Prevalence and predictor factors of respiratory impairment in a large cohort of patients with Myotonic Dystrophy type 1 (DM1): A retrospective, cross sectional study.

INTRODUCTION: Respiratory complications are relevant in DM1, leading to a significantly increased morbidity and mortality risk in these patients; however, so far only few studies concerning respiratory function have been conducted in DM1 patients. We report a retrospective, multicenter, cross sectional study on a large cohort of DM1 patients widely characterized in the phenotype, to assess prevalence and identify predictors of restrictive respiratory syndrome. METHODS: 268 DM1 subjects aged >18 years, who had recently performed spirometric tests were included; restrictive syndrome was diagnosed if forced vital capacity (FVC) <80% of predicted. This cut-off was used for statistical univariate and multivariate analysis. RESULTS: 51.9% patients showed a restrictive syndrome, and half of them had indication to non-invasive ventilation (NIV), yet only 50% resulted compliant to NIV. CTG expansion size in leukocytes, clinical muscle severity, most functional parameters of respiratory muscle involvement, presence of cardiac conduction disturbances, pacemaker (PMK), exertion dyspnea, obstructive sleep apnea, and indication and compliance to NIV were all significantly associated with restrictive syndrome at the univariate analysis; in the multivariate model only the first two factors resulted independent predictors. DISCUSSION: A high prevalence of restrictive syndrome in our DM1 cohort, mainly due to respiratory muscles weakness, was observed and documented; the severity of muscle impairment and the CTG expansion size confirmed to be independent predictors of respiratory restriction. Our data suggest that optimization of respiratory therapeutic management, particularly regarding launching of NIV, might help to reduce the rate of deaths due to respiratory complications in DM1.

A 34-year longitudinal study on long-term cardiac outcomes in DM1 patients with normal ECG at baseline at an Italian clinical centre.

Cardiac conduction and/or rhythm abnormalities (CCRA) are the most frequent and life-threatening complications in DM1. In order to determine prevalence, incidence, characteristics, age of onset and predictors of CCRA, CCRA progression and sudden cardiac death (SCD) in DM1, we collected ECG/24hECG-Holter data from a yearly updated 34-year database of a cohort of 103 DM1 patients without cardiac abnormalities at baseline, followed for at least 1 year. Fifty-five patients developed CCRA [39 developed conduction abnormalities (CCA) and 16 rhythm abnormalities (CRA)], which progressed in 22. Nine had SCD. Risk and incidence of CCRA amounted to 53.4 and 6.83% person-years (CCA: 37.9 and 4.8%; CRA 15.5 and 2%), respectively; risk and incidence of SCD amounted to 8.74 and 0.67% person-years, respectively. CTG expansion represented a predictor of CCRA incidence (HR 1.10, p = 0.04), CCRA progression (HR 1.28, p = 0.001) and SCD (HR 1.39, p = 0.002). MIRS progression during follow-up was associated with CCRA prevalence (OR 5.82, p = 0.004); older age and larger CTG expansion to SCD prevalence (OR 2.67, p = 0.012; OR 1.54, p = 0.005). Age of CCRA onset and CCRA progression was significantly lower in patients with larger CTG expansion and in those with MIRS progression. Age when SCD occurred was significantly lower in patients with larger CTG expansion. Amongst recorded cardiac abnormalities, both atrial flutter (OR 8.70; p = 0.031) and paroxysmal supraventricular tachycardia (OR 8.67; p = 0.040) were associated with SCD. Although all DM1patients may develop cardiac abnormalities at any time in their life, patients older than 30 years with larger CTG expansion and MIRS progression in particular should be carefully monitored via periodical ECG.

"I Know that You Know that I Know": Neural Substrates Associated with Social Cognition Deficits in DM1 Patients.

Myotonic dystrophy type-1 (DM1) is a genetic multi-systemic disorder involving several organs including the brain. Despite the heterogeneity of this condition, some patients with non-congenital DM1 can present with minimal cognitive impairment on formal testing but with severe difficulties in daily-living activities including social interactions. One explanation for this paradoxical mismatch can be found in patients' dysfunctional social cognition, which can be assessed in the framework of the Theory of Mind (ToM). We hypothesize here that specific disease driven abnormalities in DM1 brains may result in ToM impairments. We recruited 20 DM1 patients who underwent the "Reading the Mind in the Eyes" and the ToM-story tests. These patients, together with 18 healthy controls, also underwent resting-state functional MRI. A composite Theory of Mind score was computed for all recruited patients and correlated with their brain functional connectivity. This analysis provided the patients' "Theory of Mind-network", which was compared, for its topological properties, with that of healthy controls. We found that DM1 patients showed deficits in both tests assessing ToM. These deficits were associated with specific patterns of abnormal connectivity between the left inferior temporal and fronto-cerebellar nodes in DM1 brains. The results confirm the previous suggestions of ToM dysfunctions in patients with DM1 and support the hypothesis that difficulties in social interactions and personal relationships are a direct consequence of brain abnormalities, and not a reaction symptom. This is relevant not only for a better pathophysiological comprehension of DM1, but also for non-pharmacological interventions to improve clinical aspects and impact on patients' success in life.