Assessment of Bulbar Function in Adult Patients with 5q-SMA Type 2 and 3 under Treatment with Nusinersen

Brakemeier, Svenja; Stolte, Benjamin; Thimm, Andreas; Kizina, Kathrin; Totzeck, Andreas; Munoz-Rosales, Juan; Kleinschnitz, Christoph; Hagenacker, Tim

doi:10.3390/brainsci11091244

Cited by 16 publications

(13 citation statements)

References 35 publications

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“…Children and adults with SMA type 3 (Kugelberg-Welander disease) achieve the ability to walk independently during development and show sparse comorbidities such as scoliosis and respiratory muscle weakness of varying severity [ 2 ]. Bulbar motor dysfunction may be present in SMA type 2 and 3, while patients with SMA type 2 are more likely to be affected [ 4 ]. SMA type 4 represents the mildest form with late onset in adulthood, comprising less than 5% of all SMA cases [ 2 ].…”

Section: Introductionmentioning

confidence: 99%

Cognitive performance of adult patients with SMA before and after treatment initiation with nusinersen

et al. 2023

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Background Spinal muscular atrophy (SMA) is a genetic neuromuscular disease caused by mutations of the SMN1 gene. Deficient SMN protein causes irreversible degeneration of alpha motor neurons characterized by progressive muscle weakness and atrophy. Considering that SMA is a multi-systemic disorder and SMN protein was found to be expressed in cortical structures, the cognitive profile of adult patients with SMA has recently been of particular interest. With nusinersen, a novel, disease-modifying drug has been established, but its effects on neuropsychological functions have not been validated yet. Aim of this study was to investigate the cognitive profile of adult patients with SMA during treatment initiation with nusinersen and to reveal improvement or deterioration in cognitive performance. Methods This monocentric longitudinal study included 23 patients with SMA type 2 and 3. All patients were assessed with the Edinburgh Cognitive and Behavioral ALS Screen (ECAS) before and after 14 months of treatment initiation with nusinersen. Additionally, motor function was evaluated by Hammersmith Functional Motor Scale Expanded (HFMSE), Revised Upper Limb Module (RULM) and Amyotrophic Lateral Sclerosis Functional Rating Scale Revised (ALSFRS-R). Results Of the treatment-naive patients, only three were below the age- and education-matched cut-off for cognitive impairment in the ECAS total score. Significant differences between SMA type 2 and 3 were only detected in the domain of Language. After 14 months of treatment, patients showed significant improvement of absolute scores in all three ALS-specific domains, in the non-ALS-specific domain of Memory, in both subscores and in the ECAS total score. No associations were detected between cognitive and functional outcome measures. Conclusions In some adult patients with SMA abnormal cognitive performance in ALS-specific functions of the ECAS was evident. However, the presented results suggest no clinically significant cognitive changes during the observed treatment period with nusinersen.

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Section: Introductionmentioning

confidence: 99%

Cognitive performance of adult patients with SMA before and after treatment initiation with nusinersen

et al. 2023

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“…New disease-modifying treatment options call for objective and sensitive methods to identify motor improvement in adult SMA patients. In recent years, the evaluation of bulbar function gained more attention and increasing interest in research [ 7 , 16 , 17 , 26 , 41 ]. Measuring small changes in adult SMA patients is complex and the combined use of several outcome measures is recommended—particularly so for specific subgroups.…”

Section: Discussionmentioning

confidence: 99%

Objective measurement of oral function in adults with spinal muscular atrophy

Kruse

Shamai

Leflerovà

et al. 2023

Orphanet J Rare Dis

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Background Impairment of bulbar function in adult individuals with spinal muscular atrophy (SMA) usually is not assessed by established motor scores. Measurements of oral function including quantitative muscle and endurance tests are able to detect subtle changes. The aim of this study was to systematically evaluate the measurement of maximum bite force and endurance, maximum tongue pressure and endurance, as well as maximum mouth opening in adult individuals with SMA types 2 and 3. Methods Data from oral function tests in 43 individuals were analyzed. Differences in oral function between individuals with different SMA types and numbers of SMN2 copies were tested. Spearman´s rho correlations among oral function measures themselves as well as with established clinical outcome scales were analyzed. Results The absolute maximum measures of oral function (maximum bite force, maximum tongue pressure, maximum mouth opening) were able to discriminate between individuals with different SMA types, individuals with a different number of SMN2 copies and with different walking abilities. The pairwise correlations of the absolute maximum measures of oral function were fair to moderate in size; the same was true for their correlations with the established motor scores. All correlations assessing endurance measures of oral function were weaker and statistically insignificant. Conclusions Among the oral function tests maximum tongue pressure and maximum mouth opening are particulary promising as clinical and sensitive outcome measures for clinical trials. Oral function tests may supplement existing motor scores, in particular concerning specific questions about bulbar function or in severely affected non-ambulatory individuals where mild (treatment-related) changes would otherwise remain undetected. Trial registration DRKS, DRKS00015842. Registered 30 July 2019, https://drks.de/search/de/trial/DRKS00015842

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“…We used bulbar function items 1–3 of the Amyotrophic Lateral Sclerosis Functional Rating Scale Revised (b-ALSFRS-R) and the Sydney Swallow Questionnaire (SSQ) to assess bulbar function in this study, as published previously for patients treated with nusinersen [ 16 ]. Data were collected during regular follow-up of patients shortly before treatment initiation (T0) and at 4 months (T1) and 12 months (T2) after treatment initiation.…”

Section: Methodsmentioning

confidence: 99%

“…Bulbar dysfunction typically occurs in the early and advanced disease stages, mostly in SMA types 1 and 2 [ 13 – 15 ]. In a previous study, we evaluated bulbar function in adults with SMA under nusinersen and found no improvement but preservation over 14 months of therapy [ 16 ]. For risdiplam, pivotal studies have shown preservation of swallowing function in SMA infants with sustained oral feeding ability over 12 months, indicating a relevant effect of risdiplam on bulbar function in this patient group [ 17 ].…”

Section: Introductionmentioning

confidence: 99%

Risdiplam improves subjective swallowing quality in non-ambulatory adult patients with 5q-spinal muscular atrophy despite advanced motor impairment

Brakemeier,

Lipka,

Schlag

et al. 2024

J Neurol

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Background 5q-associated spinal muscular atrophy (SMA) is characterized by the progressive loss of motor neurons with consecutive weakness and atrophy of the limb, respiratory, and bulbar muscles. While trunk and limb motor function improve or stabilize in adults with SMA under nusinersen and risdiplam treatment, the efficacy on bulbar function in this age group of patients remains uncertain. However, it is important to assess bulbar dysfunction, which frequently occurs in the disease course and is associated with increased morbidity and mortality. Methods Bulbar function was evaluated prospectively in 25 non-ambulatory adults with type 2 and 3 SMA before and 4 and 12 months after risdiplam treatment initiation using the Sydney Swallow Questionnaire (SSQ) and the bulbar subscore of the Amyotrophic Lateral Sclerosis Functional Rating Scale Revised (b-ALSFRS-R). Extremity function was assessed using the Hammersmith Functional Motor Scale Expanded (HFMSE) and Revised Upper Limb Module (RULM). Results Subjective swallowing quality, measured with the SSQ, improved after 12 months of therapy with risdiplam. For the b-ALSFRS-R, a non-significant trend towards improvement was observed. The RULM score improved after 12 months of risdiplam therapy, but not the HFMSE score. HFMSE and RULM scores did not correlate with the SSQ but the b-ALSFRS-R score at baseline. Conclusions The improvement in subjective swallowing quality under risdiplam treatment, despite an advanced disease stage with severe motor deficits, strengthens the importance of a standardized bulbar assessment in addition to established motor scores. This may reveal relevant treatment effects and help individualize treatment decisions in the future.

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Assessment of Bulbar Function in Adult Patients with 5q-SMA Type 2 and 3 under Treatment with Nusinersen

Cited by 16 publications

References 35 publications

Cognitive performance of adult patients with SMA before and after treatment initiation with nusinersen

Cognitive performance of adult patients with SMA before and after treatment initiation with nusinersen

Objective measurement of oral function in adults with spinal muscular atrophy

Risdiplam improves subjective swallowing quality in non-ambulatory adult patients with 5q-spinal muscular atrophy despite advanced motor impairment

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