Prognostic significance of the Zone of Partial Preservation (ZPP) within 72 hours of motor complete cervical spinal cord injury: a novel MRI-based approach

Prognostic significance of the Zone of Partial Preservation (ZPP) within 72 hours of motor complete cervical spinal cord injury: a novel MRI-based approach | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article Prognostic significance of the Zone of Partial Preservation (ZPP) within 72 hours of motor complete cervical spinal cord injury: a novel MRI-based approach Kazuhiro Murotani, Osamu Kawano, Momo Irie, Kazuhiro Hata, Kensuke Kubota, and 3 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6143755/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Study Design: A retrospective case series. Objectives: To investigate the prognostic value of the Zone of Partial Preservation (ZPP) within 72 h after cervical spinal cord injury (CSCI) with American Spinal Injury Association Impairment Scale (AIS) A and B. Setting : Department of Orthopaedic Surgery, Spinal Injuries Center, Japan Methods: The study participants were sixty-five patients with an initial diagnosis of motor complete CSCI (AIS A, n=44, AIS B, n=21) within 72 h after injury. The impact of the length of motor or sensory ZPPs on the rates of motor score recovery and conversion to AIS C/D at three months after injury were investigated. MRI-based ZPPs were defined as the residual function caudal to the presumptive primary injured segment of the spinal cord inferred from MRI, whose relevance to the motor recovery was also investigated. Results: The significant better motor recovery was demonstrated in individuals with longer lengths of sensory and MRI-based sensory ZPPs (p<0.05). Sensory ZPP length of 11 or more, MRI-based sensory ZPP length of 10 or more, and MRI-based motor ZPP length of 1 were associated to be the significant higher rates of conversion to AIS C/D with the odds ratio of 10.2 (95% CI, 1.4-76.9), 21.0 (1.8-243.0), and 8.2 (2.2-31.4), respectively (p<0.05). Conclusions: Sensory ZPPs within 72 hours after injury could be a prognostic factor of the motor recovery and conversion to AIS C/D in individuals with motor complete CSCI. ZPPs may be more useful for predicting the recovery potential combined with the MRI findings. Sponsorship : N/A Health sciences/Medical research/Epidemiology Health sciences/Diseases/Trauma Health sciences/Biomarkers/Predictive markers Figures Figure 1 Figure 2 INTRODUCTION Cervical spinal cord injury (CSCI) leads to a range of functional deficits, from complete to incomplete paralysis, following various natural courses of recovery [ 1 – 5 ]. Kawano et al. reported that 35 of 203 (17%) patients who was initially diagnosed as AIS A within 72 h after injury showed recovery from AIS A by one year [ 5 ]. 34 of 35 (97%) patients showed recovery from AIS A within 8 weeks after injury. Mori et al. reported that among patients with motor complete CSCI assessed within 72 h of injury, approximately 30% of those classified as AIS A and 85% of those classified as AIS B showed neurological improvement at 6 months following conservative treatment [ 4 ]. As spinal cord injury follows a diverse range of clinical courses, the prognostic prediction can significantly contribute to optimizing treatment strategies. It is important to accurately assess neurological recovery potential in individual patients with complete CSCI. Previous studies have shown that the Zone of Partial Preservation (ZPP), defined as dermatomes and myotomes caudal to the sensory and motor levels with partially preserved function [ 6 ], is a prognostic predictors of recovery for patients with complete SCI. Longer lengths of sensory or motor ZPPs has been suggested to be associated with better AIS and motor score recoveries [ 1 – 3 , 7 – 9 ]. However, all of those reports were focusing on the ZPPs at least one or two weeks after the initial injury, and there have been limited understanding of the ZPPs within the first 72 hours in the acute phase. The MRI findings are also suggested to be correlated with the prognosis of CSCI. Matsushita et al. reported that 96.8% of patients with T1-weighted low intensity area of less than 50% of spinal cord, were able to walk at the time of discharge [ 10 ]. MRI findings obtained two to three days post-injury was suggested to be useful for neurological prognosis; with the vertical diameter of the T2-weighted high intensity area of less than 45 mm, patients were able to walk at discharge [ 11 ]. It is recognized that the MRI findings could be useful in predicting neurological prognosis. The present study was investigated to evaluate the significance of ZPPs within 72 hours after injury as a prognostic indicator of motor recovery in patients with AIS A and B CSCI. We also assessed whether or not the combination of the ZPPs and the MRI findings at the initial diagnosis could be used as a reliable prognostic predictor of motor recovery. METHODS The study was performed as a retrospective analysis at out institute. Patients who were diagnosed as a motor complete CSCI (AIS A/B) within 72h after injury from 2017 to 2023 were selected from our institute’s database. For each patient, neurological data within 72 h and at 3 months were extracted. All patients received MRI at the timing of initial diagnosis, and underwent treatments exclusively at our institute from the acute to the chronic phase under the supervision of several spine surgeons. The ZPPs were evaluated based on the revised definition in the 2019 International Standards for Neurological Classification of Spinal Cord Injury. The most caudal segment with some sensory or motor function was defined as the sensory or motor ZPP, respectively. No deep anal pressure (DAP), and no light touch and pin prick sensation in S4-5 were needed to apply sensory ZPPs whereas no voluntary anal contraction (VAC) was needed to apply motor ZPPs. In patients with AIS A, due to complete sensory and motor paralysis, both sensory and motor ZPPs were evaluated. On the other hand, in patients with AIS B, due to sensory incomplete motor complete paralysis, only motor ZPPs were evaluated except in rare cases where unilateral sensory ZPP could be applicable with unilateral LL or PP with the absence of DAP, although there were no such cases in our dataset. The patient demographics are summarized in Table 1. A total of 65 patients were included: 44 patients with AIS A (22 with bone injury and 22 without bone injury) and 21 patients with AIS B (9 with bone injury and 12 without bone injury). The mean age was 56.6 ± 19.1 years. The timing of the initial diagnosis was as follows; 37 patients with AIS A and 8 patients with AIS B received within 24 h; 4 patients with AIS A and 8 patients with AIS B received within 48 h; 3 patients with AIS A and 5 patients with AIS B received within 72 h. Timing from injury to evaluation was significantly earlier in patients with AIS A. The primary injured segment of the spinal cord was estimated from the high intensity area of the spinal cord on T2-weighted sagittal MRI at the initial diagnosis in conjunction with clinical findings. The injured segment was estimated as follows; C3/4, C4/5, C5/6, and C6/7 intervertebral injury damaged the C5, C6, C7, and C8 segment, respectively [ 12 – 13 ]. C7/T1 level injury cases were not included in this study, as many do not have any upper extremity symptoms. Then, MRI-based ZPPs were defined as the residual function caudal to the presumptive primary injured segment of the spinal cord inferred from MRI. Moreover, the length of the MRI-based ZPPs were defined as the number of segments of the spinal cord that retained partial function below the presumptive primary injured segment. For example, C6/7 intervertebral injury affected the C8 segment, whose function should not exist with a complete primary injury, and the C7 segment should be the presumptive functionally preserved segment. With some residual sensory function in the C8 and/or more caudal segments, MRI-based sensory ZPP was applicable. The length of MRI-based sensory ZPP was one when partial function was preserved in the C8 segment with no sensation in the T1 and more caudal segments, and two when partial function was preserved in the T1 segment with no sensation in the T2 and more caudal segments. A case presentation is shown in Fig. 1 . As of sensory ZPPs and MRI-based sensory ZPPs, 44 patients with only AIS A were evaluated due to the inapplicability of sensory ZPPs to patients with AIS B. As of motor ZPPs, 33 patients with AIS A and B whose motor levels were C5 or more caudal segments were evaluated. As of MRI-based motor ZPPs, total 65 patients with AIS A and B whose presumptive primary injured segments were C5 or more caudal segments were evaluated. Some patients were excluded in evaluating motor ZPPs or MRI-based motor ZPPs, because there were no key muscles above the C5 segment of the spinal cord and motor levels were affected by the sensory levels. The patient demographics of the sensory and motor ZPPs are summarized in Fig. 2 . The mean lengths of the sensory, MRI-based sensory, motor and MRI-based motor ZPPs were 6.3 ± 6.3, 4.3 ± 5.8, 1.2 ± 1.3, and 1.2 ± 2.6, respectively. It was hypothesized that longer length of ZPPs or MRI-based ZPPs might correlate with better motor recovery and conversion to AIS C/D at three months after injury. Data are expressed as the mean ± standard deviation. Statistical analyses were performed using the Chi-square test to assess the association of the length of ZPPs and the conversion to AIS C/D. Logistic regression analysis was performed to introduce the odds ratio. Linear regression analysis was used to assess the association of the length of ZPPs and the motor score recovery. P-values less than 5% was considered significant. RESULTS The conversion to AIS C/D was detected in 9 patients with AIS A (20.5%), and 14 patients with AIS B (66.7%). Table 2 showed the mean lengths of sensory or motor ZPPs with and without MRI-based assessment in each group stayed in AIS A/B or converted to C/D at three months follow up. For sensory ZPPs, the mean length was significantly greater in patients converted to AIS C/D (11.9 ± 10.5) compared in patients stayed in AIS A/B (5.1 ± 4.2) (p < 0.01). For MRI-based sensory ZPPs, the mean length was significantly greater in patients with AIS C/D (10.6 ± 10.2) compared in patients with AIS A/B (2.9 ± 3.0) (p < 0.01). For motor ZPPs and MRI-based motor ZPPs, there was no differences between groups. As for the likelihood of conversion to AIS C/D, sensory ZPP length of 11 or more, MRI-based sensory ZPP length of 10 or more, and MRI-based motor ZPP length of 1 were demonstrated to be the significant factors with the odds ratio of 10.2 (1.4–76.9), 21.0 (1.8–243.0), and 8.2 (2.2–31.4) respectively (p < 0.05) (Table 3). The significant better motor recovery was demonstrated in patients with longer lengths of sensory (p < 0.05) and MRI-based sensory ZPPs (p < 0.01), while no significant difference in patients with motor or MRI-based motor ZPPs. DISCUSSION As CSCI results in various paralysis and clinical courses, prognostic prediction remains challenging especially during the acute phase. In individuals with AIS A CSCI, the absence of both patellar tendon reflex and plantar response at the time of injury was significantly associated with an extremely low likelihood of conversion to motor incomplete status [ 14 ]. There are various prognostic factors proposed for predicting outcomes, such as Bulbocavernosus reflex within 72 h after injury [ 15 ] and T2 high-intensity area of spinal cord on MRI [ 10 – 11 , 16 ]. As the definition of ZPPs has been revised, they are also considered to be among the most important predictors of neurological recovery in individuals with complete SCI [ 17 ]. After the ISNCSCI revision in 1992, ZPPs had been applied to only complete (AIS A) injuries. The revision in 2019 made ZPPs independent of the AIS classification, and the scope of the ZPPs was changed [ 6 ]. Nowadays, it is considered that the length of the ZPPs may help predict neurological recovery, particularly conversion to motor incomplete status for patients with initial AIS A [ 3 , 7 – 8 ]. Marino et al. reported that among individuals with AIS A SCI within 7 days of injury, those with the motor ZPP length of 4 or more had an increased likelihood of conversion to AIS C/D compared to those without extended ZPP (13.3% vs. 3.6%) [ 7 ]. Zariffa et al. demonstrated that in patients with AIS A/B thoracic SCI within 2 weeks of injury, sensory ZPP length of 3 or more was correlated with higher rate of conversion to AIS C/D by 48 weeks (14.3% vs. 0% for T2-T5 subgroups, 33.3% vs. 7.7% for T6-T9, 41.2% vs. 3.5% for T10-12) [ 8 ]. However, there were some limitations; patients were adopted for the assessment in the timing prior to the revision of ISNCSCI in 1982 or 2019 and were examined retrospectively, which might have introduced speculation into the neurological findings or data; sensory dermatomes especially of T6-T9 was difficult to identify, as well as a challenge to localize accurately and repeatedly. Moreover, all of these reports were focusing on the ZPPs at 7–14 days of injury, and there are no reports discussing the significance of ZPPs at more acute phase. Here in this study, the significance of ZPPs within 72 hours after injury was evaluated whether they could be a prognostic indicator of motor recovery or AIS conversion. Early ZPP assessment could offer valuable control data for clinical trials, enhancing the evaluation of treatments by minimizing bias and improving outcome reliability. The present study demonstrated that the length of sensory ZPPs was significantly correlated with conversion to AIS C/D and better motor recovery. Although the length of sensory ZPPs was suggested to be a prognostic predictor, it is still not quite practical as the cut off value for length was 11 segments. Previous reports had demonstrated an association between length of motor ZPPs and motor recovery [ 1 – 3 , 9 , 18 ]. Muscles at the one level below the initial motor level were likely to recover to a strength of ≥ 3/5 in 75–100% of cases when their initial strength was rated as 1–2/5. In contrast, only 25–56% of muscles at this level demonstrated recovery to ≥ 3/5 strength if their initial motor grade was 0/5 [ 1 – 2 , 9 ]. Patients with complete SCI had a five-fold higher likelihood of achieving an improvement of at least two motor level segments if the motor ZPP length was greater than or equal to two levels, compared to those with a motor ZPP length of 0–1 level (relative risk = 5.0) [ 18 ]. In this study, the length of motor ZPPs was not associated with motor recovery, which was inconsistent with these reports. This discrepancy may be explained by the difficulty in interpretation of ZPPs. The functional preservation caudal to the primary injured segment of the spinal cord may reflect a favorable prognosis. However, since secondary injury often extends rostrally, leading to the ascent in the sensory/motor level, the length of ZPPs may become long from the rostrally ascended sensory/motor level. This raises concerns about whether it can be regarded as an indicator of a good prognosis. The complexity of this interpretation arises from the fact that ZPPs are based on sensory and motor levels. When considering distal functional preservation based on the level of primary spinal cord injury, rather than sensory or motor levels, it may more accurately reflect the prognosis. Given this considerations, the present study hypothesized that combining MRI findings to identify the presumptive level of primary spinal cord injury with the assessment of the distal functional preservation might provide a more accurate and reliable prognostic factor reflecting the severity of the injury. It was reported by Kawano et al. that in patients with AIS A/B CSCI within 72 hours of injury, a difference of more than one level between the Neurological Level of Injury (NLI) and the primary injured segment of the spinal cord predicted by MRI was associated with more serious damage, leading to a significantly reduced likelihood of conversion to AIS C/D at 3 months after injury [ 16 ]. They emphasized the utility of incorporating MRI findings in assessing the severity of injury and prognostic predictors. Introducing this concept, the present study aimed to explore the significance of distal functional preservation relative to the primary spinal cord injury level estimated by MRI. It was anticipated that a greater degree of functional preservation at distal levels would correlate with a mild damage and a more favorable prognosis. The MRI-based sensory ZPP length was demonstrated to be a significant predictor of conversion to AIS C/D and better motor recovery, while the cut off value for length was as long as 10. Besides, although MRI-based motor ZPP length of 1 was significantly correlated with conversion to AIS C/D, it was not with better motor recovery. The combination with MRI findings may offer potential benefits, but it is premature to make definitive conclusions, and further discussion and investigation are warranted. The optimal timing for baseline assessment following spinal cord injury remains controversial. Previous studies have reported variability in prognostic outcomes depending on the timing of the assessment. Marino et al. categorized the timing of the initial examination into two groups: earlier than three days and three to seven days after injury [ 18 ]. They found that the conversion rates from complete to incomplete status at one year were not significantly associated with the timing of the initial assessment. Blaustein et al. investigated the use of the upper extremity motor score to predict six-month motor outcomes in patients with motor complete SCI (C4-T1) [ 19 ]. They found no significant difference in predictive accuracy between assessments conducted within 24 hours of injury and those performed between 72 hours and one week post-injury. In this study, patients evaluated within 72 hours of injury were assessed, with this timeframe included as part of the inclusion criteria. However, a significant number of cases were evaluated within 24 hours, a period during which the spinal cord may be actively affected by secondary injury processes such as edema and hemorrhage. This unstable phase could contribute to considerable variability in the assessments, potentially influencing the results. Therefore, further investigation is needed to determine whether assessment within 72 hours post-injury is the most appropriate time window for prognostic prediction. Several limitations should be considered in interpreting the findings of this study. First, key muscles were not established for spinal cord levels T2-T12, which means that even if functional preservation exists at these levels, it could not be included in the evaluation of motor ZPPs. As a result, the true motor ZPP length may potentially be longer than what was assessed in this study. Second, the presumptive spinal cord injured segment inferred from MRI findings remains a prediction, subject to individual variation. It is possible that the actual injury level was not accurately identified, introducing some degree of imprecision in the assessment. Moreover, different groups of patients were intended for the assessment of the lengths of sensory/motor, and MRI-based sensory/motor ZPPs, leading to inconsistencies in the evaluation, making it challenging to interpret the results consistently across these distinct measures. The study's small sample size is also a limitation of the study. In addition, it may be essential to incorporate ZPP length with additional confounding variables (e.g. age, energy of trauma, time from injury to initial assessment, and time from injury to MRI). Further investigation into the correlations between ZPP length and these factors is needed. However, the present study is the first to explore the significance of ZPPs within 72 hours post-injury, combining with MRI findings, offering valuable insights into its potential utility in prognostic predictors. Our findings suggest that a longer sensory ZPP length may serve as a useful predictor of favorable outcomes in motor complete CSCI in the acute phase. CONCLUSIONS In patients with motor complete CSCI, sensory ZPP length within 72 hours after injury could be a prognostic factor of the motor recovery and conversion to motor incomplete status. ZPPs may be more useful for predicting the recovery potential combined with the MRI findings. These results provide valuable insight into the early assessment of SCI and highlight the need for further research to confirm the utility of ZPP length as a reliable predictor. Declarations ACKNOWLEDGEMENTS The authors declare no acknowledgements. AUTHOR CONTRIBUTION KM designed the studies, performed the statistical analysis and drafted the manuscript. OK and TM supervised the overall project. Other authors performed the data collection. All authors read and approved the final manuscript. FUNDING No funds were received in support of this work. ETHICAL APPROVAL This study was approved by the Ethics Review Board of the Spinal Injuries Center. Informed consent was obtained from all of the patients who were included in the present study. CONPETING INTERESTS The authors declare no competing interests. DATA AVAILABILITY STATEMENT Data sets generated and/or analyzed during the current study are not publicly available due to the inclusion of private information of patients but are available from the corresponding author on reasonable request. References Waters RL, Adkins RH, Yakura JS, Sie I. Motor and sensory recovery following incomplete tetraplegia. Arch Phys Med Rehabil. 1994;75(3):306–11. Burns AS, Ditunno JF. Establishing prognosis and maximizing functional outcomes after spinal cord injury: a review of current and future directions in rehabilitation management. Spine (Phila Pa 1976). 2001;26(24 Suppl):S137-45. Kirshblum S, Snider B, Eren F, Guest J. Characterizing Natural Recovery after Traumatic Spinal Cord Injury. J Neurotrauma. 2021;38(9):1267–1284. Mori E, Ueta T, Maeda T, Ideta R, Yugué I, Kawano O, et al. Sequential neurological improvements after conservative treatment in patients with complete motor paralysis caused by cervical spinal cord injury without bone and disc injury. J Neurosurg Spine. 2018;29(1):1–9. Kawano O, Maeda T, Mori E, Takao T, Sakai H, Masuda M, et al. How much time is necessary to confirm the diagnosis of permanent complete cervical spinal cord injury? Spinal Cord. 2020;58(3):284–289. Schuld C; EMSCI study group; Kirshblum S, Tansey K; ASIA International Standards Committee; Rupp R. The revised zone of partial preservation (ZPP) in the 2019 International Standards for Neurological Classification of Spinal Cord Injury: ZPP applicability in incomplete injuries. Spinal Cord. 2024;62(2):79–87. Marino RJ, Ditunno JF Jr, Donovan WH, Maynard F Jr. Neurologic recovery after traumatic spinal cord injury: data from the Model Spinal Cord Injury Systems. Arch Phys Med Rehabil. 1999;80(11):1391–6. Zariffa J, Kramer JL, Fawcett JW, Lammertse DP, Blight AR, Guest J, et al. 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Significance of the neurological level of injury as a prognostic predictor for motor complete cervical spinal cord injury patients. J Spinal Cord Med. 2023;46(3):494–500. 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. Marino RJ, Burns S, Graves DE, Leiby BE, Kirshblum S, Lammertse DP. Upper- and lower-extremity motor recovery after traumatic cervical spinal cord injury: an update from the national spinal cord injury database. Arch Phys Med Rehabil. 2011;92(3):369–75. Blaustein DM, Zafonte R, Thomas D, Herbison GJ, Ditunno JF. Predicting recovery of motor complete quadriplegic patients. 24 hour v 72 hour motor index scores. Am J Phys Med Rehabil. 1993;72(5):306–11. Tables Tables 1-3 are available in the Supplementary Files section. Additional Declarations There is no duality of interest Supplementary Files Table1.xlsx Table2.xlsx Table3.xlsx Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-6143755","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":431192506,"identity":"249d6c33-e3dc-4d1e-8ec5-be40af8bfd52","order_by":0,"name":"Kazuhiro Murotani","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA4klEQVRIiWNgGAWjYBACCSBmZjCA8j4AMRs7KVoYZ4C0MBOlBQqYeRiQuTiAZPvxZ9IFBffkdGfkPnxs82ubPB8zA+OHjzm4tUjzJKRJzzAoNja7kW5snNt327CNmYFZcuY23FrkGBKOSfMYJCRuu5HGJp3bc5sRqIWNmRefFv6HbQgtlj237QlqkZZIZkNoYfhxO5GgFskZz5itgVqMzc48Yzbsbbid3MbM2IzXLxLn0x/e5vmTIGd2PI3xwY8/t23ntzcf/PARjxZUwNgGJhuIVQ8Cf0hRPApGwSgYBSMFAAC4VUeaQbNlLwAAAABJRU5ErkJggg==","orcid":"https://orcid.org/0009-0003-9294-6839","institution":"Spinal Injuries Center","correspondingAuthor":true,"prefix":"","firstName":"Kazuhiro","middleName":"","lastName":"Murotani","suffix":""},{"id":431192507,"identity":"9dc080aa-ddf9-40d1-abea-2266a92cd997","order_by":1,"name":"Osamu Kawano","email":"","orcid":"","institution":"Spinal Injuries Center","correspondingAuthor":false,"prefix":"","firstName":"Osamu","middleName":"","lastName":"Kawano","suffix":""},{"id":431192508,"identity":"4fb3f1c7-dbf2-4e52-bbc7-37d1e1601975","order_by":2,"name":"Momo Irie","email":"","orcid":"","institution":"","correspondingAuthor":false,"prefix":"","firstName":"Momo","middleName":"","lastName":"Irie","suffix":""},{"id":431192509,"identity":"b17840e8-ea62-4886-80e9-4dd17fb63ef4","order_by":3,"name":"Kazuhiro Hata","email":"","orcid":"","institution":"Spinal Injuries Center","correspondingAuthor":false,"prefix":"","firstName":"Kazuhiro","middleName":"","lastName":"Hata","suffix":""},{"id":431192510,"identity":"430b670c-2218-43ad-b689-641e40cd696a","order_by":4,"name":"Kensuke Kubota","email":"","orcid":"","institution":"","correspondingAuthor":false,"prefix":"","firstName":"Kensuke","middleName":"","lastName":"Kubota","suffix":""},{"id":431192511,"identity":"e762c43a-11bd-4f58-bfb2-a1c8fb005e9c","order_by":5,"name":"Muneaki Masuda","email":"","orcid":"https://orcid.org/0000-0003-1992-4409","institution":"Spinal Injuries Center","correspondingAuthor":false,"prefix":"","firstName":"Muneaki","middleName":"","lastName":"Masuda","suffix":""},{"id":431192512,"identity":"328d53ff-7d34-4f8f-abab-fa4bf395821c","order_by":6,"name":"Hiroaki Sakai","email":"","orcid":"","institution":"","correspondingAuthor":false,"prefix":"","firstName":"Hiroaki","middleName":"","lastName":"Sakai","suffix":""},{"id":431192513,"identity":"dc1561b1-6d5c-440e-92c7-2c01cab84cdc","order_by":7,"name":"Takeshi Maeda","email":"","orcid":"https://orcid.org/0000-0002-2594-1128","institution":"","correspondingAuthor":false,"prefix":"","firstName":"Takeshi","middleName":"","lastName":"Maeda","suffix":""}],"badges":[],"createdAt":"2025-03-03 07:40:29","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6143755/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6143755/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":79574257,"identity":"4761db45-8edb-44b8-a543-fa9f90bb7be7","added_by":"auto","created_at":"2025-03-31 11:09:39","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":78783,"visible":true,"origin":"","legend":"\u003cp\u003eCase presentation: C6/7 intervertebral injury with two length of MRI-based sensory ZPP. The length of motor ZPP was one as partial function was preserved in the C6 segment of the spinal cord with motor level of C5. The presumptive primary injured segment was determined to be the C8 segment with the intervertebral injury of C6/7, which meant the presumptive functionally preserved segment was considered to be the C7 segment. As partial sensation was preserved in the C8, and T1 segment, the length of MRI-based sensory ZPP was defined as two.\u003c/p\u003e","description":"","filename":"1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-6143755/v1/45d32cb23685fb1d92edc70b.jpg"},{"id":79574258,"identity":"ca806b95-05ff-4cb5-b4ae-ba4eb9a2b834","added_by":"auto","created_at":"2025-03-31 11:09:39","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":45065,"visible":true,"origin":"","legend":"\u003cp\u003eThe number of cases with each segment of the spinal cord defined as the sensory and motor ZPP.\u003c/p\u003e","description":"","filename":"2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-6143755/v1/c0aabbc66d516036f7342bc4.jpg"},{"id":81649652,"identity":"1340e815-4580-413c-ad48-5cda6d6f3ea4","added_by":"auto","created_at":"2025-04-29 15:45:26","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":523493,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6143755/v1/3ba55704-f827-4eff-b943-72c911ef412a.pdf"},{"id":79574262,"identity":"76dccf74-30a0-4b9c-a6dd-bd932ca27ead","added_by":"auto","created_at":"2025-03-31 11:09:39","extension":"xlsx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":12316,"visible":true,"origin":"","legend":"","description":"","filename":"Table1.xlsx","url":"https://assets-eu.researchsquare.com/files/rs-6143755/v1/bb083378bb94cd5b18ba6053.xlsx"},{"id":79575926,"identity":"8dbda442-63ef-49a4-ac5b-437ff6ae93a5","added_by":"auto","created_at":"2025-03-31 11:17:39","extension":"xlsx","order_by":2,"title":"","display":"","copyAsset":false,"role":"supplement","size":10259,"visible":true,"origin":"","legend":"","description":"","filename":"Table2.xlsx","url":"https://assets-eu.researchsquare.com/files/rs-6143755/v1/bcc6f9f2e0fc35726431028d.xlsx"},{"id":79574261,"identity":"b716840c-137b-4a44-9fec-7c168bc7422a","added_by":"auto","created_at":"2025-03-31 11:09:39","extension":"xlsx","order_by":3,"title":"","display":"","copyAsset":false,"role":"supplement","size":10789,"visible":true,"origin":"","legend":"","description":"","filename":"Table3.xlsx","url":"https://assets-eu.researchsquare.com/files/rs-6143755/v1/4dc2a6a7bd5042477e4b6fcd.xlsx"}],"financialInterests":"There is no duality of interest","formattedTitle":"Prognostic significance of the Zone of Partial Preservation (ZPP) within 72 hours of motor complete cervical spinal cord injury: a novel MRI-based approach","fulltext":[{"header":"INTRODUCTION","content":"\u003cp\u003eCervical spinal cord injury (CSCI) leads to a range of functional deficits, from complete to incomplete paralysis, following various natural courses of recovery [\u003cspan additionalcitationids=\"CR2 CR3 CR4\" citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. Kawano et al. reported that 35 of 203 (17%) patients who was initially diagnosed as AIS A within 72 h after injury showed recovery from AIS A by one year [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. 34 of 35 (97%) patients showed recovery from AIS A within 8 weeks after injury. Mori et al. reported that among patients with motor complete CSCI assessed within 72 h of injury, approximately 30% of those classified as AIS A and 85% of those classified as AIS B showed neurological improvement at 6 months following conservative treatment [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. As spinal cord injury follows a diverse range of clinical courses, the prognostic prediction can significantly contribute to optimizing treatment strategies. It is important to accurately assess neurological recovery potential in individual patients with complete CSCI.\u003c/p\u003e \u003cp\u003ePrevious studies have shown that the Zone of Partial Preservation (ZPP), defined as dermatomes and myotomes caudal to the sensory and motor levels with partially preserved function [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e], is a prognostic predictors of recovery for patients with complete SCI. Longer lengths of sensory or motor ZPPs has been suggested to be associated with better AIS and motor score recoveries [\u003cspan additionalcitationids=\"CR2\" citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan additionalcitationids=\"CR8\" citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. However, all of those reports were focusing on the ZPPs at least one or two weeks after the initial injury, and there have been limited understanding of the ZPPs within the first 72 hours in the acute phase.\u003c/p\u003e \u003cp\u003eThe MRI findings are also suggested to be correlated with the prognosis of CSCI. Matsushita et al. reported that 96.8% of patients with T1-weighted low intensity area of less than 50% of spinal cord, were able to walk at the time of discharge [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. MRI findings obtained two to three days post-injury was suggested to be useful for neurological prognosis; with the vertical diameter of the T2-weighted high intensity area of less than 45 mm, patients were able to walk at discharge [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. It is recognized that the MRI findings could be useful in predicting neurological prognosis.\u003c/p\u003e \u003cp\u003eThe present study was investigated to evaluate the significance of ZPPs within 72 hours after injury as a prognostic indicator of motor recovery in patients with AIS A and B CSCI. We also assessed whether or not the combination of the ZPPs and the MRI findings at the initial diagnosis could be used as a reliable prognostic predictor of motor recovery.\u003c/p\u003e"},{"header":"METHODS","content":"\u003cp\u003eThe study was performed as a retrospective analysis at out institute. Patients who were diagnosed as a motor complete CSCI (AIS A/B) within 72h after injury from 2017 to 2023 were selected from our institute\u0026rsquo;s database. For each patient, neurological data within 72 h and at 3 months were extracted. All patients received MRI at the timing of initial diagnosis, and underwent treatments exclusively at our institute from the acute to the chronic phase under the supervision of several spine surgeons.\u003c/p\u003e \u003cp\u003eThe ZPPs were evaluated based on the revised definition in the 2019 International Standards for Neurological Classification of Spinal Cord Injury. The most caudal segment with some sensory or motor function was defined as the sensory or motor ZPP, respectively. No deep anal pressure (DAP), and no light touch and pin prick sensation in S4-5 were needed to apply sensory ZPPs whereas no voluntary anal contraction (VAC) was needed to apply motor ZPPs. In patients with AIS A, due to complete sensory and motor paralysis, both sensory and motor ZPPs were evaluated. On the other hand, in patients with AIS B, due to sensory incomplete motor complete paralysis, only motor ZPPs were evaluated except in rare cases where unilateral sensory ZPP could be applicable with unilateral LL or PP with the absence of DAP, although there were no such cases in our dataset.\u003c/p\u003e \u003cp\u003eThe patient demographics are summarized in Table\u0026nbsp;1. A total of 65 patients were included: 44 patients with AIS A (22 with bone injury and 22 without bone injury) and 21 patients with AIS B (9 with bone injury and 12 without bone injury). The mean age was 56.6\u0026thinsp;\u0026plusmn;\u0026thinsp;19.1 years. The timing of the initial diagnosis was as follows; 37 patients with AIS A and 8 patients with AIS B received within 24 h; 4 patients with AIS A and 8 patients with AIS B received within 48 h; 3 patients with AIS A and 5 patients with AIS B received within 72 h. Timing from injury to evaluation was significantly earlier in patients with AIS A.\u003c/p\u003e \u003cp\u003eThe primary injured segment of the spinal cord was estimated from the high intensity area of the spinal cord on T2-weighted sagittal MRI at the initial diagnosis in conjunction with clinical findings. The injured segment was estimated as follows; C3/4, C4/5, C5/6, and C6/7 intervertebral injury damaged the C5, C6, C7, and C8 segment, respectively [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. C7/T1 level injury cases were not included in this study, as many do not have any upper extremity symptoms. Then, MRI-based ZPPs were defined as the residual function caudal to the presumptive primary injured segment of the spinal cord inferred from MRI. Moreover, the length of the MRI-based ZPPs were defined as the number of segments of the spinal cord that retained partial function below the presumptive primary injured segment. For example, C6/7 intervertebral injury affected the C8 segment, whose function should not exist with a complete primary injury, and the C7 segment should be the presumptive functionally preserved segment. With some residual sensory function in the C8 and/or more caudal segments, MRI-based sensory ZPP was applicable. The length of MRI-based sensory ZPP was one when partial function was preserved in the C8 segment with no sensation in the T1 and more caudal segments, and two when partial function was preserved in the T1 segment with no sensation in the T2 and more caudal segments. A case presentation is shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eAs of sensory ZPPs and MRI-based sensory ZPPs, 44 patients with only AIS A were evaluated due to the inapplicability of sensory ZPPs to patients with AIS B. As of motor ZPPs, 33 patients with AIS A and B whose motor levels were C5 or more caudal segments were evaluated. As of MRI-based motor ZPPs, total 65 patients with AIS A and B whose presumptive primary injured segments were C5 or more caudal segments were evaluated. Some patients were excluded in evaluating motor ZPPs or MRI-based motor ZPPs, because there were no key muscles above the C5 segment of the spinal cord and motor levels were affected by the sensory levels. The patient demographics of the sensory and motor ZPPs are summarized in Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e. The mean lengths of the sensory, MRI-based sensory, motor and MRI-based motor ZPPs were 6.3\u0026thinsp;\u0026plusmn;\u0026thinsp;6.3, 4.3\u0026thinsp;\u0026plusmn;\u0026thinsp;5.8, 1.2\u0026thinsp;\u0026plusmn;\u0026thinsp;1.3, and 1.2\u0026thinsp;\u0026plusmn;\u0026thinsp;2.6, respectively. It was hypothesized that longer length of ZPPs or MRI-based ZPPs might correlate with better motor recovery and conversion to AIS C/D at three months after injury. Data are expressed as the mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation. Statistical analyses were performed using the Chi-square test to assess the association of the length of ZPPs and the conversion to AIS C/D. Logistic regression analysis was performed to introduce the odds ratio. Linear regression analysis was used to assess the association of the length of ZPPs and the motor score recovery. P-values less than 5% was considered significant.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e"},{"header":"RESULTS","content":"\u003cp\u003eThe conversion to AIS C/D was detected in 9 patients with AIS A (20.5%), and 14 patients with AIS B (66.7%). Table\u0026nbsp;2 showed the mean lengths of sensory or motor ZPPs with and without MRI-based assessment in each group stayed in AIS A/B or converted to C/D at three months follow up. For sensory ZPPs, the mean length was significantly greater in patients converted to AIS C/D (11.9\u0026thinsp;\u0026plusmn;\u0026thinsp;10.5) compared in patients stayed in AIS A/B (5.1\u0026thinsp;\u0026plusmn;\u0026thinsp;4.2) (p\u0026thinsp;\u0026lt;\u0026thinsp;0.01). For MRI-based sensory ZPPs, the mean length was significantly greater in patients with AIS C/D (10.6\u0026thinsp;\u0026plusmn;\u0026thinsp;10.2) compared in patients with AIS A/B (2.9\u0026thinsp;\u0026plusmn;\u0026thinsp;3.0) (p\u0026thinsp;\u0026lt;\u0026thinsp;0.01). For motor ZPPs and MRI-based motor ZPPs, there was no differences between groups. As for the likelihood of conversion to AIS C/D, sensory ZPP length of 11 or more, MRI-based sensory ZPP length of 10 or more, and MRI-based motor ZPP length of 1 were demonstrated to be the significant factors with the odds ratio of 10.2 (1.4\u0026ndash;76.9), 21.0 (1.8\u0026ndash;243.0), and 8.2 (2.2\u0026ndash;31.4) respectively (p\u0026thinsp;\u0026lt;\u0026thinsp;0.05) (Table\u0026nbsp;3). The significant better motor recovery was demonstrated in patients with longer lengths of sensory (p\u0026thinsp;\u0026lt;\u0026thinsp;0.05) and MRI-based sensory ZPPs (p\u0026thinsp;\u0026lt;\u0026thinsp;0.01), while no significant difference in patients with motor or MRI-based motor ZPPs.\u003c/p\u003e"},{"header":"DISCUSSION","content":"\u003cp\u003eAs CSCI results in various paralysis and clinical courses, prognostic prediction remains challenging especially during the acute phase. In individuals with AIS A CSCI, the absence of both patellar tendon reflex and plantar response at the time of injury was significantly associated with an extremely low likelihood of conversion to motor incomplete status [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. There are various prognostic factors proposed for predicting outcomes, such as Bulbocavernosus reflex within 72 h after injury [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e] and T2 high-intensity area of spinal cord on MRI [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eAs the definition of ZPPs has been revised, they are also considered to be among the most important predictors of neurological recovery in individuals with complete SCI [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. After the ISNCSCI revision in 1992, ZPPs had been applied to only complete (AIS A) injuries. The revision in 2019 made ZPPs independent of the AIS classification, and the scope of the ZPPs was changed [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. Nowadays, it is considered that the length of the ZPPs may help predict neurological recovery, particularly conversion to motor incomplete status for patients with initial AIS A [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. Marino et al. reported that among individuals with AIS A SCI within 7 days of injury, those with the motor ZPP length of 4 or more had an increased likelihood of conversion to AIS C/D compared to those without extended ZPP (13.3% vs. 3.6%) [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. Zariffa et al. demonstrated that in patients with AIS A/B thoracic SCI within 2 weeks of injury, sensory ZPP length of 3 or more was correlated with higher rate of conversion to AIS C/D by 48 weeks (14.3% vs. 0% for T2-T5 subgroups, 33.3% vs. 7.7% for T6-T9, 41.2% vs. 3.5% for T10-12) [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. However, there were some limitations; patients were adopted for the assessment in the timing prior to the revision of ISNCSCI in 1982 or 2019 and were examined retrospectively, which might have introduced speculation into the neurological findings or data; sensory dermatomes especially of T6-T9 was difficult to identify, as well as a challenge to localize accurately and repeatedly. Moreover, all of these reports were focusing on the ZPPs at 7\u0026ndash;14 days of injury, and there are no reports discussing the significance of ZPPs at more acute phase. Here in this study, the significance of ZPPs within 72 hours after injury was evaluated whether they could be a prognostic indicator of motor recovery or AIS conversion. Early ZPP assessment could offer valuable control data for clinical trials, enhancing the evaluation of treatments by minimizing bias and improving outcome reliability.\u003c/p\u003e \u003cp\u003eThe present study demonstrated that the length of sensory ZPPs was significantly correlated with conversion to AIS C/D and better motor recovery. Although the length of sensory ZPPs was suggested to be a prognostic predictor, it is still not quite practical as the cut off value for length was 11 segments. Previous reports had demonstrated an association between length of motor ZPPs and motor recovery [\u003cspan additionalcitationids=\"CR2\" citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. Muscles at the one level below the initial motor level were likely to recover to a strength of \u0026ge;\u0026thinsp;3/5 in 75\u0026ndash;100% of cases when their initial strength was rated as 1\u0026ndash;2/5. In contrast, only 25\u0026ndash;56% of muscles at this level demonstrated recovery to \u0026ge;\u0026thinsp;3/5 strength if their initial motor grade was 0/5 [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. Patients with complete SCI had a five-fold higher likelihood of achieving an improvement of at least two motor level segments if the motor ZPP length was greater than or equal to two levels, compared to those with a motor ZPP length of 0\u0026ndash;1 level (relative risk\u0026thinsp;=\u0026thinsp;5.0) [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. In this study, the length of motor ZPPs was not associated with motor recovery, which was inconsistent with these reports. This discrepancy may be explained by the difficulty in interpretation of ZPPs. The functional preservation caudal to the primary injured segment of the spinal cord may reflect a favorable prognosis. However, since secondary injury often extends rostrally, leading to the ascent in the sensory/motor level, the length of ZPPs may become long from the rostrally ascended sensory/motor level. This raises concerns about whether it can be regarded as an indicator of a good prognosis. The complexity of this interpretation arises from the fact that ZPPs are based on sensory and motor levels. When considering distal functional preservation based on the level of primary spinal cord injury, rather than sensory or motor levels, it may more accurately reflect the prognosis. Given this considerations, the present study hypothesized that combining MRI findings to identify the presumptive level of primary spinal cord injury with the assessment of the distal functional preservation might provide a more accurate and reliable prognostic factor reflecting the severity of the injury.\u003c/p\u003e \u003cp\u003eIt was reported by Kawano et al. that in patients with AIS A/B CSCI within 72 hours of injury, a difference of more than one level between the Neurological Level of Injury (NLI) and the primary injured segment of the spinal cord predicted by MRI was associated with more serious damage, leading to a significantly reduced likelihood of conversion to AIS C/D at 3 months after injury [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. They emphasized the utility of incorporating MRI findings in assessing the severity of injury and prognostic predictors. Introducing this concept, the present study aimed to explore the significance of distal functional preservation relative to the primary spinal cord injury level estimated by MRI. It was anticipated that a greater degree of functional preservation at distal levels would correlate with a mild damage and a more favorable prognosis. The MRI-based sensory ZPP length was demonstrated to be a significant predictor of conversion to AIS C/D and better motor recovery, while the cut off value for length was as long as 10. Besides, although MRI-based motor ZPP length of 1 was significantly correlated with conversion to AIS C/D, it was not with better motor recovery. The combination with MRI findings may offer potential benefits, but it is premature to make definitive conclusions, and further discussion and investigation are warranted.\u003c/p\u003e \u003cp\u003eThe optimal timing for baseline assessment following spinal cord injury remains controversial. Previous studies have reported variability in prognostic outcomes depending on the timing of the assessment. Marino et al. categorized the timing of the initial examination into two groups: earlier than three days and three to seven days after injury [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. They found that the conversion rates from complete to incomplete status at one year were not significantly associated with the timing of the initial assessment. Blaustein et al. investigated the use of the upper extremity motor score to predict six-month motor outcomes in patients with motor complete SCI (C4-T1) [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. They found no significant difference in predictive accuracy between assessments conducted within 24 hours of injury and those performed between 72 hours and one week post-injury. In this study, patients evaluated within 72 hours of injury were assessed, with this timeframe included as part of the inclusion criteria. However, a significant number of cases were evaluated within 24 hours, a period during which the spinal cord may be actively affected by secondary injury processes such as edema and hemorrhage. This unstable phase could contribute to considerable variability in the assessments, potentially influencing the results. Therefore, further investigation is needed to determine whether assessment within 72 hours post-injury is the most appropriate time window for prognostic prediction.\u003c/p\u003e \u003cp\u003eSeveral limitations should be considered in interpreting the findings of this study. First, key muscles were not established for spinal cord levels T2-T12, which means that even if functional preservation exists at these levels, it could not be included in the evaluation of motor ZPPs. As a result, the true motor ZPP length may potentially be longer than what was assessed in this study. Second, the presumptive spinal cord injured segment inferred from MRI findings remains a prediction, subject to individual variation. It is possible that the actual injury level was not accurately identified, introducing some degree of imprecision in the assessment. Moreover, different groups of patients were intended for the assessment of the lengths of sensory/motor, and MRI-based sensory/motor ZPPs, leading to inconsistencies in the evaluation, making it challenging to interpret the results consistently across these distinct measures. The study's small sample size is also a limitation of the study. In addition, it may be essential to incorporate ZPP length with additional confounding variables (e.g. age, energy of trauma, time from injury to initial assessment, and time from injury to MRI). Further investigation into the correlations between ZPP length and these factors is needed.\u003c/p\u003e \u003cp\u003eHowever, the present study is the first to explore the significance of ZPPs within 72 hours post-injury, combining with MRI findings, offering valuable insights into its potential utility in prognostic predictors. Our findings suggest that a longer sensory ZPP length may serve as a useful predictor of favorable outcomes in motor complete CSCI in the acute phase.\u003c/p\u003e"},{"header":"CONCLUSIONS","content":"\u003cp\u003eIn patients with motor complete CSCI, sensory ZPP length within 72 hours after injury could be a prognostic factor of the motor recovery and conversion to motor incomplete status. ZPPs may be more useful for predicting the recovery potential combined with the MRI findings. These results provide valuable insight into the early assessment of SCI and highlight the need for further research to confirm the utility of ZPP length as a reliable predictor.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eACKNOWLEDGEMENTS\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare no acknowledgements.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAUTHOR CONTRIBUTION\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eKM designed the studies, performed the statistical analysis and drafted the manuscript. OK and TM supervised the overall project. Other authors performed the data collection. All authors read and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFUNDING\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNo funds were received in support of this work.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eETHICAL APPROVAL\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was approved by the Ethics Review Board of the Spinal Injuries Center. Informed consent was obtained from all of the patients who were included in the present study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCONPETING INTERESTS\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare no competing interests.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDATA AVAILABILITY STATEMENT\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eData sets generated and/or analyzed during the current study are not publicly available due to the inclusion of private information of patients but are available from the corresponding author on reasonable request.\u0026nbsp;\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eWaters RL, Adkins RH, Yakura JS, Sie I. Motor and sensory recovery following incomplete tetraplegia. Arch Phys Med Rehabil. 1994;75(3):306\u0026ndash;11.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBurns AS, Ditunno JF. Establishing prognosis and maximizing functional outcomes after spinal cord injury: a review of current and future directions in rehabilitation management. Spine (Phila Pa 1976). 2001;26(24 Suppl):S137-45.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKirshblum S, Snider B, Eren F, Guest J. Characterizing Natural Recovery after Traumatic Spinal Cord Injury. J Neurotrauma. 2021;38(9):1267\u0026ndash;1284.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMori E, Ueta T, Maeda T, Ideta R, Yugu\u0026eacute; I, Kawano O, et al. Sequential neurological improvements after conservative treatment in patients with complete motor paralysis caused by cervical spinal cord injury without bone and disc injury. J Neurosurg Spine. 2018;29(1):1\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKawano O, Maeda T, Mori E, Takao T, Sakai H, Masuda M, et al. How much time is necessary to confirm the diagnosis of permanent complete cervical spinal cord injury? Spinal Cord. 2020;58(3):284\u0026ndash;289.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSchuld C; EMSCI study group; Kirshblum S, Tansey K; ASIA International Standards Committee; Rupp R. The revised zone of partial preservation (ZPP) in the 2019 International Standards for Neurological Classification of Spinal Cord Injury: ZPP applicability in incomplete injuries. Spinal Cord. 2024;62(2):79\u0026ndash;87.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMarino RJ, Ditunno JF Jr, Donovan WH, Maynard F Jr. Neurologic recovery after traumatic spinal cord injury: data from the Model Spinal Cord Injury Systems. Arch Phys Med Rehabil. 1999;80(11):1391\u0026ndash;6.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eZariffa J, Kramer JL, Fawcett JW, Lammertse DP, Blight AR, Guest J, et al. Characterization of neurological recovery following traumatic sensorimotor complete thoracic spinal cord injury. Spinal Cord. 2011;49(3):463\u0026ndash;71.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFisher CG, Noonan VK, Smith DE, Wing PC, Dvorak MF, Kwon BK. Motor recovery, functional status, and health-related quality of life in patients with complete spinal cord injuries. Spine (Phila Pa 1976). 2005;30(19):2200\u0026ndash;7.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMatsushita A, Maeda T, Mori E, Yugue I, Kawano O, Ueta T, et al. Subacute T1-low intensity area reflects neurological prognosis for patients with cervical spinal cord injury without major bone injury. Spinal Cord. 2016;54(1):24\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMatsushita A, Maeda T, Mori E, Yuge I, Kawano O, Ueta T, et al. Can the acute magnetic resonance imaging features reflect neurologic prognosis in patients with cervical spinal cord injury? Spine J. 2017;17(9):1319\u0026ndash;1324.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMatsumoto M, Ishikawa M, Ishii K, Nishizawa T, Maruiwa H, Nakamura M, et al. Usefulness of neurological examination for diagnosis of the affected level in patients with cervical compressive myelopathy: prospective comparative study with radiological evaluation. J Neurosurg Spine. 2005;2(5):535\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSeichi A, Takeshita K, Kawaguchi H, Matsudaira K, Higashikawa A, Ogata N, et al. Neurologic level diagnosis of cervical stenotic myelopathy. Spine (Phila Pa 1976). 2006;31(12):1338\u0026ndash;43.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKaneyama H, Kawano O, Morishita Y, Yamamoto T, Maeda T. Predicting motor function recovery in cervical spinal cord injury-induced complete paralysis with reflex response. Spinal Cord. 2022;60(11):1020\u0026ndash;1022.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMorishita K, Kasai Y, Ueta T, Shiba K, Akeda K, Uchida A. Patellar tendon reflex as a predictor of improving motor paralysis in complete paralysis due to cervical cord injury. Spinal Cord. 2009;47(8):640\u0026ndash;2.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKawano O, Maeda T, Sakai H, Masuda M, Morishita Y, Hayashi T, et al. Significance of the neurological level of injury as a prognostic predictor for motor complete cervical spinal cord injury patients. J Spinal Cord Med. 2023;46(3):494\u0026ndash;500.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWilson 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\u0026ndash;26.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMarino RJ, Burns S, Graves DE, Leiby BE, Kirshblum S, Lammertse DP. Upper- and lower-extremity motor recovery after traumatic cervical spinal cord injury: an update from the national spinal cord injury database. Arch Phys Med Rehabil. 2011;92(3):369\u0026ndash;75.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBlaustein DM, Zafonte R, Thomas D, Herbison GJ, Ditunno JF. Predicting recovery of motor complete quadriplegic patients. 24 hour v 72 hour motor index scores. Am J Phys Med Rehabil. 1993;72(5):306\u0026ndash;11.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003eTables 1-3 are available in the Supplementary Files section.\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"","lastPublishedDoi":"10.21203/rs.3.rs-6143755/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6143755/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eStudy Design: \u003c/strong\u003eA retrospective case series.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eObjectives: \u003c/strong\u003eTo investigate the prognostic value of the Zone of Partial Preservation (ZPP) within 72 h after cervical spinal cord injury (CSCI) with American Spinal Injury Association Impairment Scale (AIS) A and B.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSetting\u003c/strong\u003e: Department of Orthopaedic Surgery, Spinal Injuries Center, Japan\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods:\u003c/strong\u003e The study participants were sixty-five patients with an initial diagnosis of motor complete CSCI (AIS A, n=44, AIS B, n=21) within 72 h after injury. The impact of the length of motor or sensory ZPPs on the rates of motor score recovery and conversion to AIS C/D at three months after injury were investigated. MRI-based ZPPs were defined as the residual function caudal to the presumptive primary injured segment of the spinal cord inferred from MRI, whose relevance to the motor recovery was also investigated.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults:\u003c/strong\u003e The significant better motor recovery was demonstrated in individuals with longer lengths of sensory and MRI-based sensory ZPPs (p\u0026lt;0.05). Sensory ZPP length of 11 or more, MRI-based sensory ZPP length of 10 or more, and MRI-based motor ZPP length of 1 were associated to be the significant higher rates of conversion to AIS C/D with the odds ratio of 10.2 (95% CI, 1.4-76.9), 21.0 (1.8-243.0), and 8.2 (2.2-31.4), respectively (p\u0026lt;0.05).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusions:\u003c/strong\u003e Sensory ZPPs within 72 hours after injury could be a prognostic factor of the motor recovery and conversion to AIS C/D in individuals with motor complete CSCI. ZPPs may be more useful for predicting the recovery potential combined with the MRI findings.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSponsorship\u003c/strong\u003e: N/A\u003c/p\u003e","manuscriptTitle":"Prognostic significance of the Zone of Partial Preservation (ZPP) within 72 hours of motor complete cervical spinal cord injury: a novel MRI-based approach","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-03-31 11:09:34","doi":"10.21203/rs.3.rs-6143755/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"bfa18705-5580-47a9-90ff-dd3de2d7bd84","owner":[],"postedDate":"March 31st, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":45928001,"name":"Health sciences/Medical research/Epidemiology"},{"id":45928002,"name":"Health sciences/Diseases/Trauma"},{"id":45928003,"name":"Health sciences/Biomarkers/Predictive markers"}],"tags":[],"updatedAt":"2025-04-29T15:37:19+00:00","versionOfRecord":[],"versionCreatedAt":"2025-03-31 11:09:34","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-6143755","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6143755","identity":"rs-6143755","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}