Ultrastructural Changes in Brain Stem Pathways in a Patient with Ataxia Associated with SPG7 Mutations (P1.8-006)

Objective: Though magnetic resonance imaging (MRI) is a powerful tool to assess many aspects of central nervous system anatomy, its ability to quantify ultrastructural changes in the brain stem are not yet fully realized. We applied a newly-developed probabilistic atlas of brain stem pathways to identify abnormalities in an individual patient with a neurodegenerative ataxia. Background: Autosomal recessive spastic paraplegia 7 (caused by mutations in SPG7) can present with spastic paraplegia, ataxia, and deficits in social communication. Cerebellar atrophy can be evident on MRI but the underlying changes in brain stem connectivity have not been characterized. Design/Methods: The index patient was a 53 year old man with acquired ataxia, deficits in social skills, and a dys executive syndrome due to compound heterozygous mutations in the SPG7 gene. We performed diffusion MRI imaging using the Human Connectome Protocol (HCP) in this patient and 5 neurologically normal controls (age 35 – 59). Multiple brain stem pathways were delineated using recently published methods and diffusion tensor imaging measures calculated and averaged between sides. Fractional anisotropy, axial diffusivity, and radial diffusivity (RD) were compared between the SPG7 patient and controls using t-tests. Results: Gross cerebellar atrophy was evident in the SPG7 mutation carrier. RD was higher in the lateral lemniscus (0.00069 vs. 0.00058, p = 0.044) and the anterior spinocerebellar tract of the superior cerebellar peduncle (SCP, 0.00064 vs. 0.00058, p = 0.023) in the SPG7 patient. There were trends for increased RD in cerebellar outflow tracts including in the cerebellothalamic (0.00059 vs. 0.00054) and cerebellorubral (0.00063 vs. 0.00056) tracts of the SCP. Conclusions: By applying the Brain Stem Atlas to HCP data, we identified ultrastructural changes in brain stem tracts in SPG7-related disease. Changes in the spinocerebellar tract may contribute to ataxia and those in cerebellar outflow in the SCP have been previously related to autistic traits. Disclosure: Dr. Ringman has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with InnoSense, LLC, RENEW. Dr. Ringman has received research support from Avid Pharmaceuticals. Dr. Qiao has nothing to disclose. Dr. Shi has nothing to disclose.