History

Fact Explanation
Introduction Lambert Eaton Myasthaenia syndrome is a disorder of neuromuscular junction which is auto immune in aetiology. In contrast to myasthaenia gravis Lambert Eaton Myasthaenia Syndrome (LEMS) cause pre synaptic pathology. The pathophysiology is due to auto antibody mediated inhibition of voltage gated calcium channels in pre synaptic membrane of the neuromuscular junction, which interrupts the release of acetyl choline neurotransmitters in a calcium flux depended manner. Mostly the LEMS is associated with an underlying malignancy, this fact has been discussed below separately. Usually LEMS is an adult disease though rarely seen in paediatric population as well. Usually it is commoner among males. [1][2][3][4][5]
Muscular weakness of limbs The onset of the symptoms and the time of diagnosis may have a significant time interval. The disease is usually slowly progressive. Lower limb muscles mainly the proximal muscles are affected greatly and patient may complain difficulty in standing from chair, climbing and walking. The diseased limbs may be paining. 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. Again in contrast to myasthaenia gravis in LEMS short term hyper activation of the muscle causes transient improvement of the weakness and symptoms, due to transiently adequate release of acetyl choline. [6]
Drooping of eye lids and double vision. Ptosis and diplopia occur due to the involvement of extraoccular nervous system. This could occur but in to a less severe extent in compared to the limb weakness and less common in compared to myasthaenia gravis (MG). So if the ptosis is the initial or only complain the diagnosis is more towards myasthaenia gravis rather than LEMS. Again in contrast to MG in LEMS short term hyper activation of the muscle causes transient improvement of the weakness and symptoms, due to transiently adequate release of acetyl choline. When the LEMS and MG is coexistent those features would be obvious and causes diagnostic dilemmas. [7][8]
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. [9]
Difficulty in speak Dysarthria also could occur due to involvement of muscles used for speech. Again if this symptom is usually seen in MG rather than in LEMS. [9]
Respiratory difficulty The respiratory muscle weakness and consequent respiratory paralysis may occur later in the cause, but initial presentation with respiratory paralysis is less common. [10]
Autonomic features The commonest autonomic feature is dry mouth which may precede the onset of other symptoms. Therefore most patients may forget this symptom and it has to asked specifically. Other autonomic symptoms will be constipation, dry eyes, constricted pupils, impotence and postural hypo tension. [11]
Associated symptoms of malignancies LEMS is a rare entity and usually associated with a concurrent malignancy, mostly small cell carcinoma of lungs. It also can be found in patients with lymphoma, sarcoma, thymoma, malignancies of the breast, colon, stomach, gall badder, thyroid, prostate or bladder. The diseases is usually presents in adult population and more prevalent in males. The prognosis depends on several factors such as the behavior of underlying malignancy, severity of the muscle weakness and so on. The occurrence of LEMS in malignancies have been explained by the expression of similar voltage gated calcium channels in malignant cells and generation of antibody against them which also could react with the inert calcium channels. Other than with the malignancies it also could be associated with other autoimmune conditions such as thyroiditis and pancreatitis. Around 50-70% patients with LEMS will be found to have an underlying malignancy during the disease course. If presented earlier the patients may not have any symptoms of a malignancy even though with extensive LEMS. History about smoking, chonic cough, haemoptysis, anorexia and pleuritic type chest pain should be asked. In relation to other malignancies history of low grade fever, recurrent infections, lymph node enlargement, haematuria, dysphagia, per rectal bleeding, altered bowel habits etc. should be asked. Any malignancy which are associated with LEMS can be preceded, coexistent or followed the occurrence of LEMS, there fore the follow up screening is essential. [3][4][8][12]
References
  1. GIOVANNINI F, SHER E, WEBSTER R, BOOT J, LANG B. Calcium channel subtypes contributing to acetylcholine release from normal, 4-aminopyridine-treated and myasthenic syndrome auto-antibodies-affected neuromuscular junctions Br J Pharmacol [online] 2002 Aug, 136(8):1135-1145 [viewed 15 December 2014] Available from: doi:10.1038/sj.bjp.0704818
  2. TARR TB, MALICK W, LIANG M, VALDOMIR G, FRASSO M, LACOMIS D, REDDEL SW, GARCIA-OCANO A, WIPF P, MERINEY SD. Evaluation of a Novel Calcium Channel Agonist for Therapeutic Potential in Lambert–Eaton Myasthenic Syndrome J Neurosci [online] 2013 Jun 19, 33(25):10559-10567 [viewed 15 December 2014] Available from: doi:10.1523/JNEUROSCI.4629-12.2013
  3. MORRIS CS, ESIRI MM, MARX A, NEWSOM-DAVIS J. Immunocytochemical characteristics of small cell lung carcinoma associated with the Lambert-Eaton myasthenic syndrome. Am J Pathol [online] 1992 Apr, 140(4):839-845 [viewed 15 December 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC188637
  4. LEE JH, SHIN JH, KIM DS, JUNG DS, PARK KH, LEE MK, KIM JY. A Case of Lambert-Eaton Myasthenic Syndrome Associated with Atypical Bronchopulmonary Carcinoid Tumor J Korean Med Sci [online] 2004 Oct, 19(5):753-755 [viewed 15 December 2014] Available from: doi:10.3346/jkms.2004.19.5.753
  5. LINDQUIST S, STANGEL M. Update on treatment options for Lambert–Eaton myasthenic syndrome: focus on use of amifampridine Neuropsychiatr Dis Treat [online] 2011:341-349 [viewed 15 December 2014] Available from: doi:10.2147/NDT.S10464
  6. WIRTZ P, SOTODEH M, NIJNUIS M, VAN DOORN PA, VAN ENGELEN BG, HINTZEN R, DE KORT PL, KUKS J, TWIJNSTRA A, DE VISSER M, VISSER L, WOKKE J, WINTZEN A, VERSCHUUREN J. Difference in distribution of muscle weakness between myasthenia gravis and the Lambert–Eaton myasthenic syndrome J Neurol Neurosurg Psychiatry [online] 2002 Dec, 73(6):766-768 [viewed 15 December 2014] Available from: doi:10.1136/jnnp.73.6.766
  7. KIM JA, LIM YM, JANG EH, KIM KK. A Patient with Coexisting Myasthenia Gravis and Lambert-Eaton Myasthenic Syndrome J Clin Neurol [online] 2012 Sep, 8(3):235-237 [viewed 15 December 2014] Available from: doi:10.3988/jcn.2012.8.3.235
  8. RAY S, SONTHALIA N, KUNDU S, MAITRA S, SAHA M, TALUKDAR A. Lambert–Eaton myasthenic syndrome and solitary cerebellar metastasis in a patient with occult small-cell lung cancer: a rare experience BMJ Case Rep [online] :bcr1220115280 [viewed 15 December 2014] Available from: doi:10.1136/bcr.12.2011.5280
  9. KRAKER J, ŽIVKOVIć SA. Autoimmune Neuromuscular Disorders Curr Neuropharmacol [online] 2011 Sep, 9(3):400-408 [viewed 15 December 2014] Available from: doi:10.2174/157015911796558000
  10. LAROCHE CM, MIER AK, SPIRO SG, NEWSOM-DAVIS J, MOXHAM J, GREEN M. Respiratory muscle weakness in the Lambert-Eaton myasthenic syndrome. Thorax [online] 1989 Nov, 44(11):913-918 [viewed 15 December 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC462147
  11. HEATH JP, EWING DJ, CULL RE. Abnormalities of autonomic function in the Lambert Eaton myasthenic syndrome. J Neurol Neurosurg Psychiatry [online] 1988 Mar, 51(3):436-439 [viewed 15 December 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1032876
  12. PELOSOF LC, GERBER DE. Paraneoplastic Syndromes: An Approach to Diagnosis and Treatment Mayo Clin Proc [online] 2010 Sep, 85(9):838-854 [viewed 15 December 2014] Available from: doi:10.4065/mcp.2010.0099

Examination

Fact Explanation
Features of muscle weakness The patient may be specially having weakness of proximal muscle groups. The gait may be unsteady, waddling. Patient may have difficulty in reaching objects due to the upper limb weakness. The muscle power of the proximal muscle may usually be reduced. The power of the muscle can be transiently increased by little hyper activation or over exercise of the muscle for a short period. Following transient improvement of the muscle power the weakness worsen if the activity is sustaained. This transient improvement of the muscle power can be used to differentiate LEMS from MG. [1][2][3]
Deep tendon reflexes Usually the deep tendon reflexes are absent or diminished. In the same way as transient muscle power improvement with transient hyperactivity tendon reflexes also can be elicited. [2][3]
Sensory examination The sensory examination has to be normal.But associated peripheral neuropathy may be present in patients with malignancies. [4][5]
Occular and oropharyngeal examination Mild degree of ptosis, diplopia, dysphagia and dysarthria may be observed less commonly. Similar transient improvement can be seen with short lasting over activation of the muscles which again diminish with sustained activation. [6][7]
Respiratory distress and respiratory weakness Though not common in initial phases of the illness difficulty in breathing and respiratory distress may be seen in later part of the illness. [8]
Autonomic manifestations The commonest would be the dry mouth and erectile dysfunction in males. Others would be postural hypotension, pupillary constriction, urinary retention and constipation. [9]
Features of underlying malignancy As mentioned above the manifestations of malignancies may not be obvious in initial phase of the illness. The possible signs of small cell carcinoma are clubbing, cachexia and evidence of focal lesions on respiratory examination and lymphadenopathy. Other than for small cell carcinoma of lungs physical signs should be elicited in other possible malignancies such as generalized lymphadenopathy, hepatosplenomegaly, abdomina or loin masses, pelvic masses and goiters. Breast examination also have to be performed. [1][2][10][11]
References
  1. WIRTZ P, SOTODEH M, NIJNUIS M, VAN DOORN PA, VAN ENGELEN BG, HINTZEN R, DE KORT PL, KUKS J, TWIJNSTRA A, DE VISSER M, VISSER L, WOKKE J, WINTZEN A, VERSCHUUREN J. Difference in distribution of muscle weakness between myasthenia gravis and the Lambert–Eaton myasthenic syndrome J Neurol Neurosurg Psychiatry [online] 2002 Dec, 73(6):766-768 [viewed 15 December 2014] Available from: doi:10.1136/jnnp.73.6.766
  2. PELOSOF LC, GERBER DE. Paraneoplastic Syndromes: An Approach to Diagnosis and Treatment Mayo Clin Proc [online] 2010 Sep, 85(9):838-854 [viewed 15 December 2014] A
  3. JOHNS RJ, BROWN JC. The Eaton-Lambert syndrome masquerading as proximal myopathy. Trans Am Clin Climatol Assoc [online] 1968:134-138 [viewed 15 December 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2441164
  4. KRAKER J, ŽIVKOVIć SA. Autoimmune Neuromuscular Disorders Curr Neuropharmacol [online] 2011 Sep, 9(3):400-408 [viewed 15 December 2014] Available from: doi:10.2174/157015911796558000
  5. PETTY R. Lambert-Eaton myasthenic syndrome BMJ Case Rep [online] :bcr09.2008.0914 [viewed 15 December 2014] Available from: doi:10.1136/bcr.09.2008.0914
  6. TAPHOORN MJ, VAN DUIJN H, WOLTERS EC. A neuromuscular transmission disorder: combined myasthenia gravis and Lambert Eaton syndrome in one patient. J Neurol Neurosurg Psychiatry [online] 1988 Jun, 51(6):880-882 [viewed 15 December 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1033167
  7. KIM JY, PARK KD, KIM SM, SUNWOO IN. Repetitive Nerve Stimulation Test in Amyotrophic Lateral Sclerosis with Predominant Oropharyngeal Manifestations J Clin Neurol [online] 2011 Mar, 7(1):31-33 [viewed 15 December 2014] Available from: doi:10.3988/jcn.2011.7.1.3
  8. LAROCHE CM, MIER AK, SPIRO SG, NEWSOM-DAVIS J, MOXHAM J, GREEN M. Respiratory muscle weakness in the Lambert-Eaton myasthenic syndrome. Thorax [online] 1989 Nov, 44(11):913-918 [viewed 15 December 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC462147
  9. HEATH JP, EWING DJ, CULL RE. Abnormalities of autonomic function in the Lambert Eaton myasthenic syndrome. J Neurol Neurosurg Psychiatry [online] 1988 Mar, 51(3):436-439 [viewed 15 December 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1032876
  10. SENEVIRATNE U, DE SILVA R. Lambert-Eaton myasthenic syndrome Postgrad Med J [online] 1999 Sep, 75(887):516-520 [viewed 15 December 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1741360
  11. DALMAU J, ROSENFELD MR. Paraneoplastic syndromes of the CNS Lancet Neurol [online] 2008 Apr, 7(4):327-340 [viewed 15 December 2014] Available from: doi:10.1016/S1474-4422(08)70060-7

Differential Diagnoses

Fact Explanation
Myasthaenia gravis This is also a disorder of neuromuscular junction but it is post synaptic. Similar features may occur in different severity. In MG the symptoms such as ptosis, diplopia, dysphagia and dysarthria may precede limb weakness and more commonly present than in LEMS. The weakness could not be improved by transient over activation of the muscle group which is distinguishly seen in LEMS. Antibody to acetyl choline receptors will be greatly elevated in MG though little elevation is present even in LEMS. In LEMS anti body against calcium channel blockers may be seen. Nerve conduction studies and electromyogram will differentiate two conditions as discussed below. The association with the malignancies is not obvious in MG. [1][2][3]
Other myopathies Other myopathies such as inclusion body myositis, polymyositis, dermatomyositis have to be differentiated. In all situations proximal muscle weakness is present with out significant sensory impairment. History of malignancy, worsening symptoms once exposed to hot water, transient improvement of weakness with short term over activation which is followed by fatigue with sustained action, presence of autonomic features and immunological markers with nerve conduction studies will differentiate LEMS from other myopathies. [4][5]
Guillen Barrre Syndrome This is also commonly known as acute inflammatory demyelinating polyneuropathy. The history here will be ascending paralysis with sensory symptoms in acute or sub acute origin. Here also the signs of sensory loss is not present, reflexes are absent and respiratory distress could occur. Nerve conduction studies and antibody testing will differentiate two conditions further. [4][6]
Motor neuron disease Here more insidious onset illness can be seen involving lower and upper motor neurons. Sensory and autonomic symptoms could present with out significant sensory loss on examination. In contrast to LEMS upper motor signs are also seen. In motor neuron disease the extra ocular muscles are typically spared. Nerve conduction studies will show typical findings of two entities. [7][8]
Cerebro vascular events Strokes and cerebro vascular events are more acute with usual unilateral involvement. Cerebral imaging will confirm the diagnosis. [4]
Electrolyte abnormalities; Hypokalaemia, hypocalcaemia, hyponatraemia, hypomagnaesimia These electrolyte abnormalities may present with generalized body weakness with or with out sensory impairment. Other manifestations like confusion and seizures may also be present. Serum levels of those electrolytes will usually confirms the diagnosis when typical history is present. [5][9]
Hypothyroidism Hypothyroidism may also present with generalized weakness with hyporeflexia. Other features such as cold intolerance, constipation, memory impairment, horse voice, dry skin, goiter has to be assessed. TSH and T4 levels can be done for the confirmation. [10]
References
  1. NEWSOM-DAVIS J, LEYS K, VINCENT A, FERGUSON I, MODI G, MILLS K. Immunological evidence for the co-existence of the Lambert-Eaton myasthenic syndrome and myasthenia gravis in two patients. J Neurol Neurosurg Psychiatry [online] 1991 May, 54(5):452-453 [viewed 15 December 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC488548
  2. MADDISON P, NEWSOM-DAVIS J, MILLS K. Distribution of electrophysiological abnormality in Lambert-Eaton myasthenic syndrome J Neurol Neurosurg Psychiatry [online] 1998 Aug, 65(2):213-217 [viewed 15 December 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2170198
  3. WIRTZ P, SOTODEH M, NIJNUIS M, VAN DOORN PA, VAN ENGELEN BG, HINTZEN R, DE KORT PL, KUKS J, TWIJNSTRA A, DE VISSER M, VISSER L, WOKKE J, WINTZEN A, VERSCHUUREN J. Difference in distribution of muscle weakness between myasthenia gravis and the Lambert–Eaton myasthenic syndrome J Neurol Neurosurg Psychiatry [online] 2002 Dec, 73(6):766-768 [viewed 15 December 2014] Available from: doi:10.1136/jnnp.73.6.766
  4. KRAKER J, ŽIVKOVIć SA. Autoimmune Neuromuscular Disorders Curr Neuropharmacol [online] 2011 Sep, 9(3):400-408 [viewed 15 December 2014] Available from: doi:10.2174/157015911796558000
  5. PELOSOF LC, GERBER DE. Paraneoplastic Syndromes: An Approach to Diagnosis and Treatment Mayo Clin Proc [online] 2010 Sep, 85(9):838-854 [viewed 15 December 2014] Available from: doi:10.4065/mcp.2010.0099
  6. TRUFFERT A, ALLALI G, VOKATCH N, LALIVE PH. Mild clinical expression of Lambert–Eaton myasthenic syndrome in a patient with HIV infection J Neurol Neurosurg Psychiatry [online] 2007 Aug, 78(8):910-911 [viewed 15 December 2014] Available from: doi:10.1136/jnnp.2007.115089
  7. DELBONO O, GARCíA J, APPEL SH, STEFANI E. Calcium current and charge movement of mammalian muscle: action of amyotrophic lateral sclerosis immunoglobulins. J Physiol [online] 1991 Dec:723-742 [viewed 15 December 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1179958
  8. SMITH RG, ALEXIANU ME, CRAWFORD G, NYORMOI O, STEFANI E, APPEL SH. Cytotoxicity of immunoglobulins from amyotrophic lateral sclerosis patients on a hybrid motoneuron cell line. Proc Natl Acad Sci U S A [online] 1994 Apr 12, 91(8):3393-3397 [viewed 15 December 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC43583
  9. LEE CJ, LIM SH, SHIN CM, KIM YJ, CHOE YK, CHEONG SH, LEE KM, LEE JH, KIM YH, CHO KR, LEE SE, BAE JS. Lambert-Eaton myasthenic syndrome as a cause of persistent neuromuscular weakness after a mediastinoscopic biopsy -A case report- Korean J Anesthesiol [online] 2010 Jul, 59(1):45-48 [viewed 15 December 2014] Available from: doi:10.4097/kjae.2010.59.1.45
  10. SELIM M, DRACHMAN D. Ataxia associated with Hashimoto's disease: progressive non-familial adult onset cerebellar degeneration with autoimmune thyroiditis J Neurol Neurosurg Psychiatry [online] 2001 Jul, 71(1):81-87 [viewed 15 December 2014] Available from: doi:10.1136/jnnp.71.1.81

Investigations - for Diagnosis

Fact Explanation
Anti body assays Anti bodies against Voltage Gated Calcium channel can be seen in patients with LEMS. It is mostly (75-100%) present when it is associated with small cell lung cancer. It can also present (25%) even with out LEMS in patients with small cell lung cancers. Small number of patients with MG will show low titers of voltage gated calcium channel antibodies. In MG anti bodies against acetyl choline receptors are greatly present though low titers can be in in LEMS as well. [1][2][3][4]
Edrophonium (Tensilon) Test Edrophonium injection test can be used to differentiate LEMS from MG, where there will be a good response in MG. [5][6]
Repetitive nerve stimulation test This is the diagnostic test when typical features are demonstrated. Initially the compound muscle action potential (CMAP) is less than the normal and CMAP increases to around twice normal when stimulated with 20-50 Hz or voluntary contraction. [7][8][9]
Electromyography This will show the markedly unstable action potential at motor neuron unit with variability with the voluntary contraction of the muscle. [10]
Investigations to detect underlying small cell carcinoma of lungs and other malignacies. In all adult patients with LEMS thorough investigations must be carried out to exclude small cell lung cancers. Chest xray, CT scan and MRI scan of the chest have to be performed. The broncoscopy is essential if the imaging is normal. If the facilities are available positron emission tomography (PET) scanning should be considered. Even with negative investigations patient may be having early lung cancer therefore the further surveillance is must during follow up. To exclude other malignancies ultra sound scan of the neck, abdomen, pelvis, breast and mammography, CT or MRI scan, endoscopies can be performed. Serology vise markers of malignancies such as LDH, CEA, CA-125, CA-19.9 can be tested. [11][12][13]
For other differential diagnoses As mentioned above for other differential diagnoses serum electrolytes including sodium , potassium, calcium and magnesium has to be checked. For patients suspected to have hypothyroidism TSH and free T4 to be checked. [14][15][16]
References
  1. MOTOMURA M, JOHNSTON I, LANG B, VINCENT A, NEWSOM-DAVIS J. An improved diagnostic assay for Lambert-Eaton myasthenic syndrome. J Neurol Neurosurg Psychiatry [online] 1995 Jan, 58(1):85-87 [viewed 16 December 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC107327
  2. LANG B, NEWSOM-DAVIS J, PEERS C, PRIOR C, WRAY DW. The effect of myasthenic syndrome antibody on presynaptic calcium channels in the mouse. J Physiol [online] 1987 Sep:257-270 [viewed 16 December 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1192178
  3. SOMNIER FE. Clinical implementation of anti-acetylcholine receptor antibodies. J Neurol Neurosurg Psychiatry [online] 1993 May, 56(5):496-504 [viewed 16 December 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1015008
  4. VINCENT A, NEWSOM-DAVIS J. Acetylcholine receptor antibody as a diagnostic test for myasthenia gravis: results in 153 validated cases and 2967 diagnostic assays. J Neurol Neurosurg Psychiatry [online] 1985 Dec, 48(12):1246-1252 [viewed 16 December 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1028609
  5. KIM JA, LIM YM, JANG EH, KIM KK. A Patient with Coexisting Myasthenia Gravis and Lambert-Eaton Myasthenic Syndrome J Clin Neurol [online] 2012 Sep, 8(3):235-237 [viewed 16 December 2014] Available from: doi:10.3988/jcn.2012.8.3.23
  6. BENNETT DL, MILLS KR, RIORDAN‐EVA P, BARNES PR, ROSE MR. Anti‐MuSK antibodies in a case of ocular myasthenia gravis J Neurol Neurosurg Psychiatry [online] 2006 Apr, 77(4):564-565 [viewed 16 December 2014] Available from: doi:10.1136/jnnp.2005.075812
  7. KIM JY, PARK KD, KIM SM, SUNWOO IN. Repetitive Nerve Stimulation Test in Amyotrophic Lateral Sclerosis with Predominant Oropharyngeal Manifestations J Clin Neurol [online] 2011 Mar, 7(1):31-33 [viewed 16 December 2014] Available from: doi:10.3988/jcn.2011.7.1.31
  8. MADDISON P, NEWSOM-DAVIS J, MILLS K. Distribution of electrophysiological abnormality in Lambert-Eaton myasthenic syndrome J Neurol Neurosurg Psychiatry [online] 1998 Aug, 65(2):213-217 [viewed 16 December 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2170198
  9. KIM JY, PARK KD, KIM SM, SUNWOO IN. Decremental Responses to Repetitive Nerve Stimulation in X-Linked Bulbospinal Muscular Atrophy J Clin Neurol [online] 2013 Jan, 9(1):32-35 [viewed 16 December 2014] Available from: doi:10.3988/jcn.2013.9.1.32
  10. KOMATSU T, BOKUDA K, SHIMIZU T, KOMORI T, KOIDE R. Pseudomyopathic Changes in Needle Electromyography in Lambert-Eaton Myasthenic Syndrome Case Rep Neurol Med [online] 2013:369278 [viewed 16 December 2014] Available from: doi:10.1155/2013/369278
  11. GRIFFETH LK. Use of PET/CT scanning in cancer patients: technical and practical considerations Proc (Bayl Univ Med Cent) [online] 2005 Oct, 18(4):321-330 [viewed 16 December 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1255942
  12. CHUANG MT, MARCHEVSKY A, TEIRSTEIN AS, KIRSCHNER PA, KLEINERMAN J. Diagnosis of lung cancer by fibreoptic bronchoscopy: problems in the histological classification of non-small cell carcinomas. Thorax [online] 1984 Mar, 39(3):175-178 [viewed 16 December 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC459754
  13. WANG Z, TIAN YP. Clinical value of serum tumor markers CA19-9, CA125 and CA72-4 in the diagnosis of pancreatic carcinoma Mol Clin Oncol [online] 2014 Mar, 2(2):265-268 [viewed 16 December 2014] Available from: doi:10.3892/mco.2013.226
  14. BISWAS M, DAVIES JS. Hyponatraemia in clinical practice Postgrad Med J [online] 2007 Jun, 83(980):373-378 [viewed 16 December 2014] Available from: doi:10.1136/pgmj.2006.056515
  15. PELOSOF LC, GERBER DE. Paraneoplastic Syndromes: An Approach to Diagnosis and Treatment Mayo Clin Proc [online] 2010 Sep, 85(9):838-854 [viewed 16 December 2014] Available from: doi:10.4065/mcp.2010.0099
  16. STOCKIGT J. Assessment of Thyroid Function: Towards an Integrated Laboratory - Clinical Approach Clin Biochem Rev [online] 2003 Nov, 24(4):109-122 [viewed 16 December 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1853349

Investigations - for Management

Fact Explanation
For the emergency management When the patients are presenting with acute respiratory distress acute management should be done at the emergency department. There full blood count, ECG, arterial blood gas analysis, serum electrolytes and saturation should be done. [1][2][3]
Spirometry To assess the status of respiratory function spirometry which is a bed side test can be carried out which shows the vital capacity of the patient. It denotes the indication for ventilation support as well. [4]
Seek for a malignancy During the followup visits investigations must be carried out to seek for hidden malignancies. These include CT scans, MRI scans, Broncoscopies and malignancy markers as discussed above. [5][6]
FBC, Serum Calcium levels, DEXA scan, Fasting blood sugar, Upper GI endoscopies During the management with long term steroids infections can cause such as infection, osteoporosis, Diabetes mellitus and gastritis. So those should be detected early and treated timely. [7]
References
  1. MACKENZIE CF, HU P, SEN A, DUTTON R, SEEBODE S, FLOCCARE D, SCALEA T. Automatic Pre-Hospital Vital Signs Waveform and Trend Data Capture Fills Quality Management, Triage and Outcome Prediction Gaps AMIA Annu Symp Proc [online] 2008:318-322 [viewed 16 December 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC265608
  2. HOLBURN CJ, ALLEN MJ. Pulse oximetry in the accident and emergency department. Arch Emerg Med [online] 1989 Jun, 6(2):137-142 [viewed 16 December 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1285582
  3. BATRA P, DWIVEDI AK, THAKUR N. Bedside ABG, electrolytes, lactate and procalcitonin in emergency pediatrics Int J Crit Illn Inj Sci [online] 2014, 4(3):247-252 [viewed 16 December 2014] Available from: doi:10.4103/2229-5151.141467
  4. ZIBULEWSKY J. The Emergency Medical Treatment and Active Labor Act (EMTALA): what it is and what it means for physicians Proc (Bayl Univ Med Cent) [online] 2001 Oct, 14(4):339-346 [viewed 16 December 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1305897
  5. PELOSOF LC, GERBER DE. Paraneoplastic Syndromes: An Approach to Diagnosis and Treatment Mayo Clin Proc [online] 2010 Sep, 85(9):838-854 [viewed 16 December 2014] Available from: doi:10.4065/mcp.2010.0099
  6. MORRIS CS, ESIRI MM, MARX A, NEWSOM-DAVIS J. Immunocytochemical characteristics of small cell lung carcinoma associated with the Lambert-Eaton myasthenic syndrome. Am J Pathol [online] 1992 Apr, 140(4):839-845 [viewed 16 December 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1886379
  7. BEERAKA SS, NATARAJAN K, PATIL R, MANNE RK, PRATHI VS, KOLAPARTHI VS. Clinical and radiological assessment of effects of long-term corticosteroid therapy on oral health Dent Res J (Isfahan) [online] 2013, 10(5):666-673 [viewed 16 December 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3858744

Management - General Measures

Fact Explanation
Emergency management As an emergency patient may present to the emergency department with evidence of respiratory paralysis. In these situation the ABC should follow. The airway has to be maintained breathing has to be optimized. The patient may need intubation and ICU care for ventilation. Large bore cannula with adequate hydration should be ensured. With the achieve of the diagnosis plasma paresis or immunosupression may be needed who presents with acute weakness. [1][2]
Health education This should the rare occurrence of the disease, the brief pathophysiology, progression and the prognosis of the illness, importance of follow up, available treatment options and patient should be thoroughly emphasized about the high probability of having a malignancy underlying. He or she should be educated about the importance of followup with investigations in view of finding a hidden malignancy. [3][4]
Avoidance of exacerbating environmental factors The mostly identified aggravating environmental factor would be the hot ambient temperature, therefore the avoidance of such factors including hot shower baths may prevent the worsening of symptoms. [5][6]
Avoidance of exacerbating or worsening medications The drugs which may impede the transmission of neuro muscular junction will cause worsening symptoms. Therefore those medications are better avoided unless really indicated. Examples are antibiotics (aminoglycosides, fluoroquinolones and some macrolides), antiarrhythmics (quinine, quinidine, procainamide) and beta blockers. IV magnesium or Iodine containing contrast mediums also could cause worsening symptoms. [7]
Proper exercise and physiotherapy Properly arranged regular physiotherapy may help to maintain the muscle strength. [8][9]
References
  1. THIM T, KRARUP NH, GROVE EL, ROHDE CV, LøFGREN B. Initial assessment and treatment with the Airway, Breathing, Circulation, Disability, Exposure (ABCDE) approach Int J Gen Med [online] :117-121 [viewed 16 December 2014] Available from: doi:10.2147/IJGM.S28478
  2. JOLLES S, SEWELL W, MISBAH S. Clinical uses of intravenous immunoglobulin Clin Exp Immunol [online] 2005 Oct, 142(1):1-11 [viewed 16 December 2014] Available from: doi:10.1111/j.1365-2249.2005.02834.x
  3. PELOSOF LC, GERBER DE. Paraneoplastic Syndromes: An Approach to Diagnosis and Treatment Mayo Clin Proc [online] 2010 Sep, 85(9):838-854 [viewed 16 December 2014] Available from: doi:10.4065/mcp.2010.0099
  4. MERAVIGLIA MG, STUIFBERGEN A. Health-Promoting Behaviors of Low-Income Cancer Survivors Clin Nurse Spec [online] 2011, 25(3):118-124 [viewed 16 December 2014] Available from: doi:10.1097/NUR.0b013e3182157786
  5. WARD CD, MURRAY NM. Effect of temperature on neuromuscular transmission in the Eaton-Lambert syndrome J Neurol Neurosurg Psychiatry [online] 1979 Mar, 42(3):247-249 [viewed 16 December 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC490728
  6. SANDERS DB, KIM YI, HOWARD JF JR, GOETSCH CA. Eaton-Lambert syndrome: a clinical and electrophysiological study of a patient treated with 4-aminopyridine. J Neurol Neurosurg Psychiatry [online] 1980 Nov, 43(11):978-985 [viewed 16 December 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC490748
  7. KRAKER J, ŽIVKOVIć SA. Autoimmune Neuromuscular Disorders Curr Neuropharmacol [online] 2011 Sep, 9(3):400-408 [viewed 16 December 2014] Available from: doi:10.2174/15701591179655800
  8. SIMON JI, HERBISON GJ, LEVY G. Case report: a case review of Lambert–Eaton myasthenic syndrome and low back pain Curr Rev Musculoskelet Med [online] , 4(1):1-5 [viewed 16 December 2014] Available from: doi:10.1007/s12178-010-9068-1
  9. LINDQUIST S, STANGEL M. Update on treatment options for Lambert–Eaton myasthenic syndrome: focus on use of amifampridine Neuropsychiatr Dis Treat [online] 2011:341-349 [viewed 16 December 2014] Available from: doi:10.2147/NDT.S10464

Management - Specific Treatments

Fact Explanation
Treatment of underlying malignancy As mentioned previously the associated malignancy commonly the small cell carcinoma of lungs should be identified and managed promptly. The treatment of the cancer will improve the symptoms of LEMS. When the patient is having an underlying cancer the may be no or little improvement with immmunotherapy when administered prior to the treatment of cancer. When there is no underlying malignancy aggressive immunotherapy can be started. [1][2][3]
Medications which will improve the neurotranmittion via neuromuscular junction. These drugs improve the conduction through the neuromuscular junction either by improving the acetyl choline release at pre-synaptic membrane (3,4-diaminopyridine) or reducing the turn over of acetyl choline at post-synaptic membrane (pyridostigmine). [4][5][6]
Immunotherapy When the improvement with above medication is not adequate aggressive immunotherapy is indicated. This can be achieved by plasma exchange or Intravenous Immunoglobulin (IVIG 2 g/kg over 2-5 days). But it has to be followed up by long term immuno suppression. Plasma exchange has to be done 4-6 cycles over 5-7 days. Complications should be monitored, such as hypercalcaemia, bleeding and autonomic instability. [3][7][8]
Immuno suppressants The commonly used immuno suppressants are prednisolone and azathioprine, which can be used alone or in combination. Another option would be cyclosporin.The side effects has to be monitored. [3][7][9]
References
  1. MADDISON P, LANG B, MILLS K, NEWSOM-DAVIS J. Long term outcome in Lambert-Eaton myasthenic syndrome without lung cancer J Neurol Neurosurg Psychiatry [online] 2001 Feb, 70(2):212-217 [viewed 16 December 2014] Available from: doi:10.1136/jnnp.70.2.212
  2. INGRAM DA, DAVIS GR, SCHWARTZ MS, TRAUB M, NEWLAND AC, SWASH M. Cancer-associated myasthenic (Eaton-Lambert) syndrome: distribution of abnormality and effect of treatment. J Neurol Neurosurg Psychiatry [online] 1984 Aug, 47(8):806-812 [viewed 16 December 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1027943
  3. PELOSOF LC, GERBER DE. Paraneoplastic Syndromes: An Approach to Diagnosis and Treatment Mayo Clin Proc [online] 2010 Sep, 85(9):838-854 [viewed 16 December 2014] Available from: doi:10.4065/mcp.2010.0099
  4. LINDQUIST S, STANGEL M. Update on treatment options for Lambert–Eaton myasthenic syndrome: focus on use of amifampridine Neuropsychiatr Dis Treat [online] 2011:341-349 [viewed 16 December 2014] Available from: doi:10.2147/NDT.S10464
  5. SENEVIRATNE U, DE SILVA R. Lambert-Eaton myasthenic syndrome Postgrad Med J [online] 1999 Sep, 75(887):516-520 [viewed 16 December 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1741360
  6. MADDISON P, NEWSOM-DAVIS J, MILLS K. Distribution of electrophysiological abnormality in Lambert-Eaton myasthenic syndrome J Neurol Neurosurg Psychiatry [online] 1998 Aug, 65(2):213-217 [viewed 16 December 2014] Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2170198
  7. KRAKER J, ŽIVKOVIć SA. Autoimmune Neuromuscular Disorders Curr Neuropharmacol [online] 2011 Sep, 9(3):400-408 [viewed 16 December 2014] Available from: doi:10.2174/157015911796558000
  8. JOLLES S, SEWELL W, MISBAH S. Clinical uses of intravenous immunoglobulin Clin Exp Immunol [online] 2005 Oct, 142(1):1-11 [viewed 16 December 2014] Available from: doi:10.1111/j.1365-2249.2005.02834.x
  9. KLEOPA KA. Autoimmune Channelopathies of the Nervous System Curr Neuropharmacol [online] 2011 Sep, 9(3):458-467 [viewed 16 December 2014] Available from: doi:10.2174/157015911796557966