Neurophysiological differentiation of upper motor neuron damage in neurodegenerative disorders

Abstract

Objective: Using transcranial magnetic stimulation (TMS) to delineate upper motor neuron (UMN) signs of two neurodegenerative disorders: amyotrophic lateral sclerosis (ALS) and multiple system atrophy (MSA).

Methods: Medical records including clinical signs for UMN damage and TMS results were reviewed retrospectively. The UMN signs were classified into none, mild, and severe based on neurological examination of various reflexes. Then TMS-elicited motor evoked potentials (MEPs) were recorded from a hand and a leg muscle to calculate the central motor conduction time (CMCT), which represents fast, mono-synaptic conduction along the corticospinal tract. Relations between the UMN signs and CMCT were analysed for the two diseases.

Results: Prevalence and severity of the UMN signs for ALS and MSA were comparable for both upper and lower limbs. However, abnormality in CMCT was found more frequently in ALS: CMCT abnormalities were found in upper limbs for 44% in ALS patients but only for 7% in MSA patients; CMCT abnormalities in lower limbs were 55% in ALS and 20% in MSA. Some ALS patients showed abnormal CMCT in limbs without UMN signs, which was not true for most MSA patients.

Conclusions: The abnormalities of CMCT were different in ALS and MSA, even for those who clinically had similar UMN signs. Sometimes, CMCT can reveal UMN damage in the absence of clinical UMN signs. Differences presumably derive from selective degeneration of different fibres in the motor descending pathways. Longitudinal studies must be conducted to accumulate neuroimaging and pathological findings.

Significance: CMCT can be useful to differentiate ALS and MSA.

Keywords: AH, Abductor halluces; ALS, Amyotrophic lateral sclerosis; ANOVA, analysis of variance; APB, Abductor pollicis brevis; Amyotrophic lateral sclerosis; CMAP, compound muscle action potential; CMCT, central motor conduction time; Central motor conduction time; EMG, electromyography; FDI, first dorsal interosseous; LMN, lower motor neuron; M1, primary motor area; MEP, motor evoked potential; MSA, multiple system atrophy; Motor evoked potential; Multiple system atrophy; Neurophysiology; Pyramidal tract; TA, tibialis anterior; TMS, transcranial magnetic stimulation; UMN, upper motor neuron.

Fig. 1

Histograms for UMN signs of the upper (A) and lower limb (B). Numbers of limbs are presented according to disease (ALS or MSA) and severity in the UMN for the upper limb (A) and lower limb (B).

Fig. 2

Histograms for results of CMCT. Numbers of limbs are presented according to disease (ALS or MSA) and results of the CMCT testing for the upper limb (A) and lower limb (B).

Fig. 3

Relation between CMCT and UMN sign. CMCT values are shown according to disease (ALS and MSA) and UMN sign (none, mild, and severe). Each dot represents a limb: (A) FDI-CMCT, (B) TA-CMCT.