scholarly journals Central Vein Sign Profile of Newly Developing Lesions in Multiple Sclerosis

2022 ◽  
Vol 9 (2) ◽  
pp. e1120
Author(s):  
Omar Al-Louzi ◽  
Vijay Letchuman ◽  
Sargis Manukyan ◽  
Erin S. Beck ◽  
Snehashis Roy ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
White Matter Lesions ◽  
Trial Registration ◽  
Central Vein ◽  
Class Iii ◽  
Lesion Development ◽  
Clinical Trial Registration ◽  
Link Type ◽  
Younger Age

Background and ObjectivesThe central vein sign (CVS), a central linear hypointensity within lesions on T2*-weighted imaging, has been established as a sensitive and specific biomarker for the diagnosis of multiple sclerosis (MS). However, the CVS has not yet been comprehensively studied in newly developing MS lesions. We aimed to identify the CVS profiles of new white matter lesions in patients with MS followed over time and investigate demographic and clinical risk factors associated with new CVS+ or CVS− lesion development.MethodsIn this retrospective longitudinal cohort study, adults from the NIH MS Natural History Study were considered for inclusion. Participants with new T2 or enhancing lesions were identified through review of the radiology report and/or longitudinal subtraction imaging. Each new lesion was evaluated for the CVS. Clinical characteristics were identified through chart review.ResultsA total of 153 adults (95 relapsing-remitting MS, 27 secondary progressive MS, 16 primary progressive MS, 5 clinically isolated syndrome, and 10 healthy; 67% female) were included. Of this cohort, 96 had at least 1 new T2 or contrast-enhancing lesion during median 3.1 years (Q1–Q3: 0.7–6.3) of follow-up; lesions eligible for CVS evaluation were found in 62 (65%). Of 233 new CVS-eligible lesions, 159 (68%) were CVS+, with 30 (48%) individuals having only CVS+, 12 (19%) only CVS−, and 20 (32%) both CVS+ and CVS− lesions. In gadolinium-enhancing (Gd+) lesions, the CVS+ percentage increased from 102/152 (67%) at the first time point where the lesion was observed, to 92/114 (82%) after a median follow-up of 2.8 years. Younger age (OR = 0.5 per 10-year increase, 95% CI = 0.3–0.8) and higher CVS+ percentage at baseline (OR = 1.4 per 10% increase, 95% CI = 1.1–1.9) were associated with increased likelihood of new CVS+ lesion development.DiscussionIn a cohort of adults with MS followed over a median duration of 3 years, most newly developing T2 or enhancing lesions were CVS+ (68%), and nearly half (48%) developed new CVS+ lesions only. Importantly, the effects of edema and T2 signal changes can obscure small veins in Gd+ lesions; therefore, caution and follow-up is necessary when determining their CVS status.Trial Registration InformationClinical trial registration number NCT00001248.Classification of EvidenceThis study provides Class III evidence that younger age and higher CVS+ percentage at baseline are associated with new CVS+ lesion development.

scholarly journals MEBO versus topical Diltiazem versus a combination of both ointments in the treatment of acute anal fissure: a randomized clinical trial protocol

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Mohamad Hadi El Charif ◽  
Samer Doughan ◽  
Rawya Kredly ◽  
Sara Kassas ◽  
Rayan Azab ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Wound Healing ◽  
Anal Fissure ◽  
Topical Therapy ◽  
Trial Registration ◽  
Clinical Trial Registration ◽  
Anal Fissures ◽  
Link Type ◽  
Anorectal Region ◽  
Registration Date

Abstract Background Anal fissure is a common complication of the anorectal region and one of the most reported causes of anal pain. Acute anal fissure can be cured by surgery or medical treatment. There is an increase in the use of topical therapy for the treatment of anal fissures. A common topical drug used is Diltiazem (DTZ), a calcium-channel blocker, which relaxes the anal sphincter and thus promotes healing of the anal fissure. Moist exposed burn ointment (MEBO) is an ointment that is effective for the treatment of burns and wound healing and is becoming popular in the treatment of anal fissures. Methods This is a 1:1:1 randomized, controlled, parallel design, with endpoint measures of change in pain score, wound healing, defecation strain score and patient’s global impression of improvement. The study will be conducted at AUBMC over a 10-week period. Patients will be randomized to three treatment arms: MEBO, Diltiazem, and a combination of MEBO and Diltiazem ointments. Discussion The results of this study will allow physicians to assess the efficacy and safety of MEBO in the treatment of acute anal fissure, and also in comparison to Diltiazem. This trial will generate evidence-based conclusions regarding the use of a herbal/natural-based product (MEBO ointment) for the treatment of anal fissures. Trial registration ClinicalTrials.gov Identifier NCT04153032. Clinical Trial Registration Date: 06-NOVEMBER-2019.

scholarly journals Alemtuzumab CARE-MS II 5-year follow-up

Neurology ◽  
2017 ◽  
Vol 89 (11) ◽  
pp. 1117-1126 ◽  
Author(s):  
Alasdair J. Coles ◽  
Jeffrey A. Cohen ◽  
Edward J. Fox ◽  
Gavin Giovannoni ◽  
Hans-Peter Hartung ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Incidence Rates ◽  
Continuous Treatment ◽  
Inadequate Response ◽  
Class Iii ◽  
Prior Therapy ◽  
Link Type ◽  
Brain Volume Loss ◽  
Core Study ◽  
Adjusted Incidence

Objective:To evaluate 5-year efficacy and safety of alemtuzumab in patients with active relapsing-remitting multiple sclerosis and inadequate response to prior therapy.Methods:In the 2-year Comparison of Alemtuzumab and Rebif Efficacy in Multiple Sclerosis (CARE-MS) II study (NCT00548405), alemtuzumab-treated patients received 2 courses (baseline and 12 months later). Patients could enter an extension (NCT00930553), with as-needed alemtuzumab retreatment for relapse or MRI activity. Annualized relapse rate (ARR), 6-month confirmed disability worsening (CDW; ≥1-point Expanded Disability Status Scale [EDSS] score increase [≥1.5 if baseline EDSS = 0]), 6-month confirmed disability improvement (CDI; ≥1-point EDSS decrease [baseline score ≥2.0]), no evidence of disease activity (NEDA), brain volume loss (BVL), and adverse events (AEs) were assessed.Results:Most alemtuzumab-treated patients (92.9%) who completed CARE-MS II entered the extension; 59.8% received no alemtuzumab retreatment. ARR was low in each extension year (years 3–5: 0.22, 0.23, 0.18). Through 5 years, 75.1% of patients were free of 6-month CDW; 42.9% achieved 6-month CDI. In years 3, 4, and 5, proportions with NEDA were 52.9%, 54.2%, and 58.2%, respectively. Median yearly BVL remained low in the extension (years 1–5: −0.48%, −0.22%, −0.10%, −0.19%, −0.07%). AE exposure-adjusted incidence rates in the extension were lower than in the core study. Thyroid disorders peaked at year 3, declining thereafter.Conclusions:Alemtuzumab provides durable efficacy through 5 years in patients with an inadequate response to prior therapy in the absence of continuous treatment.Classification of evidence:This study provides Class III evidence that alemtuzumab provides efficacy and slowing of brain atrophy through 5 years.

scholarly journals Improved relapse recovery in paediatric compared to adult multiple sclerosis

Brain ◽  
2020 ◽  
Vol 143 (9) ◽  
pp. 2733-2741
Author(s):  
Tanuja Chitnis ◽  
Greg Aaen ◽  
Anita Belman ◽  
Leslie Benson ◽  
Mark Gorman ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Functional System ◽  
Progressive Multiple Sclerosis ◽  
Age Related ◽  
Younger Age ◽  
Disability Status ◽  
The Us ◽  
The Difference ◽  
Effect Of Age

Abstract Incomplete relapse recovery contributes to disability accrual and earlier onset of secondary progressive multiple sclerosis. We sought to investigate the effect of age on relapse recovery. We identified patients with multiple sclerosis from two longitudinal prospective studies, with an Expanded Disability Status Scale (EDSS) score within 30 days after onset of an attack, and follow-up EDSS 6 months after attack. Adult patients with multiple sclerosis (n = 632) were identified from the Comprehensive Longitudinal Investigations in Multiple Sclerosis at Brigham study (CLIMB), and paediatric patients (n = 132) from the US Network of Paediatric Multiple Sclerosis Centers (NPMSC) registry. Change in EDSS was defined as the difference in EDSS between attack and follow-up. Change in EDSS at follow-up compared to baseline was significantly lower in children compared to adults (P = 0.001), as were several functional system scores. Stratification by decade at onset for change in EDSS versus age found for every 10 years of age, EDSS recovery is reduced by 0.15 points (P < 0.0001). A larger proportion of children versus adults demonstrated improvement in EDSS following an attack (P = 0.006). For every 10 years of age, odds of EDSS not improving increase by 1.33 times (P < 0.0001). Younger age is associated with improved recovery from relapses. Age-related mechanisms may provide novel therapeutic targets for disability accrual in multiple sclerosis.

scholarly journals Serum alkaline phosphatase levels and the risk of new-onset diabetes in hypertensive adults

2020 ◽  
Vol 19 (1) ◽  
Author(s):  
Yuanyuan Zhang ◽  
Chun Zhou ◽  
Jianping Li ◽  
Yan Zhang ◽  
Di Xie ◽  
...  
Keyword(s):  
Alkaline Phosphatase ◽  
Fasting Glucose ◽  
Serum Alkaline Phosphatase ◽  
Positive Association ◽  
Trial Registration ◽  
Clinical Trial Registration ◽  
Onset Diabetes ◽  
Increased Risk ◽  
New Onset

Abstract Background The association between alkaline phosphatase (ALP) and incident diabetes remains uncertain. Our study aimed to investigate the prospective relation of serum ALP with the risk of new-onset diabetes, and explore possible effect modifiers, in hypertensive adults. Methods A total 14,393 hypertensive patients with available ALP measurements and without diabetes and liver disease at baseline were included from the China Stroke Primary Prevention Trial (CSPPT). The primary outcome was new-onset diabetes, defined as physician-diagnosed diabetes or use of glucose-lowering drugs during follow-up, or fasting glucose ≥ 7.0 mmol/L at the exit visit. The secondary study outcome was new-onset impaired fasting glucose (IFG), defined as FG < 6.1 mmol/L at baseline and ≥ 6.1 but < 7.0 mmol/L at the exit visit. Results Over a median of 4.5 years follow-up, 1549 (10.8%) participants developed diabetes. Overall, there was a positive relation of serum ALP and the risk of new-onset diabetes (per SD increment, adjusted OR, 1.07; 95% CI: 1.01, 1.14) and new-onset IFG (per SD increment, adjusted OR, 1.07; 95% CI: 1.02, 1.14). Moreover, a stronger positive association between baseline ALP (per SD increment) with new-onset diabetes was found in participants with total homocysteine (tHcy) < 10 μmol/L (adjusted OR, 1.24; 95% CI: 1.10, 1.40 vs. ≥ 10 μmol/L: adjusted OR, 1.03; 95% CI: 0.96, 1.10; P-interaction = 0.007) or FG ≥ 5.9 mmol/L (adjusted OR, 1.16; 95% CI: 1.07, 1.27 vs. < 5.9 mmol/L: adjusted OR, 1.00; 95% CI: 0.93, 1.08; P-interaction = 0.009) Conclusions In this non-diabetic, hypertensive population, higher serum ALP was significantly associated with the increased risk of new-onset diabetes, especially in those with lower tHcy or higher FG levels. Clinical Trial Registration-URL Trial registration: NCT00794885 (clinicaltrials.gov). Retrospectively registered November 20, 2008.

scholarly journals A timed activity protocol to address sleep-wake disorders in home dwelling persons living with dementia: the healthy patterns clinical trial

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Nancy A. Hodgson ◽  
Nalaka Gooneratne ◽  
Adriana Perez ◽  
Sonia Talwar ◽  
Liming Huang
Keyword(s):  
Quality Of Life ◽  
Clinical Trial ◽  
Trial Registration ◽  
Phase Iii ◽  
Poor Sleep ◽  
Sleep Wake Disorders ◽  
Clinical Trial Registration ◽  
Link Type ◽  
Home Based

Abstract Background Sleep-wake disorders occur in most persons living with dementia and include late afternoon or evening agitation, irregular sleep-wake rhythms such as daytime hypersomnia, frequent night awakenings, and poor sleep efficiency. Sleep-wake disorders pose a great burden to family caregivers, and are the principal causes of distress, poor quality of life, and institutionalization. Regulating the sleep-wake cycle through the use of light and activity has been shown to alter core clock processes and suggests that a combination of cognitive, physical, and sensory-based activities, delivered at strategic times, may be an effective mechanism through which to reduce sleep-wake disorders. Methods A definitive Phase III efficacy trial of the Healthy Patterns intervention, a home-based activity intervention designed to improve sleep-wake disorders and quality of life, is being conducted using a randomized two-group parallel design of 200 people living with dementia and their caregivers (dyads). Specific components of this one-month, home-based intervention involve 4 in-home visits and includes: 1) assessing individuals’ functional status and interests; 2) educating caregivers on environmental cues to promote activity and sleep; and 3) training caregivers in using timed morning, afternoon, and evening activities based on circadian needs across the day. The patient focused outcomes of interest are quality of life, measures of sleep assessed by objective and subjective indicators including actigraphy, subjective sleep quality, and the presence of neuropsychiatric symptoms. Caregiver outcomes of interest are quality of life, burden, confidence using activities, and sleep disruption. Salivary measures of cortisol and melatonin are collected to assess potential intervention mechanisms. Discussion The results from the ongoing study will provide fundamental new knowledge regarding the effects of timing activity participation based on diurnal needs and the mechanisms underlying timed interventions which can lead to a structured, replicable treatment protocol for use with this growing population of persons living with dementia. Clinical trial registration Clinicaltrials.gov # NCT03682185 at https://clinicaltrials.gov/; Date of clinical trial registration: 24 September 2018.

scholarly journals The “Central Vein Sign” on T2*-weighted Images as a Diagnostic Tool in Multiple Sclerosis: A Systematic Review and Meta-analysis using Individual Patient Data

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Chong Hyun Suh ◽  
Sang Joon Kim ◽  
Seung Chai Jung ◽  
Choong Gon Choi ◽  
Ho Sung Kim
Keyword(s):  
Multiple Sclerosis ◽  
White Matter ◽  
Random Effects ◽  
Diagnostic Performance ◽  
Individual Patient Data ◽  
White Matter Lesions ◽  
Patient Data ◽  
Central Vein ◽  
Random Effects Model ◽  
T2 Weighted Images

AbstractWe aimed to evaluate the pooled incidence of central vein sign on T2*-weighted images from patients with multiple sclerosis (MS), and to determine the diagnostic performance of this central vein sign for differentiating MS from other white matter lesions and provide an optimal cut-off value. A computerized systematic search of the literature in PUBMED and EMBASE was conducted up to December 14, 2018. Original articles investigating central vein sign on T2*-weighted images of patients with MS were selected. The pooled incidence was obtained using random-effects model. The pooled sensitivity and specificity were obtained using a bivariate random-effects model. An optimal cut-off value for the proportion of lesions with a central vein sign was calculated from those studies providing individual patient data. Twenty-one eligible articles covering 501 patients with MS were included. The pooled incidence of central vein sign at the level of individual lesion in patients with MS was 74% (95% CI, 65–82%). The pooled sensitivity and pooled specificity for the diagnostic performance of the central vein sign were 98% (95% CI, 92–100%) and 97% (95% CI, 91–99%), respectively. The area under the HSROC curve was 1.00 (95% CI, 0.99–1.00). The optimal cut-off value for the proportion of lesions with a central vein sign was found to be 45%. Although various T2*-weighted images have been used across studies, the current evidence supports the use of the central vein sign on T2*-weighted images to differentiate MS from other white matter lesions.

scholarly journals Value of the central vein sign at 3T to differentiate MS from seropositive NMOSD

Neurology ◽  
2018 ◽  
Vol 90 (14) ◽  
pp. e1183-e1190 ◽  
Author(s):  
Rosa Cortese ◽  
Lise Magnollay ◽  
Carmen Tur ◽  
Khaled Abdel-Aziz ◽  
Anu Jacob ◽  
...  
Keyword(s):  
White Matter Lesions ◽  
Central Vein ◽  
Class Iii ◽  
Clinical Value ◽  
3T Mri ◽  
Relapsing Remitting ◽  
Unit Increase ◽  
Sensitivity Specificity ◽  
Percent Unit

ObjectiveTo assess the value of the central vein sign (CVS) on a clinical 3T scanner to distinguish between multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD).MethodsEighteen aquaporin-4-antibody-positive patients with NMOSD, 18 patients with relapsing-remitting MS, and 25 healthy controls underwent 3T MRI. The presence of a central vein in white matter lesions on susceptibility-weighted imaging, defined as a thin hypointense line or a small dot, was recorded.ResultsThe proportion of lesions with the CVS was higher in MS than NMOSD (80% vs 32%, p < 0.001). A greater proportion of lesions with the CVS predicted the diagnosis of MS, rather than NMOSD (odds ratio 1.10, 95% confidence interval [CI] 1.04 to 1.16, p = 0.001), suggesting that each percent unit increase in the proportion of lesions with the CVS in an individual patient was associated with a 10% increase in the risk of the same patient having MS. If more than 54% of the lesions on any given scan show the CVS, then the patient can be given a diagnosis of MS with an accuracy of 94% (95% CIs 81.34, 99.32, p < 0.001, sensitivity/specificity 90%/100%).ConclusionThe clinical value of the CVS in the context of the differential diagnosis between MS and NMOSD, previously suggested using 7T scanners, is now extended to clinical 3T scanners, thereby making a step towards the use of CVS in clinical practice.Classification of evidenceThis study provides Class III evidence that the CVS on 3T MRI accurately distinguishes patients with MS from those with seropositive NMOSD.

Imaging central veins in brain lesions with 3-T T2*-weighted magnetic resonance imaging differentiates multiple sclerosis from microangiopathic brain lesions

2016 ◽  
Vol 22 (10) ◽  
pp. 1289-1296 ◽  
Author(s):  
Niraj Mistry ◽  
Rasha Abdel-Fahim ◽  
Amal Samaraweera ◽  
Olivier Mougin ◽  
Emma Tallantyre ◽  
...  
Keyword(s):  
Magnetic Resonance Imaging ◽  
Multiple Sclerosis ◽  
White Matter ◽  
Magnetic Resonance ◽  
Validation Cohort ◽  
Brain Mri ◽  
White Matter Lesions ◽  
Brain Lesions ◽  
Central Vein ◽  
Resonance Imaging

Background: White matter lesions are frequently detected using brain magnetic resonance imaging (MRI) performed for various indications. Most are microangiopathic, but demyelination, including multiple sclerosis (MS), is an important cause; conventional MRI cannot always distinguish between these pathologies. The proportion of lesions with a central vein on 7-T T2*-weighted MRI prospectively distinguishes demyelination from microangiopathic lesions. Objective: To test whether 3-T T2*-weighted MRI can differentiate MS from microangiopathic brain lesions. Methods: A total of 40 patients were studied. Initially, a test cohort of 10 patients with MS and 10 patients with microangiopathic white matter lesions underwent 3-T T2*-weighted brain MRI. Anonymised scans were analysed blind to clinical data, and simple diagnostic rules were devised. These rules were applied to a validation cohort of 20 patients (13 with MS and 7 with microangiopathic lesions) by a blinded observer. Results: Within the test cohort, all patients with MS had central veins visible in >45% of brain lesions, while the rest had central veins visible in <45% of lesions. By applying diagnostic rules to the validation cohort, all remaining patients were correctly categorised. Conclusion: 3-T T2*-weighted brain MRI distinguishes perivenous MS lesions from microangiopathic lesions. Clinical application of this technique could supplement existing diagnostic algorithms.

MANAGEMENT OF ADVERSE REACTIONS TO ALEMTUZUMAB INFUSION

2015 ◽  
Vol 86 (11) ◽  
pp. e4.23-e4 ◽  
Author(s):  
Basil Sharrack ◽  
Lori Mayer ◽  
Alasdair Coles ◽  
Hans-Peter Hartung ◽  
Eva Havrdova ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Adverse Reactions ◽  
Symptomatic Treatment ◽  
Phase 3 ◽  
Prior Therapy ◽  
Link Type ◽  
Relapsing Remitting ◽  
Treatment Naïve ◽  
Relapsing Remitting Multiple Sclerosis

In the 2-year, phase 3 CARE-MS studies of alemtuzumab in patients with relapsing-remitting multiple sclerosis, infusion-associated reactions (IARs) were the most common adverse events. Here we report on IARs during 4-year follow-up. Patients who were treatment-naive (CARE-MS I; NCT00530348) or with inadequate efficacy response to prior therapy (CARE-MS II; NCT00548405) received 2 annual courses of alemtuzumab 12 mg, and as-needed retreatment in an extension study (NCT00930553). Patients received methylprednisolone on the first 3 days of each course. IARs were any adverse event occurring between start of infusion and within 24 hours after end of infusion. 742/811 alemtuzumab-treated patients entered extension. Over 4 years, 70.4% received only 2 initial treatment courses; 22.6% and 6.1% received 3 and 4 courses, respectively. IARs were most frequent in Course 1 (84.7%) versus Courses 2 (68.5%), 3 (65.7%), and 4 (71.1%); frequency decreased on infusion Days 2 and 3 versus Day 1. IARs were predominantly mild to moderate; none led to study withdrawal or death. Serious IAR incidence was 3.1%. Most common IARs were skin disorders (predominantly rash), headache, pyrexia, and nausea. One confirmed anaphylaxis and one non-anaphylactoid hypotension event resolved with treatment. Effective IAR management included premedication, infusion monitoring, symptomatic treatment, and infusion interruption/adjustment.

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