Effects of Long-Term Paired Associative Stimulation on Strength of Leg Muscles and Walking in Chronic Tetraplegia: A Proof-of-Concept Pilot Study

Abstract

Recovery of lower-limb function after spinal cord injury (SCI) is dependent on the extent of remaining neural transmission in the corticospinal pathway. The aim of this proof-of-concept pilot study was to explore the effects of long-term paired associative stimulation (PAS) on leg muscle strength and walking in people with SCI. Five individuals with traumatic incomplete chronic tetraplegia (>34 months post-injury, motor incomplete, 3 females, mean age 60 years) with no contraindications to transcranial magnetic stimulation (TMS) received PAS to one or both legs for 2 months (28 sessions in total, 5 times a week for the first 2 weeks and 3 times a week thereafter). The participants were evaluated with the Manual Muscle Test (MMT), AIS motor and sensory examination, Modified Asworth Scale (MAS), and the Spinal Cord Independence Measure (SCIM) prior to the intervention, after 1 and 2 months of PAS, and after a 1-month follow-up. The study was registered at clinicaltrials.gov (NCT03459885). During the intervention, MMT scores and AIS motor scores increased significantly (p = 0.014 and p = 0.033, respectively). Improvements were stable in follow-up. AIS sensory scores, MAS, and SCIM were not modified significantly. MMT score prior to intervention was a good predictor of changes in walking speed (R 2 adj = 0.962). The results of this proof-of-concept pilot study justify a larger trial on the effect of long-term PAS on leg muscle strength and walking in people with chronic incomplete SCI.

Enabling and promoting walking rehabilitation by paired associative stimulation after incomplete paraplegia: a case report

“…Since only one leg was stimulated, we could stimulate all four major nerves (Table 1). In our recent work in tetraplegic patients where both lower limbs were stimulated [14], we selected the weakest nerves, limiting the number of stimulated nerves to six (and thus stimulation time to 2 h). We have recently shown in healthy subjects that administering the same amount of pulses but reducing the stimulation time to half results in weaker MEP potentiation and is therefore most probably not optimal for patients [17].…”

“…For TMS, we defined hotspots in the primary motor cortex (M1) for abductor hallucis (AH), extensor digitorum brevis (EDB), vastus medialis (VM), and gluteus maximus (GM) muscles [14]. Mapping at the suprathreshold intensity was started at the presumed anatomical location of the representation of these muscles.…”

“…TMS of AH hotspot was paired with PNS of the tibial nerve, EDB with peroneal nerve, VM with femoral nerve, and GM with gluteal nerve according to the innervation of these muscles (Table 1 ) to obtain coverage of all major muscle groups of the lower limb. PNS consisted of trains of six 1-ms pulses delivered at 100 Hz [ 12 – 14 ]. For the gluteal nerve stimulation, the electrode placement was determined by an anatomical landmark centered at the ischial tuberosity [ 14 ]; a tape roll (45 × 25 mm) was attached on top of the electrodes and the patient sat on it, thus pressing the electrodes toward the nerve (see [ 14 ]).…”

“…PNS consisted of trains of six 1-ms pulses delivered at 100 Hz [ 12 – 14 ]. For the gluteal nerve stimulation, the electrode placement was determined by an anatomical landmark centered at the ischial tuberosity [ 14 ]; a tape roll (45 × 25 mm) was attached on top of the electrodes and the patient sat on it, thus pressing the electrodes toward the nerve (see [ 14 ]). For the femoral nerve stimulation, the electrodes were placed at the crossing of the inguinal crease and femoral artery; the electrodes were slightly pressed manually to ensure that the stimulation reached the nerve.…”

“…We have reported altogether 18 patients with chronic incomplete SCI. The patients have benefited from this version of PAS and have gained increased independence and better motor function of upper or lower limbs [ 7 , 11 – 14 ], including the clinically beneficial effect of PAS on lower limb function in incomplete tetraplegic patients [ 14 ]. No reports on the effect of PAS on walking of paraplegic patients exist.…”