Tuesday, August 30, 2011

Suspensory Ligament Injuries: New Treatments, New Hope

Suspensory ligament injuries (SLIs) are a common and potentially career ending occurance in the world of performance horses.  In the Western disciplines, reining and cutting horses are particularly vulnerable to SLIs due to the high speed, high torque maneuvers required of them.  However, any horse performing an athletic activity can sustain such an injury, especially if they are working in less than ideal footing.  Until very recently, the prognosis for horses with serious SLIs was not very good, as damaged ligaments are notoriously slow and difficult to heal.   As a result, many horses with SLIs never became sound enough to return to their former level of competition, and those that did had a high risk of reinjury.  However, several promising new treatments currently being investigated by researchers are significantly brightening the outlook for horses with SLIs, with some studies suggesting that even severely injured horses may have a good chance of returning to full use.  Some of these new methods are already being utilized by practicing veterinarians, with very encouraging results.
Before one can understand why the new methods are so exciting, it is necessary to understand why traditional methods have so often failed.  The difficulties stem from the fact that ligaments and tendons have a relatively tenuous blood supply, so injuries do not have much benefit from the healing components brought by the blood to other types of wounds.  What healing does take place tends to be in the form of scar tissue, which does not have the same organization or elasticity as the original material, and is thus easily reinjured.  Traditional treatment involves months of stall rest and administration of NSAIDs, followed by slow and very careful reintroduction to exercise.  Moderate to serious injuries often take six months to a year to heal, though a large percentage of horses never return to their previous athletic capabilities.
Whether or not a horse will heal with traditional methods depends, to a great degree, on the severity of the injury. According to Nathaniel A. White II DVM MS, Diplomate ACVS, Jean Ellen Shehan Professor and Director of the Marion duPont Scott Equine Medical Center in Virginia, “Suspensory ligament injuries vary from mild to severe. The mild injuries tend to heal readily with treatment, while the more severe injuries develop core lesions where loss of the fibers that make up the suspensory ligament create a weakened area with scar tissue which makes repair much more difficult.  Severe injuries where the ligament attaches to bone -- at the origin at the top of the cannon bone and at the insertion on the sesamoid bone -- are the most difficult to heal.  These sites of injury have the most frequent recurrence of injury due to chronic inflammation and excess scar formation, which  is weaker than the normal ligament.” 
Fortunately, even the most severe injuries will likely benefit from the new treatments being developed by researchers, which share the common aim of improving the quality of the healing, though they do not all claim to speed up the healing process.  In order to help veterinarians and their clients to better understand this rather astonishing array of new developments, the American Association of Equine Practitioners (AAEP) recently published a review delineating the new therapeutic options currently available.  Their list included the following:

1.  Scaffold-Based Approach (ACell Vet® Powder)

ACell Vet powder is a pulverized form of the ACell Vet sheets that are used in wound healing applications.  The material is made from the walls of pig bladders, which contain a mixture of proteins that form a three-dimensional scaffold upon which healthy tissue can grow.  When injected into an injured ligament, the ACell material promotes the formation of new blood vessels, and also attracts bone-marrow derived cells that aid in the growth of new ligament tissue.  The ACell material then essentially disappears, leaving healthy new tissue of the type normally found in the area. Richard D. Mitchell DVM, of Fairfield Equine Associated in CT, conducted a major study on the use of ACell Vet powder to treat ligament and tendon injuries in horses.  His preliminary data showed an 81.6% recovery rate for horses with serious suspensory ligament injuries at six months or longer – a vast improvement over the results typically obtained by traditional treatments alone. 
Says Mitchell, “The 60 day examinations consistently demonstrated good fiber pattern formation and minimal edema in treated lesions.  The noted fiber pattern demonstrated good linearity along the lines of stress/loading.”  Translation:  the injured horses laid down normal, strong, elastic tendon tissue instead of disorganized, weak scar tissue.  However, the AAEP review cautions that “additional laboratory evaluations and controlled in vivo studies are required to better document the efficacy and potential adverse effects of this product.”  They point out that introducing proteins from another species could provoke a detrimental foreign-body response in treated animals, and there are some unresolved legal questions surrounding the use of ACell Powder for this application.

2.  Growth Factors

Growth factors are naturally produced molecules that regulate cellular metabolism.  They are important in the healing of tendon and ligament injuries because they increase cell proliferation and differentiation, and they also stimulate vascular growth.  There are a number of different kinds of growth factors, but the only one studied for clinical use in the horse thus far is insulin-like growth factor-I (IGF-I).  IGF-I can be injected into an injured tendon or ligament, or it can be administered through gene-therapy techniques.  Either way, it seems to promote improved healing, leading the AAEP to state that this method “holds tremendous promise for the future.”  There appear to be no detrimental side effects to this therapy, with the only drawback being that IGF-I is not readily available at this time for veterinarians in private practice.

3.  Autogenous Bone Marrow Injection

Bone marrow harvested from a horse’s own sternum can be used to promote healing of SLIs.  The bone marrow is thought to work in two ways:  First, bone marrow contains mesenchymal stem cells (MSCs), which, when injected into the injured ligament, may turn into mature ligament cells called fibroblasts.  This allows appropriate repair tissues to develop, instead of scar tissue.  Second, bone marrow is believed to contain high concentrations of growth factors, which are thought to improve the healing of ligaments and tendons.  Though this method has shown positive results in clinical testing without apparent adverse effects, the AAEP remains cautious about it, saying that there is little scientific evidence to back up the method.  They also make mention of the fact that there are actually very low numbers of MSCs in bone marrow, and as a result, the large amount that must be injected (20-30 ml) may result in damage to the area.  Furthermore, they point out that high levels of a growth factor known as TGF-ß may result in excessive scarring, which would be detrimental due to potential recovery.

4.  Adipose-Derived Adult Stem Cells

One of the most promising new developments – and one that is readily available to the average veterinarian – is the use of stem cells harvested from a small sample of adipose tissue (fat) taken from the injured horse.  Recent studies have shown that fat is a rich source of adult stem cells, and since fat samples can be easily and harmlessly removed, it is proving to be an excellent source of stem cells for therapeutic purposes.  For the treatment of SLIs, the attending veterinarian removes a small piece of fat (about two tablespoons) near the horse’s tail head in a simple standing surgery, then sends this to a laboratory for processing.  The lab isolates the MSCs, then sends them back to the veterinarian ready for injection.  All of this can happen in as little as 48 hours, which allows for rapid treatment that may be beneficial in heading off the formation of scar tissue. 
There is also no risk of an immune response to the injected material, as it is derived from the horse’s own body.  According to the AAEP review, “Adipose-derived adult stem cells seem to have an anti-inflammatory and normalizing effect on tendon architecture.  Ultimately, the architecture of the remodeled tissue is crucial to the mechanical properties of the tendon and its ability to withstand repetitive strains without reinjury.”  They state that initial indications are that horses treated with this type of stem cell therapy are successfully returning to competition, and conclude by saying, “The use of adult stem cells to enhance tendon and ligament healing is an area with tremendous potential that requires further rigorous investigation.”

5.  Extracorporeal Shock Wave Therapy

Extracorporeal shock wave therapy (ESWT) is another new therapy that is rapidly gaining popularity in the equine performance horse industry. Shock wave therapy is being used to treat many disorders in performance horses, from suspensory ligament injuries to stress fractures. Though the mechanisms by which ESWT promotes healing are not entirely understood, it is thought to work by inducing blood vessel growth, increasing the expression of various growth factors, and attracting stem cells. Horses treated with shock wave therapy can potentially return to competition sooner than those treated with traditional rehabilitation programs, though this depends on the severity of the injury. The increasing demand for shock wave therapy is due to this potential for faster healing, improved recovery rates, and reduced costs associated with layup and rehabilitation.  However, the AAEP cautions that “potential side effects include hemorrhage, mechanical cell disruption, and marked histologic changes.”

There are also new surgical options that may be appropriate and beneficial to horses with SLIs that are not responding to less invasive treatments.  These include desmoplasty (surgical splitting of the ligament), and fasciotomy (incisions through the fascia).  Says Dr. White, “The goal of the desmoplasty and fasciotomy is to decompress the swollen ligament and allow a new blood supply to grow into avascular areas which persist in the non-healing ligament.  The surgery increases the inflammatory response, which encourages new fibroblasts or tissue stem cells to form new ligament cells.”  These techniques have resulted in an 85% recovery rate for proximal suspensory desmitis.
Ultimately, future treatment for SLIs will likely involve a variety of approaches which will work synergistically to promote faster and better healing.  Recovery will still be a relatively lengthy process, as returning to exercise too quickly or too aggressively significantly increases the chance of reinjury, regardless of what kind of treatment is being used.  As Dr. White observes, “It is apparent that some severe suspensory injuries require a full year to heal even with the newer treatments.” 
Still, Dr. White agrees that the overall outlook for horses with SLIs has improved over the last few years.   He believes there is great promise in the new treatments being developed, but adds that there are other reasons why progress is being made. “The prognosis is better because we understand some of the reasons why the suspensory ligament doesn't heal.  The greater the initial inflammatory response, the more likely scar tissue will form.  By understanding the inflammatory response and the response of the scar tissue to surgical treatment the outcome has been improved.  Ultrasound has also made a great difference in diagnosis and monitoring healing, thereby preventing  over use during the remodeling phase.” 
The outlook for any individual horse may also depend on how soon the injury is recognized, and what is done or not done in the hours, days and weeks immediately following the injury.  Left undiagnosed and untreated, an SLI will start to develop scar tissue, which will make any treatment more difficult and less likely to succeed.  While some SLIs can be hard to detect, here are some things you can look for, depending on what type of SLI you are dealing with:

Proximal suspensory desmitis:  This is an injury to the uppermost quarter of the suspensory ligament, seen with equal frequency in front and hind legs.  There is often no swelling apparent because of the bony structures  surrounding the ligament in that area.  Horses may be very lame, or may simply not be performing at their best, but lameness will usually become more pronounced if the horse is trotted in a circle with the affected leg to the outside.  Flexion of the fetlock joint may also increase apparent lameness.
Suspensory body desmitis:  This is an injury to the main body of the ligament, between the proximal section and where it branches off at the fetlock.  Swelling is usually evident, and there will be pain on palpation. Lameness is usually not evident, with swelling typically being obvious long before any lameness is noted.
Avulsion (tearing) of the origin of the suspensory ligament:  Usually seen in the front legs, this injury to the attachment of the ligament does not always produce visable swelling because the origin of the suspensory ligament is surrounded by bone on three sides.  Lameness can vary from acute and severe to something that seems to come and go.  As is the case with proximal suspensory desmitis, lameness is usually worse if you trot the horse in a circle with the injured leg to the outside.
Desmitis of the branch of the suspensory ligament:  This injury is the easiest to recognize, as there will be obvious swelling that fills the normally hollow space between the ligament branch and the cannon bone.  This area will be painful to the touch, though lameness is usually not a symptom.
Suspensory breakdown:  Severe over loading of the fetlock can lead to complete failure of the suspensory apparatus, and/or breaking of the sesamoid bones.  Lameness is instant and severe, with dropping of the fetlock joint.

If you suspect a possible suspensory ligament injury of any nature, it is best to apply cold hosing or ice packs immediately, followed by the application of a support wrap.  The horse should be confined to a stall until a veterinarian can assess the injury.  These first aid procedures may make a difference in the long run, setting your horse up for the greatest possible chance of making a complete recovery.  If an SLI has gone undiagnosed for some time, recovery may be more difficult, but is not necessarily impossible.  Consult with your veterinarian regarding the best options for your horse.   You may be in for a long haul, but the road to recovery is getting easier to travel all the time.