Beyond motor impairment: investigating cognitive aspects of hereditary spastic paraplegia in a Greek case series

Hereditary spastic paraplegia (HSP) is a heterogeneous group of inherited disorders primarily characterized by progressive spasticity and lower extremity weakness. Traditionally associated with corticospinal tract dysfunction, HSP was long presumed to leave cognitive function largely unaffected. However, growing evidence increasingly recognizes cognitive impairment as a relevant feature of the condition. The primary aim of this study is to broaden the understanding of the cognitive profile in HSP, by examining cognitive impairments in a Greek cohort. A detailed neuropsychological assessment was conducted in 10 HSP patients and 30 healthy controls, including measures of executive function, memory, attention, processing speed, visual scanning, and social cognition. Our findings revealed widespread cognitive impairment, with prominent deficits in processing speed, attention, visual scanning, and social cognition, supporting reduced cognitive resilience in HSP. On a neuroanatomic level, the observed cognitive decline in HSP may indicate localized dysfunction within the frontal area of the brain among affected patients. We futher hypothesize that genetically distinct HSP subtypes converge on shared cellular disruptions that may compromise frontotemporal networks, thereby producing similar cognitive phenotypes.