Renzo Manara1, Davide Brotto2, Samuela Bugin3, Maria Federica Pelizza3, Stefano Sartori3, Margherita Nosadini3, Sara Azzolini4, Giorgio Iaconetta5, Cecilia Parazzini6, Alessandra Murgia7, Angela Peron8,9, Paola Canevini10, Francesca Labriola11, Aglaia Vignoli10, Irene Toldo3. 1. Neuroradiology, Department of Medicine and Surgery, Sezione di Neuroscienze, University of Salerno, Via S. Allende 1, 84081, Baronissi, SA, Italy. rmanara@unisa.it. 2. Otolaryngology Unit, Department of Neuroscience, University Hospital of Padova, Padova, PD, Italy. 3. Pediatric Neurology and Neurophysiology Unit, Department of Woman and Child Health, University Hospital of Padova, Padova, PD, Italy. 4. Pediatric Endocrinology Unit, Department of Woman and Child Health, University Hospital of Padova, Padova, PD, Italy. 5. Neurosurgery, School of Medicine "Scuola Medica Salernitana", University of Salerno, Fisciano, SA, Italy. 6. Department of Pediatric Radiology and Neuroradiology, Children's Hospital V. Buzzi, Milan, Italy. 7. Molecular Genetics of Neurodevelopment Laboratory, Department of Women's and Children's Health, University Hospital of Padova, Padova, PD, Italy. 8. Child Neuropsychiatry Unit - Epilepsy Center, San Paolo Hospital, Department of Health Sciences, University of Milano, Milan, Italy. 9. Department of Pediatrics, Division of Medical Genetics, University of Utah School of Medicine, Salt Lake City, UT, USA. 10. Epilepsy Center, Health Sciences Department, University of Milano, Milan, Italy. 11. Epilepsy and Sleep Medicine Center - Neuropsychiatric Unit - ASST Santi Paolo Carlo, Milan, MI, Italy.
Abstract
PURPOSE: Despite complex olfactory bulb embryogenesis, its development abnormalities in tuberous sclerosis complex (TSC) have been poorly investigated. METHODS: Brain MRIs of 110 TSC patients (mean age 11.5 years; age range 0.5-38 years; 52 female; 26 TSC1, 68 TSC2, 8 without mutation identified in TSC1 or TSC2, 8 not tested) were retrospectively evaluated. Signal and morphological abnormalities consistent with olfactory bulb hypo/aplasia or with olfactory bulb hamartomas were recorded. Cortical tuber number was visually assessed and a neurological severity score was obtained. Patients with and without rhinencephalon abnormalities were compared using appropriate parametric and non-parametric tests. RESULTS: Eight of110 (7.2%) TSC patients presented rhinencephalon MRI changes encompassing olfactory bulb bilateral aplasia (2/110), bilateral hypoplasia (2/110), unilateral hypoplasia (1/110), unilateral hamartoma (2/110), and bilateral hamartomas (1/110); olfactory bulb hypo/aplasia always displayed ipsilateral olfactory sulcus hypoplasia, while no TSC patient harboring rhinencephalon hamartomas had concomitant forebrain sulcation abnormalities. None of the patients showed overt olfactory deficits or hypogonadism, though young age and poor compliance hampered a proper evaluation in most cases. TSC patients with rhinencephalon changes had more cortical tubers (47 ± 29.1 vs 26.2 ± 19.6; p = 0.006) but did not differ for clinical severity (p = 0.45) compared to the other patients of the sample. CONCLUSIONS: Olfactory bulb and/or forebrain changes are not rare among TSC subjects. Future studies investigating clinical consequences in older subjects (anosmia, gonadic development etc.) will define whether rhinencephalon changes are simply an imaging feature among the constellation of TSC-related brain changes or a feature to be searched for possible implications in the management of TSC subjects.
PURPOSE: Despite complex olfactory bulb embryogenesis, its development abnormalities in tuberous sclerosis complex (TSC) have been poorly investigated. METHODS: Brain MRIs of 110 TSCpatients (mean age 11.5 years; age range 0.5-38 years; 52 female; 26 TSC1, 68 TSC2, 8 without mutation identified in TSC1 or TSC2, 8 not tested) were retrospectively evaluated. Signal and morphological abnormalities consistent with olfactory bulb hypo/aplasia or with olfactory bulb hamartomas were recorded. Cortical tuber number was visually assessed and a neurological severity score was obtained. Patients with and without rhinencephalon abnormalities were compared using appropriate parametric and non-parametric tests. RESULTS: Eight of110 (7.2%) TSCpatients presented rhinencephalon MRI changes encompassing olfactory bulb bilateral aplasia (2/110), bilateral hypoplasia (2/110), unilateral hypoplasia (1/110), unilateral hamartoma (2/110), and bilateral hamartomas (1/110); olfactory bulb hypo/aplasia always displayed ipsilateral olfactory sulcus hypoplasia, while no TSCpatient harboring rhinencephalon hamartomas had concomitant forebrain sulcation abnormalities. None of the patients showed overt olfactory deficits or hypogonadism, though young age and poor compliance hampered a proper evaluation in most cases. TSCpatients with rhinencephalon changes had more cortical tubers (47 ± 29.1 vs 26.2 ± 19.6; p = 0.006) but did not differ for clinical severity (p = 0.45) compared to the other patients of the sample. CONCLUSIONS: Olfactory bulb and/or forebrain changes are not rare among TSC subjects. Future studies investigating clinical consequences in older subjects (anosmia, gonadic development etc.) will define whether rhinencephalon changes are simply an imaging feature among the constellation of TSC-related brain changes or a feature to be searched for possible implications in the management of TSC subjects.
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