Discontinuation of First-Line Disease-Modifying Therapy in Patients With Stable Multiple Sclerosis: The DOT-MS Randomized Clinical Trial.

Importance: Increasing numbers of people with multiple sclerosis (MS) use disease-modifying therapy (DMT). Long-term stable disease while taking such medications provides a rationale for considering DMT discontinuation given patient burden, costs, and potential adverse effects of immunomodulating therapy.

Objective: To investigate whether first-line DMT can be safely discontinued in patients with long-term stable MS.

Serum neurofilament light and glial fibrillary acidic protein levels are not associated with wearing-off symptoms in natalizumab-treated multiple sclerosis patients.

Background: Biomarkers of neuronal and axonal damage (serum neurofilament light (sNfL) and serum glial fibrillary acidic protein (sGFAP)) may provide insight into the aetiology of natalizumab wearing-off symptoms (WoSs).

Objectives: We investigated the longitudinal association between and predictive value of sNfL and sGFAP and the occurrence of WoS in MS patients treated with natalizumab.

Methods: We performed longitudinal measurements of sNfL and sGFAP in NEXT-MS trial participants who completed a questionnaire about WoS.

Influence of personalized extended interval dosing on the natalizumab wearing-off effect - a sub-study of the NEXT-MS trial.

Background And Objectives: Wearing-off symptoms during natalizumab treatment in multiple sclerosis are characterized by an increase of MS-related symptoms prior to natalizumab administration. The influence of extended interval dosing (EID) on wearing-off symptoms are important to consider, as this might cause hesitancy in initiating or continuing EID.

Methods: Participants of the NEXT-MS trial, in which treatment intervals are adjusted based on drug concentrations, were divided into two groups: an extended group containing participants with at least one week of additional interval extension, and a group with a fixed interval during the trial (range 4-7 weeks).

Prospective trial of natalizumab personalised extended interval dosing by therapeutic drug monitoring in relapsing-remitting multiple sclerosis (NEXT-MS).

Background: Extended interval dosing (EID) of natalizumab is a promising strategy to optimise treatment in multiple sclerosis (MS). Personalised EID by therapeutic drug monitoring can enable further extension of treatment intervals.

Methods: The NEXT-MS trial is an investigator-initiated prospective phase IV non-randomised study.

Assessment of Multiple Aspects of Upper Extremity Function Independent From Ambulation in Patients With Multiple Sclerosis.

Background: Upper extremity function (UEF) is often compromised in multiple sclerosis (MS), although its importance is regularly underrecognized relative to ambulation. We explored the concurrent presence of impairment in UEF and ambulation by examining various aspects of UEF across different levels of ambulation.

Methods: The cohort consisted of 247 patients with clinically definite MS or clinically isolated syndrome according to the revised 2010 McDonald criteria.

Amplitude-Integrated Electroencephalography Evolution and Magnetic Resonance Imaging Injury in Mild and Moderate to Severe Neonatal Encephalopathy.

Objective: This study aimed to describe the evolution of amplitude-integrated electroencephalography (aEEG) in neonatal encephalopathy (NE) during therapeutic hypothermia (TH) and evaluate the association between aEEG parameters and magnetic resonance imaging (MRI) injury.

Study Design: aEEG data of infants who underwent TH were reviewed for background, sleep wake cycling (SWC), and seizures. Conventional electroencephalography (cEEG) background was assessed from the reports.

Clinical findings in 39 individuals with Bohring-Opitz syndrome from a global patient-driven registry with implications for tumor surveillance and recurrence risk.

Bohring-Opitz syndrome (BOS) is a rare genetic condition caused by pathogenic variants in ASXL1, which is a gene involved in chromatin regulation. BOS is characterized by severe intellectual disabilities, distinctive facial features, hypertrichosis, facial nevus simplex, severe myopia, a typical posture in infancy, variable anomalies, and feeding issues. Wilms tumor has also been reported in two individuals.

Improving Detection of Change in Motor Functioning in Multiple Sclerosis Using Video-Assisted Composite Measures.

Background: Assessing motor functioning is important to monitor the disease course of multiple sclerosis (MS). Video-assisted rating of classic neurologic tests and activities of daily living may improve the detection of changes in motor functioning. We investigated the value of using video-assisted composite measures for the detection of changes in mobility and upper extremity function (UEF).

Magnetic resonance venography to evaluate cerebral sinovenous thrombosis in infants receiving therapeutic hypothermia.

Background: The incidence of cerebral sinovenous thrombosis (CSVT) in infants receiving therapeutic hypothermia for neonatal encephalopathy remains controversial. The aim of this study was to identify if the routine use of magnetic resonance venography (MRV) in term-born infants receiving hypothermia is associated with diagnostic identification of CSVT.

Methods: We performed a retrospective review of 291 infants who received therapeutic hypothermia from January 2014 to March 2020.

Association of early cerebral oxygen saturation and brain injury in extremely preterm infants.

Objective: To assess the association between cerebral saturation (crSO) using Near-Infrared Spectroscopy (NIRS) and brain injury in extremely preterm infants.

Study Design: This retrospective study includes 62 infants (<28 weeks gestation) who underwent continuous NIRS monitoring in the first 5 days after birth. Median crSO were compared in 12 h increments between infants with and without germinal matrix/intraventricular hemorrhage (GM/IVH).

Hypocapnia in early hours of life is associated with brain injury in moderate to severe neonatal encephalopathy.

Objective: To evaluate the association between hypocapnia within the first 24 h of life and brain injury assessed by a detailed MRI scoring system in infants receiving therapeutic hypothermia (TH) for neonatal encephalopathy (NE) stratified by the stage of NE.

Study Design: This retrospective cohort study included infants who received TH for mild to severe NE.

Results: 188 infants were included in the study with 48% having mild and 52% moderate-severe NE.

Cross-sectional and longitudinal correlations between the Arm Function in Multiple Sclerosis Questionnaire (AMSQ) and other outcome measures in multiple sclerosis.

Background: The Arm Function in Multiple Sclerosis Questionnaire (AMSQ) is the first validated disease specific patient-reported outcome measure (PROM) designed to assess upper extremity function in patients with multiple sclerosis (MS).

Objective: To determine correlations between the AMSQ and established physician- and performance based outcome measures.

Methods: In a cross-sectional cohort of 533 patients correlations between the AMSQ and the Expanded Disability Status Scale (EDSS), its functional systems, the 9-Hole Peg Test (9-HPT) and the Timed-25 Foot Walk (T25FW) were determined.

Differences in standardized neonatal encephalopathy exam criteria may impact therapeutic hypothermia eligibility.

Background: Therapeutic hypothermia (TH) is routinely provided to those with moderate or severe neonatal encephalopathy (NE). Subtle differences exist in the standardized exams used to define NE severity. We aimed to assess if an infant's TH eligibility status differed if they were evaluated using either the NICHD/Neonatal Research Network's (NICHD-NRN) or TOBY/British Association of Perinatal Medicine's (TOBY-BAPM) neurological exam.

The U.S. National Trend for Retinopathy of Prematurity.

Objective: The use of supplemental oxygen in premature infants is essential for survival. However, its use has been associated with unintended complications. The restricted use of oxygen is associated with increased mortality and necrotizing enterocolitis (NEC), whereas its liberal use is associated with increased risk for retinopathy of prematurity (ROP).

3D FIB-SEM reconstruction of microtubule-organelle interaction in whole primary mouse β cells.

Microtubules play a major role in intracellular trafficking of vesicles in endocrine cells. Detailed knowledge of microtubule organization and their relation to other cell constituents is crucial for understanding cell function. However, their role in insulin transport and secretion is under debate.

A Delphi panel on treatment of high disease activity relapsing remitting multiple sclerosis in the Netherlands.

To gain insight into current treatment and barriers to optimal treatment for high disease activity relapsing remitting multiple sclerosis (MS) in the Netherlands. A two-round Delphi panel using an online questionnaire was conducted. Seven MS neurologists from diverse locations in the Netherlands were invited to participate.

Autoencoder as a New Method for Maintaining Data Privacy While Analyzing Videos of Patients With Motor Dysfunction: Proof-of-Concept Study.

Background: In chronic neurological diseases, especially in multiple sclerosis (MS), clinical assessment of motor dysfunction is crucial to monitor the disease in patients. Traditional scales are not sensitive enough to detect slight changes. Video recordings of patient performance are more accurate and increase the reliability of severity ratings.