Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036572 (seizures)
 80,221 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Multiple sclerosis (MS) is a chronic inflammatory and neurodegenerative disease of the central nervous system of unknown cause in which neurological impairment and disability result from demyelination and axonal loss. Physiologically, myelin loss leads to changes in axonal ion channels that cause conduction failure. Axonal loss leads to a reduction in signal strength in neuronal pathways. Fampridine (4-aminopyridine) is a potassium channel blocker that can increase action potential duration and amplitude, leading to improved conduction in demyelinated nerve fibers and to increased neurotransmitter release at synaptic endings. Fampridine treatment can improve ambulation in some MS patients, but can also cause seizures and other side effects. Pharmacokinetic studies show that improvement in neurological deficits is primarily related to the total fampridine dose, while seizure induction is related to peak serum levels. To reduce side effects, a slow-release (SR) formulation of fampridine was developed. Two Phase III studies of fampridine SR have now shown that treatment can improve leg strength and walking speed in patients with MS; a new drug application has been filed with the US FDA.
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PMID:Sustained-release fampridine for multiple sclerosis. 1954 55

Fampridine is indicated to improve walking in adult multiple sclerosis (MS) patients. Indications vary between countries and the prescribing neurologist should be aware of the labeling and indication in his own country. The prolonged-release formulation of 4-aminopyridine has reduced the risk of seizure to a level near the intrinsic MS risk, and the risk can be further minimized if it emphasized that patients should not exceed the recommended dose of 10 mg twice a day, should not catch up on missed doses and should not divide, crush or chew tablets. It is imperative to check the renal function before and during treatment and make sure the patient does not get concomitant medications affecting the renal elimination. The use of fampridine is considered safe, and the side effects are often mild and acceptable. Approximately one-third of MS patients treated with fampridine will experience an improvement of their walking speed above 20% on the timed 25-foot walk test (T25FW), which is considered to be clinically relevant.
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PMID:Prolonged-release fampridine improves walking in a proportion of patients with multiple sclerosis. 2423 1

Sustained-release fampridine, a slow release formulation of 4-aminopryridine, is a voltage-dependent potassium channel blocker licensed for the treatment of walking difficulties in multiple sclerosis (MS). Studies have demonstrated that approximately one-third of MS patients respond with a clear benefit to their walking speed. Sustained-release Fampridine is not currently available on the National Health Service (NHS), although it has been approved by the Food and Drug Administration (FDA) in the USA and European Medicine Agency (EMA). It appears to have an acceptable adverse event profile, with data from open-label extension studies now becoming available. Concerns have been raised that the use of fampridine may increase the risk of seizures, which were seen at higher rates in patients treated with high doses of sustained-release fampridine. The rate of seizures in those patients on lower doses has not been found to be significantly increased. There are significant barriers at present to the widespread use of fampridine in the UK, which have limited its use in clinical practice to date. Patients with MS are in need of interventions to improve walking and many clinicians feel that this drug may have a role in the symptomatic management of MS.
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PMID:Sustained-release fampridine in Multiple Sclerosis. 2587 67

Fampridine is the only drug approved for the treatment of walking impairment in multiple sclerosis. Around a third of the patients on treatment obtained an improvement in walking speed during the development phase. The effects are clinically significant, appear soon after the start of the treatment and are long-lasting, but disappear soon after the drug is withdrawn. In the real-world setting, the number of patients with a significant response to the treatment seems to be higher (around 70%). The tolerance is good, with mild to moderate, and transient adverse events. The most commonly reported are insomnia, headache, fatigue, back pain, dizziness, nausea and balance disorders. The main contraindications are a history of seizures, renal impairment and concomitant treatment with OCT2 inhibitors.
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PMID:Efficacy and safety of fampridine for walking disability in multiple sclerosis. 3276 92