Cortico-spinal tDCS in amyotrophic lateral sclerosis: A randomized, double-blind, sham-controlled trial followed by an open-label phase
Background: Amyotrophic lateral sclerosis (ALS) is a progressive disease for which no curative treatment is currently available. Objective: This study aimed to investigate whether cortico-spinal transcranial direct current stimulation (tDCS) could mitigate symptoms in ALS patients via a randomized,...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2023-11-01
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| Series: | Brain Stimulation |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S1935861X23019514 |
| _version_ | 1797384152252678144 |
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| author | Alberto Benussi Valentina Cantoni Mario Grassi Ilenia Libri Maria Sofia Cotelli Barbara Tarantino Abhishek Datta Chris Thomas Nadine Huber Sari Kärkkäinen Sanna-Kaisa Herukka Annakaisa Haapasalo Massimiliano Filosto Alessandro Padovani Barbara Borroni |
| author_facet | Alberto Benussi Valentina Cantoni Mario Grassi Ilenia Libri Maria Sofia Cotelli Barbara Tarantino Abhishek Datta Chris Thomas Nadine Huber Sari Kärkkäinen Sanna-Kaisa Herukka Annakaisa Haapasalo Massimiliano Filosto Alessandro Padovani Barbara Borroni |
| author_sort | Alberto Benussi |
| collection | DOAJ |
| description | Background: Amyotrophic lateral sclerosis (ALS) is a progressive disease for which no curative treatment is currently available. Objective: This study aimed to investigate whether cortico-spinal transcranial direct current stimulation (tDCS) could mitigate symptoms in ALS patients via a randomized, double-blind, sham-controlled trial, followed by an open-label phase. Methods: Thirty-one participants were randomized into two groups for the initial controlled phase. At baseline (T0), Group 1 received placebo stimulation (sham tDCS), while Group 2 received cortico-spinal stimulation (real tDCS) for five days/week for two weeks (T1), with an 8-week (T2) follow-up (randomized, double-blind, sham-controlled phase). At the 24-week follow-up (T3), all participants (Groups 1 and 2) received a second treatment of anodal bilateral motor cortex and cathodal spinal stimulation (real tDCS) for five days/week for two weeks (T4). Follow-up evaluations were performed at 32-weeks (T5) and 48-weeks (T6) (open-label phase). At each time point, clinical assessment, blood sampling, and intracortical connectivity measures using transcranial magnetic stimulation (TMS) were evaluated. Additionally, we evaluated survival rates. Results: Compared to sham stimulation, cortico-spinal tDCS significantly improved global strength, caregiver burden, and quality of life scores, which correlated with the restoration of intracortical connectivity measures. Serum neurofilament light levels decreased among patients who underwent real tDCS but not in those receiving sham tDCS. The number of completed 2-week tDCS treatments significantly influenced patient survival. Conclusions: Cortico-spinal tDCS may represent a promising therapeutic and rehabilitative approach for patients with ALS. Further larger-scale studies are necessary to evaluate whether tDCS could potentially impact patient survival. Clinical trial registration: NCT04293484. |
| first_indexed | 2024-03-08T21:31:21Z |
| format | Article |
| id | doaj.art-852b7bd38dfd4d10bdf3cf60ff7fcc1f |
| institution | Directory Open Access Journal |
| issn | 1935-861X |
| language | English |
| last_indexed | 2024-03-08T21:31:21Z |
| publishDate | 2023-11-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Brain Stimulation |
| spelling | doaj.art-852b7bd38dfd4d10bdf3cf60ff7fcc1f2023-12-21T07:30:08ZengElsevierBrain Stimulation1935-861X2023-11-0116616661676Cortico-spinal tDCS in amyotrophic lateral sclerosis: A randomized, double-blind, sham-controlled trial followed by an open-label phaseAlberto Benussi0Valentina Cantoni1Mario Grassi2Ilenia Libri3Maria Sofia Cotelli4Barbara Tarantino5Abhishek Datta6Chris Thomas7Nadine Huber8Sari Kärkkäinen9Sanna-Kaisa Herukka10Annakaisa Haapasalo11Massimiliano Filosto12Alessandro Padovani13Barbara Borroni14Neurology Unit, Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy; Neurology Unit, Department of Neurological and Vision Sciences, ASST Spedali Civili di Brescia, Brescia, ItalyNeurology Unit, Department of Clinical and Experimental Sciences, University of Brescia, Brescia, ItalyDepartment of Brain and Behavioural Sciences, Medical and Genomic Statistics Unit, University of Pavia, Pavia, ItalyNeurology Unit, Department of Clinical and Experimental Sciences, University of Brescia, Brescia, ItalyNeurology Unit, Valle Camonica Hospital, Esine, Brescia, ItalyDepartment of Brain and Behavioural Sciences, Medical and Genomic Statistics Unit, University of Pavia, Pavia, ItalyResearch & Development, Soterix Medical, Inc., New York, USAResearch & Development, Soterix Medical, Inc., New York, USAA.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, FinlandInstitute of Clinical Medicine, Neurology, University of Eastern Finland, Kuopio, FinlandInstitute of Clinical Medicine, Neurology, University of Eastern Finland, Kuopio, Finland; Department of Neurology, Kuopio University Hospital, Kuopio, FinlandA.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, FinlandNeurology Unit, Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy; NeMo-Brescia Clinical Center for Neuromuscular Diseases, Gussago, Brescia, ItalyNeurology Unit, Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy; Neurology Unit, Department of Neurological and Vision Sciences, ASST Spedali Civili di Brescia, Brescia, ItalyNeurology Unit, Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy; Neurology Unit, Department of Neurological and Vision Sciences, ASST Spedali Civili di Brescia, Brescia, Italy; Corresponding author. Clinica Neurologica, Università degli Studi di Brescia, P.le Spedali Civili 1, 25123, Brescia, Italy.Background: Amyotrophic lateral sclerosis (ALS) is a progressive disease for which no curative treatment is currently available. Objective: This study aimed to investigate whether cortico-spinal transcranial direct current stimulation (tDCS) could mitigate symptoms in ALS patients via a randomized, double-blind, sham-controlled trial, followed by an open-label phase. Methods: Thirty-one participants were randomized into two groups for the initial controlled phase. At baseline (T0), Group 1 received placebo stimulation (sham tDCS), while Group 2 received cortico-spinal stimulation (real tDCS) for five days/week for two weeks (T1), with an 8-week (T2) follow-up (randomized, double-blind, sham-controlled phase). At the 24-week follow-up (T3), all participants (Groups 1 and 2) received a second treatment of anodal bilateral motor cortex and cathodal spinal stimulation (real tDCS) for five days/week for two weeks (T4). Follow-up evaluations were performed at 32-weeks (T5) and 48-weeks (T6) (open-label phase). At each time point, clinical assessment, blood sampling, and intracortical connectivity measures using transcranial magnetic stimulation (TMS) were evaluated. Additionally, we evaluated survival rates. Results: Compared to sham stimulation, cortico-spinal tDCS significantly improved global strength, caregiver burden, and quality of life scores, which correlated with the restoration of intracortical connectivity measures. Serum neurofilament light levels decreased among patients who underwent real tDCS but not in those receiving sham tDCS. The number of completed 2-week tDCS treatments significantly influenced patient survival. Conclusions: Cortico-spinal tDCS may represent a promising therapeutic and rehabilitative approach for patients with ALS. Further larger-scale studies are necessary to evaluate whether tDCS could potentially impact patient survival. Clinical trial registration: NCT04293484.http://www.sciencedirect.com/science/article/pii/S1935861X23019514Motor neuron diseaseAmyotrophic lateral sclerosisTranscranial direct current stimulationTranscranial magnetic stimulationShort interval intracortical inhibitionClinical trial |
| spellingShingle | Alberto Benussi Valentina Cantoni Mario Grassi Ilenia Libri Maria Sofia Cotelli Barbara Tarantino Abhishek Datta Chris Thomas Nadine Huber Sari Kärkkäinen Sanna-Kaisa Herukka Annakaisa Haapasalo Massimiliano Filosto Alessandro Padovani Barbara Borroni Cortico-spinal tDCS in amyotrophic lateral sclerosis: A randomized, double-blind, sham-controlled trial followed by an open-label phase Brain Stimulation Motor neuron disease Amyotrophic lateral sclerosis Transcranial direct current stimulation Transcranial magnetic stimulation Short interval intracortical inhibition Clinical trial |
| title | Cortico-spinal tDCS in amyotrophic lateral sclerosis: A randomized, double-blind, sham-controlled trial followed by an open-label phase |
| title_full | Cortico-spinal tDCS in amyotrophic lateral sclerosis: A randomized, double-blind, sham-controlled trial followed by an open-label phase |
| title_fullStr | Cortico-spinal tDCS in amyotrophic lateral sclerosis: A randomized, double-blind, sham-controlled trial followed by an open-label phase |
| title_full_unstemmed | Cortico-spinal tDCS in amyotrophic lateral sclerosis: A randomized, double-blind, sham-controlled trial followed by an open-label phase |
| title_short | Cortico-spinal tDCS in amyotrophic lateral sclerosis: A randomized, double-blind, sham-controlled trial followed by an open-label phase |
| title_sort | cortico spinal tdcs in amyotrophic lateral sclerosis a randomized double blind sham controlled trial followed by an open label phase |
| topic | Motor neuron disease Amyotrophic lateral sclerosis Transcranial direct current stimulation Transcranial magnetic stimulation Short interval intracortical inhibition Clinical trial |
| url | http://www.sciencedirect.com/science/article/pii/S1935861X23019514 |
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