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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Differential Diagnosis of Myasthenic Syndromes