Spinal musküler atrofi tip 2-3(SMA) hastalarında nusinersen tedavisinin klinik ve laboratuvar bulguları üzerine olan etkisi
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Tarih
2023
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Necmettin Erbakan Üniversitesi Meram Tıp Fakültesi
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info:eu-repo/semantics/openAccess
Özet
Nusinersen tedavisi almak için başvuran Spinal Musküler Atrofi (SMA) Tip 2 ve Tip 3 hastaları ile belirli vizitlerde görüşme yapılarak, Nusinersen öncesinde ve ilaç dozları sırasında yaşamış oldukları tecrübeler, ilaç etki ve yan etkisinin araştırılması amaçlanmıştır. Çalışmanın sekonder amacı, T.C. Sağlık Bakanlığının Nusinersen tedavisi verilecek olan hastaların takibinde kullanılmasını önerdiği laboratuvar değerlerinin incelenmesi neticesinde, hastalarda oluşabilecek değişikliklerin kayıt altına alınmasıdır. Yöntem: Çalışmaya dâhil edilen hastalarla yapılan görüşmeler video ile kayıt altına alınmıştır. Hastalara ilaç öncesinde, 4 doz yükleme ve 5. doz idame tedavisi sonrası anket yöntemi ile hazırlanan standardize edilmiş sorular sorularak hasta ve yaşantısı hakkında bilgi edinilmiştir. Medical Research Council, Revised Upper Limb Modüle (RULM), Hammersmith Functional Motor Scale Expanded (HFMSE), 6 dakika yürüme testi ile hastaların motor fonksiyon ölçümleri yapılmıştır. Yan etkilerin değerlendirilmesi için kontrollerde rutin olarak bakılan hemogram, biyokimya, idrar analizi, beyin omurilik sıvısı biyokimya analizi, akciğer grafisi, kranial manyetik rezonans görüntüleme ve elektroensefalografi incelemesi yapılmıştır. Elde edilen veriler niteliksel kısımda fenomenolojik yöntemle, nicel kısımda ise Wilcoxon testi ile değerlendirilmiştir. Bulgular: Bu çalışmaya Necmettin Erbakan Üniversitesi Meram Tıp Fakültesi Nöroloji Polikliniği'ne Nusinersen tedavisi almak için başvuran 11 SMA hastası dâhil edildi. Hastaların %18,2'si (n=2) SMA Tip 2, %81,8'i (n=9) SMA Tip 3 tanılı, yaş ortalamaları 29,73±9,10 idi. Çalışmaya dâhil edilen hastaların ortalama tanı alma yaşları 9,09±5,95 idi. Tanı gecikme süresi ortalama 2,35±3,16 yıl olarak bulundu. Hastalık ile ilgili bilgiler çoğunlukla internet ve sosyal medya üzerinden (n=7, %63) sağlanırken, yatağa ve insanlara bağımlı olma hastaların en çok endişe edilen konuydu. (n=5, %45) Yetişkinlik dönemi tecrübelerinde eğitim alırken yaşadıkları sıkıntılar göze çarpmaktaydı. (n=8, %72) Hastalardan çoğu Nusinersen' den "çok beklentilerinin" olmadığını ifade etti. (n=4, %36) Bunu izleyen cevaplar ise "hayatımın daha konforlu olması" ve "enerji vermesi" idi. (n=3, %27) İlaçla ilgili yan etkiler nedeni ile 8 hasta korku taşımadığını ifade etti (n=8, %72). İlaçtan kazanımları konusunda ise en fazla "yürüme fonksiyonunda" iyileşme görülürken (n=8, %72), diğer etkiler kol hareketlerinde iyileşme (n=6,%54), "ayakta durma" (n=5, %45), "postür değişikliği" (n=4, %36), "yatakta dönme" (n=3, %27), "ağırlık kaldırma" (n=3, %27) oldu. Bedensel değişikliklerde en fazla görülen etki "enerji (n=9, %81)" dir. Niceliksel kısımda hastaların son ölçülen hemogram sayımlarında MCV değerleri ilk ölçümlerdeki değerlere göre istatistiksel olarak anlamlı yüksek bulundu (p=0,029). Diğer laboratuvar değerlerinde ölçümler arasında istatistiksel olarak anlamlı farklılık tespit edilmedi (p>0,05) HFMSE 1. ölçüm değerine göre 2. ve 3. ölçüm değerleri anlamlı yüksekti.(p=0,01, p= 0,027) 2. ölçüm ve 3. ölçüm değerleri istatistiksel olarak benzer saptandı (p>0,005) Sol üst ekstremite RULM 2. ölçüm 1. ölçüme göre anlamlı yüksek bulundu. (p=0,04) Hastaların toplam kas gücü değerlendirildiğinde 5. ve 6. ölçümlerde saptanan kas güçleri, 1. ölçümlerdeki kas güçlerine göre istatistiksel olarak anlamlı yüksek saptandı (p değerleri sırasıyla; p=0,005, p=0,008) Sonuç: Çalışmamızda SMA hastalığının sadece fiziksel sebeplere ek olarak hastalığın getirmiş olduğu yorgunluk, sosyal damgalanma, aileye olan fiziksel ve zihinsel bağımlılık gibi sebeplerle yaşam kalitesinin etkilendiği, hastaların eğitim ve mesleki faaliyetlerin aksadığı, sosyal hayatı daha pasif yaşamayı tercih ettikleri gösterilmiştir. Yaşamış oldukları sıkıntılara rağmen hayatlarındaki kısıtlamaları telafi etmeyi başarmışlar ve toplumsal hayatta yer edinebilmişlerdir. Hastaların tanı alma sürecinde yaşamış oldukları sıkıntılar, doktor ve hasta iletişimsizliği gibi nedenlerle hastalık ve tedavi yöntemleri hakkında sosyal medya kullanımının arttığı gösterilmiştir. Bu alanda hastaları anlayabilmek için daha fazla çalışmaya ihtiyaç vardır. Çalışmamız yetişkin dönemde de önemli etkiler meydana getirdiğinin gösterilmesi nedeniyle önemlidir. Nusinersen'in motor fonksiyonlarda iyileşmeye ek olarak bedensel ve ruhsal pozitif etkileri ile de sosyal ve mesleki alanlarda iyileşmeye sebep olduğu, hastaların yaşam kalitesini artırdığı gösterilmiştir. Hastaların ilaç almadan önce farklı fiziksel özelliklere sahip olması ve farklı etkiler görmesi sebebi ile ilaç etkisinin her hastanın kendi koşulları içerisinde değerlendirilmesi gerektiği gösterilmiştir. İlacın gün içindeki yorgunlukta azalma meydana getirmesi hastaların sosyal hayatlarını etkileyebilmesi sebebi ile Nusinersen'in yorgunluğa olan etkileri araştırılması gereken konular arasındadır. İncelenen laboratuvar parametreleri arasında dikkati çeken özellikler arasında MCV değerinde artış ve lenfosit düzeyinde % 9 oranında olan azalma olması idi. Bakılan diğer parametrelerden beyin omurilik sıvısı (BOS) incelemelerinde tüm hastalar arasında anlamlı farklılık yoktu. Bununla beraber SMA Tip 2 ile takip ettiğimiz bir hastamızda BOS proteini 1.dozda 55 iken 4 doz sonrasına yükselerek 77 oldu. Bakılan BOS mikroskobisinde eritrosit mevcut değildi. SMA Tip 3 ile takip edilen diğer hastamızda ise başlangıç BOS proteini 283, hemorajik zeminde 132 mm3/hücre %80 nötrofil, %20 lenfosit mevcuttu. 2. doz öncesi alınan BOS proteini 36 iken 6. doz öncesinde 47,1 idi. SMA Tip 3 ile takip ettiğimiz bir başka hastada ise başlangıç BOS proteini 68 iken 5.doz sonrası 56 olarak ölçüldü. Çalışmamız Türkiye'de SMA hastaları ile karma desen yöntemi kullanılarak yapılan ilk prospektif çalışma olması sebebi ile önemlidir. Anahtar kelimeler: Spinal musküler atrofi, niteliksel çalışma, fenomenolojik çalışma, Nusinersen, Hammersmith fonksiyonel motor skala indeksi, Revize edilmiş üst ekstremite modülü
The aim of this study was to interview the Spinal Muscular Atrophy (SMA) Type 2 and Type 3 patients who applied for Nusinersen treatment at certain visits, to investigate their experiences before and during the drug doses, drug effects and side effects. The second aim that record the changes that may occur in the patients as a result of the examination of the laboratory values that it recommends by Turkish Republic Ministry of Health to be used in the follow-up of the patients who will be treated with Nusinersen. METHODS: Interviews with the patients included in the study were video-recorded. Information about the patient and his life was obtained by asking standardized questions prepared by the questionnaire method before the drug, after 4 doses of loading and after the 5th dose of maintenance therapy. Motor function measurements of the patients were made by Medical Research Council, Revised Upper Limb Modulated (RULM), Hammersmith Functional Motor Scale Expanded (HFMSE), 6-minute walking test. In order to evaluate the side effects, routine hemogram, biochemistry, urine analysis, cerebrospinal fluid biochemistry analysis, chest X-ray, cranial magnetic resonance imaging and electroencephalography examination were performed. The data obtained were evaluated with the phenomenological method in the qualitative part and with the Wilcoxon test in the quantitative part. RESULTS: 11 SMA patients who applied to Necmettin Erbakan University Meram Medical Faculty Neurology Outpatient Clinic to receive Nusinersen treatment were included in this study. 18.2% (n=2) of the patients were diagnosed with SMA Type 2, 81.8% (n=9) were diagnosed with SMA Type 3, and their mean age was 29.73±9.10 years. The mean age at diagnosis of the patients included in the study was 9.09±5.95. The mean delay in diagnosis was found to be 2.35±3.16 years. While information about the disease was mostly provided via the internet and social media (n=7, 63%), being dependent on beds and people was the most worrying issue for the patients. (n=5, 45%) In their adulthood experience, the difficulties they experienced while receiving education were striking. (n=8, 72%) Most of the patients stated that they did not have "high expectations" from Nusinersen. (n=4, 36%) The answers that followed were "making my life more comfortable" and "giving energy". (n=3, 27%) Eight patients stated that they were not afraid of drug-related side effects (n=8, 72%). In terms of drug gains, the most improvement was seen in "gait function" (n=8, 72%), while other effects were improved in arm movements (n=6, 54%), "standing" (n=5, 45%), "posture change" (n=4, 36%), "turning in bed" (n=3, 27%), "weight lifting" (n=3, 27%). The most common effect on physical changes is "energy (n=9, 81%)". In the quantitative part, MCV values in the last measured hemogram counts of the patients were found to be statistically significantly higher than the values in the first measurements (p=0.029). No statistically significant difference was found between the measurements in other laboratory values (p>0.05) The second and third measurement values were significantly higher than the 1st measurement value of the HFMSE. (p=0.01, p= 0.027) The second and third measurement values were found to be statistically similar (p>0.005) Left upper extremity RULM 2nd measurement was found to be significantly higher than the 1st measurement. (p=0.04) When the total muscle strength of the patients was evaluated, the muscle strengths detected in the 5th and 6th measurements were found to be statistically significantly higher than the muscle strengths in the 1st measurements (p values, respectively; p=0.005, p=0.008). CONCLUSION: In our study, it has been shown that the quality of life of SMA disease is affected by reasons such as fatigue, social stigma, physical and mental dependence on the family, in addition to physical reasons, patients' education and professional activities are disrupted, and they prefer to live their social life more passively. Despite the difficulties they experienced, they managed to compensate for the restrictions in their lives and were able to take a place in social life. It has been shown that the use of social media about the disease and treatment methods has increased due to the problems experienced by the patients during the diagnosis process and the lack of communication between the doctor and the patient. More studies are needed to understand patients in this area. Our study is important because it has been shown that it has significant effects in adulthood as well. In addition to improving motor functions, Nusinersen has been shown to improve social and occupational areas with its positive physical and mental effects, and increase the quality of life of patients. It has been shown that the effect of the drug should be evaluated within the conditions of each patient, since patients have different physical characteristics and experience different effects before taking the drug. The effects of Nusinersen on fatigue are among the subjects that need to be investigated, since the drug reduces fatigue during the day and can affect the social lives of patients. When the laboratory parameters examined, the remarkable features were an increase in the MCV value and a 9% decrease in the lymphocyte level. There was no significant difference between all patients in the cerebrospinal fluid (CSF) examinations of other parameters. However, in a patient we followed up with SMA Type 2, the CSF protein was 55 at the first dose and increased to 77 after 4 doses. There was no erythrocyte in the CSF microscopy. In our other patient who was followed up with SMA Type 3, initial CSF protein was 283 and hemorrhagic background had 132 mm3/cell 80% neutrophils and 20% lymphocytes. CSF protein taken before the 2nd dose was 36, while it was 47.1 before the 6th dose. In another patient we followed up with SMA Type 3, the initial CSF protein was 68, while it was 56 after the 5th dose. Our study is important because it is the first prospective study using mixed design method with SMA patients in Turkey. KEYWORDS: Spinal muscular atrophy, qualitative study, phenomenological study, Nusinersen, Hammersmith functional motor scale index, Revised upper limb module
The aim of this study was to interview the Spinal Muscular Atrophy (SMA) Type 2 and Type 3 patients who applied for Nusinersen treatment at certain visits, to investigate their experiences before and during the drug doses, drug effects and side effects. The second aim that record the changes that may occur in the patients as a result of the examination of the laboratory values that it recommends by Turkish Republic Ministry of Health to be used in the follow-up of the patients who will be treated with Nusinersen. METHODS: Interviews with the patients included in the study were video-recorded. Information about the patient and his life was obtained by asking standardized questions prepared by the questionnaire method before the drug, after 4 doses of loading and after the 5th dose of maintenance therapy. Motor function measurements of the patients were made by Medical Research Council, Revised Upper Limb Modulated (RULM), Hammersmith Functional Motor Scale Expanded (HFMSE), 6-minute walking test. In order to evaluate the side effects, routine hemogram, biochemistry, urine analysis, cerebrospinal fluid biochemistry analysis, chest X-ray, cranial magnetic resonance imaging and electroencephalography examination were performed. The data obtained were evaluated with the phenomenological method in the qualitative part and with the Wilcoxon test in the quantitative part. RESULTS: 11 SMA patients who applied to Necmettin Erbakan University Meram Medical Faculty Neurology Outpatient Clinic to receive Nusinersen treatment were included in this study. 18.2% (n=2) of the patients were diagnosed with SMA Type 2, 81.8% (n=9) were diagnosed with SMA Type 3, and their mean age was 29.73±9.10 years. The mean age at diagnosis of the patients included in the study was 9.09±5.95. The mean delay in diagnosis was found to be 2.35±3.16 years. While information about the disease was mostly provided via the internet and social media (n=7, 63%), being dependent on beds and people was the most worrying issue for the patients. (n=5, 45%) In their adulthood experience, the difficulties they experienced while receiving education were striking. (n=8, 72%) Most of the patients stated that they did not have "high expectations" from Nusinersen. (n=4, 36%) The answers that followed were "making my life more comfortable" and "giving energy". (n=3, 27%) Eight patients stated that they were not afraid of drug-related side effects (n=8, 72%). In terms of drug gains, the most improvement was seen in "gait function" (n=8, 72%), while other effects were improved in arm movements (n=6, 54%), "standing" (n=5, 45%), "posture change" (n=4, 36%), "turning in bed" (n=3, 27%), "weight lifting" (n=3, 27%). The most common effect on physical changes is "energy (n=9, 81%)". In the quantitative part, MCV values in the last measured hemogram counts of the patients were found to be statistically significantly higher than the values in the first measurements (p=0.029). No statistically significant difference was found between the measurements in other laboratory values (p>0.05) The second and third measurement values were significantly higher than the 1st measurement value of the HFMSE. (p=0.01, p= 0.027) The second and third measurement values were found to be statistically similar (p>0.005) Left upper extremity RULM 2nd measurement was found to be significantly higher than the 1st measurement. (p=0.04) When the total muscle strength of the patients was evaluated, the muscle strengths detected in the 5th and 6th measurements were found to be statistically significantly higher than the muscle strengths in the 1st measurements (p values, respectively; p=0.005, p=0.008). CONCLUSION: In our study, it has been shown that the quality of life of SMA disease is affected by reasons such as fatigue, social stigma, physical and mental dependence on the family, in addition to physical reasons, patients' education and professional activities are disrupted, and they prefer to live their social life more passively. Despite the difficulties they experienced, they managed to compensate for the restrictions in their lives and were able to take a place in social life. It has been shown that the use of social media about the disease and treatment methods has increased due to the problems experienced by the patients during the diagnosis process and the lack of communication between the doctor and the patient. More studies are needed to understand patients in this area. Our study is important because it has been shown that it has significant effects in adulthood as well. In addition to improving motor functions, Nusinersen has been shown to improve social and occupational areas with its positive physical and mental effects, and increase the quality of life of patients. It has been shown that the effect of the drug should be evaluated within the conditions of each patient, since patients have different physical characteristics and experience different effects before taking the drug. The effects of Nusinersen on fatigue are among the subjects that need to be investigated, since the drug reduces fatigue during the day and can affect the social lives of patients. When the laboratory parameters examined, the remarkable features were an increase in the MCV value and a 9% decrease in the lymphocyte level. There was no significant difference between all patients in the cerebrospinal fluid (CSF) examinations of other parameters. However, in a patient we followed up with SMA Type 2, the CSF protein was 55 at the first dose and increased to 77 after 4 doses. There was no erythrocyte in the CSF microscopy. In our other patient who was followed up with SMA Type 3, initial CSF protein was 283 and hemorrhagic background had 132 mm3/cell 80% neutrophils and 20% lymphocytes. CSF protein taken before the 2nd dose was 36, while it was 47.1 before the 6th dose. In another patient we followed up with SMA Type 3, the initial CSF protein was 68, while it was 56 after the 5th dose. Our study is important because it is the first prospective study using mixed design method with SMA patients in Turkey. KEYWORDS: Spinal muscular atrophy, qualitative study, phenomenological study, Nusinersen, Hammersmith functional motor scale index, Revised upper limb module
Açıklama
Anahtar Kelimeler
Spinal musküler atrofi, Niteliksel çalışma, Fenomenolojik çalışma, Nusinersen, Hammersmith fonksiyonel motor skala indeksi, Revize edilmiş üst ekstremite modülü, Spinal muscular atrophy, Qualitative study, Phenomenological study, Nusinersen, Hammersmith functional motor scale index, Revised upper limb module
Kaynak
WoS Q Değeri
Scopus Q Değeri
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Künye
Ataman. Ş. (2023). Spinal musküler atrofi tip 2-3(SMA) hastalarında nusinersen tedavisinin klinik ve laboratuvar bulguları üzerine olan etkisi. (Yayınlanmamış tıpta uzmanlık tezi) Necmettin Erbakan Üniversitesi, Meram Tıp Fakültesi Dahili Tıp Bilimleri Bölümü Nöroloji Anabilim Dalı, Konya.
