As the release of acetylcholine at the neuromuscular junction is impaired, numerous symptoms may appear. Debilitating muscle weakness, which is the main clinical manifestation of patients suffering from LEMS [13], is accompanied by reduced or absent deep tendon reflexes [7], and by various autonomic disturbances such as constipation, impaired sexual functions, or dry mouth [5]. Muscle weakness usually starts at the proximal lower extremities and is progressive in nature, eventually spreading to both upper and lower distal extremities [1]. Respiratory failure may be observed in severe cases in whom the diagnosis is made when advanced stages of the disease have been reached. Ocular and bulbar symptoms may be present as well and their frequency ranges between 0-80% [1].

• Weakness

  Proximal muscle weakness, absent reflexes, normal serum creatine kinase, and autonomic dysfunction should prompt electrodiagnostic testing for LEMS. [pediatricneurologybriefs.com]

  Since the goal of treatment is improvement in weakness, the initial choice of treatment depends on the severity of the underlying weakness. If the weakness is mild, then pyridostigmine at a dose of 30–120 mg every 3–6 hours may be tried initially. [clinicaladvisor.com]

  The clinical presentation of LEMS usually includes proximal muscle weakness, autonomic symptoms, and loss of reflexes. The first symptom noted by patients is usually proximal leg muscle weakness (80%), followed by weakness of the arms. [ime.acponline.org]

  In most patients, weakness does not severely affect vital muscles. [slideshare.net]

  Here, we describe a patient with a 5-year history of cervical myelopathy who presented with recurrent limb weakness of her limbs and complained of recent progressive weakness. [ncbi.nlm.nih.gov]

• Fatigue

  An African 41 years-old SLE patient presented with persisting fatigue, myalgia and dyspnea, abolished reflexes and a bilateral ptosis. [ncbi.nlm.nih.gov]

  Symptoms include muscle weakness, a tingling sensation in the affected areas, fatigue, and dry mouth. LEMS is closely associated with cancer, in particular small cell lung cancer. [ninds.nih.gov]

  These proximal muscles are more likely to fatigue with use, and muscle fatigue and sometimes stiffness may be more prominent than actual weakness. The legs are particularly affected. [mda.org]

• Pain

  This syndrome causes muscle weakness (particularly in the legs), fatigue, dry mouth, drooping eyelids, and pain in the upper arms and thighs. Doctors suspect Eaton-Lambert syndrome based on symptoms, but electromyography is necessary for diagnosis. [merckmanuals.com]

  The most common side effects experienced by patients in the clinical trials were burning or prickling sensation (paresthesia), upper respiratory tract infection, abdominal pain, nausea, diarrhea, headache, elevated liver enzymes, back pain, hypertension [fda.gov]

  History about smoking, chonic cough, haemoptysis, anorexia and pleuritic type chest pain should be asked. [medicaljoyworks.com]

  Patients with LEMS typically present with fatigue, muscle pain and stiffness. The weakness is generally more marked in the lower extremity muscles, particularly of the legs and hip-girdle. [globalgenes.org]

  We ask about general symptoms (anxious mood, depressed mood, fatigue, pain, and stress) regardless of condition. Last updated: May 13, 2019 [patientslikeme.com]

• Weight Loss

  RESULTS: Age at onset, smoking behavior, weight loss, Karnofsky performance status, bulbar involvement, male sexual impotence, and the presence of Sry-like high-mobility group box protein 1 serum antibodies were independent predictors for SCLC in LEMS [ncbi.nlm.nih.gov]

  Review of symptoms was notable for a 10-lb unintentional weight loss over one month before presentation. Past medical history was significant for chronic obstructive pulmonary disease and a 75-pack year smoking history. [n.neurology.org]

  More than 50 years of age at onset of symptoms, positive history for smoking, weight loss, bulbar symptoms, male sexual impotence and Karnofsky performance status lower than 70 were established as valid predictors of SCLC, as the chances of 93.5%, 96.6% [symptoma.com]

  She also experienced a 5-pound unintentional weight loss over a 2-month period. She denied smoking, drinking alcohol, or abusing any drugs. Her medications were aspirin 81 mg oral daily and amlodipine 5 mg oral daily. [journals.sagepub.com]

  Low back pain is sometimes observed, and weight loss, perhaps attributable to the underlying disorder, may be noted. Some patients have a history of a preceding viral-type illness. [pulmonologyadvisor.com]

• Difficulty Climbing Stairs

  He reports difficulty rising from seated position and difficulty climbing stairs. He denies any blurry vision or any rashes on his body. He has a 100-pack-year history of smoking. [step1.medbullets.com]

  Weakness or loss of movement that can be more or less severe, including: Difficulty climbing stairs, walking, or lifting things Muscle pain Drooping of the head The need to use the hands to get up from a sitting or lying position Problems talking Problems [nlm.nih.gov]

• Constipation

  The Lambert-Eaton myasthenic syndrome (LEMS) is a neuromuscular disease; its unique symptoms of LEMS include dry mouth with a metallic taste, constipation, and erectile dysfunction. [ncbi.nlm.nih.gov]

  There is sensory neuropathy, weak or absent tendon reflexes, impotence, difficulties in micturition, dry mouth and constipation. Onset in middle life. It is more common in men than in women, most common in males over the age of 40 years. [whonamedit.com]

  Autonomic dysfunction includes dry mouth, constipation, and erectile dysfunction. Deep tendon reflexes are usually decreased or absent. [ime.acponline.org]

  Patients often report a dry mouth, impotence, and constipation. Very rarely these problems can be life-threatening when the weakness involves respiratory muscles. I have been undergoing infusions monthly for six years. [globalgenes.org]

• Dysphagia

  A 78-year-old man presented with dysarthria, dysphagia, staggering gait, and lower extremity muscle fatigue. [ncbi.nlm.nih.gov]

  Difficulty in swallowing Dysphagia could occur due to the involvement of muscles of deglutination. Again if this symptom is usually seen in MG rather than in LEMS. [medicaljoyworks.com]

  Case report: Herein we report an 82 year old man a known case of adenocarcinoma of bladder who came with ptosis in left eye, diplopia, and dysphagia, weakness of both lower extremities and autonomic dysfunction. [imminv.com]

• Metallic Taste

  The Lambert-Eaton myasthenic syndrome (LEMS) is a neuromuscular disease; its unique symptoms of LEMS include dry mouth with a metallic taste, constipation, and erectile dysfunction. [ncbi.nlm.nih.gov]

  Many patients report an unpleasant metallic taste. Some patients have other manifestations of autonomic dysfunction, including impotence in males and postural hypotension. [emedicine.medscape.com]

  Some report a metallic taste in the mouth.[3] On neurological examination, the weakness demonstrated with normal testing of power is often less severe than would be expected on the basis of the symptoms. [en.wikipedia.org]

• Xerostomia

  Autonomic dysfunctions, mostly xerostomia, occur in approximately 80% of the patients; other symptoms include impotence in men and loss of the libido in women 2,11. Both patients in this report presented xerostomia and reduction of the libido. [scielo.br]

  A 68‑year‑old male patient presented with a 6‑month history of progressive weakness of the proximal limbs and a 2‑month history of xerostomia. [spandidos-publications.com]

  […] positivity 0030209 EMG: decremental response of compound muscle action potential to repetitive nerve stimulation 0003403 EMG: repetitive nerve stimulation abnormality 0030000 Progressive proximal muscle weakness 0009073 Reduced tendon reflexes 0001315 Xerostomia [rarediseases.info.nih.gov]

• Hypotension

  Associated with small-cell carcinoma of the lung, sarcoidosis, thyroiditis, collagen-related vascular disease.May be accompanied by autonomic nervous system defects, including gastroparesis, orthostatic hypotension, and urinary retention Myasthenic Syndrome [openanesthesia.org]

  Paraneoplastic syndrome (PNS) with two distinct neurological features was reported in a 50-year-old man who presented initially with vertigo, ataxia, dysarthria, tremor, confusion, urinary retention and hypotension. [ncbi.nlm.nih.gov]

  Bronchogenic carcinoma associated with severe orthostatic hypotension. Ann Intern Med, 1963; 58: 669–676. PubMed Google Scholar [12] Barraclough MA, Sharpey-Schafer EP. Hypotension from absent circulatory reflexes. [link.springer.com]

• Orthostatic Hypotension

  hypotension in these patients Keyword history 73%/2010 [openanesthesia.org]

  A significant proportion of patients also have dysfunction of the autonomic nervous system that may include dry mouth, constipation, blurred vision, impaired sweating, and orthostatic hypotension. [ncbi.nlm.nih.gov]

  Bronchogenic carcinoma associated with severe orthostatic hypotension. Ann Intern Med, 1963; 58: 669–676. PubMed Google Scholar [12] Barraclough MA, Sharpey-Schafer EP. Hypotension from absent circulatory reflexes. [link.springer.com]

  hypotension due to autonomic dysfunction 0004926 Showing of 13 | Last updated: 3/1/2020 LEMS is a disorder of the immune system, also known as an autoimmune disorder. [rarediseases.info.nih.gov]

• Diplopia

  She recently developed unilateral ptosis and diplopia which dramatically improved with pyridostigmine suggesting concomitant MG. [ncbi.nlm.nih.gov]

  Case report: Herein we report an 82 year old man a known case of adenocarcinoma of bladder who came with ptosis in left eye, diplopia, and dysphagia, weakness of both lower extremities and autonomic dysfunction. [imminv.com]

  Less common features include oropharyngeal and ocular symptoms related to weakness, such as dysphagia, dysarthria, ptosis, and diplopia. The diagnosis is confirmed by electrodiagnostic studies and serology. [radiopaedia.org]

• Dry Eyes

  Ophthalmic symptoms included ptosis in 41 (23%), diplopia in 36 (20.5%), decreased vision in 24 (14%), and dry eye complaints in 12 (7%). [ncbi.nlm.nih.gov]

  Other autonomic symptoms will be constipation, dry eyes, constricted pupils, impotence and postural hypo tension. [medicaljoyworks.com]

  Symptoms related to the other parts of the nervous system often occur, and include: Blood pressure changes Dizziness upon standing Dry mouth Erectile dysfunction Dry eyes Constipation Decreased sweating The health care provider will perform a physical [nlm.nih.gov]

  Mestinon is indicated for the treatment of MG, but is often used in combination with Firdapse to treat symptoms of autonomic dysfunction (dry mouth, dry eyes, constipation, impotence and, decreased sweating). [rarediseases.org]

• Blepharoptosis

  옛 대한의협 3 의학용어 사전 검색 맞춤 검색 결과 : 15 페이지: 1 muscle weakness 근무력(筋無力). asthenia bulbar paralysis 근무력성 구(연수)마비(筋無力性球延髓 痺). blepharoptosis myasthenica<나> 근무력성 안검하수. myasthenic fatigability 근무력성 피로증(筋無力性疲勞症). myasthenic nystagmus 근무력안진 muscular asthenia 근무력증 [kmle.co.kr]

  Titulaer et al. n = 97 Male:female 32:18 84:26 55:42 Median age at onset (years) 54 62 57 Neurological findings (%) Weakness of upper extremities 82 80 82 Weakness of lower extremities 90 97 100 Decreased deep tendon reflex 92 85 92 Ophthalmoplegia NA 5 38 Blepharoptosis [onlinelibrary.wiley.com]

• Unilateral Ptosis

  She recently developed unilateral ptosis and diplopia which dramatically improved with pyridostigmine suggesting concomitant MG. [ncbi.nlm.nih.gov]

• Muscle Weakness

  After the operation, the muscle weakness symptom was significantly improved. [cancerjournal.net]

  […] such prominent eye muscle weakness. [jnnp.bmj.com]

  Neurological examination revealed muscle weakness, predominantly in the proximal parts of the limbs. Muscle weakness improved following a short period of maximum voluntary muscle contraction. [ncbi.nlm.nih.gov]

  From Wikidata Jump to navigation Jump to search an autoimmune, presynaptic disorder of neuromuscular transmission characterized by fluctuating muscle weakness and autonomic dysfunction frequently associated with small-cell lung cancer (SCLC) Eaton-Lambert [wikidata.org]

• Proximal Muscle Weakness

  It is clinically presented with proximal muscle weakness and autonomic dysfunction. Myasthenic weakness is caused by reduction of acetylcholine release induced by an immune response directed against the calcium channel complex of the nerve terminal. [nature.com]

  Proximal muscle weakness, absent reflexes, normal serum creatine kinase, and autonomic dysfunction should prompt electrodiagnostic testing for LEMS. [pediatricneurologybriefs.com]

  A patient with typical Lambert-Eaton myasthenic syndrome (LEMS) has a clinical manifestation of proximal muscle weaknesses, a larger-than-100% incremental change in repetitive nerve stimulation on high-rate stimulation electrophysiological testing, and [ncbi.nlm.nih.gov]

• Myopathy

  Lambert-Eaton myasthenic syndrome (LEMS) is a rare condition, which may mimic myopathy. [ncbi.nlm.nih.gov]

  EMG helps to differentiate LEMS from other causes of cancer-associated weakness, such as myopathy and polyneuropathy. [cmaj.ca]

  SCCMS must be considered in the differential diagnosis of congenital muscular dystrophy, congenital myopathy, autoimmune-type MG, and metabolic and mitochondrial myopathy. [intechopen.com]

• Leg Weakness

  The second case, a 73-year-old male presenting with leg weakness, was treated by PE and double-filtration plasmapheresis. [ncbi.nlm.nih.gov]

  The second case, a 73‐year‐old male presenting with leg weakness, was treated by PE and double‐filtration plasmapheresis. [doi.org]

  The most common clinical feature is progressive proximal leg weakness. Deep tendon reflexes are almost always decreased. A less prominent but characteristic feature is autonomic dysfunction, most commonly dry mouth. [radiopaedia.org]

  The primary symptoms of LEMS are leg weakness and difficulty walking. [healthline.com]

• Arm Weakness

  […] accompanied by arm weakness, at the point of maximum disease severity. [jnnp.bmj.com]

• Decreased Sweating

  Symptoms related to the other parts of the nervous system often occur, and include: Blood pressure changes Dizziness upon standing Dry mouth Erectile dysfunction Dry eyes Constipation Decreased sweating The health care provider will perform a physical [nlm.nih.gov]

  Mestinon is indicated for the treatment of MG, but is often used in combination with Firdapse to treat symptoms of autonomic dysfunction (dry mouth, dry eyes, constipation, impotence and, decreased sweating). [rarediseases.org]

  Symptoms related to the other parts of the nervous system often occur, and include: Blood pressure changes Dizziness upon standing Dry mouth Erectile dysfunction Dry eyes Constipation Decreased sweating Exams and Tests The health care provider will perform [ufhealth.org]

• Urinary Retention

  Paraneoplastic syndrome (PNS) with two distinct neurological features was reported in a 50-year-old man who presented initially with vertigo, ataxia, dysarthria, tremor, confusion, urinary retention and hypotension. [ncbi.nlm.nih.gov]

  Associated with small-cell carcinoma of the lung, sarcoidosis, thyroiditis, collagen-related vascular disease.May be accompanied by autonomic nervous system defects, including gastroparesis, orthostatic hypotension, and urinary retention Myasthenic Syndrome [openanesthesia.org]

  Constipation, urinary retention, pupillary constriction, sweating, postural hypotension, or respiratory muscle weakness may be present. Clinical manifestations of underlying malignancy (eg, cachexia) may be present. [emedicine.medscape.com]

• Limb Weakness

  A 27-year-old man as initially having the diagnosis of Addison's disease was admitted to the hospital because of fatigue, dry-mouthness and proximal limb weakness for 1 year. A diagnosis of LEMS was made from electrophysiological studies. [ncbi.nlm.nih.gov]

  Upper limb weakness may manifest with difficulty in reaching objects, combing and clothing. The weakness may worsen by exposing to hot temperature or generalized fever. [medicaljoyworks.com]

• Areflexia

  Investigators from Boston Children's Hospital; the Lahey Clinic, Burlington, MA; and Ohio State University, report 3 children presenting between ages 9 and 10 years with proximal lower extremity weakness with areflexia and low-amplitude compound muscle [pediatricneurologybriefs.com]

  We report a 73 year-old lady who presented 10 years previously with stiffness of both calves, dry mouth, fatigue, proximal weakness and areflexia in lower limbs. Neurophysiological studies were consistent with LEMS. [ncbi.nlm.nih.gov]

  Examination showed external ophthalmoplegia, facial diplegia and proximal 2/5, distal 4/5 strength with areflexia. She was intubated secondary to neuromuscular weakness. EEG showed moderate encephalopathy. [n.neurology.org]

• Dysarthria

  Neurological examination revealed ptosis, dysarthria, neck weakness, hyporeflexia of all limbs, and autonomic failure. Electrophysiologic study showed a 400% increment response to high-rate repetitive nerve stimulation. [ncbi.nlm.nih.gov]

• Paresthesia

  The side effects of 3,4-DAP are generally mild and most frequently consist of paresthesias, but epileptic seizures and arrhythmias have been described in patients using high doses. [ncbi.nlm.nih.gov]

  Side effects are usually mild, and the most frequently reported are paresthesias. The most common serious adverse events are epileptic seizures. 3,4-DAP is currently the treatment of choice in patients with Lambert–Eaton myasthenic syndrome. [doi.org]

  Results: A 64-year-female with LCNEC(stage-1A) status post wedge resection presented with one week history of encephalopathy, diplopia, generalized weakness and paresthesia. [n.neurology.org]

  The most common side effects experienced by patients in the clinical trials were burning or prickling sensation (paresthesia), upper respiratory tract infection, abdominal pain, nausea, diarrhea, headache, elevated liver enzymes, back pain, hypertension [fda.gov]

• Hyporeflexia

  Neurological examination revealed ptosis, dysarthria, neck weakness, hyporeflexia of all limbs, and autonomic failure. Electrophysiologic study showed a 400% increment response to high-rate repetitive nerve stimulation. [ncbi.nlm.nih.gov]

  It is characterized clinically by muscle weakness, hyporeflexia or areflexia, and autonomic dysfunction. [cancerjournal.net]

  History In 1953 Anderson and colleagues reported the case of a 47-year-old man with a bronchial neoplasm, progressive proximal muscle weakness and hyporeflexia who developed prolonged apnoea following administration of succinylcholine. [pmj.bmj.com]

The two most important steps in the diagnostic workup are a meticulous physical examination and EMG studies [5]. EMG will confirm a low CMAP, in which case further evaluation for SCLC through the use of chest CT, bronchoscopy and PET should be carried out as soon as possible [8]. Between 85-90% of patients test positive for VGCC antibodies, with numbers reaching 100% if LEMS is associated with SCLC [7]. Because SCLC and LEMS are strongly correlated, a prediction score has been proposed in order to aid physicians in making the diagnosis early on. More than 50 years of age at onset of symptoms, positive history for smoking, weight loss, bulbar symptoms, male sexual impotence and Karnofsky performance status lower than 70 were established as valid predictors of SCLC, as the chances of 93.5%, 96.6% and 100% for this malignancy were observed if patients had 4,5 or all 6 symptoms, respectively [9].

Current treatment principles rely on symptomatic and causative therapy, with 3,4 - DAP being currently considered as first-line therapy [6] [14]. 3,4 - DAP acts by blocking voltage-gated potassium channels, thus causing a prolonged depolarization phase at the presynaptic terminal and providing more time for acetylcholine to be released into the synaptic cleft [10]. Recent studies have additionally suggested that this drug also directly influences the activity of VGCCs, but this theory remains to be solidifies [1]. Guidelines suggest dosages of 5 milligrams every 8 hours, but up to 60 mg/day can be given [10]. This drug, however, is contraindicated in patients who suffer from epilepsy, since seizures are the most significant adverse effect. Additionally, its combination with drugs that prolong the QT interval is prohibited [10], as the drug can further cause QT prolongation. It was shown that 3,4 diaminopyridine can improve muscle strength within days after its initiation, whereas positive effects were seen with intravenous immunoglobulins over the course of weeks [9]. Corticosteroids, used together with azathioprine or cyclosporine, have proved to be successful in long-term management [15]. In addition to described therapeutic agents, a novel calcium channel agonist (GV-58) has shown significant success in animal models, especially when used together with 3,4 DAP [13]. Efficient treatment of the underline malignant disease (if present) is equally important when it comes to long-term survival rates [6].

The prognosis varies from patient to patient, but the majority of individuals have a reduced life expectancy. Non neoplastic forms have been associated with a much better prognosis compared to those in whom SCLC was discovered as the underlying cause [11], but in any case, intensive immunosuppressive therapy is necessary to maintain an adequate quality of life [11]. Although between 20 and 50% of patients enter long-term remission with appropriate therapy, studies have confirmed that the severity of symptoms at the time of diagnosis is a valid predictor of outcome, which is why an diagnosis is essential in achieving better results [11].

LEMS occurs due to suppressed presynaptic neurotransmitter release by antibodies acting on the VGCCs. Since the activity of these channels are essential for secretion of acetylcholine into the synaptic cleft, their inactivity will invariably lead to reduced signal transmission and cause numerous symptoms. In 50-90% of patients, some form of malignancy is discovered, by far the most common being SCLC [2], which is encountered in the vast majority of tumor-related LEMS [1]. Its exact role in the pathogenesis, however, remains unknown.

LEMS is considered to be a rare disease, with prevalence rates of 2.3 per 1 million individuals and an incidence of 0.5 per 1 million [7]. Other studies suggest that this disease affects approximately 1 per 100,000 individuals in the United States and Europe [8]. SCLC is by far the most important risk factor and this condition is often divided into SCLC-induced and non-SCLC induced LEMS [11]. In patients with SCLC, The onset of symptoms is most frequent > 50 years of age, with a slight predilection toward male gender [7]. On the other hand, non-SCLC LEMS Is more frequently seen in women, with the onset being most common at 35 and 60 years of age [7]. Ethnic predilection has not been established, as this condition affect all races [12].

Under physiological circumstances, neurotransmitter release at the neuromuscular junction is mediated by opening and closing of presynaptic P or Q type voltage-gated Ca+ channels (VGCCs), which are regulated by the activity and impulse of the presynaptic action potential [13]. In the setting of LEMS, the production of IgG-class antibodies that target the extracellular VGCCs leads to downregulation of calcium dependent release of acetylcholine in the presynaptic terminal [5]. Consequently, depressed tendon reflexes, proximal weakness and impairment of autonomic functions develop [11]. Apart from VGCC, other targets have been discussed, since up to 10-15% of patients have negative antibody titers, with the most prominent candidates being synaptotagmin (a synaptic vesicle protein) and muscarinic presynaptic acetylcholine receptors [8].

Because almost 100% of patients with LEMS were diagnosed with SCLC within 1 year [3], and because the diagnosis is often made several years after the onset of symptoms [12], a screening protocol consisting of chest CT and PET scans has been proposed in order to facilitate an early diagnosis [3], which can significantly prolong survival rates and be even life-saving for many patients. The prevention of LEMS is currently not possible, as the exact cause of antibody production is unknown.

Since its initial description more than 50 years ago [1], much has been revealed about Lambert-Eaton myasthenic syndrome (LEMS), an autoimmune disease featured by production of antibodies against voltage-gated calcium channels (VGCCs) at the neuromuscular junction [2]. In a substantial amount of patients (50-90%, depending on the study) [2] [3] [4], the underlying cause was determined to be small cell lung carcinoma (SCLC) [1], one of the most aggressive lung tumors encountered in clinical practice. LEMS was established as the common paraneoplastic disorders identified in SCLC patients, with a prevalence rate reaching up to 6% [5]. On the other hand, a nonparaneoplastic form of LEMS (also known as non-SCLC LEMS) comprises 10-15% of cases [6], in which the underlying cause remains unknown. In these patient, anti-VGCC antibodies are not found, consequently leading to the search for other molecules involved in the pathogenesis [7]. So far, synaptotagmin (a protein involved in the formation of synaptic vesicles) and muscarinic acetylcholine receptors located on the presynaptic terminal have been listed as potential targets [8]. The pathogenesis of SCLC-LEMS starts with delayed presynaptic signaling as a result of antibody activity and suppression of VGCCs, leading to impaired conduction of action potentials and secretion of acetylcholine into the synaptic cleft [2]. As a result, numerous neurological deficits appear, most important being progressive muscle weakness, usually starting at the lower extremities, together with diminished or completely absent deep tendon reflexes and autonomic dysfunction that manifests as dry mouth, constipation and erectile dysfunction [1]. LEMS is rarely seen in medical practice, as studies have determined an incidence rate of 0.5 per 1 million individuals [7], whereas approximately 1 in 100,000 individuals in Europe and the United States were shown to suffer from this diseases [8]. SCLC is, by far, the single most important risk factor for LEMS, but the roles of gender and age are considered to be important as well. Males are more commonly affected by SCLC-related LEMS, while non-SCLC LEMS is more frequently observed among women [7]. In terms of age, SCLC-related cases appear almost universally after 50 years of age, while the remaining patients are diagnosed at two age peaks, 35 and 60 years [1], and the exact cause for such results remains unknown. To make the diagnosis, a thorough physical examination and various laboratory and imaging studies are necessary. Electromyography (EMG) results showing low compound muscle action potential (CMAP) and elevated serum values of VGCC antibodies are diagnostic hallmarks of LEMS, in which case a detailed and prompt inspection of the chest through computed tomography (CT), positron emission tomography (PET) and bronchoscopy is pivotal to confirm SCLC [1]. A recent study has composed a predictive score for SCLC in patients with suspected LEMS, including factors such as age of > 50 years at onset, smoking, erectile dysfunction, weight loss and functional impairment assessed through the Karnofsky scale, and has shown to be highly specific in the presence of 4 or more factors [9]. Treatment principles aim to suppress the activity of antibodies, primarily through use of 3,4 - diaminopyridine (3,4-DAP). Less effective drugs include intravenous immunoglobulins (IVIG) and plasmapheresis [10]. For chronic, long-term suppression, azathioprine and corticosteroids are of significant benefit [1]. If the presence of SCLC is confirmed, its management is equally important in ensuring longer survival rates. The severity of symptoms at the time of diagnosis is established to be the most valid predictor of life expectancy [11], which is why an early diagnosis based on high clinical suspicion is of essential importance.

Lambert-Eaton myasthenic syndrome (LEMS) is an autoimmune disease most frequently appearing in the presence of a malignant tumor, most commonly small lung cell carcinoma. LEMS is, in fact, considered to be the most common paraneoplastic syndrome in small lung cell carcinoma (SCLC). In a small subset of patients (10-15%), however, LEMS is not related to any malignant tumor and its cause remains unknown. For reasons yet to be determined, production of antibodies against calcium channels that are essential cogs in proper conduction of nervous signals occurs and these antibodies are identified in high titers in the vast majority of patients. When antibodies suppress the activity of these channel, the main neurotransmitter, acetylcholine, cannot perform its physiological function and diminished nervous signaling triggers numerous deficits. Symptoms such as muscle weakness, diminished tendon reflexes and impaired autonomic functions that manifest as dry mouth, constipation or erectile dysfunction are manifestations of LEMS. To make the diagnosis, it is important to perform a full physical examination, together with electromyography (EMG) and various imaging studies to confirm or exclude the presence of small lung cell carcinoma. Computed tomography (CT scan) of the chest, positron emission tomography (PET scan) and bronchoscopy are all indicated in the setting of high clinical suspicion toward LEMS. Treatment involves administration of various drugs, but 3,4 - diaminopyridine is considered as first-line therapy. Intravenous immunoglobulins and plasmapheresis are also considered as good alternatives, especially in patients suffering from epilepsy, in whom 3,4 -diaminopyrine is contraindicated due to the fact that its most prominent adverse effect is seizures. Corticosteroids and azathioprine are used for long-term suppression. The prognosis of LEMS significantly depends on the promptness of the diagnosis, as much longer survival rates have been observed in patients with milder symptoms at their initial presentation. Although LEMS is considered to be a rare disease, appearing in 2 per 1 million individuals, it should be taken into consideration in individuals older than 50 years of age who present with progressive muscle weakness and autonomic dysfunction as the underlying cause may lead to fatal outcomes if not recognized early on.

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