scholarly journals Dalfampridine: Review of its Efficacy in Improving Gait in Patients with Multiple Sclerosis

2011 ◽  
Vol 3 ◽  
pp. JCNSD.S4868 ◽  
Author(s):  
M.A. Sahraian ◽  
A.H. Maghzi ◽  
M. Etemadifar ◽  
A. Minagar
Keyword(s):  
Multiple Sclerosis ◽  
Central Nervous System ◽  
Clinical Trials ◽  
Nervous System ◽  
Channel Blocker ◽  
Symptomatic Treatment ◽  
Walking Ability ◽  
Human Central Nervous System ◽  
Safety And Efficacy ◽  
Immune Mediated

Multiple sclerosis (MS) is a progressive immune-mediated neurodegenerative disease of human central nervous system (CNS), which causes irreversible disability in young adults. The cause and cure for MS remain unknown. Pathophysiology of MS includes two arms: inflammatory demyelination and neurodegeneration. The inflammatory demyelination of MS which is mainly promoted by a massive activation of the immune system against putative CNS antigen(s) leads to loss of oligodendrocyte/myelin complex which slows down or halts impulse conduction in denuded axons. Practically, loss of myelin significantly reduces signal conduction along the demyelinated axons through alterations in the distribution of axonal ion channels. Dalfampridine (4-aminopyridine or 4-AP) is an oral potassium channel blocker, which was recently approved by FDA for symptomatic treatment of MS. Dalfampridine, which acts at the central and peripheral nervous systems, enhances conduction in demyelinated axons and improves walking ability of MS patients. A number of clinical trials have evaluated the safety and efficacy of fampridine in MS patients with the degree of gait improvement as the main outcome. The objective of this manuscript is to provide an overview of the pharmacology, pharmacokinetics, clinical trials, side effects and interactions of dalfampridine used in treatment of MS patients.

Immune and Infectious Diseases

2018 ◽  
pp. 430-470
Author(s):  
Andrea C. Adams
Keyword(s):  
Multiple Sclerosis ◽  
Central Nervous System ◽  
Nervous System ◽  
Young People ◽  
Connective Tissue ◽  
Infectious Diseases ◽  
Temporal Profile ◽  
Immune Mediated ◽  
The Central Nervous System ◽  
The Common

Many immune-mediated diseases and infections affect the central and peripheral nervous systems. The common feature that characterizes both immune-mediated diseases and infections is a subacute temporal profile. Immune-mediated disease can affect only the nervous system or involve the nervous system as part of a systemic illness, as in vasculitis and connective tissue disease. Multiple sclerosis (MS), the most common disabling neurologic illness of young people, is the prototypical immune-mediated disease of the central nervous system (CNS).

International Pediatric Multiple Sclerosis Study Group criteria for pediatric multiple sclerosis and immune-mediated central nervous system demyelinating disorders: revisions to the 2007 definitions

2013 ◽  
Vol 19 (10) ◽  
pp. 1261-1267 ◽  
Author(s):  
Lauren B Krupp ◽  
Marc Tardieu ◽  
Maria Pia Amato ◽  
Brenda Banwell ◽  
Tanuja Chitnis ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Central Nervous System ◽  
Nervous System ◽  
Acute Disseminated Encephalomyelitis ◽  
Study Group ◽  
Pediatric Multiple Sclerosis ◽  
Immune Mediated ◽  
International Pediatric ◽  
Demyelinating Disorders ◽  
Multiple Sclerosis Study Group

Background: There has been tremendous growth in research in pediatric multiple sclerosis (MS) and immune mediated central nervous system demyelinating disorders since operational definitions for these conditions were first proposed in 2007. Further, the International Pediatric Multiple Sclerosis Study Group (IPMSSG), which proposed the criteria, has expanded substantially in membership and in its international scope. Objective: The purpose of this review is to revise the 2007 definitions in order to incorporate advances in delineating the clinical and neuroradiologic features of these disorders. Methods: Through a consensus process, in which input was sought from the 150 members of the Study Group, criteria were drafted, revised and finalized. Final approval was sought through a web survey. Results: Revised criteria are proposed for pediatric acute disseminated encephalomyelitis, pediatric clinically isolated syndrome, pediatric neuromyelitis optica and pediatric MS. These criteria were approved by 93% or more of the 56 Study Group members who responded to the final survey. Conclusions: These definitions are proposed for clinical and research purposes. Their utility will depend on the outcomes of their application in prospective research.

Dalfampridine Extended Release Tablets—Clinical Need and Use

US Neurology ◽  
2010 ◽  
Vol 06 (02) ◽  
pp. 76 ◽  
Author(s):  
Aaron Miller ◽  
Amy Perrin Ross ◽  
James Gilbart ◽  
◽  
◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Clinical Trials ◽  
Potassium Channel ◽  
Drug Administration ◽  
Extended Release ◽  
Channel Blocker ◽  
Phase Iii ◽  
Walking Ability ◽  
Phase Iii Trials ◽  
Walking Speeds

Walking impairment is one of the most serious and frequent problems reported by multiple sclerosis (MS) patients. Treatments to restore walking ability are an unmet clinical need. Dalfampridine, a potassium channel blocker, is the first US Food and Drug Administration (FDA)-approved drug to be indicated specifically to improve walking in patients with MS. In clinical trials the drug showed improved walking speeds, demonstrating efficacy in all four types of MS. In phase III trials, dalfampridine provided significant benefits to 35–43% of treated patients. Therefore, it will be critical to manage patient expectations appropriately.

scholarly journals Traditional Uses of Cannabinoids and New Perspectives in the Treatment of Multiple Sclerosis

Medicines ◽  
2018 ◽  
Vol 5 (3) ◽  
pp. 91 ◽  
Author(s):  
Francesca Gado ◽  
Maria Digiacomo ◽  
Marco Macchia ◽  
Simone Bertini ◽  
Clementina Manera
Keyword(s):  
Multiple Sclerosis ◽  
Central Nervous System ◽  
Nervous System ◽  
Disease Progression ◽  
Endocannabinoid System ◽  
Neuroprotective Effects ◽  
Demyelinating Disorder ◽  
Immune Mediated ◽  
The Central Nervous System

Recent findings highlight the emerging role of the endocannabinoid system in the control of symptoms and disease progression in multiple sclerosis (MS). MS is a chronic, immune-mediated, demyelinating disorder of the central nervous system with no cure so far. It is widely reported in the literature that cannabinoids might be used to control MS symptoms and that they also might exert neuroprotective effects and slow down disease progression. This review aims to give an overview of the principal cannabinoids (synthetic and endogenous) used for the symptomatic amelioration of MS and their beneficial outcomes, providing new potentially possible perspectives for the treatment of this disease.

scholarly journals Cellular Hypersensitivity to Basic Myelin (P2) Protein in the Guillain-Barré Syndrome

1975 ◽  
Vol 2 (2) ◽  
pp. 87-90 ◽  
Author(s):  
William Sheremata ◽  
Susan Colby ◽  
Y. Karkhanis ◽  
Edwin H. Eylar
Keyword(s):  
Multiple Sclerosis ◽  
Central Nervous System ◽  
Nervous System ◽  
Peripheral Nerve ◽  
Nervous Tissue ◽  
Acute Illness ◽  
Human Central Nervous System ◽  
Guillain Barré ◽  
Human Nerve ◽  
Basic Myelin Protein

SUMMARY:Lymphocytes of 29 subjects were assayed for MIF production in response to P2 peripheral nerve protein, crude human peripheral nerve and human central nervous system Al basic myelin protein. Seven were performed in normal control subjects, 12 in Guillain-Barré patients (GB), 5 with other polyneuropathies and 5 in patients with multiple sclerosis (MS). Only GB patients with acute illness produced MIF in response to neuritogenic P2 protein and crude human nerve. Two MS patients in the acute phase of an exacerbation and one GB patient produced MIF in Response to Al protein. The results of this study demonstrate cellular hypersensitivity to a neuritogenic constituent in peripheral nervous tissue and support the concept that this may be important in the pathogenesis of GB.

scholarly journals Fighting the Monster: Applying the Host Damage Framework to Human Central Nervous System Infections

mBio ◽  
2016 ◽  
Vol 7 (1) ◽  
Author(s):  
Anil A. Panackal ◽  
Kim C. Williamson ◽  
Diederik van de Beek ◽  
David R. Boulware ◽  
Peter R. Williamson
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Immune Responses ◽  
Host Responses ◽  
Microbial Pathogenesis ◽  
Central Nervous System Infections ◽  
Human Central Nervous System ◽  
Host Immune Responses ◽  
Immune Mediated ◽  
Damage Response

ABSTRACTThe host damage-response framework states that microbial pathogenesis is a product of microbial virulence factors and collateral damage from host immune responses. Immune-mediated host damage is particularly important within the size-restricted central nervous system (CNS), where immune responses may exacerbate cerebral edema and neurological damage, leading to coma and death. In this review, we compare human host and therapeutic responses in representative nonviral generalized CNS infections that induce archetypal host damage responses: cryptococcal menigoencephalitis and tuberculous meningitis in HIV-infected and non-HIV-infected patients, pneumococcal meningitis, and cerebral malaria. Consideration of the underlying patterns of host responses provides critical insights into host damage and may suggest tailored adjunctive therapeutics to improve disease outcome.

Sustained-Release Fampridine for Symptomatic Treatment of Multiple Sclerosis

2008 ◽  
Vol 42 (10) ◽  
pp. 1458-1465 ◽  
Author(s):  
Anne R Korenke ◽  
Michael P Rivey ◽  
Douglas R Allington
Keyword(s):  
Multiple Sclerosis ◽  
Clinical Trials ◽  
Adverse Events ◽  
Sustained Release ◽  
English Language ◽  
Walking Speed ◽  
Data Extraction ◽  
Walking Ability ◽  
Phase 3 ◽  
Safety And Efficacy

Objective: To review the pharmacology, pharmacokinetics, clinical trials, and adverse effects of sustained-release (SR) fampridine in patients with multiple sclerosis (MS). Data Sources: An English-language human data search was done using PubMed/MEDLINE (1966-August 2008) to retrieve relevant material using the search terms fampridine-SR, 4-aminopyridine. and multiple sclerosis. References of selected articles and information from the drug developer were used to further identify pertinent trials. Study Selection and Data Extraction: Article selection was based primarily on studies that evaluated the pharmacokinetics, safety, and efficacy of fampridine-SR in patients with MS. Relevant meeting abstracts were also included as part of the analysis. Data Synthesis: Fampridine-SR is a sustained-release, orally administered potassium-channel blocker acting in the central nervous system to enhance conduction in demyelinated axons Several small trials have evaluated the safety and efficacy of fampridine-SR in patients with MS to improve their walking ability. Data from a recent large Phase 3 trial indicated that walking speed improved in 42.9% of patients with MS who were treated with fampridine-SR compared with 9.3% of those who received placebo (p < 0.001), Treatment-related adverse events associated with the use of fampridine-SR include dizziness, insomnia, nausea, and paresthesia. More severe adverse events, such as seizure, have occurred in patients receiving doses higher than those currently recommended. Conclusions: Positive results from 2 Phase 3 clinical trials have put fampridine-SR on the path toward approval as a medication for improving walking speed and tower extremity strength in patients with MS.

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