Jitka Májovská1, Anita Hennig2, Igor Nestrasil3, Susanne A Schneider2, Helena Jahnová1, Manuela Vaněčková4, Martin Magner1,5, Petr Dušek6,7. 1. Department of Pediatrics and Inherited Metabolic Disorders, First Faculty of Medicine, Charles University and General University Hospital, Prague, Czech Republic. 2. Department of Neurology, Ludwig-Maximilians University, Munich, Germany. 3. Department of Pediatrics, University of Minnesota, Minneapolis, MN, USA. 4. Department of Radiology, First Faculty of Medicine, Charles University and General University Hospital, Prague, Czech Republic. 5. Department of Pediatrics, University Thomayer Hospital and First Faculty of Medicine, Charles University, Prague, Czech Republic. 6. Department of Radiology, First Faculty of Medicine, Charles University and General University Hospital, Prague, Czech Republic. pdusek@gmail.com. 7. Department of Neurology and Center of Clinical Neuroscience, First Faculty of Medicine, Charles University and General University Hospital, Prague, Czech Republic. pdusek@gmail.com.
Abstract
PURPOSE: Late-onset Tay-Sachs disease (LOTS) is a form of GM2 gangliosidosis, an autosomal recessive neurodegenerative disorder characterized by slowly progressive cerebellar ataxia, lower motor neuron disease, and psychiatric impairment due to mutations in the HEXA gene. The aim of our work was to identify the characteristic brain MRI findings in this presumably underdiagnosed disease. METHODS: Clinical data and MRI findings from 16 patients (10F/6 M) with LOTS from two centers were independently assessed by two readers and compared to 16 age- and sex-related controls. RESULTS: Lower motor neuron disease (94%), psychiatric symptoms-psychosis (31%), cognitive impairment (38%) and depression (25%)-and symptoms of cerebellar impairment including dysarthria (94%), ataxia (81%) and tremor (69%), were the most common clinical features. On MRI, pontocerebellar atrophy was a constant finding. Compared to controls, LOTS patients had smaller mean middle cerebellar peduncle diameter (p < 0.0001), mean superior cerebellar peduncle diameter (p = 0.0002), mesencephalon sagittal area (p = 0.0002), pons sagittal area (p < 0.0001), and larger 4th ventricle transversal diameter (p < 0.0001). Mild corpus callosum thinning (37.5%), mild cortical atrophy (18.8%), and white matter T2 hyperintensities (12.5%) were also present. CONCLUSION: Given the characteristic clinical course and MRI findings of the pontocerebellar atrophy, late-onset Tay-Sachs disease should be considered in the differential diagnosis of adult-onset cerebellar ataxias.
PURPOSE: Late-onset Tay-Sachs disease (LOTS) is a form of GM2 gangliosidosis, an autosomal recessive neurodegenerative disorder characterized by slowly progressive cerebellar ataxia, lower motor neuron disease, and psychiatric impairment due to mutations in the HEXA gene. The aim of our work was to identify the characteristic brain MRI findings in this presumably underdiagnosed disease. METHODS: Clinical data and MRI findings from 16 patients (10F/6 M) with LOTS from two centers were independently assessed by two readers and compared to 16 age- and sex-related controls. RESULTS: Lower motor neuron disease (94%), psychiatric symptoms-psychosis (31%), cognitive impairment (38%) and depression (25%)-and symptoms of cerebellar impairment including dysarthria (94%), ataxia (81%) and tremor (69%), were the most common clinical features. On MRI, pontocerebellar atrophy was a constant finding. Compared to controls, LOTS patients had smaller mean middle cerebellar peduncle diameter (p < 0.0001), mean superior cerebellar peduncle diameter (p = 0.0002), mesencephalon sagittal area (p = 0.0002), pons sagittal area (p < 0.0001), and larger 4th ventricle transversal diameter (p < 0.0001). Mild corpus callosum thinning (37.5%), mild cortical atrophy (18.8%), and white matter T2 hyperintensities (12.5%) were also present. CONCLUSION: Given the characteristic clinical course and MRI findings of the pontocerebellar atrophy, late-onset Tay-Sachs disease should be considered in the differential diagnosis of adult-onset cerebellar ataxias.
Authors: Orit Neudorfer; Gregory M Pastores; Bai J Zeng; John Gianutsos; Charles M Zaroff; Edwin H Kolodny Journal: Genet Med Date: 2005-02 Impact factor: 8.822
Authors: Helena Jahnová; Helena Poupětová; Jitka Jirečková; Hana Vlášková; Eva Košťálová; Radim Mazanec; Alena Zumrová; Petr Mečíř; Zuzana Mušová; Martin Magner Journal: J Neurol Date: 2019-05-10 Impact factor: 4.849
Authors: E Hund; A Grau; W Fogel; M Forsting; M Cantz; B Kustermann-Kuhn; K Harzer; R Navon; H H Goebel; H M Meinck Journal: J Neurol Sci Date: 1997-01 Impact factor: 3.181
Authors: H Mitsumoto; R J Sliman; I A Schafer; C S Sternick; B Kaufman; A Wilbourn; S J Horwitz Journal: Ann Neurol Date: 1985-04 Impact factor: 10.422
Authors: Mao-Qiang Tian; Xiao-Xi Chen; Lei Li; Chang-Hui Lang; Juan Li; Jing Chen; Xiao-Hua Yu; Xiao-Mei Shu Journal: Zhongguo Dang Dai Er Ke Za Zhi Date: 2022-06-15