Common invisible symptoms of multiple sclerosis

<p class="abstract">Multiple sclerosis (MS) with its protean manifestations of central and peripheral nervous system pose a challenge to its management in different clinical scenario. The issue becomes much more complicated with occurrence of strange and unusual symptoms intermingling with common symptoms in people living with MS. The frequency and severity of these unusual symptoms changes overtime and raise a suspicion of other neurological disease. The occurrence of any of these symptoms at times may be a sign of active disease. A reasonable understanding of these strange symptoms both to the patient and healthcare team could be of help in taking appropriate steps to manage MS more efficiently.</p><p class="abstract"> </p>

Abstract WP217: A New Index for Multiple Chronic Conditions Predicts Post-Stroke Functional Outcome: A Machine Learning Approach in the Brain Attack Surveillance in Corpus Christi Project

Introduction: Multiple chronic conditions (MCC) diminish the pre-stroke reserve that aids post-stroke adaptation and recovery. Through machine learning, we developed a MCC index that integrates pre-stroke comorbid conditions, functional and cognitive factors, as well as their interactions, to predict post-stroke functional outcome (FO) in a bi-ethnic, population-based cohort study. Methods: Ischemic stroke patients (2008-2017) were interviewed at baseline and 90 days. FO score (range 1-4, higher scores worse) at 90 days was measured by averaging 22 activities of daily living (ADL)/instrumental activities of daily living (IADL) and dichotomizing the score into favorable (1-3) and unfavorable FO (>3, a lot of difficulty with ADL/IADLs). Multiple linear regression was fit with a Lasso penalty to select predictors among 22 chronic conditions from ICD codes and medical records, pre-stroke function, cognitive impairment, social support, marital status, depression, age, initial stroke severity (NIHSS) and all pairwise interactions. We developed an MCC index by weighting selected predictors using β-coefficients. Adjusted R 2 , discrimination and calibration of the model were assessed. Results: Among 1,035 stroke survivors, 69% were Mexican American, 51% were female, mean age was 68 (SD=12), and median initial NIHSS was 4 (IQR:2-8). Median FO score was 2.36 (IQR:1.55-3.41); 32% had unfavorable FO. The final model contained the pre-stroke modified Rankin Score (mRS), initial NIHSS, age, congestive heart failure (CHF), weight loss, diabetes, other neurological disease, initial NIHSS х pre-stroke mRS, dementia х age, CHF х renal failure and pre-stroke mRS х history of stroke/TIA, which explained 44% of variability in FO score. The MCC index was well calibrated (p=0.28) and predicted unfavorable FO well (c-statistic, 0.84) in the internal validation dataset. Conclusion: A new MCC assessment tool was developed and validated to improve the prediction of post-stroke FO. Weight loss, other neurological disease and interactions between MCC were discovered as novel predictors. Efforts to improve stroke prognosis may benefit from a better understanding, prevention and management of MCC in population at high risk for stroke.

Metabolomics in multiple sclerosis disease course and progression

Multiple sclerosis (MS) is associated with changes in the metabolome. Numerous studies employing varying metabolomics platforms have examined a range of biological material ranging from brain tissue to urine and demonstrated consistently alterations in multiple metabolic pathways in MS. We review not only the studies that describe the ability of metabolomics to differentiate MS patients from healthy controls and other neurological disease but also discuss the potential of metabolomics-based methods to build predictive models that are able to stage disease, monitor progression, and select the most appropriate therapy. The increasing number of impressive claims for the capacity of metabolomics to distinguish between different types of demyelinating disease suggests that the provision of such tests may be close at hand. Besides the ability to provide potential diagnostic and prognostic biomarkers, metabolomics also provides us with unique insights into the pathophysiology of the disease and helps identify metabolic pathways that may be potential therapeutic targets. Future studies will integrate metabolomics data with other omics techniques to provide further insight into the source of these metabolic abnormalities and help with identification of the most promising targets for therapeutic intervention.

CLINICAL CHARACTERISTICS ASSOCIATED WITH DYSPHAGIA IN THE HOSPITALIZED ELDERLY

The aim of this study was to determine the factors associated with dysphagia in the hospitalized older adults. The dysphagia group consisted of 46 patients (23 men and 23 women) while the non-dysphagia group consisted of 40 patients (10 men and 30 women). The measurements included Mini Nutritional Assessment Short-Form (MNA-SF) scores, serum albumin levels, anthropometrics, and a mobility index. The dysphagia group was older and had significantly higher rates of male sex, respiratory disease on admission, dementia, other neurological disease, and impaired mobility than the non-dysphagia group. The dysphagia group also showed significantly lower values in nutritional measurements including MNA-SF scores, serum albumin levels. Logistic regression analysis showed that the factors significantly and independently associated with dysphagia were impaired mobility, dementia, and male gender. The results of present study showed that hospitalized

Serum levels of LIGHT in MS

Background: Recently, a polymorphism in the LIGHT gene was shown to increase the risk of multiple sclerosis (MS) in a genome-wide association study (GWAS). Objective: Our aim was to investigate if serum levels of LIGHT were affected by this polymorphism and by the disease itself. Methods: Serum levels of LIGHT were investigated in four cohorts; 1) MS ( n = 159) and controls ( n = 160) in relation to rs1077667 genotype; 2) MS at relapse ( n = 30) vs. healthy controls ( n = 26); 3) MS ( n = 27) vs. other neurological disease (OND, n = 33); and 4) MS patients before and after one year of treatment with natalizumab ( n = 30). Results: Carriers of the GG genotype had the lowest serum levels of LIGHT ( p=0.02). Serum levels of LIGHT were increased in MS at relapse in two separate cohorts: vs. healthy controls ( p=0.00005) and vs. remission ( p=0.00006), other neurological disease (OND) ( p=0.002) and OND with signs of inflammation (iOND; p=0.00005). Furthermore, serum levels of LIGHT were decreased by natalizumab treatment ( p=0.001). Conclusion: Soluble LIGHT is an inhibitor of T-cell activation and GG carriers of rs1077667, with the highest risk for MS, had the lowest serum levels. The increased levels of LIGHT at times of increased MS activity suggest that soluble LIGHT is protective and may act to limit inflammation.

Chronic Cerebrospinal Venous Insufficiency in Multiple Sclerosis - A Medical, Sociological and Media Controversy

In 2009, Zamboni et al. coined the term “chronic cerebrospinal venous insufficiency” (CCSVI). On the basis of transcranial and extra-cranial colour-coded Doppler ultrasonography, they operationally defined CCSVI as occurring when at least two out of five “abnormalities” were present. They claimed to find CCSVI in 100 % of 109 individuals with multiple sclerosis (MS) and in none of 177 healthy controls. Zamboni’s group subsequently reported an uncontrolled treatment trial of cerebral venoplasty, which was termed the “liberation procedure” and claimed that the procedure benefited people with MS. The Zamboni reports were received with considerable skepticism, regarding both their biological plausibility and the claims of 100 % sensitivity, specificity, positive predictive value and negative predictive value. No investigators have subsequently been able to replicate the Zamboni observations. Although some additional reports have indicated finding venous abnormalities in more MS patients than in other groups, most have either found no association of CCSVI with MS, or else have found substantial numbers of controls, either healthy or with other neurological disease, to have the abnormalities. The original Zamboni reports were widely publicised in the mainstream media, especially in Canada and sparked a raging controversy in the social media. Patients clamoured for trials of cerebral venoplasty and others demanded its availability or travelled around the globe to undergo the procedure. The Canadian Institutes of Health Research have now solicited proposals for a Phase I/II clinical trial. At this point, additional scientific studies, including many funded by the National Multiple Sclerosis Society and the Multiple Sclerosis Society of Canada, are moving toward completion and will hopefully allow a proper judgment of the validity of the concept of CCSVI in relation to MS. In the meantime, it is important that physicians remain respectful of patients’ views, but that they are not reticent about expressing their own professional opinions based on available evidence, while emphasising the importance of proper scientific research.

Impaired ubiquitin–proteasome system activity in the synapses of Huntington's disease mice

Huntington's disease (HD) is caused by the expansion of a polyglutamine tract in the N-terminal region of huntingtin (htt) and is characterized by selective neurodegeneration. In addition to forming nuclear aggregates, mutant htt accumulates in neuronal processes as well as synapses and affects synaptic function. However, the mechanism for the synaptic toxicity of mutant htt remains to be investigated. We targeted fluorescent reporters for the ubiquitin–proteasome system (UPS) to presynaptic or postsynaptic terminals of neurons. Using these reporters and biochemical assays of isolated synaptosomes, we found that mutant htt decreases synaptic UPS activity in cultured neurons and in HD mouse brains that express N-terminal or full-length mutant htt. Given that the UPS is a key regulator of synaptic plasticity and function, our findings offer insight into the selective neuronal dysfunction seen in HD and also establish a method to measure synaptic UPS activity in other neurological disease models.

Glial toxicity in urine and multiple sclerosis

The biochemical and biological characterization of a cytotoxic activity targeting macroglial cells (oligodendrocytes and astrocytes), in moncyte cultures and in CSF of a patient with multiple sclerosis, has previously been described. In further studies, cell-based tests have shown a good correlation between this glial cytotoxic (gliotoxic) activity, in CSF or in urine, and MS. We now present results obtained with urine samples from 102 MS patients, 51 patients with other neurological disease and 35 healthy subjects using a bioassay set up for the detection of an apoptosis-like effect induced in a glial cell-line. Significant gliotoxicity was detected in urine from 74/102 MS patients while only 4/51 neurological controls (P40.001) and never in healthy subjects (P40.001). Given the statistical tendency provided by this bioassay and its technical limitations for routine testing, it is now used for monitoring the molecular characterization of this `gliotoxic factor'. Its replacement by a specific immunoassay could provide more accurate routine techniques for the detection of this biological marker in MS.

Critical Pathway and Hospital-Hospital Cooperation in Acute Stroke Reduction of the Length of Hospital Stay

Stroke patients tend to stay longer in one hospital compared to patients with other neurological disease. After the introduction of 3 types of critical pathway dedicated for various severity of acute ischemic stroke in 1995, the average length of in-hospital days declined from 30.0 days (1993) to 15.3 days (1998), ie 49% reduction. This reduction was achieved by the use of critical pathway and the hospital-hospital cooperation.