The European Lambert–Eaton Myasthenic Syndrome Registry: Long-Term Outcomes Following Symptomatic Treatment

Abstract

Introduction Lambert–Eaton myasthenic syndrome (LEMS) is characterized by autoantibodies against voltage-gated calcium channels (VGCC) at the neuromuscular junction causing proximal muscle weakness, decreased tendon reflexes, and autonomic changes. The European LEMS registry aimed to collate observational safety data for 3,4-diaminopyridine phosphate (3,4-DAPP) and examine long-term outcomes for patients with LEMS. Methods Thirty centers across four countries participated in the non-interventional European LEMS registry. Any patients diagnosed with LEMS by means of clinical assessment and abnormal neurophysiological testing, or clinical assessment and positive for VGCC antibodies were eligible to participate. Patients were monitored using standard assessments for LEMS-related clinical manifestations. Results Among 96 evaluable participants, 50 (52.1%) were being treated with 3,4-DAPP, 21 (21.9%) with 3,4-diaminopyridine (3,4-DAP), and 25 (26.0%) with other treatments (e.g., pyridostigmine, corticosteroids, immunoglobulins, and azathioprine); 74 participants (77.1%) were exposed to 3,4-DAPP at any time. Quantitative myasthenia gravis scores were similar across treatment groups. Muscle strength was generally good and maintained during follow-up. Cerebellar ataxia, defined as a negative Romberg’s test and at least one other positive ataxia test, was observed in 30 (56.6%) patients. Most participants had reduced reflex tone 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.

Burden of disease in Lambert-Eaton myasthenic syndrome: taking the patient’s perspective

“…One symptom that may possibly be more common than previously reported in LEMS is ataxia. A recent study found clinical signs of cerebellar ataxia in more than half of SP (56.6%) [ 24 ]. Unfortunately, asking patients for signs of ataxia may be prone to errors as diagnosis in clinical practice is generally based on neurological examination.…”

“…Overinterpretation must be avoided especially where participant answers were missing and had to be imputed. Gender distribution was weighted; however, more women than would have been expected from epidemiological data were in this cohort [ 19 , 24 ]. Mean age of onset at 51.9 years was slightly lower than in previous publications that reported age of onset between 55 and 60 years [ 1 , 24 , 42 ].…”

“…Gender distribution was weighted; however, more women than would have been expected from epidemiological data were in this cohort [ 19 , 24 ]. Mean age of onset at 51.9 years was slightly lower than in previous publications that reported age of onset between 55 and 60 years [ 1 , 24 , 42 ]. Importantly, for LEMS, it is possible that patients suffering from an aggressive malignant disease such as SCLC are underrepresented.…”

“…Epidemiological studies estimate LEMS to be associated to carcinoma in up to 60% of cases [ 36 ]. For paraneoplastic LEMS (pLEMS) small cell lung cancer (SCLC) is the leading tumour entity, however further tumours have been described to be associated with LEMS including Merkel cell carcinoma, neuroendocrine tumours, prostate cancer and lymphomas [ 24 , 40 ]. Therapeutic options for LEMS encompass 3,4-diaminopyridine (3,4-DAP) or 3,4-diaminopyridine phosphate (3,4-DAPP) as first-line options [ 24 ] as well as acetylcholinesterase inhibitors and immunosuppressive agents also commonly used in treatment of myasthenia gravis (MG) [ 35 ].…”

Myasthenia Gravis and Lambert-Eaton Myasthenic Syndrome: New Developments in Diagnosis and Treatment

“…Oral agents including prednisone and azathioprine, as well as immune modulators such as IVIg and rituximab and in some cases antibody removal with plasma exchange are all utilized in patients having limited benefit from amifampridine. 58 , 63 , 64 …”