The effect of nusinersen treatment on clinical and laboratory findings in spinal muscular atrophy (SMA) type 2-3 patients

OBJECTIVE: 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