High-dose cyclophosphamide in the treatment of multiple sclerosis.

High dose cyclophosphamide (HDC) has been successfully used for the treatment of a variety of autoimmune diseases. In this study, we sought to determine whether the use of high dose cyclophosphamide provided stabilization of relapsing remitting MS (RRMS), secondary progressive MS (SPMS), or primary progressive MS (PPMS). The parameters evaluated were EDSS scores, lesion load and brain volumes by MRI and frequency of relapses. Twenty-three patients underwent immunoablative therapy with HDC and were followed for 3.5 years. Nine were relapsing remitting (RRMS), 11 secondary progressive (SPMS), and 3 primary progressive (PPMS). Four of 9 RRMS have had no clinical progression up to 3.5 years following treatment. Three of 9 patients maintained a normal neurologic examination with improved EDSS scores. Seven of the nine RRMS patients had reduction in flare frequency which was maintained for 3.5 years following treatment or no immunomodulating agents. Subgroup analysis in the RRMS patients of lesion load and brain parenchymal volume revealed a favorable trend in these parameters which did not reach statistical significance. The treatment was generally ineffective for SPMS and failed in the 2 PPMS patients. HDC was well tolerated, demonstrated a good safety profile and had minimal adverse effects. These results along with previous reports suggest that early use of HDC therapy in RRMS is promising.

Complete recovery from intractable complex regional pain syndrome, CRPS-type I, following anesthetic ketamine and midazolam.

OBJECTIVE: To describe the treatment of an intractable complex regional pain syndrome I (CRPS-I) patient with anesthetic doses of ketamine supplemented with midazolam. METHODS: A patient presented with a rapidly progressing contiguous spread of CRPS from a severe ligamentous wrist injury. Standard pharmacological and interventional therapy successively failed to halt the spread of CRPS from the wrist to the entire right arm. Her pain was unmanageable with all standard therapy. As a last treatment option, the patient was transferred to the intensive care unit and treated on a compassionate care basis with anesthetic doses of ketamine in gradually increasing (3-5 mg/kg/h) doses in conjunction with midazolam over a period of 5 days. RESULTS: On the second day of the ketamine and midazolam infusion, edema, and discoloration began to resolve and increased spontaneous movement was noted. On day 6, symptoms completely resolved and infusions were tapered. The patient emerged from anesthesia completely free of pain and associated CRPS signs and symptoms. The patient has maintained this complete remission from CRPS for 8 years now. CONCLUSIONS: In a patient with severe spreading and refractory CRPS, a complete and long-term remission from CRPS has been obtained utilizing ketamine and midazolam in anesthetic doses. This intensive care procedure has very serious risks but no severe complications occurred. The psychiatric side effects of ketamine were successfully managed with the concomitant use of midazolam and resolved within 1 month of treatment. This case report illustrates the effectiveness and safety of high-dose ketamine in a patient with generalized, refractory CRPS.