Search Our Scientific Publications & Authors

J Chemother 2022 May 13:1-6. Epub 2022 May 13.

Division of Medical Oncology-Hematology, Department of Internal Medicine, Kyung Hee University Hospital, Kyung Hee University College of Medicine, Seoul, Korea.

Pembrolizumab is an immune checkpoint inhibitor (ICI) against the programmed death-1 receptor. Herein, we introduce a rare adverse effect during using pembrolizumab. We present the case of an 80-year-old man with biopsy-proven unresectable double primary squamous cell carcinoma and large cell neuroendocrine carcinoma of the lung. Read More

Neurol Ther 2022 May 5. Epub 2022 May 5.

Service Système Nerveux Périphérique et Muscles, Centre Hospitalier Universitaire de Nice, Université Côte d'Azur, Nice, France.

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. Read More

Muscle Nerve 2022 May 4. Epub 2022 May 4.

Department of Neurology, the First Medical Centre, Chinese PLA General Hospital, Beijing, China.

Introduction/aims: Lambert-Eaton myasthenic syndrome (LEMS) is an autoimmune neuromuscular junction disorder. Long non-coding RNA (LncRNA) can regulate the expression of mRNA and is involved in the development of autoimmune diseases, but few genetic studies are available. This study aimed to explore the lncRNA and mRNA changes of LEMS. Read More

Cells 2022 Mar 29;11(7). Epub 2022 Mar 29.

Department of Kinesiology & Health Sciences, College of William & Mary, Williamsburg, VA 23187, USA.

Aging is associated with gradual degeneration, in mass and function, of the neuromuscular system. This process, referred to as "sarcopenia", is considered a disease by itself, and it has been linked to a number of other serious maladies such as type II diabetes, osteoporosis, arthritis, cardiovascular disease, and even dementia. While the molecular causes of sarcopenia remain to be fully elucidated, recent findings have implicated the neuromuscular junction (NMJ) as being an important locus in the development and progression of that malady. Read More

Neurol Sci 2022 Apr 7. Epub 2022 Apr 7.

Neurology Unit, Azienda Ospedaliero-Universitaria Di Modena, Modena, Italy.

Background And Aims: Antibodies against SOX1 (or anti-glial nuclear antibody, AGNA) are partially characterized onconeural antibodies, firstly described in association with small cell lung cancer (SCLC). Lambert-Eaton myasthenic syndrome is the most frequent paraneoplastic syndrome (PNS) found in patients with anti-SOX1-antibody positivity. Other associations are chronic axonal polyneuropathy, paraneoplastic limbic encephalitis, and paraneoplastic cerebellar degeneration. Read More

BMC Neurol 2022 Mar 19;22(1):106. Epub 2022 Mar 19.

Department of Neurology, the First Medical Centre, Chinese PLA General Hospital, Beijing, China.

Background: Lambert-Eaton myasthenic syndrome (LEMS) is a type of paraneoplastic syndrome that may initially manifest itself with proximal weakness and gait abnormalities. Approximately up to 50% of LEMS patients have a primary autonomic dysfunction.

Case Presentation: We present here a case of a 75-year-old male with symmetric proximal muscle weakness, dry mouth and constipation. Read More

BMJ Case Rep 2022 Feb 28;15(2). Epub 2022 Feb 28.

Department of Neurology, Yale-New Haven Hospital, New Haven, Connecticut, USA.

Lambert-Eaton Myasthenic Syndrome (LEMS) is a neuromuscular junction defect that results in weakness. It is rarely seen in children and most commonly is associated with small-cell lung cancer. Diagnosis of LEMS requires characteristic electromyogram (EMG) findings and the detection of antibodies directed against voltage-gated calcium channels. Read More

Lancet Neurol 2022 02;21(2):189-202

Department of Medicine, University of Toronto, Toronto, ON, Canada.

Myasthenia gravis and Lambert-Eaton myasthenic syndrome are antibody-mediated autoimmune diseases of the neuromuscular junction that usually present with weakness in ocular muscles and in proximal muscles of the limb and trunk. Prognosis regarding muscle strength, functional abilities, quality of life, and survival is generally good. However, some patients do not respond to treatment. Read More

Lancet Neurol 2022 02;21(2):176-188

Department of Neurology, Catholic University, Rome, Italy.

Autoimmune neuromuscular junction disorders are rare. However, myasthenia gravis is being increasingly recognised in people older than 50 years. In the past 5-10 years, epidemiological studies worldwide suggest an incidence of acetylcholine receptor antibody-positive myasthenia gravis of up to 29 cases per 1 million people per year. Read More

BMJ Case Rep 2022 Jan 13;15(1). Epub 2022 Jan 13.

Gastroenterology Department, Stoke Mandeville Hospital, Aylesbury, UK.

An 81-year-old woman presented with neck weakness, dysarthria, dysphasia and left-sided ptosis. Myasthenia gravis (MG) was strongly suspected. Voltage gated calcium channel (VGCC) antibodies, associated with Lambert-Eaton myasthenic syndrome (LEMS), were negative. Read More

Curr Opin Neurol 2021 10;34(5):648-657

Department of Neurology, University of Alabama at Birmingham, Birmingham, Alabama, USA.

Purpose Of Review: 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).

Recent Findings: 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. Read More

Intern Med 2021 Oct 26. Epub 2021 Oct 26.

Department of Respiratory Medicine, Thoracic Oncology Center, Nagoya City University West Medical Center, Japan.

We herein report a 74-year-old man who developed Lambert-Eaton myasthenic syndrome (LEMS) during atezolizumab treatment for extensive-stage small-cell lung cancer. He was started on maintenance immunotherapy with atezolizumab every three weeks after four cycles of atezolizumab plus carboplatin plus etoposide combination therapy. After 13 cycles of maintenance atezolizumab therapy, he complained of muscular weakness and fatigue. Read More

Clin Pathol 2021 Jan-Dec;14:2632010X211051741. Epub 2021 Oct 11.

Tecnologico de Monterrey, Escuela de Medicina y Ciencias de la Salud, Monterrey, México.

Lambert-Eaton syndrome is a rare paraneoplastic disorder of the neuromuscular junction, characterized by impaired release of acetylcholine, which causes proximal muscle weakness, depressed tendon reflexes, and autonomic changes. Most cases of Lambert-Eaton syndrome present in small-cell lung carcinoma, and only a few cases have been reported in other lung subtypes. Herein, we report a case of 69 years old male patient with Lambert-Eaton syndrome as a rare association with a pulmonary large-cell neuroendocrine carcinoma, which presented 5 months before neoplasm diagnosis. Read More

Clin Lung Cancer 2022 May 17;23(3):e273-e275. Epub 2021 Sep 17.

Matsusaka Municipal Hospital, Respiratory Center, Japan.

Asian Cardiovasc Thorac Ann 2021 Oct 4:2184923211051796. Epub 2021 Oct 4.

Faculté de Médecine et de Pharmacie, 97980Université Mohammed V, Rabat Morocco.

We report a very rare case of cT1N0M0 lung adenocarcinoma reveling Lambert-Eaton myasthenic syndrome (LEMS). A 69-year-old nonsmoking woman, with several comorbidities consulted for cough and dyspnea. Chest radiograph and CT scanning detected a left lower lobe mass; Needle biopsy confirmed differentiated adenocarcinoma; 18FDG-PET scan and Brain MRI eliminated metastatic disease dissemination. Read More

BMC Neurol 2021 Sep 25;21(1):371. Epub 2021 Sep 25.

Department of Neurosurgery, the First Affiliated Hospital of Nanchang University, No.17, Yongwai Street, Jiangxi Province, 330006, Nanchang, China.

Background: Lambert-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.

Methods: We 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). Read More

Curr Neuropharmacol 2022 Mar;20(3):594-610

Department of Molecular Pharmacology, Albert Einstein College of Medicine Forchheimer 209 1300 Morris Park Avenue, Bronx, NY 10461.

Neuromuscular junction (NMJ) disorders result from damage, malfunction or absence of one or more key proteins involved in neuromuscular transmission, comprising a wide range of disorders. The most common pathology is antibody-mediated or downregulation of ion channels or receptors, resulting in Lambert-Eaton myasthenic syndrome, myasthenia gravis, and acquired neuromyotonia (Isaac's syndrome), and rarely congenital myasthenic syndromes caused by mutations in NMJ proteins. A wide range of symptomatic treatments, immunomodulating therapies, or immunosuppressive drugs have been used to treat NMJ diseases. Read More

Acta Neurol Taiwan 2021 Jun;30(2):74-77

Department of Neurology, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan.

Purpose: Paraneoplastic neurological disorders associated with autoantibodies are rare diseases, causing abnormal manifestations in the central or peripheral nervous system separately or simultaneously. Early recognizing the occurrence of paraneoplastic syndrome can lead to prompt and effective management.

Case Report: We presented a patient of subacute cerebellar degeneration with cachectic and bed-ridden status, who was proven to have positive SOX1 antibody. Read More

Intern Med 2022 Apr 18;61(7):1063-1065. Epub 2021 Sep 18.

Medical Engineering Course, Department of Engineering, The Faculty of Engineering, Nagasaki Institute of Applied Science, Japan.

We herein report two P/Q-type voltage-gated calcium channel (VGCC) antibody-positive Lambert-Eaton myasthenic syndrome (LEMS) patients who responded dramatically to cholinesterase inhibitors. Patient 1, a 76-year-old man, had small-cell lung cancer and developed LEMS during chemotherapy. When symptomatic treatment was started with pyridostigmine, gait disturbance was ameliorated, and his modified Rankin scale decreased from 4 points to 3 points. Read More

Clin Biochem 2021 Nov 24;97:82-84. Epub 2021 Aug 24.

Clinical Biochemistry Department, University Clinic Hospital of Valencia, 46010 Valencia, Spain.

Background: Anti-Sry-like high mobility group box 1 (anti SOX-1) proteins are rare onconeural antibodies associated with paraneoplastic Lambert-Eaton myasthenic syndrome (LEMS). Few patients with anti-SOX-1 antibodies and negative anti-glial nuclear antibody reactivity have been described to date.

Case Subject And Methods: Our case involves a 72-year-old female patient with progressive girdle weakness, sensation of heaviness in the lower limbs, predominantly distal and associated with circulatory problems together with instability when walking, with a high suspicion of an autoimmune myopathic disorder. Read More

Brain Sci 2021 Aug 3;11(8). Epub 2021 Aug 3.

Dipartimento di Scienze Biomediche e Neuromotorie, Università di Bologna, 40138 Bologna, Italy.

The neuromuscular junction (NMJ) is the target of a variety of immune-mediated disorders, usually classified as presynaptic and postsynaptic, according to the site of the antigenic target and consequently of the neuromuscular transmission alteration. Although less common than the classical autoimmune postsynaptic myasthenia gravis, presynaptic disorders are important to recognize due to the frequent association with cancer. Lambert Eaton myasthenic syndrome is due to a presynaptic failure to release acetylcholine, caused by antibodies to the presynaptic voltage-gated calcium channels. Read More

Neurol Sci 2021 Dec 24;42(12):5377-5378. Epub 2021 Aug 24.

Service de Dermatologie, CHU de Bordeaux, Groupe Hospitalier Saint André, 1, rue Jean Burguet, 33000, Bordeaux, France.

Introduction: Myasthenia gravis (MG) Lambert-Eaton (LE) overlap syndrome is a rare condition. Here, we describe the first case of MG-LE overlap syndrome revealed by the anti-programmed cell death 1 inhibitor, nivolumab, in a patient treated for metastatic melanoma.

Case: Three months after receiving nivolumab and 1 month after brain metastasis radiotherapy, our patient developed generalized fatigue with intermittent ptosis and swallowing difficulty suggesting a myasthenic syndrome. Read More

J Immunol Methods 2021 09 21;496:113102. Epub 2021 Jul 21.

ARUP Institute for Clinical and Experimental Pathology, 500 Chipeta Way, Salt Lake City, UT 84108, USA; Department of Pathology, University of Utah, 15 N Medical Dr. East Ste. 1100, Salt Lake City, UT 84112, USA. Electronic address:

Background: In this study, we assessed the performance characteristics of a laboratory-developed radioimmunoassay (RIA) to detect N-type voltage-gated calcium channel (N-VGCC) antibodies found in several autoimmune neurologic diseases.

Methods: Four hundred and forty-five (n = 445) sera were evaluated, including 156 sera (50 positive and 106 negative for N-VGCC antibodies) previously tested at Mayo Clinic Laboratories (MCL) and 289 controls (n = 187 disease and n = 102 healthy). Specimens were analyzed with the RIA using N-VGCC labeled with I-ω-conotoxin GVIA. Read More

Rev Neurol 2021 Aug;73(3):96-100

Instituto de Investigaciones Neurológicas Dr. Raúl Carrea (FLENI), Buenos Aires, Argentina.

Introduction: Early diagnosis based on clinical findings, neurophysiological studies and serum antibody titres allows early initiation of symptomatic treatment and oncological screening. Reports of patients with LEMS in Latin America are scarce.

Aim: This article aims to describe the characteristics of patients with LEMS from a private centre in Buenos Aires, Argentina, and to compare them with those of other series that have been published. Read More

Neurooncol Pract 2021 Aug 24;8(4):362-374. Epub 2021 Feb 24.

Department of Neurology, Mayo Clinic, Rochester, Minnesota.

Paraneoplastic neurological syndrome (PNS) comprises a group of neurological disorders that result from a misguided immune response to the nervous system triggered by a distant tumor. These disorders frequently manifest before the diagnosis of the underlying neoplasm. Since the first reported case in 1888 by Oppenheim, the knowledge in this area has evolved rapidly. Read More

Neuromuscul Disord 2021 07 29;31(7):622-632. Epub 2021 May 29.

Department of Neurology, Leiden University Medical Center, the Netherlands.

Disorders of the neuromuscular junction (NMJ) comprise a spectrum of rare diseases causing muscle fatigability and weakness, leading to life-long effects on quality of life. We established the Dutch-Belgian registry for NMJ disorders, based on a unique combination of patient- and physician-reported information. Information on natural course, disease burden, prevalence of complications and comorbidity is collected through patient-reported standardized questionnaires and verified using medical documentation. Read More

Rev Med Liege 2021 May;76(5-6):413-418

Professeur émérite, Université de Liège, Belgique.

Neurological paraneoplastic syndromes are non-metastatic complications of systemic cancers, often resulting from an immune response triggered by the crossed expression of neuronal antigens by tumour cells. Several neurological syndromes such as cerebellar degeneration, sensory neuronopathy, limbic encephalitis, encephalomyelitis or the Lambert-Eaton myasthenic syndrome are most often paraneoplastic and require prompt cancer screening, particularly if the patient shows risk factors for cancer. Although there are many exceptions to this rule, a given syndrome is often associated with a particular antibody and the corresponding tumour. Read More

Neurology 2021 09 26;97(11):e1168-e1169. Epub 2021 May 26.

From the Department of Neurology (A.E.C.-F., E.d.P.E., C.O.H., E.Z.), Faculdade de Medicina da Universidade de São Paulo; and Department of Neurology (E.d.P.E.), Faculdade de Medicina Santa Marcelina, São Paulo, Brazil.

Muscle Nerve 2021 08 12;64(2):219-224. Epub 2021 Jun 12.

Department of Anesthesiology, University of California Davis, Davis, California, USA.

Introduction/aims: We studied a patient with a congenital myasthenic syndrome (CMS) caused by a dominant mutation in the synaptotagmin 2 gene (SYT2) and compared the clinical features of this patient with those of a previously described patient with a recessive mutation in the same gene.

Methods: We performed electrodiagnostic (EDX) studies, genetic studies, muscle biopsy, microelectrode recordings and electron microscopy (EM).

Results: Both patients presented with muscle weakness and bulbar deficits, which were worse in the recessive form. Read More

Neurol Res Pract 2021 May 24;3(1):30. Epub 2021 May 24.

Department of Neurology, University Hospital Essen, Essen, Germany.

Anti-glial nuclear antibody (AGNA) is an onconeuroal antibody targeting the nuclei of Bergmann glia in the cerebellum and Anti-SRY-related HMG-box 1 (SOX1). It is highly specific for small cell lung cancer (SCLC) and correlates to the appearance of paraneoplastic neurological syndromes such as Lambert-Eaton myasthenic syndrome (pLEMS) and paraneoplastic cerebellar degeneration (PCD) amongst others. Herein, we present a SCLC patient with rapidly progressive PCD, LEMS and axonal polyneuropathy associated with AGNA/SOX1-antibodies, successfully treated with plasma-exchange (PLEX). Read More