An open-label pilot study of losmapimod to evaluate the safety, tolerability, and changes in biomarker and clinical outcome assessments in participants with facioscapulohumeral muscular dystrophy type 1.

Introduction: Facioscapulohumeral muscular dystrophy (FSHD) is a genetic disease caused by aberrant DUX4 expression, leading to progressive muscle weakness. No effective pharmaceutical treatment is available. Losmapimod, a small molecule selective inhibitor of p38 α/β MAPK, showed promising results in a phase 1 trial for the treatment of FSHD, prompting additional studies.

Safety and efficacy of losmapimod in facioscapulohumeral muscular dystrophy (ReDUX4): a randomised, double-blind, placebo-controlled phase 2b trial.

Background: Facioscapulohumeral muscular dystrophy is a hereditary progressive myopathy caused by aberrant expression of the transcription factor DUX4 in skeletal muscle. No approved disease-modifying treatments are available for this disorder. We aimed to assess the safety and efficacy of losmapimod (a small molecule that inhibits p38α MAPK, a regulator of DUX4 expression, and p38β MAPK) for the treatment of facioscapulohumeral muscular dystrophy.

Quantitative Muscle Analysis in FSHD Using Whole-Body Fat-Referenced MRI: Composite Scores for Longitudinal and Cross-sectional Analysis.

Background And Objectives: Facioscapulohumeral muscular dystrophy (FSHD) is a rare, debilitating disease characterized by progressive muscle weakness. MRI is a sensitive assessment of disease severity and progression. We developed a quantitative whole-body (WB) musculoskeletal MRI (WB-MSK-MRI) protocol analyzing muscles in their entirety.

Quantitative muscle analysis in facioscapulohumeral muscular dystrophy using whole-body fat-referenced MRI: Protocol development, multicenter feasibility, and repeatability.

Introduction/aims: Functional performance tests are the gold standard to assess disease progression and treatment effects in neuromuscular disorders. These tests can be confounded by motivation, pain, fatigue, and learning effects, increasing variability and decreasing sensitivity to disease progression, limiting efficacy assessment in clinical trials with small sample sizes. We aimed to develop and validate a quantitative and objective method to measure skeletal muscle volume and fat content based on whole-body fat-referenced magnetic resonance imaging (MRI) for use in multisite clinical trials.

Phase 1 clinical trial of losmapimod in facioscapulohumeral dystrophy: Safety, tolerability, pharmacokinetics, and target engagement.

Aims: Evaluate safety, tolerability, pharmacokinetics (PK) and target engagement (TE) of losmapimod in blood and muscle in facioscapulohumeral dystrophy (FSHD).

Methods: This study included Part A: 10 healthy volunteers randomized to single oral doses of losmapimod (7.5 mg then 15 mg; n = 8) or placebo (both periods; n = 2); Part B: 15 FSHD subjects randomized to placebo (n = 3), or losmapimod 7.

Safety and efficacy of opicinumab in patients with relapsing multiple sclerosis (SYNERGY): a randomised, placebo-controlled, phase 2 trial.

Background: Opicinumab is a human monoclonal antibody against LINGO-1, an inhibitor of oligodendrocyte differentiation and axonal regeneration. Previous findings suggested that opicinumab treatment might enhance remyelination in patients with CNS demyelinating diseases. We aimed to assess the safety and efficacy of opicinumab in patients with relapsing multiple sclerosis.

Jaw clonus frequency does not support hypothesis of peripheral mechanism of self-re-excitation.

Jaw clonus is an uncommon pathological reflex thought to indicate corticospinal tract dysfunction above the Vth cranial nerve. It is useful as a sign of upper motor neuron dysfunction above the spinal cord. One theory of self excitation posits an inverse and linear relationship between clonus frequency and the length of the reflex arc, to explain the higher frequency of clonus in the ankles than the wrist.

Small-fiber degeneration in alcohol-related peripheral neuropathy.

Background: Alcohol-related peripheral neuropathy (ALN) is generally characterized as an axonal large-fiber polyneuropathy caused by thiamine deficiency. We hypothesized, based on clinical observations, that ALN is associated with a small-fiber polyneuropathy that can be diagnosed with skin biopsy in heavy alcohol drinking subjects with normal thiamine status.

Methods: Eighteen individuals (9 heavy alcohol drinking subjects and 9 healthy control subjects) were assessed for the potential utility of skin biopsies in detecting ALN-associated small nerve fiber degeneration.

Impact of preventive medications in migraine patients at Rhode Island Hospital.

Objective: Determine healthcare resource utilization in migraine patients prescribed preventive medications in the resident neurology clinic at Rhode Island Hospital.

Background: Similar institutions have demonstrated that treatment with preventive migraine medications results in significant decreases in outpatient and ED visits, CT/ MRI scans and abortive medication usage.

Methods: Retrospective chart review identified 166 patients based on icd-9 code.

Experimental model of alcohol-related peripheral neuropathy.

Introduction: The aim of this work was to determine the effect of chronic alcohol exposure on peripheral nerves in a nutritionally balanced rat model of alcoholism.

Methods: Three different strains of adult male rats were pair-fed for 8 weeks with isocaloric liquid diets containing 0% or 37% ethanol. Nerve conduction studies (NCS) were performed.

A randomized, double-blind, placebo-controlled phase II study of eculizumab in patients with refractory generalized myasthenia gravis.

Introduction: Complement activation at the neuromuscular junction is a primary cause of acetylcholine receptor loss and failure of neuromuscular transmission in myasthenia gravis (MG). Eculizumab, a humanized monoclonal antibody, blocks the formation of terminal complement complex by specifically preventing the enzymatic cleavage of complement 5 (C5).

Methods: This study was a randomized, double-blind, placebo-controlled, crossover trial involving 14 patients with severe, refractory generalized MG (gMG).

Experimental alcohol-related peripheral neuropathy: role of insulin/IGF resistance.

The mechanisms of alcohol-related peripheral neuropathy (ALPN) are poorly understood. We hypothesize that, like alcohol-related liver and brain degeneration, ALPN may be mediated by combined effects of insulin/IGF resistance and oxidative stress. Adult male Long Evans rats were chronically pair-fed with diets containing 0% or 37% ethanol (caloric), and subjected to nerve conduction studies.

Alcohol-related peripheral neuropathy: nutritional, toxic, or both?

Alcohol-related peripheral neuropathy (ALN) is a potentially debilitating complication of alcoholism that results in sensory, motor, and autonomic dysfunction. Unfortunately, ALN is rarely discussed as a specific disease entity in textbooks because it is widely assumed to primarily reflect consequences of nutritional deficiency. This hypothesis is largely based on observations first made over eight decades ago when it was demonstrated that thiamine deficiency (beriberi) neuropathy was clinically similar to ALN.

Safety of nerve conduction studies in patients with peripheral intravenous lines.

Nerve conduction studies (NCS) may be deferred because of a perceived risk of cardiac arrhythmia in the presence of same-limb peripheral intravenous lines. Patients with implanted pacemakers or defibrillators provide a model in whom this risk can be assessed. Twenty patients, seven with pacemakers and 13 with defibrillators, had peripheral intravenous lines placed during routine care and underwent NCS in the same limb.

Safety of nerve conduction studies in patients with implanted cardiac devices.

Patients with implanted cardiac devices and their physicians may defer important electrodiagnostic testing because of anxiety about potential negative effects on the device. To determine the safety of routine nerve conduction studies (NCS) in this population, 10 patients with permanent dual-chamber pacemakers of various types and five patients with implanted cardiac defibrillators (ICD) underwent nerve stimulation at sites commonly used during NCS. The implanted cardiac device was interrogated before and after the study and there was continuous monitoring of the surface electrocardiogram (ECG) and atrial and ventricular electrograms.

Identifying and treating myofascial pain syndrome.

Though common, myofascial pain syndrome can be difficult to recognize and distinguish from underlying entities. It is often confused with fibromyalgia. Diagnosis hinges on the identification of painful muscle trigger points that, when palpated, create local twitch responses and refer pain in predictable patterns.

Sever's disease and other causes of heel pain in adolescents.

Sever's disease, or apophysitis of the calcaneus, is a common but frequently undiagnosed source of heel pain in young athletes. This condition frequently occurs before or during the peak growth spurt in boys and girls, often shortly after they begin a new sport or season. Sever's disease often occurs in running and jumping sports, particularly soccer.