The Therapeutic Effect Of Low Frequency Repetitive Transcranial Magnetic Stimulation On Amyotrophic Lateral Sclerosis

Part One The change of resting motor threshold in patient with amyotrophic lateral sclerosisObjectives:The excite-toxic motor neuronal degeneration was proposed as a potential mechanism that underlies development of amyotrophic lateral sclerosis (ALS). The changes of resting motor threshold (RMT) in ALS over time were inconsistent in previous studies, which was an important parameter reflecting excitability of cortical motor neurons. In this study, we thoroughly investigated the RMT of ALS patients with different stages. Materials and methods:Forty-one patients with definite or probable ALS and 18 age-matched healthy volunteers were recruited. The RMT, compound muscle action potential (CMAP), motor evoked potential (MEP) recorded in abductor digiti minimi (ADMs) were investigated for each participant.Results:There was marked hemispheric difference of RMT of both sides in healthy subjects, with right RMT significantly lower than the left. Compared with control group, there was no significant change of RMT in patients with clinical probable or clinical probable-laboratory supported ALS, while the RMT level in patients with clinical definite ALS was significantly increased. Additionally, the RMT level detected in the right "asymptomatic" upper extremities was significantly lower than that of in control people, without significant reduction of CMAP amplitude of ADMs. However, the RMT detected in the right symptomatic upper extremities was significantly higher.Conclusion:The significant difference of RMT between two hemisphere of healthy volunteers indicated that the hemispheric difference of RMT level might be a physiological phenomenon. Moreover, the lower RMT in "asymptomatic" upper extremities of ALS patients confirmed that excitability of motor cortex was increased in very early ALS. Therefore, the hyper-excitability of cortical motor neurons might be an important target for treatment of ALS.Part Two The neurophysiologic difference of flail arm syndrome and amyotrophic lateral sclerosisObjectives:There are many clinical features of flail arm syndrome (FAS) that are different from amyotrophic lateral sclerosis (ALS), suggesting they are probably different entities. Studies on electrophysiological differences between them are limited at present, and still inconclusive. Therefore, we aimed to find clinical and neurophysiological differences between FAS and ALS patients.Materials and methods:Eighteen healthy control subjects, six FAS patients and forty-one ALS patients were recruited. The upper motor neuron signs (UMNS), split-hand index (SI), resting motor threshold (RMT), central motor conduction time (CMCT) were evaluated and compared.Results:There was no obvious upper motor neuron signs in FAS. The SI and RMT level in FAS were similar to control subjects, but significantly lower than that of in ALS. Compared with control group, the RMT and SI were both significantly increased to higher level. However, no significant difference of CMCT was found between any two of these three groups.Conclusion:The differences in clinical and neurophysiological findings between FAS and ALS, argue against they are the same disease entity. Since there was no obvious UMNS, no split-hand phenomenon, and no obvious changes of RMT and CMCT in FAS patients, the development of FAS might be probably not originated from motor cortex.Part Three The therapeutic effect of low frequency repetitive transcranial magnetic stimulation on amyotrophic lateral sclerosisObjectives:Cortical excitability can be decreased significantly by low frequency rTMS (repetitive transcranial magnetic stimulation). Since over-excitability of motor cortex is one of early neurophysiologic features of ALS, and excite-toxic effects on upper and lower motor neurons might be associated with development of ALS (amyotrophic lateral sclerosis), it might be helpful to relieve the disease progression by reduction of increased cortical motor excitability. This randomized controlled trial was aimed to investigate the effect of low frequency rTMS on the disease progression of ALS.Materials and methods:Twenty-four ALS patients were recruited, and were randomly allocated into control group or rTMS group. Patients in rTMS group were administrated with two 10 days of rTMS treatment (1Hz,110%RMT,1200 pulses/sites every day over cortical hand motor areas), while the control group received shame magnetic stimulation. The ALS functional rating scale (ALS-FRS), and activity of daily living scale (ADL) were examined before rTMS treatment (TO), and four months (T1) and eight months (T2) later. The scores of ALS-FRS and ADL of ALS patients were compared between these two groups using independent samples t-test (p<0.05 denoted significance).Results:The scores of ALS-FRS and ADL scale of patients in both groups were decreased progressively. The scores of ALS-FRS and ADL in control group were reduced from 42.4±1.1 (TO) to 39.6±1.0 (T1), then to 34.8±1.8 (T2), while those in rTMS group were reduced from 40.9±1.1 (TO) to 36.8±1.8 (T1), then to 30.2±2.6 (T2). However, there were no significant difference of changes of disease progression between these two groups.Conclusion:These results suggested that low frequency rTMS treatment might be not capable of slowing down the disease deterioration of ALS’patients.