Update on Plasmapheresis in Neurological Disease
Abstracts & Commentary
Sources: Weinshenker BG, et al. A randomized trial of plasma exchange in acute central nervous system inflammatory demyelinating disease. Ann Neurol 1999;46:878-886; Clark WF, et al. Therapeutic plasma exchange: An update from the Canadian apheresis group. Ann Intern Med 1999;131: 453-462.
Weinshenker and colleagues performed a randomized controlled trial of plasma exchange (7 exchanges, 54 mLs/kg, 1.1 plasma vol/exchange) in 22 patients with acute severe inflammatory demyelinating disease of the central nervous system (CNS). Subjects included 12 patients with multiple sclerosis (MS), five with transverse myelitis (TM), and five with acute disseminated encephalomyelitis (ADEM) or other variants. Patients with a relatively new severe neurological deficit of three to 12 weeks duration who had failed to respond to at least five days of IV corticosteroids were enrolled in a blinded, sham-controlled crossover study.
Improvement occurred with eight of 19 (42%) of the actively treated group, compared with one of 17 (6%) of the sham-treated patients. Of 13 patients who failed to improve during the treatment phase, two eventually had significant improvement in six months of follow-up. Also, four of the responders experienced relapses during a six-month follow-up period. Weinshenker et al concluded that plasmapheresis appeared to lead to functional neurologic recovery in a subset of patients with severe inflammatory CNS demyelinating disease.
An analysis of more than 100,000 plasma exchanges in the Canadian health system from 1980 to 1997 was presented by Clark and colleagues, with a helpful review of the literature. Plasma exchange was used most commonly for myasthenia gravis and chronic inflammatory demyelinating polyneuropathy. Its use for acute Guillain-Barré syndrome had declined over the past five years, which was attributed to the increased use of IVIG for this condition. Plasma exchange was rarely used for MS. Barely discernible benefits, if any, were seen in three published studies of chronic progressive MS patients, most recently by the Canadian Cooperative MS Group (Lancet 1991;337:441-446).
Plasmapheresis has been used over the decades in treating fulminant ADEM, showing benefit in anecdotal case reports (e.g., Kanter DS, et al. Neurology 1995;45: 824-827). Controlled studies of plasma exchange, however, in acute MS attacks or chronic progressive forms of MS, have not shown a significant benefit when used as an adjunct to cyclophosphamide and corticosteroids. Weinshenker et al showed in this crossover study design a possible benefit of plasma exchange in up to 42% of patients with a variety of CNS inflammatory diseases that had not responded to steroids vs. 6% of sham-treated patients. This suggests that some small subset of patients, perhaps with a pathogenic humoral component of inflammatory demyelination, could improve with plasma exchange. Nevertheless, four of the treated eight improved patients suffered new demyelinating attacks during the following six months. Weinshenker et al were unable to define any predictors of patients that were more likely to respond to this expensive (up to $18,000) and invasive form of treatment. Thus, plasma exchange should only be considered in rare catastrophic episodes of acute inflammatory demyelination with high neurologic disability that has been refractory to treatment with conventional high-dose corticosteroids and IVIG. Patients with chronic progressive MS or long-standing neurologic deficits are not candidates for such therapy, despite much recent misguided public media attention about plasma exchange for MS. ba