Journal of Critical Care 48 (2018) 269–275

Contents lists available at ScienceDirect

Journal of Critical Care

journal homepage: www.journals.elsevier.com/journal-of-critical-care

Long-term recovery profile of patients with severe disability or in

vegetative states following severe primary intracerebral hemorrhage
Lester Lee a,e, Yu Tung Lo a,e, Angela An Qi See a,e, Po-Jang Hsieh b,
Michael Lucas James c, Nicolas Kon Kam King a,d,e,⁎
a
Department of Neurosurgery, National Neuroscience Institute, Singapore
b
Neuroscience and Behavioral Disorders Program, Duke-NUS Medical School, Singapore
c
Departments of Anesthesiology and Neurology, Duke University, Durham, NC, United States
d
Duke-NUS Medical School, Singapore
e
Department of Neurosurgery, Singapore General Hospital, Singapore

a r t i c l e i n f o a b s t r a c t

Keywords: Purpose: We conducted a single-center retrospective review to investigate the long-term recovery of patients
Intracerebral hemorrhage who were severely disabled or vegetative secondary to primary intracerebral hemorrhage upon discharge
Long-term improvement from hospital from January 2009 to November 2013.
Severe disabilities
Methods: Patients were categorized into two groups based on their Glasgow outcome scale (GOS) scores at dis-
Vegetative state
charge, namely vegetative state (GOS 2; n = 91) and severely disabled (GOS 3; n = 278). Long-term outcomes at
Minimally conscious state
Recovery profile three years post discharge were defined as death, stable, deterioration and improvement from discharge to
follow-up.
Results: Lower mortality (29% versus 69%) and higher neurological improvement rates at three years (33% versus
10%) were observed in the SD compared to VS group (both p = .0001). Age was a significant predictor of survival
in the VS group (p = .03) and the SD group (p = .012). Age was also the only predictor of neurological improve-
ment in the SD group (p = .01).
Conclusions: Neurological status at discharge from hospital was not truly indicative of long-term prognosis for
patients who were severely disabled or vegetative. Patients in both groups can potentially improve in the long
term and may benefit from prolonged rehabilitation programmes to maximize their recovery potential.
© 2018 Elsevier Inc. All rights reserved.

1. Introduction upon discharge from hospital. Previous studies which attempted to

Spontaneous intracerebral hemorrhage (ICH) has been associated
with poor prognosis as well as poorer functional outcomes compared
to other types of acute brain injuries such as trauma or ischemic stroke
[1-5]. In Singapore, ICH accounts for approximately 20% of strokes with
a 17.3% mortality at 7 days and 22.9% at 30 days [6,7]. Survivors of ICH
may experience severe neurological deficits, and a significant number
of patients end up in vegetative or severely disabled states.
While younger age [8-12], smaller hematoma volume [10], lower
stroke severity [11], absence of intraventricular haemorrhage [11], and
being female [13] have been identified as favorable factors for long-
term prognosis after ICH, there remains a gap in knowledge for the
long-term recovery patterns of patients with poor neurological status
define the recovery patterns after ICH have either been performed in co-
horts with varying degrees of functional disabilities, or reported short
(i.e. 1 to 3 months) [14,15] to intermediate (i.e. 6 to 12 months)
follow-up periods [1,16-23]. Few studies have tracked patient outcomes
over long-term (e.g., 3 years) [8-13,24,25]. A better understanding of
long-term recovery profiles would be helpful for decision-making
regarding patients' care.
We conducted a single center retrospective study to investigate
the long-term recovery of patients who were in a severely dependent
or vegetative state upon discharge from hospital secondary to primary
intracerebral hemorrhage. To our knowledge, this is the first study to
review the long-term outcomes in a cohort of patients with spontane-
ous ICH.

2. Methods
Abbreviations: GCS, Glasgow Coma Scale; GOS, Glasgow Outcome Scale; ICH,
Intracerebral hemorrhage; SD, Severely disabled; VS, Vegetative state.
⁎ Corresponding author at: Department of Neurosurgery, National Neuroscience
Patients admitted to the Department of Neurosurgery at the
Institute, 11 Jalan Tan Tock Seng, 308433, Singapore. National Neuroscience Institute (a tertiary neuroscience center in
E-mail address: nicolas.kon.k.k@singhealth.com.sg (N.K.K. King). Singapore) for spontaneous ICH between January 2009 and November

https://doi.org/10.1016/j.jcrc.2018.09.010
0883-9441/© 2018 Elsevier Inc. All rights reserved.
270 L. Lee et al. / Journal of Critical Care 48 (2018) 269–275
2013 were reviewed. The three-year outcome for patients who sur-
vived an ICH but were left severely disabled or vegetative post-
discharge upon discharge was analyzed. A three-year period for
follow-up was decided to allow for sufficient time to analyze the
long-term outcomes in this group of patients from 2014 to 2017.
Ethics approval was obtained from the National Health Group domain
specific review board.
2.1. Data acquisition, inclusion and exclusion criteria
Electronic medical records as well as magnetic resonance imaging
and computed tomography scans were reviewed. Patients included in
our study had radiological diagnosis of ICH with no history of trauma;
were in a vegetative state or severely disabled at discharge from hospi-
tal; and had a follow-up of at least 3 years or death within this period.
All patients were graded according to the Glasgow Outcome Scale
(GOS) (5 = good recovery, 4 = moderate recovery, 3 = severe disabil-
ity, 2 = vegetative state, 1 = dead). Those who had a GOS score of 2 or 3
were included in this study for analysis. Patients who had ICH from vas-
cular abnormalities, tumor hemorrhage, trauma or hematological ab-
normalities, or had missing follow-up data within the three-year
follow-up period were excluded from this study.
2.2. Study groups and outcome measures
Patients were stratified into two groups depending on their GOS
score at hospital discharge. Patients with GOS scores of 2 were included
into the vegetative state (VS) group while those with GOS scores of 3,
the severely disabled (SD) group. They were followed up in the outpa-
tient clinics for at least three years and their long-term outcome at
three years was compared to their status at hospital discharge. Outpa-
tient medical notes were reviewed and their outcomes and GOS scores
were noted at 6 months, 12 months and 36 months intervals. Changes
in GOS at each interval were recorded. For patients whose functional
outcomes and GOS were not recorded in the electronic medical records,
phone calls were made to the patients or their family members to ascer-
tain their GOS. Outcomes were defined as death, stable (no change in
GOS), deterioration (decrease in GOS) and improvement (increase in
GOS) between discharge and follow-up at 3 years. Mortality and dates
of death were verified with the Singapore National Registry of Diseases
Office.
Variables recorded include age, gender, comorbidities, medication
use, Glasgow Coma Scale (GCS) on admission, presence of unilateral
or bilateral fixed pupils, median blood pressure, mean arterial pressure,
location of hemorrhage, size of hemorrhage, presence of intraventricu-
lar hemorrhage, presence of hydrocephalus, presence of subarachnoid
hemorrhage and type of surgical intervention (if performed). Patients
who were lost to follow-up within three years from hospital discharge
had their admission data and variables recorded but were excluded
from the final outcome analysis.
2.3. Statistical analysis
R version 3.3.0 was used for statistical analyses. The Shapiro-Wilk
test was used to test for normality. Non-normally distributed variables
were represented by medians and interquartile ranges, while normally
distributed variables were described using means and standard devia-
tions. A Kaplan-Meier survival graph was plotted. Fischer's t-test was
used to compare discontinuous variables to look for statistical signifi-
cance. Predictors of survival and improvement were determined using
univariate analysis followed by regression analysis for variables with p
b .2 in the univariate analysis. A p value of b0.05 was considered statis-
tically significant.
3. Results
A total of 1356 patients with ICH were screened, 298 patients died,
and 478 patients who were either in severely disabled or vegetative
states at time of discharge from hospital were eligible for the study. A
total of 109 patients (22.8% of the cohort) were excluded due to lost
to follow-up. The final sample for analysis consisted of 369 patients
(Fig. 1). A comparison between the excluded and analyzed cohorts
showed that both cohorts were matched in baseline characteristics
except in the number of patients on antiplatelet agents (p = .0084)
and previous strokes (p = .012) which was significantly higher in the
analyzed cohort (Table 1). The VS group consisted of 91 (25%) patients
with a GOS score of 2 and the SD group, 278 (75%) patients with a GOS
score of 3. The overall median age of the final analysis cohort, was
66 years (range 55–77 years; mean 67.22 ± 14) and 58% of patients
were male. Comorbidities included a history of previous cerebrovascular
events (n = 123), hypertension (n = 271), diabetes mellitus (n = 91),
hyperlipidemia (n = 162), atrial fibrillation (n = 21; Table 2). The
median GCS on presentation was 10 (range 3–15). Nine patients had
either a unilateral or bilateral fixed and dilated pupil at Accident &
Emergency department.
A total of 145 out of 369 patients (39%) died at the end of three years,
with less deaths observed in the SD group compared to VS group (29%
versus 69%, p = .0001; Fig. 2). Overall 102 patients (28%) showed im-
provement in GOS score of 1 or more, with significantly more patients
showing neurological improvements in the SD group compared to VS
group (33% versus 10%; p = .0001). Among surviving patients only,
neurological improvement at three years was not significantly higher
in the SD group compared to VS group (47% versus 32%, p = .13). The
overall mortality and improvement rates are summarized in Table 3.
Among 102 patients who improved, 56 patients (55%) improved by
6 months, 33 patients (32%) improved between 6 and 12 months, and
13 patients (13%) improved between 12 and 36 months (Fig. 3).
3.1. Patients in the vegetative state group (GOS 2)
Out of 91 patients in the VS group, 63 patients (69%) died, 19 survi-
vors (21%) remained stable at GOS 2, and 9 survivors (10%) showed im-
provement in GOS score to 3 within 3 years after discharge from
hospital.
Among the 63 patients who died within 3 years, most remained in
persistent vegetative or minimally conscious states from discharge
until their deaths. Two patients showed initial improvement at six
months, becoming minimally conversant but remained bedbound
(SD) and died within the three-year follow-up period. The causes of
death among the 63 patients were pneumonia (n = 24), stroke (n =
21), urinary tract infections (n = 5), ischemic heart disease (n = 4), ma-
lignancy (n = 4), infected sacral sore (n = 1), bowel obstruction (n =
1), hepatitis (n = 1), chronic obstructive airway disease (n = 1) and
vocal cord paralysis (n = 1) (Fig. 4).
Among the 28 survivors at 3 years in the VS group, 19 patients (68%)
remained in vegetative states after 3 years while 9 patients (32%) im-
proved, becoming conscious but remained severely disabled with a
GOS score of 3. Among the patients who improved (n = 9), four patients
showed improvement by six months, four patients by one year, and one
patient by three years (Fig. 3). Predictors of survival in VS group from
univariate analysis were younger age (p = .01) and absence of hydro-
cephalus (p = .049). Age was the only significant predictor of survival
after multivariate analysis at 3 years (p = .03).
3.2. Patients in the severely disabled group (GOS 3)
Out of the 278 patients in the SD group, 82 patients (29%) died, 8 sur-
vivors (3%) deteriorated and became vegetative, 95 survivors (34%)
remained stable and 93 survivors (33%) showed improvement in GOS
score up to 5 within 3 years after discharge from hospital.
 L. Lee et al. / Journal of Critical Care 48 (2018) 269–275 271

Fig. 1. Flow diagram showing patient recruitment and outcomes between the severely disabled (SD) group and vegetative state (VS) group.

Among the 82 patients who died within 3 years, 72 patients (88%) causes of death were pneumonia (n = 25), stroke (n = 21), ischemic
remained severely disabled since discharge up to their deaths; 6 patients heart disease (n = 15), malignancy (n = 8), urinary tract infection
(7%) deteriorated to vegetative states prior to their death; and 4 patients (n = 4), respiratory failure (n = 1), bronchiectasis (n = 1), chronic
(5%) regained independence in daily life (with residual disabilities). The obstructive pulmonary disorder (n = 1), liver cirrhosis (n = 1), renal fail-
ure (n = 1), bowel ischemia (n = 1), infected sacral sore (n = 1), acute
subdural hemorrhage (n = 1), diabetic ketoacidosis (n = 1) (Fig. 4).
Among the 196 survivors at 3 years in the SD group, 95 patients
Table 1 (48%) remained stable and severely disabled, including 13 patients
Baseline comparison between the group of patients included in the final analyses and the
group that was excluded due to missing data or who were lost to follow-up.
(14%) showed transient improvement initially but deteriorated back
to baseline by 3 years. Among the 93 survivors who improved neurolog-
Variable Included in final Excluded from p ically, 52 patients (56%) showed improvement by 6 months, 29 patients
analysis analysis
(31%) by 1 year, and 12 patients (13%) by 3 years (Fig. 3). Specifically, 63
n 369 109 patients (32% of all SD survivors; 23% of all SD patients) gained indepen-
Median (IQR) age, years 68 (57–78) 61 (52–74) b0.01
dence in daily living (GOS 4) while 30 patients (15% of all SD survivors;
Gender (male), n (%) 215 (58) 63 (58) 1
Previous stroke, n (%) 123 (33) 22 (20) 0.012 11% of all SD patients) achieved full recovery (GOS 5). The remaining
Hypertension, n (%) 271 (73) 72 (66) 0.17 eight survivors (4%) deteriorated to vegetative state by three years. Pre-
Diabetes, n (%) 91 (25) 21 (19) 0.30 dictors of survival in the SD group with univariate analysis were youn-
Hyperlipidaemia, n (%) 162 (44) 36 (33) 0.06 ger age (p b .0001), and no previous history of cerebrovascular events
Atrial Fibrillation, n (%) 21 (6) 8 (7) 0.69
Warfarin, n (%) 18 (5) 7 (6) 0.70
(p = .046). After multivariate analysis, only younger age (p = .012)
Antiplatelet Meds, n (%) 98 (27) 15 (14) b0.01 was still significant for survival. No previous history of cerebrovascular
Median (IQR) initial GCS 13 (10–15) 14 (11–15) 0.50 events was no longer significant (p = .31). Predictors of long-term im-
Pupillary dilatation, n (%) 9 (2) 0 (0) 0.21 provement with univariate analysis include younger age (p b .0001), no
Median (IQR) initial SBP 178 (149–198) 170 (148–193) 0.32
previous history of cerebrovascular events (p = .008) and higher GCS at
Side of ICH (left), n (%) 192 (52) 60 (55) 0.64
Median (IQR) vol. cm3 11.6 (4.5–28.7) 17 (5.44–28.6) 0.14 presentation (p = .0008). After multivariate analysis, only younger age
Hydrocephalus, n (%) 60 (16) 18 (17) 1 was found to be a significant predictive factor (p = .01). No history of
IVH, n (%) 136 (37) 41 (38) 0.98 cerebrovascular events (p = .37) and higher GCS at presentation (p =
SAH, n (%) 33 (9) 8 (7) 0.74 .064) became insignificant.
272 L. Lee et al. / Journal of Critical Care 48 (2018) 269–275

Table 2 Table 3
Patient demographics of the overall cohort. Patient mortality and improvement for survivors over a 3-year follow-up period.

Characteristics Overall VS SD Status VS SD p-value

n 369 91 278 n 91 278

Median (IQR) age, years 68 (57–78) 75 (65–84) 64 (54–76) Mortality
Ethnicity (Chinese: Malay: 323:26:16:4 82:4:5:0 241:22:11:4 Died by 6 months 30 (33) 16 (6) b 0.0001
Indian: Others), n Died by 12 months 42 (46) 41 (15) 0.0009
Male, n (%) 215 (58) 45 (49) 170 (61) Died by 36 months 63 (69) 82 (29) b 0.0001
Comorbidities, n (%) Survived at 36 months 28 (31) 196 (71) b 0.0001
History of cerebrovascular 123 (33) 40 (44) 83 (30) For 36-month survivors
events Deteriorated n.a. 8 (3)
Hypertension 271 (73) 72 (79) 199 (72) Stable 19 (20) 95 (34)
Diabetes mellitus 91 (25) 29 (32) 62 (22) Improved 9 (10) 63 (23)
Hyperlipidemia 162 (44) 40 (44) 122 (44) Achieved full recovery 0 30 (11)
Atrial fibrillation 21 (6) 2 (2) 19 (7)
Figures quoted in parenthesis are percentages.
Use of medications, n (%)
Warfarin 18 (5) 1 (1) 17 (6)
Antiplatelets 98 (27) 30 (33) 68 (24) [28], there were more patients with severe ICH in our population who
Antihypertensives 198 (54) 42 (46) 156 (56)
survived with maximal surgical and medical intervention, but remained
Statin 132 (36) 31 (34) 101 (36)
Median (IQR) admission GCS 13 (10–15) 10 (8–12) 14 (11–15) in vegetative or severely disabled states. Following stroke, patients
Unilateral/bilateral fixed pupils, 9 (2) 7 (8) 2 (1) would be considered for neurorehabilitation after assessment by the re-
n (%) habilitation team. They would either enter acute inpatient intensive re-
Median (IQR) blood pressure, habilitation or be discharged to a step down facility for longer term
mmHg
rehabilitation, with the eventual goal for the patients to be discharged
Systolic BP 179 170 180
(149–198) (145–195) (150–200) home. Outpatient rehabilitation such as physiotherapy and day care
Diastolic BP 90 (77–105) 87 (74–100) 91 (78–106) centers were also available. Those who were deemed to have little or
Median (IQR) mean arterial 120 113 121 no rehabilitation potential would be discharged directly back to their
pressure, mmHg (102–134) (100–129) (103–136)
residential homes or to nursing homes.
Left-sided hemorrhage, n (%) 192 (52) 52 (57) 140 (50)
Location of ICH, n (%)
To our knowledge, no study has investigated the long term potential
Lobar 270 (73) 63 (70) 207 (74) for recovery in patients with hemorrhagic strokes who have severe dis-
Basal ganglia/thalamic 65 (18) 23 (25) 42 (15) abilities or in vegetative states. In this study, we found that mortality
Brainstem 7 (2) 2 (2) 5 (2) within three years from hospital discharge was lower in the SD group
Cerebellar 26 (7) 3 (3) 23 (8)
compared to the VS group (69% versus 29%, p = .0001). In addition, im-
Multiple 1 (0.3) 0 (0) 1 (0.4)
Median (IQR) initial hematoma 12 (5–29) 16 (8–50) 9 (4–24) provement in neurological outcomes at three years was higher in the SD
size, cm3 group compared to the VS group (33% versus 10%, p = .0001). However,
Presence of intraventricular 136 (37) 48 (53) 88 (32) this difference in neurological improvement rates between the two
hemorrhage, n (%)
groups became insignificant when comparing among survivors only
Presence of hydrocephalus, n (%) 60 (16) 30 (33) 30 (11)
Presence of subarachnoid 33 (9) 18 (20) 15 (5)
(47% of SD survivors versus 32% of VS survivors, p = .13). Nonetheless,
hemorrhage, n (%) the extent of neurological improvement was significantly greater in SD
Primary surgical interventions group with 11% achieving full recovery (reflected by two-points in-
performed, n (%) crease in GOS), while all patients in the VS group who showed improve-
Decompressive craniectomy 28 (8) 10 (11) 18 (6)
ment had severe disabilities at three years (reflected by one-point
and/or hematoma evacuation
External ventricular drainage 42 (11) 14 (15) 28 (10) increase in GOS).

4. Discussion

The incidence of withdrawal of care or early “do not intubate” (DNI)

or “do not resuscitate” (DNR) rates in Singapore has been shown to be
lower than that in western populations [26], possibly due to Asian cul-
tural differences [27]. Even though our treatment results have been
found to be comparable to western population in terms of mortality

Fig. 3. Chart showing the periods from hospital discharge when patients improved
neurologically from both severely disabled (SD) group and vegetative state (VS) groups.
Fig. 2. Kaplan Meier graph showing difference in survival between the severely disabled Note that while a majority of patients improved within the first six months, there were
(SD) group and vegetative state (VS) group. patients who improved even after one year.
 L. Lee et al. / Journal of Critical Care 48 (2018) 269–275
Fig. 4. Pie chart showing the causes of death and their proportion in both the severely disabled (SD) and the vegetative state (VS) groups at the end of three years. The majority of patients
in both group died of pneumonia or stroke.
4.1. Long term outcomes for SD and VS patients
Previous studies have reported that the 30-day mortality of patients
with hemorrhagic stroke could be as high as 44% [29]. Patients with
large bleeds who underwent surgical interventions, or those who
were nursed in dedicated units with adequate blood pressure control
and the ability to perform various care processes, have shown better
long-term survival [30,31].
In our cohort, patients in the SD group had significantly different
outcomes compared to patients in the VS group at discharge. More
than half of the patients (58%) in the VS group died by 3 years compared
to 22% in the SD group. There were 33% of patients in the SD group who
showed improvement compared to 10% in the VS group. As such, the pa-
tients in the SD group had a higher three-year survival (p = .0001) and
a higher rate of neurological improvement (p = .0001) compared to pa-
tients in the VSD group. Among all the variables analyzed, younger age
was the only significant predictor of both survival and long-term im-
provement in the VS and SD group. This is consistent with previous
studies showing younger age being related to better outcomes in pa-
tients with stroke [8,11]. A lack of previous cerebrovascular events
273
was also another factor that resulted in the observed higher survival
rates in both groups and long-term neurological improvements in the
SD group. A higher GCS on presentation was also associated with
long-term improvement in the SD group and that might be due to less
cranial injury as evidenced by the better GCS score. Neurological im-
provement in many patients occurred in the first six months after the
initial stroke, although there was still a small number of patients in
our cohort who showed improvement after one year.
4.2. Patients in persistent vegetative states
The term “persistent vegetative state” is used to describe patients
with severe brain damage in whom coma has progressed to a state of
wakefulness without detectable awareness [32]. The prognosis of pa-
tients in persistent vegetative states has been extremely bleak. In our
study, more than half of the patients did not survive to 3 years. It was
traditionally believed that recovery from a non-traumatic brain injury
resulting in a PVS after three months in adults is exceedingly rare [33].
This could have resulted in the early withdrawal of care or denial of ac-
cess to rehabilitation services for some patients [34,35].
274 L. Lee et al. / Journal of Critical Care 48 (2018) 269–275
Some studies have shown that some patients in a persistent vegeta-
tive state do recover consciousness after a period of time [36,37]. In our
study, 10% of the patients with PVS regained awareness and progressed
to a SD state. None of them improved to an independent state. Despite
this, our results add to the increasing evidence that a small proportion
of PVS patients can improve. This suggests that a longer period of inter-
vention may be beneficial in this group of patients if there is potential to
regain their consciousness [38].
4.3. Long-term management and rehabilitation
Most of the studies which reported long-term neurological recovery
involved patients with traumatic brain injuries. These studies have
demonstrated the potential for recovery even years after the initial in-
jury [39-42]. There has been no study performed to investigate the pos-
sibility of long-term improvement in such a group of disabled or
vegetative patients after spontaneous primary ICH. Although previous
studies have suggested that these patients may show less improvement
compared to traumatic brain injury patients [32], the absence of long
term studies may have contributed to this nihilistic assessment. This
study has shown that up to one third of patients in severely disabled
states at discharge improved to be functionally independent. As such,
additional longer periods of rehabilitative interventions may be war-
ranted [36,38] with the potential to improve neurological outcomes in
a larger group of patients.
4.4. Study limitations
There was a large proportion of patients (n = 109) who were lost to
follow-up at three years, accounting for 22.8% of the original cohort. De-
spite this, we were able to show that the baseline characteristics of the
excluded patients were matched except for the higher use of antiplate-
let medication and more previous strokes in the analyzed cohort. Being
retrospective in nature, we had to rely on the available information re-
corded in the clinical notes. We were unable to determine the number
of patients who returned to work after ICH. Additional measures such
as GOS–E were not used as there was insufficient data available in the
documented notes.
5. Conclusion
Our study demonstrated that discharge status was not entirely indic-
ative of long-term prognoses for patients who were severely disabled or
vegetative, as these patients have the potential to improve functionally
or regain consciousness over time. Patients who were severely disabled
showed greater extents of improvement (becoming functionally or fully
independent) compared to patients who were in vegetative states. A
small proportion of patients in vegetative states managed to regain con-
sciousness despite common perceptions that improvements in vegeta-
tive patients are exceedingly rare. Patients who were severely
disabled or vegetative from primary ICH have the potential for improve-
ment in the long-term and may benefit from a longer course of rehabil-
itation or continued rehabilitation at outpatient facilities to optimize
their potential for neurological improvement.
Declaration of interest
The authors have no conflict of interest to declare.
Funding
This research did not receive any specific grant from funding agen-
cies in the public, commercial, or not-for-profit sectors.
References
[1] Daverat P, Castel JP, Dartigues JF, Orgogozo JM. Death and functional outcome after
spontaneous intracerebral haemorrhage. A prospective study of 166 cases using
multivariate analysis. Stroke 1991;22(1):1–6.
[2] Christensen MC, Mayer S, Ferran JM. Quality of life after intracerebral haemorrhage:
results of the factor seven for acute hemorrhagic stroke (FAST) trial. Stroke 2009;40:
1677–82.
[3] Chiu D, Peterson L, Elkind MSV, Rosand J, Gerber LM, Silverstein MD. Comparison of
outcomes after intracerebral haemorrhage and ischemic stroke. J Stroke Cerebrovasc
Dis 2010;19(3):225–9.
[4] Ministry of Health (Singapore). Singapore Burden of Disease Study 2010. Singapore;
2014.
[5] Jennett B, Bond M. Assessment of outcome after severe brain damage. Lancet 1975;1
(7905):480–4.
[6] National Registry of Diseases Office. Singapore Stroke Registry Report 2014.
Singapore; 2014.
[7] Ministry Of Health and the National Registry of Diseases Office. Trends in Stroke in
Singapore 2008 – 2012. Singapore; 2013.
[8] Bhalla A, Wang Y, Rudd A, Wolfe CDA. Differences in outcome and predictors be-
tween ischemic and intracerebral haemorrhage: the South London Stroke Register.
Stroke 2013;44(8):2174–81.
[9] Fogelholm R, Nuutila M, Vuorela a L. Primary intracerebral haemorrhage in the Jy-
väskylä region, central Finland, 1985-89: incidence, case fatality rate, and functional
outcome. J Neurol Neurosurg Psychiatry 1992;55(7):546–52.
[10] Fieschi C, Carolei A, Fiorelli M, Argentino C, Bozzao L, Fazio C, et al. Changing progno-
sis of primary intracerebral haemorrhage: results of a clinical and computed tomo-
graphic follow-up study of 104 patients. Stroke 1988;19(2):192–5.
[11] Koivunen R-J, Tatlisumak T, Satopää J, Niemelä M, Putaala J. Intracerebral haemor-
rhage at young age: long-term prognosis. Eur J Neurol 2015;22(7):1029–37.
[12] Rutten-Jacobs LC, Maaijwee NA, Arntz RM, Schoonderwaldt HC, Dorresteijn LD, van
Dijk EJ, et al. Clinical characteristics and outcome of intracerebral haemorrhage in
young adults. J Neurol 2014;261(11):2143–9.
[13] Tveiten A, Ljøstad U, Mygland Å, Naess H. Functioning of long-term survivors of first-
ever intracerebral haemorrhage. Acta Neurol Scand 2014;129(4):269–75.
[14] Cheung RTF, Zou L-Y. Use of the original, modified, or new intracerebral haemor-
rhage score to predict mortality and morbidity after intracerebral haemorrhage.
Stroke 2003;34(7):1717–22.
[15] Ruiz-Sandoval JL, Chiquete E, Romero-Vargas S, Padilla-Martínez JJ, González-
Cornejo S. Grading scale for prediction of outcome in primary intracerebral
haemorrhages. Stroke 2007;38(5):1641–4.
[16] Hemphill JC, Farrant M, Neill TA. Prospective validation of the ICH score for 12-
month functional outcome. Neurology 2009;73(14):1088–94.
[17] Ji R, Shen H, Pan Y, Wang P, Liu G, Wang Y, et al. China National Stroke Registry
(CNSR) investigators. A novel risk score to predict 1-year functional outcome after
intracerebral haemorrhage and comparison with existing scores. Critical Care
(London, England) 2013;17(6):R275.
[18] Weimar C, Benemann J, Diener H-C. German stroke study collaboration. develop-
ment and validation of the essen intracerebral haemorrhage score. J Neurol
Neurosurg Psychiatry 2006;77(5):601–5.
[19] Brutto OH, Sánchez J, Campos X, Santos J, Mosquera A. Non-traumatic intracerebral
haemorrhage in young adults living in Guayaquil, Ecuador (South America): analysis
of 151 patients. Funct Neurol 1999;14(1):21–8.
[20] Chen CL, Tang FT, Chen HC, Chung CY, Wong MK. Brain lesion size and location: ef-
fects on motor recovery and functional outcome in stroke patients Archives of phys-
ical medicine and rehabilitation, 81; 2000; 447–52.
[21] Mori S, Sadoshima S, Ibayashi S, Fujishima M, Iino K. Impact of thalamic haematoma
on six-month mortality and motor and cognitive functional outcome. Stroke 1995;
26(4):620–6.
[22] Lampl Y, Gilad R, Eshel Y, Sarova-Pinhas I. Neurological and functional outcome in
patients with supratentorial haemorrhages. A prospective study. Stroke 1995;26
(12):2249–53.
[23] Rathor MY, Rani MFA, Jamalludin AR, Amran M, Shahrin TCA, Shah A. Prediction
of functional outcome in patients with primary intracerebral haemorrhage
by clinical-computed tomographic correlations. J Res Med Sci 2012;17(11):
1056–62.
[24] Hansen BM, Nilsson OG, Anderson H, Norrving B, Säveland H, Lindgren A. Long term
(13 years) prognosis after primary intracerebral haemorrhage: a prospective popu-
lation based study of long term mortality, prognostic factors and causes of death. J
Neurol Neurosurg Psychiatry 2013;84(10):1150–5.
[25] Helweg-Larsen S, Sommer W, Strange P, Lester J, Boysen G. Prognosis for patients
treated conservatively for spontaneous intracerebral haematomas. Stroke 1984;15
(6):1045–8.
[26] Sahadevan S, Pang WS. Do-not-resuscitate orders: towards a policy in Singapore.
Singapore Med J 1995;36:267–70.
[27] Phua J, Kee ACL, Tan A, Mukhopadhyay A, Kay CS. End-of-life care in the
generalwards of a Singaporean hospital: an Asian perspective. J Palliat Med 2011;
14(12):1296–301.
[28] Han JX, See AAQ, King NKK. Validation of Prognostic Early Mortality in Spontaneous
Intracerebral Haemorrhage: A Cross Sectional Evaluation of a Singapore Stroke Data-
base World Neurosurgery, 109; 2018; e601–8.
[29] Broderick JP, Brott TG, Duldner JE. Volume of intracerebral hemorrhage. A powerful
and easy to use predictor of 30 day mortality. Stroke 1993;24:987–93.
[30] Lo YT, See AAQ, King NKK. Decompressive craniectomy in spontaneous intracere-
bral haemorrhage. A case controlled study. World Neurosurg 2017 July;103:
815–20.
 L. Lee et al. / Journal of Critical Care 48 (2018) 269–275
[31] Cadilhac DA, Andrew NE, Lannin NA, Middleton S, Levy CR, Dewey HM, et al. Quality
of acute care and quality of life and survival: the Australian stroke clinical registry.
Stroke 2017;48(4):1026–32.
[32] Jennett B, Plum F. Persistent vegetative state after brain damage: a syndrome in
search of a name. Lancet 1972;1:734–7.
[33] The Multi-society Task Force on PVS. Medical aspects of the persistant vegetative
state. N Engl J Med 1994;330:1499–508.
[34] Edlow BL, Chatelle C, Spencer CA, Chu CJ, Bodien YG, O'Connor KL, et al. Early detec-
tion of consciousness in patients with acute severe traumatic brain injury. Brain
2017;140:2399–414.
[35] Willmott L, White B. Persistent vegetative state and minimally conscious state: eth-
ical, legal and practical dilemmas. J Med Ethics 2017;43:425–6.
[36] Baricich A, de Sire A, Antoniono E, Gozzerino F, Lamberti G, Cisari C, et al. Recovery
from vegetative state of patients with a severe brain injury: a 4 year real practice
prospective cohort study. Funct Neurol 2017;32(3):131–6.
[37] Hodelin-Tablade R. Minimally conscious state: evolution of concept, diagnosis and
treatment. MEDICC Rev 2016 Oct;18(4):43–6.
275
[38] Klingshirn H, Grill E, Bender A, Strobl R, Mittrach R, Braitmayer K, et al. Quality of
evidence of rehabilitation interventions in long-term care for people with severe
disorders of sconsciousness after brain injury: a systemic review. J Rehabil Med
2015;47:577–85.
[39] Katz DI, Polyak M, Coughlan D, Nicols M, Roche A. Natural history of recovery from
brain injury after prolonged disorders of consciousness: outcomes of patients admit-
ted to inpatient rehabilitation with 1–4 years of follow-up. Progress Brain Res 2009;
177:73–88.
[40] Lammi MH, Smith Vh, Tate RL, Taylor CM. The minimally consciousness state and re-
covery potential: a follow-up study 2 to 5 years after traumatic brain injury. Arch
Phys Med Rehabil 2005;86:746–54.
[41] Whyte J, Nakase-Richardson R, Hammond FM, McNamee S, Giacino JT, Kalmar K,
et al. Functional outcomes in traumatic disorders of consciousness: 5 year outcomes
from the National Institute on Disability and Rehabilitation Research Traumatic
Brain Injury Model Systems. Arch Phys Med Rehabil 2013;94:1924–33.
[42] Luaute J, Maucort-Boulch D, Tell L, Quelard F, Sarraf T, Iwaz J, et al. Long-term outcomes
of chronic minimally consciousness and vegetative states. Neurology 2010;75:246–52.