In 1983, the first successful trial of 3,4-diaminopyridine (3,4-DAP) in Lambert-Eaton myasthenic syndrome (LEMS) was reported. Efficacy of amifampridine (3,4-DAP and 3,4-diaminopyridine phosphate [3,4-DAPP]) for symptomatic treatment in LEMS was proven by seven randomized studies in 3,4-DAP and two randomized studies in 3,4-DAPP. US Food Drug Administration approved 3,4-DAPP usage for adult LEMS in 2018 and for pediatric LEMS in 2022. Nineteen pediatric LEMS cases were identified in the literature. Compared with adult LEMS, the rate of malignancy is low as expected and the rate of dysautonomia is also low in pediatric LEMS. Unexpected finding is two cases of pediatric LEMS following antecedent infection. Amifampridine can be safely used as long the daily dose is less than 80 mg a day for adult LEMS patients and less than 30 mg a day for pediatric LEMS patients. Amifampridines can be supplemented with a liberal amount of pyridostigmine for long term usage. Amifampridine was used as symptomatic treatment in eight (42%) of 19 pediatric LEMS patients: 3,4-DAP in six and 3,4-DAPP in two patients. The most common practice of 3,4-DAP was a combination with pyridostigmine in four patients. With 3,4-DAP, normal activity was reported in 3 cases and mild to moderate-improvement in other 3 cases. In two patients with 3,4-DAPP, significant improvement in one and no improvement in one. Amifampridines are proven to be effective and safe drugs for the symptomatic treatment without serious side reaction in adults as well as in children as long as the dosage is properly adhered.

BACKGROUND: Lambert-Eaton myasthenic syndrome (LEMS) is an ultrarare neuromuscular disease with a triad of symptoms: muscle paresis, dysautonomy, and areflexia. Amifampridine is the symptomatic treatment of LEMS.
OBJECTIVE: To assess the effectiveness and safety of treatment in the real world.
METHODS: 14 patients with non-neoplastic LEMS treated with amifampridine were enrolled in the study (female 42.9%, mean age 48.8 ± 11.4 years). The patients were assessed using the Quantitative Myasthenia Gravis (QMG) scale, QMG limb domain (LD) score, spirometry, Hand Grip Strength (GRIP) test, and repetitive nerve stimulation study (RNS) at baseline and at the end of follow-up. Diagnostic delay since first symptoms was from seven months up to 22 years. Treatment delay ranged from one to 26 years. The patients were treated and reevaluated after 21.1 ± 12.0 weeks (range 13-48).
RESULTS: All of the patients improved in QMG score. Mean improvement was 5.1 ± 2.0 (range 1-8) points (p < 0.001) and this showed no correlation with the duration of the disease before treatment (p = 0.477). 85.7% of patients (N = 12) improved ≥ 3 points (clinically meaningful) in QMG. 78.6% of the patients improved in QMG LD (mean 2.2 ± 1.6 points (p < 0.001)). Also, forced vital capacity (FVC) improved after treatment (p = 0.031). Mean improvement in GRIP test was 7.0 ± 7.1 kg in the right hand and 5.2 ± 7.5 kg in the left hand (p < 0.001). In RNS before treatment, facilitation ( > 100%) was observed in 78.6% (N = 11) of patients, and was higher before treatment (p < 0.001). Compound muscle action potential (CMAP) amplitude was higher after treatment (p < 0.001). Mean increase of CMAP amplitude was 2.1 ± 1.6 times. In 64.3% (N = 9) of patients lowering of corticosteroid dose was achieved.
CONCLUSIONS: Amifampridine is an effective treatment in non-neoplastic LEMS patients, regardless of disease duration. The treatment is well-tolerated and allows to reduce dose of corticosteroids in the majority of patients.

Lambert-Eaton myasthenic syndrome (LEMS) is an autoimmune neuromuscular disorder caused by pathogenic autoantibodies directed against voltage-gated calcium channels present on the presynaptic nerve terminal. For LEMS patients refractory to initial symptomatic treatment with amifampridine, immunomodulatory therapy with intravenous immunoglobulin (IVIG) is often utilized. However, in the authors\' review of literature, the utility of subcutaneous immunoglobulin (SCIG) in the treatment of LEMS has been scarcely reported. Here, we present a unique case of non-paraneoplastic LEMS managed with SCIG with excellent clinical response and improvement on electromyography. SCIG therapy may be a reasonable alternative for patients with LEMS who do not tolerate the intravenous formulation.

Lambert-Eaton myasthenic syndrome (LEMS) is a rare neuromuscular junction disorder due to auto-antibodies against presynaptic voltage-gated calcium channels (VGCC). The typical manifestation of LEMS is proximal muscle weakness, autonomic dysfunction, and areflexia; however, an atypical manifestation of LEMS is weakness of respiratory muscles, leading to acute respiratory failure. Herein, we describe a case of acute respiratory failure resulting from LEMS. Our patient was a 63-year-old woman with a past medical history of metastatic small cell lung cancer (SCLC) who presented with ambulatory dysfunction, dysarthria, and progressive dyspnea. She was intubated because of hypoxia and developed acute respiratory failure without a clear pulmonary etiology, raising the suspicion of a neuromuscular junction disorder. She was diagnosed with LEMS with a positive paraneoplastic panel for VGCC antibodies, confirmed by electromyography and nerve conduction study (EMG/NCS), and treated with intravenous immunoglobulin (IVIg). The patient\'s hospital stay was complicated by pneumonia, and comfort care was ultimately pursued. Our case highlights the importance of considering LEMS in patients presenting with isolated respiratory muscle weakness without focal neurological deficits. To our knowledge, this is the first report to review all reported cases of LEMS with resultant respiratory failure. We aim to establish the association of LEMS with respiratory failure so that appropriate treatment is initiated as early as possible.

Lambert-Eaton myasthenic syndrome (LEMS), an autoimmune disorder that affects the neuromuscular junction, is characterized by proximal muscle weakness, reduction of tendon reflexes, and autonomic dysfunction. LEMS shows a prevalence of approximately 0.25-0.27 per 100,000 population. The characteristic muscle weakness observed in patients with LEMS is attributed to the role of pathogenic autoantibodies directed against voltage-gated calcium channels (VGCC) present on the presynaptic nerve terminal. Notably, 50-60% of patients with LEMS have an associated tumor, small-cell lung carcinoma (SCLC), which also expresses functional voltage-gated calcium channels (VGCC). The Japanese LEMS diagnostic criteria 2022 recommend documentation of typical electrophysiological abnormalities combined with myasthenic symptoms for accurate diagnosis. P/Q-type VGCC antibody positivity strongly supports the diagnosis. Treatment options are categorized as oncological treatment, immunotherapy, and symptomatic treatments. Effective treatment of the tumor can improve LEMS in patients with SCLC. Most patients benefit from 3,4-diaminopyridine administration for symptomatic treatment. A treatment algorithm is established by the clinical practice guidelines 2022.

Myasthenia gravis (MG) and Lambert-Eaton myasthenic syndrome (LEMS) are autoimmune disorders affecting neuromuscular transmission. Their combined occurrence is rare, and treatment remains challenging. Two women diagnosed with concomitant MG/LEMS experienced severe, increasing disease activity despite multiple immunotherapies. Anti-CD19 chimeric antigen receptor (CAR) T cells have shown promise for treating autoimmune diseases. This report details the safe application of anti-CD19 CAR T cells for treating concomitant MG/LEMS. After CAR T cell therapy, both patients experienced rapid clinical recovery and regained full mobility. Deep B cell depletion and normalization of acetylcholine receptor and voltage-gated calcium channel N-type autoantibody levels paralleled major neurological responses. Within 2 months, both patients returned to everyday life, from wheelchair dependency to bicycling and mountain hiking, and remain stable at 6 and 4 months post-CAR T cell infusion, respectively. This report highlights the potential for anti-CD19 CAR T cells to achieve profound clinical effects in the treatment of neuroimmunological diseases.

3,4-Aminopyridine or Amifampridine belongs to the aminopyridine class of drugs which is used to treat multiple sclerosis and Lambert-Eaton Myasthenic Syndrome (LEMS). Aminopyridine pharmaceuticals inhibit presynaptic potassium channels. This increases available acetylcholine in the nerve cleft which leads to improved strength in this patient population. While overdoses have been reported of 4-Aminopyridine, no case reports of acute 3.4-Aminopyridine overdose are currently available. A 67 year old man presented to the emergency department 30 min after ingesting 100 mg of amifampridine in a suicide attempt. Within an hour of ingestion he experienced tachycardia, tachypnea, hypertension and tremor. The patient then started to experience seizures and had a cardiac arrest 3 h after the ingestion. The patient achieved return of spontaneous circulation but proceeded to have refractory seizures. Despite significant and escalating doses of anti-epileptic medications, the patient continued to have seizures until 18 h after ingestion. His anti-epileptic medications were weaned over the following days and he had no more seizures. This is a report of a novel overdose of 3,4-Aminopyridine, a medication that belongs to the aminopyridine class of pharmaceuticals that have been well used for many years. Aminopyridine overdoses are commonly thought to carry low morbidity and mortality; however, our patient had both a cardiac arrest and refractory status epilepticus. Ultimately, this case suggests that patients who overdose on 3,4-Aminopyridine could become critically ill and their presentation may be far more severe than that of other medications of the same class.

A 79-year-old woman who presented ptosis and dysphagia were admitted to our hospital. Anti-acetylcholine receptor antibodies and anti-P/Q-type VGCC antibodies were both positive. Electrophysiological examination showed postsynaptic pattern which supported myasthenia gravis. She did not meet the diagnostic criteria for Lambert-Eaton myasthenic syndrome (LEMS). In cases which these antibodies coexist, careful electrophysiological evaluation is required for the diagnosis. In addition, although anti-P/Q-type VGCC antibodies have been specific to LEMS, patients with these antibodies represent various symptoms other than LEMS. Low and middle titer of the antibodies may be not specific to LEMS.

Lambert-Eaton myasthenic syndrome (LEMS) is a rare paraneoplastic neurological syndrome of the neuromuscular transmission. The symptoms often progress slowly and can be misdiagnosed in early stage. Seropositive SOX-1 antibodies are support for the diagnosis of LEMS and have high specificity for small cell lung cancer (SCLC). In this paper, we report a case of a 56-year-old man with smoking history who was admitted to hospital with progressive muscle weakness of the proximal legs. LEMS was diagnosed by repetitive nerve stimulation (RNS) testing and seropositive SOX-1 antibodies. Primary screening with chest computed tomography (CT) and integrated PET/CT did not reveal any tumor. After continuous follow-up, SCLC was found by chest CT and confirmed with pathological examination 10 months after the diagnosis of LEMS. Long-term follow-up and screening for occult SCLC in LEMS patients with positive SOX-1 antibodies are very important.

Treatment strategies in paraneoplastic neurological syndromes rely on the three pillars of tumor treatment, immunotherapy, and symptomatic treatment, the first one being by far the most important in the majority of patients and syndromes. Classically, antibodies against extracellular antigens are directly pathogenic, and patients with these syndromes are more responsive to immunomodulatory or immunosuppressive treatments than the ones with antibodies against intracellular targets. This chapter first discusses some general principles of tumor treatment and immunotherapy, followed by a closer look at specific treatment options for different clinical syndromes, focusing on symptomatic treatments.