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Repetitive Transcranial Magnetic Stimulation

Transcranial magnetic stimulation (TMS) is a non-invasive and painless method of stimulating neural activity within the corticospinal system (Tazoe and Perez, 2015). A coil is placed on the scalp over an area of interest (e.g. motor cortex) to generate an electromagnetic field, which alters electrical fields within the brain (Peterchev et al., 2012; Tazoe and Perez, 2015). Accordingly, this causes a change in neural membrane polarization, leading to an increase in neuron activity, transmission and activation of neural networks (Peterchev et al., 2012). This activity can be easily assessed using electromyographic recording electrodes to detect motor-evoked potentials (MEPs) – the output of the primary motor cortex (Tazoe and Perez, 2015). TMS may be applied as a single pulse or repetitively (rTMS) to elicit long-lasting significant improvements in aspects of sensory and motor function (Tazoe and Perez, 2015). The three main applications of rTMS in SCI are focused on improving sensory and motor function impairments, spasticity and neuropathic pain (Tazoe and Perez, 2015).

The methodological details and results from five TMS studies are listed in Table 16.

Table 16 Repetitive Transcranial Magnetic Interventions

Author Year

Country

Research Design

Score

Total Sample Size

MethodsOutcome
Tolmacheva et al. 2017

Finland

RCT

PEDro=9

N=5

Population: Mean age=48 yr; Gender: males=4, females=1; Time since injury: 3.8 yr; Level of injury: C3 – C7; Severity of injury: AISA A=0, B=1, C=3, D=1.

Intervention: Participants were randomized to receive four wk (16 sessions) of transcranial magnetic stimulation (TMS) with peripheral nerve stimulation (PNS) to one hand and PNS combined with sham TMS to the other hand. Outcome measures were evaluated before the first stimulation, after the last stimulation, and one month after the last stimulation session.

Outcome Measures: Daniels and Worthingham’s Muscle Testing scale.

1.     One month after the last stimulation session, a significant improvement was observed in the TMS/PNS group (p<0.0001).

2.     The improvement was significantly higher in TMS/PNS than PNS treated hands (p=0.046).

Gomes-Osman & Field-Fote 2014

USA

RCT

PEDro=6

N=21

Population: SCI Group (n=11): Mean Age: 46.7 yr; Gender: males=10, females=1; Severity of Injury: AIS C=5, AIS D=6.

Healthy Group (n=10): Mean Age: 33.7 yr; Gender: males=6, females=4.

Intervention: Patients and healthy volunteers were randomized to receive repetitive transcranial magnetic stimulation (rTMS) or sham-rTMS to the corticomotor region that controlled the weaker hand (trained hand). After 1 wk of treatment, the two groups were crossed over for an additional week. Both groups were asked to complete the Nine-hole Peg Test (9HPT) during each rTMS/sham-rTMS session and on days in between. The patients completed three sessions of each condition. Assessments were completed at baseline and at post treatment for each condition.

Outcome Measures: Jebsen-Taylor Hand Function Test (JTT), pinch strength, grasp strength, Nine-hole Peg Test (9HPT), motor threshold (MT).

1.     Improvements in JTT scores revealed large effect sizes for the rTMS condition (0.85) while the sham-rTMS condition yielded a smaller effect size (0.42).  Although both conditions demonstrated an improvement in time to complete the JTT but no significant differences were reported (p=0.4).

2.     Differences between the trained hand and non-trained hand approached statistical significance in time to complete the JTT (p=0.06).

3.     No significant differences were found for grasp strength and pinch strength between the two conditions from baseline to post treatment although the rTMS condition produced a larger effect size in grasp strength on the trained hand (0.67) compared to the sham-rTMS condition (0.39).

4.     Performance on the 9HPT improved significantly, regardless of condition, for the SCI group and the healthy group during the first six days of treatment (p<0.0006 and p=0.05 respectively).

5.     Resting and active MT did not differ significantly between rTMS and sham-rTMS for both the SCI group and the healthy group at post treatment.

Effect Sizes: Forest plot of standardized mean differences (SMD±95%C.I.) as calculated from pre- and post-intervention data.

Bunday et al. 2018

USA

PCT

N=31

 

Population: Intervention (n=17): Mean age=47.5±12.3 yr; Gender: males=13, females=4; Time since injury: 6.8 yr; Level of injury: C3 – C8; Severity of injury: AISA A=2, B=0, C=11, D=4.

Control (n=14): Mean age=40.9±12.3 yr; Gender: males=8, females=6.

Intervention: Participants received paired corticospinal-motor neural stimulation (PCMS) with transcranial magnetic stimulation (TMS) over the hand representation of the primary motor cortex, timed to arrive at corticospinal-motorneuronal synapses of the first dorsal interosseous (FDI) muscle 1-2 ms before antidromic potentials were elicited in motorneurons by electrical stimulation of the ulnar nerve (PCMS rest) or during small levels of isometric index finger abduction (PCMS active). Outcome measures elicited by TMS and electrical stimulation were measured in the FDI muscle before and after each protocol in participants with (n=17) and without (controls) (n=14) chronic cervical SCI.

Outcome Measures: Motor-evoked potentials (MEP).

1.     In control participants, MEPs elicited by TMS and electrical stimulation increased to a similar extent after both PCMS protocols for 30 min.

2.     In participants with SCI, MEPs elicited by TMS and electrical stimulation significantly increased after PCMS active versus PCMS rest (p=0.006).

3.     SCI patients that did not respond to PCMS rest responded after PCMS active.

4.     SCI patients that responded to both PCMS protocols, showed larger increments in corticospinal transmission after PCMS active.

Bunday et al. 2014

USA

Prospective Controlled Trial

N=43

Population: SCI population (n=23): Mean age: 51.9±11.8 yr; Gender: males=21, females=2; Level of injury: C2-C8=23; Severity of Injury: AIS-A=2, AIS-B=1, AIS-C-D=2.

Age matched controls (n=20): Mean age: 45±16.2 yr; Gender: males=8, females=12.

Intervention: Participants performed tasks requiring precision grip and index finger abduction while noninvasive cortical and cervicomedullary stimulation allowed motor evoked potentials (MEPs). The activity in intracortical and subcortical pathways were examined.

Outcome Measures: EMG activity, F-wave amplitude and persistence, Suppression of voluntary EMG by subthreshold TMS (svEMG).

1.     Significant effect of group (p=0.001) but not task (p=0.21) or interaction (p=0.19) on FDI mean rectified EMG activity.

2.     EMG activity increased in SCI patients taking baclofen (SCIBac) (p=0.001) and patients who never took baclofen (SCINo-Bac) (p=0.01) compared with controls; no significance between patient groups (p=0.95).

3.     Both SCI and control groups maintained similar EMG activity in the FDI muscle during precision grip and index finger abduction (p=0.21).

4.     During index finger abduction, controls (p=0.01), SCIBac (p<0.001) and SCINo-Bac (p=0.04) more EMG activity in FDI compared to APB at all Transcranial magnetic stimulation (TMS) intensities.

5.     Significant decrease in MEP size in controls (p<0.001) and SCIBac (p=0.001) during precision grip compared with index finger abduction.

 

6.     At increasing stimulus intensities, MEP sizes in control subjects were significantly larger than SCINo-Bac and SCIBac (p<0.001).

7.     FDI cervicomedullary MEPs decreased during precision grip compared with index finger abduction in controls (p<0.01) and SCIBac (p<0.01) but not SCINo-Bac (p=0.57).

8.     No effect of task, group or their interaction on F-wave amplitude or F-wave persistence (p>0.05).

9.     Significant effect of task (p<0.001), but not group (p=0.39) or their interaction (p=0.20) on svEMG.

10.   Significant decrease in svEMG area during precision grip compared with index finger abduction in controls (p=0.03), SCIBac (p=0.02) and SCINo-Bac (p=0.02).

Peterson et al. 2017

USA

PCT

N=17

Population: Intervention (n=5):  Mean age=26.6 yr; Gender: males=5; Time since injury: 5.8 yr; Level of injury: C3 – C5.

Control (n=12): Mean age=26.5±3.3 yr; Gender: males=9, females=3.

Intervention: Tetraplegic patients who underwent biceps transfer (n=5) to enable elbow extension were compared to healthy controls (n=12) to determine whether multi-joint arm posture affects corticomotor excitability of surgically transferred biceps similarly to non impaired biceps. Single-pulse transcranial magnetic stimulation (TMS) was delivered to the motor cortex with the arm in functional postures at rest in intervention and control groups.

Outcome Measures: Motor-evoked potential (MEP); Elbow extension.

1.     MEP amplitude was significantly greater in the transferred biceps relative to non impaired biceps in overhead reach

regardless of forearm orientation (p<0.001).

2.     Arms with greater overall corticomotor excitability generated significantly greater maximum moments during elbow extension (p=0.029), which may be beneficial for elbow extension strength.

Belci et al., 2004

UK

Pre-post

N=4

Population: Age: 41-54 yr; Gender: males=3, females=1; Level of injury: C5=4; Severity of injury: AIS D=4; Time since injury: 1.25-8 yr.

Intervention: Five days of sham repetitive transcranial magnetic stimulation (rTMS) followed by five days of therapeutic stimulation (rTMS).

Outcome Measures: ASIA Impairment Scale (AIS), Nine Hole Peg Board.

1.     No difference between patients when looking at the assessments done after baseline and after sham intervention.

2.     The level of intracortical inhibition was reduced to 37.5±8.0% of pre-treatment levels during the week of therapeutic treatment (p<0.05) and returned to 90.2±15% of pre-treatment levels during the follow-up period.

3.     This was linked to improvements in clinical measures of both motor and pinprick of 4-10% during treatment week. (p<0.05).

4.     Subjects also improved perceptual threshold to electrical stimulation of the skin and peg board test scores (p<0.05).

Discussion

A limited number of studies have investigated the use of TMS in patients with SCI. The overall magnitude of improvements in functional outcomes was mixed. Significant improvements in muscle strength and functional task testing were observed in the majority of studies. Although, one study reported no significant change from baseline, while others reported mixed results based on the functional test used (e.g. pinch versus grasp). This might be related to the broad range of different methodologies used (e.g. stimulation parameters and types of patients). Regardless of these findings, TMS may be a promising approach to facilitate aspects of recovery after SCI. For example, Peterson and colleagues investigated the application of TMS after elbow extension reconstructive surgery and found enhanced motor recovery/plasticity. In conclusion, further research in this area is necessary to investigate potential applications of TMS and their functional contribution to SCI rehabilitation. Future research should focus on evaluating ADL and FIM outcomes, as well as rTMS in combination with other therapies.

Conclusion

There is level 1b evidence (from one randomized controlled trial; Tolmacheva et al., 2017) that TMS combined with PNS significantly improves muscle function of the hand.

There is level 1b evidence (from one randomized control trial; Gomes-Osman & Field-Fote, 2014) that rTMS may reduce corticospinal inhibition and enhance clinical/functional outcomes for several weeks after treatment.

There is level 2 evidence (from two prospective controlled trialz; Bunday et al., 2018; Bunday et al., 2014) that PCMS applied during voluntary activity may enhance spinal plasticity after SCI.

There is level 2 evidence (from one prospective controlled trial; Peterson et al., 2017) that TMS delivered to the motor cortex after elbow extension reconstructive surgery significantly improves elbow extension.

There is level 4 evidence (from one pre-post study; Belci et al., 2004) that TMS may lower intracortical inhibition and improve clinical motor scores.

  • rTMS has many applications and may improve functional outcomes alone or in combination with PNS and reconstructive surgery.