Background The antisense-oligonucleotide (ASO) nusinersen has recently been approved as the first genetically modifying therapy for 5q-associated spinal muscular atrophy (SMA) based on randomized sham-controlled trials in infants and children. The efficacy in adults with long disease history and advanced disease status is still widely unknown; the same applies to specific expectations of adult SMA patients and to what extent they are met and may impact outcome measures. Methods In a longitudinal monocentric study in adult patients with SMA types 2-4, the Stanford Expectations of Treatment Scale (SETS) was assessed prior to and during nusinersen treatment. Treatment outcome was evaluated using patient-reported outcomes (PROs) as well as objectively quantifiable motor outcome measures. Results Adult SMA patients had high expectations of nusinersen treatment effectiveness regarding increase in muscle strength and disease stabilization. Via PROs, 75% stated improvements in muscle strength, endurance and independence under therapy which was in line with slight improvements in quantifiable motor scores during a ten month observation period. In contrast, patients only expressed few negative expectations which further decreased during therapy. Conclusions This study showed mainly positive treatment expectations and PROs in patients undergoing nusinersen treatment along with measurable functional improvement in adult SMA patients. Moreover, treatment expectations did not significantly influence outcome measures. Keywords Spinal muscular atrophy (SMA) • Patient-reported outcomes (PROs) • Stanford expectations of treatment scale (SETS) • Nusinersen • Antisense-oligonucleotide (ASO)

Background Efficacy of nusinersen in adult 5q-spinal muscular atrophy (SMA) patients regarding motor function has recently been demonstrated. However, additional outcome measures are needed to capture non-motor improvements. Fatigue is a common and disabling symptom in neurologic diseases, but little is known about its frequency, characteristics and associated factors in SMA. Objective To characterize fatigue in SMA patients receiving nusinersen, identify associated factors and evaluate fatigue as potential patient-reported outcome measure (PRO). Methods We assessed fatigue in adults with genetically confirmed 5q-SMA in a prospective longitudinal monocentric study using the Fatigue Severity Scale (FSS) and the Multidimensional Fatigue Inventory (MFI). Factors associated with fatigue including health-related quality of life (HRQOL) were evaluated. Results 75% of participants were abnormally fatigued with highest scores in the dimensions physical, followed by general fatigue and reduced activity. 53% agreed that fatigue was among their three most disabling symptoms. Reduced activity was reported more extensively by participants with ≥ 4 copies of the survival of motor neuron 2 gene and better motor function. General and mental fatigue correlated positively with age and disease duration. HRQOL was inversely correlated with physical fatigue, which was not associated with disease or participant characteristics. During 14 months of nusinersen treatment, fatigue measures remained mostly stable with a trend towards improvement in reduced activity, general and physical fatigue. Conclusion Fatigue is a frequent and relevant complaint in adult SMA patients. Fatigue should be taken into consideration as additional outcome measure, but needs further evaluation in a larger patient cohort over a longer observation period.

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease that causes progressive autonomy loss and need for care. This does not only affect patients themselves, but also the patients’ informal caregivers (CGs) in their health, personal and professional lives. The big efforts of this multi-center study were not only to evaluate the caregivers’ burden and to identify its predictors, but it also should provide a specific understanding of the needs of ALS patients’ CGs and fill the gap of knowledge on their personal and work lives. Using standardized questionnaires, primary data from patients and their main informal CGs (n = 249) were collected. Patients’ functional status and disease severity were evaluated using the Barthel Index, the revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R) and the King’s Stages for ALS. The caregivers’ burden was recorded by the Zarit Burden Interview (ZBI). Comorbid anxiety and depression of caregivers were assessed by the Hospital Anxiety and Depression Scale. Additionally, the EuroQol Five Dimension Five Level Scale evaluated their health-related quality of life. The caregivers’ burden was high (mean ZBI = 26/88, 0 = no burden, ≥24 = highly burdened) and correlated with patients’ functional status (rp = −0.555, p < 0.001, n = 242). It was influenced by the CGs’ own mental health issues due to caregiving (+11.36, 95% CI [6.84; 15.87], p < 0.001), patients’ wheelchair dependency (+9.30, 95% CI [5.94; 12.66], p < 0.001) and was interrelated with the CGs’ depression (rp = 0.627, p < 0.001, n = 234), anxiety (rp = 0.550, p < 0.001, n = 234), and poorer physical condition (rp = −0.362, p < 0.001, n = 237). Moreover, female CGs showed symptoms of anxiety more often, which also correlated with the patients’ impairment in daily routine (rs = −0.280, p < 0.001, n = 169). As increasing disease severity, along with decreasing autonomy, was the main predictor of caregiver burden and showed to create relevant (negative) implications on CGs’ lives, patient care and supportive therapies should address this issue. Moreover, in order to preserve the mental and physical health of the CGs, new concepts of care have to focus on both, on not only patients but also their CGs and gender-associated specific issues. As caregiving in ALS also significantly influences the socioeconomic status by restrictions in CGs’ work lives and income, and the main reported needs being lack of psychological support and a high bureaucracy, the situation of CGs needs more attention. Apart from their own multi-disciplinary medical and psychological care, more support in care and patient management issues is required.

Approval of nusinersen, an intrathecally administered antisense oligonucleotide, for the treatment of 5q-spinal muscular atrophy (SMA) marked the beginning of a new therapeutic era in neurological diseases. Changes in routine cerebrospinal fluid (CSF) parameters under nusinersen have only recently been described in adult SMA patients. We aimed to explore these findings in a real-world setting and to identify clinical and procedure-associated features that might impact CSF parameters. Routinely collected CSF parameters (leukocyte count, lactate, total protein, CSF/serum albumin quotient (QAlbumin), oligoclonal bands) of 28 adult SMA patients were examined for up to 22 months of nusinersen treatment. Total protein and QAlbumin values significantly increased in the first 10 months, independent of the administration procedure. By month 14, no further increases were detected. Two patients developed transient pleocytosis. In two cases, positive oligoclonal bands were found in the beginning and in four patients throughout the whole observation period. No clinical signs of inflammatory central nervous system disease were apparent. Our data confirm elevated CSF total protein and QAlbumin during nusinersen treatment. These alterations may be caused by both repeated lumbar punctures and the interval between procedures rather than by the medication itself. Generally, there were no severe alterations of CSF routine parameters. These results further underline the safety of nusinersen therapy.

Background: Nusinersen was the first approved disease-modifying therapy for all 5q-spinal muscular atrophy (SMA) patients regardless of age or disease severity. Its efficacy in adults has recently been demonstrated in a large cohort by motor outcome measures, which were only partially suitable to detect changes in very mildly or severely affected patients. Patient-reported outcome measures (PROs) have been suggested as a valuable addition. Here, we aimed to assess treatment satisfaction and investigate whether it may be a useful PRO to monitor SMA patients. Methods: We enrolled 91 mainly adult 5q-SMA patients treated with nusinersen in a national, multicenter, cross-sectional observational study. 21 patients underwent longitudinal follow up. Patients’ satisfaction with treatment in four dimensions (global, effectiveness, convenience, side effects) was assessed by the Treatment Satisfaction Questionnaire for Medication German version 1.4 (TSQM-1.4©) and related to clinical parameters, motor scores, and treatment duration. Results: More than 90% of SMA patients were consistently satisfied over a median treatment duration of 10 months. Highest mean scores were observed in the dimensions ‘side effects,’ ‘global satisfaction,’ and ‘effectiveness’ (93.5 ± 14.8 versus 73.1 ± 21.0 and 64.8 ± 20.6, respectively). Patients’ satisfaction with the convenience of treatment was considerably lower (43.6 ± 20.2). Interestingly, satisfaction with the effectiveness was higher in ambulatory ( p = 0.014) compared with non-ambulatory patients and directly correlated to motor outcome measures. Five non-ambulatory patients withdrew from therapy. All of them presented with a deterioration of motor outcome measures and reported dissatisfaction with treatment effectiveness and convenience. Conclusion: Most patients were satisfied with nusinersen treatment effectiveness. Less severely affected patients indicated higher satisfaction. The TSQM-1.4© helped to identify therapy non-responders, who mainly addressed dissatisfaction with effectiveness and convenience. We suggest introducing the TSQM-1.4© as an additional PRO in SMA into clinical practice.