J Neurosurg 120:908918, 2014

AANS, 2014

Patients with brain contusions: predictors of outcome and

relationship between radiological and clinical evolution

Clinical article
Corrado Iaccarino, M.D.,1 Paolo Schiavi, M.D.,1 Edoardo Picetti, M.D., 2
Matteo Goldoni, Ph.D., 3 Davide Cerasti, M.D., 4 Marialuisa Caspani, M.D., 2
and Franco Servadei, M.D.1
1
Arcispedale Santa Maria NuovaIstituto di Ricovero e Cura a Carattere Scientifico, Reggio Emilia; and
Neurosurgery-Neurotraumatology Unit, 2Intensive Care Unit, 3Department of Biostatistics, and 4Department
of Neuroradiology, University Hospital of Parma, Parma, Italy

Object. Traumatic parenchymal mass lesions are common sequelae of traumatic brain injuries (TBIs). They
occur in up to 8.2% of all TBI cases and 13%35% of severe TBI cases, and they account for up to 20% of surgical
intracranial lesions. Controversy exists concerning the association between radiological and clinical evolution of
brain contusions. The aim of this study was to identify predictors of unfavorable outcome, analyze the evolution of
brain contusions, and evaluate specific indications for surgery.
Methods. In a retrospective, multicenter study, patients with brain contusions were identified in separate patient
cohorts from 11 hospitals over a 4-year period (20082011). Data on clinical parameters and course of the contusion
were collected. Radiological parameters were registered by using CT images taken at the time of hospital admission
and at subsequent follow-up times. Patients who underwent surgical procedures were identified. Outcomes were
evaluated 6 months after trauma by using the Glasgow Outcome Scale-Extended.
Results. Multivariate analysis revealed the following reliable predictors of unfavorable outcome: 1) increased
patient age, 2) lower Glasgow Coma Scale score at first evaluation, 3) clinical deterioration in the first hours after
trauma, and 4) onset or increase of midline shift on follow-up CT images. Further multivariate analysis identified the
following as statistically significant predictors of clinical deterioration during the first hours after trauma: 1) onset
of or increase in midline shift on follow-up CT images (p < 0.001) and 2) increased effacement of basal cisterns on
follow-up CT images (p < 0.001).
Conclusions. In TBI patients with cerebral contusion, the onset of clinical deterioration is predictably associated
with the onset or increase of midline shift and worsened status of basal cisterns but not with hematoma or edema
volume increase. A combination of clinical deterioration and increased midline shift/basal cistern compression is the
most reasonable indicator for surgery.
(http://thejns.org/doi/abs/10.3171/2013.12.JNS131090)

Key Words cerebral contusion radiological evolution outcome

clinical deterioration traumatic brain injury

T
raumatic brain injury (TBI) is the most disabling
of traumatic injuries, often leading to lifelong
physical, cognitive, behavioral, and emotional
impairment.17 The incidence of TBI throughout Europe
ranges from 91 to 546 cases per 100,000 population per
year. If the extreme rates are deleted, the overall rate be-
comes about 235 cases per 100,000 population per year.34
In North America, the incidence ranges between 47 and
618 cases per 100,000 population per year.12 Common se-
quelae of TBIs are traumatic parenchymal mass lesions,
Abbreviations used in this paper: GCS = Glasgow Coma Scale;
GOSE = Glasgow Outcome Scale-Extended; ICP = intracranial
pressure; IQR = interquartile range; ROC = receiver operating char-
acteristic; TBI = traumatic brain injury.
which occur in up to 8.2% of all TBI cases, in 13%35%
of severe TBI cases, and which account for up to 20% of
all surgical intracranial lesions in a representative series.2
Although the frequency of posttraumatic mass lesions is
higher among comatose patients, these lesions also occur
in patients with mild or moderate head injury. Most of
these patients will recover without deleterious sequelae,
but a few will progressively deteriorate, even to death
(talk-and-die cases).24 Repeated imaging of cerebral con-
tusions typically shows a progressive increase in mass le-
sions.4,6,21,22,32 These events may represent the effects of
hematoma expansion, of perihematoma edema, or even of
the development of new lesions in previously uninjured
brain areas.27,32
The current scientific literature lacks uniformity in

908 J Neurosurg / Volume 120 / April 2014

Brain contusions: radiological and clinical evolution
defining the term radiological evolution, and the lack of
agreement regarding this clinical definition might be one
reason for the wide range of reported hemorrhagic pro-
gressions of contusions (from 16.4% to 51.0%) reported by
different clinical studies.1,4,6,21,22,35,37 Considering the natu-
ral history of cerebral contusion, a major clinical question
remains as to when and how to perform surgery for a pa-
tient harboring a brain contusion.
More than 20 years ago, Marshall et al.18 proposed
a classification of head injury based on cerebral CT im-
ages. They stratified head injury according to the status
of the mesencephalic cisterns, the presence of midline
shift (> 5 mm), and the volume of the main intracranial
lesion (> 25 ml). Patients with a lesion volume greater than
25 ml who had not undergone surgical intervention were
classified as a nonoperated mass lesion cohort, indirectly
suggesting that surgery was indicated for such patients.
According to a recent review by the Brain Trauma Foun-
dation,2 current clinical indications for surgery for trau-
matic brain contusions comprise an amalgam of clinical
and radiographic criteria, including lower Glasgow Coma
Scale (GCS) score, presence of neurological deteriora-
tion, location of contusion, increased lesion volume, CT
image appearance (increased midline shift and/or basal
cistern compression), and increased intracranial pressure
(ICP). Among these parameters, the most frequent factors
used by attending neurosurgeons as criteria for surgical
intervention for posttraumatic parenchymal damage are
radiological and clinical deterioration.25 Our aim was to
evaluate specific clinical factors that might be accurately
predictive of outcome and to investigate the association
between clinical and radiological deterioration. We also
analyzed indications for surgery in patients with cerebral
contusion.
Methods
Inclusion and Exclusion Criteria
We identified and retrospectively analyzed data from
a prospectively registered database. We selected the re-
cords of all patients with a history of TBI and a CT diag-
nosis of cerebral contusion who had been treated during
from January 2008 to December 2011 in 11 hospitals of
the northwestern Emilia region of Italy. In this area there
are 2 central hospitals with neurosurgical departments
(Parma and Reggio Emilia) and 9 peripheral hospitals that
are connected by a continuous teleradiology service that
enables decision making with regard to the suitability of
transferring a patient on the basis of imaging and clinical
information. The teleradiology system is combined with
area guidelines for management of head injuries.10
Patients with the following characteristics were con-
sidered eligible for inclusion in the study: a cerebral con-
tusion as the main posttraumatic intracranial lesion; a di-
agnosis of cerebral contusion with hemorrhagic volume
greater than 1 ml, as also reported by Chang et al.;4 at least
3 CT scans acquired during hospitalization; complete and
available clinical data with particular attention to any al-
terations in neurological examination findings during the
first hours after trauma; and hospitalization on the 1st day
of TBI.
J Neurosurg / Volume 120 / April 2014
We initially identified 629 patients but subsequently
excluded 277 patients from the study because of 1 or more
of the following: cerebral contusion volume less than 1
ml, unsatisfactory and incomplete clinical report, lack
of available follow-up CT scans, and impossibility of as-
sessing patients outcome after 6 months. The remaining
352 patients were included in the data analyses associated
with this study.
Clinical Data Collection
The following clinical data were collected and ana-
lyzed for all patients: age, sex, mechanism of injury, re-
sults of first GCS evaluation, history of concurrent condi-
tions (hypertension and/or cardiopathy and/or diabetes),
treatment with an antiaggregant or anticoagulant, onset
of neurological deterioration during the first 12 hours af-
ter trauma, and neurosurgical intervention. Patients were
classified as neurologically deteriorating if the GCS score
decreased by at least 2 points or if onset of pupillary ab-
normalities (as defined by Morris et al.20) was registered.
The mechanism of injury was classified as either high-
energy trauma or low-energy trauma.31 All other data
were identified from clinical reports. The neurosurgical
procedures were identified from an online register from
the neurosurgical hospitals.
Radiological Assessment
For each patient, we collected the first 3 CT scans,
including the one taken at the time of hospital admission.
The CT images were reread by a central reader (D.C., a
neuroradiologist), who was mostly blinded as to the time
of the scan. Other radiological data collected and analyzed
included the number of cerebral contusions, the cerebral
contusion location, hematoma volume, edema volume, the
presence of midline shift (> 5 mm), the presence of basal
cistern effacement, the presence of other posttraumatic
intracranial lesions (subarachnoid hemorrhage, subdural
hematoma, extradural hematoma, intraventricular hem-
orrhage, cranial fracture), and the number of intracranial
lesions identified in association with the cerebral contu-
sion. As many as 5 cerebral contusions per patient were
recorded. The location of the cerebral contusion was dis-
tinguished regionally as frontal, temporal, parietal, oc-
cipital, posterior fossa (cerebellum or brainstem), or basal
nucleus. Hematoma volume was calculated by using the
following formula: volume = (ABC)/2 (cm3).16 For patients
with more than 1 cerebral contusion, the volume of each
contusion was calculated and then added to obtain the
total volume of contusion. For most patients, the edema
component had a hypodense circumferential, not regular,
aspect. According to the attending neuroradiologists, we
registered 2 measurements: one including only the hyper-
dense (hemorrhagic) component and the other including
the hypodense (pericontusion edema) and hyperdense
(hemorrhagic) components of the lesion. By subtract-
ing the first measurement from the second, we obtained
a volume that was considered a reliable estimate of the
hypodense component constituted by edematous tissue in
the first few hours after trauma.24 The midline shift was
measured by 2 physicians, and the cases were divided ac-
909

cording to a midline shift of more or less than 5 mm. The
status of basal cisterns was categorized as normal versus
abnormal (compressed or absent). On the second and third
set of CT scans, we assessed the following specific pa-
rameters: percentage increase of hematoma size, expan-
sion of the edema, new onset or an increase of at least 2
mm in the midline shift, worsening of the status of the
basal cisterns, expansion of at least one other posttrau-
matic intracranial lesion. The CT scans were reread by
a central reader (D.C.), who was mostly blinded as to the
time of the scan. Evolution of hematoma size was defined
as significant if enlargement of 30% of the original size
was noted on CT scans, according to a recently published
study.1 Before choosing this expansion cutoff, we searched
the literature for a recognized cutoff. We identified a cut-
off of 30% volume increase in accordance with the more
recent articles published on this issue, which considered
increases of 25%, 30%, and 33%.1,22,35
The percentage increase of hematoma size was also
inserted into the database as a linear variable. Unlike
hemorrhage, a cutoff value for expansion of the edema
component of a contusion has not been established in the
medical literature. In agreement with the previously de-
fined cutoff,1 an increase of more than 30% of edema vol-
ume was considered significant. A worsening in the status
of the basal cisterns was registered if a normal parameter
became abnormal (compressed or absent cisterns). Expan-
sion of other posttraumatic intracranial lesions was evalu-
ated by the attending neuroradiologist; all patients were
stratified into 2 categories: 1) those with stable lesions or
2) those with an increase of at least 1 intracranial lesion.
Outcome Measurements
Initially, we carefully searched for death certificates
in the archives to identify those patients who died during
the first 6 months after TBI. Subsequently, after obtain-
ing informed consent, we administered a Glasgow Out-
come Scale-Extended (GOSE) by telephone to all patients
6 months after trauma. If it was not possible to evaluate
the patients outcome, we excluded the patient from the
collective database. According to published studies,36 the
outcome was classified as either favorable (GOSE Scores
58) or unfavorable (GOSE Scores 14).
Statistical Analyses
Prognostic factors were assessed by means of binary
logistic regression models as follows: 1) univariate p value
was calculated by using a logistic regression with single
variables as predictors; and 2) multivariate p value was
calculated by using an adjusted logistic regression model,
including all predictors with a p value of at least 0.2 in the
univariate model. Furthermore, multicollinearity was ex-
cluded by performing a correlation matrix analysis (Pear-
son and Spearman correlation tests), considering the most
clinically significant prognostic factor when the coeffi-
cient of determination (R2) is greater than 0.5. Residual
output was also assessed to check residual values above
or below 5 SDs, a cutoff based on the sample size of our
patient group. For assessment of the diagnostic power of
a given prognostic factor, a receiver operating characteris-
tic (ROC) curve was used to calculate the area under the
910
C. Iaccarino et al.
curve with 95% CIs and the cutoff value (for example, the
flex point of the curve, where the sum of sensitivity and
specificity was the maximum).
Results
Patient Demographics and Cerebral Contusion
Characteristics
A total of 352 patients met the inclusion criteria for
the study; their demographic data are listed in Table 1.
The GCS scores at the time of admission were distrib-
uted as follows: 41.5% mild head injury (GCS score of
1415), 29.8% moderate head injury (GCS score of 913),
and 28.7% severe head injury (GCS score of 38). Most
patients (n = 281 [80%]) were treated in hospitals with a
neurosurgical unit, whereas only 71 (20%) were admitted
to peripheral hospitals under neurosurgical supervision,
where all inclusion criteria were observed. The mean time
from injury to initial CT scan was 2 hours (range 47 min-
utes11 hours, interquartile range [IQR] 6398 minutes).
The second set of CT images was obtained at an average
of 9 hours (range 218 hours, IQR 154312 minutes) after
the initial scan. The third set of CT scans was obtained an
average of 38 hours (range 1055 hours, IQR 1214 hours)
after the initial scan. Computed tomography parameters
at the time of admission (admission CT) are shown in
Table 2.
Of the 352 patients, 91 (25.9%) had more than 1 ce-
rebral contusion. The average volume of intraparenchy-
mal bleeding was 12.2 10.7 ml (range 2121 ml). For
307 patients, the volume of the single contusion was 110
ml; for 28 patients, the volume was 1025 ml; and for 17
patients, the volume was more than 25 ml. The average
( SD) edema volume detected on admission CT imag-
es was 3.7 4.9 ml. Most cerebral contusions were lo-
cated in the frontal (53.2%) and temporal (29.8%) lobes;
the rest were scattered throughout the parietal (5.9%) and
occipital (0.6%) lobes, posterior fossa (5.3%), and basal
nucleus (5.2%). The cerebral contusion was in the right
hemisphere for 41% of patients and in the left hemisphere
for 51.9%. Most patients had at least 1 other intracranial
posttraumatic lesion. Frequency of associated lesions is
shown in Table 2. An urgent neurosurgical procedure was
performed for 15 patients (4.3%) after admission CT scan,
and a delayed neurosurgical intervention was performed
for 46 (13.1%) patients (41 after the second CT scan and
5 after the third CT scan). All patients surgically treated
after the first CT scan had had a severe TBI and more than
20 ml of intraparenchymal bleeding; of these 15 patients,
14 had a midline shift, 12 had basal cistern effacement,
and 11 had a single cerebral contusion. For 13 of these
15 patients, a decompressive craniectomy was performed
in association with lesion evacuation. Of the 46 patients
who underwent delayed neurosurgical intervention, 35 un-
derwent a craniotomy with evacuation of cerebral contu-
sion and 11 also underwent a decompressive craniectomy.
Characteristics of patients who underwent surgical treat-
ment after the second CT scan are shown in Table 3. The
mean SD age for all 61 patients undergoing surgery was
47.8 29.4 years.
J Neurosurg / Volume 120 / April 2014
Brain contusions: radiological and clinical evolution
TABLE 1: Description of population: epidemiological data TABLE 2: Parameters measured on CT images taken at time of
admission
Variable No. of Patients (%)*
Variable No. of Patients (%)
treatment site
neurosurgical hospital 1 236 (67.1) no. of cerebral contusions
neurosurgical hospital 2 45 (12.8) 1 261 (74.1)
peripheral hospital 71 (20.1) 2 91 (25.9)
patient sex total intraparenchymal bleeding (ml)
M 256 (72.7) 110 307 (87.2)
F 96 (27.3) 1025 28 (8.1)
comorbidities >25 17 (4.7)
absent 217 (64.5) midline shift >5 mm on admission CT image
present 125 (35.5) present 76 (21.6)
antiaggregant therapy absent 276 (78.4)
absent 273 (77.6) basal cisterns status on admission CT image
present 79 (22.4) absent or compressed 69 (19.6)
anticoagulant therapy normal 283 (80.4)
absent 330 (93.8) other associated lesions
present 22 (6.2) subdural hematoma 169 (48)
mechanism of injury subarachnoid hemorrhage 242 (68.8)
high-energy trauma 206 (41.3) epidural hematoma 40 (11.4)
low-energy trauma 145 (58.7) intraventricular hemorrhage 32 (9.1)
GCS score at admission cranial fracture 145 (41.2)
38 101 (28.7)
913 105 (29.8)
1415 146 (41.5) between the first and the second CT scans, for 135 (65.5%)
surgical procedure 45 (12.7) volume increased by 30% or more. Moreover, between the
GOSE score second and the third CT scan, for only 14 patients (36.8%),
patient age 398 yrs lesion volume increased by more than 30%. Overall, a
significant (> 30%) evolution of total intraparenchymal
unfavorable 121 (34.4)
bleeding was observed for 149 patients (42.3%). Increased
favorable 231 (65.6) cerebral edema was noted for 162 patients; among those,
patient age 1860 yr the increase was noted between the first and second CT
unfavorable 65 (18.4) scans for 59 patients (36.4%) and between the second and
favorable 287 (81.6) third CT scans for 103 patients (63.6%). A verifiable mid-
line shift was documented on the admission CT scans for
* Mean patient age SD was 59.1 23.4 years. 76 (18.1%) patients. Overall, for 97 patients, a worsening
Parma, Italy. of midline shift was observed on follow-up CT scans. For
Reggio Emilia, Italy. 70 patients, a new midline shift appeared on the second
CT scan in the absence of any previous signs of shift (Fig.
1). For 27 patients, a midline shift was document on the
admission CT scans and increased on follow-up CT scans.
Evolution of Neurological and Radiological Parameters on
CT Images
For 107 patients, worsening of the status of the bas-
al cisterns was observed on follow-up CT scans. For 76
The evolution of clinical and radiological parameters patients, although the appearance of the basal cisterns
is shown in Table 4. During the first 12 hours after trauma, was normal on the admission CT scans, on the follow-up
neurological examinations revealed the following: clinical scans, the basal cisterns had become compressed or ab-
deterioration for 111 (31.5%) patients, clinical improve- sent. Of the 31 patients in whom basal cisterns were absent
ment for 22 (6.3%), and stable neurological function for or compressed on the admission CT scans, the status of
219 (62.2%). Concerning CT parameters assessed in this the cisterns had worsened at the time of follow-up CT.
study, lesion volume decreased for 43 (12.2%) patients Analysis of the variables associated with a single con-
and remained unchanged between the first and second tusion (coexistence of other cerebral contusion, localiza-
CT scans for 103 (29.3%). All lesions that showed reduced tion, and volume at first CT scan) revealed that the volume
volume contained less than 2 ml. No lesions showing a re- of the single contusion is predictive for the evolution of the
duction between the first and the second CT scan showed hematoma (ROC curve documented that a value of 4 ml
an evolution between the second and the third CT scan. or less has a sensitivity of 95% and specificity of 75% for
Of the 206 patients in whom hematoma volume increased predicting absence of evolution).

J Neurosurg / Volume 120 / April 2014 911

 C. Iaccarino et al.
TABLE 3: Association between clinical and radiological parameters and need for surgery after second CT scan

Variable Surgery (n = 46) No Surgery (n = 291) Univariate p Value Multivariate p Value*

GCS score at admission
1415 2 144 <0.0001 0.03
913 12 93 0.5 0.078
38 32 54 <0.0001 0.019
mean patient age (yrs) SD 55.6 28.3 74. 25.1 <0.0001 <0.0001
worsening clinical condition 36 75 <0.0001 0.03
radiological appearance
increase or onset of midline shift 31 66 <0.0001 0.013
worsening of basal cistern status 29 78 <0.0001 0.002
evolution of hematoma 28 121 0.02 0.277
increased edema 22 140 0.06 0.102
patient outcome
favorable 21 (45.6%) 204 (70.1%)
severe disability 18 (39.1%) 44 (15.1%)
death 7 (15.2%) 43 (14.7%)

* Boldface indicates statistical significance.

Outcome Prognostic Factors
The results of univariate and multivariate analysis
to identify factors predicting a favorable outcome are
shown in Table 5. The analyzed data excluded an asso-
ciation between outcome and intraventricular hemorrhage
and expansion of other intracranial lesions. There was no
relevant difference in the risk for unfavorable outcome
among patients treated in hospitals with or without a neu-
rosurgical department (p = 0.315), indirectly suggesting
that patients admitted to and treated in peripheral hos-
pitals after a selection is made via telemedicine do not

TABLE 4: Clinical and radiological evolution for 352 patients

Variable No. of Cases (%)

neurological deterioration
absent 241 (68.5)
present 111 (31.5)
evolution of hematoma
absent 203 (57.7)
present 149 (42.3)
increased edema vol
absent 190 (54)
present 162 (46)
midline shift on 1st CT
absent 276 (21.6)
present 76 (78.4)
appearance or increase of midline shift
absent 255 (72.4)
present 97 (27.6)
basal cistern status on admission CT
absent or compressed 69 (19.6)
normal 283 (80.4)
Fig. 1. Axial CT scans of TBI patient. A and B: Scan obtained at
onset of or increase in basal cistern effacement time of admission, showing a small amount of temporobasal bleeding in
absent 245 (69.6) the absence of documented midline shift. C and D: Scan acquired 5
present 107 (30.4) hours after admission, showing a temporal cerebral contusion and the
onset of midline shift.

912 J Neurosurg / Volume 120 / April 2014

Brain contusions: radiological and clinical evolution

TABLE 5: Predictors of favorable/unfavorable outcome*

Predictor Univariate p Value Multivariate p Value Exp(B) 95% CI per EXP(B)

age <0.0001 0.000 0.943 0.9140.972
sex 0.012 0.395 1.505 0.5873.857
hypertension 0.012 0.791 1.143 0.4263.065
cardiopathy <0.0001 0.863 0.902 0.2802.905
diabetes 0.013 0.395 1.765 0.4766.537
antiaggregant therapy <0.0001 0.588 1.336 0.4693.801
anticoagulant therapy 0.235 0.350 0.333 0.0333.351
INR at admission <0.0001 0.323 0.448 0.0912.203
mechanism of injury <0.0001 0.434 0.662 0.2351.862
GCS score at admission
38 <0.0001 0.000
913 <0.0001 0.000 0.034 0.0100.113
1415 <0.0001 0.005 0.211 0.0720.621
SAH (1st scan) 0.001 0.748 1.160 0.4702.862
SDH (1st scan) 0.006 0.349 1.509 0.6383.565
EDH (1st scan) 0.861 0.461 1.639 0.4416.094
cranial fracture 0.363 0.136 0.518 0.2191.229
total hematoma vol <0.0001 0.366 0.969 0.9061.037
midline shift on admission CT <0.0001 0.234 0.396 0.0861.819
clinical deterioration <0.0001 0.003 6.316 1.86721.373
surgery 0.018 0.419 0.616 0.1901.995
hematoma evolution 0.002 0.099 2.159 0.8655.390
edema vol evolution <0.0001 0.520 0.713 0.2542.000
midline shift on follow-up CT <0.0001 0.000 10.668 3.26834.827
basal cistern status on admission CT <0.0001 0.293 0.474 0.1181.907
basal cistern status on follow-up CT <0.0001 0.210 1.914 0.6945.280
increased hematoma vol <0.0001 0.663 1.001 0.9971.004

* EDH = epidural hematoma; INR = international normalized ratio; SAH = subarachnoid hemorrhage; SDH = subdural hematoma.

have a worse outcome than do patients directly admitted
to neurosurgery. For all other variables, univariate analy-
sis documented statistical significance. To document the
predictive power for unfavorable outcome, we created a
logistic regression model with 26 parameters. The follow-
ing factors showed statistical significance: 1) older patient
age (p < 0.001); 2) low GCS scores at first evaluation (p <
0.001); 3) clinical deterioration in the first hours after trau-
ma (p = 0.003); and 4) onset or increase of midline shift at
follow-up CT (p < 0.001). To evaluate whether there was a
reliable cutoff after which prognosis rapidly worsens, we
created an ROC curve for prognostic value of patient age.
The identified cutoff age was 69 years, but the sensitivity
(72.7%) and the specificity (75.3%) of the analysis were
too low to authorize use of this cutoff in medical practice.
No association was found between evolution of parenchy-
mal bleeding and outcome. Similarly, no predictive prog-
nostic power was documented for edema expansion.
To investigate whether a dichotomization for hema-
toma expansion with a higher cutoff would give differ-
ent results, we performed 2 univariate analyses. The first
analysis compared patients with a hematoma expansion
cutoff of 50% (288 patients without and 64 patients with
hematoma expansion), and the second analysis compared
patients with a doubling in hematoma size (313 patients
without and 39 patients with doubling). No statistical sig-
nificance was documented by either analysis (p = 0.152
and p = 169, respectively).
Correlation Between Radiological Progression and
Clinical Deterioration
To prove the association between clinical deteriora-
tion and specific radiological parameters, we performed
univariate and logistic regression analyses (Table 6). For
all patients with a midline shift greater than 5 mm, to-
tal intraparenchymal bleeding greater than 12 ml was
documented. The mean total intraparenchymal bleeding
among patients with midline shift was higher (16.3 ml)
than that among patients without midline shift (8.1 ml).
Moreover, the mean edema volume among patients with
midline shift was higher (5.7 ml) than that among patients
without midline shift (2.1 ml). Using multivariate analysis,
we identified that the ability of onset or increase in mid-
line shift at follow-up CT to predict clinical deterioration
was statistically significant (p < 0.001) as was increased

J Neurosurg / Volume 120 / April 2014 913


TABLE 6: Predictors of clinical deterioration
Predictor Univariate p Value
midline shift on admission CT 0.676
total hematoma vol 0.0003
edema vol evolution <0.0001
midline shift on follow-up CT <0.0001
basal cisterns on admission CT <0.0001
basal cisterns on follow-up CT <0.0001
hematoma evolution <0.0001
increased hematoma vol <0.0001
basal cistern effacement at follow-up CT (p < 0.001) (Fig.
2). These same parameters as measured on admission CT
scans were not significantly associated with clinical de-
terioration. The distribution of the different radiological
parameters among patients with and without worsening of
neurological function is shown in Table 7.
Discussion
Brain contusions are the most frequent type of post-
traumatic intracerebral lesions. Because they usually oc-
cur in combination with other types of hematoma, it is
difficult to collect a pure series of patients with isolated
brain contusions. Unlike previously published studies,1
our study included only those patients for whom the brain
contusion was the main lesion and/or the primary reason
for surgery. Because many of these patients are in hospitals
that do not have a neurosurgical unit but that are linked to
a neurosurgery department via image transmission,14 we
included patients who received treatment at both the pri-
mary hospital neurosurgical unit and the peripheral hos-
pitals under supervision. Unlike the United States, where
only 10% of patients are transferred to neurosurgical units
of major hospitals from peripheral hospitals,13 in Europe,
more than 40% are transferred to a major trauma center
from other smaller hospitals; some countries like Italy,
France, or the United Kingdom report well above 50% re-
ferrals from other hospitals.13 Our data demonstrate that
among patients with brain contusions, the management of
a minority of cases (71 patients [20.1%]) outside a major
neurosurgical center, with the aid of teleradiology and
area guidelines,10 was not detrimental to patient outcome.
In our study, older age was associated with worse out-
comes in a continuous way (linear relationship), as pre-
viously reported.13 When patient age exceeded 70 years,
clinical prognosis worsened but with very low specificity
and sensitivity (sensitivity 72.7%; specificity 75.3%). Age
was found to be so prognostic that all medical risk fac-
tors (heart disease, diabetes, and hypertension) that are
significant on univariate analysis are included by age on
multivariate analysis.
In previous studies, we have shown how the use of
antiplatelet agents in elderly patients increases the risk for
intracranial lesions (mainly contusions) after mild trau-
matic head injury.11 These data were only partially con-
914
C. Iaccarino et al.
Multivariate p Value Exp(B) 95% CI per EXP(B)
0.655 1.408 0.3146.325
0.927 0.957 0.3772.429
0.753 0.856 0.3262.249
0.000 0.009 0.0030.027
0.988 1.011 0.2643.867
0.000 0.054 0.0200.145
0.177 1.051 0.9781.130
0.225 1.002 0.9991.005
firmed because, in our study, the use of antiplatelet agents
clearly interacted with age in the multivariate analysis.
Other studies have shown that a low number of platelets
(< 100,000) is associated with hematoma progression and
a 9-fold increased risk for death.1 Glasgow Coma Scale
scores have also been shown to be highly predictive of
prognosis.6,32,35 One of the most interesting observations
of our study is the high percentage (32% [111/352]) of
patients showing clinical deterioration during hospital-
ization. A worsening of neurological outcome occurred
overall for 1 patient out of 3 and, more specifically, for 5%
of patients with mild TBI, 39% of patients with moder-
ate TBI, and 62% of patients with severe TBI. As previ-
ously suggested,8 these data confirm that neurosurgeons
on duty await clinical deterioration before deciding in fa-
vor of surgery. Another interesting finding is the high risk
for clinical deterioration in patients with moderate head
injury (39%). In a previous multicenter study of patients
with moderate TBI, harboring all types of intracranial he-
matomas, clinical worsening occurred for 28%,7 thus con-
firming the high risk of deterioration for this population.
Multivariate analyses revealed that none of the prog-
nostic parameters of admission CT scans (hematoma vol-
ume, presence of associated lesions, midline shift, and
basal cistern status) were associated with clinical out-
come. Admission CT scans did not predict outcome be-
cause contusions by definition are lesions prone to evolve
and outcomes are related to the evolved CT scan as previ-
ously reported.26 We defined an evolved hematoma as one
that increased by more than 30%. This limit was arbitrari-
ly chosen and is in agreement with previously published
criteria.1 Increases in cerebral contusion volume of 25%22
and 50%6 have also been considered. When TBI results
in a contusion, the hemorrhagic lesion often expands or
a new hemorrhagic lesion might develop remotely (non-
contiguously) from the original contusion during the first
several hours after impact. Hemorrhagic progression of a
contusion might be detected on CT scans even in patients
with mild head injury.17 For a delayed progression of hem-
orrhage to occur, microvessels must have been ruptured at
the time of impact or microvessels unaffected at the time
of impact must show subsequent rupture, hours after the
impact, causing extravasation of blood. Recent findings
suggest that the latter scenario prevails.23,29
Severe cerebral contusion is often associated with
nonhemorrhagic mass effects that progress rapidly within
J Neurosurg / Volume 120 / April 2014
Brain contusions: radiological and clinical evolution
Fig. 2. Upper: Patient with 2 cerebral contusions; intracranial hy-
pertension and midline shift are present. Lower: Patient with 2 large
frontal bilateral cerebral contusions; common signs of intracranial hy-
pertension and midline shift are absent.
1248 hours after trauma. The mechanisms underlying
such a rapid progression of mass effect cannot be fully
explained by classic concepts of vasogenic and cytotoxic
brain edema. Data from previous clinical trials, includ-
ing diffusion-weighted MR imaging studies, have indi-
cated that cells in the central (core) area of the contusion
undergo shrinkage, disintegration, and homogenization,
whereas cellular swelling is located predominantly in the
peripheral (rim) area during this period.17 A recent study
J Neurosurg / Volume 120 / April 2014
by Kawamata et al.15 demonstrated that cerebral contu-
sion induces a rapid increase in tissue osmolality with-
out contribution from inorganic ion fluxes. Furthermore,
in this study, the authors suggest that the increase in col-
loid osmotic pressure through the metabolic production
of osmoles or the release of idiogenic osmoles is probably
the main cause of contusion edema. According to the lit-
erature, factors predicting hematoma evolution include
the presence of subarachnoid hemorrhage,6,22 presence of
an associated subdural hematoma,1,22 and high volume of
contusion at admission.1,4 Contusions of less than 10 ml
were never associated with hematoma evolution.1 In our
study, we found a similar observation for single lesions
of less than 4 ml, confirming a link between hematoma
evolution and contusion size at admission. Regarding
the existing issue of multiple contusions (98/352 patients
[27.8%]), we believe that the risk for clinical deterioration
is associated with the sum of the volumes of the different
hematomas, so we considered the additive volume of the
different intraparenchymal hematomas as a risk factor for
every patient. Since publication of the Marshall classifi-
cation18 for CT scans of TBI patients, the limit of 25 ml
has been used as the clinical standard and guideline for
surgical evacuation of hematomas, including those show-
ing minor changes.2 We suggest that when 25 ml is used
as a limit for surgical intervention, the fact that patients
with multiple contusions differ from patients with a single
contusion must be considered. We believe that the 25-ml
cumulative index might be more a sensitive and predictive
prognostic index of outcome and is therefore more useful.
Somewhat surprisingly, according to multivariate
analysis, the most reliable CT parameter related to out-
come was the appearance or increase of midline shift.
Midline shift in trauma patients has long been considered
an influential parameter in CT classification, but it has
never been shown to be superior to other CT data. In our
study, we attempted to correlate clinical worsening with
deterioration on CT scans. Our univariate analysis data
(Table 7) demonstrated that worsening of the clinical neu-
rological function is associated with hematoma evolution,
edema increase, onset or increase of midline shift, and
onset or increase of basal cistern effacement; our multi-
variate analysis data demonstrated that only onset and in-
crease of midline shift and basal cistern effacement were
significant. Our observations confirm those of Alahmadi
et al.,1 who reported that not all patients with hematoma
progression subsequently showed clinical deterioration.
Conversely, Narayan et al.21 documented a link between
hematoma increase and clinical deterioration, although
in a limited case series. These observations have a clear
implication for surgical indications for patients with con-
tusion. The factors currently used as guidelines typically
include clinical deterioration, hematoma progression, and
increased ICP (in monitored comatose patients). But what
can we decide when hematoma progression does not cor-
respond to clinical worsening (86/149 cases [57.7%]) or, to
the contrary, when clinical worsening does not correspond
to hematoma progression (48/203 cases [23.6%])?
The correlation between radiological and clinical
evolution remains a controversial issue. In a study of 116
patients, Smith et al.30 reported that 5% of patients re-
915

TABLE 7: Patients with and without neurological deterioration: distribution of different neuroradiological parameters
Parameter
hematoma evolution
yes (n = 149)
no (n = 203)
edema increase
yes (n = 162)
no (n =190)
onset or increase in midline shift
yes (n = 97)
no (n = 255)
onset or increase in effacement of basal cisterns
yes (n = 107)
no (n = 245)
quired neurosurgical intervention after routine follow-up
head CT indicating delayed cerebral lesions. However, in
the above-cited study, the patients who required delayed
surgery always exhibited associated clinical changes.
Furthermore Alahmadi et al.1 analyzed 98 patients with
brain contusions and reported that about half of the contu-
sions managed conservatively would progress radiologi-
cally over time in hospitalized patients. However, not all
patients with radiological progression showed clinical de-
terioration or required surgical intervention. Alahmadi et
al. reported that of the 17 patients who underwent delayed
surgery, only 4 required a craniotomy for evacuation of
cerebral contusions and the others underwent surgery for
extracerebral posttraumatic hematoma or for insertion of
an ICP monitor. Conversely, in our study, we restricted the
definition of surgically treated patients to those requiring
surgery for brain contusion. It seems that in many pa-
tients with brain contusions a correlation between clini-
cal and radiological parameters (hematoma and/or ede-
ma increase) is lacking. For our patient cohort, surgery
to remove contusions was both early (4.3%) and delayed
(11.6%). Of the 61 patients who underwent surgery, for
only 15 was it performed early. In another recently pub-
lished study, Compagnone et al.8 evaluated surgical man-
agement in a group of 729 patients with intradural lesions;
surgery was performed early for 404 patients (12.6% for
contusions) and was delayed for 154 patients (31.2% for
contusions). Taken together, the results of our study and
those of the above-mentioned study suggest that patients
with cerebral contusions seem to require delayed surgery
on a more frequent basis.
Our data suggest that a combination of clinical pa-
rameters (neurological deterioration) together with se-
lected radiological parameters (including appearance or
increase of midline shift and/or appearance of cisternal
compression) are better predictors of outcome than simple
hematoma evolution alone, as previously advocated.3,19
Future studies are warranted to investigate whether these
radiological parameters can predict clinical deterioration
and therefore can be useful as guidelines for surgical in-
916
C. Iaccarino et al.
Neurological Deterioration
(No. [%])
Present (n = 111) Absent (n = 241) Univariate p Value Multivariate p Value
0.0003 0.927
63 (56.7) 86 (35.7)
48 (43.3) 155 (64.3)
<0.0001 0.753
77 (69.4) 85 (35.3)
34 (30.6) 156 (64.7)
<0.0001 <0.0001
89 (80.2) 8 (3.3)
22 (19.8) 233 (96.7)
<0.0001 <0.0001
74 (66.7) 33 (13.7)
37 (33.3) 208 (86.3)
dications before the onset of GCS score worsening. The
reasons underlying why hematoma increase and/or peri-
contusion edema increase do not influence clinical dete-
rioration are probably associated with the complexity of
the anatomic lesions in these TBI patients. Many patients
have multiple contusions and/or small extracerebral hema-
tomas that contribute to brain compliance and genesis of
mass effect. Only midline shift and cisternal compression
are able to accurately depict brain compression leading to
clinical deterioration.
Another reason for the lack of correlation between
hematoma evolution and clinical evolution could be a low
(30%) cutoff for considering significant hematoma evo-
lution. This cutoff was identified in accordance with the
more recent articles published on this issue.1,22,35 Addition-
al analyses performed with a 50% increase and hematoma
doubling confirmed the absence of a link between expan-
sion of a single hematoma and patient outcome.
We monitored ICP in 45 comatose patients after the
second follow-up CT scan. In 18 patients (40%), pressure
increased over 25 mm Hg despite CSF drainage and re-
inforced medical therapy.33 Of these 18 patients, 16 un-
derwent surgical intervention (10 also received an asso-
ciated decompressive craniectomy). A recent prospective
study demonstrated the lack of significant differences in
outcome between comatose patients with or without ICP
monitoring.5 Additional prospective9 and large retrospec-
tive studies28 further demonstrated worsened outcomes
in aggressively monitored and treated patients. Our study
results suggest that ICP is the most useful guideline for
surgical intervention in comatose patients with potentially
evolving brain contusions. When measurements of clini-
cal outcome are unavailable, ICP monitoring has clinical
utility for surgical decision making for patients with post-
traumatic intracranial mass lesions.
This study has some limitations. These limitations are
the retrospective design, the total number of participants
(which remains small overall but larger than that of many
other published studies), the potential for subjective de-
termination of clinical and radiological measures among
J Neurosurg / Volume 120 / April 2014
Brain contusions: radiological and clinical evolution
multiple centers, and potential selection bias for treatment
regimens among patients.
Conclusions
Among patients with intracranial contusions, the fol-
lowing features are heterogeneous: clinical status (mild
moderate and severe TBI), radiological findings (single
or multiple lesions, association with other hematomas,
hematoma evolution), and outcomes. Establishing surgi-
cal indications among this patient population is difficult;
the most reasonable indicator is a combination of clini-
cal deterioration and increased midline shift/basal cistern
compression.
Disclosure
The authors report no conflict of interest concerning the mate-
rials or methods used in this study or the findings specified in this
paper.
Author contributions to the study and manuscript preparation
include the following. Conception and design: Servadei, Iaccarino,
Schiavi, Caspani. Acquisition of data: Iaccarino, Schiavi, Picetti,
Cerasti. Analysis and interpretation of data: Servadei, Picetti, Gol
doni, Cerasti. Drafting the article: Iaccarino, Schiavi, Picetti. Criti
cally revising the article: all authors. Reviewed submitted version of
manuscript: all authors. Approved the final version of the manuscript
on behalf of all authors: Servadei. Statistical analysis: Goldoni.
Administrative/technical/material support: Iaccarino, Schiavi, Gol
doni, Cerasti. Study supervision: Servadei, Caspani.
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Manuscript submitted May 26, 2013.
Accepted December 11, 2013.
Portions of this work were presented orally at the XV World
Congress of Neurosurgery, Seoul, South Korea, September 813,
2013.
Please include this information when citing this paper: published
online February 7, 2014; DOI: 10.3171/2013.12.JNS131090.
Address correspondence to: Franco Servadei, M.D., Department
of Emergency Medicine, Neurosurgery-Neurotraumatology Unit,
University Hospital of Parma and ASMN-IRCCS Reggio Emilia,
Viale Gramsci 14, Parma 43100, Italy. email: fservadei@ao.pr.it.
J Neurosurg / Volume 120 / April 2014