Hereditary spastic paraplegias: time for an objective case definition and a new nosology for neurogenetic disorders to facilitate biomarker/therapeutic studies.

摘要: Hereditary spastic paraplegias (HSPs) are heterogeneous neurodegenerative disorders characterized by progressive lower limb weakness and spasticity as core symptoms of the degeneration corticospinal motor neurons. Even after exclusion infectious toxic mimickers these disorders, definitive diagnosis remains tricky, mainly in sporadic forms, there is significant overlap with other disorders. Since their first description, various attempts failed to reach an appropriate classification. This was due constant expansion clinical spectrum diseases discovery new genes, a number them involved overlapping diseases. Areas covered: In this perspective review, extensive literature study conducted on historical progress HSP research. We also revised previous current classifications closely related neurogenetic analyzed areas overlap. Expert opinion: There undeniable need for objective case definition reclassification all including HSPs, prerequisite improve patient follow-up, biomarker identification develop therapeutics. The challenge understand why mutations can give rise multiple phenotypic presentations along which tract affected.