Plasma Exchange for Treating Neurologic Disorders: American Academy of Neurology Guideline

The American Academy of Neurology is an association of more than 22,500 neurologists and neuroscience professionals.  A neurologist is a doctor with specialized training in diagnosing, treating and managing disorders of the brain and nervous system such as Alzheimer's disease, stroke, migraine, multiple sclerosis, brain injury, Parkinson's disease and epilepsy.

A new guideline from the American Academy of Neurology recommends using plasma exchange to treat people with severe relapses in multiple sclerosis (MS) and related diseases, as well as those with certain kinds of nerve disorders known as neuropathies. The guideline is published in the January 18, 2011, print issue of Neurology, the medical journal of the American Academy of Neurology.  Evidence-based guideline update: Plasmapheresis in neurologic disorders; Report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology, I. Cortese, MD, V. Chaudhry, MD, Y.T. So, MD, PhD, F. Cantor, MD, D.R. Cornblath, MD, A. Rae-Grant, MD, Neurology 2011;76:294–300.

The objective was to reassess the role of plasmapheresis in the treatment of neurologic disorders.  The authors evaluated the available evidence based on a structured literature review for relevant articles from 1995 through September 2009. 

Plasma exchange, also known as plasmapheresis, is the process of taking blood out of the body, removing constituents in the blood's plasma thought to be harmful, and then transfusing the rest of the blood (mainly red blood cells) mixed with replacement plasma back into the body.  Plasma is the liquid part of blood. The solid parts are white and red blood cells.  In plasma exchange, blood is drawn from the person.  The plasma is separated from the solid parts of the blood.  It is then replaced with plasma from a plasma donor.  The donor plasma is pumped into the person. A machine sends the plasma through a tube into the body.  If no donated plasma is available, albumin solution can be used. Albumin is an important protein in plasma.  Like any medical procedure, plasma exchange poses some risks.  It is invasive. This means it involves an object—in this case, a tube—entering the body. Side effects of plasma exchange include infection and blood-clotting issues. You should discuss the benefits and risks of this treatment with your doctor.

The guideline recommends doctors consider using plasma exchange as a secondary treatment for severe flares in relapsing forms of MS and related diseases. The treatment was not found to be effective for secondary progressive and chronic progressive forms of MS. According to the guideline, doctors should offer plasma exchange for treatment of severe forms of Guillain-Barré syndrome and for temporary treatment of chronic inflammatory demyelinating polyneuropathy. Plasma exchange may also be considered for treatment of some other kinds of inflammatory neuropathies.  These types of neurologic disorders occur when the body's immune system mistakenly causes damage to the nervous system. Plasma exchange helps because it removes factors in the plasma thought to play a role in these disorders.  The guideline authors also looked at the use of plasma exchange for other neurologic disorders, including myasthenia gravis and pediatric autoimmune neuropsychiatric disorders (PANDAS), but there was not enough evidence to determine whether it is an effective treatment.

New studies show that plasma exchange can help treat certain inflammatory diseases of the central nervous system.  This system is made up of the brain and spinal cord. These diseases involve demyelination. This is when the protective coating around certain nerves is damaged. The diseases also involve inflammation (swelling).

Multiple sclerosis (MS) is an autoimmune disease. This means it results from the immune system attacking the body. The nerve damage from MS worsens over time. MS takes different forms. In relapsing forms of MS, symptoms come and go. In other forms of MS, the condition often gets steadily worse.  The cause of MS is unknown. In relapsing forms of MS, there is good evidence that plasma exchange can help treat some severe acute flares.  However, the treatment should be used only for a short time. In inflammatory diseases that come on suddenly, weak evidence shows plasma exchange may help when high-dose steroid treatments have failed. Examples of these diseases are transverse myelitis and neuromyelitis optica. Their cause often is not known. Strong evidence shows that plasma exchange is not effective for treating chronic progressive or secondary progressive MS. There are no studies comparing plasma exchange to other treatment methods in MS.

After the experts review all of the published research studies, they describe the strength of the evidence supporting each recommendation:
Strong evidence = more than one high-quality scientific study.
Good evidence = at least one high-quality scientific study or two or more studies of a lesser quality.
Weak evidence = the studies, while supportive, are weak in design or strength of the findings.
Not enough evidence = either different studies have come to conflicting results or there are no studies of reasonable quality.

The results of the AAN Guidelines for the efficacy of plasmapheresis in the treatment of CNS demyelinating disease are summarized as follows:

Strong evidence: Plasmapheresis should not be offered for chronic progressive or secondary progressive multiple sclerosis (MS).
Good evidence: Plasmapheresis should be considered for the adjunctive treatment of exacerbations in relapsing forms of MS.
Weak evidence: Plasmapheresis may be considered in the treatment of fulminant CNS demyelinating diseases that fail to respond to high-dose corticosteroid treatment.
Clinical context: No studies on the efficacy of plasmapheresis compared to other treatment options in MS are available.

The evaluation, conclusions and recommendations in regard to CNS demyelinating disorders, other than MS, are based exclusively on the 1999 Weinshenker Study.  (Weinshenker BG, O'Brien PC, Petterson TM, et al. A trial of plasma exchange in acute central nervous system inflammatory demyelinating disease. Ann Neurol 1999;46:878–886).  The following discussion, conclusions and recommendations are quoted directly from the AAN report in regard to the Weinshenker study of PLEX (p. 297):

Since the previous TTA report, there has been an additional Class II, randomized, double-blind, shamcontrolled trial which included 22 patients with acute, severe attacks of CNS demyelination who had failed to improve after at least 5 days of high-dose parenteral steroids. 

Patients were included in the trial if they had clinically definite or laboratory supported MS or if they had idiopathic inflammatory demyelinating CNS diseases (confirmed by biopsy when necessary) and acute neurologic deficit affecting consciousness, language, and brainstem function, or spinal cord function with impairment in one or more of the targeted neurologic deficits (coma, aphasia, acute severe cognitive dysfunction, hemiplegia, paraplegia, or quadriplegia). While the inclusion criteria are clearly defined, they are broad and encompass a heterogeneous group of inflammatory conditions with potentially diverse underlying pathogenic mechanisms. For this reason, this study is considered Class II rather than Class I. In all, the study included 12 patients with MS, 4 patients with transverse myelitis (TM), 1 patient with acute disseminated encephalomyelitis (ADEM), 1 patient with Marburg variant, 2 patients with neuromyelitis optica (NMO), 1 patient with recurrent myelitis, and 1 patient with focal cerebral demyelination. The primary outcome measures were evaluated by masked assessment by 2 neurologists (A and B) based on changes on standardized clinical scales for the targeted neurologic deficits. Treated patients showed a 42.1% response rate vs a 5.9% response rate in controls (p _ 0.032 according to Neurologist A and p _0.011 according to Neurologist B).  

Conclusions. Based on a single Class II study, plasmapheresis is possibly effective for acute fulminant CNS demyelinating diseases (including MS, ADEM, NMO, and TM) that fail to respond to high-dose corticosteroid treatment. Because the study included subgroups of patients with demyelinating diseases, it is not possible to determine if plasmapheresis is more or less effective in patients with different demyelinating diseases.

Recommendations. Plasmapheresis may be considered in the treatment of fulminant CNS demyelinating diseases that fail to respond to high-dose corticosteroid treatment....

The AAN report makes the following critically important recommendations for future research as focused on the CNS demyelinating disorders other than MS.

1. For all indications, the optimal plasma exchange protocol (number of exchanges and volumes exchanged) remains to be established through future research.

6. The role of plasmapheresis in fulminant demyelinating CNS disease that has not responded to first-line treatment with corticosteroids will need to be confirmed. Individual demyelinating diseases (e.g., NMO, MS, TM) should be addressed separately in future studies to clarify the role of plasmapheresis in each (p. 298).

The AAN included the following disclaimer in their materials.  This is an educational service of the American Academy of Neurology. It is designed to provide members with evidence-based guideline recommendations to assist the decision making in patient care. It is based on an assessment of current scientific and clinical information and is not intended to exclude any reasonable alternative methodologies. The AAN recognizes that specific patient care decisions are the prerogative of the patient and the physician caring for the patient, and are based on the circumstances involved. Physicians are encouraged to carefully review the full AAN guidelines so they understand all recommendations associated with care of these patients.