Ophthalmoparesis as an unusual manifestation of anti-3‑hydroxy-3-methyl-glutaryl-coenzyme A reductase antibody-associated myopathies.

We describe two anti-3‑hydroxy-3-methyl-glutaryl-coenzyme A reductase (HMGCR) antibody-positive patients with treatment-responsive ophthalmoparesis. Patient 1 was a 53-year-old male with progressive proximal limb weakness, dysphagia, ptosis, and diplopia over 6 weeks and creatine kinase (CK) of 3,512 units/L. Patient 2 was a 55-year-old female with progressive proximal weakness, dysarthria, ptosis, diplopia, and dyspnea over 2 weeks with CK of 31,998 units/L.

Improving Documentation of Impulse Control Disorders at a Movement Disorder Program During the COVID-19 Pandemic.

Background And Objectives: Impulse control disorders (ICD) are a group of behaviors in Parkinson disease (PD), (compulsive buying, gambling, binge eating, craving sweets, and hypersexuality) that occur in up to 20% of individuals with PD, sometimes with devastating results. We sought to determine the rate of ICD screening based on 2020 quality measures for PD care by the American Academy of Neurology.

Methods: We conducted a quality improvement project to document and improve physician ICD screening in a tertiary movement disorder program.

Novel p.Asp27Glu ACTA1 variant features congenital myopathy with finger flexor weakness, cardiomyopathy, and cardiac conduction defects.

Pathogenic variants in the skeletal muscle α-actin 1 gene (ACTA1) cause a spectrum of myopathies with clinical and myopathological diversity. Clinical presentations occur from the prenatal period to adulthood, commonly with proximal-predominant weakness and rarely preferential distal weakness. Myopathological findings are wide-ranging, with nemaline rods being most frequent.

Canadian Guidelines for Hereditary Transthyretin Amyloidosis Polyneuropathy Management.

Hereditary transthyretin-mediated (hATTR) amyloidosis is a progressive disease caused by mutations in the TTR gene leading to multisystem organ dysfunction. Pathogenic TTR aggregation, misfolding, and fibrillization lead to deposition of amyloid in multiple body organs and frequently involve the peripheral nerve system and the heart. Common neurologic manifestations include: sensorimotor polyneuropathy (PN), autonomic neuropathy, small-fiber PN, and carpal tunnel syndrome.

Pharmacodynamic Properties of Subcutaneous Immunoglobulin in Myasthenia Gravis: Sub-analyses From an Open-Label Trial.

We previously reported an open-label prospective trial of subcutaneous immunoglobulin (SCIg) in mild to moderate exacerbations of myasthenia gravis (MG). The effective dose of SCIg in MG and whether measured immunoglobulin G (IgG) levels correlated with measures of disease burden were not reported. To understand the relationship between SCIg dosing and serum IgG levels on measures of disease burden: quantitative MG (QMG), MG activities of daily living (MG-ADL), MG composite (MGC), and manual muscle testing (MMT) scores.

Left atrial remodelling, mid-regional pro-atrial natriuretic peptide, and prognosis across a range of ejection fractions in heart failure.

Aims: Measures of structural and functional remodelling of the left atrium (LA) are emerging as useful biomarkers in heart failure (HF). We hypothesized that LA volume and its contribution to stroke volume (SV) would predict a composite endpoint of HF hospitalization or death in patients with HF.

Methods And Results: We recruited 57 controls and 86 patients with HF, including preserved and reduced left ventricular ejection fraction (LVEF).

Elevated Inflammatory Plasma Biomarkers in Patients With Fabry Disease: A Critical Link to Heart Failure With Preserved Ejection Fraction.

Background Because systemic inflammation and endothelial dysfunction lead to heart failure with preserved ejection fraction, we characterized plasma levels of inflammatory and cardiac remodeling biomarkers in patients with Fabry disease ( FD ). Methods and Results Plasma biomarkers were studied in multicenter cohorts of patients with FD (n=68) and healthy controls (n=40). Plasma levels of the following markers of inflammation and cardiac remodeling were determined: tumor necrosis factor ( TNF ), TNF receptor 1 ( TNFR 1) and 2 ( TNFR 2), interleukin-6, matrix metalloprotease-2 ( MMP -2), MMP -8, MMP -9, galectin-1, galectin-3, B-type natriuretic peptide ( BNP ), midregional pro-atrial natriuretic peptide ( MR -pro ANP ), and globotriaosylsphingosine.

Normal left-atrial structure and function despite concentric left-ventricular remodelling in a cohort of patients with Anderson-Fabry disease.

Aims: Anderson-Fabry Disease (AFD) is an important cause of cardiomyopathy characterized by concentric left-ventricular hypertrophy (LVH). We evaluated the extent of left-atrial (LA) structural and functional remodelling in this group of patients given that LA remodelling is a marker of adverse outcomes in the presence of LVH.

Methods And Results: Clinical profiles were obtained and cardiac MRI was performed in cohorts of patients with AFD (n = 31), healthy controls (n = 23), and a positive control cohort with known concentric remodelling and LVH (CR/H, n = 21).

Gender-specific plasma proteomic biomarkers in patients with Anderson-Fabry disease.

Aims: Anderson-Fabry disease (AFD) is an important X-linked metabolic disease resulting in progressive end-organ involvement, with cardiac disease being the dominant determinant of survival in a gender-dependent manner. Recent epidemiological screening for AFD suggests the prevalence is much higher than previously recognized, with estimates of 1:3000. Our aim was to discover novel plasma biomarker signatures in adult patients with AFD.

Hydroxychloroquine-induced cardiomyopathy: case report, pathophysiology, diagnosis, and treatment.

Drug-induced heart and vascular disease remains an important health burden. Hydroxychloroquine and its predecessor chloroquine are medications commonly used in the treatment of systemic lupus erythematosus, rheumatoid arthritis, and other connective tissue disorders. Hydroxychloroquine interferes with malarial metabolites, confers immunomodulatory effects, and also affects lysosomal function.

Anderson-Fabry cardiomyopathy: prevalence, pathophysiology, diagnosis and treatment.

Anderson-Fabry disease (AFD) is a lysosomal storage disease caused by the inappropriate accumulation of globotriaosylceramide in tissues due to a deficiency in the enzyme α-galactosidase A (α-Gal A). Anderson-Fabry cardiomyopathy is characterized by structural, valvular, vascular and conduction abnormalities, and is now the most common cause of mortality in patients with AFD. Large-scale metabolic and genetic screening studies have revealed AFD to be prevalent in populations of diverse ethnic origins, and the variant form of AFD represents an unrecognized health burden.

Circulating levels of tumor necrosis factor-alpha receptor 2 are increased in heart failure with preserved ejection fraction relative to heart failure with reduced ejection fraction: evidence for a divergence in pathophysiology.

Background: Various pathways have been implicated in the pathogenesis of heart failure (HF) with preserved ejection fraction (HFPEF). Inflammation in response to comorbid conditions, such as hypertension and diabetes, may play a proportionally larger role in HFPEF as compared to HF with reduced ejection fraction (HFREF).

Methods And Results: This study investigated inflammation mediated by the tumor necrosis factor-alpha (TNFα) axis in community-based cohorts of HFPEF patients (n = 100), HFREF patients (n = 100) and healthy controls (n = 50).

Targeting angiotensin-converting enzyme 2 as a new therapeutic target for cardiovascular diseases.

Angiotensin-converting enzyme 2 (ACE2) is a monocarboxypeptidase that metabolizes several vasoactive peptides, including angiotensin II (Ang-II; a vasoconstrictive/proliferative peptide), which it converts to Ang-(1-7). Ang-(1-7) acts through the Mas receptor to mediate vasodilatory/antiproliferative actions. The renin-angiotensin system involving the ACE-Ang-II-Ang-II type-1 receptor (AT1R) axis is antagonized by the ACE2-Ang-(1-7)-Mas receptor axis.

Angiotensin II induced proteolytic cleavage of myocardial ACE2 is mediated by TACE/ADAM-17: a positive feedback mechanism in the RAS.

Angiotensin converting enzyme (ACE) 2 is a key negative regulator of the renin-angiotensin system where it metabolizes angiotensin (Ang) II into Ang 1-7. We hypothesize that Ang II suppresses ACE2 by increasing TNF-α converting enzyme (TACE) activity and ACE2 cleavage. Ang II infusion (1.

Systolic and diastolic function assessment in fabry disease patients using speckle-tracking imaging and comparison with conventional echocardiographic measurements.

Background: Fabry cardiomyopathy is characterized by progressive left ventricular hypertrophy (LVH) associated with diastolic dysfunction and is the most common cause of death in Fabry disease (FD). However, LVH is not present in all subjects, particularly early in disease progression and in female patients. Direct assessment of myocardial deformation by strain and strain rate (SR) analysis may be sensitive to detect subclinical Fabry cardiomyopathy independent of the presence of LVH.

Manipulating angiotensin metabolism with angiotensin converting enzyme 2 (ACE2) in heart failure.

Angiotensin converting enzyme 2 (ACE2), is a monocarboxypeptidase which metabolizes several peptides including the degradation of Ang II, a peptide with vasoconstrictive/proliferative/effects, to generate Ang 1-7, which acting through its receptor Mas exerts vasodilatory/anti-proliferative actions. The classical pathway of the RAS involving the ACE-Ang II-AT receptor axis is antagonized by the second arm constituted by the ACE2-Ang 1-7/Mas receptor axis. Loss of ACE2 enhances the adverse pathological remodeling susceptibility to pressure-overload and myocardial infarction.