Treatment Of Lambert-Eaton Myasthenic Syndrome Research Articles

Diagnosis and Treatment of Lambert-Eaton Myasthenic Syndrome

Approximately 90% of patients with Lambert-Eaton myasthenic syndrome (LEMS) show positive P/Q-type voltage-gated calcium channels antibodies, which can be broadly classified clinically as paraneoplastic, particularly with small cell lung carcinoma and non-paraneoplastic without cancer. The first Japanese guideline for LEMS was developed in May 2022 as MG/LEMS Practice Guideline 2022. This article describes the epidemiology, symptoms, diagnosis, examination, treatment, and prognosis of this condition, based on the LEMS guidelines.

Pharmacological treatment of Lambert-Eaton Myasthenic Syndrome

Lambert-Eaton myasthenic syndrome (LEMS) is a very rare antibody-mediated autoimmune disease of the neuromuscular junction. Therapy can be divided in symptomatic treatment and immunosuppressive treatment. Symptomatic treatment with amifampridine is the only therapy currently authorized for use in LEMS patients. In the Netherlands the first choice drug is amifampridine base in an extended release formulation instead of the currently authorized amifampridine phosphate. This formulation has lower costs and is possibly safer due to lower peak concentrations. Other therapy used in LEMS patients is prescribed off-label and is based on experience in patients with myasthenia gravis. In many cases pyridostigmine is added as symptomatic treatment. In almost half of patients immunosuppressive therapy is started, mostly corticosteroids with or without azathioprine. Intravenous immunoglobulins and plasma exchange are used as emergency treatment.
 Currently no randomized clinical trials with new therapies are ongoing or announced in patients with LEMS, although multiple new therapies for myasthenia gravis are being investigated. These future therapies can be differentiated in symptomatic and immunomodulating drugs. The immunomodulating drugs can be further differentiated in early stage drugs which target the B-cell, later stage drugs which target the circulating antibodies and targeted therapy which have a disease-specific target. Some early and later stage immunomodulating drugs show promising results in myasthenia gravis although high cost and uncertain long term safety may be limiting for incorporating these drugs in LEMS treatment guidelines.
 Clinical trials in LEMS patients are lacking due to the rarity of the disease and we suggest the following requirements for future trials of potential new treatments: Sufficient power by performing multicenter or n-of-1 trials when appropriate, a cross-over design to reduce the number of patients and using a LEMS-specific quantitative primary outcome measure like the 3TUG score.

An unusual case of delayed recovery from spinal anesthesia in a patient with Lambert-Eaton myasthenic syndrome—a case report

BackgroundThe Lambert-Eaton myasthenic syndrome (LEMS) is a rare disorder characterized by proximal muscle weakness and autonomic dysfunction due to involvement of the neuromuscular junction A case of delayed unilateral recovery from spinal anesthesia in a patient with LEMS undergoing open cholecystectomy is described.Case presentationA 42-year-old lady, on treatment for LEMS with pyridostigmine, prednisolone, and azathioprine presented with cholelithiasis and was scheduled for open cholecystectomy. Neuraxial anesthesia combined with a light plane of general anesthesia provided adequate muscle relaxation without the use of neuromuscular blocking drugs. In spite of perioperative continuation of anticholinesterases, the patient required 12 h post-surgery for complete bilateral motor recovery from spinal anesthesia.ConclusionsA combination of spinal anesthesia with a light plane of general anesthesia appears to be a safe anesthetic technique for managing patients with Lambert-Eaton myasthenic syndrome undergoing open cholecystectomy. However, neurologically asymptomatic patients with good treatment compliance may also show an unusual delay in recovery from neuraxial anesthesia.

Lambert-Eaton Myasthenic Syndrome and Botulism

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. 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. 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.

Amifampridine phosphate (Firdapse)


 CADTH reimbursement reviews are comprehensive assessments of the clinical effectiveness and cost-effectiveness, as well as patient and clinician perspectives, of a drug or drug class.
 The assessments inform non-binding recommendations that help guide the reimbursement decisions of Canada's federal, provincial, and territorial governments, with the exception of Quebec.
 This review assesses amifampridine phosphate (Firdapse), 10 mg oral tablets.
 Indication: For the symptomatic treatment of Lambert-Eaton myasthenic syndrome in adults.

Amifampridine Phosphate (Firdapse)


 CADTH recommends that Firdapse be reimbursed by public drug plans for the treatment of Lambert-Eaton myasthenic syndrome (LEMS) only if certain conditions are met.
 Firdapse should only be covered to treat patients who are 18 years of age and older and have LEMS.
 Firdapse should only be reimbursed if the patient is under the care of a neurologist with expertise in managing LEMS and if the price of Firdapse is reduced.

3,4-diaminopyridine treatment for Lambert-Eaton myasthenic syndrome in adults: a meta-analysis of randomized controlled trials

BackgroundLambert-Eaton myasthenic syndrome (LEMS) is a rare autoimmune disorder of neuromuscular transmission. The objective was to examine the efficacy and safety of 3,4-diaminopyridine (3,4-DAP) in patients with LEMS.MethodsWe searched several databases to identify relevant studies, including PubMed, EMBASE, Web of Science, MEDLINE, Cochrane Neuromuscular Disease Group Specialized Register and the Cochrane Central Register of Controlled Trials(CENTRAL). The primary outcome, quantitative myasthenia gravis (QMG) score and the secondary outcome, compound muscle action potentials (CMAP) amplitude were pooled by meta-analysis.ResultsSix randomised controlled trials (RCTs) involving 115 patients with LEMS were included. QMG score showed a significant decrease (improvement) of 2.76 points (95 % CI, -4.08 to -1.45, p < 0.001) after treatment with 3, 4-DAP. Moreover, the overall mean CMAP amplitude improved significantly in LEMS patients with 3, 4-DAP treatment, compared with placebo treatment (mean difference 1.34 mV, 95 % CI, 0.98 to 1.70, p < 0.001). The overall assessment of all included trials showed a low risk of bias and low heterogeneity.ConclusionsThe pooled results of RCTs demonsrated with moderate to high evidence that 3,4-DAP has a significant effect on LEMS treatment, with improvements in muscle strength score and CMAP amplitude.

Neuromuscular junction disorders beyond myasthenia gravis.

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). 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. 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.

Orphan designation: 3,4-diaminopyridine phosphate (amifampridine), Treatment of Lambert-Eaton myasthenic syndrome

Orphan designation: 3,4-diaminopyridine phosphate (amifampridine), Treatment of Lambert-Eaton myasthenic syndrome

Amifampridine to treat Lambert-Eaton myasthenic syndrome.

Lambert-Eaton myasthenic syndrome (LEMS) is a presynaptic autoimmune disabling neuromuscular disease caused by antibodies against presynaptic voltage-gated calcium channels. It reduces the quantal release of acetylcholine (Ach), causing muscle weakness, reduced or absent reflex and dysautonomia. About half of LEMS patients have associated small cell lung cancer. For symptomatic treatment, amifampridine (3,4-diaminopyridine [3,4-DAP]) is ideal because it increases the release of Ach at the presynaptic membrane. Since the first use of 3,4-DAP in LEMS patients in the 1980s, 136 LEMS patients were treated with amifampridines in the open-label studies and 208 patients in the eight randomized studies. These studies showed that amifampridine is the most effective drug for symptomatic treatment in LEMS. Now, 3,4-DAPP (3,4-DAP phosphate) is approved for adult LEMS patients and 3,4-DAP for pediatric patients. The recommended dose is 80 mg a day, divided 3 or 4 times a day. Side effects are usually mild, and the most frequently reported are paresthesia.

Amifampridine tablets for the treatment of Lambert-Eaton myasthenic syndrome

ABSTRACTIntroduction: Lambert-Eaton myasthenic syndrome is an autoimmune disease of the neuromuscular junction characterized by a presynaptic defect of neuromuscular transmission resulting in muscle weakness and fatigability. Diagnostic features are specific neurophysiological alterations and autoantibody detection. The present review is focused on the use of Amifampridine Phosphate to treat LEMS patients.Areas covered: Medline search from 1990 to 2019 was examined using the free subject terms: Lambert-Eaton myasthenic syndrome, LEMS, Amifampridine, 3,4-diaminopyridine, which were then combined with Treatment, Therapy, Clinical Trial, Controlled Clinical Trial, Randomized Clinical Trial and Cochrane Review. The author has done a supervised analysis of the retrieved articles and focused on those subjectively evaluated as most relevant.Expert commentary: Data from randomized clinical trials and case series have demonstrated that Lambert-Eaton myasthenic syndrome symptoms were successfully treated by Amifampridine Phosphate. Hence, the drug represents a substantial step forward in the symptomatic treatment of the disease due to its efficacy, safety and reliable GMP formulation. As Amifampridine Phosphate works by enhancing the release of acetylcholine at the neuromuscular junction by blocking K+ efflux at the pre-synaptic membrane, it is also conceivable to use it for other diseases of the neuromuscular junction in which such an effect is searched for.

Lambert-Eaton myasthenic syndromes

Lambert Eaton Myasthenic Syndrome (LEMS) is a rare disorder of the neuromuscular junction characterized by a presynaptic defect in neuromuscular transmission. It can either be paraneoplastic in about half of the cases, or a primary autoimmune disease. It is caused by autoantibodies directed against the P/Q type voltage gated calcium channels (VGCC), which results in reduced influx of calcium during depolarization, interfering with the calcium dependent release of acetylcholine in the synaptic cleft. LEMS is usually a disease of adults, with the clinical features of weakness, more so in the lower limbs but also affecting upper limbs, hypo or areflexia, and autonomic dysfunction such as dry mouth. Besides the typical clinical features, the diagnosis is dependent on electrodiagnostic findings, characterized by low compound muscle action potentials (CMAP) with prominent post exercise potentiation, a CMAP amplitude decrement on low frequency repetitive stimulation, but with an increment on high frequency repetitive stimulation. Serum anti-P/Q-type VGCC can be detected in about 50% of cases. However, about 90% of paraneoplastic LEMS cases associated with small cell lung cancer (SCLC), test positive for the antibody. Sixty-four percent of LEMS patients with SCLC also test positive for antibodies against SOX1, which may play a role as an early marker for predisposition to LEMS/SCLC. Anti- SOX1 antibodies are 95% specific and about 65% sensitive for LEMS with SCLC. Once LEMS is diagnosed, the patient should be screened for cancer. If cancer is not detected initially, the patient should continue to be screened every 3 to 6 months for at least two years. Treatment of LEMS consists of treating the primary cancer in paraneoplastic cases. The drug of choice for symptomatic treatment of LEMS is 3,4- diaminopyridine. Immunosuppressive therapy with azathioprine and corticosteroids might be helpful in patients who do not respond to symptomatic treatment.

Amifampridine for the treatment of Lambert-Eaton myasthenic syndrome

ABSTRACT Introduction: The present status of amifampridine (AFP) for the treatment of Lambert-Eaton myasthenic syndrome (LEMS) is reviewed. Areas covered: All relevant literature identified through a PubMed search under treatment of LEMS, aminopyridine, and amifampridine are reviewed. An expert opinion on AFP was formulated. Expert opinion: 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.

Pharmacokinetics and tissue distribution of 3,4-diaminopyridine in rats.

Lambert-Eaton myasthenic syndrome (LEMS) is characterized by muscle weakness, amyotrophy, easy fatigability, and depressed tendon reflexes. 3,4-Diaminopyridine (3,4-DAP) is the recommended therapy for the treatment of LEMS. However, estimations of 3,4-DAP pharmacokinetics in human and animals, such as rats, are rarely reported because 3,4-DAP is an orphan drug for the treatment of a very rare disease (LEMS). In particular, little is known about its tissue distribution. Therefore, the pharmacokinetics of 3,4-DAP were studied, with particular focus on tissue distribution, in rats. After intravenous administration of 3,4-DAP to rats, the half-life of 3,4-DAP was 15.9±3.9min and the volume of distribution at steady-state was 2.8±0.7L/kg. The tissue-to-plasma partition coefficient (Kp) was high in the kidney, heart, and muscle. In addition, with increased steady state plasma concentration (Css), a tendency toward increased Kp was found in most tissues. In the muscle, a likely target region of 3,4-DAP in LEMS patients, the Kp was higher than in the plasma. Furthermore, more than 68% of 3,4-DAP was distributed to the muscle as determined by the ratio of 3,4-DAP distribution calculated from the apparent volumes of distribution. Hence, 3,4-DAP may provide for more effective and long-lasting effects.

Amifampridine for the Management of Lambert-Eaton Myasthenic Syndrome: A New Take on an Old Drug.

Objective: 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. Data Sources: PubMed, TRIP database, and EMBASE searches were conducted without a back date (current to June 2019) utilizing the following search terms: amifampridine, 3,4-diaminopyridine, and Lambert-Eaton myasthenic syndrome. Completed trials were also reviewed at clinicaltrials.gov. Study Selection and Data Extraction: 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. Data Synthesis: 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. Relevance to Patient Care and Clinical Practice: With an improved stability profile and decreased dose variability, amifampridine will likely assume the role of first-line management of LEMS. Conclusions: Amifampridine has been shown to improve symptoms of LEMS and is generally well tolerated.

FDA approves first treatment for Lambert-Eaton myasthenic syndrome, a rare autoimmune disorder

FDA approves first treatment for Lambert-Eaton myasthenic syndrome, a rare autoimmune disorder

P/Q-type Calcium Channel Antibodies in Lambert-Eaton Myasthenic Syndrome

Lambert-Eaton myasthenic syndrome (LEMS) is an autoimmune disease of the neuromuscular junction. Approximately 50-60% of patients with LEMS have a tumor, most often small cell lung cancer (SCLC), making LEMS a paraneoplastic neurological syndrome. In Japan, the clinical picture is a male: female ratio of 3:1; mean age, 62 years (17-80 years); and 61% of LEMS patients have SCLC (SCLC-LEMS), with the remainder of patients having no cancer. Patients with LEMS develop a unique set of clinical characteristics, which include proximal muscle weakness, depressed tendon reflexes with post-tetanic potentiation, and autonomic symptoms. Interestingly, less than 10% of patients with LEMS have cerebellar ataxia (LEMS with paraneoplastic cerebellar degeneration). Considering its pathomechanisms, LEMS is a presynaptic disorder of neuromuscular transmission in which quantal release of acetylcholine is impaired by autoantibodies against P/Q-type voltage-gated calcium channels (P/Q-VGCCs) at active zones reducing quantal release of acetylcholine, although an animal model using immunization with purified P/Q-VGCCs has not yet been established. The diagnosis can be confirmed by finding a reduced compound muscle action potential amplitude that increases by over 60% following maximum voluntary activation or 50 Hz nerve stimulation. Approximately 90% of patients who satisfy the above electrophysiological diagnostic criteria are positive for P/Q-VGCC antibodies have their diagnosis confirmed. Specific tumor therapy in SCLC-LEMS will often improve the neurologic deficit. Tumor removal is the primary treatment for LEMS. If primary tumor screening is negative, screening should be repeated after 3-6 months, followed by screening every 6 months until 2 years post diagnosis. Most patients benefit from 3,4-diaminopyridine being administered with pyridostigmine. In those with severe weakness, high-dose intravenous gamma-globulin (IVIg) or plasmapheresis confers short-term benefits. Prednisone, alone or combined with immunosuppressive drugs, can achieve long-term control of the disorder. The results of a prospective cohort study showed that the presence of LEMS with SCLC had a significant survival advantage independent of other prognostic factors including disease extent, age, sex, performance status, and serum sodium values.

A retrospective study of the effects of 3,4-diaminopyridine treatment in Lambert-Eaton myasthenic syndrome

In this independent clinical study, we analyzed retrospectively the clinical features of 9 cases (6 male and 3 female) of Lambert-Eaton myasthenic syndrome that were administered 3,4-diaminopyridine (3,4-DAP). Four cases showed no cancer and 5 cases had small cell lung carcinoma. Seven cases were positive for anti voltage-gated calcium channel antibodies. Activities of daily living (ADL) were improved by 3,4-DAP in 8 cases that showed mainly weakness of the extremities, but did not improve ADL in 1 case with cerebellar ataxia of paraneoplastic cerebellar degeneration (PCD). Seven cases showed autonomic symptoms, and 6 cases were improved with 3,4-DAP. The maintenance dose varied widely among individuals, with a single dose ranging from 10 to 40 mg. Each patient was prescribed a maintenance dose 3 to 7 times a day. The daily dosage ranged from 36 to 100 mg. Two cases showed adverse effects to the treatment. Of those 2 cases, 1 case treated at 45 mg/day discontinued treatment, but another case treated at 100 mg/day reduced the dosage and continued treatment. The administration period was 1 to 149 months. Three cases have continued 3,4-DAP for more than 10 years. Four cases have discontinued 3,4-DAP, with 2 cases discontinuing due to death, 1 case discontinuing due to progression of cancer, and 1 case discontinuing due to an adverse reaction. Our results suggest that 3,4-DAP treatment is effective for weakness and autonomic symptoms, but may be ineffective for ataxia of PCD. Treatment with 3,4-DAP can be tolerated for a long period, but the optimal dosage varies widely among individuals.

Too Weak to Breathe: An Odd Case of Lambert Eaton Myasthenic Syndrome

SESSION TITLE: Critical Care 3 SESSION TYPE: Affiliate Case Report Poster PRESENTED ON: Tuesday, October 31, 2017 at 01:30 PM - 02:30 PM INTRODUCTION: Lambert Eaton Myasthenic Syndrome (LEMS) is a rare autoimmune disorder of the neuromuscular junction characterized by the presence of antibodies against voltage gated calcium channels (VGCC) often associated with an underlying neoplasm. CASE PRESENTATION: 52 year old Caucasian female was admitted to an outside hospital with lethargy, shortness of breath and was intubated for acute hypercapnic respiratory failure which ultimately resolved and she was extubated. Her discharge diagnosis was presumed obstructive sleep apnea. Three weeks later she presented to our hospital with the same symptoms. Physical exam was significant for diminished breath sounds bilaterally and musculoskeletal exam was normal on presentation. Arterial blood gas was 7.26/79/118/35 after 30 minutes on non-invasive positive pressure ventilation, prompting intubation. On the ventilator she was awake and alert without sedation, but failed repeated breathing trials due to apnea, low tidal volumes and a negative inspiratory force of -10 cmH2O. Her persistant, profound and unexplained respiratory muscle weakness, raised concerns for a neuromuscular disorder and neurology was consulted. Electromyogram and nerve conduction studies revealed a post exercise increase in compound muscle action potential response > 200%, her VGCC antibodies were positive and acetylcholine receptor antibodies were negative. Computerized Tomography of the chest demonstrated a right suprahilar mass with a paratracheal lymph node which was hypermetabolic on Positron Emission Tomography. Endobronchial Ultrasound with biopsy of the lymph node confirmed small cell lung carcinoma. She was treated with pyridostigmine and plasma exchange with excellent response and was extubated several days later. She received three cycles of etoposide, cisplatin, chest radiation and is currently on mestinon and 3,4 diaminopyridine for her LEMS. DISCUSSION: LEMS classically presents as proximal muscle weakness, autonomic dysfunction and areflexia. Respiratory failure is a common primary manifestation of Myasthenia Gravis, however the literature rarely documents LEMS as presenting this way. This case highlights the importance of considering occult neuromuscular diseases in cases of unexplained respiratory failure even if other classical symptoms such as muscle weakness are absent. Our patient had repeated episodes of respiratory failure requiring intubation that was initially misdiagnosed, leading to missed treatment opportunities, a poor quality of life and an unchecked pulmonary malignancy. CONCLUSIONS: LEMS often presents early in the neoplastic course, thus diagnosis has important implications. Treatment of LEMS can be effective in relieving the neuromuscular symptoms and early detection of the underlying malignancy can be lifesaving. Reference #1: Fatima. U., Shah. T., Dedhia.P., Devine. S., Lambert Eaton Syndrome: Unique Presentation of the Disease with Isolated Respiratory Muscle Weakness. CHEST. Abstract 326A. October 2013. DISCLOSURE: The following authors have nothing to disclose: Caryn Brehm, Christopher Barrios, James Caress, Daniel Files, Daniel LoVerde No Product/Research Disclosure Information

Establishing a relationship between EQ-5D-5L and QMG in patients with Lambert-Eaton myasthenic syndrome

Background: Lambert-Eaton myasthenic syndrome (LEMS) is a rare presymptomatic disorder of neuromuscular transmission in which quantal release of acetylcholine is impaired, causing clinical characteristics including proximal muscle weakness, depressed tendon reflexes, post-tetanic potentiation, and autonomic changes, impacting a patient’s quality of life. LEMS is a para-neoplastic syndrome in 40-50% of patients, but can present in the absence of any underlying tumour. In Europe, Amifampridine (3,4-diaminopyridine) phosphate (Firdapse®) has been the only licensed treatment for LEMS since 2009.