H. van de Meent

Biomarkers in spinal cord injury

Study design:Literature review.Objectives:In traumatic spinal cord injury (SCI), much effort has been put into the evaluation of SCI severity and the prediction of recovery potential. An accurate prediction of the initial damage of the spinal cord that differentiates between the severities of SCI however, may help physicians in choosing a particular neuroprotective treatment in the acute phase. Neurochemical biomarkers may possibly fulfil these requirements. The aim of this review was to describe (1) the current status of neurochemical biomarkers in SCI; (2) their potential diagnostic role in SCI.Methods:MEDLINE was searched from 1966 to 2008 to identify publications concerning biomarkers in traumatic SCI.Results:The biomarkers S-100β, neuron-specific enolase, neurofilament light chain, and Glial fibrillary acidic protein are significantly increased in cases of (experimental) spinal cord injury. Furthermore, increased serum concentrations of S-100β have been correlated with an unfavourable functional outcome. Although biomarkers in SCI show promising results, considerations and shortcomings, such as polytrauma, haemolysis, extracerebral sources, and poor resuscitation, must be studied in greater detail before biomarkers can be utilised in the clinical care of SCI.Conclusions:Quantitative standards for determining the extent of SCI during the acute phase must be developed and validated. Even though increased concentrations of neurochemical biomarkers have been identified in patients with SCI, these do not yet provide a sensitive prognostic tool. Considering the limited availability of sensitive prognostic tools, neurochemical biomarkers of SCI should be evaluated and validated in future clinical trials.

ASIA impairment scale conversion in traumatic SCI: is it related with the ability to walk? A descriptive comparison with functional ambulation outcome measures in 273 patients.

Study design:Prospective multicenter longitudinal cohort study.Objectives:To determine the relationship between improvements of the American Spinal Injury Association/International Spinal Cord Society (ASIA/ISCoS) neurological standard scale (AIS) outcome measure and improvements of functional ambulatory outcome measures in patients with traumatic spinal cord injury (SCI).Setting:European multicenter study of human SCI (EM-SCI).Methods:In 273 eligible patients with traumatic SCI, acute (0–15 days) and chronic phase (6 or 12 months) AIS grades, timed up and go (TUG) test and 10-m walk test (10MWT) outcome measurements were analyzed. Subanalysis of those patients who did have AIS conversion was performed to assess its relation with functional ambulatory outcomes.Results:Studied population consisted of 161 acute phase AIS grade A patients; 37 grade B; 43 grade C and 32 acute phase AIS grade D patients. Forty-two patients (26%) converted from AIS grade A, 27 (73%) from grade B, 32 (75%) from grade C and five patients (16%) from AIS grade D. The frequencies of AIS conversions and functional ambulation recovery outcomes were significantly different (P<0.001) in patients with motor complete SCI. The ratio of patients with both recovery of ambulatory function and AIS conversion (n=101) differed significantly (P<0.001) between the acute phase AIS grade scores; AIS grade A (6/40 patients, 15%), B (9/27 patients, 33%), C (23/29 patients, 79%) and D (5/5 patients 100%).Conclusions:The AIS conversion outcome measure is poorly related to the ability to walk in traumatic SCI patients. Therefore, the authors recommend the use of functional ambulation recovery outcome measures in prognosticating the recovery of walking capacity and performance of patients with SCI.

Is determination between complete and incomplete traumatic spinal cord injury clinically relevant? Validation of the ASIA sacral sparing criteria in a prospective cohort of 432 patients.

Study design:Prospective multicenter longitudinal cohort study.Objective:To validate the prognostic value of the acute phase sacral sparing measurements with regard to chronic phase-independent ambulation in patients with traumatic spinal cord injury (SCI).Setting:European Multicenter Study of Human Spinal Cord Injury (EM-SCI).Methods:In 432 patients, acute phase (0–15 days) American Spinal Injury Association (ASIA)/International Spinal Cord Society neurological standard scale (AIS) grades, ASIA sacral sparing measurements, which are S4–5 light touch (LT), S4–5 pin prick (PP), anal sensation and voluntary anal contraction; and chronic phase (6 or 12 months) indoor mobility Spinal Cord Independence Measure (SCIM) measurements were analyzed. Calculations of positive and negative predictive values (PPV/NPV) as well as univariate and multivariate logistic regressions were performed in all four sacral sparing criteria. The area under the receiver-operating characteristic curve (AUC) ratios of all regression equations was calculated.Results:To achieve independent ambulation 1-year post injury, a normal S4–5 PP score showed the best PPV (96.5%, P<0.001, 95% confidence interval (95% CI): 87.9–99.6). Best NPV was reported in the S4–5 LT score (91.7%, P<0.001, 95% CI: 81.6–97.2). The use of the combination of only voluntary anal contraction and the S4–5 LT and PP sensory scores (AUC: 0.906, P<0.001, 95% CI: 0.871–0.941) showed significantly better (P<0.001, 95% CI: 0.038–0.128) discriminating results in prognosticating 1-year independent ambulation than with the use of currently used distinction between complete and incomplete SCI (AUC: 0.823, P<0.001, 95% CI: 0.781–0.864).Conclusions:Out of the four sacral sparing criteria, the acute phase anal sensory score measurements do not contribute significantly to the prognosis of independent ambulation. The combination of the acute phase voluntary anal contraction and the S4–5 LT and PP scores, predicts significantly better chronic phase-independent ambulation outcomes than the currently used distinction between complete and incomplete SCI.Sponsorship:This study was granted by ‘Acute Zorgregio Oost’ and the ‘Internationale Stiftung für Forschung in Paraplegie (IFP)’.

Structural biomarkers in the cerebrospinal fluid within 24 h after a traumatic spinal cord injury: a descriptive analysis of 16 subjects

Study design:Prospective cohort study.Objectives:To characterize the cerebrospinal fluid (CSF) concentrations of glial fibrillary acidic protein, neuron specific enolase (NSE), S-100β, tau and neurofilament heavy chain (NFH) within 24 h of an acute traumatic spinal cord injury (SCI), and to correlate these concentrations with the baseline severity of neurologic impairment as graded by the American Spinal Injury Association impairment scale (AIS).Methods:A lumbar puncture was performed to obtain CSF from 16 acute traumatic SCI patients within 24 h post injury. Neurological examinations were performed within 24 h of injury and again at 6 or 12 months post injury. The correlations between the CSF concentrations and initial AIS were calculated by using Pearson correlation coefficients. In addition, an independent Student’s t-test was used to test for differences in CSF concentrations between patients of different AIS grades.Results:The CSF NSE concentrations were significantly correlated with the baseline neurologic impairment being either ‘motor complete’ (AIS A, B) or ‘motor incomplete’ (AIS C, D) (r=0.520, P<0.05). The mean S-100β concentration in motor complete patients was significantly higher compared with motor incomplete patients; 377.2 μg l−1 (s.d.±523 μg l−1) vs 57.1 μg l−1 (s.d.±56 μg l−1) (P<0.05), respectively. Lastly, the mean NFH concentration in motor complete patients was significantly higher compared with motor incomplete patient, 11 813 ng l−1 (s.d.±16 195 ng l−1) vs 1446.8 ng l−1 (s.d.±1533 ng l−1), (P<0.05), respectively.Conclusion:In this study we identified differences in the structural CSF biomarkers NSE, S-100β and NFH between motor complete and motor incomplete SCI patients. Our data showed no clear differences in any of the protein concentrations between the different AIS grades.

Diagnostic criteria of traumatic central cord syndrome. Part 1: a systematic review of clinical descriptors and scores.

Study design:Systematic review.Background:The applied definition of traumatic central cord syndrome (TCCS) lacks specific quantified diagnostic criteria.Objective:To review currently applied TCCS diagnostic criteria and quantitative data regarding the ‘disproportionate weakness’ between the upper and lower extremities described in original studies reporting on TCCS subjects.Methods:A MEDLINE (1966 to 2008) literature search was conducted. The descriptors applied to define TCCS were extracted from all included articles. We included original studies that reported on the differences in motor score (based on the Medical Research Council scale) between the total upper extremity motor score (UEMS) and the total lower extremity motor score (LEMS), in a minimum of five TCCS patients at the time of hospital admission. The mean difference between the total UEMS and the total LEMS of the patients included in each study was calculated. Case reports were excluded.Results:None of the identified studies on TCCS patients reported inclusion and/or exclusion criteria using a quantified difference between the UEMS and LEMS. Out of 30 retrieved studies, we identified seven different clinical descriptors that have been applied as TCCS diagnostic criteria. Nine studies reporting on a total of 312 TCCS patients were eligible for analysis. The mean total UEMS was 10.5 motor points lower than the mean total LEMS.Conclusions:There is no consensus on the diagnostic criteria for TCCS. Nevertheless, this review revealed an average of 10 motor points between the UEMS and LEMS as a possible TCCS diagnostic criterion. However, further discussion by an expert panel will be required to establish definitive diagnostic criteria.

How does knowledge about spinal cord injury-related complications develop in subjects with spinal cord injury? A descriptive analysis in 214 patients.

Study design:Monocentric cohort study.Objective:To investigate the acquisition of knowledge about spinal cord injury (SCI)-related complications in SCI patients.Setting:Level 1 trauma center.Methods:All patients with a traumatic or non-traumatic SCI were included in the study. Data were collected at admission, post-admission at 1 and 3 months and post-discharge at 6, 18 and 30 months. The discharge of all patients was between 3 and 6 months post-admission. Knowledge about pressure ulcers and bladder management was tested using the ‘Knowledge’ score. This score has a minimum and maximum of 0 and 20 points. To detect differences across the multiple time intervals, the Friedman test was used. Differences in the number of patients with poor (0–8), average (9–12) and good knowledge (13–20) between the different age classifications (age at injury) were calculated using a χ 2-test.Results:A total of 214 patients were included. At discharge subjects had increased their knowledge score to 11.2 compared with 5.4 on admission (P<0.001). After 30 months, however, the mean score decreased to 10.8 points. At the time of discharge, the number of patients who achieved poor, average or good knowledge were 48 (22.4%), 65 (30.4%) and 101 (47.2%), respectively. Subjects of ∼50 years old and tetraplegics had better (P<0.001) knowledge compared with subjects of ∼50 years old and paraplegics, respectively.Conclusion:In this study, less than 50% of SCI patients had good knowledge about bladder management and pressure ulcers after being discharged.

Is the outcome in acute spinal cord ischaemia different from that in traumatic spinal cord injury? A cross-sectional analysis of the neurological and functional outcome in a cohort of 93 paraplegics

Study design:Retrospective cohort study.Objectives:To compare the neurological outcome between paraplegic patients with acute spinal cord ischaemia syndrome (ASCIS) or traumatic spinal cord injury (tSCI) and to investigate the influence of SCI aetiology on the total Spinal Cord Independence Measure (SCIM)-II score.Setting:Level 1 trauma centre.Methods:Initial (0–40 days) and chronic-phase (6–12 months) American Spinal Injury Association (ASIA) sensory scores, lower extremity motor score (LEMS) and chronic-phase total SCIM-II scores were analysed. Differences between ASCIS and tSCI patients were calculated using Students t-tests and Wilcoxon signed-rank tests. To assess which variables give rise to the prediction of total SCIM-II score, a multiple linear regression analysis was used. These predictor variables included complete (ASIA impairment scale A) or incomplete SCI (AIS B, C, and D), aetiology, age and gender.Results:Out of 93 included patients, 20 ASCIS and 73 tSCI patients were identified. In the complete SCI group, the initial pinprick scores were higher (P<0.05) in ASCIS patients compared with tSCI patients, 37.9 (95% Confidence Interval (CI), 23.3–52.5) and 27.3 (95% CI, 24.1–30.4), respectively. No other relevant differences in neurological outcome were identified between ASCIS and tSCI patients; however, the total SCIM-II scores were higher (P<0.05) in tSCI patients after 12 months. Using the linear regression analysis, we were able to predict 31.4% of the variability. The aetiology was not significant in this model.Conclusion:The neurological outcome was independent of the diagnosis ASCIS or tSCI. Furthermore, the diagnosis ASCIS or tSCI was not a significant predictor for total SCIM II scores after 12 months.Sponsorship:This study was granted by the ’Internationale Stiftung für Forschung in Paraplegie‘ (IFP), Zürich, Switzerland.

Comparison of bone-anchored prostheses and socket prostheses for patients with a lower extremity amputation: a systematic review

Abstract Purpose: This study aimed to provide an overview of a) the used measurement instruments in studies evaluating effects on quality of life (QoL), function, activity and participation level in patients with a lower extremity amputation using bone-anchored prostheses compared to socket prostheses and b) the effects themselves. Method: A systematic literature search was conducted in MEDLINE, Cochrane, EMBASE, CINAHL and Web of Science. Included studies compared QoL, function, activity and/or participation level in patients with bone-anchored or socket prostheses. A best-evidence synthesis was performed. Results: Out of 226 studies, five cohort and two cross-sectional studies were eligible for inclusion, all had methodological shortcomings. These studies used 10 different measurement instruments and two separate questions to assess outcome. Bone-anchored prostheses were associated with better condition-specific QoL and better outcomes on several of the physical QoL subscales, outcomes on the physical bodily pain subscale were inconclusive. Outcomes on function and activity level increased, no change was found at participation level. The level of evidence was limited. Conclusions: There is a need for a standard set of instruments. There was limited evidence that bone-anchored prostheses resulted in higher QoL, function and activity levels than socket prostheses, in patients with socket-related problems. Implications for Rehabilitation Use of bone-anchored prostheses in combination with intensive outpatient rehabilitation may improve QoL, function and activity level compared with socket prosthesis use in patients with a transfemoral amputation and socket-related problems. All clinicians and researchers involved with bone-anchored prostheses should use and publish data on QoL, function, activity and participation level. There needs to be an agreement on a standard set of instruments so that interventions for patients with a lower extremity amputation are assessed consistently.

International standards for neurological classification of spinal cord injury: classification skills of clinicians versus computational algorithms.

Study design:This is a retrospective analysis.Objectives:The objective of this study was to describe and quantify the discrepancy in the classification of the International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI) by clinicians versus a validated computational algorithm.Settings:European Multicenter Study on Human Spinal Cord Injury (EMSCI).Methods:Fully documented ISNCSCI data sets from EMSCI’s first years (2003–2005) classified by clinicians (mostly spinal cord medicine residents, who received in-house ISNCSCI training by senior SCI physicians) were computationally reclassified. Any differences in the scoring of sensory and motor levels, American Spinal Injury Association Impairment Scale (AIS) or the zone of partial preservation (ZPP) were quantified.Results:Four hundred and twenty ISNCSCI data sets were evaluated. The lowest agreement was found in motor levels (right: 62.1%, P=0.002; left: 61.8%, P=0.003), followed by motor ZPP (right: 81.6%, P=0.74; left 80.0%, P=0.27) and then AIS (83.4%, P=0.001). Sensory levels and sensory ZPP showed the best concordance (right sensory level: 90.8%, P=0.66; left sensory level: 90.0%, P=0.30; right sensory ZPP: 91.0%, P=0.18; left sensory ZPP: 92.2%, P=0.03). AIS B was most often misinterpreted as AIS C and vice versa (AIS B as C: 29.4% and AIS C as B: 38.6%).Conclusion:Most difficult classification tasks were the correct determination of motor levels and the differentiation between AIS B and AIS C/D. These issues should be addressed in upcoming ISNCSCI revisions. Training is strongly recommended to improve classification skills for clinical practice, as well as for clinical investigators conducting spinal cord studies.Sponsorship:This study is partially funded by the International Foundation for Research in Paraplegia, Zurich, Switzerland.

Relevance of the diagnosis traumatic cervical Brown-Sequard-plus syndrome: an analysis based on the neurological and functional recovery in a prospective cohort of 148 patients.

Study design:Prospective multi-center cohort study.Objectives:To compare the neurological and functional recovery between tetraplegic Brown-Séquard-plus syndrome (BSPS) and incomplete tetraplegia (non-BSPS).Setting:European Multicenter Study of Human Spinal Cord Injury (EM-SCI).Methods:BSPS was defined as a traumatic incomplete spinal cord injury (SCI) with ipsilateral weakness and contralateral loss of pinprick sensation at neurologic levels C2–T1. Acute (0–15 days) and chronic phase (6 or 12 months) were assessed for the American Spinal Injury Association (ASIA) sensory scores, upper extremity motor scores and lower extremity motor scores. Furthermore, chronic phase scores of all Spinal Cord Independence Measure (SCIM) II items were analyzed. Differences in neurological and functional outcome between BSPS patients and non-BSPS patients were calculated using Students t-tests and Wilcoxon signed rank tests.Results:Out of 148 tetraplegic patients, 30 were diagnosed with BSPS. Patients with an ASIA impairment scale (AIS) B were significantly (P<0.001) more identified in non-BSPS patients (25%) compared with BSPS patients (3%), respectively. After 12 months, the median scores for sphincter management of the bladder for both BSPS and non-BSPS patients were 15. Both 25 and 75% quartile median scores were 15 for BSPS patients and 12 and 15 for non-BSPS patients (P<0.02). Except for the difference in bladder function, no significant differences were identified in other SCIM II subitems and ASIA motor or sensory scores between BSPS and non-BSPS patients when stratified for injury severity by excluding AIS B patients.Conclusion:Compared with incomplete tetraplegic patients, patients with cervical BSPS have a similar neurological and functional recovery when matched for the AIS.