-
Current Opinion in Rheumatology Nov 2019This article provides an update on the most recent advances in diagnostic procedures and therapeutic approaches for myasthenia gravis, spanning from autoantibody and... (Review)
Review
PURPOSE OF REVIEW
This article provides an update on the most recent advances in diagnostic procedures and therapeutic approaches for myasthenia gravis, spanning from autoantibody and neuroelectrophysiological tests as diagnostic tools, to innovative and promising treatments based on biological drugs.
RECENT FINDINGS
Novel studies performed by cell-based assays (CBAs) indicate an improvement in the chance of identifying serum autoantibodies in myasthenic patients. Clinical trials on the use of biological drugs were recently concluded, providing important data on safety and efficacy of eculizumab, efgartigimod and amifampridine phosphate: the first, a complement blocker, showed long-term safety and efficacy in acetylcholine receptor (AChR)-positive myasthenic patients with refractory generalized disease; the second, the neonatal Fc receptor blocker, was well tolerated and clinically effective in both AChR-specific and muscle-specific kinase receptor (MuSK)-positive patients; the third, a blocker of presynaptic potassium channels, was found to be well tolerated and effective in MuSK-positive patients.
SUMMARY
CBAs can lead to a significant reduction of seronegative patients, improving myasthenia gravis diagnostic process. New biological drugs offer innovative approaches to treat myasthenic patients with generalized disease, promising to change the paradigm of treatment and to significantly enhance therapeutic success within a precision medicine framework.
Topics: Autoantibodies; Biological Factors; Electromyography; Humans; Immunosuppressive Agents; Myasthenia Gravis; Treatment Outcome
PubMed: 31385879
DOI: 10.1097/BOR.0000000000000647 -
International Journal of Molecular... Feb 2023Congenital myasthenic syndromes (CMS) are a heterogeneous group of disorders characterized by impaired neuromuscular signal transmission due to germline pathogenic... (Review)
Review
Congenital myasthenic syndromes (CMS) are a heterogeneous group of disorders characterized by impaired neuromuscular signal transmission due to germline pathogenic variants in genes expressed at the neuromuscular junction (NMJ). A total of 35 genes have been reported in CMS (). The 35 genes can be classified into 14 groups according to the pathomechanical, clinical, and therapeutic features of CMS patients. Measurement of compound muscle action potentials elicited by repetitive nerve stimulation is required to diagnose CMS. Clinical and electrophysiological features are not sufficient to identify a defective molecule, and genetic studies are always required for accurate diagnosis. From a pharmacological point of view, cholinesterase inhibitors are effective in most groups of CMS, but are contraindicated in some groups of CMS. Similarly, ephedrine, salbutamol (albuterol), amifampridine are effective in most but not all groups of CMS. This review extensively covers pathomechanical and clinical features of CMS by citing 442 relevant articles.
Topics: Humans; Albuterol; Amifampridine; Cholinesterase Inhibitors; Mitochondrial Proteins; Mutation; Myasthenic Syndromes, Congenital; NAV1.4 Voltage-Gated Sodium Channel; Neuromuscular Junction; Receptors, Cholinergic; Symporters; Synaptic Transmission
PubMed: 36835142
DOI: 10.3390/ijms24043730 -
Current Opinion in Neurology Oct 2021To give an overview of the recent data on three autoimmune neuromuscular junction disorders with the recent Food Drug Administration (FDA) approval of amifampridine... (Review)
Review
PURPOSE OF REVIEW
To give an overview of the recent data on three autoimmune neuromuscular junction disorders with the recent Food Drug Administration (FDA) approval of amifampridine [3,4-Diaminopyridine (3,4-DAP) and 3,4-diaminopyridine phosphate (3,4-DAPP) for the treatment of Lambert-Eaton myasthenic syndrome (LEMS).
RECENT FINDINGS
In LEMS, the most important recent development is the introduction of FDA approved amifampridine for the symptomatic treatment. Randomized controlled studies showed an extremely effective improvement with amifampridine with daily dose of ≤ 80 mg with minimal side reactions. The next important development is in the electrodiagnostic criteria. Now 10 s exercise and an incremental response ≥ 60% either after 10 s exercise or at the high-rate stimulation in the repetitive nerve stimulation test are recommended as the standard tests.In 2016, myasthenia-gravis Lambert-Eaton overlap syndrome (MLOS) was coined as new syndrome for patients with myasthenia gravis and LEMS combined symptoms in same patients.In Isaacs syndrome, voltage gated calcium channel antibody order is no longer recommended because of low specificity for immunotherapy responsive disorders. Instead, ' leucine-rich glioma-inactivated 1 (LGI1) and contactin-associated like-2 (CASPR2) autoantibody tests' are recommended.
SUMMARY
In LEMS, amifampridine (3,4 DAP and 3,4-DAPP) is approved by the FDA as an effective symptomatic treatment. MLOS is coined as new syndrome recently. In Isaacs syndrome, LGI1 and CASPR2 antibody tests are recommended.
Topics: Amifampridine; Antibodies; Humans; Lambert-Eaton Myasthenic Syndrome; Myasthenia Gravis
PubMed: 34914667
DOI: 10.1097/WCO.0000000000000972 -
Muscle & Nerve May 2018
Topics: Amifampridine; Humans; Lambert-Eaton Myasthenic Syndrome
PubMed: 29406616
DOI: 10.1002/mus.26089 -
The Annals of Pharmacotherapy Jan 2020The purpose of this article is to review the literature for both 3,4-diaminopyridine (3,4-DAP) and amifampridine for the treatment of Lambert-Eaton myasthenic syndrome... (Review)
Review
The purpose of this article is to review the literature for both 3,4-diaminopyridine (3,4-DAP) and amifampridine for the treatment of Lambert-Eaton myasthenic syndrome (LEMS). Amifampridine (Firdapse) is the salt form of 3,4-DAP and was approved by the Food and Drug Administration for the treatment of LEMS. PubMed, TRIP database, and EMBASE searches were conducted without a back date (current to June 2019) utilizing the following search terms: , and . Completed trials were also reviewed at clinicaltrials.gov. Criteria for article inclusion consisted of human subjects, age ≥18 years, phase II or III clinical trials, and English language for both drugs. Observational and pharmacokinetic studies for amifampridine were also included. Prior to the approval of amifampridine, 3,4-DAP was first-line for the management of LEMS symptoms. Two phase III trials have evaluated amifampridine to confirm efficacy, both showing superiority over placebo in the management of LEMS symptoms, with minimal adverse effects. A significant improvement in both quantitative myasthenia gravis scores and Subjective Global Impression scores was established at days 4 and 14. With an improved stability profile and decreased dose variability, amifampridine will likely assume the role of first-line management of LEMS. Amifampridine has been shown to improve symptoms of LEMS and is generally well tolerated.
Topics: Adult; Amifampridine; Databases, Factual; Fees, Pharmaceutical; Female; Humans; Lambert-Eaton Myasthenic Syndrome; Middle Aged; Neuromuscular Agents; United States; United States Food and Drug Administration
PubMed: 31319693
DOI: 10.1177/1060028019864574 -
Expert Review of Clinical Immunology Oct 2019: The present status of amifampridine (AFP) for the treatment of Lambert-Eaton myasthenic syndrome (LEMS) is reviewed. : All relevant literature identified through a... (Review)
Review
: The present status of amifampridine (AFP) for the treatment of Lambert-Eaton myasthenic syndrome (LEMS) is reviewed. : All relevant literature identified through a PubMed search under treatment of LEMS, aminopyridine, and amifampridine are reviewed. An expert opinion on AFP was formulated. : AFPs, 3,4-DAP and 3,4-DAPP, are the most studied drugs in neuromuscular diseases. Randomized and non-randomized studies showed the most effective drug as symptomatic medication for LEMS. AFPs are safe and tolerable. Thus, AFPs should be the drug of choice for the symptomatic treatment in LEMS. As long as the daily dose is less than 80 mg a day, there is no concern for the serious side-reaction, seizure. Because of short-acting drug effects, it should be given three or four times a day. Peri-oral and finger paresthesia, the most common side-reaction, is accepted as a sign of drug-intake by many patients. Gastro-intestinal side reactions, the next common side-reaction of AFPs, are tolerable. AFPs are also the drug of choice and life-saving for LEMS crisis. For the long-term usage, it is proven to be safe and AFPs can be supplemented with liberal amount of pyridostigmine to sustain a symptomatic improvement without any undue side-reaction.
Topics: Amifampridine; Cholinesterase Inhibitors; Drug and Narcotic Control; Guanidine; Humans; Lambert-Eaton Myasthenic Syndrome; Potassium Channel Blockers; Practice Guidelines as Topic; Randomized Controlled Trials as Topic
PubMed: 31533480
DOI: 10.1080/1744666X.2020.1670061 -
Australian Prescriber Oct 2022
Review
PubMed: 36382167
DOI: 10.18773/austprescr.2022.056 -
Continuum (Minneapolis, Minn.) Dec 2022This article reviews the pathophysiology, epidemiology, clinical features, diagnosis, and treatment of Lambert-Eaton myasthenic syndrome (LEMS) and botulism, presynaptic... (Review)
Review
PURPOSE OF REVIEW
This article reviews the pathophysiology, epidemiology, clinical features, diagnosis, and treatment of Lambert-Eaton myasthenic syndrome (LEMS) and botulism, presynaptic disorders of neuromuscular transmission in which rapid diagnosis improves long-term outcomes.
RECENT FINDINGS
Therapy for LEMS has seen significant advances in recent years due to the approval of amifampridine-based compounds. LEMS is likely still underdiagnosed, particularly when no underlying malignancy is identified. Clinicians must have a strong suspicion for LEMS in any patient presenting with proximal weakness and autonomic dysfunction. Botulism is another rare disorder of presynaptic neuromuscular transmission that is most commonly associated with improper storage or preservation of food products. Over the past 2 decades, wound botulism has been increasingly reported among users of black tar heroin. A high degree of clinical suspicion and electrodiagnostic studies can be beneficial in distinguishing botulism from other acute neurologic disorders, and early involvement of state and federal health authorities may assist in confirming the diagnosis and obtaining treatment. When botulism is suspected, electrodiagnostic studies can provide clinical evidence of disordered neuromuscular transmission in advance of serologic confirmation, and providers should not wait for confirmation of the diagnosis to initiate treatment.
SUMMARY
A targeted clinical history and a thorough neurologic examination with support from serologic and electrodiagnostic studies are key to early diagnosis of LEMS and botulism. Early diagnosis of both conditions creates opportunities for therapy and improves outcomes.
Topics: Humans; Lambert-Eaton Myasthenic Syndrome; Botulism; Amifampridine; Autonomic Nervous System Diseases
PubMed: 36537971
DOI: 10.1212/CON.0000000000001205