A research group from the University of Brescia in Italy conducted a study to test the effectiveness of a two-week treatment with corticospinal tDCS to improve the quality of life in ALS patients. Specifically, the scientists sought to: (i) Evaluate the long-term effects of multiple sessions of bilateral anodal motor cortex tDCS and cathodal spinal tDCS in patients with ALS; (ii) determine whether two cycles of tDCS treatment are more effective than a single treatment; (iii) explore potential effects on ALS prognostic markers, such as serum neurofilament light chain and survival rates.
This study aimed to determine whether transcranial corticospinal direct current stimulation (tDCS) could alleviate symptoms in ALS patients via a randomized, double-blind, sham-controlled trial followed by an open-label phase.
Thirty-one participants were randomized into two groups for the initial controlled phase.
Group 1: At baseline (T0), group 1 received placebo stimulation (sham tDCS),
Group 2: Group 2 received corticospinal stimulation (real tDCS) for five days/week for two weeks (T1), with a randomized, double-blind, sham-controlled 8-week follow-up (T2).
At the 24-week follow-up (T3), all participants (groups 1 and 2) received a second treatment of bilateral anodal motor cortex and cathodal spinal stimulation (real tDCS) for five days/week for two weeks (T4).
Follow-up assessments were performed at 32 weeks (T5) and 48 weeks (T6) (open phase). At each time point, clinical assessment, blood sampling, and intracortical connectivity measures using transcranial magnetic stimulation (TMS) were assessed. Additionally, they assessed survival rates.
Compared to sham stimulation, corticospinal tDCS improved overall strength, caregiver burden, and quality of life scores, correlating with the restoration of intracortical connectivity measures. Serum neurofilament light levels decreased in patients receiving real tDCS, but not in those receiving sham tDCS. The number of completed 2-week tDCS treatments significantly influenced patient survival.
If I extrapolate from Figure 6, patients with two treatments would live 13 years longer than patients without treatment. This improvement is considerable, if we ignore the statistical hallucinations of pharmaceutical companies, the current improvements simply relate to a few months of survival. We will see below that we can doubt this result.
Yet the number of tDCS treatments completed over 2 weeks significantly influenced survival rates, suggesting a possible dose-dependent effect of tDCS on disease progression.
Elevation of serum NfL levels correlates with neuronal damage in a spectrum of neurodegenerative diseases, including ALS. A decrease in serum NfL levels, as observed in their study, could potentially suggest a neuroprotective effect of tDCS.
However, despite certain positive results, their study presents several limitations which deserve to be taken into consideration. First, the very small sample size and high attrition rate (~50%) raises questions about the side effects that must have been difficult to bear.
Furthermore, no significant effect was observed on the ALSFRS-R. We can wonder how a study that announces being capable of significantly extending survival is incapable of at least showing a slowdown in the progression of the disease. This seems a difficult contradiction to resolve. Another example of a statistical anomaly is that the control group appears to have undergone significant improvement as measured by the ALSAQ-40 scale.
Yet the promising results of their study highlight the potential of corticospinal tDCS as a therapeutic intervention for ALS opening several avenues for future research. One possible direction is to explore the synergistic effects of combining in ALS centers, tDCS with other therapeutic interventions, such as pharmacological treatments or physical therapy, which could potentially amplify their effects by modulating neural networks and promoting neuroplasticity, thus leading to better clinical outcomes..