White matter abnormalities in 15 subjects with SPG76

• Published in: Journal of neurology Vol. 270; no. 12; pp. 5784 - 5792
• Main Authors: Alkhalifa, Abdulrahman, Chen, Shihan, Hasiloglu, Zehra Isik, Filosto, Massimiliano, Cali, Elisa, Houlden, Henry, Sgobbi de Souza, Paulo, Alavi, Afagh, Goizet, Cyril, Stevanin, Giovanni, Taithe, Frederic, Nicita, Francesco, Vasco, Gessica, Tozza, Stefano, Cocozza, Sirio, Carboni, Nicola, Figus, Andrea, Wu, Jianjun, Basak, A. Nazli, Brais, Bernard, Rouleau, Guy, La Piana, Roberta
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.12.2023; Springer Nature B.V; Springer Verlag
• Subjects: Atrophy; Calpain; Cerebellum; Genetic disorders; Hereditary spastic paraplegia; Humans; Life Sciences; Longitudinal studies; Magnetic Resonance Imaging; Medicine; Medicine & Public Health; Neurology; Neurons and Cognition; Neuroradiology; Neurosciences; Original Communication; Paraparesis, Spastic; Retrospective Studies; Spastic Paraplegia, Hereditary - diagnostic imaging; Spastic Paraplegia, Hereditary - genetics; Substantia alba; White Matter - diagnostic imaging; White Matter - pathology; Hereditary spastic paraplegia; White matter abnormalities; SPG76; CAPN1
• ISSN: 0340-5354; 1432-1459; 1432-1459
• DOI: 10.1007/s00415-023-11918-5

Background and objectives Hereditary spastic paraplegias (HSPs) are heterogenous genetic disorders characterized by progressive pyramidal tract involvement. SPG76 is a recently identified form of HSP, caused by biallelic calpain-1 ( CAPN1 ) variants. The most frequently described MRI abnormality in SPG76 is mild cerebellar atrophy and non-specific white matter abnormalities were reported in only one case. Following the identification of prominent white matter abnormalities in a subject with CAPN1 variants, which delayed the diagnosis, we aimed to verify the presence of MRI patterns of white matter involvement specific to this HSP. Methods We performed a retrospective radiological qualitative analysis of 15 subjects with SPG76 (4 previously unreported) initially screened for white matter involvement. Moreover, we performed quantitative analyses in our proband with available longitudinal studies. Results We observed bilateral, periventricular white matter involvement in 12 subjects (80%), associated with multifocal subcortical abnormalities in 5 of them (33.3%). Three subjects (20%) presented only multifocal subcortical involvement. Longitudinal quantitative analyses of our proband revealed increase in multifocal white matter lesion count and increased area of periventricular white matter involvement over time. Discussion SPG76 should be added to the list of HSPs with associated white matter abnormalities. We identified periventricular white matter involvement in subjects with SPG76, variably associated with multifocal subcortical white matter abnormalities. These findings, in the presence of progressive spastic paraparesis, can mislead the diagnostic process towards an acquired white matter disorder.