Fingolimod is a sphingosine 1-phosphate (S1P) receptor modulator approved to treat relapsing-remitting multiple sclerosis (MS). Initiation of treatment with fingolimod has been found to produce transient bradycardia and/or slowing of atrioventricular impulse conduction in a small proportion of patients. This effect is thought to be due to the interaction of fingolimod with S1P receptors on the surface membrane of atrial myocytes causing a vagomimetic effect, similar to the action of acetylcholine on muscarinic receptors. As a precaution, patients are under electrocardiogram (ECG) monitoring for 6 h after receiving their first dose. Fingolimod is contraindicated in patients with overt or concealed cardiac diseases. However, the Fingolimod Initiation and caRdiac Safety Trial (FIRST), which was designed specifically to investigate the cardiac profile of fingolimod, did not show an increased risk of clinically relevant cardiac events with fingolimod. This review examines the electrophysiology and pathophysiology of cardiac impulse formation in the context of fingolimod. It concludes that these vagomimetic effects should be considered benign and should not prevent the effective use of fingolimod in the treatment of patients with MS.
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http://dx.doi.org/10.1111/cns.12283 | DOI Listing |
IDCases
January 2025
Department of Infectious Diseases, Osaka City General Hospital, Osaka, Japan.
A 65-year-old woman with Multiple Sclerosis treated with fingolimod developed headaches and convulsions. Cerebrospinal fluid (CSF) culture indicated . A literature review of 20 cases of cryptococcal meningitis indicated that headache was the most common initial symptom, and all cases were positive for serum and/or CSF cryptococcal antigens.
View Article and Find Full Text PDFMol Biol Rep
January 2025
Department of Pharmacology, School of Health Sciences, Central University of Punjab, Bathinda, 151401, India.
Background: Multiple sclerosis (MS) is a chronic autoimmune condition that damages the myelin sheath of neurons in the central nervous system, resulting in compromised nerve transmission and motor impairment. The astrocytopathy is considered one of the prominent etiological factor in the pathophysiology of demyelination in MS. The expression level of ceramide synthase-2 (CS-2) is yet to be established in the pathophysiology of astrocytopathy although the derailed ceramide biosynthetic pathways is well demonstrated in the pathophysiology of demyelination.
View Article and Find Full Text PDFPreviously, our metabolomic, transcriptomic, and genomic studies characterized the ceramide/sphingomyelin pathway as a therapeutic target in Alzheimer's disease, and we demonstrated that FTY720, a sphingosine-1-phospahate receptor modulator approved for treatment of multiple sclerosis, recovers synaptic plasticity and memory in APP/PS1 mice. To further investigate how FTY720 rescues the pathology, we performed metabolomic analysis in brain, plasma, and liver of trained APP/PS1 and wild-type mice. APP/PS1 mice showed area-specific brain disturbances in polyamines, phospholipids, and sphingolipids.
View Article and Find Full Text PDFBMJ Open
January 2025
Collaboration for Outcomes Research and Evaluation (CORE), Faculty of Pharmaceutical Sciences, The University of British Columbia, Vancouver, British Columbia, Canada
Introduction: Long-term population-based safety studies, applying advanced causal inference techniques, including an active comparator with new-user design, are needed to investigate skin cancer outcomes among individuals with multiple sclerosis (MS) treated with fingolimod. This study aims to describe a protocol for investigating the relationship between fingolimod use and the incidence of skin cancer among individuals with MS.
Methods And Analysis: We will use population-based administrative health data from two Canadian provinces (British Columbia and Alberta) to conduct an observational cohort 'trial emulation' study with an active comparator and new-user design.
CNS Neurosci Ther
January 2025
Department of Neurology, Isfahan University of Medical Sciences, Isfahan, Iran.
Background: Multiple sclerosis (MS) is an autoimmune disorder affecting the central nervous system, with varying clinical manifestations such as optic neuritis, sensory disturbances, and brainstem syndromes. Disease progression is monitored through methods like MRI scans, disability scales, and optical coherence tomography (OCT), which can detect retinal thinning, even in the absence of optic neuritis. MS progression involves neurodegeneration, particularly trans-synaptic degeneration, which extends beyond the initial injury site.
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