Journal OF MILITARY PHARMACO - MEDICINE N02 - 2022 CLINICAL AND ELECTROMYOGRAPHICAL FEATURES IN EARLY DIAGNOSIS OF LAMBERT-EATON MYASTHENIA SYNDROME: A RARE CASE REPORT Nguyen Van Tuan1, Tran Anh Tuan2 Nguyen Cong Tan3, Vuong Cong Toan3, Vu Thi Hinh4 SUMMARY Introduction: Lambert-Eaton myasthenic syndrome (LEMS) is a rare disorder of neuromuscular junction transmission in which the primary clinical manifestations are proximal muscle weakness and possible autonomic symptoms The amount of acetylcholine (ACh) released from the pre-synaptic nerve terminals is reduced due to antibodies directed against the voltage-gated calcium channel Electrodiagnostic evaluation is characterized by the type of presynaptic damage Objectives: We present a clinical case of LEMS with lung tumor diagnosed by clinical and electromyography Results: The 56-year-old male patient had an onset of progressive muscle weakness, weight loss of kg per months After months, the patient had respiratory failure, limbs muscle weakness (muscle strength 2/5 - 4/5), mechanical ventilation although he was still awake The deep tendon reflexes were absent He also had a dry mouth, dry eyes but no sensation and ocular symptoms Electromyography showed a decreased amplitude of compound muscle action potential (CMAP), repetitive stimulation study (RNS) with Hz showed a decrement of more than 10% Short exercise testing and rapid high frequency RNS demonstrated an increment of CMAP amplitude of more than 100% Lung computerized tomography scan showed a left lung tumor Conclusion: LEMS is a disease that is easily misdiagnosed in clinical practice and is often confused with other diseases Clinical and electromyography play an important role in the early and accurate diagnosis of LEMS * Keywords: Clinical features; Electromyography; Myasthenia gravis; Lambert-Eaton myasthenia gravis INTRODUCTION Lambert-Eaton myasthenic syndrome is a rare autoimmune disorder with a decrement of presynaptic acetylcholine caused by autoantibodies directed against the voltage-gated calcium channel (VGCC) The prevalence of the disease is about 1/1 million, male/female ratio is roughly 3/1 [1]; about 60% of cases develop lung cancers [2, 3] The clinical features of LEMS are fatigue, limb muscle weakness, decreased or absence, loss of tendon reflexes, autonomic symptoms and normal sensory [4, 5] Electromyography indicates pre-synaptic damage Centre of Neurology, Bach Mai Hospital Radiology of Department, Bach Mai Hospital Intensive Care Unit, Bach Mai Hospital Department of Neurology, Tam Anh Hospital Corresponding author: Nguyen Van Tuan (ngtuan21965@gmail.com) Date received: 13/12/2022 Date accepted: 05/01/2022 145 Journal OF MILITARY PHARMACO - MEDICINE N02 - 2022 In Vietnam, LEMS is very rare, we report a clinical case with sufficient clinical and electromyographic evidence, Lung tumor was found on chest CT scans The patient was treated by plasma exchange therapy and neostigmine Clinically, the injury of cervical disc herniation found on magnetic resonance imaging was incompatible and eliminated by electromyography This study was conducted: To review several clinical and electromyographical features of LEMS with a lung tumor CLINICAL CASE A 56-year-old male patient had experienced an illness for months His symptoms started with progressive extremity weakness, followed by difficulty breathing requiring mechanical ventilation After months, he lost weight kg Physical examination: awake, limbs weakness, normal sensation, no cranial nerve paralysis, no significant muscle atrophy, but need ventilation because of respiratory failure The patient developed quadriparesis, typically involving proximal muscle function, dry eyes, and dry mouth There were no signs of Babinski or Hoffmann The deep tendon reflexes were slightly depressed Initially, we thought of myasthenia gravis and tested neostigmine After 15 minutes of injection, the patient could breathe easily without ventilation Then, he was treated as myasthenia gravis, plasma exchange times, discharged from the hospital but still needed the support during walking Two months later, the patient had difficulty breathing again, the symptoms were similar to the first time He had limbs weakness (Medical Research Council Scale for Muscle Strength 3/5 - 4/5), blurred vision, and dry eyes After physical examination and brief period of voluntary exercise, the patient had recovery of depressed deep tendon reflexes and improvement in muscle strength RESULTS OF ELECTROMYOGRAPHY - The sensory was normal - The CMAP of resting muscle was absent in lower limbs and decreased in upper limbs Table 1: Nerve conduction study (NR: No Response) Nerves Latency (ms) Amplitude (mV) Conduction velocity (m/s) Left median 3.7 1.77 56 Right median 3.6 1.93 42 Left ulnar 3.4 0.21 Right ulnar 4.1 0.66 Left axillary 4.4 0.26 Right axillary 2.9 0.79 Left peroneal NR NR NR Right peroneal NR NR NR Left tibial NR NR NR Right tibial NR NR NR 146 54 Journal OF MILITARY PHARMACO - MEDICINE N02 - 2022 * Voluntary exercise: Figure 1: An increase in the CMAP amplitude > 100% after 10 seconds of maximal voluntary exercise Figure 2: A decrease in the CMAP amplitude > 10% after Hz RNS (left: 25.4%; right: 42.6%) Figure 3: An increase in the CMAP amplitude 102% after 50 Hz RNS 147 Journal OF MILITARY PHARMACO - MEDICINE N02 - 2022 Figure 4: Left lung tumor Figure 5: Cervical disk herniation The patient was diagnosed with LEMS.A lung tumor was detected on chest CT scans (figure 4) but unfortunately, he had a respiratory failure during the lung biopsy and his family decided to take him home DISCUSSION Because patients had limbs weakness and sometimes, he complained of numbness on both sides of the shoulder but no signs of root injury; we had cervical resonance imaging (figure 5) However, the result was not incompatible with the clinical examination 148 Before being diagnosed with LEMS, at the first discharge, due to the misdiagnosis of myasthenia gravis, the patient had only been treated with Mestinon 60mg, tablets/day Two months later, the patient had difficulty breathing and had to be hospitalized for mechanical ventilation The reason for this phenomenon Journal OF MILITARY PHARMACO - MEDICINE N02 - 2022 is that in clinical practice, it is difficult to distinguish between myasthenia gravis and LEMS Most LEMS patients present with slowly progressive proximal muscle weakness, particularly involving the legs, with or without autonomic symptoms Ocular symptoms may occur but are rarely the main feature of this disease In LEMS, antibodies against P/Q-type voltage-gated calcium channels (P/Q-VGCCs) are positive, whereas myasthenia gravis usually affects the ocular and medulla muscles, no autonomic symptoms, and antibodies to acetylcholine receptor are positive [6, 7, 8] In this patient, acetylcholine receptor (AChR) antibody testing result was negative Unfortunately, we could not perform the P/Q-VGCC antibody test and the family took the patient home early because he developed respiratory failure when undergoing lung biopsy Perhaps in Vietnam, most electromyographer pay too much attention to the post-synaptic lesion while conducting RNS For this reason, they usually stop the test after finding a decrease of CMAP over 10%, and sometimes, they ignore the decreased amplitude of CMAP an important sign of presynaptic disease like LEMS In reality, LEMS is very rare in Viet Nam Although there are many similarities between LEMS and myasthenia gravis, clinical examination, electromyography, and antibody testing can help to differentiate these diseases [1, 5, 8, 9] Our patient met the criteria for diagnosis of LEMS according to Titulaer, 2011 [5], and many other authors [4], 7], 10], with the triad of muscle weakness, autonomic dysfunction, depressed tendon reflexes, and suitable electromyographic findings (decreased CMAP amplitude, positive 3Hz RNS test, positive result after maximal voluntary exercise testing and highfrequency RNS) The results of the nerve conduction study showed absent CMAP in lower limbs and low CMAP in upper limbs that were similar to many authors [3, 5] In LEMS, antibodies against the VGCC that interfere with the normal calcium flux are required for the release of ACh The number of presynaptic acetylcholine (ACh) reduces, therefore, the binding to the post-synaptic membrane receptors also reduces Then, the endplate potential is lower, followed by the amplitude of CMAP decreases The amplitude of CMAP increased by 100%, from 0.21 mV to 0.41 mV after 10-second maximal voluntary exercise testing (figure 1) and 102% after 50Hz RNS in the abductor pollicis brevis (Figure 3) The reason is that in LEMS, the exercise test and high-frequency RNS allow more ACh to be released and the endplate potential reaches the threshold to generate CMAP Therefore, the amplitude of CMAP increases significantly, usually more than 100% [3] CONCLUSION LEMS is a rare disease that usually is confused with myasthenia gravis, myopathy, cervical disease Physical examination, electromyography (nerve conduction, maximal voluntary exercise test, and repetitive nerve stimulation with high frequency) are necessary to make an early diagnosis as well as a prompt and effective treatment 149 Journal OF MILITARY PHARMACO - MEDICINE N02 - 2022 REFERENCES Matsumo H and Ugawa Y Lambert-Eaton Myasthenic Syndrome: A Review General and Family Medicine 2016; 17:138-143 Wirtz P.W., Smallegange T.M., Wintzen A.R., et al Differences in clinical features between the Lambert-Eaton myasthenic syndrome with and without cancer: an analysis of 227 published cases Clin Neurol Neurosurg 2002;104 (4):359-63 Titulaer M.J., Maddison P., Sont J.K., et al Clinical Dutch-English Lambert-Eaton Myasthenic syndrome (LEMS) tumor association prediction score accurately predicts small-cell lung cancer in the LEMS J Clin Oncol 2011; 29(7):902-8 Bodkin C., Pascuzzi R.M Update in the Management of Myasthenia Gravis and Lambert-Eaton Myasthenic Syndrome Neurol Clin 2021; 39(1):133-146 Kesner V.G., Oh S.J., Dimachkie M.M., et al Lambert-Eaton Myasthenic Syndrome Neurol Clin 2018; 36(2):379-394 Sanders D.B., Guptill J.T Myasthenia gravis and Lambert-Eaton myasthenic syndrome Continuum (Minneap Minn) 2014, 20 (5 Peripheral Nervous System Disorders):1413-25 Ivanovski T., Miralles F Lambert-Eaton Myasthenic syndrome: early diagnosis is key Degener Neurol Neuromuscul Dis 2019; 9:27-37 Oh S.J Myasthenia gravis LambertEaton overlap syndrome Muscle Nerve 2016; 53(1):20-6 Titulaer M.J., Lang B., Verschuuren J.J Lambert-Eaton myasthenic syndrome: from clinical characteristics to therapeutic strategies Lancet Neurol 2011; 10(12):1098-107 10 O'Neill J.H., Murray N.M., NewsomDavis J The Lambert-Eaton myasthenic syndrome A review of 50 cases Brain 1988; 111(Pt 3):577-96 150 ... CT scans The patient was treated by plasma exchange therapy and neostigmine Clinically, the injury of cervical disc herniation found on magnetic resonance imaging was incompatible and eliminated... LEMS In reality, LEMS is very rare in Viet Nam Although there are many similarities between LEMS and myasthenia gravis, clinical examination, electromyography, and antibody testing can help to... Dimachkie M.M., et al Lambert- Eaton Myasthenic Syndrome Neurol Clin 2018; 36(2):379-394 Sanders D.B., Guptill J.T Myasthenia gravis and Lambert- Eaton myasthenic syndrome Continuum (Minneap Minn)