Acute improvement in exacerbating multiple sclerosis produced by intravenous administration of mannitol

The mode of action of adrenocorticotropic hormone (ACTH) treatment in exacerbating multiple sclerosis was studied by short-term infusions of agents that mimic specific and limited pharmacological actions of ACTH and observing for temporally phase-locked clinical changes. The study was double blinded, and agents were administered while the patients were being treated with a standard course of 10-day intramuscular ACTH therapy (40 U twice daily). Antiedema, alkalotic-hypocalcemic, extraadrenal, and sodium-retaining actions were studied using infusions of mannitol, sodium bicarbonate, ACTH, and sodium chloride, respectively. Seven of 8 patients receiving placebo infusions (2.5% glucose) showed no significant clinical change and 1 exhibited an equivocal improvement. Five of 9 patients receiving mannitol showed definite signs of clinical improvement phase-locked to drug administration, with subsequent gradual reversal to baseline. Similar improvements occurred with infusions of NaHCO3 in 5 of 8 patients and of ACTH in 4 of 8 patients. Three of 7 patients given NaCl infusion showed possible mild improvements. The results indicate that mannitol and NaHCO3 induced transient acute improvement in signs at the 95% confidence level in patients with exacerbating multiple sclerosis, with ACTH having a similar effect at the 90% confidence level. These agents mimic some of the known effects of ACTH, which may be important in the therapeutic action of ACTH in multiple sclerosis. A possible role for mannitol and high-dose ACTH in the treatment of demyelinating disease warrants further study.