3,4-DAPP were associated with sustained or improved functioning and improved individual quality of life during follow-up in this real-world population, which is usually consistent with previous observations. Patients with LEMS often have a poor or very poor health status and impaired quality of life, with 75% of patients reporting activities of daily living always or often being affected by LEMS [7]. The observations made in this study are consistent with an earlier case series that reported improved daily function over 5years of treatment with 3,4-DAPP [21]. any time. Quantitative myasthenia gravis scores were comparable across treatment groups. Muscle mass strength was generally good and managed during follow-up. Cerebellar ataxia, defined as a negative Rombergs test and at least one other positive ataxia test, was observed in 30 (56.6%) patients. Most participants had reduced reflex firmness and limited functioning. Sustained or improved functioning was observed in participants administered 3,4-DAPP. Inconsistent and sporadic functional improvement and regression was observed with 3, 4-DAP and other treatments. Fifty-five treatment-related adverse events (AEs) were reported by 32 (33.3%) participants. Eight (8.3%) participants reported nine treatment-related serious AEs. No new safety signals were identified. == Conclusion == No new safety signals were observed following long-term management of LEMS with 3,4-DAPP. == Supplementary Information == The online version contains supplementary material available at 10.1007/s40120-022-00354-8. Keywords:Amifampridine, LambertEaton myasthenic syndrome, Paraneoplastic, Quality of life, Observational study, Real world, Safety == Important Summary Points == == Introduction == LambertEaton myasthenic syndrome (LEMS) is usually a rare autoimmune disorder that affects 34 in every one million people [1,2]. LEMS can be autoimmune or paraneoplastic in origin, with patients with BRAF inhibitor autoimmune LEMS tending to present in their BRAF inhibitor mid-30s, whereas paraneoplastic LEMS tends to occur in patients in their 50s or 60s, most commonly in conjunction with a diagnosis of small cell lung malignancy (SCLC) [3]. Among patients with SCLC, 0.53% will develop LEMS [4]. LEMS is generally characterized by autoantibodies against presynaptic voltage-gated calcium channels (VGCC; P/Q type) at the neuromuscular junction causing proximal muscle mass weakness, decreased tendon reflexes, and autonomic changes [2,46]. Accordingly, patients with LEMS often present with a multitude of BRAF inhibitor symptoms, including neuromuscular, cranial, and autonomic symptoms, as well as fatigue [4,6,7]. In particular, more than 90% of patients experience lower leg weakness and more than 80% statement general fatigue. First-line treatment of patients with LEMS is designed to improve neurotransmission, while immunosuppressant therapy may be used to reduce anti-VGCC antibody production and activity in patients with an inadequate response to symptomatic therapy [3,8,9]. For example, the potassium channel blocker 3,4-diaminopyridine (3,4-DAP) enhances neurotransmission by prolonging presynaptic depolarization, enhancing calcium transport into the nerve ending [3,4], and is recommended as a first-line treatment for patients with LEMS [8]. Treatment with 3,4-DAP has been shown to improve isometric muscle strength, neurologic disability score, and quantitative myasthenia gravis (QMG) score in patients with LEMS [1012]. Furthermore, 3,4-DAP offers improved symptomatic outcomes compared with the cholinesterase inhibitor pyridostigmine, which may be offered as adjunctive therapy [8,13]. However, 3,4-DAP has generally been provided as a compounded product, which has not met Good Manufacturing Practice requirements for regularity of active ingredient [14]. In contrast, the 3,4-DAP salt 3,4-diaminopyridine phosphate (3,4-DAPP) offers a standardized tablet formulation for treating patients with LEMS that is more stable than 3,4-DAP base [12,15]. 3,4-DAPP has also exhibited efficacy and security for the symptomatic treatment of LEMS in a randomized, placebo-controlled study [16,17]. The European LEMS registry aimed to collate observational security data on treatments offered to patients with LEMS, particularly 3,4-DAPP, which was approved in the year before the registry was initiated [18]. The registry also aimed to examine long-term outcomes for patients with LEMS [18]. This analysis disseminates the final results from a registry study investigating how LEMS is usually managed in a real-world setting with a particular focus on the efficacy and security of BRAF inhibitor 3,4-DAPP, expanding on a preliminary statement of the baseline demographics and clinical characteristics of participants in the European LEMS registry [18]. == Methods == Thirty centers across four countries (Germany, Italy, Spain, and the UK) participated in the non-interventional European LEMS TSPAN9 registry as part of the post-approval monitoring program for 3,4-DAPP. Any individual diagnosed with LEMS by means of clinical assessment and abnormal neurophysiological screening, or clinical assessment and positive result for VGCC antibodies, not participating in a clinical study of 3,4-DAPP, was eligible to participate. Recruitment began on 5 May 2010 and the last patient was enrolled on 2 August 2016. The study was completed in August 2019. Full study methodology and an interim analysis of the baseline characteristics for patients enrolled in the European LEMS registry was published previously (and is available open access) [18]. The protocol, patient information sheet,.