A serologic test for these antibodies (anti-VGKC) is available and is performed to confirm the diagnosis. Even in patients without detectable antibodies against voltage-gated calcium channels, passive transfer experiments indicate the presence of a circulating factor with similar activity. Muscle biopsy is normal or shows only the same slight, nonspecific changes as in myasthenia gravis. The thymus is, of course, normal.
Recognition of the Lambert-Eaton syndrome should lead to a search for an occult tumor, particularly of the lung. A positron emission tomography (PET) scan of the body may be useful for this purpose, although CT of the lungs is usually adequate. If found, it should be treated; this alone may result in improvement in the neurologic syndrome. If none is found, the search should be repeated at regular intervals, as the tumors at first are small and may be inapparent even at autopsy. Numerous cases of the more typical paraneoplastic syndromes discussed in Chap. 30, such as cerebellar degeneration, may coexist with the Lambert-Eaton syndrome, most of them are a result of small cell lung cancer (see Mason and colleagues) while others are a result of idiopathic antibodies to the calcium channels.
Treatment Most patients with this disorder benefit mildly or moderately from administration of 3,4-diaminopyridine (3,4-DAP), an agent that blocks potassium channels in the distal motor terminal, thus prolonging depolarizations and enhancing the release of ACh vesicles. The drug is given as 20 mg, up to 5 times a day, either alone or in conjunction with pyridostigmine (Lundh et al). It is not approved by the FDA in the United States and must be obtained from specialty pharmacies but nonetheless, has replaced the formerly used guanidine hydrochloride that had hematologic and renal toxicity with long-term use. With regard to long-term relief, numerous regimens have been tried and favored by different groups. Streib and Rothner were able to achieve improvement with prednisone. Dau and Denys have claimed the best results in nontumor cases with repeated courses of plasmapheresis in combination with prednisone and azathioprine. Intravenous immune globulin has also been effective in a few reported cases. Bain and coworkers indicate that the benefit is a result of reduction in calcium channel autoantibodies, but the mechanism whereby intravenous immune globulin produces this effect could not be established. Many clinicians prefer alternate-day administration of prednisone and azathioprine (prednisone 25 to 60 mg/d, and azathioprine 2 to 3 mg/kg body weight daily) supplemented intermittently as needed by intravenous immune globulin. The response to treatment tends to be slow, over a period of months and sometimes up to a year. Some patients recover fully; in others, restoration of power is incomplete.
Diagnosis A syndrome of symmetrical weakness and fatigability of proximal muscles coupled with dry mouth, sphincter disturbances, aching muscles, and diminished reflexes are diagnostic. The illnesses with which it might be confused are myasthenia gravis, inclusion body myopathy, and polymyositis. There is a superficial resemblance to hysterical paralysis, where the patient may do better with encouragement on making a succession of voluntary contractions, and arthritis, where pain hampers the first movements more than the successive ones. Then the electrodiagnostic and specific serologic tests are of value.