Postexercise reflex facilitation in Lambert-Eaton myasthenic syndrome.

A 62-year-old woman had 6 months of proximal weakness, fatigue and occasional diplopia, symptoms normally suggesting myasthenia gravis or inflammatory myopathy. Postexercise reflex facilitation is a bedside clinical sign that points to a diagnosis of the rarer alternative, Lambert-Eaton myasthenic syndrome (LEMS). We confirmed this diagnosis using electrodiagnostic short exercise testing and serum assay for voltage-gated calcium channel antibodies. Further investigation identified a small cell neuroendocrine carcinoma of the gallbladder, not previously associated with LEMS. Postexercise reflex facilitation is an important bedside clinical finding that helps clinicians to distinguish LEMS from its mimics.

[A 50 year old man with progressive weakness in lower limbs].

Lambert-Eaton Myasthenic Syndrome (LEMS) is a rare neurological disorder caused by autoimmune antibodies attacking the presynaptic neuromuscular junction, in some cases caused by underlying cancer. The main clinical finding is fluctuating weakness of the extremities and a triad of symtoms can help physicians suspect the disease. A key to the diagnosis are the electrophysiological abnormalities seen in this group of diseases. Treatment with symtomatic and/or immunosuppressive therapy is important as well as a workup for possible malignancy. This article identifies the clinical features, diagnosis and treatment of this uncommon disease.

Autonomic dysfunction detected by skin sympathetic response in Lambert-Eaton myasthenic syndrome: a case report.

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. The cutaneous response to scratch and upright tilt-table testing were positive. A repetitive nerve stimulation test showed that there was a decremental response of compound muscle action potential (CMAP) amplitude at 3 Hz while an incremental response at 20 Hz. The presence of antibodies against voltage-gated calcium channels (VGCC) confirmed the diagnosis. Because of the prominent symptom of autonomic disorder, the patient further underwent the test of skin sympathetic response (SSR). Lower amplitude and longer response duration were found in palms, while it evoked no response in soles. CONCLUSIONS: In this case, we present the detailed results of SSR test on a patient suffering LEMS with autonomic disorder. Since autonomic dysfunction has a significant impact on clinical management and SSR test is an effective detection method, we recommend that SSR test be performed on patients with LEMS regularly.

SOX-1 antibodies in a patient with Crohn's disease: a case report.

BACKGROUND: The anti-SOX-1 antibodies have been mainly associated with Lambert-Eaton Myasthenic Syndrome (LETMS) and Small-Cell Lung Cancer (SCLC). In this report, we describe the interesting case of a patient with serum anti-SOX-1 antibodies and Crohn's Disease (CD) with ensuing neurological symptoms. CASE PRESENTATION: A Caucasian 67-year-old female was admitted to the Emergency Department with seizures, vertigo, emesis, nausea, postural instability and recurrent falls, over a period of 10 days. She had been affected by Crohn's Disease since 1991. A CT scan failed to detect any ischemic or haemorrhagic lesion. A brain MRI revealed signs of leukoencephalopathy. Western blot analysis of her serum revealed a high titre of the onconeural antibody anti-SOX1, consistent with a neurological, cerebellar type, paraneoplastic syndrome. In spite of multiple efforts to unmask a possible underlying malignancy, no neoplastic lesion cropped up during hospitalization. Her clinical conditions progressively deteriorated, up to respiratory failure; a few days later she died, due to ensuing septic shock and Multiple Organ Failure. CONCLUSIONS: Our experience may usher and reveal a new role of anti-neural antibodies, so far reckoned an early indicator of associated malignancy, suggesting that neurological syndromes associated with such antibodies may complicate also chronic Gastrointestinal (GI) diseases. As of now, testing for anti-neuronal antibodies appeared unnecessary within the diagnostic assessment of gastroenterological disorders, which may lead to overlooking incident neurologic autoimmune diseases. Further exploration of such research hypothesis in clinical grounds appears intriguing.

[Diagnostics and treatment of clinically relevant paraneoplastic syndromes]. / Diagnostik und Therapie klinisch relevanter paraneoplastischer Syndrome.

Paraneoplastic syndromes (PS) are rare disorders with often complex clinical manifestations that occur in association with a tumor without being triggered by direct tumor invasion or compression. They arise from tumor secretions of hormones, peptides or cytokines or from immune cross-reactivity between malignant and healthy tissue. They are categorized into endocrine, neurological, dermatological, rheumatological, and hematological PS. The PS most commonly occurs in small cell lung carcinoma but also in association with other respiratory tract tumors, gynecological tumors, and hematological malignancies. The PS can precede a tumor diagnosis, therefore timely diagnosis can improve the prognosis of a malignant disease. The diagnostics are based on the clinical presentation as well as diagnostic methods depending on the underlying pathogenesis. The most important treatment approach involves the best possible treatment of the tumor and a targeted treatment is only sometimes possible. This review focuses on the clinically most frequently encountered PS.

Neuromuscular junction disorders beyond myasthenia gravis.

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. 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. SUMMARY: 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.

Muscular pathological features in patients with Lambert-Eaton myasthenic syndrome associated with small cell lung carcinoma.

AIMS: Lambert-Eaton myasthenic syndrome (LEMS) is a kind of autoimmune disease of the neuromuscular junction that is often misdiagnosed as a peripheral nerve disease or myopathy. For some difficult cases, muscle biopsy examination is useful for differential diagnosis. However, studies about the pathological findings of LEMS patients are rare, especially of patients who were diagnosed with small cell lung carcinoma (SCLC). This study aimed to describe several pathological muscle features in patients with LEMS associated with SCLC. MATERIALS AND METHODS: The 5 patients enrolled in this study were diagnosed with LEMS associated with SCLC by clinical manifestation, electromyography, and lung biopsy. Muscle biopsies were performed for the patients, and enzyme histopathology was assessed. RESULTS: The hematoxylin and eosin (H & E) stain showed different sizes of fibers, and the shape of atrophic fibers were angular or polygonal. The adenosine triphosphatase (ATPase) stain demonstrated that the majority of atrophic fibers were type II. Type II fiber predominance was observed in case 1 and case 5. Also, scattered muscle fiber necrosis was shown in case 3. CONCLUSION: Type II fiber atrophy and type II fiber predominance may often be found in patients with LEMS associated with SCLC. Also, scattered fiber necrosis may appear in this disease.

Anti-SOX1 Antibody-Positive Paraneoplastic Syndrome Presenting with Subacute Cerebellar Degeneration and Lambert-Eaton Myasthenic Syndrome: A Case Report.

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. A coexisting Lambert-Eaton myasthenic syndrome was also documented by electrophysiological study. CONCLUSION: Intensive and regular follow up for an occult malignancy is crucial in patients with SOX1 antibody. Coadministration of therapies for underlying malignancy and LEMS improve the functional disability.

[Paraneoplastic neurological syndromes]. / Les syndromes neurologiques paranéoplasiques.

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. A prompt diagnosis of neurological paraneoplastic syndrome is of major importance as it often reveals the underlying tumour. The treatment relies on both the elimination of the neoplasia and the control of the immune response.

Les syndromes neurologiques paranéoplasiques sont des complications neurologiques non métastatiques de cancers systémiques résultant, le plus souvent, d'une réaction immunitaire croisée dirigée contre des antigènes neuronaux membranaires ou intracellulaires. Certains de ces syndromes paranéoplasiques sont classiques comme les ataxies cérébelleuses, les neuronopathies sensitives ou ganglionopathies, l'encéphalite limbique, les encéphalomyélites ou le syndrome de Lambert-Eaton. Devant de tels tableaux cliniques, une étiologie paranéoplasique doit, surtout chez les patients présentant des facteurs de risque, être systématiquement recherchée. Bien que cette règle souffre de nombreuses exceptions, il y a souvent concordance entre un syndrome clinique spécifique, un type d'anticorps et une tumeur associée. Le diagnostic d'un syndrome neurologique paranéoplasique est essentiel puisqu'il révèle souvent le cancer sous-jacent. Le traitement comporte deux axes principaux : celui du cancer responsable et le contrôle de la réponse immunitaire.

Lowering the cutoff value for increment increases the sensitivity for the diagnosis of Lambert-Eaton myasthenic syndrome.

BACKGROUND: Increment of compound muscle action potential amplitude is a diagnostic hallmark of Lambert-Eaton myasthenic syndrome (LEMS). Making a diagnosis can be challenging, therefore, a proper cutoff for abnormal increment is highly relevant for improved recognition of this rare disease. METHODS: We determined the sensitivity and specificity of 60% and 100% cutoff values in all consecutive patients who underwent increment testing in our hospital from 1999 to 2016. RESULTS: We included 156 patients, 63 with LEMS and 93 without LEMS. Sensitivity of a 60% cutoff for increment testing was 77.8% (95% confidence interval 65.5%-87.3%) and 58.7% (45.6%-71.0%) for 100%. Specificity was 98.9% (94.2%-100%) and 100% (96.1%-100%) using a threshold of 60% and 100%, respectively. CONCLUSIONS: Lowering the cutoff value for abnormal increment to 60% greatly increases sensitivity to diagnose LEMS without an overt loss in specificity.

Assessment of the compound muscle action potential amplitude return time between exercises or tests in the repetitive nerve stimulation test for Lambert-Eaton myasthenic syndrome.

INTRODUCTION: When performing postexercise facilitation (PEF) as part of the repetitive nerve stimulation (RNS) test in Lambert-Eaton myasthenic syndrome (LEMS), it is important to avoid any influence of the previous exercise or RNS test on the compound muscle action potential (CMAP) amplitude. METHODS: To measure the CMAP amplitude return time (ART) to that at rest, a single CMAP was obtained every 30 seconds until the amplitude was within 5% of that at rest in three exercise periods (10, 20, and 30 seconds) and in 10-second postexercise (PE) 3-Hz RNS testing with 17 tests in 10 LEMS patients. RESULTS: Adequate ART between tests is 150 seconds for 10-second exercise (Ex) and 10-second PE 3-Hz RNS test, 120 seconds for 20-second Ex, and 90 seconds for 30-second Ex. DISCUSSION: We recommend 150 seconds as adequate ART between the PEF test and the next test when performing RNS test in LEMS.

Case 261: Thymoma Embedded in Thymus with Pleural Implant in Myasthenia Gravis Lambert-Eaton Overlap Syndrome.

History A 29-year-old woman presented with a 6-month history of progressive general fatigue, fluctuating limb weakness, and difficulty climbing stairs. She initially experienced occasional episodes of transient diplopia that developed while reading in the evening. She subsequently started to experience dry eyes and mouth, difficulty chewing, and mild dysphagia that worsened throughout the day. Her medical history included hypothyroidism from Hashimoto thyroiditis and pneumonia with left pleural effusion. She had no smoking history, and her body mass index was normal (23.8 kg/m2). No medication use was reported at admission. Physical examination revealed mild bilateral ptosis, reduced muscle tone and strength that worsened in proximal leg muscles, and decreased deep tendon reflexes. An edrophonium test revealed improvement in muscle strength and eyelid ptosis. Repetitive nerve stimulation revealed low amplitude of compound muscle action potential at rest (0.21 mV), with a marked increase (700%; normal increase, <60%) at high-rate stimulation (50 Hz). Laboratory work-up was unremarkable except for detection of acetylcholine receptor antibodies in the serum (21.30 nmol/L) and P/Q-type voltage-gated calcium channel antibodies (220 pmol/L). Recent MRI of the brain and spine at an outside hospital showed no abnormal findings. At admission, the patient underwent CT of the chest, abdomen, and pelvis followed by thoracic MRI to further evaluate CT findings.

Repetitive nerve stimulation test in myasthenic crisis.

INTRODUCTION: Herein we report our experience with the repetitive nerve stimulation (RNS) test in myasthenia gravis (MG) crisis. METHODS: The various parameters of the RNS tests in 26 patients with MG crisis were analyzed. RESULTS: In 18 (69%) patients, MG crisis is the first manifestation of MG. RNS tests were abnormal in 24 (92%) patients by decrement at low-rate stimulation in any of 4 tested muscles. Three patterns of abnormality were found: MG pattern (decrement at low-rate stimulation) in 23 patients; Lambert-Eaton myasthenic syndrome pattern in 1 patient; and cholinergic crisis pattern in 1 patient. DISCUSSION: During MG crisis, the RNS test can serve as a rapid and sensitive diagnostic tool for MG in a majority of patients. Muscle Nerve 59:544-544, 2019.

Reliability of the triple-timed up-and-go test.

INTRODUCTION: We report the reliability of a new measure, the triple-timed up-and-go (3TUG) test, for assessing clinical function in patients with Lambert-Eaton myasthenia (LEM). METHODS: Intrarater reproducibility and interrater agreement of the 3TUG test were assessed in 25 control participants, 24 patients with non-LEM neuromuscular disease, and 12 patients with LEM. The coverage probability (CP) method was the primary measure of reproducibility and agreement. The a priori acceptable range was < 20% difference in 3TUG test times and a CP ≥0.90 confirmed agreement. RESULTS: CP values > 0.90 for intrarater and interrater tests confirmed acceptable reproducibility and agreement for all groups. DISCUSSION: The 3TUG test is a quick, noninvasive, and reproducible measure that is easy to perform, measures clinically important weakness in LEM patients, and requires little training. Additional evaluation in a larger number of LEM patients is in progress to validate the 3TUG test as a clinical measure in LEM. Muscle Nerve 57: 136-139, 2017.

Myasthenia gravis Lambert-Eaton overlap syndrome.

INTRODUCTION: To assess whether a myasthenia gravis (MG) Lambert-Eaton overlap syndrome (MLOS) exists. METHODS: Case reports that met the universally accepted diagnostic criteria for MG and Lambert-Eaton myasthenic syndrome (LEMS) were sought through a PubMed search. Fifty-five possible cases of MLOS were identified. RESULTS: Thirty-nine cases met the diagnostic criteria for MG and LEMS. Analysis of clinical features showed that these patients have common MG and LEMS symptoms: oculo-bulbar paresis and good response to anti-cholinesterase for MG and limb weakness and decreased or absent reflexes for LEMS. All had the classical LEMS pattern in the repetitive nerve stimulation test: low compound muscle action potential amplitude and incremental response > 60% with brief exercise or at high rate of stimulation. Eight patients had combined positive acetylcholine receptor antibody (AChR-ab) or muscle-specific kinase-ab and voltage-gated calcium channel- ab tests. CONCLUSIONS: A myasthenia gravis Lambert-Eaton overlap syndrome (MLOS) does exist.

Review of the Diagnostic Challenges of Lambert-Eaton Syndrome Revealed Through Three Case Reports.

Lambert-Eaton syndrome (LES) is a rare immune-mediated disorder characterized by proximal leg weakness, autonomic symptoms and hypoactive tendon reflexes. The paraneoplastic form is associated with small-cell lung cancer in 50-60% of cases, whereas the remaining cases are found in younger adults with a higher likelihood of coexisting autoimmune disease. The early recognition of LES is crucial for improving clinical outcomes but remains a major challenge. In this review, we analyze the clinical characteristics and diagnostic considerations in treating LES through a series of three case studies, one of which showed definitive response to pyridostigmine and corticosteroid combination therapy, followed by spontaneous remission. Patients were assessed by image-based screening, serological testing and electrophysiological evaluations, which included respiratory and autonomic testing. A better understanding of the common pitfalls in the clinical, serological and neurophysiologic diagnosis of LES through assessment of typical LES dysfunction throughout the nervous system should enable improved recognition and treatment of this syndrome.

Lambert-Eaton Myasthenic Syndrome: Ocular Signs and Symptoms.

BACKGROUND: To evaluate ocular signs and symptoms in Lambert-Eaton myasthenic syndrome (LEMS) and determine the frequency of ophthalmic involvement. METHODS: A retrospective review of the medical records of all patients diagnosed with LEMS at the Mayo Clinic in Rochester, MN, from January, 1976, to December, 2010, was performed with special attention to ophthalmic symptoms and signs. RESULTS: One hundred seventy-six patients met the inclusion criteria. Ophthalmic symptoms included ptosis in 41 (23%), diplopia in 36 (20.5%), decreased vision in 24 (14%), and dry eye complaints in 12 (7%). Ophthalmic signs included ptosis in 45 (26%), abnormal ocular motility in 15 (8.5%), strabismus in 14 (8%), pupillary dysfunction in 12 (7%), and findings consistent with dry eyes in 4 (2%). CONCLUSIONS: A significant number of patients reported ophthalmic symptoms, and many had objective findings on clinical examination consistent with these symptoms. To our knowledge, this is the largest case series of ophthalmic findings in patients with LEMS and indicates that these patients warrant a complete ophthalmic examination.