August 11, 2005
Study Demonstrates Patients’ Multiple Sclerosis Lesion Type Dictates Effective Treatment
ROCHESTER, Minn. -- A Mayo Clinic study demonstrates that only those multiple sclerosis (MS) patients with evidence for antibody deposition or complement activation -- immune cells that can cause tissue destruction -- in their lesions are likely to respond to plasma exchange, a treatment for acute MS attacks. This is the first evidence that differences in pathological subtypes of MS may predict response to treatment. The findings will be published in the Aug. 13 issue of The Lancet.
"The new findings may partly explain why some patients respond to a particular treatment and others do not," says Claudia Lucchinetti, M.D., Mayo Clinic neurologist and the paper's senior and corresponding author. "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 to a given treatment the same. Thus, MS treatments may need to be more individualized and tailored for different types of patients."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. Mayo Clinic MS experts including Moses Rodriguez, M.D., Brian Weinshenker, M.D.; and Mark Keegan, M.D.; previously found plasma exchange may help restore neurological function in approximately 45 percent of those experiencing sudden, severe MS attacks whose resulting disabilities did not respond to high doses of steroid treatment.
Dr. Keegan, first author of the study, points out that plasma exchange is a treatment for severe MS attacks when standard treatment with corticosteroids fails; it is not a treatment to suppress future attacks or to restore neurological function that has been absent for more than three months.
The study was conducted retrospectively in an attempt to unravel the "all or none" response Mayo Clinic MS experts had witnessed with plasma exchange treatment for acute attacks in 19 patients who at one point had undergone a brain biopsy in the course of their disease when the diagnosis of MS was still in question. Patients were seen at Mayo Clinic, the University of Vermont or a European center, and all included in the study had severe disabilities, including paralysis and loss of speech, which failed to improve with standard anti-inflammatory steroid treatment.
Since tissue was already available on these patients, Dr. Lucchinetti and her team classified their lesions into four patterns based on the types of immune cells present and the pattern of myelin injury. Previously, Dr. Lucchinetti and her European collaborators, Professors Hans Lassmann of the Brain Research Institute at the University of Vienna, Austria; and Wolfgang Bruck of the University of Gottingen, Germany; developed and described a classification system for MS patients by lesion type into patterns I, II, III and IV. The investigators found that the 10 patients with pattern II MS lesions which contain large quantities of immunoglobulin (proteins that serve as antibodies) and complement activation (the ability to combine with antibodies to destroy tissue) 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.
The investigators postulate 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 only present in pattern II MS lesions.
The findings published in The Lancet validate a theory held by Drs. Lucchinetti, Lassmann and Bruck 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.
"Our work suggests that the development of MS may vary from patient to patient," says Dr. Lucchinetti. "This recent data on the correlation of plasma exchange response to tissue pathology supports 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 done in MS patients -- they are only performed when excluding another diagnosis such as tumor or infection, according to Dr. Lucchinetti. Therefore, she explains that it is necessary to identify specific markers. either from blood, DNA or MRI, which can distinguish between these four patterns without the need for a brain biopsy.
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