Developments of fast emittance monitors for ion sources at RCNP.

Recently, several developments of low energy beam transport line and its beam diagnostic systems have been performed to improve the injection efficiency of ion beam to azimuthally varying field cyclotron at Research Center for Nuclear Physics, Osaka University. One of those is the fast emittance monitor which can measure within several seconds for the efficient beam development and a Pepper-Pot Emittance Monitor (PPEM) has been developed. The PPEM consists of pepper-pot mask, multichannel plate, fluorescent screen, mirror, and CCD camera. The CCD image is taken via IEEE1394b to a personal computer and analyzed immediately and frequently, and then real time measurement with about 2 Hz has been achieved.

Studies of extraction and transport system for highly charged ion beam of 18 GHz superconducting electron cyclotron resonance ion source at Research Center for Nuclear Physics.

An 18 GHz superconducting electron cyclotron resonance ion source is installed to increase beam currents and to extend the variety of ions especially for highly charged heavy ions which can be accelerated by cyclotrons of Research Center for Nuclear Physics (RCNP), Osaka University. The beam production developments of several ions from B to Xe have been already done [T. Yorita, K. Hatanaka, M. Fukuda, M. Kibayashi, S. Morinobu, H.Okamura, and A. Tamii, Rev. Sci. Instrum. 79, 02A311 (2008) and T. Yorita, K. Hatanaka, M. Fukuda, M. Kibayashi, S. Morinobu, H.Okamura, and A. Tamii, Rev. Sci. Instrum. 81, 02A332 (2010)] and the further studies for those beam extraction and its transport have been done in order to increase the beam current more. The plasma electrode, extraction electrode, and einzel lens are modified. Especially extraction electrode can be applied minus voltage for the beam extraction and it works well to improve the extracted beam current. The extraction voltage dependences of transmission and emittance also have been studied for beam current improvement which is injected into azimuthally varying field cyclotron at RCNP.

GM1/GalNAc-GD1a complex: a target for pure motor Guillain-Barre syndrome.

BACKGROUND: GM1 and GalNAc-GD1a are located on the axolemma of the motor nerves and are believed to be the antigens associated with pure motor Guillain-Barré syndrome (GBS). Furthermore, GM1 and GalNAc-GD1a may exist nearby and colocalize on the axolemma. Ganglioside complex (GSC) antigens associated with GM1 or GalNAc-GD1a can be target antigens in pure motor GBS. We investigated GBS sera for antibodies to a GSC consisting of GM1 and GalNAc-GD1a (GM1/GalNAc-GD1a) and analyzed the clinical and electrophysiologic findings of patients with antibodies to GM1/GalNAc-GD1a. METHODS: Sera from 224 patients with GBS were surveyed for antibodies to GSCs consisting of two of nine gangliosides (GM1, GM2, GM3, GD1a, GD3, GT1a, GT1b, GQ1b, and GalNAc-GD1a). We analyzed the clinical and electrophysiologic features of patients with IgG antibodies to the GM1/GalNAc-GD1a complex. RESULTS: Ten patients with GBS had IgG antibodies to the GM1/GalNAc-GD1a complex. The clinical findings of the 10 patients with GBS were characterized by preserved sensory system and infrequent cranial nerve deficits. According to the criteria established by Hadden et al., electrodiagnostic studies showed a demyelinating pattern in four patients and axonal neuropathy pattern in two. Early motor conduction block at intermediate nerve segments was found in five patients. CONCLUSIONS: GM1 and GalNAc-GD1a may form a complex in the axolemma at nodes of Ranvier or paranodes of the motor nerves, and may be a target antigen in pure motor Guillain-Barré syndrome, especially in the form of acute motor conduction block neuropathy.

GD1b-specific antibody induces ataxia in Guillain-Barre syndrome.

BACKGROUND: Rabbit ataxic neuropathy and several case reports have suggested a close association of IgG anti-GD1b antibodies with ataxia in Guillain-Barré syndrome (GBS). However, about half of the patients with GBS having IgG anti-GD1b antibodies with no reactivities against other gangliosides (GD1b-mono IgG) do not exhibit ataxia. Antibodies specific to ganglioside complexes (GSCs) containing GD1b have been found in sera from some patients with GBS. OBJECTIVE: To investigate whether the reactivities of anti-GD1b IgG to such complexes are different between ataxic and nonataxic patients. METHODS: The authors examined sera from 17 patients with GBS (9 with ataxia and 8 without ataxia) who had GD1b-mono IgG, with the use of an ELISA in which wells were coated with a mixture of GD1b and each of nine gangliosides (GM1, GM2, GM3, GD1a, GD3, GT1a, GT1b, GQ1b, and GalNAc-GD1a). The binding activities of the anti-GD1b IgG antibodies against such mixture antigens were compared between ataxic and nonataxic patients. RESULTS: The reactivities to antigens, such as GD1b combined with GD1a, GT1b, GQ1b, and GalNAc-GD1a, were significantly reduced in ataxic compared with nonataxic patients. Sera from all nonataxic patients had antibody activities to GSCs not containing GD1b. CONCLUSIONS: The addition of another ganglioside may cause conformational change of GD1b. Given the inhibition of the binding ability of the anti-GD1b IgG antibodies by such a conformational change, the anti-GD1b IgG antibodies in ataxic patients may interact closely with GD1b. IgG antibodies highly specific for GD1b may induce ataxia in Guillain-Barré syndrome.

Ganglioside complexes containing GQ1b as targets in Miller Fisher and Guillain-Barre syndromes.

BACKGROUND: Serum antibodies to GQ1b are associated with Miller Fisher syndrome (MFS) and Guillain-Barré syndrome (GBS) with ophthalmoplegia. Antibodies to ganglioside complexes (GSCs) have not yet been examined in a large population of patients with MFS or GBS. This study aimed to determine the clinical significance of antibodies to GSCs in MFS and GBS. METHODS: The study investigated serum anti-GSC antibodies and the clinical features in 64 MFS patients, 53 GBS patients with ophthalmoplegia (GBS-OP(+)) and 53 GBS patients without ophthalmoplegia (GBS-OP(-)). RESULTS: Thirty patients with MFS (47%), 25 with GBS-OP(+) (47%) and none with GBS-OP(-) had antibodies to GSCs containing GQ1b or GT1a. Patients with MFS and GBS-OP(+) were subdivided according to the antibody reactivities; patients with antibodies specific to GQ1b and/or GT1a (without anti-GSCs antibodies) were placed in Group 1, those with antibodies against GSCs with a total of two sialic acids in the terminal residues, such as GQ1b/GM1, were placed in Group 2, and those with antibodies against GSCs with a total of three sialic acids in the terminal residue, such as GQ1b/GD1a, were placed in Group 3. In MFS, sensory disturbances were infrequent in Group 2 compared with the other groups (p<0.0001). Antibodies specific to GQ1b were observed more often in MFS than in GBS-OP(+) (p = 0.0002). CONCLUSIONS: IgG antibodies to GSCs containing GQ1b or GT1a were closely associated with the development of ophthalmoplegia in GBS, as well as MFS. Both GQ1b and clustered epitopes of GSCs containing GQ1b or GT1a may be prime target antigens for MFS and GBS-OP(+).

Asymptomatic self-limiting diffuse white matter lesions in subacute to chronic stage of herpes simplex encephalitis.

This study evaluated white matter changes in the subacute and chronic stages of herpes simplex encephalitis (HSE). Subjects comprised 15 patients with HSE. All patients were examined using MRI at onset, and then at seven to ten days, three to five weeks and two to three months after onset. In addition, the six patients who displayed white matter signal abnormalities were examined at six months and

Anti-ganglioside complex antibodies associated with severe disability in GBS.

Ganglioside complexes (GSCs) are known as target antigens in Guillain-Barré syndrome (GBS). To elucidate the clinical importance of the anti-GSC antibodies in GBS, we investigated serum antibodies to GSCs containing two of the gangliosides, GM1, GD1a, GD1b and GT1b, and analyzed clinical features of anti-GSC-positive GBS patients. Thirty-nine (17%) of 234 GBS patients had IgG anti-GSC antibodies. Anti-GSC-positive GBS had antecedent gastrointestinal infection and lower cranial nerve deficits more frequently than control GBS. The presence of antibody specificity to GD1a/GD1b and/or GD1b/GT1b was significantly associated with severe disability and a requirement for mechanical ventilation.

Disinhibition of somatosensory evoked potential recovery in alcoholics.

The pathogenesis of cognitive impairment in alcoholics remains unclear. Previous studies suggested that diffuse white matter atrophy is associated with cognitive impairment in alcoholics. To elucidate this issue, the present study evaluated alcoholics with cognitive impairment using the somatosensory evoked potential (SEP) recovery method, which is suitable for detecting subtle dysfunction at the cortical level. Subjects comprised 12 alcoholics with mild cognitive impairment [Mild group: Mini Mental State Examination Score (MMSE), > or =24; mean, 27.9 +/- 1.6], 12 alcoholics with moderate to severe cognitive impairment (Moderate group: MMSE score, < 24; mean, 21.0 +/- 2.5) and 12 normal subjects (Control group). SEP was recorded from the hand sensory area contralateral to the median nerve stimulated at the wrist. Single-pulse or paired-pulse stimuli at various interstimulus intervals (10-300 ms) were administered. Recovery functions of N9 (a peripheral nerve component), N20, N20-P25 and P25-N33 (cortical components) were studied. N20 recovery curves of both alcoholic groups were less suppressive than those of Controls, and P25-N33 recovery curves of the Moderate group were more excitatory than those of the Mild or Control groups. A disinhibited recovery pattern of N20 indicates subcortical dysfunction, and a disinhibited pattern of P25-N33 would be induced by cortical dysfunction. Therefore, subcortical dysfunction indicated by an abnormal N20 recovery pattern may contribute to the early cognitive impairment of alcoholics, whilst the cortical dysfunction indicated by an abnormal P25-N33 recovery pattern may contribute to the later cognitive impairment of alcoholics.

Anti-ganglioside complex antibodies in Miller Fisher syndrome.

BACKGROUND: Some ganglioside complexes (GSCs) are target antigens for serum antibodies in patients with Guillain-Barré syndrome (GBS). Anti-GSC antibodies may be associated with particular clinical features of GBS. OBJECTIVE: To investigate antibodies to GSCs in the sera of patients with Miller Fisher syndrome (MFS) characterised by elevation of the IgG anti-GQ1b antibody. RESULTS: In all, 7 of 12 (58%) consecutive patients with MFS were found to have IgG antibodies to GSCs containing GQ1b, of whom 5 had IgG antibodies to GQ1b-GM1 complex (GQ1b/GM1) and 2 had antibodies to GQ1b/GD1a; 4 of 5 patients without sensory symptoms had anti-GQ1b/GM1 antibodies. CONCLUSIONS: At least three different specificities in MFS-associated antibodies, GQ1b-specific, anti-GQ1b/GM1-positive and anti-GQ1b/GD1a-positive, were observed. In patients with MFS not only GQ1b itself but also clustered epitopes of GSCs, including GQ1b, may be considered to be prime target antigens for serum antibodies. A tendency to escape sensory disturbances is shown by anti-GQ1b/GM1-positive MFS.

Cognitive impairment and diffuse white matter atrophy in alcoholics.

OBJECTIVE: Diffuse brain white matter atrophy is often seen in chronic alcoholics, but its relation with cognitive impairment remains to be solved. In order to address this issue, in alcoholics with cognitive impairment at different levels, we studied relations of the central sensory conduction time (CSCT) or brain magnetic resonance imaging (MRI) findings with the cognitive function. METHODS: Subjects were 35 alcoholics with mild cognitive impairment (mini-mental state examination score, MMSE, >/=24; mean+/-SD, 27.7+/-1.9), 12 with moderate to severe cognitive impairment (MMSE<24; 20.3+/-2.7), 15 with Alzheimer's disease (AD) (MMSE, 18.9+/-4.3) (disease control) and 20 healthy volunteers (MMSE, 28.5+/-1.6) (normal control). Median nerve SEPs were recorded in the all subjects, and the latencies and amplitudes of their N9, N11, P13/14, N20 and P25 components were measured. The ventriculocranial ratio (VCR) and the width of cortical sulci were measured on MRIs. These physiological parameters and MRI findings were compared between the 4 groups of the subject, and correlations between those all features were also analyzed. RESULTS: CSCT and VCR were significantly greater in alcoholics with moderate to severe cognitive impairment than those in the other 3 groups. Pearson's product-moment correlation analyses of the alcoholics disclosed that both the CSCT and VCR had significant negative correlations with the MMSE score. Moreover, the CSCT and VCR were positively correlated. CONCLUSIONS: Both physiological and morphological estimates of the white matter function (CSCT and VCR) had a significant correlation with the cognitive dysfunction. SIGNIFICANCE: The diffuse white matter atrophy may be one of the factors causing cognitive impairment in chronic alcoholics.

Intraspinal sarcoidosis: clinical features, MR imaging and electrophysiological study.

We presented the case of a 58-year-old woman with spinal sarcoidosis at the C4-C6 level. The lesion itself as visualized with magnetic resonance imaging, and its neurological findings responded favorably to treatment with prednisolone. Comparison of pre- and post-treatment values for somatosensory evoked potential (SEP) and central motor conduction time (CMCT) also showed improvement. Analysis of SEP and CMCT can be a useful tool for following up spinal sarcoidosis.

Anti-GQ1b antibody as a factor predictive of mechanical ventilation in Guillain-Barré syndrome.

Compared with 87 unventilated patients with Guillain-Barré syndrome (GBS), 44 ventilated patients with GBS more frequently had multiple cranial nerve involvement (91 vs 50%; p < 0.001) and IgG anti-GQ1b antibody (27 vs 8%; p = 0.006). In GBS patients without ophthalmoparesis, the presence of IgG anti-GQ1b antibody was associated with respiratory failure (12 [3/25] vs 0% [0/67]; p = 0.04). The presence of the antibody may be a factor predictive of respiratory failure in GBS.

Seasonal variation of multiple sclerosis exacerbations in Japan.

Several reports have described the seasonal variation of multiple sclerosis (MS) attacks in the European countries and in the US. Some have insisted that attacks occurred more frequently in winter or spring. We investigated the possibility of a seasonal variation in the frequency of MS attacks among patients in Japan. A total of 172 MS exacerbations in 34 MS patients were analyzed retrospectively. Attacks were divided into two groups: opticospinal type and brain type. The 12 months of the year were assigned to 6 groups based on average monthly temperature. Of the 172 MS exacerbations, 123 were opticospinal type and 49 were brain type of attacks. The total number of attacks was significantly more frequent in the warmest (July and August) and coldest (January and February) months. The heat of summer in warmer, low latitude areas may be a risk factor for MS attacks.

GalNAc-GD1a in human peripheral nerve: target sites of anti-ganglioside antibody.

BACKGROUND: The authors previously reported that immunoglobulin G (IgG) antibody to the ganglioside N-acetylgalactosaminyl GD1a (GalNAc-GD1a) is associated with the pure motor variant of Guillain-Barré syndrome (GBS). Elucidation of the localization of GalNAc-GD1a in human peripheral nerve tissue may lead to understanding of the pathogenetic role of anti-GalNAc-GD1a antibody in GBS. METHODS: IgG anti-GalNAc-GD1a-monospecific antibody was purified from anti-GalNAc-GD1a antibody-positive rabbit sera through an affinity column. Anti-neurofilament-200 monoclonal and anti-HNK-1 monoclonal antibodies were used as the markers for axon and myelin. Immunohistochemical study using double fluorescence labeling technique was conducted in human ventral roots (VR), dorsal roots (DR), intramuscular nerves, and sural nerves. Human teased ventral fibers also were studied. RESULTS: Anti-GalNAc-GD1a antibody immunostained an inner part of compact myelin and additionally a periaxonal-axolemma-related portion in the VR, small-diameter DR fibers, and IM nerves. In sural nerves, small fibers were selectively stained. In VR, the staining was localized in the paranodal region. CONCLUSION: Anti-GalNAc-GD1a antibodies in patients' sera may bind to those regions in the VR and IM nerves where GalNAc-GD1a is localized, and may function in the pathogenesis of pure motor type GBS. Further investigation is needed to explain the discrepancy between the immunolocalization of GalNAc-GD1a in sensory nerves and the absence of sensory disturbance in patients with GBS with IgG anti-GalNAc-GD1a antibodies.

Dysferlin mutations in Japanese Miyoshi myopathy: relationship to phenotype.

OBJECTIVE: To study dysferlin gene mutations and genotype-phenotype correlations in Japanese patients with Miyoshi myopathy (MM). BACKGROUND: MM is an autosomal recessive distal muscular dystrophy that arises from mutations in the dysferlin gene. This gene is also mutated in families with limb girdle muscular dystrophy 2B. METHODS: The authors examined 25 Japanese patients with MM. Genomic DNA was extracted from the peripheral lymphocytes of the patients. The PCR products of each of 55 exons were screened by single strand conformation polymorphism or direct sequencing from the PCR fragments. RESULTS: The authors identified 16 different mutations in 20 patients with MM; 10 were novel. Mutations in Japanese patients are distributed along the entire length of the gene. CONCLUSIONS: Four mutations (C1939G, G3370T, 3746delG, and 4870delT) are relatively more prevalent in this population, accounting for 60% of the mutations in this study. This study revealed that the G3370T mutation was associated with milder forms of MM and the G3510A mutation was associated with a more severe form.

Primary Sjögren's syndrome initially manifested by optic neuritis: MRI findings.

We herein describe the MRI findings in a patient clinically diagnosed with primary Sjögren's syndrome (SjS) initially manifested by retrobulbar optic neuritis. A 63-year-old woman suddenly had left ocular pain and progressive visual disturbance. MR T2-weighted images revealed hyperintensity in the left optic nerve, with swelling. Contrast-enhanced T1-weighted images showed no abnormal enhancement. Follow-up MRI 6 months after admission revealed no significant changes in the affected optic nerve. To our knowledge, optic neuritis as a complication of SjS has been reported in ten patients [1, 2, 3, 4, 5, 6] and MRI findings in only one of them [6]. We thought MR images were useful for visualizing optic nerve involvement in SjS and observing its course.

Hemophagocytic syndrome and adult Still's disease associated with meningoencephalitis and unconsciousness.

We describe a 19-year-old woman with hemophagocytic syndrome and adult Still's disease who showed rare features of central neurological involvement, including cerebellar symptoms and the sudden onset of unconsciousness with pleocytosis in the cerebrospinal fluid during the early course of the illness. As this patient's serum showed a high level of interferon-gamma and soluble interleukin 2 receptor, this might play a pathologic role in the development of central nervous system symptoms. Intensive treatment consisting of methylprednisolone pulse therapy followed by the oral administration of methylprednisolone and cyclosporine, as well as plasma exchange, was found to achieve good results.