Neuropsychology and MRI correlates of neurodegeneration in SPG11 hereditary spastic paraplegia

Orphanet J Rare Dis. 2022 Jul 29;17(1):301. doi: 10.1186/s13023-022-02451-1.


Background: SPG11-linked hereditary spastic paraplegia is characterized by multisystem neurodegeneration leading to a complex clinical and yet incurable phenotype of progressive spasticity and weakness. Severe cognitive symptoms are present in the majority of SPG11 patients, but a systematic and multidimensional analysis of the neuropsychological phenotype in a larger cohort is lacking. While thinning of the corpus callosum is a well-known structural hallmark observed in SPG11 patients, the neuroanatomical pattern of cortical degeneration is less understood. We here aimed to integrate neuropsychological and brain morphometric measures in SPG11.

Methods: We examined the neuropsychological profile in 16 SPG11 patients using a defined neuropsychological testing battery. Long-term follow up testing was performed in 7 patients. Cortical and subcortical degeneration was analyzed using an approved, artificial intelligence based magnetic resonance imaging brain morphometry, comparing patients to established reference values and to matched controls.

Results: In SPG11 patients, verbal fluency and memory as well as frontal-executive functions were severely impaired. Later disease stages were associated with a global pattern of impairments. Interestingly, reaction times correlated significantly with disease progression. Brain morphometry showed a significant reduction of cortical and subcortical parenchymal volume following a rostro-caudal gradient in SPG11. Whereas performance in memory tasks correlated with white matter damage, verbal fluency measures showed strong associations with frontal and parietal cortical volumes.

Conclusions: The present data will help define neuropsychological and imaging read out parameters in early as well as in advanced clinical stages for future interventional trials in SPG11.

Keywords: Brain morphometry; Neuropsychology; SPG11; Spastic paraplegia; Verbal fluency.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Artificial Intelligence
  • Humans
  • Magnetic Resonance Imaging / methods
  • Mutation
  • Neuropsychology
  • Proteins / genetics
  • Spastic Paraplegia, Hereditary* / diagnostic imaging
  • Spastic Paraplegia, Hereditary* / genetics
  • Spastic Paraplegia, Hereditary* / pathology


  • Proteins
  • SPG11 protein, human

Supplementary concepts

  • Spastic paraplegia 11, autosomal recessive