Adverse effect of dopamine agonist therapy in a patient with motor-intentional neglect

doi:10.1016/S0003-9993(99)90205-8

Archives of Physical Medicine and Rehabilitation

Volume 80, Issue 5, May 1999, Pages 600-603

https://doi.org/10.1016/S0003-9993(99)90205-8 Get rights and content

Abstract

Studies in animals and humans report dopamine agonists can improve neglect. Because dopamine deficit reduces intention to act, it has been suspected the dopamine agonist bromocriptine would improve deficient hemispatial intention. Thus, the effect of bromocriptine on line bisection was examined in a patient with neglect and failure of the action-intention system. The 58-year-old patient had left-sided neglect from a right cerebral infarction involving both cortical and subcortical (striatal) structures. It was determined that neglect on a line bisection task was attributable to a motor-intentional bias by testing under congruous and incongruous video monitoring. Testing sessions were held before starting bromocriptine, on 20mg/d, and after stopping bromocriptine. The patient's ipsilesional bias increased on bromocriptine, and improved when bromocriptine was stopped. Bromocriptine may worsen neglect if putamenal receptors are damaged. Dopamine agonists may activate the normal hemisphere, increasing an intentional bias. Clinicians using dopaminergic pharmacotherapy should assess patients for this possible adverse effect.

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Cited by (64)

Reward sensitivity predicts dopaminergic response in spatial neglect
2020, Cortex
It has recently been revealed that spatial neglect can be modulated by motivational factors including anticipated monetary reward. A number of dopaminergic agents have been evaluated as treatments for neglect, but the results have been mixed, with no clear anatomical or cognitive predictors of dopaminergic responsiveness. Given that the effects of incentive motivation are mediated by dopaminergic pathways that are variably damaged in stroke, we tested the hypothesis that the modulatory influences of reward and dopaminergic drugs on neglect are themselves related.
We employed a single-dose, double-blind, crossover design to compare the effects of Co-careldopa and placebo on a modified visual cancellation task in patients with neglect secondary to right hemisphere stroke. Whilst confirming that reward improved visual search in this group, we showed that dopaminergic stimulation only enhances visual search in the absence of reward. When patients were divided into REWARD-RESPONDERs and REWARD-NON-RESPONDERs, we found an interaction, such that only REWARD-NON-RESPONDERs showed a positive response to reward after receiving Co-careldopa, whereas REWARD-RESPONDERs were not influenced by drug. At a neuroanatomical level, responsiveness to incentive motivation was most associated with intact dorsal striatum.
These findings suggest that dopaminergic modulation of neglect follows an ‘inverted U’ function, is dependent on integrity of the reward system, and can be measured as a behavioural response to anticipated reward.
The cingulate cortex and spatial neglect
2019, Handbook of Clinical Neurology
Citation Excerpt :
This suggests that limb activation–based therapeutic benefits can be obtained during routine wheelchair training, based on optimal configuration of the wheelchair joystick equipment. Dopaminergic pharmacotherapy may improve spatial neglect in humans, and neglect symptoms sensitive to dopaminergic supplementation may be identified with intentional premotor exploratory function (Fleet et al., 1987; Coslett et al., 1990; Tegner and Levander, 1991; Barrett et al., 1999; Mukand et al., 2001; Mapstone et al., 2003; Heilman, 2004). Rotigotine, a dopamine agonist with relatively high affinity for D1 receptors (Gorgoraptis et al., 2012), improved visual search and selective attention, without improving spatial representational functions such as working memory.
Spatial neglect is asymmetric attention, orienting, and action causing functional disability. It is linked to higher-order cortical sensory processing; however, spatial motor “Aiming” processing is critical to fundamental, adaptive environmental movement and daily life function. The cingulate cortex, in particular the anterior cingulate and anterior midcingulate cortex, is strongly linked to spatial Aiming deficits and likely to predict daily life disability in spatial neglect. The authors review the impact and mechanisms of spatial neglect and then describe specific symptoms associated with spatial neglect that are theoretically linked to cingulate cortical functions or associated with lesions extending to cingulate regions in a well-characterized spatial neglect cohort. The treatment implications for a link between cingulate cortex spatial Aiming neglect and therapies that improve spatial action, arousal, and persistence are discussed. Clinicians may want to consider theoretically motivated treatments targeted at specific symptoms as well as use treatments supported for spatial neglect based on unselected and uncharacterized groups.
Asymmetries in initiation of aiming movements in schizophrenia
2018, Neuropsychologia
Several studies have reported motor symptoms in schizophrenia (SCZ), in some cases describing asymmetries in their manifestation. To date, biases were mainly reported for sequential movements, and the hypothesis was raised of a dopamine-related hemispheric imbalance. Aim of this research is to better characterize asymmetries in movement initiation in SCZ by exploring single actions. Fourteen SCZ patients and fourteen healthy subjects were recruited. On a trial-by-trial basis, participants were instructed to reach for one of eight possible targets. Measures of movement initiation and execution were collected. Starting point, target and moving limb were systematically varied to check for asymmetric responses. Results showed that SCZ patients, besides being overall slower than controls, additionally presented with a bias affecting both the moving hand and the side from which movements were initiated. This finding is discussed in relation to hemispheric lateralization in motor control.
Right Brain Stroke Syndromes
2018, Stroke Rehabilitation
The right brain critically mediates a number of fundamental cognitive functions. In this chapter, we review the definitions and history, pathophysiology and neuroanatomy, clinical presentation, and approach to rehabilitation of four major cognitive syndromes associated with right brain injury. Although these disorders can occur in other neurological disorders, stroke is the most common setting to observe disabling spatial neglect, anosognosia for hemiplegia, emotional processing disorder, including emotional aprosodia, and alien hand syndrome (callosal and posterior types). We urge physicians, nurses, psychologists and therapists to incorporate rehabilitation of right brain stroke syndrome into acute and chronic rehabilitation plans. Better identification and treatment of right brain stroke may reduce the significant long-term disability associated with these cognitive problems, and may improve poststroke family and community reintegration.
Pharmacological Treatment of Visuospatial Neglect: A Systematic Review
2017, Journal of Stroke and Cerebrovascular Diseases
Citation Excerpt :
One study was considered to be of moderate quality.45 The remaining 6 studies were considered to be of low quality.4,30,41-44 First, Gorgoraptis et al45 used a double-blind, placebo-controlled A-B-A design to study the effects of rotigotine on VSN, spatial working memory, selective and sustained attention, and motor control.
The aims of the current review were (1) to give an overview of human studies investigating pharmacotherapy to ameliorate visuospatial neglect and (2) to evaluate the quality of those studies.
A systematic literature search using PubMed, Scopus, and ResearchGate was conducted in regard to studies that evaluated pharmacological interventions aiming to ameliorate poststroke visuospatial neglect. The search was limited in the following features: species (human), adults (≥18 years of age), language (English), and type of neglect (visuospatial). Two independent authors extracted data on study content and effectiveness and evaluated the quality of studies and methods.
A total of 11 studies were identified. Three studies were considered to be of moderate quality, the others of low quality. Seven studies represented dopaminergic treatment; 3 studies represented cholinergic treatment; and 1 study represented noradrenergic treatment. Three dopaminergic studies showed primarily positive effects of dopaminergic stimulation on visuospatial neglect, whereas three others showed adverse effects. All 3 cholinergic studies found positive effects in some outcome measures concerning visuospatial neglect. Noradrenergic stimulation improved maintenance of attention when exploring space.
Currently, cholinergic therapy might be the best option for future research. However, we must emphasize the explorative nature and the limited quality of the reviewed studies.
Motivation and attention following hemispheric stroke
2016, Progress in Brain Research
Spatial neglect (SN) is an extremely common disorder of attention; it is most frequently a consequence of stroke, especially to the right cerebral hemisphere. The current view of SN is that it is not a unitary deficit but a multicomponent syndrome. Crucially, it has been repeatedly shown that it has a considerable negative impact on rehabilitation outcome. Although a number of behavioral and pharmacological therapies have been developed, none of these appears to be applicable to all patients with SN or has proved unequivocally successful in clinical trials.
One potential avenue for therapeutic intervention in neglect relates to the interaction between motivation and attention. A number of investigators, including ourselves, have observed a possible motivational component to the syndrome and showed that motivational stimulation can temporarily improve attention in patients with SN.
In this chapter we review previous work looking at how motivation can modulate attention in healthy individuals and how it may be affected by neurological disease before discussing how motivational impairments may contribute to neglect, and how motivation has been used to modulate neglect. In the final section, we present recent experimental work examining how reward interacts with attentional biases in patients with SN. In this study, we adapted the classic Landmark task to explore the mechanisms behind the effect of reward in SN, and found that centrally located stimuli that were explicitly associated with reward appeared to improve neglect and reduce rightward bias. Our results suggest that positive motivation, in the form of anticipated monetary reward, may influence attentional bias via more general mechanisms, such as alerting and task engagement, rather than directly increasing salience of items in contralesional space. We conclude by discussing how motivation might be practically integrated into the rehabilitation of patients with this debilitating disorder.

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^☆: Supported by Department of Veterans Affairs Merit Review grant 114-30-4813.

^☆☆: Presented at the 49th annual meeting of the American Academy of Neurology, April 17, 1997, Boston, MA, and published in abstract form in Neurology 1997; 48: A374.

^★: No commercial party having a direct financial interest in the results of the research supporting this article has or will confer a benefit upon the authors or upon any organization with which the authors are associated.

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Clinical noteAdverse effect of dopamine agonist therapy in a patient with motor-intentional neglect☆,☆☆,★

Abstract

Exp Neurol

Exp Neurol

Arch Phys Med Rehabil

Cortex

Prog Neuropsychopharmacol Biol Psychiatry

Neglect and related disorders

Attention, confusional states, and neglect

Dopamine agonist therapy for neglect in humans

Neurology

Pharmacotherapy for recovery of function after brain injury

Crit Rev Neurobiol

Neuropharmacologic management of hemi-inattention after brain injury

Neurol Rehabil

Clinical note
Adverse effect of dopamine agonist therapy in a patient with motor-intentional neglect☆,☆☆,★