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During platelet and plasmapheresis, a significant amount of blood is lost through the initial test blood collection and the residual blood that remains in the disposable plastic sets. To address this issue, we examined ferritin levels in 523 blood donors who had not donated whole blood within the previous year. We compared ferritin levels between two groups: those who used only machines with low residual blood (group C) and those with high residual blood (group T). The study revealed that ferritin levels were less than 12 ng/mi in 33.3% of male donors and 61.1% of female donors who donated 13 to 24 times within the previous year. As donation frequency increased among male donors, the mean ferritin level decreased. However, there was no significant difference in ferritin levels between group C and T among those with 12 or fewer annual donations. Our findings suggest that an elevated number of lifetime blood donations also impacted iron deficiency. These findings emphasize the importance of regularly monitoring donors' ferritin levels, iron supplementation, reducing donation frequency, and adopting the saline reinfusion procedure to prevent iron depletion. [ABSTRACT FROM AUTHOR]

Treatments for acute attacks of neuromyelitis optica (NMO) include steroid pulse therapy, plasma exchange, and intravenous immunoglobulin. Oral immunosuppressants, such as prednisolone and azathioprine, have also been used to prevent relapse. Recently, biologic agents such as eculizumab, satralizumab, inebilizumab, and rituximab have been approved for use in Japan. Although side effects caused by steroid therapy have been issues for patients in the past, active use of the newly approved biologics is expected to help patients avoid the adverse effects of steroids and improve their qualities of life.

Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is an autoimmune peripheral neuropathy with chronic progression over 2 months or more. In this review, we provide an overview of key clinical studies involved in the development of CIDP therapy, as well as a discussion of changes in the concept of treatment. Although a definitive therapy has not yet been established, international and Japanese clinical guidelines recommend three first-line treatment options for symptom improvement, namely corticosteroids, intravenous immunoglobulin (IVIg), and plasmapheresis, based on the results of clinical studies conducted before the early 2000s. Since 2010, several treatments for the prevention of CIDP relapse (maintenance therapy) have been developed and more recently, studies have focused on the optimization of each treatment. On the other hand, CIDP treatment is associated with several limitations, including a lack of biomarkers for prediction of disease progression, differences in response to treatment between CIDP subtypes, and difficulties in the selection of appropriate maintenance therapy. Several studies aimed at resolving these issues are currently being conducted. (Received 22 May, 2020; Accepted 12 January, 2021; Published 1 July, 2021).

Immunosuppressive agents (cytotoxic agents) may be effective in cases of central nervous system autoimmune/inflammatory diseases that do not respond to steroids, plasmapheresis, or intravenous immunoglobulin therapy. Cytotoxic drugs can cause serious side effects. Therefore, it is important to obtain adequate informed consent after a timely decision based on the indication has been made. It is important to be prepared in advance for opportunistic infections and adverse events and to closely monitor the subsequent course.

Thrombotic thrombocytopenic purpura (TTP) is a rare and potentially life-threatening disease that is characterized by microangiopathic hemolytic anemia, consumptive thrombocytopenia, and ischemic organ damage resulting from the formation of platelet-rich thrombi in the microvasculature. It is especially related to a severe deficiency of ADAMTS13, the specific von Willebrand factor-cleaving protease. Thus, <10% of the normal activity of ADAMTS13 is an essential diagnostic marker for establishing a diagnosis of TTP. TTP can be of congenital form that is termed the Upshaw-Schulman syndrome (USS) that is caused by genetic abnormality of ADAMTS13 and acquired form that is caused by autoantibodies against ADAMTS13. The congenital form is treated with the infusion of fresh frozen plasma, and the treatment of the acquired form involves plasma exchange combined with immunosuppressive therapy that uses corticosteroids and rituximab. Recently, the efficacy and safety of new drugs caplacizumab, single-domain antibody against ADAMTS13, and recombinant ADAMTS13 products have been reported in large-scale clinical trials conducted in other countries. These results suggested the better outcome in the treatment for the patients with TTP in the near future.

Acquired thrombotic thrombocytopenic purpura (aTTP) is a life-threatening systemic thrombotic microangiopathy characterized by the presence of anti-ADAMTS13 antibodies (inhibitor). Here we report the case of a patient with refractory aTTP successfully treated with cyclosporine. A 69-year-old man presenting with hematuria and petechiae was referred to our hospital; he was disoriented and febrile. Laboratory results revealed Coombs-negative hemolytic anemia, thrombocytopenia, and renal failure. Undetectable ADAMTS13 activity and presence of anti-ADAMTS13 antibodies (inhibitor) confirmed the diagnosis of aTTP. Despite performing plasma exchange and administering prednisolone and rituximab (375 mg/m 2 ), we were unable to restore his platelet counts to the normal level. Therefore, he was treated with cyclophosphamide (500 mg/bodyweight), vincristine (1.4 mg/m 2 ), bortezomib (1.3 mg/m 2 ), and cyclosporine (2.5 mg/kg). After the cyclosporine therapy, his platelet counts gradually normalized. Continuous cyclosporine maintenance therapy led to complete disappearance of the inhibitor. Therapeutic strategies for refractory aTTP have not yet been established. Further investigations are warranted to establish a therapeutic strategy for refractory aTTP.

The key clinical symptoms of thrombotic thrombocytopenic purpura (TTP) are severe thrombocytopenia, microangiopathic hemolytic anemia, and organ ischemia/infarction due to microthrombi. Hemolytic anemia in TTP is characterized by mechanical damage to red blood cells. TTP is caused by a severe deficiency of ADAMTS13 activity, which is caused by mutations in the ADAMTS13 gene (congenital TTP) or by autoantibodies affecting the function or clearance of ADAMTS13 (immune TTP). Patients with congenital TTP receive fresh frozen plasma (FFP) transfusion for the supplementation of ADAMTS13. Meanwhile, those with immune TTP receive plasma exchange therapy using FFP for the supplementation of ADAMTS13 and the removal of anti-ADAMTS13 autoantibodies. Corticosteroid therapy is concurrently administered to suppress autoantibody production. In terms of novel treatment, the use of rituximab, a humanized anti-CD20 monoclonal antibody, in patients with immune TTP was approved by the Japanese health insurance in 2020. Novel and promising drugs are currently developed. A first-in-human study of recombinant ADAMTS13 for congenital TTP was reported in 2017. Caplacizumab is a humanized nanobody that inhibits the interaction between von Willebrand factor and platelets. This drug can prevent early thrombus formation and organ damage in patients with immune TTP. Therefore, these novel drugs can improve mortality in patients with TTP.

A 51-year-old man with a past history of hypothyroidism suddenly became comatose after a few days of general malaise and headache. On admission to our hospital, his consciousness level was Japan Coma Scale III-200, but no focal neurological deficits were evident. Serum anti-thyroglobulin antibody was >4,000 IU/ml and anti-thyroid peroxidase antibody was 265 IU/ml. Well characterized neuronal antibodies were not fully examined in this case, but based on high titers of serum thyroid antibodies, methylprednisolone pulse therapy was started under diagnosis of suspected Hashimoto encephalopathy. Although methylprednisolone pulse therapy was effective, every time the dose of oral prednisolone was reduced, relapse attacks similar to the first episode occurred, a total of seven times. At each relapse, cerebrospinal fluid findings and MRI findings were normal. Plasmapheresis and azathioprine were added, until two years after onset, when further acute neurological attacks no longer occurred, but attention and memory impairments persisted. Relapse in Hashimoto encephalopathy is not rare; careful, long-term follow-up is needed.

A 75-year-old Japanese woman developed myelitis 3years prior to her admission. She was diagnosed with HTLV-1-related myelitis and had taken prednisolone. Her myelitis relapsed several times, and serum aquaporin-4 was positive in an ELISA. She developed a sudden headache, consciousness disturbance, dysarthria, and left limb paralysis, and was admitted to our hospital. The CSF analysis revealed pleocytosis dominated by morphonuclear cells and hypoglycorrhachia. Magnetic resonance imaging revealed abnormalities in the corpus callosum, bilateral thalamus, and corticospinal tracts. We initially suspected a relapse of neuromyelitis optica spectrum disorder (NMOSD) and infection. We treated the patient with methylprednisolone pulse and antibacterial and antiviral treatment, which were not effective. Plasmapheresis was performed five times, and she gradually improved. Immunosuppressive treatment was added. It is rare for NMOSD to cause hypoglycorrhachia. This case suggests that infection may trigger an autoimmune response in NMOSD. (Received February 13, 2018; Accepted July 12, 2018; Published October 1, 2018).

A 17-year-old male underwent a second bone marrow transplantation using a 6/8 allele HLA-matched unrelated donor. On day 100 after transplantation, steroid treatment for chronic graft-versus-host disease (GVHD) was started. On day 766, the patient experienced general fatigue, followed by double vision, ptosis, and dysphagia on day 810. Based on the positivity of the acetylcholine receptor antibody and a waning electromyography pattern, he was diagnosed with GVHD-related myasthenia gravis (MG). On day 861, we initiated plasmapheresis (PE), followed by the administration of intravenous immunoglobulin (IVIg) ; this treatment attenuated the bulbar symptoms of MG. Although the steroid treatment was continued, we restarted the administration of tacrolimus. On day 2,739 after transplantation, we stopped the steroid treatment, and the patient remained in remission for MG following the cessation of the steroid treatment on day 2,897. This case suggests that PE followed by IVIg could be an effective therapeutic alternative for MG associated with GVHD.

Sporadic late onset nemaline myopathy (SLONM) associated with monoclonal gammopathy of undetermined significance (MGUS) is an adult onset myopathy with poor clinical outcomes, requiring high-dose intravenous melphalan with autologous peripheral blood stem cell transplantation (HDM-SCT). Here we report two cases of SLONM associated with MGUS in which improvements were achieved only with immunotherapy. A 39-year-old woman had a two-year history of dropped head syndrome and progressive proximal weakness. On admission, she was able to walk with assistance and had lordosis with camptocormia. Combination therapy with plasmapheresis and intravenous immunoglobulin in addition to intravenous methylprednisolone pulse therapy ameliorated camptocormia and proximal weakness after one year. A 51-year-old man had difficulty in raising his arms and required walking assistance prior to visiting our hospital. He had proximal weakness and atrophy, winged scapulae, and gait disturbance. After combination immunotherapy, no progression was observed for 13 years. In both cases, patients did not desire to undergo HDM-SCT, and IgG kappa monoclonal protein was positive, of which the levels were normalized after immunotherapy. Combination immunotherapy can be a possible alternative to HDM-SCT in patients with SLONM. Both patients showed myogenic changes with abundant fibrillation, and needle EMG revealed positive sharp waves. Case 1 showed high signal intensities in MRI STIR/T2WI in muscles showing weakness. These findings are commonly observed in patients with myositis, suggesting that, without muscle biopsy, SLONM may be misdiagnosed as myositis. Muscle biopsy revealed scattered fibers with nemaline bodies without type 2B deficiency, which are important pathological findings that differentiate SLONM from congenital nemaline myopathy.

A 10-year-old boy developed bilateral optic neuritis and myelitis after a suspected viral infection and appendicitis. Magnetic resonance imaging (MRI) showed multiple lesions in both optic nerves, the optic chiasm, and the spinal cord. Several small lesions were also observed in the cerebellum and cerebral white matter. The serum tested negative for anti-aquaporin (AQP)-4 antibody and positive for anti-myelin oligodendrocyte glycoprotein (MOG) antibody. The diagnosis was neuromyelitis optica spectrum disorder (NMOSD). Two courses of high-dose methylprednisolone were administered; however, only a small improvement in his visual acuity was achieved. He underwent 3 courses of plasma exchange to achieve sufficient visual acuity. After the serum anti-MOG antibody titer decreased to the cut-off level, oral prednisolone and azathioprine administration were also stopped, 10 months after onset. Recently, NMO and NMOSD cases positive for anti-MOG antibodies have been reported, which showed clinical features different from those of NMO cases positive for anti-AQP4 antibody. Although most of the reported cases responded to steroid therapy, plasma exchange was required in our case. Further analysis on larger numbers of cases is needed to establish treatments for anti-MOG antibody-positive NMO and NMOSD.

We report a case of a 57-year-old woman with thymoma-associated generalized myasthenia gravis (MG) showing severe bulbar and respiratory symptoms, moderate weakness of the neck muscles, and mild weakness of extremity muscles. Corticosteroid treatment with various types of immunosuppressive agents, such as cyclosporine, tacrolimus, and azathioprine, did not improve her symptoms. Plasma exchange transiently improved her symptoms, and she was required to undergo plasmapheresis every 4 weeks. At first, cyclophosphamide pulse therapy was administered, which improved her symptoms transiently. Thereafter, rituximab (RTX) was administered. Six months after RTX administration, respiratory distress and dysphagia improved gradually, and reduction in the dosage of corticosteroids from 30 mg/day to 10 mg/day did not result in symptom deterioration. Therefore, the interval between successive plasmapheresis treatments was increased from 4 to 9 weeks 19 months after the first RTX administration. During a 26-month period from the first administration of RTX, the number of CD20+ B cells in peripheral blood decreased and remained at 0% to 26% of that before RTX treatment. The titer of anti-acetylcholine receptor antibodies did not change during the first course of treatment (0.6-0.9 nmol/l). The clinical symptom worsened with the increase of the number of CD20+ B cells in peripheral blood in the 27 month after 1st RTX administration. Therefore, RTX was administered a second time, after which the patient's clinical symptoms again improved gradually. The titer of anti-acetylcholine receptor antibodies came to be stable with 0.5-0.7 nmol and low level during the 2nd course. Corticosteroids could be discontinued in the 16th month. The findings suggest that RTX can be one of the choices for pharmacological therapy in patients with intractable MG accompanied by the presence of anti-acetylcholine receptor antibodies.

This review described current status and perspectives of treatment for immune-mediated neuropathies, such as Guillain-Barre syndrome, chronic inflammatory demyelinating polyneuropathy (CIDP), multifocal motor neuropathy, and demyelinating neuropathy with anti-MAG neuropathy. corticosteroids, immunoglobulin therapy, and plasmapheresis are conventional treatments for these neuropathies, but the responsiveness to the treatments significantly differ among the disorders. Promising new treatment options include anti-complement monoclonal antibody (Eculizumab, anti-C5) for Guillain-Barre syndrome, and rituximab (anti-CD20) for anti-MAG neuropathy. For CIDP, different treatments would be required according to the clinical subtypes; typical CIDP and asymmetric variabt). For multifocal neuropathy, maintainance treatment with immunoglobulin is necessary.

Myasthenia gravis (MG) was first described in 17(th) century. It was after 1960s, when it became clear that MG was an autoimmune disease targeting AChR. Recently, anti-MuSK and anti-Lrp4 antibodies were found as novel antibodies in MG. In 1980s, in addition to cholinesterase inhibitors, high-dose corticosteroid treatment was introduced. This dramatically reduced the mortality rate of MG, but now we recognized that side effects of steroid have influenced patients significantly, and that high dose of steroid correlate with poor QOL. Since we have more means to treat MG at present, and also in the future, we should shift to the strategy in which steroid dose is kept low.

A 71-year-old woman developed advanced thermal hypoalgesia, bathyesthesia, and significant sensory ataxia 1 year ago. She also had difficulty maintaining a sitting posture. Patchy and reduced thermal nociception corresponding to a dermatome was found in her four extremities and trunk. On the basis of several tests, she was diagnosed with ataxic sensory neuronopathy due to dorsal root ganglionitis associated with Sjögren's syndrome. Generally, dorsal root ganglionitis associated with Sjögren's syndrome is refractory. After treatment with simple plasmapheresis, she was able to maintain a sitting posture. Finally, her symptoms stabilized after the inclusion of oral D-penicillamine to her treatment regimen. Although the clinical course was observed for about one year, we report this case because of its valuable finding, i.e., her symptoms improved after simple plasmapheresis and oral administration of D-penicillamine.

CIDP is a motor and sensory neuropathy characterized by chronic, step-wised, or relapsing progression. Both cellular and humoral autoimmunity targeting the myelin sheath is assumed as the main mechanism of CIDP pathogenesis. While the AAN diagnostic criteria have been the main method in Japan, the EFNS/PNS criteria recently replaced them because of their good diagnostic sensitivity and clinical superiority. The first-line therapy for CIDP patients in Japan is intravenous immunoglobulin (IVIg), corticosteroids, and phasmapheresis, the same as in other countries. Regarding therapeutics, two major differences between Japan and other countries exist. Firstly, while half-dose IVIg (1 g/kg body weight) every three weeks was established as maintenance therapy as a result of the ICE study in 2008, full-dose IVIg (2 g/kg body weight over five days) once a month is still accepted in Japan for highly recurrent patients. Secondly, Japanese clinicians prefer immune adsorption plasmapheresis (IAPP) instead of plasma exchange (PE) among three types of plasmapheresis (IAPP, PE, and double-filtered plasmapheresis [DFPP]). These differences could be due to the characteristic and independent health insurance system in Japan. Using recent knowledge and diagnostic criteria, clinical trials have been based on these global platforms. Recently, efforts have been made to share these platforms with a worldwide vision.

Plasmapheresis (PP) and intravenous immunoglobulin (IVIG) are both effective for treatment of crisis and acute exacerbation of myasthenia gravis. The 1(st) clinical problem is that effect of both treatments usually lasts for only 2-3 weeks. Additional immunosuppressive treatments may be necessary for prevention of the relapse. The 2(nd) problem is adverse effects and complications associated with each treatment. Hypotension, including shock, thromboembolism, and opportunistic infections are major adverse events of PP. Awareness of these complications and careful practice should be solutions. IVIG complicates less adverse effects than PP. The cost of each treatment, which is expensive particularly in IVIG use, may become the 3(rd) problem. It should be important to clarify the appropriate number of PP and the dose of IVIG to improve myasthenic crisis.

Neuromyelitis optica (NMO), an inflammatory demyelinating disease of the central nervous system, is characterized by relapsing optic neuritis and transverse myelitis. The detection of pathogenic anti-aquaporin-4 (AQP4) antibody distinguishes NMO from other demyelinating disorders, such as multiple sclerosis. Although early administration of high-dose intravenous methyl-prednisolone may improve symptoms that occur during relapses, the application of plasmapheresis is often required for sufficient recovery from each attack. The management of relapses is done with early steroid treatment, typically 1g intravenous methyl-prednisolone for 3 to 5 days followed by oral prednisone. Relapses that do not respond to intravenous steroids could benefit from plasmapheresis. Treatments for the prevention that have been used to date for NMO have generally been immunosuppressive drugs rather than immunomodulatory agents that are commonly used for multiple sclerosis (MS). Although low dose oral prednisolone is reported to be effective for prevention in Japanese NMO, non-steroidal immuno-suppressive agents are recommended in other countries to be changed from prednisolone within six months to avoid the side effects of steroids.

Few studies have indicated the efficacy of plasmapheresis in children with multiple sclerosis (MS). We report a 10-year-old girl with MS who was successfully treated with plasmapheresis. She experienced the first episode (vomiting and unconsciousness) at the age of eight years. After two years and six months remission period, she had a relapse with left hemiplegia. Her symptoms did not respond to high-dose intravenous methylprednisolone or immunoglobulin therapies, and rapidly deteriorated. After bulbar palsy was observed, plasmapheresis (total : every two days, seven times) was initiated at the 17th day during the relapse. Neurological symptoms improved remarkably after the second trial of plasmapheresis. There were no complications associated with plasmapheresis. Plasmapheresis may be effective as an additional therapy for exacerbation of acute neurological symptoms in children with MS.

Neuromyelitis optica (NMO) is a unique inflammatory condition characterized by selective involvement of the optic nerves and spinal cord. The cardinal features of NMO and a tendency of recurrence led to the classification of NMO as a subtype of multiple sclerosis (MS); however, it can be distinguished from MS on the basis of clinicoradiological and serological findings. In particular, NMO is characterized by the presence of spinal cord lesions that are longer than the total length of 3 vertebral segments and presence of anti-aquaporin 4 antibodies. Secondary progression of this condition is usually not observed, and therapy for NMO patients is designed to prevent acute exacerbations and limit irreversible neurological disability. Intravenous administration of a high dose of methylprednisolone is a standard treatment for patients with acute exacerbations of this condition, and patients with refractory cases are often responsive to plasmapheresis. To reduce the frequency of relapses and severity, standard therapies for MS, such as interferon-beta therapy, are not effective; further, a long-term immunosuppressive therapy is required for NMO patients. Immunosuppressive therapies often involve oral administration of prednisolone with or without azathioprine; patients who are refractory to the oral therapy may be treated by parental administration of cyclophosphamide, mitoxantrone, or rituximab. At present, there is no cure for NMO; early and precise diagnosis is critical to initiate immunosuppressive therapy for prevention of relapse.

We report the case of a 31-year-old woman who presented with neuromyelitis optica (NMO) associated with Sjögren syndrome and distal renal tubular acidosis. She was hospitalized because of cervical transverse myelopathy and right optic neuritis. She had been clinically diagnosed with Sj6gren syndrome, with a high titer of anti-SS-A antibody (1:500) and anti-SS-B antibody (1:498). She also showed hypokalemia, metabolic acidosis, and nephrocalcinosis caused by distal renal tubular acidosis associated with Sjögren syndrome. T2-weighted magnetic resonance imaging (MRI) revealed long lesions extending from the medulla oblongata to the lower thoracic cord. In addition, gadolinium-enhanced MRI revealed a right optic nerve lesion in the optic canal. High titer of anti-aquaporin-4 (AQP4) antibody was detected in the patient's serum (1:131,072). A combination therapy comprising steroid pulse therapy and plasmapheresis improved her clinical symptoms, and the administration of oral prednisolone (20 mg/ day) was effective in preventing the recurrence of NMO. In patients with myelitis/transverse myelopathy associated with autoimmune disorders such as Sjögren syndrome, examining the titer values of anti-AQP4 antibody is indispensable in determining the appropriate therapy.

Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis (EBV-HLH) is more common in children, and is characterized by pancytopenia, liver dysfunction and coagulopathy caused by interactions between EBV-infected T cells and activated macrophages. We describe here five adults with EBV-HLH. The median age was 17 years (range 16 approximately 40). HLH developed in 4 patients within 2 months after the primary infection, and in the other one during the reactivation. All patients had a high EBV viral load in peripheral blood (2 x 10(2)-3 x 10(6) copies/ml) and monoclonal proliferation of EBV-infected T cells. All patients received immunosuppressive therapy with or without etoposide, and two patients required plasmapheresis due to the severity. Three patients are alive in complete remission (follow up periods; 13, 19, 30 months), while two patients became refractory to chemo-immunotherapy and died despite multidrug chemotherapy. EBV-HLH should be more widely recognized in adults in order to achieve early diagnosis and appropriate treatment.

Myasthenia gravis (MG) is an autoimmune disease characterized by muscle weakness and fatigability. Women with MG have increased risk of pregnancy-related complications and an adverse pregnancy outcome. Maternal changes in pregnancy can also affect MG. The course of the disease in pregnancy is unpredictable. Delivery via caesarean section is very stressful and may cause severe myasthenic crisis. Therefore, if caesarean section is selected, coordinated management by a gynecologist, a neurologist and an anesthesiologist is necessary. We describe a 30-year-old woman with MG diagnosed during pregnancy. She was hospitalized on 33rd gestational week and was planned for delivery via caesarian section at 37th gestational week. In addition to her usual medications, we performed plasmapheresis to improve her condition for the operation not with fresh frozen plasma but with albumin solution just before the operation. No obvious abnormality of coagulation system was observed, and combined spinal and epidural anesthesia was performed with no adverse outcome. We managed her perioperative period free from myasthenic crisis.

Acute poststreptococcal glomerulonephritis (APSGN) typically recovers within 2 weeks with conservative therapy, but severe cases are known to develop acute renal failure and or nephrotic syndrome. We experienced 3 adult cases of APSGN with acute renal failure. All 3 cases required hemodialysis, 2 cases received double filtration plasmapheresis, and 2 cases received steroid therapy. In all cases, renal biopsy specimens showed endocapillary proliferative glomerulonephritis. One case had 25% cellular crescents and the others showed wide subendothelial deposits. There were no tubulointerstitial lesions. These 3 cases of severe APSGN with acute renal failure showed the benefits of combination therapy, hemodialysis, double filtration plasmapheresis and steroid therapy. Further clinical study is required to determine which therapy, double filtration plasmapheresis or steroid therapy, is useful.

Anti-NMDAR encephalopathy is included in paraneoplastic limbic encephalopathy and show the good response to treatment compared to other paraneoplastic syndromes. Treatment of anti-NMDAR encephalopathy includes immunotherapy and/or tumor removal. About 65% of patients with anti-NMDAR encephalopathy had fully or near-full recovery. Immunotherapy is principally necessary and effective in patients with and without tumor. Corticosteroids and intravenous immunoglobulin are most frequently used. It is likely that patients who do not respond to one form of immunotherapy might respond to others regimens including plasmapheresis, cyclophosphamide, and rituximab. A tumor was found in 58% of patients with anti-NMDAR encephalopathy. Early removal of tumor should be considered based on following reasons. First, patients with ovarian teratoma showed higher mortality and higher titer of anti-NMDAR antibody compared with those without. Second, relapsing neurological symptoms occurred in 13% of patients, usually related to a delay in tumor diagnosis. Third, when a tumor was found and removed, recovery was faster and predictable. However, early removal of tumor cannot be conducted because of unstable conditions such as hypoventilation and dyskinesias. In supportive cares, severe central hypoventilation requires mechanical ventilation. The involuntary movements and facial dyskinesias are refractory to anti-epileptic drugs. In conclusion, search for and removal of an ovarian teratoma should be promptly considered after the diagnosis of anti-NMDAR encephalopathy.

Cold agglutinin (CA) reacts reversibly with red blood cells at a low temperature and may cause thromboembolism of various organs. Therefore, special consideration is required in patients with cold agglutinin disease (CAD) undergoing cardiovascular surgery requiring hypothermia. Case 1: A 71-year-old man with elevated CA was scheduled to undergo total aortic arch replacement. Preoperatively, the patient received double filtration plasmapheresis to reduce CAs. The operation was performed at a higher temperature than the patient's thermal amplitude (TA) of 30 degrees C. Case 2: A 72-year-old man with CAD underwent a coronary artery bypass grafting. The patient's TA was 32 degrees C. The operation was performed on the beating heart with normothermic cardiopulmonary bypass. We performed an agglutination test at the temperature of 24 degrees C using the blood sample from the cardiopulmonary bypass circuit and no signs of agglutination were found. In both cases, no symptom of microembolism due to cold agglutination was recognized. This may indicate the possibility that the clinical risk is smaller than the risk recognized in vitro analysis. However, no safety standards for perioperative management of patients with CA are clearly established. Generally, it is more important to figure out the TA and to prevent the low-temperature exposure below the TA. In cases of normothermic procedures, further consideration for cerebral and myocardial protection is important.

Based on previous randomized controlled-trials (RCTs), plasma exchange (PE) has been established as an effective treatment for Guillain-Barré syndrome (GBS). Double filtration plasmapheresis (DFPP) and immunoadsorption plasmapheresis (IAPP) may be effective for GBS, however their effectiveness have not been established because any RCTs have not been available so far. Intravenous immunoglobulin (IVIG) has also been established to be effective for GBS according to several RCTs, however complications have been more frequent in PE than IVIG. Therefore IVIg treatment should be considered as the first choice for GBS, and PE treatment remains as the second-line if IVIg treatment is contraindicated.

Although not common, thrombotic thrombocytopenic purpura (TTP) is one of the most serious complications in patients with systemic lupus erythematosus (SLE). This study aimed to characterize the association between SLE and TTP by examining clinical features and treatment outcomes. We evaluated eight patients diagnosed over two years in our hospital. The mean disease duration of SLE until TTP onset was 13.2 years. One patient had a simultaneous diagnosis of SLE and TTP. CNS lupus and lupus nephritis were involved in 6 patients, respectively. The mean value of the SLE disease activity index was 40.5. Five out of 7 patients who have been examined the von Willebrand factor cleaving protease showed moderately decreased activity. Seven out of the 8 patients were treated with plasmapheresis, and 7 received immunosuppressive therapy including cyclophosphamide and rituximab. Seven patients recovered, but one died from an exacerbation of the disease. These data indicated that plasmapheresis and immunosuppressive therapy improved prognosis of TTP associated with SLE.

A 65-year-old man was admitted due to rapidly progressing dyspnea experienced over a 3-day period. Chest radiography and computed tomography conducted upon admission showed diffuse bilateral interstitial infiltrate. Bronchoalveolar lavage fluid contained blood and siderophores, which suggested pulmonary alveolar hemorrhage. Laboratory data showed that the serum MPO-ANCA level was elevated, and so ANCA-associated pulmonary hemorrhage was diagnosed. Although aggressive immunosuppressive agents were administered, including steroids and cyclophosphamides, the patient's condition worsened. Plasmapheresis using fresh frozen plasma was performed on day 5, after which his symptoms improved dramatically. Plasmapheresis was done 6 times, and the pulmonary lesions resolved. The patient was discharged 6 months later. This case report suggests that plasmapheresis may be an effective treatment for ANCA-associated vasculitis with diffuse alveolar hemorrhage that is resistant to aggressive immunosuppressive therapy.

We report a patient with severe thrombotic thrombocytopenic purpura (TTP) refractory to plasmapheresis who was successfully treated with rituximab. A 57-year-old male patient was referred to our department for further differential diagnosis and treatment of anemia and severe thrombocytopenia. Progressive psychoneurotic symptoms, hemolytic anemia, thrombocytopenia, renal function insufficiency and fever led us to the diagnosis of TTP. ADAMTS13 activity was below 3% and an inhibitor for ADAMTS13 was detected. Treatment with plasmapheresis and high-dose steroid was initiated but without clinical benefit. Two weeks following the initiation of plasmapheresis, we decided to treat the patient with 7 cycles of rituximab. No severe rituximab-related adverse effects were observed. After treatment with rituximab, the disease remitted, and the ADAMTS13 activity level increased. The patient has remained in complete remission for more than 1 year. Our data suggest that rituximab may be the optimal immunosuppressive therapy for refractory thrombotic thrombocytopenic purpura caused by an anti-ADAMTS 13 inhibitor.

Antiphospholipid syndrome (APS) is well known as an autoimmune thrombotic syndrome with recurrent thromboses. In APS, thromboses occurs both artery and vein, and from large to micro vessels. In contrast, so called catastrophic antiphospholipid syndrome, CAPS, develops multiple thromboses at microvessels mainly within a few weeks and induces to poor prognosis. CAPS often occurs in patients with SLE or primary APS after a change of antithrombotic therapy, infection, and operation. Treatments for CAPS have not established although plasma exchange is carried out usually as well as intensive anticoagulation and immunosuppressive therapy. We treated with immunoadsorption plasmapheresis (IAPP) for 5 CAPS patients and they improved their clinical symptoms and ameliorated their titers of antiphospholipid antibodies. IAPP could be an useful treatment skill for CAPS and we have started prospective study.

We report an anti-GBM antibody-positive crescentic glomerulonephritis patient who benefitted from maintenance hemodialysis 4 months after the initial treatment, which included steroid pulse therapy and plasma exchange. A-29-year-old male was referred to our hospital because of high fever, abnormal urinary findings (leukocytes 3+, protein 2+, occult blood 3+) and a moderate degree of azotemia(S-Cr 2.9 mg/dl). C-reactive protein (CRP) was 18.9 mg/dl and antibiotics were administered intravenously for 7 days under the diagnosis of pyelonephritis. High fever persisted, however, and S-Cr increased to 9.2 mg/dl even though a sufficient volume of urine was maintained. Blood and urine cultures were negative for bacteria. A kidney biopsy was performed and cellular crescents were observed around the glomeruli. No abnormal finding was observed in the lung and the nasopharyngeal region. To treat the crescentic glomerulonephritis, steroid and cyclophosphamide were administered while hemodialysis was carried out simultaneously. Although P-ANCA and C-ANCA were negative, anti-GBM antibody was proven to be positive thereafter (169 U) and six sessions of plasmapheresis were additionally performed to remove the antibody. Two months after the last plasmapheresis, the reduced urine volume (300 ml/day) gradually returned to normal. Hemodialysis was terminated because the S-Cr concentration reached a plateau at 4 mg/dl. Repeated biopsy revealed marked glomerulosclerosis, hence hypertension treatment and a low protein diet were ordered. In conclusion, residual renal function might improve even after 4 months of hemodialysis in cases of intensively treated anti-GBM-positive crescentic glomerulonephritis, though consecutive renoprotective therapy is required.

A 48-year-old woman with systemic sclerosis (SSc) and rheumatoid arthritis was admitted to our hospital because of renal dysfunction. She had no hypertension at the time of admission and mild hypertension for only one and a half months until the time of admission. After admission, she received angiotensin-converting enzyme-inhibitor, but her renal dysfunction did not improve. She then had thrombotic microangiopathy with thrombocytopenia, and was treated with plasma exchange five times, but her renal dysfunction persisted. The renal biopsy specimens showed an arteriosclerotic lesion with intimal thickening and luminal narrowing and ischemic glomerular changes. These findings suggest that there is chronic vascular injury in a patient who has no hypertension with SSc and that once hypertension supervenes, whether severe or not, exacerbation of the vascular injury and renal dysfunction may occur.

In December 2000, health insurance in Japan was instituted for the use of intravenous immunoglobulin (IVIg) therapy for the acute phase of Guillain-Barré syndrome (GBS) that required aid to walk or worse. A nation-wide questionnaire survey was made to investigate the changes in treatment. In September 2002, a letter of inquiry was sent to experienced physicians in 620 teaching hospitals associated with the Societas Neurologica Japonica and 417 associated with the Societas Paediatrica Japonica. Totally, 356 neurologists (57%) and 223 pediatricians (53%) responded. After the introduction of IVIg health insurance coverage, more than 90% thought that GBS patients should be hospitalized and given treatment. The frequency of hospitals with an intensive care unit, however, was 70%. Before IVIg therapy's inclusion in health insurance coverage, many neurologists selected plasmapheresis (88%) rather than IVIg (4%) therapy, whereas pediatricians preferred IVIg (49%) to plasmapheresis (12%). After its inclusion, 75% of neurologists selected IVIg rather than plasmapheresis (21%), whereas pediatricians selected IVIg (86%) over plasmapheresis (5%). In March 2003, new payment system based on Diagnosis Procedure Combination was introduced into 82 large hospitals, and leads to difficulties to select IVIg in the hospitals. The payment system should be revised.

We report a 27-year-old man with Guillain-Barré syndrome (GBS) preceded by cytomegalovirus infection. He was admitted to our hospital because of distal dominant weakness and sensory disturbance 5 days after fever. Double filtration plasmapheresis (DFPP) was performed and clinical symptoms temporary but dramatically improved. However facial nerve palsy, difficulty in swallowing food, weakness, dysautonomia and respiratory failure rapidly progressed within 5 days after the onset. Repeated DFPP failed to improve his symptoms. Two months after the onset, he did not improve at all. On T1-weighted MRI, nerve roots were still enhanced with gadolinium, and CSF examination revealed 1,324 mg/dl of protein. These findings suggested us the existence of continuous inflammation on nerve roots. We gave steroid-pulse therapy. He dramatically improved after this treatment. We repeated steroid-pulse therapy for seven times. He was discharged without any major complication 6 months after the onset. Steroid-pulse therapy should be considered in GBS patients associated with CMV infection when other conventional treatments are ineffective.