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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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