Treatment Use of 3,4-Diaminopyridine

The diagnosis of LEM or CMS will have been made based on clinical and electromyographic
findings, and all patients will have been referred to the PI for DAP treatment. This study
will enroll minors and adults.

CMS patients under age 18 years will be included if their parent or guardian gives written
permission. Minors who turn 18 while in the program will be re-consented as adults.

The dose of DAP will be determined individually for each patient. Adults will start with a
dose of 10 mg 3-4 times daily, increasing over several weeks to the dose that produces the
maximum symptomatic response, not to exceed 100 mg daily. Pyridostigmine bromide (PB) may be
added at low doses, increasing to the dose that produces the best response, not to exceed 360
mg daily. In children, equivalent doses of these medications will be given calculated on a
surface area basis. The doses of DAP and PB will be periodically adjusted to assure that the
smallest effective doses are used.

Patients who achieve significant clinical benefit from DAP, as judged by the study PI and the
patient, may continue taking DAP as long as the drug is available from the sponsor, and as
long as they return for regular follow-up evaluations at the Duke MG Clinic. Patients who are
unable to return for regular follow-up will be required to have their local physician obtain
DAP for them from the sponsor.

Inclusion Criteria:

- Diagnosis of either Lambert Eaton myasthenic syndrome (LEMS) or congenital myasthenic
syndrome (CMS)

- Women of childbearing potential must have negative pregnancy test and agree to
practice adequate contraception while taking DAP

- Must be competent to give consent

Exclusion Criteria:

- Known seizure disorder

- Pregnancy

- Known cardiac arrhythmia or evidence of significant arrhythmia on screening ECG

- Known hepatic, renal or hematologic disease