Oculomotor Dysfunction in Motor Neuron Disease.

INTRODUCTION: Though eye movements are relatively spared in motor neuron disease (MND), recent literature suggests patients may exhibit oculomotor dysfunction (OD). Frontal lobe involvement has been postulated based on oculomotor pathway anatomy and clinical overlap of amyotrophic lateral sclerosis (ALS) with frontotemporal dementia. We examined oculomotor characteristics in patients with MND presenting to an ALS Center, hypothesizing that patients with prominent upper motor neuron involvement or pseudobulbar affect (PBA) may demonstrate greater OD. METHODS: This was a single-center prospective observational study. Patients with diagnosis of MND were examined at bedside. Center for Neurologic Study-Liability Scale (CNS-LS) was administered to screen for pseudobulbar affect. Primary outcome was OD and the secondary outcome was the association between presence of OD in patients with MND experiencing symptoms of PBA or upper motor neuron dysfunction. Wilcoxon rank-sum scores and Fisher's exact tests were used to perform statistical analyses. RESULTS: 53 patients with MND underwent the clinical ophthalmic evaluation. On bedside examination, 34 patients (64.2%) presented with OD. There were no significant associations between locations of MND at presentation and the presence or type of OD. OD was associated with increased disease severity as measured by reduced FVC (p = 0.02). There was no significant association between OD and CNS-LS (p = 0.2). DISCUSSION: Though our study did not find a significant association between OD and upper versus lower MND at presentation, OD may be useful as an additional clinical marker for advanced disease.

Correlations of disease severity outcome measures in inclusion body myositis.

This study aimed to evaluate the correlation between various outcome measures used to assess disease severity and progression in inclusion body myositis (IBM) clinical trials. A cross-sectional study, involving 51 IBM patients meeting the European Neuromuscular Center (ENMC) 2011 criteria for clinically defined or probable IBM, was completed at the University of California, Irvine. Clinical details, demographic data, and functional data including timed get up (TGU), manual muscle testing, hand grip, pinch dynamometry, as well as IBM functional rating scale (IBMFRS), modified Rankin score, forced vital capacity (FVC), and modified ocular bulbar facial respiratory scale (mOBFRS) were collected on all patients. Descriptive statistics and Pearson's r correlation were performed to analyze the data. Age of the patient did not correlate with any of the outcome measures. Greater severity of IBMFRS scores correlated with longer disease duration as well as greater severity for FVC, strength outcomes, TGU, modified Rankin, and mOBFRS. Additionally, TGU strongly correlated with muscle strength measurements, modified Rankin, and mOBFRS. mOBFRS moderately correlated with IBMFRS, muscle strength, FVC, TGU and modified Rankin score. We demonstrate moderate to strong correlations among the disease severity outcome measures in this study.

Clinical utility of anti-cytosolic 5'-nucleotidase 1A antibody in idiopathic inflammatory myopathies.

OBJECTIVE: To define the clinicopathologic features and diagnostic utility associated with anti-cytosolic 5'-nucleotidase 1A (NT5C1A) antibody seropositivity in idiopathic inflammatory myopathies (IIMs). METHODS: Anti-NT5C1A antibody status was clinically tested between 2014 and 2019 in the Washington University neuromuscular clinical laboratory. Using clinicopathologic information available for 593 patients, we classified them as inclusion body myositis (IBM), dermatomyositis, antisynthetase syndrome, immune-mediated necrotizing myopathy (IMNM), nonspecific myositis, or noninflammatory muscle diseases. RESULTS: Of 593 patients, anti-NT5C1A antibody was found in 159/249 (64%) IBM, 11/53 (21%) dermatomyositis, 7/27 (26%) antisynthetase syndrome, 9/76 (12%) IMNM, 20/84 (24%) nonspecific myositis, and 6/104 (6%) noninflammatory muscle diseases patients. Among patients with IBM, anti-NT5C1A antibody seropositive patients had more cytochrome oxidase-negative fibers compared with anti-NT5C1A antibody seronegative patients. Among 14 IBM patients initially negative for anti-NT5C1A antibody, three patients (21%) converted to positive. Anti-NT5C1A antibody seropositivity did not correlate with malignancy, interstitial lung disease, response to treatments in dermatomyositis, antisynthetase syndrome, and IMNM, or survival in IIMs. INTERPRETATION: Anti-NT5C1A antibody is associated with IBM. However, the seropositivity can also be seen in non-IBM IIMs and it does not correlate with any prognostic factors or survival.

Regulatory decision-making under uncertainty: are costs proportionate to benefits when restricting dangerous chemicals on European markets?

Since 2007 regulation 1907/2006/EC concerning the Registration, Evaluation, Authorization and Restriction of Chemicals (REACH) is in force in Europe to reduce the adverse effects of hazardous chemical substances on human health and the environment. Implementation of the regulation by the European Chemicals Agency (ECHA) is supported by a Socio-Economic Analysis (SEA) Committee, consisting of European experts who help prepare ECHA's opinion on proposals for either restricting or authorizing dangerous substances. This paper presents the outcomes of the SEA underlying the first restriction proposals. Member states proposing a restriction have to show that it will reduce the risks to an acceptable level at a cost which is proportionate to the avoided risk. What is considered proportionate is not clearly defined in REACH. The opinion making process is characterized by many uncertainties: the expert group had no previous experiences to fall back on and limited information about the expected costs and benefits of the proposed restrictions. The study provides insight into expert opinions on environmental and health risks under uncertainty in the specific context of REACH. Particular attention is paid to the confidence experts place on the estimated socio-economic benefits of the avoided risks compared to the estimated compliance costs.

Maternal isolation alters the expression of neural proteins during development: 'Stroking' stimulation reverses these effects.

Rat pups reared apart from their siblings, mother, and nest environment in the 'pup-in-a-cup' regime show many alterations in behavior reminiscent of the Institutional Inattention/Overactivity Syndrome that characterizes children whose first few months are spent in institutions. In this report, we compare mother-reared (MR) and artificially reared (AR) male rats in concentrations and distributions of brain proteins that are involved in normal brain development. When assessed during the juvenile period and in adulthood, AR animals showed elevations in Neu-N (a neuronal marker) and in S-100 (an astrocyte marker) but reductions in synaptophysin (synapse protein), N-CAM (cell-adhesion molecule), GAP-43 (axon elongation protein), and BDNF (brain derived neurotrophic factor) in comparison to MR controls in many brain sites involved in attention, impulsivity, activity, and social behavior. Daily 'licking-like' stimulation provided to AR animals (AR-MAX) throughout early development that reverses many of the behavioral deficits, also reverses many of the isolation effects on brain proteins. Study 2 showed that elevations in the number of neurons in combination with decreases in functionality are associated with a reduction in neuronal pruning and apoptosis during the very early post-partum period in AR animals and their reversal through daily 'licking-like' stimulation.