Clinical and magnetic resonance imaging findings in a family with hereditary spastic paraplegia with mutation in NIPA1 / 中华神经科杂志

ABSTRACT

Objective To study features of the MRI and clinic in a family with pure hereditary spastic paraplegia (PHSPG) type 6.Methods Target loci (SPG3, 4, 6, 8 10 and 12) linkage analysis was performed in a SPG pedigree having 6 affected individuals using microsatellite markers and NIPA1 gene was screened for mutation by PCR-amplification and sequencing. MRI of brain and cervical and thoracic spinal cord were examined in these 6 patients and 6 normal controls matched for age and sex by two independent radiologists blinded to the clinical diagnosis. Cross-sectional areas and anteroposterior and transverse diameters of the spinal cord at the levels of C2～3, C7, T1～4, T9 were measured and data was statistically analyzed using the student's t test. Results A missense mutation of 316g→c in NIPA1 was identified in the affected subjects, presumably resulting in substitution of glutamic acid for arginine in residue 106. Evaluation of the brain MRI images revealed non-specific brain abnormalities. All patients presented thinning of cervical and upper thoracic spine with atrophy in both gray and white matter and enlarged subarachnoid cavity. In severe atrophic segments, a distinct boundary between grey and white matter was observed and the lesions in grey matter presented literal high intensity spots or patches with clear boundary on transaxial T2-weighted images (T2WI) and high signal intensity longitudinal strip on the sagittal T2WI. Cross-sectional areas and anteroposterior and transverse diameters of the spinal cord at C2～3, C7, T1～4 were significantly smaller in patients than in controls, while at the T9 level only transverse diameter showed significant difference (7.22±0.08 vs 8.17±0.41, t=2.870, P=0.046). Conclusions These findings indicate that the disease process in patients with SPG6 might be confined to the cervical and thoracic spinal cord, with atrophy in both white and grey matter having a distinct boundary.