Hereditary spastic paraplegia

Hereditary spastic paraplegia (HSP), also known as familial spastic paraplegia or Strümpell-Lorrain disease, is a group of inherited neurological disorders characterized by progressive weakness and spasticity (stiffness) of the lower limbs. The condition primarily affects the longest nerve fibers in the corticospinal tract, which are responsible for carrying signals from the brain to the legs. Over time, these nerve fibers undergo progressive degeneration, leading to the hallmark symptoms of the disease. HSP is broadly classified into two forms: uncomplicated (pure) and complicated (complex). In uncomplicated HSP, the primary symptoms are progressive lower limb spasticity, weakness, and urinary urgency, often accompanied by impaired vibration sense in the feet and hyperreflexia. Complicated forms present with additional neurological features such as cognitive impairment, epilepsy, ataxia (impaired coordination), peripheral neuropathy, thin corpus callosum, optic atrophy, or extrapyramidal signs. Walking difficulty is the most prominent functional impairment, and many patients eventually require assistive devices such as canes, walkers, or wheelchairs. More than 80 genetic subtypes (designated SPG1 through SPG80+) have been identified, with mutations in genes such as SPAST (SPG4), ATL1 (SPG3A), REEP1 (SPG31), and KIF5A (SPG10) being among the most common. Inheritance can be autosomal dominant, autosomal recessive, or X-linked, depending on the subtype. There is currently no cure for HSP. Treatment is symptomatic and supportive, focusing on physical therapy to maintain mobility and reduce spasticity, oral antispasticity medications (such as baclofen or tizanidine), intrathecal baclofen pump therapy for severe cases, botulinum toxin injections, and orthopedic interventions when needed. Regular follow-up with a multidisciplinary team including neurologists, physiotherapists, and occupational therapists is recommended.

Data sourced from FDA regulatory filings and ClinicalTrials.gov. Updated periodically.

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