The history of the European Neurological Society (1986-2014)-10 years later.

Background And Purpose: The European Academy of Neurology (EAN) was a merger from two parent societies: the European Neurological Association (ENS, founded in 1986) and the European Federation of Neurological Societies (EFNS, founded in 1987).

Methods: This article was written by nine former presidents, three of whom were also founders of the ENS, and is based on recollections and documents. It follows up on a review of the ENS history stored in the EAN archive.

Statins in hereditary myopathies: to give or not to give.

Hyperlipidemia is not uncommon in patients with hereditary myopathies who get older and also in several conditions in which it is frequently observed. Thus, using the common cholesterol reducing medications of the stains group could be considered. However, the side effects of these drugs include myalgia, myopathy and rhabdomyolysis typically associated with high serum creatine kinase (CK).

Induced Muscle and Liver Absence of Gne in Postnatal Mice Does Not Result in Structural or Functional Muscle Impairment.

Background: GNE Myopathy is a unique recessive neuromuscular disorder characterized by adult-onset, slowly progressive distal and proximal muscle weakness, caused by mutations in the GNE gene which is a key enzyme in the biosynthesis of sialic acid. To date, the precise pathophysiology of the disease is not well understood and no reliable animal model is available. Gne KO is embryonically lethal in mice.

GNE myopathy: can homozygous asymptomatic subjects give a clue for the identification of protective factors?

GNE myopathy is caused by bi allelic recessive mutations in the GNE gene. The largest identified cohort of GNE myopathy patients carries a homozygous mutation- M743T (the "Middle Eastern" mutation). More than 160 such patients in 67 families have been identified by us.

Pre Clinical Assessment of AAVrh74.MCK.GNE Viral Vector Therapeutic Potential: Robust Activity Despite Lack of Consistent Animal Model for GNE Myopathy.

Background: GNE myopathy is a unique adult onset rare neuromuscular disease caused by recessive mutations in the GNE gene. The pathophysiological mechanism of this disorder is not well understood and to date, there is no available therapy for this debilitating disease. We have previously established proof of concept that AAV based gene therapy can effectively deliver the wild type human GNE into cultured muscle cells from human patients and in mice, using a CMV promoter driven human wild type GNE plasmid delivered through an adeno associated virus (AAV8) based platform.

Two intronic cis-acting variants in both alleles of the POLR3A gene cause progressive spastic ataxia with hypodontia.

POLR3A encodes the largest subunit of the DNA-dependent RNA polymerase III. Pathogenic variants in this gene are associated with dysregulation of tRNA production and other non-coding RNAs. POLR3A-related disorders include variable phenotypes.

Dysphagia in adult myopathies.

Dysphagia (impaired swallowing) is not a rare problem in various neuromuscular disorders, both in the pediatric and the adult patient population. On many occasions such patients are first presented to other medical specialists or health professionals. Disorders of deglutition are probably underrecognized in patients with a neuromuscular disease as a result of patient's and doctor's delay.

Description of 3 patients with myasthenia gravis and COVID-19.

Background: The COVID-19 pandemic presents two main concerns for patients with myasthenia gravis (MG); chronic immunosuppression may put them at greater risk, and some proposed treatments for COVID-19 could cause MG exacerbation.

Case Description: We present three patients with generalized seropositive MG who developed COVID-19. All patients had a favorable outcome, with only one patient experiencing exacerbation.

Upregulation of Hallmark Muscle Genes Protects GneM743T/M743T Mutated Knock-In Mice From Kidney and Muscle Phenotype.

Background: Mutations in GNE cause a recessive, adult onset myopathy characterized by slowly progressive distal and proximal muscle weakness. Knock-in mice carrying the most frequent mutation in GNE myopathy patients, GneM743T/M743T, usually die few days after birth from severe renal failure, with no muscle phenotype. However, a spontaneous sub-colony remains healthy throughout a normal lifespan without any kidney or muscle pathology.

genotype explains 20% of phenotypic variability in GNE myopathy.

Objective: To test the hypothesis that common mutations influence disease severity; using statistical analysis of patient cohorts from different countries.

Methods: Systematic literature review identified 11 articles reporting 759 patients. GNE registry data were used as a second data set.

A Preliminary Videofluoroscopic Investigation of Swallowing Physiology and Function in Individuals with Oculopharyngeal Muscular Dystrophy (OPMD).

Dysphagia is one of the primary symptoms experienced by individuals with Oculopharyngeal Muscular Dystrophy (OPMD). However, we lack understanding of the discrete changes in swallowing physiology that are seen in OPMD, and the resulting relationship to impairments of swallowing safety and efficiency. This study sought to describe the pathophysiology of dysphagia in a small sample of patients with OPMD using a videofluoroscopy examination (VFSS) involving 3 × 5 mL boluses of thin liquid barium (22% w/v).

Phenotypic stratification and genotype-phenotype correlation in a heterogeneous, international cohort of GNE myopathy patients: First report from the GNE myopathy Disease Monitoring Program, registry portion.

GNE myopathy is a rare distal myopathy, caused by mutations in the GNE gene, affecting sialic acid synthesis. Clinical presentation varies from asymptomatic early stage patients to severely debilitating forms. This first report describes clinical presentations and severity of the disease, using data of 150 patients collected via the on-line, patient-reported registry component of the GNE Myopathy Disease Monitoring Program (GNEM-DMP).

Characterization of Strength and Function in Ambulatory Adults With GNE Myopathy.

Objective: To characterize the pattern and extent of muscle weakness and impact on physical functioning in adults with GNEM.

Methods: Strength and function were assessed in GNEM subjects (n = 47) using hand-held dynamometry, manual muscle testing, upper and lower extremity functional capacity tests, and the GNEM-Functional Activity Scale (GNEM-FAS).

Results: Profound upper and lower muscle weakness was measured using hand-held dynamometry in a characteristic pattern, previously described.

Congenital myasthenic syndrome in Israel: Genetic and clinical characterization.

The objective of the study was to evaluate the epidemiology of patients with congenital myasthenic syndrome (CMS) in Israel. Targeted mutation analysis was performed based on the clinical symptoms and electrophysiological findings for known CMS. Additional specific tests were performed in patients of Iranian and/or Iraqi Jewish origin.

Aceneuramic Acid Extended Release Administration Maintains Upper Limb Muscle Strength in a 48-week Study of Subjects with GNE Myopathy: Results from a Phase 2, Randomized, Controlled Study.

Background: GNE Myopathy (GNEM) is a progressive adult-onset myopathy likely caused by deficiency of sialic acid (SA) biosynthesis.

Objective: Evaluate the safety and efficacy of SA (delivered by aceneuramic acid extended-release [Ace-ER]) as treatment for GNEM.

Methods: A Phase 2, randomized, double-blind, placebo-controlled study evaluating Ace-ER 3 g/day or 6 g/day versus placebo was conducted in GNEM subjects (n = 47).

Safety and Clinical Effects of Mesenchymal Stem Cells Secreting Neurotrophic Factor Transplantation in Patients With Amyotrophic Lateral Sclerosis: Results of Phase 1/2 and 2a Clinical Trials.

Importance: Preclinical studies have shown that neurotrophic growth factors (NTFs) extend the survival of motor neurons in amyotrophic lateral sclerosis (ALS) and that the combined delivery of these neurotrophic factors has a strong synergistic effect. We have developed a culture-based method for inducing mesenchymal stem cells (MSCs) to secrete neurotrophic factors. These MSC-NTF cells have been shown to be protective in several animal models of neurodegenerative diseases.

GNE Myopathy: Two Clusters with History and Several Founder Mutations.

GNE myopathy (previous names: HIBM, DMRV, IBM2) is a unique distal myopathy with quadriceps sparing. This recessively inherited myopathy has been diagnosed in various regions of the world with more than 150 disease-causing mutations already identified. Several of those are proven or suspected to be founder mutations in certain regional clusters and are described in this review.

Frequent misdiagnosis of adult polyglucosan body disease.

Adult polyglucosan body disease (APBD) is a rare glycogenosis manifesting progressive spastic paraparesis, sensorimotor polyneuropathy and neurogenic bladder. Misdiagnosis of APBD may lead to unnecessary investigations and to potentially harmful therapeutic interventions. To examine the frequency of misdiagnosis of APBD, we retrospectively reviewed the clinical data of 30 patients diagnosed between 1991 and 2013.

Nonsyndromic Early-Onset Cone-Rod Dystrophy and Limb-Girdle Muscular Dystrophy in a Consanguineous Israeli Family are Caused by Two Independent yet Linked Mutations in ALMS1 and DYSF.

Genetic analysis of clinical phenotypes in consanguineous families is complicated by coinheritance of large DNA regions carrying independent variants. Here, we characterized a family with early onset cone-rod dystrophy (CRD) and muscular dystrophy. Homozygosity mapping (HM) followed by whole exome sequencing revealed a nonsense mutation, p.

Corrigendum to "Presymptomatic treatment with acetylcholinesterase antisense oligonucleotides prolongs survival in ALS (G93A-SOD1) mice".

[This corrects the article DOI: 10.1155/2013/845345.].

GNE myopathy: a personal trip from bedside observation to therapeutic trials.

The trip is not over yet as definite therapy for GNE myopathy is not yet available. Also the exact mechanisms by which GNE defects lead to isolated muscle disease in humans are not fully recognized. But in the Gaetano Conte lecture of 2013 I have tried to describe how much a progress was made in several research laboratories and clinical institutes in the investigation of this unique myopathy.