Correlation Between Maximal Tongue Pressure and Swallowing Function in Spinal and Bulbar Muscular Atrophy

Background: Spinal and bulbar muscular atrophy (SBMA) is an X-lined motor neuron disease characterized by progressive muscle weakness, bulbar palsy, and dysphagia. Dysphagia is associated with tongue weakness, which is a common manifestation of SBMA. This study aimed to investigate the correlations between tongue pressure and dysphagia in patients with SBMA.Materials and Methods: Thirty-nine genetically confirmed SBMA patients underwent a videofluoroscopic swallowing study (VFSS) and tongue pressure assessment. Then, we analyzed the maximal tongue pressure (MTP), oral transit time, penetration-aspiration scale (PAS), videofluoroscopic dysphagia scale (VDS), amyotrophic lateral sclerosis functional rating scale-revised (ALSFRS-R), and 6-min walk test (6MWT). Pearson and Spearman correlation coefficients were calculated to analyze the association of the MTP with clinical, swallowing, and functional parameters.Results: In the correlation analysis, MTP was negatively correlated with disease duration (r = −0.396, p = 0.013) and VDS (r = −0.426, p = 0.007), and positively correlated with ALSFRS-R (r = 0.483, p = 0.002) and 6MWT (r = 0.396, p = 0.013). The bulbar (r = 0.367, p = 0.022) and gross motor (r = 0.486, p = 0.002) domains of the ALSFRS-R were correlated with MTP.Conclusion: Tongue pressure assessment can be used as a safe and easy tool to assess swallowing function in SBMA patients. Moreover, MTP reflects functional states, including activities of daily living and gait performance, showing it to be a potential biomarker for physical performance in SBMA.

Download Full-text

Longitudinal Changes of Tongue Thickness and Tongue Pressure in Neuromuscular Disorders

BMC Neurology ◽

10.1186/s12883-021-02225-5 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

George Umemoto ◽

Shinsuke Fujioka ◽

Hajime Arahata ◽

Nobutaka Sakae ◽

Naokazu Sasagasako ◽

...

Keyword(s):

Neuromuscular Disorders ◽

The Other ◽

Tongue Pressure ◽

Swallowing Function ◽

Longitudinal Changes ◽

Swallowing Dysfunction ◽

The Relationship ◽

Lateral Sclerosis

Abstract Background Swallowing dysfunction is related to major cause of adverse events and an indicator of shorter survival among patients with neuromuscular disorders (NMD). It is critical to assess the swallowing function during disease progression, however, there are limited tools that can easily evaluate swallowing function without using videofluoroscopic or videoendoscopic examination. Here, we evaluated the longitudinal changes in tongue thickness (TT) and maximum tongue pressure (MTP) among patients with amyotrophic lateral sclerosis (ALS), myotonic dystrophy type 1 (DM1), and Duchenne muscular dystrophy (DMD). Methods Between 2010 and 2020, TT and MTP were measured from 21 ALS, 30 DM1, and 14 DMD patients (mean ages of 66.9, 44.5, and 21.4 years, respectively) at intervals of more than half a year. TT was measured, by ultrasonography, as the distance from the mylohyoid muscle raphe to the tongue dorsum, and MTP was determined by measuring the maximum compression on a small balloon when pressing the tongue against the palate. Then we examined the relationship between these evaluations and patient background and swallowing function. Results Mean follow-up periods were 24.0 months in the ALS group, 47.2 months in the DM1group, and 61.1 months in the DMD group. The DMD group demonstrated larger first TT than the other groups, while the DM1 group had lower first MTP than the ALS group. The ALS group showed a greater average monthly reduction in mean TT than the DM1 group and greater monthly reductions in mean body weight (BW) and MTP than the other groups. Significant differences between the first and last BW, TT, and MTP measures were found only in the ALS group. Conclusions This study suggests that ALS is associated with more rapid degeneration of tongue function over several years compared to DMD and DM1.

Download Full-text

A Retrospective Cross-Sectional Analyses of Swallowing and Tongue Functions in Maxillectomy Patients

10.21203/rs.3.rs-159878/v1 ◽

2021 ◽

Author(s):

Yoichiro Ogino ◽

Natsue Fujikawa ◽

Sayuri Koga ◽

Ryoji Moroi ◽

Kiyoshi Koyano

Keyword(s):

Soft Palate ◽

Assessment Tool ◽

Correlation Coefficients ◽

Tongue Pressure ◽

Continuous Variables ◽

Swallowing Function ◽

Cross Sectional ◽

Oral Dryness ◽

History Of ◽

Oral Diadochokinesis

Abstract Purpose To investigate the profiles of swallowing and tongue functions, and to identify factors influencing swallowing in maxillectomy patients. Methods Maxillectomy patients whose swallowing function defined by Eating Assessment Tool (EAT-10) score and tongue functions (oral diadochokinesis: ODK, maximum tongue pressure: MTP) with or without maxillofacial prostheses had been evaluated were enrolled in this study. The effects of the history of radiotherapy or soft palate resection on swallowing function were evaluated. The effect of radiotherapy on oral dryness was also evaluated. To examine correlations of swallowing function with continuous variables, Spearman correlation coefficients were calculated. Results A total of 47 maxillectomy patients (23 males and 24 females, median age:71 [IQR: 63–76]) were registered. The median value of EAT-10 scores was 3 [IQR: 0–14]. Patients with the history of radiotherapy, but not with soft palate resection, showed significantly declined swallowing function. ODK and MTP of patients wearing maxillofacial prostheses were significantly improved. No significant effect of radiotherapy on oral dryness was found. A significant correlation was found between EAT-10 score and MTP (P = 0.04). Conclusions Swallowing function in maxillectomy patients was relatively impaired and the patients with the history of radiotherapy showed lower swallowing function. Maxillofacial prostheses could contribute to the improvement of MTP and ODK (/ta/). MTP may play a crucial role in swallowing in maxillectomy patients.

Download Full-text

Errata: Measuring Disease Severity in Duchenne and Becker Muscular Dystrophy

Journal of Methods and Measurement in the Social Sciences ◽

10.2458/v1i2.12366 ◽

2011 ◽

Vol 1 (2) ◽

Author(s):

Melinda F. Davis ◽

Katalin H. Scherer ◽

Timothy M. Miller ◽

F. John Meaney

Keyword(s):

Amyotrophic Lateral Sclerosis ◽

Muscular Dystrophy ◽

Disease Severity ◽

Muscle Weakness ◽

Respiratory Function ◽

Rating Scale ◽

Becker Muscular Dystrophy ◽

Progressive Muscle Weakness ◽

Lateral Sclerosis ◽

Disease Specific

Reports an error in Davis et al. (2010). The functional motor scale used in Davis et al. (2010) was the EK (Egen Klassifikation) Scale, rather than the Amyotrophic Lateral Sclerosis Functional Rating Scale (Steffensen et al., 2002; Cedarbaum & Stambler, 1997). Both scales are 10-item, disease-specific measures that assess mobility and respiratory function in individuals with progressive muscle weakness. This error does not change the conclusions. DOI:10.2458/azu_jmmss_v1i2_davis

Download Full-text

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

Brain Sciences ◽

10.3390/brainsci11091244 ◽

2021 ◽

Vol 11 (9) ◽

pp. 1244

Author(s):

Svenja Brakemeier ◽

Benjamin Stolte ◽

Andreas Thimm ◽

Kathrin Kizina ◽

Andreas Totzeck ◽

...

Keyword(s):

Antisense Oligonucleotide ◽

Treatment Initiation ◽

Rating Scale ◽

Muscular Atrophy ◽

Therapeutic Effects ◽

Measurement Instruments ◽

Sydney Swallow Questionnaire ◽

Bulbar Dysfunction ◽

Lateral Sclerosis

The antisense oligonucleotide nusinersen has been shown to improve trunk and limb motor function in patients with spinal muscular atrophy (SMA). Bulbar dysfunction, which is regularly present in SMA, is not captured by standard motor scores, and validated measurement instruments to assess it have not yet been established. Data on whether and how bulbar function changes under gene-based therapies in adult SMA patients are also unavailable. Here, we present data on the course of bulbar dysfunction assessed prospectively before nusinersen treatment initiation and 6 and 14 months later in 23 adult SMA patients using the Sydney Swallow Questionnaire (SSQ) and the bulbar subscore of the Amyotrophic Lateral Sclerosis Functional Rating Scale Revised (ALSFRS-R). While no improvement in bulbar scores was observed under treatment with nusinersen, the absence of a decline still implies a therapeutic effect of nusinersen on bulbar dysfunction. The results of this study aim to contribute to a standardized assessment of bulbar function in adult SMA patients, which may show therapeutic effects of gene-based therapies that are not evident from standard motor scores.

Download Full-text

Treatment with Creatine Monohydrate in Spinal and Bulbar Muscular Atrophy: Protocol for a Randomized, Double-Blind, Placebo-Controlled Trial (Preprint)

10.2196/preprints.8655 ◽

2017 ◽

Author(s):

Yasuhiro Hijikata ◽

Masahisa Katsuno ◽

Keisuke Suzuki ◽

Atsushi Hashizume ◽

Amane Araki ◽

...

Keyword(s):

Skeletal Muscle ◽

Clinical Trial ◽

Skeletal Muscles ◽

Rating Scale ◽

Muscular Atrophy ◽

Creatine Monohydrate ◽

Tongue Pressure ◽

Double Blind ◽

Maximum Voluntary Isometric Contraction ◽

Double Blind Placebo

BACKGROUND Although spinal and bulbar muscular atrophy (SBMA) has been classified as a motor neuron disease, several reports have indicated the primary involvement of skeletal muscle in the pathogenesis of this devastating disease. Recent studies reported decreased intramuscular creatine levels in skeletal muscles in both patients with SBMA and transgenic mouse models of SBMA, which appears to contribute to muscle weakness. OBJECTIVE The present study aimed to examine the efficacy and safety of oral creatine supplementation to improve motor function in patients with SBMA. METHODS A randomized, double-blind, placebo-controlled, three-armed clinical trial was conducted to assess the safety and efficacy of creatine therapy in patients with SBMA. Patients with SBMA eligible for this study were assigned randomly in a 1:1:1 ratio to each group of placebo, 10 g, or 15 g daily dose of creatine monohydrate in a double-blind fashion. Participants took creatine or placebo orally 3 times a day for 8 weeks. Outcome measurements were results of neurological assessments, examinations, and questionnaires collected at baseline and at weeks 4, 8, and 16 after a washout period. The primary endpoint was the change in handgrip strength values from baseline to week 8. The secondary endpoints included the following: results of maximum voluntary isometric contraction tests of extremities; tongue pressure; results of the 15-foot timed walk test and the rise from bed test; modified quantitative myasthenia gravis score; respiratory function test results; activities of daily living assessed with the Revised Amyotrophic Lateral Sclerosis Functional Rating Scale and the Spinal and Bulbar Muscular Atrophy Functional Rating Scale; skeletal muscle mass measured with dual-energy X-ray absorptiometry; urinary 8-hydroxydeoxyguanosine levels; and questionnaires examining the quality of life, swallowing function, and fatigue. RESULTS Participant enrollment in the trial started from June 2014 and follow-up was completed in July 2015. The study is currently being analyzed. CONCLUSIONS This is the first clinical trial evaluating creatine therapy in SBMA. Given that creatine serves as an energy source in skeletal muscles, recovery of intramuscular creatine concentration is expected to improve muscle strength. CLINICALTRIAL University Hospital Medical Information Network Clinical Trials Registry UMIN000012503; https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000014611 (Archived by WebCite at http://www.webcitation.org/6xOlbPkg3).

Download Full-text

Nusinersen in adult patients with 5q spinal muscular atrophy: a multicenter observational cohorts study

10.1101/2021.06.15.21258262 ◽

2021 ◽

Author(s):

Juan F Vazquez Costa ◽

Monica Povedano ◽

Andres E Nascimento-Osorio ◽

Antonio Moreno Escribano ◽

Solange Kapetanovic Garcia ◽

...

Keyword(s):

Spinal Muscular Atrophy ◽

Vital Capacity ◽

Rating Scale ◽

Muscular Atrophy ◽

Response To Treatment ◽

Benefit Ratio ◽

Safety And Efficacy ◽

Global Impression Of Change ◽

Lateral Sclerosis

Objective To assess safety and efficacy of nusinersen in adult 5q spinal muscular atrophy (SMA) patients. Methods Patients older than 15 years and followed at least for 6 months with one motor scale (Hammersmith Functional Motor Scale Expanded, HFMSE; Revised Upper Limb module, RULM) in five referral centers were included. Clinical and patients global impression of change (CGI-C and PGI-C) were recorded in treated patients at the last visit. Functional scales (Egen Klassification, EK2; Revised Amyotrophic Lateral Sclerosis Functional Rating Scale, ALSFRS-R) and the percent-predicted forced vital capacity were collected when available. Results Seventy-nine SMA patients (39 treated with nusinersen) were included. Compared with untreated patients, treated patients showed a significant improvement of 2 points (±0.46) in RULM (p<0.001) after six months. After a mean follow-up of 16 months, nusinersen treatment was associated with a significant improvement in HFMSE (OR=1.15, p=0.006), 6MWT (OR=1.07, p<0.001), and EK2 (OR=0.81, p=0.001). Compared with untreated patients, more treated patients experienced clinically meaningful improvements in all scales, but these differences were statistically significant only for RULM (p=0.033), ALSFRS-R (p=0.005), and EK2 (p<0.001). According to the CGI-C and PGI-C, 64.1% and 61.5% of treated patients improved with treatment. Being non-sitter was associated with less response to treatment, while longer time of treatment was associated with better response. Most treated patients (77%) presented at least one adverse event, mostly mild. Conclusions Nusinersen treatment associates to some improvements in adult SMA patients. Most severely affected patients with complex spines are probably those with the most unfavorable risk-benefit ratio.

Download Full-text

Errata: Measuring Disease Severity in Duchenne and Becker Muscular Dystrophy

Journal of Methods and Measurement in the Social Sciences ◽

10.2458/jmm.v1i2.12366 ◽

2011 ◽

Vol 1 (2) ◽

Author(s):

Melinda F. Davis ◽

Katalin H. Scherer ◽

Timothy M. Miller ◽

F. John Meaney

Keyword(s):

Amyotrophic Lateral Sclerosis ◽

Muscular Dystrophy ◽

Disease Severity ◽

Muscle Weakness ◽

Respiratory Function ◽

Rating Scale ◽

Becker Muscular Dystrophy ◽

Progressive Muscle Weakness ◽

Lateral Sclerosis ◽

Disease Specific

Download Full-text

Dissociated leg muscle atrophy in amyotrophic lateral sclerosis/motor neuron disease: the ‘split-leg’ sign

Scientific Reports ◽

10.1038/s41598-020-72887-7 ◽

2020 ◽

Vol 10 (1) ◽

Author(s):

Young Gi Min ◽

Seok-Jin Choi ◽

Yoon-Ho Hong ◽

Sung-Min Kim ◽

Je-Young Shin ◽

...

Keyword(s):

Amyotrophic Lateral Sclerosis ◽

Motor Neuron ◽

Motor Neuron Disease ◽

Muscle Atrophy ◽

Rating Scale ◽

Muscular Atrophy ◽

Compound Muscle Action Potential ◽

Healthy Controls ◽

Abductor Hallucis ◽

Lateral Sclerosis

Abstract Disproportionate muscle atrophy is a distinct phenomenon in amyotrophic lateral sclerosis (ALS); however, preferentially affected leg muscles remain unknown. We aimed to identify this split-leg phenomenon in ALS and determine its pathophysiology. Patients with ALS (n = 143), progressive muscular atrophy (PMA, n = 36), and age-matched healthy controls (HC, n = 53) were retrospectively identified from our motor neuron disease registry. We analyzed their disease duration, onset region, ALS Functional Rating Scale-Revised Scores, and results of neurological examination. Compound muscle action potential (CMAP) of the extensor digitorum brevis (EDB), abductor hallucis (AH), and tibialis anterior (TA) were reviewed. Defined by CMAPEDB/CMAPAH (SIEDB) and CMAPTA/CMAPAH (SITA), respectively, the values of split-leg indices (SI) were compared between these groups. SIEDB was significantly reduced in ALS (p < 0.0001) and PMA (p < 0.0001) compared to the healthy controls (HCs). SITA reduction was more prominent in PMA (p < 0.05 vs. ALS, p < 0.01 vs. HC), but was not significant in ALS compared to the HCs. SI was found to be significantly decreased with clinical lower motor neuron signs (SIEDB), while was rather increased with clinical upper motor neuron signs (SITA). Compared to the AH, TA and EDB are more severely affected in ALS and PMA patients. Our findings help to elucidate the pathophysiology of split-leg phenomenon.

Download Full-text

Validation of serum neurofilaments as prognostic and potential pharmacodynamic biomarkers for ALS

Neurology ◽

10.1212/wnl.0000000000009559 ◽

2020 ◽

Vol 95 (1) ◽

pp. e59-e69 ◽

Cited By ~ 8

Author(s):

Michael Benatar ◽

Lanyu Zhang ◽

Lily Wang ◽

Volkan Granit ◽

Jeffrey Statland ◽

...

Keyword(s):

Sample Size ◽

Rating Scale ◽

Limit Of Detection ◽

Muscular Atrophy ◽

Serum Samples ◽

Neurofilament Light ◽

Baseline Serum ◽

Coefficients Of Variation ◽

Pharmacodynamic Biomarkers ◽

Lateral Sclerosis

ObjectiveTo identify preferred neurofilament assays and clinically validate serum neurofilament light (NfL) and phosphorylated neurofilament heavy (pNfH) as prognostic and potential pharmacodynamic biomarkers relevant to amyotrophic lateral sclerosis (ALS) therapy development.MethodsIn this prospective, multicenter, longitudinal observational study of patients with ALS (n = 229), primary lateral sclerosis (n = 20), and progressive muscular atrophy (n = 11), biological specimens were collected, processed, and stored according to strict standard operating procedures (SOPs). Neurofilament assays were performed in a blinded manner by independent contract research organizations.ResultsFor serum NfL and pNfH measured using the Simoa assay, there were no missing data (i.e., technical replicates below the lower limit of detection were not encountered). For the Iron Horse and Euroimmun pNfH assays, such missingness was encountered in ∼4% and ∼10% of serum samples, respectively. Mean coefficients of variation for NfL in serum and CSF were both ∼3%. Mean coefficients of variation for pNfH in serum and CSF were ∼4%–5% and ∼2%–3%, respectively, in all assays. Baseline serum NfL concentration, but not pNfH, predicted the future Revised ALS Functional Rating Scale (ALSFRS-R) slope and survival. Incorporation of baseline serum NfL into mixed effects models of ALSFRS-R slopes yields an estimated sample size saving of ∼8%. Depending on the method used to estimate effect size, use of serum NfL (and perhaps pNfH) as pharmacodynamic biomarkers, instead of the ALSFRS-R slope, yields significantly larger sample size savings.ConclusionsSerum NfL may be considered a clinically validated prognostic biomarker for ALS. Serum NfL (and perhaps pNfH), quantified using the Simoa assay, has potential utility as a pharmacodynamic biomarker of treatment effect.

Download Full-text

Longitudinal Changes of Tongue Thickness and Tongue Pressure in Neuromuscular Disorders

10.21203/rs.3.rs-74174/v1 ◽

2020 ◽

Author(s):

George Umemoto ◽

Shinsuke Fujioka ◽

Hajime Arahata ◽

Nobutaka Sakae ◽

Naokazu Sasagasako ◽

...

Keyword(s):

Neuromuscular Disorders ◽

The Other ◽

Tongue Pressure ◽

Swallowing Function ◽

Longitudinal Changes ◽

Swallowing Dysfunction ◽

The Relationship ◽

Lateral Sclerosis

Abstract Background: Swallowing dysfunction is related to major cause of adverse events and an indicator of shorter survival among patients with neuromuscular disorders (NMD). It is critical to assess the swallowing function during disease progression, however, there are limited tools that can easily evaluate swallowing function without using videofluoroscopic or videoendoscopic examination. Here, we evaluated the longitudinal changes in tongue thickness (TT) and maximum tongue pressure (MTP) among patients with amyotrophic lateral sclerosis (ALS), myotonic dystrophy type 1 (DM1), and Duchenne muscular dystrophy (DMD).Methods: Between 2010 and 2020, TT and MTP were measured from 21 ALS, 30 DM1, and 14 DMD patients (mean ages of 66.9, 44.5, and 21.4 years, respectively) at intervals of more than half a year. TT was measured, by ultrasonography, as the distance from the mylohyoid muscle raphe to the tongue dorsum, and MTP was determined by measuring the maximum compression on a small balloon when pressing the tongue against the palate. Then we examined the relationship between these evaluations and patient background and swallowing function.Results: Mean follow-up periods were 24.0 months in the ALS group, 47.2 months in the DM1group, and 61.1 months in the group. The DMD group demonstrated larger initial TT than the other groups, while the DM1 group had lower initial MTP than the ALS group. The ALS group showed a greater average monthly reduction in mean TT than the DM1 group and greater monthly reductions in mean BW and MTP than the other groups. Significant differences between the first and last BW, TT, and MTP measures were found only in the ALS group.Conclusions: This study suggests that ALS is associated with more rapid degeneration of tongue function over several years compared to DMD and DM1.

Download Full-text