Effect of sodium phenylbutyrate and taurursodiol on plasma concentrations of neuroinflammatory biomarkers in amyotrophic lateral sclerosis: results from the CENTAUR trial.

Background: An oral sodium phenylbutyrate and taurursodiol combination (PB and TURSO) significantly reduced functional decline in people living with amyotrophic lateral sclerosis (ALS) in the CENTAUR trial. Biomarkers linking clinical therapeutic effect with biological changes are of high interest in ALS. We performed analyses of neuroinflammatory biomarkers associated with ALS in the literature, including YKL-40 (also known as chitinase-3-like protein 1), chitinase 1 (CHIT1) and C reactive protein (CRP), in plasma samples collected in CENTAUR.

Impact of Baseline Characteristics on the Efficacy and Safety of Eptinezumab in Patients With Migraine: Subgroup Analyses of PROMISE-1 and PROMISE-2.

Purpose: In the PROMISE-1 (Prevention of Migraine via Intravenous ALD403 Safety and Efficacy-1) and PROMISE-2 (Prevention of Migraine via Intravenous ALD403 Safety and Efficacy-2) clinical trials, eptinezumab 100 mg and 300 mg met the primary efficacy end point, significantly reducing mean monthly migraine days across weeks 1 to 12. Clinical efficacy was also shown across key secondary end points. However, to determine if clinical efficacy varies across subgroups, it is necessary to determine efficacy in patients with different sociodemographic features and headache characteristics.

Eptinezumab treatment initiated during a migraine attack is associated with meaningful improvement in patient-reported outcome measures: secondary results from the randomized controlled RELIEF study.

Background: Demonstrating therapeutic value from the patient perspective is important in patient-centered migraine management. The objective of this study was to investigate the impact of eptinezumab, a preventive migraine treatment, on patient-reported headache impact, acute medication optimization, and perception of disease change when initiated during a migraine attack.

Methods: RELIEF was a randomized, double-blind, placebo-controlled trial conducted between 2019 and 2020 in adults with ≥1-year history of migraine and 4-15 migraine days per month in the 3 months prior to screening.

Preventive migraine treatment with eptinezumab reduced acute headache medication and headache frequency to below diagnostic thresholds in patients with chronic migraine and medication-overuse headache.

Objective: This post hoc analysis in patients medically diagnosed with chronic migraine (CM) and medication-overuse headache (MOH) evaluated reductions in the use of acute headache medication (AHM) and sustained changes in the diagnostic status of CM and MOH following eptinezumab treatment in the PROMISE-2 study.

Background: Eptinezumab, a monoclonal antibody that inhibits calcitonin gene-related peptide, is approved in the United States for the preventive treatment of migraine. A previous analysis showed that eptinezumab reduced monthly migraine days and was well tolerated in the subgroup of PROMISE-2 patients diagnosed with both CM and MOH.

Effects of Intravenous Eptinezumab vs Placebo on Headache Pain and Most Bothersome Symptom When Initiated During a Migraine Attack: A Randomized Clinical Trial.

Importance: Intravenous eptinezumab, an anti-calcitonin gene-related peptide antibody, is approved for migraine prevention in adults. It has established onset of preventive efficacy on day 1 after infusion.

Objective: To evaluate the efficacy of and adverse events related to eptinezumab when initiated during a migraine attack.

Safety and tolerability of eptinezumab in patients with migraine: a pooled analysis of 5 clinical trials.

Background: The humanized anti-CGRP monoclonal antibody eptinezumab has been evaluated in five large-scale clinical trials conducted in patients with migraine. This integrated analysis was conducted to evaluate the comprehensive safety and tolerability of eptinezumab in patients with migraine across these studies.

Methods: Data were pooled from four randomized, double-blind, placebo-controlled studies and the first year of one open-label study.

Long-term safety and tolerability of eptinezumab in patients with chronic migraine: a 2-year, open-label, phase 3 trial.

Background: Eptinezumab, an anti-calcitonin gene-related peptide monoclonal antibody recently approved in the United States for preventive treatment of migraine in adults, was found to be well tolerated in double-blind, placebo-controlled studies in patients with episodic and chronic migraine. The objective of the PREVAIL study was to evaluate the long-term safety, immunogenicity, and impact on patient-reported outcomes of repeat doses of eptinezumab in patients with chronic migraine.

Methods: PREVAIL was an open-label, phase 3 trial comprising a 48-week treatment phase followed by a second 48-week treatment phase.

Efficacy, tolerability, and safety of eptinezumab in patients with a dual diagnosis of chronic migraine and medication-overuse headache: Subgroup analysis of PROMISE-2.

Objective: To evaluate the efficacy, tolerability, and safety of eptinezumab 100 and 300 mg compared with placebo in patients with the dual diagnosis of chronic migraine (CM) and medication-overuse headache (MOH).

Background: Eptinezumab, a humanized monoclonal antibody targeting calcitonin gene-related peptide, may be effective for treating patients with a dual diagnosis of CM and MOH.

Methods: PROMISE-2 (NCT02974153) was a double-blind, randomized, placebo-controlled, phase 3 study that comprised a screening visit, a 28-day pretreatment period, and a 32-week study duration.

Five years of ocrelizumab in relapsing multiple sclerosis: OPERA studies open-label extension.

Objective: To assess over 3 years of follow-up the effects of maintaining or switching to ocrelizumab (OCR) therapy on clinical and MRI outcomes and safety measures in the open-label extension (OLE) phase of the pooled OPERA: I/II studies in relapsing multiple sclerosis.

Methods: After 2 years of double-blind, controlled treatment, patients continued OCR (600 mg infusions every 24 weeks) or switched from interferon (IFN)-β-1a (44 μg 3 times weekly) to OCR when entering the OLE phase (3 years). Adjusted annualized relapse rate, time to onset of 24-week confirmed disability progression (CDP)/improvement (CDP), brain MRI activity (gadolinium-enhanced and new/enlarging T2 lesions), and percentage brain volume change were analyzed.

Immune Response to Seasonal Influenza Vaccine in Patients with Relapsing-Remitting Multiple Sclerosis Receiving Long-term Daclizumab Beta: A Prospective, Open-Label, Single-Arm Study.

Background: For patients with relapsing-remitting multiple sclerosis (RRMS) undergoing continuous immunomodulatory therapy, understanding whether vaccinations can be performed safely and effectively is important. We tested the immune response to inactivated seasonal influenza vaccine during long-term daclizumab beta treatment.

Methods: In this prospective, open-label, single-arm extension SELECTED study, an optional vaccine substudy was performed on patients with RRMS who had already received daclizumab beta for 1 to 2 years in previous studies.

Safety and efficacy of natalizumab in patients with acute ischaemic stroke (ACTION): a randomised, placebo-controlled, double-blind phase 2 trial.

Background: In animal models of acute ischaemic stroke, blocking of the leukocyte-endothelium adhesion by antagonism of α4 integrin reduces infarct volumes and improves outcomes. We assessed the effect of one dose of natalizumab, an antibody against the leukocyte adhesion molecule α4 integrin, in patients with acute ischaemic stroke.

Methods: In this double-blind, phase 2 study, patients with acute ischaemic stroke (aged 18-85 years) from 30 US and European clinical sites were randomly assigned (1:1) to 300 mg intravenous natalizumab or placebo with stratification by treatment window and baseline infarct size.

Prolonged-release fampridine treatment improved subject-reported impact of multiple sclerosis: Item-level analysis of the MSIS-29.

Prolonged-release (PR) fampridine is approved to treat walking impairment in persons with multiple sclerosis (MS); however, treatment benefits may extend beyond walking. MOBILE was a phase 2, 24-week, double-blind, placebo-controlled exploratory study to assess the impact of 10mg PR-fampridine twice daily versus placebo on several subject-assessed measures. This analysis evaluated the physical and psychological health outcomes of subjects with progressing or relapsing MS from individual items of the Multiple Sclerosis Impact Scale (MSIS-29).

Identifying an important change estimate for the Multiple Sclerosis Walking Scale-12 (MSWS-12v1) for interpreting clinical trial results.

Background: The 12-question Multiple Sclerosis Walking Scale (MSWS-12v1) is a widely-used patient-reported outcome (PRO) measure of walking ability in multiple sclerosis (MS).

Objective: To estimate the magnitude of an important change in MSWS-12v1 scores for the interpretation of meaningful subject-level improvements across a 6-month trial of MS patients with walking disability.

Methods: MOBILE was a 6-month exploratory study assessing fampridine's effect on walking ability in 132 people with MS.

Prolonged-release fampridine and walking and balance in MS: randomised controlled MOBILE trial.

Background: Mobility impairment is a common disability in MS and negatively impacts patients' lives.

Objective: Evaluate the effect of prolonged-release (PR) fampridine (extended-release dalfampridine in the United States) on self-assessed walking disability, dynamic/static balance and safety in patients with MS.

Methods: MOBILE was a randomised, double-blind, exploratory, placebo-controlled trial.

Effect of daclizumab high-yield process in patients with highly active relapsing-remitting multiple sclerosis.

Patients with highly active relapsing-remitting multiple sclerosis (RRMS) are at greater risk for disease progression and may respond differently to MS therapeutics than those with less active disease. The current post hoc analysis evaluated the effects of daclizumab high-yield process (DAC HYP) vs. placebo in patients with highly active RRMS in the SELECT study.

Disease-activity-free status in patients with relapsing-remitting multiple sclerosis treated with daclizumab high-yield process in the SELECT study.

Background: Daclizumab high-yield process (DAC HYP) is a humanized anti-CD25 monoclonal antibody that inhibits high-affinity interleukin-2 receptor signaling.

Objective: The objective of this paper is to assess the proportion of DAC HYP- versus placebo-treated patients who were free from disease activity.

Methods: SELECT was a randomized, double-blind, multicenter study of DAC HYP 150 mg or 300 mg, or placebo, administered subcutaneously every four weeks for 52 weeks.

The syndrome of delayed post-hypoxic leukoencephalopathy.

Delayed post-hypoxic leukoencephalopathy (DPHL) is a demyelinating syndrome characterized by acute onset of neuropsychiatric symptoms days to weeks following apparent recovery from coma after a period of prolonged cerebral hypo-oxygenation. It is diagnosed, after excluding other potential causes of delirium, with a clinical history of carbon monoxide poisoning, narcotic overdose, myocardial infarction, or another global cerebral hypoxic event. The diagnosis can be supported by neuroimaging evidence of diffuse hemispheric demyelination sparing cerebellar and brainstem tracts, or by an elevated cerebrospinal fluid myelin basic protein.

A randomized trial of memantine as treatment for spasticity in multiple sclerosis.

We report the results of a single center randomized, double-blind, placebo-controlled, parallel group trial of memantine in adults with multiple sclerosis and spasticity conducted over 12 weeks. Eligible MS patients had to have an Ashworth spasticity rating of 2 or higher in at least one lower extremity muscle group. Subjects were randomized to receive either placebo or memantine 10 mg twice a day.

Polyunsaturated fatty acids and their potential therapeutic role in multiple sclerosis.

Considerable interest has been shown in the potential anti-inflammatory effects of polyunsaturated fatty acids (PUFAs) in multiple sclerosis (MS) and other autoimmune inflammatory disorders. Studies suggest a modest association between consumption of low levels of unsaturated fat and an increased incidence of MS. Moreover, in vitro and in vivo studies have demonstrated that omega-3 and omega-6 PUFA supplementation can reduce immune-cell activation via a number of complex pathways.

Sporadic fatal insomnia masquerading as a paraneoplastic cerebellar syndrome.

Background: Sporadic fatal insomnia is a rare prion disease that has recently been recognized.

Objective: To report a unique case of sporadic fatal insomnia in a woman with progressive cerebellar deterioration who was originally thought to have a paraneoplastic cerebellar syndrome.

Design: Case report describing a patient with autopsy-proven sporadic fatal insomnia.

Neuromyelitis optica spectrum disorder in a patient with systemic lupus erythematosus and anti-phospholipid antibody syndrome.

Neuromyelitis optica (NMO) is a demyelinating disease of the central nervous system characterized by severe episodes of optic nerve and spinal cord inflammation. NMO-IgG (anti-aquaporin-4) has been recently described as a sensitive and specific marker for NMO. As there have been prior published reports of an association between NMO and systemic autoimmune diseases, the prognostic value of the antibody test in these cases is uncertain.

Fatal granulomatous Acanthamoeba encephalitis mimicking a stroke, diagnosed by correlation of results of sequential magnetic resonance imaging, biopsy, in vitro culture, immunofluorescence analysis, and molecular analysis.

Amebic infections involving the central nervous system are rare and difficult to diagnose. Magnetic resonance imaging (MRI) at timed intervals may be helpful, where scans reveal enhancing lesions and increased signal. We report a unique case of granulomatous amebic encephalitis that was proven pathologically with progressive radiological findings on MRI.