Search

Plasmapheresis not only removes circulating antibodies but also modulates cellular immunity, including lymphocyte subsets. To investigate the effect of double-filtration plasmapheresis (DFPP) on the ratio of lymphocyte subsets in patients with myasthenia gravis (MG), we examined the percentages of B-cells, T-cells, T helper (Th) cells, T suppressor (Ts) cells, natural killer (NK) cells, NKT cells, and Th/Ts ratio before and after a single DFPP session and after a course of DFPP. A total of 26 patients were recruited; their peripheral blood lymphocyte subsets were assayed using flow cytometry. After a single session of DFPP treatment, the percentages of T-cells (P = 0.0200), Th cells (P = 0.0178), and the Th/Ts ratio (P = 0.0309) decreased significantly, whereas the percentage of NK cells (P = 0.0007) increased significantly. More importantly, after one course of DFPP treatment, the reduced clinical quantitative MG (QMG) score was correlated with the decrease of the percentage of T-cells (r = 0.5005, P = 0.0092). Fourteen thymectomized MG patients had decreased percentages of T-cells (P = 0.0304) and Th cells (P = 0.0444), whereas they had increased NK cells (P = 0.0197) after a single DFPP session. Here, transiently decreased percentages of T-cells after the full DFPP course could enhance the effectiveness of plasmapheresis for MG patients.

Background and purpose: Myasthenia gravis (MG) is an autoimmune disorder that may involve natural killer (NK) cells. Although NK cells are part of the innate immune system, they also influence adaptive immune responses. Double-filtration plasmapheresis (DFP) is an effective therapy for MG crisis. Thus, we examined the effects of DFP on the cytotoxicity of NK cells. Methods: A total of 20 patients with MG and 16 healthy controls were recruited for the study. Ficoll-Paque-isolated peripheral blood mononuclear cells (PBMCs) and K562 cells were used as the effector and target cells, respectively. NK cell cytotoxicity was analyzed using flow cytometry immediately before and after DFP and upon course completion. Results: Double-filtration plasmapheresis treatment decreased significantly the NK cell cytotoxicity in patients with MG, especially in good responders, those who were positive for acetylcholine receptor (AChR) antibodies, and those receiving immunosuppressants. Conclusions: The decrease in NK cell cytotoxicity after DFP and the decline of AChR antibody titer were observed in good responders indicating that this could benefit patients with MG.

The purpose of this study was to evaluate the influence of plasmapheresis on sleep in patients with generalized myasthenia gravis and no respiratory symptoms. Seven myasthenia gravis patients, four women and three men, aged 24-52 years, underwent plasmapheresis treatment because of recent worsening of clinical weakness and poor response to previous treatments. We prospectively recorded the myasthenia gravis score, measured acetylcholine-receptor antibody concentration, performed polysomnography, and checked the Epworth Sleepiness Scale at baseline and 1 day after completion of the last session of plasmapheresis. Myasthenic weakness was ameliorated following plasmapheresis in all patients with a median decrease in myasthenia gravis score of 2 points (P = 0.0002) and a median clearance of 43.3% of acetylcholine-receptor antibody. However, there was no significant change in polysomnographic parameters, except for a trend toward shorter duration of the longest apnea period (P = 0.0763) following the treatment. Plasmapheresis did not affect polysomnographic parameters despite improved clinical weakness along with decreased myasthenia gravis score and acetylcholine-receptor antibody concentration.

Background: The effect of plasmapheresis on cytokine levels in patients with myasthenia gravis (MG) has not been well established. Methods: Cytokine levels were measured in 19 patients with MG before and after treatment with one course of double-filtration plasmapheresis (DFP). The control group comprised 6 age- and sex-matched healthy volunteers. Results: At baseline, patients with MG had higher levels of IL-10 than normal controls. The levels of IL-2, IL-4, IL-5, and tumor necrosis factor-α were almost undetectable in MG patients. After a single session of DFP treatment, IL-10 levels were significantly increased. After three sessions, IL-10 levels were still higher than those at baseline. Elevated IL-10 level was significantly associated with use of immunosuppressant drugs, thymectomy, and good response to DFP treatment. Conclusions: Interleukin-10 might play a crucial role in the pathogenesis and perpetuation of MG.

An 85-year-old man with dry type age-related macular degeneration (AMD) in his right eye and a disciform scar in his left eye received double-filtration plasmapheresis (DFPP) for the treatment of his right eye. The protocol for plasmapheresis followed the Multicenter Investigation of Rheopheresis for AMD (MIRA) trial and consisted of four pulses of paired sessions of plasmapheresis with a two-day interval within 10 weeks. The pre-DFPP best corrected visual acuity (BCVA) for the right eye was 6/15 (0.4). Six months after DFPP treatment, the BCVA of the right eye was 6/10 (0.6) and remained unchanged at the 12th month; however, comparison of the right eye fundus picture, fluorescein angiogram, and optical coherence tomography of the macular area before and 6 and 12 months after plasmapheresis revealed no discernable changes. The per-session and per-course clearance rates were highest for IgM (63.8% and 90.8%) and lowest for albumin (11% and 15.4%). No plasmapheresis-related complications, such as hypotension, hemolysis or infection, occurred. Thus, DFPP treatment can provide effective treatment for dry type AMD with minimal side-effects.

Circulating antibodies of the acetylcholine receptor (AchRAb) are detectable in most patients with generalized myasthenia gravis (MG). A newly discovered antibody against muscle-specific kinase (MuSKAb) has been detected in 40–70% of AchRAb-negative MG patients. We report a series of Taiwanese MuSKAb-positive patients, and compare their clinical features with MuSKAb-negative patients and also with MuSKAb-positive Caucasians. Five out of 44 seronegative generalized MG patients (11.4%) were positive for MuSKAb. Patients with MuSKAb tended to have severe disability and bulbar involvement, and more often experienced crisis or impending crisis. Although all of these patients showed an initial response to immunosuppressant therapy, they had greater disability at follow-up. The clinical features of Taiwanese MuSKAb-positive patients were not different from those of Caucasians, except for a lower prevalence.

To evaluate the optimal session of double filtration plasmapheresis (DFP) in terms of the maximal clearance rates for various serum substances, the laboratory parameters of 152 consecutive patients treated with different sessions of DFP following a standard protocol on an alternate-day basis was studied. Immunoglobulin M (IgM) and lipoprotein cholesterol had the most effective clearance by a minimum of two sessions of DFP treatment, and the clearance rates remained relatively constant despite the increase in the number of treatment sessions, while the clearance rates for other serum proteins increased steadily with further treatments. Using the clearance rate of the 2-session group as reference, the highest slopes for clearance of albumin, globulin, and triglyceride were found in the 4-session group, while the slopes for IgA and IgG were highest in the 5-session group. In conclusion, for the clearance of IgM and lipoprotein cholesterol, two sessions of DFP treatment are adequate. However, the best clearance of IgG and other globulins cannot be achieved until the fourth session of DFP treatment. Therefore, a minimum of 4 sessions of DFP treatment at 2-day intervals is needed for most immunological diseases.

Plasma exchange before thymectomy may decrease the time on mechanical ventilation (MV) and shorten the stay in the intensive care unit (ICU) for patients with myasthenia gravis (MG). This study evaluated the effects of prethymectomy plasmapheresis. A total of 29 myasthenic patients, 18 women and 11 men aged 20-73 years, were treated with double filtration plasmapheresis (DFP) for two to five consecutive sessions over a period between 2 and 21 days (mean 8.1 days) before transsternal thymectomy. Acetylcholine receptor antibody (AchRAb) titers, vital capacity (VC), maximal inspiratory pressure (Pimax), and MG score were measured before and after the course of DFP. Three outcome measures including duration of postoperative hospital stay, duration of ICU stay, and duration of MV were analyzed for correlation with clinical variables. The duration of MV ranged from 6 to 93 h, with a median of 21 h. The median ICU stay was one day and the median postoperative hospital stay was 10 days. A higher removal rate of AchRAb was associated with a shorter duration of ICU and postoperative hospital stay (P = 0.001 and 0.019, respectively). Postoperative hospital stay was strongly correlated with post-DFP Pimax (P = 0.010), and marginally correlated with pre-DFP VC (P = 0.047) and to a lesser extent with pre-DFP Pimax (P = 0.063). Univariate analysis using the log rank test revealed that removal rate of AchRAb

BACKGROUND: Double-filtration plasmapheresis (DFP) removes high-molecular-weight molecules semiselectively, thereby minimizing albumin loss, but with subsequent need for fluid substitution. The purpose of this study was to establish the overall incidence of complications during DFP and to analyze the possible contributory factors. STUDY DESIGN AND METHODS: From November 1993 to October 2003, a total of 2502 plasmapheresis procedures were performed during 515 courses of plasmapheresis in 335 patients. The medical and technical records for these patients were reviewed. RESULTS: The overall frequency of complications was 67.5 percent per patient, 60.0 percent per course, and 26.3 percent per procedure. The rate of major complications was 18.2 percent of patients, 13.2 percent of courses, and 2.7 percent of procedures. Hemolysis, the most common complication of DFP, occurred in 20 percent of patients. A total of 83 (3.3%) episodes of hypotension were documented in 63 patients. Vascular-access-related complications constituted approximately 17 percent of the total. There was one documented episode of clinically overt bleeding from laboratory coagulopathy necessitating infusion of fresh plasma to stop bleeding. There was no allergic reaction or mortality associated with the DFP procedures. The per-patient frequency of hypotension was higher in cases of chronic inflammatory neuropathy (35.1%) compared to the other illness categories (15.4%-17.3%), with marginal significance demonstrated (p = 0.0611). CONCLUSION: The safety of DFP treatment has been confirmed by this study. High-risk patients should be monitored carefully during treatment to minimize the occurrence of complications.

Objective – To evaluate the clinical course of patients with myasthenia gravis (MG) up to 3 months after double filtration plasmapheresis (DFP). Material and methods – We recorded the MG score and measured the level of acetylcholine receptor antibody (AchRAb) at baseline and day 1 (D1), week 1 (W1), 1 month (M1), 2 (M2) and 3 months (M3) after DFP in 16 MG patients. Based on the difference in score during follow-up, we divided our patients into clinical improvement (CI) and clinical worsening (CW) groups. Results – The MG score decreased in all courses from a mean of 8.1 at baseline to 5.6 at D1, and to 4.7, 4.0, 3.8, and 3.7 at W1, M1, M2, and M3, respectively. In the CW group, AchRAb levels were significantly higher at M1 (P = 0.022). The AchRAb level at W1 correlated significantly with the MG score at M3 (P = 0.027) and the changes of MG score from W1 to M1 (P = 0.029). The ratio of AchRAb levels of M1 to W1 correlated well with MG score at W1 (P = 0.032), at M3 (P = 0.001), and the changes of MG score from W1 to M1 (P = 0.004). Conclusion – Excessive rebounds of AchRAb level at W1 may suggest clinical worsening and further increases in AchRAb level at M1 predict poorer outcome after DFP.

Objectives To examine the prognostic factors and outcome of myasthenia gravis (MG) patients in crisis with double filtration plasmapheresis (DFP) treatment. Material and methods - A total of 15 patients experienced 20 episodes of crisis during the study period. Plasmapheresis was carried out using a double filtration method. Demographic information, clinical features of crisis, and associated complications were analyzed. Results - The median duration of crisis was 9 days. Chest infection was the most common precipitant of crisis. Twelve out of the 20 episodes (60%) responded well to DFP and mechanical ventilation was discontinued after the third session of DFP in 8 of them. Three significant predictors for prolonged crisis were shorter intervals between the onset of MG and the first crisis (P=0.04), higher serum bicarbonate levels at baseline (P=0.03) and the thymic pathology of thymoma (P=0.03). Conclusion - DFP can ameliorate the profound weakness in crisis and seems to be a rational therapy for patients with myasthenic crisis.

Intensive plasma exchange can transiently alter the hemostatic system. However, the effect of serial double filtration plasmapheresis (DFP) on the hemostatic system has not been adequately described. In this study, we sought to characterize the hemostatic effects of DFP in 32 myasthenia gravis patients who received one course of DFP treatment for five consecutive sessions within 10 days. Platelet count, prothrombin time (PT), partial thromboplastin time (PTT), and serum levels of albumin, globulin, cholesterol, and fibrinogen were measured before and after the course of DFP. Patients were divided into mild hypofibrinogenemia (MH) and severe hypofibrinogenemia (SH) groups based on post-plasmapheresis residual levels of fibrinogen above or below 70 mg/dl. The baseline fibrinogen level was significantly lower in the SH group (P < 0.01). After five sessions of DFP, the fibrinogen level was reduced to below 70 mg/dl in 14 patients (44%). The percentage of excessive prolongation of PT or PTT was significantly higher in the SH group. The SH group also had higher reduction rates of globulin and cholesterol (P < 0.05). Oozing in the punctured site of the central venous catheter occurred in 6 out of 26 patients, with four cases in the MH group and two in the SH group. There was no difference in the overall incidence of bleeding complications between the two groups. Only one episode of clinically overt bleeding occurred during the study after a large-bore femoral catheter was removed soon after the patient had received five consecutive daily treatments. The bleeding stopped after transfusion of 6 units of fresh frozen plasma. In conclusion, despite the obvious reduction of fibrinogen level and the modest decrease in platelet count after an intensive course of DFP treatment, the low incidence of clinically overt bleeding confirmed the safety of DFP.

Sjögren’s syndrome (SS) is an important but poorly recognized cause of peripheral neuropathy. Several forms of peripheral nerve dysfunction occur, including trigeminal sensory neuropathy, mononeuropathy multiplex, distal sensorimotor polyneuropathy and pure sensory neuronopathy. The pathological findings vary and the definite treatment is not known. Here we present 4 cases of acute ataxic sensory polyneuropathy with SS, and the experience of treatment with plasmapheresis (PP). The 4 patients were all females; ages ranged from 30 to 58 years. All had prominent loss of kinesthetic and proprioceptive sensation. The course ranged from acute to subacute onset. Patients were treated with 5–9 sessions of PP. Two patients with initiation of treatment within 2 weeks of onset showed dramatic and sustained responses after PP, while the other 2 had no detectable effects. Our experience showed that PP should be considered in patients who present with sensory neuropathy associated with SS, and the treatment should be given as early as possible.

Systematic investigations of hemodynamic status during double filtration plasmapheresis (DFP) are rare in the literature. To investigate the hemodynamic effects of the vascular access chosen for DFP, variations in blood pressure (BP) and pulse rate (PR) induced acutely by DFP were prospectively analyzed in 46 myasthenia gravis (MG) patients a standard DFP protocol with isovolumetric saline fluid replacement. BP and PR were monitored at 30-min intervals (baseline, M30, M60, M90, and M120) during the procedures. The patients were randomized into central vein (CV) and peripheral vein (PV) groups based on the vascular access used. Systolic BP (SBP) dropped significantly at M60 (P < 0.05), M90 (P < 0.001), and M120 (P < 0.001) when compared to the baseline level. Symptomatic hypotension was not observed in any of the 46 sessions. SBP values during DFP in the CV group were significantly lower than the PV group's at M60 (93.1 vs. 101.0%, P < 0.05) and marginally lower at M90 (91.2 vs. 97.2%, P = 0.06). There was no significant difference in diastolic BP changes between the two groups. In the CV and PV groups, PR changes during plasmapheresis also differed at M90 (103.4 vs. 94.5%, P < 0.001) and M120 (101.3 vs. 95.0%, P < 0.05). The significantly lower SBP during DFP in the CV group at M60 may be due to the high central vein flow rate and resultant delay in volume replacement. In conclusion, the vascular access selected for DFP plays a role in the pathogenesis of plasmapheresis-related hypotension. Controlling flow rates may help to prevent hypotension.

Hypotension is an uncommon complication of procedures involving extracorporeal circulation, including plasmapheresis. From November 1993 to March 1999, we treated 139 patients who underwent a total of 1,137 sessions of double filtration plasmapheresis (DFP). Hypotension was defined as a systolic blood pressure (BP) < 80 mm Hg or any decrease of systolic BP with systemic reactions. A total of 17 (1.5%) episodes of hypotension were documented in 15 patients during the study period. Hypotensive episodes occurred in 2.3% of patients with inflammatory neuropathy, 1.2% of patients with myasthenia gravis, and 1.2% of patients with all other medical diseases. Involvement of the autonomic nerve system (ANS) and a low baseline BP were associated with the occurrence of hypotension. Eight (47%) of 17 episodes were symptomatic and 2 were complicated with seizure. Patients with symptomatic hypotension had a higher level of systolic BP prior to DFP and a larger drop of systolic BP and pulse rate during hypotensive attacks compared to asymptomatic patients. Most hypotensive episodes were resolved briefly after intravenous infusion of saline within 30 min. Eight (47%) of the hypotensive episodes occurred during the first session of DFP treatment. Twelve (71%) of 17 episodes occurred during the last half period of treatment; 6 of them were noted during the terminating stage of DFP. In conclusion, in this series plasmapheresis-related hypotension occurred in 1.5% of DFP sessions and had a higher prevalence in patients with ANS instability and low BP. Extra caution in monitoring BP during DFP therapy is warranted in these vulnerable patients, especially during the termination phase of the first DFP session.

Immunotherapy is currently the standard therapy for myasthenia gravis (MG) although some patients may be refractory to treatment. We describe the use of sequential plasmapheresis and intravenous immunoglobulin (IVIG) therapy for treatment of advanced MG in a patient refractory to all forms of medical treatment including corticosteroids, immunosuppressants, and intermittent plasmapheresis. The patient, a 37-year-old woman with systemic lupus erythematosus (SLE), had initially responded well to treatment with high dose corticosteroids and intermittent plasmapheresis, with the duration of response ranging from 3 to 4 months. However, after 18 months of therapy, the duration of response had gradually decreased to 1 month. She responded well to a 5 day trial of plasmapheresis followed by high dose IVIG, and the duration of response increased to 6 months. The SLE activity was relatively silent during each relapse. This report indicates the potential usefulness of sequential plasmapheresis and IVIG in the treatment of patients with refractory MG and SLE.

The selection of the technical parameters of plasmapheresis in the treatment of patients with MG varies widely due to the lack of sufficient data from controlled studies to standardize the plasmapheresis procedure. Eight myasthenia gravis (MG) patients (Osserman IIb and III) received either immunoadsorption plasmapheresis (IA) with a IM-TR 350 (Asahi Medical Co., Tokyo, Japan) or double filtration plasmapheresis (DF) with a Cascadeflo AC-1770, with four in each group. A Plasmaflo AP 05 W (Asahi Medical Co., Tokyo, Japan) was used as the plasma separator in both groups. Each course of treatment consisted of five sessions of aphereses on alternate days. Plasma was sampled before and after passing through the column. Samples of plasma were analyzed for acetylcholine receptor antibody (AchRAb) at the start of plasmapheresis and sequentially after every 0.5 L of plasma treated. The IA method cleared significantly more AchRAb during the initial treatment of 1. 5 L of plasma than the DF method, especially in the initial 1 L (P < 0.01). The column saturated after treatment of 1.5 to 2 L of plasma. It is known that over-saturation of column may release the already adsorbed/filtrated antibodies. Longitudinal analysis on the serological changes during the five sessions revealed that the clearance obtained using the IA method was significantly higher and more sustained after the first session of treatment compared to the DF method (P < 0.05). The titers of AchRAb were also noted to rise after the fourth session. These results suggest that 2 L of processed volume is optimal in terms of the functional capacity of a plasmapheresis column in either IA or DF methods, and that a total of four sessions of treatment in one course may provide optimal elimination of AchRAb.

Therapeutic plasma exchange (TPE) is a standard treatment in Guillain-Barre syndrome. TPE may require exogenous fluid for replacement of plasma and, depending on the equipment used, varying extracorporeal volumes. Potential adverse effects include allergic reaction, infection, and hypotension. From September 1993 to December 1997, we treated 16 patients with Guillain-Barre syndrome by a newly developed method of automated double filtration plasmapheresis (DFPP). Patients (ten males and six females, age ranged from 16 to 73) suffering from acute ascending motor weakness and fulfilling the diagnostic criteria for GBS were chosen for DFPP. Each patient received at least five sessions of apheresis in 7 to 10 days and approximately 2.5 to 3.0 L of plasma was treated in each session. Patients were evaluated by disability grade according to a Hughes scale. The mean grade of disability was 3.62 at treatment and improved to 2.37 four weeks after the start of DFPP. The median time to grade 2 (walk without support) was 19 days. There were five patients (41.6%) in need of respirator support. The median time to weaning off the respirator was 9 days. Only two patients (12.5%) could not reach grade 2 at the end of 6 months. Our results were comparable to previously published results of TPE. We conclude that DFPP may be as effective as TPE in the treatment of GBS.

Assessment of respiratory function using combined oximetry-cutaneous capnography has never been evaluated in patients with myasthenia gravis (MG). We investigated the effects of double filtration plasmapheresis (DFPP) on respiratory status in 18 MG patients. Results of combined oximetry and transcutaneous capnography, MG scores, and acetylcholine receptor antibody titers before and after DFPP treatment were compared. The respiratory monitoring was performed at three time periods (morning, afternoon, and sleep). Mean MG score was markedly lower after DFPP treatment (5.7) than before treatment (7.9). Before DFPP, the minimum pulse oximetric saturation (SpO2 ) level obtained during the night session was significantly lower (P = 0.0513 and P = 0.0199) than the levels obtained during the two daytime sessions. A similar phenomenon was noted for maximum transcutaneous carbon dioxide tension (PtcCO2 ). After DFPP treatment, the maximum and mean PtcCO2 levels were significantly higher (P = 0.0056) in the morning than in the afternoon. Of all the respiratory function parameters measured, only minimum SpO2 levels obtained during morning sessions before DFP treatment differed significantly from those obtained after DFPP treatment (P = 0.0322). Overall, however, minimum SpO2 levels as well as mean and maximum PtcCO2 levels improved significantly during sleep after DFPP. In conclusion, we found that respiratory function abnormalities were common in myasthenic patients without clinical respiratory symptoms. DFPP treatment resulted in minimal improvement of respiratory parameters.

Plasmapheresis not only removes circulating antibodies but also modulates cellular immunity, including lymphocyte subsets. To investigate the effect of double-filtration plasmapheresis (DFPP) on the ratio of lymphocyte subsets in patients with myasthenia gravis (MG), we examined the percentages of B-cells, T-cells, T helper (Th) cells, T suppressor (Ts) cells, natural killer (NK) cells, NKT cells, and Th/Ts ratio before and after a single DFPP session and after a course of DFPP. A total of 26 patients were recruited; their peripheral blood lymphocyte subsets were assayed using flow cytometry. After a single session of DFPP treatment, the percentages of T-cells (P = 0.0200), Th cells (P = 0.0178), and the Th/Ts ratio (P = 0.0309) decreased significantly, whereas the percentage of NK cells (P = 0.0007) increased significantly. More importantly, after one course of DFPP treatment, the reduced clinical quantitative MG (QMG) score was correlated with the decrease of the percentage of T-cells (r = 0.5005, P = 0.0092). Fourteen thymectomized MG patients had decreased percentages of T-cells (P = 0.0304) and Th cells (P = 0.0444), whereas they had increased NK cells (P = 0.0197) after a single DFPP session. Here, transiently decreased percentages of T-cells after the full DFPP course could enhance the effectiveness of plasmapheresis for MG patients.

Knowledge about the postintervention psychosocial status of myasthenia gravis (MG) is limited and based on questionnaire studies. In this study, the effects of improvement in muscle strength with plasmapheresis treatment on both quality of life (QoL) and psychological status of MG patients were studied. Between January 2008 and December 2009, 29 MG patients were enrolled to receive one course of plasmapheresis treatment. Differences in baseline and posttherapy clinical, laboratory, and psychosocial measures were determined. The mean MG score decreased from 7.8 points at baseline to 4.2 after plasmapheresis, accompanied by the mean antibody clearance of 56%. Psychosocial tests showed significant pre- and posttherapy differences in illness identity (mean scores 23.62 and 20.79 points, respectively) and disability (mean scores 11.28 and 7.63 points, respectively) (p

The purpose of this study was to evaluate the influence of plasmapheresis on sleep in patients with generalized myasthenia gravis and no respiratory symptoms. Seven myasthenia gravis patients, four women and three men, aged 24-52 years, underwent plasmapheresis treatment because of recent worsening of clinical weakness and poor response to previous treatments. We prospectively recorded the myasthenia gravis score, measured acetylcholine-receptor antibody concentration, performed polysomnography, and checked the Epworth Sleepiness Scale at baseline and 1 day after completion of the last session of plasmapheresis. Myasthenic weakness was ameliorated following plasmapheresis in all patients with a median decrease in myasthenia gravis score of 2 points (P = 0.0002) and a median clearance of 43.3% of acetylcholine-receptor antibody. However, there was no significant change in polysomnographic parameters, except for a trend toward shorter duration of the longest apnea period (P = 0.0763) following the treatment. Plasmapheresis did not affect polysomnographic parameters despite improved clinical weakness along with decreased myasthenia gravis score and acetylcholine-receptor antibody concentration.

Miller Fisher syndrome is characterized by external ophthalmoplegia, ataxia, and areflexia. Most researchers favor a peripheral origin while others suggest a brainstem inflammatory lesion or a combination of central and peripheral demyelination. We report 2 cases of Miller Fisher syndrome with the typical triad of ataxia, areflexia, and ophthalmoplegia. Strong clinical evidence of central involvement included initial drowsiness, bilateral Babinski sign, and quadriparesis. Evoked potential studies showed prolongation of central conduction time. Plasmapheresis was performed to relieve respiratory failure in Patient 1 and to shorten the duration of nasogastric tube feeding due to severe bulbar palsy in Patient 2. Significant improvement of electrophysiologic parameters was recorded after plasmapheresis. Abnormal evoked potentials, together with clinical evidence of central nervous system abnormalities, support the hypothesis that there is a combination of peripheral and central involvement in Miller Fisher syndrome in our patients. Plasmapheresis is highly effective in relieving the profound neurological deficits of this atypical syndrome.

To investigate the direct impact of membrane plasmapheresis on the distribution of lymphocyte subsets, paired blood specimens from 18 healthy volunteers were studied before and immediately after a single session of double-filtration plasmapheresis (DFP). After a single session of DFP treatment, the number of helper T cells had increased by 2.34% (P = .0142), whereas the suppressor T cells decreased by 2.22% (P = .0095), with consequent increases in the T-helper/T-suppressor (Th/Ts) ratio (P.0001). The number of B cells was also significantly increased (P = .0012) after DFP treatment; however, total T and natural killer cells did not differ after treatment. Older volunteers (40 years) had significantly higher percentages of B (P = .0002) and helper T (P = .0432) cells after treatment. In contrast, younger subjects had a lower percentage of suppressor T cells (P = .0174). However, the Th/Ts ratio increased significantly irrespective of age group (P = .0016) and sex (P = .0016). A single session of membrane plasmapheresis seemed to activate the cellular immune system in our sample of 18 healthy volunteers, increasing the number of B cells and the Th/Ts ratio.

To evaluate the relationship of antibody clearance and clinical improvement for myasthenia gravis (MG) patients with MuSK antibody (MuSKAb) receiving one course of double-filtration plasmapheresis (DFP) treatment, we prospectively recorded their MG scores and measured MuSKAb concentrations before and after each DFP treatment session in two MuSKAb-positive patients. The clinical improvement trends roughly paralleled the reductions of MG score, except for the late rebound of MuSKAb in the 6th DFP treatment session, without concomitant clinical worsening in one patient. Longitudinal analysis on the serological changes during the serial sessions revealed that the levels of MuSKAb fell by 44%, 59%, 79%, 82%, 92%, and 71% in patient 1 and 52%, 70%, 78%, 87%, and 90% in patient 2. The titers of MuSKAb decreased constantly during the first 5 DFP treatment sessions. MuSKAb clearance per session for the 11 sessions ranged from 19% to 56%, with a mean of 45%. In conclusion, DFP was effective for MuSKAb removal and amelioration of clinical weakness for our two patients with MuSKAb. A 5-session protocol cleared 90% of serum MuSKAb.

Patients with triglyceride levels over 1,000 mg/dl are at high risk of developing acute pancreatitis. This study aimed to determine the effectiveness of plasma exchange (PE) in reducing triglyceride levels during an acute attack of hyperlipidemic pancreatitis (HLP). A total of 17 hypertriglyceridemic patients with the complication of acute pancreatitis received one course of PE treatment for one or two consecutive sessions. The respective mean removal rates during a single PE for triglyceride, cholesterol, amylase, and lipase were 66.3, 62.1, 70.0, and 84.8%, respectively. An additional one exchange increased the removal rate to 83.3, 66.2, 85.5, and 87.0%, respectively. For the two-sessions of treatment, the removal rates were higher for triglyceride (P=0.0015) and amylase with a borderline statistical significance (P=0.0641). Better triglyceride clearance correlated well with lower levels of transmembrane pressure (TMP) at 90 minutes after PE (r2=0.5782, P=0.0010) and shorter plasmapheresis duration (r2=0.2241, P=0.0427). Thirteen of seventeen patients (76.5%) recovered completely, eight patients in a single-session, and five in two-sessions. Two patients developed intra-abdominal abscess, necessitating surgical drainage and two patients died due to both septic shock and multi-organ failure. No significant predictor of clinical outcome was identified. In summary, PE treatment is an effective method to clear lipids and enzymes from plasma in a single session for most HLP patients. A greater extraction of triglyceride would result in a reduced TMP and a shorter duration of PE treatment.

The aim of this study was to investigate the changes in pulmonary function tests for patients with myasthenia gravis (MG) after treatment with double filtration plasmapheresis (DFP) and to evaluate whether pulmonary function tests predict the efficacy of DFP treatment. Thirty-five MG patients (20 females and 15 males, age range 21-69 years) underwent DFP for between four and eight consecutive sessions. Vital capacity (VC), maximal inspiratory pressure (Pi(max)), and MG score were measured before and after DFP. Based on the results of pulmonary function tests, the patients were divided into dyspnea (VC1.0 L or Pi(max)-25 cm H(2)O) and control groups (VC1.0 L and Pi(max)-25 cm H(2)O). The dyspnea group had a significantly better response to DFP treatment, reflected in the decrease of the MG-score (P=0.0327), and the increase in VC value (P=0.0561). Higher clearance rates of acetylcholine receptor antibody (AchRAb) had a trend toward higher changes of VC. In conclusion, VC might better serve as a predictor for the effect of DFP in the dyspnea patient group because of better correlation with clinical improvement and AchRAb clearance.

Double filtration plasmapheresis (DFP) is a widely used and effective way to clear autoantibodies from plasma. It can, however, transiently alter the hemostatic system and cause a bleeding tendency in some patients. There is limited data on the consecutive effect of serial DFP on the hemostatic system, especially on fibrinogen and von Willebrand factor (vWF) levels. This study measured fibrinogen and vWF serially before and after each session of DFP in 8 patients who received one course of DFP treatment for 3 to 5 consecutive sessions on an alternate-day basis. In each session of DFP, the clearance rate of fibrinogen and vWF exceeded 63 and 45%, respectively. The final levels of fibrinogen and vWF after a full course of DFP were reduced to 14.3 and 51.2% of baseline level, respectively. No bleeding tendency was observed in any of the 34 DFP sessions. In conclusion, although an obvious decrease in fibrinogen level and the modest decrease in vWF were observed after an intensive course of DFP treatment, the low incidence of clinically important bleeding confirms the hemostasis-related safety of DFP.

Patients with extremely high triglyceride levels and associated lipemia are at high risk for acute pancreatitis. To evaluate plasmapheresis efficacy for severe hypertriglyceridemia, 18 patients who had not responded to previous therapies were selected for either the plasma-exchange (PE) or double-filtration (DF) treatment variants. After treatment, the mean serum concentrations for triglyceride and cholesterol fell significantly from 1,977.1 and 436.7 mg/dl to 692.6 and 222 mg/dl, respectively. The cholesterol-removal rate was significantly higher for the PE group (P = 0.0082), which also had a lower incidence of hemolysis during the plasmapheresis treatment (P = 0.0430). Improved clearance of serum triglyceride was strongly associated with a lower level of maximal transmembrane pressure (TMP; P = 0.0030), reduced plasmapheresis duration (P = 0.0035), and higher rates of plasma (P = 0.0255) and blood flow (P = 0.0480) during plasmapheresis. In comparison to reports in the literature, the removal rates for serum lipids were lower in our study, possibly as a consequence of early saturation of the plasma separator resulting from blockage caused by the extremely high level of triglyceride-containing lipoproteins. Therefore, PE may be more suitable for the initial treatment of severe hypertriglyceridemia as saturation is prevented. Increasing blood and plasma flow rates, reduction of the TMP level, and reducing effective plasmapheresis duration will improve the clearance of serum lipids during treatment.

Although hypotension is a potential complication for all procedures involving extracorporeal circulation, including plasmapheresis, the effects of serial double-filtration plasmapheresis (DFP) on hemodynamic status have rarely been reported. Blood pressure (BP) and pulse rate (PR) were prospectively monitored at 30-minute intervals (baseline, M30, M60, M90, and Ml20) during procedures for 20 myasthenia gravis patients who underwent one course of five consecutive DFP treatments on alternate days, with hemodynamic parameters recorded and analyzed for all sessions. To evaluate the hemodynamic influence of protein loss resulting from serial DFP treatment, additional analysis of serum protein levels including albumin and globulin was conducted before and after the entire course of treatment. Longitudinal analysis on the systolic BP (SBP) changes over five sessions revealed that the SBP at baseline and at M30 dropped significantly during the third and fourth sessions, in comparison to the first (P < 0.05). By contrast, SBP at M120 rose significantly (P < 0.05) after the second session of treatment. A similar trend was revealed for the diastolic BP (DBP) with a significant fall recorded at baseline and at M30 for the fourth session. The PR did not differ significantly during consecutive DFP treatments. Globulin removal rates were correlated significantly with falls in SBP (r2 = 0.250, P = 0.048) and DBP (r2 = 0.405, P = 0.008). However, analogous albumin removal rate was not correlated with these hemodynamic parameters. In conclusion, our results confirm that hypoproteinemia is an important factor for contributing to unstable hemodynamics during serial DFP. J. Clin. Apheresis 17:33–37, 2002. © 2002 Wiley-Liss, Inc.

Two techniques for plasmapheresis are used in the treatment of myasthenia gravis (MG): immunoadsorption (IA) and double filtration (DF). This controlled study evaluated the differences between these techniques in clinical effects and serological changes. Five patients with generalized MG (clinical states IIb and III) were enrolled; each patient received IA and DF plasmapheresis on separate occasions. Immunosorba TR-350 with an affinity to acetylcholine receptor antibodies (AchRAb) was used for IA, while Evaflux 4A was used as the plasma fractionator for DF. Each course of treatment consisted of five sessions of apheresis. MG score, titers of AchRAb, immunoglobulins (Ig), and plasma biochemistry were assessed by blinded examiners before and immediately after the entire course of treatment. Both treatments effectively ameliorated symptoms of MG. There were no significant changes in MG score between the two groups (IA vs. DF: 2.2 vs. 2.6, P> 0.5). IA had a higher clearance rate of AchRAb than DF (66 % vs. 54 %, P< 0.05), while DF removed more IgA (72% vs. 21%, P< 0.05) and IgM (89% vs. 57%, P< 0.01) than did IA. Although IA removed AchRAb more effectively than DF, the clinical effects between these two treatments were similar. The titers of AchRAb cannot reflect the clinical severity. Some circulating factors other than AchRAb may contribute to the pathogenesis of MG.

Objectives - The aim of this study was to evaluate the efficacy of double filtration plasmapheresis (DFP) in the treatment of patients with myasthenia gravis (MG) and to analyze the possible prognostic factors related to responsiveness to DFP. Materials and methods - We treated 45 MG patients, 26 women and 19 men aged 21-72 years, with DFP for 5 consecutive sessions. All were affected by severe generalized or respiratory weakness with an Osserman's classification of group 2 or 3 and had not responded to previous treatments. Results - Thirty-eight out of 45 patients (84%) achieved significant improvements after DFP. The baseline MG score and removal rate for immunoglobulin G (IgG) were significantly higher in the patients with good response than in the other response groups. Poor responders were more likely to have thymoma and a longer interval among sessions of DFP. Better response in patients with age at onset of less than 40 years was associated with higher MG score. Serum concentration of all proteins tested fell as follows (mean ± SD): IgM, 88 ± 7%; IgA, 71 ± 11%; IgG, 59 ± 14%; globulin, 52 ± 11%; AchRAb, 47 ± 14%; and albumin, 27 ± 10%. All the patients tolerated plasmapheresis well except for 2.2% who experienced hypotension. Conclusion - In this study, DFP was effective and safe in the treatment of patients with severe generalized MG. The factors correlating with the better clinical response were high MG score, a thymic pathology of non-thymoma, daily apheresis, young age at onset, and high removal rate for IgG.

Twelve cases of recognized inflammatory polyneuropathy were treated by plasmapheresis (PP) at Shin-Kong Wu Ho-Su Memorial Hospital from November 1993 to November 1995. These include 6 cases of acute inflammatory demyelinating polyneuropathy (AIDP), 4 cases of chronic inflammatory demyelinating polyneuropathy (CIDP), one case of Fisher syndrome, and one case of Sjogren's syndrome with polyneuropathy. The patients chosen for PP met the inclusion criteria of severely disabled, i.e., Grade 4 (bed or chair bound) or Grade 5 (required assisted ventilation), or an unremittingly progressive course. Plasmapheresis was carried out by the double filtration method. Each patient received a standard course of at least 4 sessions of pheresis. All the patients receiving PP showed a beneficial response. The treatment for 10 patients was judged to be effective. The other 2 patients (one AIDP and one CIDP), though improved, were unable to reach Grade 2. Among the complications of PP, only 4 episodes of symptomatic hypotension were noted in a total of 73 sessions of PP. In conclusion, PP is safe and effective in treating inflammatory polyneuropathy.—