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Abstrak :
Pendahuluan: Epilepsi merupakan salah satu kelainan neurologis terbanyak di dunia, kurang lebih 20-30% diantaranya merupakan epilepsi resistan obat. Salah satu penyebab epilepsi resistan obat adalah autoimun, yang diperantari antibodi saraf. Antibodi saraf yang paling sering ditemukan dan diteliti adalah antibodi anti N-Methyl-D-Aspartate (NMDAR). Diagnosis pasti epilepsi autoimun adalah ditemukannya antibodi saraf di serum atau cairan serebrospinal (CSS), namun saat ini ketersediaanya terbatas dan harganya cukup mahal di Indonesia. Skor Antibody Prevalence in Epilepsy and Encephalopathy 2 (APE2) dan Antibody Contributing to Focal Epilepsy Signs and Symptoms (ACES) merupakan dua piranti klinis yang dapat digunakan untuk menduga adanya antibodi saraf, namun belum ada penelitiannnya di Indonesia. Tujuan: Penelitian ini adalah uji diagnostik untuk menilai kemampuan APE2 dan ACES dalam menduga adanya antibodi saraf anti NMDAR di serum pasien epilepsi resisten obat. Metode: Pasien epilepsi resistan obat yang datang ke Poli Neurologi Anak Rumah Sakit Umum Pusat Nasional dr. Cipto Mangunkusumo Jakarta dan Rumah Sakit Umum Daerah dr. Soetomo Surabaya pada bulan Maret hingga Agustus 2023 dinilai menggunakan APE2 dan ACES lalu diperiksa serum antibodi anti NMDAR. Hasil: Didapatkan 90 subyek penelitian yang memenuhi kriteria inklusi dan eksklusi penelitian. Antibodi NMDAR serum ditemukan pada 10 dari mereka. Skor APE2 memiliki sensitivitas 60%, spesifisitas 82,5%, PPV 30%, NPV 94,3%, LR+ 3,43, dan LR- 0,48. Poin skor APE2 yang memiliki nilai bermakna adalah perubahan status mental (p 0,042) dan gejala prodormal sebelum kejang (p 0,005). Skor ACES memiliki sensitivitas 85,71% spesifisitas 72,22%, PPV 37,5%, NPV 96,3%, LR+ 3,08, dan LR- 0,198. Poin skor ACES yang memiliki nilai bermakna adalah gangguan kognitif (p 0,033) dan gangguan bicara (p 0,028). Pada kejang fokal, APE2 memiliki nilai sensitivitas, PPV, NPV dan LR+ yang lebih rendah namun spesifisitas dan LR- yang lebih tinggi dibandingkan dengan ACES. Kesimpulan: Skor APE2 kurang sensitif namun cukup spesifik dengan NPV yang tinggi. Skor ACES cukup sensitif dan spesifik dengan NPV yang tinggi. Keduanya dapat digunakan untuk skrining awal epilepsi terutama bila ada gejala perubahan status mental, gejala prodormal virus, gangguan kognitif dan gangguan bicara sebelum atau saat awal awitan kejang. Diperlukan penelitian lanjutan untuk menilai antibodi saraf lain, dengan pemeriksaan antibodi di CSS dan tidak terbatas pada epilepsi resisten obat saja serta yang awitan kejangnya dibawah 1 tahun.

Kata kunci: ACES, APE2, epilepsi autoimun, epilepsi resisten obat, NMDAR ......Epilepsy is one of the most common neurological disorders in the world, approximately 20-30% of which are drug-resistant epilepsy. One cause of drug-resistant epilepsy is autoimmune disease, mediated by neural antibodies. The most frequently found and studied neural antibody is the anti-N-Methyl-D-Aspartate (NMDAR) antibody. The definitive diagnosis of autoimmune epilepsy is the discovery of neural antibodies in serum or cerebrospinal fluid (CSF), but currently their availability is limited and the price is quite expensive in Indonesia. The Antibody Prevalence in Epilepsy and Encephalopathy 2 (APE2) score and Antibody Contributing to Focal Epilepsy Signs and Symptoms (ACES) are two clinical tools that can be used to suspect the presence of neural antibodies, but there has been no research in Indonesia. Purpose: This research is a diagnostic test to assess the ability of APE2 and ACES to predict the presence of anti-NMDAR neural antibodies in the serum of drug-resistant epilepsy patients. Methods: Drug-resistant epilepsy patients who seek treatment at the Pediatric Neurology Outpatient clinic at the National Central General Hospital, dr. Cipto Mangunkusumo Jakarta and the Regional General Hospital dr. Soetomo Surabaya from March to August 2023 were assessed using APE2 and ACES, then checked for serum anti NMDAR antibody. Results: There were 90 research subjects who met the research inclusion and exclusion criteria. Serum NMDAR antibodies were found in 10 of them. The APE2 score has a sensitivity of 60%, specificity of 82.5%, PPV of 30%, NPV of 94.3%, LR+ 3.43, and LR- 0.48. In this study, the APE2 score points that had significant values were changes in mental status (p 0.042) and prodromal symptoms before seizures (p 0.005). The ACES score has a sensitivity of 85.71%, a specificity of 72.22%, PPV 37.5%, NPV 96.3%, LR+ 3.08, and LR- 0.198. In this study, the ACES score points that had significant values were cognitive symptoms (p 0.033) and speech problem (p 0.028). In focal seizures, APE2 has lower sensitivity, PPV, NPV and LR+ values but higher specificity and LR- compared to ACES. The APE2 score is less sensitive but quite specific with a high NPV. The ACES score is quite sensitive and specific with a high NPV. Both can be used for initial epilepsy screening, especially if there are symptoms of changes in mental status, viral prodromal symptoms, cognitive symptoms and speech problem before or at the onset of seizures. Further research is needed to assess other neural antibodies, examining neural antibodies in CSF and also including those whose seizure onset is less than 1 year, not limiting to drug-resistant epilepsy only.

Abstrak :
Latar Belakang: Epilepsi resisten terhadap obat adalah salah satu permasalahan pada epilepsi sehingga terjadi kejang berulang dan diperlukan pengobatan polifarmasi obat anti epilepsi. Kedua kondisi ini menyebabkan semakin meningkatkan stres oksidatif yang merugikan bagi otak dalam menjalankan fungsi fisiologis, terutama pada penderita epilepsi. Tujuan dari penelitian ini untuk mengetahui peran pemberian vitamin C dan E dalam menurunkan stres oksidatif dan frekuensi kejang pada pasien epilepsi resisten obat. Metode: Penelitian dengan uji klinis acak tersamar ganda dengan plasebo, desain paralel dan dilakukan randomisasi blok. Subjek penelitan adalah pasien epilepsi resisten obat usia 1-18 tahun yang mendapat pengobatan rutin di RSUPN Dr. Cipto Mangunkusumo. Randomisasi dilakukan pada 100 subjek yang terbagi menjadi kelompok perlakuan dan plasebo. Subjek mendapatkan vitamin C dosis 100 mg/hari , vitamin E dosis <5 tahun 200 IU/hari, ≥5 tahun 400 IU/hari dan plasebo yang diberikan selama 8 minggu. Pemeriksaan malondialdehida dan penilaian frekuensi kejang dilakukan sebelum dan sesudah intervensi. Hasil penelitian: Sebanyak 100 orang subjek pasien epilepsi resisten obat berpartisipasi dalam penelitian ini. Pemantauan sampai akhir penelitian pada kelompok perlakuan 42 subjek dan kelompok plasebo 46 subjek. Kadar MDA sebelum diberikan intervensi tidak berbeda bermakna pada kelompok perlakuan dan plasebo (p=0,920). Kadar MDA sesudah intervensi tidak berbeda bermakna antara kelompok perlakuan dan plasebo (p=0,880). Kadar MDA sebelum dan sesudah perlakuan terdapat perbedaan bermakna pada kelompok perlakuan (p= <0,001) dan plasebo (p= 0,028). Perubahan kadar sebelum dan sesudah intervensi pada kedua kelompok tidak didapatkan perbedaan yang bermakna (p=0,181). Tidak terdapat hubungan yang bermakna perubahan kadar MDA dengan frekuensi kejang baik di kelompok perlakuan (p=0,967) dan plasebo (0,065). Penurunan frekuensi kejang didapatkan perbedaan yang bermakna (p<0,001). Simpulan: Pemberian vitamin C dan E dapat menurunkan frekuensi kejang pada pasien epilepsi resisten obat. ......Background: Drug-resistant epilepsy is one of the problems in epilepsy resulting in recurrent seizures and polypharmacy treatment of anti-epileptic drugs is needed. Both of these conditions lead to further increase in oxidative stress which is detrimental to the brain in carrying out its physiological functions, especially in people with epilepsy. The purpose of this study was to determine the role of vitamins C and E in reducing oxidative stress and seizure frequency in drug-resistant epilepsy patients. Methods: This study was a double-blind randomized clinical trial with a placebo, parallel design and block randomization. The research subjects were drug-resistant epilepsy patients aged 1-18 years who received routine treatment at RSUPN Dr. Cipto Mangunkusumo. Randomization was performed on 100 subjects which were divided into treatment and placebo groups. Subjects received a vitamin C dose of 100 mg/day, a vitamin E dose of <5 years 200 IU/day, ≥5 years 400 IU/day and a placebo given for 8 weeks. Examination of malondialdehyde and assessment of seizure frequency was carried out before and after the intervention. Results: A total of 100 subjects of drug-resistant epilepsy patients participated in this study. Monitoring until the end of the study in the treatment group of 42 subjects and the placebo group of 46 subjects. MDA levels before being given the intervention were not significantly different in the treatment and placebo groups (p=0.920). MDA levels after the intervention did not differ significantly between the treatment and placebo groups (p=0.880). There were significant differences in MDA levels before and after treatment in the treatment (p=<0.001) and placebo (p=0.028) groups. There was no significant difference in the changes in levels before and after the intervention in the two groups (p=0.181). There was no significant relationship between changes in MDA levels and seizure frequency in both. Conclusion: Administration of vitamins C and E can reduce the frequency of seizures in drug-resistant epilepsy patients.