Non-invasive electrical brain stimulation for vision restoration after stroke: An exploratory randomized trial (REVIS)

Silja Räty, Carolin Borrmann, Giuseppe Granata, Lizbeth Cárdenas-Morales, Ariel Schoenfeld, Michael Sailer, Katri Silvennoinen, Juha Holopainen, Francesca De Rossi, Andrea Antal, Paolo M Rossini, Turgut Tatlisumak, Bernhard A Sabel, Silja Räty, Carolin Borrmann, Giuseppe Granata, Lizbeth Cárdenas-Morales, Ariel Schoenfeld, Michael Sailer, Katri Silvennoinen, Juha Holopainen, Francesca De Rossi, Andrea Antal, Paolo M Rossini, Turgut Tatlisumak, Bernhard A Sabel

Abstract

Background: Occipital strokes often cause permanent homonymous hemianopia leading to significant disability. In previous studies, non-invasive electrical brain stimulation (NIBS) has improved vision after optic nerve damage and in combination with training after stroke.

Objective: We explored different NIBS modalities for rehabilitation of hemianopia after chronic stroke.

Methods: In a randomized, double-blinded, sham-controlled, three-armed trial, altogether 56 patients with homonymous hemianopia were recruited. The three experiments were: i) repetitive transorbital alternating current stimulation (rtACS, n = 8) vs. rtACS with prior cathodal transcranial direct current stimulation over the intact visual cortex (tDCS/rtACS, n = 8) vs. sham (n = 8); ii) rtACS (n = 9) vs. sham (n = 9); and iii) tDCS of the visual cortex (n = 7) vs. sham (n = 7). Visual functions were evaluated before and after the intervention, and after eight weeks follow-up. The primary outcome was change in visual field assessed by high-resolution and standard perimetries. The individual modalities were compared within each experimental arm.

Results: Primary outcomes in Experiments 1 and 2 were negative. Only significant between-group change was observed in Experiment 3, where tDCS increased visual field of the contralesional eye compared to sham. tDCS/rtACS improved dynamic vision, reading, and visual field of the contralesional eye, but was not superior to other groups. rtACS alone increased foveal sensitivity, but was otherwise ineffective. All trial-related procedures were tolerated well.

Conclusions: This exploratory trial showed safety but no main effect of NIBS on vision restoration after stroke. However, tDCS and combined tDCS/rtACS induced improvements in visually guided performance that need to be confirmed in larger-sample trials.NCT01418820 (clinicaltrials.gov).

Keywords: Electrical stimulation; homonymous hemianopia; occipital stroke; randomized controlled trial; rehabilitation; vision restoration.

Conflict of interest statement

BS is a shareholder of SAVIR-Center, a vision rehabilitation outpatient clinic, where NIBS methods are used. Other authors have no disclosures.

Figures

Fig. 1
Fig. 1
Flowchart of the study. ACS, alternating current stimulation; DCS/ACS, combined direct current stimulation/alternating current stimulation; DCS, direct current stimulation; HRP, high-resolution perimetry; DVA, dynamic visual acuity.
Fig. 2
Fig. 2
Results of primary outcomes in Experiments 1, 2, and 3. Median changes from baseline, 95% -CIs, and between-group p values, calculated with Mann-Whitney U test or Kruskal-Wallis analysis of variance test in case of more than two groups, are given. ACS, alternating current stimulation; DCS/ACS, combined direct current stimulation/alternating current stimulation; DCS, direct current stimulation; DA, detection accuracy; MS, mean sensitivity; ILE, ipsilesional eye; CLE, contralesional eye. *Sham vs. ACS, calculated from post hoc pairwise comparison.
Fig. 3
Fig. 3
Changes of foveal sensitivity of the ipsilesional eye from baseline in Experiment 1. Median changes from baseline, 95% -CIs, and between-group p values, calculated with Kruskal-Wallis analysis of variance test are given. ACS, alternating current stimulation; DCS/ACS, combined direct current stimulation/alternating current stimulation; FS, foveal sensitivity ILE, ipsilesional eye. *ACS vs. Sham, calculated from post hoc pairwise comparison.

References

    1. Alber, R., Moser, H., Gall, C., & Sabel, B. A. (2017). Combined transcranial direct current stimulation and Vision Restoration training in subacute stroke rehabilitation: A Pilot study. PM & R, 9(8), 787–794.
    1. Ali, M., Hazelton, C., Lyden, P., Pollock, A., & Brady, M. (2013). Recovery from poststroke visual impairment: Evidence from a clinical trials resource. Neurorehabilitation and Neural Repair, 27(2), 133–141.
    1. Antal, A., Alekseichuk, I., Bikson, M., Brockmöller, J., Brunoni, A. R., Chen, R.,... Paulus, W. (2017). Low intensity transcranial electric stimulation: Safety, ethical, legal regulatory and application guidelines. Clinical Neurophysiology, 128(9), 1774–1809.
    1. Antal, A., Boros, K., Poreisz, C., Chaieb, L., Terney, D., & Paulus, W. (2008). Comparatively weak after-effects of transcranial alternating current stimulation (tACS) on cortical excitability in humans. Brain Stimulation, 1(2), 97–105.
    1. Bola, M., Gall, C., Moewes, C., Fedorov, A., Hinrichs, H., & Sabel, B. A. (2014). Brain functional connectivity network breakdown and restoration in blindness. Neurology, 83(6), 542–551.
    1. Dougherty, B. E., Flom, R. E., & Bullimore, M. A. (2005). An evaluation of the MARS letter contrast sensitivity test. Optometry and Vision Science, 82(11), 970–975.
    1. Foik, A. T., Kublik, E., Sergeeva, E. G., Tatlisumak, T., Rossini, P. M., Sabel, B. A., & Waleszczyk, W. J. (2015). Retinal origin of electrically evoked potentials in response to transcorneal alternating current stimulation in the rat. Investigative Ophthalmology & Visual Science, 56(3), 1711–1718.
    1. Gall, C., Franke, G. H., & Sabel, B. A. (2010). Vision-related quality of life in first stroke patients with homonymous visual field defects. Health & Quality of Life Outcomes, 8, 33.
    1. Gall, C., Schmidt, S., Schittkowski, M. P., Antal, A., Ambrus, G. G., Paulus, W.,... Sabel, B. A. (2016). Alternating current stimulation for vision restoration after optic nerve damage: A randomized clinical trial. PloS One, 11(6), e0156134.
    1. Gall, C., Silvennoinen, K., Granata, G., de Rossi, F., Vecchio, F., Brosel, D.,... Sabel, B. A. (2015). Non-invasive electric current stimulation for restoration of vision after unilateral occipital stroke. Contemporary Clinical Trials, 43, 231–236.
    1. Gray, C. S., French, J. M., Bates, D., Cartlidge, N. E., Venables, G. S., & James, O. F. (1989). Recovery of visual fields in acute stroke: Homonymous hemianopia associated with adverse prognosis. Age & Ageing, 18(6), 419–421.
    1. Halko, M. A., Datta, A., Plow, E. B., Scaturro, J., Bikson, M., & Merabet, L. B. (2011). Neuroplastic changes following rehabilitative training correlate with regional electrical field induced with tDCS. Neuroimage, 57(3), 885–891.
    1. Herring, J. D., Esterer, S., Marshall, T. R., Jensen, O., & Bergmann, T. O. (2019). Low-frequency alternating current stimulation rhythmically suppresses gamma-band oscillations and impairs perceptual performance. Neuroimage, 184, 440–449.
    1. Huang, Y. Y., Colino, A., Selig, D. K., & Malenka, R. C. (1992). The influence of prior synaptic activity on the induction of long-term potentiation. Science, 255(5045), 730–733.
    1. Kanai, R., Chaieb, L., Antal, A., Walsh, V., & Paulus, W. (2008). Frequency-dependent electrical stimulation of the visual cortex. Current Biology, 18(23), 1839–1843.
    1. Kasten, E., Wust, S., Behrens-Baumann, W., & Sabel, B. A. (1998). Computer-based training for the treatment of partial blindness. Nature Medicine, 4(9), 1083–1087.
    1. Lang, N., Siebner, H. R., Ernst, D., Nitsche, M. A., Paulus, W., Lemon, R. N., & Rothwell, J. C. (2004). Preconditioning with transcranial direct current stimulation sensitizes the motor cortex to rapid-rate transcranial magnetic stimulation and controls the direction of after-effects. Biological Psychiatry, 56(9), 634–639.
    1. Larcombe, S. J., Kulyomina, Y., Antonova, N., Ajina, S., Stagg, C. J., Clatworthy, P. L., & Bridge, H. (2018). Visual training in hemianopia alters neural activity in the absence of behavioural improvement: A pilot study. Ophthalmic & Physiological Optics, 38(5), 538–549.
    1. Matteo, B. M., Viganò, B., Cerri, C. G., Meroni, R., Cornaggia, C. M., & Perin, C. (2017). Transcranial direct current stimulation (tDCS) combined with blindsight rehabilitation for the treatment of homonymous hemianopia: A report of two-cases. Journal of Physical Therapy Science, 29(9), 1700–1705.
    1. Murphy, T. H., & Corbett, D. (2009). Plasticity during stroke recovery: From synapse to behaviour. Nature Reviews Neuroscience, 10(12), 861–872.
    1. Nitsche, M. A., Cohen, L. G., Wassermann, E. M., Priori, A., Lang, N., Antal, A.,... Pascual-Leone, A. (2008). Transcranial direct current stimulation: State of the art. Brain Stimulation, 1(3), 206–223.
    1. Ozen, S., Sirota, A., Belluscio, M. A., Anastassiou, C. A., Stark, E., Koch, C., & Buzsáki, G. (2010). Transcranial electric stimulation entrains cortical neuronal populations in rats. The Journal of Neuroscience, 30(34), 11476–11485.
    1. Plow, E. B., Obretenova, S. N., Fregni, F., Pascual-Leone, A., & Merabet, L. B. (2012). Comparison of visual field training for hemianopia with active versus sham transcranial direct cortical stimulation. Neurorehabilitation and Neural Repair, 26(6), 616–626.
    1. Plow, E. B., Obretenova, S. N., Halko, M. A., Kenkel, S., Jackson, M. L., Pascual-Leone, A., & Merabet, L. B. (2011). Combining visual rehabilitative training and noninvasive brain stimulation to enhance visual function in patients with hemianopia: A comparative case study. PM & R, 3(9), 825–835.
    1. Pollock, A., Hazelton, C., Rowe, F. J., Jonuscheit, S., Kernohan, A., Angilley, J.,... Campbell, P. (2019). Interventions for visual field defects in people with stroke. Cochrane Database of Systematic Reviews, (5).
    1. Poppel, E., Held, R., & Frost, D. (1973). Leter: Residual visual function after brain wounds involving the central visual pathways in man. Nature, 243(5405), 295–296.
    1. Raninen, A., Vanni, S., Hyvarinen, L., & Nasanen, R. (2007). Temporal sensitivity in a hemianopic visual field can be improved by long-term training using flicker stimulation. Journal of Neurology, Neurosurgery & Psychiatry, 78(1), 66–73.
    1. Rossini, P. M., Calautti, C., Pauri, F., & Baron, J. (2003). Post-stroke plastic reorganisation in the adult brain. Lancet Neurology, 2(8), 493–502.
    1. Rowe, F. J., Hepworth, L. R., Howard, C., Hanna, K. L., Cheyne, C. P., & Currie, J. (2019). High incidence and prevalence of visual problems after acute stroke: An epidemiology study with implications for service delivery. PloS One, 14(3), e0213035.
    1. Sabel, B. A., Henrich-Noack, P., Fedorov, A., & Gall, C. (2011). Vision restoration after brain and retina damage: The “residual vision activation theory”. Progress in Brain Research, 192, 199–262.
    1. Sabel, B. A., Thut, G., Haueisen, J., Henrich-Noack, P., Herrmann, C. S., Hunold, A.,... Antal, A. (2020). Vision modulation, plasticity and restoration using non-invasive brain stimulation - an IFCN-sponsored review. Clinical Neurophysiology, 131(4), 887–911.
    1. Sahraie, A., Trevethan, C. T., MacLeod, M. J., Murray, A. D., Olson, J. A., & Weiskrantz, L. (2006). Increased sensitivity after repeated stimulation of residual spatial channels in blindsight. Proceedings of the National Academy of Sciences of the United States of America, 103(40), 14971–14976.
    1. Strbian, D., Ahmed, N., Wahlgren, N., Kaste, M., Tatlisumak, T., SITS Investigators. (2012). Intravenous thrombolysis in ischemic stroke patients with isolated homonymous hemianopia: Analysis of Safe Implementation of Thrombolysis in Stroke-International Stroke Thrombolysis Register (SITS-ISTR. Stroke, 43(10), 2695–2698.
    1. Tiel, K., & Kolmel, H. W. (1991). Patterns of recovery from homonymous hemianopia subsequent to infarction in the distribution of the posterior cerebral-artery. Neuro-Ophthalmology, 11(1), 33–39.
    1. Trauzettel-Klosinski, S., & Dietz, K. (2012). Standardized assessment of reading performance: The new international reading speed texts IReST. Investigative Ophthalmology & Visual Science, 53(9), 5452–5461.
    1. Weiskrantz, L., Warrington, E. K., Sanders, M. D., & Marshall, J. (1974). Visual capacity in the hemianopic field following a restricted occipital ablation. Brain, 97(4), 709–728.
    1. Wist, E. R., Ehrenstein, W. H., Schrauf, M., & Schraus, M. (1998). A computer-assisted test for the electrophysiological and psychophysical measurement of dynamic visual function based on motion contrast. Journal of Neuroscience Methods, 80(1), 41–47.
    1. Zaehle, T., Rach, S., & Herrmann, C. S. (2010). Transcranial alternating current stimulation enhances individual alpha activity in human EEG. PloS One, 5(11), e13766.
    1. Zhang, X., Kedar, S., Lynn, M. J., Newman, N. J., & Biousse, V. (2006). Natural history of homonymous hemianopia. Neurology, 66(6), 901–905.

Source: PubMed

Sponsorit ja yhteistyökumppanit

Sairaudet

Huumeiden interventiot

3
Tilaa