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Citation: Li, S. Stroke Recovery Is a
Journey: Prediction and Potentials of
Motor Recovery after a Stroke from a
Practical Perspective. Life 2023,13,
2061. https://doi.org/10.3390/
life13102061
Academic Editors: Li-Wei Chou,
Jiunn-Horng Kang, Krisna Piravej
and Karen Sui Geok Chua
Received: 31 August 2023
Revised: 1 October 2023
Accepted: 14 October 2023
Published: 15 October 2023
Copyright: © 2023 by the author.
Licensee MDPI, Basel, Switzerland.
This article is an open access article
distributed under the terms and
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Attribution (CC BY) license (https://
creativecommons.org/licenses/by/
4.0/).
life
Article
Stroke Recovery Is a Journey: Prediction and Potentials of
Motor Recovery after a Stroke from a Practical Perspective
Sheng Li 1,2
1
Department of Physical Medicine and Rehabilitation, McGovern Medical School, University of Texas Health
Science Center—Houston, Houston, TX 77025, USA; sheng.li@uth.tmc.edu
2TIRR Memorial Hermann Hospital, Houston, TX 77030, USA
Abstract:
Stroke recovery is a journey. Stroke survivors can face many consequences that may last
the rest of their lives. Assessment of initial impairments allows reasonable prediction of biological
spontaneous recovery at 3 to 6 months for a majority of survivors. In real-world clinical practice,
stroke survivors continue to improve their motor function beyond the spontaneous recovery period,
but management plans for maximal recovery are not well understood. A model within the interna-
tional classification of functioning (ICF) theoretical framework is proposed to systematically identify
opportunities and potential barriers to maximize and realize the potentials of functional recovery
from the acute to chronic stages and to maintain their function in the chronic stages. Health conditions
of individuals, medical and neurological complications can be optimized under the care of special-
ized physicians. This permits stroke survivors to participate in various therapeutic interventions.
Sufficient doses of appropriate interventions at the right time is critical for stroke motor rehabilitation.
It is important to highlight that combining interventions is likely to yield better clinical outcomes.
Caregivers, including family members, can assist and facilitate targeted therapeutic exercises for
these individuals and can help stroke survivors comply with medical plans (medications, visits), and
provide emotional support. With health optimization, comprehensive rehabilitation, support from
family and caregivers and a commitment to a healthy lifestyle, many stroke survivors can overcome
barriers and achieve potentials of maximum recovery and maintain their motor function in chronic
stages. This ICF recovery model is likely to provide a guidance through the journey to best achieve
stroke recovery potentials.
Keywords: stroke; motor recovery; proportional recovery; spasticity; ICF
Key Contribution:
The article describes and discusses the current status of prediction and potentials
of motor recovery after a stroke. It proposes an ICF recovery model that provides a guidance through
the journey of stroke recovery.
1. Introduction
Strokes are a leading cause of adult disability [
1
]. There are approximately a total
of 7 million stroke survivors in the U.S [
2
], and about 133 million worldwide [
1
]. Stroke
survivors can face consequences that may last the rest of their lives. These consequences
include impairments related to thinking or memory, movement, sensation (e.g., vision or
hearing), verbal, swallowing, or emotional functioning (e.g., personality changes, depres-
sion). These impairments not only affect individuals, but can also have lasting effects on
families, caregivers and communities. Among the important goals of stroke rehabilitation
are to improve body function and to maximize functional independence, participation
and social reintegration, via coordinated delivery of therapies and interventions in an
interdisciplinary approach.
Life 2023,13, 2061. https://doi.org/10.3390/life13102061 https://www.mdpi.com/journal/life
Life 2023,13, 2061 2 of 13
2. Prediction of Motor Recovery
More than 80% of hospitalized patients after a stroke have some degrees of hemipare-
sis [
3
]. Hemiparesis includes negative symptoms, such as weakness and loss of dexterity,
and positive symptoms, such as spasticity and abnormal synergy. Stroke survivors recover
from hemiparesis spontaneously, but only to a certain degree. Spontaneous motor recovery
occurs mainly in the first 3 to 6 months post stroke [
4
,
5
]. Prediction of who will recover after
a stroke and to what extent has been a constant focus for researchers, clinicians, patients
and family members in the field of rehabilitation. Motor impairment and recovery are often
assessed and tracked by the Fugl-Meyer Motor Assessment (FMA) scale [
6
]. Prabhakaran
et al. [
7
] proposed a proportional recovery rule. According to this rule, the majority of
stroke survivors are expected to recover approximately 70% of their maximum potentials
at 3 months after a stroke. For the upper limb, the maximal potential recovery is the differ-
ence between the maximal possible FMA score (66) and the initial FMA score (FMA
initial
)
within the first week after the stroke. The predicted amount of motor recovery (
∆in FMA)
equals 0.7
×
(66—FMA
initial
). This rule has been replicated in many studies on upper-limb
recovery [
8
], but limited to those with mild to moderate motor impairments, i.e., fitters. The
non-fitters whose recovery does not follow the proportional recovery rule often have severe
motor impairments, i.e., a very low initial FMA score. This proportional recovery rule was
also observed in recovery of lower limb motor impairments [
9
], as well as in other domains,
including somatosensory impairment [
10
], spatial-visual neglect [
11
,
12
] and aphasia after
a stroke [
12
]. These consistent observations on recovery in different domains indicate
that there exists a general extent of spontaneous recovery in the first three months for a
subgroup of stroke survivors. However, the proportional recovery rule has been challenged
due to various confounds, namely mathematical coupling and statistical bias [
13
], or the
ceiling effects of FMA particularly in those with mild motor impairment [14].
These clinical observations of proportional recovery are accompanied by relevant
parallel neurophysiological measures. Byblow et al. found that, in a cohort of 93 first-ever
ischemic stroke survivors, those with the presence of motor evoked potentials (MEP+)
from the paretic wrist extensors 5 days after a stroke recovered approximately 70% of the
maximum recovery possible by 12 weeks; similarly, the ipsilesional resting motor thresh-
old was also resolved by 70%, while MEP- survivors did not demonstrate proportional
recovery [
15
]. Since the presence of MEP reflects integrity of the corticospinal tract, these
results provide physiological support for this rule of proportional recovery in those fitters,
at least at the population level. To better predict motor recovery for individuals, other
confounding factors are included in a later prediction algorithm (PREP2), such as age; the
presence or absence of the upper-limb motor evoked potentials elicited with transcranial
magnetic stimulation; and the stroke lesion load obtained from MRI or stroke severity
assessed with the NIHSS score [
16
]. The algorithm makes correct predictions of upper-limb
functional outcomes at 3 months after a stroke, however, only for 75% of patients [
16
]. In
these observational studies [
7
,
8
,
15
,
16
], the proportional recovery rule appears to reflect
spontaneous biological recovery and predict the extent of motor recovery for the majority
(about 70%) of stroke survivors.
The proportional rule offers valuable information to provide a reasonable prediction
of spontaneous recovery for majority of stroke patients in the early recovery phase. For
some patients with severe impairments, spontaneous recovery may take longer and the
initial assessment may not accurately reflect their recovery potentials. For example, 6 out
of 11 initially MEP- subjects later recovered MEPs at varying times with various levels of
recovery [
15
]. In the early spontaneous recovery period, CNS is highly plastic and sensitive
to interventions [
17
]. With neuromodulation and motor training, MEP- patients can achieve
meaningful functional gains [18].
3. Functional Recovery and an ICF Model of Stroke Recovery
In real-world clinical practice, stroke survivors continue to improve their motor func-
tion beyond the spontaneous recovery period, though at a lower rate in the subacute and
Life 2023,13, 2061 3 of 13
chronic stages [
19
–
21
]. For example, a person with left hemiparesis continues to improve
his walking from walking with parallel bars, to walking with a cane, and then walking
without assistance at a moderate speed at 2 years post stroke, although he still walks
in an abnormal pattern with compensatory mechanisms (Figure 1). According to the In-
ternational Classification of Functioning, Disability and Health (ICF), improvement in
walking performance is considered “recovery”, i.e., functional recovery [
22
]. However, the
development of complications, such as spasticity [
23
] and sarcopenia [
24
,
25
], is likely to
interfere with motor function in the later phase of motor recovery, as shown in Figure 1.
Life 2023, 13, x FOR PEER REVIEW 3 of 14
Figure 1. A gentleman had a middle cerebral artery ischemic stroke and resultant left hemiparesis
at the age of 60. He was able to walk 2 months post-stroke, with support from parallel bars on his
right side. As his recovery progressed, spasticity emerged and developed in his left arm and leg
muscles, i.e., spastic hemiplegia in the chronic phase. His gait continued to improve and he walked
with a cane. His left arm was in a flexed posture and did not swing. His knee was in mild flexion
during the stance phase, and his ankle was plantarflexed during the swing phase. At 2 years post-
stroke, he was able to walk at a moderate speed with legs alternating during walking. His hip flexor
spasticity progressively worsened. At 7 years post-stroke, he was still able to walk, but at a very slow
speed. His right leg was not able to advance and pass the left foot because of his left hip flexor
spasticity, i.e., step-to gait [19].
3. Functional Recovery and an ICF Model of Stroke Recovery
In real-world clinical practice, stroke survivors continue to improve their motor func-
tion beyond the spontaneous recovery period, though at a lower rate in the subacute and
chronic stages [20–22]. For example, a person with left hemiparesis continues to improve
his walking from walking with parallel bars, to walking with a cane, and then walking
without assistance at a moderate speed at 2 years post stroke, although he still walks in
an abnormal paern with compensatory mechanisms (Figure 1). According to the Inter-
national Classification of Functioning, Disability and Health (ICF), improvement in walk-
ing performance is considered “recovery”, i.e., functional recovery [23]. However, the de-
velopment of complications, such as spasticity [24] and sarcopenia [25,26], is likely to in-
terfere with motor function in the later phase of motor recovery, as shown in Figure 1.
Conceivably, in addition to factors that are important for spontaneous recovery [16],
the extent and duration of continuous functional recovery depend on a number of other
factors, such as management of complications and comorbidities, access to and participa-
tion in rehabilitation, and family and societal support. However, management approaches
for maximum recovery are not well understood and articulated. Within the ICF theoretical
framework, optimal recovery and independence of an individual with hemiparesis could
be achieved through a combination of optimization of medical and neurological condi-
tions, effective therapeutic interventions and assistive devices, and strong environmental
and family support. Accordingly, an ICF recovery model is proposed to understand the
ways to optimize the potentials of stroke recovery (Figure 2). This model allows a system-
atic approach to identify opportunities and manage potential barriers to maximize and
realize the potentials of functional recovery. These factors are elaborated in details in the
following sections.
Figure 1.
A gentleman had a middle cerebral artery ischemic stroke and resultant left hemiparesis at
the age of 60. He was able to walk 2 months post-stroke, with support from parallel bars on his right
side. As his recovery progressed, spasticity emerged and developed in his left arm and leg muscles,
i.e., spastic hemiplegia in the chronic phase. His gait continued to improve and he walked with a
cane. His left arm was in a flexed posture and did not swing. His knee was in mild flexion during the
stance phase, and his ankle was plantarflexed during the swing phase. At 2 years post-stroke, he
was able to walk at a moderate speed with legs alternating during walking. His hip flexor spasticity
progressively worsened. At 7 years post-stroke, he was still able to walk, but at a very slow speed.
His right leg was not able to advance and pass the left foot because of his left hip flexor spasticity, i.e.,
step-to gait [26].
Conceivably, in addition to factors that are important for spontaneous recovery [
16
],
the extent and duration of continuous functional recovery depend on a number of other
factors, such as management of complications and comorbidities, access to and participa-
tion in rehabilitation, and family and societal support. However, management approaches
for maximum recovery are not well understood and articulated. Within the ICF theoretical
framework, optimal recovery and independence of an individual with hemiparesis could
be achieved through a combination of optimization of medical and neurological conditions,
effective therapeutic interventions and assistive devices, and strong environmental and
family support. Accordingly, an ICF recovery model is proposed to understand the ways
to optimize the potentials of stroke recovery (Figure 2). This model allows a systematic
approach to identify opportunities and manage potential barriers to maximize and re-
alize the potentials of functional recovery. These factors are elaborated in details in the
following sections.
3.1. Optimization of Health Conditions (Medical and Neurological)
There is well-established evidence that a dedicated stroke unit and two critically impor-
tant inventions—intravenous thrombolytic drug treatment and endovascular mechanical
thrombectomy—can significantly impact a patient’s clinical outcome at stroke onset and
ultimately the recovery course. Risks of medical and neurological complications are high
in the early recovery phase. Immediately after a stroke, a neuroinflammatory process starts
in the brain, triggering a systemic immunodepression mainly through excessive activation
of the autonomous nervous system [
27
]. Stroke patients are susceptible to infections. The
most common infections are pneumonia and urinary tract infection; both occur in
≈
10% of
Life 2023,13, 2061 4 of 13
ischemic patients [
28
] and
≈
40% in hemorrhagic patients [
29
]. Experimental and clinical
data suggest that systemic infections enhance autoreactive immune responses against
brain antigens and thus negatively affect outcomes [
28
]. Pneumonia increases unfavorable
outcomes and mortality in patients with strokes. Seizures are frequently seen after cere-
brovascular accidents. About 6% of cases developed early seizures (within 1 week) [
30
,
31
].
Acute symptomatic or early seizures affect between 3% and 6% of all stroke patients [
32
].
In addition to infection and seizure, intracranial hemorrhage, recurrent ischemic stroke and
ischemic heart disease are the most common causes of acute care transfer among stroke
inpatients, thus interrupting stroke rehabilitation [
33
]. Other conditions may interrupt the
rehabilitation process temporarily, such as pulmonary embolus and deep vein thrombosis
(DVT). The overall incidence of DVT after an acute stroke within two weeks was 14.4% [
34
].
Life 2023, 13, x FOR PEER REVIEW 4 of 14
Figure 2. An ICF model of stroke recovery. See text for details.
3.1. Optimization of Health Conditions (Medical and Neurological)
There is well-established evidence that a dedicated stroke unit and two critically im-
portant inventions—intravenous thrombolytic drug treatment and endovascular mechan-
ical thrombectomy—can significantly impact a patient’s clinical outcome at stroke onset
and ultimately the recovery course. Risks of medical and neurological complications are
high in the early recovery phase. Immediately after a stroke, a neuroinflammatory process
starts in the brain, triggering a systemic immunodepression mainly through excessive ac-
tivation of the autonomous nervous system [27]. Stroke patients are susceptible to infec-
tions. The most common infections are pneumonia and urinary tract infection; both occur
in ≈10% of ischemic patients [28] and ≈40% in hemorrhagic patients [29]. Experimental
and clinical data suggest that systemic infections enhance autoreactive immune responses
against brain antigens and thus negatively affect outcomes [28]. Pneumonia increases un-
favorable outcomes and mortality in patients with strokes. Seizures are frequently seen
after cerebrovascular accidents. About 6% of cases developed early seizures (within 1
week) [30,31]. Acute symptomatic or early seizures affect between 3% and 6% of all stroke
patients [32]. In addition to infection and seizure, intracranial hemorrhage, recurrent is-
chemic stroke and ischemic heart disease are the most common causes of acute care trans-
fer among stroke inpatients, thus interrupting stroke rehabilitation [33]. Other conditions
may interrupt the rehabilitation process temporarily, such as pulmonary embolus and
deep vein thrombosis (DVT). The overall incidence of DVT after an acute stroke within
two weeks was 14.4% [34].
Some complications can limit their participation in therapy, for example pain and
depression. Stroke-related pain is present in 21% of stroke survivors and is associated with
sensorimotor impairments and depression [35]. The complex regional pain syndrome
(CRPS) that occurs after a stroke is often called shoulder–hand syndrome. Its prevalence
ranges from 12.5% to 50% [36–38]. Post-stroke pain is often insufficiently recognized or
inadequately treated. Patients’ activities of daily living and participation in therapy are
negatively affected [39]. It has been shown that the activity status of the affected upper
limb was negatively associated with the pain intensity in patients with post-stroke CRPS
[40]. Post-stroke depression (PSD) is recognized as the most common neuropsychiatric
complication following a stroke. Its symptoms develop within three to six months after a
Figure 2. An ICF model of stroke recovery. See text for details.
Some complications can limit their participation in therapy, for example pain and
depression. Stroke-related pain is present in 21% of stroke survivors and is associated
with sensorimotor impairments and depression [
35
]. The complex regional pain syndrome
(CRPS) that occurs after a stroke is often called shoulder–hand syndrome. Its prevalence
ranges from 12.5% to 50% [
36
–
38
]. Post-stroke pain is often insufficiently recognized or
inadequately treated. Patients’ activities of daily living and participation in therapy are
negatively affected [
39
]. It has been shown that the activity status of the affected upper limb
was negatively associated with the pain intensity in patients with post-stroke CRPS [
40
].
Post-stroke depression (PSD) is recognized as the most common neuropsychiatric compli-
cation following a stroke. Its symptoms develop within three to six months after a stroke
event and affect 20–65% of stroke patients [
41
]. (please move the highlighted sentence on
depression here for a better flow) Vision impairment is prevalent and persistent (up to
93% of stroke survivors). This negatively affects their participation and engagement in
therapy [
42
,
43
]. Depression is associated with less engagement in therapy and a worse
functional outcome [
44
]. Cognitive impairment is a frequent consequence of strokes [
45
]
and impacts patient engagement during inpatient stroke rehabilitation as well [46].
Nutritional support plays a critical role in health optimization for stroke recovery. In
the acute phase, the risk of malnutrition is high. Malnutrition was identified in 25.8% of
patients in a recent multicenter prospective study of 2962 acute stroke patients without
Life 2023,13, 2061 5 of 13
pre-stroke disability [
47
]). Malnutrition is likely attributable to oropharyngeal dysphagia
at this stage, which is found in up to 45% of stroke patients, using bedside screening
techniques [
48
]. Delay in early screening for swallowing capacity in acute stroke patients
is detrimental to outcomes, possibly due to delaying nutritional provision or through
inappropriate feeding leading to aspiration. Compared to those who received swallow
screening within 4 h of admission, a delay between 4 and 72 h was associated with greater
risks of pneumonia, prolonged length of stay in a hyperacute stroke unit, and even mortality
rate [
49
]. Although dysphagia itself was not a significant predictor of any of the outcomes
measured, overall functional dependency was the most significant predictor of poor oral
fluid intake and fluid-related adverse health outcomes in sub-acute strokes [50].
Taken together, stroke patients may have an initial poor functional assessment due
to acute events and complications. However, after successful treatments and health op-
timization, more than 40% recover to good outcomes within 1 year [
51
]. These factors
could account for a good recovery of non-fitters in the proportional recovery observational
studies, and they should be taken into account for prediction of motor recovery. It is
thus prudent to avoid early pessimistic prognostication until after successful treatment of
these complications.
3.2. Effective Therapeutic Interventions
A comprehensive rehabilitation program is essential for stroke recovery. A standard
motor rehabilitation program involves physical therapy and occupational therapy, which
are usually delivered with assistive devices and technologies. The effectiveness of thera-
peutic interventions with pharmacological agents and advanced technologies and devices
has been extensively explored. Optimal interventions, including content and modality,
dosing, timing and combinations of these are still under investigation.
3.2.1. Pharmacological Interventions
Numerous experiments have studied pharmacological interventions for motor re-
covery. Selective serotonin reuptake inhibitors (SSRI) are the most studied medication,
including the FLAME [
52
], FOCUS [
53
], AFFINITY [
54
] and EFFECTS [
55
] trials. Although
the initial FLAME trial showed promising results, a meta-analysis of 76 studies with
13,029 participants has revealed high-quality evidence that SSRIs alone do not make a
difference to disability or independence after strokes as compared to a placebo or usual
care [
56
]. Similarly, after promising results of dopamine agents on enhancing motor recov-
ery when given in combination with physical therapy from 53 stroke participants [
57
], a
large DARS trial with 1574 participants reported that co-careldopa in combination with
routine therapies did not improve walking after strokes [
58
]. Other medications, such
as D-amphentamine, Niacin, inosine and citicoline all showed some positive results in
studies with small samples, but not in studies with large samples [
59
]. Many cofounding
factors are discussed, such as stroke lesions, subject selections and outcome assessments.
Pharmacological interventions benefit a subgroup of stroke survivors, e.g., SSRIs are given
to patients with depression to improve their participation in therapy thus to facilitate motor
recovery. In other words, stroke recovery is likely to be improved by precision medicine.
On the other hand, it is of the same importance to avoid medications that could
negatively affect stroke survivors. It has been shown that anticholinergics and sedatives
are independent factors associated with the time to recovery of activities of daily living and
postural balance [60].
3.2.2. Timing of Physical Interventions and Modalities
Spontaneous biological recovery is mostly attributable to a time-limited period of
neuroplasticity [
61
]. To maximize the effectiveness of rehabilitative therapies after stroke,
it is critical to determine when the brain is most responsive (i.e., plastic) to sensorimotor
intervention and to focus such efforts within this period. In a recent clinical trial, Dromerick
et al. compared an additional 15 to 20 h of upper-limb motor intervention given after
Life 2023,13, 2061 6 of 13
fewer than 30 days (acute), 2 to 3 months (subacute) or greater than 6 months (chronic)
with standard care (control). The outcome (the Action Research Arm Test, ARAT) was
assessed over a year after the stroke. The results showed that only the subacute group
surpassed the minimum clinically important difference on ARAT in comparison with the
control group (ARAT = +6.87
±
2.63 points). The acute group showed significant but
smaller improvement (+5.25
±
2.59 points). The chronic group showed no significant
improvement compared with controls (+2.41
±
2.25 point). This trial demonstrated that
an early sensitive window exists, consistent with the first 2 to 3 months after the stroke.
Additional therapy interventions during this critical period may change the recovery
trajectory [
17
]. The optimal intervention dose and content to deliver within the sensitive
window is an important question for future research.
3.2.3. Optimizing the Intervention Dose
Motor recovery requires repetitions. Intensive and repetitive task-specific training of
motor tasks and activities is recommended after a stroke [
62
,
63
]. In the acute rehabilitation
phase (within 3 weeks post-stroke), robotic-assisted gait training (RAGT) is feasible to
provide a higher dose of task-specific gait training for non-ambulatory stroke survivors. As
compared to the conventional group (527 steps/day), the RAGT group had a much higher
number of steps (1870 steps/day) and greater motor gain (32.3 vs. 17.9) at discharge [
64
].
When given in the subacute period, stroke survivors had clinically meaningful improve-
ment after 20 h of additional therapy [
17
]. In the chronic phase, Ward et al. reported
significant improvement in the upper-limb function in stroke survivors after a total of 90 h
of therapy over 3 weeks (6 h per day), and the improvement was maintained at 6 months
after the intervention [
65
]. In another study, chronic stroke survivors with moderate to
severe motor impairments had significant improvement in their upper-limb function after
150 h of training and continued to improve after 300 h of training (5 h/day, 5 days/week
for 12 weeks). The improvement was sustained for at least 3 months [
66
]. According to
a recent Cochrane review, there is currently insufficient evidence to recommend a mini-
mum beneficial daily amount in clinical practice. However, if the increase in time spent in
rehabilitation exceeds a threshold, this may lead to improved outcomes [67].
Current inpatient and outpatient therapy sessions are not optimal, as compared to the
above literature reports. Typical inpatient rehabilitation sessions in the United States last
~39 min/day for ~12 days poststroke [
68
]. Outpatient rehabilitation sessions in the United
States last ~36 min/day with patients engaging in an average of 12 purposeful movements
in an otherwise unstructured treatment session, continuing for a few weeks [
69
]. Ad-
vancements in technology applications in stroke rehabilitation make it possible to increase
therapy time and the patient’s engagement. Robot-assisted training with videogaming
appears to be an attractive approach for upper-limb recovery for inpatient stroke rehabilita-
tion [
70
]. Home-based robot-assisted training or virtual-reality training make it feasible to
supplement outpatient therapy sessions [71–73].
3.2.4. Interventions to Address Complications
Along with continuous recovery, other motor impairments, such as abnormal synergy
and spasticity, are likely to develop. Spasticity is present in up to 97% of stroke survivors
with moderate to severe motor impairments [
74
]. Spasticity can interact with weakness,
and worsen the motor functions (difficulty walking, reaching, grasping etc). For example,
intended hand opening could result in hand closing due to involuntary activation associated
with finger flexor spasticity [
75
]. In the acute phase, early detection and suppression of
spasticity via botulinum toxin injections can prevent contracture development and maintain
the range of motion of affected joints, while progress in motor recovery is not negatively
affected [
76
]. In the chronic phase, appropriate and adequate management of ankle plantar
flexor spasticity can correct ankle and foot joint abnormality and placement [
77
], and
improve gait speed in ambulatory stroke survivors with spastic equinus foot [78].
Life 2023,13, 2061 7 of 13
3.2.5. Combination of Interventions
It is of scientific rigor to control confounding factors and assess the effectiveness
of an individual intervention. In real practice, combining different interventions and
modalities is likely to yield better clinical outcomes, especially when interventions target
different areas. For example, to improve hand function in stroke patients with spastic
hemiplegia, a botulinum toxin injection was used to reduce finger flexor spasticity, and
electrical stimulation to strengthen finger extensor muscles. In addition, the patient received
intense therapy 1 h per day for 4 weeks [
79
]. Although it is known that medication alone
(botulinum toxin therapy) [
80
] or electrical stimulation alone ([
81
,
82
] is not effective in
improving the motor function of the hand in chronic stroke survivors, results from this
study [
79
] demonstrated that different interventions could work synergistically to achieve
optimal clinical results. This concept of combining interventions to better recovery after
a stroke is supported by results from other studies, such as medication and tDCS [
83
],
tDCS and robot-assisted training [
84
], mirror therapy and electrical stimulation [
85
], mirror
therapy and non-invasive brain stimulation [
86
], Vagus nerve stimulation and intense
therapies [87].
3.3. Maintenance of Motor Function
There are heterogeneous reports in the literature on motor function after discharge
from inpatient rehabilitation. Many studies have reported that the motor function of stroke
survivors continues to improve up to 2~3 years post-stroke [
20
,
88
,
89
] (Figure 3). Stroke
survivors with regular exercises can maintain motor functions and overall quality of life
4 years after the incident [
90
]. Others have reported functional decline over time since the
discharge to home [
89
,
91
]. Meyer et al. reported that the functional and motor outcome
at 5 years after a stroke is equivalent to the outcome at 2 months [
92
]. Some patient
characteristics or clinical variables are associated with deterioration of the outcome several
years after stroke rehabilitation, including higher age, stroke severity, concomitant chronic
disorders, cognitive problems, and depression [93,94].
Life 2023, 13, x FOR PEER REVIEW 8 of 14
Figure 3. Schematic illustration of longitudinal view of recovery and maintenance of motor function
after a stroke. Stroke survivors have a predicted curve of motor recovery (red line). With a program-
matic approach, they may be able to maintain their motor function (blue line) as compared to age-
matched counterparts (green) with a normal rate of decline. Many factors may lead to a faster func-
tional decline (brown line).
Some factors are modifiable and play an important role in the maintenance of motor
functions in chronic stroke survivors. Even after stroke survivors return to living in the
community, their levels of physical activity remain lower than their age-matched counter-
parts [95]. Community-dwelling stroke survivors spend the vast majority of their waking
time siing down [96]. A decreased physical activity level is associated with an increased
risk of cardiovascular disease and diabetes [97]. Furthermore, the risk of malnutrition is
high, especially in older stroke survivors [98,99]. Both a decline in mobility and malnutri-
tion contribute to wasting of skeletal muscles, i.e., sarcopenia [25], which in turn nega-
tively affects muscle strength and motor function [100]. Motivation and social participa-
tion as well as resources available to stroke survivors often generate synergy to maintain
and improve their activities of daily living [88,101]. Collectively, programmatic ap-
proaches targeting exercise, nutrition and motivation can enable stroke survivors to build
confidence to engage in self-managed practice routines and maintenance of motor func-
tion [102].
3.4. Family and Societal Support
Stroke recovery can be a long and challenging process for the family and society as
well. The inability of stroke survivors to adequately perform basic activities imposes a
significant burden on their caregivers, specifically informal caregivers who are not hired
to provide caregiving services, usually family members [103,104]. At least one-third of
caregivers reported having spent a moderate to a great deal of time assisting with nursing,
personal care, walking, and transfer (e.g., from bed to a chair) tasks. More than two-thirds
spent a moderate to a great deal of time providing emotional support, monitoring the
stroke survivor’s progress, talking to health care professionals regarding the stroke survi-
vor’s condition and treatment plan, providing transportation, helping with additional
tasks at home and outside the home, and managing the stroke survivor’s finances and
medical bills [104]. Furthermore, this study also found that the caregiver’s burden in-
creased with the level of the stroke survivor’s disability [104]. Informal caring for stroke
survivors is associated with humanistic costs including decrements in health-related qual-
ity of life. Another study reported caregivers had significant humanistic burdens such as
depression and anxiety [105]. Overall, it has been reported that the quality of life of care-
givers has been significantly affected [103]. The family’s ability to provide adequate care-
giving services is important for stroke survivors to stay engaged in their rehabilitation
program and to set achievable goals for themselves. A recent study revealed that pre-
stroke socioeconomic status (SES) predicts upper-limb motor recovery after inpatient
Figure 3.
Schematic illustration of longitudinal view of recovery and maintenance of motor func-
tion after a stroke. Stroke survivors have a predicted curve of motor recovery (red line). With a
programmatic approach, they may be able to maintain their motor function (blue line) as compared
to age-matched counterparts (green) with a normal rate of decline. Many factors may lead to a faster
functional decline (brown line).
Some factors are modifiable and play an important role in the maintenance of motor
functions in chronic stroke survivors. Even after stroke survivors return to living in
the community, their levels of physical activity remain lower than their age-matched
counterparts [
95
]. Community-dwelling stroke survivors spend the vast majority of their
waking time sitting down [
96
]. A decreased physical activity level is associated with
an increased risk of cardiovascular disease and diabetes [
97
]. Furthermore, the risk of
malnutrition is high, especially in older stroke survivors [
98
,
99
]. Both a decline in mobility
Life 2023,13, 2061 8 of 13
and malnutrition contribute to wasting of skeletal muscles, i.e., sarcopenia [
24
], which in
turn negatively affects muscle strength and motor function [
100
]. Motivation and social
participation as well as resources available to stroke survivors often generate synergy to
maintain and improve their activities of daily living [
88
,
101
]. Collectively, programmatic
approaches targeting exercise, nutrition and motivation can enable stroke survivors to
build confidence to engage in self-managed practice routines and maintenance of motor
function [102].
3.4. Family and Societal Support
Stroke recovery can be a long and challenging process for the family and society as
well. The inability of stroke survivors to adequately perform basic activities imposes a
significant burden on their caregivers, specifically informal caregivers who are not hired
to provide caregiving services, usually family members [
103
,
104
]. At least one-third of
caregivers reported having spent a moderate to a great deal of time assisting with nursing,
personal care, walking, and transfer (e.g., from bed to a chair) tasks. More than two-thirds
spent a moderate to a great deal of time providing emotional support, monitoring the stroke
survivor’s progress, talking to health care professionals regarding the stroke survivor’s
condition and treatment plan, providing transportation, helping with additional tasks at
home and outside the home, and managing the stroke survivor’s finances and medical
bills [
104
]. Furthermore, this study also found that the caregiver’s burden increased with
the level of the stroke survivor’s disability [
104
]. Informal caring for stroke survivors is
associated with humanistic costs including decrements in health-related quality of life.
Another study reported caregivers had significant humanistic burdens such as depression
and anxiety [
105
]. Overall, it has been reported that the quality of life of caregivers has been
significantly affected [
103
]. The family’s ability to provide adequate caregiving services is
important for stroke survivors to stay engaged in their rehabilitation program and to set
achievable goals for themselves. A recent study revealed that pre-stroke socioeconomic
status (SES) predicts upper-limb motor recovery after inpatient neurorehabilitation [
106
].
Higher pre-stroke SES is associated with more frequent use of outpatient therapy, and better
access to resources, thus better long-term recovery after discharge from rehabilitation [
106
].
Understanding these factors is important to advocate policy changes to improve access to
healthcare for all stroke survivors.
4. Concluding Remarks
Stroke recovery is a journey for stroke survivors. The journey starts with the stroke
onset and may last for the rest of their life. Prediction of who will recover after a stroke and
to what extent has been a constant focus in the field of rehabilitation. Assessment of initial
impairments allows a reasonable prediction of biological spontaneous recovery at 3 to
6 months poststroke. Stroke survivors usually continue to improve their motor function for
the first several years, but their motor function is likely to decline afterwards. A recovery
model within the ICF theoretical framework is proposed here to identify opportunities and
manage barriers to achieve maximum recovery and maintain motor function throughout
the journey. The ICF recovery model involves health optimization, comprehensive rehabili-
tation, support from family and caregivers, and a commitment to a healthy lifestyle. Health
conditions of individuals and medical and neurological complications can be optimally
managed under the care of specialized physicians. Health optimization is particularly
important in early recovery to minimize the interruption of and to facilitate participation in
various therapies and therapeutic interventions. This could potentially change the trajectory
of motor recovery. Applications of novel interventions can improve the motor functions
and independent living of these individuals. A sufficient dose of appropriate interventions
at the right time is critical for stroke motor rehabilitation. There is evidence of a critical
period when stroke survivors are most plastic and sensitive to therapeutic interventions.
However, there is currently insufficient evidence to recommend a minimum beneficial
daily amount in clinical practice. It is important to highlight that combining interventions
Life 2023,13, 2061 9 of 13
is likely to yield the best clinical outcomes. Caregivers, including family members, can
assist and facilitate targeted therapeutic exercises for these individuals, through planned
independent-living training. Furthermore, caregivers can help them comply with medical
plans (medications, visits), and provide emotional support. Family support and adequate
nutrition and a commitment to a healthy lifestyle are key to maintaining their motor func-
tion and independence in the later phase of motor recovery. This interdisciplinary care
approach is likely to achieve their recovery potentials. The ICF recovery model is likely to
provide a guidance through the journey to best achieve stroke recovery potentials. At the
present time, the evidence of ICF usage in stroke rehabilitation is scarce [
107
,
108
]. Clinicians
often face the burden of extracting the ICF codes. A recent report showed the applicability
of Chat-GPT to extract ICF codes to assist clinical decision making [109].
Funding: This research received no external funding.
Data Availability Statement:
The datasets used to support the findings of this study are available
from the corresponding author upon request.
Conflicts of Interest: The author declares no conflict of interest.
References
1.
Feigin, V.L.; Brainin, M.; Norrving, B.; Martins, S.; Sacco, R.L.; Hacke, W.; Fisher, M.; Pandian, J.; Lindsay, P. World Stroke
Organization (WSO): Global Stroke Fact Sheet 2022. Int. J. Stroke Off. J. Int. Stroke Soc. 2022,17, 18–29. [CrossRef]
2.
Tsao, C.W.; Aday, A.W.; Almarzooq, Z.I.; Alonso, A.; Beaton, A.Z.; Bittencourt, M.S.; Boehme, A.K.; Buxton, A.E.; Carson, A.P.;
Commodore-Mensah, Y.; et al. Heart Disease and Stroke Statistics—2022 Update: A Report From the American Heart Association.
Circulation 2022,145, e153–e639. [CrossRef] [PubMed]
3.
Rathore, S.S.; Hinn, A.R.; Cooper, L.S.; Tyroler, H.A.; Rosamond, W.D. Characterization of incident stroke signs and symptoms:
Findings from the atherosclerosis risk in communities study. Stroke 2002,33, 2718–2721. [CrossRef] [PubMed]
4.
Kwakkel, G.; Kollen, B.; Lindeman, E. Understanding the pattern of functional recovery after stroke: Facts and theories. Restor.
Neurol. Neurosci. 2004,22, 281–299. [PubMed]
5.
Jørgensen, H.S.; Nakayama, H.; Raaschou, H.O.; Olsen, T.S. Recovery of walking function in stroke patients: The copenhagen
stroke study. Arch. Phys. Med. Rehabil. 1995,76, 27–32. [CrossRef]
6.
Fugl Meyer, A.R.; Jaasko, L.; Leyman, I. The post stroke hemiplegic patient. I. A method for evaluation of physical performance.
Scand. J. Rehabil. Med. 1975,7, 13–31. [CrossRef]
7.
Prabhakaran, S.; Zarahn, E.; Riley, C.; Speizer, A.; Chong, J.Y.; Lazar, R.M.; Marshall, R.S.; Krakauer, J.W. Inter-individual
variability in the capacity for motor recovery after ischemic stroke. Neurorehabilit. Neural Repair 2008,22, 64–71. [CrossRef]
8.
Winters, C.; Van Wegen, E.E.H.; Daffertshofer, A.; Kwakkel, G. Generalizability of the Proportional Recovery Model for the Upper
Extremity After an Ischemic Stroke. Neurorehabilit. Neural Repair 2015,29, 614–622. [CrossRef]
9.
Smith, M.C.; Byblow, W.D.; Barber, P.A.; Stinear, C.M. Proportional Recovery From Lower Limb Motor Impairment After Stroke.
Stroke 2017,48, 1400–1403. [CrossRef]
10.
Boccuni, L.; Meyer, S.; Kessner, S.S.; De Bruyn, N.; Essers, B.; Cheng, B.; Thomalla, G.; Peeters, A.; Sunaert, S.; Duprez, T.; et al. Is
There Full or Proportional Somatosensory Recovery in the Upper Limb After Stroke? Investigating Behavioral Outcome and
Neural Correlates. Neurorehabilit. Neural Repair 2018,32, 691–700. [CrossRef]
11.
Winters, C.; van Wegen, E.E.; Daffertshofer, A.; Kwakkel, G. Generalizability of the Maximum Proportional Recovery Rule to
Visuospatial Neglect Early Poststroke. Neurorehabilit. Neural Repair 2017,31, 334–342. [CrossRef]
12.
Marchi, N.A.; Ptak, R.; Di Pietro, M.; Schnider, A.; Guggisberg, A.G. Principles of proportional recovery after stroke generalize to
neglect and aphasia. Eur. J. Neurol. 2017,24, 1084–1087. [CrossRef] [PubMed]
13.
Hope, T.M.H.; Friston, K.; Price, C.J.; Leff, A.P.; Rotshtein, P.; Bowman, H. Recovery after stroke: Not so proportional after all?
Brain 2019,142, 15–22. [CrossRef] [PubMed]
14.
Lee, H.H.; Kim, D.Y.; Sohn, M.K.; Shin, Y.I.; Oh, G.J.; Lee, Y.S.; Joo, M.C.; Lee, S.Y.; Han, J.; Ahn, J.; et al. Revisiting the Proportional
Recovery Model in View of the Ceiling Effect of Fugl-Meyer Assessment. Stroke 2021,52, 3167–3175. [CrossRef] [PubMed]
15.
Byblow, W.D.; Stinear, C.M.; Barber, P.A.; Petoe, M.A.; Ackerley, S.J. Proportional recovery after stroke depends on corticomotor
integrity. Ann. Neurol. 2015,78, 848–859. [CrossRef] [PubMed]
16.
Stinear, C.M.; Byblow, W.D.; Ackerley, S.J.; Smith, M.C.; Borges, V.M.; Barber, P.A. PREP2: A biomarker-based algorithm for
predicting upper limb function after stroke. Ann. Clin. Transl. Neurol. 2017,4, 811–820. [CrossRef]
17.
Dromerick, A.W.; Geed, S.; Barth, J.; Brady, K.; Giannetti, M.L.; Mitchell, A.; Edwardson, M.A.; Tan, M.T.; Zhou, Y.; Newport, E.L.;
et al. Critical Period After Stroke Study (CPASS): A phase II clinical trial testing an optimal time for motor recovery after stroke in
humans. Proc. Natl. Acad. Sci. USA 2021,118, e2026676118. [CrossRef] [PubMed]
18.
Powell, E.S.; Westgate, P.M.; Goldstein, L.B.; Sawaki, L. Absence of Motor-Evoked Potentials Does Not Predict Poor Recovery in
Patients With Severe-Moderate Stroke: An Exploratory Analysis. Arch. Rehabil. Res. Clin. Transl. 2019,1, 100023. [CrossRef]
Life 2023,13, 2061 10 of 13
19.
Ingwersen, T.; Wolf, S.; Birke, G.; Schlemm, E.; Bartling, C.; Bender, G.; Meyer, A.; Nolte, A.; Ottes, K.; Pade, O.; et al. Long-term
recovery of upper limb motor function and self-reported health: Results from a multicenter observational study 1 year after
discharge from rehabilitation. Neurol. Res. Pract. 2021,3, 66. [CrossRef]
20.
Borschmann, K.N.; Hayward, K.S. Recovery of upper limb function is greatest early after stroke but does continue to improve
during the chronic phase: A two-year, observational study. Physiotherapy 2020,107, 216–223. [CrossRef] [PubMed]
21.
Ballester, B.R.; Maier, M.; Duff, A.; Cameirao, M.; Bermudez, S.; Duarte, E.; Cuxart, A.; Rodriguez, S.; San Segundo Mozo, R.M.;
Verschure, P. A critical time window for recovery extends beyond one-year post-stroke. J. Neurophysiol.
2019
,122, 350–357.
[CrossRef] [PubMed]
22.
World Health Organization. ICF Practical Manual (Draft). Available online: https://www.who.int/standards/classifications/
international-classification-of-functioning-disability-and-health (accessed on 5 July 2023).
23.
Li, S.; Francisco, G.E.; Rymer, W.Z. A New Definition of Poststroke Spasticity and the Interference of Spasticity With Motor
Recovery From Acute to Chronic Stages. Neurorehabilit. Neural Repair 2021,35, 601–610. [CrossRef] [PubMed]
24.
Li, S.; Gonzalez-Buonomo, J.; Ghuman, J.; Huang, X.; Malik, A.; Yozbatiran, N.; Magat, E.; Francisco, G.E.; Wu, H.; Frontera,
W.R. Aging after stroke: How to define post-stroke sarcopenia and what are its risk factors? Eur. J. Phys. Rehabil. Med.
2022
,58,
683–692. [CrossRef] [PubMed]
25.
Nozoe, M.; Kanai, M.; Kubo, H.; Yamamoto, M.; Shimada, S.; Mase, K. Prestroke sarcopenia and functional outcomes in elderly
patients who have had an acute stroke: A prospective cohort study. Nutrition 2019,66, 44–47. [CrossRef] [PubMed]
26.
Li, S. Stiff Knee Gait Disorders as Neuromechanical Consequences of Spastic Hemiplegia in Chronic Stroke. Toxins
2023
,15, 204.
[CrossRef]
27.
Jiang, Q.; Stone, C.R.; Elkin, K.; Geng, X.; Ding, Y. Immunosuppression and Neuroinflammation in Stroke Pathobiology. Exp.
Neurobiol. 2021,30, 101–112. [CrossRef]
28.
Westendorp, W.F.; Dames, C.; Nederkoorn, P.J.; Meisel, A. Immunodepression, Infections, and Functional Outcome in Ischemic
Stroke. Stroke 2022,53, 1438–1448. [CrossRef]
29.
Yokobatake, K.; Ohta, T.; Kitaoka, H.; Nishimura, S.; Kashima, K.; Yasuoka, M.; Nishi, K.; Shigeshima, K. Safety of early
rehabilitation in patients with aneurysmal subarachnoid hemorrhage: A retrospective cohort study. J. Stroke Cerebrovasc. Dis.
2022,31, 106751. [CrossRef] [PubMed]
30.
So, E.L.; Annegers, J.F.; Hauser, W.A.; O’Brien, P.C.; Whisnant, J.P. Population-based study of seizure disorders after cerebral
infarction. Neurology 1996,46, 350–355. [CrossRef]
31.
Beghi, E.; D’Alessandro, R.; Beretta, S.; Consoli, D.; Crespi, V.; Delaj, L.; Gandolfo, C.; Greco, G.; La Neve, A.; Manfredi, M.; et al.
Incidence and predictors of acute symptomatic seizures after stroke. Neurology 2011,77, 1785–1793. [CrossRef]
32.
Merlino, G.; Gigli, G.L.; Bax, F.; Serafini, A.; Corazza, E.; Valente, M. Seizures Do Not Affect Disability and Mortality Outcomes of
Stroke: A Population-Based Study. J. Clin. Med. 2019,8, 2006. [CrossRef] [PubMed]
33.
Pongratanakul, R.; Thitisakulchai, P.; Kuptniratsaikul, V. Factors related to interrupted inpatient stroke rehabilitation due to acute
care transfer or death. Neurorehabilitation 2020,47, 171–179. [CrossRef] [PubMed]
34.
Pan, X.; Wang, Z.; Chen, Q.; Xu, L.; Fang, Q. Development and Validation of a Nomogram for Lower Extremity Deep Venous
Thrombosis in Patients after Acute Stroke. J. Stroke Cerebrovasc. Dis. 2021,30, 105683. [CrossRef]
35.
Lundström, E.; Smits, A.; Terént, A.; Borg, J. Risk factors for stroke-related pain 1 year after first-ever stroke. Eur. J. Neurol.
2009
,
16, 188–193. [CrossRef]
36. Van Ouwenaller, C.; Laplace, P.M.; Chantraine, A. Painful shoulder in hemiplegia. Arch. Phys. Med. Rehabil. 1986,67, 23–26.
37.
Kocabas, H.; Levendoglu, F.; Ozerbil, O.M.; Yuruten, B. Complex regional pain syndrome in stroke patients. Int. J. Rehabil. Res.
2007,30, 33–38. [CrossRef]
38.
Gokkaya, N.K.; Aras, M.; Yesiltepe, E.; Koseoglu, F. Reflex sympathetic dystrophy in hemiplegia. Int. J. Rehabil. Res.
2006
,29,
275–279. [CrossRef]
39.
Timm, A.; Knecht, S.; Florian, M.; Pickenbrock, H.; Studer, B.; Schmidt-Wilcke, T. Frequency and nature of pain in patients
undergoing neurorehabilitation. Clin. Rehabil. 2021,35, 145–153. [CrossRef]
40.
Katsura, Y.; Ohga, S.; Shimo, K.; Hattori, T.; Yamada, T.; Matsubara, T. Post-Stroke Complex Regional Pain Syndrome and Upper
Limb Inactivity in Hemiplegic Patients: A Cross-Sectional Study. J. Pain. Res. 2022,15, 3255–3262. [CrossRef]
41.
Saxena, S.K.; Ng, T.P.; Yong, D.; Fong, N.P.; Koh, G. Subthreshold depression and cognitive impairment but not demented in
stroke patients during their rehabilitation. Acta Neurol. Scand. 2008,117, 133–140. [CrossRef]
42.
Pollock, A.; Hazelton, C.; Rowe, F.J.; Jonuscheit, S.; Kernohan, A.; Angilley, J.; Henderson, C.A.; Langhorne, P.; Campbell, P.
Interventions for visual field defects in people with stroke. Cochrane Database Syst. Rev.
2019
,5, Cd008388. [CrossRef] [PubMed]
43.
Wijesundera, C.; Crewther, S.G.; Wijeratne, T.; Vingrys, A.J. Vision and Visuomotor Performance Following Acute Ischemic Stroke.
Front. Neurol. 2022,13, 757431. [CrossRef] [PubMed]
44.
Etherton, M.R.; Shah, S.; Haolin, X.; Xian, Y.; Maisch, L.; Hannah, D.; Lindholm, B.; Lytle, B.; Thomas, L.; Smith, E.E.; et al.
Patterns of antidepressant therapy and clinical outcomes among ischaemic stroke survivors. Stroke Vasc. Neurol.
2021
,6, 384–394.
[CrossRef]
45.
Gibson, E.; Koh, C.L.; Eames, S.; Bennett, S.; Scott, A.M.; Hoffmann, T.C. Occupational therapy for cognitive impairment in stroke
patients. Cochrane Database Syst. Rev. 2022,3, Cd006430. [CrossRef]
Life 2023,13, 2061 11 of 13
46.
Lowder, R.J.; Jaywant, A.; Fridman, C.B.; Toglia, J.; O’Dell, M.W. Cognitive impairment predicts engagement in inpatient stroke
rehabilitation. Int. J. Rehabil. Res. 2022,45, 359–365. [CrossRef]
47.
Fluck, D.; Fry, C.H.; Gulli, G.; Affley, B.; Robin, J.; Kakar, P.; Sharma, P.; Han, T.S. Association of risk of malnutrition with adverse
outcomes and early support on discharge in acute stroke patients without prestroke disability: A multicenter, registry-based
cohort study. Nutr. Clin. Pract. 2022,37, 1233–1241. [CrossRef]
48.
Martino, R.; Foley, N.; Bhogal, S.; Diamant, N.; Speechley, M.; Teasell, R. Dysphagia after stroke: Incidence, diagnosis, and
pulmonary complications. Stroke 2005,36, 2756–2763. [CrossRef]
49.
Han, T.S.; Lean, M.E.; Fluck, D.; Affley, B.; Gulli, G.; Patel, T.; Barrett, C.; Kakar, P.; Sharma, S.; Sharma, P. Impact of delay in early
swallow screening on pneumonia, length of stay in hospital, disability and mortality in acute stroke patients. Eur. J. Clin. Nutr.
2018,72, 1548–1554. [CrossRef]
50.
Murray, J.; Scholten, I.; Doeltgen, S. Factors Contributing to Hydration, Fluid Intake and Health Status of Inpatients With and
Without Dysphagia Post Stroke. Dysphagia 2018,33, 670–683. [CrossRef]
51.
Shah, V.A.; Thompson, R.E.; Yenokyan, G.; Acosta, J.N.; Avadhani, R.; Dlugash, R.; McBee, N.; Li, Y.; Hansen, B.M.; Ullman, N.;
et al. One-Year Outcome Trajectories and Factors Associated with Functional Recovery Among Survivors of Intracerebral and
Intraventricular Hemorrhage With Initial Severe Disability. JAMA Neurol. 2022,79, 856–868. [CrossRef]
52.
Chollet, F.; Tardy, J.; Albucher, J.F.; Thalamas, C.; Berard, E.; Lamy, C.; Bejot, Y.; Deltour, S.; Jaillard, A.; Niclot, P.; et al. Fluoxetine
for motor recovery after acute ischaemic stroke (FLAME): A randomised placebo-controlled trial. Lancet Neurol.
2011
,10, 123–130.
[CrossRef] [PubMed]
53.
Dennis, M.; Mead, G.; Forbes, J.; Graham, C.; Hackett, M.; Hankey, G.J.; House, A.; Lewis, S.; Lundström, E.; Sandercock, P.; et al.
Effects of fluoxetine on functional outcomes after acute stroke (FOCUS): A pragmatic, double-blind, randomised, controlled trial.
Lancet 2019,393, 265–274. [CrossRef] [PubMed]
54.
Hankey, G.J.; Hackett, M.L.; Almeida, O.P.; Flicker, L.; Mead, G.E.; Dennis, M.S.; Etherton-Beer, C.; Ford, A.H.; Billot, L.; Jan,
S.; et al. Safety and efficacy of fluoxetine on functional outcome after acute stroke (AFFINITY): A randomised, double-blind,
placebo-controlled trial. Lancet Neurol. 2020,19, 651–660. [CrossRef] [PubMed]
55.
Lundström, E.; Isaksson, E.; Näsman, P.; Wester, P.; Mårtensson, B.; Norrving, B.; Wallén, H.; Borg, J.; Dennis, M.; Mead,
G.; et al. Safety and efficacy of fluoxetine on functional recovery after acute stroke (EFFECTS): A randomised, double-blind,
placebo-controlled trial. Lancet Neurol. 2020,19, 661–669. [CrossRef] [PubMed]
56.
Legg, L.A.; Rudberg, A.S.; Hua, X.; Wu, S.; Hackett, M.L.; Tilney, R.; Lindgren, L.; Kutlubaev, M.A.; Hsieh, C.F.; Barugh, A.J.; et al.
Selective serotonin reuptake inhibitors (SSRIs) for stroke recovery. Cochrane Database Syst. Rev. 2021,11, Cd009286. [CrossRef]
57.
Scheidtmann, K.; Fries, W.; Müller, F.; Koenig, E. Effect of levodopa in combination with physiotherapy on functional motor
recovery after stroke: A prospective, randomised, double-blind study. Lancet 2001,358, 787–790. [CrossRef]
58.
Ford, G.A.; Bhakta, B.B.; Cozens, A.; Hartley, S.; Holloway, I.; Meads, D.; Pearn, J.; Ruddock, S.; Sackley, C.M.; Saloniki, E.C.; et al.
Safety and efficacy of co-careldopa as an add-on therapy to occupational and physical therapy in patients after stroke (DARS): A
randomised, double-blind, placebo-controlled trial. Lancet Neurol. 2019,18, 530–538. [CrossRef]
59.
Szelenberger, R.; Kostka, J.; Saluk-Bijak, J.; Miller, E. Pharmacological Interventions and Rehabilitation Approach for Enhancing
Brain Self-repair and Stroke Recovery. Curr. Neuropharmacol. 2020,18, 51–64. [CrossRef]
60.
Ogawa, Y.; Nibe, F.; Ogawa, R.; Sakoh, M. Anticholinergic and Sedative Drug Burden and Functional Recovery after Cerebrovas-
cular Accident: A Retrospective Descriptive Study. Prog. Rehabil. Med. 2020,5, 20200010. [CrossRef] [PubMed]
61.
Krakauer, J.W.; Carmichael, S.T.; Corbett, D.; Wittenberg, G.F. Getting neurorehabilitation right: What can be learned from animal
models? Neurorehabilit. Neural Repair 2012,26, 923–931. [CrossRef]
62.
Winstein, C.J.; Stein, J.; Arena, R.; Bates, B.; Cherney, L.R.; Cramer, S.C.; Deruyter, F.; Eng, J.J.; Fisher, B.; Harvey, R.L.; et al.
Guidelines for Adult Stroke Rehabilitation and Recovery: A Guideline for Healthcare Professionals From the American Heart
Association/American Stroke Association. Stroke 2016,47, e98–e169. [CrossRef]
63.
French, B.; Thomas, L.H.; Coupe, J.; McMahon, N.E.; Connell, L.; Harrison, J.; Sutton, C.J.; Tishkovskaya, S.; Watkins, C.L.
Repetitive task training for improving functional ability after stroke. Cochrane Database Syst. Rev.
2016
,11, Cd006073. [CrossRef]
64.
Cao, N.; Packel, A.; Marcy, E.; Sprik, K.; Harold, E.; Xiao, R.; Esquenazi, A. Implementing Robotic-Assisted Gait Training in Acute
Inpatient Stroke Rehabilitation: A Quality Improvement Initiative. J. Int. Soc. Phys. Rehabil. Med. 2021,4, 168–173. [CrossRef]
65.
Ward, N.S.; Brander, F.; Kelly, K. Intensive upper limb neurorehabilitation in chronic stroke: Outcomes from the Queen Square
programme. J. Neurol. Neurosurg. Psychiatry 2019,90, 498–506. [CrossRef] [PubMed]
66.
Daly, J.J.; McCabe, J.P.; Holcomb, J.; Monkiewicz, M.; Gansen, J.; Pundik, S. Long-Dose Intensive Therapy Is Necessary for Strong,
Clinically Significant, Upper Limb Functional Gains and Retained Gains in Severe/Moderate Chronic Stroke. Neurorehabilit.
Neural Repair 2019,33, 523–537. [CrossRef] [PubMed]
67.
Clark, B.; Whitall, J.; Kwakkel, G.; Mehrholz, J.; Ewings, S.; Burridge, J. The effect of time spent in rehabilitation on activity
limitation and impairment after stroke. Cochrane Database Syst. Rev. 2021,10, Cd012612. [CrossRef]
68.
Latham, N.K.; Jette, D.U.; Coster, W.; Richards, L.; Smout, R.J.; James, R.A.; Gassaway, J.; Horn, S.D. Occupational therapy
activities and intervention techniques for clients with stroke in six rehabilitation hospitals. Am. J. Occup. Ther.
2006
,60, 369–378.
[CrossRef] [PubMed]
69.
Lang, C.E.; MacDonald, J.R.; Gnip, C. Counting repetitions: An observational study of outpatient therapy for people with
hemiparesis post-stroke. J. Neurol. Phys. Ther. JNPT 2007,31, 3–10. [CrossRef]
Life 2023,13, 2061 12 of 13
70.
Krakauer, J.W.; Kitago, T.; Goldsmith, J.; Ahmad, O.; Roy, P.; Stein, J.; Bishop, L.; Casey, K.; Valladares, B.; Harran, M.D.; et al.
Comparing a Novel Neuroanimation Experience to Conventional Therapy for High-Dose Intensive Upper-Limb Training in
Subacute Stroke: The SMARTS2 Randomized Trial. Neurorehabilit. Neural Repair 2021,35, 393–405. [CrossRef]
71.
Wolf, S.L.; Sahu, K.; Bay, R.C.; Buchanan, S.; Reiss, A.; Linder, S.; Rosenfeldt, A.; Alberts, J. The HAAPI (Home Arm Assistance
Progression Initiative) Trial:A Novel Robotics Delivery Approach in Stroke Rehabilitation. Neurorehabilit. Neural Repair
2015
,29,
958–968. [CrossRef]
72.
Zondervan, D.K.; Augsburger, R.; Bodenhoefer, B.; Friedman, N.; Reinkensmeyer, D.J.; Cramer, S.C. Machine-Based, Self-guided
Home Therapy for Individuals With Severe Arm Impairment After Stroke: A Randomized Controlled Trial. Neurorehabilit. Neural
Repair 2015,29, 395–406. [CrossRef]
73.
Laver, K.E.; Lange, B.; George, S.; Deutsch, J.E.; Saposnik, G.; Crotty, M. Virtual reality for stroke rehabilitation. Cochrane Database
Syst. Rev. 2017,11, Cd008349. [CrossRef]
74.
Pundik, S.; McCabe, J.; Skelly, M.; Tatsuoka, C.; Daly, J.J. Association of spasticity and motor dysfunction in chronic stroke. Ann.
Phys. Rehabil. Med. 2019,62, 397–402. [CrossRef]
75.
Kamper, D.G.; Rymer, W.Z. Impairment of voluntary control of finger motion following stroke: Role of inappropriate muscle
coactivation. Muscle Nerve 2001,24, 673–681. [CrossRef]
76.
Lindsay, C.; Ispoglou, S.; Helliwell, B.; Hicklin, D.; Sturman, S.; Pandyan, A. Can the early use of botulinum toxin in post stroke
spasticity reduce contracture development? A randomised controlled trial. Clin. Rehabil.
2020
,35, 399–409. [CrossRef] [PubMed]
77.
Li, S. Ankle and Foot Spasticity Patterns in Chronic Stroke Survivors with Abnormal Gait. Toxins
2020
,12, 646. [CrossRef]
[PubMed]
78.
Baricich, A.; Picelli, A.; Carda, S.; Smania, N.; Cisari, C.; Santamato, A.; de Sire, A.; Invernizzi, M. Electrical stimulation of
antagonist muscles after botulinum toxin type A for post-stroke spastic equinus foot. A randomized single-blind pilot study. Ann.
Phys. Rehabil. Med. 2019,62, 214–219. [CrossRef] [PubMed]
79.
Lee, J.M.; Gracies, J.M.; Park, S.B.; Lee, K.H.; Lee, J.Y.; Shin, J.H. Botulinum Toxin Injections and Electrical Stimulation for Spastic
Paresis Improve Active Hand Function Following Stroke. Toxins 2018,10, 426. [CrossRef]
80.
Andringa, A.; van de Port, I.; van Wegen, E.; Ket, J.; Meskers, C.; Kwakkel, G. Effectiveness of botulinum toxin treatment for
upper limb spasticity after stroke over different ICF domains: A systematic review and meta-analysis. Arch. Phys. Med. Rehabil.
2019,100, 1703–1725. [CrossRef]
81.
Kristensen, M.G.H.; Busk, H.; Wienecke, T. Neuromuscular Electrical Stimulation Improves Activities of Daily Living Post Stroke:
A Systematic Review and Meta-analysis. Arch. Rehabil. Res. Clin. Transl. 2022,4, 100167. [CrossRef]
82.
Eraifej, J.; Clark, W.; France, B.; Desando, S.; Moore, D. Effectiveness of upper limb functional electrical stimulation after stroke
for the improvement of activities of daily living and motor function: A systematic review and meta-analysis. Syst. Rev.
2017
,6, 40.
[CrossRef]
83.
Keser, Z.; Dehgan, M.W.; Shadravan, S.; Yozbatiran, N.; Maher, L.M.; Francisco, G.E. Combined Dextroamphetamine and
Transcranial Direct Current Stimulation in Poststroke Aphasia. Am. J. Phys. Med. Rehabil.
2017
,96, S141–S145. [CrossRef]
[PubMed]
84.
Fonte, C.; Varalta, V.; Rocco, A.; Munari, D.; Filippetti, M.; Evangelista, E.; Modenese, A.; Smania, N.; Picelli, A. Combined
transcranial Direct Current Stimulation and robot-assisted arm training in patients with stroke: A systematic review. Restor.
Neurol. Neurosci. 2021,39, 435–446. [CrossRef] [PubMed]
85.
Wang, H.; Fang, X.Y.; Yao, J. Synergic effect of the combination of mirror therapy and electrical stimulation for lower extremity
motor function recovery in stroke survivors: A meta-analysis of randomized controlled trials. Top. Stroke Rehabil.
2023
,30, 73–83.
[CrossRef] [PubMed]
86.
Zhao, Q.; Li, H.; Liu, Y.; Mei, H.; Guo, L.; Liu, X.; Tao, X.; Ma, J. Non-invasive brain stimulation associated mirror therapy for
upper-limb rehabilitation after stroke: Systematic review and meta-analysis of randomized clinical trials. Front. Neurol.
2022
,13,
918956. [CrossRef] [PubMed]
87.
Dawson, J.; Liu, C.Y.; Francisco, G.E.; Cramer, S.C.; Wolf, S.L.; Dixit, A.; Alexander, J.; Ali, R.; Brown, B.L.; Feng, W.; et al. Vagus
nerve stimulation paired with rehabilitation for upper limb motor function after ischaemic stroke (VNS-REHAB): A randomised,
blinded, pivotal, device trial. Lancet 2021,397, 1545–1553. [CrossRef] [PubMed]
88.
Mutai, H.; Furukawa, T.; Nakanishi, K.; Hanihara, T. Longitudinal functional changes, depression, and health-related quality of
life among stroke survivors living at home after inpatient rehabilitation. Psychogeriatrics 2016,16, 185–190. [CrossRef]
89.
Löfgren, B.; Nyberg, L.; Mattsson, M.; Gustafson, Y. Three years after in-patient stroke rehabilitation: A follow-up study.
Cerebrovasc. Dis. 1999,9, 163–170. [CrossRef]
90.
Langhammer, B.; Lindmark, B.; Stanghelle, J.K. Physiotherapy and physical functioning post-stroke: Exercise habits and
functioning 4 years later? Long-term follow-up after a 1-year long-term intervention period: A randomized controlled trial. Brain
Inj. 2014,28, 1396–1405. [CrossRef]
91.
Reutter-Bernays, D.; Rentsch, H.P. Rehabilitation of the elderly patient with stroke: An analysis of short-term and long-term
results. Disabil. Rehabil. 1993,15, 90–95. [CrossRef]
92.
Meyer, S.; Verheyden, G.; Brinkmann, N.; Dejaeger, E.; De Weerdt, W.; Feys, H.; Gantenbein, A.R.; Jenni, W.; Laenen, A.; Lincoln,
N.; et al. Functional and motor outcome 5 years after stroke is equivalent to outcome at 2 months: Follow-up of the collaborative
evaluation of rehabilitation in stroke across Europe. Stroke 2015,46, 1613–1619. [CrossRef] [PubMed]
Life 2023,13, 2061 13 of 13
93.
van de Port, I.G.; Kwakkel, G.; van Wijk, I.; Lindeman, E. Susceptibility to deterioration of mobility long-term after stroke: A
prospective cohort study. Stroke 2006,37, 167–171. [CrossRef] [PubMed]
94.
Pettersen, R.; Dahl, T.; Wyller, T.B. Prediction of long-term functional outcome after stroke rehabilitation. Clin. Rehabil.
2002
,16,
149–159. [CrossRef]
95.
English, C.; Healy, G.N.; Coates, A.; Lewis, L.; Olds, T.; Bernhardt, J. Sitting and Activity Time in People With Stroke. Phys. Ther.
2016,96, 193–201. [CrossRef]
96.
English, C.; Manns, P.J.; Tucak, C.; Bernhardt, J. Physical activity and sedentary behaviors in people with stroke living in the
community: A systematic review. Phys. Ther. 2014,94, 185–196. [CrossRef]
97.
Biswas, A.; Oh, P.I.; Faulkner, G.E.; Bajaj, R.R.; Silver, M.A.; Mitchell, M.S.; Alter, D.A. Sedentary time and its association with risk
for disease incidence, mortality, and hospitalization in adults: A systematic review and meta-analysis. Ann. Intern. Med.
2015
,
162, 123–132. [CrossRef]
98.
Wong, H.J.; Harith, S.; Lua, P.L.; Ibrahim, K.A. Possible Sarcopenia and Its Association with Nutritional Status, Dietary Intakes,
Physical Activity and Health-Related Quality of Life among Older Stroke Survivors. Ann. Geriatr. Med. Res.
2022
,26, 162–174.
[CrossRef] [PubMed]
99.
Zoellner, E.R.; Patterson, M.A.; Sharrief, A.Z.; Savitz, S.I.; Tucker, W.J.; Miketinas, D.C. Dietary intake and quality among stroke
survivors in the National Health and Nutrition Examination Survey: 1999–2018. J. Nutr. 2023,153, 3032–3040. [CrossRef]
100.
Kameyama, Y.; Ashizawa, R.; Honda, H.; Take, K.; Yoshizawa, K.; Yoshimoto, Y. Sarcopenia Affects Functional Independence
Measure motor Scores in Elderly Patients with Stroke. J. Stroke Cerebrovasc. Dis. 2022,31, 106615. [CrossRef]
101.
Morris, J.H.; Oliver, T.; Kroll, T.; Joice, S.; Williams, B. Physical activity participation in community dwelling stroke survivors:
Synergy and dissonance between motivation and capability. A qualitative study. Physiotherapy 2017,103, 311–321. [CrossRef]
102.
Schnabel, S.; van Wijck, F.; Kidd, L. Supporting stroke survivors to meet their personal rehabilitation needs in community-based
arm rehabilitation: Development of initial programme theories to explore what may work for whom, how and under what
circumstances. Front. Neurol. 2023,14, 1089547. [CrossRef] [PubMed]
103.
Zorowitz, R.D.; Gillard, P.J.; Brainin, M. Poststroke spasticity: Sequelae and burden on stroke survivors and caregivers. Neurology
2013,80, S45–S52. [CrossRef] [PubMed]
104.
Ganapathy, V.; Graham, G.D.; Dibonaventura, M.D.; Gillard, P.J.; Goren, A.; Zorowitz, R.D. Caregiver burden, productivity loss,
and indirect costs associated with caring for patients with poststroke spasticity. Clin. Interv. Aging
2015
,10, 1793–1802. [CrossRef]
[PubMed]
105.
Denno, M.S.; Gillard, P.J.; Graham, G.D.; Dibonaventura, M.D.; Goren, A.; Varon, S.F.; Zorowitz, R. Anxiety and depression
associated with caregiver burden in caregivers of stroke survivors with spasticity. Arch. Phys. Med. Rehabil.
2013
,94, 1731–1736.
[CrossRef]
106.
Wolf, S.; Holm, S.E.; Ingwersen, T.; Bartling, C.; Bender, G.; Birke, G.; Meyer, A.; Nolte, A.; Ottes, K.; Pade, O.; et al. Pre-stroke
socioeconomic status predicts upper limb motor recovery after inpatient neurorehabilitation. Ann. Med.
2022
,54, 1265–1276.
[CrossRef] [PubMed]
107.
Wong, M.N.; Tong, H.; Cheung, M.K.; Ng, Y.M.; Yuan, H.L.; Lam, B.Y.; Fu, S.N.; Chan, C.C.H. Goal-setting and personalization
under the International Classification of Functioning, Disability, and Health framework: Community reintegration program for
post-stroke patients. Front. Rehabil. Sci. 2023,4, 1219662. [CrossRef]
108.
Martino Cinnera, A.; Picerno, P.; Bisirri, A.; Koch, G.; Morone, G.; Vannozzi, G. Upper limb assessment with inertial measurement
units according to the international classification of functioning in stroke: A systematic review and correlation meta-analysis. Top.
Stroke Rehabil. 2023, 1–20. [CrossRef]
109.
Zhang, L.; Tashiro, S.; Mukaino, M.; Yamada, S. Use of artificial intelligence large languagemodels as a clinical tool in rehabilitation
medicine: A comparative test case. J. Rehabil. Med. 2023,55, jrm13373. [CrossRef]
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