Heriditary Spastic Paraplegia

GUIDELINES RELEVANT FOR HSP

  • Gasser T, Finsterer J, Baets J, Van Broeckhoven C, Di Donato S, Fontaine B, DeJonghe P, Lossos A, Lynch T, Mariotti C, Schöls L, Spinazzola A, Szolnoki Z, Tabrizi SJ, Tallaksen CM, Zeviani M, Burgunder JM, Harbo HF; EFNS. EFNS guidelines on the molecular diagnosis of ataxias and spastic paraplegias. Eur J Neurol. 2010 Feb;17(2):179-88.

CONSENSUS PAPERS

  • Dressler D, Berweck S, Chatzikalfas A, Ebke M, Frank B, Hesse S, Huber M,Krauss JK, Mücke KH, Nolte A, Oelmann HD, Schönle PW, Schmutzler M, PickenbrockH, Van der Ven C, Veelken N, Vogel M, Vogt T, Saberi FA. Intrathecal Baclofen therapy in Germany: Proceedings of the IAB-Interdisciplinary Working Group for Movement Disorders Consensus Meeting. J Neural Transm (Vienna). 2015 Nov;122(11):1573-9. doi: 10.1007/s00702-015-1425-1. Epub 2015 Jul 16.

DIAGNOSTIC ALGORITHMS

  • n.a.

EVIDENCE

Disease modifying therapies
  • Schols 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.
Medical management of spasticity
  • Broggi G, Servello D, Brock S, Dones I. The treatment of spasticity by intrathecal administration of baclofen: a preliminary personal experience. J Neurosurg Sci 1993; 37(4): 203-8.
  • 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(2): 147-53.
  • Franco-Hernandez JA, Rodriguez LM, Ortiz de Landazuri PJ, Hernandez AG. Use of sugammadex in Strumpell-Lorrain disease: a report of two cases. Braz J Anesthesiol 2013; 63(1): 113-5.
  • Geva-Dayan K, Domenievitz D, Zahalka R, Fattal-Valevski A. Botulinum toxin injections for pediatric patients with hereditary spastic paraparesis. J ChildNeurol. 2010 Aug;25(8):969-75.
  • 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; 23(2): 228-33.
  • Klebe S, Stolze H, Kopper F, Lorenz D, Wenzelburger R, Deuschl G, et al. Objective assessment of gait after intrathecal baclofen in hereditary spastic paraplegia. J Neurol 2005; 252(8): 991-3.
  • 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.
  • 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. Current pharmaceutical design 2016; 22(6): 758-63.
  • Scheuer KH, Svenstrup K, Jennum P, Rogvi-Hansen B, Werdelin L, Fenger K, et al. Double-blind crossover trial of gabapentin in SPG4-linked hereditary spastic paraplegia. Eur J Neurol 2007; 14(6): 663-6.
Physical Therapy and neurorehabilitative treatments
  • Bertolucci F, Di Martino S, Orsucci D, Ienco EC, Siciliano G, Rossi B, Mancuso M, Chisari C. Robotic gait training improves motor skills and quality of life in hereditary spastic paraplegia. NeuroRehabilitation. 2015;36(1):93-9.
  • Seo HG, Oh BM, Kim K. Robot-assisted gait training in a patient with hereditary spastic paraplegia. PM R. 2015 Feb;7(2):210-3.
  • Meythaler JM, Steers WD, Tuel SM, Cross LL, Sesco DC, Haworth CS. Intrathecal baclofen in hereditary spastic paraparesis. Arch Phys Med Rehabil 1992; 73(9): 794-7.
  • Nonnekes J, van Lith B, van de Warrenburg BP, Weerdesteyn V, Geurts ACH. Pathophysiology, diagnostic work-up and management of balance impairments and falls in patients with hereditary spastic paraplegia. J Rehabil Med 2017; 49(5): 369-77.
  • Sweet LA, O'Neill LM, Dobbs MB. Serial casting for neuromuscular flatfoot and vertical talus in an adolescent with hereditary spastic paraplegia. Pediatric physical therapy : the official publication of the Section on Pediatrics of the American Physical Therapy Association 2014; 26(2): 253-64.
  • 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(4): 1074-9.
Management of urinary symptoms and pain
  • Ribeiro AM, Ferreira CH, Cristine Lemes Mateus-Vasconcelos E, Moroni RM, Brito LM, Brito LG. Physical therapy in the management of pelvic floor muscles hypertonia in a woman with hereditary spastic paraplegia. Case Rep Obstet Gynecol 2014; 2014: 306028.
Others
  • Bensmail D, Quera Salva MA, Roche N, Benyahia S, Bohic M, Denys P, et al. Effect of intrathecal baclofen on sleep and respiratory function in patients with spasticity. Neurology 2006; 67(8): 1432-6.
Diagnosis (non-genetic)
  • Bonnefoy-Mazure A, Turcot K, Kaelin A, De Coulon G, Armand S. Full body gait analysis may improve diagnostic discrimination between hereditary spastic paraplegia and spastic diplegia: a preliminary study. Research in developmental disabilities 2013; 34(1): 495-504.

REGISTRIES

Hereditary spastic paraplegia and spinocerebellar studies

CLINICAL RATING SCALES

Spastic Paraplegia Rating Scale
  • Schule 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(3): 430-4.
  • Spastic Paraplegia Rating Scale (SPRS) is suitable for all subtypes of SP including familial and sporadic forms as well as pure and complicated phenotypes. As SPRS uses standard neurological examination procedures in most of its items, instructions for test performance and scoring could be kept short for most items without endangering interrater reliability. Completion of SPRS requires less than 15 minutes and does not depend on any special equipment. The variety of signs and symptoms that accounts for clinical variability in complicated forms of SP is listed in an inventory. This inventory thus provides a standardized tool to document multisystem involvement of the disease. The inventory is adapted to a routine neurological examination and avoids additional time-consuming tests.
Spinocerebellar Degeneration Functional Score (SDFS)
  • Le Ber I, Moreira MC, Rivaud-Péchoux S, Chamayou C, Ochsner F, Kuntzer T, Tardieu M, Saïd G, Habert MO, Demarquay G, Tannier C, Beis JM, Brice A, Koenig M, Dürr A. Cerebellar ataxia with oculomotor apraxia type 1: clinical and genetic studies. Brain. 2003 Dec;126(Pt 12):2761-72. Epub 2003 Sep 23.
  • Spinocerebellar Degeneration Functional Score (SDFS), which rates the disability stages from 0 (asymptomatic) to 7 (bedridden)

NETWORKS AND STUDY GROUPS

  • Alliance for Treatment in HSP and PLS is an international network with the intention to further the development of trial readiness and therapies in HSP and PLS
  • SPATAX
  • German HSP Registry
    The German HSP Registry (R. Schüle, L. Schöls) was started in 2004 through funding of the German Ministry for Research and Education (GeNeMove network, BMBF) and receives input from clinical sites all over Germany. It is currently jointly funded by the HSP patient organization ‘HSP Selbsthilfegruppe Deutschland’ and the German Center for Neurodegenerative Diseases (DZNE). Participating sites have harmonized standards of diagnosis and clinical examination across the network and have developed the Spastic Paraplegia Rating Scale (SPRS), a clinical rating scale to measure disease severity in HSP [7].
  • Clinical Research in ALS and Related Disorders for Therapeutic Development Consortium (CReATe) is a Rare Diseases Clinical Research Consortium (RDCRC) that forms part of the NIH’s Rare Diseases Clinical Research Network (RDCRN). It includes an administrative unit, a network of clinical sites, a distributed genetics core, a training program and an outreach and advocacy core. CReATe aims to characterize the longitudinal/natural history phenotype of patients with genetically confirmed ALS, PLS, HSP and FTD
  • CanHSP is a nationwide research platform connecting physicians and scientists from various Universities and Hospitals across Canada. It was established in 2011 and is funded by the Canadian Institutes for Health Research (CIHR).
  • The UK HSP Registry was started in 2014 but the specialist HSP clinic has been collecting clinical data and DNA since 1980 when Anita Harding established the department. It has established diagnosis and clinical examination and use the SPRS rating scale as part of the NHS practice.
  • NeurOmics
  • BRAIN-TEAM network  is a National French Network for Rare Neurological diseases including 10 certified centres of reference, 142 competent centres, 26 patient associations and ~10,000 patients.

Textversion ausgeblendet

HSP RESOURCES

Guidelines relevant for HSP

  • Gasser T, Finsterer J, Baets J, Van Broeckhoven C, Di Donato S, Fontaine B, DeJonghe P, Lossos A, Lynch T, Mariotti C, Schöls L, Spinazzola A, Szolnoki Z, Tabrizi SJ, Tallaksen CM, Zeviani M, Burgunder JM, Harbo HF; EFNS. EFNS guidelines on the molecular diagnosis of ataxias and spastic paraplegias. Eur J Neurol. 2010 Feb;17(2):179-88.

Consensus papers

  • Dressler D, Berweck S, Chatzikalfas A, Ebke M, Frank B, Hesse S, Huber M,Krauss JK, Mücke KH, Nolte A, Oelmann HD, Schönle PW, Schmutzler M, PickenbrockH, Van der Ven C, Veelken N, Vogel M, Vogt T, Saberi FA. Intrathecal Baclofen therapy in Germany: Proceedings of the IAB-Interdisciplinary Working Group for Movement Disorders Consensus Meeting. J Neural Transm (Vienna). 2015 Nov;122(11):1573-9. doi: 10.1007/s00702-015-1425-1. Epub 2015 Jul 16.

Diagnostic algorithms

  • n.a.

Evidence

Disease modifying therapies
  • Schols 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.
Medical management of spasticity
  • Broggi G, Servello D, Brock S, Dones I. The treatment of spasticity by intrathecal administration of baclofen: a preliminary personal experience. J Neurosurg Sci 1993; 37(4): 203-8.
  • 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(2): 147-53.
  • Franco-Hernandez JA, Rodriguez LM, Ortiz de Landazuri PJ, Hernandez AG. Use of sugammadex in Strumpell-Lorrain disease: a report of two cases. Braz J Anesthesiol 2013; 63(1): 113-5.
  • Geva-Dayan K, Domenievitz D, Zahalka R, Fattal-Valevski A. Botulinum toxin injections for pediatric patients with hereditary spastic paraparesis. J ChildNeurol. 2010 Aug;25(8):969-75.
  • 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; 23(2): 228-33.
  • Klebe S, Stolze H, Kopper F, Lorenz D, Wenzelburger R, Deuschl G, et al. Objective assessment of gait after intrathecal baclofen in hereditary spastic paraplegia. J Neurol 2005; 252(8): 991-3.
  • 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.
  • 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. Current pharmaceutical design 2016; 22(6): 758-63.
  • Scheuer KH, Svenstrup K, Jennum P, Rogvi-Hansen B, Werdelin L, Fenger K, et al. Double-blind crossover trial of gabapentin in SPG4-linked hereditary spastic paraplegia. Eur J Neurol 2007; 14(6): 663-6.
Physical Therapy and neurorehabilitative treatments
  • Bertolucci F, Di Martino S, Orsucci D, Ienco EC, Siciliano G, Rossi B, Mancuso M, Chisari C. Robotic gait training improves motor skills and quality of life in hereditary spastic paraplegia. NeuroRehabilitation. 2015;36(1):93-9.
  • Seo HG, Oh BM, Kim K. Robot-assisted gait training in a patient with hereditary spastic paraplegia. PM R. 2015 Feb;7(2):210-3.
  • Meythaler JM, Steers WD, Tuel SM, Cross LL, Sesco DC, Haworth CS. Intrathecal baclofen in hereditary spastic paraparesis. Arch Phys Med Rehabil 1992; 73(9): 794-7.
  • Nonnekes J, van Lith B, van de Warrenburg BP, Weerdesteyn V, Geurts ACH. Pathophysiology, diagnostic work-up and management of balance impairments and falls in patients with hereditary spastic paraplegia. J Rehabil Med 2017; 49(5): 369-77.
  • Sweet LA, O'Neill LM, Dobbs MB. Serial casting for neuromuscular flatfoot and vertical talus in an adolescent with hereditary spastic paraplegia. Pediatric physical therapy : the official publication of the Section on Pediatrics of the American Physical Therapy Association 2014; 26(2): 253-64.
  • 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(4): 1074-9.
Management of urinary symptoms and pain
  • Ribeiro AM, Ferreira CH, Cristine Lemes Mateus-Vasconcelos E, Moroni RM, Brito LM, Brito LG. Physical therapy in the management of pelvic floor muscles hypertonia in a woman with hereditary spastic paraplegia. Case Rep Obstet Gynecol 2014; 2014: 306028.
Others
  • Bensmail D, Quera Salva MA, Roche N, Benyahia S, Bohic M, Denys P, et al. Effect of intrathecal baclofen on sleep and respiratory function in patients with spasticity. Neurology 2006; 67(8): 1432-6.
Diagnosis (non-genetic)
  • Bonnefoy-Mazure A, Turcot K, Kaelin A, De Coulon G, Armand S. Full body gait analysis may improve diagnostic discrimination between hereditary spastic paraplegia and spastic diplegia: a preliminary study. Research in developmental disabilities 2013; 34(1): 495-504.

Registries

Hereditary spastic paraplegia and spinocerebellar studies

Clinical Rating Scales

Spastic Paraplegia Rating Scale
  • Schule 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(3): 430-4.
  • Spastic Paraplegia Rating Scale (SPRS): SPRS is suitable for all subtypes of SP including familial and sporadic forms as well as pure and complicated phenotypes. As SPRS uses standard neurologic examination procedures in most of its items, instructions for test performance and scoring could be kept short for most items without endangering interrater reliability. Completion of SPRS require less than 15 minutes and does not depend on any special equipment. The variety of signs and symptoms that accounts for clinical variability in complicated forms of SP is listed in an inventory. This inventory thus provides a standardized tool to document multisystem involvement of the disease. The inventory is adapted to a routine neurologic examination and avoids additional time-consuming tests.
Spinocerebellar Degeneration Functional Score (SDFS)
  • Le Ber I, Moreira MC, Rivaud-Péchoux S, Chamayou C, Ochsner F, Kuntzer T, Tardieu M, Saïd G, Habert MO, Demarquay G, Tannier C, Beis JM, Brice A, Koenig M, Dürr A. Cerebellar ataxia with oculomotor apraxia type 1: clinical and genetic studies. Brain. 2003 Dec;126(Pt 12):2761-72. Epub 2003 Sep 23.
  • Spinocerebellar Degeneration Functional Score (SDFS), which rates the disability stages from 0 (asymptomatic) to 7 (bedridden)

Networks and study groups

  • Alliance for Treatment in HSP and PLS: international network with the intention to further the development of trial readiness and therapies in HSP and PLS
  • SPATAX https://spatax.wordpress.com/
  • German HSP Registry (https://www.dzne.de/forschung/forschungsbereiche/klinische-forschung/studien/hsp-net-tb001.html)
    The German HSP Registry (R. Schüle, L. Schöls) was started in 2004 through funding of the German Ministry for Research and Education (GeNeMove network, BMBF) and receives input from clinical sites all over Germany. It is currently jointly funded by the HSP patient organization ‘HSP Selbsthilfegruppe Deutschland’ and the German Center for Neurodegenerative Diseases (DZNE). Participating sites have harmonized standards of diagnosis and clinical examination across the network and have developed the Spastic Paraplegia Rating Scale (SPRS), a clinical rating scale to measure disease severity in HSP [7].
  • CReATe Clinical Research in ALS and Related Disorders for Therapeutic Development Consortium is a Rare Diseases Clinical Research Consortium (RDCRC) that forms part of the NIH’s Rare Diseases Clinical Research Network (RDCRN) (http://www.rarediseasesnetwork.org). It includes an administrative unit, a network of clinical sites, a distributed genetics core, a training program and an outreach and advocacy core. CReATe aims to characterize the longitudinal/natural history phenotype of patients with genetically confirmed ALS, PLS, HSP and FTD
  • CanHSP is a nationwide research platform connecting physicians and scientists from various Universities and Hospitals across Canada. It was established in 2011 and is funded by the Canadian Institutes for Health Research (CIHR).
  • The UK HSP Registry was started in 2014 but the specialist HSP clinic has been collecting clinical data and DNA since 1980 when Anita Harding established the department. It has established diagnosis and clinical examination and use the SPRS rating scale as part of the NHS practice.
  • NeurOmics rd-neuromics.eu/
  • BRAIN-TEAM network: National French Network for Rare Neurological diseases including 9 certified centres of reference, 25 specialized centers, 25 competent centres, >260 CNS diseases, 37 patient associations, and ~100,000 patients (website under development).

Advocacy and support groups