Muscular Impairment Rating Scale Research Articles

Muscle MRI as a biomarker of disease activity and progression in myotonic dystrophy type 1: a longitudinal study

IntroductionMyotonic dystrophy type 1 (DM1) is an autosomal dominant disease characterized by myotonia and progressive muscular weakness and atrophy. The aim of this study was to investigate the usefulness of longitudinal muscle MRI in detecting disease activity and progression in DM1, and to better characterize muscle edema, fat replacement and atrophy overtime.Materials and methodsThis is a prospective, observational, longitudinal study including 25 DM1 patients that performed at least two muscle MRIs. Demographic and genetic characteristics were recorded. Muscular Impairment Rating Scale (MIRS) and MRC score were performed within 3 months from MRIs at baseline (BL) and at follow-up (FU). We analysed 32 muscles of lower body (LB) and 17 muscles of upper body (UB) by T1 and STIR sequences. T1-, STIR- and atrophy scores and their variations were evaluated. Correlations between MRIs’ scores and demographic, clinical and genetic characteristics were analysed.ResultsEighty (80%) of patients showed fat replacement progression at FU. The median T1 score progression (ΔT1-score) was 1.3% per year in LB and 0.5% per year in UB. The rate of fat replacement progression was not homogenous, stratifying patients from non-progressors to fast progressors (> 3% ΔT1-score per year). Half of the STIR-positive muscles at BL showed T1-score progression at FU. Two patients with normal MRI at baseline only showed STIR-positive muscle at FU, marking the disease activity onset. STIR positivity at baseline correlated with fat replacement progression (ΔT1-score; p < 0.0001) and clinical worsening at FU (ΔMRC-score; p < 0.0001). Sixty-five (65%) of patients showed STIR- and fat replacement-independent muscle atrophy progression, more evident in UB.ConclusionsMuscle MRI represents a sensitive biomarker of disease activity, severity, and progression in DM1. STIR alterations precede fat replacement and identify patients with a higher risk of disease progression, while T1-sequences reveal atrophy and fat replacement progression before clinical worsening.

Cognitive and sleep evaluation of Myotonic dystrophy type I: A protocol for a case‐control study

AbstractBackgroundMyotonic dystrophy type 1 (DM1) is one of the most common inherited muscular dystrophies in adults. It is caused by CTG repeat expansions in the 3' untranslated region (UTR) of the DMPK gene on Chromosome 19. Apart from muscle, the disease can involve the eye, heart, brain and endocrine system. Cognitive and sleep disturbances are common but poorly recognized non‐motor manifestations of DM1.MethodWe plan to recruit 30 genetically proven DM1 patients from the prospective MRC‐funded International Centre for Genomic Medicine in Neuromuscular Diseases (ICGNMD) cohort. Neuromuscular phenotyping will be done by the same neuromuscular expert. The muscle strength will be assessed by the Medical Research Council scale and Muscular Impairment Rating Scale (MIRS). We will exclude patients with severe depression. An age and sex‐matched control group of 30 healthy participants will be included to evaluate patients’ cognitive profiles. A comprehensive neuropsychological evaluation (NPS) to assess multiple cognitive domains will be conducted on all patients. A prescheduled sleep history, Epworth Sleepiness Scale (ESS), Pittsburg sleep quality index (PSQI) and full‐night diagnostic polysomnography will be done in all patients.ResultThe outcomes include the NPS domains comparing cognitive impairment compared to controls and the severity and type of sleep apnea (apnea‐hypopnea index [AHI])ConclusionThe study will investigate the DM1 cognitive profile and its relationship with sleep disturbance using motor scales, neuropsychological assessment and polysomnography.

Urinary titin in myotonic dystrophy type 1.

Urinary titin, an easy-to-obtain marker, has been investigated in muscular dystrophies, but not in myotonic dystrophy type 1 (DM1). We investigated the role of titin as a biomarker of muscle injury in DM1. We compared the urinary titin N-fragment/creatinine ratio in 29 patients with DM1 vs. 30 healthy controls. We also recorded clinical data such as muscle strength, serum creatine kinase, DM1-related outcome measures, and the 20-item DM1-activ questionnaire. The severity of the disease was graded using the Muscular Impairment Rating Scale (MIRS). The titin/creatinine ratio was significantly higher in the urine samples of DM1 patients than of healthy controls (median ± mean absolute deviation [MAD]: 39.313 ± 26.546 vs. 6.768 ± 5.245 pmol/mg creatinine; P < .001), and was related to muscle impairment graded by MIRS (τ = 0.503, P = .038). Urinary titin may be a biomarker for DM1. Long-term follow-up of DM1 patients is needed to investigate the potential role of titin as a biomarker for disease activity and progression.

A Multimodal Neuroimaging Feature Extraction Framework for Biomarker Discovery in Myotonic Dystrophies (P8-4.004)

<h3>Objective:</h3> Myotonic dystrophies (DM) are neuromuscular conditions that cause widespread effects throughout the body. New therapeutics are being developed that attack the RNA mechanism underlying DM. Here, we address the urgent need of identifying DM neuroimaging biomarkers that can be used in trials. <h3>Background:</h3> DTI shows decreased white matter connectivity in DM patients and MRI reveals decreased parietal, frontal, and temporal resting state metabolism. Additionally, DTI studies of DM have shown that the white matter abnormalities are diffuse as opposed to multi-focal. <h3>Design/Methods:</h3> Extracting important features from neuroimaging data is challenging due to the high feature dimension and low sample-size problem. This work utilizes a sparse matrix decomposition method and a manifold regularization approach to identify the most discriminative features and improves spatial and temporal resolutions of neuroimaging data. To this end, neuroimaging data of 46 DM1, 17 DM2 patients and 92 healthy controls were analyzed using a ten-fold-cross-validation technique. In addition to neuroimaging data, additional clinical assessments including Quebec Muscular Impairment Rating Scale and Quebec Daytime Sleepiness Scale were calculated for DM patients. Wavelet approximation and detailed coefficients were calculated to consider both long term and short-term fluctuations caused by the disease process. <h3>Results:</h3> Normalized sub-band energy calculated based on wavelet coefficients can characterize DM1 and DM2. Patients with DM1 have widespread white matter volume reductions that are correlated with distal to proximal progression of the muscular involvement in DM1. A significant difference can be seen between DM1 and healthy controls in terms of executive function, motor speed, processing speed, and memory. <h3>Conclusions:</h3> The proposed method can potentially be used to develop and validate key predictors of DM type, severity, and progression of DM central nervous system abnormalities using brain morphometry. Identified features can also potentially provide multidisciplinary biomarkers that help unravel our understanding of fatigue, sleepiness, and attention. <b>Disclosure:</b> Ms. Kamali has nothing to disclose. Dr. Day has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Affinia Therapeutics. Dr. Day has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis Gene Therapy. Dr. Day has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biogen. Dr. Day has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche/Genentech. Dr. Day has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sarepta. Dr. Day has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Scholar Rock. Dr. Day has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Avidity. Dr. Day has received personal compensation in the range of $10,000-$49,999 for serving as an officer or member of the Board of Directors for Muscular Dystrophy Association. The institution of Dr. Day has received research support from Audentes. The institution of Dr. Day has received research support from Novartis Gene Therapy. The institution of Dr. Day has received research support from Biogen. The institution of Dr. Day has received research support from Cytokinetics. The institution of Dr. Day has received research support from Roche/Genentech. The institution of Dr. Day has received research support from Sanofi/Genzyme. The institution of Dr. Day has received research support from Sarepta. The institution of Dr. Day has received research support from Scholar Rock. Dr. Day has received intellectual property interests from a discovery or technology relating to health care. Dr. Sampson has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Dyne Therapeutics. Dr. Sampson has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Expansion Therapeutics. Dr. Sampson has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Viking Therapeutics. Dr. Sampson has received research support from Marigold Foundation. Dr. Sampson has a non-compensated relationship as a Scientific Advisory Committee with Myotonic Dystrophy Foundation that is relevant to AAN interests or activities. Dr. Murad has received personal compensation for serving as an employee of UCB. Dr. Murad has received personal compensation for serving as an employee of Skyhawk Therapeutics. Dr. Murad has stock in Forma Therapeutics. Dr. Murad has stock in Skyhawk Therapeutics. Mr. Chaufty has received personal compensation for serving as an employee of UCB. Mr. Chaufty has stock in UCB. Mr. Chaufty has received intellectual property interests from a discovery or technology relating to health care.

Myotonic dystrophy type 1: A comparison between the adult- and late-onset subtype.

Although the extent of muscle weakness and organ complications has not been well studied in patients with late-onset myotonic dystrophy type 1 (DM1), adult-onset DM1 is associated with severe muscle involvement and possible life-threatening cardiac and respiratory complications. In this study we aimed to compare the clinical phenotype of adult-onset vs late-onset DM1, focusing on the prevalence of cardiac, respiratory, and muscular involvement. Data were prospectively collected in the Dutch DM1 registry. Two hundred seventy-five adult-onset and 66 late-onset DM1 patients were included. Conduction delay on electrocardiogram was present in 123 of 275 (45%) adult-onset patients, compared with 24 of 66 (36%) late-onset patients (P = .218). DM1 subtype did not predict presence of conduction delay (odds ratio [OR] 0.706; confidence interval [CI] 0.405 to 1.230, P=.219). Subtype did predict indication for noninvasive ventilation (NIV) (late onset vs adult onset: OR, 0.254; CI, 0.104 to 0.617; P=.002) and 17% of late-onset patients required NIV compared with 40% of adult-onset patients. Muscular Impairment Rating Scale (MIRS) scores were significantly different between subtypes (MIRS 1 to 3 in 66% of adult onset vs 100% of late onset [P < .001]), as were DM1-activC scores (67 ± 21 in adult onset vs 87 ± 15 in late onset; P < .001). Although muscular phenotype was milder in late-onset compared with adult-onset DM1, the prevalence of conduction delay was comparable. Moreover, subtype was unable to predict the presence of cardiac conduction delay. Although adult-onset patients had an increased risk of having an NIV indication, 17% of late-onset patients required NIV. Despite different muscular phenotypes, screening for multiorgan involvement should be equally thorough in late-onset as in adult-onset DM1.

P.205 Utility of electrical bioimpedance as a biomarker in myotonic dystrophy type I

Myotonic dystrophy type 1 (DM1) is frequently associated with endocrinopathies. Body composition analysis by electrical bioimpedance study is useful in the nutritional assessment of these patients. The aim of this study is to investigate its usefulness as a biomarker of clinical progression/severity in DM1. We carried out a cross-sectional study of 47 patients with DM1 attended in the last year who underwent impedancemetry with the InBody S10 device for segmental multifrequency analysis. Muscle weakness was classified according to severity using the muscular impairment rating scale (MIRS). 18 men and 29 women were evaluated. Mean age was 46.11 years. By means of Spearman's Rho correlation, a highly statistically significant concordance was identified between the MIRS scale and the global phase angle (PA) at 50 kHz (p 0.000 and R -0.717) and also with the skeletal muscle mass index (SMMI) (p 0.000 and R -0.549). However, no relationship was observed between MIRS with classical nutritional indicators such as BMI or percentage weight loss. In logistic regression models, PA and SMMI adjusted by age and sex decrease statistically significantly as muscle weakness progresses with high explanatory value. There is a highly significant correlation between clinical severity measured by the MIRS scale and PA and SMMI. PA and SMMI are more sensitive, early and constant as a marker of muscle deterioration than any of the GLIM phenotypic criteria for the diagnosis of malnutrition that are usually related to muscle weakness, thus postulating themselves as a possible useful biomarker of progression in DM1.

The characteristics of dysphagia and the incidence of pneumonia in Myotonic dystrophy type 1 patients especially concerning swallowing function evaluated by endoscopy

ObjectiveThe objectives of the study were to clarify the characteristics of dysphagia and the incidence of pneumonia in Myotonic dystrophy type 1 (DM1) patients, and to investigate the relationship between the development of pneumonia and the DM1 patient's background, especially concerning swallowing function evaluated by endoscopy. MethodsThe subjects were 88 DM1 patients who underwent swallowing function evaluation. The severity of disease in DM1patients was assessed based on the muscular impairment rating scale (MIRS), and the number of CTG repeats. Patients were divided into two groups; those who developed aspiration pneumonia within two years after swallowing assessment and those who did not develop aspiration pneumonia. Swallowing function was assessed using the food intake level scale (FILS), repetitive saliva swallowing test (RSST), the modified water swallowing test (MWST), and the Hyodo score. ResultsOnset of pneumonia within two years of assessment was observed in 22 cases (25%). Age, FILS, and Hyodo score were significantly different between pneumonia and non-pneumonia groups. There was a significant difference in swallowing function tests such as FILS, RSST, and Hyodo score between males and females. The Hyodo score cutoff value for predicting pneumonia within two years was determined by ROC analysis. A cutoff value of 6 was found to have a sensitivity of 0.545 and a specificity of 0.833 (area under the curve=0.722). ConclusionIt is important to evaluate the swallowing function of DM1 patients by endoscopy to prevent aspiration pneumonia. In addition, male patients are more likely to deteriorate in swallowing function and should be carefully monitored.

Opioid use may be associated with postoperative complications in myotonic dystrophy type 1 with high-grade muscular impairment

Individuals with myotonic dystrophy type 1 (DM1) reportedly have a higher risk of postoperative complications than those without DM1; however, factors related to perioperative complications in DM1 patients remain unclear. We aimed to identify the risk factors that may be associated with postoperative complications in DM1 patients. We reviewed medical records of 256 patients with DM1 from 1998 to 2018, among whom 42 (16.4%) had previously undergone 51 surgeries under general and regional anaesthesia. Among the 42 patients, 11 (21.5%) had 13 postoperative complications including respiratory complications, sustained hypotension, wound infection and dehiscence, artery thrombosis and occlusion, and delayed recovery from anaesthesia. There were significant inter-group differences between the non-complicated and complicated groups considering the following parameters: high-grade (≥ 3) muscular impairment rating scale (MIRS), extubation time, postoperative opioid use, and hospital length of stay. Furthermore, univariate analysis revealed that an MIRS score ≥ 3 (odds ratio [OR] 9.346, confidence interval [CI] 1.761–49.595, p = 0.009) and postoperative opioid use (OR 8.000, CI 1.772–36.127, p = 0.007) were the only statistically significant factors. Therefore, clinicians should be cautious in administering opioids, particularly in patients with a high-grade MIRS score during the perioperative period.

Gender effect on cardiac involvement in myotonic dystrophy type 1.

Cardiac involvement is observed in about 80% of subjects with myotonic dystrophy type 1 (DM1) and is mainly characterized by cardiac conduction and/or rhythm abnormalities (CCRAs), possibly leading to sudden cardiac death (SCD). Our objective was to investigate whether the gender difference may influence the cardiac involvement and SCD in DM1. We analyzed prevalence and incidence of cardiological abnormalities in males versus females in 151 consecutive DM1 patients over a 35-year follow-up period. Fifty-five patients, 35 males (62.5%) and 20 females (42.5%), developed some type of CCRA during the follow-up period (mean 7.82±6.21years). CCRA overall, and specifically cardiac conduction abnormalities (CCAs), were significantly more frequent in males than in females (p=0.043 and p=0.031, respectively). CCRAs progressed in 16 males (45.7%) and six females (30%). Twenty-four patients, 14 males (25.0%) and 10 females (21.3%), died during the follow-up. Nine of them, six males (10.7%) and three females (6.4%), had SCD. After correction for Muscular Impairment Rating Scale progression, cytosine thymine-guanine expansion, and follow-up duration, a higher prevalence of CCAs was independently associated with male gender (p=0.039), but independent association with gender was not detected for CCRAs overall, cardiac rhythm abnormalities, and SCD prevalence, even if prevalence was higher in males than females. The overall risk of occurrence of CCAs in DM1 is significantly higher in males than females regardless of genetic background and disease severity and progression. Moreover, the data also suggest a similar impact for male gender for CCRAs overall, CCAs, and SCD even if not statistically significant.

Cognitive Decline and White Matter Integrity Degradation in Myotonic Dystrophy Type I.

Myotonic Dystrophy Type I (DM1) is a neurodegenerative, genetic, and multisystemic disorder with a large variety of symptoms due to a CTG trinucleotide expansion located onDystrophia Myotonica Protein Kinase (DMPK) gene. Previous reports have shown cognitive deterioration in these patients. Given that white matter (WM) degradation has also been reported in DM1 patients, here we explored if alterations in the cognitive profile of DM1 patients could be related to the deterioration of WM. A total of 22 classic DM1 patients with age range (18-56 years) and 22 matched healthy control subjects were neuropsychological evaluated by the Cambridge Neuropsychological Test Automated (CANTAB). Patients were evaluated with the Muscular Impairment Rating Scale (MIRS). We then evaluated the cerebral WM integrity using the Fractional Anisotropy (FA) index obtained from the Diffusion Tensor Imaging (DTI) data acquired with a 3T MR scanner. DM1 patients showed generalized reduction of WM integrity across the brain. Similarly, patients' neuropsychological evaluation showed significant deficits in memory and problem-solving tasks. Correlation analyses showed a significant correlation between FA deterioration at frontal, temporomedial, and parietal lobes and delayed matched to sample deficits. Our results suggest that despite the pervasive WM integrity loss in DM1 disorder, specific memory impairments can be associated to discreet areas of WM deterioration in these patients.

Swallow-related quality of life and oropharyngeal dysphagia in myotonic dystrophy

PurposeThis study describes swallow-related quality of life (SWAL-QOL) in patients with myotonic dystrophy type 1 (DM1) and investigates its association with swallowing function and disease severity.MethodsA SWAL-QOL questionnaire was completed by 75 DM1 patients and 25 healthy control subjects. The severity of the disease was evaluated using the muscular impairment rating scale (MIRS). Twenty-eight DM1 patients underwent a videofluroscopic swallowing examination (VFS). Spearman’s correlation coefficient was used to measure the direction and strength of associations.ResultsThe SWAL-QOL median scores were significantly lower for the DM1 group than for the healthy control group. The scores for the majority of the SWAL-QOL domains were lower in patients with proximal muscular weakness (MIRS 4 and 5). Postswallow vallecular pooling and piecemeal deglutition were the most impaired VFS outcome variables.ConclusionOur results suggest that a multidimensional swallowing assessment is recommended for DM1 patients as SWAL-QOL and VFS measure different aspects of the swallowing function, thus providing complementary information.

Lower limb muscle magnetic resonance imaging in Chinese patients with myotonic dystrophy type 1

ABSTRACTObjectives: Muscle magnetic resonance imaging (MRI) is a reliable noninvasion tool for detecting muscle abnormalities of myopathies. This study aimed to investigate the MRI features of lower limb muscles in Chinese patients with myotonic dystrophy type 1 (DM1) and to evaluate the correlation between clinical factors and muscle MRI.Methods: We retrospectively reviewed the medical records and lower limb muscle MRI in 24 Chinese DM1 patients. Muscular Impairment Rating Scale (MIRS) was used to assess the clinical muscular impairment. Modified Mercuri’s scale was used to assess the degree of fatty infiltration. Spearman rank correlation test was used to analyze the relationship between fatty degeneration score with age, age of onset, disease duration, MIRS grading and creatinine kinase (CK) level.Results: Fatty infiltration was found in 22 of 24 DM1 patients and 8 patients were asymmetrically affected. The medial gastrocnemius was the most affected muscle, followed by soleus and tibialis anterior muscles in lower legs. At thigh level, the anterior compartment was usually the most affected region with the rectus femoris relatively spared. 79.2% of DM1 patients had edema in lower limb muscles. The total mean score of fatty infiltration correlated with MIRS grading, age and disease duration but did not correlate with the age of onset or CK level.Conclusion: Here, we found fatty infiltration present in most Chinese DM1 patients with a selective involvement pattern. There is a correlation between the total mean score of fatty infiltration and MIRS grading, age and disease duration.

Characteristics of respiratory muscle involvement in myotonic dystrophy type 1

The pathophysiology of respiratory muscle weakness in myotonic dystrophy type 1 (DM1) remains incompletely understood. 21 adult patients with DM1 (11 men, 42 ± 13 years) and 21 healthy matched controls underwent spirometry, manometry, and diaphragm ultrasound. In addition, surface electromyography of the diaphragm and the obliquus abdominis muscle was performed following cortical and posterior cervical magnetic stimulation (CMS) of the phrenic nerves or magnetic stimulation of the lower thoracic nerve roots. Magnetic stimulation was combined with invasive recording of the twitch transdiaphragmatic and gastric pressure (twPdi and twPgas) in 10 subjects per group. The following parameters were reduced in DM1 patients compared to control subjects: maximum inspiratory pressure (MIP; 40.3 ± 19.2 vs. 95.8 ± 28.5 cmH2O, p < 0.01), diaphragm thickening ratio (DTR; 2.0 ± 0.4 vs. 2.7 ± 0.6, p < 0.01), twPdi following CMS (10.8 ± 8.3 vs. 21.4 ± 10.1 cmH2O, p = 0.03), and amplitude of diaphragm compound muscle action potentials (0.10 ± 0.25 vs. 0.46 ± 0.35 mV; p = 0.04). MIP and DTR were significantly correlated with the muscular impairment rating scale (MIRS) score. Maximum expiratory pressure (MEP) was reduced in DM1 patients compared to controls (41.3 ± 13.4 vs. 133.8 ± 28.0 cmH2O, p < 0.01) and showed negative correlation with the MIRS score. Pgas following a maximum cough was markedly lower in patients than in controls (71.9 ± 43.2 vs. 102.4 ± 35.5 cmH2O) but without statistical significance (p = 0.06). In DM1, respiratory muscle weakness relates to clinical disease severity and involves inspiratory and probably expiratory muscle strength. Axonal phrenic nerve pathology may contribute to diaphragm dysfunction.

Clinical use of bioelectrical impedance analysis in patients affected by myotonic dystrophy type 1: A cross-sectional study.

Myotonic dystrophy type 1 (DM1) is an inherited muscle disorder characterized by slowly progressive weakness due to muscle degeneration. The Muscular Impairment Rating Scale (MIRS) is validated to assess clinical muscle severity of patients with DM1, although the scale is not sensitive enough to assess disease progression in time intervals fit for clinical trials. The aim of this study was to analyze bioelectrical whole body and arm segmental parameters in patients with DM1 to explore a correlation between bioelectrical impedance analysis (BIA) parameters and disease stage. Forty patients with DM1 were enrolled in a cross-sectional study. In all patients, MIRS, handgrip strength (HGS), and BIA were assessed. A Kruskal-Wallis test was used to assess the difference in continuous variables according to MIRS. Correlation between BIA values and HGS were made by Pearson's coefficient analysis. A linear regression analysis was performed. Eighteen of 40 patients were men (45%). The median age of the cohort was 42 y (30-58 y). Four patients (10%) were classified as MIRS 1; 20 (50%) MIRS 2; 11 (27.5%) MIRS 3; and 5 (12.5%) as MIRS 4. A correlation was observed between phase angle and MIRS (P = 0.0001). MIRS correlated with other BIA values such as resistance, impedance ratio, and capacitance (P = 0.005, P = 0.0001, P = 0.0006, respectively). At linear regression analysis, segmental resistance, phase angle, impedance ratio, and capacitance of both arms significantly correlated with HGS. Results from the study support the use of BIA as a suitable procedure for staging DM1 muscle involvement and as a measure of muscle disease outcome, in clinical practice and in clinical trial design of therapeutic drugs.

Uncovering health and social care needs among myotonic dystrophy patients: Utility of the Needs and Provisions Complexity Scale.

Myotonic dystrophy type 1 (DM1) is a slowly progressive multisystem disorder. Guidelines recommend multidisciplinary follow-up. We aimed to investigate the presence of unmet health and social care needs among patients with DM1 and whether unmet needs correlated with motor function, cognitive impairments, or quality of life. Patients were 22 adults with DM1. "Needs and Provisions Complexity Scale" (NPCS) was applied to evaluate the individual's needs and provision of health and social services. The Muscular Impairment Rating Scale (MIRS) was used to measure motor function and disease stage. All patients underwent neuropsychological testing. The EQ-5D-3L questionnaire was used to evaluate the patients' health-related quality of life (HRQoL). Median time from diagnosis was 11years (range: 1-40). Twenty patients had developed needs related to social care, personal care, and rehabilitation that had not been met, whereas need for medical follow-up was largely met. The more pronounced the muscular impairment, the more unmet needs were experienced by DM1 patients (r=0.50, P=0.019). Degree of unmet needs did not correlate with full-scale IQ (r=-0.27, P=0.23) or HRQoL (r=-0.14, P=0.55). Using NPCS, we discovered that patients with DM1 had unmet needs with respect to social care, personal care, and rehabilitation although their need for medical follow-up was met. Thus, the use of NPCS helped bring our practice in better accordance with guidelines. A higher MIRS grade should alert the clinician to the likelihood of unmet needs.

Myocardial fibrosis by late gadolinium enhancement cardiovascular magnetic resonance in myotonic muscular dystrophy type 1: highly prevalent but not associated with surface conduction abnormality

BackgroundConduction disease and arrhythmias represent a major cause of mortality in myotonic muscular dystrophy type 1 (MMD1). Permanent pacemaker (PPM) implantation is the cornerstone of therapy to reduce cardiovascular mortality in MMD1. Cardiovascular magnetic resonance (CMR) studies demonstrate a high prevalence of myocardial fibrosis in MMD1, however the association between CMR myocardial fibrosis with late gadolinium enhancement (CMR-LGE) and surface conduction abnormality is not well established in MMD1.We investigated whether myocardial fibrosis by CMR-LGE is associated with surface conduction abnormalities meeting criteria for PPM implantation according to current guidelines in a cohort of patients with genetically confirmed MMD1.MethodsPatients with genetically confirmed MMD1 were retrospectively evaluated. 12-lead electrocardiography (ECG) performed within 6 months of CMR was necessary for inclusion. The severity and extent of MMD1 was quantified using a validated Muscular Impairment Rating Scale (MIRS). Based on current guidelines for device-based therapy of cardiac rhythm abnormalities, we defined surface conduction abnormality as the presence of ECG alterations meeting criteria for PPM implant (class I or II indications): PR interval > 200 ms (type I atrioventricular (AV) block) and/or mono or bifascicular block (QRS > 120 ms), or evidence of advanced AV block. Balanced steady-state free precession sequences (bSSFP) were used for assessment of left ventricular (LV) volumes and ejection fraction. MOdified Look-Locker Inversion Recovery (MOLLI) acquisition schemes were used to acquire T1 maps. Patients’ charts were reviewed up to 12 months post-CMR for occurrence of PPM implantation.ResultsFifty-two patients (38% male, 41 ± 14 years) were included. Overall, 31 (60%) patients had a surface conduction abnormality and 22 (42%) demonstrated midwall myocardial fibrosis by CMR-LGE. After a median of 57 days from CMR exam, 15 patients (29%) underwent PPM implantation. Subjects with vs. without surface conduction abnormality had significantly longer disease length (15.5 vs. 7.8 years, p = 0.015) and higher disease severity on the MIRS scale (p = 0.041). High prevalence of myocardial fibrosis by CMR-LGE was detected in subjects with and without surface conduction abnormality with no significant difference between the two cohorts (42% vs. 43%, p = 0.999). By multivariate logistic regression analysis, disease length was the only independent variable associated with surface conduction abnormality (OR 1.071, 95%CI 1.003–1.144, p = 0.040); while CMR-LGE was not associated with conduction abnormality (ρ = − 0.009, p = 0.949).ConclusionsMyocardial fibrosis by CMR-LGE is highly prevalent in MMD1 but not related to surface conduction abnormality meeting current guideline criteria for PPM implantation .

Validation of the Nine Hole Peg Test as a measure of dexterity in myotonic dystrophy type 1

We aimed to validate the Nine Hole Peg Test as a measure of dexterity in myotonic dystrophy type 1 (DM1). Fifty patients with adult-onset, genetically confirmed DM1 were evaluated by Nine Hole Peg Test and re-evaluated at one week. Myotonia was not a limiting factor. The first test was compared with that performed by normal subjects (n = 28). Contextually, patients underwent handgrip and three-finger pinch assessments by handheld dynamometer. The Nine Hole Peg Test showed high intra-rater and inter-rater reliability in DM1 [ICC 0.86/0.83 for dominant and 0.90/0.88 for non-dominant hand, respectively]. Inverse correlation with handgrip and pinch strength values (r = −0.4; p < 0.01) and direct correlation with Muscular Impairment Rating Scale (r = 0.4; p < 0.01) were found for both DH and NDH. The test was able to differentiate severe DM1 patients, stratified by extent of muscle impairment, from mildly affected and normal controls, with a sensitivity of 97% and 95% for dominant hand and non-dominant hand, respectively (p < 0.0001). In conclusion, we showed that the Nine Hole Peg Test is a reliable, valid and sensitive test of dexterity in DM1, and that it can be considered as a candidate outcome measure to monitor natural history of disease and, possibly, therapeutic response in clinical trials.

Relationships between Lower Limb Muscle Strength Impairments and Physical Limitations in DM1.

Although adult and late-onset DM1 phenotypes DM1 present distinct lower limb weaknesses portraits, resulting physical limitations have never been described separately for each phenotype. To characterize the lower limb weaknesses and physical limitations among the DM1 adult and late-onset phenotypes separately and to document the contribution of weaknesses on mobility to optimize the management of this population. The strength of four muscle groups among 198 participants was quantified. Participants were categorized according to the severity of their muscular involvement using the Muscular Impairment Rating Scale (MIRS). Physical limitations were assessed using the Timed up-and-go (TUG), Berg Balance Scale (BBS) and 10 meters comfortable walking speed (10MWT). Multiple linear regressions were performed to identify the contribution of each muscle group to the mobility tests scores. Late-onset demonstrated less weakness and physical limitations (p < 0.001 - 0.002) than the adult phenotype, but 21.9-47.5% of participants with this phenotype showed mobility scores below reference values. Physical limitations were observed in the first two MIRS grades (37.5-42.1% of the participants) for the TUG and 10MWT. Ankle dorsiflexors and knee extensors were the two muscle groups that showed the strongest relationships with mobility scores. Although less impaired, the late-onset phenotype shows significant lower limb muscle weakness associated with physical limitations. The surprising presence of quantitative lower limb muscle weakness in the first two MIRS grades needs to be considered when using this scale. Both ankle dorsiflexors and knee extensors appear to be good indicators of physical limitations in DM1.

Prospective measurement of quality of life in myotonic dystrophy type 1.

Generic patient reported outcome measures have had varied success in tracking QoL in myotonic dystrophy type 1 (DM1). To analyze changes of Individualized Neuromuscular Quality of Life questionnaire (INQoL) scores in clinic patients with DM1 over a 6-year period. Patients completed the INQoL at baseline and after a 6-year period through their attendance in a neurology outpatient clinic. Severity of muscular involvement in DM1 was analyzed using the Muscular Impairment Rating Scale (MIRS). Ninety-nine DM1 patients completed a baseline visit. Sixty-seven of these patients were retested at an interval time. The overall INQoL score improved in our sample of patients (P<.05) as did the following subscales: myotonia (P<.05), pain (P<.05), activities (P<.01), social relationships (P<.01), and body image (P<.05). No changes were observed for the independence and emotions scales. There were no differences in mean change of INQoL scores between patients with worsened MIRS and those with no change in MIRS scale after follow-up (P>.05). Individualized Neuromuscular Quality of Life questionnaire scores improved in our cohort of DM1 patients during a 6-year period. INQoL score did not correlate with progression of muscle weakness. This must be better understood before the selection of the instrument for use in trials to measure therapeutic benefit in DM1 patients.

Redox imbalance in peripheral blood of type 1 myotonic dystrophy patients

Objectives: The aim of our study was to determine if redox imbalance caused by the activities of antioxidant enzymes existed in erythrocytes of type 1 myotonic dystrophy (DM1) patients.Methods: The activities of erythrocyte superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase were measured in 30 DM1 patients and 15 healthy controls (HCs). The obtained values were correlated with the Muscular Impairment Rating Scale (MIRS) score and creatine kinase (CK).Results: Superoxide dismutase and catalase activities were lower in DM1 patients compared to HCs. A positive correlation was found between disease duration and MIRS score as well as with glutathione reductase activity. In DM1 patients, there were positive correlations between catalase, glutathione peroxidase, and glutathione reductase activities. After sub-dividing DM1 patients according to CK levels, superoxide dismutase activity was still statistically different from HCs. However, catalase activity was significantly lower only in DM1 patients with increased CK.Discussion: Undesirable alterations in antioxidant enzyme activities during DM1 disease progression may result in conditions favoring oxidative stress and changes in metabolism which together could contribute to muscle wasting.