CONCLUSIONS: The long-axis diameter of a CEL is the best translational predictor of subsequent PRL formation at follow-up. This measure holds promise as a method to identify patients at high risk of chronic active lesion formation during the acute inflammatory window.

CONCLUSIONS: PRL convey high specificity for MS and can aid in the diagnostic evaluation. Modest sensitivity limits their use as single diagnostic indicators. Including lesions with lower confidence ("possible" PRL) rapidly erodes specificity and should be interpreted with caution given the potential harms associated with misdiagnosis.

Multiple sclerosis (MS) is an inflammatory demyelinating disease with heterogeneous clinical presentations and variable long-term disability accumulation. There are currently no standard criteria to accurately predict disease outcomes. In this study we investigated the cross-sectional relationship between disease phenotype and immune-modulating cytokines and chemokines in cerebrospinal fluid (CSF). We analyzed CSF from 20 DMT-naïve MS patients using Olink Proteomics' Target 96 Inflammation panel...

Concepts of multiple sclerosis (MS) biology continue to evolve, with observations such as "progression independent of disease activity" challenging traditional phenotypic categorization. Iron-sensitive, susceptibility-based imaging techniques are emerging as highly translatable MR imaging sequences that allow for visualization of at least 2 clinically useful biomarkers: the central vein sign and the paramagnetic rim lesion (PRL). Both biomarkers demonstrate high specificity in the discrimination...

Multiple sclerosis (MS) is a chronic neurological disease frequently associated with significant fatigue, anxiety, depression, and stress. These symptoms are difficult to treat, and prominently contribute to the decreases in quality of life observed with MS. The underlying mechanisms of these "silent" symptoms are not well understood and include not just the psychological responses to a chronic disease, but also biological contributions from bidirectional psycho-neuro-immune (dys)regulation of...

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CONCLUSION: Heterogeneous methodology limited generalization and meta-analysis. EBV antibody levels are unlikely to represent prognostic biomarkers in MS. The areas of highest ongoing promise relate to diagnostic exclusion and pharmacodynamic/disease response. Use of EBV antibodies as biomarkers in clinical practice remains additionally limited by lack of methodological precision, reliability, and validation.

Chronic active lesions (CAL) are an important manifestation of chronic inflammation in multiple sclerosis and have implications for non-relapsing biological progression. In recent years, the discovery of innovative MRI and PET-derived biomarkers has made it possible to detect CAL, and to some extent quantify them, in the brain of persons with multiple sclerosis, in vivo. Paramagnetic rim lesions on susceptibility-sensitive MRI sequences, MRI-defined slowly expanding lesions on T1-weighted and...

CONCLUSION: PRLs, an emerging noninvasive biomarker of chronic neuroinflammation, are confirmed to be associated with greater disease severity and newly shown to be preliminarily associated with blood-brain barrier disruption.

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CONCLUSION: Higher SES was associated with a lower burden of psychiatric symptoms and with a higher likelihood of self-reported symptom recovery after receiving mental health treatment. Attitudes regarding mental health care delivery in MS varied according to racial and ethnic background. Future longitudinal studies in more diverse populations should assess whether co-location of mental health services with MS care helps to reduce the gap between access and need of mental health care in MS.

BACKGROUND. Multiple sclerosis (MS) is characterized by both acute and chronic intrathecal inflammation. A subset of MS lesions show paramagnetic rims on susceptibility-weighted MRI sequences, reflecting iron accumulation in microglia. These para-magnetic rim lesions have been proposed as a marker of compartmentalized smoldering disease. Paramagnetic rim lesions have been shown at 7 T and, more recently, at 3 T. As susceptibility effects are weaker at lower field strength, it remains unclear if...

CONCLUSIONS: Circulating monocytes and serum albumin are significantly associated with albuminuria, but not eGFR in DKD. These results support the potential role of the innate immune system in diabetic microvascular end-organ damage and urinary protein loss, and may be readily translatable clinical markers to incorporate into risk-assessment models for prognostication in diabetes.

The emergence of immunomodulators as effective cancer treatments has been an important advance in cancer therapy. The combination therapy of BRAF/MEK inhibition with or without anti-CTLA-4 treatment causes an immunostimulatory effect that has greatly reduced death from melanoma. In this article, we present the case of a patient with prior multiple sclerosis (MS) and who later developed metastatic malignant melanoma, had a marked increase of magnetic resonance imaging (MRI) findings after...

Multiple sclerosis (MS) is a chronic and progressive neurological disease characterized by recurrent episodes of inflammatory demyelination of the brain and spinal cord. Alemtuzumab has been previously shown in large phase III trials to be an effective therapy in reducing MS clinical flares as well as new radiological activity and atrophy rates. The purpose of this study was to examine real-world effectiveness and safety data from a large cohort of people treated with alemtuzumab at an academic...

CONCLUSIONS: The data from our cohort of MS patients suggest an indirect contribution of cervical spondylosis to disability by increasing the risk of developing localized cord lesions. While further studies are needed to confirm the findings and clarify disease mechanisms, closer attention should be paid to worsening spondylosis in patients with MS.

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Despite their ubiquitous presence, placebos and placebo effects retain an ambiguous and unsettling presence in biomedicine. Specifically focused on chronic pain, this review examines the effect of placebo treatment under three distinct frameworks: double blind, deception, and open label honestly prescribed. These specific conditions do not necessarily differentially modify placebo outcomes. Psychological, clinical, and neurological theories of placebo effects are scrutinized. In chronic pain,...

Human herpesviruses 6A and 6B, often referred to collectively as human herpesvirus 6, are a pair of beta-herpesviruses known to cause a variety of clinical syndromes in both immunocompetent and immunocompromised individuals. Most humans are infected with human herpesvirus 6B, and many with human herpesvirus 6A. Primary infection typically occurs in early childhood, although large-scale reviews on the topic are limited. Herein, the authors explore the clinical manifestations of human herpesvirus...

CONCLUSIONS: MRI-defined MS phenotypes show high conversion rates characterized by the continuation of either predominant neurodegeneration or inflammation and support the partial independence of these 2 measures. MicroRNA signatures of these phenotypes suggest a role for blood-brain barrier integrity.

CONCLUSIONS: Elevated NLR and MLR may represent hematopoetic bias toward increased production and pro-inflammatory priming of the myeloid innate immune system (numerator) in conjunction with dysregulated adaptive immune processes (denominator), and consequently reflect a complementary and independent marker for severity of MS-related neurological disability and MRI outcomes.

CONCLUSION: In patients with post-hematopoietic stem cell transplant HHV6 associated PALE, lower CSF viral load may be associated with a higher likelihood to have seizures. This may indicate a primary infection as opposed to secondary reactivation phenomenon.

CONCLUSION: Whole-brain atrophy metrics may not be interchangeable between proportional- and registration-based automated pipelines from 3T MRI in patients with MS.

CONCLUSIONS: The 5-week group positive psychology intervention was feasible and acceptable to patients with MS. A randomized controlled trial is necessary to further explore the effectiveness of the group intervention.

Since its technical development in the early 1980s, magnetic resonance imaging (MRI) has quickly been adopted as an essential tool in supporting the diagnosis, longitudinal monitoring, evaluation of therapeutic response, and scientific investigations in multiple sclerosis (MS). The clinical usage of MRI has increased in parallel with technical innovations in the technique itself; the widespread adoption of clinically routine MRI at 1.5T has allowed sensitive qualitative and quantitative...

CONCLUSIONS: Collectively, these data suggest that AHR agonists in serum are dynamically modulated during the course of MS. These findings may guide the development of biomarkers to monitor disease activity as well as the design of novel therapeutic interventions for MS.

Background. Initially developed to excite peripheral nerves, magnetic stimulation was quickly recognized as a valuable tool to noninvasively activate the cerebral cortex. The subsequent discovery that repetitive transcranial magnetic stimulation (rTMS) could have long-lasting effects on cortical excitability spawned a broad interest in the use of this technique as a new therapeutic method in a variety of neuropsychiatric disorders. Although the current outcomes from initial trials include some...

Humans have a prodigious capacity to perform multiple tasks simultaneously. Being distracted while, for example, performing a complex motor skill adds complexity to a task and thus leads to a performance impairment. Yet, it may not be just the presence or absence of a distraction that affects motor performance. Instead, the characteristics of the distraction may play a critical role in affecting human motor performance. Here, we show that performance of a motor sequence can be substantially...

Visual input from the left and right visual fields is processed predominantly in the contralateral hemisphere. Here we investigated whether this preference for contralateral over ipsilateral stimuli is also found in high-level visual areas that are important for the recognition of objects and faces. Human subjects were scanned with functional magnetic resonance imaging (fMRI) while they viewed and attended faces, objects, scenes, and scrambled images in the left or right visual field. With our...

The lateral-occipital tactile-visual area (LOtv) is activated when objects are recognized by vision or touch. We report here that the LOtv is also activated in sighted and blind humans who recognize objects by extracting shape information from visual-to-auditory sensory substitution soundscapes. Recognizing objects by their typical sounds or learning to associate specific soundscapes with specific objects do not activate this region. This suggests that LOtv is driven by the presence of shape...