Although ACTHAR gel is approved for the treatment of acute relapses, it is currently not widely used. Thus, we propose to conduct a small open-label proof-of-concept trial to evaluate the response to ACTHAR gel therapy in patients who have failed to make a satisfactory recovery after treatment with high dose IVMP. Documentation of the clinical course as well as any adverse events related to IVMP use will be made. The investigators propose to study the potential benefit of a 14-day course (the dose historically used since the landmark clinical trial of Rose et al1) of subcutaneous ACTHAR gel in 10 patients who have demonstrated inadequate improvement after a course of IVMP, 1000 mg daily, for 5 treatments (over a maximum of 8 days). These would be patients for whom PLEX would be considered as a treatment possibility. The primary outcome measure will be improvement in the targeted neurological deficit, as measured on the appropriate functional system score (FSS) of the EDSS.

This is an open-label, small, proof-of-concept study examining the safety, tolerability, and extent of recovery of a two-week course of subcutaneous Acthar Gel therapy in patients with MS relapse who have failed to make a satisfactory recovery after treatment with high dose methylprednisolone. Eligible patients will be given 80 units of Acthar for 14 days. Patients will be evaluated at baseline, at 1 week of Acthar treatment, at completion of Acthar treatment, and 1 week after completion of treatment. For those who do not undergo plasmapheresis an additional evaluation will be conducted 2 weeks after completion of treatment. Monitoring will include blood pressure determination and blood sugar determination.

Inclusion Criteria:

• Ages 18-65
• EDSS of 2.0 - 7.5 (inclusive)
• Sustained a significant MS exacerbation affecting vision, brainstem, motor, or cerebellar function AND were initially treated with a 5 day course of IVMP within 10 days of the onset of symptoms.
• Failed to make adequate improvement and must initiate Acthar Gel therapy within two weeks (+/- 72 hours) after the first day of 5 treatments with 1000 mg IVMP, as judged by their treating neurologist.
• Must be able to comply with the requirements of the protocol as determined by the investigator.
• Ability to understand the purpose and risks of the study and provide signed and date informed consent and authorization to use protected health information (PHI) in accordance with national and local subject privacy regulations.

Exclusion Criteria:

• Patients whose relapse consists of pure sensory or bowel/bladder symptoms
• History of ACTHAR gel use or other forms of ACTH with failure to improve or with occurrence of significant adverse experiences.
• Diagnosis of scleroderma, systemic fungal infections, ocular herpes simplex, congestive heart failure, and/or uncontrolled hypertension, and/or any clinically relevant medical disease that would put the patient at risk by participating in the study
• Persistent significant or severe infection
• Recent history of drug or alcohol abuse
• Concomitant use or prior use in the preceding 6 months of any investigational drug.
• Pregnant or nursing
• Recent surgery (up to the investigator's discretion what constitutes recent)
• History of, or the presence of, a peptic ulcer
• Known sensitivity to proteins of porcine origin
• Received a live or live attenuated vaccine in the last 30 days before baseline