1279

CLINICAL NOTE

Dopaminergic Therapy With Carbidopa L-Dopa for Left
Neglect After Stroke: A Case Series
Jon A. Mukand, MD, PhD, Thomas J. Guilmette, PhD, Deborah G. Allen, MS, CCC-SLP,
Lois K. Brown, MS, CCC-SLP, Suzanne L. Brown, OTR/L, Kelly L. Tober, OTR/L,
Walter R. VanDyck, OTR/L, BCN
ABSTRACT. Mukand JA, Guilmette TJ, Allen DG, Brown
LK, Brown SL, Tober KL, VanDyck WR. Dopaminergic
therapy with carbidopa L-dopa for left neglect after stroke: a
case series. Arch Phys Med Rehabil 2001;82:1279-82.
Objective: To evaluate the efficacy of carbidopa L-dopa
(Sinemet) in reducing left spatial neglect after stroke.
Design: Case series.
Setting: Inpatient neurorehabilitation unit in a regional rehabilitation center.
Participants: A convenience sample of 4 women with right
brain strokes and left neglect.
Intervention: A trial of carbidopa L-dopa to treat left neglect, if indicated by selected subtests of the Behavioral Inattention Test (BIT).
Main Outcome Measures: Baseline and posttreatment evaluation with the modified BIT and the FIM™ instrument.
Results: Three of 4 subjects had significant improvements in
their modified BIT scores (8%, 12%, 27%, respectively) and
their functional status on the FIM.
Conclusion: With further study, carbidopa L-dopa may be
shown to reduce unilateral spatial neglect and thereby improve
rehabilitation outcomes.
Key Words: Carbidopa; Cerebrovascular accident; Dopamine agonists; Left neglect; Levodopa; Rehabilitation
© 2001 by the American Congress of Rehabilitation Medicine and the American Academy of Physical Medicine and
Rehabilitation
NILATERAL SPATIAL NEGLECT is often found in
neurologic patients and is characterized by impaired
U
attention or reactions to stimuli presented contralateral to the
1,2

brain lesion. It is far more common and severe in patients with
damage to the nondominant hemisphere,3 usually on the right.
Unilateral spatial neglect has been associated with poor safety
awareness, disrupted daily activities, and the decreased likelihood of returning to work or driving.4,5 Patients may dress only
1 side, ignore food on half the plate, read only 1 side of a page,
or bump into objects on the neglected side. Overall, unilateral
spatial neglect can be a major impediment to functional recov-

From the Southern New England Rehabilitation Center, Providence, RI (Mukand,
Guilmette, Allen, Brown, Brown, Tober, VanDyck); Department of Physical Medicine and Rehabilitation, Boston University, Boston MA (Mukand); Department of
Physical Medicine and Rehabilitation, Tufts University School of Medicine, Boston,
MA (Mukand); Department of Orthopedics and Rehabilitation, Brown University,
Providence, RI (Mukand); Providence College and Brown University School of
Medicine, Providence, RI (Guilmette).
Accepted in revised form November 14, 2000.
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 author(s) or upon any
organization with which the author(s) is/are associated.
Reprint requests to Jon A. Mukand, MD, PhD, Southern New England Rehabilitation Center, 21 Peace St, Providence, RI 02907.
0003-9993/01/8209-6207$35.00/0
doi:10.1053/apmr.2001.25149

ery in rehabilitation.6 Estimates of its incidence after stroke
range from 12% to 90%, depending on the operational definition of this phenomenon.1
Despite the impact of unilateral spatial neglect on the recovery of functional abilities, a standardized therapeutic program
for this condition has yet to be developed.7 Behavioral interventions include visual scanning, perceptual retraining, imagery, and right hemispheric activation.5,8,9 Music therapy, vestibular stimulation, and eye patching have also produced some
benefit.10 Although numerous advances have been made recently,8-11 there is insufficient evidence to support 1 therapy
over another.
A contributing factor to a lack of systematic therapy for
unilateral spatial neglect is that its neuropathology is not well
understood. Although it is believed to reflect a deficit with
spatial attention, different aspects of attention and orienting
responses have been implicated.1 Neuroanatomically, unilateral spatial neglect occurs most frequently with damage to the
nondominant parietal lobe, and less often with frontal, thalamic, and basal ganglia lesions.12 Evidence from animal studies supports the role of dopaminergic pathways in the motor
and perceptual components of neglect. For example, sensory
inattention in rats has been reduced through the use of apomorphine, a dopamine agonist.13-15 In monkeys, hemineglect
has been induced by the infusion of a dopaminergic neurotoxin
in the caudate nucleus.16
Apomorphine temporarily reverses the off state in Parkinson’s disease,17 and was studied in 4 patients with left neglect
due to right ischemic lesions.18 It produced a transient but
significant improvement in perceptual-motor and perceptual
functions. The authors concluded that “dopaminergic neuronal
networks may mediate, in different ways, both perceptive and
premotor components of the unilateral neglect syndrome.”18
A literature search revealed no reports on carbidopa L-dopa
(Sinemet) for the treatment of neglect after stroke. Levodopa
(L-dopa) is a metabolic precursor of dopamine and presumably
treats Parkinson’s disease by increasing dopamine levels in the
brain. We hypothesized that increased dopaminergic activity in
the brain would also reduce unilateral spatial neglect.
METHOD
Four right-handed female patients with a right brain stroke
and left unilateral spatial neglect were given a shortened version of the Behavioral Inattention Test19 (BIT) before and after
1 week of carbidopa L-dopa to obtain a standardized functional
assessment of unilateral spatial neglect. A modified test was
used because the BIT was developed and validated with patients who stayed in the acute setting for long periods20; in
contrast, our patients had an average acute stay of only 6 days
and could have become fatigued with the lengthy original
version. Some redundancies also exist in the standard BIT
(letter and star cancellation, 3 reading subtests). Also because
of concerns about fatigue, the BIT was administered in the
morning.
Arch Phys Med Rehabil Vol 82, September 2001

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CARBIDOPA L-DOPA FOR LEFT NEGLECT AFTER STROKE, Mukand
Table 1: Patient Characteristics

Subject

Age (yr)

Location of Right CVA

BIT Gain(%)

FIM-A

FIM-C

FIM-D

FIM Gain (%)

1
2
3
4

76
75
66
70

Frontoparietal hemorrhage
Basal ganglia infarct
Occipital/posteromedial temporal infarcts
Middle cerebral artery territory infarct

27
8
12
NM*

49
59
62
27

64
69
66
47

84
80
87
52

31
16
32
11

Abbreviations: CVA, cerebrovascular accident; FIM-A, FIM score on admission; FIM-C, FIM score at initiation of carbidopa L-dopa; FIM-D, FIM
score at discharge; FIM Gain, % gain after carbidopa L-dopa.
* BIT scores were inconsistent and the gain is not meaningful (NM).

In our protocol an occupational therapist administered a
subtest of the conventional section of the BIT (paper and pencil
tasks) and a speech language pathologist administered a subtest
of the behavioral section (functional tasks). For the former we
used line-crossing, star cancellation, figure and shape copying,
and line bisection (maximum score, 103). Items from the
behavioral section included telephone dialing, telling and setting the time, address and sentence copying, and coin sorting
(maximum score, 36). These subtests19 appear to assess fully
perceptual and functional abilities while eliminating unnecessary duplication.
If a patient had functional deficits and a BIT score below
120, a trial of carbidopa L-dopa was started. The Sinemet dose
was 25/100mg, half a tablet 3 times daily for 2 days and then
1 tablet 3 times daily. Patients and family members gave
informed consent and were advised about possible side effects
including movement disorders, psychiatric symptoms, nausea,
and orthostatic hypotension. Gains in functional status were
measured with the FIM™ instrument score. All patients received at least 3 hours each day of physical, occupational, and
speech therapy as part of our standard stroke rehabilitation
program.21 The ages, diagnoses, BIT gains (%) after 1 week of
carbidopa L-dopa, and FIM scores (admission, premedication,
discharge) are listed in table 1. Figure 1 shows BIT scores preand postadministration of Sinemet.
Case 1
This patient presented with dense left hemiplegia, mild lethargy, left facial weakness, and dysarthria. She had reduced
sensation to light touch and pain at the left lower extremity.
The functional assessment revealed poor balance and maximum assistance for mobility and activities of daily living
(ADLs). Her poor attention and concentration affected her
short-term memory, reading, writing, and safety. Baseline test-

Fig 1. Modified BIT scores before and after carbidopa L-dopa.

Arch Phys Med Rehabil Vol 82, September 2001

ing with the modified BIT revealed 87/103 on the conventional
subtest and 21/36 on the behavioral one. After carbidopa Ldopa for 1 week, the scores improved to 101 and 36. At
discharge, she required supervision or contact guard with mobility and most ADLs. She was able to read short paragraphs
with only occasional verbal cues for left-sided scanning. Overall, fewer verbal cues were necessary for attention and redirection to the left side.
Case 2
This patient had left hemiplegia and hypertonicity, distractibility, and difficulty with multiple-step commands. Cues were
necessary for scanning to the left with tasks such as letter
cancellation, but her neglect was not as severe during functional tasks. Her BIT scores improved from 25 to 32 on the
behavioral portion and 88 to 90 on the conventional items after
1 week of treatment with carbidopa L-dopa. Her balance as
well as her functional status improved. At discharge she required supervision for most ADLs, except for minimal assistance with toileting and lower body functions.
Case 3
A patient with left central facial weakness, mild dysarthria,
occasional diplopia, and vertical nystagmus had a dense left
homonymous hemianopsia and inattention. Her functional assessment revealed minor difficulties with 3-step commands and
paragraph comprehension. She could transfer with minimal
assistance but needed moderate cues for safety. She required
moderate assistance and cues to attend to her left side, especially with bathing and dressing. After a trial of carbidopa
L-dopa, she improved with attending to the left and required
fewer cues to scan to the left. Her conventional BIT score
improved from 51 to 62 and the behavioral part had a slight
decrease (22 to 20), but her total score showed a gain from 73
to 82 (12%). She was discharged with supervision for most of
her ADLs.
Case 4
This patient was admitted with severe hypertension (220/
114), dense left hemiplegia, left facial weakness and ptosis,
lethargy, left neglect, and anxiety. She needed maximal assistance of 2 people for bed mobility and transfers, and was
dependent for her ADLs. BIT testing revealed scores of 1/36
and 32/103. After a trial of carbidopa L-dopa, her BIT score
improved from 33 to 46, but because she had no significant
functional gains the medication was discontinued after a week.
Retesting off carbidopa L-dopa yielded a score of only 28,
which was lower than her baseline score. In view of these
inconsistent results and the lack of functional progress, the
medication was not resumed. On discharge, she required maximal assistance for all ADLs, mobility, and reading.

CARBIDOPA L-DOPA FOR LEFT NEGLECT AFTER STROKE, Mukand

DISCUSSION
The beneficial response of 3 patients (fig 1, table 1) to
carbidopa L-dopa provides further support for the dopaminergic theory of unilateral spatial neglect that has been studied
in animals13-16 and with apomorphine in humans.17,18 At
present, apomorphine is not available in the United States, but
other dopaminergic options include ropinirole (Requip) and
pramipexole (Mirapex).
The dopamine agonist bromocriptine has also been effective
for the treatment of unilateral spatial neglect in humans, although in a small study.22 Dopaminergic therapy with bromocriptine has also benefited akinetic mutism, a condition that
may be described as severe bilateral neglect.23 Bromocriptine
has some early side effects that are problematic in patients with
stroke, including dizziness, drowsiness, and fainting. In studies
conducted for the treatment of Parkinson’s disease, adverse
reactions included nausea, dyskinesias, hallucinations, and
confusion. In addition, a recent case report24 described an
adverse effect of bromocriptine on left neglect. None of our
patients developed any side effects related to carbidopa Ldopa.
It is uncertain why carbidopa L-dopa has not been studied as
an agent for improving unilateral spatial neglect. This dopamine agonist improves cognitive functions, presumably by
increasing the level of arousal,25 and it may be difficult to
differentiate this effect from that on unilateral spatial neglect.
Clinicians may resist using carbidopa L-dopa for this reason,
but it could be at the expense of a beneficial effect on cognition
as well as neglect. In fact, the 3 patients in our series who
responded favorably to the medication all had cognitive deficits
to some extent. Future studies should include detailed cognitive
testing before and after carbidopa L-dopa.
Although our findings are encouraging, it is important to
note the limitations of the present study: the absence of
control subjects, of blinded staff, and of a large sample size.
A larger randomized controlled study should address the
issues of dosage, duration of treatment, and refined criteria
for a carbidopa L-dopa trial, eg, a BIT threshold. Such a
study would determine if BIT and FIM scores have improved due to spontaneous recovery, to the medication, or to
both. A larger study could also assess if the modified BIT is
helpful in screening candidates for carbidopa L-dopa. Based
on the absent response of the fourth patient, who had severe
left neglect and a very low BIT score, it seems reasonable to
suggest a BIT threshold above which a medication trial of
carbidopa L-dopa is indicated. Conversely, patients with
high BIT scores may respond to nonpharmacologic treatments and may not require carbidopa L-dopa. Improved BIT
scores after carbidopa L-dopa should be correlated with the
FIM or a more detailed instrument that focuses on activities
affected by unilateral spatial neglect. This approach would
help determine if the medication should be continued, as in
the fourth patient. If neglect and functional status improve,
one may consider a trial period off carbidopa L-dopa. In any
event, the medication should be stopped after 6 months to
avoid the long-term complication of dyskinesias.
The present series of cases also confirms earlier findings that
unilateral spatial neglect may occur after a variety of lesions.
Patients who responded to carbidopa L-dopa had lesions in the
right frontoparietal and right subcortical areas as well as the
territory of the posterior cerebral artery (temporal and occipital
lobes). The patient who did not respond had a large right
middle cerebral artery stroke. Therefore, it appears that patients
should neither be included nor excluded from a trial of carbi-

1281

dopa L-dopa based solely on the anatomic location of the
cerebrovascular accident.
CONCLUSION
Unilateral spatial neglect is thought to be multifactorial, and
current hypotheses focus on deficits with perceptual, attentional, and representational functions. A deafferentation hypothesis ascribes unilateral spatial neglect to a combination of
deficits such as hemianopsia and disorientation for person,
place, or time; finally, there is an interhemispheric hypothesis
that blames the undamaged left hemisphere for excessive attention to the right side.26 Therefore, carbidopa L-dopa should
not be used without other approaches such as right hemisphere
activation,5 imagery,8 and scanning.9
Because today’s health care climate is oriented to short
hospitalizations, it is important to accelerate the patient’s
recovery process and to gain the maximal benefit from the
inpatient therapeutic environment. Carbidopa L-dopa may
eventually be shown to reduce unilateral spatial neglect,
which may enhance the recovery process and reduce the
length of the inpatient stay. Additional benefits may be
fewer complications of stroke, such as falls, fractures, depression, and social isolation, all of which are important for
the patient’s quality of life.
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