Relapsing and Progressive Complications of Severe Hypertriglyceridemia: Effective Long-Term Treatment with Double Filtration Plasmapheresis.

BACKGROUND: Severe hypertriglyceridemia (HTG) is associated with major complications such as acute or relapsing pancreatitis (AP) and atherosclerotic cardiovascular disease (ASCVD). Rapid elimination of triglyceride (TG)-rich lipoproteins (LP) with double filtration plasmapheresis (DFPP) without need for substitution has been found to be effective for the acute, short-term treatment of HTG-induced AP. Data on the long-term use of DFPP to prevent HTG-associated complications are scarce. OBJECTIVES: To evaluate the use and efficacy of regular DFPP treatment in clinical practice for preventing recurrence of HTG-associated complications in thera-py refractory patients. METHODS: Retrospective multicenter study in patients with severe symptomatic drug and diet refractory HTG with regular DFPP treatment. Patients' incidence of HTG-associated pancreatic or cardiovascular complications was compared before treatment and with regular DFPP treatment. RESULTS: Ten patients (3 female) were identified with baseline maximal TG concentrations of 2,587-28,090 mg/dL (median 5,487 mg/dL; interquartile range [IQR] 4,340-12,636). The mean observation period was 3.9 ± 3.4 years before and 3.8 ± 3.0 years after commencement of DFPP. In 5 patients, severe HTG was related to chylomicronemia, 2 patients had familial partial lipodystrophy Dunnigan, and 1 patient had additional LP(a)-hyperlipoproteinemia. The main HTG-associated complication was recurrent AP in 8 patients, including 1 patient treated during pregnancy. Two patients presented severe progressive ASCVD. With long-term DFPP treatment, the annual rate of HTG-associa-ted pancreatic or cardiovascular complications declined from median 1.4 (IQR 0.7-2.6) to 0 (IQR 0.0-0.4; p < 0.005). The absolute number of events was reduced by 77%. In 6 patients (60%) episodes of AP did not occur, nor was progression of ASCVD detected clinically or by routine imaging techniques. DFPP was effective in the elimination of TG-rich LP from plasma, and was safe and well-tolerated. CONCLUSION: Long-term, regular DFPP treatment resulted in stabilization of patients with severe HTG and related recurrent AP or progression of ASCVD, who were refractory to conventional dietary and drug therapy.

Escalation Therapy of Steroid Refractory Multiple Sclerosis Relapse with Tryptophan Immunoadsorption - Observational Multicenter Study with 147 Patients.

BACKGROUND: A marked proportion of multiple sclerosis (MS) relapses is followed by incomplete recovery. Our aim was to considerably increase the evidence of the clinical use of immunoadsorption (IA) as escalation therapy for patients with MS relapse. METHODS: A retrospective multicenter study was performed in MS patients with steroid refractory relapse who were treated with tryptophan IA. The main outcome parameter was change of acute relapse-related disability assessed by Expanded Disability Status Scale (EDSS) and visual acuity (VA) measurements for patients with optic neuritis (ON). IA treatments were performed using single-use tryptophan adsorbers. RESULTS: Data of 147 MS patients and 786 single IA treatments were analyzed. Treatment with IA was commenced in mean 32 ± 35 days after the onset of relapse. One hundred and five out of 147 patients (71.4%) improved functionally after mean 5.4 IA treatments within 7-10 days. EDSS improved from median 5 (interquartile range, IQR 3.5) to 4 (IQR 2.5) (p < 0.001). In patients with ON (n = 32), VA improved after the IA series in 84% of cases from median 0.2 (IQR 0.6) to 0.6 (IQR 0.66) (p < 0.001). In 98.9% of IA treatments, no clinically relevant side effect was reported. CONCLUSION: Tryptophan IA was found to be effective and well tolerated as escalation therapy for MS relapse.

Immunoadsorption as maintenance therapy for refractory neuromyelitis optica spectrum disorder.

Background: Neuromyelitis optica spectrum disorder (NMOSD) is a rare relapsing autoimmune disease of the central nervous system, affecting mainly optic nerves and spinal cord. NMOSD pathophysiology is associated with anti-aquaporin-4 (AQP4) immunoglobulin G (IgG) autoantibodies. Rapid extracorporeal elimination of autoantibodies with apheresis techniques, such as immunoadsorption (IA), was proven to be an effective treatment of NMOSD attacks. Data on the long-term use of IA to prevent attacks or progression of NMOSD are lacking. Objectives: The aim of this study was to evaluate efficacy and safety of maintenance IA for preventing recurrence of NMOSD attacks in patients refractory to other immunotherapies. Design: Case study. Methods: Retrospective analysis of two female patients with severe NMOSD refractory to conventional immunotherapies was performed. Both patients had responded to tryptophan IA (Tr-IA) as attack therapy and subsequently were treated with biweekly maintenance Tr-IA. Results: Patient 1 (AQP4-IgG seropositive, age 42 years) had 1.38 attacks of optic neuritis per year within 10.1 years before commencing regular Tr-IA. With maintenance Tr-IA for 3.1 years, one mild attack occurred, which was responsive to steroid pulse therapy. Expanded Disability Status Scale (EDSS) was stable at 5.0. Visual function score of the last eye improved from 3 to 1. Patient 2 (AQP4-IgG seronegative, age 43 years) experienced 1.7 attacks per year, mainly acute myelitis and optic neuritis, during the period of 10.0 years before the start of Tr-IA. During regular Tr-IA treatment, no further NMOSD attack occurred. The patient was clinically stable without any additional immunosuppressive treatment for 5.3 years. EDSS improved from 6.0 to 5.0, and the ambulation score from 7 to 1. Tolerability of Tr-IA was good in both patients. No serious adverse events occurred during long-term clinical trajectories. Conclusion: Tr-IA was well tolerated as maintenance treatment and resulted in clinical stabilization of two patients with highly active NMOSD, who were refractory to standard drug therapy.

Immunoadsorption in patients with chronic inflammatory demyelinating polyradiculoneuropathy with unsatisfactory response to first-line treatment.

BACKGROUND/AIMS: First-line treatment options for chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) are corticosteroids, intravenous immunoglobulin, and plasma exchange. In a significant number of patients, first-line therapy fails, and long-term maintenance treatment still remains a therapeutic challenge. Immunoadsorption (IA) may be an alternative to classical plasma exchange in the therapy of immune-mediated neurologic diseases. The aim of this investigation was to evaluate efficacy and safety of IA in patients with CIDP with unsatisfactory response to first-line treatment options. METHODS: CIDP patients received adjunct IA treatment using tryptophan-immune adsorbers. The inflammatory neuropathy cause and treatment disability (INCAT) score was used to grade disability and monitor treatment effects. RESULTS: In total, 14 CIDP patients were analyzed. Ten patients were treated in hospital. After one IA treatment series, the INCAT score decreased significantly in all 10 patients. Four of these 14 patients were treated in outpatient clinics using long-term maintenance IA with 1-2 treatments per week. In these 4 patients, effects of long-term maintenance IA resulted in an improvement of overall disability. In all patients, IA was safe, well tolerated, and no severe adverse effects occurred. CONCLUSION: IA could be an effective and safe option for CIDP patients with unsatisfactory response to first-line treatment options and for long-term maintenance treatment.

Prospective, randomized, controlled clinical study evaluating the efficacy of Rheopheresis for dry age-related macular degeneration. Dry AMD treatment with Rheopheresis Trial-ART.

PURPOSE: To evaluate Rheopheresis for the treatment of patients with high-risk dry age-related macular degeneration and no therapeutic alternative. Rheopheresis is a method of therapeutic apheresis using the methodology of double filtration plasmapheresis to treat microcirculatory disorders. METHODS: The dry AMD treatment with Rheopheresis trial (ART) was a randomised, controlled clinical study. Patients with the diagnosis of AMD in both eyes, with the study eye presenting dry AMD and soft drusen (the fellow eye had advanced AMD) were randomly assigned in a 1:1 ratio to receive ten Rheopheresis treatments within 17 weeks or to remain untreated. The primary outcome was change in best-corrected ETDRS-visual acuity (mean logMar change) after 7.5 months compared to baseline visual acuity for both groups. RESULTS: Forty-three eyes of 43 patients (22 treatment and 21 control group) were analysed. The mean baseline BCVA in study eyes was 0.58 in the treatment group and 0.66 in the control group (n.s. p = 0.19). At the primary efficacy endpoint 7.5 months post baseline, there was a statistically significant mean difference of 0.95 ETDRS lines (p = 0.01) between the Rheopheresis and control groups. Nine percent of eyes in the group treated with Rheopheresis gained 2 or more ETDRS lines, as compared with 0% of eyes with no treatment. None of the treated patients had a loss in visual acuity in their study eyes, as compared with 24% of patients without treatment who lost 1 ETDRS line or more; 19% lost 2 ETDRS lines or more. Rheopheresis treatment was safe and well-tolerated. CONCLUSION: The results of ART provide further evidence that Rheopheresis is a safe and effective therapeutic option for high-risk patients with dry AMD and no therapeutic alternative. A series of Rheopheresis treatments can improve the natural course of AMD for selected patients.

Lipoprotein(a) and mortality-a high risk relationship.

Lipoprotein(a) (Lp(a)) is an independent cardiovascular risk factor playing a causal role for atherosclerotic cardiovascular disease (ASCVD). Early or progressive ASCVD or a familial predisposition are key findings which can be associated with Lp(a)-hyperlipoproteinemia (Lp(a)-HLP). The German guideline for the indication of lipoprotein apheresis in patients with Lp(a)-HLP has proved to be of value to identify patients at highest risk, using the composite of a Lp(a) threshold >60 mg/dl (>120 nmol/l) and clinical ASCVD progression despite effective LDL-C lowering therapy. In particular for such patients it appears to be plausible that Lp(a)-associated risk would increase cardiovascular mortality as the most important part of total mortality in Western populations. By the majority of existing investigations an association of Lp(a) concentration on total or cardiovascular mortality was demonstrated. However, inconsistency in the findings between studies exists without a clear trend for any study feature to explain this. Genetic homogeneity of the population, long-term follow-up, and clinically guided selection of patients might be important to further clarify the impact of Lp(a) concentration on progression of ASCVD, and finally total or cardiovascular mortality. LDL and Lp(a) particles exhibit a mutual effect modification on related ASCVD risk. Therefore, LDL-C levels and concomitant LDL-C lowering treatment must be considered in this context. Prospective evaluation is needed to document that specific Lp(a)-lowering additional to targeted LDL-C lowering will in fact reduce cardiovascular or total mortality.

Lipoprotein(a) - Marker for cardiovascular risk and target for lipoprotein apheresis.

Lipoprotein(a) (Lp(a)) consists of an LDL particle whose apolipoprotein B (apoB) is covalently bound to apolipoprotein(a) (apo[a]). An increased Lp(a) concentration is a causal, independent risk factor for atherosclerotic cardiovascular disease (ASCVD) and a predictor of incident or recurrent cardiovascular events. Although Lp(a) was first described as early as 1963, only the more recent results of epidemiological, molecular, and genetic studies have led to this unequivocal conclusion. More than 20% of Western populations have elevated Lp(a) values. Lp(a) concentrations should be always part of the lipid profile when ASCVD risk is assessed. However, presence of other risk factors, laboratory findings, medical history and family history must be considered to conclude on its clinical relevance in an individual patient. Early or progressive ASCVD or a familial predisposition are key findings which can be associated with elevated Lp(a). The cholesterol portion contained in Lp(a) is also included in the various methods of LDL-C measurement. To assess proximity to the cardiovascular risk related target value for LDL-C, appropriate correction should be applied when high Lp(a) values are obtained to estimate the LDL-C that can actually be treated by lipid lowering drugs. Initial study data show that antisense oligonucleotides, which selectively decrease apolipoprotein(a), are promising as future treatment options. Currently, lipoprotein apheresis, which has a reimbursement guideline in Germany, is the therapy of choice for patients with Lp(a)-associated progressive ASCVD, with the aim of sustained prevention of further cardiovascular events.

Tryptophan immunoadsorption during pregnancy and breastfeeding in patients with acute relapse of multiple sclerosis and neuromyelitis optica.

BACKGROUND: Up to every fourth woman with multiple sclerosis (MS) or neuromyelitis optica spectrum disorder (NMOSD) suffers a clinically relevant relapse during pregnancy. High doses of steroids bear some serious risks, especially within the first trimester of pregnancy. Immunoadsorption (IA) is an effective and more selective treatment option in disabling MS relapse than plasma exchange. Data on the use of IA during pregnancy and breastfeeding are scarce. METHODS: In this retrospective multicenter study, we analyzed the safety and efficacy of IA treatment in acute relapses during pregnancy or breastfeeding. The primary outcome parameter - change of acute relapse-related disability after IA - was assessed using Expanded Disability Status Scale (EDSS) and visual acuity (VA) measurements for patients with optic neuritis (ON). RESULTS: A total of 24 patients were analyzed, 23 with relapsing-remitting MS, and 1 with NMOSD. Twenty patients were treated with IA during pregnancy. Four patients received IA postnatally during the breastfeeding period. Treatment was started at a mean 22.5 [standard deviation (SD) 13.9] days after onset of relapse. Patients were treated with a series of 5.8 (mean, SD 0.7) IA treatments within 7-10 days. Sixteen patients received IA because of steroid-refractory relapse, eight were treated without preceding steroid pulse therapy. EDSS improved clinically relevant from 3.5 [median, interquartile range (IQR) 2] before IA to 2.5 (median, IQR 1.1) after IA, p < 0.001. In patients with ON, VA improved in four out of five patients. Altogether, in 83% of patients, a rapid and marked improvement of relapse-related symptoms was observed after IA with either a decrease of ⩾1 EDSS grade or improvement in VA ⩾20%. No clinically relevant side effect was reported in 138 IA treatments. CONCLUSIONS: Tryptophan-IA was found to be effective and well tolerated in MS/NMOSD relapses, both as an escalation option after insufficient response to steroid pulse therapy and as first-line relapse treatment during pregnancy and breastfeeding.

Prevention of cardiovascular complications in patients with Lp(a)-hyperlipoproteinemia and progressive cardiovascular disease by long-term lipoprotein apheresis according to German national guidelines.

Lipoprotein(a) (Lp(a)) is an independent cardiovascular risk factor playing a causal role for atherosclerotic cardiovascular disease (CVD). Lipoprotein apheresis (LA) is a safe well-tolerated outpatient treatment to lower LDL-C and Lp(a) by 60-70%, and is the ultimate escalating therapeutic option in patients with hyperlipoproteinemias (HLP) involving LDL particles. Major therapeutic effect of LA is preventing cardiovascular events. Lp(a)-HLP associated with progressive CVD has been approved as indication for regular LA in Germany since 2008. The Pro(a)LiFe-study investigated with a prospective multicenter design the long-term preventive effect of LA on incidence rates of cardiovascular events prospectively over a period of 5 years in 170 consecutive patients who commenced regular LA. During a median period of 4.7 years of the pre-LA period, Lp(a) associated progressive CVD became apparent. Apolipoprotein(a) (apo(a)) isoforms and polymorphisms at the apo(a) gene (LPA) were analyzed to assess hypothetical clinical correlations. 154 patients (90.6%) completed 5­years follow-up. Significant decline of the mean annual major adverse cardiac event (MACE) rate was observed from 0.41 ± 0.45 two years prior to regular LA to 0.06 ± 0.11 during 5 years with regular LA (p < 0.0001). 95.3% of patients expressed at least one small apo(a) isoform. Calculation of isoform specific concentrations allowed to confirm the equivalence of 60 mg/dl or 120 nmol/l as Lp(a) thresholds of the German LA guideline. Results of 5 years prospective follow-up confirmed that LA has a lasting effect on prevention of cardiovascular events in patients with Lp(a)-HLP and afore progressive CVD.

Immunoadsorption for autoimmune encephalitis.

Autoimmune encephalitis is a severe inflammatory disorder of the brain. The discovery that several non-infectious forms of encephalitis are associated with autoantibodies was a breakthrough in the care of this previously untreatable group of patients. The correlation of antibody type and titer with pattern and severity of symptoms was essential for the initiation of immunotherapies. First line therapy consists of steroids, intravenous immunoglobulins, plasma exchange or immunoadsorption. Rapid elimination of autoantibodies using selective immunoadsorption and avoiding the disadvantage of plasma substitution is a pathophysiologically guided therapeutic approach, and has been proven to be an effective therapeutic option as part of multimodal immunotherapy.

Lipoprotein(a)-hyperlipoproteinemia as cause of chronic spinal cord ischemia resulting in progressive myelopathy - successful treatment with lipoprotein apheresis.

High concentrations of lipoprotein(a) (Lp(a)) represent an important independent and causal risk factor associated with adverse outcome in atherosclerotic cardiovascular disease (CVD). Effective Lp(a) lowering drug treatment is not available. Lipoprotein apheresis (LA) has been proven to prevent cardiovascular events in patients with Lp(a)-hyperlipoproteinemia (Lp(a)-HLP) and progressive CVD. Here we present the course of a male patient with established peripheral arterial occlusive disease (PAOD) at the early age of 41 and coronary artery disease (CAD), who during follow-up developed over 2 years a progressive syndrome of cerebellar and spinal cord deficits against the background of multifactorial cardiovascular risk including positive family history of CVD. Spastic tetraplegia and dependency on wheel chair and nursing care represented the nadir of neurological deficits. All conventional risk factors including LDL-cholesterol had already been treated and after exclusion of other causes, genetically determined Lp(a)-HLP was considered as the major underlying etiologic factor of ischemic vascular disease in this patient including spinal cord ischemia with vascular myelopathy. Treatment with an intensive regimen of chronic LA over 4.5 years now was successful to stabilize PAOD and CAD and led to very impressive neurologic and overall physical rehabilitation and improvement of quality of life.Measurement of Lp(a) concentration must be recommended to assess individual cardiovascular risk. Extracorporeal clearance of Lp(a) by LA should be considered as treatment option for select patients with progressive Lp(a)-associated ischemic syndromes.

Lipoprotein apheresis for Lp(a)-hyperlipoproteinemia with progressive cardiovascular disease--Additional particular aspects of the Pro(a)LiFe multicenter trial.

Lipoprotein apheresis (LA) can lower LDL-cholesterol and Lp(a) by 60%-70% and is the final escalating option in patients with hyperlipoproteinemias involving LDL or Lp(a) particles. Major therapeutic effect of LA is preventing cardiovascular events. In Germany since 2008 a reimbursement guideline has been implemented accepting to establish the indication for LA not only for familial or severe forms of hypercholesterolemia but also based on Lp(a)-hyperlipoproteinemia associated with a progressive course of cardiovascular disease, that persists despite effective treatment of other concomitant cardiovascular risk factors. The Pro(a)LiFe-study confirmed with a prospective multicenter design that LA can be regarded as an important therapeutic approach to effectively reduce Lp(a) plasma levels and prevent cardiovascular events in this particular high-risk patient group. Results support that Lp(a) may be a major causal factor for precipitating mechanisms of accelerated progression of cardiovascular disease (CVD). Indication for LA based on measurement of Lp(a) as part of risk assessment is supported by the following conditions: progressive CVD as assessed clinically and with imaging techniques, established maximally tolerated lipid lowering drug treatment, recent cardiovascular events despite efficient drug treatment, out of the ordinary frequency of cardiovascular events, early CVD, or positive family history of early CVD. Still existing difficulties with Lp(a) laboratory measurement require a practical approach to establish the indication for LA considering the 60 mg/dl threshold of German guidelines with selecting an Lp(a) assay which has been calibrated for mass.

Lipoprotein apheresis results in plaque stabilization and prevention of cardiovascular events: comments on the prospective Pro(a)LiFe study.

Elevated lipoprotein(a) (Lp(a)) has emerged as an important independent cardiovascular risk factor, and causal association has been accepted with adverse outcome in atherosclerotic disease. Lipoprotein apheresis (LA) can lower low-density lipoprotein (LDL)-cholesterol and Lp(a) by 60-70 % and is the final escalating therapeutic option in patients with hyperlipoproteinemias (HLP) involving LDL or Lp(a) particles. Major therapeutic effect of LA is preventing cardiovascular events. Stabilizing plaque morphology might be an important underlying mechanism of action. In Germany, since 2008, a reimbursement guideline has been implemented to establish the indication for LA not only for familial or severe forms of hypercholesterolemia but also for Lp(a)-HLP associated with a progressive course of cardiovascular disease, that persists despite effective treatment of other concomitant cardiovascular risk factors, i.e. isolated Lp(a)-HLP. The Pro(a)LiFe-study confirmed with a prospective multicenter design that LA can effectively reduce Lp(a) plasma levels and prevent cardiovascular events.

Lipidfiltration--safe and effective methodology to perform lipid-apheresis.

Familial hypercholesterolemia (FH) not adequately responding to diet and drug therapy represents an indication for extracorporeal lipid-apheresis, which has become an highly effective and approved therapy for those patients in several countries. Based on different methodology, five treatment options of lipid-apheresis exist and are in widespread practical use covered by regular reimbursement in Germany. All methods are safe and demonstrate equivalent efficacy of reducing LDL cholesterol with respect to the single apheresis session as well as during long-term treatment. Therefore German reimbursement guidelines leave the choice of the method to the discretion of the apheresis center. Related to properties of the used technology all methods exhibit characteristic patterns of additional plasma protein elimination, which do not impair, but in part may increase the therapeutic benefit of lipid-apheresis. Fibrinogen reduction has to be mentioned as an example. The Lipidfiltration system is based on plasmafiltration previously referred to as membrane differential filtration (MDF), synonymous with double filtration plasmapheresis (DFPP). The new term Lipidfiltration was the result of technological progress in the manufacturing process of the plasmafilter resulting in enhanced sieving characteristics and capacity. The Lipidfiltration system is completed by a specifically designed therapy machine with optimised performance characteristics.

Clinical studies to implement Rheopheresis for age-related macular degeneration guided by evidence-based-medicine.

In the majority of age-related macular degeneration (AMD) patients the therapeutic situation is very unsatisfactory, especially for patients with dry AMD. Rheopheresis is a safe and effective modality of therapeutic apheresis to treat microcirculatory disorders, and represents a novel therapeutic approach for patients with dry AMD and soft drusen. Elimination of a defined spectrum of high molecular weight proteins from human plasma including pathophysiologically relevant risk factors for AMD such as fibrinogen, LDL-cholesterol, alpha 2-macroglobulin, fibronectin, and von-Willebrand factor results in the reduction of blood and plasma viscosity as well as erythrocyte and thrombocyte aggregation. Pulses of lowering blood and plasma viscosity performed as series of Rheopheresis treatments lead to rapid changes of blood flow, subsequently inducing sustained improvement of microcirculation, and recovery of retinal function. Two controlled randomized clinical trials demonstrated safety and efficacy of Rheopheresis for the treatment of AMD patients, especially with the dry form. Recently the interim-analysis of the sham-controlled, double blinded, randomized multicenter MIRA-I trial confirmed these results. The RheoNet-registry and the development and continuous update of therapy guidelines provide an appropriate framework for the quality management of the interdisciplinary cooperation between ophthalmologists with apheresis specialists. A hypothesis based upon current knowledge of pathogenic mechanisms of the development and progression of AMD can be conclusively linked with the putative mechanism of action of Rheopheresis for AMD. A recommendation for high-risk AMD-patients was defined. Based on the positive results of the MIRA-1 interim analysis eight Rheopheresis treatments are currently recommended as the initial treatment series.

From membrane differential filtration to lipidfiltration: technological progress in low-density lipoprotein apheresis.

Extracorporeal low-density lipoprotein (LDL) apheresis is an established and highly effective therapy for patients with familial hypercholesterolemia (FH) not adequately responding to diet and drug therapy alone. Based on different methodology, five treatment options of LDL apheresis are available and in widespread practical use in Germany. All methods are safe and demonstrate equivalent efficacy of reducing LDL cholesterol with respect to the single apheresis session as well as during long-term treatment. Owing to methodological properties all methods also exhibit characteristics of additional plasma protein elimination, which do not impair, but in part, increase the beneficial therapeutic effect of LDL apheresis. Fibrinogen reduction has to be mentioned as an example. The lipidfiltration system is based on plasmafiltration previously named membrane differential filtration (MDF), synonymous with double filtration plasmapheresis (DFPP). The new term lipidfiltration was the result of technological progress leading to a significant improvement of the efficiency. The system consists of a novel lipid filter with enhanced sieving characteristics and capacity, and is completed by an enhanced therapy machine with an optimized heating unit.

Neurologic diseases of the central nervous system with pathophysiologically relevant autoantibodies--perspectives for immunoadsorption.

Immediate antibody elimination, pulsed induction of antibody redistribution, and immunomodulation are major forces of efficacy of therapeutic apheresis (i.e. plasma exchange [PE] or immunoadsorption [IA]) for autoimmune neurologic disorders. Therapeutic apheresis can offer rapid response for severe acute neurologic symptoms, and stable rehabilitation in long-term clinical courses being refractory to drug based strategies or complicated by drug side effects. PE or IA in these situations must be considered as part of multimodal or escalating immune treatment strategies in combination or in competition with intravenously administered immunoglobulins (ivIg), corticosteroids, the full spectrum of immunosuppressive drugs, and bioengineered antibodies. Selective IA is increasingly replacing PE due to its superior safety profile and increasing knowledge on pathogenic relevance of autoantibodies. Recent experiences in autoimmune diseases of the central nervous system, e.g. multiple sclerosis, neuromyelitis optica, and autoimmune encephalitis confirmed this concept.

RheoNet registry analysis of rheopheresis for microcirculatory disorders with a focus on age-related macular degeneration.

The purpose of establishing the RheoNet registry was to evaluate the safety and efficacy of rheopheresis, a specific method of therapeutic apheresis used to treat microcirculatory disorders. Apheresis centers providing rheopheresis therapy and physicians caring for the underlying disease were asked to participate in the registry, and the registry data were analyzed for safety and tolerability. Age-related macular degeneration (AMD) was selected as a model disease to evaluate efficacy. The RheoNet registry was successfully established recording 7722 rheopheresis treatments of 1110 patients, including 833 AMD patients. The mean age of patients was 72 years. Adverse events (AE) were reported in 5.67% of treatments, but termination of the treatment session was only required in 0.48%. Transient hypotension was the most frequently reported AE. No age-related increase in AE was observed. Ophthalmological data of 428 eyes (of 279 treated patients) with dry AMD could be analyzed; 85 eyes of 55 untreated AMD patients served as the control. At 6.75 +/- 5.25 months post-baseline, 42% of the treated eyes had improved visual acuity. The proportion of eyes with a decline in visual acuity was 17%, compared to 40% in the untreated controls (P < 0.01). The RheoNet registry has been successfully established and data analysis revealed that rheopheresis is a safe outpatient treatment for microcirculatory disorders. Moreover, RheoNet currently provides the largest evaluation of the efficacy of rheopheresis for dry AMD. Registry analysis contributes to a safe and appropriate use of rheopheresis in clinical practice.

Plasma exchange and immunoadsorption for autoimmune neurologic diseases - current guidelines and future perspectives.

There is increasing interest from neurologists to use therapeutic apheresis in autoimmune neurologic diseases due to growing knowledge of pathogenic relevance of autoantibodies. Developments in that field have been summarized in this review focusing on German guidelines and recent results from clinical research. Therapeutic apheresis can offer a therapeutic armamentarium with rapid response for severe acute neurologic symptoms, and a drug-free option for clinical courses being refractory to drug based strategies or complicated by drug side effects. Plasma exchange (PE) as the classical method has become part of current guidelines within basic and escalating immunomodulatory treatments of autoimmune neurologic diseases, and in daily practice gets increasingly replaced by selective immunoadsorption (IA) due to its equivalent efficacy in combination with a superior safety profile. Therapeutic effects of PE and IA in autoantibody mediated diseases can be attributed to 3 major mechanisms: immediate intravascular reduction of (auto-)antibody concentration, pulsed induction of antibody redistribution, and subsequent immunomodulatory changes. 5 treatments over a period of 8-10 days seem to be an appropriate regimen to restore neurologic function in acute flares or relapses of autoimmune neuropathies, e.g. myasthenic crisis, Guillain-Barré-syndrome, and steroid refractory relapse of multiple sclerosis. Especially in MS a better understanding is needed, who are the best candidates for IA.

Rheopheresis for sudden sensorineural hearing loss.

Patients suffering from sudden sensorineural hearing loss (SSHL), especially those with hearing impairment refractory to infusion therapy, need new therapeutic options. Fibrinogen-LDL-apheresis, covering Rheopheresis and HELP-apheresis for the indication of SSHL, proved to be an effective treatment option within the therapeutic armamentarium for SSHL in two randomized controlled trials including each more than 200 patients, and has also been shown to be an effective treatment option for patients refractory to the first line standard treatment. Fibrinogen-LDL-apheresis effects an immediate pulsed reduction of plasma viscosity as well as whole blood viscosity, hypothesized to lead to a sustained microcirculatory recovery, thus improving the natural course of acute microcirculatory impairment significantly. The solid body of evidence provided by investigations on fibrinogen-LDL-apheresis in recent years has been recognized by German SSHL guidelines, proposing fibrinogen-lowering treatments like this as part of a multimodality approach. Superiority of fibrinogen-LDL-apheresis over established first line standard treatments could not been shown in general. In consequence, no regular reimbursement by health insurances is available, in particular facing the current policy of health insurances for initial therapeutic nihilism at the acute onset of SSHL. Patients can apply for individual reimbursement or must pay the cost for the treatment. Refractory patients hopefully will profit by growing experiences.