Prevalence of Axonal Sensory Neuropathy With IgM Binding to Trisulfated Heparin Disaccharide in Patients With Fibromyalgia.

Objective: To assess the intraepidermal nerve fiber density in patients diagnosed with fibromyalgia (FM) and to evaluate the role of IgM binding to trisulfated heparin disaccharide (TS-HDS) in these patients.

Methods: FM is a poorly understood pain disorder with several proposed pathophysiologic mechanisms. It is characterized by widespread pain, fatigue, and sleep abnormalities.

CANOMAD and other chronic ataxic neuropathies with disialosyl antibodies (CANDA).

Introduction: CANOMAD/CANDA are syndromes characterized by ataxic neuropathy, ophthalmoplegia, monoclonal gammopathy, cold agglutinins and disialosyl antibodies.

Methods: A retrospective review of our neuromuscular autoantibody panel database was performed. Anti-GD1b seropositive patients with ataxia were included.

Defining SOD1 ALS natural history to guide therapeutic clinical trial design.

Importance: Understanding the natural history of familial amyotrophic lateral sclerosis (ALS) caused by SOD1 mutations (ALS) will provide key information for optimising clinical trials in this patient population.

Objective: To establish an updated natural history of ALS.

Design, Setting And Participants: Retrospective cohort study from 15 medical centres in North America evaluated records from 175 patients with ALS with genetically confirmed SOD1 mutations, cared for after the year 2000.

Myelinated and unmyelinated endoneurial axon quantitation and clinical correlation.

Introduction: Different disease patterns result from loss of myelinated and unmyelinated axons, but quantitation to define their loss has been difficult.

Methods: We measured large and small endoneurial axons in axonal neuropathies by staining them with peripherin and comparing their area to that of nonmyelinating Schwann cells stained with neural cell adhesion molecule (NCAM).

Results: Loss of myelinated and unmyelinated axons was typically proportional, with predominant myelinated or unmyelinated axon loss in a few patients.

Targeted sequencing and identification of genetic variants in sporadic inclusion body myositis.

Sporadic inclusion body myositis (sIBM) has clinical, pathologic and pathomechanistic overlap with some inherited muscle and neurodegenerative disorders. In this study, DNA from 79 patients with sIBM was collected and the sequencing of 38 genes associated with hereditary inclusion body myopathy (IBM), myofibrillar myopathy, Emery-Dreifuss muscular dystrophy, distal myopathy, amyotrophic lateral sclerosis and dementia along with C9orf72 hexanucleotide repeat analysis was performed. No C9orf72 repeat expansions were identified, but; 27 rare (minor allele frequency <1%) missense coding variants in several other genes were identified.

Autophagic vacuolar pathology in desminopathies.

Autophagic vacuolar myopathies are an emerging group of muscle diseases with common pathologic features. These include autophagic vacuoles containing both lysosomal and autophagosomal proteins sometimes lined with sarcolemmal proteins such as dystrophin. These features have been most clearly described in patients with Danon's disease due to LAMP2 deficiency and X-linked myopathy with excessive autophagy (XMEA) due to mutations in VMA21.

Myovascular innervation: axon loss in small-fiber neuropathies.

Introduction: Vascular denervation occurs in some neuropathies, but measurement of small perivascular axons has been difficult.

Methods: We evaluated 31 consecutive patients who had both muscle and skin biopsies. We quantitated myovascular innervation by staining unmyelinated axons with peripherin and non-myelinating Schwann cells with neural cell adhesion molecule and comparing their areas.

Cramps and small-fiber neuropathy.

Introduction: Muscle cramps are a common complaint and are thought to arise from spontaneous discharges of the motor nerve terminal. Polyneuropathy is often causative, but small-fiber neuropathy (SFN) has not been assessed.

Methods: We performed skin biopsies on consecutive patients with cramps but without neuropathic complaints.

Exome sequencing reveals DNAJB6 mutations in dominantly-inherited myopathy.

Objective: To identify the causative gene in an autosomal dominant limb-girdle muscular dystrophy (LGMD) with skeletal muscle vacuoles.

Methods: Exome sequencing was used to identify candidate mutations in the studied pedigree. Genome-wide linkage was then used to narrow the list of candidates to a single disease-associated mutation.

Inflammatory demyelinating neuropathies.

The primary goal of therapy in patients with the Guillain-Barré syndrome (GBS) and chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is improved strength and functional ability. Improvement in pain, sensory loss, gait disorder, and autonomic instability are other goals of therapy. Patients with very mild symptoms that do not interfere with activities of daily living can be observed for deterioration without treatment.

Familial ALS with extreme phenotypic variability due to the I113T SOD1 mutation.

We describe a large family with amyotrophic lateral sclerosis (ALS) caused by an I113T mutation in superoxide dismuatse type 1 (SOD1). The proband developed symptoms typical for ALS at age 39 years and is still walking five years later. Marked phenotypic variability is manifested by her mother with onset of gait difficulty and decision-making problems at age 67 years and a five-year course marked by progressive mild upper motor neuron weakness, frontotemporal dementia and chorea.

Motor neuron disease associated with copper deficiency.

Copper deficiency in humans is a rare cause of myeloneuropathy that usually presents with a spastic ataxic gait, hyperreflexia, and distal sensory loss similar to that seen in patients with subacute combined degeneration. We describe three copper-deficient patients, two of whom were referred with a presumptive diagnosis of amyotrophic lateral sclerosis, who had progressive asymmetric weakness or electrodiagnostic findings of proximal and distal denervation suggestive of lower motor neuron disease. Copper replacement resulted in stabilization or mild improvement in weakness.

Brachio-cervical inflammatory myopathies: clinical, immune, and myopathologic features.

Objective: To characterize patients with inflammatory myopathies who present with weakness in the proximal regions of the arms.

Methods: Clinical, laboratory, and myopathologic features were evaluated in 10 patients, identified consecutively over 12 years, with inflammatory myopathies and weakness that was most severe in the proximal regions of the arms. The features of these brachio-cervical inflammatory myopathy (BCIM) syndromes were compared with those of other inflammatory and immune-mediated myopathies evaluated during the same period.

Peripheral neuropathy in an outpatient cohort of patients with Sjögren's syndrome.

Peripheral neuropathy is common in patients with Sjögren's syndrome (SS), but its precise prevalence is unknown. Most prior studies were conducted at neurology or rheumatology specialty clinics and likely selected for a more severely affected population. We evaluated 22 SS patients and 10 controls for evidence of neuropathy in an outpatient setting at a regional meeting of the Sjögren's Syndrome Foundation.

Treatment of chronic inflammatory demyelinating polyneuropathy with high-dose intermittent intravenous methylprednisolone.

Background: Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) causes progressive disability due to weakness but responds to immunomodulating medication, including oral prednisone and intravenous (IV) immunoglobulin (IVIg). However, there is no consensus on initial therapy, and both of these treatments have drawbacks with long-term treatment.

Objective: To review the efficacy and safety of high-dose, intermittent IV methylprednisolone (IVMP) as initial and long-term maintenance therapy for patients with CIDP.

Severe sensory ataxia and demyelinating polyneuropathy with IgM anti-GM2 and GalNAc-GD1A antibodies.

Several polyneuropathy syndromes have been described with polyclonal serum immunoglobulin G (IgG) or immunoglobulin M (IgM) binding to gangliosides GM2 and GalNAc-GD1a that contain the terminal trisaccharide moiety GalNAc(beta1-4)Gal(alpha2-3)NeuAc. We describe the clinical and electrodiagnostic features in two patients with serum IgM monoclonal anti-GM2 and anti-GalNAc-GD1a antibodies. These patients had slowly progressive, panmodal sensory loss with severe sensory ataxia.