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TEKNIK ENDOSCOPIC THIRD VENTRICULOSTOMY DIBANDINGKAN

DENGAN VENTRICULOPERITONEAL SHUNTING PADA HIDROSEFALUS


OBSTRUKTIF: PERBAIKAN KLINIS DAN PERUBAHAN
INTERLEUKIN-1β, INTERLEUKIN-6, DAN NEURAL GROWTH FACTOR
CAIRAN SEREBROSPINALIS

Maliawan, S., Andi Asadul, I., Bakta, M.


Program Pascasarjana S3 Universitas Udayana

Abstract
Teknik Endoscopic Third Ventriculostomy (ETV) merupakan alternatif terapi
hidrosefalus obstruktif (HO), tanpa pemasangan alat, lebih murah dan angka keberhasilan
yang tinggi dibandingkan dengan VP Shunting. Tujuan penelitian ini untuk mengetahui
teknik mana yang memberikan luaran klinis lebih baik dan penurunan IL-1β, IL-6, dan
NGF CSS pasca operasi lebih besar (kadarnya dalam CSS diukur dengan Elisa).
Penelitian ini merupakan penelitian eksperimental, menggunakan rancangan
randomized pretest-posttest control group design. Penelitian ini dilakukan di Bagian
Bedah RSUP Sanglah Denpasar dengan besar sample dihitung dengan rumus Pocock.
Kemudian dilakukan uji normalitas K-S, t-test dan uji Mann-Whitney.
Hasil penelitian adalah; rata-rata penurunan kadar IL-1β pada teknik VP shunting
4,49 ± 1,54 pg/ml, berbeda bermakna dibandingkan dengan rata-rata penurunan kadar
IL-1β dengan teknik ETV yaitu 6,95 ± 3,54 pg/ml ( p < 0,05). Rata-rata penurunan kadar
IL-6 pada teknik VP shunting yang didapatkan sebesar 13,71 ± 8,94 pg/ml berbeda
bermakna dengan rata-rata penurunan kadar IL-6 pada teknik ETV yaitu 25,61 ± 14,28
pg/ml ( p < 0,05). Rata-rata penurunan kadar NGF pada teknik VP shunting sebesar 35,93
± 20,68 pg/ml berbeda bermakna dengan rata-rata penurunan kadar NGF pada teknik
ETV yang besarnya 47,51 ± 23,20 pg/ml ( p < 0,05). Luaran klinis berupa diplopia
(strabismus convergen), sunset phenomena, respon membuka mata, spastisitas otot,
respon motorik, dan respon verbal diamati dalam kurun waktu pre-operasi dan enam
bulan pasca operasi. Luaran klinis pada ETV enam bulan pasca operasi lebih baik
dibandingkan dengan VP shunting, berbeda bermakna, ditunjukkan p < 0,05 untuk
kelima parameter tersebut. Angka revisi VP shunting 40% dan ETV tidak ada revisi
setelah enam bulan pasca operasi.
Teknik ETV adalah teknik alternatif terapi HO yang lebih baik dibandingkan
dengan VP shunting dalam hal perbaikan luaran klinis, penurunan IL-1β, IL-6, dan NGF
CSS , komplikasi (angka revisi) lebih rendah, faktor kesulitan lebih rendah, dan biaya
lebih murah. Teknik ETV harus dijadikan pilihan pertama terapi hidrosefalus obstruktif.

Kata kunci: ETV, VP shunting, experimental, biomarker, luaran klinis.

Pendahuluan
Hidrosefalus merupakan meningkatnya tekanan intrakranial akibat akumulasi
cairan serebro spinalis (CSS) pada sistem ventrikel otak karena tidak seimbangnya
produksi dan absorbsi CSS. (Piatt, 2003).
Hidrosefalus dapat dikelompokkan menjadi dua yaitu hidrosefalus obstruktif
(HO) dan hidrosefalus komunikan (HK). (Suny, 2003).

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Prevalensi hidrosefalus di dunia cukup tinggi, di Belanda dilaporkan terjadi kasus
sekitar 0,65 permil pertahun dan di Amerika sekitar 2 permil pertahun (Platenkamp, dkk.
2007). Sedangkan di Indonesia mencapai 10 permil (Maliawan, dkk. 2006; 2007).
Terapi definitif hidrosefalus “ gold standar” adalah VP shunting menggunakan kateter
silikon dipasang dari ventrikel otak ke peritonium. Kateter dilengkapi klep pengatur
tekanan dan mengalirkan CSS satu arah yang kemudian diserap oleh peritonium dan
masuk ke aliran darah. Bisa terjadi bermacam-macam komplikasi, seperti; diskoneksi
komponen alat, alat yang putus, erosi alat ke kulit atau organ perut, over shunting, under
shunting, buntu di proksimal atau distal, letak alat tidak pas, perdarahan subdural, dan
infeksi. Menurut Shermann, dkk. (2007) komplikasi pada bulan pertama mencapai 25-50
%, setelah itu, pertahun 4-5 % dan setiap komplikasi berarti harus dilakukan revisi. Setiap
VP shunting memiliki kemungkinan risiko revisi sekitar 3 kali dalam 10 tahun pasca
operasi (Piatt dan Carlson, 1993).
Operasi dengan teknik ETV prinsipnya adalah pengaliran CSS dari dasar ventrikel
III ke sisterna basalis yaitu ruang subarakhnoid di belakang sela tursika. Pada teknik ETV
tidak ada alat yang dipasang, sehingga aliran CSS dibuat hampir mendekati aliran
fisiologis menuju sistem penyerapan pada vili arakhnoid. Teknik ETV hanya dilakukan
pada hidrosefalus obstruktif (HO). Para peneliti mendapatkan angka keberhasilan yang
berbeda-beda dari 40 - 100 % (Van-Gelder, dkk. 2005; Bergsneider, dkk. 2006; O’Brien,
dkk. 2006). Pada penderita HO yang berumur di bawah 2 tahun dengan ETV didapatkan
perbaikan klinis 70 % dan perbaikan radiologis 63 %, sedangkan yang berumur di atas 2
tahun didapatkan perbaikan klinis 100 % dan perbaikan radiologis 73 % (Singh, dkk.
2003; Gaab dan Schroeder, 1998; Decq, dkk. 2000; Van Aalst, dkk. 2002). Pada infantil
hidrosefalus keberhasilan mencapai 46 %, sedangkan untuk penderita dengan usia di atas
2 tahun keberhasilannya mencapai 64-74 %. Di Indonesia umumnya dan di Bali
khususnya masalah utama adalah harga alat yang relatif mahal apalagi kalau terjadi
penggantian waktu revisi, akan sangat membebani keluarga penderita
Keuntungan teknik ETV lainnya adalah sekali tindakan saja, berarti tidak
memerlukan perawatan lebih lanjut, biaya murah dan sederhana, sangat ideal untuk
penderita di Indonesia. Di Rumah Sakit Sanglah Bali teknik ETV dilakukan pertama kali
pada tanggal 7 Maret 2005 dan juga merupakan yang pertama di Indonesia. Oleh karena
itu bila dari kedua teknik ini tidak mendapatkan perhatian yang serius, maka para klinikus
sangat sulit untuk menentukan metode mana yang lebih aman digunakan pada
penanggulangan penderita HO. Berdasarkan pemikiran tersebut maka peneliti berupaya
untuk menentukan efektivitas kedua teknik tersebut, sehingga teknik yang lebih efektif
dapat digunakan pada penanggulangan penderita hidrosefalus obstruktif atau dapat
digunakan sebagai gold standard penatalaksanaan hidrosefalus obstruktif.
Untuk itu diperlukan data yang valid tentang bagaimana luaran klinik kedua
tehnik tersebut, bagaimana kadar sitokin proinflamasi (IL-1ß, Il-6 dan NGF) CSS.
Penderita hidrosefalus yang dioperasi dengan teknik ETV maupun VP shunting berakibat
terjadi penurunan tekanan CSS dan mengalami reperfusi oksigen. Kondisi ini akan
menurunkan pelepasan sitokin proinflamasi dan NGF CSS. Penurunan NGF CSS ini
dapat digunakan sebagai parameter pertumbuhan sel neuron otak (Ishimaru, dkk. 1998).
Hari kedua sampai hari ke empat setelah ETV absorbsi CSS oleh vili arakhnoid
sudah memadai. Dengan teknik ETV memungkinkan membuka sistim drainase dan kalau
vili arakhnoid masih berfungsi memerlukan waktu antara 2- 4 hari untuk kembalinya

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sistem drainage CSS yang fisiologis, dan pada hari ke 7 sistem drainase sudah boleh
dikatakan optimal (Nishiyama, dkk. 2003; Van Aalst, dkk. 2002).

Metode Penelitian
Penelitian ini merupakan penelitian experimental dengan rancangan “randomized
pre test post test control group design”. Besar sampel dihitung dengan rumus Pocock.
Dilakukan di SMF Bedah Saraf RSUP Sanglah Denpasar. Sebanyak 40 orang penderita
hidrosefalus obstruktif umur antara 1 – 72 bulan memenuhi kriteria inklusi penelitian.
Dari ke-40 orang penderita tersebut, sebanyak 20 orang (50%) dioperasi menggunakan
teknik ETV, sedangkan sisanya 20 orang (50%) menggunakan teknik VP shunting.

Hasil Dan Pembahasan


Penurunan kadar IL-1ß, IL-6 Dan NGF CSS
Rata-rata kadar IL-1β pra operasi VP shunting 17,50 ± 1,87pg/ml dan pada ETV
16,40 ± 3,52 pg/ml (p>0,05). Rata-rata penurunan kadar IL-1β pra-operasi dan pos-
operasi pada kelompok VP shunting 4,49±1,54 pg/ml, lebih rendah dibandingkan dengan
kelompok ETV 6,95 ± 3,54pg/ml (p<0,05).
Rata-rata kadar IL-6 pra-operasi VP shunting 36,22 ± 11,53 pg/ml dan pada ETV
41,28 ± 18,61 pg/ml (p>0,05). Rata-rata penurunan kadar IL-6 pra-operasi dan pos-
operasi pada kelompok VP shunting 1371±8,94 pg/ml, lebih rendah dibandingkan dengan
kelompok ETV 25,61 ± 14,28pg/ml (p<0,05).
Rata-rata kadar NGF pra-operasi VP shunting 72,21 ± 16,60pg/ml dan pada
ETV 72,40 ± 26,03pg/ml (p>0,05). Rata-rata penurunan kadar NGF pra-operasi dan pos-
operasi pada kelompok VP shunting 35,93±20,68pg/ml, lebih rendah dibandingkan
dengan kelompok ETV 47,51 ± 23,20pg/ml (p<0,01).
Berarti kadar sitokin proinflamasi pada Vp shunting pos-operasi masih lebih
tinggi dibandingkan ETV, ini berhubungan dengan adanya inplan yang terpasang
permanen. Sitokin pro inflamasi ini akan mengindusir neuroglia untuk mengekpresikan
NGF (Kosmann, dkk. 1997) terbukti dengan kadar NGF pos- operasi VP shunting masih
signifikan lebih tinggi dibandingkan dengan pada ETV.
Luaran Klinis
Hal in sangat erat hubungannya dengan luaran klinis 6 bulan pos-operasi, dimana
terjadi perbaikan klinis yang lebih baik secara signifikan pada kelompok ETV
dibandingkan dengan Kelompok VP shunting. Perbaikan luaran klinis yang dinilai adalah
diplopia (strabismus convergen), sunset phenomena, spastisitas otot, respon motorik, dan
respon verbal dimana p<0,05. Kecuali pada respon membuka mata dimana perbaikannya
tidak berbeda signifikan (p>0,05). Hasil ini sejalan dengan penelitian Anderson, dkk.
(2004).
Komplikasi
Pada kontrol setelah 6 bulan, ada revisi sebanyak 8 kasus (40%) pada kelompok
VP shunting , bahkan pada 1 kasus dilakukan 3 kali revisi selama 6 bulan. Terjadi infeksi
pada 3 kasus (15%). Tidak ada revisi maupun infeksi pada ETV.

Kebaharuan

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1. Temuan baru penelitian berupa validasi (dengan metode penelitian baku) terhadap
hasil teknik ETV pada HO, dimana sebelumnya tidak ada yang valid mengenai
perbaikan klinis.
2. Penelitian ini juga memberikan bukti baru yang valid mengenai perubahan
biomarkers (IL-1β, IL-6, dan NGF pada CSS) setelah pemakaian teknik ETV.
3. Penelitian ini memberikan bukti empirik mengenai keunggulan teknik ETV
dibandingkan dengan teknik VP shunting dimana teknik ETV memberikan respon
inflamasi yang lebih rendah dibandingkan dengan VP shunting

Simpulan
Berdasarkan hasil penelitian, analisis, dan pembahasan pada penelitian ini dapat
disimpulkan:
1. Rata-rata penurunan kadar IL-1β CSS operasi HO dengan ETV lebih tinggi
dibandingkan dengan rata-rata penurunan kadar IL-1β dengan teknik VP shunting. (p
< 0,05).
2. Rata-rata penurunan kadar IL-6 CSS pada operasi HO dengan metode ETV lebih
tinggi dibandingkan dengan operasi VP shunting, (p < 0,05).
3. Rata-rata penurunan kadar NGF CSS pada operasi HO dengan metode ETV lebih
tinggi dibandingkan dengan metode VP shunting, (p < 0,05).
4. Perbaikan luaran klinis pada operasi hidrosefalus obstruktif dengan metode ETV
lebih baik dibandingkan dengan metode VP shunting (p<0,05).

Saran
Berdasarkan pada simpulan penelitian dapat disarankan beberapa hal yang
berkaitan dengan perbandingan penerapan teknik operasi VP shunting dan ETV dalam
menangani hidrosefalus obstruktif.
1. Penanganan hidrosefalus obstruktif memang sebaiknya ditangani menggunakan
teknik ETV.
2. Pada penelitian ini hanya dievaluasi penurunan biomarker CSS IL-1β, IL-6, dan
NGF, maka untuk menunjang hasil ini perlu dilakukan evaluasi terhadap biomarker
CSS lainnya seperti: neuropeptida (somatostatin, peptida vasoaktif intestin);
neurotransmiter, metabolit serebral (laktat dan radikal bebas), enzim (enolase, dan
prostaglandin D sintase).
3. Perlu dilakukan penelitian mengenai long term outcome menyangkut kemampuan
kognitif dan afektif terhadap objek penelitian termasuk monitoring IQ dan
perkembangan kemampuan mereka di sekolah.

Kepustakaan
Andersson, S., Persson, E. K., Aring, E., Hård, A. L., Uvebrant, P., Dutton, G., and
Hellström, A. 2004. Abnormal Visual Functions in Children with Hydrocephalus.
Cerebrospinal Fluid Research. I (Suppl I): S9.
Bergsneider, M., Egnor, M.R., Johnston, M., Kranz, D., Madsen, J. R., McAllister II, J.P.,
Stewart, C., Walker, M.L., and Williams, M. A. 2006. What We Don’t (but
Should) Know about Hydrocephalus. J. Neurosurg, (3 Suppl Pediatrics) 104:157–
159.

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Decq, P., Le Guerinel, C., Palfi, S., Djindjian, M., Keravel, Y., and Nyuyen, J. P. 2000.
A New Device for Endoscopic Third Ventriculostomy. Technical Note, J.
Neurosurg, 93:509–512.
Gaab, M. R., and Schroeder, H. W. S.1998. Neuroendoscopic Approach to
Intraventricular Lesions. J. Neurosurg, 88:496–505.
Ishimaru, H., Takahashi, A., Ikarashi, Y., and Maruyama,Y. 1998. NGF Delays Rather
than Prevents the Cholinergic Terminal Damage and Delayed Neuronal Death in
the Hippocampus after Ischemia. Brain. Res, 789:194-200.
Kossmann, T., Stahel, P. F., Lenzlinger, P. M., Heinz, R., Rolf, W. D., Otmar, T.,
Guenter, S., and Morganti-Kossmann, M. C. 1997. Interleukin-8 Released into
the Cerebrospinal Fluid After Brain Injury is Associated with Blood-Brain
Barrier Dysfunction and Nerve Growth Factor Production. Journal of Cerebral
Blood Flow and Metabolism. 17: p. 280 – 289.
Maliawan, S., Golden, N., dan Mahadewa, T. G. 2006. Endoscopic 3rd Ventriculostomy
versus V-p Shunt in: Annual Scientific Meeting of Indonesian Society of
Neurological Surgeons in Conjunction with The World Federation of
Neurological Societies (WFNS). Nusa Dua, Bali – Indonesia, 42.
Maliawan, S., Asadul.A.I., Mahadewa. T. 2007. The Clinical Improvement between
Ventriculoperitoneal Shunt and Endoscopic third Ventriculostomy. World
Federation of Neurosurgical Societies, 13th Interim Meeting/The 12th Asian-
Australian Congress of Neurological Surgeons. November 18-22. EP18-6-1.
Nishiyama, K., Mori, H., and Tanaka, R. 2003. Changes in Cerebrospinal Fluid
Hydrodynamics Following Endoscopic Third Ventriculostomy for Shunt-
Dependent Noncommmunicating Hydrocephalus. J. Neurosurg, 98:1027-1031.
O’Brien, D.F., Hayhurst, C., Pizer, B., and Mallucci, C.L.2006. Outcomes in Patients
Undergoing Single-Trajectory Endoscopic Third Ventriculostomy and
Endoscopic Biopsy for Midline Tumors Presenting with Obstructive
Hydrocephalus. J. Neurosurg, (3 Suppl Pediatrics) 105:219–226.
Piatt, J. H. Jr., and Carlson, C. V. 1993. A Search for Determinants of Cerebrospinal
Fluid Shunt Survival: Retrospective Analysis of a 14 Year Institutional
Experience. Pediatr. Neurosurg, 19:233–242.
Piatt, J. H. Jr. 2003. About Hydrocephalus: For Parents and Patients. Drexel University
College of Medicine.
Platenkamp., M., Hanlo, P. W., Fischer, K., and Gooskens, R. H. J. M. 2007. Outcome in
pediatric hydrocephalus: a comparison between previously used outcome
measures and the Hydrocephalus Outcome Questionnaire. J Neurosurg (1 Suppl
Pediatrics). 107:26 - 31.
Sherman, C.S., Wensheng, Guo. 2007. A Mathematical Model of Survival in a Newly
Inserted Venticular Shunt. J. Neurosug. (6 Suppl. Pediatics) 107: 448 – 454.
Singh, D., Gupta, V., Goyal, A., Singh, H., Sinha, S., Singh, A., and Kumar, S. 2003.
Endoscopic Third Ventriculostomy in Obstructed Hydrocephalus. Neurol. India,
51:39-42.
Suny, 2003. Suny Upstete Medical University, Last Modified: March 26.

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ABSTRACT

COMPARISON OF ENDOSCOPIC THIRD VENTRICULOSTOMY AND


VENTRICULOPERITONEAL SHUNTING TECHNIQUES IN OBSTRUCTIVE
HYDROCEPHALUS: THE SIGNIFICANCE OF CLINICAL FINDING AND
CEREBROSPINAL FLUID INTERLEUKIN-1β, INTERLEUKIN-6, AND
NEURAL GROWTH FACTOR

Endoscopic Third Ventriculostomy (ETV) is an alternative procedure for


obstructive hydrocephalus (OH), with no device needed, cheaper, and with higher
successful rate. The purpose of this study is to evaluate which procedure is better, looking
specifically at “clinical findings” and cerebrospinal fluid (CSF) IL-1β, IL-6 and NGF of
ETV technique in comparison to standard VP shunting technique.
This was an experimental study, with the use of randomized pretest-posttest
control group design. All study activities were carried out at Central Hospital Denpasar.
Sample size was estimated by Pocock formula. Then K-S normality test, t-test group and
Mann Whitney test were conducted. The level of CSF IL-1β, IL-6 and NGF were
measured by ELISA.
The results of the study revealed that the reducing level of IL-1β with VP
shunting technique was 4.49 ± 1.54 pg/ml, and with ETV technique the reducing level of
IL-1β was approximately 6.95 ± 3.54 pg/ml. There was a significant difference between
those two IL-1β reducing levels with p < 0.05. The study had shown there were reducing
level of IL-6 with VP shunting technique 13.71 ± 8.94 pg/ ml and 25.61 ± 14.28 pg/ ml
with ETV technique. The difference was statistically significant with p < 0.05. For The
NGF levels in these two groups, there was a difference reduction of NGF between VP
shunting technique 35.93 ± 20.68 pg/ml, and ETV 47.51 ± 23.20 pg/ ml. This difference
was statistically significant with p < 0.05. In this study those CSF IL-1β, IL-6, and NGF
reduction with ETV technique were all statistically significant with p < 0.05 compared to
VP shunting technique. Clinical outcomes such as diplopia (strabismus convergent),
sunset phenomena, eyes opening, muscular spasticity and verbal response were evaluated
within 6 months period postoperative. The results of the study for those five parameters
were significantly better in the ETV technique group compared to VP shunting technique
with p < 0.05. Revision of VP shunting group after 6 months, were 40% while ETV none.
ETV was an alternative operation technique for obstructive hydrocephalus. ETV
technique had been proven, in this study, to have better results than the classical VP
shunting technique as far as clinical outcomes, and reduction of CSF IL-1β, IL-6, and
NGF. Endoscopic third ventriculostomy had a lower revision rate and lower cost, so that
ETV technique should be considered as the first choice for obstructive hydrocephalus
therapy.

Key word: ETV, VP shunting, experimental, biomarker, clinical outcomes.

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Introduction
Hydrocephalus is an intracranial pressure increase by the cerebrospinal fluid
(CSF) accumulation due to imbalance of the CSF production and absorption in the brain
ventricle system. (Piatt, 2003).
Hydrocephalus could be categorized into two groups i.e. Obstructive
Hydrocephalus (OH) and Communicants Hydrocephalus (CH). (Suny, 2003).
Hydrocephalus prevalence is high in the world; in Dutch it was reported about
0,65 per mil annually and in USA, about 2 per mil annually (Platenkamp, et al. 2007).
Meanwhile in Indonesia, reached 10 per mil (Maliawan, et al. 2006; 2007). The
Definitive treatment as a gold standard is VP shunting using silicon catheter fixed from
the brain ventricle to the peritoneum. The catheter is added with pressure regulated cleft
and the CSF diverses through one way system which is absorbed by the peritoneum to the
blood. Some complications might occur such as. shunt device disconnection, cut off, skin
or gut erosion by the device, over shunting, under shunting, proximal or distal blocked,
not properly placed, subdural hemorrhage, and infection. According to Shermann, et al.
(2007), the complication within the first month is 25-50 %, then, 4-5 % annually and each
time the complication occurs it means revision. Each VP shunting has a revision risk
about 3 times in 10 years after surgery (Piatt and Carlson, 1993).
The surgery using ETV technique principally is CSF diversion from the third
ventricle bottom to the basal cistern in the subarachnoid space posterior to the sella. In
ETV there is no device to be planted, by then the CSF flow is made as almost as
physiologic flow to be absorbed at arachnoid villi. ETV is only for OH. Various studies
have shown different successful rate from 40 - 100 % (Van-Gelder, et al. 2005;
Bergsneider, et al. 2006; O’Brien, et al. 2006). In OH cases below 2 years old with ETV
have a 70% clinical improvement and 63% radiological improvement, meanwhile for
greater than 2 years old have a 100% clinical improvement and 73% radiological
improvement (Singh, et al. 2003; Gaab and Schroeder, 1998; Decq, et al. 2000; Van
Aalst, et al. 2002). In Infantile hydrocephalus successful rate is 46% and 64-74% for the
age greater than 2 years old. In Indonesia, especially in Bali the main problem is the cost
of the device which is relatively expensive moreover there is a replacement on revision
surgery that will cost the family a lot.
The advantage of ETV technique is that the procedure is only once, cheaper and
simple, very ideal for Indonesian people. In Sanglah Hospital, Bali the ETV procedure
was done for the first time on 7th March 2005 and also for the first time in Indonesia.
Regarding these techniques, attention should be given seriously, in order to select the
safety method for clinicians to treat OH cases. Based on this thinking, the author tried to
determine the effectivity of the 2 techniques; the most effective one could be used for OH
cases or for the Gold Standard in the management of Obstructive Hydrocephalus.
For that reason a valid data is demanded about the clinical outcome of the 2
techniques, how much is the Cytokines Pro inflammation level (IL-1ß, Il-6 and NGF) in
the CSF. Hydrocephalus patient who has been treated with ETV or VP Shunting
techniques have both relieved from intracranial CSF pressure and oxygen reperfusion
period. These conditions will decrease Cytokines Pro inflammation release and CSF NGF
level. The decrease of NGF CSF could be used as a parameter for the brain neuronal
growth. (Ishimaru, et al.1998).

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The second up to the fourth day after ETV, CSF absorption by the arachnoidea
villi has been enough. By the ETV, it is possible to open the drainage system and if the
arachnoidea villi are still functioning, in the period of 2-4 days for the physiologic
drainage system for recovery, and on the day 7th optimal function is reached. (Nishiyama,
et al. 2003; Van Aalst, et al. 2002).

Research Methods
This research is an experimental one with randomized pre test post test control
group design. The sample size was counted by Pocock formula, 40 patients with
obstructive hydrocephalus, aged between 1-72 months fulfilled the research’s inclusion
criteria. From the 40 patients, 20 patients (50%) was operated by ETV technique, the
remain using VP shunting.

Results and Discussion


Decrease of IL-1ß, IL-6 level and CSF NGF
The mean of IL-1β level pre operatively in VP shunting is 17,50 ± 1,87pg/ml and in ETV
is 16,40 ± 3,52 pg/ml (p>0,05). The decrease mean level of IL-1β pre-operation and post-
operation in VP shunting group is 4,49±1,54 pg/ml, lower than ETV group: 6,95 ±
3,54pg/ml (p<0,05).
The mean of IL-6 level pre-operation in VP shunting is 36,22 ± 11,53 pg/ml and
in ETV group is 41,28 ± 18,61 pg/ml (p>0,05). The decrease mean level of IL-6 pre-
operation and post-operation in VP shunting group is 1371±8,94 pg/ml, coger than ETV
group: 25,61 ± 14,28pg/ml (p<0,05).
The mean of NGF level pre-operation in VP shunting is 72,21 ± 16,60pg/ml and
in ETV group is 72,40 ± 26,03pg/ml (p>0,05). The decrease mean level of NGF pre-
operation and post-operation in VP shunting group is 35,93±20,68pg/ml, lower than ETV
group: 47,51 ± 23,20pg/ml (p<0,01).
It is suggested that Cytokines pro inflammation level in VP shunting group post-
operation is higher than ETV group, related with a permanent device inplant. Cytokines
pro inflammation can induce neuroglia to express NGF (Kosmann, at al. 1997), and
proved that NGF level in VP shunting group is significantly higher than ETV group.
Clinical Outcome
These findings have a close relationship with the clinical outcome of 6 months
post-operation, in which the better clinical improvement is significantly in ETV group
compared to VP shunting group. Clinical improvement examined included diplopia
(strabismus convergen), sunset phenomena, muscle spasticity, motor respon, and verbal
respon with p<0,05. Except in open eye respon that was not significant (p>0,05), these
findings are in accordance with Anderson, et al. (2004).
Complication
In 6 months follow up, there were revision of 8 cases (40%) in VP shunting
group, even in 1 case 3 times revision have been done in 6 months. Infection occured in 3
cases (15%). No revision or infection in ETV group.

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Novelty
1. Novelty of this research is the validation (in a valid study method) of the ETV
result in obstructive hydrocephalus cases, which has never been validated before
in terms of clinical improvement.
2. This research has also provided a new valid facts of biomarkers (IL-1β, IL-6, and
CSF NGF) changes after ETV procedure.
3. This research contributed an empirical proof of ETV advantages compared to VP
shunting, in which ETV contributed lower inflammation respon than VP shunting

Conclusion
Based on the analysis and discussion in this research, it can be concluded that
1. The decrease mean level of IL-1β CSF in OH with ETV was higher than the
decrease mean level of IL-1β with VP shunting. (p < 0,05).
2. The decrease mean level of IL-6 CSF in OH with ETV was higher than VP
shunting. (p < 0,05).
3. The decrease mean level of NGF CSF in OH with ETV was higher than VP
shunting. (p < 0,05).
4. Clinical outcome improvements in obstructive hydrocephalus with ETV were
better than VP shunting (p<0,05).

Suggestion
Based on the conclusión, some suggestions could be made concerning some
issues related with the comparation of the application surgery techniques of VP shunting
and ETV in the management of obstructive hydrocephalus cases.
1. The management of obstructive hydrocephalus cases is recommended to be
treated with ETV technique.
2. Since in this research, the evaluation only concerns with the decrease of CSF
biomarker of IL-1β, IL-6, and NGF, therefore to support these findings evaluation
on other CSF biomarkers such as: neuropeptide (somatostatin, intestin vasoactive
peptide); neurotransmiter, cerebral metabolite (lactat and free radical), enzymes
(enolase, and prostaglandin D sintetase) are needed.
3. Long term clinical outcome study needs to be carried out regarding cognitive and
affective abilities to the research object including IQ monitoring and their ability
development at school.

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