Ayumi Uchibori

Autoantibodies in postinfectious acute cerebellar ataxia

The authors found serum immunoglobulin M (IgM) autoantibody in a patient with typical acute cerebellar ataxia (ACA) and identified the antigen molecule as triosephosphate isomerase (TPI). TPI antigenicity to the patient’s antibody was the highest in the cerebellar tissue. Eight of 23 patients with ACA had increased IgM anti-TPI antibody titers vs those of healthy controls. Preceding Epstein–Barr virus infection was confirmed serologically in all 8 patients. Anti-TPI antibody decreased with clinical improvement.

Anti-TIF1-γ antibody and cancer-associated myositis A clinicohistopathologic study

Objective:We aimed to analyze the clinical and histopathologic features of cancer-associated myositis (CAM) in relation to anti–transcriptional intermediary factor 1 &ggr; antibody (anti-TIF1-&ggr;-Ab), a marker of cancer association. Methods:We retrospectively studied 349 patients with idiopathic inflammatory myopathies (IIMs), including 284 patients with pretreatment biopsy samples available. For the classification of IIMs, the European Neuromuscular Center criteria were applied. Patients with CAM with (anti-TIF1-&ggr;-Ab[+] CAM) and without anti-TIF1-&ggr;-Ab (anti-TIF1-&ggr;-Ab[−] CAM) were compared with patients with IIM without cancers within and beyond 3 years of myositis diagnosis. Results:Cancer was detected in 75 patients, of whom 36 (48%) were positive for anti-TIF1-&ggr;-Ab. In anti-TIF1-&ggr;-Ab(+) patients with CAM, cancers were detected within 1 year of myositis diagnosis in 35 (97%) and before 1 year of myositis diagnosis in 1. All the anti-TIF1-&ggr;-Ab(+) patients with CAM satisfied the dermatomyositis (DM) criteria, including 2 possible DM sine dermatitis cases, and were characterized histologically by the presence of perifascicular atrophy, vacuolated fibers (VFs), and dense C5b-9 deposits on capillaries (dC5b-9). In contrast, 39 anti-TIF1-&ggr;-Ab(−) patients with CAM were classified into various subgroups, and characterized by a higher frequency of necrotizing autoimmune myopathy (NAM). Notably, all 7 patients with CAM classified into the NAM subgroup were anti-TIF1-&ggr;-Ab(−) and exhibited no dC5b-9 or VFs. Conclusions:CAM includes clinicohistopathologically heterogeneous disease entities. Among CAM entities, anti-TIF1-&ggr;-Ab(+) CAM has characteristically shown a close temporal association with cancer detection and the histopathologic findings of dC5b-9 and VFs, and CAM with NAM is a subset of anti-TIF1-&ggr;-Ab(−) CAM.

Association of Acute Cerebellar Ataxia and Human Papilloma Virus Vaccination: A Case Report

INTRODUCTION We report the case of a patient who developed symptoms of acute cerebellar ataxia (ACA) after administration of the human papilloma virus (HPV)-16/18 vaccine. PATIENT AND METHOD This patient developed symptoms of ACA, including nausea, vertigo, severe limb and truncal ataxia, and bilateral spontaneous continuous horizontal nystagmus with irregular rhythm, 12 days after administration of the HPV-16/18 AS04-adjuvanted cervical cancer vaccine. After this, the patient received methylprednisolone pulse and intravenous immunoglobulin (IVIG) therapies as well as immunoadsorption plasmapheresis. RESULTS Severe ACA symptoms did not improve after methylprednisolone pulse and IVIG therapies, but the patient recovered completely after immunoadsorption plasmapheresis. CONCLUSION This temporal association strongly suggests that ACA was induced by the vaccination.

Unilateral hypoglossal nerve palsy with asymmetric facial and limb paresis in axonal Guillain–Barré syndrome

We report a 45‐year‐old man with motor axonal Guillain–Barré syndrome who developed left facial nerve palsy, right hypoglossal nerve palsy, and predominantly left‐sided upper limb paresis and left lower limb paresis. Blood examination identified immunoglobulin G antibodies against gangliosides GD1a, GD1b and GQ1b, and GD1b/GD1a and GD1b/GT1b complexes. He was treated with intravenous immunoglobulin (400 mg/kg/day for 5 days) twice, and tongue deviation and facial palsy resolved in 3 months. Unilateral or asymmetric involvement of the cranial and limb nerves represent a variant form of axonal Guillain–Barré syndrome.

A Case of CV2/CRMP5-antibody-related Paraneoplastic Optic Neuropathy Associated with Small-cell Lung Cancer

A 61-year-old woman who had smoked for 41 years developed subacute dizziness, ataxic gait, opsoclonus, and right visual impairment. She had right optic disc swelling and optic nerve gadolinium enhancement on magnetic resonance imaging. She had small-cell lung cancer (SCLC), with CV2/collapsin response mediator protein (CRMP)5 and HuD antibodies in her serum and cerebrospinal fluid. She was diagnosed with paraneoplastic optic neuropathy (PON) accompanied by paraneoplastic opsoclonus-ataxia syndrome. Her symptoms improved after removing the SCLC. Classical PON is rare in Japan. We recommend assaying for CV2/CRMP5 antibodies and searching for cancer in elderly patients with subacute painless visual impairment.

Anti-ganglioside complex antibody profiles in a recurrent complicated case of GQ1b-seronegative miller fisher syndrome and Bickerstaff brainstem encephalitis: a case report

BackgroundGuillain-Barré syndrome (GBS), Miller Fisher syndrome (MFS) and Bickerstaff brainstem encephalitis (BBE) are a group of autoimmune neurological disorders (GBS spectrum disorder) that rarely recur. Recently, anti-ganglioside complex antibodies (GSC-Abs) were identified in patients with GBS spectrum disorder. However, there has been no case report describing GSC-Abs profiles in a recurrent case showing different phenotypes.Case presentationWe report the case of a 33-year-old male patient with GQ1b-seronegative BBE-GBS after two prior episodes of MFS-GBS. Our patient showed ophthalmoplegia, ataxia, areflexia and a weakness of the extremities (MFS and GBS symptoms) in all episodes. In the episode reported here, our patient showed disturbed consciousness and an extensor response to cutaneous plantar stimulation was observed (BBE symptoms), with severe disability and requirement for artificial respiration management. GSC-Abs detected in previous episodes were also detected in the subsequent episodes, while new GSC-Abs emerged in each episode. Interestingly, whereas antibodies to GA1/GQ1b and GA1/GT1a, which are commonly identified in patients with GBS, MFS or BBE, appeared in all episodes, antibodies to GD1a/GD1b and GD1b/GT1b, which are predominantly associated with severe disability and the requirement for artificial respiration management in GBS, emerged for the first time in this episode.ConclusionThis study reports novel phenomena about the GSC-Abs profiles and its relationship with clinical features in a case with recurrent GBS spectrum disorder, showing different phenotypes in different episodes. Further studies are required to reveal the significance of the GSC-Abs profiles in recurrent GBS spectrum disorder.

The correlation between the change of distal motor latency of the median nerve and the abundant A-waves in Guillain-Barré syndrome.

A-waves are intermediate components that are observed between the compound muscle action potential (CMAP) and the F-waves. We recently suggested that abundant A-waves in Guillain-Barre syndrome (GBS) can be a novel marker of demyelination because they were strongly correlated with the acute inflammatory demyelinating polyneuropathy (AIDP) subtype and the absence of anti-glycolipid antibodies.1 Hiraga et al 2 reported that patients with AIDP without anti-ganglioside antibodies showed progressive prolongation of the distal motor latency (DML) of the median nerve, whereas the DML of patients with AIDP with anti-ganglioside antibodies may initially be prolonged but rapidly return to normal, suggesting an essentially axonal pathology. These results imply the possibility that the time course of DML of the median nerve (median DML) can be used as another marker of demyelination. In this report, we reanalysed the data collected in our previous study1 and compared the A-waves with other parameters, using the time course of the median DML as a gold standard. The data of 30 patients with GBS (21 men and 9 women, 43.7±19.5 years old) were reanalysed. The abundant A-waves were defined as three or more identifiable peaks between the CMAP and F-waves, observed in the median or ulnar nerves at least once during weeks 3–6 from onset.1 Clinical features of patients with abundant A-waves were compared with those without. Patients were classified into two groups using three different criteria, which were already determined in the preceding study.1 The first criterion was the abundant A-waves, which were positive in 9 and negative in 21patients. The second was Hos criteria,3 applied …

Paraneoplastic neuromyelitis optica spectrum disorder manifesting as intractable nausea and acute cerebellar ataxia associated with lung adenocarcinoma

We report a 65‐year‐old woman with neuromyelitis optica spectrum disorder manifesting acute cerebellar ataxia, and intractable nausea and vomiting. She tested positive for anti‐aquaporin 4 antibodies and had a lung adenocarcinoma simultaneously. She underwent partial pulmonary resection, and tumor cells of the lung adenocarcinoma were stained with an anti‐aquaporin 4 antibody. By administering intravenous methyl prednisolone and plasma exchange, aquaporin 4 antibody titer was reduced, and neurological deficits and the lesion status on magnetic resonance imaging markedly improved. Paraneoplastic neuromyelitis optica spectrum disorder in conjunction with lung adenocarcinoma was a reasonable diagnosis.

Study on assay system for anti-synapsin 1a antibody

Glioblastoma multiforme (GBM) is the most common and aggressive primary brain tumor. GBM is characterized by cellular heterogeneity, rapid proliferation, angiogenesis and extensive invasion. Glioma tumor cells actively recruit to the tumor site microglia as well as peripheral macrophages, named Tumor Associate Macrophages (TAMs). TAMs have been shown to be deeply involved in tumor microenvironment by their ability to induce immunosuppression, angiogenesis and invasion. Macrophages that infiltrate cancer tissues can be classified inM1 (proinflammatory) and M2 (anti-inflammatory) according to their “activation” state. M1 macrophages produce type I proinflammatory cytokines, participate in antigen presentation and have an anti-tumorigenic role. Conversely, M2 macrophages produce type II cytokines, promote antiinflammatory responses and have pro-tumorigenic functions. Recent antitumor strategies are aiming to target TAMs with different approaches: inhibiting their recruitment, suppressing their survival, enhancing M1 like and blocking M2 activities. We focused our attention on M1 polarized macrophages and how they could influence glioma cells. We attempted to explore whether soluble factors secreted by M1 polarized microglia/macrophages could impact the cell fate of U251 glioma cells. Our preliminary experiments showed that M1 conditioned medium (M1CM) inhibits tumor cell proliferation aswell as promotes apoptosis. Extracellular vesicles have emerged as important mediators of intercellular communication in cancer. Among them, exosomes are defined as vesicles characterized by a size of 30–100 nm in diameter and microvesicles from 50 nm to 1000 nm, both recognized as important mediators of cell-to-cell communication. Currently studies in other type of cancers indicate that nanovesicles present in the CMplay a role in the modulation of tumor microenvironment. In line with these observations, we found that treatment of U251 cells with exosomes derived from M1 polarized microglia/macrophages decreases glioma cell proliferation. Interestingly, both M1 exosomes and microvesicles were more effective thanM1 total conditionedmedium.Wehypothesize that exosome re-polarization toward an M1 phenotype might oppose glioma progression. These findings shed new light on the complex communication networks in theGBMmicroenvironment and open new future therapeutic strategies.

A study on the mechanism of antigen–antibody reaction increased by ganglioside-complex in Guillain–Barré syndrome

Background & Objective: The mechanism of anti-ganglioside complex (GSC) antibody phenomenon in Guillain–Barre syndrome (GBS) is not revealed yet. In most case, one of the two gangliosides forming GSC is GM1, GD1b, or asialo-GM1 (GA1), which contains common neutral oligosaccharide structure, Gal(beta1-3)GalNAc, in non-reducing terminal, and patients shows clinical features of antibody against the other ganglioside. This suggests a possibility that the neutral oligosaccharide structure changes accessibility or affinity of the antibody to the pendant, not forming a novel conformational epitope. We studied the effect of the neutral oligosaccharide structure to the anti-GSC. Methods: Sera from patients with GBS or Fisher syndrome with antibodies against GSCs composed of GA1 and one of GD1a, GD1b, and GQ1b were studied on the effect of the replacement of GA1 in the GSCs with other neutral glycolipids or lipidwith partial common structure. Antibody titers were measured by enzyme-linked immunosorbent assay (ELISA). The neutral glycolipids and lipid examined were following: asialoGM2(GA2), globoside, trihexosylceramide, paragloboside, glucosaminyl lactosylceramide, lactosylceramide, glucosylceramide and ceramide. Results: Four of 11 GA1/GD1a antibody-positive cases and four of 11 GA1/ GD1b antibody-positive cases also showed an enhancement of the antibody reaction by mixing with other neutral glycolipids instead of GA1. In these cases, the degree of the enhancementwasweaker compared to mixing with GA1. Nine of 16 GA1/GQ1b antibody-positive cases, also showed an enhancement of the antibody reaction by mixing with other neutral glycolipids. In five of them, the degree of the enhancement was equal or stronger than in GA1/GQ1b complex. Twelve cases showed enhancement bymixingwith ceramide. In these cases, ELISAwith reduced amount of the single ganglioside, which had been mixed with ceramide, showed decrement of the titer in seven cases and increment in three. Conclusions: There would be non-conformational, i.e. structure-nondependent, mechanism in enhancement of antigen–antibody reaction by mixing two gangliosides, as well as structure-dependent one. In the cases who showed enhanced reaction by reducing the quantity of ganglioside antigen, it is possibly considered that accessibility of antibody to antigen has improved by reduction of antigen density. One of the gangliosides in GSC might act as spacer separating true antigenic epitope in some cases.