Hereditary spastic paraparesis: a review of new developments

Hereditary spastic paraparesis (HSP) or the Strümpell-Lorrain syndrome is the name given to a heterogeneous group of inherited disorders in which the main clinical feature is progressive lower limb spasticity.Before the advent of molecular genetic studies into these disorders, several classifications had been proposed, based on the mode of inheritance, the age of onset of symptoms, and the presence or otherwise of additional clinical features.Families with autosomal dominant, autosomal recessive, and X-linked inheritance have been described. Historical aspectsIn 1880 Strümpell published what is considered to be the first clear description of HSP.He reported a family in which two brothers were aVected by spastic paraplegia.The father was said to be "a little lame", suggesting autosomal dominant transmission. 1Both Strümpell and Lorrain added similar cases to the literature in subsequent years. 2 3 Shortly after these landmark descriptions, numerous reported cases of HSP appeared in the literature.However, Pratt, who considered the presence of additional neurological features to be incompatible with the original descriptions, labelled many of these as HSP plus syndromes. 4 Early reviews of these and other cases attempted to identify "pure" cases as had been described by Strümpell.6][7][8] It was Harding in 1981 who, after detailed clinical evaluation of 22 families, suggested criteria for classifying HSP into pure and complicated forms which have since been adopted and are discussed below. 9Further subdivision of pure HSP was also suggested by Harding based on the age of onset of the disease.It was found that families could be separated into two groups, one with onset before 35 years (type I) and the other with onset after 35 years (type II).There seemed to be clinical diVerences between the groups, with the type I patients having a slow and variable course compared with the more rapidly evolving type II, in which muscle weakness, urinary symptoms, and sensory loss were more marked. 9Neither of these classifications are ideal, with many families not easily fitting the criteria.As is the case in other hereditary neurodegenerative disorders, the unravelling of the molecular genetic mechanisms underlying he-reditary spastic paraparesis will no doubt provide a more useful and relevant classification.