3,4-diaminopyridine Phosphate in the Treatment of Lambert-Eaton Myasthenic Syndrome

2012 ◽  
Vol 7 (1) ◽  
pp. 56
Author(s):  
Jörn Peter Sieb ◽  
Keyword(s):  
Neuromuscular Transmission ◽  
Autoimmune Disorder ◽  
Special Treatment ◽  
Orphan Medicinal Product ◽  
Local Hospital ◽  
Correct Dose ◽  
The Us ◽  
Myasthenic Syndrome ◽  
Drug Doses ◽  
Variable Quality

3,4-diaminopyridine (3,4-DAP, amifampridine) is the leading treatment for Lambert–Eaton myasthenic syndrome (LEMS), an autoimmune disorder with impaired neuromuscular transmission, for which few effective medications are currently available. 3,4-DAP has been available as a therapy for LEMS in special treatment programmes for approximately 25 years. As an unlicensed drug, doses for oral administration are required to be compounded by local, hospital or other compounding pharmacies from the base chemical. Administering the correct dose of 3,4-DAP is critical; overdosing can increase the risk of seizures and other adverse events, while underdosing can result in a substantial loss of efficacy or even treatment failure. Two recent studies, have shown a wide variation in the 3,4-DAP content of compounded preparations (22.2–125.2 %, n=9) and (53.5–128.5 %, n=21), thereby reflecting the possibility of patients receiving dosages that might be above safety limits or even markedly below efficacy limits. This inconsistency results from the variable quality and instability of the base chemical and compounding errors. A formulation of 3,4-DAP phosphate salt has now been licensed in Europe and the US with orphan medicinal product status and appears to be as efficacious as the base in relieving the symptoms of LEMS.

Update on Amifampridine as a Drug of Choice in Lambert-Eaton Myasthenic Syndrome

US Neurology ◽  
2014 ◽  
Vol 10 (02) ◽  
pp. i ◽  
Author(s):  
Shin J Oh ◽  
Jörn Peter Sieb ◽  
◽  
Keyword(s):  
Drug Application ◽  
Clinical Trial Data ◽  
Autoimmune Disorder ◽  
Phase Iii ◽  
Drug Status ◽  
Double Blind ◽  
Drug Of Choice ◽  
Qt Intervals ◽  
The Us ◽  
Myasthenic Syndrome

Lambert-Eaton myasthenic syndrome (LEMS) is a disabling autoimmune disorder involving impairment of neuromuscular transmission and producing serious muscle weakness, for which few effective medications are currently available. 3,4-diaminopyridine (3,4-DAP, INN/USAN: amifampridine) is the leading treatment for LEMS and has been available for over 25 years as an unapproved drug under treatment and expanded access protocols filed with the US Food and Drug Administration (FDA) or from compounding pharmacies in the US. Administering the correct dose of 3,4-DAP is critical—overdosing can increase the risk for seizures and other adverse events, while underdosing can result in a substantial loss of efficacy or even treatment failure. Two recent studies have shown a wide variation in the 3,4-DAP content of compounded preparations. A tablet formulation of 3,4-DAP phosphate salt (FIRDAPSETM) has been licenced in Europe with orphan medicinal product status since 2009 and appears to be as efficacious as the base in relieving the symptoms of LEMS. The product has also received orphan drug status in the US and is currently being evaluated in a multicenter, double-blind, placebo-controlled phase III trial to support New Drug Application (NDA) approval in the US. A recent safety trial in healthy volunteers using doses at and above normal levels has shown no effect on QT intervals, heart rate, or cardiac depolarization. Based on available clinical trial data, amifampridine phosphate was recently given Breakthrough Therapy designation by the FDA, which may enable fast-track NDA approval, thus increasing the potential for more patients with LEMS to receive an effective therapy.

scholarly journals COVID-19 in a Cohort of Patients with Congenital Myasthenic Syndrome

2021 ◽  
pp. 1-3
Author(s):  
Setareh Alabaf ◽  
Karen O'Connell ◽  
Sithara Ramdas ◽  
David Beeson ◽  
Jacqueline Palace
Keyword(s):  
High Risk ◽  
Neuromuscular Transmission ◽  
Genetic Disorders ◽  
Severe Disease ◽  
Congenital Myasthenic Syndrome ◽  
Referral Centre ◽  
History Of ◽  
Myasthenic Syndrome ◽  
The Uk ◽  
Rare Group

Congenital Myasthenic Syndrome (CMS) are a rare group of genetic disorders of neuromuscular transmission. Some subtypes of CMS can be associated with respiratory and bulbar weakness and these patients may therefore be at high risk of developing a severe disease from COVID-19. We screened 73 patients with genetically confirmed CMS who were attending the UK national referral centre for evidence of previous Severe Acute Respiratory Syndrome Corona Virus 2 infection and their clinical outcome. Of 73 patients, seven had history of confirmed COVID-19. None of the infected patients developed a severe disease, and there were no signals that CMS alone carries a high risk of severe disease from COVID-19.

scholarly journals Presynaptic Paraneoplastic Disorders of the Neuromuscular Junction: An Update

2021 ◽  
Vol 11 (8) ◽  
pp. 1035
Author(s):  
Maria Pia Giannoccaro ◽  
Patrizia Avoni ◽  
Rocco Liguori
Keyword(s):  
Potassium Channels ◽  
Neuromuscular Junction ◽  
Calcium Channels ◽  
Myasthenia Gravis ◽  
Neuromuscular Transmission ◽  
Voltage Gated ◽  
Voltage Gated Calcium Channels ◽  
Immune Mediated ◽  
Recent Developments ◽  
Myasthenic Syndrome

The neuromuscular junction (NMJ) is the target of a variety of immune-mediated disorders, usually classified as presynaptic and postsynaptic, according to the site of the antigenic target and consequently of the neuromuscular transmission alteration. Although less common than the classical autoimmune postsynaptic myasthenia gravis, presynaptic disorders are important to recognize due to the frequent association with cancer. Lambert Eaton myasthenic syndrome is due to a presynaptic failure to release acetylcholine, caused by antibodies to the presynaptic voltage-gated calcium channels. Acquired neuromyotonia is a condition characterized by nerve hyperexcitability often due to the presence of antibodies against proteins associated with voltage-gated potassium channels. This review will focus on the recent developments in the autoimmune presynaptic disorders of the NMJ.

scholarly journals Nosocomial infections in the Intensive care unit: global problem of modern medicine

2018 ◽  
Vol 1 (2) ◽  
pp. 5-19
Author(s):  
Zara Vezirova
Keyword(s):  
Nosocomial Infections ◽  
Metastatic Cancer ◽  
Intensive Therapy ◽  
Treatment Modalities ◽  
Critical Conditions ◽  
Special Treatment ◽  
Surgical Interventions ◽  
Hospital Acquired Infections ◽  
The Us ◽  
Hospital Acquired

Increased volume of surgical interventions, improvement of efficiency of special treatment modalities and modes of respiratory support, as well as development of new generation antibiotic medications has led to significant improvement of clinical outcomes of intensive therapy for critical conditions. At the same time, introduction of innovative and largely invasive interventions resulted in the emergence of new disease entities. Presently, the development of hospital-acquired infections (HAI) has become one of the riveting and serious problems of modern hospitals. These infections often lead to prolonged hospital stay, which in turn adds to the morbidity and mortality, worsen patient quality of life and also has significant economic consequences [1-5]. There are number of varying definitions of infections related to medical care [6]. According to the WHO, infections that develop 48 hours after hospitalization, excluding the incubation period, are called hospital-acquired or nosocomial infections. Some authors also include here infections that develop 4 weeks after patient’s discharge from hospital or 30 days after surgical interventions are also included in this category. Infections that develop within 30 days after last chemotherapy in patients with metastatic cancer are also included as additional criteria according to a medical literature [7]. Other authors conclude that readmission of patients with established infection that was the result of previous hospitalization as well as any infectious diseases of hospital employee that develops secondary to the work in the hospital, irrespective to the time of onset of symptoms (during or after the hospital visit or stay) shall also be regarded as the hospital-acquired infections (HAI) [8-10]. The average prevalence of HAI is around 3.5-10.5% or 9.0-91.7 cases per 1000 patient-days [11]. It is estimated that the probability of infectious complications increases after five days of hospitalization [12]. According to the modern medical knowledge, the prevalence of HAI of various causes among the hospitalized patients in North America and Europe is around 5-10% and those in Latin America and Asia is around 40% [13,14]. The mortality among patients with HAI is seven times higher than among other patients aligned based on age, sex, main disease and comorbidities and severity of disease. According to the official statistics, HAIs are fourth most common cause of mortality in the US leading to 90.000 deaths annually. Annual economic burden and additional costs associated with the treatment of HAIs in the US is about 2.4-4.5 billion US dollars [15-17].

Building the World War II Memorials, 1945–1960

2018 ◽  
pp. 183-221
Author(s):  
Thomas H. Conner
Keyword(s):  
World War Ii ◽  
Second Generation ◽  
Family Members ◽  
Special Treatment ◽  
World War ◽  
The Public ◽  
The Us ◽  
The World ◽  
Us Government ◽  
The Creation

This chapter looks at the longer aftermath of WWII and traces the creation of the second generation of ABMC sites. Focusing on the process of securing grounds overseas, allowing family members to decide where their loved ones would be buried, and obtaining US government clearance on designs, the account is reminiscent of the start of the ABMC and its first project. By 1960, fourteen cemetery memorials had been dedicated. This chapter also highlights the leadership of the agency’s second chairman, General George C. Marshall, and his direction of the building of memorials in eight countries to remember the 400,000 Americans who had died and the 16 million who had served in WWII. Marshall’s high standing in the US government and in the public esteem, just as was true of Pershing, greatly helped the agency to fulfill its renewed mission. The special treatment shown the grave of General George S. Patton in the Luxembourg American Cemetery is also detailed.

scholarly journals 3,4-diaminopyridine treatment for Lambert-Eaton myasthenic syndrome in adults: a meta-analysis of randomized controlled trials

BMC Neurology ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Na Zhang ◽  
Daojun Hong ◽  
Taohui Ouyang ◽  
Wei Meng ◽  
Jingwei Huang ◽  
...  
Keyword(s):  
Meta Analysis ◽  
Autoimmune Disorder ◽  
Placebo Treatment ◽  
Secondary Outcome ◽  
Controlled Trials ◽  
Cochrane Central Register ◽  
Central Register ◽  
Compound Muscle Action Potentials ◽  
Myasthenic Syndrome ◽  
Randomised Controlled

Abstract Background Lambert-Eaton myasthenic syndrome (LEMS) is a rare autoimmune disorder of neuromuscular transmission. The objective was to examine the efficacy and safety of 3,4-diaminopyridine (3,4-DAP) in patients with LEMS. Methods We searched several databases to identify relevant studies, including PubMed, EMBASE, Web of Science, MEDLINE, Cochrane Neuromuscular Disease Group Specialized Register and the Cochrane Central Register of Controlled Trials(CENTRAL). The primary outcome, quantitative myasthenia gravis (QMG) score and the secondary outcome, compound muscle action potentials (CMAP) amplitude were pooled by meta-analysis. Results Six randomised controlled trials (RCTs) involving 115 patients with LEMS were included. QMG score showed a significant decrease (improvement) of 2.76 points (95 % CI, -4.08 to -1.45, p < 0.001) after treatment with 3, 4-DAP. Moreover, the overall mean CMAP amplitude improved significantly in LEMS patients with 3, 4-DAP treatment, compared with placebo treatment (mean difference 1.34 mV, 95 % CI, 0.98 to 1.70, p < 0.001). The overall assessment of all included trials showed a low risk of bias and low heterogeneity. Conclusions The pooled results of RCTs demonsrated with moderate to high evidence that 3,4-DAP has a significant effect on LEMS treatment, with improvements in muscle strength score and CMAP amplitude.

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