POST-TBI MEDICAL MANAGEMENT AND SECONDARY MEDICAL COMPLICATIONS OF TBI
Study
Main Purpose
Drug-based Neuroprotection
Roberts et al.,
Evaluate the
2004
efficacy of
intravenous
methyplprednisolone (MP)
Research Design
Sample
Randomized,
placebo- controlled
study;
multi-site: 239
centers
10,008 adults with
TBI, Glasgow
Coma Score
(GCS): 14 or less,
within 8 hours of
injury
Outcome
Measures
Results
Study Type
Level of
Evidence
Mortality,
Glasgow
Outcome
Score-E
(GOS-E)
No reduction in mortality with
MP; a rise in the death rate at
2 weeks in the treatment
group. Mortality for all groups
appears higher than in other
recent data sets.
Therapeutic
intervention
I
Six-months: no significant
difference in outcome.
Subanalysis suggested
possible effect in males with
SAH. Concern: group
imbalances in prognostic
variables, i.e., hypotension and
hypoxia.
When evaluated with logistic
regression, possible long-term
benefit at 0.04mg/kg group; no
difference in serious adverse
effects.
Well-tolerated safety profile,
no significant differences
noted via the neurobehavioral
rating scale. [need to list in
Outcome Measures]
Therapeutic
intervention
I
Therapeutic
intervention
III
Therapeutic
intervention
III
Dexabinol was safe and well
tolerated a trend toward
improved neurologic outcome
was noted. Significant
improvement noted in ICP.
Therapeutic
intervention
III
Marshall et al.,
1998
Evaluate the
impact of
tirilazad
mesylate
Randomized,
placebo- controlled
trial;
multi-site
1,120 persons with
head injury; 85%
of the population:
GCS 4-8; 15%:
GCS 9-12
Mortality,
GOS
Lepeintre et al.,
2004
Determine the
safety and
preliminary
efficacy of
gagycolidine
Evaluate the
safety and
efficacy of
CP,101-606
Phase II,
randomized,
placebo- controlled
double-blind trial
48 persons with
severe TBI
Mortality,
GOS
Phase II, doubleblind, placebocontrolled
53 subjects (45
with TBI, 8 with
stroke)
Mortality,
GOS, side
effects,
neurobehavior
al rating scale
Evaluate the
safety and
efficacy of
dexabinol
Phase II,
randomized,
double-blind
placebo- controlled
trial;
multi-site
67 persons with
TBI, GCS 4-8,
within 6 hours of
injury
Mortality,
GOS, ICP
Merchant et al.,
1999
(Phase III of
CP-101,606
trial not yet
published- study
terminated
early)
Knoller et al.,
2002
(Phase III study
results releasednot yet
published)
Study
Main Purpose
Research Design
Non-pharmacologic Treatment in the Acute Setting
Cooper et al.,
Evaluate the
Prospective,
2004
efficacy of
double-blind
hypertonic saline randomized,
resuscitation
controlled trial;
multi-site
Taylor et al.,
1999
Evaluate the role
of enhanced
nutrition
Prospective
randomized
controlled trial
Clifton et al.,
2001a
Evaluate the role
of hypothermia
in the treatment
of TBI
National Acute
Brain Injury Study:
Hypothermia
(NABISH);
prospective,
randomized
controlled trial;
multi-site
Data from
NABISH- I
Clifton et al.,
2001b
Clifton et al.,
2002
Reanalyze
hypothermia data
(see above)
Henderson et
al., 2003
Evaluate prior
studies of
hypothermia
treatment
Meta-analysis
McIntyre et al.,
2003
Evaluate prior
studies of
hypothermia
treatment
Meta-analysis
Sample
Outcome
Measures
Results
Study Type
Level of
Evidence
229 persons with
TBI and
hypotension
(systolic blood
pressure
<100mHg)
82 persons with
severe TBI
requiring
mechanical
ventilation
GOS-E
No significant difference in
outcome at 6 months.
Therapeutic
intervention
I
GOS,
metabolic
parameters
(energy and
nitrogen)
Therapeutic
intervention
III
392 persons with
TBI, age 16-65
Mortality,
GOS
Improved nitrogen balance at
1 week, a trend toward better
outcome at 3 months, but
similar neurologic outcome at
6 months in the enhanced
group.
Treatment not effective in
improving outcomes. Higher
complication rate in the
hypothermia group. Wide
differences across clinical
sites.
Therapeutic
intervention
I
102 persons with
TBI (62 from the
hypothermia group
and 40 from the
normothermia
group)
748 persons with
TBI from 8
randomized
controlled trials
Mortality,
GOS
Those hypothermic at
admission and <age 45 had
significantly better outcomes
than those who were
normothermic upon
admission.
Benefit of hypothermia: a
potential marginal impact on
neurologic outcome. No clear
change in mortality.
Therapeutic
intervention
II
Metaanalysis
NA
12 trials with
eligibility criteria
Mortality,
GOS
Hypothermia
associated with a 19%
reduction in risk of death and
22% reduction in poor
outcome.
Metaanalysis
NA
Mortality,
GOS, multiple
other
Palmer et al.,
2001
Evaluate the role
of the BTF
guidelines
Randomized trial
Fakhry et al.,
2004
Evaluate the role
of the BTF
guidelines
Bulger et al.,
2002
Evaluate the role
of the BTF
guidelines
Retrospective study
comparing data
before the
guidelines and after
Retrospective study
to correlate
outcome with the
guidelines
Study
Main Purpose
Post-TBI Seizure Disorders
Schierhout and
Determine the
Roberts, 2001
value of antiepileptic drug
prophylaxis
Temkin et al.,
Evaluate the use
1999
of valproic acid
in posttraumatic
seizure
prophylaxis
Watson et al.,
2004
Temkin, 2001
Evaluation of
glucocorticoids
in the
development of
post-traumatic
seizure disorder
Determine the
value of AED
37 persons prior to
the guidelines and
56 after the
guidelines
830 persons with
TBI who survived
more than 48 hours
GOS,
intracerebral
pressure
9.13 odds ratio of a good
outcome with the use of the
guidelines.
Therapeutic
intervention
III
GOS, length of
stay
A significant decrease in
hospital days and charges.
Therapeutic
intervention
III
34 academic
medical centers
Mortality,
GOS
Considerable national
variation exists in compliance.
Aggressive management using
the guidelines is associated
with decreased mortality. No
significant difference in
functional status among
survivors.
Results
Therapeutic
intervention
III
Study Type
Level of
Evidence
Prophylactic anticonvulsants
are useful in the early, but not
the late, prevention of
posttraumatic seizures.
Valproate shows no benefit
over short-term phenytoin
therapy for early or late
seizures.
Trend toward higher mortality
in valproate group.
Metaanalysis
NA
Therapeutic
intervention
I
Research Design
Sample
Outcome
Measures
Cochrane analysis
10 studies; 2,036
persons with TBI
Several
Randomized,
placebo-controlled
study
Rate of late
posttraumatic
seizures,
mortality
Prospective cohort
study
People with
moderate-severe
TBI
N=132: 1 week
phenytoin
N=120: 1 month
valproate
N=127: 6 months
valproate
404 patients with
severe TBI
Development
of posttraumatic
seizures
Those treated with
glucocorticoids within one day
of TBI were at higher risk for
seizures.
Therapeutic
intervention
III
Meta-analysis of antiepileptogenesis and
47 trials
evaluating
Several
For unprovoked seizures, no
drug therapy has been shown
Metaanalysis
NA
Annegers et al.,
1998
Englander et al.,
2003
Angeleri et al.,
1999
Diaz-Arrastia et
al., 2003
Vespa et al.,
1999
Hudak et al.,
2004
prophylaxis
seizure- prevention
trials
multiple
etiologies,
including 12 for
TBI
4,541 adults and
children with
TBI; 1935-1984
to be effective.
Identification of
risk factors
associated with
post-traumatic
seizures
Identification of
risk factors
associated with
post-traumatic
seizures
Retrospective
database review
Retrospective
database review
647 adults with
TBI; 66
developed late
post-traumatic
seizures
Development
of seizure
activity
Determine risk
factors for
posttraumatic
seizures using
EEG,
neuroimaging
Determine if
APOE-epsilon4
allele is
associated with
increased risk of
post-traumatic
seizures
Determine the
frequency of
convulsive and
non-convulsive
seizures in the
ICU setting
Evaluate the
ability of video
EEG monitoring
for the diagnosis
of seizures in
persons with TBI
Prospective
137 individuals
with TBI
EEG,
neuroimaging
(CT, MRI)
Prospective
106 patients with
moderate and
severe TBI
Prospective
Retrospective
Development
of seizures
Severity of injury, subdural
hematoma, skull fracture,
LOC >1 day, age >65: all
associated with increased
seizure frequency.
Biparietal contusions (66%),
dural penetration with bone or
metal fragments (62.5%) and
multiple intracranial
operations (33.4%): associated
with increased seizures.
An EEG focus 1 month after
TBI is a risk factor 3.49 times
higher than for patients
without such EEG changes.
Prognostic
III
Prognostic
III
Prognostic
II
GOS,
development
of seizure
activity
Epsilon4 allele associated with
increased relative risk (2.41)
of late post-traumatic seizures.
Prognostic
III
94 patients with
moderate or
severe TBI in the
ICU
Presence of
seizure activity
Seizures occurred in 22% of
patients; in 52% the seizures
were non-convulsive.
Descriptive
III
127 patients with
TBI referred to
an epilepsy
monitoring unit
Presence of
seizure activity
Monitoring estabilished a
diagnosis in 82% of cases:
62% focal seizures, 6%
generalized seizures, 33%
psychogenic nonepileptic
seizures.
Diagnostic
III
Marwitz et al.,
2001
Evaluate the
incidence and
cause of
rehospitalization
s after TBI
Prospective database
review
895 patients with
TBI, followed 1
and 5 years after
injury
Rates and
causes of
rehospitalizati
on
Shavelle et al.,
2001
Evaluate the
long-term causes
of death after
TBI
Retrospective
database review
2,320
Californians with
long-term
disability due to
TBI
Mortality
Study
Main Purpose
Research Design
Sample
Outcome
Measures
Case series
20 patients with
TBI, 25 elbows;
no prior
treatment with
bisphosphonates
or radiation
18 persons with
hip HO sustained
after brain
injury, 21
persons with hip
HO after hip
injury, and 25
persons with HO
and both hip and
brain injuries
26 persons with
TBI and HO
Heterotopic Ossification and TBI
Denormandie et Evaluation of
al., 1999
outcomes from
surgical
resection of HO
at the elbows
Ebinger et al.,
2000
Evaluation of
outcomes from
surgical
resection of HO
at the hip in
persons with and
without TBI
Case series
Johns et al.,
1999
Comparison of
outcomes of TBI
Retrospective, with
matched controls
The incidence of
rehospitalization ranged from
22.9% 1 year after injury to
17.0% at 5 years. At 1 year,
one-third of rehospitaliza-tions
were for elective reasons.
Seizures were a prominent
cause of rehospitalization.
Mortality was higher between
1 and 5 years postinjury than
after 5 years and was strongly
related to reduced mobility.
Death rates were elevated for
circulatory and respiratory
diseases, choking/suffocation
and seizures, with seizure
deaths being relatively
frequent, even among the most
ambulatory.
Results
Descriptive
III
Descriptive
III
Study type
Level of
Evidence
ROM,
mobility on
follow-up
examination
58% cases classified as having
a good outcome, with >70%
gain in mobility, 42% with
gain of 40-70% mobility.
Therapeutic
intervention
IV
Radiographs,
ROM
Those with hip injury alone
did best functionally on 1- and
5-year follow-up; no
difference seen in
reoccurrence of HO. Those
with more severe TBI had
more significant HO.
Therapeutic
intervention
IV
Functional
Independence
Patients with HO had lower
functional FIM scores upon
Correlationa
l
III
rehabilitation
inpatients with
and without HO
Study
Main Purpose
Deep Vein Thrombosis and TBI
Agnelli et al.,
Efficacy of
1998
enoxaparin and
compression
stockings in the
prevention of
DVT in
neurosurgical
patients
Raabe et al.,
Determine safety
2001
of heparin for
DVT
prophylaxis in
neurosurgical
patients
matched with 26
persons with TBI
and no HO, all
admitted to acute
inpatient
rehabilitation
Sample
Measure
(FIM) scores,
discharge
disposition
Randomized, doubleblind, placebocontrolled trial
307 acute
inpatients total
(154 treatment
and 153 placebo)
Retrospective case
series
1,564 patients
total, 1,197
receiving major
neurosurgery,
367 with
shunting or
extraventricular
drain placement
(minor
procedure)
950 acute
inpatients who
underwent
neurosurgery,
152 of whom
underwent
cranial surgery
100 patients
admitted to an
acute hospital for
craniotomy
Research Design
Wen and Hall,
1998
Evaluate early
administration of
heparin for DVT
prophylaxis in
neurosurgical
patients
Case series
Macdonald et al.,
2003
Comparison of
unfractionated
heparin and
dalteparin for
DVT
prophylaxis in
Randomized
prospective study
admission and discharge. No
differences noted on cognitive
FIM scores. Patients with HO
also had lower FIM efficiency
and were more likely to be
discharged to a facility.
Results
Prognostic
Study Type
Level of
Evidence
Presence of
DVT or
hemorrhage
32% placebo versus
22% in treatment group with
DVT; 13% versus 5% for
proximal DVT; no difference
in major bleeding.
Therapeutic
intervention
I
Hemorrhage
Hemorrhage rate of
heparinized patients was
1.8%: all in major-surgery
group.
Therapeutic
intervention
III
Hemorrhagic
events
2 minor hemorrhagic events
(both in cranial cases) and 3
major bleeding complications
(2 in laminectomy cases, 1 in a
cranial case) were noted.
Therapeutic
intervention
III
Hemorrhage,
pulmonary
embolism or
DVT
No significant difference in
hemorrhage, thromboembolic
events or thrombocytopenia in
either group.
Therapeutic
intervention
III
Outcome
Measures
Iorio and
Agnelli, 2000
Kim et al., 2002
Norwood et al.,
2002
Yablon et al.,
2004
Akman, et al.,
2004
persons
receiving
craniotomy
Determine the
safety and
efficacy of
heparinoids in
prevention of
DVT in
neurosurgical
patients
Evaluate the
safety and
efficacy of the
early use of
heparin for DVT
prophylaxis in
persons with
intracranial
hemorrhage
Evaluation of
safety and
efficacy of
enoxaparin for
DVT
prophylaxis in
persons with
blunt head
trauma
Determination of
prevalence and
risk factors for
DVT in
rehabilitation
inpatients
Evaluation of the
D-dimer test as a
Meta-analysis of
clinical trials
1,022 acute
patients for
safety analysis,
827 for efficacy
analysis
Development
of DVT, PE or
hemorrhage
Rate of 22.6%
thromboembolic events;
heparin prophylaxis resulted in
45% relative risk reduction.
Number needed to treat to
prevent VTE was 7.7, 16 for
prevention of proximal DVT.
Number needed to harm was
102 for heparin and 115 for
LMWH (low molecular
weight heparin).
No increase in bleeding was
seen in the group treated early
with heparin. No difference
was seen in VTE between the
two groups.
Metaanalysis
NA
Retrospective case
series
64 acutely
hospitalized
patients with
intracranial
hemorrhage
Development
of DVT, PE or
hemorrhage
Therapeutic
intervention
III
Prospective case
series
150 acute head
trauma inpatients
Progression of
ICH
(intracranial
hemorrhage),
development
of DVT
23% had progression of ICH
on follow-up CT scans, 19%
prior to initiation of
enoxaparin,4% after. All
patients who had further ICH
after treatment survived. DVT
found in 2%.
Therapeutic
intervention
III
Prospective case
series
709 consecutive
rehabilitation
admissions with
brain injury
(TBI=360)
Presence of
DVT
DVT prevalence of 11.1%;
6.7% in the TBI subgroup.
Positive D-dimer assay highly
correlated with DVT
(p=0.001).
Descriptive
Correlationa
l
III
Prospective case
series
68 consecutive
rehabilitation
Presence of
DVT
D-dimer had sensitivity of
95.2%, but specificity of only
Screening
III
screening tool
for DVT
Meythaler et al.,
2003
Comparison of
two methods of
D-dimer assays
in predicting
DVT
Prospective case
series
Wagner et al.,
1999
Evaluation of the
effect of DVT on
rehabilitation
outcome in TBI
patients
Consecutive case
series with casematched controls
Study
Main Purpose
Research Design
Post-TBI Spasticity
Meythaler et al.,
Evaluation of
2001
tizanidine in the
treatment of
spasticity of
CNS origin
Meythaler et al.,
Evaluation of
2004
baclofen in the
treatment for
spasticity due to
brain injury
Meythaler et al.,
Evaluation of
1999a
intrathecal
baclofen in the
treatment of
spasticity of
CNS origin
Meythaler et al.,
Evaluation of
1999b
intrathecal
baclofen in the
Randomized, doubleblind, placebocontrolled crossover
trial
facility
admissions (TBI
=4)
35 persons
admitted to an
acute facility
with TBI
55.3%.
Presence of
DVT
Screening
III
Prognostic
III
46 TBI patients
with lower
extremity (LE)
DVT at
rehabilitation
admission and 46
matched controls
with TBI and no
DVT
Sample
Discharge
disposition,
FIM scores,
rehabilitation
LOS, presence
of DVT
Outcome
Measures
Results
Study Type
Level of
Evidence
17 patients total,
9 with stroke, 8
with TBI, >6
months of
spasticity
35 patients total,
22 with TBI, all
at least 6 months
post injury
Significant decrease in LE
Ashworth, LE spasm and
upper extremity (UE)
Ashworth scores. Increase in
motor strength.
In TBI patients, decrease in
LE Ashworth scores and
reflex scores; no change in UE
spasticity measures. 17%
incidence of somnolence.
Decrease in LE Ashworth,
spasm and reflex scores; no
decrease in motor strength of
the unaffected side.
Therapeutic
intervention
III
Therapeutic
intervention
IV
Therapeutic
intervention
III
Decrease in baseline
Ashworth, spasm and reflex
scores in UE and LE.
Therapeutic
intervention
IV
Randomized, doubleblind, placebocontrolled crossover
trial
6 persons with
hemiplegia and
spasticity due to
stroke (n=3) or
TBI (n=3)
Ashworth and
spasm scores,
muscle
strength, side
effects
Ashworth and
spasm scores,
tendon
reflexes, motor
strength
Ashworth and
spasm scores,
deep tendon
reflexes, motor
strength
Case series
17 patients with
TBI and
spasticity
Ashworth,
spasm and
reflex scores
Uncontrolled trial
Latex agglutination assay and
ELIZA correlated well with
each other, but remained
significantly elevated
throughout the trial. No
patients developed VTE.
No significant difference in
LOS, rehabilitation costs or
FIM scores. Persons with
DVT were more likely to be
discharged home.
Rawicki, 1999
Francois et al.,
2001
Dario et al., 2002
Pavesi et al.,
1998
Francisco et al.,
2002
Singer et al.,
2004
treatment of
TBI-related
spasticity
Evaluation of the
use of intrathecal
baclofen as longterm
management of
spasticity of
cerebral origin
Evaluation of the
use of intrathecal
baclofen to treat
autonomic
instability and
tone in acute
severe TBI
Evaluation of
intrathecal
baclofen with
thoracic level
catheter
placement in
anoxic brain
injury
Evaluation of
botulinum toxin
(BT) in the
treatment of UE
tone in TBI
Evaluation of
botulinum toxin
in two different
dilutions for UE
spasticity
Determine
incidence of
ankle contracture
in acute inpatient
TBI
Case series
18 patients with
spasticity of
cerebral origin
Functional
status,
evaluation of
tone
17/18 patients with significant
reduction in tone, increased
function and/or decreased
nursing care needs.
Therapeutic
intervention
IV
Case series
4 persons with
severe TBI and
autonomic
instability
Medical
outcome,
Ashworth
scores, blood
pressure, pulse
1 patient died of urosepsis; all
remaining patients showed
improvement in Ashworth
scores and decrease in
autonomic instability.
Therapeutic
intervention
IV
Case series
14 patients with
TBI or anoxic
injury with
significant
spasticity
Spasm scores,
Ashworth
score
Improvements noted in
Ashworth scores and spasm
frequency scores.
Therapeutic
intervention
IV
Case series
6 patients with
TBI and UE
spasticity
Evaluation of
arm function,
Ashworth
scores
Improvements noted in
Ashworth score and arm
function.
Therapeutic
intervention
IV
Randomized
controlled trial
13 patients total,
10 with
spasticity due to
stroke and 3 due
to TBI
105 admissions
to inpatient
rehabilitation
with diagnosis of
moderate or
Ashworth
scores
Decreased spasticity in both
groups; no difference in
efficacy due to dilution of
botulinum toxin.
Therapeutic
intervention
III
Muscle tone,
range of
motion,
mobility status
Spastic tone was noted in
13.3% of patients, dystonic
tone in 21.9%. Dystonic tone
significantly associated with
development of ankle
Descriptive
Prognostic
IV
Case series
rehabilitation
Study
Main Purpose
Post-TBI Dysautonomia
Baguley et al.,
Describe the
2004
clinical treatment
and
complications of
those with
dysautonomia
Becker et al.,
2000
Cuny et al.,
2001
Baguley et al.,
1999
Study
Demonstrate a
role for
intrathecal
baclofen in the
treatment of
severe
dysautonomia
Describe use of
intrathecal
baclofen for
severe
dysautonomia
Evaluate the
impact of
dysautonomia on
outcome
Main Purpose
Post-TBI Hydrocephalus
Phuenpathom et Determine rates
al., 1999
and risk factors
for the
development of
post-traumatic
hydrocephalus
severe TBI
Research Design
Sample
Outcome
Measures
Controlled case series
35 cases of
persons with
dysautonomia,
35 controls
Documentatio
n of clinical
treatments and
symptom
complexes
Case series
4 persons with
brain insults (2
SAH, 1 TBI, 1
ICH)
Severe
dysautonomic
symptoms
Case series
4 persons with
acute TBI and
dysautonomia
Controlled case series
Research Design
Retrospective chart
review
contractures. Weak
association between severity
of injury and development of
ankle contractures.
Results
Study Type
Level of
Evidence
Dysautonomic patients more
likely to receive medications
with CNS action; midazolam
and morphine often used to
control heart and respiratory
rate; chlorpromazine used for
respiratory rate.
3 of 4 patients’ autonomic
symptoms successfully treated
with intrathecal baclofen.
Correlationa
l
IV
Therapeutic
intervention
IV
Clinical
symptoms of
dysautonomia
All cases improved by day 6
of trial.
Therapeutic
intervention
IV
35 persons with
TBI, noted to
have
dysautonomia
Sample
GOS, post
traumatic
amnesia
(PTA), LOS
Outcome
Measures
Dysautonomic group had
longer rehabilitation LOS,
longer PTA, lower GOS
scores.
Results
Prognostic
IV
Study Type
Level of
Evidence
1,008 patients
seen at acute
care hospitals
after brain injury
Development
of
hydrocephalus
17 patients with
hydrocephalus (1.6% of
sample); high correlation with
those who had received
decompressive craniotomy.
Descriptive
Prognostic
IV
Mazzini et al.,
2003
Determine rates
and outcomes
from posttraumatic
hydrocephalus
Retrospective chart
review
140 patients with
severe TBI
admitted to
inpatient
rehabilitation
Development
of
hydrocephalus
and post-injury
epilepsy, GOS,
Disability
Rating Scale
(DRS), FIM
Tribl and Oder,
2000
Determine
outcomes from
ventriculoperitoneal shunt
placement for
post-traumatic
hydrocephalus
Observational
48 patients with
severe TBI who
had undergone
VP shunt
placement for
hydrocephalus
Development
of post-shunt
seizures and
other
complications/
outcomes
Study
Main Purpose
Research Design
Sample
Outcome
Measures
Determine the
value of S-100B
as a biomarker of
TBI
Meta-analysis
18 clinical trials
Evaluate the role
of S-100B in
predicting
outcome in mild
TBI
Evaluate the role
of S-100B in
predicting
outcome
Evaluate the role
of S-100B in
predicting
outcome 6
months post
Observational
TBI Prognosis
Raabe et al.,
2003
Stranjalis et al.,
2004
Townend et al.,
2002
Raabe and
Seifert, 2000
Hydrocephalus found in 45%
of patients, severe in 11%.
Presence of hydrocephalus
correlated with age, duration
of coma and decompressive
craniotomy; correlated at 1
year with GOS, DRS, FIM and
development of post-traumatic
epilepsy.
An average 3.3 years post
surgery, 52.1% benefited from
shunt implantation. Posttraumatic seizures seen in 31
patients. Shunt revision
required in 15 patients. Best
predictor of good outcome
was higher GOS prior to
surgery.
Results
Descriptive
Prognostic
IV
Therapeutic
intervention
IV
Study Type
Level of
Evidence
Brain damage
Extracranial release present,
but impact limited; S-100B is
a serum biomarker of brain
damage.
Metaanalysis
NA
100 subjects with
mild TBI
Return to work
Elevated S-100B correlated
with decreased rate of return
to work by one week.
Prognostic
II
Observational study
148 adults with
TBI within 6
hours of injury
GOS-E
A significant inverse
correlation between serum S100B and GOS-E.
Prognostic
II
Observational study
25 persons with
TBI evaluated at
6 hours and
serial lab –S100B for up to
GOS at 6
months
For patients with unfavorable
outcome, S-100B markedly
increased, and a second peak
was noted at 6 days.
Prognostic
III
study
Chatfield et al.,
2002
Lima et al.,
2004
Vos et al., 2004
Wagner et al.,
2004
Chiang et al.,
2003
Crawford et al.,
2002
Lichtman et al.,
2000
Groswasser et
Evaluate the role
of c-tau and S100B in
predicting
outcome post
TBI
Evaluate the role
of NSE in
predicting
outcome
Observational study
Observational study
Evaluate the role
of biomarkers in
predicting
outcome
Evaluate
cerebrospinal
fluid (CSF)
biomarkers and
the contribution
of gender
Determine the
role of APOE
polymorphism in
the outcome of
persons with TBI
Determine the
role of APOE
polymorphism
on memory of
persons with TBI
Determine the
role of APOE
polymorphism in
rehabilitation
outcome
Determine the
10 days
20 persons with
TBI
GOS
S-100B, but not c-tau,
correlated with poor outcome.
Prognostic
III
4 groups of
mixed
neurologic
dysfunction;
51 subjects
GOS
Prognostic
III
Observational study
85 persons with
severe TBI
GOS at 6
months
Serum NSE may not be
sensitive to fine neuronal or
clincial outcome changes ,but
patients with lower GOS
scores had higher NSE levels
than those with lower GOS
scores.
S100b, GFAP and NSE all
predicted poor outcome.
Prognostic
III
Prospective
evaluation of CSF
parameters
68 persons with
severe TBI
Measures of
oxidative
stress
Females evidenced smaller
oxidative stress load.
Response to stress declines
with age.
Correlationa
l
II
Observational study
100 persons with
severe TBI
GOS
Significant association
between APOE allele and sixmonth outcome.
Prognostic
II
Observational study
110 persons with
TBI in the
Defense and
Veterans Head
Injury Program
31 persons with
TBI
who completed a
neurorehabilitati
on program
74 persons with
Measures of
executive
function and
memory
Significant correlation of
APOE allele and memory
dysfunction.
Prognostic
II
APOE
polymorphism,
FIM
Presence of APOE4 allele
adversely affects rehabilitation
outcome.
Prognostic
III
Return to
Third ventricle ratio on late
Prognostic
III
Observational study
Retrospective
al., 2002
Englander et al.,
2003
Gerber et al.,
2004
Scheid et al.,
2003
Hattori et al.,
2003
Bergsneider et
al., 2001
Bergsneider et
al., 2000
Ricker et al.,
2001
ability of CT
ventricle ratios to
evaluate longterm outcome
Evaluate the
ability of CT to
predict
functional
outcome at
rehabilitation
discharge
Evaluate the role
of MRI in
detecting lesions
after TBI
Evaluate the role
of MRI in
detecting lesions
after TBI
Evaluate the role
of PET in
detecting
dysfunction after
TBI
Evaluate the
relationship
between PET
and functional
status
Evaluate the
relationship
between PET
and level of
awareness
Compare PET
changes in verbal
recall between
those with and
without TBI
analysis of CT data
penetrating TBI
and 34 with
closed TBI
work,
measures of
cognitive
functioning
DRS, FIM
Prospective
longitudinal design
1,839 persons
within the TBI
Model Systems
Comparative analysis
of MRI data
43 persons with
TBI
Presence of
lesions
Prospective MRI
imaging
66 persons with
TBI
Presence of
lesions
Comparison group
study
23 persons with
TBI and 11
healthy
volunteers
Level of
activation in
brain regions
Observational study
13 persons with
TBI studied via
PET
DRS
Observational study
42 persons with
severe TBI
Comparison group
study
5 persons with
severe TBI and 4
healthy controls
CT scan is a powerful
predictor of cognitive outcome
and return to work.
Midline shift of greater than
5mm associated with
supervision needs.
Those with subcortical
contusions were more likely to
require assist in ambulation
and lower body dressing.
T2 gradient echo more
sensitive for detecting
hemorrhagic lesions and
related to PTA.
T2 gradient echo superior at
the detection of DAI.
Prognostic
II
Screening
Correlationa
l
II
Screening
III
Differences in subcortical and
cerebellar activation among
those with greater level of
arousal as compared to those
functioning at lower levels.
Quantative FDG-PET
correlated with level of global
functional recovery (DRS).
Correlationa
l
IV
Prognostic
IV
Level of
consciousness
Dissociation was found
between cerebral glucose
metabolism and level of
consciousness.
Correlationa
l
III
Changes in
PET activation
TBI group lacked change in
cerebellar region during free
recall.
Correlationa
l
III
Ptak et al., 2003
Huisman et al.,
2004
Garnett et al.,
2000
Friedman et al.,
1999
Uzan et al.,
2003
Evaluate the
relationship of
MRI cerebral
fractional
anisotropy
(CFAST) in
detecting white
matter
Evaluate the
relationship of
MRI detecting
white matter
change via
diffusion tensor
imaging (MRIDTI) and
severity
parameters
Evaluate the
ability of
magnetic
resonance
spectroscopy
(MRS) to predict
outcome
Evaluate the
ability of MRS
to predict
outcome
Observational study
30 persons from
ED and 15 from
trauma service
[CFAST
Hospital LOS,
mortality,
intensive care
unit (ICU)
LOS
Rehabilitation
discharge
Rankin score
CFAST correlates with
outcome measures.
Prognostic
III
Comparison study of
imaging and
outcomes
20 persons with
TBI
MRI- DTI correlated with
acute GCS and Rankin score.
Prognostic
III
Observational study
19 persons with
TBI
GOS
DRS
NAA/CHO and CHO/CR
correlate with outcome.
Prognostic
III
Observational study
14 persons with
TBI studied soon
after injury and
again at 6
months
14 persons with
severe TBI in
vegetative state
Neuropsycholo
g-ical
performance,
GOS
NAA predicted
neuropsychological
performance and GOS.
Prognostic
III
Evaluate the
ability of MRS
to predict those
likely to remain
in vegetative
state
Observational study
Measures of
arousal
NAA/CR ratio was lower in
those who remained in
vegetative state.
Prognostic
IV
Sleigh et al.,
1999
Evaluate the
ability of SSEP
to predict
outcome
Observational study
105 persons with
severe TBI, GCS
6 or less
GOS
Bilateral absence associated
with poor outcome. Bilaterally
normal: 51% chance of good
outcome.
Prognostic
III
Lew et al., 1999
Evaluate the
potential of P300
to predict
outcome
Evaluate the
potential of P300
to predict
outcome
Observational study
22 healthy adults
and 6 persons
with TBI
Mortality
Correlationa
l
IV
Comparison study
III
Correlational study of
prospective cohort
P300
responses,
auditory and
visual reaction
time tests
GOS
DRS
Correlationa
l
Evaluate the
ability of longlatency
responses to
predict outcome
Evaluate the
relationship
between MRI
findings and P50
potential
Compare P50 in
controls and
those with TBI
Evaluate
physiological
factors that may
be associated
with poor
outcome from
TBI
Determine the
power of early
acute scores to
predict discharge
disposition
11 persons with
TBI (with
favorable
recovery) and 11
controls
21 persons with
severe TBI and
11 volunteers
Prognostic
III
Observational study
10 persons with
TBI and 10
controls
P50 response
2 persons with no response
died; those with less severe
injuries evidenced a larger
response.
Diminished amplitude and
prolonged latency P300 were
seen in those with TBI.
Reaction time tests also
prolonged.
Those with lower GOS scores
at 1 year had significantly
longer latency and lower
amplitude long-latency
responses.
Hippocampal injury was
related to P50 non-supression
post TBI.
Correlationa
l
III
Comparison study
20 persons with
TBI and 20
controls
81 patients with
blunt TBI in an
acute care
hospital
P50 response
P50 was significantly greater
in those with TBI.
Correlationa
l
III
Mortality,
hospital LOS
Hypotension, hyperglycemia
and hypothermia associated
with increased mortality.
Metabolic acidosis and
hypoxia were associated with
longer hospital stays.
Correlationa
l
IV
378 patients with
TBI admitted to
a level 1 trauma
hospital
Discharge
disposition
Revised Trauma Score and
Injury Severity Score
predicted discharge to home or
to inpatient rehabilition.
Prognostic
IV
Lew et al., 2004
Mazzini et al.,
2001
Arciniegas et
al., 2001
Arcinegas et al.,
2000
Jeremitsky et
al., 2003
Wagner et al.,
2000
Observational study
Observational study
Duong et al.,
2004
Determine the
impact of
strength, balance
and swallowing
deficits on
outcomes
Observational study
2,363 persons
with TBI in
inpatient
rehabilitation
FIM scores,
need for
assistance after
discharge
Greenwald et
al., 2001
Determine
relationship of
severity
measures to
sitting and
standing balance
Main Purpose
Observational study
908 patients with
TBI in acute
inpatient
rehabilitation
None
Research Design
Sample
Retrospective review
of database
Database of 18
brain injury units
in France, 876
person with TBI
Study
Rehabilitation Interventions
Mazaux et al.,
Evaluate the
2001
impact of early
rehabilitation
interventions on
outcome
Leg strength less than 3/5 on
admission to rehabilitation,
swallowing disorders, and
decreased balance were
associated with increased need
for assistance after
rehabilitation discharge and at
1 year.
Balance skills on admission
were correlated with age,
injury severity and acute care
complications.
Prognostic
IV
Correlationa
l
IV
Outcome
Measures
Results
Study Type
Level of
Evidence
Improved outcome and lower
cost with early intervention.
Therapeutic
intervention
IV
Stimulation early in care may
help therapy. Stimulation
resulted in changes in heart
rate and respiration. The
absence of any response to
early stimulation carries a
potential unfavorable
prognosis.
Early rehabilitation consults
(<48 hours) resulted in
decreased LOS and improved
FIM scores at discharge from
acute care.
Age predicted intensity of
services;
therapy intensity was
Therapeutic
intervention
IV
Therapeutic
intervention
III
Correlationa
l
Prognostic
III
Lippert-Gruner
et al., 2002
Evaluate the role
of early
stimulation
(multi-modal,
early onset
stimulation) in
TBI
Case series
16 persons with
severe TBI and
coma of at least
48 hours
Medical
complications,
GOS,
European
Head Injury
Evaluation
Chart
ADL
Behavioral and
sensorimotor
exam
Wagner et al.,
2003
Determine the
value of early
rehabilitation
intervention in a
trauma system
Identify factors
relating to
intensity of
Retrospective
analysis
1,866 persons
with non-fatal
TBI
LOS, FIM at
acute care
discharge
Multi-center,
prospective
nonrandomized study
491 persons with
TBI in inpatient
rehabilitation
Services
provided, FIM,
LOS
Cifu et al.,
2003
Zhu et al., 2001
Cannning et al.,
2003
Page and
Levine, 2003
Karman et al.,
2003
Wilson et al.,
2002
Mossberg et al.,
2002
rehabilitation
services
Determine the
role of therapy
intensity on
outcome
Determine the
role of an
intensive sit-tostand program on
motor
performance
Determine the
efficacy of a
modified
constraintinduced therapy
program
Randomized
controlled, assessorblind trial
36 persons with
TBI
FIM and GOS
Single-blind,
randomized
controlled pilot study
24 subjects with
severe TBI
(experimental
treatment group
13; standard
group 11)
3 subjects with
TBI and upper
limb
hemiparesis, at
least one year
post injury
Measures of
exercise
capacity
Multiple base line,
pre-post case series
Evaluate the
feasibility and
efficacy of
constraintinduced
movement
therapy in
acquired brain
injury
Document
recovery pattern
of persons using
partial weightbearing support
Multiple case series
7 children with
acquired brain
injury and
hemiparesis
Case series
2 patients with
TBI (one less
than 6 months
post injury and
one more than 2
years post injury)
Assess
cardiorespiratory
response of
treadmill
Repeated-measures,
pre-post design
40 subjects with
TBI
predictive of motor function at
discharge.
Trend toward improved FIM
and GOS at 3 and 6 months in
those receiving more intense
services.
62% improvement in motor
performance, compared with
18% for the control group.
Therapeutic
intervention
III
Therapeutic
intervention
IV
Action
Research Arm
Test, Wolf
Motor
Function,
Motor Activity
Log
Actual
Amount of
Use Test,
Quality of
Movement
Scale
Subjects displayed improved
task performance and motor
function.
Therapeutic
intervention
IV
Improved quality of limb use
and actual amount of use.
Therapeutic
intervention
IV
Missouri
Assisted Gait
Scale
(MAGS),
standing
balance,
muscle
strength
Aerobic
capacity,
movement
efficiency
Improvement in MAGS was
found.
Therapeutic
intervention
IV
Improved aerobic capacity and
movement efficiency was
found.
Therapeutic
intervention
III
Study
ambulation after
ABI
Main Purpose
Pharmacology and Depression
Perino et al.,
Evaluate
2001
citalopram and
carbamazepine
in the treatment
of post-TBI
major depression
Research Design
Sample
Outcome
Measures
Results
Study Type
Level of
Evidence
Prospective open
label
20 persons with
TBI and
psychiatric or
behavioral
disturbance
Brief
Psychiatric
Rating Scale
(BPRS) and
Clinical
Global
Impression
scale (CGI)
Results suggest efficacy for
citalopram and carbamazpine.
Therapeutic
intervention
III