BACKGROUND: Accurate prediction of walking function after a traumatic spinal cord injury (SCI) is crucial for an appropriate tailoring and application of therapeutical interventions. Long-term outcome of ambulation is strongly related to residual muscle function acutely after injury and its recovery potential. The identification of the underlying determinants of ambulation, however, remains a challenging task in SCI, a neurological disorder presented with heterogeneous clinical manifestations and recovery trajectories. OBJECTIVES: Stratification of walking function and determination of its most relevant underlying muscle functions based on stratified homogeneous patient subgroups. METHODS: Data from individuals with paraplegic SCI were used to develop a prediction-based stratification model, applying unbiased recursive partitioning conditional inference tree (URP-CTREE). The primary outcome was the 6-minute walk test at 6 months after injury. Standardized neurological assessments ≤15 days after injury were chosen as predictors. Resulting subgroups were incorporated into a subsequent node-specific analysis to attribute the role of individual lower extremity myotomes for the prognosis of walking function. RESULTS: Using URP-CTREE, the study group of 361 SCI patients was divided into 8 homogeneous subgroups. The node specific analysis uncovered that proximal myotomes L2 and L3 were driving factors for the differentiation between walkers and non-walkers. Distal myotomes L4-S1 were revealed to be responsible for the prognostic distinction of indoor and outdoor walkers (with and without aids). CONCLUSION: Stratification of a heterogeneous population with paraplegic SCI into more homogeneous subgroups, combined with the identification of underlying muscle functions prospectively determining the walking outcome, enable potential benefit for application in clinical trials and practice.

Berufsgenossenschaftliche Kliniken Bergmannstrost Zentrum für Rückenmarkverletzte und Klinik für Orthopädie Halle Germany

Biomedical Data Science Lab Department of Health Sciences and Technology ETH Zurich Zurich Switzerland

ETH Zurich Zurich Switzerland

ICORD University of British Columbia and Vancouver Coastal Health Blusson Spinal Cord Centre Vancouver BC Canada

Neuroscience Center Zurich University of Zurich Zurich Switzerland

Schulthess Clinic Zurich Switzerland

Spinal Cord Injury Center Balgrist University Hospital Zurich Switzerland

Spinal Cord Injury Center Heidelberg University Hospital Heidelberg Germany

Spinal Cord Unit University Hospital Motol Prague Czech Republic

Spinal Unit and Spinal Rehabilitation Lab IRCCS Fondazione S Lucia Rome Italy

Swiss Paraplegic Center Nottwil Switzerland

Trauma Center Murnau Murnau Germany

See more in PubMed

Anderson KD. Targeting recovery: priorities of the spinal cord-injured population. J Neurotrauma. 2004;21(10):1371-1383. doi:10.1089/neu.2004.21.1371 PubMed DOI

Franz M, Richner L, Wirz M, et al.Physical therapy is targeted and adjusted over time for the rehabilitation of locomotor function in acute spinal cord injury interventions in physical and sports therapy. Spinal Cord. 2018;56(2):158-167. doi:10.1038/s41393-017-0007-5 PubMed DOI

Kucher K, Johns D, Maier D, et al.First-in-man intrathecal application of neurite growth-promoting anti-nogo-A antibodies in acute spinal cord injury. Neurorehabil Neural Repair. 2018;32(6-7):578-589. doi:10.1177/1545968318776371 PubMed DOI

Wagner FB, Mignardot JB, Le Goff-Mignardot CG, et al.Targeted neurotechnology restores walking in humans with spinal cord injury. Nature. 2018;563(7729):65-93. doi:10.1038/s41586-018-0649-2 PubMed DOI

Stieglitz LH, Hofer AS, Bolliger M, et al.Deep brain stimulation for locomotion in incomplete human spinal cord injury (DBS-SCI): protocol of a prospective one-armed multi-centre study. BMJ Open. 2021;11(9). doi:10.1136/BMJOPEN-2020-047670 PubMed DOI PMC

Steeves JD, Lammertse D, Curt A, et al.Guidelines for the conduct of clinical trials for spinal cord injury (SCI) as developed by the ICCP panel: clinical trial outcome measures. Spinal Cord. 2007;45(3):206-221. doi:10.1038/sj.sc.3102008 PubMed DOI

Zörner B, Blanckenhorn WU, Dietz V, Curt A. Clinical algorithm for improved prediction of ambulation and patient stratification after incomplete spinal cord injury. J Neurotrauma. 2010;27(1):241-252. doi:10.1089/neu.2009.0901 PubMed DOI

van Middendorp JJ, Hosman AJF, Donders ART, et al.A clinical prediction rule for ambulation outcomes after traumatic spinal cord injury: a longitudinal cohort study. Lancet. 2011;377(9770):1004-1010. doi:10.1016/S0140-6736(10)62276-3 PubMed DOI

Wilson JR, Grossman RG, Frankowski RF, et al.A clinical prediction model for long-term functional outcome after traumatic spinal cord injury based on acute clinical and imaging factors. J Neurotrauma. 2012;29(13):2263-2271. doi:10.1089/neu.2012.2417 PubMed DOI PMC

Hicks KE, Zhao Y, Fallah N, et al.A simplified clinical prediction rule for prognosticating independent walking after spinal cord injury: a prospective study from a Canadian multicenter spinal cord injury registry. Spine J. 2017;17(10):1383-1392. doi:10.1016/j.spinee.2017.05.031 PubMed DOI

DeVries Z, Hoda M, Rivers CS, et al.Development of an unsupervised machine learning algorithm for the prognostication of walking ability in spinal cord injury patients. Spine J. 2020;20(2):213-224. doi:10.1016/j.spinee.2019.09.007 PubMed DOI

Cathomen A, Sirucek L, Killeen T, et al.Inclusive trial designs in acute spinal cord injuries: prediction-based stratification of clinical walking outcome and projected enrolment frequencies. Neurorehabil Neural Repair. 2022;36(4-5):274-285. doi:10.1177/15459683221078302 PubMed DOI PMC

Waters RL, Adkins R, Yakura J, Vigil D. Prediction of ambulatory performance based on motor scores derived from standards of the American Spinal Injury Association. Arch Phys Med Rehabil. 1994;75(7):756-760. doi:10.1017/CBO9781107415324.004 PubMed DOI

Wirz M, van Hedel HJ, Rupp R, Curt A, Dietz V. muscle force and gait performance: relationships after spinal cord injury. Arch Phys Med Rehabil. 2006;87(9):1218-1222. doi:10.1016/j.apmr.2006.05.024 PubMed DOI

Crozier KS, Cheng LL, Graziani V, Zorn G, Herbison G, Ditunno JF. Spinal cord injury: Prognosis for ambulation based on quadriceps recovery. Paraplegia. 1992;30(11):762-767. doi:10.1038/sc.1992.147 PubMed DOI

Kim CM, Eng JJ, Whittaker MW. Level walking and ambulatory capacity in persons with incomplete spinal cord injury: Relationship with muscle strength. Spinal Cord. 2004;42(3):156-162. doi:10.1038/sj.sc.3101569 PubMed DOI PMC

Scivoletto G, Romanelli A, Mariotti A, et al.Clinical factors that affect walking level and performance in chronic spinal cord lesion patients. Spine. 2008;33(3):259-264. doi:10.1097/BRS.0B013E3181626AB0 PubMed DOI

Moon J, Yu J, Choi J, Kim MY, Min K. Degree of contribution of motor and sensory scores to predict gait ability in patients with incomplete spinal cord injury. Ann Rehabil Med. 2017;41(6):969-978. doi:10.5535/ARM.2017.41.6.969 PubMed DOI PMC

Jean S, Mac-Thiong JM, Jean MC, Dionne A, Bégin J, Richard-Denis A. Early clinical prediction of independent outdoor functional walking capacity in a prospective cohort of traumatic spinal cord injury patients. Am J Phys Med Rehabil. 2021;100(11):1034-1041. doi:10.1097/PHM.0000000000001812 PubMed DOI

Enright PL. The six-minute walk test. Respir Care. 2003;48(8):783-785. PubMed

Hothorn T, Hornik K, Zeileis A. Unbiased recursive partitioning: a conditional inference framework. J Comput Graph Stat. 2006;15(3):651-674. doi:10.1198/106186006X133933 DOI

Schuld C, Wiese J, Franz S, et al.Effect of formal training in scaling, scoring and classification of the international standards for neurological classification of spinal cord injury. Spinal Cord. 2013;51(4):282-288. doi:10.1038/sc.2012.149 PubMed DOI

Wilson JR, Cadotte DW, Fehlings MG. Clinical predictors of neurological outcome, functional status, and survival after traumatic spinal cord injury: a systematic review. J Neurosurg Spine. 2012;17(1 Suppl):11-26. doi:10.3171/2012.4.AOSPINE1245 PubMed DOI

Rupp R, Biering-Sørensen F, Burns SP, et al.international standards for neurological classification of spinal cord injury: revised 2019. Top Spinal Cord Inj Rehabil. 2021;27(2):1-22. doi:10.46292/SCI2702-1 PubMed DOI PMC

Van Hedel HJ, Wirz M, Dietz V. Assessing walking ability in subjects with spinal cord injury: validity and reliability of 3 walking tests. Arch Phys Med Rehabil. 2005;86(2):190-196. doi:10.1016/j.apmr.2004.02.010 PubMed DOI

Itzkovich M, Gelernter I, Biering-Sorensen F, et al.The Spinal Cord Independence Measure (SCIM) version III: reliability and validity in a multi-center international study. Disabil Rehabil. 2007;29(24):1926-1933. doi:10.1080/09638280601046302 PubMed DOI

Ditunno JF, Ditunno PL, Scivoletto G, et al.The Walking Index for Spinal Cord Injury (WISCI/WISCI II): nature, metric properties, use and misuse. Spinal Cord. 2013;51(5):346-355. doi:10.1038/SC.2013.9 PubMed DOI

Van Hedel HJA. Gait speed in relation to categories of functional ambulation after spinal cord injury. Neurorehabil Neural Repair. 2009;23(4):343-350. doi:10.1177/1545968308324224 PubMed DOI

Kopp MA, Druschel C, Meisel C, et al.The SCIentinel study–prospective multicenter study to define the spinal cord injury-induced immune depression syndrome (SCI-IDS)–study protocol and interim feasibility data. BMC Neurol. 2013;13(1):168-179. doi:10.1186/1471-2377-13-168 PubMed DOI PMC

Weiskopf NG, Rusanov A, Weng C. Sick patients have more data: the non-random completeness of electronic health records. AMIA Annu Symp Proc. 2013;2013:1472-1477. PubMed PMC

Buri M, Tanadini LG, Hothorn T, Curt A. Unbiased recursive partitioning enables robust and reliable outcome prediction in acute spinal cord injury. J Neurotrauma. 2021;39(3-4):266-276. doi:10.1089/neu.2020.7407 PubMed DOI

R Core Team. R: A Language and Environment for Statistical Computing; 2013. Accessed March 15, 2021. http://www.r-project.org/

Hothorn T, Hornik K, Strobl C, Zeileis A. Party: a laboratory for recursive partytioning. R package version 1.3-7; 2020. Accessed March 15, 2021. https://cran.r-project.org/package=party

Hussey RW, Stauffer ES. Spinal cord injury: requirements for ambulation. Arch Phys Med Rehabil. 1973;54(12):544-547. Accessed August 29, 2019. http://www.ncbi.nlm.nih.gov/pubmed/4759444 PubMed

Tanadini LG, Hothorn T, Jones LAT, et al.Toward inclusive trial protocols in heterogeneous neurological disorders: prediction-based stratification of participants with incomplete cervical spinal cord injury. Neurorehabil Neural Repair. 2015;29(9):867-877. doi:10.1177/1545968315570322 PubMed DOI

Geisler FH, Coleman WP, Grieco G, Poonian D, Sygen Study Group. The Sygen multicenter acute spinal cord injury study. Spine. 2001;26(24 Suppl):S87-S98. doi:10.1097/00007632-200112151-00015 PubMed DOI

Steeves JD, Kramer JK, Fawcett JW, et al.Extent of spontaneous motor recovery after traumatic cervical sensorimotor complete spinal cord injury. Spinal Cord. 2011;49(2):257-265. doi:10.1038/sc.2010.99 PubMed DOI

Coleman WP, Geisler FH. Injury severity as primary predictor of outcome in acute spinal cord injury: retrospective results from a large multicenter clinical trial. Spine J. 2004;4(4):373-378. doi:10.1016/j.spinee.2003.12.006 PubMed DOI

Vasquez N, Gall A, Ellaway PH, Craggs MD. Light touch and pin prick disparity in the International Standard for Neurological Classification of Spinal Cord Injury (ISNCSCI). Spinal Cord. 2013;51(5):375-378. doi:10.1038/SC.2012.175 PubMed DOI

Furlan JC, Fehlings MG. The impact of age on mortality, impairment, and disability among adults with acute traumatic spinal cord injury. J Neurotrauma. 2009;26(10):1707-1717. doi:10.1089/neu.2009.0888 PubMed DOI PMC

Poynton AR, O’Farrell DA, Shannon F, Murray P, Mcmanus F, Walsh MG. Sparing of sensation to pin prick predicts recovery of a motor segment after injury to the spinal cord. J Bone Jt Surg. 1997;79(6):952-954. doi:10.1302/0301-620X.79B6.7939 PubMed DOI

Oleson CW, Burns AS, Ditunno JF, Geisler FH, Coleman WP. Prognostic value of pinprick preservation in motor complete, sensory incomplete spinal cord injury. Arch Phys Med Rehabil. 2005;86(5):988-992. doi:10.1016/j.apmr.2004.09.031 PubMed DOI