Transcranial magnetic stimulation (TMS): compared sensitivity of different motor response parameters in ALS

Abstract

Owing to the low sensitivity of clinical signs in assessing upper motor neuron (UMN) involvement in ALS, there is a need for investigative tools capable of detecting abnormal function of the pyramidal tract. Transcranial magnetic stimulation (TMS) may contribute to the diagnosis by reflecting a UMN dysfunction that is not clinically detectable. Several parameters for the motor responses to TMS can be evaluated with different levels of significance in healthy subjects compared with ALS patients. The central motor conduction time, however, is not sensitive in detecting subclinical UMN defects in individual ALS patients. The amplitude of the motor evoked potential (MEP), expressed as the percentage of the maximum wave, also has a low sensitivity. In some cases, the corticomotor threshold is decreased early in the disease course as a result of corticomotor neuron hyperexcitability induced by glutamate. Later, the threshold increases, indicating a loss of UMN. In our experience, a decreased silent period duration appears to be the most sensitive parameter when using motor TMS in ALS. TMS is also a sensitive technique for investigating the corticobulbar tract, which is difficult to study by other methods. TMS is a widely available, painless and safe technique with a good sensitivity that can visualize both corticospinal and corticobulbar tract abnormalities. The sensitivity can be improved further by taking into account the several MEP parameters, including latency and cortical silent period decreased duration.

Magnetic stimulation including the triple‐stimulation technique in amyotrophic lateral sclerosis

“…One of our most striking findings is that TMS was more sensitive than clinical examination in patients with suspected or possible ALS, revealing UMN dysfunction in 75% (9 of 12) of the upper limbs. The sensitivity of CMCT in supporting the diagnosis reportedly increases with the number of muscles studied, 10,12,14,35,38,40,47 and this may apply to the parameters studied herein. We believe that, as for electromyography, several regions of the body, including muscles innervated by bulbar nerves, should be tested to increase the sensitivity of TMS in supporting a diagnosis of ALS.…”

“…CMCT is reportedly not a sensitive variable for the diagnosis of ALS. 9,14,15,34,40,46,47 A decrease in SP duration 1,11,40,43,45 or an increase in RMT 47 seem to be sensitive variables for diagnosing ALS. By contrast, the amplitude of the MEP is not a reliable marker of UMN dysfunction; even in healthy subjects, MEPs are much smaller than the compound muscle action potentials (CMAPs) evoked by peripheral stimulation.…”

“…Transcranial magnetic stimulation (TMS) is a useful tool for diagnosing UMN dysfunction in ALS and provides a sensitive means of assessing cortical excitatory and inhibitory dysfunction. 10,12,14,35,38,40,47 The most frequently studied variables, which are generally recorded by conventional TMS using simple stimulation techniques, are central motor conduction time (CMCT), amplitude of motor evoked potentials (MEPs), resting motor threshold (RMT), and duration of silent period (SP). CMCT is reportedly not a sensitive variable for the diagnosis of ALS.…”

Changes in cortically induced inhibition in amyotrophic lateral sclerosis with time

“…Several studies showed that the silent period duration, which is a measure of the inhibitory response to TMS from many MUs, is shortened in ALS compared with normal control. 1,12,31,40 However, the silent period, which reflects both spinal and cortical inhibitory processes, is correlated with the size of the excitatory response. 2 The silent period decreases over time in relation to the loss of excitatory responses.…”

Amyotrophic lateral sclerosis: considerations on diagnostic criteria

“…Moreover, the atrophy of the motor cortex, with severe loss of grey substance (cell body) and its brain connections are highlighted by recent advances in radiology and proton emission through tomography (PET), which quantifies the metabolism of regional areas of motor cortex, associated with quantifying the volume by voxel, making early diagnoses possible 27 . Transcranial magnetic stimulation has become an auxiliary method for early diagnosis through the quantification of the decrease in speed within the motor central nervous system in patients with MND / ALS 28 . Pyramidal signs and muscle atrophy -Characteristically in ALS, the signals of pyramidal release must be present at sites above the sites where the muscular atrophy is evident.…”