Plasma Exchange

In a practice guideline released Monday, the American Academy of Neurology formally endorsed plasma exchange for treatment for severe exacerbations in relapsing-remitting multiple sclerosis (RR-MS), as well as several other acute and chronic neuropathies.

The new guideline, published in the Jan. 18 issue of Neurology, updates recommendations issued by the AAN in 1996 that called plasma exchange merely "promising" and "possibly useful" for severe RR-MS flares. Now the AAN classifies the procedure as "probably effective" for this purpose.

And, while now endorsing plasma exchange or plasmapheresis for MS flares, the AAN indicated that the procedure appeared to have no value in secondary or chronic progressive forms of MS.

Likewise, the new guideline concluded that there was "insufficient evidence" to warrant endorsing plasma exchange for treating myasthenia gravis.

The determination of insufficient evidence in myasthenia gravis represented a significant downgrade from the 1996 recommendation, which declared that plasma exchange was an "established" treatment -- although it also noted that there had been no control clinical trials to prove its efficacy.

The new guideline was developed by the AAN's Therapeutics and Technology Assessment subcommittee, with Irene Cortese, MD, of the National Institutes of Health in Bethesda, Md., as lead author.

In researching the new guideline, Cortese and colleagues found that the evidence base had hardly changed, still with no randomized clinical trials.

What had changed were the standards for making recommendations in treatment guidelines. Now, the lack of rigorous trials means that the evidence must be designated as insufficient to make a recommendation -- even though, as the guideline authors noted, plasma exchange "is used at many medical centers" in conjunction with myasthenia gravis prethymectomy and for acute crises.

The new guideline also confirmed the validity of plasma exchange for certain neuropathies for which the procedure was recommended in the 1996 recommendations, including acute demyelinating polyneuropathy associated with Guillain-Barré syndrome and for short-term treatment of chronic inflammatory demyelinating polyneuropathy.

For RR-MS flares, publication of a small but randomized and sham-controlled trial in 1999 tipped the balance for Cortese and colleagues. The trial, with 12 patients with MS and 10 with other acute demyelinating conditions, found that 42% of treated patients achieved predefined levels of clinical response compared with 6% of controls (P<0.05).

The bottom line, according to Cortese and colleagues: "Plasmapheresis should be considered for the adjunctive treatment of exacerbations in relapsing forms of MS," they wrote, and also for fulminant CNS demyelinating disorders that do not respond to high-dose steroid therapy.

The committee also made tweaks to recommendations on immunoglobulin gammopathy-related polyneuropathies. In the 1996 recommendation, use of plasma exchange in neuropathies associated with IgA and IgG gammopathies received a designation of "established," whereas for IgM gammopathies it was listed as "investigational."

In the new guideline, plasma exchange was declared "probably effective" for neuropathies related to IgA or IgG pathology, but "probably ineffective" for those seen with IgM gammopathy.

As with myasthenia gravis, the altered language had more to do with shifting standards for recommendations than with new science. However, for IgM-related neuropathy, Cortese and colleagues took note of a 1995 study not included in the earlier assessment that found no benefit with plasma exchange.

Finally, the authors determined that there was too little evidence to support recommendations either way on plasma exchange for Sydenham chorea or certain neuropsychiatric symptoms seen in some children with streptococcal infection (a condition known as PANDAS).

They also took no position on plasma exchange for MS patients with progressive multifocal leukoencephalopathy (PML) after treatment with natalizumab (Tysabri). Although one study had indicated it could speed clearance of the drug, the effect on PML symptoms and survival was not addressed.

The guideline concluded with a research wish list, topped by a plea for studies focusing on the optimal numbers of exchanges and the volumes involved.

Not surprisingly, Cortese and colleagues also called for more research on the procedure for conditions they listed in the "insufficient evidence" and "probably effective" categories.

Source: MedPage Today   © 2011 Everyday Health, Inc (18/01/11)

Researchers at Aurora St. Luke's Medical Center in Milwaukee report that plasma exchange therapy or PLEX dramatically improves the health of multiple sclerosis patients who fail to respond to conventional therapies.

"There is no other treatment that brings about such a reversal in multiple sclerosis," says Bhupendra Khatri, M.D., the study's principal investigator and director of Aurora's Regional Multiple Sclerosis Center. "This treatment can turn lives around."

Over 25 years, Dr. Khatri and his team followed 271 patients with chronic and progressive multiple sclerosis. These patients had not responded to drug therapy and were experiencing an increasing decline in their motor and verbal abilities. Patients received weekly plasma exchange treatments for 10 weeks, with the pace of plasma exchange therapy slowing over time or as their condition improved.

Out of 271 patients, 217 or 80 percent, saw a long-term improvement in their disability.

Unlike conventional multiple sclerosis treatments, such as chemotherapy drugs, which can have serious side effects such as heart damage or leukemia, the plasma exchange therapy was found to be safe, with no serious side effects.

The study, "Sustained Long-Term Improvement in Disability with Plasma Exchange in Patients with Worsening Multiple Sclerosis: Results of a 25-Year Study," was presented at the American Academy of Neurology annual meeting in Seattle.

Dr. Khatri explained that patients with chronic, progressive multiple sclerosis may see their condition stabilize with conventional therapies, but they generally do not see any improvement in their condition. This is what makes the plasma exchange therapy all the more remarkable, according to Dr. Khatri. Not only did the majority of patients with worsening symptoms respond to plasma exchange, over time many patients found their weak limbs became stronger, their steps steadier and their speech clearer. Some grew strong enough that they could return to work.

Plasma exchange is a process where the patient's blood is run through a centrifuge, which separates out the plasma. The plasma is replaced with a synthetic fluid, and the blood is returned to the patient. Plasma exchange is thought to work because it filters out the agents that attack the nervous system. Once the bloodstream is cleared, the body has the opportunity to repair itself.

Multiple sclerosis is a disease where the body's immune system attacks the protective sheath surrounding the nerves. The National Multiple Sclerosis Society estimates 400,000 people in the United States have the disease. There is no cure for multiple sclerosis though there are several drugs that can slow or stop its progress. Symptoms can include blurred vision, loss of coordination and short-term or long-term memory loss.

Multiple sclerosis has been linked to vitamin D deficiency, and its geographic distribution is tied to sunshine.

Source: PR Newswire © 1996-2009 PR Newswire Association (30/04/09)