On the Forefront: Studying the effects of polyethylene glycol in dogs with acute spinal cord injuries

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Mar 01, 2005


Rags is recuperating from a thoracolumbar hemilaminectomy. Dogs that have had a recent acute intervertebral disk herniation may be able to participate in a clinical trial evaluating the efficacy of adjunct therapy with polyethylene glycol in treating spinal cord injury.
Spinal cord injury is common in both dogs and people. A high incidence of acute intervertebral disk rupture occurs in dogs, particularly the chondrodystrophic breeds, such as dachshunds, Pekingese, Lhasa apsos, Shih Tzus, cocker spaniels, and crosses of these breeds. The prolapsed disk focally compresses the spinal cord and can result in irreversible loss of voluntary motor activity and central recognition of pain (conscious pain perception).

In dogs, explosive disk herniation closely mimics the anatomical response of human spinal cords to severe compression injury.1-4 Multiple therapeutic modalities have been described in both species, including surgical decompression, drug therapy (e.g. injectable corticosteroids such as methylprednisolone sodium succinate, prednisolone sodium succinate, and the 21-aminosteroids [lazaroids], as well as dimethyl sulfoxide), oscillating field stimulation, and alternative therapies (e.g. acupuncture) or combinations thereof.5,6

The Department of Veterinary Clinical Sciences at the Iowa State University College of Veterinary Medicine, in collaboration with the Center for Paralysis Research at Purdue University, is continuing a promising multi-institutional study that was recently reported in the Journal of Neurotrauma. That preliminary study (conducted through the Departments of Veterinary Clinical Sciences at Purdue University and Texas A&M University, the Department of Neurosurgery at Indiana University Medical Center, and the Department of Biomedical Engineering and the Center for Paralysis Research at Purdue University) involved the use of intravenous surfactants to treat dogs with acute paraplegia.3 The hydrophilic polymers investigated were polyethylene glycol and poloxamer 188. Such polymers have been shown to seal defects in axonal cell membranes and are theorized to help prevent secondary tissue death that can occur subsequent to initial injury. These polymers have been investigated in standardized experiments involving spinal cord injury in guinea pigs at the Center for Paralysis Research at Purdue University.7-12

The recent multi-institutional study mentioned above and the continuing investigation at Iowa State University involve the use of intravenously administered polyethylene glycol to help reunite and fuse transected cell processes and to seal anatomical breaches in cell membranes produced by mechanical insult to the spinal cord tissue.7 The results of the preliminary investigation were encouraging, but further investigation is warranted.

The study details

The purpose of the polyethylene glycol study at Iowa State University is to further characterize the benefits of this treatment in a larger number of dogs with naturally occurring, neurologically complete (posterior paralysis and loss of conscious pain perception) spinal cord injury secondary to intervertebral disk rupture. To be enrolled in this double blind prospective study, dogs must:

1. Be between the ages of 1 and 10 years

2. Weigh less than 50 lb (22.7 kg)

3. Be free of concurrent life-threatening illnesses

4. Be presented to Iowa State University's veterinary neurology section within 72 hours of the onset of the posterior paralysis

5. Have a neurologically complete injury (i.e. a T3-L3 spinal cord lesion secondary to suspected intervertebral disk herniation resulting in paraplegia and absence of conscious pain perception in the hindlimbs)

Each dog will be evaluated with a thorough physical examination, a digitally recorded neurologic examination, a complete blood count, a serum chemistry profile, and a urinalysis. After this initial evaluation, each dog will be anesthetized, and an electrodiagnostic procedure called a somatosensory evoked response, which evaluates spinal cord integrity between the limbs and the brain, will be performed. After this procedure, an intravenous dose of either polyethylene glycol or a control solution of sterile saline will be administered in a random fashion to each study participant. Myelography and a hemilaminectomy and durotomy will then be performed. Four to six hours after the initial injection, another injection of the polyethylene glycol or the sterile saline will be given.

Postoperatively, digitally recorded neurologic examinations will be performed at three and seven days, and a repeat somatosensory evoked response procedure will be performed one week after surgery. Neurologic examinations will be repeated at six to eight weeks and six months after surgery. All study-related medical and surgical costs incurred for the dogs enrolled will be paid for by the study.