Functional Gain After Inpatient Stroke Rehabilitation

Correlates and Impact on Long-Term Survival

Domenico Scrutinio, MD; Vincenzo Monitillo, MD; Pietro Guida, PhD;
Roberto Nardulli, MD; Vincenzo Multari, MD; Francesco Monitillo, MD;
Gianluigi Calabrese, MD; Pietro Fiore, MD

Background and Purpose—Prediction of functional outcome after stroke rehabilitation (SR) is a growing field of interest.
The association between SR and survival still remains elusive. We sought to investigate the factors associated with
functional outcome after SR and whether the magnitude of functional improvement achieved with rehabilitation is
associated with long-term mortality risk.
Methods—The study population consisted of 722 patients admitted for SR within 90 days of stroke onset, with an admission
functional independence measure (FIM) score of <80 points. We used univariable and multivariable linear regression
analyses to assess the association between baseline variables and FIM gain and univariable and multivariable Cox
analyses to assess the association of FIM gain with long-term mortality.
Results—Age (P<0.001), marital status (P=0.003), time from stroke onset to rehabilitation admission (P<0.001), National
Institutes of Health Stroke Scale score at rehabilitation admission (P<0.001), and aphasia (P=0.021) were independently
associated with FIM gain. The R2 of the model was 0.275. During a median follow-up of 6.17 years, 36.9% of the patients
died. At multivariable Cox analysis, age (P<0.0001), coronary heart disease (P=0.018), atrial fibrillation (P=0.042), total
cholesterol (P=0.015), and total FIM gain (P<0.0001) were independently associated with mortality. The adjusted hazard
ratio for death significantly decreased across tertiles of increasing FIM gain.
Conclusions—Several factors are independently associated with functional gain after SR. Our findings strongly suggest
that the magnitude of functional improvement is a powerful predictor of long-term mortality in patients admitted for
SR.   (Stroke. 2015;46:2976-2980. DOI: 10.1161/STROKEAHA.115.010440.)
Key Words: mortality ◼ prognosis ◼ regression analysis ◼ rehabilitation ◼ stroke

S troke is a leading cause of death and long-term disability in

developed countries.1 Because of the aging population and
the declining early mortality after stroke,1 the demand for stroke
rehabilitation (SR), as well as the economic, social, and family
burden of stroke, is expected to increase in the coming years.
Thus, prediction of functional outcome after SR has become a
growing field of interest as it may have important implications
for planning management strategies and informing patients and
relatives.2,3 Age, initial stroke severity, and functional status at
rehabilitation admission emerged as the most informative pre-
dictors of functional outcome in previous studies.4 In the recent
large study of Brown et al,5 functional independence measure
(FIM) motor score at rehabilitation hospital admission domi-
nated prediction of outcome at discharge. The model, including
age, admission FIM motor score, and distance walked, how-
ever, explained only 10.7% of the variance in overall FIM gain.5
Importantly, the possible association between SR and
long-term survival still remains elusive.6 In a rehabilitation-
based study, functional status at 6 months was a significant
predictor of long-term mortality, generating the hypothesis
that “Interventions that improve post-stroke functional status
may have a protective effect on mortality.”7
We sought to identify the factors associated with func-
tional outcome after SR and to investigate whether the magni-
tude of functional improvement achieved with rehabilitation is
associated with long-term mortality risk.
Methods
The study population consisted of 1010 patients consecutively admit-
ted for SR from January 2002 to October 2011. Patients were includ-
ed in the study if they had been admitted within 90 days of onset of
an ischemic or hemorrhagic stroke and had an admission FIM score
of <80 points.8 Patients who were admitted >90 days after stroke
(n=144; 14.3%), had an admission FIM score of ≥80 points (n=77;
7.6%), were transferred to an acute care facility (n=51; 5%) or dis-
charged against medical advice (n=7; 0.7%), or died during in-hospi-
tal stay (n=9; 0.9%) were excluded. Thus, 722 patients were available
for analysis. Patients’ data were deidentified. The setting was the in-
patient neurological rehabilitation unit of the Maugeri Rehabilitation

Received June 15, 2015; final revision received July 29, 2015; accepted August 11, 2015.
From the Department of Cardiology and Cardiac Rehabilitation (D.S., P.G., F.M.) and Department of Neurorehabilitation (V. Monitillo, R.N., V.
Multari), “S. Maugeri” Foundation, IRCCS, Institute of Cassano Murge, Bari, Italy; Department of Neurorehabilitation, “S. Maugeri” Foundation, Marina
di Ginosa, Taranto, Italy (G.C.); and Department of Neuroscience and Sense Organs, Physical Medicine and Rehabilitation, University of Bari, Italy (P.F.).
Correspondence to Domenico Scrutinio, MD, Department of Cardiology and Cardiac Rehabilitation, Fondazione “S. Maugeri” IRCCS, 70020 Cassano
Murge (Bari), Italy. E-mail domenico.scrutinio@fsm.it
© 2015 American Heart Association, Inc.
Stroke is available at http://stroke.ahajournals.org DOI: 10.1161/STROKEAHA.115.010440

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 Scrutinio et al   Functional Gain After Stroke Rehabilitation    2977

Institute, which has a regional user base and is certified (ISO9001,
quality management systems) for activities of rehabilitation. Our in-
terdisciplinary SR team comprises the following professionals with
expertise in SR: neurologist, physiatrist, physiotherapist, occupa-
tional therapist, speech and language therapist, neuropsychologist,
and nurse. The patients received physical and occupational therapy
for 3 hours per day for 5 days and for 1 hour for 1 day of each week.
Patients with more severe initial disability were managed with lower
intensity programs. Admission and discharge FIM scores were re-
corded by trained therapists, as a part of our formal rehabilitation

Table 1.  Baseline Characteristics

Admission Discharge P Value
Age, y, mean (SD) 72 (12)
Male sex, % 57.1
Marital status
 Married, % 78.8
 Not married (single, divorced, and widow), % 21.2
Employment status
 Retired,% 72.6
 Not retired, % 27.4
Hypertension, % 72.4
Diabetes mellitus, % 31.0
Chronic obstructive pulmonary disease,% 7.5
Coronary heart disease, %* 9.8
Valvular heart disease, % 5.0
Atrial fibrillation, % 18.1
Time from stroke onset to rehabilitation 31 (19)
admission, d, mean (SD)
Type of stroke
 Ischemic,% 80.9
  
Lacunar, %† 9.1
 Hemorrhagic, % 19.1
Side of impairment
 Right, % 43.8
 Left, % 56.2
Aphasia, % 46.8
NIHSS score, mean (SD) 9.6 (2.9) 8.4 (3.0) <0.0001
 Mild stroke, 0–3, % 0.6 4.3 <0.0001
 Moderate stroke, 4–10, % 57.3 69.4
 Severe stroke, >10, % 42.1 26.3
Total FIM score, mean (SD) 41.6 (16.9) 71.3 (27.1) <0.0001
Motor FIM score, mean (SD) 22.8 (10.9) 47.0 (21.4) <0.0001
Cognitive FIM score, mean (SD) 18.8 (9.2) 24.3 (8.3) <0.0001
Regained functional independence,‡ % … 5.3
BUN, mg/dL, mean (SD) 20 (9)
eGFR, mL/min per 1.73 m2, mean (SD) 85 (25)
eGFR <60 mL/min per 1.73 m2, % 15.8
BUN/creatinine ratio, mean (SD) 23 (9)
Serum sodium, mmol/L, mean (SD) 140.8 (3.9)
Hemoglobin, g/dL, mean (SD) 13.0 (1.6)
Total cholesterol, mg/dL, mean (SD) 173 (43)
Uric acid, mg/dL, mean (SD) 5.1 (1.8)
Length of stay, d, mean (SD) 53 (13)
Statins at discharge, % 33.9
Diuretics at discharge, % 31.3
BUN indicates blood urea nitrogen; eGFR, estimated glomerular filtration rate; FIM, functional independence
measure; and NIHSS, National Institutes of Health Stroke Scale.
*Documented previous myocardial infarction, percutaneous coronary angioplasty, or coronary artery bypass
grafting.
†Ascertained in 84.8% of the patients with ischemic stroke.
‡≥6 points for all 13 items of motor FIM score.

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2978  Stroke  October 2015

Table 2.  Results of Univariable and Multivariable Regression Analyses: Linear Regression Analyses
Univariable Multivariable
Significant Predictors of Total FIM Gain β-Coefficient (SE) P Value β-Coefficient (SE) P Value
Male sex 2.7±1.4 0.047
Age, per 10-y increase −4.3±0.6 <0.001 −3.9±0.7 <0.001
Marital status, married 4.3±1.6 0.009 4.3±1.5 0.003
Employment status, employed 5.2±1.5 0.001
Time from stroke onset to rehabilitation admission −2.1±0.4 <0.001 −1.9±0.3 <0.001
(per 10-d increase)
Hemorrhagic stroke 3.2±1.7 0.065 2.9±1.5 0.055
Right side impairment −4.3±1.3 0.001
Aphasia 2.6±1.3 0.054 4.7±2.0 0.021
Hypertension −3.0±1.5 0.049
Atrial fibrillation −5.7±1.7 0.001
Hemoglobin 1.2±0.4 0.003
Admission NIHSS score −2.2±0.2 <0.001 −2.4±0.3 <0.001
Admission total FIM score (per 10-U increase) 2.1±0.4 <0.001
FIM indicates functional independence measure; and NIHSS, National Institutes of Health Stroke Scale score.

program. Postdischarge vital status was ascertained in 686 residents
by linking with the regional health information systems. FIM gain
was calculated as the difference in total FIM score before and after
rehabilitation. This study was approved by the local institutional re-
view board.
Statistical Analysis
Data were 99.9% complete. We used univariable and multivariable
linear regression analyses to assess the association between base-
line variables and FIM gain and univariable and multivariable Cox
regression analyses to assess the association of FIM gain with long-
term postdischarge mortality risk. All continuous covariates were
treated as such. Redundant variables (Pearson coefficient, >0.50)
were dropped from the multivariable model, including that with the
strongest effect size. Candidate baseline variables with P≤0.10 at
univariable analysis were retained for inclusion in the multivariable
analysis. Discrimination of the model was assessed by calculating the
C-index. The statistical interaction between FIM gain and admission
or discharge total FIM score in predicting mortality was evaluated by
likelihood ratio test comparing models with and without interaction
terms. Analyses were conducted using STATA software, version 12
(StataCorp LP, College Station, TX).
Results
Baseline characteristics and changes in FIM scores from
admission to discharge are reported in Table 1. The mean FIM
gain was 29.7±18.1 points.

Table 3.  Results of Univariable and Multivariable Regression Analyses: Cox Regression Analysis
Univariable Multivariable
Significant Predictors of Mortality C-Index HR (95% CI) P Value HR (95% CI) P Value
Age (per 10-y increase) 0.704 2.14 (1.85–2.49) <0.001 1.99 (1.66–2.39) <0.0001
Employment status, employed 0.578 0.36 (0.25–0.52) <0.001
Ischemic stroke 0.533 1.59 (1.11–2.27) 0.011
Chronic obstructive pulmonary disease 0.518 1.60 (1.03–2.48) 0.036
Diabetes mellitus 0.532 1.33 (1.03–1.73) 0.029
Coronary heart disease 0.518 1.45 (1.00–2.11) 0.053 1.61 (1.08–2.39) 0.018
Atrial fibrillation 0.555 1.87 (1.41–2.49) <0.001 1.37 (1.01–1.86) 0.042
BUN (per 10-U increase) 0.549 1.16 (1.04–1.30) 0.010
eGFR (per 10-U increase) 0.564 0.90 (0.86–0.95) <0.001
Total cholesterol (per 10-U increase) 0.545 0.96 (0.93–0.99) 0.005 0.96 (0.93–0.99) 0.015
Serum uric acid, mg/dL 0.548 1.10 (1.03–1.17) 0.003
Admission NIHSS score 0.545 1.05 (1.00–1.10) 0.046
Admission total FIM score (per 10-point increase) 0.603 0.83 (0.77–0.90) <0.001
Total FIM gain (per 10-point increase) 0.667 0.73 (0.67–0.79) <0.001 0.81 (0.74–0.87) <0.0001
Regained functional independence at discharge 0.520 0.31 (0.13–0.74) 0.009
Diuretics 0.547 1.54 (1.20–1.99) 0.001
BUN indicates blood urea nitrogen; CI, confidence interval; eGFR, estimated glomerular filtration rate; FIM, functional independence measure;
and NIHSS, National Institutes of Health Stroke Scale.

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 Scrutinio et al   Functional Gain After Stroke Rehabilitation    2979
Figure. Mortality curves by tertiles of functional independence
measure (FIM) gain. CIs indicates confidence intervals; HR, haz-
ard ratio; and N, number of patients.
Correlates of FIM Gain
Table 2 shows the results of univariable and multivariable linear
regression analyses. At multivariable analysis, age (P<0.001),
marital status (P=0.003), time from stroke onset to rehabilita-
tion admission (P<0.001), National Institutes of Health Stroke
Scale score at rehabilitation admission (P<0.001), and aphasia
(P=0.021) were independently associated with FIM gain. The
R2 of the model was 0.275.
Mortality
During a median follow-up of 6.17 years, 253 of the 686 resi-
dents (36.9%) died. Table 3 shows the results of univariable
and multivariable Cox regression analyses. FIM gain had a
univariable C-index of 0.667. At multivariable analysis, age
(P<0.0001), coronary heart disease (P=0.018), atrial fibril-
lation (P=0.042), total cholesterol (P=0.015), and FIM gain
(P<0.0001) were independently associated with mortality.
The C-index of the predictive model was 0.745. The Figure
shows survival curves of the patients stratified by tertiles of
FIM gain. The adjusted hazard ratio for death significantly
decreased across tertiles of increasing FIM gain. No interac-
tion between FIM gain and admission (P=0.800) or discharge
(P=0.127) total FIM score was found, indicating that the asso-
ciation of FIM gain with mortality risk was independent of
admission or discharge total FIM score.
Discussion
There are 2 major findings of this study: (1) several variables
were independently associated with total FIM gain; the model
explained 27% of the variance in FIM gain and (2) after
adjusting for established mortality risk markers in patients
with stroke, FIM gain resulted to be a powerful predictor of
long-term mortality risk.
Consistent with previous studies,4 age, a measure of stroke
severity (National Institutes of Health Stroke Scale score), and
a process of care indicator were significant predictors of func-
tional gain. The finding that time from stroke onset to rehabili-
tation admission is positively associated with functional gain
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can be a relevant issue for clinicians involved in decision mak-
ing about admission to rehabilitation hospital and policy mak-
ers.4 The significant association between married status and
functional improvement is a novel finding,4 which is difficult
to interpret. However, this finding is in line with the Oxford
Vascular Study where nonpartnered patients were more likely
to be disabled at 6 months after index stroke.9 However, the
proportion of explained variance in FIM gain was modest,
indicating that other unmeasured processes of care-related or
patient-related factors contribute to functional outcome.
In a recent population-based study, early SR was associ-
ated with a lower risk of mortality, after accounting for age and
sex.10 De Wit et al7 showed that functional status at 6 months
predicts long-term mortality. To the best of our knowledge, this
study is the first to report an independent, strong association
between the magnitude of functional improvement achieved
with rehabilitation and long-term mortality risk in stroke sur-
vivors. Adjusting for established markers of mortality risk in
patients with stroke, such as age, sex, diabetes mellitus, coro-
nary heart disease, renal function, and stroke severity,11 FIM
gain emerged as a highly significant predictor of long-term
mortality. There was a significant graded and independent
decrease in the hazard ratio for death across tertiles of increas-
ing FIM gain. The patients in the highest FIM gain tertile had
a 60% lower likelihood of dying compared with their counter-
parts in the lowest FIM gain tertile. The finding that admission
National Institutes of Health Stroke Scale was a highly signifi-
cant independent predictor of FIM gain suggests that some of
the relationship between FIM gain and mortality may really
represent a relationship between stroke severity and mortal-
ity. Although a significant association does not prove a cause–
effect relationship, our findings strongly suggest that continued
efforts should be devoted to enhancing the effectiveness of SR
to improve not only disability and quality of life but also, hope-
fully, life expectancy of stroke survivors.
Limitations
The main limitation of this study is its retrospective nature.
However, all consecutive patients admitted for SR during
the index period were considered for inclusion in the study
and selected according to prespecified criteria; moreover, the
data set was >99% complete. We excluded patients with mild
stroke. Ideally, a measure of functioning and disability should
not be susceptible to ceiling effect.12 Ceiling effects, indeed,
may limit the ability of a measure to accurately assess patient
improvement and lead to type I error inflation.13,14 A ceiling
effect for FIM score has been demonstrated.13 To minimize
ceiling effect, we excluded patients with an FIM score of
≥80.8 This was a single-center study. Although this ensures the
uniformity of data collection and treatment across the studied
population, it may limit the generalizability of the results.
Conclusions
Although several predictors of functional improvement were
identified, the explained variation in functional gain was mod-
est, suggesting the need for continued research aimed at iden-
tifying additional process of care- and patient-related factors
influencing the effectiveness of SR. Our findings strongly
2980  Stroke  October 2015
suggest that the magnitude of functional improvement is a
powerful predictor of long-term mortality in patients admitted
for SR. Studies are needed to investigate the pathophysiologi-
cal mechanisms underlying this association.
Acknowledgments
We thank all physicians, therapists, and nurses who were involved in
the care of the patients and Francesco Colucci for his assistance in
acquiring the data.
Disclosures
None.
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 Functional Gain After Inpatient Stroke Rehabilitation: Correlates and Impact on
Long-Term Survival
Domenico Scrutinio, Vincenzo Monitillo, Pietro Guida, Roberto Nardulli, Vincenzo Multari,
Francesco Monitillo, Gianluigi Calabrese and Pietro Fiore

Stroke. 2015;46:2976-2980; originally published online September 3, 2015;

doi: 10.1161/STROKEAHA.115.010440
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