Journal of Rehabilitation Medicine 51-4inkOmslag | Page 31

Impact of PiD on outcome after TBI and aSAH
cognitive disturbances after acquired brain injury.
The BNIS has documented validity (11–13), is easily
applicable in clinical routine and has been used in
some studies of TBI (13, 14) as well as stroke (15, 16).
In 2 previous studies (17, 18) of PiD in a prospec-
tive cohort of patients with moderate and severe TBI
or aSAH, we observed frequencies of PiDs within the
same range, as reported in recent reviews (1, 2). Most
PiDs were transient, with no need for replacement th-
erapy, but a small subgroup (7%) needed such therapy.
In this cohort of patients, who were recruited from the
neurointensive care unit at one university hospital and
who went through the same structured neurorehabi-
litation and follow-up programme, we also assessed
cognitive and global function until one year after the
event (19). Cognitive and global function improved
significantly over time in both diagnostic groups and
was not significantly different between groups at 12
months. Higher age was associated with lower BNIS
T-scores after TBI, but not after aSAH, and lower ini-
tial GCS scores were associated with poorer cognitive
outcome after TBI, but not after aSAH. Data from this
cohort enable us to explore the potential impact of PiD
on cognitive and global outcome after TBI and aSAH.
Thus, the aim of the present study was after TBI and
aSAH to explore associations between PiD and cog-
nitive and global outcome at 12 months post-injury,
controlling for age, gender and acute injury variables.
MATERIAL AND METHODS
Study design and participants
The design of this prospective, observational study of patients
with moderate or severe TBI and aSAH has been described
previously (17, 18). Patients were included at the neurointensive
care unit (NICU) at Karolinska University Hospital (KUH) from
March 2009 to June 2012, and subsequently followed at the
Department of Rehabilitation Medicine at Danderyd University
Hospital, Stockholm, Sweden, at 3, 6 and 12 months post-event.
Hormone testing was performed at Department of Endocrino-
logy, KUH. Inclusion required a lowest Glasgow Coma Scale
(GCS) score during the first day after the event of 3–13, age
≥ 18 years, living in the Stockholm region, and obtained infor-
med consent. For patients who were unconscious or otherwise
unable to give informed consent, the closest relative was asked.
The study was approved by the Regional Ethics Review Board
in Stockholm (no: 2008/3:9 2008/1574-31/3).
Data collection
Severity grading. Clinical severity measures included the GCS
score (20, 21) (3–8 severe injury, 9–13 moderate injury), serum
levels of S100B (highest level of S100B between 12–36 h after
injury was categorized as normal if < 0.11, mild 0.11–0.25,
moderate 0.26–0.50, and severe if ≥ 0.51μg/l), and pupil light
reactions (categorized as normal or abnormal).
Endocrine function. Analyses of thyroid function; serum free
thyroxine (S-fT4), serum thyroid-stimulating hormone (S-TSH),
265
serum free triiodothyronine (S-fT3) and the synacthen test were
performed 10 days post-event.
Analyses at 3, 6 and 12 months comprised thyroid function
and S-cortisol. At 6 and 12 months analyses were performed for
S-insulin-like growth factor I (IGF-I), S-prolactin, S-oestradiol
in females, S-follicle-stimulating hormone (FSH) in females,
S-luteinizing hormone (LH) in females, and S-testosterone in
males.
Blood was sampled between 8 and 10 am. S-cortisol ≥400
nmol/l was set as normal. At 3, 6 and 12 months post-event a
synacthen test was performed in patients with a morning S-
cortisol < 400 nmol/l.
The synacthen test was performed by intravenous adminis-
tration of 250 µg synacthen. Blood samples were taken before
and 30 min after injection. A normal response to the synacthen
test was defined as S-cortisol at 30 min > 550 nmol/l. Cortisol
responses were arbitrarily categorized as < 550 nmol/l, between
550 and 1,000 nmol/l or > 1,000 nmol/l.
Hypothyroidism was defined as fT4 level below the normal
reference range. The reference data for S-fT4 is shown in
Table SI 1 .
An age-dependent reference range (geometrical mean±2
standard deviation (SD)) for IGF-I, independent of sex, was
calculated based on the equation for the regression line in all
patients: 10 log [IGF-I (μg/l)]= 2.581–0.00693 × age (years), with
SD = 0.120 (22). Decreased secretion of growth hormone (GH)
was presumed if IGF-I <–2SD and high level if S-IGF-I >+2SD.
Gonadotrophin dysfunction in men was defined as S-testoste-
rone below reference range, and in post-menopausal women was
defined as S-FSH, and S-LH or S-oestradiol below the normal
reference range, in pre-menopausal women in combination with
amenorrhoea or oligomenorrhoea. The reference range of S-
testosterone, S-oestradiol, S-FSH, S-LH are shown in Table SI 1 .
Patients were divided in groups of those who showed normal,
low or high hormone levels at any time-points during the first
year after the event. Patients with low and high hormones at
different time-points during the study period were excluded
from the calculations.
Analysis of all blood samples were performed at the Depart-
ment of Clinical Chemistry in KUH using routine commercial
kits.
Cognitive and global outcome
The Barrow Neurological Institute Screen for Higher Cerebral
Functions (BNIS) (10) includes a pre-screen test (level of arou-
sal 3 points, basic communication 3 points, and cooperation 3
points). The patients must achieve at least 2 points on each of the
items to continue with assessment of higher cerebral functions:
speech and language (15 points), orientation (3 points), atten-
tion/concentration (3 points), visual and visuospatial problem
solving (8 points), memory (7 points), affect (4 points) and
awareness of own performance (1 point), corresponding to a
total score of maximally 50 p. A cut-off score of < 47 was set
for identifying brain dysfunction for patients < 60 years, < 46
for patients 60–69 years and <44 for patients > 70 years (12,
13, 23). Total BNIS raw scores are converted to age-corrected
standard T-points (< 1–71). Cut-off for cognitive dysfunction
for T-points was set at < 40 (i.e. <–1 SD) (24).
Patients who failed pre-screen test were assigned a T-point
of 0.
http://www.medicaljournals.se/jrm/content/?doi=10.2340/16501977-2507
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J Rehabil Med 51, 2019