Pharmacogenetic and microRNA mechanisms of beta blocker use on bone.

Motivated by studies showing an association between beta blocker (BB) use and positive bone outcomes, a pilot randomized control trial (RCT) was performed at the Mayo Clinic which randomized postmenopausal women to placebo, propranolol (40 or 80 mg twice daily), atenolol (50 mg/day), or nebivolol (5 mg/day) to determine changes in bone turnover markers (BTMs) and in bone mineral density (BMD) over 20 weeks. Pharmacogenetic effects and microRNA-mediated mechanisms involving beta adrenergic receptor and related genes have previously been found. We sought to validate these effects and discover new candidates in an ancillary study to the pilot clinical trial.

Expert consensus recommendations for improving and standardising the assessment of patients with generalised myasthenia gravis.

Background: Regular and consistent disease assessment could provide a clearer picture of burden in generalised myasthenia gravis (gMG) and improve patient care; however, the use of assessment tools in practice lacks standardisation. This modified Delphi approach was taken to review current evidence on assessment tool use in gMG and develop expert-derived consensus recommendations for good practice.

Methods: A European expert panel of 15 experienced gMG neurologists contributed to development of this consensus, four of whom formed a lead Sub-committee.

The Queen Square Encephalitis Multidisciplinary Team Meeting - experience over three years, pre and post the COVID-19 pandemic.

Background: Patients with suspected encephalitis continue to represent a diagnostic and therapeutic challenge, even in highly resourced centres. In February 2018, we set up a monthly in-person multidisciplinary team meeting (MDT). We describe the experience and outcomes of the MDT over three years.

Neuromuscular Features in XL-MTM Carriers: A Cross-sectional Study in an Unselected Cohort.

Background And Objective: X-linked myotubular myopathy (XL-MTM) is an early-onset congenital myopathy characterized by mild to severe muscle weakness in male individuals. The objective was to characterize the clinical spectrum of neuromuscular features in X-linked myotubular myopathy (XL-MTM) carriers.

Methods: We performed a nationwide cross-sectional study focusing on neuromuscular features in an unselected cohort of Dutch XL-MTM carriers.

Bortezomib for anti-NMDAR encephalitis following daclizumab treatment in a patient with multiple sclerosis.

Background: Daclizumab is an anti-CD25 monoclonal antibody developed for the treatment of relapsing remitting multiple sclerosis, which was withdrawn worldwide in March 2018, due to emerging serious immune-mediated systemic andcentral nervous system adverse events. We report a case of anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis occurring 14 weeks after stopping daclizumab, which responded to the proteasome inhibitor bortezomib.

Methods: Following lack of effective clinical response to first line (corticosteroid, plasma exchange, intravenous immunoglobulin) and second line (rituximab) treatments, bortezomib therapy was commenced.

Spectrum of Clinical Features in X-Linked Myotubular Myopathy Carriers: An International Questionnaire Study.

Objective: To characterize the spectrum of clinical features in a cohort of X-linked myotubular myopathy (XL-MTM) carriers, including prevalence, genetic features, clinical symptoms, and signs, as well as associated disease burden.

Methods: We performed a cross-sectional online questionnaire study among XL-MTM carriers. Participants were recruited from patient associations, medical centers, and registries in the United Kingdom, Germany, and the Netherlands.

Prolonged Ventilatory Support for Patients Recovering From Guillain-Barré Syndrome.

Background: Recovery from Guillain-Barré syndrome (GBS) may be protracted, and patients may need prolonged ventilatory support. We present clinical data from a tertiary referral weaning center managing patients with GBS requiring prolonged ventilatory support.

Methods: A retrospective review of patients managed in a 34-bed specialist ventilator weaning facility in London, United Kingdom, between 2006 and 2017.

Signal, bias, and the role of transcriptome assembly quality in phylogenomic inference.

Background: Phylogenomic approaches have great power to reconstruct evolutionary histories, however they rely on multi-step processes in which each stage has the potential to affect the accuracy of the final result. Many studies have empirically tested and established methodology for resolving robust phylogenies, including selecting appropriate evolutionary models, identifying orthologs, or isolating partitions with strong phylogenetic signal. However, few have investigated errors that may be initiated at earlier stages of the analysis.

Thromboembolic risk with IVIg: Incidence and risk factors in patients with inflammatory neuropathy.

Our objective was to evaluate whether IV immunoglobulin (IVIg) increases the risk of thromboembolic events in neurology outpatients with inflammatory neuropathies, as there is conflicting evidence supporting this hypothesis, mainly from non-neurologic cohorts. We investigated this question over 30 months in our cohort of patients with inflammatory neuropathies receiving regular IVIg and found a greater incidence of arterial and venous thromboembolic events than population-based rates determined by hospital admissions data. Vascular risk factors were more common in the event group but there were no IVIg administration factors that contributed to the risk.

Rhombencephalitis and Myeloradiculitis Caused by a European Subtype of Tick-Borne Encephalitis Virus.

We report a case of a previously healthy man returning to the United Kingdom from Lithuania who developed rhombencephalitis and myeloradiculitis due to tick-borne encephalitis. These findings add to sparse data on tick-borne encephalitis virus phylogeny and associated neurologic syndromes and underscore the importance of vaccinating people traveling to endemic regions.

Lambert-Eaton syndrome IgG inhibits transmitter release via P/Q Ca2+ channels.

Objective: To determine whether immunoglobulin G (IgG) from patients with Lambert-Eaton myasthenic syndrome (LEMS) decreases action potential–evoked synaptic vesicle exocytosis,and whether the effect is mediated by P/Q-type voltage-gated calcium channels (VGCCs).

Methods: IgG was obtained from 4 patients with LEMS (3 males, 1 female), including 2 patients with lung malignancy. Antibodies against P/Q-type VGCCs were detected in all 4 patients, and against N-type VGCCs in 2.

Diagnosis of skeletal muscle channelopathies.

Introduction: Skeletal muscle channelopathies are rare disorders of muscle membrane excitability. Their episodic nature may result in diagnostic difficulty and delays in diagnosis. Advances in diagnostic clinical electrophysiology combined with DNA-based diagnosis have improved diagnostic accuracy and efficiency.

Slow channel congenital myasthenic syndrome responsive to a combination of fluoxetine and salbutamol.

Introduction: Slow channel congenital myasthenic syndrome is a dominant disorder characterized by prolonged acetylcholine receptor ion-channel activation.

Methods: Molecular genetic techniques, electrophysiology, and binding studies in human embryonic kidney (HEK) 293 cells determined mutant function and expression levels. Patient response to treatment was measured by quantitative myasthenic gravis and Medical Research Council grade strength scores.

History central to diagnosing myasthenia gravis.

Myasthenia gravis (MG) is caused by failure of chemical transmission at the neuromuscular junction. It is an autoimmune disorder in which antibodies interfere with neuromuscular transmission. It has a prevalence of around 20 per 100,000.

Myasthenia and related disorders of the neuromuscular junction.

Our understanding of transmission at the neuromuscular junction has increased greatly in recent years. We now recognise a wide variety of autoimmune and genetic diseases that affect this specialised synapse, causing muscle weakness and fatigue. These disorders greatly affect quality of life and rarely can be fatal.

Spectrum of peripheral neuropathies associated with surgical interventions; A neurophysiological assessment.

Background: We hypothesized that a wide range of surgical procedures may be complicated by neuropathies, not just in close proximity but also remote from procedural sites. The aim of this study was to classify post-operative neuropathies and the procedures associated with them.

Methods: We retrospectively identified 66 patients diagnosed with post-procedure neuropathies between January 2005 and June 2008.