Liran Tzipory, DVM, DACVIM
Traumatic spinal cord injury (SCI) in dogs and cats is uncommon, and often is the result of automobile accidents, falling from heights, gunshots, and “little dog – big dog fights”. The most common spinal cord injury in dogs is intervertebral disc disease (IVDD). This article will discuss the primary insult and the secondary events happening in traumatic SCI, the differences and similarities of such injuries and IVDD. Management and treatment recommendations of both traumatic SCI and IVDD will be discussed.
In traumatic SCI, there are two main events; the compressive insult and the secondary events, i.e. the intrinsic sequels. The intrinsic sequels are primarily the result of the contusive injury, and are characterized by vascular, biochemical and inflammatory events, leading to secondary tissue damage.
The compressive injury is easy to understand and no controversy exists. The most common extradural tissue found within the vertebral canal is the nucleus pulposus and the annulus fibrosus. Other, such as hematoma and bone fragments may be present, especially when significant trauma occurs. The compressive injury affects the proper blood supply to the injured area, which in turn affects the ability of the
body itself to repair some of the intrinsic changes.
The vascular and biochemical damages
Acute injury to the spinal cord causes both systemic and local vascular abnormalities, leading to progressive decrease in perfusion and necrosis of the injured section of the spinal cord. Decreased spinal cord perfusion and ischemia develop within hours of the injury; hence rapid intervention is imperative for increasing successful outcome. At the level of the spinal cord, initial hypertension rapidly changes to hypotension, and furthermore the injury to the spinal cord also leads to loss of autoregulation. Normally, the spinal cord blood flow stays relatively constant regardless of systemic blood pressure changes. The loss of autoregulation results in progressive decrease in spinal cord blood flow leading to vasospasm, destruction of microvasculature, and thrombosis. Alteration of spinal cord blood flow and injury severity are inversely related; thus supporting systemic blood pressure is a very important step.
Vasospasm is the result of increase in intracellular Calcium. Calcium enters the cells via direct membrane damage, voltage-gated calcium cannels triggered by membrane depolarization, and activation of N-methyl D-aspartate (NMDA) receptors by the excitatory neurotransmitter glutamate. The high concentration of intracellular calcium leads to activation of intracellular proteases and phospholipase A2 (These are involved in cell signaling processes, such as inflammatory response), and other changes, such as impairment of mitochondrial function, spasms of vascular smooth muscle, and binding of phosphates, which results in depletion of cellular energy.
Free radicals production secondary to increased intracellular calcium, ischemia, hemorrhage (the presence of iron and copper), and reperfusion, interacts with cellular enzymes and unsaturated fatty acids in cell membranes causing lipid peroxidation. The lipid peroxidative damage to neuronal tissue and glial cells increases spinal cord ischemia and damage.
The use and abuse of steroids
Free radicals production leading to lipid peroxidation, calcium influx, and anti-inflammatory effects have been investigated widely in several animal model studies, as well as large clinical trials in humans. Methylprednisolone Sodium Saccinate (MPSS) is a glucocorticoid that has free radical scavenging properties when used in high doses. The neuroprotective effect of MPSS is most effective when given at the time of, or within minutes after spinal cord injury. Another important fact is that treatment is aimed at maintaining therapeutic concentrations during the first 24-48 hours post spinal cord injury.
Three large, randomized clinical trials, the National Acute Spinal Cord Injury Studies (NASCIS I, II and III) examined the effect of steroid administration in patients with acute spinal cord injury. In NASCIS I improvement in motor function in specific muscles and in light touch and pinprick sensation from baseline were studied. The study found no benefit from methylprednisolone, however it was determined that the dose used was below the therapeutic threshold determined from animal models. In NASCIS II, a multicenter, prospective, randomized, double-blind trial, the MPSS dose used was much higher, and patients were randomly assigned to receive a 24-hour infusion of MPSS (a bolus of 30mg/kg followed by a 5.4mg/kg as a CRI for 24 hours), naloxone or placebo within 12 hours after acute spinal cord injury. Again, no overall clinical benefit was found between the groups. However, post hoc analyses (note: post hoc analyses looks at statistical significance and not clinical significance) detected a small gain in the total motor and sensory score in a subgroup of patients who had received MPSS within 8 hours after their injury. In this study, motor strength was measured using the American Spine Injury Association (ASIA) 0-5 scale in 14 muscle groups, giving a maximum possible score of 70. Pin prick & touch sensation were assessed in 29 dermatomes, with a maximum sensory score of 58. Analysis only used scores from the right side of the body, and there was no mention of left-sided scores, although both sides were examined. The post-hoc analysis identified a statistically significant improvement of 5 motor points improvement at 1 year. Is this clinically significant? An improvement of 5 motor points in one muscle group is unlikely – but even so would not confer any increased functionality on a spinal cord injured patient. Similarly, and increase of 1 motor point across 5 different muscle groups will also have little impact on functional ability. Unfortunately, high dose of MPSS was implied as standard of care despite considerable criticism of the validity of such a post hoc analysis.
SCI in Veterinary Medicine
Veterinary medicine quickly adopted this “standard of care” to our patients, which includes the same doses used in humans and has not been adjusted or re-evaluated in dogs. For many years, and still to this day, there are many veterinarians that treat various spinal cord injuries with high doses of steroids. It is important to note here that Prednisone and Dexamethasone, commonly used steroids in veterinary medicine, do not possess the same free radical scavenging as MPSS does; hence the use of these steroids is not recommended. Additionally, intermittent dosing throughout the day is also not recommended as maintaining a high concentration of MPSS has shown to be most effective.
The most common acute spinal cord injury in dogs is IVDD resulting in spinal cord compression and varying degree of contusion. It is very important to distinguish between traumatic SCI and disc herniation. The compressive injury (i.e. primary insult) can be very similar, however, in traumatic SCI, the secondary events are usually much more severe. In most dogs with SCI secondary to disc herniation, the secondary events are usually mild to moderate in severity. Certainly, there are dogs that present with a per-acute to acute onset of signs and progress rapidly, which can resemble traumatic SCI, but luckily these are not the majority of cases. Most cases that present in a neurologic state where surgery is recommended (i.e. being non-ambulatory paraparetic or worse) have a few days history of progressive neurologic signs. As noted earlier, high doses of steroids have not shown to be beneficial in traumatic, per-acute SCI, hence in these sub-acute to chronic cases, high doses of steroids are not recommended.
An anti-inflammatory dose of steroids can be used when trying to manage conservatively a dog with suspected SCI secondary to IVDD. In this instance, the aim is the treatment of the local inflammatory process, but not any potential vascular and biochemical damages, especially if Prednisone or Dexamethasone is used. The most important aspect of conservative management is strict rest. Minimizing mobility is the only way to try to help the body to heal the damaged annulus fibrosus. It usually takes 4-6 weeks to the fibrous tissue/“scar tissue” to be formed in order to prevent further extrusion of the nucleus polposus and spinal cord compression. The most common side effect of steroids in dogs, even at an anti-inflammatory dose, is PU/PD. Thus, using steroids defeats the purpose of strict rest, because now the owner has to take their dog outside more often, and if this is not possible, then most dogs will be restless in their crate due to the urge to urinate. For the purpose of treating the local inflammation and pain associated with it, Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) have been shown to be a valid and potentially better treatment option compared to steroids.
A study comparing steroids and NSAIDs as a treatment for IVDD did not show any Difference in neurologic outcome, but did show increased morbidity (UTI, pneumonia, delayed wound healing) with steroid use. The perception that steroids are “better” compared to NSAIDs for IVDD inflammation has not been proven.
Another potential benefit of NSAIDs over steroids in these cases is the fact that if conservative management is successful initially, then these drugs can be stopped and/or being given as needed, in comparison to steroids, which have to be tapered over time.
IVDD is a surgical disease. In my experience, dogs with intact pain perception that undergo surgery have a 99% chance of recovery. Improving blood supply by decompression has been shown to be the most effective way to improve spinal cord function. However, in about 50% of cases, when neurologic dysfunction is minimal (mild to moderate ataxia and being ambulatory paretic), conservative management can be successful. Based on my experience and a review of the literature in both human and veterinary medicine, my recommendation for first line medical management of IVDD is strict cage rest and anti-inflammatory therapy with NSAIDs. Other medications that I have found to help with rest and comfort include gabapentin and potentially Tramadol (however, the analgesia efficacy in dogs is questionable).
I hope this information will help guide your therapy for dogs with IVDD. If you have any questions or concerns please do not hesitate to contact me.