Summary of identified studies using non-invasive brain stimulation techniques in ALS with the aim of prolonged neuromodulation62–68 70–73
Transcranial magnetic stimulation | |||||||||||
Study | Trial design | Subjects | Site | Protocol | Schedule | Sham | Riluzole | Inclusion criteria | Exclusion criteria | Outcome measures | Findings |
Di Lazzaro et al 66 | Pilot | 4 ALS | Bilateral motor cortex | 1 Hz or 20 Hz | Variable | None | 2 taking | Definite ALS | Not stated | Norris Scale, MRC | Well tolerated. Trend to slower progression in 1 Hz. |
Angelucci et al 67 | Cross-sectional | 4 ALS 10 healthy | Bilateral motor cortex | 1 Hz or 20 Hz | 8 days | None | Not stated | Definite ALS | Not stated | Serum BDNF | 20 Hz rTMS transiently reduces BDNF in ALS. 1 Hz reduces BDNF in controls but not ALS. |
Zanette et al 68 | RCT | 10 ALS 5 active 5 sham | Bilateral motor cortex | 5 Hz | 5 days per week/2 weeks | Sham coil | All | Probable/Definite ALS | Not stated | ALSFRS-R, MRC, grip strength, fatigue, QoL | No effect on ALSFRS-R and MRC. Improved grip strength and QoL at 1 week, not significant at 2 weeks. |
Di Lazzaro et al 62 | RCT | 20 ALS 10 active 10 sham | Bilateral motor cortex | cTBS | 5 days per month/12 months | Sham coil | All | Probable/Definite ALS, age >18 | TMS risk, severe medical condition | ALSFRS-R, MRC, AMT, CMCT | Active rTMS reduced rate of ALSFRS-R decline at 6 months, but insignificant at 12 months. No effect on AMT/CMCT. |
Di Lazzaro et al 63 | Pilot | 1 ALS | Bilateral motor cortex | cTBS | 5 days per month/26 months | None | All | Definite ALS | Not stated | ALSFRS-R, MEP, CMCT | Well tolerated. Both patients deteriorated. |
Munneke et al 64 | Cross-sectional | 10 ALS 10 healthy | Left motor cortex | cTBS | 5 days | None | All | Probable/Definite ALS, spinal onset within 6–36 months | Familial ALS, TMS risk | CMAP, MEP, RMT, SICI, ICF | rTMS reduces MEP amplitude and resting motor threshold in both patients with ALS and controls. |
Di Lazzaro et al 65 | Open-label | 3 ALS | Bilateral motor cortex | cTBS | 5 days per month/6 months | None | All | Completed 2009 trial | TMS risk, comorbidity | ALSFRS-R, respiratory failure, tracheostomy | Trend towards reduced rate of ALSFRS-R decline with rTMS. |
Ceccanti et al 70 | Cross-sectional | 24 ALS | Non-dominant motor cortex | 0.3 Hz | 2 days | None | Pre/Post riluzole | Probable/Definite ALS | Not stated | MEP, RMT, median nerve sensory threshold | Paired associative stimulation increases MEP amplitude in both patients with ALS and controls. Effect significantly reduced postriluzole. |
Transcranial direct current stimulation | |||||||||||
Study | Trial design | Subjects | Electrode montage | Protocol | Schedule | Sham | Riluzole | Inclusion criteria | Exclusion criteria | Outcome measures | Findings |
Quartarone et al 71 | Cross-sectional | 8 ALS 8 healthy | L motor cortex, R frontal | 1 mA anodal/cathodal | 2×7 min 1 week apart | None | 1 taking | Definite ALS | MEP not elicited | MEP, RMT, AMT, SICI, ICF | After-effects of both anodal and cathodal tDCS seen in controls but not in ALS. |
Munneke et al 72 | Cross-sectional | 10 ALS 10 healthy | L motor cortex, R frontal | 1 mA cathodal | 3× (7,11 or 15 min) 1 week apart | None | All | Probable ALS | Not stated | MEP, motor threshold, SICI, ICF | tDCS reduces MEP amplitude in controls but not ALS. |
Madhavan et al 73 | Pilot | 1 ALS | L motor cortex, R frontal | 2 mA anodal/cathodal/sham | 12×20 min over 4 weeks | 30 s ramp | Not stated | Not stated | Not stated | Muscle strength, ALSFRS-R, MEP | No significant effects. MEP could not be evoked before or after stimulation. |
ALS, amyotrophic lateral sclerosis; ALSFRS-R, ALS Functional Rating Scale (revised); AMT, active motor threshold; BDNF, brain-derived neurotrophic factor; CMAP, compound motor action potential; CMCT, central motor conduction time; ICF, intracortical facilitation; L, left; MEP, motor evoked potential; MRC, Medical Research Council Power Scale; QoL, quality of life; R, right; RCT, randomised controlled trial; RMT, resting motor threshold; SICI, short-interval cortical inhibition; cTBS, continuous theta burst stimulation; rTMS, repetitive transcranial magnetic stimulation; tDCS, transcranial direct current stimulation.