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Plasmapheresis is the removal, treatment, and return of (components of) blood plasma from blood circulation. The procedure is used to treat a variety of disorders, including those of the immune system and is performed at an infusion center.
Some stiff-person patients reported improvements in symptoms and serological and electrophysiological markers. An equal number had no benefit. Patients showing improvement were on concomitant medications. There has been no reported randomized placebo-controlled study to date.
There are no long-term effects of plasmapheresis on the disease course. It is neither a cure nor an agent of remission. In one referenced study, serum anti-GAD65 antibody titers remained high (>200-fold the normal values) despite the frequency of PE. This finding has also been observed after short cycles of PE. The discrepancy between clinical improvement and high levels of anti-GAD65 antibodies calls into question the pathogenic role of these antibodies in SPS. The therapeutic effect of plasmapheresis in those cases may be related to the elimination of other pathogenic autoantibodies, complement, or cytokines or to the modulation of other components of the immune system.
Plasmapheresis is used as therapy for other autoimmune disorders where the rapid removal of disease-causing autoantibodies from the circulation is required in addition to other medical therapy. It is important to note that plasma exchange therapy in and of itself is useful to temper the disease process, while simultaneous medical and immunosuppressive therapy is required for long-term management. Plasma exchange offers the quickest short-term answer to removing harmful autoantibodies; however, the production of autoantibodies by the immune system must also be suppressed, usually by the use of medications such as prednisone, cyclophosphamide, cyclosporine, mycophenolate mofetil, rituximab, or a mixture of these.
Why it may not work: Antibodies are secreted by plasma cells, which originate in germinal centers from activated B cells that have been selected for high-affinity binding to antigen. A subset of the plasma cells will become long-lived forming the humoral memory of the human immune system, which may persist over decades. Since plasma cells do not express the B cell surface marker CD20 they are not removed by treatment with monoclonal antibodies like rituximab, which is depleting all CD20+ B cells through mechanisms including antibody-dependent cellular cytotoxicity, complement-dependent cytotoxicity, and apoptosis. Since it has been proposed that a substantial fraction of antibodies against microbial antigens like pneumococcal polysaccharides or tetanus toxoid (TT) is secreted by long-lived plasma cells, B cell depletion has little effects on the long-term humoral memory against these antigens. Link to article
The time of plasmapheresis, amount of supplementary albumin, and other parameters are controlled on a patient-by-patient basis by the pathologist running the blood bank involved in the procedure.
One cycle of five treatments series administered every other day is considered a standard regimen for autoimmune diseases, but longer and shorter regimens have been used.
The efficacy is then evaluated and further treatment is decided on a patient-by-patient basis, usually as a collaborative effort with the insurance company physicians because it is such an expensive procedure.
Possible adverse effects include hypotension, bleeding, arrhythmias, and infection.
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1. De la Casa-Fages B, Anaya F, Gabriel-Ortemberg M, Grandas. Treatment of stiff-person syndrome with chronic plasmapheresis. Mov Disord. 2013 Mar;28(3):396-7. doi: 10.1002/mds.25167. Epub 2012 Dec 12. Link to article
2. Brashear R, Phillips II HL. Autoantibodies to gabaergic neurons and response to plasmapheresis in stiff-man syndrome. Neurology 1991, 41:1588–1592. Link to article
“We describe a patient with progressive stiff-man syndrome and high titers of GAD-like immunoreactivity in serum but not spinal fluid. Plasmapheresis resulted in lowered antibody titers, decreased exteroceptive reflex responses, reduced motor unit activity, and marked clinical improvement. Immunohistochemistry using patient serum and plasma produced specific labeling of human and experimental animal tissue consistent with GABAergic neurons and terminal fields. This antibody response was not present in samples from more than 200 other patients. These results provide additional evidence of an autoimmune mechanism for stiff-man syndrome and indicate plasmapheresis may be beneficial in some patients.”
3. Fogan L. Progressive encephalomyelitis with rigidity responsive to plamapheresis and immunosuppression. Ann Neurol 1996, 40:451–453. Link to article
“The stiff-man syndrome is reported in a 55-year-old woman who also had signs of severe bulbar musculature hypercontraction. These clinical features correspond to the progressive encephalomyelitis with rigidity syndrome. Diazepam was minimally beneficial, but after treatment with plasmapheresis and corticosteroids, she was still asymptomatic when seen 5 years later.”
4. Gerhardt CL. Stiff-man syndrome revisited. South Med J. 1995 Aug;88(8):805-8. Review. Link to article
“Favorable responses to plasmapheresis have been reported, and new treatment modalities are being studied.”
5. Coles A. Barker R. A case of stiff limb syndrome responsive to plasma exchange. J Neurol Neurosurg Psychiatry 2001;70:407-408 doi:10.1136/jnnp.70.3.407a. Link to article
“The patient failed to respond to baclofen and diazepam and could not tolerate intravenous immunoglobulin but did have a dramatic and sustained response to plasma exchange, although the need for repeated courses of this treatment has led to her being started on cyclophosphamide.”
6. Hao W, Davis C, Hirsch IB, Eng LJ, Daniels T, Walsh D, Lernmark A. Plasmapheresis and immunosuppression in stiff-man syndrome with type 1 diabetes: a 2-year study. J Neurol. 1999 Aug; 246(8):731-5. Link to article
7. Harding AE, Thompson PD, Kocen RS, et al. Plasma exchange and immunosuppresion in the stiff man syndrome. Lancet 1989, 14:915. Link to article
8. Hayashi A, Nakamagoe K, Ohkoshi N, Hoshino S, Shoji S. Double filtration plasma exchange and immunoadsorption therapy in a case of stiff-man syndrome with negative anti-GAD antibody. J Med. 1999;30(5-6):321-7. Link to article
“The patient underwent a course of four double filtration plasma exchanges, which resulted in marked clinical improvement. Painful muscle cramps disappeared and muscle stiffness reduced within a day after the first plasma exchange. The patient's improvement continued, but his condition declined again about ten months after plasma exchange. Immunoadsorption therapy was then performed, and this treatment was also effective.”
9. Pagano MB, Murinson BB, Tobian AAR, King KE. Efficacy of therapeutic plasma exchange for treatment of tiff-person syndrome. Transfusion. Received for publication April 19, 2013; revision received November 7, 2013, and accepted November 14, 2013. doi: 10.1111/trf.12573. Link to article
Eighteen publications were found from the literature review, which resulted in a total of 26 patients diagnosed with SPS. Eleven patients had a significant symptomatic improvement after TPE treatment, and two patients developed adverse events.
10. Schröder A, Linker RA, Gold R. Plasmapheresis for neurological disorders. Expert Rev Neurother. 2009 Sep;9(9):1331-9. doi: 10.1586/ern.09.81. Link to article
“PE has been applied successfully in chronic inflammatory demyelinating polyneuropathy, paraproteinemic polyneuropathy, stiff person syndrome, and may also be tried in several diseases of paraneoplastic origin, and steroid-unresponsive relapses of multiple sclerosis Possible adverse reactions mainly relate to vascular access, the use of replacement fluids and the need for anticoagulation.”
11. Shariatmadar S, Noto TA. Plasma Exchange in Stiff-Man Syndrome.Therapeutic Apheresis and Dialysis. 2001;5:1, 64-67. Link to article
“We report on the use of plasma exchange (PE) in 2 patients with SPS whose serum and cerebrospinal fluid were negative for GAD autoantibodies. One patient showed minimal clinical improvement following PE while the second reported subjective improvement, but not any different from that with medications. Based on the results of PE in our patients, it seems that those who are autoantibody negative are less likely to respond. Whether a more aggressive approach to PE will be beneficial remains speculative.”
12. Vicari AM, Folli F, Pozza G, et al. Plasmapharesis in the treatment of stiff-man syndrome. N Engl J Med 1989;320:1499 . Link to article
13. Weinstein R. Therapeutic apheresis in neurological disorders. J Clin Apher. 2000;15(1-2):74-128. Review. Link to article
14. Therapeutic Apheresis (Merck Manual). Link to article