Twenty-four-hour ambulatory ECG monitoring relevancy in myotonic dystrophy type 1 follow-up: Prognostic value and heart rate variability evolution.

BACKGROUND: Patient prognosis in type 1 myotonic dystrophy (DM1) is very poor. Annual 24-hour holter ECG monitoring is recommended but its relevance is debated. Main objective was to determine whether holter ECG parameters could predict global death in DM1 patients and secondarily to assess whether they could predict cardiovascular events and sudden cardiac death, to compare DM1 patients and healthy controls, and to assess their evolution in DM1 over a 5-year period. METHODS: This retrospective study included genetically confirmed DM1. Primary endpoint was global death. Secondary endpoints were labeled "sudden cardiac death" which was a composite of sudden cardiac death, aborted sudden cardiac death, implantable cardioverter defibrillator therapy, sustained ventricular tachycardia, atrioventricular block grade 3, pause >3 s; and "cardiovascular events" which was a composite of all-cause mortality, pacemaker or cardioverter defibrillator implantation, sustained ventricular tachycardia, supraventricular tachycardia, hospitalization for acute cardiac cause and heart failure. RESULTS: Forty-seven patients (22 women, 40 ± 13 years old) were included. Three (7%) DM1 patients died, 9 (19%) experienced "sudden cardiac death" endpoint and 21 (45%) experienced "cardiovascular event" endpoint during mean follow-up of 95 ± 22 months. None of holter ECG parameters were discriminant to predict death or secondary endpoints. Compared to healthy controls, DM1 patients had higher SDNN and LF/HF ratio. Finally, heart rate variability parameters remained stable over a mean interval of 61 ± 15 months excepting pNN50 which decreased significantly. CONCLUSION: Results suggest that annually-repeated holter ECG in DM1 is not useful for stratifying risk of sudden death and cardiovascular outcomes.

Dysregulation of calcium metabolism in type 1 myotonic dystrophy.

BACKGROUND: Patients with type 1 myotonic dystrophy (DM1) have a higher incidence of hypercalcaemia compared with the general population. The nature and effects of dysregulated calcium metabolism underpinning this phenomenon have not been fully characterised. AIMS: To determine the characteristics of dysregulated calcium metabolism in patients with DM1 and its association with bone mineral density. METHODS: A retrospective review of medical records of patients with DM1 attending a DM clinic at Logan Hospital, Brisbane, Queensland, between 2005 and 2018 and who had concurrent serum assays performed of corrected serum calcium, 25 hydroxyvitamin D, parathyroid hormone (PTH) and phosphate and for whom results were available for estimated glomerular filtration rate, bone mineral densitometry tests and urinary calcium clearance to creatinine clearance ratio (UCCR). RESULTS: Forty-four patients with DM1 (22 females, 22 males) were reviewed of whom 14 (32%) had elevated corrected serum calcium and inappropriate PTH. Another 10 patients (23%) had raised PTH with normocalcaemia. Eighteen of 19 (94.7%) patients with hypercalcaemia or high PTH level completed 24-h urinary calcium. All had UCCR ≤0.02. Twelve patients had UCCR <0.01. Seven of 44 (16%) had low 25 hydroxy vitamin D. All patients had normal estimated glomerular filtration rate. None was osteoporotic. CONCLUSIONS: One in three patients with DM1 was hypercalcaemic with unsuppressed PTH. Their clinical features and biochemical pictures resemble those of familial hypocalciuric hypercalcaemia (FHH) and raises the possibility that impaired activity of calcium-sensing receptors, due to abnormal splicing of the calcium-sensing receptor messenger RNA in DM1, causes a FHH-like syndrome ('pseudo-FHH of DM1').

Probenecid: An Oral Inotrope for End-Stage Heart Failure in a Case With Myotonic Dystrophy.

A 56-year-old man with multiple cardiac manifestations of type 1 myotonic dystrophy, including severe, nonischemic cardiomyopathy, presented in refractory cardiogenic shock requiring inotropic therapy. Given his wishes to die without having any intravenous medications, he was started on oral probenecid therapy, which allowed for successful elimination of his intravenous therapies. (Level of Difficulty: Intermediate.).

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.

Markers of brain illness may be hidden in your olfactory ability: a Japanese perspective.

There is evidence that impaired human cognitive abilities are reflected by loss of olfactory abilities. Declining olfactory perception may be a biomarker for impairment of cognitive function and of impending neurogenerative disorders. As olfactory perception may differ between culture and ethnic group, we sought to confirm this relationship with Japanese participants. In this study, we examined possible relationships between age and olfactory abilities in healthy Japanese subjects (control subjects) over a wide range of ages and compared this relationship with that observed in three neurodegenerative disorders; patients with Parkinson's disease (PD), Type 1 myotonic dystrophy (DM1) and Alzheimer's disease (AD). In control subjects, both threshold and recognition abilities decreased with age. Ability to detect odors was generally intact in most control subjects, however, we found that the abilities of individuals in the three different patient populations to recognize odors were impaired relative to control subjects. All three types of patients exhibited decreased or impaired odor-recognition compared with age-matched controls. Previous studies showed the causes of olfactory impairments in PD and AD patients were attributable to pathological changes and MRI signal abnormalities in limbic areas, including the amygdala (AMG), entorhinal cortex (ENT), hippocampus (HI), and orbitofrontal cortex (OFC). Another study reported that DM1 patients have bilateral lesions in anterior temporal areas, including the subcortical white matter, AMG, ENT and insula. Our findings underscore the need to pay careful attention to significant decreases of odor identification abilities caused by diverse forms of abnormal brain function, especially in the AMG, ENT and HI.