title: Long-term observation of incremental response and antibodies to voltage-gated calcium channels in patients with Lambert-Eaton myasthenic syndrome: two case reports.
abstract: BACKGROUND
  Lambert-Eaton myasthenic syndrome is a rare autoimmune disorder of neuromuscular transmission due to the presence of antibodies to presynaptic P/Q-type voltage-gated calcium channels. The gold standard of therapy is the potassium channel blocker 3,4-diaminopyridine. To the best of our knowledge, no clinical reports have been published to date about long-term follow-up outcomes in patients who discontinued 3,4-diaminopyridine therapy. In addition, we know of no recent articles in which the natural history in patients with autoimmune-mediated Lambert-Eaton myasthenic syndrome has been addressed. In this report, we describe the cases of two such patients.
  
  
  METHODS
  Patient 1 was a Caucasian man who had been diagnosed at age 15 years with Lambert-Eaton myasthenic syndrome with symptoms of fluctuating muscle weakness and easy fatigability. These symptoms stabilized, and his electrophysiological parameters normalized, during treatment with a maintenance dose of 50mg/day of 3,4-diaminopyridine. After 5.5 years, however, he wished to discontinue the treatment. After that point, his electrophysiological parameters and presynaptic P/Q-type voltage-gated calcium-channel antibody titer remained stable. During the 15-year follow-up period, patient 1 reported mild exertion-induced complaints but did not feel restricted in his occupation and most daily activities. Patient 2 was a Caucasian man diagnosed at 32 years of age with a moderate limb girdle syndrome. He was treated with up to 80 mg/day of 3,4-diaminopyridine. Because of the drug's very short-lasting effect (<1 hour), however, he took it mostly irregularly (≤ 1 × 20 mg/day). During the 14- year period of observation, his repetitive nerve stimulation responses and presynaptic P/Q-type voltage-gated calcium-channel antibody titer remained stable, his compound muscle action potential amplitudes were decreasing and his clinical symptoms did not deteriorate. At his last follow-up examination, patient 2 was independent in all of his daily activities.
  
  
  CONCLUSIONS
  Some patients with autoimmune-mediated Lambert-Eaton myasthenic syndrome show a stable clinical long-term course without treatment. The benefit of each long-term therapy should be critically assessed during follow-up, and possible side effects should be balanced against the quality of life in these patients.
authors.affiliation: Department of Neurology, Martin-Luther-University Halle-Wittenberg, Ernst-Grube-Strasse 40, D-06120, Halle (Saale), Germany. ilka.schneider@uk-halle.de.
authors.forename: Ilka
authors.initials: I
authors.lastname: Schneider
authors.affiliation: Department of Neurology, Martin-Luther-University Halle-Wittenberg, Ernst-Grube-Strasse 40, D-06120, Halle (Saale), Germany. malte.kornhuber@medizin.uni-halle.de.
authors.forename: Malte E
authors.initials: ME
authors.lastname: Kornhuber
authors.affiliation: Department of Neurology, Martin-Luther-University Halle-Wittenberg, Ernst-Grube-Strasse 40, D-06120, Halle (Saale), Germany. hanisch.frank@gmx.de.|Department of Neurology, Vivantes Humboldt-Klinikum, Am Nordgraben 2, D-13509, Berlin, Germany. hanisch.frank@gmx.de.
authors.forename: Frank
authors.initials: F
authors.lastname: Hanisch
mesh_terms: D015761:4-Aminopyridine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D000328:Adult; D000077770:Amifampridine; D015220:Calcium Channels / Q000276:immunology; D005500:Follow-Up Studies; D006801:Humans; D016756:Immunoglobulins, Intravenous / Q000627:therapeutic use; D015624:Lambert-Eaton Myasthenic Syndrome / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D026902:Potassium Channel Blockers / Q000008:administration & dosage*
chemical_list: D015220:Calcium Channels; D016756:Immunoglobulins, Intravenous; D026902:Potassium Channel Blockers; D015761:4-Aminopyridine; D000077770:Amifampridine