Atsuro Chiba

IgG4 anti-neurofascin155 antibodies in chronic inflammatory demyelinating polyradiculoneuropathy: Clinical significance and diagnostic utility of a conventional assay.

We aimed to validate the diagnostic utility of enzyme-linked immunosorbent assay (ELISA) for the detection of anti-neurofascin (NF) 155 antibody in 191 patients with chronic inflammatory demyelinating polyneuropathy (CIDP). Human NF155-based ELISA clearly distinguished between anti-NF155 antibody-positive and -negative sera. Fifteen CIDP patients (8%) were IgG4 anti-human NF155 antibody-positive, which were confirmed by western blot, cell-based assay and immunohistochemical study. None of disease controls or healthy subjects had positive results. Clinical presentation of IgG4 anti-NF155 antibody-positive patients was consistent with those in previous reports. This ELISA combined with determination of the IgG4 subclass is useful in screening for anti-NF155 antibodies.

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.

Markers for Guillain-Barré syndrome with poor prognosis: a multi-center study

Guillain‐Barré syndrome (GBS) is an acute monophasic neuropathy. Prognostic tools include the modified Erasmus GBS outcome score (mEGOS), Erasmus GBS respiratory insufficiency score (EGRIS), and the increase in serum IgG levels (ΔIgG) 2 weeks after intravenous immunoglobulin (IVIg) treatment. Given that proportions of GBS subtypes differ between Western countries and Japan, the usefulness of these tools in Japan or other countries remains unknown. We enrolled 177 Japanese patients with GBS from 15 university hospitals and retrospectively obtained mEGOS and EGRIS for all and ΔIgG status for 79 of them. High mEGOS scores on admission or on day 7 were significantly associated with poorer outcomes (unable to walk independently at 6 months). High EGRIS scores (≥5 points) were associated with an increased risk for mechanical ventilation. Patients with ΔIgG <1,108 mg/dl had significantly poorer outcomes. We suggest that mEGOS, EGRIS, and ΔIgG in GBS are clinically relevant in Japan.

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.

O-2-31. The usefulness of electrophysiological examinations in the diagnosis of tarsal tunnel syndrome

TTS is usually diagnosed based on clinical symptoms and signs, and electrodiagnostic (EDx) tests, typically nerve conduction studies. We aimed to present a case series of TTS and investigate the diagnostic role of EDx. We searched our EMG database from 2008 to 2016 with the keyword of TTS, and retrospectively reviewed clinical and EMG records of extracted patients. The entry criteria were: (1) clinical diagnosis of TTS by the referring doctor, (2) numbness of sole and a positve Tinel’s sign at the ankle, and (3) both the tibial motor conduction study (MCS) and plantar sensory conduction study (SCS) were conducted. Enrolled were 12 patients (20–82 years, 9 men and 3 women). Some EDx tests were abnormal in 8 patients. Plantar SCS was abnormal on the affected side in 5 patients. In 2 of them, tibial MCS showed a bilobed compound muscle action potential (CMAP) indicating the isolated delay of the medial plantar nerve. One patient had abnormal F wave, and 2 patients was shown denervation potentials in the FHB muscle. TTS is in general difficult to confirm electrodiagnostically, although this study supported the role of EDx. Bilobed tibial CMAP may be a previously undescribed sign of TTS.

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 …

A new pitfall in a sensory conduction study of the lateral antebrachial cutaneous nerve: spread to the radial nerve.

Introduction: We describe a previously unreported pitfall, spread of the stimulus at the elbow to the radial nerve, in an antidromic sensory nerve conduction study of the lateral antebrachial cutaneous (LAC) nerve. Methods: Subjects consisted of 80 healthy volunteers, and both sides were examined for each subject. Besides routine recording of the LAC nerve, sensory nerve action potentials (SNAPs) of the radial nerve were recorded distally. Results: The spread phenomenon occurred in 73 of 160 arms (46%), and the SNAP amplitude increased due to contamination of the radial SNAP up to 6.7 times the genuine LAC SNAP. In 10 arms (6%), the spread started before the LAC SNAP was saturated, and the genuine LAC SNAP was unknown due to an anatomical variation in at least 1 arm. Conclusions: Without monitoring distal radial SNAPs, the spread phenomenon will remain unrecognized. This pitfall undermines the reliability of the test. Muscle Nerve 50:186–192, 2014

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.