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Baclofen, an agonist of γ-amino butyric acid, is one of the most effective drugs in the treatment of spastic movement disorders. However, higher oral dosages required for sufficient spasticity control are related to intolerable central side effects. In this situation, continuous intrathecal application of baclofen in microgram dosages has proved its efficacy in numerous series of patients with spasticity of cerebral or spinal origin.1–,3 Nevertheless, the use of intrathecally administered baclofen in amyotrophic lateral sclerosis, representing the most common degenerative motor neuron disease in adult life,4 has been mentioned in only one short communication.5 In this context our experience with intrathecal baclofen therapy is worth presenting. These two patients are the only ones we have treated in this manner and both experienced a marked improvement in their quality of life.
Patient 1, a 25 year old man, was previously reported in brief 5; he is still alive and benefiting from intrathecal baclofen therapy. Five years ago he noticed progressive gait disturbance, weakness of his right foot, and painful nocturnal cramps in his legs. At that time he exhibited neurologically mild pareses of his right hand and foot, generalised fasciculations, and spasticity. Amyotrophic lateral sclerosis was diagnosed and oral antispastic treatment with baclofen and memantine was started. The patient remained ambulatory but an increase in spasticity due to the underlying disease required subsequent increases in dosage of baclofen. After 1 year a daily dose of 80 mg baclofen was reached but spasticity was no longer ameliorated. The patient was still able to walk a few steps with help but had to use a wheelchair otherwise. Furthermore, he complained of central side effects, such as weakness, daytime fatigue, and sleepiness. Intrathecal baclofen therapy was started, and at a daily dose of 160 μg the patient showed only minimal clinical signs of spasticity. He was able to walk at large without help and could even climb stairs. Spasticity increased during the next 21 months; however, by adjustment of the daily dosage up to 540 μg the patient remained able to walk without additional devices and was capable of caring for himself. Then increasing pareses due to progression of amyotrophic lateral sclerosis came into prominence, and the patient is tetraparetic to a high degree depending on special care. Attempts to reduce baclofen dosage led to a significant increase in spasticity and painful muscle cramps, resulting in substantial discomfort. Thus a daily dose of 540 μg baclofen was maintained.
Due to bulbar involvement the patient was supplied with a nasofacial mask for non-invasive intermittent ventilation to alleviate symptoms of nocturnal hypoventilation. He has been followed up now for 49 months, and no complications related to intrathecal baclofen therapy have been seen.
Patient 2, a 39 year old man, experienced progressive stiffness and weakness of his legs 2 years ago. Amyotrophic lateral sclerosis was diagnosed, and medical treatment consisting of riluzole and baclofen was started. Initially the patient remained ambulatory for 6 months but then he rapidly developed a severe spastic tetraparesis. He was able to stand with help, but confined to a wheelchair otherwise and completely in need of care. The major sources of discomfort were frequent nocturnal pain attacks due to uncontrolled spasms and central side effects related to oral baclofen medication. Intrathecal baclofen therapy was initiated, and at a daily dose of 80 μg painful spasms stopped despite preservation of some spasticity on purpose for support and improvement in general ease of care.
None the less, quality of life was improved considerably as the patient was able to sleep the night through. Further progress of disease resulted in rapid development of complete tetraplegia and respiratory insufficiency necessitated the use of non-invasive intermittent ventilation. Recently the patient died after 25 months of follow up. No complications related to intrathecal baclofen therapy had occurred.
Amyotrophic lateral sclerosis is a degenerative motor neuron disease characterised by severe movement disorders. Although progressive pareses result in increasing debilitation of the patient and finally death due to respiratory insufficiency, spasticity and painful muscle cramps are disabling symptoms markedly reducing the patients's quality of life. As the aetiopathogenesis of amyotrophic lateral sclerosis remains unresolved and no causative therapy is available prognosis is poor, demanding optimal palliative treatment. As with all other palliative measures, the primary goal is improvement of quality of life rather than life prolongation. 4 Thus, symptomatic treatment comprises a diverse range of medical and physical measures aiming at relieving the specific symptoms of the patient at any point in the continuous progression of the disease. This includes the administration of antispastic agents. Several antispastic drugs such as baclofen, memantine, or benzodiazepines can effectively relieve spasticity but their use is restricted when the maximum daily dose is reached and side effects occur. Due to the drug's limited ability to penetrate the blood-brain barrier and to reach its site of action this is generally the situation with baclofen when an oral daily dose of 80 mg is exceeded. Continuous intrathecal administration of baclofen produces CSF concentrations that are 10 times higher than those achieved with oral administration even though the amounts infused are 100 times less than those taken orally. Thus intrathecal infusion simultaneously increases the effect of baclofen on spasms and reduces the incidence of side effects.
Despite its widespread use and proved efficacy in numerous series of patients with spasticity of cerebral or spinal origin, this form of treatment has not been mentioned in regard to amyotrophic lateral sclerosis apart from one short communication. 5 However, as patients with amyotrophic lateral sclerosis need adequate palliative treatment more than anything else 4 the intrathecal application of baclofen offers the maintenance of a functional status for a prolonged period of time and an appreciable improvement in quality of life. It is a marked reduction of disabling spasticity that helps to achieve these goals and not the influence on prevalent muscle weakness. Our clinical findings show that even in the terminal phase of the disease the patients still benefit by relief of painful spasms, making immobility more tolerable. This form of palliative treatment has proved to be a safe procedure without substantial risks.