MRI and Electrophysiological Characterization of Patients Suffering from Pure and Complicated Hereditary Spastic Paraplegia

Hereditary spastic paraplegia (HSP) is a phenotypically and genotypically heterogeneous neurodegenerative disease encompassing a group of disorders mainly characterized by spastic paraparesis of the lower limbs. From the clinical point of view, HSP can be classified into complicated and pure forms. The present study contains clinical, magnetic resonance imaging (MRI), and electrophysiological investigations of a total of 33 HSP patients suffering from pure (n=22) and complicated forms (n=11), respectively. The MRI standard protocol was performed both for the brain (including a volume-rendering MP-RAGE data set, voxel size 1 mm3) and for the cervical spinal cord (T1- and T2-weighted sequences). Besides visual evaluation of the cerebral MRI and classical thickness measurements of the spinal cord, 3-D MRI of the brains were analysed by the observer-independent technique of voxel-based morphometry (VBM), both in comparison to an age-matched normal data base and in the comparison between complicated and pure forms. With respect to the electrophysiological investigations (e.g., nerve conduction velocities), we present an overview of possible affections of the peripheral nervous system both in pure and complicated forms. It could be demonstrated that clinical presentation and electrophysiological data help to characterize the phenotype of different HSP subtypes. Despite the obvious heterogeneity of complicated HSP, MRI was helpful to elucidate certain patterns of cerebral changes (e.g., of the white matter), and VBM exhibited regional signal alterations (atrophy) of the brain, in particular with respect to morphology of the corpus callosum. In summary, our data showed the different types of involvement of extrapyramidal cerebral and extracerebral structures in a sizeable group of HSP patients and might help to improve the characterization and pathophysiological understanding in this heterogeneous disease.