Brain Injury

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The effect of time on cognitive impairments after

non-traumatic subarachnoid haemorrhage and
after traumatic brain injury

Anna Tölli, Charlotte Höybye, Bo-Michael Bellander, Fredrik Johansson &

Jörgen Borg

To cite this article: Anna Tölli, Charlotte Höybye, Bo-Michael Bellander, Fredrik Johansson
& Jörgen Borg (2018) The effect of time on cognitive impairments after non-traumatic
subarachnoid haemorrhage and after traumatic brain injury, Brain Injury, 32:12, 1465-1476, DOI:
10.1080/02699052.2018.1497203

To link to this article: https://doi.org/10.1080/02699052.2018.1497203

© 2018 The Author(s). Published by Taylor &

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Published online: 16 Jul 2018.

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BRAIN INJURY
2018, VOL. 32, NO. 12, 1465–1476
https://doi.org/10.1080/02699052.2018.1497203

The effect of time on cognitive impairments after non-traumatic subarachnoid

haemorrhage and after traumatic brain injury
Anna Töllia, Charlotte Höybyeb, Bo-Michael Bellanderc, Fredrik Johanssond, and Jörgen Borga
a
Dep. of Clinical Sciences, Danderyd Hospital, Karolinska Institutet, Stockholm, Sweden; bDep. of Molecular Medicine and Surgery, Karolinska
Institutet and Department of Endocrinology, Metabolism and Diabetology, Karolinska University Hospital, Stockholm, Sweden; cDep. of Clinical
Neuroscience, Section for Neurosurgery, Karolinska Institutet, Stockholm, Sweden; dMedical library, Danderyd Hospital, Stockholm, Sweden

ABSTRACT ARTICLE HISTORY

Objectives: To compare the effect of time on cognitive impairments after Subarachnoid Haemorrhage Received 15 October 2017
and Traumatic Brain Injury and explore associations with baseline variables and global function. Revised 28 April 2018
Methods: Patients with a Glasgow Coma Scale score of 3–13, were assessed at 3, 6 and 12 months post Accepted 2 July 2018
injury by use of BNIS for cognitive impairment, RLAS-R to categorise cognitive and behavioural function, KEYWORDS
Barthel Index to assess performance of daily living, HADS to screen for depression and anxiety, and Traumatic brain injury;
EuroQoL-5D, LiSat-11 and Glasgow Outcome Scale Extended to assess global function. subarachnoid haemorrhage;
Results: BNIS T-scores did not differ significantly between groups and the proportion of patients with outcome; cognitive
cognitive impairments was not significantly different at any time point. Cognition improved significantly impairments
between all time points in both groups except from 6 to 12 months after TBI. Generalised estimating
equation showed non-significant signs of slower recovery of BNIS T-scores over time after SAH. Acute
GCS scores were associated with BNIS T-scores after TBI but not after SAH. At 12 months, similar
proportions of patients with SAH and TBI had good outcome.
Conclusions: Cognitive improvements after SAH and TBI exhibit similarities and correlate with global
function. GCS scores are associated with outcome after TBI but not after SAH.

Background parameters reflecting the impact of the bleed, as well as time

on mechanical ventilation, were associated with neuropsycho-
Patients with non-traumatic subarachnoid haemorrhage
logical outcome at one year (10). However, even patients with
(SAH) and moderate or severe, traumatic brain injury (TBI)
severe SAH, presenting with a Hunt and Hess Grade V, may
often follow a similar pathway of care from neurointensive
have a good recovery of cognitive function (11). A recent
care units to rehabilitation services. While cognitive impair-
multicentre study of 158 patients with aneurysmal SAH
ments and rehabilitation needs after TBI have been exten-
reported that cognitive impairment assessed by Montreal
sively studied, less is known for SAH.
Cognitive Assessment (MoCA) early after the event correlated
Subarachnoid haemorrhage accounts for 5% of all strokes
with functional outcome at 1 year but did not accurately
(1) and 27% of all stroke-related years of potential life lost
predict functional outcome (12).Thus, the need for further
before the age of 65. The annual incidence of ruptured aneur-
studies on the clinical course and prediction of long-term
ysms, constituting 85% of all SAH (2), rates from 9 in most
outcome after SAH remains (13) as also highlighted in recent
European regions to 20 per 100 000 inhabitants in Finland (3).
reviews (14,15). Impairments after SAH may depend not only
Mortality rate is around 50% (4). Of survivors, it has been
on the primary lesion but also on aneurysm treatment method
estimated that 36–55% regain independence, defined as mod-
(16,17), on spasm related secondary ischemia (18–21) and
ified Rankin Scale (mRS) scores of 0–3, during the first
other secondary insults (22) and critical illness (23,24). In
year (5).
this respect and regarding the role of cognitive impairments
Cognitive impairments are common after SAH and may
for long term disability, SAH resembles TBI (25). A compar-
impact on activities of daily living and quality of life (6–8). In
ison of the recovery of cognition after SAH and TBI may
a population-based interview survey of 230 participants at one
elucidate potentially common determinants of recovery and
year after SAH, 46% reported incomplete recovery and of
long-term outcome and support further prediction studies as
these 50% reported memory problems (9). No patient or
well as rehabilitation planning.
disease characteristics that predicted good recovery were iden-
The estimated total incidence rate of TBI in Europe ranges
tified. In a prospective study of 32 patients, who were followed
from 235 (26) to 262 (27) per 100.000 inhabitants and year.
until12 months after SAH (10), motor and psychomotor
Most injuries are mild and the estimated proportion with
impairments recovered within 6 months while verbal memory
moderate and severe TBI varies from around 2.5% to 29%
did not improve significantly within this time period. Clinical
(27). There is a huge literature on cognitive function and

CONTACT Anna Tölli anna.tolli@ki.se Department of Clinical Sciences, Danderyd Hospital, Karolinska Institutet, Stockholm 182 88, Sweden.
Color versions of one or more of the figures in the article can be found online at www.tandfonline.com/ibij.
© 2018 The Author(s). Published by Taylor & Francis.
This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License (http://creativecommons.org/licenses/by-nc-nd/4.0/),
which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited, and is not altered, transformed, or built upon in any way.
1466 A. TÖLLI ET AL.
outcome after TBI as illustrated by reviews on mild TBI (28)
and on moderate and severe TBI (25) and prediction rules for
moderate and severe TBI are evolving (29–31). Outcome is
most often categorised by use of the Glasgow Outcome Scale
(GOS) or the extended version (GOSE) (32).
Some recent studies have applied the Barrow Neurological
Institute Screen for Higher Cerebral Functions (BNIS) (33) to
screen for cognitive and affective disturbances after acquired
brain injury. BNIS has documented validity (34–36), is easily
applicable in clinical routine and has been used in some
studies of TBI (36–38) as well as stroke (39,40). A recent
study of patients with severe TBI with BNIS reported that
most improvement occurred during the first three months
after the injury while cognition was fairly stable between 3
and 12 months (41).
The primary aim of our study was to compare the course
and outcome of cognitive impairments by use of BNIS during
the first year after non-traumatic SAH with corresponding
data from patients with moderate and severe TBI admitted to
the same neurointensive care unit at one university hospital
and exposed to a similar neurorehabilitation and follow up
program. A secondary aim was to explore relations between
baseline characteristics and outcomes.
Materials and methods
Study design and participants
This was a prospective, observational study of patients with
non-traumatic, aneurysmal subarachnoid haemorrhage and
after moderate or severe traumatic brain injury. Study design
has been described previously (42,43). In brief, inclusion
required a SAH due to a ruptured aneurysm or moderate or
severe TBI, a lowest GCS score during the first day after the
event of 3–13, age ≥ 18 years, living in the Stockholm region
and obtained informed consent. For patients, who were
unconscious or otherwise unable to give informed consent,
the closest relative was asked.
Patients were included at the neurointensive care unit
(NICU) at the Department of Neurosurgery at Karolinska
University Hospital from March 2009 until June 2012.
Inclusion was not performed during holidays for logistic and
administrative reasons.
After inclusion, acute (clinical and radiological para-
meters) and socioeconomic data were attained from medical
records and via interview. Patients were assessed at three
time points, 3, 6 and 12 months post injury/illness at the
Department of Rehabilitation Medicine at Danderyd
University Hospital, Stockholm, Sweden. Assessments
included clinical examination and a battery of standardised
assessment instruments and were performed by the same,
experienced assessor (AT). In patients unable to communi-
cate, the presence of a possible Disorder of Consciousness
was evaluated by clinical examination and with the Coma
Recovery Scale Revised.
The study was approved by the Regional Ethics Committee
of Stockholm, Sweden (No: 2008/3:9 2008/1574–31/3) and
complies with the Strobe checklist for observational studies.
Severity grading
In addition to the GCS score (44) (3–8 severe injury,
9–13 moderate injury), clinical severity in patients with SAH
severity was graded according to the Hunt-Hess scale (HH)
(45). The CT lesion after SAH was graded according to Fisher
scale (FS) (46). Aneurysms were verified by computed tomo-
graphy angiography (CTA) or digital subtraction angiography
(DSA). Aneurysms were divided into aneurysm from the
anterior cerebral circulation and the posterior cerebral circu-
lation. Computed tomography (CT) lesion (46) grading of
TBI was according to the CRASH model (47) with addition
of brain oedema, basilar skull fractures and facial fracture
data. Coma Recovery Scale Revised (CRS-R) (48) was used
to assess disorders of consciousness (DOC) (49).
Cognitive and affective function
The Barrow Neurological Institute Screen for Higher Cerebral
Functions (BNIS) (33) was used to screen cognitive and
affective disturbances. The BNIS starts with three pre-screen
items that assess level of arousal yielding maximally 3 points
(p), basic communication level (3 p) and level of cooperation
(3 p), to assess whether the patient is capable of participating
in further assessment. The patients must achieve at least two
points on each of the items to continue with items that assess
the range of higher cerebral functions: speech and language
(15 p), orientation (3 p), attention/concentration (3 p),
visual and visuospatial problem solving (8 p), memory
(7 p), affect (4 p) and awareness of own performance (1 p),
corresponding to a total score of maximally 50 (sum of pre-
screen and the 7 subscale scores). Total BNIS raw scores are
converted to age-corrected standard Τ-points. Higher scores
indicate better functioning. A cut-off score of < 47 was set
for identifying brain dysfunction for patients < 60 years, < 46
for patients 60–69 years and ≤ 43 for patients > 70 years
(35,36,50). BNIS has good sensitivity (92%) to brain dysfunc-
tion and acceptable specificity (56%) (34). In a Swedish study
the sensitivity was 88% and the specificity 78% (36). Cut-off
for cognitive dysfunction for T-points was set at < 40 (i.e. <
−1SD) (51).
Rancho Los Amigos Cognitive Scale-Revised (RLAS-R) (52)
was used to categorise level of cognitive and behavioral func-
tion. RLAS-R is a clinical scale with scores from 1 to 10,
describing 10 stages of recovery after brain injury by assessing
responsiveness to stimuli, ability to follow commands, pre-
sence of non-purposeful behavior, cooperation, confusion,
attention to environment, verbal ability, memory, orientation
and higher cognitive ability. RLAS-R levels were dichotomised
into ‘inferior functioning’ (RLAS-R 1–8) and ‘superior func-
tioning’ (RLAS-R 9–10).
The Hospital Anxiety and Depression Scale (HADS) (53)
was used to screen for depression and anxiety. HADS com-
prises 14 items (7 items in each subscale) which are assessed
on a four point scale (range 0–3), where the total score is the
sum of each subscale (range 0–21). Severity was classified
using the two subscales as normal (0–7), mild (8–10), mod-
erate (11–14) or severe (15–21,54).

Activities of daily living
The Barthel Index (BI) was used to measure performance in
activities of daily living (ADL) (55). The BI scale allow evaluation
of functional independence in 10 activities of daily and yields a
sum score from 0 to 100. BI was dichotomised into two cate-
gories ‘dependence’ (BI 0–95) and ‘independence’ (BI 96–100).
Global measures
Global outcome and independence was assessed by use of the
Glasgow Outcome Scale Extended (GOSE) (56,57). GOSE has
demonstrated good validity interrater reliability when applied
by standardised interview (32,58).The eight categories span
from ‘Dead’ (score 1) to ‘Upper Good Recovery’ (score 8).
GOSE scores were dichotomised into ‘unfavourable outcome
(GOSE 1–4) and ‘favourable outcome’ (GOSE 5–8).
Quality of life (QoL) was assessed by use of the EuroQoL
5D (EQ-5D) (59). EQ-5D index estimates health in five
dimensions and each dimension is scored as one of three
levels allowing for 243 permutations of unique health states
and are revised into an index with a range from −0.594 to 1,
with 1.00 indicating full health. The EQ-5D also includes a
visual analogue scale (VAS) ranging from 0 to 100.
Satisfaction with life was assessed by use of the 11-item
version of Life Satisfaction Questionnaire (LiSat-11) (60,61).
The LiSat-11 is a generic self-reported checklist comprising an
estimate of satisfaction with life as a whole as well as for 10
specific domains. Each question is scored on a six-grade
ordinal scale. Item scores was dichotomised into unsatisfied
(1–4) and satisfied (5,6) to report results on item level.
Statistics
Statistical analysis was performed using IBM SPSS Statistics
version 22 (IBM Corporation, Armonk, New York, USA).
This observational study reports descriptive data with central
measures (mean, median or percent) and measures of spread
(SD, percentile, min-max). Nonparametric methods were used
Figure 1: Flowchart of study participants.
BRAIN INJURY 1467
as data were not normally distributed according to Shapiro-
Wilk’s test of normality. Wilcoxon signed ranks test was used
for analysis of BNIS T-scores, RLAS-R levels, EQ-5D index,
EQ-5D VAS, Barthel Index, HADS depression and anxiety
over time. The Z-test for proportions was used to for analyses
of populations’ proportion. Friedmans test was used for com-
parisons of LiSat.
The Mann-Whitney U test was used for non-response
analysis with respect to these variables: age and GCS. The
chi-squared test was used for non-response analysis with
respect to gender. Generalised estimating equation (GEE)
was used to explore the effect of time on cognitive function
according to BNIS. The Spearman correlation coefficient was
used for the analysis of bivariate correlation between BNIS
and GCS, HH, FS, gender, age, GOSE, RLAS, HADS, BI and
LiSat-11. In all cases, significance level was set at p < 0.05.
Results
Study population
Included were 127 patients, 45 with SAH and 82 with TBI. Of
these, 10 patients with SAH and 26 patients with TBI dropped
out due to the following reasons. Four patients with SAH and
10 with TBI died before 3 months follow up. Five patients
with SAH and 12 with TBI declined further participation in
the study. One patient with SAH and 4 with TBI moved
abroad. For patients with SAH or TBI who dropped out
there was no significant difference in gender (p = 0.095/
p = 0.121), age (p = 0.280/p = 0.094) or GSC (p = 0.205/
p = 0.073). A flowchart and drop-out of patients with SAH
and TBI are presented in Figure 1.
Demographical and clinical characteristics
Of the 35 patients with SAH, 27 were women and 8 men,
mean age was 57.4 ± 9.9 years, 22 patients had severe and 13
patients a moderate brain injury according to the admission
GCS score (mean GCS score 7.9 ± 4.2). GCS scores for
1468 A. TÖLLI ET AL.

patients with SAH and TBI respectively were not significantly Table 1: Baseline data of patients with subarachnoid haemorrhage and traumatic
brain injury.
different (p = 0.144). For patients with SAH, most frequent
Hunt & Hess scores at admission were 4 and 3 and all had TBI n = 56 SAH n = 35
SAH visible on CT scan (Fisher grades 2–4). Out of 56 (mean ± S.D.) (mean ± S.D.)
(min-max) (min-max)
patients with TBI, 15 were women and 41 men, mean age Age, years 47.1 ± 16.6 57.4 ± 9.9
was 47.1 ± 16.6 years, 44 patients had a severe brain injury (19–79) (28–76)
BMI 25.6 ± 4.8 25.7 ± 4.3
and 12 patients a moderate brain injury according to the (18.5–42.2) (20.3–36.5)
admission GCS score (mean GCS score 6.3 ± 2.9). Data are GCS 6.3 ± 2.9 (3–13) 7.9 ± 4.2 (3–13)
displayed in Table 1. n (%) n (%)
Age groups
18–59 40 (71.4) 19 (54.3)
60–69 13 (23.2) 15 (42.9)
70–87 3 (5.4) 1 (2.9)
BNIS Education
< 12 years 8 (14.8) 11 (31.4)
Equally large proportions of patients with SAH and TBI could = 12 years 23(42.6) 10(28.6)
perform the BNIS at three months [25/35 (71%) of patients > 12 years 23(42.6) 14(40.0)
Gender
with SAH and 41/56 (73%) with TBI, p = 0.853], at six Male 41 (73.2%) 8 (22.9%)
months [28/34 (82%) and 43/54 (80%) p = 0.753] and at Female 15 (26.8%) 27 (77.1%)
GCS
12 months [30/35 (86%) and 46/56 (82%) p = 0.655] and Moderate (9–13) 12 (21.4%) 13 (37.1%)
equally large proportions failed pre-screen at 3 months [10/ Severe (3–8) 44 (78.6%) 22 (62.9%)
35 (29%) of patients with SAH and 15/56 (27%) with TBI, Hunter & Hess grade
1 1 (2.9%)
p = 0.853], 6 months [6/34 (18%) and 11/54 (20%), p = 0.753] 2 3 (8.6%)
and 12 months [5/35 (14%) and 10/56 (18%), p = 0.655]. 3 14 (40.0%)
4 15 (42.9%)
Numbers and proportions of patients who performed BNIS, 5 2 (5.7%)
of those who did not pass the prescreen and of patients who Fisher grade
were not able to be prescreened due to ongoing disorders of 1 0
2 3 (8.6%)
consciousness are presented in Table 2. 3 8 (22.9%)
After SAH, 19/25 (76%) of those who performed the test, 4 24 (68.6%)
Trauma cause
scored below cut-off for cognitive dysfunction (T-points < 40 Traffic accident 25 (44.6%)
or < −1 SD) at three months, 19/27 (70%) at six months and Fall 28 (50%)
17/29 (59%) at 12 months. After TBI, 26/41 (63%) of those Assault 2 (3.6%)
Other 1 (1.8%)
who performed the test, scored below cut-off for cognitive CT scan
dysfunction at 3 months, 23/43 (54%) at six months and 15/42 Cerebral contusions 45 (80.8%)
Obliteration of the third ventricle or 15 (26.8%)
(36%) at 12 months. Differences in proportions of patients basal cisterns
with SAH and TBI below the cut-off were not significant at 3 Subarachnoid bleed 45 (80.4%)
(p = 0.287), 6 (p = 0.160), or 12 (p = 0.057) months post Midline shift > 5mm 21 (37.5%)
Subdural/epidural haematoma 48 (85.7%)
event. The distribution of patients with SAH and TBI above Brain oedema 12 (21.4%)
and below the cut-off for cognitive dysfunction are presented Basilar skull fractures 26 (46.4%)
Facial fracture 17 (30.4%)
in Table 2. Aneurysm localisation
BNIS data could be collected at all three time points from Anterior cerebral circulation AACA
Anterior communicating artery ACoA 15 (42.9%)
22 patients with SAH and 37 patients with TBI and these data Middle cerebral artery MCA 8 (22.9%)
were used for the analyses of change over time. Anterior choroidal artery AChA 1 (2.9%)
Internal carotid artery ICA 3 (8.6%)
Pericallosal artery 1 (2.9%)
Posterior cerebral circulation APCC
Change of BNIS over time Posterior communicating artery PCoA 3 (8.6%)
Basilar artery 1 (2.9%)
After SAH, median BNIS T-scores improved significantly from Vertebral artery 1 (2.9%)
Posterior inferior cerebellar artery 1 (2.9%)
3 months to 6 months (p = 0.017), from 6 months to 12 months PICA
(p = 0.010) and from 3 months to 12 months (p = 0.004). After AACA + APCC
MCA + PCoA 1 (2.9%)
TBI, BNIS T-scores improved significantly from 3 months to
6 months (p = 0.003) and from 3 months to 12 months BMI, Body Mass Index (kg/m2)
(p = 0.001), while the improvement from 6 months to 12 months
was not significant (p = 0.065). BNIS T-scores at 3, 6 and
BNIS subscales
12 months after SAH and TBI are presented in Figure 2.
Median BNIS T-scores were lower after SAH than after TBI In the analyses of BNIS subscales, the age groups 60–69 and
but the difference was not significant between the groups at 70–87 years were merged due to the low number of BNIS data
3 months (p = 0.064), 6 months (p = 0.069) or 12 months in the oldest age group (n = 1–2).
(p = 0.148) post event. Change of BNIS T-scores over time Changes between 3 and 6 months: After SAH, in age
from 3 to 12 months according to GEE was not significantly group 18–59 years, scores improved significantly for lan-
different for SAH and TBI (p = 0.591), as illustrated in Figure 3. guage (p = 0.020), memory (p = 0.004), affect (p = 0.034)
 BRAIN INJURY 1469

Table 2: BNIS T-points results at 3, 6 and 12 months after SAH and TBI.
TBI SAH
3 months 6 months 12 months 3 months 6 months 12 months
(n = 41) (n = 43) (n = 42) (n = 25) (n = 27) (n = 29)
BNIS assessable Results description n (%) n (%) n (%) n (%) n (%) n (%)
Superior 2 (4.9) 5 (11.6) 10 (23.8) 3 (12.0) 2 (7.4) 2 (6.9)
T-points > 60
Average 13 (31.7) 15 (34.9) 17 (40.5) 3 (12.0) 6 (22.2) 10 (34.5)
T-points 40–60
Borderline 8 (19.5) 6 (14.0) 3 (7.1) 4 (16.0) 2 (7.4) 2 (6.9)
T-points 30–39
Extremely low 18 (43.9) 17 (39.5) 12 (28.6) 15 (60.0) 17 (63.0) 15 (51.7)
T-points < 30
Not assessable 15 11 10 10 6 5
Missing data 0 2 4 0 2 1

Figure 2: BNIS T-scores at 3, 6 and 12 months after SAH (n=22) and TBI (n=37). Dashed line illustrates cut-off level for cognitive dysfunction.

group 60–87 years for orientation (p = 0.034), but not in

the younger age group.
Changes between 6 and 12 months: After TBI, scores
improved significantly for memory (p = 0.028) and awareness
(p = 0.034) in age group 18–59 years, but not in the older age
group or in either age group after SAH.
Changes between 3 and 12 months: After SAH, significant
improvement was observed in patients aged 18–59 years for
language (p = 0.020), for orientation
(p = 0.038), memory (p = 0.003), and awareness
(p = 0.014), while no significant changes were observed
in the older age group. In patients with TBI during the
same period, awareness (p = 0.011), and language
(p = 0.031) improved in the younger age group while
no significant changes were observed in the older age
group

Figure 3: Illustration av result av GEE analyse.

BNIS by injury severity, gender and years of education
and awareness (p = 0.046), while no significant changes When data at all three time points were merged, BNIS-T-
were observed in the older age group. After TBI, improve- scores were significantly correlated with acute GCS for TBI
ments during the same period were observed in the age (r = 0.453, p < 0.001), but not for SAH (r = 0.045, p = 0.720).
1470 A. TÖLLI ET AL.

Similar associations were observed for data at 3 months RLAS

(r = 0.440, p = 0.006), 6 months (r = 0.447, p = 0.006), and
RLAS-R improved significantly after SAH from 3 months to
12 months (r = 0.498, p = 0.002) after TBI but not for SAH
6 months (p < 0.001), from 6 months to 12 months (p = 0.001)
(3 months, r = 0.123, p = 0.585; 6 months, r = 0.070,
and from 3 months to 12 months (p < 0.001).
p = 0.758; 12 months, r = - 0.082, p = 0.716).
RLAS-R improved significantly after TBI from 3 months to
Patients with severe SAH had a significant improvement in
6 months (p < 0.001), from 6 months to 12 months (p < 0.001)
BNIS T-score between 3 and 12 months (p = 0.037), but not
and from 3 months to 12 months (p < 0.001).
between 3 and 6 months (p = 0.110) or between 6 and
At 12 months, 21/35 (60%) patients with SAH had ‘inferior
12 months (p = 0.065). Patients with moderate SAH had a
cognitive functioning’ and 14/35 (40%) had ‘superior cognitive
significant improvement in BNIS T-score between 3 and
functioning’; 25/56 (45%) patients with TBI had ‘inferior cog-
6 months (p = 0.046) and 3 and 12 months (p = 0.028), but
nitive functioning’ and 31/56 (55%) ‘superior cognitive func-
not between 6 and 12 months (p = 0.068).
tioning’. The proportion of patients with ‘superior cognitive
Patients with severe TBI had a significant improvement in
functioning’ at 12 months was not significantly less after SAH
BNIS T-score between 3 and 12 months (p = 0.008), and
than after TBI (p = 0.154). RLAS data are presented in Table 3
between 3 and 6 months (p = 0.019) but not between 6
and Figure 4.
and 12 months (p = 0.119). Patients with moderate TBI
We found strong correlations between BNIS T-scores and
had a significant improvement in BNIS T-score between 3 and
RLAS-R at 3 (r = 0.890, p < 0.001), 6 (r = 0.827, p < 0.001), and 12
12 months (p = 0.017), but not between 3 and 6 months
(r = 0.750, p < 0.001) months after SAH and at 6 (r = 0.752,
(p = 0.079) or between 6 and 12 months (p = 0.362).
p < 0.001), and 12(r = 0.716, p < 0.001) months after TBI, and
BNIS-T-scores after SAH were not related to Hunt-Hess
moderate correlation at 3 (r = 0.698, p < 0.001) months after TBI.
scale scores (r = - 0.117, p = 0.35) or Fischer scale scores
(r = - 0.149, p = 0.233).
BNIS-T-scores were negative correlated to age (r = - 0.450,
HADS
p < 0.001) for TBI but not for SAH (r = 0.029, p = 0.817). After
TBI, this was observed for BNIS results at 3 (r = - 0.493, p = 0.002), No statistically significant differences were found for HADS
6 (r = - 0.515, p = 0.001) and 12 months (r = - 0.384, p = 0.019) but depression or anxiety scores between the consecutive time
not after SAH at 3 (r = 0.142, p = 0.529), 6 (r = 0.046, p = 0.839) or points or between 3 and 12 months after SAH or TBI. The
12 months (r = - 0.139, p = 0.537). proportion of patients who fulfilled criteria for mild or mod-
There was no relation between BNIS-T-scores and gender erate depression at 12 months was 7/30 (23%) after SAH and
in patients with SAH (p = 0.169) or TBI (p = 0.400). 9/41 (22%) after TBI. The proportion of patients who fulfilled
Patients with more than 12 years of education had criteria for mild, moderate or severe anxiety at 12 months was
higher BNIS T-scores at 3, 6 and 12 months after SAH 6/30 (20%) after SAH group and 12/41 (29%) after TBI.
and after TBI when compared with patients with less than After TBI, there were weak correlations between BNIS
12 years of education, but the differences were T-scores both HADS scores for depression at 3 (r = - 0.506,
nonsignificant. p = 0.002) and 12 months (r = - 0.396, p = 0.018), and for

Table 3: Outcome measured with RLAS-R 3, 6 and 12 months post SAH and TBI.
TBI (n = 56) SAH (n = 35)
RLAS-R 3 mn 6 mn 12 mn 3 mn 6 mn 12 mn
Level I 0 0 0 0 0 0
No response: total assistance
Level II 0 0 0 1 0 0
Generalized response: total assistance
Level III 5 1 2 1 1 1
Localised response: total assistance
Level IV 6 8 3 5 1 0
Confused/agitated: maximal assistance
Level V 6 4 6 10 6 2
Confused, inappropriate non-agitated:
maximal assistance
Level VI 4 5 7 3 6 5
Confused, appropriate: moderate assistance
Level VII 8 4 3 7 7 7
Automatic, appropriate: minimal assistance for routine daily living skills
Level VIII 15 8 4 3 5 6
Purposeful, appropriate: stand-by assistance
Level IX 9 16 13 4 3 4
Purposeful, appropriate: stand-by assistance on request
Level X 2 8 18 1 5 10
Purposeful, appropriate: modified independent
Missing data 1 2 0 0 1 0
Median 7 8 9 6 7 8
(25th, 75th percentiles) (5,8) (5.75, 9) (6,10) (5,7) (5.75,8.25) (7,10)
m: months

anxiety (r = - 0.446, p = 0.006 at 3 months and r = - 0.412,
p = 0.014 at 12 months), but not at 6 months. We found no
correlations between BNIS T-scores and HADS depression
and anxiety at 3, 6 and 12 months after SAH.
Barthel index
Barthel Index improved significantly after SAH from 3 months
to 6 months (p < 0.008) and from 3 months to 12 months
(p < 0.001), but non-significantly from 6 months to 12 months
(p = 0.066). BI improved significantly after TBI from 3 months
to 6 months (p = 0.001) and from 6 months to 12 months
(p = 0.017) and from 3 months to 12 months (p = 0.001). At
12 months 21/35 (60%) patients with SAH and 33/56 (59%)
with TBI are totally independent (p = 0.919).
After SAH, there was a strong correlation between BNIS
T-scores and BI at 6 months (r = 0.729, p < 0.001) and
moderate at 3 (r = 0.623, p = 0.002) and 12 months
(r = 0.678, p = 0.001). After TBI, there was moderate correla-
tion between BNIS T-scores and BI at 12 months (r = 0.565,
p < 0.001) and a weak correlation at 3 (r = 0.441, p = 0.006)
and 6 months (r = 0.474, p = 0.003).
GOSE
GOSE scores improved significantly from 3 months to
6 months (p < 0.001), from 6 months to 12 months
(p = 0.001) and from 3 months to 12 months (p < 0.001)
after SAH, and from 3 months to 6 months (p < 0.001), from
6 months to 12 months (p = 0.019) and from 3 months to
12 months (p < 0.001) after TBI.
At 12 months, 13/35 (37%) of patients with SAH had a bad
outcome and 22/35 (63%) had a good outcome; 21/56 (38%) of
patients with TBI had a bad outcome and 35/56 (62%) had a
good outcome. These differences were not significant (p = 0.973).
GOSE data at 3, 6 and 12 months after SAH and TBI are
presented in Figure 5.
Figure 4: RLAS-R scores at 3, 6 and 12 months.
BRAIN INJURY 1471
After SAH, there was a strong correlation between BNIS
T-scores and GOSE for SAH at 3 (r = 0.771, p < 0.001), 6
(r = 0.846, p < 0.001) and 12 (r = 0.751, p < 0.001) months.
After TBI, there was a moderate correlation between BNIS
T-scores and GOSE at 3 (r = 0.644, p < 0.001), 6 (r = 0.592,
p < 0.001) and 12 (r = 0.694, p < 0.001) months.
LiSat-11
At 3 months, 13/24 (54%) patients with SAH and 14/38 (37%)
with TBI were satisfied or very satisfied with life (‘as a whole’),
while 11/24 (46%) patients with SAH and 24/38 (63%) with
TBI reported different degrees of dissatisfaction. At 6 months
12/28 (43%) patients with SAH and 17/43 (40%) with TBI
were satisfied or very satisfied with life, while 16/28 (57%)
patients with SAH and 26/43 (60%) with TBI reported differ-
ent degrees of dissatisfaction.
At 12 months 13/30 (43%) patients with SAH and 17/44
(39%) with TBI were satisfied or very satisfied with life, while
17/30 (57%) patients with SAH and 27/44 (61%) with TBI
reported different degrees of dissatisfaction. Changes were not
significant between 3 [SAH median 5, Q1-Q3 (3–6), TBI med-
ian 4, Q1-Q3 (4,5)], 6 [SAH median 4, Q1-Q3 (3–5), TBI
median 4, Q1-Q3 (4,5)], and 12 months [SAH median 4, Q1-
Q3 (4–6), TBI median 4, Q1-Q3 (3–5)] after SAH (p = 0.185)
or TBI (p = 0.730), as well as satisfaction in the 10 specific
domains. There was no correlation between BNIS T-scores and
LiSat 11 for SAH or TBI at 3, 6 or 12 months post event.
EQ-5D
EQ-5D index improved significantly after TBI from 3
(mean 0.623 ± 0.281) months to 12 (mean 0.708 ± 0.250)
months (p = 0.034), but not between the other time points
after TBI or SAH. EQ-VAS improved significantly after
SAH from 3 (mean 64.05 ± 20.1) months to 12 (mean
1472 A. TÖLLI ET AL.
Figure 5: GOSE scores at 3, 6 and 12 months after SAH (n=34) and TBI (n=52). Dashed line illustrates lower cut-off level for unfavorable outcome.
76.05 ± 15.5) months (p = 0.007), but not between the
other time points after TBI or SAH.
Discussion
The main findings of this prospective study are that cognitive
function is still impaired in most patients at three months
after moderate and severe TBI and SAH but improves in both
groups until one year after the event. Improvements were
significant in both groups and cognitive or global outcome
at 12 months was not significantly different between groups.
BNIS data exhibited strong correlations to other measures of
cognitive (RLAS) and global function including GOSE. While
initial GCS scores, as expected, correlated with BNIS at
12 months after TBI, this was not so for either the initial
GCS or the Hunt and Hess scores after SAH.
Change of BNIS T-scores over time
Median BNIS T-scores improved significantly both early and
late after SAH while improvements after TBI were significant
only during the early (3–6 months) time interval. This indica-
tion of differential recovery rates between the diagnostic
groups is also supported by the GEE analysis. Stratifying
BNIS data by injury severity and considering that the majority
of patients in both diagnostic group had a severe injury. This
finding seems mainly to reflect differential recovery rates in
patients with severe injuries, i.e. that recovery after severe
SAH is delayed when compared with severe TBI. However,
regarding the small sample sizes, this interpretation must be
cautious and need to be confirmed in larger study groups.
The observation that most improvement of cognitive
function according to BNIS occurs within the first
6 months after TBI is in agreement with the findings in
a study of patients with severe TBI where BNIS scores
improved most until 3 months after the injury [41].
However, it should be pointed out that both clinical
experience and previous studies (60) show that cognitive
improvements may proceed even years after TBI but these
may require longer observation periods and/or compre-
hensive neuropsychological assessment to be captured.
However, since BNIS was used in both our diagnostic
groups, the observation that recovery after severe SAH is
delyed when compared to severe TBI, deserves further
attention. Several factors may explain a differential time
line of recovery, including different patterns of the pri-
mary brain pathology and secondary insults and of related
differential induction and character of beneficial neuro-
plasticity processes. Even though the primary pathology
after SAH and TBI overlaps, diffuse axonal injury is a
hallmark of TBI, as recently reviewed by van Eijck et al.
(63), while cerebral infarction plays a key role for outcome
after subarachnoid haemorrhage (20).
Associations between cognitive function and gender, age,
or injury severity scores
We did not see an association to gender in either the SAH or
the TBI groups. Age correlated significantly to BNIS T scores
after TBI but not after SAH.
While initial GCS scores were associated with better cog-
nitive outcome after TBI, this was not the case after SAH,
neither was there any association between cognitive recovery
and Hunt and Hess scores. These observations indicate that
other acute variables may be more relevant for prediction of
cognitive outcome after SAH. It should be pointed out that
the GCS was introduced as ‘a practical scale’ in 1974 to
standardise the recording of levels of impaired consciousness
[44]. Since then, the scale has been validated and extensively
used in clinical research and practice mainly for patients with
TBI (64), but also for other patients including those with
SAH, as has also been recommended (65). Further, we
found no correlation between Fisher data and BNIS after
SAH, which is in accordance with findings in previous study
by Wong et al. (12).

Anxiety and depression are potential confounders of cog-
nitive performance. However, in our study sample, HADS
anxiety or depression scores did not change significantly
between the consecutive time points or over the total observa-
tion period from 3 to 12 months after SAH or TBI and we
observed no obvious correlations between BNIS T scores and
HADS scores. At 12 months, approximately one fifth of
patients in both groups fulfilled criteria for depression or
anxiety, which is in accordance with previous studies (66–67).
Change of BNIS subscales over time
Most frequent impairments were observed for awareness and
orientation. Deviations were less pronounced or frequent for
language and memory, which were only observed in younger
SAH and TBI patients. Comparison of scores of BNIS subscales
at the different time points, showed significant improvements
in our study on some subscales from 3 months to 12 months
post event. However, frequencies varied by age and diagnostic
groups and over time, which hampered conclusions on the
relative impact of time on different cognitive domains.
Relation between BNIS t scores and global function over
time
There was a strong correlation between BNIS T-scores and
GOSE scores after both SAH and TBI. These findings agree
with the findings by Wong et al. (12), who reported strong
associations between cognition, according to Montreal
Cognitive Assessment, and excellent outcome after aneurys-
mal SAH. In our study, we also found strong or moderate
correlations between BNIS T-scores and RLAS-R at 12 months
in both diagnostic groups.
Changes in life satisfaction according to LiSat were not
significant over the study period after SAH or TBI, which is
in agreement with the findings in a previous study of patients
with severe TBI [41], and were not correlated to BNIS. It may
be assumed that these findings reflect the complexity of ‘life
satisfaction’ according to LiSat 11, which reflects both cogni-
tive, emotional and aspirational factors (60) and is related to
sociodemographic, health and physical activity parameters (63).
EQ-5D data improved significantly in both diagnostic
groups from 3 to 12 months in both diagnostic groups and
EQ-VAS improved significantly from 3–12 months after SAH.
These findings are in agreement with previous reports on
quality of life after TBI and SAH (69,70).
Study limitations and strengths
This study included patients from only one university hospital
managed by the same heath care providers. While this, as well
as the sample size, might limit generalisability, it also reduces
potential effects of divergent follow-up and rehabilitation inter-
ventions. Further, we were not able to apply BNIS earlier than
at three months after the event. Even though this is a limita-
tion, the proportion of patients unable to pass the pre-screen
would probably have been higher closer to the event. The study
protocol did not include comprehensive neuropsychological
assessment. This was due both to limited study resources and
BRAIN INJURY 1473
to minimise the risk for fatigue during extended assessment
sessions. BNIS allows rapid and valid assessment of a broad
range of higher cognitive functions (34) and enabled us to
follow the time course in the whole study sample.
Strengths of this study are the low dropout rate and that all
non-acute assessments were performed by the same person (AT)
even though the risk for systematic bias of scoring must be
considered. However, most assessments are highly standardised
and the assessor was aware of this risk, why we consider the
risk low.
Conclusions
Significant improvements in cognition occurred from 3 to
12 months after both SAH and TBI. Adjusting for injury sever-
ity, relatively more improvement occurred from 6 to 12 months
after severe SAH than after severe TBI, but outcomes at
12 months were not significantly different between the groups.
We suggest that even though the SAH and TBI brain pathology
overlaps, the different recovery rates mainly reflect differences
of the primary pathology and neuroplasticity processes. While
GCS scores were associated with outcome after TBI, neither
GCS or Hunt and Hess scores were associated with 12 months’
outcome after SAH, indicating that other acute severity vari-
ables should be used for prediction. Cognitive function accord-
ing to BNIS correlated with cognitive function according to
RLAS and with global outcome according to GOSE.
This exploratory study adds information on cognitive
impairments until one year after moderate or severe SAH or
TBI and may support rehabilitation planning. Data indicate a
need for both early and late interventions to support cognitive
recovery. Data may also support further attempts to identify
predictor variables for cognitive outcome after SAH.
Competing interests
Authors have no competing interests to declare.
Funding
The study was partly funded by an unrestricted research grant from
Pfizer, Sweden (102230). Anna Tölli has received support by grants
from Stockholm County Council (ALF-grants 20090410), Novo
Nordisk and a grant provided by Lars Hedlund (Karolinska Institutet
Dnr 2-1582/2016).
Authors’ contribution
All authors contributed to the design data collection, analyses and
reporting of this study.
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