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.

[Treatment of multiple sclerosis].

Multiple sclerosis is a chronic inflammatory disease of the central nervous system, caused by an autoimmune reaction. Treatment options have largely increased over the years. In this article, we present two clinical cases.

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.

Decrease of natalizumab drug levels after switching from intravenous to subcutaneous administration in patients with multiple sclerosis.

Background: Natalizumab is effective in the treatment of multiple sclerosis (MS). In 2021, the European Medicines Agency approved the subcutaneous (SC) variant of natalizumab which can be used instead of intravenous administration. However, the course of drug levels varies between administration routes, and the Food and Drug Administration rejected the request for approval of natalizumab SC for reasons that were not disclosed.

Natalizumab concentrations during pregnancy in three patients with multiple sclerosis.

In women with very active multiple sclerosis (MS), natalizumab can be continued during pregnancy to prevent rebound disease activity. Our aim was to evaluate changes in serum natalizumab trough concentrations during pregnancy. Blood samples of 3 patients were collected before, during, and after pregnancy.

Personalized B-cell tailored dosing of ocrelizumab in patients with multiple sclerosis during the COVID-19 pandemic.

In this observational study, 159 patients with multiple sclerosis received personalized dosing of ocrelizumab incentivized by the COVID-19 pandemic. Re-dosing was scheduled when CD19 B-cell count was ⩾10 cells/µL (starting 24 weeks after the previous dose, repeated 4-weekly). Median interval until re-dosing or last B-cell count was 34 [30-38] weeks.

Second intravenous immunoglobulin dose in patients with Guillain-Barré syndrome with poor prognosis (SID-GBS): a double-blind, randomised, placebo-controlled trial.

Background: Treatment with one standard dose (2 g/kg) of intravenous immunoglobulin is insufficient in a proportion of patients with severe Guillain-Barré syndrome. Worldwide, around 25% of patients severely affected with the syndrome are given a second intravenous immunoglobulin dose (SID), although it has not been proven effective. We aimed to investigate whether a SID is effective in patients with Guillain-Barré syndrome with a predicted poor outcome.

Personalized extended interval dosing of natalizumab in MS: A prospective multicenter trial.

Objective: To determine whether natalizumab efficacy is maintained when switching to personalized extended interval dosing based on individual natalizumab trough concentrations in patients with relapsing-remitting multiple sclerosis (RRMS).

Methods: This was a prospective multicenter single-arm trial with 1 year follow-up and a 1-year extension phase. Participants were adult persons with RRMS treated with natalizumab without disease activity in the year prior to enrollment.

Fecal Microbiota Transplantation in Neurological Disorders.

Several studies suggested an important role of the gut microbiota in the pathophysiology of neurological disorders, implying that alteration of the gut microbiota might serve as a treatment strategy. Fecal microbiota transplantation (FMT) is currently the most effective gut microbiota intervention and an accepted treatment for recurrent infections. To evaluate indications of FMT for patients with neurological disorders, we summarized the available literature on FMT.

Patients' expectations of autologous hematopoietic stem cell transplantation as a treatment for MS.

Background: Autologous hematopoietic stem cell transplantation (aHSCT) receives increasing attention as a treatment option for MS. However, as there are no randomized controlled trials comparing aHSCT to best medical treatment as yet, aHSCT is not generally advised and implemented as a treatment option for MS. Neurologists are increasingly faced with patients asking questions regarding aHSCT and seeking commercially offered aHSCT abroad.

CLIPPERS and its mimics: evaluation of new criteria for the diagnosis of CLIPPERS.

Objective: To evaluate the accuracy of the recently proposed diagnostic criteria for chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS).

Methods: We enrolled 42 patients with hindbrain punctate and/or linear enhancements (<3 mm in diameter) and tested the CLIPPERS criteria.

Results: After a median follow-up of 50 months (IQR 25-82), 13 out of 42 patients were CLIPPERS-mimics: systemic and central nervous system lymphomas (n=7), primary central nervous system angiitis (n=4) and autoimmune gliopathies (n=2).

[Paroxysmal hypothermia in multiple sclerosis].

Background: Multiple sclerosis (MS) can be accompanied by paroxysmal symptoms. These are diverse in nature and often not well known.

Case Description: In the emergency department, we repeatedly saw a 49-year-old man with secondary progressive MS with recurrent episodes of hypothermia, loss of consciousness, thrombocytopenia and worsening of pre-existing neurological deficits.

Disease activity following pregnancy-related discontinuation of natalizumab in MS.

Objective: To investigate disease activity and disability progression following pregnancy-related discontinuation of natalizumab (NTZ) in patients with relapsing-remitting MS.

Methods: A retrospective cohort study of clinical and radiologic data in patients who discontinued NTZ for pregnancy-related reasons.

Results: Twenty-two pregnancy-related NTZ discontinuations in 17 patients were evaluated.

Neuromyelitis optica spectrum disorder mimicking multiple sclerosis.

Background: MS is a demyelinating CNS disease and has distinct clinical and radiological features. Neuromyelitis optica spectrum disorder (NMOSD) is an antibody related auto-immune disease known for invalidating episodes of myelitis and optic neuritis.

Objective: Reporting the case of a 29-year old woman with a disease course typical for relapsing remitting MS with consistent radiological and spinal fluid findings, who developed longitudinally extensive transverse myelitis (LETM) with positive aquaporin 4 antibodies, fulfilling the diagnostic criteria for NMOSD.

Progressive multifocal leukoencephalopathy in patients treated with fumaric acid esters: a review of 19 cases.

Progressive multifocal leukoencephalopathy (PML) is a rare and potentially fatal condition caused by a brain infection with JC polyomavirus (JCV). PML develops almost exclusively in immunocompromised patients and has recently been associated with use of fumaric acid esters (FAEs), or fumarates. We reviewed the literature and the Dutch and European pharmacovigilance databases in order to identify all available FAE-associated PML cases and distinguish possible common features among these patients.

[Progressive cognitive disturbances in a 17-year-old boy].

Background: Subacute sclerosing panencephalitis (SSPE) is a fatal encephalitis manifesting a number of years after a primary measles infection. This disease has become very rare since the introduction of immunisation against measles in 1976.

Case Description: A 17-year-old boy presented with progressive cognitive disturbances and extrapyramidal symptoms that had developed over a few weeks.