Julio C. Furlan

Timing of Decompressive Surgery of Spinal Cord after Traumatic Spinal Cord Injury: An Evidence-Based Examination of Pre-Clinical and Clinical Studies

While the recommendations for spine surgery in specific cases of acute traumatic spinal cord injury (SCI) are well recognized, there is considerable uncertainty regarding the role of the timing of surgical decompression of the spinal cord in the management of patients with SCI. Given this, we sought to critically review the literature regarding the pre-clinical and clinical evidence on the potential impact of timing of surgical decompression of the spinal cord on outcomes after traumatic SCI. The primary literature search was performed using MEDLINE, CINAHL, EMBASE, and Cochrane databases. A secondary search strategy incorporated articles referenced in prior meta-analyses and systematic and nonsystematic review articles. Two reviewers independently assessed every study with regard to eligibility, level of evidence, and study quality. Of 198 abstracts of pre-clinical studies, 19 experimental studies using animal SCI models fulfilled our inclusion and exclusion criteria. Despite some discrepancies in the results of those pre-clinical studies, there is evidence for a biological rationale to support early decompression of the spinal cord. Of 153 abstracts of clinical studies, 22 fulfilled the inclusion and exclusion criteria. While the vast majority of the clinical studies were level-4 evidence, there were two studies of level-2b evidence. The quality assessment scores varied from 7 to 25 with a mean value of 12.41. While 2 of 22 clinical studies assessed feasibility and safety, 20 clinical studies examined efficacy of early surgical intervention to stabilize and align the spine and to decompress the spinal cord; the most common definitions of early operation used 24 and 72 h after SCI as timelines. A number of studies indicated that patients who undergo early surgical decompression can have similar outcomes to patients who received a delayed decompressive operation. However, there is evidence to suggest that early surgical intervention is safe and feasible and that it can improve clinical and neurological outcomes and reduce health care costs. Based on the current clinical evidence using a Delphi process, an expert panel recommended that early surgical intervention should be considered in all patients from 8 to 24 h following acute traumatic SCI.

Autonomic Dysreflexia in Acute Spinal Cord Injury: An Under-Recognized Clinical Entity

While autonomic dysreflexia (AD) is well recognized in the chronic stage of spinal cord injury (SCI) this potentially life-threatening complication has been only rarely documented in the acute phase (1 month) after SCI. Based on our clinical experience we hypothesized that AD is under-recognized in the acute phase of SCI. This study was undertaken to determine the incidence and clinical associations of early AD in our center. We reviewed the charts of patients with acute traumatic SCI admitted to the Toronto Western Hospital Spinal Program between 1998 and 2000. Among 58 patients with acute traumatic SCI (15F, 43M; ages 17-89 years, mean of 55.4), all three individuals who developed evidence of early AD had complete cervical tetraplegia (1F, 2M; ages 31-42 years, mean of 38.3). The incidence of early AD was 5.2% (3 of 58), whereas the adjusted incidence for the population at risk (SCI at T6 or above) was 5.7% (3 of 53). A significant number of patients in this series (87.9%, or 51 of 58) had a cervical SCI. While the mean resting systolic arterial blood pressure among these three individuals was 105.7+/-3 mm Hg, the mean systolic blood pressure at the time of early AD was 173.3+/-14.8 mm Hg (increase in systolic blood pressure over baseline ranged from 35.5% to 95%). The earliest episode of AD occurred on the 4(th) post-injury day. The trigger mechanisms for AD were somatic pain, fecal impaction, and abdominal distention. Although numerous reports emphasize AD as a potential complication of chronic SCI, our study demonstrates that AD occurs in 5.7% of patients with acute SCI above T6. Patients with severe cervical SCI are particularly susceptible to the early onset of AD. Clinicians need to be aware and highly vigilant of the potential development of AD in the acute phase of SCI.

Cardiovascular complications after acute spinal cord injury: pathophysiology, diagnosis, and management.

Cardiovascular complications in the acute stage following traumatic spinal cord injury (SCI) require prompt medical attention to avoid neurological compromise, morbidity, and death. In this review, the authors summarize the neural regulation of the cardiovascular system as well as the pathophysiology, diagnosis, and management of major cardiovascular complications that can occur following acute (up to 30 days) traumatic SCI. Hypotension (both supine and orthostatic), autonomic dysreflexia, and cardiac arrhythmias (including persistent bradycardia) are attributed to the loss of supraspinal control of the sympathetic nervous system that commonly occurs in patients with severe spinal cord lesions at T-6 or higher. Current evidence-based guidelines recommend: 1) monitoring of cardiac and hemodynamic parameters in the acute phase of SCI; 2) maintenance of a minimum mean arterial blood pressure of 85 mm Hg during the hyperacute phase (1 week after SCI); 3) timely detection and appropriate treatment of neurogenic shock and cardiac arrhythmias; and 4) immediate and adequate treatment of episodes of acute autonomic dysreflexia. In addition to these forms of cardiovascular dysfunction, individuals with acute SCIs are at high risk for deep venous thrombosis (DVT) and pulmonary embolism due to loss of mobility and, potentially, altered fibrinolytic activity, abnormal platelet function, and impaired circadian variations of hemostatic and fibrinolytic parameters. Current evidence supports a recommendation for thromboprophylaxis using mechanical methods and anticoagulants during the acute stage up to 3 months following SCI, depending on the severity and level of injury. Low-molecular-weight heparin is the first choice for anticoagulant prophylaxis in patients with acute SCI. Although there is insufficient evidence to recommend (or refute) the use of screening tests for DVT in asymptomatic adults with acute SCI, this strategy may detect asymptomatic DVT in at least 9.4% of individuals who undergo thromboprophylaxis using lowmolecular- weight heparin. Indications and treatment of DVT and acute pulmonary embolism are well established and are summarized in this review. Recognition of cardiovascular complications after acute SCI is essential to minimize adverse outcomes and to optimize recovery.

Descending vasomotor pathways in humans: correlation between axonal preservation and cardiovascular dysfunction after spinal cord injury.

Cardiovascular dysfunction is common after cervical spinal cord injury (SCI) in humans. At least three spinal cord elements involved in cardiovascular control have been identified: descending vasomotor pathways (DVPs), sympathetic preganglionic neurons, and spinal afferents. However, little is known about the localization of the DVPs within the human spinal cord, which limits our understanding of the mechanisms of cardiovascular dysfunction after SCI. This study was undertaken to examine the association of cardiovascular abnormalities after SCI in humans with the severity of degeneration and axonal loss within the DVPs. A detailed chart review and histopathological examination of postmortem spinal cord tissue was conducted in individuals with cervical SCI (n = 7) and control individuals with an intact central nervous system (n = 5). Individuals with SCI were divided into group 1 (severe cardiovascular abnormalities) and group 2 (no/minor cardiovascular disturbances). The area of degeneration and the number of preserved axons within different areas of the spinal cord were quantitated using EMPIX imaging software. Two areas of possible localization of DVPs were investigated: area I, within the dorsal aspects of the lateral funiculus; and area II, within the white matter adjacent to the dorsolateral aspect of the lateral horn. Comparison of the extent of axonal degeneration in both SCI groups demonstrated that individuals in group 1 had more extensive axonal degeneration than those in group 2. The number of intact axons within areas I and II in individuals from group 1 was significantly lower than those from group 2 or control cases (p = 0.029; p = 0.028). The most dramatic axonal loss was observed within area I in individuals with cardiovascular dysfunction. We conclude that loss and degeneration of DVPs, which are localized within the dorsolateral aspects of the human spinal cord, contributes to abnormal cardiovascular control after SCI. This information adds to our knowledge of pathobiology of cardiovascular dysfunction after human SCI and may ultimately suggest novel therapeutic strategies as regenerative and reparative approaches become translated to the clinic.

Functional and clinical outcomes following surgical treatment in patients with cervical spondylotic myelopathy: a prospective study of 81 cases.

OBJECT Cervical spondylotic myelopathy (CSM) is the most common cause of spinal dysfunction in the elderly. Operative management is beneficial for most patients with moderate/severe myelopathy. This study examines the potential confounding effects of age, sex, duration of symptoms, and comorbidities on the functional outcomes and postoperative complications in patients who underwent cervical decompressive surgery. METHODS We included consecutive patients who underwent surgery from December 2005 to October 2007. Functional outcomes were assessed using the Nurick grading system and the modified Japanese Orthopaedic Association and Berg Balance scales. Comorbidity indices included the Charlson Comorbidity Index and the number of ICD-9 codes. RESULTS There were 57 men and 24 women with a mean age of 57 years (range 32-88 years). The mean duration of symptoms was 25.2 months (range 1-120 months). There was a significant functional recovery from baseline to 6 months after surgery (p < 0.01). Postoperative complications occurred in 18.5% of cases. Although the occurrence of complications was not significantly associated with sex (p = 0.188), number of ICD-9 codes (p = 0.113), duration of symptoms (p = 0.309), surgical approach (p = 0.248), or number of spine levels treated (p = 0.454), logistic regression analysis showed that patients who developed complications were significantly older than patients who had no complications (p = 0.018). Only older age (p < 0.002) and greater number of ICD-9 codes (p < 0.01) were significantly associated with poorer functional recovery after surgical treatment. However, none of the studied factors were significantly associated with clinically relevant functional recovery after surgical treatment for CSM (p > 0.05). CONCLUSIONS Our results indicate that surgery for CSM is associated with significant functional recovery, which appears to reach a plateau at 6 months after surgery. Age is a potential predictor of complications after decompressive surgery for CSM. Whereas older patients with a greater number of preexisting medical comorbidities had less favorable functional outcomes after surgery for CSM in the multivariate regression analysis, none of the studied factors were associated with clinically relevant functional recovery after surgery in the logistic regression analysis. Therefore, age-matched protocols based on preexisting medical comorbidities may reduce the risk for postoperative complications and improve functional outcomes after surgical treatment for CSM.

Assessment of Impairment in Patients with Acute Traumatic Spinal Cord Injury: A Systematic Review of the Literature

The most common primary end-point of the trial on treatment of traumatic spinal cord injury (SCI) is the degree of impairment. The American Spinal Injury Association (ASIA) Standards have been widely used to assess motor function and pin-prick and light-touch sensory function. In addition, pain assessment is another clinically relevant aspect of the impairment in individuals with SCI. Given this, we sought to systematically review the studies that focused on the psychometric properties of ASIA Standards and all previously used outcome measures of pain in the SCI population in the acute care setting. For the primary literature search strategy, the MEDLINE, CINAHL, EMBASE, and Cochrane databases were sought out. Subsequently, a secondary search strategy was carried out using the articles listed in the references of meta-analysis, systematic, and non-systematic review articles. Two reviewers (JCF and VN) independently selected the articles that fulfill the inclusion and exclusion, assessed the level of evidence of each article, and appraised the psychometric properties of each instrument. Divergences during those steps were solved by consensus between both reviewers. Of 400 abstracts captured in our primary search strategy on the ASIA Standards, 16 full articles fulfilled the inclusion and exclusion criteria. An additional 40 references were obtained from two prior systematic reviews on ASIA Standards. While 45 of 56 of the studies on ASIA Standards provided level 4 evidence, there were 11 level 2b evidence studies. Convergent construct validity (n = 34), reliability (n = 12), and responsiveness (n = 10) were the most commonly studied psychometric properties of the ASIA Standards, but two prior studies examined their content validity. Of the 267 abstracts yielded in our primary search on pain assessment, 24 articles with level 4 evidence fulfilled the inclusion and exclusion criteria. 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. In conclusion, the ASIA Standards represent an appropriate instrument to categorize and evaluate spinal cord injured adults over time with respect to their motor and sensory function. Nevertheless, 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 (VAS) is the most commonly studied instrument of assessment of pain intensity in the SCI population. However, further investigation is required with regard to its reliability and responsiveness in the SCI population. Our results also suggest that there is no instrument with appropriate psychometric properties for this particular population.

Medical co-morbidities, secondary complications, and mortality in elderly with acute spinal cord injury.

Despite an increasing incidence of spinal cord injury (SCI) in the elderly and evidence that age appears to influence outcome after neurotrauma, surprisingly little is known regarding clinical outcomes and secondary complications in elderly with an acute SCI. This study was undertaken to evaluate the effect of age on clinical outcomes after acute traumatic SCI managed in an acute care unit by a multidisciplinary team. A retrospective chart review of all patients with acute SCI admitted to an acute care unit at a university hospital between 1998 and 2000 was performed. Data on clinical outcomes and secondary complications in younger individuals (group 1: age < 60 years) were compared to elderly subjects (group 2: age > or = 60 years). There were 28 elderly (age 60-89 years) and 30 younger (age 17-56 years) individuals. The severity and level of SCI were similar in both groups (p = 0.11; p = 0.93). Co-morbidities were more frequent in the elderly (p < 0.01). There was a trend, which did not achieve significance, for an increased incidence of secondary complications in the elderly (57.1% versus 33.3%; p = 0.11). The most common secondary complications in both groups were infections, psychiatric disorders, pressure sores, and cardiovascular complications. Mortality rates in elderly and younger individuals with acute SCI (p = 0.41) were not significantly different. Our data suggest that rigorous attention to principles of acute SCI care can minimize previously reported higher susceptibility for secondary complications in the elderly. A multidisciplinary team approach to the management of the elderly with acute SCI is essential to minimize or prevent secondary complications.

Epidemiology and clinical outcomes of acute spine trauma and spinal cord injury: experience from a specialized spine trauma center in Canada in comparison with a large national registry.

BACKGROUND Because relevant changes in the epidemiology of the traumatic spinal cord injury (SCI) has been reported, we sought to examine the demographics, injury characteristics, and clinical outcomes of patients with spine trauma who have been treated in our spine trauma center. METHODS All consecutive patients with acute spine trauma who were admitted in our center from 1996 to 2007 were included. Comparisons among the four triennia were performed for demographics, injury characteristics, and clinical outcomes. Also, our 2001/2002 SCI data were compared with the National Trauma Registry (NTR) dataset. RESULTS There were 569 patients (394 males, 175 females; ages from 15 to 102 years, mean age of 50 years) who were admitted with acute spine trauma. Although demographic profile has been steady over the last four triennia, the frequency of more severe spine trauma at the lumbosacral levels due to falls has increased overtime. The mean length of stay and in-hospital mortality rates have not significantly changed during the past 12 years. Our in-hospital mortality rate (4%) was significantly lower than the provincial rate from the Ontario Trauma Registry (7.5%; p = 0.005). Comparisons between our SCI data and the NTR dataset showed significant differences regarding age groups. CONCLUSIONS Our results indicate that significant differences in the characteristics of acute spine trauma but not demographics have occurred overtime in our institution. Also, there were significant differences between our database and the NTR regarding age distribution. Our reduced in-hospital mortality rates in comparison with the provincial data reinforce the recommendations for early management of SCI patients in a spine trauma center.

Motor and Sensory Assessment of Patients in Clinical Trials for Pharmacological Therapy of Acute Spinal Cord Injury: Psychometric Properties of the ASIA Standards

With the resurgence of clinical trials in spinal cord injury (SCI), there is intense interest in whether the American Spinal Injury Association (ASIA) standards are sensitive enough to discriminate neurological recovery. We conducted a systematic review to examine the psychometric properties of the ASIA Standards in assessing motor and sensory function of individuals with acute traumatic SCI. Papers, which examined the psychometric properties of the ASIA Standards, were obtained from Medline, CINAHL, and EMBASE databases (1982-2008). Of 39 publications primarily identified, 18 fulfilled the inclusion and exclusion criteria. An additional 51 publications were captured in a secondary search using the bibliographies from original articles and published reviews. The 2000 version of the ASIA Standards appear to be more reliable than the previous versions, although two prospective studies indicate that the ASIA Standards do not reliably assess children less than 4 years with SCI. Responsiveness studies indicate that (a) a detailed neurological examination using the ASIA Standards at 72 h should be obtained for comparison with subsequent neurological assessments following SCI; (b) the use of ASIA upper- and lower-extremity motor subscores instead of a single ASIA motor score is recommended; (c) further investigation of the minimal clinically important difference of the ASIA Standards is required; and (d) the functionally meaningful ASIA score threshold to document the benefit of a novel therapeutic intervention varies according to the level and severity of SCI. Although the ASIA Standards cannot be evaluated in terms of criterion validity, several studies suggested their divergent and convergent construct validity. Therefore, the ASIA Standards represent an appropriate instrument to discriminate and evaluate patients with SCI in a longitudinal manner. Nonetheless, further investigation of the ASIA Standards is recommended due to a paucity of studies focused on some key elements of the measurement responsiveness, including minimal clinically important difference.

Management of anticoagulation following central nervous system hemorrhage in patients with high thromboembolic risk

Summary.  Background: Patients who present with central nervous system (CNS) hemorrhage while on anticoagulation (AC) for thromboembolic (TE) risk factors are a challenge to manage. Objective: We sought to inform decisions surrounding the timing and intensity of AC resumption by performing a systematic review. Methods: Three reviewers screened publications from Medline and EMBASE and extracted data. Hemorrhagic and TE adverse events that occurred subsequent to the index hemorrhage were recorded, as was their timing relative to presentation and covariates that might influence their occurrence. Results: Data were extracted from 63 publications detailing 492 patients; 7.7% of patients experienced hemorrhagic complications and 6.1% experienced TE complications. Hemorrhagic complications were more common within 72 h of presentation while TE complications were more common thereafter. Patients restarted on AC after 72 h were significantly more likely to have a TE complication (P = 0.006) and those restarted before 72 h were more likely to hemorrhage (P = 0.0727). Factors associated with re‐hemorrhage included younger age, traumatic cause, subdural hematomas and failure to reverse AC. TE complications were more common in younger patients and those with spinal hemorrhage, multiple hemorrhages, and non‐traumatic causes of the index hemorrhage. Re‐initiation of AC at a lower intensity also significantly increased the risk of TE complications. Interpretation: Our results suggest that it may be prudent to re‐initiate AC earlier than previously thought, with the timing and intensity modified based on predictors of TE and hemorrhagic complications. These findings must be explored in a prospective study because of limitations inherent to the analyzed studies.