Risk Prediction of a Multiple Sclerosis Diagnosis

Multiple sclerosis (MS) is a chronic autoimmune disease that affects the central nervous system. The progression and severity of MS varies by individual, but it is generally a disabling disease. Although medications have been developed to slow the disease progression and help manage symptoms, MS research has yet to result in a cure. Early diagnosis and treatment of the disease have been shown to be effective at slowing the development of disabilities. However, early MS diagnosis is difficult because symptoms are intermittent and shared with other diseases. Thus most previous works have focused on uncovering the risk factors associated with MS and predicting the progression of disease after a diagnosis rather than disease prediction. This paper investigates the use of data available in electronic medical records (EMRs) to create a risk prediction model; thereby helping clinicians perform the difficult task of diagnosing an MS patient. Our results demonstrate that even given a limited time window of patient data, one can achieve reasonable classification with an area under the receiver operating characteristic curve of 0.724. By restricting our features to common EMR components, the developed models also generalize to other healthcare systems

Course of neuromyelitis optica during inadvertent pregnancy in a patient treated with rituximab

In neuromyelitis optica (NMO), the monoclonal B-cell antibody rituximab is a therapeutic option. Little is known about the course of NMO and the safety of rituximab during pregnancy. In this study, we report the clinical course of a patient with NMO after application of rituximab 1 week before inadvertent conception. Mother and child did not experience any adverse event, and the postpartum development of the baby was completely normal up to 15 months. Clinical course of NMO was stable during the entire pregnancy. This case illustrates a favorable outcome in a pregnant NMO patient and her child after therapy with rituximab

Risk Factors For Multiple Sclerosis In Volyn Region (Ukraine)

The prevalence rate of multiple sclerosis (MS) in Volyn Region (101.0 per 100000) is the highest in Ukraine. To study MS risk factors in Volyn Region, special questionnaires were distributed among all MS patients residing in Volyn region. Results were obtained from 227 respondents including 154 women and 73 men of mean age 43±10.6 years. The control group included 105 healthy respondents inhabiting Volyn region.We found associated risk factors for MS to be: mother of Volyn origin, maternal age after 27 years old and paternal age after 29 years old at birth of respondent, subject\u27s born as a third child, brestfeeding for less than one year, living in the zone of industrial pollution, near mobile, TV- and radio re-translators, full traffic automobile roads, time spending outdoors less than one hour in winter and less than eight hours in summer, consumption of fruit and vegetables less than 5 times a week, of beef less than 3 times a week, poultry meet less than 3, berries less than 3, cereals less than 4 times a week, chronic stressful situations in life. Patients with MS more frequently reported AVRI, hepatitis and herpes simplex virus. Among patients with MS there were fewer respondents with history of chickenpox, rubella and DPT (diphtheria, pertussis, tetanus), BCG immunizations.Here, we introduced a novel study of MS risk factors within Volyn Region. The Registry established in 2012 is being constantly updated and can be a database for a long-term retrospective study involving a large number of patients

Defining and distinguishing infant behavioral states using acoustic cry analysis: is colic painful?

BackgroundTo characterize acoustic features of an infant's cry and use machine learning to provide an objective measurement of behavioral state in a cry-translator. To apply the cry-translation algorithm to colic hypothesizing that these cries sound painful.MethodsAssessment of 1000 cries in a mobile app (ChatterBabyTM). Training a cry-translation algorithm by evaluating >6000 acoustic features to predict whether infant cry was due to a pain (vaccinations, ear-piercings), fussy, or hunger states. Using the algorithm to predict the behavioral state of infants with reported colic.ResultsThe cry-translation algorithm was 90.7% accurate for identifying pain cries, and achieved 71.5% accuracy in discriminating cries from fussiness, hunger, or pain. The ChatterBaby cry-translation algorithm overwhelmingly predicted that colic cries were most likely from pain, compared to fussy and hungry states. Colic cries had average pain ratings of 73%, significantly greater than the pain measurements found in fussiness and hunger (p < 0.001, 2-sample t test). Colic cries outranked pain cries by measures of acoustic intensity, including energy, length of voiced periods, and fundamental frequency/pitch, while fussy and hungry cries showed reduced intensity measures compared to pain and colic.ConclusionsAcoustic features of cries are consistent across a diverse infant population and can be utilized as objective markers of pain, hunger, and fussiness. The ChatterBaby algorithm detected significant acoustic similarities between colic and painful cries, suggesting that they may share a neuronal pathway

Oxidative Stress and Mitochondrial Injury in Chronic Multisymptom Conditions: From Gulf War Illness to Autism Spectrum Disorder

Background: Overlapping chronic multisymptom illnesses (CMI) include Chronic Fatigue Syndrome (CFS), fibromyalgia, irritable bowel syndrome, multiple chemical sensitivity, and Gulf War illness (GWI), and subsets of autism spectrum disorder (ASD). GWI entails a more circumscribed set of experiences that may provide insights of relevance to overlapping conditions.
Objectives: To consolidate evidence regarding a role for oxidative stress and mitochondrial dysfunction (OSMD), as primary mediators in CMI, using GWI as a departure point.
Methods: Exposure relations, character, timecourse and multiplicity of symptoms, and objective correlates of GWI are compared to expectation for OSMD. Objective correlates of OSMD in GWI and overlapping conditions are examined. 
Discussion: OSMD is an expected consequence of known GWI exposures; is compatible with symptom characteristics observed; and accords with objective markers and health conditions linked to GWI, extending to autoimmune disease and infection. Emergent triangulating evidence directly supports OSMD in multisymptom “overlap” CMI conditions, with similarities to, and diagnosed at elevated rates in, GWI, suggesting a common role in each. 
Conclusions: GWI is compatible with a paradigm by which uncompensated exposure to oxidative/nitrative stressors accompanies and triggers mitochondrial dysfunction, cell energy compromise, and multiple downstream effects such as vulnerability to autoantibodies. This promotes a profile of protean symptoms with variable latency emphasizing but not confined to energy-demanding post-mitotic tissues, according with (and accounting for) known properties of multisystem overlap conditions. This advances understanding of GWI; health conditions attending GWI at elevated rates; and overlap conditions like CFS and ASD, providing prospects for vulnerability assessment, mitigation of progression, treatment, and future prevention – with implications germane to additive and excessive environmental oxidative stressor exposures in the civilian setting.
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Minimal breast milk transfer of rituximab, a monoclonal antibody used in neurological conditions.

ObjectiveTo determine the transfer of rituximab, an anti-CD20 monoclonal antibody widely used for neurologic conditions, into mature breast milk.MethodsBreast milk samples were collected from 9 women with MS who received rituximab 500 or 1,000 mg intravenous once or twice while breastfeeding from November 2017 to April 2019. Serial breast milk samples were collected before infusion and at 8 hours, 24 hours, 7 days, and 18-21 days after rituximab infusion in 4 patients. Five additional patients provided 1-2 samples at various times after rituximab infusion.ResultsThe median average rituximab concentration in mature breast milk was low at 0.063 μg/mL (range 0.046-0.097) in the 4 patients with serial breast milk collection, with an estimated median absolute infant dose of 0.0094 mg/kg/d and a relative infant dose (RID) of 0.08% (range 0.06%-0.10%). Most patients had a maximum concentration at 1-7 days after infusion. The maximum concentration occurred in a woman with a single breast milk sample and was 0.29 μg/mL at 11 days postinfusion, which corresponds with an estimated RID of 0.33%. Rituximab concentration in milk was virtually undetectable by 90 days postinfusion.ConclusionsWe determined minimal transfer of rituximab into mature breast milk. The RID for rituximab was less than 0.4% and well below theoretically acceptable levels of less than 10%. Low oral bioavailability would probably also limit the absorption of rituximab by the newborn. In women with serious autoimmune neurologic conditions, monoclonal antibody therapy may afford an acceptable benefit to risk ratio, supporting both maternal treatment and breastfeeding

An Interesting Case Of Acute Disseminated Encephalomyelitis

Acute disseminated encephalomyelitis (ADEM) is an uncommon inflammatory demyelinating disease of the central nervous system. The disease typically occurs after infections or vaccinations. However, in many patients with ADEM, no evidence of prior infection or vaccination can be found. We are reporting a patient who developed clinical and radiological features of acute disseminated encephalomyelitis after trauma of repeated attempts at lumber puncture for spinal anesthesi

Fighting viral infections and virus-driven tumors with cytotoxic CD4+ T cells

CD4+ T cells have been and are still largely regarded as the orchestrators of immune responses, being able to differentiate into distinct T helper cell populations based on differentiation signals, transcription factor expression, cytokine secretion, and specific functions. Nonetheless, a growing body of evidence indicates that CD4+ T cells can also exert a direct effector activity, which depends on intrinsic cytotoxic properties acquired and carried out along with the evolution of several pathogenic infections. The relevant role of CD4+ T cell lytic features in the control of such infectious conditions also leads to their exploitation as a new immunotherapeutic approach. This review aims at summarizing currently available data about functional and therapeutic relevance of cytotoxic CD4+ T cells in the context of viral infections and virus-driven tumors

Retinal nerve fibre layer thinning is associated with drug resistance in epilepsy.

Retinal nerve fibre layer (RNFL) thickness is related to the axonal anterior visual pathway and is considered a marker of overall white matter 'integrity'. We hypothesised that RNFL changes would occur in people with epilepsy, independently of vigabatrin exposure, and be related to clinical characteristics of epilepsy