Surgically Cured, Relapsed Pneumococcal Meningitis Due to Bone Defects, Non-invasively Identified by Three-dimensional Multi-detector Computed Tomography.

A 43-year-old Japanese man presented with a history of bacterial meningitis (BM). He was admitted to our department with a one-day history of headache and was diagnosed with relapse of BM based on the cerebrospinal fluid findings. The conventional imaging studies showed serial findings suggesting left otitis media, a temporal cephalocele, and meningitis. Three-dimensional multi-detector computed tomography (3D-MDCT) showed left petrous bone defects caused by the otitis media, and curative surgical treatment was performed. Skull bone structural abnormalities should be considered a cause of relapsed BM. 3D-MDCT was useful for revealing the causal minimal bone abnormality and performing pre-surgical mapping.

Open-label study to evaluate the pharmacodynamics, clinical efficacy, and safety of meropenem for adult bacterial meningitis in Japan.

The aim of this study was to assess the efficacy, safety, and concentration of meropenem in cerebrospinal fluid when meropenem (2 g every 8 h) was administered to Japanese adult patients with bacterial meningitis. Five Japanese patients (mean age 60.6 years [range 35-71]) were enrolled. Infection with Streptococcus pneumoniae (three patients), Streptococcus salivarius (one patient), and Staphylococcus aureus (one patient) was confirmed by cerebrospinal fluid culture. Meropenem (2 g every 8 h) was administered to all five patients. Treatment duration ranged from 14 to 28 days (mean 22.6 days). All the patients were successfully treated. The concentration of meropenem in cerebrospinal fluid ranged from 0.27 to 6.40 µg/ml up to 8.47 h and was over 1 µg/ml 3 h after starting meropenem infusion. In each patient, the present study confirmed for the first time that the concentration of meropenem in cerebrospinal fluid exceeded the minimal inhibitory concentration for these pathogens. Eleven clinical and laboratory adverse events considered to be related to meropenem were observed in all patients, but no serious adverse event and no discontinuance of treatment due to adverse events occurred. Thus meropenem appeared to be a well-tolerated and effective agent for Japanese adult patients with bacterial meningitis. 2 g every 8 h of meropenem was delivered to CSF and its concentration was exceed in MICs for the detected pathogens.

3-dimensional composite scaffolds consisting of apatite-PLGA-atelocollagen for bone tissue engineering.

We fabricated 3-dimensional scaffolds consisting of biodegradable poly(D, L-lactide-co-glycolic acid)(PLGA)(75/25) with hydroxyapatite particles containing atelocollagen (aAC). The aim of this study was to evaluate this new type of scaffold in regard to its basic properties and biocompatibility. Characterization of the obtained scaffolds was performed to know the porosity, shrinkage, diametral tensile strength, and biocompatibility. Composite scaffolds made of PLGA with hydroxyapatite particles containing atelocollagen (PL-aAC) showed a greater strength and stability than PLGA scaffolds. PL-aAC also exhibited superior performance in terms of cell attachment and proliferation as compared to PLGA, while histological findings showed that PL-aAC had an excellent response toward soft tissues. Our results strongly suggest that PL-aAC is more useful for cell transplantation as compared to PLGA for bone tissue engineering.

[Acute non-herpetic encephalitides].

"Acute non-herpetic encephalitis" was consisted of several non-herpetic encephalitides including "acute juvenile female non-herpetic encephalitis (AJFNHE)" and "non-herpetic limbic encephalitis(NHLE)". In 1997, we first reported five young adult female patients with acute non-herpetic encephalitis who presented with severe prolonged coma and status epilepticus, but achieved a good recovery. Following this report, the results of a clinical analysis on 89 serial patients with encephalitides indicated that such patients presented specific and different clinical features, including the frequent detection of anti-glutamate receptor (GluR) antibody as compared with other etiologies of encephalitis. Since all of their 11 patients were young adult women, we designated these patients as "acute juvenile female non-herpetic encephalitis (AJFNHE)". In 2007, Dalmau et al. reported anti-N-methyl-D-aspartate receptor(NMDAR) encephalitis associated with ovarian teratoma. We recently reported the results of a nationwide survey on AJFNHE in Japan. This result was indicated that AJFNHE and anti-NMDAR encephalitis were inferred to be almost identical condition. AJFNHE thus represented a clinical concept based on the specific clinical features, and anti-NMDAR encephalitis represented a clinical entity based on the neuro-oncological findings including the NMDAR NR1 and NR2 heteromer antibody.

[Case of Fisher syndrome with ocular flutter].

We report a case of Fisher syndrome accompanied by ocular flutter. A 19-year-old man presented with diplopia and vertigo, associated with preceding symptoms of common cold. Since symmetric weakness of abduction in both eyes, truncal ataxia, diminution of tendon reflexes, and gaze nystagmus were noted, he was diagnosed as having Fisher syndrome. Ocular flutter also was noticed during horizontal gaze. Serum anti-GQ1b antibody and anti-GM1 antibody were detected. He was followed without therapy and the symptoms resolved. The accompanying ocular flutter may suggest that a central nervous system disorder may also be present in Fisher syndrome.

Pathological study of pseudohypertrophy of the inferior olivary nucleus.

There have been only a few reports about the immunohistochemical study of pseudohypertrophy of the inferior olivary nucleus (PH-IO). We therefore performed the detailed immunohistochemical study of 10 PH-IOs in 8 patients to clarify the mechanism of neuronal degeneration and its related phenomenon of PH-IO. We used various antibodies to alphaB-crystallin (alphaBC), synaptophysin (SYP), microtubule-associated protein 2 (MAP2), Lys-Asp-Glu-Leu (KDEL) receptors, heat shock protein (HSP) 27 as well as SMI-31. We found alphaBC-positive neurons on the ipsilateral side of 10 PH-IOs. SMI-31-positive neurons were also observed in 6 PH-IOs. Confocal laser microscopy showed co-localization of alphaBC and SMI-31 in some neurons. However, there were no HSP27-positive neurons or astrocytes in any of the 10 PH-IOs. MAP2 immunostaining showed MAP2-positive hypertrophic thick neurites around hypertrophic neurons on the ipsilateral side of 7 PH-IOs and demonstrated "glomeruloid structures" in 3 PH-IOs. In addition, fine granular SYP-immunoreactivity was decreased in the neuropils on the ipsilateral side of all 10 PH-IOs. SYP-immunoreactive dots were scattered in the neuropils and on the neuronal cell bodies on the side of 7 PH-IOs, and the aggregation of SYP-immunoreactive dots scattered in the neuropils was shown in 3 PH-IOs. Double-immunostainings using anti-MAP2 and anti-SYP antibodies demonstrated frequent SYP-immunoreactive dots along the MAP2-positive hypertrophic thick neurites and their cell bodies. Periphery-stained KDEL-positive neurons were also found on the side of 7 PH-IOs. We showed that the change of the distribution of presynaptic terminals correlated well to the hypertrophic thick neurites in PH-IO. Our immuohistochemical stainings demonstrated various changes which occurred to the neurons in PH-IO, and their neurites and presynaptic terminals. We considered that alphaBC was expressed in the neurons in PH-IO, induced by cellular stress. Such a detailed immunohistochemical investigation has not been reported previously.

Hospital-based study of the prognostic factors in adult patients with acute community-acquired bacterial meningitis in Tokyo, Japan.

BACKGROUND: Prognostic factors related to community-acquired bacterial meningitis (BM) in adult patients have been evaluated using multivariate analysis in The Netherlands, where the rate of antibiotic resistance was low. However, an evaluation of these factors in countries with a high rate of antibiotic resistance has not yet been done. Thus, we studied the prognostic factors in adults with community-acquired BM in our hospitals, which are located in Tokyo, Japan, where the rate of antibiotic resistance is high. METHODS: We selected 71 consecutive adult patients with community-acquired BM in which the pathogens were identified and then classified the patients into two groups based on the Glasgow Outcome Scale: a favorable outcome group (n=48), and an unfavorable outcome group (n=23). Their clinical and laboratory variables were analyzed using single logistic regression analysis followed by multiple logistic regression analysis. RESULTS: The overall mortality rate was 23%. The rate of antibiotic resistance was 54.9%. The most common resistant bacteria were penicillin-resistant Streptococcus pneumoniae, followed by methicillin-resistant Staphylococcus aureus. The Glasgow Coma Scale score (GCS) at the initiation of antibiotic therapy and a low thrombocyte count were identified as significant unfavorable prognostic factors (GCS: p=0.020, odds ratio=0.528, 95%CI=0.309-0.902; thrombocyte count: p=0.037, odds ratio=0.802, 95%CI=0.652-0.987). The presence of antibiotic-resistant bacteria was not identified as a prognostic factor. CONCLUSION: Patients with a low GCS at the initiation of antibiotic therapy and low thrombocyte counts had unfavorable outcomes. With appropriate antibiotic administration, the antibiotic-resistant bacteria were not identified as an unfavorable prognostic factor, even in an area with a high rate of antibiotic resistance.

[Fisher syndrome with optic neuropathy].

UNLABELLED: Fisher syndrome with optic neuropathy has been rarely reported. We report a 78-year-old Frenchman with Fisher syndrome. The patient complained of dizziness and bilateral blurred vision. His corrected visual acuity was 0.03 in the right eye, and 0.02 in the left eye. Deep tendon reflexes were absent. A few days later, bilateral complete external ophthalmoplegia appeared. Both pupils were dilated and pupillary reflexes were absent. Serum anti-GQlb antibodies and anti-GT1a antibodies were detected. After intravenous immunoglobulin treatments, all neurological symptoms including optic neuropathy and external ophthalmoplegia disappered except for pupillary dilatation associated with light-near dissociation. Tonic pupil indicated disorder of the peripheral nervous system. CONCLUSION: Fisher syndrome may complicate optic neuropathy.

Ubiquitin-positive inclusions in ependymal cells.

Ubiquitin-positive inclusions (UbIs) have not been well studied in ependymal cells. Since we detected such UbIs in the central canals of the medulla and spinal cord while investigating UbIs in neurodegenerative diseases, we studied UbIs in the entire ependymal system of 42 patients with various neurological diseases and of 10 non-neurological controls. UbIs were located in the cytoplasm of the ependymal cells, and were round to oval in shape, measuring 4-11 microm in diameter. The UbIs were non-argyrophilic and undetectable by hematoxylin and eosin staining, but mildly reactive to periodic acid-Schiff staining with and without digestion. The UbIs were variably immunoreactive for anti-epithelial membrane antigen (EMA) antibody, but did not react with several other antibodies. The co-existence of ubiquitin and EMA was confirmed by confocal laser microscopy. Throughout the ependymal system, UbIs were variably found in ependymal cells as well as in subependymal cells. There was no significant difference in the overall incidence of either ependymal or subependymal UbIs between the patients with neurological diseases and controls. However, ependymal UbIs in the central canal were more frequent in the neurological disease patients than in controls, although there was no disease specificity. This is the first comprehensive report to show common occurrence of UbIs in the ependymal cells of adult human brains.

Neuronal expression of alphaB crystallin in cerebral infarction.

alphaB crystallin (alphaBC) is one of the heat shock proteins that are induced under stressful conditions. In normal brains, alphaBC is present in oligodendrocytes and astrocytes, but not in neurons. Neuronal alphaBC expression in the central nervous system under pathological conditions has been investigated in several previous studies, most of which dealt with various neurodegenerative diseases with and without ballooned neurons. Neuronal expression of alphaBC has seldom been studied in cerebral infarction (CI), and the frequency of alphaBC-positive neurons in the various stages of CI is unknown. To investigate this issue, we examined 48 autopsy brains of patients with CI, and found neuronal expression of alphaBC in 68.8% of the cases. We found three types of alphaBC-positive neurons: normal morphological, convex, and ballooned neurons. Although alphaBC-positive neurons were present in the every stage of CI, they were more frequent later than 10 days after the onset of CI, and the frequency of alphaBC-positive ballooned neurons was particularly increased in the later stages of CI. This may indicate that morphologically normal neurons gradually swelled up through convex neurons, finally forming ballooned neurons. Previous studies indicated that alphaBC might have a cytoprotective function as a molecular chaperone, and we speculate that alphaBC is expressed in neurons subjected to ischemic stress, and exerts a cytoprotective effect on the neurons.