Action of 5 Hz repetitive transcranial magnetic stimulation on sensory, motor and autonomic function in human spinal cord injury

Abstract

Objective

To assess the effectiveness of physiological outcome measures in detecting functional change in the degree of impairment of spinal cord injury (SCI) following repetitive transcranial magnetic stimulation (rTMS) of the sensorimotor cortex.

Methods

Subjects with complete or incomplete cervical (or T1) SCI received real and sham rTMS in a randomised placebo-controlled single-blinded cross-over trial. rTMS at sub-threshold intensity for upper-limb muscles was applied (5 Hz, 900 stimuli) on 5 consecutive days. Assessments made before and for 2 weeks after treatment comprised the ASIA (American Spinal Injuries Association) impairment scale (AIS), the Action Research Arm Test (ARAT), a peg-board test, electrical perceptual test (EPT), motor evoked potentials, cortical silent period, cardiovascular and sympathetic skin responses.

Results

There were no significant differences in AIS outcomes between real and sham rTMS. The ARAT was increased at 1 h after real rTMS compared to baseline. Active motor threshold for the most caudally innervated hand muscle was increased at 72 and 120 h compared to baseline. Persistent reductions in EPT to rTMS occurred in two individuals.

Conclusions

Changes in cortical motor threshold measures may accompany functional gains to rTMS in SCI subjects.

Significance

Electrophysiological measures may provide a useful adjunct to ASIA impairment scales.

Introduction

The ability to detect physiological change associated with rehabilitation or treatments to effect axonal regeneration in spinal cord injury (SCI) will be challenging using the widely employed American Spinal Injuries Association (ASIA) impairment scales (AIS) for sensory and motor function (ASIA, 2002, Marino et al., 2003). Despite many revisions to the AIS standard neurological assessment there remains a perceived need for more sensitive, quantitative and objective outcome measures. The aim of this study (Stage 2 of the ISRT Clinical Initiative) was to examine the ability of identified physiological tests (Ellaway et al., 2004) to reveal functional improvements in SCI and compare them with AIS measures. As an intervention that was expected to improve functional outcome, repetitive transcranial magnetic stimulation (rTMS) was applied to the motor cortex in stable (chronic) SCI subjects who were at least >1 year post-injury (see Fawcett et al., 2007). rTMS induces short lasting modulation of cortical circuitry (Pascual-Leone et al., 1994b) that tends to produce depression of corticospinal output at low frequencies (<1 Hz) (Chen and Seitz, 2001) and facilitation at higher frequencies (>5 Hz) (Peinemann et al., 2004), although the effects appear inconsistent and depend upon stimulation parameters other than frequency (Fitzgerald et al., 2006, Hiscock et al., 2008, Rothkegel et al., 2010).

rTMS has been used extensively as a potential therapeutic intervention in neurological disorders including motor conditions, such as stroke (Fregni et al., 2006, Talelli et al., 2007), spasticity in multiple sclerosis (Centonze et al., 2007) and Parkinson’s disease (Pascual-Leone et al., 1994a, Siebner et al., 2000) with some short term but inconsistent (Ghabra et al., 1999) functional improvements (for review, see Ridding and Rothwell, 2007). Application of rTMS in spinal cord injury has produced inconsistent results regarding amelioration of pain (Defrin et al., 2007, Kang et al., 2009). Belci et al. (2004) examined somatomotor functional recovery in SCI and showed a short term reduction in cortical inhibition during treatment with improved AIS measures of sensory and motor function and improved hand function that lasted into a recovery period. Reductions in spasticity have also been reported in SCI with the effect outlasting the period of rTMS application (Kumru et al., 2010).