Bellofatto Marta, De Michele Giovanna, Iovino Aniello, Filla Alessandro, Santorelli Filippo M
Department of Neurosciences and Reproductive and Odontostomatological Sciences, Federico II University, Naples, Italy.
Molecular Medicine, IRCCS Fondazione Stella Maris, Pisa, Italy.
Front Neurol. 2019 Jan 22;10:3. doi: 10.3389/fneur.2019.00003. eCollection 2019.
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 ( = 17 articles), physical therapy ( = 5), surgical treatment ( = 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.
遗传性痉挛性截瘫（HSP）是一组临床和遗传异质性的神经退行性疾病，其特征为下肢进行性痉挛和无力。目前尚无针对HSP的特异性疗法，治疗仅为对症治疗，旨在减轻肌肉痉挛，增强力量和改善步态。作者着手运用Cochrane协作方法，对有关HSP治疗的现有科学文献进行全面系统的综述。检索了谷歌学术、PubMed和Scopus电子数据库，以查找相关的随机对照试验（RCT）、开放标签干预研究、补充剂、药物和物理治疗的前瞻性及回顾性观察研究，以及病例报告和病例系列。两位作者独立分析了根据一系列纳入标准选出的27篇文章。他们采用最佳证据综合方法，评估这些文章的方法学质量。使用标准化评分系统获得评分者间评估结果。分歧通过讨论解决。这27篇文章聚焦于药物治疗（17篇）、物理治疗（5篇）、手术治疗（5篇）。17篇关于药物治疗的文章中使用的药物有：加巴喷丁、普罗加比、达氟吡啶、肉毒杆菌毒素、左旋多巴、降胆固醇药物、甜菜碱和亚叶酸。加巴喷丁、普罗加比、达氟吡啶和肉毒杆菌毒素用作抗痉挛剂；评估加巴喷丁疗效的研究设计良好，但未显示出任何显著改善。左旋多巴、降胆固醇药物、甜菜碱和亚叶酸仅用于特定的HSP亚型。评估降胆固醇药物（在SPG5患者中）的三项研究中有两项设计良好，显示特定血清生物标志物（氧化甾醇）显著降低，但未评估临床结果。聚焦于物理治疗和手术治疗的文章质量为低/中等，因此未能阐明这些方法在HSP中的作用。尽管最近在HSP发病机制的理解方面取得了进展，并且在几个中心有可能获得更精确和快速的分子诊断，但仍然没有足够的证据基础来推荐各种已发表的疗法。需要设计良好的RCT来评估对症治疗和病因治疗的疗效。
