[Hereditary spastic paraplegias]

Abstract

Hereditary spastic paraplegias (HSP) are characterised by symmetric spastic paraplegia, pallhypaesthesia, and urinary dysfunction (uncomplicated HSP). Complicated HSP is present if uncomplicated HSP additionally presents with epilepsy, dementia, cataract, extrapyramidal dysfunction, amyotrophy, polyneuropathy, or ichthyosis. Clinically, HSP are similar but genetically even more heterogeneous. The disease course is slowly progressive and, the earlier the disease onset, the slower the course. Causes of HSP are mutations in 20 different genes, of which eight have been identified so far. A single mutation can cause complicated and uncomplicated HSP. Onset and severity can be quite variable between both groups and within families. Despite molecular genetic advances, diagnosis of HSP still relies on clinical features and the exclusion of various differential diagnoses. Neuropathologically, there is degeneration of corticospinal, posterior column, and spinocerebellar axons. Most likely, degeneration of the longest CNS axons is due to an impaired energy supply of the anterograde and retrograde axonal transport.