General description

Hereditary spastic paraplegia (HSP) is a genetic disorder characterized by slowly progressive spasticity and muscular weakness affecting the bilateral lower extremities. HSP is driven by “dying-back” degeneration of the longest central axons, especially those of the lateral corticospinal and dorsal column pathways. More than 80 genes converge on a limited set of cellular mechanisms including:

• impaired microtubule severing and axonal transport (e.g., SPAST/SPG4, KIF5A, KIF1A)
• disturbed endoplasmic-reticulum and endosomal membrane dynamics (ATL1/SPG3A, REEP1/SPG31, SPG11)
• mitochondrial dysfunction and oxidative stress (SPG7, SPG13)
• defective autophagy and lipid metabolism (SPG11, SPG15, SPG35)
  Age at onset spans infancy to late adulthood; earlier onset often predicts slower motor progression, whereas complicated phenotypes are more frequent in autosomal-recessive forms such as SPG11.

HSP can be categorized into two distinct types: the pure form, in which only the cardinal manifestations of spastic paraparesis and vesicourinary disturbances are present, and the complex form, which is accompanied by additional symptomatology such as cerebellar ataxia, sensory deficits, visual disturbance, auditory disturbance, scoliosis, and hip dislocation in addition to the presentation of pure form.

References

1. Fink, John K. "Hereditary spastic paraplegia: clinico-pathologic features and emerging molecular mechanisms." Acta neuropathologica 126.3 (2013): 307-328.
2. Awuah, Wireko Andrew, et al. "Hereditary spastic paraplegia: Novel insights into the pathogenesis and management." SAGE open medicine 12 (2024): 20503121231221941.
3. Hourani, R., et al. "MR imaging findings in autosomal recessive hereditary spastic paraplegia." American journal of neuroradiology 30.5 (2009): 936-940.