Does Dystonia Respond to Baclofen?

Scientists continue to unravel the mystery of complex regional pain syndrome (CRPS). CRPS is a condition that develops after surgery or some other type of trauma. The patient develops exquisite pain and/or tenderness usually of one extremity (arm or leg). Symptoms of sweating, hair growth, swelling, and changes in skin color and temperature develop in that extremity. Changes in nail growth and nail strength are also common symptoms of CRPS.

No one knows exactly what causes CRPS to develop — or why only certain people (usually women) are affected. There appears to be involvement of both the immune system and the nervous system. In one out of five patients affected by CRPS, an additional problem develops: dystonia. Dystonia is the abnormal movement of a body part. The patient experiences involuntary (not under their control) muscle contractions. The arm or leg twists, freezes into one position, or twitches repetitively.

In this study, researchers from the Department of Neurology at Leiden University Medical Center in The Netherlands used baclofen to treat the dystonia. Baclofen is a drug that has been used to reduce spasticity by stopping the messages that go from the muscles to the spine. The baclofen works by inhibiting the GABA receptors in the nervous system. The result is to prevent the release of neurotransmitters. Neurotransmitters are chemicals that send and receive signals between a neuron (nerve cell) and the rest of the body.

To test out the theory that baclofen might help with dystonia, 36 patients with CRPS-related dystonia received an injection of baclofen into the spinal cord. The authors were interested in finding out how much of a dose is needed to be effective and whether such a dose is safe. The baclofen was delivered through a pump into the subarachnoid space of the thoracic spine.

The subarachnoid space refers to an area between a layer of tissue that covers and protects the spinal cord and the spinal cord. Cerebrospinal fluid is contained within the space. The brain and spinal cord float in cerebrospinal fluid. The fluid is designed to act as a cushion or buffer for the nervous system.

From previous studies, the authors learned that continuous infusion of baclofen is needed to get the desired result. The patients were given the baclofen every day until the desired effect was reached. They started with 150 micrograms/day and gradually increased the dosage. This approach is called dose-escalation. If the patient developed side effects, the dose was lowered. The goal of any drug (including baclofen) is to obtain the maximum benefit with the least amount of adverse effects.

The pump used to deliver the baclofen was placed in the patient’s abdomen just under the skin. A thin tube called a catheter went from the device to the subarachnoid space in the midthoracic spine. A special X-ray called fluoroscopy was used to help guide the surgeon when putting the device in place. The catheter was put in the same place within the midthoracic subarachnoid space no matter where the patient was having pain/symptoms (arm or leg).

All patients in the study had tried an oral (pill taken by mouth) dose of baclofen but either got no benefit or had too many side effects to use it on a regular basis. Everyone had CRPS from an injury affecting at least one extremity. The majority (62 per cent) had CRPS of all arms and legs. Patients with CRPS-related dystonia from birth injuries and head trauma were not included. The programmable pump-catheter system was left in place and only removed if there were problems.

Every hour for five days, the patients filled out a form rating their pain, mobility, function, and limitations. Everyone was followed for 12 months. The severity of the dystonia was rated before and during treatment using a special tool called the Burke-Fahn-Marsden (BFM) dystonia rating scale. Other questionnaires were used to assess mobility, daily activities, and health-related quality of life. All this information gathered helped show that the treatment was very effective.

Safety was another concern measured by the type, severity, and number of adverse events. This included problems with the pump/catheter system, cerebrospinal fluid leakage, nausea, vomiting, headache, and difficulty sleeping. Many of these problems cleared up by stopping the drug temporarily or by lowering the dose.

There were a total of 89 problems counted in 26 patients. Most of the problems were related to the device. The catheter got kinked or blocked, pain developed around the pump or in the back, or some part of the pump/catheter system failed.

In a few cases, the drug seemed to help but then the patients got worse again. This was always caused by a catheter complication and could be reversed with a little trouble-shooting. Pump migration (movement of the pump) with failure of drug delivery was reported in two obese patients.

In a few cases, depression or psychosis developed but cleared up when the drug was stopped. There were three patients who developed an infection in the pocket where the device was implanted under the skin. In those cases, the pump had to be removed.

Only one patient did not respond to the baclofen. Everyone else seemed to get the maximum benefit using up to 450 micrograms of the drug. A beneficial response to the drug was observed within the first two days. Pain was reduced and function improved. Some patients who had to use a wheelchair before treatment could walk again. There were patients who could walk with a walker or cane before the study who could walk independently after getting the baclofen pump. And some who were bedfast could start using a wheelchair.

Maximum improvement seemed to occur after about three months. Smaller benefits were observed up to six months. After that, the changes seemed to stabilize. The improved ability to use the arm(s) or leg(s), changes in mobility and function, and reduced disability were clear indications that intrathecal baclofen is an effective treatment for CRPS-induced dystonia.

The authors conclude that although dose-escalation intrathecal baclofen is an effective way to treat dystonia, the high rate of complications is a major safety problem. More study is needed to improve the pump/catheter system. It may also be possible to select a more specific subgroup of patients who are less prone to problems.