Repetitive transcranial magnetic stimulation for ALS

Abstract

Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease affecting upper and lower motor neurons characterized by progressive weakness, respiratory failure and death within 3-5 years. It has been proposed that glutamate-related excitotoxicity may promote motor neuron death in ALS. Glutamatergic circuits of the human motor cortex can be activated noninvasively using transcranial magnetic stimulation (TMS) of the brain, and repetitive TMS (rTMS) can produce changes in neurotransmission that outlast the period of stimulation. In recent years a remarkable number of papers about the potential effects of rTMS in several neurological disorders including ALS has been published. Preliminary studies have shown that rTMS of the motor cortex, at frequencies that decrease cortical excitability, causes a slight slowing in the progression rate of ALS, suggesting that these effects might be related to a diminution of glutamate-driven excitotoxicity. RTMS could also interfere with motor neuron death through different mechanisms: rTMS could modulate the production of brain-derived neurotrophic factor (BDNF), a potent survival factor for neurons, that in turn might represent a promoter of motor neuron sparing in ALS. Despite some promising preliminary data, recent studies have demonstrated a lack of significant long-term beneficial effects of rTMS on neurological deterioration in ALS. However, further studies are warranted to evaluate the potential efficacy of different protocols of motor cortex stimulation (in terms of technique, duration and frequency of stimulation), particularly during the early stages of the disease when the progression rate is more pronounced.