Variability of the Penn upper motor neuron score in amyotrophic lateral sclerosis: need for a revised score.

There is a need for a consensus on a clinical scale for evaluating upper motor neuron (UMN) burden in amyotrophic lateral sclerosis (ALS) to improve consistency in clinical diagnosis, research and monitoring of disease progression. The Penn upper motor neuron score (PUMNS) is the most commonly published scale, however, the reliability of the scale has only been evaluated in a single study involving two raters. The objective of this study was to evaluate the inter-rater reliability of the PUMNS in ALS patients among multiple raters, and to discuss an updated UMN score including the signs with the highest inter-rater reliability.

Minimal manifestation status and prednisone withdrawal in the MGTX trial.

Objective: To examine whether sustained minimal manifestation status (MMS) with complete withdrawal of prednisone is better achieved in thymectomized patients with myasthenia gravis (MG).

Methods: This study is a post hoc analysis of data from a randomized trial of thymectomy in MG (Thymectomy Trial in Non-Thymomatous Myasthenia Gravis Patients Receiving Prednisone Therapy [MGTX]). MGTX was a multicenter, randomized, rater-blinded 3-year trial that was followed by a voluntary 2-year extension for patients with acetylcholine receptor (AChR) antibody-positive MG without thymoma.

4-Pyridoxic Acid/Pyridoxine Ratio in Patients with Type 2 Diabetes is Related to Global Cardiovascular Risk Scores.

Background: Vascular diseases are multifactorial and several risk factors may have synergetic effect on the global vascular risk. Among patients with diabetes, we investigated whether vitamin B6 species differ according to global cardiovascular risk.

Methods: The present observational study included 122 patients with type 2 diabetes (mean (SD) age = 69.

Long-term effect of thymectomy plus prednisone versus prednisone alone in patients with non-thymomatous myasthenia gravis: 2-year extension of the MGTX randomised trial.

Background: The Thymectomy Trial in Non-Thymomatous Myasthenia Gravis Patients Receiving Prednisone (MGTX) showed that thymectomy combined with prednisone was superior to prednisone alone in improving clinical status as measured by the Quantitative Myasthenia Gravis (QMG) score in patients with generalised non-thymomatous myasthenia gravis at 3 years. We investigated the long-term effects of thymectomy up to 5 years on clinical status, medication requirements, and adverse events.

Methods: We did a rater-blinded 2-year extension study at 36 centres in 15 countries for all patients who completed the randomised controlled MGTX and were willing to participate.

Randomized Trial of Thymectomy in Myasthenia Gravis.

Background: Thymectomy has been a mainstay in the treatment of myasthenia gravis, but there is no conclusive evidence of its benefit. We conducted a multicenter, randomized trial comparing thymectomy plus prednisone with prednisone alone.

Methods: We compared extended transsternal thymectomy plus alternate-day prednisone with alternate-day prednisone alone.

cFLIP overexpression in T cells in thymoma-associated myasthenia gravis.

Objective: The capacity of thymomas to generate mature CD4+ effector T cells from immature precursors inside the tumor and export them to the blood is associated with thymoma-associated myasthenia gravis (TAMG). Why TAMG(+) thymomas generate and export more mature CD4+ T cells than MG(-) thymomas is unknown.

Methods: Unfixed thymoma tissue, thymocytes derived thereof, peripheral blood mononuclear cells (PBMCs), T-cell subsets and B cells were analysed using qRT-PCR and western blotting.

Factors Predicting Survival in ALS Patients--Data from a Population-Based Registry in Rhineland-Palatinate, Germany.

Background: The possibility to survive with amyotrophic lateral sclerosis (ALS) varies considerably and survival extends from a few months to several years. A number of demographic and clinical factors predicting survival have been described; however, existing data are conflicting. We intended to predict patient survival in a population-based prospective cohort of ALS patients from variables known up to the time of diagnosis.

Vitamin B status in patients with type 2 diabetes mellitus with and without incipient nephropathy.

Aim: To investigate the vitamin B status, with particular focus on vitamin B6, in adults with and without incipient nephropathy secondary to type 2 diabetes mellitus.

Methods: Plasma and/or urine concentrations of vitamins B₆, B₁, B₁₂, related vitamers and biomarkers (including total homocysteine, methylmalonic acid) were measured in 120 adults with type 2 diabetes (including 46 patients with microalbuminuria) and 52 non-diabetic control subjects.

Results: Plasma concentrations of pyridoxal 5'-phosphate (PLP) were significantly lower in patients with type 2 diabetes than in control subjects (median: 22.

Factors predicting one-year mortality in amyotrophic lateral sclerosis patients--data from a population-based registry.

Background: Survival in amyotrophic lateral sclerosis varies considerably. About one third of the patients die within 12 months after first diagnosis. The early recognition of fast progression is essential for patients and neurologists to weigh up invasive therapeutic interventions.

Variability and prognostic relevance of different phenotypes in amyotrophic lateral sclerosis - data from a population-based registry.

Objectives: The clinical spectrum of amyotrophic lateral sclerosis (ALS) is characterized by a considerable variation. Different phenotypes have been described by previous studies. We assessed clinical variability and prognostic relevance of these phenotypes in a prospective, population-based cohort of ALS patients in Rhineland-Palatinate, Germany.

Incidence of amyotrophic lateral sclerosis in Rhineland-Palatinate, Germany.

There is a lack of prospective and population based epidemiological data on amyotrophic lateral sclerosis in Germany to date. The ALS registry Rhineland-Palatinate was established to investigate the incidence, course and phenotypic variety of ALS in this south-west German state of about 4 million inhabitants. During the period 2010-2011, consecutive incident patients with amyotrophic lateral sclerosis according to the revised El Escorial criteria were included and followed up using multiple overlapping sources of case ascertainment.

Anti-Apoptotic Signature in Thymic Squamous Cell Carcinomas - Functional Relevance of Anti-Apoptotic BIRC3 Expression in the Thymic Carcinoma Cell Line 1889c.

The molecular pathogenesis of thymomas and thymic carcinomas (TCs) is poorly understood and results of adjuvant therapy are unsatisfactory in case of metastatic disease and tumor recurrence. For these clinical settings, novel therapeutic strategies are urgently needed. Recently, limited sequencing efforts revealed that a broad spectrum of genes that play key roles in various common cancers are rarely affected in thymomas and TCs, suggesting that other oncogenic principles might be important.

Late-onset myasthenia gravis - CTLA4(low) genotype association and low-for-age thymic output of naïve T cells.

Late-onset myasthenia gravis (LOMG) has become the largest MG subgroup, but the underlying pathogenetic mechanisms remain mysterious. Among the few etiological clues are the almost unique serologic parallels between LOMG and thymoma-associated MG (TAMG), notably autoantibodies against acetylcholine receptors, titin, ryanodine receptor, type I interferons or IL-12. This is why we checked LOMG patients for two further peculiar features of TAMG - its associations with the CTLA4(high/gain-of-function) +49A/A genotype and with increased thymic export of naïve T cells into the blood, possibly after defective negative selection in AIRE-deficient thymomas.

Autoimmune associations and autoantibody screening show focused recognition in patient subgroups with generalized myasthenia gravis.

Autoimmune associations in myasthenia gravis (MG)-patients and their relatives have not been re-assessed since their separation into early- or late-onset MG (EOMG, LOMG), or thymoma-associated MG. Here, we analysed 226 EOMG-, 97 LOMG-, and 150 thymoma-patients for autoimmune disorders in themselves and their relatives. From 283 of them sera were tested for different organ- and non-organ-specific autoantibodies (autoAbs) by immunofluorescence test (IFT) and ELISA; genotyping was performed in 213 patients.

Thymus pathology observed in the MGTX trial.

The MGTX trial is the first prospective, randomized clinical trial that aims to evaluate the impact of extended transsternal thymectomy on myasthenic symptoms, prednisone requirements, and quality of life in patients with nonthymomatous, anti-acetylcholine receptor autoantibody-positive myasthenia gravis (MG). Here, we give an overview of the rationale of thymectomy and the standardized macroscopic and histopathological work-up of thymectomy specimens as fixed in MGTX standard operating procedures, including the grading of thymic lymphofollicular hyperplasia and the morphometric strategy to assess thymic involution.

Impact of medical audit on electrodiagnostic medicine in polyneuropathy.

Objective: The aim of the study was to investigate whether experienced physicians' electrodiagnostic practice and criteria can be influenced by international collaboration involving peer review medical audit.

Methods: Data was obtained from the ESTEEM project, an ongoing collaboration since 1991 among European neurophysiologists concerned with quality improvement in electrodiagnostic medicine. Three sets of the physicians' polyneuropathy examinations performed with intervals of 2-4 years were analysed.

The autoimmune regulator AIRE in thymoma biology: autoimmunity and beyond.

Thymomas are tumors of thymic epithelial cells. They associate more often than any other human tumors with various autoimmune diseases; myasthenia gravis is the commonest, occurring in 10-50% of thymoma patients, depending on the World Health Organization-defined histologic subtype. Most thymomas generate many polyclonal maturing T lymphocytes but in disorganized microenvironments Failure to induce self-tolerance may be a key factor leading to the export of potentially autoreactive CD4 progeny, thus predisposing to autoimmune diseases.

Variation in the neurophysiological examination of amyotrophic lateral sclerosis in Europe.

Our objective was to analyse how patients with amyotrophic lateral sclerosis (ALS) are examined neurophysiologically at different European centres in order to identify possible areas with variation or disagreement in the neurophysiological examination of ALS. Ninety-three prospectively collected examinations from six out of seven neurophysiologists in the European ESTEEM project were analysed. All examinations were peer reviewed with an electromyographic consensus diagnosis of motor neuron disease and the diagnosis of ALS confirmed by clinical follow-up.

A follicular dendritic cell sarcoma of the mediastinum with immature T cells and association with myasthenia gravis.

Follicular dendritic cell (FDC) sarcoma is a very rare neoplasm showing morphologic and phenotypic features of FDCs. It occurs primarily in lymph nodes but also in extranodal sites. So far, there have been no reports on FDC sarcoma associated with myasthenia gravis.

The ageing and myasthenic thymus: a morphometric study validating a standard procedure in the histological workup of thymic specimens.

The thymus is believed to play an important role in the pathogenesis of myasthenia gravis (MG). The 80% of MG patients with anti-acetylcholine receptor autoantibodies fall into three clinical subgroups: 1) thymoma; 2) early-onset MG ( View Article and Find Full Text PDF

Common cellular and diverse genetic basis of thymoma-associated myasthenia gravis: role of MHC class II and AIRE genes and genetic polymorphisms.

Generation of autoreactive CD4(+) effector T cells and defective production of regulatory CD4(+) T cells inside thymomas contribute to the development of myasthenia gravis (MG) in >90% of MG(+) thymomas. The molecular basis of these abnormalities is unknown. We report here that a) expression levels of class II major histocompatibility complex (MHCII) genes are variably decreased in thymomas, most prominently in histological WHO types A and AB; b) epithelial cells of type A and AB thymomas exhibit signal transducer and activator of transcription (STAT-1)-related defects of interferon-gamma (IFN-gamma) signaling and human leukocyte antigen (HLA)-DR expression in vitro; c) the promoter III (pIII)- and pIV-driven splice variants of the MHCII transactivator (CIITA) play a key role in MHCII gene expression in thymus and thymomas; and d) the pIV CIITA promoter is heavily methylated in thymomas.

A prospective multicentre study on sural nerve action potentials in ALS.

Objective: To evaluate sensory nerve conduction studies in ALS in a prospective multicentre study involving 7 neurophysiologists from 6 European countries.

Methods: Bilateral sural potentials were obtained in 35 ALS patients and 35 age-matched controls according to a standardised examination protocol using antidromic surface technique. The recordings from the right sural nerve of the controls were used for reference values.

Influence of peer review medical audit on pathophysiological interpretation of nerve conduction studies in polyneuropathies.

Objective: To evaluate the possible influence of peer review medical audit on experienced physicians' pathophysiological interpretation of nerve conduction studies in polyneuropathy patients.

Methods: Since 1992, 7 European neurophysiologists have collected samples of their patient examinations for regular review where the physicians interpret each other's cases electronically and subsequently discuss them at regular workshop meetings (i.e.

The "Mainzer EMF-Wachhund": results from a watchdog project on self-reported health complaints attributed to exposure to electromagnetic fields.

The "Mainzer EMF-Wachhund," a watchdog project, offered a system of self-notification of health complaints attributed to exposures to electromagnetic fields (EMFs) to a population of a part of Germany with about 4 million inhabitants. By using a self-administered questionnaire, which was provided online and for download from the Internet, 192 persons reported such health complaints in the period from October 2003 to March 2005. Of these, 56% classified themselves as electromagnetic hypersensitive (EH).

A CTLA4high genotype is associated with myasthenia gravis in thymoma patients.

Myasthenia gravis (MG) in thymoma patients depends critically on intratumorous generation and export of mature autoreactive CD4+ T cells. Why non-MG thymomas fail to produce CD4+ T cells is unknown. We studied three single-nucleotide polymorphisms of the cytotoxic T-lymphocyte-associated antigen 4(CTLA4) gene in thymoma patients, nonthymoma early-onset MG patients, and control subjects.