Structural and metabolic damage in brains of patients with SPG11-related spastic paraplegia as detected by quantitative MRI

J Neurol. 2011 Dec;258(12):2240-7. doi: 10.1007/s00415-011-6106-x. Epub 2011 May 29.

Abstract

The goal of this work was to assess brain structural and metabolic abnormalities of subjects with SPG11 and their relevance to clinical disability by using quantitative magnetic resonance (MR) metrics. Autosomal recessive hereditary spastic paraplegia (AR-HSP) with thin corpus callosum and cognitive decline is a complex neurological disorder caused by mutations in the SPG11 gene in most cases. Little is known about the process leading to corticospinal and white matter degeneration. We performed conventional MRI/MR spectroscopic imaging ((1)H-MRSI) examinations in 10 HSP patients carrying an SPG11 mutation and in 10 demographically matched healthy controls (HC). We measured in each subject cerebral white matter hyperintensities (WMHs), normalized global and cortical brain volumes, and (1)H-MRSI-derived central brain levels of N-acetylaspartate (NAA) and choline (Cho) normalized to creatine (Cr). Clinical disability was assessed according to patients' autonomy in walking. Conventional MRI showed WMHs in all patients. Global brain volumes were lower in patients than in HC (p < 0.001). Decreased values were diffusely found also in cortical regions (p < 0.01). On (1)H-MRSI, NAA/Cr values were lower in SPG11 patients than in HC (p = 0.002). Cho/Cr values did not differ between patients and HC. Cerebral volume decreases and NAA/Cr in the corona radiata correlated closely with increasing disability scores (p < 0.05). Quantitative MR measures propose that widespread structural and metabolic brain damage occur in SPG11 patients. The correlation of these MR metrics with measures of patients' disease severity suggests that they might represent adequate surrogate markers of disease outcome.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Brain / metabolism*
  • Brain / pathology*
  • Female
  • Humans
  • Image Interpretation, Computer-Assisted
  • Magnetic Resonance Imaging
  • Magnetic Resonance Spectroscopy*
  • Male
  • Middle Aged
  • Spastic Paraplegia, Hereditary / metabolism*
  • Spastic Paraplegia, Hereditary / pathology*
  • Young Adult

Supplementary concepts

  • Spastic paraplegia 11, autosomal recessive