Lamina-associated polypeptide-1 interacts with the muscular dystrophy protein emerin and is essential for skeletal muscle maintenance.

X-linked Emery-Dreifuss muscular dystrophy is caused by loss of function of emerin, an integral protein of the inner nuclear membrane. Yet emerin null mice are essentially normal, suggesting the existence of a critical compensating factor. We show that the lamina-associated polypeptide1 (LAP1) interacts with emerin.

A novel mutation in PNPLA2 leading to neutral lipid storage disease with myopathy.

Background: Mutations in PNPLA2, a gene encoding adipose triglyceride lipase, lead to neutral lipid storage disease with myopathy.

Objective: To report the clinical and molecular features of a case of neutral lipid storage disease with myopathy resulting from a novel mutation in PNPLA2.

Design: Case report.

Senataxin mutations and amyotrophic lateral sclerosis.

We studied three patients with mutations in the senataxin gene (SETX). One had juvenile onset of ALS. The second case resembled hereditary motor neuropathy.

Utility of skin biopsy to evaluate peripheral neuropathy.

Skin biopsy for epidermal nerve fiber analysis provides an important objective test for the diagnosis of peripheral neuropathy, particularly small fiber sensory neuropathy (SFSN). The determination of epidermal nerve fiber density (ENFD) is reliable, with high diagnostic specificity and good sensitivity. Because of false negatives, biopsy results must be interpreted in conjunction with neurologic findings and laboratory results, including objective tests of sensory and autonomic function.

A prospective cohort study of neuropsychological test performance in ALS.

Our objective was to determine the prevalence and predictors of cognitive impairment in ALS, measure differences in survival among impaired and unimpaired patients, and assess changes in neuropsychological test performance over time. Fifty patients were enrolled in a prospective cohort study of neuropsychological performance. ANOVA and chi(2) tests assessed differences in clinical characteristics and neuropsychologic test results; general estimating equations assessed change in test performance; multiple regression determined which variables contributed to cognitive status; and Cox models compared survival.

Collagen nerve protector in rat sciatic nerve repair: A morphometric and histological analysis.

Peripheral nerve repair is often complicated by fibroblastic scar formation, nerve dysfunction, and traumatic neuroma formation. Use of bio-absorbable protective wraps may improve outcomes of these repairs. This study histologically compared the incidence of neuroma formation, connective tissue proliferation, and axonal regrowth in transected rat sciatic nerves repaired with and without tubular collagen nerve sleeves.

Small fiber neuropathy following vaccination for rabies, varicella or Lyme disease.

Neuropathy following vaccination has been reported; however, biopsy-confirmed small fiber neuropathy has not been described. We report five patients who developed paresthesias within one day to two months following vaccination for rabies, varicella zoster, or Lyme disease. On examination, there was mild sensory loss in distal extremities, preserved strength, normal or minimally abnormal electrodiagnostic findings, and decreased epidermal nerve fiber densities per skin biopsy.

Reduction of a 4q35-encoded nuclear envelope protein in muscle differentiation.

Muscular dystrophy and peripheral neuropathy have been linked to mutations in genes encoding nuclear envelope proteins; however, the molecular mechanisms underlying these disorders remain unresolved. Nuclear envelope protein p19A is a protein of unknown function encoded by a gene at chromosome 4q35. p19A levels are significantly reduced in human muscle as cells differentiate from myoblasts to myotubes; however, its levels are not similarly reduced in all differentiation systems tested.

Amyotrophic lateral sclerosis and neurosarcoidosis: a case report.

Amyotrophic lateral sclerosis (ALS) remains a clinical diagnosis without definable biomarkers. The pathomechanism of motor neuron degeneration in ALS has yet to be elucidated. Here we present a case of limb-onset ALS, with autopsy findings of Bunina bodies and skein-like inclusions, as well as sarcoid granulomas predominating among motor neurons.

Amyotrophic lateral sclerosis with ragged-red fibers.

Background: Motor neuron diseases (amyotrophic lateral sclerosis [ALS] and spinal muscular atrophy [SMA]) have been rarely associated with mitochondrial respiratory chain defects.

Objectives: To describe a patient with typical ALS and the finding of ragged-red fibers in muscle biopsy specimens and to review the literature on respiratory chain defects in ALS and SMA.

Design: Case report and review of the literature.

X-linked dominant scapuloperoneal myopathy is due to a mutation in the gene encoding four-and-a-half-LIM protein 1.

Scapuloperoneal (SP) syndrome encompasses heterogeneous neuromuscular disorders characterized by weakness in the shoulder-girdle and peroneal muscles. In a large Italian-American pedigree with dominant SP myopathy (SPM) previously linked to chromosome 12q, we have mapped the disease to Xq26, and, in all of the affected individuals, we identified a missense change (c.365G-->C) in the FHL1 gene encoding four-and-a-half-LIM protein 1 (FHL1).

Inducible overexpression of wild-type prion protein in the muscles leads to a primary myopathy in transgenic mice.

The prion protein (PrP) level in muscle has been reported to be elevated in patients with inclusion-body myositis, polymyositis, dermatomyositis, and neurogenic muscle atrophy, but it is not clear whether the elevated PrP accumulation in the muscles is sufficient to cause muscle diseases. We have generated transgenic mice with muscle-specific expression of PrP under extremely tight regulation by doxycycline, and we have demonstrated that doxycycline-induced overexpression of PrP strictly limited to muscles leads to a myopathy characterized by increased variation of myofiber size, centrally located nuclei, and endomysial fibrosis, in the absence of intracytoplasmic inclusions, rimmed vacuoles, or any evidence of a neurogenic disorder. The PrP-induced myopathy correlates with accumulation of an N-terminal truncated PrP fragment in the muscle, and the muscular PrP displayed consistent mild resistance to protease digestion.

RAGE: a journey from the complications of diabetes to disorders of the nervous system - striking a fine balance between injury and repair.

The Receptor for Advanced Glycation End Products (RAGE) is a multiligand member of the immunoglobulin superfamily. RAGE interacts with AGEs, the products of nonenzymatic glycation/oxidation of proteins and lipids that accumulate in diverse settings, such as diabetes, inflammation, renal failure, pro-oxidant states and natural aging. In addition, RAGE is also a receptor for amyloid-beta peptide and beta-sheet fibril species.

Sporadic amyotrophic lateral sclerosis and breast cancer: Hyaline conglomerate inclusions lead to identification of SOD1 mutation.

Autopsy of patients with sporadic amyotrophic lateral sclerosis (ALS) rarely provides clues to a genetic etiology. We studied a 66-year-old woman who developed progressive weakness, fasciculations and upper motor neuron signs 1 year after mastectomy and chemotherapy for a breast carcinoma. She died 14 months after the onset of neurological symptoms.

Adult-onset nemaline myopathy and monoclonal gammopathy.

A 45-year-old man with severe proximal muscle weakness had findings diagnostic of adult-onset nemaline myopathy. He also had a monoclonal gammopathy. This is the fifth report of adult-onset nemaline myopathy in a patient with monoclonal gammopathy, suggesting that the occurrence of these entities may be more than a chance association.

Altered subicular MAP2 immunoreactivity in schizophrenia.

We wished to test independently a previously reported loss of subicular microtubule-associated protein 2 (MAP2) in the brains of deceased individuals who had suffered from schizophrenia, and to determine whether there were any clinical characteristics attached to such a loss. Immunohistochemistry for MAP2 was examined in the hippocampal region from 94 psychiatric patients: 64 with a primary diagnosis of schizophrenia or schizoaffective disorder, 12 with a primary diagnosis of major depressive or bipolar disorders, and 18 with a primary diagnosis of dementia; and from 17 individuals without psychiatric disease. Lifelong symptomatology was evaluated with the modified Diagnostic Evaluation After Death.

Benign course of glycogen storage disease type IIb in two brothers: nature or nurture?

Two brothers with the childhood variant of type II glycogenosis (GSD-IIb) treated with nutrition and exercise therapy (NET) from a young age showed an unusually benign course. Muscle biopsy from the older brother, which showed characteristic vacuolar glycogen accumulation at age 2, had reverted to normal by age 16. A muscle biopsy from the younger brother was normal at 5 years.

Early-onset toe walking in rippling muscle disease due to a new caveolin-3 gene mutation.

The authors describe a family with autosomal dominant rippling muscle disease (RMD) and prominent early-onset toe walking. Molecular analysis revealed a novel heterozygous G > A transition at nucleotide position 136 in exon 2 of the caveolin-3 gene (CAV3). The role of Achilles tendon lengthening in more severe forms of RMD is discussed.

Small-fiber neuropathy/neuronopathy associated with celiac disease: skin biopsy findings.

Background: Celiac disease (CD) is increasingly recognized in North America and is associated with a peripheral neuropathy.

Objective: To report the clinical characteristics and skin biopsy results in patients with CD and small-fiber neuropathy symptoms.

Design: Case series.

Fatal CNS vasculopathy in a patient with refractory celiac disease and lymph node cavitation.

Celiac disease is an enteropathy occurring in genetically predisposed individuals due to a dietary intolerance to gluten. Patients with celiac disease may develop a neurological disorder of unknown cause, although autoimmune mechanisms are suspected. We report on a 56-year-old man with celiac disease, who became refractory to a gluten-free diet and died of a rapidly progressive encephalopathy.

Gene expression profiling in chronic inflammatory demyelinating polyneuropathy.

Gene expression in archived frozen sural nerve biopsies of patients with chronic inflammatory demyelinating polyneuropathy (CIDP) was compared to that in vasculitic nerve biopsies (VAS) and to normal nerve (NN) by DNA microarray technology. Hierarchical clustering analysis demonstrated distinct gene expression patterns distinguishing these disease groups. Of particular interest were: (1) Tachykinin precursor 1, which may be involved in pain mediation; (2) Stearoyl-CoA-desaturase, which may be a marker for remyelination and (3) the Allograft Inflammatory Factor 1 (AIF-1), a modulator of immune response during macrophage activation.

RAGE modulates peripheral nerve regeneration via recruitment of both inflammatory and axonal outgrowth pathways.

Axotomy of peripheral nerve stimulates events in multiple cell types that initiate a limited inflammatory response to axonal degeneration and simultaneous outgrowth of neurites into the distal segments after injury. We found that pharmacological blockade of RAGE impaired peripheral nerve regeneration in mice subjected to RAGE blockade and acute crush of the sciatic nerve. As our studies revealed that RAGE was expressed in axons and in infiltrating mononuclear phagocytes upon injury, we tested the role of RAGE in these distinct cell types on nerve regeneration.