Repetitive Transcranial Magnetic Stimulation in the treatment of Huntington’s Chorea

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Huntington’s disease (HD) is an autosomal dominant neurodegenerative illness characterized by disorders of movement, cognition, behavior, and functional capacity. In Huntington's disease (HD), the cerebral cortex is involved early in the disease process, and this region has been shown to have abnormal excitability characteristics prior to illness onset, as well as different long term potentiation. Repetitive Transcranial Magnetic Stimulation (rTMS) is a potential new treatment for depression, and other psychiatric disorders. Using TMS, circuits of the human motor cortex can be activated non-invasively, and because the excitability of neural circuits in the cerebral cortex is not static, repetitive TMS (rTMS) can produce changes in neurotransmission that outlast the period of stimulation. rTMS has been shown to modify excitability in the motor cortex in general, has been used extensively in the treatment of movements in Parkinson’s and other dyskinesias, and has positive preliminary findings in the treatment of Huntington’s chorea. The purpose of the study is twofold: to investigate the short term effects (up to 24 hours) of inhibitory rTMS on choreic movements as have been reported previously; and to seek to establish a lasting effect of rTMS in a double blind, randomized, sham-controlled study. Firstly, we intend to replicate previous work, using the standard protocol for decreasing excitability in the motor cortex (1Hz). This is also the “best practice” protocol in limited previous studies in this area. The hypothesis, based on previous findings, is that a group receiving rTMS treatment will experience a reduction in choreic movement rating scores when compared with their pre-treatment scores. In addition, the study will extend investigation by applying a complete treatment set of 6 sessions of real treatment, putatively sufficient to induce long term potentiation effects. If such effect is shown, then a sham crossover trial will be continued to compare real and sham effects. The hypothesis is that real rTMS stimulation will be more effective in its long term effect, than the sham form. The Statewide Department of Neurophysiology has experience in using rTMS in the treatment of depression. In addition, Dr Lee with the Huntington’s Study Group (HSG) at the Neurosciences Unit, Graylands Hospital has extensive experience with this patient population. Patients who attended that unit, who have choreic movements, and for whom the movements are especially intrusive or poorly controlled, will be offered the option of the rTMS trial. This is the rationale for an investigation that combines both fields in an assessment of rTMS as a treatment of choreic movements with Huntington’s disease.

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