Management of Hereditary Spastic Paraplegia: A Systematic Review of the Literature

Abstract

The term hereditary spastic paraplegia (HSP) embraces a clinically and genetically heterogeneous group of neurodegenerative diseases characterized by progressive spasticity and weakness of the lower limbs. There currently exist no specific therapies for HSP, and treatment is exclusively symptomatic, aimed at reducing muscle spasticity, and improving strength and gait. The authors set out to perform a comprehensive systematic review of the available scientific literature on the treatment of HSP, applying Cochrane Collaboration methods. The Google Scholar, PubMed and Scopus electronic databases were searched to find relevant randomized control trials (RCTs) and open-label interventional studies, prospective, and retrospective observational studies of supplements, medications, and physical therapy, as well as case reports and case series. Two authors independently analyzed 27 articles selected on the basis of a series of inclusion criteria. Applying a best-evidence synthesis approach, they evaluated these articles for methodological quality. A standardized scoring system was used to obtain interrater assessments. Disagreements were resolved by discussion. The 27 articles focused on pharmacological treatment (n = 17 articles), physical therapy (n = 5), surgical treatment (n = 5). The drugs used in the 17 articles on pharmacological therapy were: gabapentin, progabide, dalfampridine, botulinum toxin, L-Dopa, cholesterol-lowering drugs, betaine, and folinic acid. Gabapentin, progabide, dalfampridine, and botulinum toxin were used as antispastic agents; the study evaluating gabapentin efficacy was well-designed, but failed to demonstrate any significant improvement. L-Dopa, cholesterol-lowering drugs, betaine, and folinic acid were only used in specific HSP subtypes. Two of the three studies evaluating cholesterol-lowering drugs (in SPG5 patients) were well-designed and showed a significant reduction of specific serum biomarkers (oxysterols), but clinical outcomes were not evaluated. The articles focusing on physical treatment and surgical therapy were found to be of low/medium quality and, accordingly, failed to clarify the role of these approaches in HSP. Despite recent advances in understanding of the pathogenesis of HSP and the possibility, in several centers, of obtaining more precise and rapid molecular diagnoses, there is still no adequate evidence base for recommending the various published therapies. Well-designed RCTs are needed to evaluate the efficacy of both symptomatic and pathogenetic treatments.

Mobility Characteristics of Children with Spastic Paraplegia Due to a Mutation in the KIF1A Gene

“…A recent systematic review evaluated treatment options in HSP, taking into account both pure and complicated forms. 17 Several pharmacological and physical therapies were assessed, as were intrathecal baclofen and dorsal rhizotomy. Most studies included were of low quality, the ones that were well-designed showed no significant improvement, or did not evaluate clinical outcomes.…”

Pallidopyramidal Syndrome and Hereditary Spastic Paraplegia common features and diagnostic approach and therapeutic considerations

“…There are studies that support the contribution of oxidative stress to neuronal death initiation and also as an to neurodegenerative process augmentation. Therefore the anti oxidative therapy (39,40) and cholesterol lowering drugs added to anti spastic therapy , K+ channel blocker drugs, levodopa therapy, folic acid therapy and other rehabilitation therapies (41,42,43,44,45,46) could constitute a future strategy for improving the quality of life for this patients.…”

Physical activity and exercise interventions for people with rare neurological disorders: a scoping review of systematic reviews

“…HSP was one of the included conditions, however, no systematic reviews were identified at the time of searches. The overall literature in this condition is limited to case studies of rehabilitation interventions (61) and small studies of hydrotherapy (62) or robot gait training (63,64), as confirmed in a recent systematic review, identified subsequently to our scoping review searches (23). The authors of this recent systematic review rated the overall quality of physical interventions in HSP as low.…”

“…These interventions widely comprise "Any bodily movement produced by skeletal muscles that requires energy expenditure" and any type of structured exercise (15) including gait and balance training, video-gaming (16)(17)(18) and cognitive behaviour interventions (19)(20)(21). However, although physical activities are promoted as an essential part of the clinical management across RNCs, evidence supporting physical activity interventions is still lacking in these conditions (22)(23)(24)(25)(26)(27). To date, there are significant gaps in understanding about which types of activities maintain physical functioning and increase participation in activities and quality of life across RNCs.…”