Medical and Health Science Journal, Vol. 4, No.

2, August 2020

ORIGINAL ARTICLE
THE EFFECT OF CITICOLIN IN MOTORIC IMPROVEMENT OF
ACUTE ISCHEMIC STROKE PATIENTS IN SITI KHODIJAH
SEPANJANG HOSPITAL

Dza’wan Maula Iwanatud Diana1, Laily Irfana2*, Yelvi Levani3, Uning Marlina4
1
Medical student, University of Muhammadiyah Surabaya
Faculty of Medicine University of Muhammadiyah Surabaya
2,3,4

*Corresponding Author: [email protected]

ARTICLE INFO ABSTRACT

Article history: Background: According to WHO, stroke is most common cause of morbidity and
Submitted: mortality around 5,54 millions death. Stroke is classified into ischemic stroke and
June, 26 2020 hemorrhagic stroke. Ischemic stroke is caused by vascular blockage in the brain,
Received in revised whereas hemorrhagic stroke is caused by vascular ruptures. Ischemic stroke is
form: treated by thrombolytic for reperfuison and anticoagulant or antiplatelet to prevent
August,08 2020 the formation of thrombus collateral blood brain. Moreover, it also can add
Accepted: neuroprotectant to inhibit further tissue and cellular damage due to cytotoxic effect.
August, 18 2020 The common used of neuroprotectant are piracetam and citicolin. They increase
erythrocyte capability in blood vessels without alter shape or function of
erytrhocyte. Citicolin improves neuronal cells membrane by increasing synthesis of
phosphatidylcholine as main component of cells membrane. Citicolin often chosen
because cheaper and there is no significance different effect between both of them.
Objective: To investigate motoric improvement in acute ischemic stroke patients in
Siti Khodijah Sepanjang Hospital. Methods: Study design is observational
retrospective case-control using medical record from January-September 2019. We
devided 72 patients into two groups: control group who received antiplatelet 100
Keywords: mg/day for 5 days and treatment group who received combination of antiplatelet
Ischemic Stroke, 100 mg/day and citicolin 500 mg/day for 5 days. Patients were examined using
Citicolin, Motoric Medical Research Council Manual Muscle Test Scale on first and fifth day. The
Improvement criteria of motoric improvement is Manual Muscle Testing Scale score increased >
1 score in one of extremitas muscles. Results: statistic test used chi-square test and
wilcoxon test with each significance grade 0,00 and 0,01 (<0,05). Conclusion: Our
study indicated that citicolin 500 mg/day for 5 days significantly improved motoric
in acute ischemic stroke patients in Siti Khodijah Sepanjang Hospital.

@2020 Medical and Health Science Journal. 10.33086/mhsj.v4i1.1415

INTRODUCTION is thrombolytic treatment for brain reperfusion.

Stroke is the global burden disease that The second step is anticoagulant or antiplatelet
can cause death or disablities problem. Stroke, to prevent thrombus growth in collateral blood
based on its etiology, classified into ischemic vessels. The third is a neuroprotectant treatment
and hemorrhagic stroke. Ischemic stroke is in order to ovoid expansion of neuroglia injury
caused by vascular blockage in the brain, as a result of cytotoxic process1.
whereas hemorrhagic stroke is caused by Neuroprotectant commonly used is
vascular ruptures. Ischemic and hemorrhagic piracetam and citicoline, both single and
stroke can be treated with general therapy and combination2. Piracetam attempts to increase
special therapy, which is obviously different. erythrocyte capability in blood vessels without
Based on its patophysiology, ischemic stroke causing neither transformation nor erythrocyte
treatment divided into three steps. The first step function. Therefore ischemic brain parenchyma
Correspondence: Laily Irfana
@2020 Medical and Health Science Journal. 10.33086/mhsj.v4i1.1415
Available at http://journal2.unusa.ac.id/index.php/MHSJ
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 Medical and Health Science Journal, Vol. 4, No.2, August 2020

will be recovered3,4. Citicoline attempts to patients who got first attack, (ii) diagnosed with
increase the main component of cell membrane < (-1) siriraj score, (iii) obtained standard
synthesis, phosphatidylcholine that is increasing antiplatelet therapy (aspilet 100 mg per-oral),
neuronal cells membrane improvement4,5. (iv) strength muscles will be measured by
Ischemic stroke can cause motoric MMTS (Manual Muscle Testing Scale) scale in
dysfunction, including pareses or muscle a range 0-4 and was graded by comparing the
weakness. The muscle strength test is used to left and right body side6. The patient’s motoric
evaluate muscle weakness. This test is used for strength was examined in Musculus biseps
patients who are suspected of neurologic brachii and Musculus quadriseps femoris. The
abnormality, especially in stroke, head injury, exclusion criteria were patients who had
spinal cord injury, and neuropathy. The scale of repetitive stroke profiles and being
this test uses Medical Research Council Manual hospitalization less than 5 days.
Muscle Testing Scale (MMTS) 6. In siriraj interpretation < (-1) score means
Based on previous studies, the evaluation ischemic and > 1 score means hemorrhagic
of neuroprotectant effect in motoric function, stroke. Control group was given antiplatelet 100
cognitive, consciousness and activity daily mg/day for 5 days. While treatment group was
living of stroke ischemic patients, that have been given the combination of antiplatelet 100
reviewed with NIHSS (National Institutes of mg/day and citicoline 500 mg/day for 5 days.
Health Stroke Scale), GCS (Glasgow Coma The patient’s motoric strength was examined
Scale), Barthel Index and another score showed using MMTS on the first and fifth day of
different result. Therefore, this study aimed to therapy. Criteria for motoric improvement was
evaluate the effect of neuroprotectant treatment increasing of MMTS score > 1 score in one of
for motoric improvement used Medical the measured extremity muscles. Data collection
Research Council Manual Muscle Testing Scale and statistical analysis procedure used SPSS 25
(MMTS) in acute ischemic stroke patients. version (with p < 0.05 means a significant
result). Health Ethic Research Committee of
STUDY METHOD Siti Khodijah Sepanjang Hospital has approved
This study was observational with case- this study with a code number 024/KET-
control approach. The design of this study was KEPK/XII-2019.
retrospective by analyzing ischemic stroke
patient medical records. This study used a RESULTS
medical record of ischemic stroke patients on 1. The Characteristic of Ischemic
the period January-September 2019. The total Stroke Patients in Siti Khodijah
sample was 72 patients divided into two groups, Sepanjang Hospital
control group, and treatment group, each of them Table 1 indicates that most of the
was 36 patients. This study used patients who fit ischemic stroke patients aged was 55-64 years
to exclusion and inclusion criteria. The inclusion (33,3%). Ischemic stroke patients were
criteria were ischemic (i) stroke dominated by females. Hypertension and

SIRIRAJ SCORE
(2,5 x consciousness) + (2 x vomit) + (2 x headache) + (0,1 x diastolic pressure)
– (3 x atheroma) – 12 =
0 1 2
Consciousness Aware Sleepy, stupor Semi-coma, coma
Vomit No Yes
Headache in 2 hours No Yes
Atheroma (diabetes
No Yes
mellitus, angina)

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 Medical and Health Science Journal, Vol. 4, No.2, August
diabetes mellitus were the risk factors of hypertension, and more than half patients had
ischemic stroke. From 72 ischemic stroke diabetes mellitus.
patients, there were 56 (77,8%) patients who had

Table 1 The Characteristic of Ischemic Stroke Patients

The Characteristic of Ischemic Stroke Patients Frequency Persentage
33-44 7 9.7
45-54 17 23.6
Age 55-64 24 33.3
65-74 15 20.8
>75 9 12.5
Female 43 59.7
Gender
Male 29 40.3
Having hipertension profile 56 77.8
Hipertension
Nothing hipertension profile 16 22.2
Having diabetes profile 39 54.2
Diabetes mellitus
Nothing diabetes profile 33 45.8

2. Result of motoric capability on the first day and fifth day

Table 2 MMTS score of control group and treatment group on the first day of therapy

MMTS Control group Treatment group

score Superior Superior Inferior Inferior Superior Superior Inferior Inferior
dextra sinistra dextra sinistra dextra sinistra dextra sinistra
N N N N N N N N
1 0 3 0 3 1 1 1 1
% 0% 8.3% 0% 8.3% 2.8% 2.8% 2.8% 2.8%
2 3 5 3 5 3 5 3 5
% 8.3% 13.9% 8.3% 13.9% 8.3% 13.9% 8.3% 13.9%
3 2 3 2 3 1 2 2 2
% 5.6% 8.3% 5.6% 8.3% 2.8% 5.6% 5.6% 5.6%
4 17 12 17 12 20 17 19 17
% 47.2% 33.3% 47.2% 33.3% 55.6% 47.2% 52.8% 47.2%
5 14 13 14 13 11 11 11 11
% 38.9% 36.1% 38.9% 36.1% 30.6% 30.6% 30.6% 30.6%
N 36 36 36 36 36 36 36 36
Table 2 indicates that MMTS score of control group and treatment group at the first day therapy were
not quite different.

Table 3 MMTS score of control group and treatment on fifth day of therapy
MMTS Control group Case group
score
Superior Superior Inferior Inferior Superior Superior Inferior Inferior
dextra sinistra dextra sinistra dextra sinistra dextra sinistra
1 2 3 2 3 0 1 0 1

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% 5.6% 8.3% 5.6% 8.3% 0% 2.8% 0% 2.8%

2 2 4 2 4 0 1 0 1
% 5.6% 11.1% 5.6% 11.1% 0% 2.8% 0% 2.8%
3 6 3 6 4 3 0 3 0
% 16.7% 8.3% 16.7% 11.1% 8.3% 0% 8.3% 0%
4 10 16 10 15 14 15 14 15
% 27.8% 44.4% 27.8% 41.7% 38.9% 41.7% 38.9% 41.7%
5 16 10 16 10 19 19 19 19
% 44.4% 27.8% 44.4% 27.8% 52.8% 52.8% 52.8% 52.8%
N 36 36 36 36 36 36 36 1

Tables 2 and 3 indicate that there are becomes 41.7%, and score 5 decreased from
some changes in every score of control group. 36.1% becomes 27.8%.
The number of patients in dextra superior Whereas, alteration score of treatment
extremity and dextra inferior escalated on score group indicates that the number of patients on
5, 3 and 1. Score 5 from 38.9% becomes 44.4%, dextra superior extremity and dextra inferior
score 3, from 5.6% becomes 16.7% and score 1, escalated on score 5 and 3. Score 5 escalated
from 0% becomes 5.6%. Score 2 and 4 have from 30.6% becomes 52.8%, score 3 escalated
decreased, from 8.3% becomes 5.6% and score from 2.8% (dextra superior extremity) and 5.6%
4 from 47.2% becomes 27.8%. (dextra inferior extremity) becomes 8.3%. Score
The number of control group in sinistra 4 deflated 16.7% (dextra superior extremity) and
superior extremity decreased on score 5 of 13.9% (dextra inferior extremity). Score 1 and 2
36.1% becomes 27.8%, and score 2 from 13.9% deflated become 0%.
becomes 11.1%, while score 4 increased 33.3% Number of patients on sinistra inferior and
becomes 44.4% and another score is constant. sinistra superior extremity were escalated. Score
On sinistra inferior extremity, number of 5 from 30.6% becomes 52.8%, while score 2, 3
patients escalated on score 4 from 33.3% and 4 deflated 11.1%, 5.6% and 5.5%,
respectively. While score 1 is constant 2.8%.
Table 4 Median of control group and treatment group on first day and fifth day
Group Extremity First median Final median N p
Superior dextra 4 4 36 0,256
Control Superior sinistra 4 4 36 0,768
group Inferior dextra 4 4 36 0,256
Inferior sinistra 4 4 36 0,572
Superior dextra 4 5 36 0,01
Treatment Superior sinistra 4 5 36 0,01
group Inferior dextra 4 5 36 0,01
Inferior sinistra 4 5 36 0,01

Table 4 indicates that control group is (p<0.05) can be concluded that there is a
in same median on first day and fifth day. It can significant motoric improvement in a treatment
be seen from significant result by alfa wilcoxon group.
test that > 0,05. While in treatment group, there
was increasing median from 4 to 5. After
wilcoxon test was done, derived alfa 0.01

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 Medical and Health Science Journal, Vol. 4, No.2, August
3. Correlation of Citicolin Treatment with Motoric Improvement Based on MMTS

Table 5 Quantity of ischemic stroke sample in Siti Khodijah Sepanjang Hospital

Group Motoric improvement

Total p* p**
Good Not good
N N N
Treatment
group 23 31.9% 13 18% 36 50% 0.000 0.434
Control group
6 8.3% 30 41.6% 36 50%
*: chi-square test
**: contingency coefficient test
Table 5 indicates that ischemic stroke human has a different condition. The risk
patients experience motoric improvement on ischemic stroke can be reduced by healthful
treatment group are 23 patients (63.8%), while lifestyle such as minimize greasy food, eating
patients who do not experience motoric more fruits, and quit smoking that glucose is
improvement are 13 patients (36.2%). And well controlled. This study is in line with a
ischemic stroke patients who experienced previous study that showed stroke patients on
motoric improvement on control group are 6 female was 54,17%, whereas male was 45,81%7.
patients (16.6%) and patients who do not Hypertension and Diabetes Mellitus are
experience motoric improvement are 43 patients the risk factors for stroke ischemic. This study
(58.9%). revealed that most patients had hypertension.
The result of the chi-square test indicates This study is in line with previous studies that
that citicoline treatment in ischemic stroke showed from 60 ischemic stroke patients, 44
patients with motoric improvement based on patients had hypertension (73,33%)7.
MMTS has a significance result amount of Hypertension causes lesion on tunica intima
0.000 (p<0.05). This result indicates that there is endothelial’s blood vessels that disturb a real
a significant effect from citicoline treatment in function of blood vessels, anti-thrombosis.
motoric improvement patients. The contingency Hypertension causes platelet aggregation or the
coefficient test was effectuated to evaluate the clumping of platelet in the blood that triggers
correlation between of citicoline and motoric brain tissue hyperfusion8.
improvement; the result was found that p=0.434 Besides hypertension, most of the
positive. It can be concluded that motoric patients had diabetes mellitus. Diabetes mellitus
improvement by citicoline treatment in ischemic can cause a lesion on tunica intima so it can
stroke patients has an effective amount of 0.434, cause platelet aggregation and ischemic due to
it means the effect is moderate. blood vessel constriction. This study is related to
a previous study in RSUD dr. Moerwardi in
DISCUSSION 2010, they showed that from 66 ischemic stroke
patients, there were 47 (71,2%) patients who had
Ischemic stroke is the dynamic process
diabetes mellitus9.
whereby the occlusion of the brain blood vessel
Basically, ischemic stroke patients related
can cause large infarct, so the goal of treatment
to several factors that result in different
is to re-open the occlusion and to stop the
outcomes according to the condition. The factors
sequence of neuron cell injury. Ischemic stroke
that influenced the outcomes of ischemic stroke
can cause impairment motoric and cognitive
are the patient’s age, disease profile, lesion size
function. This study revealed that ischemic
in a brain, and GCS (Glasgow Coma Scale)
stroke attacks more on females rather than
during attack. Age is related to decreasing of
males. This happened due to the fact that every
neuronal regeneration process and decreasing

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blood vessel elasticity. Likewise, another hemorrhagic stroke patients. They reported that
pathology condition such as hyperglycemia and the patient firstly came with complaining about
hypertension, also have an effect on reducing facial paralysis and dropped in the right side of
neuron cell recovery10. The level of the body, GCS 456, 3/5 superior dextra or
consciousness also affects ischemic stroke sinistra extremity by MMTS examination, 3/5
outcome. It has been proven from previous dextra sinistra inferior extremity by MMTS
study that showed stroke patients who had low examination and scored 9 by NIHSS (National
consciousness with GCS<11 had poor functional Institutes of Health Stroke Scale) examination.
improvement than GCS >1111. After that, 500 mg/day of citicoline and aspilet
This study was accomplished by were provided. In the third day, the patient had
analyzing ischemic stroke patient medical 4/5 MMTS score and began to speak slowly.
records who given citicoline treatment provided Therapy continued until the sixth day, and the
per-oral with 500 mg/day, which was provided result is patients can talk as good as usual and
for first five days of stroke attack. Citicoline is got 5/5 for muscle strength score, and also 2 for
composed from two essential element of NIHSS14.
phospholipids; cytidine and coline. Citicolin This study found out that patients with
attempts to increase the main component of cells 500 mg/day citicoline treatment for five days
membrane synthesis, phosphatidylcoline that have significant motoric improvement as big as
increasing neuronal cells membrane muscles examined, Musculus biseps brachii and
improvement . 4,5
Musculus quadriseps femoris. Citicoline has
The data collection procedure was several stages of therapy effect in acute ischemic
accomplished by citicoline treatment for five stroke. First, it stabilizes cell membranes by
days due to the fact that most stroke patients increasing phosphatidylcholine and
used BPJS. BPJS only allowed provided sphingomyelin synthesis15. Citicoline inhibits the
citicoline therapy for five days for acute release of free fatty acids and glutamate during
ischemic stroke patients during hospitalization. ischemia16. Citicoline can decrease the free
In addition, the effectivity of the first five-days radical and delayed the ischemic brain injury
citicoline treatment period is consistent with process17. It can also increase synaptic outgrowth
Ulfa’s study (2017). Her study showed that there and neuroplasticity18. These several mechanisms
was a significant improvement in first until fifth- of citicoline can allow the improvement of
day therapy, while in the next days, there was motoric functional in ischemic stroke patients.
insignificance improvement12. However, the researcher realizes that this study
This study used citicoline treatment with needs more, larger sample and long term
500 mg doses/day. This dosage is in line with periods. The direct research to patients and the
Davalos et al study (2010) about oral citicoline same examiner can increase validity and
dosage in an acute ischemic stroke. They studied minimize valuation subjectivities in MMTS
different doses of oral citicoline for acute scoring.
ischemic stroke patients; 500 mg/day, 1000
mg/day, and 2000 mg/day. The study showed CONCLUSION
that oral citicoline with 500 mg and 2000 mg
This study showed citicoline gives
doses/day gave significance improvement for
benefits for ischemic stroke patients. There is a
acute ischemic stroke patients13.
significant motoric improvement in ischemic
Patients in a treatment group had a
stroke patients with treatment by citicoline 500
significant motoric improvement rather than in
mg/day for 5 days. Further studies required to
the control group. This study result is in line
prove the effectivity of citicoline for the long
with Taufiqurrahman and Merry’s case report
term period.
(2016) about the benefit of citicoline in non-

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