External carotid artery aneurysm developing after embolization of a ruptured posterior inferior cerebellar artery aneurysm in a patient with cervicocephalic fibromuscular dysplasia--case report

A 30-year-old man presented with an aneurysm of the left posterior inferior cerebellar artery manifesting as subarachnoid hemorrhage and cerebellar infarction. Angiography demonstrated string-of-beads sign typical of fibromuscular dysplasia (FMD) in the extracranial carotid and vertebral arteries. The aneurysm and the parent artery were successfully embolized with Guglielmi detachable coils. Severe vasospasm developed 1 week after admission, and was treated several times by selective injection of vasodilator. A new aneurysm of the left external carotid artery became evident 1 month later, whereas only slight dilation had previously been apparent. This angiographic sequence demonstrated a new arterial dissection. Despite the possibility of damage to the artery during multiple catheterizations, arterial wall changes caused by FMD appear to have been primarily responsible. This case emphasizes the need for particular care in performing vascular interventional procedures in the presence of FMD.     

Molecular pathophysiology of schizophrenia and preventive strategy in pubertal period

A novel frameshift mutation in glyoxalase 1 (GLO1) gene was detected in a patient with schizophrenia of a pedigree with multiple affected individuals. The patient carrying the mutation showed decreased enzymatic activity by 50%, 3.7 times high level of advanced glycation end products (AGEs) that is substrate of GLO1 and 20% of serum vitamin B6 compared to controls. Case-control study of GLO1 gene suggested that Ala allele of Glu111Ala was associated with schizophrenia. In vitro study using COS-7 cells transfected with cDNA of GLO1 yielded that enzymatic activity is lower in GLO1 with Ala111 than that of Glu111. The homozygotes of Ala111 showed 16% decreased GLO1 activities in RBC as compared with that of Glu111/Ala111 and Glu111/Glu111. Plasma AGEs levels were significantly high and serum vitamin B6 was significantly low in 45 schizophrenics than that of 61 control subjects. Supplementation of vitamin B6 to cases with the genetic defect of GLO1 before onset of psychosis is suggested to be possible strategy for prevention of schizophrenia until pubertal stage since such mutation carriers could have been exposed by high level of AGEs for a long time before disease onset.     

Usefulness of quantitative H-MR spectroscopy for the differentiation between radiation necrosis and recurrence of anaplastic oligodendroglioma

We report a case, in which quantitative 1H-MR spectroscopy (MRS) was useful for the differentiation between radiation necrosis and a recurrent tumor. The present case is a 44-year-old man who underwent the subtotal removal of a mass lesion in the left frontal lobe. The histological diagnosis was anaplastic oligodendroglioma (WHO grade III). Postoperatively, a fractionated radiotherapy (total 64Gy) and chemotherapy were performed. MRI after the radiotherapy showed no contrast enhancing lesion. MRI, 5 years after the radiotherapy, showed a growing enhancing lesion and a T1 hypointensity lesion without enhancement, both of which indicated a recurrent tumor. MR spectroscopy was performed for the differential diagnosis of these lesions. The spectrum was acquired by the point resolved spectroscopy (PRESS) method by TR/TE=2,000 ms/68 ms, 136 ms, and 272 ms and evaluated with peak pattern and quantification value of metabolite. MRS of the enhancing lesion demonstrated a decrease of the Choline-containing compounds (Cho) concentration, disappearance of N-acetylaspartate (NAA), decrease of Creatine/ Phosphocreatine (t-Cr) and presence of Lipids (Lip) and Lactate (Lac), all of which are characteristic finding of a radiation necrosis. The histological diagnosis of this lesion showed evidence also of radiation necrosis. On the other hand, MRS of the T1 hypointensity lesion without enhancement showed, a marked high peak of the Cho concentration, which is characteristic for a recurrent tumor. The histological findings of this lesion showed a diffuse proliferation of recurrent tumor cells. Quantitative 1H-MRS is a useful tool for the differentiation between radiation necrosis and recurrent tumors.     

Spontaneous superficial temporal artery pseudoaneurysm in elderly women--three case reports

Three women older than 75 years presented with spontaneous superficial temporal artery (STA) pseudoaneurysms manifesting as a pulsatile mass in the preauricular region. None of the patients had a history of trauma. Histological examination of the surgically removed masses identified pseudoaneurysms based on the presence of connective tissue and adventitia. Spontaneous STA pseudoaneurysms are extremely rare. We suggest that all 3 aneurysms were associated with latent dissection and external force exerted by the frames of glasses.     

Association of the HSPG2 Gene with Neuroleptic-Induced Tardive Dyskinesia

Tardive dyskinesia (TD) is characterized by repetitive, involuntary, and purposeless movements that develop in patients treated with long-term dopaminergic antagonists, usually antipsychotics. By a genome-wide association screening of TD in 50 Japanese schizophrenia patients with treatment-resistant TD and 50 Japanese schizophrenia patients without TD (non-TD group) and subsequent confirmation in independent samples of 36 treatment-resistant TD and 136 non-TD subjects, we identified association of a single nucleotide polymorphism, rs2445142, (allelic p=2 × 10⁻⁵) in the HSPG2 (heparan sulfate proteoglycan 2, perlecan) gene with TD. The risk allele was significantly associated with higher expression of HSPG2 in postmortem human prefrontal brain (p<0.01). Administration of daily injection of haloperidol (HDL) for 50 weeks significantly reduced Hspg2 expression in mouse brains (p<0.001). Vacuous chewing movements (VCMs) induced by 7-week injection of haloperidol–reserpine were significantly infrequent in adult Hspg2 hetero-knockout mice compared with wild-type littermates (p<0.001). Treatment by the acetylcholinesterase inhibitor, physostigmine, was significantly effective for reduction of VCMs in wild-type mice but not in Hspg2 hetero-knockout mice. These findings suggest that the HSPG2 gene is involved in neuroleptic-induced TD and higher expression of HSPG2, probably even after antipsychotic treatment, and may be associated with TD susceptibility.     

A novel scale including strabismus and 'cuspidal ear' for distinguishing schizophrenia patients from controls using minor physical anomalies

The present study explored minor physical anomaly items relevant to schizophrenia in order to establish a scale that can distinguish schizophrenia from controls using newly identified items along with items from the refined Waldrop scale. Seven items were significantly more frequent among schizophrenia patients (N=218) than controls (N=226). Among these seven items, two novel features, strabismus and 'cuspidal ear' showed markedly different prevalence rates between schizophrenia and control groups. A six-item scale, including the newly identified strabismus and cuspidal ear, was selected for most accurately discriminating patients with schizophrenia from controls. This scale correctly classified 59.6% of patients and 78.9% of control subjects. This new scale is procedurally more exacting and quantitative, and more relevant to schizophrenia than the original Waldrop scale. The validity of this scale should be sound since it was tested on a larger number of cohorts than used in previous research. Our scale can be used as a biomarker for predicting risk for future development of schizophrenia. The scale may also facilitate the identification of schizophrenia susceptibility genetic/environmental factors by stratifying etiologically heterogeneous patients according to physical abnormalities.     

Measurement of Drug Concentration in the Stomach After Intragastric Administration of Drug Solution to Healthy Volunteers: Analysis of Intragastric Fluid Dynamics and Drug Absorption

Purpose

To evaluate the time-profile of intragastric fluid volume in humans after intragastric administration of drug solution.

Methods

Eight healthy volunteers were intragastrically administered 150 mL of drug solution containing atenolol (non-absorbable marker) and salicylic acid, then, aliquots of gastric fluid (ca. 2 mL) were sampled for 2 h through the catheter. Rate constants for secretion and emptying of the fluid were obtained by fitting the time-course of atenolol concentration to the simple gastric fluid transit model. Absorption of salicylic acid from the stomach was estimated by comparing its gastric concentration with that of atenolol.

Results

Kinetic analysis of atenolol concentration in the stomach indicated a rapid emptying of the fluid with an average half-life of 4.2 min. Steady-state intragastric fluid volume in 8 volunteers was estimated as 4–133 mL with an average of 42 mL. Intragastric concentration (normalized by dose) of salicylic acid was always lower than that of atenolol, showing approximately 40% of salicylic acid was absorbed from the stomach before emptying to the intestine.

Conclusions

This study provided valuable information on intragastric fluid dynamics and gastric drug absorption in humans to establish a better in vitro-in vivo correlation in oral drug absorption.     

Extended analyses support the association of a functional (GT)n polymorphism in the GRIN2A promoter with Japanese schizophrenia

Dysfunction of the N-methyl-D-aspartate (NMDA) type glutamate receptor has been proposed as a mechanism in the etiology of schizophrenia. Recently, we identified a variable (GT)n repeat in the promoter region of the NMDA NR2A subunit gene (GRIN2A), and showed its association with schizophrenia in a case-control study, together with a correlation between the length of the repeat and severity of chronic outcome. In this study, we extended our analyses, by increasing the number of case-control samples to a total of 672 schizophrenics and 686 controls, and excluded potential sample stratification effects. We confirmed the significant allelic association between the repeat polymorphism and disease (P = 0.011), and as in the previous study, we observed an over-representation of longer alleles in schizophrenia. These results suggest a probable genetic effect for the GRIN2A promoter (GT)n variation on the predisposition to schizophrenia in Japanese cohorts.     

Optimal ROI setting on the anatomically normalized I-123 FP-CIT images using high-resolution SPECT

Objective

The aim of this study is to establish the optimal regions of interest (ROIs) in anatomically normalized I-123 FP-CIT SPECT images for the quantification of dopamine transporter binding.

Methods

The subjects comprised 16 normal controls and 14 Parkinsonian patients. All of the normal control subjects underwent I-123 FP-CIT SPECT and MRI. The SPECT device used in this study was a Toshiba GCA-9300R with triple head detectors. I-123 FP-CIT (148 MBq) was intravenously administered as a bolus, and the SPECT scan started 4 h after the administration. The data were collected over 20 min for each subject, and reconstructed using a 3D-OSEM algorithm. The data were analyzed using SPM8. I-123 FP-CIT SPECT images were anatomically normalized to the MNI space using an I-123 FP-CIT template, and then divided by the background counts automatically measured using the ROIs set for the cerebral cortices.

Results

In the normal control subjects, the specific binding ratios of the MRI-based ROIs were lowest in the caudate nucleus, while the ratios of the I-123 FP-CIT-based ROIs were almost the same throughout all three parts. In contrast, in Parkinsonian patients, the specific binding ratios of the I-123 FP-CIT-based ROIs revealed rostrocaudal decline, while those of the MRI-based ROIs were highest in the anterior putamen.

Conclusion

We created an ROI template on the anatomically normalized MRI and I-123 FP-CIT images, and concluded that I-123 FP-CIT-based ROIs are more suitable for obtaining quantitative values than MRI-based ones.