, Jose Alberto Israel Romero Rangel4, Carla Daniela Anania3, Mehmet Zileli5
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2Department of Neurosurgery, Liaquat National Hospital & Medical College, Karachi, Pakistan JFIF d d Ducky d qhttp://ns.adobe.com/xap/1.0/ |er˭|I|-fGK.rΛp8XV1%K6mvG+tc+qE &ǸC_Nm:l=_/m5^[dߌڇ.c<%:)tQ$Ow~-aY;UJ >=F)2[nk؆?훐 M=l6[4(O.]2#-H^n#->&mp5~Fӛ+|| S,xag% qkEUzUgæBhߕP(7]kFnq?֖Cpru Z6*rEڊtS|*tI*E}7R<,nUU֫^I7Q*mSly%rdȓd8hE<9oHhMfNSRj[i7D[Rj݊+kდq{"$$H?p \̅S?㭻;t~ R߁ )^/>Qj`yt[w ԛ;² ~+ ߔ_ YW~|o] ?x^ᯛ `ʼn;g)T@vWn]>&4l p+$D̢1l|ȨF%-} .9[}w~
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3Department of Neurosurgery, Humanitas Clinical and Research Center – IRCCS, Rozzano, Italy JFIF d d Ducky d qhttp://ns.adobe.com/xap/1.0/ |er˭|I|-fGK.rΛp8XV1%K6mvG+tc+qE &ǸC_Nm:l=_/m5^[dߌڇ.c<%:)tQ$Ow~-aY;UJ >=F)2[nk؆?훐 M=l6[4(O.]2#-H^n#->&mp5~Fӛ+|| S,xag% qkEUzUgæBhߕP(7]kFnq?֖Cpru Z6*rEڊtS|*tI*E}7R<,nUU֫^I7Q*mSly%rdȓd8hE<9oHhMfNSRj[i7D[Rj݊+kდq{"$$H?p \̅S?㭻;t~ R߁ )^/>Qj`yt[w ԛ;² ~+ ߔ_ YW~|o] ?x^ᯛ `ʼn;g)T@vWn]>&4l p+$D̢1l|ȨF%-} .9[}w~
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4American British-Cowdray Medical Center IAP, Mexico City, Mexico JFIF d d Ducky d qhttp://ns.adobe.com/xap/1.0/ |er˭|I|-fGK.rΛp8XV1%K6mvG+tc+qE &ǸC_Nm:l=_/m5^[dߌڇ.c<%:)tQ$Ow~-aY;UJ >=F)2[nk؆?훐 M=l6[4(O.]2#-H^n#->&mp5~Fӛ+|| S,xag% qkEUzUgæBhߕP(7]kFnq?֖Cpru Z6*rEڊtS|*tI*E}7R<,nUU֫^I7Q*mSly%rdȓd8hE<9oHhMfNSRj[i7D[Rj݊+kდq{"$$H?p \̅S?㭻;t~ R߁ )^/>Qj`yt[w ԛ;² ~+ ߔ_ YW~|o] ?x^ᯛ `ʼn;g)T@vWn]>&4l p+$D̢1l|ȨF%-} .9[}w~
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5Department of Neurosurgery, Ege University, Izmir, Turkey JFIF d d Ducky d qhttp://ns.adobe.com/xap/1.0/ |er˭|I|-fGK.rΛp8XV1%K6mvG+tc+qE &ǸC_Nm:l=_/m5^[dߌڇ.c<%:)tQ$Ow~-aY;UJ >=F)2[nk؆?훐 M=l6[4(O.]2#-H^n#->&mp5~Fӛ+|| S,xag% qkEUzUgæBhߕP(7]kFnq?֖Cpru Z6*rEڊtS|*tI*E}7R<,nUU֫^I7Q*mSly%rdȓd8hE<9oHhMfNSRj[i7D[Rj݊+kდq{"$$H?p \̅S?㭻;t~ R߁ )^/>Qj`yt[w ԛ;² ~+ ߔ_ YW~|o] ?x^ᯛ `ʼn;g)T@vWn]>&4l p+$D̢1l|ȨF%-} .9[}w~
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Copyright © 2020 by the Korean Spinal Neurosurgery Society
This is an open access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
| Study | Data collection | Level of evidence | Bias | Clinical tool | Rx | Biomarkers | Parameter | Conclusion |
|---|---|---|---|---|---|---|---|---|
| Pouw et al. [75] 2009 | Retrospective | Systematic review: 12 human studies, 6 animal studies | Very serious (not PRISMA) | ASIA | CT | S-100b | Elevated in acute spinal injury (experimental) at 6 hours | Do not yet provide a sensitive prognostic tool. |
| Neuron-specific enolase (NSE) | ||||||||
| Neurofilament light chain (pNF-H) | ||||||||
| Glial fibrillary acidic protein (GFAP) | ||||||||
| Ahadi et al. [10] 2015 | Prospective | Prospective cohort | Not serious nonblinded (bioquimical evaluation) | ASIA | None | Serum levels of pNF-H and NSE were signifi cantly higher during 24 and 48 hr after injury in patients. | Higher serum levels in ASIA A and B | During 48 hours after injury, estimation of serum levels of pNF-H, NSE, and GFAP, combined with neurological testing, could predict the presence of SCI and severity prior to spinal computed tomography and surgical or conservative interventions. |
| The level of GFAP was appropriate for estimating the severity of SCI in the fi rst 24 hours after injury | ||||||||
| Wu et al. [11] 2016 | Prospectiv | Prospective cohort | Not serious nonblinded (biochemical evaluation) | ASIA ISNCSCI | None | CSF: citruline N-acetylputrescine Lactic acid glycerol N1, N12-diacetylspermine N-methyl-S-aspartic acid | CSF metabolites were identified as potential biomarkers of baseline injury severity, and good classification performance (AUC>0.869) was achieved by using combinations of these metabolites in pair-wise comparisons of AIS A, B and C patients | Using the universal metabolome standard strategy, the current data set can be expanded to a larger cohort for biomarker validation, as well as discovering biomarkers for predicting neurologic outcome |
| Elizei et al. [76] 2017 | Review | Review | Very serious (not PRISMA) | ASIA ISNCSCI Frankel | None | CSF: ubiquitin B-terminal hydrolase-L1 (UCH-L1), spectrin breakdown products (SBDP), myelin basic protein (MBP), and GFAP nitric oxide (NO) interleukin (IL)-6, IL-8 | UCH-L1, SBDP, GFAP, MBP Elevated in SCI with correlation in severity and improvement | CSF biomarkers could be incorporated into a model that had an 83.3% accuracy at predicting AIS improvement over 6 months |
| Not specified | TNF-R1 levels | NO elevated in FRANKEL A and B (MCP)-1, tau, S100β, and GFAP, peak at 24-36 hr and decresed at 72 hr | ||||||
| Nonsystematic review | MCP-1, tau, serum neurofilament light chain phosphorylated neurofilament heavy chain (pNF-H), and NSE | IL-6 , GFAP, tau and S100β different in severity injury GFAP, phosphorylated neurofilament heavy chain (pNF-H), and NSE | GFAP levels were correlated with injury severity. | |||||
| Ferbert et al. [8] 2016 | Prospective | Prospective cohort | Nor serious | ASIA | None | IGF-1, TGF-β1 and sCD95L | Both groups showed a very similar distribution in TGF-β1 levels as described above. IGF-1 | Demonstrated a possible relationship between cytokine concentration in peripheral blood samples and neurological remission |
| Nonblinded (biochemical evaluation) | ||||||||
| Ydens et al. [77] 2017 | Review | Review | Nor serious | None | None | Oligodendrocyte- and astrocyte-associated proteins such as S100B, GFAP, and MBP have CSF: NSE, tau, and neurofilaments | Even though elevated concentrations of potential biomarkers have been identified in patients with SCI, the current candidate biomarkers do not yet provide a sensitive diagnostic or prognostic tool. | The panel of biomarkers could even predict motor outcome at 6 months better than the standard clinical AIS classification |
| Nonsystematic review: 14 animal studies, 36 human studies | Nonblinded (biochemical evaluation) | Independent replication studies are needed to confirm the validity and reproducibility of these markers. | ||||||
| Tong et al. [9] 2018 | Retrospective | Retrospective cohort | Serious indirectness imprecise | ASIA | None | Serum albumin concentrations were obtained as part of routine blood chemistry analysis, at trial entry (24-72 hours), 1, 2, and 4 weeks after injury. | Serum albumin concentration was only weakly associated with neurological outcome at baseline (24-72 hours according to our primary analysis) and only significant within individual AIS grades by 4 weeks post injury. | Serum albumin concentrations are a useful biomarker for the prognosis of long-term neurological outcome after an acute SCI. |
| Tigchelaar et al. [7] 2019 | Prospective | Nonrandomized trial | Not serious | ASIA ISNCSCI | None | Serum and CSF: micro RNA | This set of 70 microRNA had crossvalidated AUC=0.75 when classifying AIS A patients vs. all other AIS grades. | Further testing in an independent cohort of acute SCI patients will be necessary to validate (and potentially improve) the microRNA model. |
| This set of 30 microRNA had crossvalidated AUC=0.75 when 22 classifying AIS grade A patients who went on to improve at least 1 grade, at 6 months post injury, from those that did not. MiR-423, as one of the strongest prognosticators. |
Rx, radiology; PRISMA, Preferred Reporting Items for Systematic Reviews and Meta-Analyses; ASIA, American Spinal Injury Association Impairment; CT, computed tomography; CSF, cerebrospinal fluid; AUC, area under the curve; AIS, ASIA Impairment Scale; SCI, spinal cord injury; ISNCSCI, International Standards for Neurological Classification of Spinal Cord Injury.
| Study | Data collection | Study type | Neurological outcome measures | No. of patients | Level of injury | Outcomes | Lenght of follow-up |
|---|---|---|---|---|---|---|---|
| Nandoe Tewarie et al. [78] 2010 | Review | Comprehensive review | ASIA, LEMS | N/A | N/A | The assessment of functional loss after SCI has been standardized in the larger part of the world. The AIS is often used to assess the level and the completeness of SCI. | N/A |
| Hadley et al. [74] 2013 | Review | Comprehensive review | ASIA, SCIM | N/A | N/A | Neurological Examination: Level II: • The ASIA international standards for neurological and functional classification of spinal cord injury are recommended as the preferred neurological examination tool for clinicians involved in the assessment and care of acute spinal cord injury patients. | N/A |
| Functional Outcome Assessment: Level I: • The Spinal Cord Independence Measure III is recommended as the preferred functional outcome assessment tool for clinicians involved in the assessment, care, and follow-up of patients with spinal cord injuries. | |||||||
| Pain Associated With Spinal Cord Injury: Level I: • The International Spinal Cord Injury Basic Pain Data Set is recommended as the preferred means to assess pain, including pain severity, physical functioning, and emotional functioning, among SCI patients | |||||||
| Boese and Lechler [15] 2013 | PRISMA | Systematic review | AIS & MRI Patterns and clinical correlation | 52 Papers | N/A | At admission, neurologic deficit assessed by the AIS in 567 patients was A in 19.1%, B in 18.5%, C in 39.7%, and D in 22.8%. At final follow-up, these were 6.5%, 4.8%, 20.1%, and 44.3%, respectively. In 7.1%, no MRI abnormalities (type I) were detected, and 92.9% exhibited abnormal scan results (type II). Of the latter, 11.7% revealed extraneural (type IIa), 36.9% revealed intraneural (type IIb), and 44.3% revealed combined abnormalities (type IIc). Statistical analysis of neurologic impairment at admission and follow-up revealed significant differences in outcome between patients with different imaging findings. | N/A |
| Carrasco-López et al. [16] 2016 | Prospective | Prospective cohort | ASIA, ISNCSCI, UEMS, JTHFT, 9HPT | 29 | Rostral to T1 | Both the JTHFT and 9HPT can be similarly used to quantify functional impairment after cervical SCI. The upper extremity motor score, JTHFT, and 9HPT strongly correlate with the AIS (graded from A to E), but not with the lesion level. | 10 Months |
| Harrop et al. [79] 2018 | Non-PRISMA | Systematic review | SCIM, AIS, Sacral sensation, Ankle spasticity Urethral and rectal sphincter, AbH motor function, Abductor Hallucis, Frankel, Sunnyrook scales, FIM | 13 Papers | N/A | Numerous neurological assessment scales (Functional Independence Measure, Sunnybrook Cord Injury Scale, and Frankel Scale for Spinal Cord Injury) have demonstrated internal reliability and validity in the management of patients with thoracic and lumbar fractures. Unfortunately, other contemporaneous measurement scales (i.e,. American Spinal Cord Injury Association Impairment Scale) have not been specifically studied in patients with thoracic and lumbar fractures. | N/A |
| Entry AIS grade, sacral sensation, ankle spasticity, urethral and rectal sphincter function, and AbH motor function can be used to predict neurological function and outcome in patients with thoracic. | |||||||
| Furlan et al. [17] 2009 | Review | Systematic review | The psychometric properties of ASIA Standards and all previously used outcome measures of pain in the SCI population in the acute care setting | 56 Papers | N/A | There was no study that examined pain assessment in the acute care setting. While 18 of 24 articles studied an instrument for assessment of pain intensity, the remaining six studies were focused on classifications of pain in the SCI population. Further investigation of the psychometric properties of the ASIA Standards is recommended due to a lack of studies focused on some key elements of responsiveness, including minimal clinically important difference. The visual analog scale is the most commonly studied instrument of assessment of pain intensity in the SCI population | N/A |
| Patel et al. [25] 2010 | Retrospective | Retrospective cohort | SLIC classification for subaxial cervical spine Injury | 65 | C2-T1 | A widely accepted classification of subaxial cervical trauma does not exist. The SLIC system has been developed to address limitations of prior systems. | N/A |
| The SLIC system provides diagnostic information and can guide surgical versus nonsurgical treatment. | |||||||
| An algorithm based on the SLIC system can guide surgical approach in the operative treatment of subaxial cervical trauma. References | |||||||
| Kirshblum et al. [80] 2011 | Review | Comprehensive review | AIS ISMCSCI | N/A | N/A | ISMCSCI and AIS definitions | N/A |
| Berney et al. [19] 2011 | Prospective | Prospective cohort | AIS | 114 | Above C8 | For patients suffering an ASIA A injury (n¼72), 48 patients received a tracheostomy (66.7%) and in incomplete injuries 47.6% received a tracheostomy. All patients with injuries above the C4 level received a tracheostomy. | N/A |
| Patients with an ASIA A injury are more likely to require a tracheostomy | |||||||
| Tsou et al. [26] 2011 | Retrospective | Retrospective cohort | Data extraction included demographics, mechanism of injury, and neurologic function at the time of admission. | 333 | C3-7 | This study demonstrated that the determinants for a comprehensive cervical spine injury severity assessment model should include neural impairment, pre- and postinjury available spinal canal sagittal diameter, and pathomorphology of the injury, each of which may individually predict the probability of surgical intervention. Patho-morphology evaluation is best separated into its two components, actual osseoligamentous failure and displacement. For ease of injury severity recognition, statistical analysis, and outcome comparisons, a model based on separate but similarly scaled numeric scoring for each determinant is a useful tool. | N/A |
| A detailed evaluation of the pathomorphology and spinal canal sagittal diameter measurements were performed on the cervical spine CT scans and/or MRI images | |||||||
| Radclif et al. [23] 2012 | Prospective | Prospective cohort | To proof if the load-sharing score (LSS) predicts ligamentous or neurological injury. | 44 | T10-L2 | The most common neurological injury pattern was ASIA grade C (43%), followed by ASIA grade E (30%). Twenty-five of the patients (57%) were treated with operative stabilization. The mean ASIA motor score was 83.0. | N/A |
| The LSS does not uniformly correlate with the PLC injury, neurological status, or empirical clinical decision making | |||||||
| Krishna et al. [6] 2013 | Review | Comprehensive review | AIS rational and limitations | N/A | N/A | ASIA impairment grades result in assessments of variable resolution and groupings of heterogeneous populations with different individual recovery potentials. This results in large variations from the mean on outcome measures and a need to enroll a large number of patients in clinical trials | N/A |
| Vasquez et al. [22] 2013 | Retrospective | Retrospective cohort | To confirm a tendency for light touch (LT) to score higher than pin prick (PP) in SCI subjects and discuss possible reasons for such disparity. The clinical neurological evaluation included level of injury and the ISNCSCI scores in total and at each spinal segmental level for LT, PP, upper extremity motor and lower extremity motor function | 99 | Below C2 to S4/5 | The discrepancies between LT and PP could relate to the greater complexity of the PP test or a difference in the extent of injury to the posterior columns (LT) and spinothalamic (PP) tracts. Further interpretation would benefit from additional electrophysiological sensory tests | N/A |
| Marino et al. [21] 2016 | Prospective | Prospective cohort | To determine whether pressure sensation at the S3 dermatome (a new test) could be used in place of deep anal pressure (DAP) to determine completeness of injury as part of the ISNCSCI Design. | 141 | N/A | S3 pressure sensation is reliable and has substantial agreement with DAP in persons with SCI at least 1-month postinjury. We suggest S3 pressure as an alternative test of sensory sacral sparing for supraconus SCI, at least in cases where DAP cannot be tested. Further research is needed to determine whether S3 pressure could replace DAP for classification of SCI. Archives | 6–12 Months |
| Walden et al. [24] 2016 | Retrospective | Retrospective cohort | To describe the development and validation of a computerized application of the ISNCSCI | 2,520 | Any | The RHI-ISNCSCI Algorithm provides a standardized method to accurately derive the level and severity of SCI from the raw data of the ISNCSCI examination. The web interface assists in maximizing usability while minimizing the impact of human error in classifying SCI. | N/A |
| Kaul et al. [20] 2017 | Prospective | Prospective study | To determine whether the recently introduced AOSpine Classification and Injury Severity System has better interrater and intrarater reliability than the already existing TLICS for thoracolumbar spine injuries and their clinical Correlation with ISNCSCI | 550 | Any | Recently proposed AOSpine classification has better reliability for identifying fracture morphology than the existing TLICS Near perfect interrater and intrarater agreement was seen concerning neurological status for both the classification systems | N/A |
| Layer et al. [1] 2017 | Prospective | Prospective cohort | To evaluate the clinical effectiveness of the Neuro-Spinal Scaffold, including improvement in AIS grade, sensory scores, motor scores, bladder and bowel function, Spinal Cord Independence Measure III, and Quality of Life Index (QLI-SCI III), as well as possibly decreased pain. | 9 | T3-T11 | Following durotomy, 2 forms of cord damage were observed. In contusion-type injuries, the cord surface is intact. In compound-type injuries, the pia is breached and there is visible but incomplete cord parenchymal separation (Fig. 4). Both injuries were successfully implanted with the Neuro-Spinal Scaffold and AIS improvements were seen in both pathological types. | Up to 12 months |
| Yugué et al. [18] 2018 | Prospective | Prospective cohort | The sensitivity and specificity of the ‘knee-up test’ were evaluated in patients with acute CSCI classified as AIS C or D | 200 | Above C8 | The sensitivity, specificity, positive predictive and negative predictive values of this test for all patients were 99.1, 76.8, 82.5, and 98.7, respectively. | N/A |
| The knee-up test may allow easy and highly accurate estimation, without the need for special skills, of AIS classification for patients with incomplete CSCI. |
ASIA, American Spinal Injury Association Impairment; LEMS, Lower Extremity Motor Score; SCIM, Spinal Cord Independence Measure; N/A, not available; SCI, spinal cord injury; AIS, ASIA Impairment Scale; CT, computed tomography; MRI, magnetic resonance imaging; UEMS, Motor Score combines the Upper Extremity Motor Score; TLICS, Thoracolumbar Injury Classification and Severity Score; JTHFT, Jebsen-Taylor Hand Function Test, 9HPT, 9 Hole Peg Test; SLIC, subaxial cervical injury classification system; CSCI, cervical spinal cord injury; RHI-ISNCSCI, Rick Hansen Institute-International Standards for Neurological Classification of Spinal Cord Injury.
| Study | Data collection | Level of evidence | Sesgos | Clinical | Rx | Parameters | Results | Conclusion |
|---|---|---|---|---|---|---|---|---|
| Fehlings et al. [36] 2017 | Review | I: Consensus on systematic review No PRISMA mentioned GRADE evaluations | Indirect ness No gold standard | Frankel | MRI | *Evidence Level. 1 prospective study by Papadopoulos et al (2002) that evaluated the effect of pre-treatment MRI on neurological outcomes | *Emergency MRI provided an essential tool for the accurate diagnosis of spinal cord compression and directly influenced our initial clinical management in the majority of protocol patients.” | *We suggest that MRI be performed in adult patients with acute spinal cord injury prior to surgical intervention, when feasible, to facilitate improved clinical decision making. |
| Quality of Evidence: Very Low Strength of Recommendation: Weak | ||||||||
| We suggest that MRI should be performed in adult patients in the acute period following SCI, before or after surgical intervention, to improve prediction of neurologic outcome. | ||||||||
| Quality of Evidence: Low Strength of Recommendation: Weak Introduction | ||||||||
| Kleiser et al. [34] 2010 | Prospective | Prospective cohort | Multicentric | N/A | MRI | T2-weighted turbo spine echo (TSE) sequence, sagittal orientation, T1-weighted TSE sequence, sagittal orientation, T1-weighted TSE sequence, sagittal orientation, T2-weighted GE sequence | The SCI was clearly visible as a hyperintense area in the T2-weighted images on day 4. On day 7, the spinal cord lesion was visible on 2 up to 4 sagittal sections. The lesions of the spinal cord injury remained constant for the subsequent observation times (Fig. 2) and were clearly evident still on day 84. | • Gadolinium-enhancement starts approximately 4 days after the traumatic spinal cord lesion and is maximal between day 7 and 28. |
| • Gadolinium accumulates in the spinal cord lesion 5 minutes after intravenous injection, reaching a stable enhancement after 10 minutes for up to 30 minutes. | ||||||||
| • Detection of the disrupted blood-spinal cord barrier requires MR imaging at least 10 minutes after intravenous gadolinium injection | ||||||||
| Ghasemi et al. [32] 2015 | Prospective | Prospective cohort | Small sample | ASIA A-D | MRI contrst Dutarm (gadoterate meglumine) | MRI finding: Level of spine involvement, type of cord injury (edema-hemorrhagia combined),9,10 and percentage of cord injury (>50%–50% to 75%–<75%) | A classification with 3 patterns of SCIs. Type I, decreased signal intensity consistent with acute intraspinal hemorrhage. Type II: bright signal intensity consistent with acute cord edema. Type III: mixed signal of hypointensity centrally and hyperintensity peripherally consistent with contusion. | We recommend the MRI with contrast only used in cases of suspected severe soft tissue injury, which have been ignored by detection MRI without contrast. |
| Cheran et al. [33] 2011 | Prospective | Prospective cohort | Nonrandomized | ASIA hystoric control | MRI | MR imaging was performed 1 hr–5 days after injury. Imaging was performed within 6 hour of injury | The 2-way interaction between ASIA and λ was able to predict with an overall classification accuracy of 86.4% (p<0.0026) | The study demonstrated that regional and injury site MR DTI parameter measurements reflect the severity and are reliable makers of spinal cord injury. Among the DTI parameters, λ and FA values appear to be the most sensitive measurements at the injury site. |
| DWI | ||||||||
| DTI | ||||||||
| Gupta et al. [43] 2014 | Prospective | Prospective cohort | Do not describe moment of MRI Not blinded | ASIA | MRI | Based on the MRI findings, patients were divided into six patterns Pattern zero: Normal findings Pattern I: Hemorrhage | The best predictors for baseline ASIA score were MCC, cord oedema and cord hemorrhage. For the final ASIA score, the best predictors were baseline ASIA score and cord hemorrhage | MRI is excellent imaging modality for detecting and assessing severity of spinal trauma. In our study, presence of cord hemorrhage, MCC and cord oedema were best predictors of baseline neurological status at presentation, whereas baseline ASIA score and cord hemorrhage were best predictors of final neurological outcome. |
| Pattern II: Oedema | ||||||||
| Pattern III: Contusion | Presence of cord oedema, cord hemorrhage and MCC best correlate with neurological deficit at presentation. While poor baseline ASIA score and cord hemorrhage confers a poor long-term outcome. On the other hand, absence of cord hemorrhage usually indicates some potential for neurological recovery. | |||||||
| Pattern IV: Compression | ||||||||
| Pattern V: Transection pattern | ||||||||
| D’Souza et al. [42] 2017 | Prospective | IV: Case and Contros | Done within 7 days of injury | Frankel | MRI DTI | Scoring of extent of clinical severity was done based on the Frankel grading system. MRI was performed on a 3T system within 7 days of sustaining trauma. | Mean FA value at the level of injury (was less than the Mean FA value of cervical spine. | DTI was superior to conventional. |
| MRI scans in depicting changes in spinal cord integrity after traumatic injury. Qualitative tractography enabled the delineation of changes in the white matter tract of spinal cord, both obvious as well as subtle. Quantitative indices in the form of FA and MD were a more useful parameter for detection of spinal cord injury. FA value was significantly decreased while MD value was significantly increased at the level of injury in cases as compared to controls. FA showed significant correlation with the Frankel score, a clinical measure of the motor and sensory status. Long-term studies would be needed to see if DTI could be used as a reliable prognostic marker of neurological outcome in spinal cord injury | ||||||||
| Spearman’s correlation(r=0.86) was found between FA values at the level of injury and clinical grading | ||||||||
| Talekar et al. [81] 2016 | Review | Review | Comprehensive review | CT and MRI | MRI DTI | Non systematic | Conventional MR techniques do not appear to differentiate edema from axonal injury. They | While MRI and DTI will likely never provide the same high level of granularity as that of a good quality neurologic examination, it does offer three distinct advantages over the INSCSCI assessment: (1) speed, (2) objectivity and (3) direct visualization of the end organ (the spinal cord). |
| Huang and Ou [41] 2014 | Prospective | Prospective Cohort | N/A | ASIA Respiratory failure | MRI | Surgery was indicated if the neurological deficits were compatible with the abnormal findings of the MRI scans | There was a statistically significant intergroup difference in the imaging level of CSCI (p<0.001) | The imaging level of injury at C3 is more frequently associated with respiratory failure than injury to the lower cervical levels. Additionally, the presence of spinal cord edema is a predictor that contributes to respiratory failure. In order to prevent secondary spinal cord injury from prolonged hypoxia and to facilitate pulmonary care, definitive airways with assisted ventilation should be established early in the high-risk patients. |
| Chandra et al. [82] 2012 | Review | Comprehensive review | Nonsytemized | ASIA | MRI | Review | Review | MRI is an essential tool to define the site and nature of cord injury in addition to associated disc, ligamentous and vertebral injuries. The magnetic resonance (MR) appearances of cord hematoma, severity of maximal cord compression and length of cord oedema are all significantly associated with worse long-term functional independence scores and are important considerations in planning acute management. Neurological deterioration in the subacute period constitutes a medical emergency and MRI is pivotal in determing the underlying cause. |
| Freund et al. [40] 2013 | Prospective | Prospective | None | ISNCSCI SCIM | MRI | We assessed patients clinically and by MRI at baseline, 2 months, 6 months, and 12 months, and controls by MRI at the same timepoints | Improvements in SCIM scores at 12 months were associated with a reduced loss in cross-sectional spinal cord) and reduced white matter volume of the corticospinal tracts at the level of the right internal capsule Improvements in ISNCSCI motor scores were associated with less white matter volume change encompassing the corticospinal tract at the level of the right internal capsule | Extensive upstream atrophic and microstructural changes of corticospinal axons and sensorimotor cortical areas occur in the first months after spinal cord injury, with faster degenerative changes relating to poorer recovery. Structural volumetric and microstructural MRI protocols remote from the site of spinal cord injury could serve as neuroimaging biomarkers in acute spinal cord injury. |
| Mabray et al. [39] 2016 | Prospective | Prospetive cohort | AIS TLICS | MRI At 14 hr | BASIC grading Grade 1: normal spinal cord signal; Grade 2: hyperintense intramedullary signal with longitudinal extent confined to a single vertebral level; Grade 3: >1 vertebral level edema; Grade 4: represented mixed hemorrhage and edema. | In a multiple variable model, BASIC was the only statistically significant predictor of AIS at discharge. | This study validates the use of BASIC and other MRI measures of acute SCI specifically in the setting of thoracic SCI. PC analysis identified two distinct patterns of variance: PC1, which was highly related to AIS at discharge, and PC2, which was highly related to surgical decompression. The highest individual correlation with AIS at discharge was seen with the BASIC system, although all metrics of spinal cord signal abnormality had a high degree of individual negative correlation with AIS at discharge. The relationship of MCC and MSCC with AIS at discharge was found to be more complex, likely reflecting the use of these metrics along with TLICS in surgical decision making. A multiple variable regression model identified BASIC as the only statistically significant predictor of AIS at discharge, signifying that BASIC best captured the variance in AIS within our study population | |
| Martin et al. [31] 2015 | Review | Systematic review | Low | MRI | Evidence Low 1 Very Low 1, Insufficient 2 | Diagnostic MRI utility: Biomarker utility | Moderate evidence indicates that the quantitative DTI metric FA successfully correlates with impairment in a number of neurological disorders | |
| Prisma 104 | 1 Moderate | DTI has produced the most substantial results to date, but acquisition methods, data processing, and interpretation require further refinement, followed by standardization and cross-vendor validation, before this technology is ready for widespread clinical adoption. | ||||||
| Articles | 1 Insufficient | |||||||
| 1 Low | ||||||||
| Jeong et al. [38] 2018 | Retrospective | Retrospective cohort | N/A | ASIA | MRI | Authors analyzed the factors believed to increase the risk of requiring a tracheostomy, including the severity of SCI, the level of injury as determined by radiological assessment, three quantitative MR imaging parameters, and eleven qualitative MR imaging parameters | Five factors were detected on multivariate analysis complete SCI, the radiological level of C5 and above, canal compromise, lesion length, and osteophyte formation 40–50 mm | The American Spinal Injury Association grade A, a radiological injury level of C5 and above, an MCC ≥50%, a lesion length ≥20 mm, and osteophyte formation at the level of injury were considered to be predictive values for requiring tracheostomy intervention in patients with cervical SCI. |
| Seif et al. [37] 2018 | Prospective | IV case and control | Low sample Nonrandomized | ISNCSCI | MRI | MRI protocol sensitive to myelin and iron. Patients were examined clinically at baseline, 2, 6, 12, and 24-month post-SCI. | Importantly, early volume and microstructural changes of the cord and cerebellum predicted functional recovery following injury | Neurodegenerative changes rostral to the level of lesion occur early in SCI, with varying temporal and spatial dynamics. Early qMRI markers of spinal cord and cerebellum are predictive of functional recovery. These neuroimaging biomarkers may supplement clinical assessments and provide insights into the potential of therapeutic interventions to enhance neural plasticity. |
| Talbott et al. [35] 2015 | Retrospective | Retrospective cohort | Nonrandomized | ASIA AIS | Five distinct patterns of intramedullary spinal cord T2 signal abnormality were defined in the axial plane at the injury epicenter. These patterns were assigned ordinal values ranging from 0 to 4, referred to as the BASIC scores, which encompassed the spectrum of SCI severity. | The BASIC score strongly correlated with neurological symptoms at the time of both hospital admission and discharge. It also distinguished patients initially presenting with complete injury who improved by at least one AIS grade by the time of discharge from those whose injury did not improve. The authors’ proposed score was rapid to apply. | The authors describe a novel 5-point ordinal MRI score for classifying acute SCIs on the basis of axial T2-weighted imaging. The proposed BASIC score stratifies the SCIs according to the extent of transverse T2 signal abnormality during the acute phase of the injury. The new score improves on current MRI-based prognostic descriptions for SCI by reflecting functionally and anatomically significant patterns of intramedullary T2 signal abnormality in the axial plane. |
MRI, magnetic resonance imaging; SCI, spinal cord injury; ASIA, American Spinal Injury Association Impairment; DWI, Diffusion-weighted imaging; DTI, diffusion tensor imaging; CSCI, cervical spinal cord injury; MCC, maximum canal compromise; MSCC, maximum spinal cord compression; TLICS, Thoracolumbar Injury Classification and Severity Score; FA, fractional anisotropy; ISNCSCI, International Standards for Neurological Classification of Spinal Cord Injury; BASIC, Brain and Spinal Injury Center; qMRI, quantitative MRI.
| Study | Data collection | Early decompression | Late decompression | Conclusions |
|---|---|---|---|---|
| Lee et al. [46] 2018 | Retrospective | < 8 hr | > 8 < 24 hr | Early decompression shows better neurological outcome |
| From C1 to L2 Complete and incomplete SCI | From C1 to L2 | Better improvement in patients with incomplete SCI | ||
| Complete and incomplete SCI | ||||
| Grassner et al. [47] 2016 | Retrospective analysis on prospective collected data | < 8 hr | > 8 hr | Early surgical intervention after cervical traumatic SCI may lead to a better functional outcome of affected individuals (SCIM and AIS scores) |
| Cervical complete and incomplete SCI | Cervical complete and incomplete SCI | |||
| Liu et al. [48] 2016 | Metanalysis | < 24 hr | > 24 hr | Urgent surgery within 24 hours was associated with higher total motor scores, better neurologic improvement, shorter hospital stay and fewer complications compared with those of late surgery |
| Ter Wengel et al. [53] 2019 | Metanalysis | < 24 hr | > 24 hr | Similar neurological recovery was observed after early and late surgery in this meta-analysis of thoracic and thoracolumbar tSCI |
| Complete and incomplete thoracic SCI | Complete and incomplete thoracic SCI | |||
| Ter Wengel et al. [50] 2019 | Metanalysis LoE II | < 72 hr | < 72 hr | Early decompression in complete SCI shows a better neurological outcome than late decompression Early decompression in incomplete SCI shows a similar neurological outcome than incomplete SCI Decompression within 24 hr in complete SCI shows better results |
| Complete and incomplete cervical SCI | Complete and incomplete cervical SCI |
| Study | Data collection | Study type | Neurological outcome measures | No. of patients | Level of injury | Outcomes | MAP goal (mmHg) | MAP goal duration | Length of follow-up |
|---|---|---|---|---|---|---|---|---|---|
| Saadeh et al. [56] 2017 | Prospective and retrospective data | Systematic Review 11 cohort studies | AIS grade, ASIA motor score Modified Frankel score, Yale Scale score | Variable* | C, T, and L spine | 127 Patients, report stable or improved neurological function following management to elevated MAP target during the early phase of care [4] | Variable | ||
| Sabit et al. [57] 2018 | Prospective and retrospective data | Systematic Review of 9 cohort studies | AIS grade, ASIA motor score Modified Frankel score, Yale Scale score | Variable* | C, T, and L spine | Four of nine studies showed neurological improvement associated with higher MAP targets. | Variable | ||
| Two studies found episodes of hypotension related to poor recovery. [5] | |||||||||
| Squair et al. [83] 2019 | Prospective | Case series | ISNCSCI, AIS grade | 92 | C, T and L Spine | Adherence to SCPP targets was the best indicator of improved neurologic recovery (60–65 mmHg) [6] | 6 Months | ||
| Dakson et al. [84] 2017 | Retrospective | Comparative | AIS grade, ASIA motor score | 94* | C, T, and L spine | > 85 | 5 Days | After neurorehabilitation | |
| Kepler et al. [85] 2015 | Retrospective | Case Series | ASIA motor score | 92 | C, T, and L spine | > 85 | ≥ 5 Days | Until hospital day 5 | |
| Martin et al. [31] 2015 | Retrospective | Case Series | AIS motor score | 105 | C & T spine | NS | NS | Until discharge | |
| Hawryluk et al. [61] 2015 | Retrospective | Case Series | AIS grade | 74 | C, T, and L | > 85 | 5 Days | Until discharge | |
| Inoue et al. [86] 2014 | Retrospective | Case Series | AIS grade | 131 | C, T, and L spine | > 82 | 7 Days | Until discharge | |
| Vale et al. [55] 1997 | Prospective | Case Series | AIS grade, ASIA motor score | 77 | C and T spine | > 85 | 7 Days | 12 Months | |
| Levi et al. [59] 1993 | Prospective | Case Series | Frankel grade | 50 | C Spine only | > 90 | 7 Days | 6 Weeks | |
| Wolf et al. [87] 1991 | Retrospective | Case Series | Modified Frankel score, Yale Scale | 52 | C spine only score | > 85 | 5 Days | 12 Months |
| Study | Data collection | Level of evidence | Bias | Clinical tool | Rx | Biomarkers | Parameter | Conclusion |
|---|---|---|---|---|---|---|---|---|
| Pouw et al. [75] 2009 | Retrospective | Systematic review: 12 human studies, 6 animal studies | Very serious (not PRISMA) | ASIA | CT | S-100b | Elevated in acute spinal injury (experimental) at 6 hours | Do not yet provide a sensitive prognostic tool. |
| Neuron-specific enolase (NSE) | ||||||||
| Neurofilament light chain (pNF-H) | ||||||||
| Glial fibrillary acidic protein (GFAP) | ||||||||
| Ahadi et al. [10] 2015 | Prospective | Prospective cohort | Not serious nonblinded (bioquimical evaluation) | ASIA | None | Serum levels of pNF-H and NSE were signifi cantly higher during 24 and 48 hr after injury in patients. | Higher serum levels in ASIA A and B | During 48 hours after injury, estimation of serum levels of pNF-H, NSE, and GFAP, combined with neurological testing, could predict the presence of SCI and severity prior to spinal computed tomography and surgical or conservative interventions. |
| The level of GFAP was appropriate for estimating the severity of SCI in the fi rst 24 hours after injury | ||||||||
| Wu et al. [11] 2016 | Prospectiv | Prospective cohort | Not serious nonblinded (biochemical evaluation) | ASIA ISNCSCI | None | CSF: citruline N-acetylputrescine Lactic acid glycerol N1, N12-diacetylspermine N-methyl-S-aspartic acid | CSF metabolites were identified as potential biomarkers of baseline injury severity, and good classification performance (AUC>0.869) was achieved by using combinations of these metabolites in pair-wise comparisons of AIS A, B and C patients | Using the universal metabolome standard strategy, the current data set can be expanded to a larger cohort for biomarker validation, as well as discovering biomarkers for predicting neurologic outcome |
| Elizei et al. [76] 2017 | Review | Review | Very serious (not PRISMA) | ASIA ISNCSCI Frankel | None | CSF: ubiquitin B-terminal hydrolase-L1 (UCH-L1), spectrin breakdown products (SBDP), myelin basic protein (MBP), and GFAP nitric oxide (NO) interleukin (IL)-6, IL-8 | UCH-L1, SBDP, GFAP, MBP Elevated in SCI with correlation in severity and improvement | CSF biomarkers could be incorporated into a model that had an 83.3% accuracy at predicting AIS improvement over 6 months |
| Not specified | TNF-R1 levels | NO elevated in FRANKEL A and B (MCP)-1, tau, S100β, and GFAP, peak at 24-36 hr and decresed at 72 hr | ||||||
| Nonsystematic review | MCP-1, tau, serum neurofilament light chain phosphorylated neurofilament heavy chain (pNF-H), and NSE | IL-6 , GFAP, tau and S100β different in severity injury GFAP, phosphorylated neurofilament heavy chain (pNF-H), and NSE | GFAP levels were correlated with injury severity. | |||||
| Ferbert et al. [8] 2016 | Prospective | Prospective cohort | Nor serious | ASIA | None | IGF-1, TGF-β1 and sCD95L | Both groups showed a very similar distribution in TGF-β1 levels as described above. IGF-1 | Demonstrated a possible relationship between cytokine concentration in peripheral blood samples and neurological remission |
| Nonblinded (biochemical evaluation) | ||||||||
| Ydens et al. [77] 2017 | Review | Review | Nor serious | None | None | Oligodendrocyte- and astrocyte-associated proteins such as S100B, GFAP, and MBP have CSF: NSE, tau, and neurofilaments | Even though elevated concentrations of potential biomarkers have been identified in patients with SCI, the current candidate biomarkers do not yet provide a sensitive diagnostic or prognostic tool. | The panel of biomarkers could even predict motor outcome at 6 months better than the standard clinical AIS classification |
| Nonsystematic review: 14 animal studies, 36 human studies | Nonblinded (biochemical evaluation) | Independent replication studies are needed to confirm the validity and reproducibility of these markers. | ||||||
| Tong et al. [9] 2018 | Retrospective | Retrospective cohort | Serious indirectness imprecise | ASIA | None | Serum albumin concentrations were obtained as part of routine blood chemistry analysis, at trial entry (24-72 hours), 1, 2, and 4 weeks after injury. | Serum albumin concentration was only weakly associated with neurological outcome at baseline (24-72 hours according to our primary analysis) and only significant within individual AIS grades by 4 weeks post injury. | Serum albumin concentrations are a useful biomarker for the prognosis of long-term neurological outcome after an acute SCI. |
| Tigchelaar et al. [7] 2019 | Prospective | Nonrandomized trial | Not serious | ASIA ISNCSCI | None | Serum and CSF: micro RNA | This set of 70 microRNA had crossvalidated AUC=0.75 when classifying AIS A patients vs. all other AIS grades. | Further testing in an independent cohort of acute SCI patients will be necessary to validate (and potentially improve) the microRNA model. |
| This set of 30 microRNA had crossvalidated AUC=0.75 when 22 classifying AIS grade A patients who went on to improve at least 1 grade, at 6 months post injury, from those that did not. MiR-423, as one of the strongest prognosticators. |
| Study | Data collection | Study type | Neurological outcome measures | No. of patients | Level of injury | Outcomes | Lenght of follow-up |
|---|---|---|---|---|---|---|---|
| Nandoe Tewarie et al. [78] 2010 | Review | Comprehensive review | ASIA, LEMS | N/A | N/A | The assessment of functional loss after SCI has been standardized in the larger part of the world. The AIS is often used to assess the level and the completeness of SCI. | N/A |
| Hadley et al. [74] 2013 | Review | Comprehensive review | ASIA, SCIM | N/A | N/A | Neurological Examination: Level II: • The ASIA international standards for neurological and functional classification of spinal cord injury are recommended as the preferred neurological examination tool for clinicians involved in the assessment and care of acute spinal cord injury patients. | N/A |
| Functional Outcome Assessment: Level I: • The Spinal Cord Independence Measure III is recommended as the preferred functional outcome assessment tool for clinicians involved in the assessment, care, and follow-up of patients with spinal cord injuries. | |||||||
| Pain Associated With Spinal Cord Injury: Level I: • The International Spinal Cord Injury Basic Pain Data Set is recommended as the preferred means to assess pain, including pain severity, physical functioning, and emotional functioning, among SCI patients | |||||||
| Boese and Lechler [15] 2013 | PRISMA | Systematic review | AIS & MRI Patterns and clinical correlation | 52 Papers | N/A | At admission, neurologic deficit assessed by the AIS in 567 patients was A in 19.1%, B in 18.5%, C in 39.7%, and D in 22.8%. At final follow-up, these were 6.5%, 4.8%, 20.1%, and 44.3%, respectively. In 7.1%, no MRI abnormalities (type I) were detected, and 92.9% exhibited abnormal scan results (type II). Of the latter, 11.7% revealed extraneural (type IIa), 36.9% revealed intraneural (type IIb), and 44.3% revealed combined abnormalities (type IIc). Statistical analysis of neurologic impairment at admission and follow-up revealed significant differences in outcome between patients with different imaging findings. | N/A |
| Carrasco-López et al. [16] 2016 | Prospective | Prospective cohort | ASIA, ISNCSCI, UEMS, JTHFT, 9HPT | 29 | Rostral to T1 | Both the JTHFT and 9HPT can be similarly used to quantify functional impairment after cervical SCI. The upper extremity motor score, JTHFT, and 9HPT strongly correlate with the AIS (graded from A to E), but not with the lesion level. | 10 Months |
| Harrop et al. [79] 2018 | Non-PRISMA | Systematic review | SCIM, AIS, Sacral sensation, Ankle spasticity Urethral and rectal sphincter, AbH motor function, Abductor Hallucis, Frankel, Sunnyrook scales, FIM | 13 Papers | N/A | Numerous neurological assessment scales (Functional Independence Measure, Sunnybrook Cord Injury Scale, and Frankel Scale for Spinal Cord Injury) have demonstrated internal reliability and validity in the management of patients with thoracic and lumbar fractures. Unfortunately, other contemporaneous measurement scales (i.e,. American Spinal Cord Injury Association Impairment Scale) have not been specifically studied in patients with thoracic and lumbar fractures. | N/A |
| Entry AIS grade, sacral sensation, ankle spasticity, urethral and rectal sphincter function, and AbH motor function can be used to predict neurological function and outcome in patients with thoracic. | |||||||
| Furlan et al. [17] 2009 | Review | Systematic review | The psychometric properties of ASIA Standards and all previously used outcome measures of pain in the SCI population in the acute care setting | 56 Papers | N/A | There was no study that examined pain assessment in the acute care setting. While 18 of 24 articles studied an instrument for assessment of pain intensity, the remaining six studies were focused on classifications of pain in the SCI population. Further investigation of the psychometric properties of the ASIA Standards is recommended due to a lack of studies focused on some key elements of responsiveness, including minimal clinically important difference. The visual analog scale is the most commonly studied instrument of assessment of pain intensity in the SCI population | N/A |
| Patel et al. [25] 2010 | Retrospective | Retrospective cohort | SLIC classification for subaxial cervical spine Injury | 65 | C2-T1 | A widely accepted classification of subaxial cervical trauma does not exist. The SLIC system has been developed to address limitations of prior systems. | N/A |
| The SLIC system provides diagnostic information and can guide surgical versus nonsurgical treatment. | |||||||
| An algorithm based on the SLIC system can guide surgical approach in the operative treatment of subaxial cervical trauma. References | |||||||
| Kirshblum et al. [80] 2011 | Review | Comprehensive review | AIS ISMCSCI | N/A | N/A | ISMCSCI and AIS definitions | N/A |
| Berney et al. [19] 2011 | Prospective | Prospective cohort | AIS | 114 | Above C8 | For patients suffering an ASIA A injury (n¼72), 48 patients received a tracheostomy (66.7%) and in incomplete injuries 47.6% received a tracheostomy. All patients with injuries above the C4 level received a tracheostomy. | N/A |
| Patients with an ASIA A injury are more likely to require a tracheostomy | |||||||
| Tsou et al. [26] 2011 | Retrospective | Retrospective cohort | Data extraction included demographics, mechanism of injury, and neurologic function at the time of admission. | 333 | C3-7 | This study demonstrated that the determinants for a comprehensive cervical spine injury severity assessment model should include neural impairment, pre- and postinjury available spinal canal sagittal diameter, and pathomorphology of the injury, each of which may individually predict the probability of surgical intervention. Patho-morphology evaluation is best separated into its two components, actual osseoligamentous failure and displacement. For ease of injury severity recognition, statistical analysis, and outcome comparisons, a model based on separate but similarly scaled numeric scoring for each determinant is a useful tool. | N/A |
| A detailed evaluation of the pathomorphology and spinal canal sagittal diameter measurements were performed on the cervical spine CT scans and/or MRI images | |||||||
| Radclif et al. [23] 2012 | Prospective | Prospective cohort | To proof if the load-sharing score (LSS) predicts ligamentous or neurological injury. | 44 | T10-L2 | The most common neurological injury pattern was ASIA grade C (43%), followed by ASIA grade E (30%). Twenty-five of the patients (57%) were treated with operative stabilization. The mean ASIA motor score was 83.0. | N/A |
| The LSS does not uniformly correlate with the PLC injury, neurological status, or empirical clinical decision making | |||||||
| Krishna et al. [6] 2013 | Review | Comprehensive review | AIS rational and limitations | N/A | N/A | ASIA impairment grades result in assessments of variable resolution and groupings of heterogeneous populations with different individual recovery potentials. This results in large variations from the mean on outcome measures and a need to enroll a large number of patients in clinical trials | N/A |
| Vasquez et al. [22] 2013 | Retrospective | Retrospective cohort | To confirm a tendency for light touch (LT) to score higher than pin prick (PP) in SCI subjects and discuss possible reasons for such disparity. The clinical neurological evaluation included level of injury and the ISNCSCI scores in total and at each spinal segmental level for LT, PP, upper extremity motor and lower extremity motor function | 99 | Below C2 to S4/5 | The discrepancies between LT and PP could relate to the greater complexity of the PP test or a difference in the extent of injury to the posterior columns (LT) and spinothalamic (PP) tracts. Further interpretation would benefit from additional electrophysiological sensory tests | N/A |
| Marino et al. [21] 2016 | Prospective | Prospective cohort | To determine whether pressure sensation at the S3 dermatome (a new test) could be used in place of deep anal pressure (DAP) to determine completeness of injury as part of the ISNCSCI Design. | 141 | N/A | S3 pressure sensation is reliable and has substantial agreement with DAP in persons with SCI at least 1-month postinjury. We suggest S3 pressure as an alternative test of sensory sacral sparing for supraconus SCI, at least in cases where DAP cannot be tested. Further research is needed to determine whether S3 pressure could replace DAP for classification of SCI. Archives | 6–12 Months |
| Walden et al. [24] 2016 | Retrospective | Retrospective cohort | To describe the development and validation of a computerized application of the ISNCSCI | 2,520 | Any | The RHI-ISNCSCI Algorithm provides a standardized method to accurately derive the level and severity of SCI from the raw data of the ISNCSCI examination. The web interface assists in maximizing usability while minimizing the impact of human error in classifying SCI. | N/A |
| Kaul et al. [20] 2017 | Prospective | Prospective study | To determine whether the recently introduced AOSpine Classification and Injury Severity System has better interrater and intrarater reliability than the already existing TLICS for thoracolumbar spine injuries and their clinical Correlation with ISNCSCI | 550 | Any | Recently proposed AOSpine classification has better reliability for identifying fracture morphology than the existing TLICS Near perfect interrater and intrarater agreement was seen concerning neurological status for both the classification systems | N/A |
| Layer et al. [1] 2017 | Prospective | Prospective cohort | To evaluate the clinical effectiveness of the Neuro-Spinal Scaffold, including improvement in AIS grade, sensory scores, motor scores, bladder and bowel function, Spinal Cord Independence Measure III, and Quality of Life Index (QLI-SCI III), as well as possibly decreased pain. | 9 | T3-T11 | Following durotomy, 2 forms of cord damage were observed. In contusion-type injuries, the cord surface is intact. In compound-type injuries, the pia is breached and there is visible but incomplete cord parenchymal separation (Fig. 4). Both injuries were successfully implanted with the Neuro-Spinal Scaffold and AIS improvements were seen in both pathological types. | Up to 12 months |
| Yugué et al. [18] 2018 | Prospective | Prospective cohort | The sensitivity and specificity of the ‘knee-up test’ were evaluated in patients with acute CSCI classified as AIS C or D | 200 | Above C8 | The sensitivity, specificity, positive predictive and negative predictive values of this test for all patients were 99.1, 76.8, 82.5, and 98.7, respectively. | N/A |
| The knee-up test may allow easy and highly accurate estimation, without the need for special skills, of AIS classification for patients with incomplete CSCI. |
| Study | Data collection | Level of evidence | Sesgos | Clinical | Rx | Parameters | Results | Conclusion |
|---|---|---|---|---|---|---|---|---|
| Fehlings et al. [36] 2017 | Review | I: Consensus on systematic review No PRISMA mentioned GRADE evaluations | Indirect ness No gold standard | Frankel | MRI | *Evidence Level. 1 prospective study by Papadopoulos et al (2002) that evaluated the effect of pre-treatment MRI on neurological outcomes | *Emergency MRI provided an essential tool for the accurate diagnosis of spinal cord compression and directly influenced our initial clinical management in the majority of protocol patients.” | *We suggest that MRI be performed in adult patients with acute spinal cord injury prior to surgical intervention, when feasible, to facilitate improved clinical decision making. |
| Quality of Evidence: Very Low Strength of Recommendation: Weak | ||||||||
| We suggest that MRI should be performed in adult patients in the acute period following SCI, before or after surgical intervention, to improve prediction of neurologic outcome. | ||||||||
| Quality of Evidence: Low Strength of Recommendation: Weak Introduction | ||||||||
| Kleiser et al. [34] 2010 | Prospective | Prospective cohort | Multicentric | N/A | MRI | T2-weighted turbo spine echo (TSE) sequence, sagittal orientation, T1-weighted TSE sequence, sagittal orientation, T1-weighted TSE sequence, sagittal orientation, T2-weighted GE sequence | The SCI was clearly visible as a hyperintense area in the T2-weighted images on day 4. On day 7, the spinal cord lesion was visible on 2 up to 4 sagittal sections. The lesions of the spinal cord injury remained constant for the subsequent observation times ( |
• Gadolinium-enhancement starts approximately 4 days after the traumatic spinal cord lesion and is maximal between day 7 and 28. |
| • Gadolinium accumulates in the spinal cord lesion 5 minutes after intravenous injection, reaching a stable enhancement after 10 minutes for up to 30 minutes. | ||||||||
| • Detection of the disrupted blood-spinal cord barrier requires MR imaging at least 10 minutes after intravenous gadolinium injection | ||||||||
| Ghasemi et al. [32] 2015 | Prospective | Prospective cohort | Small sample | ASIA A-D | MRI contrst Dutarm (gadoterate meglumine) | MRI finding: Level of spine involvement, type of cord injury (edema-hemorrhagia combined),9,10 and percentage of cord injury (>50%–50% to 75%–<75%) | A classification with 3 patterns of SCIs. Type I, decreased signal intensity consistent with acute intraspinal hemorrhage. Type II: bright signal intensity consistent with acute cord edema. Type III: mixed signal of hypointensity centrally and hyperintensity peripherally consistent with contusion. | We recommend the MRI with contrast only used in cases of suspected severe soft tissue injury, which have been ignored by detection MRI without contrast. |
| Cheran et al. [33] 2011 | Prospective | Prospective cohort | Nonrandomized | ASIA hystoric control | MRI | MR imaging was performed 1 hr–5 days after injury. Imaging was performed within 6 hour of injury | The 2-way interaction between ASIA and λ was able to predict with an overall classification accuracy of 86.4% (p<0.0026) | The study demonstrated that regional and injury site MR DTI parameter measurements reflect the severity and are reliable makers of spinal cord injury. Among the DTI parameters, λ and FA values appear to be the most sensitive measurements at the injury site. |
| DWI | ||||||||
| DTI | ||||||||
| Gupta et al. [43] 2014 | Prospective | Prospective cohort | Do not describe moment of MRI Not blinded | ASIA | MRI | Based on the MRI findings, patients were divided into six patterns Pattern zero: Normal findings Pattern I: Hemorrhage | The best predictors for baseline ASIA score were MCC, cord oedema and cord hemorrhage. For the final ASIA score, the best predictors were baseline ASIA score and cord hemorrhage | MRI is excellent imaging modality for detecting and assessing severity of spinal trauma. In our study, presence of cord hemorrhage, MCC and cord oedema were best predictors of baseline neurological status at presentation, whereas baseline ASIA score and cord hemorrhage were best predictors of final neurological outcome. |
| Pattern II: Oedema | ||||||||
| Pattern III: Contusion | Presence of cord oedema, cord hemorrhage and MCC best correlate with neurological deficit at presentation. While poor baseline ASIA score and cord hemorrhage confers a poor long-term outcome. On the other hand, absence of cord hemorrhage usually indicates some potential for neurological recovery. | |||||||
| Pattern IV: Compression | ||||||||
| Pattern V: Transection pattern | ||||||||
| D’Souza et al. [42] 2017 | Prospective | IV: Case and Contros | Done within 7 days of injury | Frankel | MRI DTI | Scoring of extent of clinical severity was done based on the Frankel grading system. MRI was performed on a 3T system within 7 days of sustaining trauma. | Mean FA value at the level of injury (was less than the Mean FA value of cervical spine. | DTI was superior to conventional. |
| MRI scans in depicting changes in spinal cord integrity after traumatic injury. Qualitative tractography enabled the delineation of changes in the white matter tract of spinal cord, both obvious as well as subtle. Quantitative indices in the form of FA and MD were a more useful parameter for detection of spinal cord injury. FA value was significantly decreased while MD value was significantly increased at the level of injury in cases as compared to controls. FA showed significant correlation with the Frankel score, a clinical measure of the motor and sensory status. Long-term studies would be needed to see if DTI could be used as a reliable prognostic marker of neurological outcome in spinal cord injury | ||||||||
| Spearman’s correlation(r=0.86) was found between FA values at the level of injury and clinical grading | ||||||||
| Talekar et al. [81] 2016 | Review | Review | Comprehensive review | CT and MRI | MRI DTI | Non systematic | Conventional MR techniques do not appear to differentiate edema from axonal injury. They | While MRI and DTI will likely never provide the same high level of granularity as that of a good quality neurologic examination, it does offer three distinct advantages over the INSCSCI assessment: (1) speed, (2) objectivity and (3) direct visualization of the end organ (the spinal cord). |
| Huang and Ou [41] 2014 | Prospective | Prospective Cohort | N/A | ASIA Respiratory failure | MRI | Surgery was indicated if the neurological deficits were compatible with the abnormal findings of the MRI scans | There was a statistically significant intergroup difference in the imaging level of CSCI (p<0.001) | The imaging level of injury at C3 is more frequently associated with respiratory failure than injury to the lower cervical levels. Additionally, the presence of spinal cord edema is a predictor that contributes to respiratory failure. In order to prevent secondary spinal cord injury from prolonged hypoxia and to facilitate pulmonary care, definitive airways with assisted ventilation should be established early in the high-risk patients. |
| Chandra et al. [82] 2012 | Review | Comprehensive review | Nonsytemized | ASIA | MRI | Review | Review | MRI is an essential tool to define the site and nature of cord injury in addition to associated disc, ligamentous and vertebral injuries. The magnetic resonance (MR) appearances of cord hematoma, severity of maximal cord compression and length of cord oedema are all significantly associated with worse long-term functional independence scores and are important considerations in planning acute management. Neurological deterioration in the subacute period constitutes a medical emergency and MRI is pivotal in determing the underlying cause. |
| Freund et al. [40] 2013 | Prospective | Prospective | None | ISNCSCI SCIM | MRI | We assessed patients clinically and by MRI at baseline, 2 months, 6 months, and 12 months, and controls by MRI at the same timepoints | Improvements in SCIM scores at 12 months were associated with a reduced loss in cross-sectional spinal cord) and reduced white matter volume of the corticospinal tracts at the level of the right internal capsule Improvements in ISNCSCI motor scores were associated with less white matter volume change encompassing the corticospinal tract at the level of the right internal capsule | Extensive upstream atrophic and microstructural changes of corticospinal axons and sensorimotor cortical areas occur in the first months after spinal cord injury, with faster degenerative changes relating to poorer recovery. Structural volumetric and microstructural MRI protocols remote from the site of spinal cord injury could serve as neuroimaging biomarkers in acute spinal cord injury. |
| Mabray et al. [39] 2016 | Prospective | Prospetive cohort | AIS TLICS | MRI At 14 hr | BASIC grading Grade 1: normal spinal cord signal; Grade 2: hyperintense intramedullary signal with longitudinal extent confined to a single vertebral level; Grade 3: >1 vertebral level edema; Grade 4: represented mixed hemorrhage and edema. | In a multiple variable model, BASIC was the only statistically significant predictor of AIS at discharge. | This study validates the use of BASIC and other MRI measures of acute SCI specifically in the setting of thoracic SCI. PC analysis identified two distinct patterns of variance: PC1, which was highly related to AIS at discharge, and PC2, which was highly related to surgical decompression. The highest individual correlation with AIS at discharge was seen with the BASIC system, although all metrics of spinal cord signal abnormality had a high degree of individual negative correlation with AIS at discharge. The relationship of MCC and MSCC with AIS at discharge was found to be more complex, likely reflecting the use of these metrics along with TLICS in surgical decision making. A multiple variable regression model identified BASIC as the only statistically significant predictor of AIS at discharge, signifying that BASIC best captured the variance in AIS within our study population | |
| Martin et al. [31] 2015 | Review | Systematic review | Low | MRI | Evidence Low 1 Very Low 1, Insufficient 2 | Diagnostic MRI utility: Biomarker utility | Moderate evidence indicates that the quantitative DTI metric FA successfully correlates with impairment in a number of neurological disorders | |
| Prisma 104 | 1 Moderate | DTI has produced the most substantial results to date, but acquisition methods, data processing, and interpretation require further refinement, followed by standardization and cross-vendor validation, before this technology is ready for widespread clinical adoption. | ||||||
| Articles | 1 Insufficient | |||||||
| 1 Low | ||||||||
| Jeong et al. [38] 2018 | Retrospective | Retrospective cohort | N/A | ASIA | MRI | Authors analyzed the factors believed to increase the risk of requiring a tracheostomy, including the severity of SCI, the level of injury as determined by radiological assessment, three quantitative MR imaging parameters, and eleven qualitative MR imaging parameters | Five factors were detected on multivariate analysis complete SCI, the radiological level of C5 and above, canal compromise, lesion length, and osteophyte formation 40–50 mm | The American Spinal Injury Association grade A, a radiological injury level of C5 and above, an MCC ≥50%, a lesion length ≥20 mm, and osteophyte formation at the level of injury were considered to be predictive values for requiring tracheostomy intervention in patients with cervical SCI. |
| Seif et al. [37] 2018 | Prospective | IV case and control | Low sample Nonrandomized | ISNCSCI | MRI | MRI protocol sensitive to myelin and iron. Patients were examined clinically at baseline, 2, 6, 12, and 24-month post-SCI. | Importantly, early volume and microstructural changes of the cord and cerebellum predicted functional recovery following injury | Neurodegenerative changes rostral to the level of lesion occur early in SCI, with varying temporal and spatial dynamics. Early qMRI markers of spinal cord and cerebellum are predictive of functional recovery. These neuroimaging biomarkers may supplement clinical assessments and provide insights into the potential of therapeutic interventions to enhance neural plasticity. |
| Talbott et al. [35] 2015 | Retrospective | Retrospective cohort | Nonrandomized | ASIA AIS | Five distinct patterns of intramedullary spinal cord T2 signal abnormality were defined in the axial plane at the injury epicenter. These patterns were assigned ordinal values ranging from 0 to 4, referred to as the BASIC scores, which encompassed the spectrum of SCI severity. | The BASIC score strongly correlated with neurological symptoms at the time of both hospital admission and discharge. It also distinguished patients initially presenting with complete injury who improved by at least one AIS grade by the time of discharge from those whose injury did not improve. The authors’ proposed score was rapid to apply. | The authors describe a novel 5-point ordinal MRI score for classifying acute SCIs on the basis of axial T2-weighted imaging. The proposed BASIC score stratifies the SCIs according to the extent of transverse T2 signal abnormality during the acute phase of the injury. The new score improves on current MRI-based prognostic descriptions for SCI by reflecting functionally and anatomically significant patterns of intramedullary T2 signal abnormality in the axial plane. |
| Study | Data collection | Early decompression | Late decompression | Conclusions |
|---|---|---|---|---|
| Lee et al. [46] 2018 | Retrospective | < 8 hr | > 8 < 24 hr | Early decompression shows better neurological outcome |
| From C1 to L2 Complete and incomplete SCI | From C1 to L2 | Better improvement in patients with incomplete SCI | ||
| Complete and incomplete SCI | ||||
| Grassner et al. [47] 2016 | Retrospective analysis on prospective collected data | < 8 hr | > 8 hr | Early surgical intervention after cervical traumatic SCI may lead to a better functional outcome of affected individuals (SCIM and AIS scores) |
| Cervical complete and incomplete SCI | Cervical complete and incomplete SCI | |||
| Liu et al. [48] 2016 | Metanalysis | < 24 hr | > 24 hr | Urgent surgery within 24 hours was associated with higher total motor scores, better neurologic improvement, shorter hospital stay and fewer complications compared with those of late surgery |
| Ter Wengel et al. [53] 2019 | Metanalysis | < 24 hr | > 24 hr | Similar neurological recovery was observed after early and late surgery in this meta-analysis of thoracic and thoracolumbar tSCI |
| Complete and incomplete thoracic SCI | Complete and incomplete thoracic SCI | |||
| Ter Wengel et al. [50] 2019 | Metanalysis LoE II | < 72 hr | < 72 hr | Early decompression in complete SCI shows a better neurological outcome than late decompression Early decompression in incomplete SCI shows a similar neurological outcome than incomplete SCI Decompression within 24 hr in complete SCI shows better results |
| Complete and incomplete cervical SCI | Complete and incomplete cervical SCI |
| Study | Data collection | Study type | Neurological outcome measures | No. of patients | Level of injury | Outcomes | MAP goal (mmHg) | MAP goal duration | Length of follow-up |
|---|---|---|---|---|---|---|---|---|---|
| Saadeh et al. [56] 2017 | Prospective and retrospective data | Systematic Review 11 cohort studies | AIS grade, ASIA motor score Modified Frankel score, Yale Scale score | Variable* | C, T, and L spine | 127 Patients, report stable or improved neurological function following management to elevated MAP target during the early phase of care [4] | Variable | ||
| Sabit et al. [57] 2018 | Prospective and retrospective data | Systematic Review of 9 cohort studies | AIS grade, ASIA motor score Modified Frankel score, Yale Scale score | Variable* | C, T, and L spine | Four of nine studies showed neurological improvement associated with higher MAP targets. | Variable | ||
| Two studies found episodes of hypotension related to poor recovery. [5] | |||||||||
| Squair et al. [83] 2019 | Prospective | Case series | ISNCSCI, AIS grade | 92 | C, T and L Spine | Adherence to SCPP targets was the best indicator of improved neurologic recovery (60–65 mmHg) [6] | 6 Months | ||
| Dakson et al. [84] 2017 | Retrospective | Comparative | AIS grade, ASIA motor score | 94* | C, T, and L spine | > 85 | 5 Days | After neurorehabilitation | |
| Kepler et al. [85] 2015 | Retrospective | Case Series | ASIA motor score | 92 | C, T, and L spine | > 85 | ≥ 5 Days | Until hospital day 5 | |
| Martin et al. [31] 2015 | Retrospective | Case Series | AIS motor score | 105 | C & T spine | NS | NS | Until discharge | |
| Hawryluk et al. [61] 2015 | Retrospective | Case Series | AIS grade | 74 | C, T, and L | > 85 | 5 Days | Until discharge | |
| Inoue et al. [86] 2014 | Retrospective | Case Series | AIS grade | 131 | C, T, and L spine | > 82 | 7 Days | Until discharge | |
| Vale et al. [55] 1997 | Prospective | Case Series | AIS grade, ASIA motor score | 77 | C and T spine | > 85 | 7 Days | 12 Months | |
| Levi et al. [59] 1993 | Prospective | Case Series | Frankel grade | 50 | C Spine only | > 90 | 7 Days | 6 Weeks | |
| Wolf et al. [87] 1991 | Retrospective | Case Series | Modified Frankel score, Yale Scale | 52 | C spine only score | > 85 | 5 Days | 12 Months |
Rx, radiology; PRISMA, Preferred Reporting Items for Systematic Reviews and Meta-Analyses; ASIA, American Spinal Injury Association Impairment; CT, computed tomography; CSF, cerebrospinal fluid; AUC, area under the curve; AIS, ASIA Impairment Scale; SCI, spinal cord injury; ISNCSCI, International Standards for Neurological Classification of Spinal Cord Injury.
ASIA, American Spinal Injury Association Impairment; LEMS, Lower Extremity Motor Score; SCIM, Spinal Cord Independence Measure; N/A, not available; SCI, spinal cord injury; AIS, ASIA Impairment Scale; CT, computed tomography; MRI, magnetic resonance imaging; UEMS, Motor Score combines the Upper Extremity Motor Score; TLICS, Thoracolumbar Injury Classification and Severity Score; JTHFT, Jebsen-Taylor Hand Function Test, 9HPT, 9 Hole Peg Test; SLIC, subaxial cervical injury classification system; CSCI, cervical spinal cord injury; RHI-ISNCSCI, Rick Hansen Institute-International Standards for Neurological Classification of Spinal Cord Injury.
MRI, magnetic resonance imaging; SCI, spinal cord injury; ASIA, American Spinal Injury Association Impairment; DWI, Diffusion-weighted imaging; DTI, diffusion tensor imaging; CSCI, cervical spinal cord injury; MCC, maximum canal compromise; MSCC, maximum spinal cord compression; TLICS, Thoracolumbar Injury Classification and Severity Score; FA, fractional anisotropy; ISNCSCI, International Standards for Neurological Classification of Spinal Cord Injury; BASIC, Brain and Spinal Injury Center; qMRI, quantitative MRI.
SCI, spinal cord injury; SCIM, Spinal Cord Independence Measure; AIS, American Spinal Injury Association Impairment Scale; tSCI, traumatic spinal cord injury.
MAP, mean arterial pressure; ASIA, American Spinal Injury Association; AIS, ASIA Impairment Scale. ISNCSCI, International Standards for Neurological Classification of Spinal Cord Injury; NS, not specified; C, T, and L, cervical, thoracic, and lumbar; SCPP, spinal cord perfusion pressure.
