Animal Studies in Timing of Surgery for Spinal Cord Injury

Animal studies have been easier to design and complete than human trials. Multiple animal studies have suggested the benefit of early surgical decompression. Typically, the studies have been performed with extradural balloon, static weight, clip, piston impactor, or circumferential cable models of spinal cord injury (SCI).

Carlson studied 16 dogs undergoing a sustained spinal cord compression for 30 or 180 minutes using a hydraulic piston. Somatic sensory evoked potentials were monitored during a 60-minute recovery period as well as at 28 days postinjury. Functional motor recovery was assessed at 26 days. Magnetic resonance imaging (MRI) and histologic analysis were performed to assess the volume of the lesion and tissue damage. Improved motor function and balance were noted in the 30-minute group as compared to the 180-minute group. The longer duration of compression produced spinal cord lesions of greater volume, which corresponded to poorer long-term functional outcomes.

Dimar and colleagues studied the influence of spinal canal narrowing and timing of decompression on neurologic recovery after spinal cord contusion using a spacer model of injury in 40 adult rats. The results of this study led the researchers to conclude that there was strong evidence that the prognosis for neurologic recovery was adversely affected by both a higher percentage of canal narrowing and a longer duration of canal narrowing after an SCI. They concluded that the tolerance for spinal canal narrowing with a contused cord appears diminished, indicating that an injured spinal cord may benefit from early decompression. They also demonstrated that the longer the spinal cord compression exists after an incomplete cord injury, the worse the prognosis for neurologic recovery.

Carlson also studied the early time-dependent decompression for spinal cord injury in 21 beagles and proposed vascular mechanisms of recovery. His results indicated that after precise dynamic spinal cord loading to a point of functional conduction deficit (50% decline in evoked potential amplitude), a critical time period exists where intervention in the form of early spinal cord decompression can lead to effective recovery of electrophysiologic function in the 1- to 3-hour post decompression period.

Delamarter also studied spinal cord recovery after immediate and delayed decompression in dogs. He studied 30 dogs with a cable constriction SCI model with periods of compression from 1 hour up to 1 week. Somatosensory evoked potentials (SSEPs), neurologic examinations, and histologic and electron microscopy studies were performed. All dogs were paraplegic after the compression of the cord, but the dogs that underwent immediate decompression or decompression within 1 hour of compression recovered the ability to walk as well as bowel and bladder control, and had improvement in SSEPs. When compression lasted 6 hours or more, there was no neurologic recovery and progressive necrosis of the spinal cord was observed. Somatosensory evoked potential recovery by 6 weeks after the decompression was significantly related to the duration of the compression. Delamarter concluded that longer periods of displacement allowed propagation of the chronic axonal response, resulting in lack of recovery of SSEPs, limited functional recovery, and more extensive tissue damage.

Multiple other animal models of SCI have also shown the positive effect of early decompressive surgery to improve neurologic recovery. Animal studies have been fairly consistent demonstrating that neurologic injury appears to be inversely related to the extent and duration of spinal cord compression after primary acute SCI and early decompression of the spinal cord, especially within the first hour improved neurologic function.

Some of these landmark studies include canine studies by Delamarter showing that decompression is inversely proportional to duration of spinal cord compression and by Carlson showing that removal of the pressure piston on the spinal cord at 5 minutes, 30 minutes, and 1 hour improves recovery of evoked potentials. Dimar’s rat study observed that neurologic recovery was inversely related to extent and duration on cord compression. Kobrine’s primate cord compression model suggested that mechanical forces of compression, rather than ischemia, are mainly responsible for the loss of neural conduction.

Human Studies on Timing of Surgery

Unfortunately, human studies on timing of SCI have been harder to control and interpret than animal studies. The inability to control the initial injury with respect to mechanism of injury, force, velocity, and interpatient variabilities leaves many variables unfounded. The time of injury to medical stabilization and the time of injury to surgical decompression and stabilization are not always apparent in the data, making further comparisons difficult, as well as what defines early surgery (< 24 hours, < 72 hours). van Middendorp addressed these difficulties in traumatic SCI controlled trials. The definition seems to change over time and appears to be more of an arbitrary cutoff point. For the sake of consistency, we will define early surgery as < 24 hours.

Many protocols and evidence-based medicine guidelines developed to treat SCI have made great strides to optimize and standardize many of the prehospital and diagnostic recommendations for acute traumatic SCI. The initial cardiopulmonary management is designed to optimize cord blood flow by correcting hypotension and maintaining mean arterial pressures between 85 and 90 for the first 7 days following an acute SCI. It is thought that these measures will minimize the secondary injury associated with hypotension and ischemia. Aggressive treatment of hypoxia or respiratory insufficiency is also thought to minimize some of the secondary insult cascade of SCI such as decreasing edema, vasospasm, inflammation, ischemia, and neural cell death. Consistent class III evidence has shown improved clinical outcomes with aggressive management of hypotension and respiratory insufficiency following acute SCI. Current guidelines published by the Congress of Neurological Surgeons, American Association of Neurological Surgeons (AANS), and Joint Section for acute SCI do not recommend administration of methylprednisolone or GM1 ganglioside (Sygen).

Early closed reduction of cervical fractures/dislocations, by application of cervical traction, is recommended to optimize alignment and minimize compressive or distractive forces on the spinal cord. The timing of these guidelines are limited on their recommendation due to the level of the timing literature. Surgery is still controversial, in part due to the heterogeneity of the sacroiliac injuries. More data are being accumulated to support early surgery based on safety, feasibility, decreased complication rates, and reduced health care costs. It remains difficult to determine improved clinical and neurologic outcomes, but multiple evidence-based medicine reviews and guidelines have compiled ample data to support the safety of early surgical intervention. Furlan has also shown that the potential for neurologic recovery among elderly survivors of SCI is similar to that of younger individuals.

Bourassa-Moreau and Mac-Thiong retrospectively reviewed 431 traumatic SCIs at a single institution and compared postoperative complication rates for spine surgeries at 24 hours and 72 hours. The effect of surgical timing on complication rate was adjusted for potential confounding variables (level of injury, American Spinal Injury Association [ASIA] grade, Injury Severity Score, age, sex). They were able to conclude that shorter surgical delay after SCI decreases the rate of complications during acute phase hospitalization, recommending that surgery be performed earlier than 24 hours and if medical or practical reasons preclude this, that efforts should still be made to perform surgery earlier than 72 hours postinjury.

An evidence-based examination of preclinical and clinical studies performed by Furlan and colleagues showed 19 animal SCI studies that provided evidence for a biologic rationale to support early cord decompression and 22 clinical studies, mostly level 4 evidence, supporting the safety and feasibility for early decompressive surgery for spinal cord injury. Included in this review were two studies with higher levels of evidence (2b) that had conflicting conclusions. Cengiz studied 27 acute TL SCIs and found 83.3% of patients in the early surgery group showed improvement in the Asia Injury Scale compared to 26.6% in the late surgery group (p < 0.05). Cengiz also showed a decreased incidence of complications in the early surgery group compared to the late surgery group. Another 2b level study by Vaccaro and associates prospectively studied cervical SCI patients operated on at <72 hours versus waiting longer than 5 days. Comparison showed no significant difference in length of acute postoperative intensive care unit stay, length of inpatient rehabilitation, or improvement in American Spinal Injury Association grade or motor score between early surgery (mean 1.8 days) and late surgery (mean 16.8 days). McKinley and Stevens found no differences in neurologic or functional improvements between early and late surgery groups in patients with acute SCI.

The Surgical Timing Acute Spinal Cord Injury Scale (STASCIS) performed an international, multicenter prospective cohort study to determine the relative effectiveness of early (< 24 hours after injury) versus late (≥ 24 hours after injury) decompressive surgery after traumatic cervical spinal cord injury. In this follow-up, 19.8% of patients undergoing early surgery showed a ≥ 2 grade improvement on the ASIA Impairment Scale (AIS) compared to 8.8% in the late decompression group. After multivariate analysis adjusting for preoperative neurologic status and steroid administration, the odds of at least a 2 grade AIS improvement were 2.8 times higher among those who underwent early surgery as compared to those who underwent late surgery. Complications occurred in 24.2% of the early surgery patients and 30.5% of the late surgery patients (p = 0.21).

Similarly, in a study of the Rick Hansen Spinal Cord Registry, 1410 patients who sustained acute traumatic SCI with baseline AIS grades A, B, C, or D, were treated surgically and analyzed to determine the effect of the timing of surgery (24, 48, or 72 hours from injury) on motor recovery and length of stay. Persons with incomplete AIS B, C, or D injuries from C2-L2 demonstrated motor recovery improvement of an additional 6.3 motor points (p < 0.03) when they underwent surgical treatments within 24 hours of injury compared to those with surgery later than 24 hours postinjury. No benefit of early surgery or motor recovery was seen on AIS A complete SCI patients, but AIS A and B patients with early surgery did have shorter hospital lengths of stay. From this study by Dvorak and coworkers, they were able to provide evidence that for an incomplete acute traumatic SCI in the cervical, thoracic, or thoracolumbar spine, surgery performed within 24 hours from injury improves motor neurologic recovery. Early surgery also reduced hospital length of stay. Molliqaj reviewed acute traumatic central cord syndrome and also found early surgery to be safe and effective.

A study by Galvin and Freedman compared the surgical morbidity of early spine surgery in multiply injured patients versus stable patients in the setting of military casualties in Afghanistan, despite being a rather small study of 30 patients with 31 spine surgeries during a 12-month period. This study demonstrated that early spine surgery can represent a considerable physiologic insult to patients with multiple injuries, which is a group considered at risk for serious complications. These borderline unstable patients observed a longer operative time, higher blood loss, and higher transfusion requirements. Only 12% of the borderline unstable cases showed improvement in neurologic status as compared to 42% of stable patients with any neurologic deficit. This paper concluded that the perceived benefits of early intervention seen in civilian populations must be carefully weighed when extrapolated to SCI received in combat trauma. Stundner found an increased incidence of pulmonary complications with staged spine surgery, more so than the actual effect of surgical timing.