Only those multiple sclerosis (MS) patients with evidence for antibody deposition or complement activation in their lesions are likely to respond to plasma exchange, a treatment for acute MS attacks, according to a study in the August 13 Lancet.

“The new findings may partly explain why some patients respond to a particular treatment and others do not,” said senior author Claudia Lucchinetti, MD, Division Chair of Neurology at the Mayo Clinic College of Medicine in Rochester, Minnesota. “The biological basis for the variable response to current MS treatments is not well understood. It may be that not all MS patients form lesions in the same way and therefore would not be expected to respond the same to a given treatment. Thus, MS treatments may need to be more individualized and tailored for different types of patients.”

FAVORABLE EXCHANGE

During plasma exchange treatment, the patient’s blood is removed and the blood cells are mechanically separated from the fluid plasma. The patient’s blood cells are then mixed with replacement plasma and the mixture is returned to the patient. Investigators have previously found that plasma exchange may help restore neurologic function in approximately 45% of those patients experiencing sudden, severe MS attacks, whose resulting disabilities did not respond to high doses of steroids.

Mark Keegan, MD, Mayo Clinic neurologist and lead author of the current study, emphasized that plasma exchange is a treatment for severe MS attacks when the standard treatment with corticosteroids fails; it is not a treatment to suppress future attacks or to restore neurologic function that has been absent for more than three months.

PREDICTIVE PATTERN

The study by Dr. Lucchinetti and colleagues was conducted retrospectively in an attempt to unravel the “all or none” response Mayo Clinic investigators had witnessed with plasma exchange treatment for acute attacks in 19 patients with MS who had undergone a brain biopsy during the course of their disease when the diagnosis of MS was still in question. Patients were seen at the Mayo Clinic, the University of Vermont, or a European center; all had severe disabilities, including paralysis and loss of speech, which failed to improve with standard anti-inflammatory steroid treatment.

Since tissue from these patients was already available, Dr. Lucchinetti and her team classified their lesions into one of four patterns based on the types of immune cells present and the pattern of myelin injury, according to a system developed by Dr. Lucchinetti and her European collaborators. The investigators found that the 10 patients with pattern II MS lesions—which contain large quantities of immunoglobulin and complement activation—experienced moderate to marked improvement after treatment with plasma exchange. These patients experienced major gains in cerebral, motor, brain stem/cranial nerve, cerebellar, and/or sensory function. Improvement began after an average of three days. However, none of the MS patients with lesions typical of either patterns I or III—which lack evidence for antibody or complement activation—achieved such improvement, Dr. Lucchinetti reported. Therefore, the investigators postulated that only the pattern II MS patients’ attacks responded to treatment because of the way in which plasma exchange works—by removing disease-causing factors in the blood and plasma, such as antibodies and complement, which are present only in pattern II MS lesions.

INDIVIDUALIZING MS THERAPY

The findings validate the theory that there are distinct patterns of tissue injury in different MS patients—that MS is not the same disease in all patients and therefore cannot be treated the same way in everyone—according to Dr. Lucchinetti. “Our work suggests that the development of MS may vary from patient to patient,” she said. “These recent data on the correlation of plasma exchange response to tissue pathology support our hypothesis that different patterns of tissue damage in MS may require different treatment approaches.”

However, brain biopsies such as those undergone by the patients studied are not routinely performed in patients with MS—they are only performed as part of the exclusion of another diagnosis such as tumor or infection, Dr. Lucchinetti noted. Thus, it is necessary to identify specific markers—either from blood, DNA, or MRI—that can distinguish between these four patterns without the need for a brain biopsy, she concluded.

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Suggested Reading
Keegan M, Konig F, McClelland R, et al. Relation between humoral pathological changes in multiple sclerosis and response to therapeutic plasma exchange. Lancet. 2005;366:579-582.
Lucchinetti C, Bruck W, Parisi J, et al. Heterogeneity of multiple sclerosis lesions: implications for the pathogenesis of demyelination. Ann Neurol. 2000;47:707-717.
Weinshenker BG, O’Brien PC, Petterson TM, et al. A randomized trial of plasma exchange in acute central nervous system inflammatory demyelinating disease. Ann Neurol. 1999;46:878-886.

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