<scp>MUNIX</scp> in children with spinal muscular atrophy: An unexpected journey

Neuwirth, Christoph; Weber, Markus

doi:10.1002/mus.27053

Cited by 3 publications

(4 citation statements)

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“…Unfortunately, there are no known modifiers that can be routinely tested to predict progression, which makes counselling families with SMA and 4 SMN2 copies diagnosed through a newborn screening program very difficult. In general, the value of electrophysiology, such as EMG to detect denervation/re-innervation, or the Motor Unit Number Index MUNIX, which has been shown to be feasible in children after the age of 5 in proximal muscles in older children [ 38 , 39 ], can be helpful in making treatment decisions. However, these are invasive procedures that are increasingly unavailable in paediatric treatment centres and are, therefore, more theoretical (also reflected in the fact that almost no electrophysiological data from our patient cohort are recorded in the registry).…”

Section: Discussionmentioning

confidence: 99%

5qSMA: standardised retrospective natural history assessment in 268 patients with four copies of SMN2

Vill,

Tacke,

König

et al. 2024

J Neurol

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Newborn screening for 5qSMA offers the potential for early, ideally pre-symptomatic, therapeutic intervention. However, limited data exist on the outcomes of individuals with 4 copies of SMN2, and there is no consensus within the SMA treatment community regarding early treatment initiation in this subgroup. To provide evidence-based insights into disease progression, we performed a retrospective analysis of 268 patients with 4 copies of SMN2 from the SMArtCARE registry in Germany, Austria and Switzerland. Inclusion criteria required comprehensive baseline data and diagnosis outside of newborn screening. Only data prior to initiation of disease-modifying treatment were included. The median age at disease onset was 3.0 years, with a mean of 6.4 years. Significantly, 55% of patients experienced symptoms before the age of 36 months. 3% never learned to sit unaided, a further 13% never gained the ability to walk independently and 33% of ambulatory patients lost this ability during the course of the disease. 43% developed scoliosis, 6.3% required non-invasive ventilation and 1.1% required tube feeding. In conclusion, our study, in line with previous observations, highlights the substantial phenotypic heterogeneity in SMA. Importantly, this study provides novel insights: the median age of disease onset in patients with 4 SMN2 copies typically occurs before school age, and in half of the patients even before the age of three years. These findings support a proactive approach, particularly early treatment initiation, in this subset of SMA patients diagnosed pre-symptomatically. However, it is important to recognize that the register will not include asymptomatic individuals.

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Section: Discussionmentioning

confidence: 99%

5qSMA: standardised retrospective natural history assessment in 268 patients with four copies of SMN2

Vill,

Tacke,

König

et al. 2024

J Neurol

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“…95 These techniques can detect differences at an asymptomatic stage of SMA, while a reduction of at least 50% of motor neurons results in significant differences measured in muscle strength. 97 Hence, these techniques are feasible as new biomarkers with a high sensitivity. [98][99][100] An important advantage of these techniques is the lower dependency of daily subjective variations compared to voluntary functional outcome measures.…”

Section: Non-voluntary Electrodiagnosticsmentioning

confidence: 99%

“…[98][99][100] An important advantage of these techniques is the lower dependency of daily subjective variations compared to voluntary functional outcome measures. 97 In future studies it would be interesting to combine electrodiagnostics, sEMG and 31 P-MRS when examining the differences between the existing number of motor units and dynamic maximal voluntary myofiber recruitment. This could ultimately help in assessing the opportunity to increase motor unit recruitment capacity using therapies with a training or pharmaceutical approach.…”

Section: Non-voluntary Electrodiagnosticsmentioning

confidence: 99%

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Skeletal muscle function in patients with spinal muscular atrophy

Habets¹

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ObjectiveTo investigate the availability of any motor unit reserve capacity during fatiguing endurance testing in patients with spinal muscular atrophy (SMA). MethodsWe recorded surface electromyography (sEMG) of various muscles of upper-and lower extremities of 70 patients with SMA types 2-4 and 19 healthy controls performing endurance shuttle tests (ESTs) of arm and legs. We quantitatively evaluated the development of fatigability and motor unit recruitment using time courses of median frequencies and amplitudes of sEMG signals. Linear mixed effect statistical models were used to evaluate group differences in median frequency and normalized amplitude at onset and its time course. ResultsNormalized sEMG amplitudes at onset of upper body ESTs were significantly higher in patients compared to controls, yet submaximal when related to maximal voluntary contractions, and showed an inverse correlation to SMA phenotype. sEMG median frequencies decreased and amplitudes increased in various muscles during execution of ESTs in patients and controls. ConclusionsDecreasing median frequencies and increasing amplitudes reveal motor unit reserve capacity in individual SMA patients during ESTs at submaximal performance intensities. SignificancePreserving, if not expanding motor unit reserve capacity may present a potential therapeutic target in clinical care to reduce fatigability in individual patients with SMA.

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Advancing understanding and treatment of spinal muscular atrophy with four SMN2 copies: a critical review

Rangwala,

Rangwala

2024

J Neurol

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MUNIX in children with spinal muscular atrophy: An unexpected journey

Abstract: We confirm that we have read the Journal's position on issues involved in ethical publication and affirm that this report is consistent with those guidelines.

Cited by 3 publications

References 13 publications

5qSMA: standardised retrospective natural history assessment in 268 patients with four copies of SMN2

5qSMA: standardised retrospective natural history assessment in 268 patients with four copies of SMN2

Skeletal muscle function in patients with spinal muscular atrophy

Advancing understanding and treatment of spinal muscular atrophy with four SMN2 copies: a critical review

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