Spasticity, in multiple sclerosis

Metz L and Page S (2003). Oral cannabinoid for spasticity in multiple sclerosis Will attitude continue to limit use Lancet, 362, 1513. 

Cutter, N.C., Scott, D.D., Johnson, J.C., and Whiteneck, G. (2000) Gabapentin effect on spasticity in multiple sclerosis a placebo-controlled, randomized trial. Arch Phys Med Rehabil 81 164-169. 

It is mainly used in the treatment of spasticity in multiple sclerosis, spastic spinal paralysis etc. It is also used in the treatment of trigeminal neuralgia. 

Rudick RA, Breton D, KraU RL. The GABA-agonist progabide for spasticity in multiple sclerosis. Arch Neurol 1987 44(10) 1033-6. 

Rinne UK. Tizanidine treatment of spasticity in multiple sclerosis and chronic myelopathy. Curr Ther Res 1980 28 827. 

This pharmacological evidence obtained in animal models has provided solid experimental support to previous anecdotal, uncontrolled, or prechnical data that suggested a beneficial effect for marijuana when smoked by multiple sclerosis patients to alleviate such symptoms as spasticity, dystonia, tremor, ataxia, and pain (for a review, see Consroe, 1998). In this hne, a clinical trial has recently finalized in the U.K. using oral administration of placebo, cannabis extract, or A -THC in a population of 667 patients with stable multiple sclerosis and muscle spasticity. The results of this trial have suggested that cannabinoids did not have a beneficial effect on spasticity in multiple sclerosis patients but increased the patient s perception of improvement of other signs including pain (Zajicek et al., 2003). 

Baclofen is a GABA agonist at GABA B receptors and it has a presynaptic inhibitory function by reducing calcium influx. Its indication is increased extensor tone and clonus. Intrathecal administration may control severe spasticity pain. It is used for the treatment of spastic movement, especially in instances of spinal cord injury, spastic diplegia, multiple sclerosis and amyotrophic lateral sclerosis. Its central nervous system effects include drowsiness, somnolence and seizure activity in epileptic patients. 

Benzodiazepines also possess muscle relaxant activity. Their pharmacology is discussed in Chapter 30. Diazepam Valium) has been used for control of flexor and extensor spasms, spinal spasticity, and multiple sclerosis. The muscle relaxant effect of the benzodiazepines may be mediated by an action on the primary afferents in the spinal cord, resulting in an increased level of presynaptic inhibition of muscle tone. Polysynaptic reflexes are inhibited. The most troublesome side effect is drowsiness, which is dose dependent. Tolerance to both the therapeutic effects and the side effects develops. 

Lapierre Y, Bouchard S, Tansey C, Gendron D, Barkas WJ, Francis GS. Treatment of spasticity with tizanidine in multiple sclerosis. Can 1 Neurol Sci 1987 14(Suppl 3) 513-17. 

Spasticity is a common symptom in multiple sclerosis. It is defined as an increase in muscle tone characterized by initial resistance to passive movement followed by sudden relaxation. Spasticity can be treated with a number of drugs. 

Other drugs for different spasticities include baclofen (this chapter, earlier), which is useful in multiple sclerosis and spinal cord trauma but not rheumatoid conditions the centrally acting orphenadrine (Chapter 8, Fig. 8-4) for Parkinson-like symptoms and the BZDs, particularly diazepam (considered later). 

Currently, baclofen is the only clinically used GAB Ab receptor agonist. It is used as a muscle relaxant for treatment of spasticity in spinal injury and multiple sclerosis. The cloning of GABAb receptors has renewed the interest in the search for more selective diugs and novel therapeutic indications. 

There have been a number of studies to evaluate the therapeutic effect of carmabinoids against spastic disorders, including multiple sclerosis and spinal cord injury. For example, a randomised placebo-controlled trial in more than... 

Baker D, Pryce G, Croxford JL. Cannabinoids control spasticity and tremor in a multiple sclerosis model. Nature 2000 404 84-87. 

Baker D, Pryce G, Croxford JL, Brown P, Pertwee RG, Makriyannis A, Khanolkar A, Layward L, Fezza F, Bisogno T, Di Marzo V. Endocanna-binoids control spasticity in a multiple sclerosis model. FASEB J 2001 15 300-302. 

Skeletal muscle relaxants may be nsed for relief of spasticity in nenromnscular diseases, snch as multiple sclerosis, as well as for spinal cord injnry and stroke. They may also be used for pain relief in minor strain injnries and control of the mnscle symptoms of tetanus. Dantrolene (Dantrium) has been nsed to prevent or treat malignant hyperthermia in surgery. 

Oral - For the control of clinical spasticity resulting from upper motor neuron disorders such as spinal cord injury, stroke, cerebral palsy, or multiple sclerosis. It is of particular benefit to the patient whose functional rehabilitation has been retarded by the sequelae of spasticity. Such patients must have presumably reversible spasticity where relief of spasticity will aid in restoring residual function. 

P. Jobin, et al. Efficacy, safety and tolerability of an orally administered cannabis extract in the treatment of spasticity in patients with multiple sclerosis a randomized, double-blind, placebo-controlled, crossover study. 

Luo, J., J. H. Yin, H. Z. Wu, and Q. Wei. Extract from Fructus cannabis activating calcineurin improved learning and memory in mice with chemical drug-induced dysmnesia. Acta Pharmacol Sin 2003 24(11) 1137-1142. Degenhardt, L., W. Hall, and M. Lynskey. Exploring the association between cannabis use and depression. Addiction 2003 98(11) 1493-1504. Zajicek, J., P. Pox, H. Sanders, et al. Cannabinoids for treatment of spasticity and other symptoms related to multiple sclerosis (CAMS study) multicentre randomised placebo-controlled trial. Lancet 2003 362(9395) 1517-1526. 

The safety and efficacy of gabapentin as adjunctive therapy to CBZ and/or phenytoin has been assessed in adults, adolescents (Bruni, 1998), and children (Khur-ana et ah, 1996) with partial seizures. A decrease of 50% or more in frequency of complex partial -I- secondary generalized seizures was reported in 71% of patients on a mean maintenance dose of gabapentin of 1600 mg/day (Bruni, 1998). It has also been used in the treatment of spasticity in adolescents with multiple sclerosis (Cutter et al., 2000) and in adults and adolescents with neuropathic pain (Rosenberg et al.,... 

It is indicated in spasticity due to neurological disorders e.g., multiple sclerosis, chronic myelopathy, degenerative diseases of the spinal cord, cerebrovascular accidents and cerebral palsy painful muscle spasm associated with static and functional disorders of the spine (cervical and lumbar syndromes) painful muscle spasm following surgery e.g., for herniated intervertebral disc or for osteoarthritis of the hip. 

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