To assess the presence of white matter abnormalities in patients with SPG76 and verify that these abnormalities configure an MRI pattern of white matter involvement characteristic of SPG76.

Hereditary spastic parapareses (HSPs) are genetic disorders characterized by progressive pyramidal tract involvement with variable clinical and genetic profile. The most common radiological features are cerebellar and spinal cord atrophy associated in some forms with corpus callosum thinning and white matter abnormalities. SPG76 is one of the most recently identified forms of HSP, described to date in 43 published subjects, and is caused by biallelic calpain-1 (CAPN1) gene mutations. The most reported MRI abnormality in SPG76 is mild cerebellar atrophy and only one case had mild white matter abnormalities interpreted as non-specific. Following the diagnosis of SPG76 in a patient presenting a predominant white matter involvement, we performed this retrospective review.

We performed a retrospective radiological analysis of 11 patients with SPG76, 3 of which not previously reported in the literature. 

The brain MRI studies were analysed by using a qualitative assessment. Morevoer, in our proband with available longitudinal studies, we performed a quantitative analysis using a segmentation tool to measure the white matter changes in terms of lesion count and volume over time.

We documented multifocal white matter abnormalities in 8 subjects (8/11; 72.7%) and a characteristic pattern of periventricular white matter involvement in 7 (7/11; 63.6%). The longitudinal quantitative analysis performed in our proband revealed increase in subcortical white matter lesion count and increased area of periventricular white matter involvement over time.

In our cohort of subjects with SPG76, white matter abnormalities were more frequent than what reported in literature.  Besides multifocal white matter changes, bilateral and symmetric periventricular involvement can represent a pattern characteristic of SPG76 and needs to be validated in larger cohorts.