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

Marta Bellofatto, Giovanna De Michele, Aniello Iovino, Alessandro Filla, Filippo M Santorelli, Marta Bellofatto, Giovanna De Michele, Aniello Iovino, Alessandro Filla, Filippo M Santorelli

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.

Keywords: genetic; literature review; quality of study; spastic paraplegia; therapy.

Figures

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Figure 1
The search strategy.

References

    1. Parodi L, Coarelli G, Stevanin G, Brice A, Durr A. Hereditary ataxias and paraparesias: clinical and genetic update. Curr Opin Neurol. (2018) 31:462–71. 10.1097/WCO.0000000000000585
    1. Ruano L, Melo C, Silva MC, Coutinho P. The global epidemiology of hereditary ataxia and spastic paraplegia: a systematic review of prevalence studies. Neuroepidemiology (2014) 42:174–83. 10.1159/000358801
    1. Fink JK, Hedera P. Hereditary spastic paraplegia: genetic heterogeneity and genotype-phenotype correlation. Semin Neurol. (1999) 19:301–9. 10.1055/s-2008-1040846
    1. Rietberg MB, Brooks D, Uitdehaag BM, Kwakkel G. Exercise therapy for multiple sclerosis. Cochrane Database Syst Rev. (2005) 25:CD003980 10.1002/14651858.CD003980.pub2
    1. Sills GJ. The mechanisms of action of gabapentin and pregabalin. Curr Opin Pharmacol. (2006) 6:108–13. 10.1016/j.coph.2005.11.003
    1. Scheuer KH, Svenstrup K, Jennum P, Rogvi-Hansen Bá, Werdelin L, Fenger K, et al. . Double-blind crossover trial of gabapentin in SPG4-linked hereditary spastic paraplegia. Eur J Neurol. (2007) 14:663–6. 10.1111/j.1468-1331.2007.01812.x
    1. Ravnborg M, Grønbech-Jensen M, Jønsson A. The MS impairment scale: a pragmatic approach to the assessment of impairment in patients with multiple sclerosis. Mult Scler. (1997) 3:31–42. 10.1177/135245859700300104
    1. Tallaksen CM, Durr A. SPATAX – european network for hereditary spinocerebellar degenerative disorders. Acta Neurol Scand. (2003) 107:432–3. 10.1034/j.1600-0404.2003.00125_18.x
    1. Mondrup K, Pedersen E. The clinical effect of the GABA-agonist, progabide, on spasticity. Acta Neurol Scand. (1984) 69:200–6. 10.1111/j.1600-0404.1984.tb07802.x
    1. Béreau M, Anheim M, Chanson JB, Tio G, Echaniz-Laguna A, Depienne C, et al. . Dalfampridine in hereditary spastic paraplegia: a prospective, open study. J Neurol. (2015) 262:1285–8. 10.1007/s00415-015-7707-6
    1. Schüle R, Holland-Letz T, Klimpe S, Kassubek J, Klopstock T, Mall V, et al. . The spastic paraplegia rating scale (SPRS): a reliable and valid measure of disease severity. Neurology (2006) 67:430–4. 10.1212/01.wnl.0000228242.53336.90
    1. Uygunoglu U, Gunduz A, Tutuncu M, Akalin MA, Saip S, Siva A. The effects of dalfampridine on hereditary spastic paraparesis. Eur Neurol. (2016) 76:152–3. 10.1159/000449375
    1. de Niet M, de Bot ST, van de Warrenburg BP, Weerdesteyn V, Geurts AC. Functional effects of botulinum toxin type-A treatment and subsequent stretching of spastic calf muscles: a study in patients with hereditary spastic paraplegia. J Rehabil Med. (2015) 47:147–53. 10.2340/16501977-1909
    1. Hecht MJ, Stolze H, Auf dem Brinke M, Giess R, Treig T, Winterholler M, et al. Botulinum neurotoxin type A injections reduce spasticity in mild to moderate hereditary spastic paraplegia–report of 19 cases. Mov Disord. (2008) 30:228–33. 10.1002/mds.21809
    1. Riccardo M, Angela L, Angela D, Vita P, Giulio L, Pietroq F, et al. Combined treatment Fkt-botulinum toxin type A (Btx-A) in patients with Strumpell-Lorrain disease. Curr Pharm Des. (2016) 2016:758–63. 10.2174/1381612822666151204001830
    1. Kang SY, Lee MH, Lee SK, Sohn YH. Levodopa-responsive parkinsonism in hereditary spastic paraplegia with thin corpus callosum. Parkinsonism Relat Disord. (2004) 10:425–7. 10.1016/j.parkreldis.2004.05.003
    1. Guidubaldi A, Piano C, Santorelli FM, Silvestri G, Petracca M, Tessa A, et al. . Novel mutations in SPG11 cause hereditary spastic paraplegia associated with early-onset levodopa-responsive Parkinsonism. Mov Disord. (2011) 26:553–6. 10.1002/mds.23552
    1. Vanderver A, Tonduti D, Auerbach S, Schmidt JL, Parikh S, Gowans GC, et al. . Neurotransmitter abnormalities and response to supplementation in SPG11. Mol Genet Metab. (2012) 107:229–33. 10.1016/j.ymgme.2012.05.020
    1. Wijemanne S, Jankovic J. Dopa-responsive dystonia–clinical and genetic heterogeneity. Nat Rev Neurol. (2015) 11:414–24. 10.1038/nrneurol.2015.86
    1. Bettencourt C, Morris HR, Singleton AB, Hardy J, Houlden H. Exome sequencing expands the mutational spectrum of SPG8 in a family with spasticity responsive to L-DOPA treatment. J Neurol. (2013) 260:2414–6. 10.1007/s00415-013-7044-6
    1. Mignarri A, Malandrini A, Del Puppo M, Magni A, Monti L, Ginanneschi F, et al. . Treatment of SPG5 with cholesterol-lowering drugs. J Neurol. (2015) 262:2783–5. 10.1007/s00415-015-7971-5
    1. Schöls L, Rattay TW, Martus P, Meisner C, Baets J, Fischer I, et al. . Hereditary spastic paraplegia type 5: natural history, biomarkers and a randomized controlled trial. Brain (2017) 140:3112–27. 10.1093/brain/awx273
    1. Marelli C, Lamari F, Rainteau D, Lafourcade A, Banneau G, Humbert L, et al. . Plasma oxysterols: biomarkers for diagnosis and treatment in spastic paraplegia type 5. Brain (2018) 141:72–84. 10.1093/brain/awx297
    1. Lossos A, Teltsh O, Milman T, Meiner V, Rozen R, Leclerc D, et al. . Severe methylenetetrahydrofolate reductase deficiency: clinical clues to a potentially treatable cause of adult-onset hereditary spastic paraplegia. JAMA Neurol. (2014) 71:901–4. 10.1001/jamaneurol.2014.116
    1. Perna A, Masciullo M, Modoni A, Cellini E, Parrini E, Ricci E, et al. . Severe 5,10-methylenetetrahydrofolate reductase deficiency: a rare, treatable cause of complicated hereditary spastic paraplegia. Eur J Neurol. (2018) 25:602–5. 10.1111/ene.13557
    1. Pease WS. Therapeutic electrical stimulation for spasticity: quantitative gait analysis. Am J Phys Med Rehabil. (1998) 77:351–5. 10.1097/00002060-199807000-00021
    1. Bertolucci F, Di Martino S, Orsucci D, Ienco EC, Siciliano G, Rossi B, et al. . Robotic gait training improves motor skills and quality of life in hereditary spastic paraplegia. NeuroRehabilitation (2015) 36:93–9. 10.3233/NRE-141196
    1. Seo HG, Oh BM, Kim K. Robot-assisted gait training in a patient with hereditary spastic paraplegia. PM R. (2015) 7:210–3. 10.1016/j.pmrj.2014.09.008
    1. Zhang Y, Roxburgh R, Huang L, Parsons J, Davies TC. The effect of hydrotherapy treatment on gait characteristics of hereditary spastic paraparesis patients. Gait Posture (2014) 39:1074–9. 10.1016/j.gaitpost.2014.01.010
    1. Samuel AJ, Aranha VP, Kamath T, Pokhrel M. Physical therapy interventions for the patients with hereditary spastic paraparesis. An exploratory case reports. Int J Physioth Res. (2013) 3:110–3.
    1. Margetis K, Korfias S, Boutos N, Gatzonis S, Themistocleous M, Siatouni A, et al. . Intrathecal baclofen therapy for the symptomatic treatment of hereditary spastic paraplegia. Clin Neurol Neurosurg. (2014) 123:142–5. 10.1016/j.clineuro.2014.05.024
    1. Dan B, Cheron G. Intrathecal baclofen normalizes motor strategy for squatting in familial spastic paraplegia: a case study. Neurophysiol Clin. (2000) 30:43–8. 10.1016/S0987-7053(00)88866-8
    1. Heetla HW, Halbertsma JP, Dekker R, Staal MJ, van Laar T. Improved gait performance in a patient with hereditary spastic paraplegia after a continuous intrathecal baclofen test infusion and subsequent pump implantation: a case report. Arch Phys Med Rehabil. (2015) 96:1166–9. 10.1016/j.apmr.2015.01.012
    1. Kai M, Yongjie L, Ping Z. Long-term results of selective dorsal rhizotomy for hereditary spastic paraparesis. J Clin Neurosci. (2014) 21:116–20. 10.1016/j.jocn.2013.04.020
    1. Sharma J, Bonfield C, Steinbok P. Selective dorsal rhizotomy for hereditary spastic paraparesis in children. Childs Nerv Syst. (2016) 32:1489–94. 10.1007/s00381-016-3122-2
    1. Lo Giudice T, Lombardi F, Santorelli FM, Kawarai T, Orlacchio A. Hereditary spastic paraplegia: clinical-genetic characteristics and evolving molecular mechanisms. Exp Neurol. (2014) 261:518–39. 10.1016/j.expneurol.2014.06.011
    1. Havlicek S, Kohl Z, Mishra HK, Prots I, Eberhardt E, Denguir N, et al. . Gene dosage-dependent rescue of HSP neurite defects in SPG4 patients' neurons. Hum Mol Genet. (2014) 23:2527–41. 10.1093/hmg/ddt644
    1. Julien C, Lissouba A, Madabattula S, Fardghassemi Y, Rosenfelt C, Androschuk A, et al. . Conserved pharmacological rescue of hereditary spastic paraplegia-related phenotypes across model organisms. Hum Mol Genet. (2016) 25:1088–99. 10.1093/hmg/ddv632
    1. Pirozzi M, Quattrini A, Andolfi G, Dina G, Malaguti MC, Auricchio A, et al. . Intramuscular viral delivery of paraplegin rescues peripheral axonopathy in a model of hereditary spastic paraplegia. J Clin Invest. (2006) 116:202–8. 10.1172/JCI26210
    1. Mishra HK, Prots I, Havlicek S, Kohl Z, Perez-Branguli F, Boerstler T, et al. . GSK3ß-dependent dysregulation of neurodevelopment in SPG11-patient induced pluripotent stem cell model. Ann Neurol. (2016) 79:826–840. 10.1002/ana.24633
    1. Boutry M, Branchu J, Lustremant C, Pujol C, Pernelle J, Matusiak R, et al. . Inhibition of lysosome membrane recycling causes accumulation of gangliosides that contribute to neurodegeneration. Cell Rep. (2018) 23:3813–26. 10.1016/j.celrep.2018.05.098

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