Phase 2 trial in acetylcholine receptor antibody-positive myasthenia gravis of transition from intravenous to subcutaneous immunoglobulin: The MGSCIg study.

Background And Purpose: Data on maintenance therapy with subcutaneous immunoglobulin (SCIg) in myasthenia gravis (MG) are limited. We report on transitioning acetylcholine receptor (AChR) antibody-positive (Ab+) MG patients on stable intravenous immunoglobulin (IVIg) regimens as part of routine clinical care to SCIg 1:1.2.

Patient Assisted Intervention for Neuropathy: Comparison of Treatment in Real Life Situations (PAIN-CONTRoLS): Bayesian Adaptive Comparative Effectiveness Randomized Trial.

Importance: Cryptogenic sensory polyneuropathy (CSPN) is a common generalized slowly progressive neuropathy, second in prevalence only to diabetic neuropathy. Most patients with CSPN have significant pain. Many medications have been tried for pain reduction in CSPN, including antiepileptics, antidepressants, and sodium channel blockers.

Small Fiber Neuropathy.

Small fiber neuropathy has a broad array of presentations. Length-dependent symptoms and findings present little diagnostic difficulty, but non-length-dependent or multifocal symptoms can be challenging. Intraepidermal nerve fiber density (IENFD) testing in apparent fibromyalgia warrants further study, but skin biopsy testing of this patient population is reasonable.

Diagnosis of mast cell activation syndrome: a global "consensus-2".

The concept that disease rooted principally in chronic aberrant constitutive and reactive activation of mast cells (MCs), without the gross MC neoplasia in mastocytosis, first emerged in the 1980s, but only in the last decade has recognition of "mast cell activation syndrome" (MCAS) grown significantly. Two principal proposals for diagnostic criteria have emerged. One, originally published in 2012, is labeled by its authors as a "consensus" (re-termed here as "consensus-1").

Review process for IVIg treatment: Lessons learned from INSIGHTS neuropathy study.

Background: This project is an effort to understand how orders for IV immunoglobulin (IVIg) are documented and prescribed by physicians, and subsequently, how they are reviewed by insurance companies for the treatment of immune neuropathies.

Methods: A panel of neuromuscular specialists reviewed case records from 248 IVIg-naive patients whose in-home IVIg infusion treatment was submitted to insurance for authorization. After reviewing a case record, 1 panelist was asked to make a diagnosis and to answer several questions about the treatment.

Rasagiline for amyotrophic lateral sclerosis: A randomized, controlled trial.

Introduction: Rasagiline is a monoamine oxidase B (MAO-B) inhibitor with possible neuroprotective effects in patients with amyotrophic lateral sclerosis (ALS).

Methods: We performed a randomized, double-blind, placebo-controlled trial of 80 ALS participants with enrichment of the placebo group with historical controls (n = 177) at 10 centers in the United States. Participants were randomized in a 3:1 ratio to 2 mg/day rasagiline or placebo.

Modeling and Preventing Progressive Hearing Loss in Usher Syndrome III.

Usher syndrome type III (USH3) characterized by progressive loss of vision and hearing is caused by mutations in the clarin-1 gene (CLRN1). Clrn1 knockout (KO) mice develop hair cell defects by postnatal day 2 (P2) and are deaf by P21-P25. Early onset profound hearing loss in KO mice and lack of information about the cochlear cell type that requires Clrn1 expression pose challenges to therapeutic investigation.

Renal and hematologic side effects of long-term intravenous immunoglobulin therapy in patients with neurologic disorders.

Introduction: For patients receiving intravenous immunoglobulin (IVIg), renal and hemolytic side effects are well recognized. However, there are very few data on the effects of chronic IVIg therapy.

Methods: We retrospectively analyzed laboratory data on 166 patients who received IVIg for 12 months with a dose range of 0.

Phase I clinical trial of safety of L-serine for ALS patients.

We performed a randomized, double-blind phase I clinical trial for six months on the effects of oral L-serine in patients with ALS. The protocol called for enrollment of patients with a diagnosis of probable or definite ALS, age 18-85 years, disease duration of less than three years and forced vital capacity (FVC) ≥ 60%. Patients were randomly assigned to four different oral twice-daily dose regimens (0.

A randomized controlled trial of methotrexate for patients with generalized myasthenia gravis.

Objective: To determine the steroid-sparing effect of methotrexate (MTX) in patients with symptomatic generalized myasthenia gravis (MG).

Methods: We performed a 12-month multicenter, randomized, double-blind, placebo-controlled trial of MTX 20 mg orally every week vs placebo in 50 acetylcholine receptor antibody-positive patients with MG between April 2009 and August 2014. The primary outcome measure was the prednisone area under the dose-time curve (AUDTC) from months 4 to 12.

Safety and Proof-of-Concept Study of Oral QLT091001 in Retinitis Pigmentosa Due to Inherited Deficiencies of Retinal Pigment Epithelial 65 Protein (RPE65) or Lecithin:Retinol Acyltransferase (LRAT).

Unlabelled: Restoring vision in inherited retinal degenerations remains an unmet medical need. In mice exhibiting a genetically engineered block of the visual cycle, vision was recently successfully restored by oral administration of 9-cis-retinyl acetate (QLT091001). Safety and visual outcomes of a once-daily oral dose of 40 mg/m2/day QLT091001 for 7 consecutive days was investigated in an international, multi-center, open-label, proof-of-concept study in 18 patients with RPE65- or LRAT-related retinitis pigmentosa.

Progressive Muscular Atrophy.

Progressive muscular atrophy (PMA) is a rare, sporadic, adult-onset motor neuron disease, clinically characterized by isolated lower motor neuron features; however, clinically evident upper motor neuron signs may emerge in some patients. Subclinical upper motor neuron involvement is identified pathologically, radiologically, and neurophysiologically in a substantial number of patients with PMA. Patients with subclinical upper motor neuron involvement do not fulfill the revised El Escorial criteria to participate in amyotrophic lateral sclerosis clinical trials.

A multi-center screening trial of rasagiline in patients with amyotrophic lateral sclerosis: Possible mitochondrial biomarker target engagement.

Rasagiline, a monoamine oxidase B inhibitor, slowed disease progression in the SOD1 mouse, and in a case series of patients with amyotrophic lateral sclerosis (ALS). Here we determine whether rasagiline is safe and effective in ALS compared to historical placebo controls, and whether it alters mitochondrial biomarkers. We performed a prospective open-label, multicenter screening trial of 36 ALS patients treated with 2 mg oral rasagiline daily for 12 months.

Routine use of punch biopsy to diagnose small fiber neuropathy in fibromyalgia patients.

Fibromyalgia is a clinical syndrome that currently does not have any specific pathological finding to aid in diagnosis. Therefore, fibromyalgia is most likely a heterogeneous group of diseases with similar symptoms. Identifying and understanding the pathological basis of fibromyalgia will allow physicians to better categorize patients, increasing prospective treatment options, and improving potential therapeutic endeavors.

Acquired immune demyelinating neuropathies.

Purpose Of Review: Acquired immune demyelinating neuropathies refer to a group of disorders that share overlapping sensory, motor, and autonomic clinical, laboratory, and electrodiagnostic features. It is important to recognize acquired immune demyelinating neuropathies as they are generally responsive to immunosuppressive or immunomodulatory therapies.

Recent Findings: This article reviews recently developed early prognostic tools in Guillain-Barré syndrome and discusses the evolving understanding of chronic demyelinating phenotypes with differing treatment responsiveness.

Oral 9-cis retinoid for childhood blindness due to Leber congenital amaurosis caused by RPE65 or LRAT mutations: an open-label phase 1b trial.

Background: Leber congenital amaurosis, caused by mutations in RPE65 and LRAT, is a severe form of inherited retinal degeneration leading to blindness. We aimed to assess replacement of the missing chromophore 11-cis retinal with oral QLT091001 (synthetic 9-cis-retinyl acetate) in these patients.

Methods: In our open-label, prospective, phase 1b trial, we enrolled patients (aged ≥6 years) with Leber congenital amaurosis and RPE65 or LRAT mutations at McGill University's Montreal Children's Hospital.

Laboratory evaluation of peripheral neuropathy.

The question of how to evaluate peripheral neuropathies is complicated by there being hundreds of potential causes, both acquired and inherited. This article focuses on a targeted and thoughtful approach to the laboratory evaluation of patients with peripheral neuropathy, designed to allow the identification of treatable neuropathies without undue expense and risk to patients. After determining which clinical patterns are present, the patterns are used to define a discrete manageable subset of diseases underlying these neuropathies.

Usefulness of skin biopsies in the evaluation and management of patients with suspected small fiber neuropathy.

Objective: To assess the usefulness of skin biopsy in the assessment of patients with suspeted small fiber neuropathy (SFN).

Methods: Retrospective chart review of patients with sensory symptoms or findings restricted to small nerve fibers and normal nerve conduction studies (NCS) seen in a subspecialty neuromuscular private practice.

Results: Assessments were made on 145 patients.

A Pilot Trial of Pioglitazone HCl and Tretinoin in ALS: Cerebrospinal Fluid Biomarkers to Monitor Drug Efficacy and Predict Rate of Disease Progression.

Objectives. To determine if therapy with pioglitazone HCl and tretinoin could slow disease progression in patients with ALS. Levels of tau and pNFH in the cerebrospinal fluid were measured to see if they could serve as prognostic indicators.