Serum NfL but not GFAP predicts cognitive decline in active progressive multiple sclerosis patients.

Background: Cognitive decline is inadequately captured by the standard neurological examination. Serum neurofilament light chain (sNfL) and glial fibrillary acidic protein (sGFAP) are biomarkers of neuronal damage and astrocytic reactivity that may offer an accessible measure of the multiple sclerosis (MS) pathology linked to cognitive decline.

Objective: To investigate the association of sNfL and sGFAP with cognitive decline in MS patients at high risk for progressive pathology.

A novel classification of fatigue in multiple sclerosis based on longitudinal assessments.

Background: Magnetic resonance imaging (MRI) studies of multiple sclerosis-related fatigue had limited reproducibility. Temporal fatigue fluctuations have not been considered.

Objective: To investigate whether a novel group allocation that reflects temporal dynamics of fatigue improves our ability to detect fatigue-associated structural brain abnormalities.

Brain anatomical correlates of fatigue in multiple sclerosis.

Fatigue is one of the most debilitating symptoms in patients with multiple sclerosis (MS). Despite its clinical significance, the aetiology and pathophysiology of MS-related fatigue are not well understood. Current evidence and understanding of the neuroanatomical underpinnings of MS-related fatigue are reviewed in this article.

Microstructural fronto-striatal and temporo-insular alterations are associated with fatigue in patients with multiple sclerosis independent of white matter lesion load and depression.

Background: Fatigue in multiple sclerosis (MS) has been inconsistently associated with disruption of specific brain circuitries. Temporal fluctuations of fatigue have not been considered.

Objective: The aim of this study was to investigate the association of fatigue with brain diffusion abnormalities, using robust criteria for patient stratification based on longitudinal patterns of fatigue.

Changes to the septo-fornical area might play a role in the pathogenesis of anxiety in multiple sclerosis.

Background: Reports on the relationships between white matter lesion load (WMLL) and fatigue and anxiety in multiple sclerosis (MS) are inconsistent.

Objective: To investigate the association of total and tract-specific WMLL with fatigue and anxiety.

Methods: Total and regional T2 WMLL was assessed for 19 tracts in 48 MS patients (30 females).

Exploration of machine learning techniques in predicting multiple sclerosis disease course.

Objective: To explore the value of machine learning methods for predicting multiple sclerosis disease course.

Methods: 1693 CLIMB study patients were classified as increased EDSS≥1.5 (worsening) or not (non-worsening) at up to five years after baseline visit.

The central vein sign and its clinical evaluation for the diagnosis of multiple sclerosis: a consensus statement from the North American Imaging in Multiple Sclerosis Cooperative.

Over the past few years, MRI has become an indispensable tool for diagnosing multiple sclerosis (MS). However, the current MRI criteria for MS diagnosis have imperfect sensitivity and specificity. The central vein sign (CVS) has recently been proposed as a novel MRI biomarker to improve the accuracy and speed of MS diagnosis.

Posterior lobules of the cerebellum and information processing speed at various stages of multiple sclerosis.

Background: Cerebellar damage has been implicated in information processing speed (IPS) impairment associated with multiple sclerosis (MS) that might result from functional disconnection in the frontocerebellar loop. Structural alterations in individual posterior lobules, in which cognitive functioning seems preponderant, are still unknown. Our aim was to investigate the impact of grey matter (GM) volume alterations in lobules VI to VIIIb on IPS in persons with clinically isolated syndrome (PwCIS), MS (PwMS) and healthy subjects (HS).

Hippocampal microstructural damage correlates with memory impairment in clinically isolated syndrome suggestive of multiple sclerosis.

Objective: We investigated whether diffusion tensor imaging (DTI) could reveal early hippocampal damage and clinically relevant correlates of memory impairment in persons with clinically isolated syndrome (CIS) suggestive of multiple sclerosis (MS).

Methods: A total of 37 persons with CIS, 32 with MS and 36 controls prospectively included from 2011 to 2014 were tested for cognitive performances and scanned with 3T-magnetic resonance imaging (MRI) to assess volumetric and DTI changes within the hippocampus, whole brain volume and T2-lesion load.

Results: While there was no hippocampal atrophy in the CIS group, hippocampal fractional anisotropy (FA) was significantly decreased compared to controls.

Cerebral blood flow MRI in the nondemented elderly is not predictive of post-operative delirium but is correlated with cognitive performance.

Three-dimensional Arterial Spin Labeling (ASL) MRI was performed before surgery in a cohort of 146 prospectively enrolled subjects ≥ 70 years old scheduled to undergo elective surgery. We investigated the prospective association between ASL-derived measures of cerebral blood flow (CBF) before surgery with postoperative delirium incidence and severity using whole-brain and globally normalized voxel-wise analysis. We also investigated the cross-sectional association of CBF with patients' baseline performance on specific neuropsychological tests, and with a composite general cognitive performance measure (GCP).

A Sensitive and Automatic White Matter Fiber Tracts Model for Longitudinal Analysis of Diffusion Tensor Images in Multiple Sclerosis.

Diffusion tensor imaging (DTI) is a sensitive tool for the assessment of microstructural alterations in brain white matter (WM). We propose a new processing technique to detect, local and global longitudinal changes of diffusivity metrics, in homologous regions along WM fiber-bundles. To this end, a reliable and automatic processing pipeline was developed in three steps: 1) co-registration and diffusion metrics computation, 2) tractography, bundle extraction and processing, and 3) longitudinal fiber-bundle analysis.

Early Fiber Number Ratio Is a Surrogate of Corticospinal Tract Integrity and Predicts Motor Recovery After Stroke.

Background And Purpose: The contribution of imaging metrics to predict poststroke motor recovery needs to be clarified. We tested the added value of early diffusion tensor imaging (DTI) of the corticospinal tract toward predicting long-term motor recovery.

Methods: One hundred seventeen patients were prospectively assessed at 24 to 72 hours and 1 year after ischemic stroke with diffusion tensor imaging and motor scores (Fugl-Meyer).

Neural substrates of vulnerability to postsurgical delirium as revealed by presurgical diffusion MRI.

Despite the significant impact of postoperative delirium on surgical outcomes and the long-term prognosis of older patients, its neural basis has not yet been clarified. In this study we investigated the impact of premorbid brain microstructural integrity, as measured by diffusion tensor imaging before surgery, on postoperative delirium incidence and severity, as well as the relationship among presurgical cognitive performance, diffusion tensor imaging abnormalities and postoperative delirium. Presurgical diffusion tensor imaging scans of 136 older (≥70 years), dementia-free subjects from the prospective Successful Aging after Elective Surgery study were analysed blind to the clinical data and delirium status.

Fatigue predicts disease worsening in relapsing-remitting multiple sclerosis patients.

Background: It is unclear whether fatigue is a consequence or a predictive trait of disease worsening.

Objective: To investigate the predictive value of fatigue toward conversion to confirmed moderate-severe disability in patients with relapsing-remitting multiple sclerosis (RRMS).

Methods: We retrospectively selected from the Comprehensive Longitudinal Investigations in MS at the Brigham and Women's Hospital (CLIMB) study cohort RRMS patients who converted to confirmed (⩾2 years) Expanded Disability Status Scale (EDSS) score ⩾3 within a follow-up period ⩾3 years.

Head circumference as a useful surrogate for intracranial volume in older adults.

Background: Intracranial volume (ICV) has been proposed as a measure of maximum lifetime brain size. Accurate ICV measures require neuroimaging which is not always feasible for epidemiologic investigations. We examined head circumference as a useful surrogate for ICV in older adults.

Stroke Location Is an Independent Predictor of Cognitive Outcome.

Background And Purpose: On top of functional outcome, accurate prediction of cognitive outcome for stroke patients is an unmet need with major implications for clinical management. We investigated whether stroke location may contribute independent prognostic value to multifactorial predictive models of functional and cognitive outcomes.

Methods: Four hundred twenty-eight consecutive patients with ischemic stroke were prospectively assessed with magnetic resonance imaging at 24 to 72 hours and at 3 months for functional outcome using the modified Rankin Scale and cognitive outcome using the Montreal Cognitive Assessment (MoCA).

Multiple sclerosis lesion formation and early evolution revisited: A weekly high-resolution magnetic resonance imaging study.

Background: Several magnetic resonance imaging (MRI) studies investigated the evolution of multiple sclerosis (MS) lesions to understand the pathophysiological mechanisms leading to blood-brain barrier breakdown and lesion formation. Only a few assessed the early natural history of MS lesions using short-interval longitudinal MRI.

Objective: The purpose of this study was to characterize MS lesion occurrence and early evolution on high-resolution MRI acquired at weekly intervals.

Handling changes in MRI acquisition parameters in modeling whole brain lesion volume and atrophy data in multiple sclerosis subjects: Comparison of linear mixed-effect models.

Magnetic resonance imaging (MRI) of the brain provides important outcome measures in the longitudinal evaluation of disease activity and progression in MS subjects. Two common measures derived from brain MRI scans are the brain parenchymal fraction (BPF) and T2 hyperintense lesion volume (T2LV), and these measures are routinely assessed longitudinally in clinical trials and observational studies. When measuring each outcome longitudinally, observed changes may be potentially confounded by variability in MRI acquisition parameters between scans.

Using multiple imputation to efficiently correct cerebral MRI whole brain lesion and atrophy data in patients with multiple sclerosis.

Automated segmentation of brain MRI scans into tissue classes is commonly used for the assessment of multiple sclerosis (MS). However, manual correction of the resulting brain tissue label maps by an expert reader remains necessary in many cases. Since automated segmentation data awaiting manual correction are "missing", we proposed to use multiple imputation (MI) to fill-in the missing manually-corrected MRI data for measures of normalized whole brain volume (brain parenchymal fraction-BPF) and T2 hyperintense lesion volume (T2LV).

Cardiovascular risk factors and small vessel disease of the brain: Blood pressure, white matter lesions, and functional decline in older persons.

Several potential vascular risk factors exist for the development and accumulation of subcortical white matter disease in older people. We have reported that in older people followed for up to 4 years white matter hyperintensity (WMH) lesions on magnetic resonance imaging nearly doubled in volume and were associated with alterations in mobility and cognitive function. Herein we review the genetic, metabolic, and vascular risk factors that have been evaluated in association with the development and pathogenesis of WMH in older persons.

Brain atrophy and white-matter hyperintensities are not significantly associated with incidence and severity of postoperative delirium in older persons without dementia.

Postoperative delirium is a common complication in older people and is associated with increased mortality, morbidity, institutionalization, and caregiver burden. Although delirium is an acute confusional state characterized by global impairments in attention and cognition, it has been implicated in permanent cognitive impairment and dementia. The pathogenesis of delirium and the mechanisms leading to these disabling consequences remain unclear.

Weekly multimodal MRI follow-up of two multiple sclerosis active lesions presenting a transient decrease in ADC.

Background And Purpose: Blood-brain barrier disruption during the earliest phases of lesion formation in multiple sclerosis (MS) patients is commonly ascribed to perivenular inflammatory activity and is usually accompanied by increased diffusivity. Reduced diffusivity has also been shown in active lesions, albeit less frequently. This study aimed to characterize the development and natural history of contrast-enhanced lesions by weekly following five relapsing remitting (RR) MS patients.

An expanded composite scale of MRI-defined disease severity in multiple sclerosis: MRDSS2.

The objective of this study was to test a new version of the Magnetic Resonance Disease Severity Scale (MRDSS2), incorporating cerebral gray matter (GM) and spinal cord involvement from 3 T MRI, in modeling the relationship between MRI and physical disability or cognitive status in multiple sclerosis (MS). Fifty-five MS patients and 30 normal controls underwent high-resolution 3 T MRI. The patients had an Expanded Disability Status Scale score of 1.