title: Multimodal MRI-based study in patients with SPG4 mutations.
abstract: Mutations in the SPG4 gene (SPG4-HSP) are the most frequent cause of hereditary spastic paraplegia, but the extent of the neurodegeneration related to the disease is not yet known. Therefore, our objective is to identify regions of the central nervous system damaged in patients with SPG4-HSP using a multi-modal neuroimaging approach. In addition, we aimed to identify possible clinical correlates of such damage. Eleven patients (mean age 46.0 ± 15.0 years, 8 men) with molecular confirmation of hereditary spastic paraplegia, and 23 matched healthy controls (mean age 51.4 ± 14.1years, 17 men) underwent MRI scans in a 3T scanner. We used 3D T1 images to perform volumetric measurements of the brain and spinal cord. We then performed tract-based spatial statistics and tractography analyses of diffusion tensor images to assess microstructural integrity of white matter tracts. Disease severity was quantified with the Spastic Paraplegia Rating Scale. Correlations were then carried out between MRI metrics and clinical data. Volumetric analyses did not identify macroscopic abnormalities in the brain of hereditary spastic paraplegia patients. In contrast, we found extensive fractional anisotropy reduction in the corticospinal tracts, cingulate gyri and splenium of the corpus callosum. Spinal cord morphometry identified atrophy without flattening in the group of patients with hereditary spastic paraplegia. Fractional anisotropy of the corpus callosum and pyramidal tracts did correlate with disease severity. Hereditary spastic paraplegia is characterized by relative sparing of the cortical mantle and remarkable damage to the distal portions of the corticospinal tracts, extending into the spinal cord.
authors: Departament of Neurology, University of Campinas (UNICAMP), Campinas, São Paulo, Brazil.
authors: Thiago J R
authors: TJ
authors: Rezende
authors: Departament of Neurology, University of Campinas (UNICAMP), Campinas, São Paulo, Brazil.
authors: Milena
authors: M
authors: de Albuquerque
authors: Departament of Neurology, University of Campinas (UNICAMP), Campinas, São Paulo, Brazil.
authors: Gustavo M
authors: GM
authors: Lamas
authors: Departament of Neurology, University of Campinas (UNICAMP), Campinas, São Paulo, Brazil.
authors: Alberto R M
authors: AR
authors: Martinez
authors: Departament of Neurology, University of Campinas (UNICAMP), Campinas, São Paulo, Brazil.
authors: Brunno M
authors: BM
authors: Campos
authors: Departament of Neurology, University of Campinas (UNICAMP), Campinas, São Paulo, Brazil.
authors: Raphael F
authors: RF
authors: Casseb
authors: Departament of Neurology, University of Campinas (UNICAMP), Campinas, São Paulo, Brazil.
authors: Cynthia B
authors: CB
authors: Silva
authors: Departament of Neurology, University of Campinas (UNICAMP), Campinas, São Paulo, Brazil.
authors: Lucas M T
authors: LM
authors: Branco
authors: Departament of Neurology, University of Campinas (UNICAMP), Campinas, São Paulo, Brazil.
authors: Anelyssa
authors: A
authors: D'Abreu
authors: Department of Medical Genetics, University of Campinas (UNICAMP), São Paulo, Campinas, Brazil.
authors: Iscia
authors: I
authors: Lopes-Cendes
authors: Departament of Neurology, University of Campinas (UNICAMP), Campinas, São Paulo, Brazil.
authors: Fernando
authors: F
authors: Cendes
authors: Departament of Neurology, University of Campinas (UNICAMP), Campinas, São Paulo, Brazil.
authors: Marcondes C
authors: MC
authors: França
mesh_terms: D000251:Adenosine Triphosphatases / Q000235:genetics*; D000328:Adult; D000368:Aged; D001921:Brain / Q000473:pathology*; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D008875:Middle Aged; D064847:Multimodal Imaging; D009154:Mutation; D012720:Severity of Illness Index; D015419:Spastic Paraplegia, Hereditary / Q000235:genetics / Q000473:pathology*; D000074181:Spastin; D013116:Spinal Cord / Q000473:pathology*
chemical_list: D000251:Adenosine Triphosphatases; D000074181:Spastin; C400283:SPAST protein, human