Rhinencephalon changes in tuberous sclerosis complex
Despite complex olfactory bulb embryogenesis, its development abnormalities in tuberous sclerosis complex (TSC) have been poorly investigated.
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.
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.
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.
KeywordsTuberous sclerosis complex Olfactory bulb Olfactory sulcus MRI
Compliance with ethical standards
No funding was received for this study.
Conflict of interest
The authors declare that they have no conflict of interest.
All procedures performed in the studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. For this type of study formal consent is not required.
For this type of retrospective study formal consent is not required.
- 3.Northrup H, Krueger DA, on behalf of the International Tuberous Sclerosis Complex Consensus Group: Tuberous Sclerosis Complex Diagnostic Criteria Update (2013) Recommendations of the 2012 International Tuberous Sclerosis Complex Consensus Conference. Pediatr Neurol 49:243–254CrossRefPubMedPubMedCentralGoogle Scholar
- 4.Kingswood C, Bolton P, Crawford P, Harland C, Johnson SR, Sampson JR, Shepherd C, Spink J, Demuth D, Lucchese L, Nasuti P, Gray E, Pinnegar A, Magestro M (2016) The clinical profile of tuberous sclerosis complex (TSC) in the United Kingdom: a retrospective cohort study in the Clinical Practice Research Datalink (CPRD). Eur J Paediatr Neurol 20(2):296–308CrossRefPubMedGoogle Scholar
- 13.Wong AM, Wang HS, Schwartz ES, Toh CH, Zimmerman RA, Liu PL, Wu YM, Ng SH, Wang JJ (2013) Cerebral diffusion tensor MR tractography in tuberous sclerosis complex: correlation with neurologic severity and tract-based spatial statistical analysis. AJNR Am J Neuroradiol 34:1829–1835CrossRefPubMedGoogle Scholar
- 14.Ottaviano G, Cantone E, D'Errico A, Salvalaggio A, Citton V, Scarpa B, Favaro A, Sinisi AA, Liuzzi R, Bonanni G, Di Salle F, Elefante A, Manara R, Staffieri A, Martini A, Brunetti A (2015) Sniffin’ Sticks and olfactory system imaging in patients with Kallmann syndrome. Int Forum Allergy Rhinol 5(9):855–861CrossRefPubMedGoogle Scholar
- 16.Manara R, Bugin S, Pelizza MF, Sartori S, Nosadini M, Labriola F, Canevini P, Vignoli A, Toldo I (2018) Genetic and imaging features of cerebellar abnormalities in tuberous sclerosis complex: more insights into their pathogenesis. Dev Med Child Neurol 60(7):724-725Google Scholar
- 18.Au KS, Williams AT, Roach ES, Batchelor L, Sparagana SP, Delgado MR, Wheless JW, Baumgartner JE, Roa BB, Wilson CM, Smith-Knuppel TK, Cheung MY, Whittemore VH, King TM, Northrup H (2007) Genotype/phenotype correlation in 325 individuals referred for a diagnosis of tuberous sclerosis complex in the United States. Genet Med 9:88–100CrossRefPubMedGoogle Scholar