Motor neuron degeneration in spastic paraplegia 11 mimics amyotrophic lateral sclerosis lesions

Paola S. Denora, Katrien Smets, Federica Zolfanelli, Chantal Ceuterick De Groote, Carlo Casali, Tine Deconinck, Anne Sieben, Michael Gonzales, Stephan Zuchner, Frederic Darios, Dirk Peeters, Alexis Brice, Alessandro Malandrini, Peter De Jonghe, Filippo M. Santorelli, Giovanni Stevanin, Jean Jacques Martin, Khalid H. El Hachimi

Research output: Contribution to journalArticlepeer-review


The most common form of autosomal recessive hereditary spastic paraplegia is caused by mutations in the SPG11/KIAA1840 gene on chromosome 15q. The nature of the vast majority of SPG11 mutations found to date suggests a loss-of-function mechanism of the encoded protein, spatacsin. The SPG11 phenotype is, in most cases, characterized by a progressive spasticity with neuropathy, cognitive impairment and a thin corpus callosum on brain MRI. Full neuropathological characterization has not been reported to date despite the description of4100 SPG11 mutations. We describe here the clinical and pathological features observed in two unrelated females, members of genetically ascertained SPG11 families originating from Belgium and Italy, respectively. We confirm the presence of lesions of motor tracts in medulla oblongata and spinal cord associated with other lesions of the central nervous system. Interestingly, we report for the first time pathological hallmarks of SPG11 in neurons that include intracytoplasmic granular lysosome-like structures mainly in supratentorial areas, and others in subtentorial areas that are partially reminiscent of those observed in amyotrophic lateral sclerosis, such as ubiquitin and p62 aggregates, except that they are never labelled with anti-TDP-43 or anti-cystatin C. The neuropathological overlap with amyotrophic lateral sclerosis, associated with some shared clinical manifestations, opens up new fields of investigation in the physiopathological continuum of motor neuron degeneration.

Original languageEnglish
Pages (from-to)1723-1734
Number of pages12
Issue number6
Publication statusPublished - 2016


  • Amyotrophic lateral sclerosis
  • Lipofuscin
  • Lysosome
  • Spastic paraplegia 11
  • Spatacsin

ASJC Scopus subject areas

  • Clinical Neurology


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