Non-invasive brain stimulation as add-on therapy for subacute post-stroke aphasia: a randomized trial (NORTHSTAR)

Anna Zumbansen; Sandra E Black; Joyce L Chen; Dylan J Edwards; Alexander Hartmann; Wolf-Dieter Heiss; Sylvain Lanthier; Paul Lesperance; George Mochizuki; Caroline Paquette; Elizabeth A Rochon; Ilona Rubi-Fessen; Jennie Valles; Heike Kneifel; Susan Wortman-Jutt; Alexander Thiel; NORTHSTAR-study group

doi:10.1177/2396987320934935

Non-invasive brain stimulation as add-on therapy for subacute post-stroke aphasia: a randomized trial (NORTHSTAR)

Eur Stroke J. 2020 Dec;5(4):402-413. doi: 10.1177/2396987320934935. Epub 2020 Jun 30.

Authors

Anna Zumbansen¹, Sandra E Black², Joyce L Chen³, Dylan J Edwards^{4

5

6}, Alexander Hartmann⁷, Wolf-Dieter Heiss⁸, Sylvain Lanthier⁹, Paul Lesperance¹⁰, George Mochizuki¹¹, Caroline Paquette¹², Elizabeth A Rochon¹³, Ilona Rubi-Fessen¹⁴, Jennie Valles¹⁵, Heike Kneifel¹⁴, Susan Wortman-Jutt^{4

15}, Alexander Thiel¹; NORTHSTAR-study group

Affiliations

¹ Jewish General Hospital, Lady Davis Institute for Medical Research, Department of Neurology & Neurosurgery, McGill University, Montreal, Quebec.
² Department of Medicine-Neurology and Heart and Stroke Foundation Canadian Partnership for Stroke Recovery, Sunnybrook Research Institute, University of Toronto, Toronto, Ontario.
³ Faculty of Kinesiology and Physical Education, and Rehabilitation Sciences Institute, University of Toronto, Toronto, Ontario.
⁴ Burke Neurological Institute, White Plains, NY, USA.
⁵ Moss Rehabilitation Research Institute, Elkins Park, PA, USA.
⁶ School of Medical and Health Sciences, Edith Cowan University, Joondalup, Australia.
⁷ Department of Neurosurgery, Hospital of the City of Cologne, University of Witten-Herdecke, Germany.
⁸ Max Planck Institute für Stoffwechsel Forschung -- MPI for Metabolism Research, and Department of Neurology, Universität zu Köln, Cologne, Germany.
⁹ Hôpital du Sacré-Cœur de Montreal, and Department of medicine, Université de Montréal, Quebec.
¹⁰ CHUM, Université de Montréal, Montreal, Quebec.
¹¹ School of Kinesiology and Health Science, York University, Toronto, Ontario.
¹² Department of Kinesiology and Physical Education, McGill University, Montreal, Quebec.
¹³ Toronto Rehabilitation Institute, and Department of Speech-Language Pathology, University of Toronto, Toronto, Ontario.
¹⁴ RehaNova Neurologische Rehabilitationsklinik, Cologne, Germany.
¹⁵ Burke Rehabilitation Hospital, White Plains, NY, USA.

Abstract

Introduction: Non-invasive brain stimulation (NIBS) with speech therapy might improve recovery from post-stroke aphasia. This three-armed sham-controlled blinded prospective proof-of-concept study tested 1 Hz subthreshold repetitive transcranial magnetic stimulation (rTMS) and 2-mA cathodal transcranial direct current stimulation (ctDCS) on the right pars triangularis in subacute post-stroke aphasia.

Patients and methods: Sixty-three patients with left middle cerebral artery infarcts were recruited in five hospitals (Canada/United States/Germany, 01-2014/03-2018) and randomized to receive rTMS (N = 20), ctDCS (N = 24) or sham stimulation (N = 19) with ST for 10 days. Primary outcome variables were Z-score changes in naming, semantic fluency and comprehension tests and adverse event frequency. Secondary outcome variable was the percent change in the Unified Aphasia Score. Intention-to-treat analyses tested between-group effects at days 1 and 30 post-treatment with a pre-planned subgroup analysis for lesion location (affecting Broca's area or not).

Results: Naming was significantly improved by rTMS (median = 1.91/interquartile range = 0.77/p = .01) at 30 days versus ctDCS (median = 1.11/interquartile range = 1.51) and sham stimulation (median = 1.02/interquartile range = 1.71). All other primary results were non-significant. The rTMS effect was driven by the patient subgroup with intact Broca's area where NIBS tended to improve UnAS (median = 33.2%/interquartile range = 46.7%/p = .062) versus sham stimulation (median = 12.5%/interquartile range = 7.9%) at day 30. Conversely, in patients with infarcted Broca's area, UnAS tended to improve more with sham stimulation (median = 75.0%/interquartile range = 86.9%/p = .053) versus NIBS (median = 12.7%/interquartile range = 31.7).Conclusion: We found a delayed positive effect of low-frequency rTMS targeting the right pars triangularis on the recovery of naming performance in subacute post-stroke aphasia. This intervention may be beneficial only in patients with morphologically intact Broca's area.

Keywords: Aphasia; language therapy; randomized control trial; speech therapy; stroke; transcranial direct current stimulation; transcranial magnetic stimulation.