Does recovery occur after spinal cord injury?

Many doctors tell patients and families that recovery does not occur after spinal cord injury. This is not true. Recovery is the rule, not the exception after spinal cord injury.

• Segmental recovery. Most patients recover 1-2 segments below the injury site, even after so-called “complete” spinal cord injuries. For example, a person with a C4/5 injury may have deltoid function on admission and then recover biceps (C5), wrist extensors (C6), and perhaps even triceps (C7) after several months, and the associated dermatomes.

• Recovery due to methylprednisolone. The second National Acute Spinal Cord Injury Study (NASCIS 2) showed that patients with “complete” spinal cord injuries and who did not receive the high-dose steroid methylprednisolone recovered on average 8% of motor function they had lost. If they received methylprednisolone within 8 hours after injury, they recovered on average 21% of what they had lost. In contrast, people with “incomplete” spinal cord injury recovered on average 59% of motor function and 75% if treated with high dose methylprednisolone.

• Recovery of postural reflexes. Most people with cervical or upper thoracic spinal cord injury are initially unable to control their trunk muscles. However, most will recover better trunk control over months or even years after injury.

• Walking quads and paras. Most people with “incomplete” spinal cord injuries, i.e. ASIA C, will recover standing or walking. Walking recovery after “complete” spinal cord injuries, i.e. ASIA A, are rare but can occur in 5% of the cases. In the 1980’s, less than 40% of spinal cord injuries admitted to hospital were “incomplete”. However, in the 1990’s, over 60% of spinal cord injuries are “incomplete” and thus the incidence of “walking quads” or “walking paras” may be higher than most people think.

Both animal and human studies indicate that as little as 10% of spinal cord tracts can support substantial function, including locomotion. People often can walk even though a tumor has damaged 90% of their spinal cord. This is due to the redundancy and plasticity of the spinal cord. Multiple spinal pathways serve similar or overlapping functions. Plasticity refers to the ability of axons to sprout and make new connections. Because transected spinal cords are rare, most people have some spinal axons crossing the injury site. This is the basis of the hope that even slight regeneration of the spinal cord will restore substantial function.

Experimental Therapies for Subacute Spinal Cord Injury

Several experimental therapies are being tested in clinical trial for spinal cord injury during the first days or weeks after injury.

• Monosialic ganglioside (GM1, Sygen). In 1991, Fred Geisler and colleagues reported that GM1 injected daily for 6 weeks after injury improve locomotor recovery 37 patients. Fidia Pharmaceutical subsequently tested this therapy in a large multicenter clinical trial in 800 patients, showing that the GM1 accelerated recovery during the first six weeks but did not significantly improve the extent of recovery at 6-12 months after injury. Note that this trial is no longer active. Although the drug is still available in Europe and South America, the company Fidia has been bought by another company. CareCure Forum (GM1) Link

• Activated macrophage transplants. In 1998, Michal Schwartz at the Weizmann Institute reported that activated macrophages obtained from blood and transplanted to the spinal cord improve functional recovery in rats. The company Proneuron initiated phase 1 clinical trials to assess feasibility and safety of macrophage transplants in human spinal cord injury. Preliminary reports suggest that the treatment is feasible and safe. All the patients had “complete” thoracic spinal cord injury and received macrophage transplants within 2 weeks after injury. Three of the 8 patients recovered from ASIA A to ASIA C, more than the expected 5%. A phase 1 clinical trial is continuing at Erasmus Hospital in Brussels, Belgium. A phase 2 trial is being planned in two U.S. centers including Craig Hospital in Denver (CO) and Mt. Sinai in New York City (NY). CareCure Forum (Macrophage) Link

• Alternating Current Electrical Stimulation. In 1999, Richard Borgens and colleagues at Purdue University reported that alternating currents applied to dog spinal cords stimulated regeneration and recovery of function in dogs with spinal cord injury. A clinical trial has commenced at Purdue University for people who are within 2 weeks after acute spinal cord injury. CareCure Forum (AC Stim) Link

• AIT-082 (Neotrofin). This is a guanosine analog that can be taken orally and reportedly increases neurotrophins or neural growth factors in the brain and spinal cord. Neotherapeutics tested this drug in patients with Alzheimer’s disease. They started a multicenter clinical trial at Ranchos Los Amigos in Downey (CA), Gaylord Hospital in Wallingford (CT), and Thomas Jefferson Hospital in Philadelphia. The treatment must be started within 2 weeks after spinal cord injury. CareCure Forum (AIT-082) Link

Experimental Therapies for Chronic Spinal Cord Injury

Several therapies are being tested in clinical trials for chronic spinal cord injury, i.e. people whose neurological recovery has stabilized one or more years after injury. Many other treatments are being considered for clinical trial (see article on Advances in Spinal Cord Injury Therapy 25 November 2002).

• 4-aminopyridine (4-AP). This drug is a small molecule that blocks fast voltage sensitive potassium channel blockers. The drug can be obtained by physician prescription from compounding pharmacies in the United States. In addition, Acorda Therapeutics is carrying out a multicenter phase 3 clinical trial of a sustained release formulation of the drug in people who are more than one and a half years after “incomplete” spinal cord injury. The drug may improve conduction of demyelinated axons in the spinal cord and preliminary clinical trial results suggest that the drug may reduce spasticity and improve motor or sensory function in as many as a third of people with chronic spinal cord injury. See CareCure Forum (4-AP) Link

• Fetal porcine stem cell transplants. Embryonic stem cells have attracted much attention. Several studies of human fetal cell transplants have been carried out in Sweden, Russia, and the United States, showing that transplanted fetal cells will engraft in human spinal cords. However, due in part of the lack of availability of adult human stem cells for transplantation and politics associated with the use of embryonic human stem cells, the first and only stem cell therapy trial for spinal cord injury in the United States used fetal stem cells from pigs. A phase 1 clinical trial at Washington University in St. Louis (MO) and Albany Medical Center in Albany (NY) has transplanted fetal stem obtained from pig fetuses and treated with antibodies to reduce the immune rejection. Sponsored by Diacrin, this trial is aiming to test 10 patients. See CareCure Forum (Diacrin) Link

• Olfactory ensheathing glial transplants. Olfactory ensheathing glia (OEG) reside in the olfactory nerve and the olfactory bulb. They are believed to be why the olfactory nerve continuously regenerates in adults. OEG cells are made in the nasal mucosa and migrate up the nerve to the olfactory bulb. Several laboratories have shown that OEG transplants facilitate regeneration of the spinal cord. Three clinical trials have started in Lisbon (Portugal), Brisbane (Australia), and Beijing (China). In Lisbon, they are transplanting nasal mucosa obtained from the patient into the spinal cord. In Brisbane, they are culturing OEG cells from nasal mucosa and transplanting the cells to the spinal cord. In Beijing, they are culturing OEG from human fetal olfactory bulbs and transplanting into the spinal cord. See CareCure Forum Link (Brisbane) and CareCure Forum Link (Beijing)

Summary

Spinal cord injury is devastating, not only for the injured person but for families and friends. While much information is available on Internet, most of the material is scattered and out of date. This article summarizes answers to some of the most frequently asked questions by people who are encountering spinal cord injury for the first time. Spinal cord injury disconnects the brain from the body. This leads not only to loss of sensation and motor control below the injury site but may be associated with abnormal activities of the spinal cord both above and below the injury site, resulting in spasticity, neuropathic pain, and autonomic dysreflexia. Many functions of our body that we take for granted, such as going to the bathroom, sexual function, blood pressure and heart rate, digestion, temperature control and sweating, and other autonomic functions may not only be lost but may be abnormally active. Finally, contrary to popular notions about spinal cord injury, recovery is the rule and not the exception in spinal cord injury. The recovery takes a long time and may be slowed down or blocked by the muscle atrophy and learned non-use. Finally, there is hope. Many therapies have been shown to regenerate and remyelinate the spinal cord. Some of these are now in clinical trials and many more should be in clinical trial soon.

Recovery and Treatment
Wise Young, MD, PhD