Doctors at the Mayo Clinic claim they may have an explanation for why some patients may respond to a form of multiple sclerosis therapy known as plasma exchange and others do not. The findings are reported in the August 13 issue of the medical journal The Lancet.1
An Alternative to Steroids
While plasma exchange is not the main therapy for people with multiple sclerosis, anecdotal reports over the past 20 years have suggested that this form of treatment may be beneficial to people with MS who otherwise fail to respond to IV corticosteroids.2 Corticosteroid treatment may involve doses of oral prednisone followed by IV methylprednisolone. While these steroids are not a cure for MS, they're used to help manage the illness' symptoms. But they're usually prescribed for a short term to avoid complications like osteoporosis, ulcers, and diabetes.3
According to this study's investigators, plasma exchange is a treatment to relieve acute MS attacks. It involves removing a portion of the patient's blood, then mechanically separating the blood cells from the plasma, replacing the plasma with a new plasma sample, then infusing the blood back into the patient.
A team of Mayo Clinic researchers previously found that plasma exchange may help restore neurological function in nearly half of MS patients experiencing sudden, MS-related attacks whose resulting disabilities did not respond to steroid therapy.4 But the researchers pointed out that plasma exchange is not a therapy designed to suppress future MS attacks or to restore functionality that's been absent for longer than three months.
Predicting Response to Plasma Exchange
A new finding of this study is that patients should be expected to respond to plasma exchange, based on the specific makeup of their brain lesions, the study authors claim. The lesions, a form of tissue injury, are formed as a result of the damage incurred when MS progresses. Doctors analyze brain lesions using a type of diagnostic examination known as magnetic resonance imaging (MRI). Patients whose lesions contain levels of certain immune cells that can cause tissue destruction are more likely to respond to plasma exchange than other patients, the researchers claim. Experts theorize that the immune system plays a key role in the central nervous system destruction seen in multiple sclerosis.5
"The new findings may partly explain why some patients respond to a particular treatment and others do not," explained Claudia Lucchinetti, MD, a Mayo Clinic neurologist who headed the investigation. "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."
Comparing Response to Lesion Makeup
In the latest Mayo study, a group of 19 patients were retrospectively followed. They had each undergone a brain biopsy when their MS diagnosis was still uncertain. All patients had severe disability, including paralysis and loss of speech, and had failed standard anti-inflammatory steroid therapy.
Lucchinetti and her colleagues divided the biopsy samples collected into four distinct categories based on the types of immune cells present in their tissue, as well as each patient's extent of myelin damage. Myelin is a fatty substance that insulates nerve endings in the brain and spinal cord. It is the main target of destruction in MS, which results in the disease's symptoms.5
The investigators learned that the patients in one category were the only ones who had responded to plasma exchange. These patients had large quantities of immunoglobulin (proteins that serve as antibodies) and other specific immune cells in their brain lesions compared to the patients in the other categories. They also had moderate to significant improvement after plasma exchange treatment. That included gains in cerebral, motor, brain stem/cranial nerve, cerebellar, and/or sensory function. This improvement was first noticed just three days after plasma exchange treatment was completed, the investigators reported.
None of the patients in the other categories had such improvement.
MS Injury Varies from Patient to Patient?
The research team isn't exactly sure why this sole group of patients responded so much better, but they theorize that the way plasma exchange works—removing certain disease-causing factors and antibodies in the blood and plasma—only benefits patients with such factors in their brain tissue. In other words, if you don't have immunoglobulins or these disease-causing factors to remove, there's no benefit derived.
These findings also validate another theory proposed by Lucchinetti and her team—that there are distinct patterns of tissue injury in multiple sclerosis; since MS is not the same disease in all patients, not all patients can be treated in the same way.
"Our work suggests that the development of MS may vary from patient to patient," Lucchinetti pointed out. "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."
Diagnostic Applications: What's Practical?
Currently, there aren't any methods that doctors use to determine which patients may or may not respond to plasma exchange. In this study, brain biopsies were performed, but Lucchinetti doesn't advocate that invasive approach as a practical diagnostic application. Such biopsies are only performed to confirm a tumor or infection, she said. Thus, tests to locate certain biological markers, either from blood, DNA, or MRI, would be much more practical to help doctors distinguish which patients have the type of lesion that would be responsive to plasma exchange therapy.
But increasingly effective diagnosis is only one clinical implication of the study, the research team stated. Based on the findings, it is evident that "MS treatments may need to be more individualized and tailored for different types of patients," Lucchinetti said.
1. Keegan M, Konig F, McClelland R et al. Relation between humoral pathological changes in multiple sclerosis and response to therapeutic plasma exchange. Lancet 2005 Aug 13;366(9485):579-82.
2. Weinshenker BG. Therapeutic plasma exchange for acute inflammatory demyelinating syndromes of the central nervous system. J Clin Apher 1999;14(3):144-8.
3. Beers, MH, Bogin RM, Fletcher AJ. Neurologic Disorders. Demyelinating Diseases. In: The Merck Manual of Diagnosis and Therapy 17th ed. Whitehouse Station, NJ: Merck Research Laboratories;1999:1476.
4. Keegan M, Pineda A, McClelland RL, Darby CH, Rodriguez M, Weinshenker BG. Plasma exchange for severe attacks of CNS demyelination: predictors of response. Neurology 2002 Jan 8;58(1):143-6.
5. MS Foundation. MS Info. What Causes MS? Available at: http://www.msfacts.org/info/info_faq.html. Accessed August 5, 2005.
John Martin is a long-time health journalist and an editor for Priority Healthcare. His credits include overseeing health news coverage for the website of Fox Television's The Health Network, and articles for the New York Post and other consumer and trade publications.
