Induction Therapy With a Single High Dose Bolus of Intravenous Methotrexate With Leucovorin Rescue, Prior to Initiation of AVONEX® Treatment, in Patients Presenting With a First Acute Demyelinating Event.

The participant will receive weekly intramuscular treatment with AVONEX® (interferon beta
1-a) and a one-time high dose intravenous methotrexate with Leucovorin rescue, along with the
standard solumedrol treatment before beginning AVONEX® treatment.

At study entrance, baseline lab work (complete blood count, platelet count, routine
electrolytes, blood urea nitrogen, creatinine, liver function tests, 24 hour urine collection
for creatinine clearance, urine pregnancy test, urinalysis and urine culture and sensitivity
if needed), and an electrocardiogram (measurement of heart activity) will be done. A complete
medical history, neurological and opthamological examination will be performed, including
measurements of vital signs (heart rate and blood pressure), as well as magnetic resonance
imaging (MRI), EDSS, and Visual Evoked Response test (VER's) to document status of disease. A
Multiple Sclerosis Functional Composite Score (MSFC) consists of the Timed 25 Foot Walk, Nine
Hole Peg Test (9HPT), and Paced Auditory Serial Addition Test 3 (PASAT3) will be performed at
screen as well. At months 6, 12, 18, 24, 30 and 36 the tests and evaluations will include
MRI, MSFC, VER's and blood tests of immune cells. Other safety evaluations (previously
mentioned blood and urine tests) will be conducted according to the date of treatment. These
tests include a laboratory test (methotrexate level) two days following treatment, as well as
routine lab tests 2 weeks following the methotrexate treatment. This treatment would be under
the supervision of Dr. Rowe.

The patients will continue their AVONEX® intramuscular injections of 30 micrograms
(administered by patient or caregiver) on a weekly basis. The methylprednisolone treatment
and methotrexate infusion will be performed in our outpatient infusion center. The patient
will be required to complete a patient diary during the course of the trial, participate in
and keep all scheduled appointments, and to inform the research staff and physician of any
change in concomitant medications or adverse events that they may experience.

To be eligible for entry into this study, candidates must meet the following eligibility
criteria at the time of enrollment, which are the same as in the CHAMPS study [1]:

- Between the ages of 18 and 50 years, inclusive.

- As in the CHAMPS study [1] patients must have had a first isolated, well-defined
neurologic event consistent with demyelination and involving the optic nerve
(unilateral optic neuritis), spinal cord (incomplete transverse myelitis), or brain
stem or cerebellum (brain stem or cerebella syndrome). They must also have two or more
clinically silent lesions of the brain that were at least 3 mm in diameter on MRI
scans and were characteristic of MS (at least one lesion must be periventricular or
ovoid).

- The onset of the visual or neurological symptoms must have occurred no more than
twelve days before the MTX treatment, so that the methylprednisolone treatment is
begun no more than fourteen days after the onset of symptoms, as in CHAMPS.

- Patients must give written informed consent prior to any testing under this protocol,
including screening tests and evaluations that are not considered part of the
subject's routine care.