Randomised, double-blind, placebo-controlled crossover study of single-dose guanfacine in unilateral neglect following stroke

Edwin S Dalmaijer, Korina M S Li, Nikos Gorgoraptis, Alexander P Leff, David L Cohen, Andrew D Parton, Masud Husain, Paresh A Malhotra, Edwin S Dalmaijer, Korina M S Li, Nikos Gorgoraptis, Alexander P Leff, David L Cohen, Andrew D Parton, Masud Husain, Paresh A Malhotra

Abstract

Objective: Unilateral neglect is a poststroke disorder that impacts negatively on functional outcome and lacks established, effective treatment. This multicomponent syndrome is characterised by a directional bias of attention away from contralesional space, together with impairments in several cognitive domains, including sustained attention and spatial working memory. This study aimed to test the effects of guanfacine, a noradrenergic alpha-2A agonist, on ameliorating aspects of neglect.

Methods: Thirteen right hemisphere stroke patients with leftward neglect were included in a randomised, double-blind, placebo-controlled proof-of-concept crossover study that examined the effects of a single dose of guanfacine. Patients were tested on a computerised, time-limited cancellation paradigm, as well as tasks that independently assessed sustained attention and spatial working memory.

Results: On guanfacine, there was a statistically significant improvement in the total number of targets found on the cancellation task when compared with placebo (mean improvement of 5, out of a possible 64). However, there was no evidence of a change in neglect patients' directional attention bias. Furthermore, Bayesian statistical analysis revealed reliable evidence against any effects of guanfacine on search organisation and performance on our sustained attention and spatial working memory tasks.

Conclusions: Guanfacine improves search in neglect by boosting the number of targets found but had no effects on directional bias or search organisation, nor did it improve sustained attention or working memory on independent tasks. Further work is necessary to determine whether longer term treatment with guanfacine may be effective for some neglect patients and whether it affects functional outcome measures.

Trial registration number: NCT00955253.

Conflict of interest statement

Competing interests: None declared.

© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Figures

Figure 1
Figure 1
Individual lesion maps for all 13 participants. Patients 1001–1010 had some degree of cortical frontal involvement, whereas patients 2001–2003 did not.
Figure 2
Figure 2
Total number of correctly marked targets in a cancellation task (A), as well as the difference between the number of correctly marked targets on the right and the left sides of the task (B) and the centre of cancellation where positive values indicate a rightward bias (C) in the baseline (green) condition and after placebo (blue) or guanfacine (red) administration. Solid horizontal lines indicate the mean, and error bars indicate within-participant 95% CIs. Each set of three connected dots represents a participant (grey for patients with cortical frontal involvement, and orange for without).

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