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Background: This prospective study investigates the pattern of pareses in 5q-associated spinal muscular atrophy (SMA) to identify disease-specific characteristics and potential differences from amyotrophic lateral sclerosis (ALS) and spinobulbar muscular atrophy (SBMA). Detailed knowledge about pareses patterns in SMA facilitates differential diagnosis and supports therapeutic monitoring. Methods: Between January 2021, and June 2021, 66 SMA patients (59.1% male, aged 33.6 ± 15.2 years) were included in the study. Most patients had SMA type II (n = 28) or SMA type III (n = 28), seven patients had SMA type I, and three patients had SMA type IV. We analyzed the pattern of pareses using the UK Medical Research Council (MRC) scoring system. Results: In both, upper and lower limbs muscle weakness was less pronounced in distal (upper limbs: MRC median 3.0 (interquartile range 1.5–3.5); lower limbs: 1.5 (0.5–3.0)) compared to proximal muscle groups (upper limbs: 2.0 (1.5–2.6); p < 0.001; lower limbs: 0.5 (0.5–1.5); p < 0.001). Thenar muscles were stronger than other small hand muscles (3.0 (2.0–3.5) vs 3.0 (1.5–3.5); p = 0.004). Muscles had more strength in upper (2.3 (1.5–3.1)) compared to lower limbs (1.1 (0.5–2.3); p < 0.001) and in flexors compared to extensors. Conclusion: We identified a specific pattern of muscle paresis in SMA which is different from the pattern of paresis in ALS and SBMA. As a rule of thumb, the pattern of pareses is similar, but not identical to ALS in distal, but different in proximal muscle groups. [ABSTRACT FROM AUTHOR]

Objective: To determine the diagnostic and monitoring value of serum neurofilament light chain (NfL) in spinal muscular atrophy (SMA). Methods: We measured serum NfL in 46 SMA patients at baseline and over 14 months of treatment with the antisense-oligonucleotide (ASO) nusinersen using the ultrasensitive single molecule array (Simoa) technology. Serum NfL levels of SMA patients were compared to controls and related to cerebrospinal fluid (CSF) NfL, blood-CSF barrier function quantified by the albumin blood/CSF ratio (Qalb) and motor scores (Hammersmith Functional Motor Scale Expanded, HFMSE; Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised, ALSFRS-R). Results: Serum NfL levels of SMA patients were in the range of controls (p = 0.316) and did not correlate with CSF NfL (ρ = 0.302, p = 0.142) or Qalb (ρ = − 0.160, p = 0.293). During therapy, serum NfL levels were relatively stable with notable concentration changes in single SMA patients, however, within the control range. Higher NfL levels were associated with worse motor performance in SMA (baseline: HFMSE ρ = − 0.330, p = 0.025, ALSFRS-R ρ = − 0.403, p = 0.005; after 10 months: HFMSE ρ = − 0.525, p = 0.008, ALSFRS-R ρ = − 0.537, p = 0.007), but changes in motor scores did not correlate with changes in serum NfL. Conclusion: Diagnostic and monitoring performance of serum NfL measurement seems to differ between SMA subtypes. Unlike to SMA type 1, in adolescent and adult SMA type 2 and 3 patients, neurodegeneration is not reflected by increased NfL levels and short-term therapeutic effects cannot be observed. Long-term follow-up has to be performed to see if even low levels of NfL might be good prognostic markers. [ABSTRACT FROM AUTHOR]

Motor neuron diseases, such as spinal muscular atrophy (SMA) and amyotrophic lateral sclerosis (ALS), share several clinical similarities while differing substantially in etiology, disease onset and progression. Cognitive dysfunction, a clinically relevant non-motor feature in a substantial proportion of ALS patients, has been less frequently investigated in SMA. In this prospective multicenter cross-sectional study, cognitive function was assessed by the Edinburgh Cognitive (and Behavioural) ALS Screen (ECAS) and a German vocabulary test (Wortschatztest, WST) in 34 adult patients with SMA types 2–4 and in 34 patients with ALS. Demographic and clinical parameters were assessed to identify factors that potentially influence cognitive function. While SMA and ALS patients were comparable in the vocabulary test, on average, SMA patients performed better than ALS patients in the cognitive domains of memory, language and executive function. Better cognitive abilities in SMA patients seemed to be related to the early onset, rather than the extent or the duration, of their physical handicap. Future studies should focus on disease-specific cognitive functions in SMA. [ABSTRACT FROM AUTHOR]

Motor neuron diseases, such as spinal muscular atrophy (SMA) and amyotrophic lateral sclerosis (ALS), share several clinical similarities while differing substantially in etiology, disease onset and progression. Cognitive dysfunction, a clinically relevant non-motor feature in a substantial proportion of ALS patients, has been less frequently investigated in SMA. In this prospective multicenter cross-sectional study, cognitive function was assessed by the Edinburgh Cognitive (and Behavioural) ALS Screen (ECAS) and a German vocabulary test (Wortschatztest, WST) in 34 adult patients with SMA types 2-4 and in 34 patients with ALS. Demographic and clinical parameters were assessed to identify factors that potentially influence cognitive function. While SMA and ALS patients were comparable in the vocabulary test, on average, SMA patients performed better than ALS patients in the cognitive domains of memory, language and executive function. Better cognitive abilities in SMA patients seemed to be related to the early onset, rather than the extent or the duration, of their physical handicap. Future studies should focus on disease-specific cognitive functions in SMA.

With Nusinersen, a first causative treatment for 5q-associated spinal muscular atrophy (SMA) has been available in Europe since 2017. Real-world data from neuromuscular clinical centers in Germany increasingly show a therapeutic benefit of nusinersen also in adult SMA patients of both sexes: in many cases, relevant improvements in or at least a stabilization of motor functions are achieved, potentially leading to enhanced autonomy in activities of daily life and to improved quality of living. Even in patients with severe spinal deformities, intrathecal application is usually feasible and safe using imaging modalities. Regular systematic evaluation of the motor status with validated instruments is crucial for adequate monitoring of the therapeutic effects. The documentation in SMA registries enables systematic development of a database for further development of this novel treatment paradigm. Relevant aspects of this novel therapeutic principle were discussed at an experts conference in Frankfurt / Main in February 2019., Competing Interests: Der Beitrag entstand im Rahmen eines von Biogen unterstützten Expertenworkshops, in dem die Autoren beratend tätig waren.T. Hagenacker ist als Berater für Advisory Boards, sowie als Referent für Fortbildungsveranstaltungen und wissenschaftliche Veranstaltungen der Firma Biogen tätig. Außerdem hat er finanzielle Forschungsuntertützung von Biogen erhalten. M.C. Walter hat an Advisory boards der Firmen, Avexis, Biogen, Novartis, Roche, Santhera, Sarepta, PTC Therapeutics, Ultragenyx, Wave Sciences teilgenommen, hat Vortragshonorare von Novartis, Biogen, Ultragenyx, Santhera, PTC Therapeutics erhalten und war als Ad-Hoc-Beraterin für AskBio, Audentes Therapeutics, Biogen Pharma GmbH, Fulcrum Therapeutics, GLG Consult, Guidepoint Global, Gruenenthal Pharma, Novartis, PTC Therapeutics tätig.M. Weiler hat an wissenschaftlichen Veranstaltungen teilgenommen, die von der Firma Biogen gesponsort wurden. Er ist zudem als Berater für Advisory Boards sowie als Referent für Fortbildungsveranstaltungen der Firma Biogen tätig.A. Hermann ist als Berater für Advisory Boards der Firma Biogen und DESITIN tätig.C. Kamm hat an wissenschaftlichen Veranstaltungen teilgenommen, die von der Firma Biogen gesponsert wurden. Er ist zudem als Berater für Advisory Boards sowie als Referent für Fortbildungsveranstaltungen der Firma Biogen tätig.C.D. Wurster ist als Beraterin für Advisory Boards sowie als Referentin für Fortbildungsveranstaltungen der Firma Biogen tätig. Sie ist zudem als Beraterin der Firma Hoffmann-La Roche tätig.R. Günther hat an wissenschaftlichen Veranstaltungen teilgenommen, die von der Firma Biogen gesponsort wurden. Er ist zudem als Berater für Advisory Boards sowie als Referent für Fortbildungsveranstaltungen der Firma Biogen tätig.C. Kleinschnitz ist als Berater für Advisory Boards sowie als Referent für Fortbildungsveranstaltungen und wissenschaftliche Veranstaltungen der Firma Biogen, Novartis und Roche tätig., (© Georg Thieme Verlag KG Stuttgart · New York.)