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Differential diagnosis myasthenic syndromes

Differential Diagnosis of Myasthenic Syndromes

Acetylcholine Receptor Autoantibodies
Calcium Channel Autoantibodies
Diagnosis of Lambert-Eaton Syndrome Myasthenia gravis is an acquired, humoral The primary physiological disorder in the Specific acetylcholine
Lambert-Eaton myasthenic syndrome (LEMS) is
receptor autoantibodies (ACHRAB) lead to a
a reduced release of the neurotransmitter reduced impulse transmission to the postsynaptic acetylcholine from the nerve terminals into the membrane of the neuromuscular end-plate. T-helper cells which have been activated in the thymus probably stimulate the production of the autoantibodies against a membrane protein of the acetylcholine receptor autoantibodies. These nerve cell, the voltage-gated calcium channel
react mainly with the α-subunit of the receptors, (VGCC). These channels are also described as reducing the functional activity at the postsynaptic active zone of the presynaptic membrane. Lambert-Eaton Syndrome
Myasthenia gravis
Autoantibodies against the presynaptic voltage- Clinical Features
The main features in myasthenia gravis are The Lambert-Eaton syndrome occurs less often weakness and fatiguability of sceletal muscles. than myasthenia gravis. The main characteristics Ptosis and diplopia occur early in the majority of are a weakness of the proximal muscles, reduced patients. Weakness remains localized to the tendon reflexes as well as autonomous disorders extraocular and eyelid muscles in about 15 % of like visual disorders, dry mouth, reduced patients (ocular myasthenia). The facial and transpiration and tear fluid, constipation and bulbar muscles can be affected (mild generalized disease). Generalized weakness develops in about 85 % of patients and can lead to a life- threatening impairment of respiration (severe paraneoplastic syndrome, associating specifically with small-cell lung carcinoma (SCLC). In the remaining cases no carcinoma can be found The disease occures during all ages, from infancy up to old age. The prevalence is 5-12 cases per 100,000 population. Women are affected twice as LEMS is usually diagnosed prior to any clinical manifestation of the tumour. Typically the In the severe generalized disease even low strain radiological appearance of the cancer by 2 years causes respiratory insufficiency. Sitting up as well and sometimes by 5 years or more. The diagnosis as walking or standing is no longer possible of LEMS can give the earliest clue to an without help. The limb muscels are almost immobilized. Chewing and swallowing may be Therefore, patients with LEMS should have strongly impaired and patients may aspirate. repeated pulmonary check-ups. X-ray examina- Because of these life-threatening conditions it can tions of the chest are recommended every 3 be necessary to look after the patients in an months and a bronchoscopy every 6 months. The Lambert-Eaton syndrome usually occurs Patients with an initially severe generalized after the age of 30 and is twice as common in myasthenia gravis have a poor prognosis. men as in women. The disease is rare with Sometimes a myasthenic crisis with respiratory insufficiency can occur within a short time. The typical symptomes in LEMS are very similar to the generalized symptomes of myasthenia psychological impairment can cause a change for gravis (MG). Therefore, LEMS may initially be The most important different characteristics of the two diseases are shown in the following table: Myasthenia gravis
Lambert-Eaton syndrome
additional increment at 20-Hz stimulation autoantibodies calcium channel autoantibodies Diagnosis
The history and physical findings are usually the For the diagnosis of the Lambert-Eaton syndrome most important initial clues to the diagnosis of methods like testing of the tendon reflexes and MG. Confirmatory laboratory testing like the repetitive nerve stimulation can be used. In Tensilon® test, the 3-Hz repeated stimulation and addition the radioimmunological measurement of the single-fiber electromyography are essential. antibodies against the voltage-gated calcium channels are of help. The use of P/Q-VGCCs, antibodies against acetylcholine receptors is of labelled with 125I-ω-Conotoxin MVIIC results in a great importance for the differential diagnosis. 90% to 100% of patients with Lambert-Eaton syndrome and small-cell lung carcinoma are Pathological concentrations of antibodies are positive in the test. 80% to 90% of the patients detectable in about 90 to 95% of patients with with LEMS but without SCCL are found positive. generalized myasthenia gravis and in about There are only very few cases of normal healthy 45% of patients with ocular MG. The absolute blood-donors and patients with other neurological antibody concentration does not correlate with the severity of the disease, but in more than rheumatoid arthritis or SLE, who are found low 90% of the patients there is a good individual correlation between the change of antibody concentration and clinical features. Therefore, the measurement of the antibodies is of great help in concentration of antibodies seems not to be the therapeutic management and follow-up of correlated with the severity of the disease. But for myasthenia gravis. Above all it has been shown, the individual patient the increase or decrease of that an increase of the autoantibodies can often the concentration of antibodies may reflect the be found several weeks before the onset of Anticholinesterase agents (Prostigmine, Pyrido- For a Lambert-Eaton syndrome associated with stigmine) are used as the first line of treatment for small-cell carcinoma of the lung, priority is given myasthenia gravis at all stages of severity and to the therapy of the tumour. The surgical removal grades of the disease. They are the basis used for the focal disease, restricted to ocular muscles. improvement of the neurological symptomes. suppressive treatment with corticosteroids and azathioprine is indicated for more severe generalized disorders. The single steps of 4-Aminopyridine (possibly in combination with treatment depend on the severity of the clinical pyridostigmine) seems to be ideally suited for the symptomatic treatment of the Lambert-Eaton After thymectomy, clinical remission occures in approximately 30 % of the patients (mainly at terminals. If there is no sufficient improvement, females) and improvement is seen in another particularly in patients without tumour, an 45 %. Plasma exchange produces short-term immunosuppressive therapy with prednisolone clinical improvement. It is used primarily to and/or azathioprine is indicated. In some cases stabilize the condition of patients in myasthenic crisis or in patients who do not respond to other Plasmapheresis is an effective treatment for Literature
J. Newsom-Davis
Diseases of the Neuromuscular Junction
in: Diseases of the Nervous System. A.K. Asbury, G.M. McKhann, W.I. McDonald, Eds.
WB Saunders, Philadelphia 1992; 197-212
R. Voltz, R. Hohlfeld, A. Fateh-Moghadam, T.N. Witt, C. Reimers, B. Siegele, H. Wekerle
Myasthenia gravis: measurement of anti-AChR autoantibodies using cell line TE671
Neurology 1991; 41: 1836-38
B. Stuhlmüller, J.R. Kalden, R. Fahlbusch, N. Hain, B. Manger
Immunological and functional properties of acetylcholine receptor expressed on the human cell
line TE671

Eur. J. Clin. Chem. Clin. Biochem. 1993; 31: 657-665
P.F. Kennel, J.T. Vilquin, S. Braun, P. Fonteneau, J.M. Warter, P. Poindron
Myasthenia gravis: comparative autoantibody assays using human muscle, TE671 and
glucocorticoid-treated TE671 cells as sources of antigen
Clin. Immunol. Immunopathol. 1995; 74: 293-296
M. Motomura, I. Johnston, B. Lang, A. Vincent, J. Newsom-Davis
An improved diagnostic assay for Lambert-Eaton myasthenic syndrome.
J. Neurol. Neurosurg. Psychiatry 1995; 58: 85-87
V.A. Lennon, Th.J. Kryzer, G.E. Griesmann, P.E. O'Suilleabhain, A.J. Windebank, A. Woppmann, G.P.
Miljanich, E.H. Lambert
Calcium channel antibodies in the Lambert-Eaton syndrome and other paraneoplastic syndromes.
N. Engl. J. Med. 1995; 332: 1467-1474
B. Lang, J. Newsom-Davis
Immunopathology of the Lambert-Eaton myasthenic syndrome.
Springer Seminars in Immunopathology 1995;17:3-15
G.M. Elrington, N.M.F. Murray, S.G. Spiro, J. Newsom-Davis
Neurological paraneoplastic syndromes in patients with small cell lung cancer. A prospective
survey of 150 patients.

J. Neurol. Neurosurg. Psychiatry 1991;54:764-767
Further literature upon request

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