Pharmacological interventions for unilateral spatial neglect after stroke.

BACKGROUND: Unilateral spatial neglect (USN) is characterized by the inability to report or respond to people or objects presented on the side contralateral to the lesioned side of the brain and has been associated with poor functional outcomes and long stays in hospitals and rehabilitation centers. Pharmacological interventions (medical interventions only, use of drugs to improve the health condition), such as dopamine and noradrenergic agonists or pro-cholinergic treatment, have been used in people affected by USN after stroke, and effects of these treatments could provide new insights for health professionals and policy makers. OBJECTIVES: To evaluate the effectiveness and safety of pharmacological interventions for USN after stroke. SEARCH METHODS: We searched the Cochrane Stroke Group Trials Register (April 2015), the Cochrane Central Register of Controlled Trials (April 2015), MEDLINE (1946 to April 2015), the Cumulative Index to Nursing and Allied Health Literature (CINAHL) (1982 to April 2015), EMBASE (1980 to April 2015), PsycINFO (1806 to April 2015) and Latin American Caribbean Health Sciences Literature (LILACS) (1982 to April 2015). We also searched trials and research registers, screened reference lists, and contacted study authors and pharmaceutical companies (April 2015). SELECTION CRITERIA: We included randomized controlled trials (RCTs) and quasi-randomized controlled trials (quasi-RCTs) of pharmacological interventions for USN after stroke. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed risk of bias in the included studies and extracted data. MAIN RESULTS: We included in the review two studies with a total of 30 randomly assigned participants. We rated the quality of the evidence as very low as the result of study limitations, small numbers of events, and small sample sizes, with imprecision in the confidence interval (CI). We were not able to perform meta-analysis because of heterogeneity related to the different interventions evaluated between included studies. Very low-quality evidence from one trial (20 participants) comparing effects of rivastigmine plus rehabilitation versus rehabilitation on overall USN at discharge showed the following: Barrage (mean difference (MD) 0.30, 95% confidence interval (CI) -0.18 to 0.78); Letter Cancellation (MD 10.60, 95% CI 2.07 to 19.13); Sentence Reading (MD 0.20, 95% CI -0.69 to 1.09), and the Wundt-Jastrow Area Illusion Test (MD -4.40, 95% CI -8.28 to -0.52); no statistical significance was observed for the same outcomes at 30 days' follow-up. In another trial (10 participants), study authors showed statistically significant reduction in omissions in the three cancellation tasks under transdermal nicotine treatment (mean number of omissions 2.93 ± 0.5) compared with both baseline (4.95 ± 0.8) and placebo (5.14 ± 0.9) (main effect of treatment condition: F (2.23) = 11.06; P value < 0.0001). One major adverse event occurred in the transdermal nicotine treatment group, and treatment was discontinued in the affected participant. None of the included trials reported data on several of the prespecified outcomes (falls, balance, depression or anxiety, poststroke fatigue, and quality of life). AUTHORS' CONCLUSIONS: The quality of the evidence from available RCTs was very low. The effectiveness and safety of pharmacological interventions for USN after stroke are therefore uncertain. Additional large RCTs are needed to evaluate these treatments.

Rehabilitation of spatial neglect.

Spatial neglect is a frequent cause of disability associated with high costs and duration of hospital stay, increased family burden, and requirements for skilled chronic care. This condition is disproportionately more frequent with right than left hemispheric injury and it is characterized by perceptual, representational, and behavioral deficits involving or directed towards the left hemispace or the left hemibody. Spatial dysfunction is conceptualized into two major components: the perceptual/representational "where" component that results mainly from injury to posterior brain regions and the premotor/intentional "aiming" component that results mostly from damage to anterior brain regions. Additionally, deficits in arousal, vigilance, affective symptoms, and disorders of emotional communication may compound the clinical manifestations of spatial neglect. Evidence-based sources that evaluate the effectiveness of rehabilitation treatments for neglect are, unfortunately, unable to provide a unified consensus for the efficacy of a given treatment approach. The reasons for this failure are related to internal inconsistencies defining appropriate criteria for treatment success and lack of characterization of neglect mechanisms and considerations of patient characteristics related to treatment failure. In this chapter we advocate the use of visual scanning, limb activation therapy, and "general treatment" because we believe that they are appropriately supported by different sources and they may be useful for experimental trials and standardized clinical care. We advocate an integrative approach that takes advantage of the same rehabilitation strategy or task to treat different perceptual, representational, and premotor components of neglect. A variety of therapies that may be familiar to the rehabilitation team may be useful as long as they are applied in a systematized program and are based on good clinical judgment. Information regarding adjuvant pharmacological therapy is sparse but different agents with aminergic and cholinergic activity may be useful. Medication with sedative, antidopaminergic or anticholinergic properties may interfere with the rehabilitation process and should be avoided.