Transcranial magnetic stimulation in mild to severe hemiparesis early after stroke: a proof of principle and novel approach to improve motor function

Abstract

Low-frequency repetitive transcranial magnetic stimulation (rTMS) of the unaffected hemisphere can enhance function of the paretic hand in patients with mild motor impairment. Effects of low-frequency rTMS to the contralesional motor cortex at an early stage of mild to severe hemiparesis after stroke are unknown. In this pilot, randomized, double-blind clinical trial we compared the effects of low-frequency rTMS or sham rTMS as add-on therapies to outpatient customary rehabilitation, in 30 patients within 5–45 days after ischemic stroke, and mild to severe hand paresis. The primary feasibility outcome was compliance with the interventions. The primary safety outcome was the proportion of intervention-related adverse events. Performance of the paretic hand in the Jebsen–Taylor test and pinch strength were secondary outcomes. Outcomes were assessed at baseline, after ten sessions of treatment administered over 2 weeks and at 1 month after end of treatment. Baseline clinical features were comparable across groups. For the primary feasibility outcome, compliance with treatment was 100% in the active group and 94% in the sham group. There were no serious intervention-related adverse events. There were significant improvements in performance in the Jebsen–Taylor test (mean, 12.3% 1 month after treatment) and pinch force (mean, 0.5 Newtons) in the active group, but not in the sham group. Low-frequency rTMS to the contralesional motor cortex early after stroke is feasible, safe and potentially effective to improve function of the paretic hand, in patients with mild to severe hemiparesis. These promising results will be valuable to design larger randomized clinical trials.

Combined motor cortex and spinal cord neuromodulation promotes corticospinal system functional and structural plasticity and motor function after injury

“…Neural activation approaches can overcome this limitation and promote function by relying less on active movement production and more on motor systems stimulation. M1 electrical stimulation intends to promote “top down” voluntary control mediated by the corticospinal system both in animal (Adkins et al, 2006; Carmel et al, 2010; Carmel et al, 2014; Kleim et al, 2003) and human (Conforto et al, 2012; Di Lazzaro et al, 2013; Huang et al, 2005; Nouri and Cramer, 2011) models. After pyramidal tract lesion (PTX), stimulation of the intact M1 in rats promotes spared CST axon sprouting (Brus-Ramer et al, 2007; Carmel et al, 2013; Carmel et al, 2014) and restores voluntary motor function (Carmel et al, 2010; Carmel et al, 2014).…”

Invasive Neurostimulation in Stroke Rehabilitation

“…Our speculation aligns with the success of noninvasive cortical stimulation that is less focal. Using transcranial magnetic stimulation (TMS) [31], or transcranial direct current stimulation (tDCS), as in Bolognini et al [32], or in our ongoing study [33], a>5-point gain in Fugl-Meyer assessment is noted within a few weeks. Thus, it is important to realize the perfect balance between focality and potency of stimulation, as well as the drawbacks of the surgical process itself, which can take a toll on patients' function, attenuating gains in rehabilitation.…”

Noninvasive brain stimulation in neurorehabilitation

“…Repeated application over several days (Fregni et al, 2006; Boggio et al, 2007; Kirton et al, 2008; Khedr et al, 2009; Emara et al, 2010; Kakuda et al, 2010a, b, 2012; Nair et al, 2011; Sasaki et al, 2011; Avenanti et al, 2012; Conforto et al, 2012), alone or in combination with motor training protocols (Takeuchi et al, 2008, 2009; Emara et al, 2010; Kakuda et al, 2010a, b, 2012; Nair et al, 2011; Avenanti et al, 2012), produces lasting effects on hand motor function. Some of these studies reported improvements maintained for up to 1–2 weeks (Fregni et al, 2006; Boggio et al, 2007; Takeuchi et al, 2008), 1 month (Conforto et al, 2012; Kakuda et al, 2012), and 3 months (Khedr et al, 2009; Emara et al, 2010) after the end of interventions.…”

“…Some of these studies reported improvements maintained for up to 1–2 weeks (Fregni et al, 2006; Boggio et al, 2007; Takeuchi et al, 2008), 1 month (Conforto et al, 2012; Kakuda et al, 2012), and 3 months (Khedr et al, 2009; Emara et al, 2010) after the end of interventions. In one report, however, Talelli and colleagues (2007) did not find beneficial effects of application of cTBS.…”

“…Although the majority of these studies tested chronic stroke patients (>6 months after stroke), inhibitory 1-Hz rTMS also appears to influence motor function in patients tested less than 6 months after stroke (Liepert et al, 2007; Di Lazzaro et al, 2008; Nowak et al, 2008; Khedr et al, 2009; Grefkes et al, 2010; Conforto et al, 2012). In patients with moderate to severe motor impairment of the affected hand, Conforto and associates (2012) showed improvement of the Jebsen–Taylor test (mean 12.3% 1 month after treatment) and pinch force (mean 0.5 N) in the real NIBS group, but not in the sham group.…”