Diffusive persistence on disordered lattices and random networks.

To better understand the temporal characteristics and the lifetime of fluctuations in stochastic processes in networks, we investigated diffusive persistence in various graphs. Global diffusive persistence is defined as the fraction of nodes for which the diffusive field at a site (or node) has not changed sign up to time t (or, in general, that the node remained active or inactive in discrete models). Here we investigate disordered and random networks and show that the behavior of the persistence depends on the topology of the network. In two-dimensional (2D) disordered networks, we find that above the percolation threshold diffusive persistence scales similarly as in the original 2D regular lattice, according to a power law P(t,L)∼t^{-θ} with an exponent θ≃0.186, in the limit of large linear system size L. At the percolation threshold, however, the scaling exponent changes to θ≃0.141, as the result of the interplay of diffusive persistence and the underlying structural transition in the disordered lattice at the percolation threshold. Moreover, studying finite-size effects for 2D lattices at and above the percolation threshold, we find that at the percolation threshold, the long-time asymptotic value obeys a power law P(t,L)∼L^{-zθ} with z≃2.86 instead of the value of z=2 normally associated with finite-size effects on 2D regular lattices. In contrast, we observe that in random networks without a local regular structure, such as Erdos-Rényi networks, no simple power-law scaling behavior exists above the percolation threshold.

Modelling epidemic spread in cities using public transportation as a proxy for generalized mobility trends.

We study how public transportation data can inform the modeling of the spread of infectious diseases based on SIR dynamics. We present a model where public transportation data is used as an indicator of broader mobility patterns within a city, including the use of private transportation, walking etc. The mobility parameter derived from this data is used to model the infection rate. As a test case, we study the impact of the usage of the New York City subway on the spread of COVID-19 within the city during 2020. We show that utilizing subway transport data as an indicator of the general mobility trends within the city, and therefore as an indicator of the effective infection rate, improves the quality of forecasting COVID-19 spread in New York City. Our model predicts the two peaks in the spread of COVID-19 cases in NYC in 2020, unlike a standard SIR model that misses the second peak entirely.

Autologous Hematopoietic Stem Cell Transplantation in Active Multiple Sclerosis: A Real-world Case Series.

OBJECTIVE: To examine outcomes in people with multiple sclerosis (PwMS) treated with autologous hematopoietic stem cell transplantation (AHSCT) in a real-world setting. METHODS: This was a retrospective cohort study of PwMS treated with AHSCT at 2 centers in London, UK, consecutively between 2012 and 2019 who had ≥6 months of follow-up or died at any time. Primary outcomes were survival free of multiple sclerosis (MS) relapses, MRI new lesions, and worsening of Expanded Disability Status Scale (EDSS) score. Adverse events rates were also examined. RESULTS: The cohort includes 120 PwMS; 52% had progressive MS (primary or secondary) and 48% had relapsing-remitting MS. At baseline, the median EDSS score was 6.0; 90% of the evaluable cases showed MRI activity in the 12 months preceding AHSCT. Median follow-up after AHSCT was 21 months (range 6-85 months). MS relapse-free survival was 93% at 2 years and 87% at 4 years after AHSCT. No new MRI lesions were detected in 90% of participants at 2 years and in 85% at 4 years. EDSS score progression-free survival (PFS) was 75% at 2 years and 65% at 4 years. Epstein-Barr virus reactivation and monoclonal paraproteinemia were associated with worse PFS. There were 3 transplantation-related deaths within 100 days (2.5%), all after fluid overload and cardiac or respiratory failure. CONCLUSIONS: Efficacy outcomes of AHSCT in this real-world cohort are similar to those reported in more stringently selected clinical trial populations, although the risks may be higher. CLASSIFICATION OF EVIDENCE: This study is rated Class IV because of the uncontrolled, open-label design.

An Inexpensive model to teach hemorrhage control in resource limited settings.

We have created a bleeding leg simulator using inexpensive and readily available materials to teach civilians in resource-poor settings how to control exsanguinating hemorrhage until the patient can be brought to the hospital, as commercially available mannequins are often too expensive in these settings. Items used include a leg of lamb, IV tubing, IV fluids, and food coloring. The model was consistently rated as ''nearly - real'' to ''life like'' by ten physicians and surgeons, cost less than fifty dollars to make, and provided a fairly realistic model for teaching hemorrhage control.

A Diagnosis of Multiple Sclerosis Following Whiplash Injury: Is There a True Association?

We report a case of a previously well, 25-year-old Caucasian female whose diagnosis of multiple sclerosis (MS) followed significant trauma. Her symptoms and signs developed quickly and satisfied the criteria for rapidly evolving relapsing-remitting MS. She was started on natalizumab (Tysabri) and was stabilized. We discuss the existing literature on traumatic demyelination and possible underlying mechanisms.

Divergent Strategy for Diastereocontrolled Synthesis of Small- and Medium-Ring Architectures.

Nitrogen and oxygen medium rings, in particular nine-membered rings, epitomize a unique area of chemical space that occurs in many natural products and biologically appealing compounds. The scarcity of 8- to 12-membered rings among clinically approved drugs is indicative of the difficulties associated with their synthesis, principally owing to the unfavorable entropy and transannular strain. We report here a scandium triflate-catalyzed reaction that allows for a modular access to a diverse collection of nine-membered ring heterocycles in a one-pot cascade and with complete diastereocontrol. This cascade features an intramolecular addition of an acyl group-derived enol to a α,ß-unsaturated carbonyl moiety, leading to N- and O-derived medium-ring systems. Computational studies using the density functional theory support the proposed mechanism. Additionally, a one-pot cascade leading to hexacyclic chromeno[3',4':2,3]indolizino[8,7-b]indole architectures, with six fused rings and four contiguous chiral centers, is reported. This novel cascade features many concerted events, including the formation of two azomethine ylides, [3 + 2]-cycloaddition, 1,3-sigmatropic rearrangement, Michael addition, and Pictet-Spengler reaction among others. Phenotypic screening of the resulting oxazonine collection identified chemical probes that regulate mitochondrial membrane potential, adenosine 5'-triphosphate contents, and reactive oxygen species levels in hepatoma cells (Hepa1-6), a promising approach for targeting cancer and metabolic disorders.

Development of Autoimmune Thyroid Disease in Multiple Sclerosis Patients Post-Alemtuzumab Improves Treatment Response.

CONTEXT: Alemtuzumab is an anti-CD52 monoclonal antibody used in the treatment of relapsing-remitting multiple sclerosis (MS). Between 20% and 40% of alemtuzumab-treated MS patients develop autoimmune thyroid disease (AITD) as a side effect. OBJECTIVE: The objective of this work is to determine whether MS disease progression following alemtuzumab treatment differs in patients who develop AITD compared to those who do not. DESIGN, SETTING, AND PATIENTS: A retrospective analysis of 126 patients with relapsing-remitting MS receiving alemtuzumab from 2012 to 2017 was conducted at a tertiary referral center. MAIN OUTCOME MEASURES: Thyroid status, new relapses, Expanded Disability Status Scale (EDSS) score change, and disability progression following alemtuzumab were evaluated. RESULTS: Twenty-six percent (33 out of 126, 25 female, 8 male) of alemtuzumab-treated patients developed AITD, 55% of which was Graves disease. EDSS score following alemtuzumab was reduced in patients who developed AITD compared to those who did not (median [interquartile range]; AITD: -0.25 [-1 to 0.5] vs non-AITD: 0 [1-0]. P = .007]. Multivariable regression analysis confirmed that the development of AITD was independently associated with EDSS score improvement (P = .011). Moreover, AITD patients had higher relapse-free survival following alemtuzumab (P = .023). There was no difference in the number of new focal T2 lesions and contrast-enhancing magnetic resonance imaging lesions developed following alemtuzumab between the 2 groups. CONCLUSION: Graves disease was the most common form of AITD developed by MS patients following alemtuzumab. This study suggests that MS patients who develop AITD may have an improved response to alemtuzumab, as measured by reduced disability and lower relapse rate.

Using amyloid PET imaging to diagnose Alzheimer's disease in patients with multiple sclerosis.

BACKGROUND: Cognitive dysfunction affects 40-60% of individuals with multiple sclerosis (MS). The neuropsychological profile commonly consists of a subcortical pattern of deficits, although a proportion of patients have a severe progressive cortical dementia. However, patients with MS can be affected by other neurodegenerative diseases, such as Alzheimer's disease (AD). Little is known about the co-existence of these two conditions but distinguishing dementia due to MS alone from a coexisting neurodegenerative disease is challenging. Amyloid PET imaging has allowed improved AD diagnosis, especially in patients with atypical presentations or multiple possible causes of cognitive impairment. Amyloid PET demonstrates increased cortical signal in AD, whereas reductions in subcortical uptake are associated with demyelination. To the authors knowledge, there are no reports of clinical Amyloid PET use in MS patients with dementia. METHODS: Here, three MS patients presenting to the Cognitive Neurology Clinic with progressive cognitive impairment are described. Due to lack of diagnostic clarity from standard investigations, they underwent Amyloid PET Imaging with 18F-florbetapir according to established appropriate use criteria and after review by a multidisciplinary team. RESULTS: Two patients were diagnosed with AD based on positive Amyloid PET imaging and were subsequently started on cholinesterase inhibitor treatment. The other patient had a negative scan, leading to further investigations and identification of another potential cause of worsening cognitive impairment. CONCLUSIONS: The experience from this case series suggests that Amyloid PET Imaging may be of diagnostic value in selected patients with MS and dementia. In these individuals, it may provide diagnostic clarity and assist with therapeutic decisions.

Computer algorithm compared with routine clinical practice in screening for deep venous thrombosis in the leg in an emergency department.

OBJECTIVE: To audit routine clinical practice in screening patients admitted to an accident and emergency department for deep venous thrombosis in the leg (DVT) and compare it with a computer algorithm. DESIGN: Retrospective study of case notes with data subsequently entered into a computer algorithm followed by a comparison of the diagnosis and recommended management from each modality. SETTING: Emergency department at a London teaching hospital. POPULATION OR SAMPLE: A convenience sample of 43 patients attending the emergency department. METHODS: Evaluation of clinical notes for completeness of assessment and correct diagnosis; entry of the same data into the computer algorithm. MAIN OUTCOME MEASURES: Completeness of data collection, diagnosis of presence or absence of DVT, and recommended therapy. RESULTS: The Wells score was missing in the clinical evaluation in 60% of cases. Clinicians relied primarily on the results of ultrasound scans and in six cases the absence of required D-Dimer measurements meant that the algorithm stalled. Clinical and algorithm analysis and recommendations were not compliant in 10 cases (23%). CONCLUSIONS: Clinical assessment of potential DVT in the accident and emergency department is poorly performed when compared with a computerised algorithm. Clinicians rely heavily on scan reports rather than clinical assessment which may have cost implications.

Prevalence, Risk Factors, Treatment, and Overall Impact of BK Viremia on Kidney Transplantation.

BK viremia (BKV) is a recognized and potentially serious problem in renal transplantation. The risk factors and the impact of BKV on renal allograft and patient survival are controversial. This study reports an 8-year, single-center experience on the prevalence, risk factors, and outcomes of BKV in kidney transplant recipients. This is a retrospective analysis of all patients who received a kidney transplant at the University of Kentucky and had BK viral titers available from 2009 to 2017. BKV was defined by a polymerase chain reaction viral load of ≥ 10,000 copies per mL. Demographic, clinical, and laboratory data generated during routine outpatient follow up and inpatients records were collected. Independent risk factors for BKV were determined using uni- and multivariate analysis. Graft and patient survival was compared using Kaplan-Meier analysis, and the severity of polyomavirus nephropathy on biopsy was scored using the Banff 2017 classification. We identified 122 BK positive (19%) and 527 BK negative (81%) patients. BKV developed after a median of 115 days (range, 80-249 days) following kidney transplantation. The 1-, 5-, and 10-year graft survival was 97%, 75%, and 33% in the BKV group and 96%, 85%, and 71% in the BK negative group, respectively. Likewise, the 1-, 5-, and 10-year patient survival was 98%, 84%, and 52% in the BKV group and 98%, 92%, and 84% in the BK negative group. Male sex, age at transplantation, maintenance steroids, and alemtuzumab induction were associated with developing BKV in the multivariate analysis. We concluded that BKV is not uncommon after renal transplantation. The determinants for BKV are male sex, older transplant recipients, and maintenance steroids. BKV adversely affected graft and patient survival. A unified approach for BKV and polyomavirus nephropathy treatment is needed.

Epstein-Barr Virus and Monoclonal Gammopathy of Clinical Significance in Autologous Stem Cell Transplantation for Multiple Sclerosis.

INTRODUCTION: Autologous hematopoietic stem cell transplantation (AHSCT) with anti-thymocyte globulin (ATG) conditioning as treatment of active multiple sclerosis (MS) is rapidly increasing across Europe (EBMT registry data 2017). Clinically significant Epstein-Barr virus reactivation (EBV-R) following AHSCT with ATG for severe autoimmune conditions is an underrecognized complication relative to T-cell deplete transplants performed for hematological diseases. This retrospective study reports EBV-R associated significant clinical sequelae in MS patients undergoing AHSCT with rabbit ATG. METHODS: Retrospective data were analyzed for 36 consecutive MS-AHSCT patients at Kings College Hospital, London. All patients routinely underwent weekly EBV DNA polymerase chain reaction monitoring and serum electrophoresis for monoclonal gammopathy (MG or M-protein). EBV-R with rising Epstein-Barr viral load, M-protein, and associated clinical sequelae were captured from clinical records. RESULTS: All patients had evidence of rising EBV DNA-emia, including 7 who were lost to long-term follow-up, with a number of them developing high EBV viral load and associated lymphoproliferative disorder (LPD). Nearly 72% (n = 18/29) developed de novo MG, some with significant neurological consequences with high M-protein and EBV-R. Six patients required anti-CD20 therapy (rituximab) with complete resolution of EBV related symptoms. Receiver operating characteristics estimated a peak EBV viremia of >500 000 DNA copies/mL correlated with high sensitivity (85.5%) and specificity (82.5%) (area under the curve: 0.87; P = .004) in predicting EBV-R related significant clinical events. CONCLUSION: Symptomatic EBV reactivation increases risk of neurological sequelae and LPD in MS-AHSCT. We recommend regular monitoring for EBV and serum electrophoresis for MG in MS patients in the first 3 months post-AHSCT.

Impact of Recent Clinical Trials on Nephrology Practice: Are We in a Stagnant Era?

BACKGROUND: Although renal replacement therapy prevents death from uremia, survival among patients with acute and chronic kidney diseases (CKD) remains an imperative concern. The expected life span of US dialysis patients 60-64 years of age is approximately 4.5 years; this is similar to that of patients with lung cancer. Despite substantial progress in many medical specialties over the past decades (e.g., notable reductions in myocardial infarction, stroke, and mortality rates in the general population), survival among dialysis patients has not improved significantly over the same period. A few decades ago, HIV infection and AIDS were pretty much a death sentence. Because of progress in HIV treatment, now it can be controlled with a daily pill, and ongoing research is pushing treatment even further and controls the virus with longer-acting treatment. A cure is no longer impossible for HIV and other viral infections such as hepatitis B and C and many malignancies, but so far there is no cure for CKD. SUMMARY: Billions of dollars have been spent on kidney disease research in the past decades, with no tangible progress in clinical practice. The challenges of improving the quantity and quality of trials in nephrology are enormous. The number of randomized controlled trials (RCTs) published in nephrology is lower than that in other medical subspecialties, and most of the big RCTs in nephrology yield negative results. Nephrology studies evaluating hard clinical endpoints or surrogate endpoints are scarce. KEY MESSAGE: Herein we discuss the slow progress in nephrology research that has impacted clinical practice over the last couple of decades and highlight the major obstacles, challenges, and potential solutions.

Impact of human leukocyte antigen and calculated panel reactive antibody on BK viremia in kidney transplant recipients: A single-center experience and literature review.

BACKGROUND: The aim of this retrospective analysis was to investigate the effect of human leukocyte antigen (HLA) and calculated panel reactive antibody (cPRA) on BK virus activation as evidenced by BK viremia (BKV). PATIENTS AND METHODS: At our institution, 649 kidney transplant patients were screened for BKV from 2009 to 2017. Patients were considered to have BKV if they had >10 000 copies/mL of BK DNA in their blood. Donor and recipient HLA and cPRA, demographic, clinical and laboratory data, as well as immunosuppressive medications were collected. RESULTS: We identified 122 BK positive and 527 BK negative patients. Only 25% of the patients had cPRA of 20% or more, and 64% had more than three HLA-A, -B, and -DR mismatches. In both univariate and multivariate analyses, male gender, age, and maintenance of steroid therapy significantly increased the risk of BKV (P = 0.005, 0.005 and <0.001, respectively). The degree of cPRA and the individual HLA allele and HLA allele matching did not significantly affect BKV. CONCLUSION: Neither the degree of HLA mismatching nor cPRA appears to affect BKV. Moreover, no specific HLA allele, HLA allele matching, or cPRA were associated with BKV.

One-Pot Synthesis of Diverse Collections of Benzoxazepine and Indolopyrazine Fused to Heterocyclic Systems.

The development of efficient and modular synthetic methods for the synthesis of diverse collection of privileged substructures needed for a drug design and discovery campaign is highly desirable. Benzoxazepine and indolopyrazine ring systems form the core structures of distinct members of biologically significant molecules. Several members of these families have gained attention due to their broad biological activities, which depend on the type of ring-fusion and peripheral substitution patterns. Despite the potential applications of these privileged substructures in drug discovery, efficient, atom-economic, and modular strategies for their access are underdeveloped. Herein, a one-step build/couple/pair strategy that uniquely allows access to diversely functionalized benzoxazepine and indolopyrazine scaffolds is described. The methodology features a one-pot combination of condensation, Mannich, oxidation, and aza-Michael addition reactions, employing a variety of functionalized anilines and aldehydes suitably poised with Micheal acceptor. Scandium triflate (Sc(OTf)3) in acetonitrile (ACN) was found to promote the construction of benzoxazepines scaffolds, while sodium metabisulfite (Na2S2O5) in aqueous EtOH rapidly enhanced the cascade reaction that led to diverse collections of indolopyrazine frameworks. These protocols represent modular, efficient, and atom-economic access of constrained benzoxazepine and indolopyrazine systems with more than 10 points of diversity and large substrate tolerance.

Do we use antibiotics judiciously enough? A study in Accident & Emergency Department of tertiary care hospital in Pakistan.

OBJECTIVE: To determine whether antibiotics are necessary for all minor wounds presenting to the Accident and Emergency Department at a tertiary care Centre in Pakistan. METHODS: One hundred and five patients presenting to the Accident & Emergency Department, Jinnah Postgraduate Medical Centre, Karachi, with open wounds were included in the study and divided into two: Groups A (study) and B (control), with Group-A receiving conservative therapy. Eighty-four patients were included in the final analysis as the rest were lost to follow up. Follow up was done after one week to see how many patients had developed infection. RESULTS: The average age of patients was 27.3 +/-9.7 years with similar baseline characteristics. From these, 51% had superficial wounds; average number of wounds was 1.63 +/-0.99, with an average length of 2.7 +/-1.6 cm. A total of 10 out of 84 patients developed infection at 7-10 days after presentation to the A&E. From these, 3 patients receiving conservative treatment (A, 10%, OR=0.107), and seven patients receiving prophylactic antibiotics (B, 12.96%, OR=0.149) developed an infection. Calculated odds ratio for increased risk of infection in Group-A = 0.72. CONCLUSION: A conservative approach to antibiotic prescription for minor trauma may be appropriate despite absence of strict asepsis during emergency wound care.

Neuroinflammation and its relationship to changes in brain volume and white matter lesions in multiple sclerosis.

Brain magnetic resonance imaging is an important tool in the diagnosis and monitoring of multiple sclerosis patients. However, magnetic resonance imaging alone provides limited information for predicting an individual patient's disability progression. In part, this is because magnetic resonance imaging lacks sensitivity and specificity for detecting chronic diffuse and multi-focal inflammation mediated by activated microglia/macrophages. The aim of this study was to test for an association between 18 kDa translocator protein brain positron emission tomography signal, which arises largely from microglial activation, and measures of subsequent disease progression in multiple sclerosis patients. Twenty-one patients with multiple sclerosis (seven with secondary progressive disease and 14 with a relapsing remitting disease course) underwent T1- and T2-weighted and magnetization transfer magnetic resonance imaging at baseline and after 1 year. Positron emission tomography scanning with the translocator protein radioligand 11C-PBR28 was performed at baseline. Brain tissue and lesion volumes were segmented from the T1- and T2-weighted magnetic resonance imaging and relative 11C-PBR28 uptake in the normal-appearing white matter was estimated as a distribution volume ratio with respect to a caudate pseudo-reference region. Normal-appearing white matter distribution volume ratio at baseline was correlated with enlarging T2-hyperintense lesion volumes over the subsequent year (ρ = 0.59, P = 0.01). A post hoc analysis showed that this association reflected behaviour in the subgroup of relapsing remitting patients (ρ = 0.74, P = 0.008). By contrast, in the subgroup of secondary progressive patients, microglial activation at baseline was correlated with later progression of brain atrophy (ρ = 0.86, P = 0.04). A regression model including the baseline normal-appearing white matter distribution volume ratio, T2 lesion volume and normal-appearing white matter magnetization transfer ratio for all of the patients combined explained over 90% of the variance in enlarging lesion volume over the subsequent 1 year. Glial activation in white matter assessed by translocator protein PET significantly improves predictions of white matter lesion enlargement in relapsing remitting patients and is associated with greater brain atrophy in secondary progressive disease over a period of short term follow-up.

Programmed death 1 is highly expressed on CD8+ CD57+ T cells in patients with stable multiple sclerosis and inhibits their cytotoxic response to Epstein-Barr virus.

Growing evidence points to a deregulated response to Epstein-Barr virus (EBV) in the central nervous system of patients with multiple sclerosis (MS) as a possible cause of disease. We have investigated the response of a subpopulation of effector CD8+ T cells to EBV in 36 healthy donors and in 35 patients with MS in active and inactive disease. We have measured the expression of markers of degranulation, the release of cytokines, cytotoxicity and the regulation of effector functions by inhibitory receptors, such as programmed death 1 (PD-1) and human inhibitor receptor immunoglobulin-like transcript 2 (ILT2). We demonstrate that polyfunctional cytotoxic CD8+ CD57+ T cells are able to kill EBV-infected cells in healthy donors. In contrast, an anergic exhaustion-like phenotype of CD8+ CD57+ T cells with high expression of PD-1 was observed in inactive patients with MS compared with active patients with MS or healthy donors. Detection of CD8+ CD57+ T cells in meningeal inflammatory infiltrates from post-mortem MS tissue confirmed the association of this cell phenotype with the disease pathological process. The overall results suggest that ineffective immune control of EBV in patietns with MS during remission may be one factor preceding and enabling the reactivation of the virus in the central nervous system and may cause exacerbation of the disease.

Role of antimicrobials in the treatment of adult patients presenting to the emergency department with acute gastroenteritis - A mini review.

BACKGROUND & OBJECTIVE: Acute gastroenteritis is generally considered a self-limiting illness that does not require the use of antibiotics. However, many emergency departments in the country frequently prescribe antibiotics to patients presenting with diarrhoea. This review attempts to determine whether this practice is reasonable. Our objective was to determine the role of antimicrobials in the empiric management of acute gastroenteritis. METHODS: The online data base "PubMed", as well as the World Wide Web, were searched for relevant articles (RCTs, Reviews, Prospective studies, etc.) with key words such as "gastroenteritis AND antibiotics", "Management AND gastroenteritis", "Treatment AND diarrhoea" etc. and covered the years 1960-2016. Fifty articles were studied, of which 43 were chosen on the basis of relevance for qualitative assessment. RESULTS: The articles reviewed for this paper suggest that antimicrobial therapy is not appropriate for the majority of cases of (uncomplicated) gastroenteritis, as risks (antibiotic-associated diarrhoea, hypersensitivity reactions, etc.) outweigh benefits. However, there are instances where antibiotics are clearly indicated. Further, it is noted that there have not been any recent trials to clarify the role of antimicrobials in adult diarrhoeal illness. CONCLUSIONS: The focus in management of patients presenting with diarrhoea in the Emergency Department should be on rehydration and that only certain patients, such as those with fever or dysentery, or those with an impaired immune response should receive empiric antimicrobial therapy. More studies are needed to determine in what instances antimicrobials are of greatest benefit, so that adverse effects of rampant antibiotic prescription can be curtailed.

11C-PBR28 and 18F-PBR111 Detect White Matter Inflammatory Heterogeneity in Multiple Sclerosis.

The objective of this study was to assess microglial activation in lesions and in normal-appearing white matter (NAWM) of multiple sclerosis (MS) patients using PET. Methods: Thirty-four MS patients (7 with secondary progressive MS [SPMS], 27 with relapsing remitting MS [RRMS]) and 30 healthy volunteers, genetically stratified for translocator protein (TSPO) binding status, underwent PET scanning with TSPO radioligands (11C-PBR28 or 18F-PBR111). Regional TSPO availability was measured as a distribution volume ratio (DVR) relative to the caudate (a pseudoreference region). White matter lesions (WMLs) were classified as "active" (DVR highest in the lesion), "peripherally active" (perilesional DVR highest), "inactive" (DVR highest in surrounding NAWM), or "undifferentiated" (similar DVR across lesion, perilesional and NAWM volumes). Results: The mean DVR in NAWM of patients was greater than that of the healthy volunteer white matter for both radioligands. Uptake for individual WML in patients was heterogeneous, but the median WML DVR and NAWM DVR for individual patients were strongly correlated (ρ = 0.94, P = 4 × 10-11). A higher proportion of lesions were inactive in patients with SPMS (35%) than RRMS (23%), but active lesions were found in all patients, including those on highly efficacious treatments. Conclusion: TSPO radioligand uptake was increased in the brains of MS patients relative to healthy controls with 2 TSPO radiotracers. WML showed heterogeneous patterns of uptake. Active lesions were found in patients with both RRMS and SPMS. Their independent prognostic significance needs further investigation.