The breakdown of the blood-brain barrier (BBB) is a key step in the pathogenesis of multiple sclerosis (MS). We previously identified the auto-antigen responsible for the BBB impairment in secondary progressive MS using 2D electrophoresis of hole cell-preparation of brain microvascular endothelial cells (HBMECs). However, this method required much work to select the targeted cell-surface antigens from huge number of protein-spots in all cell fractions. Our aim is to construct the new method to efficiently investigate for the targeted antigens from the membrane-protein fraction of HBMECs in relapsing-remitting MS (RRMS). Sera from the patient of RRMS (N=1) which can downregulate BBB function of HBMECs was selected. The membrane of HBMECs were biotinylated and its plasma membrane fraction was isolated by ultracentrifugation. The extracted membrane-protein were immunoprecipitated with IgG from the RRMS or normal subjects (N=4). After separating eluted proteins by SDS-PAGE, specific bands in the RRMS were determined by mass spectrometry. We identified the 21 membrane-proteins as targeted auto-antigens in the RRMS. One of them was known to be relevant to BBB function. In 10 RRMS patients, three patients had the auto-antibody against this molecule. We succeeded in construction of the method that allows us to efficiently investigate targeted antigens from plasma membrane fraction of HBMEC, using the biotinylation of HBMECs and the isolation of membrane fraction by ultracentrifugation. This identified antigen could be an immunological target molecule, contributing to the BBB breakdown in RRMS.

Background: Most cases of chronic inflammatory demyelinating polyneuropathy (CIDP) well respond to the immunotherapies as the first line therapy, but some cases are refractory or inadequate to the first therapy. Because the proportion of refractory cases in CIDP would change by a definition of refractory to the immunotherapies, the actual frequency of refractory cases remains unclear.

Background: Distal limb weakness of Guillain-Barré syndrome (DL-GBS) is a recently proposed reginal variant of GBS, which shows muscular weakness limitedly at distal limbs (wrists, hand, ankles, and toes) with preserved muscle power at proximal limbs (shoulders, elbows, hips, and/or knees) throughout the disease course.

Background: Eosinophilic granulomatosis with polyangiitis (EGPA) is a multisystemic disorder, defined pathologically as the combination of extravascular granulomas, small and medium-sized vessels vasculitis, and the eosinophilic infiltrates. As anti-neutrophil cytoplasmic antibody (ANCA) have been demonstrated in 30-40% EGPA patients with neuropathy, ANCA is considered as one of the main factors to cause peripheral neuropathy; namely, ANCA-associated vasculitis and subsequent acute ischemia in peripheral nerves. On the other hand, in ANCA-negative EGPA patients, the mechanisms of neuropathy and the histological finding are still unknown.

Background: It is said that dementia is increasing in Japan, but the proportion of dementia patients who actually visit hospitals is still small. Meanwhile, in hospitals having dementia specialized outpatient clinics, medical treatment is also carried out for early diagnosis and management of dementia in recent years, but the trend of consultation of patients with dementia is not clear.

Background: Although there has been a growing interest in etiological and phenotypic variation of autoimmune encephalitis (AE), information regarding its epidemiological background is limited.

Background: Non-motor symptoms in Parkinson's disease (PD) are considered as an important factor related to the quality of life in PD patients. However, treatment strategies for these symptoms have yet been established. Zonisamide was reported to improve motor functions of PD and have various effects on nervous systems. The present study investigated the efficacy of zonisamide in non-motor symptoms of PD. Methods: 20 patients with PD participated in this study and were treated with zonisamide (25 mg/day) for 12 weeks. When subjects entered in this study, written informed consent was acquired from each subject. General symptoms were evaluated using the Unified PD Rating Scale (UPDRS). Non-motor symptoms were measured by Non Motor Symptom Scale (NMSS), which consists of 9 subdomains. The study protocol got the approval of the Institutional Review Board. Results: Median UPDRS part III score significantly decreased from 25.5 points at baseline to 20.6 points at 12 weeks (p = 0.004). In addition, NMSS total score showed significant improvement from 55.9 +/- 51.6 to 44.3 +/- 50.4 (p = 0.044). Within each NMSS subdomain, significant amelioration was observed in mood/cognition (from 11.9 +/- 18.0 to 7.3 +/- 12.8, p = 0.020) and attention/memory (from 7.3 +/- 8.9 to 4.8 +/- 7.6, p = 0.021) domains. Conclusions: This study suggests that zonisamide improves non-motor symptoms, especially psychical and cognitive symptoms in PD patients.

We described a 58-year-old woman with Guillain-Barré syndrome, who initially showed rapid progression of brainstem infarction-like signs. She developed superficial sensory disturbance on the left side, dysarthria, and left-predominant limb weakness within a few hours. She showed bilateral extensor plantar responses and head CT scan detected no abnormality. It was difficult to be distinguished from brainstem infarction until symmetrical limb weakness and generalized areflexia appeared. Serum anti-GD1b IgG antibody with cross-reactivity with GM1b was detected. Cerebrospinal fluid examination revealed albuminocytologic dissociation on day 5. After 5 sessions of immunoadsorption therapy, her symptoms gradually lessened. Anti-GD1b antibody has been detected in patients with sensory ataxic neuropathy. Our patient, however, was characterized with early involvement of brainstem with ataxia of cerebellar type. Our case suggests that anti-GD1b antibody-associated neuropathy has a broad spectrum of clinical features, which are related to cross-reactivity of this antibody.

Objective: To examine the association between Miller Fisher syndrome (MFS) and antecedent Haemophilus influenzae infection. Background: Little is known about agents in prior respiratory tract infection of MFS, whereas antecedent upper respiratory symptoms are frequent. H. influenzae is a major pathogen that can cause human respiratory tract infection. Methods: The authors used ELISA to detect serum antibody against the bacterium in 70 consecutive patients with MFS and 110 with Guillain-Barre syndrome (GBS). Results: Serum anti-H. influenzae IgG and IgM antibody activities were significantly higher in the MFS group than in age- and sex-matched patients with other neurologic diseases (n = 62) and normal control subjects (n = 82). The GBS group showed no significant increase in any class of antibody activities compared with control groups. Serologic evidence of recent infection was found in five (7%) of the patients with MFS and two (2%) of 110 patients with GBS, all of whom had a history of antecedent respiratory tract infection. They frequently showed ophthalmoplegia, but other neurologic features were not remarkable. Serum anti-GQ1b IgG antibody that had cross-reactivity with GT1a ganglioside was detected in six of these seven patients. Thin-layer chromatography with immunostaining showed that serum IgG from H. influenzae-seropositive patients with high anti-GQ1b and anti-GT1a IgG antibody titers bound to the lipopolysaccharide fraction extracted from the type b H. influenzae serostrain. These bands were also stained by anti-GT1a monoclonal antibody (GMR11), indicating that the lipopolysaccharide bears the GT1a epitope. Conclusions: These findings point to H. influenzae being an agent associated with MFS. Epitopic overlap between H. influenzae and human nerve tissue may be involved in the development of MFS much as GBS is associated with Campylobacter jejuni enteritis.