T2 Lesions Research Articles

#2631 Efficacy and safety of Telitacicept combined with low-dose mycophenolate mofetil in IgA nephropathy

Abstract Background and Aims Currently, there is no specific agent blocking for IgA nephropathy. The KDIGO guideline recommends basic treatment with renin-angiotensin-aldosterone system (RAAS) antagonists. MMF can be used for Chinese patients. Telitacicept is a fusion protein composed of transmembrane activator and calcium modulating cyclophilin ligand interactor and fragment crystallizable portion of immunoglobulin G (IgG), which neutralizes the B lymphocyte stimulator and a proliferation-inducing ligand. Telitacicept (240 mg qw ih) treatment led to a clinically meaningful reduction in proteinuria in patients with IgAN in the present phase 2 clinical trial. This study intends to observe the efficacy of Telitacicept (160 mg qw ih) combined with low-dose MMF in the treatment of IgA nephropathy. Method Retrospective analysis involving all biopsy proven IgA nephropathy patients with complete clinical data in our department. After RAAS inhibitor treatment for 3 months, the patient's urinary protein more than 0.75 g/24 h, he or she was given Telitacicept (160 mg qw) combined with Mycophenolate mofetil (1 g, twice a day) was treated for 6 months, and follow-up for 6-12 months. The quantification of 24-hour urinary protein and immunity functional, renal function was observed. Results 25 patients with IgA nephropathy confirmed by renal biopsy were enrolled, 14 males and 11 females, aged 34.32 ± 9.68 years’ old, 3 patients with Lee's grade II, Grade III 17 patients, Grade IV 3 patients, and Grade V 2 patients. For Oxford classification, there were 3 cases with M0, 22 cases with M1 lesions, 20 cases with E0, 5 cases with E1 lesions, 1 case with S0, 24 cases with S1 lesions, 10 cases with T0, 15 cases with T1 lesions, and 17 cases with C0, 8 cases with C1 lesions. The patient's urine protein quantification was 2.52 ± 1.82 g before treatment, after Telitacicept and MMF treatment for 2 months, the proteinuria was 1.05 ± 0.55 g (compared with that before treatment, P = 0.0004), and at 4 months, it was 0.71 ± 0.39 g (compared with that before treatment, P < 0.0001), 0.53 ± 0.31 g at 6 months (compared with than before treatment, P < 0.0001). And the 24-hour urine protein quantification of 13 patients was all lower than 0.5 g/24 hours. The renal function of all patients was stable during the observation period. The serum creatinine before treatment was 83.16 ± 21.85 μmol/L and it was 81.88 ± 19.48 μmol/L (P = 0.83) after 6 months. There were no patients with worsening renal function after treatment. Among them, the renal function of 3 patients was better than that after treatment. During follow-up period for 6- to 12-month, the patient did not develop any pulmonary infection requiring for hospitalization or other infections. Some patients experienced adverse reactions such as pain at the site of injection, but no patient discontinued treatment due to adverse reactions. Conclusion Telitacicept combined with low-dose mycophenolate mofetil is a alternative method for the treatment of IgA nephropathy. It is more effective than mycophenolate mofetil or Telitacicept use alone, and with fewer adverse reactions, especially with S or C lesions of Oxford classification. This is an observational retrospective study with a few cases, it's worthy further randomized clinical study to prove.

Lower arterial cerebral blood flow is associated with worse neuroinflammation and immunomodulation composite proteomic scores

BackgroundBrain hypoperfusion is linked with worse physical, cognitive and MRI outcomes in multiple sclerosis (MS). Understanding the proteomic signatures related to hypoperfusion could provide insights into the pathophysiological mechanism. Methods140 people with MS (pwMS; 86 clinically isolated syndrome (CIS)/relapsing-remitting (RRMS) and 54 progressive (PMS)) were included. Cerebral arterial blood flow (CABF) was determined using ultrasound Doppler measurement as the sum of blood flow in the bilateral common carotid arteries and vertebral arteries. Proteomic analysis was performed using the Multiple Sclerosis Disease Activity (MSDA) test assay panel performed on the Olink™ platform. The MSDA test measures the concentrations of 18 proteins that are age and sex-adjusted. It utilizes a stacked classifier logistic regression model to determine 4 disease pathway scores (immunomodulation, neuroinflammation, myelin biology, and neuroaxonal integrity) as well as an overall disease activity score (1 to 10). MRI measures of T2 lesion volume (LV) and whole brain volume (WBV) were derived. ResultsThe pwMS were on average 54 years old and had an average CABF of 951 mL/min. There were no differences in CABF between CIS/RRMS vs. PMS groups. Lower CABF levels were correlated with the overall disease activity score (r = -0.26, p = 0.003) and with the neuroinflammation (r = -0.29, p = 0.001), immunomodulation (r = -0.26, p = 0.003) and neuroaxonal integrity (r = -0.23, p = 0.007) pathway scores. After age and body mass index (BMI)-adjustment, lower CABF remained associated with the neuroinflammatory (r = -0.23, p = 0.011) and immunomodulation (r = -0.20, p = 0.024) pathway scores. The relationship between CABF and the neuroinflammation pathway score remained significant after adjusting for T2-LV and WBV (p = 0.038). Individual analyses identified neurofilament light chain, CCL-20 and TNFSF13B as contributors. When compared to the highest quartile (>1133.5 mL/min), the pwMS in the lowest CABF quartile (<764 mL/min) had greater overall disease activity score (p = 0.003), neuroinflammation (p = 0.001), immunomodulation (p = 0.004) and neuroaxonal integrity pathway scores (p = 0.007). ConclusionLower cerebral arterial perfusion in MS is associated with changes in neuroinflammatory/immunomodulation pathways and their respective proteomic biomarkers. These findings may suggest a relationship between the hypoperfusion and pro-inflammatory MS changes rather than being merely an epiphenomenon subsequent to lower energy demands.

Factors Impacting Provider Treatment Decision-Making in Early Glottic Cancer.

Transoral laser microsurgery (TLMS) and radiotherapy (XRT) are mainstays of treatment for early glottic carcinoma (EGC). Here, we investigated case-dependent provider treatment preferences and identify factors which impact decision-making in EGC. This cross-sectional survey of laryngologists, head-and-neck surgeons, and radiation oncologists presented five diagrammatic cases of progressively advanced EGC (T1/2, N0). Respondents indicated preference for TLMS or XRT and ranked factors which influenced their recommendation for each case. Analysis utilized descriptive statistics, Fischer's exact tests, and Kruskal-Wallis tests for nonparametric data. A total of 141 complete responses (69.5% laryngologists) were received. Most respondents practiced in academic settings (93.5%) and within multidisciplinary teams (94.0%). Anterior commissure involvement was the most important a priori tumor factor for case-independent treatment recommendation (Likert Scale: 4.22/5), followed by Laterality (Likert Scale: 4.02/5). Across all specialties, TLMS was recommended for unilateral T1a lesions. Laryngologists continued recommending TLMS in T2 lesions (41.0%) more than head-and-neck surgeons (5.0%) and radiation oncologists (0.0%). Across all cases, survival and voice outcomes were the most important clinical factors impacting treatment decisions. Radiation oncologists weighed voice more heavily than laryngologists in more complex presentations of EGC (rank: 1.6 vs. 2.7, Kruskall-Wallis: p < 0.05). In more complex clinical presentations of EGC, preference for TLMS compared to XRT differed across specialists, despite similar rankings of factors driving these treatment recommendations. This may be driven by differing experiences and viewpoints on case-dependent voice outcomes following TLMS versus XRT, suggesting a need for increased understanding of how tumor location and depth impact voice outcomes. 5 Laryngoscope, 134:3686-3694, 2024.

Effect of Prior Treatment With Fingolimod on Early and Late Response to Rituximab/Ocrelizumab in Patients With Multiple Sclerosis.

Real-life studies noted that the risk of disease activity in multiple sclerosis (MS) after switching to rituximab (RTX) or ocrelizumab (OCR) may be unequal depending on prior disease-modifying therapy (DMT), with a higher risk associated with fingolimod (FING). We performed a retrospective analysis of a structured prospective data collection including all consecutive patients with relapsing MS who were prescribed RTX/OCR in the MS center of Marseille. Cox proportional hazards models were applied to clinical and MRI outcomes. We included 321 patients with a median (interquartile range [IQR]) follow-up of 3.5 years (1.5-5) after RTX/OCR initiation. At the first RTX/OCR infusion, the mean (SD) age of patients was 37 (10) years, and the median (IQR) disease duration was 8 years (3-15): 68 patients did not receive treatment before RTX/OCR and 108 switched from FING, 47 from low efficacy therapy, and 98 from natalizumab. For statistical analysis, the group "FING" was divided into "short-FING" and "long-FING" groups according to the median value of the group's washout period (27 days). On Cox proportional hazards analysis, for only the "long-FING" group, the risk of relapse within the first 6 months of RTX/OCR was increased as compared with patients without previous DMT (hazard ratio [HR]: 8.78; 95% CI 1.72-44.86; p < 0.01). Previous DMT and washout period duration of FING had no effect on B-cell levels at 6 months. Beyond the first 6 months of RTX/OCR, age <40 years was associated with increased risk of relapse (HR: 3.93; 95% CI 1.30-11.89; p = 0.01), male sex with increased risk of new T2 lesions (HR: 2.26; 95% CI 1.08-4.74; p = 0.03), and EDSS ≥2 with increased risk of disability accumulation (HR: 3.01; 95% CI 1.34-6.74; p < 0.01). Previous DMT had no effect on the effectiveness of RTX/OCR beyond 6 months after initiation. For patients switching from FING to RTX/OCR, the risk of disease reactivation within the first 6 months of treatment was increased as compared with patients with other DMT or no previous DMT only when the washout period exceeded 26 days. Neither FING nor other previous DMT reduced the effectiveness of RTX/OCR beyond the first 6 months of treatment.

Robotic thoracic surgery for neurogenic tumors.

Thoracic neurogenic tumors usually present as benign nerve sheath tumors that can be resected via transthoracic or posterior approaches, depending on the anatomical location. Robot-assisted thoracic surgery (RATS) is increasingly being used for the transthoracic approach, but evidence is very limited. The authors initiated the current study to evaluate the efficacy and safety of RATS for thoracic neurogenic tumors. This retrospective study is based on a prospectively created database that includes all RATS surgeries between 2018 and 2023. All patients with histologically confirmed neurogenic tumors were included in the study. The patients' medical and surgical records as well as radiological and pathological findings were analyzed. During a 5-year period, 27 patients underwent robotic resection of neurogenic tumors at a high-volume thoracic surgery center. Two patients had previously undergone posterior laminectomy for resection of the intraspinal components. The pathologies included schwannomas (18, 64%), ganglioneuromas (8, 29%), 1 paraganglioma, and 1 neurofibroma occurring close to a schwannoma unilaterally in the same patient. The median tumor size was 4.7 cm (range 0.9-11.4 cm). The median operating time was 69 minutes (range 27-169 minutes), and the median postoperative stay was 3 days (range 1-19 days). There was one conversion due to adhesions after a previous surgery. No major bleeding occurred. There was no perioperative mortality. Morbidity included a lymphatic fistula (n = 1), pneumonia (n = 1), prolonged air leak (n = 1), and 4 cases of postoperative pain persisting for more than 4 weeks. Neurological complications were mostly observed in patients with tumors located at the thoracic apex: 2 cases of Horner's syndrome, 2 cases with compensatory hyperhidrosis, 1 patient with paresis of the recurrent laryngeal nerve, and a T1 lesion resulting in a minor motor deficit of the small hand muscles (Medical Research Council grade 4) and hypoesthesia of the respective dermatome. RATS for thoracic neurogenic tumors is feasible and safe. Tumors at the thoracic apex are at high risk of neurological deficit and should be approached with care. Close interdisciplinary collaboration between neurosurgeons and thoracic surgeons is necessary for optimal patient selection and a good postoperative outcome.

Clinical and magnetic resonance imaging outcomes in pediatric-onset MS patients on fingolimod and ocrelizumab

BackgroundObservational studies looking at clinical a++nd MRI outcomes of treatments in pediatric MS, could assess current treatment algorithms, and provide insights for designing future clinical trials. ObjectiveTo describe baseline characteristics and clinical and MRI outcomes in MS patients initiating ocrelizumab and fingolimod under 18 years of age. MethodsMS patients seen at 12 centers of US Network of Pediatric MS were included in this study if they had clinical and MRI follow-up and started treatment with either ocrelizumab or fingolimod prior to the age of 18. ResultsEighty-seven patients initiating fingolimod and 52 initiating ocrelizumab met the inclusion criteria. Before starting fingolimod, mean annualized relapse rate was 0.43 (95 % CI: 0.29 – 0.65) and 78 % developed new T2 lesions while during treatment it was 0.12 (95 % CI: 0.08 – 1.9) and 47 % developed new T2 lesions. In the ocrelizumab group, the mean annualized relapse rate prior to initiation of treatment was 0.64 (95 % CI: 0.38–1.09) and a total of 83 % of patients developed new T2 lesions while during treatment it was 0.09 (95 % CI: 0.04–0.21) and none developed new T2 lesions. ConclusionThis study highlights the importance of evaluating current treatment methods and provides insights about the agents in the ongoing phase III trial comparing fingolimod and ocrelizumab.

Teriflunomide in pediatric patients with relapsing multiple sclerosis: Open-label extension of TERIKIDS

Background: The double-blind TERIKIDS study demonstrated the efficacy and safety of teriflunomide. Objective: To evaluate the efficacy, safety, and tolerability of continuous teriflunomide treatment in the TERIKIDS open-label extension. Methods: In the double-blind period, children with relapsing MS were randomized to placebo or teriflunomide (14 mg adult-equivalent dose) for ⩽ 96 weeks. Participants received teriflunomide for ⩽ 192 weeks post-randomization in the open-label extension. Results: The mean age at screening was 14.6 years. For teriflunomide/teriflunomide versus placebo/teriflunomide, estimated clinical relapse risk was reduced by 38% (hazard ratio (HR) 0.62; 95% confidence interval (CI) 0.39–0.98; p = 0.11) and numbers of gadolinium-enhancing T1 and new/enlarging T2 lesions were reduced by 43% (relative risk (RR) 0.570; 95% CI 0.33–0.98; p = 0.043) and 49% (RR 0.511; 95% CI 0.34–0.76; p = 0.001), respectively, in the combined double-blind and open-label periods. There was a trend toward reduced risk of 24-week sustained disability progression for teriflunomide/teriflunomide versus placebo/teriflunomide (HR 0.47; 95% CI 0.23–0.96). During the open-label extension, incidences of safety-related discontinuations were 4.0% (teriflunomide/teriflunomide) and 13.5% (placebo/teriflunomide), including two children who developed pancreatitis in the teriflunomide/teriflunomide group. Conclusion: Teriflunomide reduced the long-term risk of focal inflammatory activity, with generally manageable tolerability and no new safety signals. Further evidence would strengthen clinical efficacy findings. ClinicalTrials.gov: NCT02201108.

Vaccine Safety and Immunogenicity in Patients With Multiple Sclerosis Treated With Natalizumab

Vaccination in patients with highly active multiple sclerosis (MS) requiring prompt treatment initiation may result in impaired vaccine responses and/or treatment delay. To assess the immunogenicity and safety of inactivated vaccines administered during natalizumab treatment. This self-controlled, prospective cohort study followed adult patients with MS from 1 study center in Spain from September 2016 to February 2022. Eligible participants included adults with MS who completed immunization for hepatitis B virus (HBV), hepatitis A virus (HAV), and COVID-19 during natalizumab therapy. Data analysis was conducted from November 2022 to February 2023. Patients were categorized according to their time receiving natalizumab treatment at the time of vaccine administration as short-term (≤1 year) or long-term (>1 year). Demographic, clinical, and radiological characteristics were collected during the year before vaccination (prevaccination period) and the year after vaccination (postvaccination period). Seroprotection rates and postvaccination immunoglobulin G titers were determined for each vaccine within both periods. Additionally, differences in annualized relapse rate (ARR), new T2 lesions (NT2L), Expanded Disability Status Scale (EDSS) scores, and John Cunningham virus (JCV) serostatus between the 2 periods were assessed. Sixty patients with MS (mean [SD] age, 43.2 [9.4] years; 44 female [73.3%]; 16 male [26.7%]; mean [SD] disease duration, 17.0 [8.7] years) completed HBV, HAV, and mRNA COVID-19 immunization during natalizumab treatment, with 12 patients in the short-term group and 48 patients in the long-term group. The global seroprotection rate was 93% (95% CI, 86%-98%), with individual vaccine rates of 92% for HAV (95% CI, 73%-99%), 93% for HBV (95% CI, 76%-99%), and 100% for the COVID-19 messenger RNA vaccine (95% CI, 84%-100%). Between the prevaccination and postvaccination periods there was a significant reduction in the mean (SD) ARR (0.28 [0.66] vs 0.01 [0.12]; P = .004) and median (IQR) NT2L (5.00 [2.00-10.00] vs 0.81 [0.00-0.50]; P = .01). No changes in disability accumulation were detected (median [IQR] EDSS score 3.5 [2.0-6.0] vs 3.5 [2.0-6.0]; P = .62). No differences in safety and immunogenicity were observed for all vaccines concerning the duration of natalizumab treatment. The findings of this cohort study suggest that immunization with inactivated vaccines during natalizumab therapy was both safe and immunogenic, regardless of the treatment duration. Natalizumab may be a valuable option for proper immunization, averting treatment delays in patients with highly active MS; however, this strategy needs to be formally evaluated.

Prognostic Value of On-treatment Serum Neurofilament Light Chain for New or Enlarging T2 Lesions in People with Relapsing Multiple Sclerosis: Pooled Analysis of the ASCLEPIOS I/II Trials (S42.003)

Prognostic Value of On-treatment Serum Neurofilament Light Chain for New or Enlarging T2 Lesions in People with Relapsing Multiple Sclerosis: Pooled Analysis of the ASCLEPIOS I/II Trials (S42.003)

Time course of tumorigenesis of a newly developed sporadic hemangioblastoma in an elderly patient: illustrative case.

von Hippel-Lindau disease-associated hemangioblastomas (HBs) account for 20%-30% of all HB cases, with the appearance of new lesions often observed in the natural course of the disease. By comparison, the development of new lesions is rare in patients with sporadic HB. A 65-year-old man underwent clipping for an unruptured aneurysm of the anterior communicating artery. Fourteen years later, follow-up magnetic resonance imaging (MRI) revealed a strongly enhanced mass in the right cerebellar hemisphere, diagnosed as a sporadic HB. A retrospective review of MRI studies obtained over the follow-up period revealed the gradual development of peritumoral edema and vascularization before mass formation. Newly appearing high-intensity T2 lesions in the cerebellum may represent a preliminary stage of tumorigenesis. Careful monitoring of these patients would be indicated, which could provide options for early treatment to improve patient outcomes.

Perioperative and oncological outcomes following robotic en bloc multivisceral resection for colorectal cancer.

As multidisciplinary treatment strategies for colorectal cancer have improved, aggressive surgical resection has become commonplace. Multivisceral and extended resections offer curative-intent resection with significant survival benefit. However, limited data exist regarding the feasibility and oncological efficacy of performing extended resection via a minimally invasive approach. The aim of this study was to determine the perioperative and long-term outcomes following robotic extended resection for colorectal cancer. We describe the population of patients undergoing robotic multivisceral resection for colorectal cancer at our single institution. We evaluated perioperative details and investigated short- and long-term outcomes, using the Kaplan-Meier method to analyse overall and recurrence-free survival. Among the 86 patients most tumours were T3 (47%) or T4 (47%) lesions in the rectum (78%). Most resections involved the anterior compartment (72%): bladder (n = 13), seminal vesicle/vas deferens (n = 27), ureter (n = 6), prostate (n = 15) and uterus/vagina/adnexa (n = 27). Three cases required conversion to open surgery; 10 patients had grade 3 complications. The median hospital stay was 4 days. Resections were R0 (>1 mm) in 78 and R1 (0 to ≤1 mm) in 8, with none being R2. The average nodal yield was 26 and 48 (55.8%) were pN0. Three-year overall survival was 88% and median progression-free survival was 19.4 months. Local recurrence was 6.1% and distant recurrence was 26.1% at 3 years. Performance of multivisceral and extended resection on the robotic platform allows patients the benefit of minimally invasive surgery while achieving oncologically sound resection of colorectal cancer.

Retrospective Evaluation of Attacks, EDSS Scores, and MRI Changes Before the Start of Treatment and One Year After the Start of Treatment in Patients Followed by a Diagnosis of Multiple Sclerosis and Using Ocrelizumab in Our Clinic

Objective: Depletion of B cells by anti-CD20 monoclonal antibodies has been proven to reduce relapsing remitting multiple sclerosis (RRMS) activity and progression of primary progressive MS (PPMS). In our study, we aimed to retrospectively present our clinical experience and contribute to real-life data after the use of Ocrelizumab. Material and Methods: Patients aged 18-55 years using Ocrelizumab and diagnosed with MS by McDonald's 2017 criteria were included. Neurological examination findings and EDSS findings available in our file records were used to evaluate the level of disability. Patients with MRI lesions consistent with their clinical complaint lasting more than 24 hours were evaluated as an attack. Patients' ages, MS diagnosis times, and previous immune modulatory treatments were recorded. The number of T2, FLAIR sequence MRI lesions, EDSS before ocrelizumab, and the number of T2, FLAIR sequence MRI lesions 1 year after receiving ocrelizumab were recorded. After 1 year of follow-up, the absence of attacks, no increase in the number of lesions in MRI, and no progress in EDSS were accepted as NEDA 3. Results: Our cases in this study include 30 MS patients. Patients were 26.7% relapsing remitting MS (RRMS), 26.7% primary progressive MS (PPMS), and 46.7% secondary progressive MS (SPMS). There was no attack in 87.5% of the RRMS patient group. In the SPMS patient group, no attacks were observed after ocrelizumab in the cases with attacks. In our study, the rate of patients who did not develop new T2 lesions and whose lesions disappeared was 62.5% in the RRMS patient group, 78.5% in the SPMS patient group, and 75% in the PPMS patient group. In the total patient group, the rate of patients without EDSS increase was 93% (28 patients). Conclusion: In our study, it was determined that ocrelizumab was effective by reducing the attack rates, preserving the EDSS scores and preventing the increase in the lesion burden. Our findings are consistent with real-life data.

Structural MRI measures are associated with fatigue severity and persistence in a large, real-world cohort of people with multiple sclerosis

Background: Results of research on radiological hallmarks of multiple sclerosis (MS) fatigue have been conflicting. Objective: To investigate the associations of lesion and brain compartment volumes with fatigue severity and persistence in people with multiple sclerosis (PwMS). Methods: The Multiple Sclerosis Partners Advancing Technology and Health Solutions (MS PATHS) network collects standardized data during routine care of PwMS from 10 healthcare institutions. Magnetic resonance imaging (MRI) predictors included baseline brain parenchymal (BPF) and gray matter fractions (GMF) and T2 lesion volume (T2LV). The Quality of Life in Neurological Disorders (Neuro-QOL) fatigue subscore was analyzed linearly and categorically using T-score cutpoints, with a period of elevated symptoms defined as T-score ⩾ mean + 0.5 SD over follow-up. Results: At baseline, of 4012 participants (average age: 45.6 ± 11.8 years; 73% female; 31% progressive MS), 2058 (51%) had no fatigue, 629 (16%) had mild fatigue, and 1325 (33%) had moderate-to-severe fatigue. One SD greater baseline BPF and GMF were associated with 0.83 (p < 0.001) and 0.38 (p = 0.02) lower values in the baseline Neuro-QOL fatigue T-score. A 1 SD lower log of total T2LV was associated with a 0.49 (p < 0.001) lower baseline fatigue T-score. Higher BPF and lower T2LV at baseline were associated with lower odds of subsequent periods of elevated fatigue. Conclusion: Baseline lesion burden and lower generalized whole-brain volumes were associated with MS fatigue in cross-sectional and longitudinal analyses in a large, real-world cohort of PwMS.

Evaluating persistent T1-weighted lesions without concurrent abnormal enhancement on breast MRI in neoadjuvant chemotherapy patients: implications for complete pathological response.

This study aims to determine whether persistent T1-weighted lesions signify a complete pathological response (pCR) in breast cancer patients treated with neoadjuvant chemotherapy and surgery, and to evaluate their correlation with imaging responses on MRI. A retrospective review was conducted on data from breast cancer patients treated between January 2011 and December 2018. Patients who underwent breast MRI and pre- and post-neoadjuvant chemotherapy followed by surgery were included. Those with distant metastasis, no planned surgery, pre-surgery radiation, ineligibility for neoadjuvant chemotherapy, or unavailable surgical pathology were excluded. Groups with and without persistent T1-weighted lesions were compared using the chi-square test for categorical variables and the Student t test or Wilcox rank sum test for continuous variables. Univariate logistic regression was used to evaluate the association of the final pathological response with the presence of T1-persistent lesion and other characteristics. Out of 319 patients, 294 met the inclusion criteria (breast cancer patients treated with neoadjuvant chemotherapy and subsequent surgery); 157 had persistent T1 lesions on post-chemotherapy MRI and 137 did not. A persistent T1 lesion indicated reduced likelihood of complete pathological response (14% vs. 39%, p < 0.001) and imaging response (69% vs. 93%, p < 0.001). Multivariable analysis confirmed these findings: OR 0.37 (95% CI 0.18-0.76), p = 0.007. No other characteristics correlated with T1 residual lesions. Persistent T1-weighted lesions without associated abnormal enhancement on post-treatment breast MRI correlate with lower complete pathological and imaging response rates. The study underscores the importance of persistent T1-weighted lesions on breast MRI as vital clinical markers, being inversely related to a complete pathological response following neoadjuvant chemotherapy; they should be a key factor in guiding post-neoadjuvant chemotherapy treatment decisions. • Persistent T1 lesions on post-chemotherapy breast MRI indicate a reduced likelihood of achieving a complete pathological response (14% vs. 39%, p < 0.001) and imaging response (69% vs. 93%, p < 0.001). • Through multivariable analysis, it was confirmed that the presence of a persistent T1 lesion on breast MRI post-chemotherapy is linked to a decreased likelihood of complete pathological response, with an odds ratio (OR) of 0.37 (95% CI 0.18-0.76; p = 0.007). • In addition to the convention of equating the absence of residual enhancement to complete imaging response, our results suggest that the presence or absence of residual T1 lesions should also be considered.

Emerging Cerebrospinal Fluid Biomarkers of Disease Activity and Progression in Multiple Sclerosis

Biomarkers distinguishing nonrelapsing progressive disease biology from relapsing biology in multiple sclerosis (MS) are lacking. Cerebrospinal fluid (CSF) is an accessible fluid that most closely reflects central nervous system biology. To identify CSF biological measures associated with progressive MS pathobiology. This cohort study assessed data from 2 prospective MS cohorts: a test cohort provided serial CSF, clinical, and imaging assessments in a multicenter study of patients with relapsing MS (RMS) or primary progressive MS (PPMS) who were initiating anti-CD20 treatment (recruitment: 2016-2018; analysis: 2020-2023). A single-site confirmation cohort was used to assess CSF at baseline and long-term (>10 year) clinical follow-up (analysis: 2022-2023). Test-cohort participants initiated standard-of-care ocrelizumab treatment. Confirmation-cohort participants were untreated or received standard-of-care disease-modifying MS therapies. Twenty-five CSF markers, including neurofilament light chain, neurofilament heavy chain, and glial fibrillary acid protein (GFAP); 24-week confirmed disability progression (CDP24); and brain magnetic resonance imaging measures reflecting focal injury, tissue loss, and progressive biology (slowly expanding lesions [SELs]). The test cohort (n = 131) included 100 patients with RMS (mean [SD] age, 36.6 [10.4] years; 68 [68%] female and 32 [32%] male; Expanded Disability Status Scale [EDSS] score, 0-5.5), and 31 patients with PPMS (mean [SD] age, 44.9 [7.4] years; 15 [48%] female and 16 [52%] male; EDSS score, 3.0-6.5). The confirmation cohort (n = 68) included 41 patients with RMS and 27 with PPMS enrolled at diagnosis (age, 40 years [range, 20-61 years]; 47 [69%] female and 21 [31%] male). In the test cohort, GFAP was correlated with SEL count (r = 0.33), greater proportion of T2 lesion volume from SELs (r = 0.24), and lower T1-weighted intensity within SELs (r = -0.33) but not with acute inflammatory measures. Neurofilament heavy chain was correlated with SEL count (r = 0.25) and lower T1-weighted intensity within SELs (r = -0.28). Immune markers correlated with measures of acute inflammation and, unlike GFAP, were impacted by anti-CD20. In the confirmation cohort, higher baseline CSF GFAP levels were associated with long-term CDP24 (hazard ratio, 2.1; 95% CI, 1.3-3.4; P = .002). In this study, activated glial markers (in particular GFAP) and neurofilament heavy chain were associated specifically with nonrelapsing progressive disease outcomes (independent of acute inflammatory activity). Elevated CSF GFAP was associated with long-term MS disease progression.

Intrathecal B cell activation and memory impairment in multiple sclerosis

BackgroundCognitive impairment (CI) is a common and disabling feature of people with multiple sclerosis (pwMS), but its underlying mechanisms are heterogenous and not fully understood. A role of infiltrating immune cells in the meninges and brain parenchyma has been hypothesized. This study aimed to explore the hypothesis that intrathecal B cells might influence cognitive performance in pwMS. MethodsA retrospective study was performed on 39 newly diagnosed pwMS who underwent cerebrospinal fluid (CSF) analysis. Kappa (κ)-index was measured as a biomarker of intrathecal B cell activation. Cognitive performance was assessed using the Brief Repeatable Battery of Neuropsychological Tests (BRBN). Brain T2 lesions number (T2LN) and volume (T2LV) together with brain, cortical grey matter, thalamic and hippocampal volumes were calculated to account for MRI-visible damage. Resultsκ-index was higher in pwMS with verbal memory impairment (median 99.6, range 58.5–195.2 vs. median 37.2, range 2.3–396.9, p < 0.001), and it was negatively associated with BRBN tests exploring verbal memory and information processing speed. In multivariate models, higher κ-index was confirmed to be independently associated with worse scores of BRBN tests exploring verbal memory and with a higher probability of verbal memory impairment. ConclusionIntrathecal B cells might drive memory impairment in pwMS independently of brain damage visible on MRI scans.

Magnetic resonance imaging prognostic factors for survival and relapse in dogs with meningoencephalitis of unknown origin.

Canine meningoencephalitis of unknown origin (MUO) is a debilitating disease associated with high mortality. The prognostic value of magnetic resonance imaging (MRI) findings for predicting survival at 12 months and long-term relapse remains uncertain. This was a retrospective cohort study evaluating the prognostic value of different MRI variables using multivariable logistic regression and Cox proportional hazards analysis. In total, 138 dogs were presumptively diagnosed with MUO. The most common location for lesions identified on MRI were the white matter tracts of the corona radiata and corpus callosum, followed by the frontal, sensorimotor and temporal cortices. Lower T2 lesion load (p = 0.006, OR = 0.942, CI = 0.902-0.983) was associated with longer survival and higher T1 post-contrast lesion load (p = 0.023, OR = 1.162, CI = 1.021-1.322) was associated with relapse. This study has identified prognostic factors that may help identify dogs at higher risk of death and relapse and therefore guide treatment recommendations.

Disparities in DMT treatment: Demographic and neurocognitive differences between MS patients currently treated versus not treated with disease-modifying therapies

BackgroundCurrent treatment guidelines recommend consideration of disease-modifying therapy (DMT) for all multiple sclerosis (MS) patients, but barriers to access have begun to be identified. In particular, prior studies have found that people with higher education have better access to DMTs, perhaps explained by the association of higher education with higher income. And while the majority of people with MS are women, being male is also associated with higher income. These factors argue for the need to better understand whether there are differences in DMT uptake based on sex and education. Finally, in addition to well-documented benefits of DMTs for slowing disease progression, there is growing evidence to suggest benefits of DMTs for cognitive functioning. ObjectiveDetermine whether rates of DMT treatment differ based on education and sex. Secondarily, we investigate whether neurocognitive test performance differs in treated versus not treated groups. MethodsIn cross-sectional data, mixed effects linear regression evaluated differences in education and sex of those treated versus not treated with DMTs. Models included the following predictors: age, disease duration, MS subtype, sex/education, disability, atrophy, and T2 lesion volume. Propensity score weights were extracted to obtain unbiased estimates of the relationship between DMT status and each outcome of interest. The same models evaluated performance differences between groups on an iPad-based processing speed test (PST) and manual dexterity test (MDT). ResultsControlling for covariates, individuals with less education (OR=1.09, 95 % CI=[1.03, 1.14], p = 0.003) and women (OR=0.80, 95 % CI=[0.72, 0.90], p < 0.001) were less likely to be currently treated with DMTs. Small effect size association was shown for DMT treatment with better performance on PST (beta=0.09, CI=[0.06, 0.13], p < 0.001) and MDT (beta=0.05, CI=[0.01,0.08], p = 0.011). ConclusionsWomen and people with lower education had a lower likelihood of being currently treated with DMTs. After controlling for all relevant variables, an independent (small) association of DMT treatment to better performance on tests of processing speed and fine motor dexterity was found. Reasons for disparities remain to be investigated in future work, and may include employment status, health insurance coverage, or sex differences in risk tolerance.

Prognostic value of preoperative diffusion restriction in glioblastoma.

Although glioblastoma (GBM) has a very poor prognosis, overall survival (OS) in treated patients shows great difference varying from few days to several months. Identifying factors explaining this difference would improve management of patient treatment. To determine the relevance of diffusion restriction in newly diagnosed treatment-naïve GBM patients. Preoperative magnetic resonance scans of 33 patients with GBM were reviewed. Regions of interest including all the T2 hyperintense lesion were drawn on diffusion weighted B0 images and transferred to the apparent diffusion coefficient (ADC) map. For each patient, a histogram displaying the ADC values within in the regions of interest was generated. Volumetric parameters including tumor regions with restricted diffusion, parameters derived from histogram and mean ADC value of the tumor were calculated. Their relationship with OS was analyzed. Patients with mean ADC value < 1415x10-6 mm2/s had a significantly shorter OS (p=0.021). Among volumetric parameters, the percentage of volume within T2 lesion with a normalized ADC value <1.5 times that in white matter was significantly associated with OS (p=0.0045). Patients with a percentage>23.92% had a shorter OS. Among parameters derived from histogram, the 50th percentile showed a trend towards significance for OS (p=0.055) with patients living longer when having higher values of 50th percentile. A difference in OS was observed between patients according to ADC peak of histogram but this difference did not reach statistical significance (p=0.0959). Diffusion magnetic resonance imaging may provide useful information for predicting GBM prognosis.

Needle electromyography does not meaningfully impact findings in MR-neurography/-myography.

Magnetic resonance neurography (MRN) and myography (MRM) are emerging imaging methods for detecting diseases of the peripheral nerve system (PNS). Most patients with PNS diseases also undergo needle electromyography (EMG). This study examined whether EMG led to lesions that were detectable using MRN/MRM and whether these lesions could impair image interpretation. Ten patients who underwent clinically indicated EMG were recruited. MRN/MRM was performed before and 2-6 h after EMG, and if achievable, 2-3 days later. T2 signal intensity (SI) of the tibialis anterior muscle (TA) was quantified, and sizes and SI of the new lesions were measured. Visual rating was performed independently by three neuroradiologists. T2 lesions at the site of needle insertion, defined as focal edema, were detectable in 9/10 patients. The mean edema size was 31.72 mm2 (SD = 14.42 mm2 ) at the first follow-up. Susceptibility-weighted imaging lesions, defined as (micro) hematomas were detected in 5/10 patients (mean size, 23.85 mm2 [SD = 12.59 mm2 ]). General muscle SI of the TA did not differ between pre- and post-EMG examinations. Lesions size was relatively small, and the readers described image interpretation as not impaired by these lesions. This study showed that focal edema and hematomas frequently occurred after needle EMG and could be observed using MRN/MRM. As general muscle SI was not affected and image interpretation was not impaired, we concluded that needle EMG did not interfere with MRN/MRM.