cases) and anterior brainstem clefting (6 cases). DTI revealed abnormal transverse pontine fibres (13 cases), fusion of corticospinal tracts and medial lemnisci (9 cases) and a small decussation of the superior cerebellar peduncles (7 cases). CONCLUSIONS: Conventional/anatomical MRI and DTI reveal a complex pattern of brainstem malformations associated with tubulin genes mutations. KEY POINTS: • Brainstem malformations affect 93% patients with mutated tubulin genes • MRI shows homolateral and crossed brainstem asymmetries, clefts and pons hypoplasia • DTI demonstrates irregular representation of transverse pontine fibres and fusion of corticospinal tracts.
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