[Cryptococcal Meningitis with Inadequate Response to Antifungal Therapy or Drug-Induced Side Effects That Make It Difficult to Continue Treatment: Eleven Clinical Issues in Medical Practice].

Cryptococcal meningoencephalitis is mainly caused by Cryptococcus neoformans and accounts for 90% of fungal meningitis cases in Japan. Cryptococcal meningoencephalitis is a rare disease, and similar to tuberculosis meningitis. It often exhibits subacute or chronic progression symptoms such as headache, fever, coma, personality changes, and memory disturbance. Cryptococcal meningoencephalitis often develops in immunosuppressed hosts, but can sometimes occur in healthy individuals, and the mortality rate is 10-25%, indicating a poor prognosis. For the treatment of cryptococcal meningoencephalitis, introduction therapy using a combination of liposomal amphotericin B and flucytosine is recommended. However, in practice, cryptococcal meningoencephalitis is refractory and often requires prolonged treatment; therefore, it is the most difficult to treat among the central nervous system infections. We discuss the following 11 issues: I. Sustainability of first-line treatments, II. Treatment options in case of decreased renal function, III. Association with increased intracranial pressure IV. Causes of visual impairment, V. Necessary steps when symptoms/laboratory findings worsen during antifungal treatment, VI. Cerebral infarction, VII. Difficulty in controlling underlying and comorbid diseases, VIII. Indications for lumbar and ventricular drainage (Ommaya reservoir placement), IX. Pros and cons of concomitant use of corticosteroids, X. Treatment evaluation index: usefulness of head MRI, and XI. Determining the end of treatment and the need for preventive medication.

Improving transport and optimizing deceleration of ion beams from electron cyclotron resonance multicharged ion sources.

Electron cyclotron resonance ion sources (ECRISs) are widely applied for ion beam applications, e.g., plasma processing, cancer therapy, and ion engine of an artificial satellite. In our ECRIS, we aim at producing and extracting various ion beams from this device, in particular, Xeq+ ion beams at low energy. In the aerospace engineering field, there are problems of accumulated damages on various component materials caused by low energy of Xe ions from the engine. There are not enough experimental sputtering data for satellite materials at the Xeq+ in the low energy region. Then, we are trying to investigate the sputtering yield experimentally by irradiating the low energy Xe ion beams. To perform this experiment, it is necessary to acquire a certain amount of beam current with low energy. Then, we generate the low energy ion beams by the following steps: First, the ion beams are extracted from the ECRIS at high voltage. Next, these are transported to an ion beam irradiation system (IBIS). Finally, the ion beams are decelerated by the deceleration voltage in the IBIS. We adjusted the beamline. We measure the characteristics of the transport efficiency and decelerated ion beam currents. In this paper, we describe the experimental setup using an existing ECRIS for decelerated heavy ion beams and the results of decelerated ion beam currents.

Improving multipole magnets and background vacuum conditions on electron cyclotron resonance ion sources.

Electron cyclotron resonance ion sources (ECRISs) are used in various fields such as accelerator physics, engineering, cancer therapy, and ion engines in the satellite. We are aiming to improve the production of multicharged ions efficiently at the point of view from the length of multipole magnets and vacuum conditions in the ECRIS. The diameter of the connection pipe between the main chamber and diffusion pump was made larger to improve vacuum conductance. Moreover, the length of multipole magnets with the direction along the geometrical axis in the ECRIS was extended. The effects of these improvements are investigated experimentally to measure the pressure in the vacuum chamber, beam intensity, charge state distributions of extracted ion beams, and plasma parameters. The purity of extracted ion beams and magnetic confinement have been enhanced. These results are expected to have positive effects on the production of various species and synthesized ion beams, e.g., production of iron endohedral fullerene in the future experiments in the ECRIS.

[Dementia in Patients with Central Nervous System Mycosis].

Central nervous system (CNS) mycosis is a potentially life-threatening but treatable neurological emergency. CNS mycoses progress slowly and are sometimes difficult to distinguish from dementia. Though most patients with CNS mycosis have an underlying disease, such as human immunodeficiency virus (HIV) infection, cancer, diabetes mellitus, and/or use of immunosuppressants, cryptococcosis can occur in non-immunosuppressed persons. One of the major difficulties in accurate diagnosis is to detect the pathogen in patients' cerebrospinal fluid (CSF) cultures. Thus, the clinical diagnosis is often made by combining circumstantial evidence, including mononuclear cell-dominant pleocytosis with low glucose and protein elevation in the CSF, as well as positive results from an antigen-based assay and a (1-3)-beta-D-glucan assay using plasma and/or CSF. Polymerase chain reaction (PCR)-based diagnostics, which are not performed as routine examinations and are mostly performed as part of academic research in Japan, are sensitive tools for the early diagnosis of CNS mycosis. Mognetic resonance imaging (MRI) is useful to assess the complications of fungal meningitis, such as abscess, infarction, and hydrocephalus. Clinicians should realize the advantages and disadvantages of these diagnostic tools. Early and accurate diagnosis, including identification of the particular fungal species, enables optimal antifungal treatment that produces good outcomes in patients with CNS mycosis.

Adult-onset Satoyoshi syndrome with prominent laterality of clinical features.

We herein report the case of a patient with adult-onset Satoyoshi syndrome. Alopecia was detected on the patient's head, left leg and abdomen, with pigmentation on the left thigh and abdomen. Painful muscle spasms were also noted in the abdomen and left upper and lower extremities, and a sensory disturbance was present in the left thigh. A skin biopsy of this field showed lymphocyte infiltration, and the patient was found to be positive for antinuclear antibodies and rheumatoid factor. These clinical findings were atypical, as they were lateralized. This case is the first report of Satoyoshi syndrome associated with a sensory disturbance. The patient's histological findings and positivity for autoantibodies indicated the presence of immunological abnormalities in this case of Satoyoshi syndrome.

Validation of a new mass screening tool for cognitive impairment: Cognitive Assessment for Dementia, iPad version.

BACKGROUND: We have developed a new screening test for dementia that runs on an iPad and can be used for mass screening, known as the Cognitive Assessment for Dementia, iPad version (CADi). The CADi consists of items involving immediate recognition memory for three words, semantic memory, categorization of six objects, subtraction, backward repetition of digits, cube rotation, pyramid rotation, trail making A, trail making B, and delayed recognition memory for three words. The present study examined the reliability and validity of the CADi. METHODS: CADi evaluations were conducted for patients with dementia, healthy subjects selected from a brain checkup system, and community-dwelling elderly people participating in health checkups. RESULTS: CADi scores were lower for dementia patients than for healthy elderly individuals and correlated significantly with Mini-Mental State Examination scores. Cronbach's alpha values for the CADi were acceptable (over 0.7), and test-retest reliability was confirmed via a significant correlation between scores separated by a one-year interval. CONCLUSION: These results suggest that the CADi is a useful tool for mass screening of dementia in Japanese populations.

Opsoclonus-myoclonus syndrome following influenza a infection.

A 60-year-old woman developed opsoclonus-myoclonus syndrome (OMS) a week after being diagnosed with influenza A infection by a rapid antigen test. She had no loss of consciousness. Opsoclonus, myoclonus, and truncal ataxia were noted. Two weeks after treatment with intravenous immunoglobulin and corticosteroids, her opsoclonus, myoclonus, and truncal ataxia disappeared. No malignant tumors were detected during the 3-year follow-up period. There has been no previous report of postinfectious OMS following confirmed influenza A infection. OMS without a loss of consciousness has been reported to be statistically less common in cases of non-paraneoplastic OMS. This finding was consistent with the present patient's clinical manifestations.

Nationwide survey of acute juvenile female non-herpetic encephalitis in Japan: relationship to anti-N-methyl-D-aspartate receptor encephalitis.

OBJECTIVE: To study the incidence and clinical features of acute juvenile female non-herpetic encephalitis (AJFNHE) in Japan. METHODS: A nationwide questionnaire on patients with severe non-herpetic encephalitis of unknown etiology with a prolonged clinical course or death was sent to the departments of Internal Medicine, Neurology, Pediatrics, and Emergency and Critical Care at all hospitals with 200 beds or more in Japan. RESULTS: The recovery rate was 25% (1,279 out of 5,030 departments) and 90 patients were enrolled in this study. The annual incidence was 0.33/10(6) population. 85% of patients were female. The means and standard deviations of age at onset and hospital stay were 26+/-10 years and 180+/-228 days. As first symptoms, fever and psychosis were presented in 90%. Among the neurological symptoms, disturbance of consciousness was presented in 92%, convulsions in 65%, and involuntary movements in 55%. Respiratory failure during hospitalization was observed in 71% and required care with mechanical ventilation. The detection rate of anti-GluR epsilon2 and/or delta1 antibodies was 67% of patients. Anti-N-methyl-D-aspartate receptor NR1/NR2 antibody was detected in all four examined patients with anti-GluR epsilon2 antibody, and also detected in both of the two examined patients without anti-GluR epsilon2 antibody. As for outcome, 46% returned to work and 37% returned home, but 7% died. Associated tumors were demonstrated in 39%. All reported patients had ovarian tumors, among which teratoma was the most frequent. CONCLUSION: A nationwide survey provided data for the annual incidence and clinical features of AJFNHE in Japan.

Prognostic value of cerebrospinal fluid cytokine changes in herpes simplex virus encephalitis.

A recent trial suggested that corticosteroid was beneficial in herpes simplex virus encephalitis (HSVE), but that precise role remains unclear. We assessed the differences of cerebrospinal fluid (CSF) cytokine changes between different outcomes and between patients with and without corticosteroid administration at the acute stage of HSVE. Interleukin (IL)-1beta, IL-2, IL-6, IL-10, interferon (IFN)-gamma, and tumor necrosis factor-alpha were measured in 56 serial CSFs taken from 20 adult HSVE patients. Their outcomes were poor in 7 and good in 13 patients, and corticosteroid was administered in 10. The differences in the initial and maximum cytokine values were assessed among the different outcomes. The decline rate of cytokine values between the initial and second CSF samples was also assessed between patients with and without corticosteroid. The initial IFN-gamma and maximum IL-6 with a poor outcome were higher than those with a good outcome (p=0.019 for IFN-gamma and p=0.013 for IL-6). The decline rate of IL-6 in patients with corticosteroid was higher than that without corticosteroid (p=0.034). The initial IFN-gamma and maximum IL-6 CSF values represented prognostic biomarkers in HSVE. One pharmacological mechanism related to corticosteroid in HSVE is apparently inhibition of pro-inflammatory cytokines such as IL-6.