263 The use of 3,4-Diaminopyridine (3,4-DAP) in the management of life-threatening paraneoplastic Lambert Easton Myasthenic Syndrome (LEMS) - A case report

Abstract

Introduction LEMS is a debilitating neuromuscular junction disorder caused by antibodies to P/Q type voltage gated calcium channels (VGCC), which can either be a paraneoplastic or primary autoimmune phenomenon. VGCC antibodies cause a reduction in acetylcholine release from pre-synaptic neurone surfaces, inducing characteristic symptoms such as proximal weakness and diplopia. 3,4-DAP is recommended as first line management for LEMS by the National Organisation for Rare Diseases (NORD), however in the UK it is not routinely commissioned. 1,2. Methods This case report outlines the difficult management of paraneoplastic LEMS, requiring 3,4-DAP, in a patient with lung NET. Results A 56-year-old female presented in late 2023 with a constellation of symptoms including diplopia and dysarthria. Initially these symptoms were attributed to a locally invading glossal tumour and she was discharged with ENT follow-up only. However, in 2024 she was admitted with acute respiratory failure requiring intubation and ventilation. During this admission both LEMS and primary lung NET were diagnosed. This first LEMS crisis was managed with prednisolone, pyridostigmine, intravenous immunoglobulins (IVIG) and one cycle of Carboplatin-Etoposide. However, shortly after discharge she was readmitted with respiratory failure and due to latency of response to IVIG, 3,4-DAP and azathioprine were then added. She rapidly improved and discharge was achieved with prednisolone, 3,4-DAP, pyridostigmine, Azathioprine and domiciliary NIV. Despite her NET progressing through 4 cycles of Carboplatin-Etoposide, the patient has had no significant LEMS crises since starting combination therapy. Conclusions This case of delayed diagnosis and difficult to manage LEMS displays that a combination approach with steroids, steroid sparing agent, IVIG, 3,4-DAP and anticancer treatment should be standard of care for LEMS. Disclosure No significant relationships.