SPG11 mutations cause widespread white matter and basal ganglia abnormalities, but restricted cortical damage

Ingrid Faber, Alberto Rolim Muro Martinez, Thiago Junqueira Ribeiro de Rezende, Carlos Roberto Martins, Melina Pazian Martins, Charles Marques Lourenço, Wilson Marques, Celeste Montecchiani, Antonio Orlacchio, Jose Luiz Pedroso, Orlando Graziani Povoas Barsottini, Íscia Lopes-Cendes, Marcondes Cavalcante França

Research output: Contribution to journalArticlepeer-review


SPG11 mutations are the major cause of autosomal recessive Hereditary Spastic Paraplegia. The disease has a wide phenotypic variability indicating many regions of the nervous system besides the corticospinal tract are affected. Despite this, anatomical and phenotypic characterization is restricted. In the present study, we investigate the anatomical abnormalities related to SPG11 mutations and how they relate to clinical and cognitive measures. Moreover, we aim to depict how the disease course influences the regions affected, unraveling different susceptibility of specific neuronal populations. We performed clinical and paraclinical studies encompassing neuropsychological, neuroimaging, and neurophysiological tools in a cohort of twenty-five patients and age matched controls. We assessed cortical thickness (FreeSurfer software), deep grey matter volumes (T1-MultiAtlas tool), white matter microstructural damage (DTI-MultiAtlas) and spinal cord morphometry (Spineseg software) on a 3 T MRI scan. Mean age and disease duration were 29 and 13.2 years respectively. Sixty-four percent of the patients were wheelchair bound while 84% were demented. We were able to unfold a diffuse pattern of white matter integrity loss as well as basal ganglia and spinal cord atrophy. Such findings contrasted with a restricted pattern of cortical thinning (motor, limbic and parietal cortices). Electromyography revealed motor neuronopathy affecting 96% of the probands. Correlations with disease duration pointed towards a progressive degeneration of multiple grey matter structures and spinal cord, but not of the white matter. SPG11-related hereditary spastic paraplegia is characterized by selective neuronal vulnerability, in which a precocious and widespread white matter involvement is later followed by a restricted but clearly progressive grey matter degeneration.

Original languageEnglish
Pages (from-to)848-857
Number of pages10
JournalNeuroImage: Clinical
Publication statusPublished - Jan 1 2018


  • Complicated hereditary spastic paraplegia
  • Grey matter
  • Motor neuron disorder
  • SPG11
  • Spinal cord
  • Thinning of the corpus callosum
  • White matter

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging
  • Neurology
  • Clinical Neurology
  • Cognitive Neuroscience


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