Muscle & nerve. Supplement最新文献

Botulinum toxin (BTX), a purified form of the neurotoxin responsible for botulism, is used worldwide for the treatment of abnormal muscle contractions. The ability of BTX to block acetylcholine release in a long-lasting but reversible fashion with few side effects has made it an important tool in a wide variety of neuromuscular disorders, including the dystonias, tremor, tics, and spasticity. There are seven antigenically distinct toxins. BTX-A has been in clinical use for almost two decades, with an outstanding efficacy and safety profile. Clinical effects are often seen within 1 week of injection, and benefits typically last from 3-6 months. Patient selection and the proper choice of dose and administration site are the most important determinants of a favorable response to BTX treatment.

Systemic pharmacologic treatments may be indicated in conditions in which the distribution of muscle overactivity is diffuse. Antispastic drugs act in the CNS either by suppression of excitation (glutamate) enhancement of inhibition (GABA, glycine), or a combination of the two. Only four drugs are currently approved by the US FDA as antispactic agents: baclofen, diazepam, dantrolene sodium, and tizanidine. However, there are a number of other drugs available with proven antispastic action. This chapter reviews the pharmacology, physiology of action, dosage, and results from controlled clinical trials on side effects, efficacy, and indications for 21 drugs in several categories. Categories reviewed include agents acting through the GABAergic system (baclofen, benzodiazepines, piracetam, progabide); drugs affecting ion flux (dantrolene sodium, lamotrigine, riluzole; drugs acting on monoamines (tizanidine, clonidine, thymoxamine, beta blockers, and cyproheptadine); drugs acting on excitatory amino acids (orphenadrine citrate); cannabinoids; inhibitory neuromediators; and other miscellaneous agents. The technique, advantages and limitations of intrathecal administration of baclofen, morphine, and midazolam are reviewed. Two consistent limitations appear throughout the controlled studies reviewed: the lack of quantitative and sensitive functional assessment and the lack of comparative trials between different agents. In the majority of trials in which meaningful functional assessment was included, the study drug failed to improve function, even though the antispastic action was significant. Placebo-controlled trials of virtually all major centrally acting antispastic agents have shown that sedation, reduction of global performance, and muscle weakness are frequent side effects. It appears preferable to use centrally acting drugs such as baclofen, tizanidine, and diazepam in spasticity of spinal origin (spinal cord injury and multiple sclerosis), whereas dantrolene sodium, due to its primarily peripheral mechanism of action, may be preferable in spasticity of cerebral origin (stroke and traumatic brain injury) where sensitivity to sedating effects is generally higher. Intrathecal administration of antispastic drugs has been used mainly in cases of muscle overactivity occurring primarily in the lower limbs in nonambulatory, severely disabled patients but new indications may emerge in spasticity of cerebral origin. Intrathecal therapy is an invasive procedure involving long-term implantation of a foreign device, and the potential disadvantages must be weighed against the level of disability in each patient and the resistance to other forms of antispastic therapy. In all forms of treatment of muscle overactivity, one must distinguish between two different goals of therapy: improvement of active function and improvement of hygiene and comfort. The risk of global performance reduction associated with general or regional administration of antispastic d

Stair navigation, particularly stair descent, is an extremely challenging and dangerous locomotor task, yet studies suggest that most elderly are unlikely to move to new residences in order to avoid this challenge. The knee and ankle are the key joints where adequate strength and power are required for safe stair descent, and it is not yet clear if sarcopenia in the elderly is likely to result in residual strength below that which is required for successful stair performance. Sensory cues are also critical, and the lack of literature on the specific roles of the various intrinsic and extrinsic factors that affect stair navigation is a clear indication of the need for such research in order to define safer strategies and optimal conditions for elderly individuals to transit between living areas of differing levels.