The effect of adrenocorticotropic analog on clinical outcome of diffuse axonal

injury patients in Dr. Soetomo general hospital

Gozi FF*, Wicaksono P**, Wahyuhadi J**
*Resident, Department of Neurosurgery Faculty of Medicine Universitas Airlangga/dr. Soetomo General Hospital, Surabaya,
Indonesia
**Department of Neurosurgery Faculty of Medicine Universitas Airlangga/dr. Soetomo General Hospital, Surabaya, Indonesia

Abstract
Objective: This study was conducted to investigate the effect of analog
adrenocorticotropic on clinical outcome in diffuse axonal injury patients.
Methods: From June 2013 to July 2014. We retrospectively investigated patients with
diffuse axonal injury that were treated at Dr. Soetomo general hospital. We studied
GCS score at the time of admission and discharge, Barthel Index and GOS score. We
divided the patients into groups and we analyzed the data with SPSS version 12.0.
Result: From the total sample of 90 patients, obtained 38 samples of the complete
successfully followed, 26 patients in control group, 12 patients are a group of analog
ACTH administration. Median GCS upon admission is 8.13, in the control group was
8.5 and in the treatment group was 8.0. GOS Comparison on exit, in the third and
sixth months was not significant (p> 0.05). In Barthel Index comparison, significant
results obtained on comparison of control and treatment in the third month (p =
0.046).
Conclusion: Our study results suggest that the administration of ACTH analogues
have clinical output higher than the control. Barthel Index Value in the third month
observation has significant differences in comparison ACTH analog administration
and control.
Keywords Brain injury, DAI, ACTH analog, GOS, Barthel Index

Introduction
Diffuse Axonal Injury is widespread damage to axons in the white matter of the brain
[1,2,3]. In a study reported the mortality rate reached 23.9% in patients with diffuse
injury and 40.4% in patients with focal injury. DAI, contusions and lacerations of the
brain will produce immediate clinical effects that lead to coma and death [1,2,4].
The clinical output often used in patients with brain injury is the Glasgow Outcome
Score (GOS) and the Barthel scale. GOS which has been widely accepted as the
standard size to describe the output of a brain injury, has had a narrow validity and
inter-observer variability. The clinical output of brain injury patients is a dynamic
process and time-dependent. Although the longer the period of follow-up data
obtained more convincing, but is comparable to the high level of the patient's missing
from the observation [4,5,6].
There is controversy in the used of neuroprotective in patients with brain injury.
Numerous studies have been performed on neuroprotective therapy in brain injury.
One thriving example is type of neuropeptide adrenocorticotropic analog (ACTH)
[7,8]. This study aimed to investigate the effect of analog adrenocorticotropic on
clinical outcome in diffuse axonal injury patients.
Methods
Ninety patients who had been diagnosed with diffuse axonal injury and underwent a
CT scan at our hospital from June 2013 to July 2014 were included in this study. A
total of 17 patients died, 28 patients refused to participate the research, and 7 patients
did not control in hospital after discharge (loss of observation). Patients are
categorized drop-out with a total of 52 patients. Thus, the sample data that can be
processed is 38 patients. All the medical records and radiographic findings were
reviewed retrospectively. Various clinical parameters such as sex, age, DAI category,
initial Glasgow Coma Scale (GCS) score, follow-up GCS score, Glasgow Outcome
Scale (GOS) and Barthel scale were investigated. Recovery of consciousness was

defined as opening eyes to verbal stimulus and obedience to command. The outcome
that assessed by GOS was as GR (good recovery), MD (mild disability), SD (severe
disability), PVS (persistent vegetative state), and death otherwise the outcome that
assessed by Barthel scale was as independent need minimal help with ADL, partially
dependent, very dependent and totally dependent. Statistical analysis was conducted
with the SPSS program (version 12.0) (SPSS Inc., Chicago, IL, USA). Statistical
significance was defined as p < 0.05.
Results
All cases are presented in table 1. All patients were transferred to our hospital within
one day from injury. The male/female ratio was 3,2 : 1, and the mean age was 30.94
years. The patients had several coincidental injuries such as rib fracture, long bone
fracture, and scanty amount of intracranial hemorrhage (subdural hematoma,
contusion, subarachnoid hemorrhage, and intraventricular hemorrhage).
Table 1. Characteristic of the study
Caracteristic
Male
Female
Age
Mean (+ SD)
Brain injury category
SBI
MBI
DAI category
Grade I
Grade II
Grade III
Treatment
Control
Analog ACTH
Sex

n
29
9

Persentages (%)
76,3
23,7
30,94 (11,82)

21
17

55,3
44,7

19
6
13

50
15,8
34,2

26
12

68,4
31,6

The average GCS score of all patients on admission was 8.13, and the average GCS
score of all patients on discharge was 11.3. Fig.2 shows the treatment effect of ACTH
group, the median GCS score of all patients on admission was 8.00, whereas the
control group median GCS score values obtained during the admission was 8.5. the

median GCS score when patients discharge on ACTH treatment group was 11.5,
while the control group was 11.0. GCS score differences on patients discharge from
these two groups was not statistically significant (p = 0.609).
Table 2. Characteristic and Comparison of two groups
Variable
GCS score when

Median
8,13

Intercuartile Deviation
0,935

Admission
control
Analog ACTH

8,5
8,0
11,37

1,25
1.5
1,42

0,359

control
Analog ACTH

11,0
11,5

2,0
1,75

0,609

GCS score when

discharge

By using the GOS score to classify outcomes, fig.1. Shows the GOS score at each
time of observation in each group. The figure shows the GOS score at the admission
on ACTH analog administration group was higher than the control group. In the third
month and sixth six month, GOS score of both groups reached the same value.
3.5
3
2.5
2
Median GOS

1.5
1
0.5
0
Saat KRS

Bulan 3
Time Observation
Kontrol

Analog ACTH

Figure 1. GOS score in each groups

Bulan 6

The comparison GOS score at discharge time, third and sixth months (Table 3.)
shows an upward trend higher in the group giving ACTH analog. In the control
group, the difference in GOS score at discharge, third months and sixth month had
significant values (p <0.05). However, In the group of ACTH analog administration, a
significant difference only showed in the comparison of the GOS score at discharge
and third months. In the third and sixth month, the comparison of GOS score did not
have a significant difference.
Group
Control
Analog ACTH
Discharge
2,0 (+ 1,0)a
3,0 (+ 1,0)a
b
Third month
3,0 (+ 1,0)
3,0 (+ 0,75)b
c
Sixth month
3,0 (+ 1,0)
3,0 (+ 1,0)bc
p (Anova Friedman)
0.000
0.001
Different superscripts show significant results (p<0,05)
with Wilcoxon Signed Rank Test
GOS

Table 3. GOS score comparison on each groups

Fig. 2. shows the median Barthel index at each time of observation of each group.
The value of Barthel Index ACTH analog administration group was higher than the
control group, as well as in the third and sixth. Increasing the Barthel Index value of
discharge period for the third month was also higher in the ACTH analog
administration compared with the control group.

50
45
40
35
30
Median Barthel Index

25
20
15
10
5
0
Saat KRS

Bulan 3

Bulan 6

Time Observation
kontrol

Analog ACTH

Figure 2. Barthel index score in each groups

In the control group, the difference in Barthel Index score when discharge, third
months and sixth month had significant values (p <0.05). In the group of ACTH
analog administration, the difference value in comparison to meaningfully Barthel
Index score when discharge and third months. In the third and sixth month
comparison, Barthel Index score does not have a significant difference.

Kelompok
Kontrol
Analog ACTH
Keluar rumah sakit
20,00 (+ 13,0)a
22,5 (+ 19,0)a
b
Bulan 3
30,0 (+ 16,0)
40,0 (+ 21,0)b
c
Bulan 6
40,0 (+ 25,0)
45,0 (+ 28,0)b
Different superscripts show significant results (p<0,05)
with Wilcoxon Signed Rank Test
Barthel Index

Table 4. Barthel Index score comparison on each groups

Discussion

In our study, the data shows the domination of male as subject with a ratio of 3.2: 1.
This is consistent with the prevalence of brain injury in which men more often than
women suffered a brain injury. Patients clinically classified as moderate brain injury
(COS) and severe traumatic brain injury (COB) (55.3%). While the classification of
Diffuse Axonal Injury (DAI) were classified as grade I, as many as 19 samples
(50%), followed by DAI grade III (13; 34.2%) and the latter DAI grade II (6;
15.8% ). In this study, DAI grade I most commonly found, but the classification of
brain injury, the most abundant is the COB. The severity of brain injuries is not
always proportional to the severity of radiograph. Patients with COB can come up
with DAI grade I from CT Scan image. This is due picture axonal damage that may
lead to severe traumatic brain injury was not detected on CT scan modality.
Although significant results were obtained in the variable clinical outcomes, Barthel
Index and the observation of each group, there are still some results that are not in
accordance with the literature. This study has several limitations, namely in terms of
sampling, observation time and observation variables.
Samples were patients who entered the inclusion criteria with a total sampling
method. Patients that were observed in our study were limited because many DAI
patients who transferred to our hospital did not agree with this study.
Variables were observational clinical output in the form of the Glasgow Outcome
Scale (GOS) and Barthel Index (BI). This study needs other variables to determine
the outcome of the examination eg cognitive or motor examination. Not only GCS,
GOS and Barthel index, but also some biomarkers that can be examined in serial.
Conclusion
This study shows a comparison between ACTH analog administration to control
group who did not treated with ACTH analog. ACTH analog treatment has a higher
Glasgow Outcome Scale score than without ACTH analog treatment and Barthel
Index patients that treated with ACTH analog were higher than controls. There is

clinical improvement of GOS score and Barthel Index score of the observations at
discharge period, third and sixth month of ACTH analog administration group.
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