Chorea-acanthocytosis: Time-dependent changes of symptoms and imaging findings.

BACKGROUND AND PURPOSE: Chorea-acanthocytosis, a rare neurodegenerative disease, affects both the striatum and the medial temporal lobe which may cause involuntary movements and epilepsy, respectively. We examined the imaging changes of the hippocampus/amygdala and the striatum as well as clinical symptoms. MATERIALS AND METHODS: We retrospectively reviewed 29 MRI and 13 SPECT studies and the clinical findings of seven genetically confirmed chorea-acanthocytosis patients. We evaluated the time-dependent imaging changes of the hippocampus/amygdala and striatum and examined the relationships among these images and symptoms. RESULTS: The initial symptom was epilepsy in four patients and involuntary movements in three patients. These symptoms were eventually noted in five and all seven patients, respectively. On MRI, most patients showed striatum atrophy before a hippocampus/amygdala abnormality emerged, but one patient showed a hippocampus/amygdala abnormality before striatum atrophy. Abnormal MRI findings of hippocampus/amygdala were noted in five patients and atrophy of striatum in all seven patients. SPECT demonstrated hypoperfusion of hippocampus/amygdala in three patients and that of striatum in all five available patients. Four patients demonstrated hypoperfusion of striatum earlier than that of hippocampus/amygdala and one patient showed hypoperfusion of both simultaneously. Many imaging abnormal lesions were accompanied by their corresponding symptoms, but not always so. CONCLUSION: Striatum abnormalities were the initial imaging findings in many chorea-acanthocytosis patients, but epilepsy or hippocampus/amygdala imaging abnormalities may be the only findings at the early stage. It is important to understand the detailed clinical and imaging time courses for the diagnosis of chorea-acanthocytosis.

Brain abnormalities in myalgic encephalomyelitis/chronic fatigue syndrome: Evaluation by diffusional kurtosis imaging and neurite orientation dispersion and density imaging.

BACKGROUND: Diffusional kurtosis imaging (DKI) and neurite orientation dispersion and density imaging (NODDI) metrics provide more specific information regarding pathological changes than diffusion tensor imaging (DTI). PURPOSE: To detect microstructural abnormalities in myalgic encephalomyelitis (ME) / chronic fatigue syndrome (CFS) patients by using DKI and NODDI metrics. STUDY TYPE: Prospective. POPULATION: Twenty ME/CFS patients and 23 healthy controls were recruited. FIELD STRENGTH/SEQUENCE: Three-b value DWI (b-values = 0, 1000, and 2000 sec/mm2 ) and 3D T1 -weighted images were at 3.0T. ASSESSMENT: Mean kurtosis (MK), neurite density index (NDI), orientation dispersion index (ODI), fractional anisotropy (FA), and mean diffusivity (MD) were calculated. STATISTICAL TESTING: The two-sample t-test analysis in SPM12 software was used to compare the differences between ME/CFS and control groups. RESULTS: In the ME/CFS patients, we observed significant FA decreases in the genu of the corpus callosum and the anterior limb of the right internal capsule (P < 0.05), but no significant difference in MD (P = 0.164); there were also significant MK decreases in the right frontal area, anterior cingulate gyrus, superior longitudinal fasciculus (SLF), and left parietal area (P < 0.05). Significant NDI decreases were observed in the right posterior cingulate gyrus, SLF, and left frontal area of the ME/CFS patients (P < 0.05). Significant ODI decreases were seen in the bilateral occipital areas, right superior temporal gyrus, the anterior limb of internal capsule, and the posterior cingulate gyrus (P < 0.05), and significant ODI increases were revealed in the bilateral occipital and right temporal areas (P < 0.05). DATA CONCLUSION: Right SLF abnormalities may be a diagnostic marker for ME/CFS. LEVEL OF EVIDENCE: 1 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2019;49:818-824.

Total Corpus Callosotomy via Posterior Approach with Endoscopic-Alone Technique.

Two main surgical techniques are available for corpus callosotomy (CC): conventional microscopic CC and endoscopic CC.1 Microscopic CC is more familiar to neurosurgeons and allows three-dimensional visualization, but it requires a larger craniotomy and has a narrower visual angle in the deep part. Endoscopic CC has only recently been introduced to epilepsy surgery, but it is gaining increasing interest among epilepsy surgeons. The endoscope provides two-dimensional visualization and requires a camera as an additional instrument inserted into the surgical corridor. The merits of endoscopic CC include the smaller craniotomy and smaller skin incision, potentially reducing invasiveness.2 Bridging veins to the superior sagittal sinus are also less problematic because of the reduced need for brain retraction. The lack of need of arachnoid dissection is another advantage. Generally, an anterior approach is applied for CC, but this approach makes interhemispheric fissure dissection mandatory, especially at the cingulate gyri. In some cases, this procedure can take a long time. On the other hand, a posterior approach requires less interhemispheric arachnoid dissection, or sometimes none at all, due to the anatomy of the falx cerebri. These reasons have driven the development of a posterior approach for an endoscopic-alone technique.3 Here, we present a 5-year-old girl with medically intractable epileptic spasms that were diagnosed as infantile epileptic spasms syndrome, who underwent endoscopic total CC via a posterior approach to control her seizures (Video 1).

Evaluation of focus laterality in temporal lobe epilepsy: a quantitative study comparing double inversion-recovery MR imaging at 3T with FDG-PET.

PURPOSE: To quantitatively compare the diagnostic capability of double inversion-recovery (DIR) with F-18 fluorodeoxyglucose positron emission tomography (FDG-PET) for detection of seizure focus laterality in temporal lobe epilepsy (TLE). METHODS: This study was approved by the institutional review board, and written informed consent was obtained. Fifteen patients with TLE and 38 healthy volunteers were enrolled. All magnetic resonance (MR) images were acquired using a 3T-MRI system. Voxel-based analysis (VBA) was conducted for FDG-PET images and white matter segments of DIR images (DIR-WM) focused on the whole temporal lobe (TL) and the anterior part of the temporal lobe (ATL). Distribution of hypometabolic areas on FDG-PET and increased signal intensity areas on DIR-WM were evaluated, and their laterality was compared with clinically determined seizure focus laterality. Correct diagnostic rates of laterality were evaluated, and agreement between DIR-WM and FDG-PET was assessed using κ statistics. KEY FINDINGS: Increased signal intensity areas on DIR-WM were located at the vicinity of the hypometabolic areas on FDG-PET, especially in the ATL. Correct diagnostic rates of seizure focus laterality for DIR-WM (0.80 and 0.67 for the TL and the ATL, respectively) were slightly higher than those for FDG-PET (0.67 and 0.60 for the TL and the ATL, respectively). Agreement of laterality between DIR-WM and FDG-PET was substantial for the TL and almost perfect for the ATL (κ = 0.67 and 0.86, respectively). SIGNIFICANCE: High agreement in localization between DIR-WM and FDG-PET and nearly equivalent detectability of them show us an additional role of MRI in TLE.

Anterior temporal lobe white matter abnormal signal (ATLAS) as an indicator of seizure focus laterality in temporal lobe epilepsy: comparison of double inversion recovery, FLAIR and T2W MR imaging.

OBJECTIVES: To investigate the diagnostic capability of anterior temporal lobe white matter abnormal signal (ATLAS) for determining seizure focus laterality in temporal lobe epilepsy (TLE) by comparing different MR sequences. METHODS: This prospective study was approved by the institutional review board and written informed consent was obtained. Three 3D sequences (double inversion recovery (DIR), fluid-attenuated inversion recovery (FLAIR) and T2-weighted imaging (T2WI)) and two 2D sequences (FLAIR and T2WI) were acquired at 3 T. Signal changes in the anterior temporal white matter of 21 normal volunteers were evaluated. ATLAS laterality was evaluated in 21 TLE patients. Agreement of independent evaluations by two neuroradiologists was assessed using κ statistics. Differences in concordance between ATLAS laterality and clinically defined seizure focus laterality were analysed using McNemar's test with multiple comparisons. RESULTS: Pre-amygdala high signals (PAHS) were detected in all volunteers only on 3D-DIR. Inter-evaluator agreement was moderate to almost perfect for each sequence. Correct diagnosis of seizure laterality was significantly more frequent on 3D-DIR than on any other sequences (P ≤ 0.031 for each evaluator). CONCLUSIONS: The most sensitive sequence for detecting ATLAS laterality was 3D-DIR. ATLAS laterality on 3D-DIR can be a good indicator for determining seizure focus localization in TLE.

Focal cortical dysplasia imaging discrepancies between MRI and FDG-PET: Unique association with temporal lobe location.

PURPOSE: Although magnetic resonance imaging (MRI) and 18F-2-fluorodeoxyglucose-positron emission tomography (FDG-PET) are used for pre-surgical assessment of focal cortical dysplasia (FCD), they often disagree. This study aimed to identify factors that contribute to discrepancies in FCD imaging between MRI and FDG-PET. METHODS: Sixty-two patients (mean age, 18.9 years) with a FCD type I or II were retrospectively selected. These patients were visually categorized into two groups: 1) extent of PET abnormality larger than MRI abnormality and 2) vice versa or equivalent. Predictive factors of these two groups were analyzed by multivariate logistic regression. The extent of hypometabolic transient zone surrounding FCDs and their mean standardized uptake values were measured and compared by the Mann-Whitney U-test. RESULTS: FCDs were detected on MRI and PET in 46 and 55 patients, respectively, whereas no abnormality was detected in 4 patients. The PET hypometabolic areas were larger than the MRI abnormal areas in 26 patients (88 % in the temporal lobe), whereas the PET hypometabolic areas were equivalent or smaller than the MRI abnormal areas in 32 patients (69 % in the frontal lobe). The temporal lobe location was an independent predictor for differentiating the two groups (OR = 35.2, 95 % CI = 6.81-168.0, P < .001). The temporal lobe lesions had significantly wider transient zones and lower standardized uptake values than those in the other lobes (P < .001, both). CONCLUSION: The discrepancies between MRI and FDG-PET findings of FCD were associated with temporal lobe location.

Altered MR imaging findings in a Japanese female child with PRUNE1-related disorder.

Autosomal recessive PRUNE1 mutations on chromosome 1q21.3 are reported to cause a neurodevelopmental disorder with microcephaly, hypotonia, and variable brain malformations. Here, we report a Japanese case with a reported PRUNE1 mutation whose brain magnetic resonance imaging (MRI) showed specific imaging findings that have not been reported before. The patient was a 12-month-old girl, the first child of healthy and nonconsanguineous Japanese parents. She showed global developmental delay, intellectual disability, hypotonia, spastic quadriparesis, and hyperreflexia. Brain MRI showed cerebral and cerebellar atrophy, thin corpus callosum, white matter changes, and abnormal signal intensity of the brainstem, all of which were reported in the literature. In addition, we emphasize the three following imaging findings: a transient cerebral subcortical white matter lesion, atrophy of the midbrain and pontine tegmentum with a preserved pontine base, and abnormal signal intensity of the bilateral swelling putamina and medial portions of the thalami, which emerged after 4 years of age. The whole-exome sequencing (WES) analysis performed at the age of 4 years identified biallelic PRUNE1 variants, namely compound heterozygous mutations (c.[316G > A];[540 T > A],p.[Asp106Asn];[Cys180*]). Although the diagnosis of PRUNE1-related disorder requires WES, we think that these new characteristic MRI findings may help in the diagnosis of PRUNE1-related disorder.

Discriminating chorea-acanthocytosis from Huntington's disease with single-case voxel-based morphometry analysis.

BACKGROUND AND PURPOSE: Chorea-acanthocytosis is clinically difficult to distinguish from Huntington's disease because these disorders have similar symptoms and MR imaging findings. We evaluated the usefulness of single-case voxel-based morphometry (VBM) analysis for differentiating the two diseases as well as VBM analysis. MATERIALS AND METHODS: We examined five genetically proven chorea-acanthocytosis patients and 11 Huntington's disease patients to detect differences in the gray and white matter atrophic pattern by using single-case VBM analysis in each patient and their clinical findings. We also evaluated VBM analysis for a group comparison in both disease and control groups. RESULTS: The single-case VBM analysis results demonstrated a gray matter volume loss in caudate nucleus in all 16 patients. A characteristic symmetrical white matter volume loss was detected in globus pallidus, putamen, and thalamus on both sides in all the chorea-acanthocytosis patients, but this pattern of atrophy was not seen in any of the Huntington's disease patients. With the VBM analysis, a significant gray matter volume loss was noted in caudate nucleus on both sides in chorea-acanthocytosis patients compared with Huntington's disease patients, and a more extensive white matter volume loss around the basal ganglia and thalamus was observed in chorea-acanthocytosis patients compared to Huntington's disease patients, consistent with the single-case VBM analysis results. Genetic testing identified two novel pathogenic mutations, exon 1 c.16_22delGTGGTCG and exon 55 c.7736-7739delGAGA in a chorea-acanthocytosis patient. CONCLUSIONS: Single-case VBM analysis may be useful to differentiate chorea-acanthocytosis from Huntington's disease with a focus on white matter atrophy.

A critical role for eukaryotic elongation factor 1A-1 in lipotoxic cell death.

The deleterious consequences of fatty acid (FA) and neutral lipid accumulation in nonadipose tissues, such as the heart, contribute to the pathogenesis of type 2 diabetes. To elucidate mechanisms of FA-induced cell death, or lipotoxicity, we generated Chinese hamster ovary (CHO) cell mutants resistant to palmitate-induced death and isolated a clone with disruption of eukaryotic elongation factor (eEF) 1A-1. eEF1A-1 involvement in lipotoxicity was confirmed in H9c2 cardiomyoblasts, in which small interfering RNA-mediated knockdown also conferred palmitate resistance. In wild-type CHO and H9c2 cells, palmitate increased reactive oxygen species and induced endoplasmic reticulum (ER) stress, changes accompanied by increased eEF1A-1 expression. Disruption of eEF1A-1 expression rendered these cells resistant to hydrogen peroxide- and ER stress-induced death, indicating that eEF1A-1 plays a critical role in the cell death response to these stressors downstream of lipid overload. Disruption of eEF1A-1 also resulted in actin cytoskeleton defects under basal conditions and in response to palmitate, suggesting that eEF1A-1 mediates lipotoxic cell death, secondary to oxidative and ER stress, by regulating cytoskeletal changes critical for this process. Furthermore, our observations of oxidative stress, ER stress, and induction of eEF1A-1 expression in a mouse model of lipotoxic cardiomyopathy implicate this cellular response in the pathophysiology of metabolic disease.

Exploring the frequency and clinical background of the "zebra sign" in amyotrophic lateral sclerosis and multiple system atrophy.

In amyotrophic lateral sclerosis (ALS), the "zebra sign" in the precentral gyrus on phase difference enhanced magnetic resonance imaging (PADRE) recently has been reported as a possible imaging biomarker for upper motor neuron (UMN) involvement. A previous study has shown that the "zebra sign" allowed us to differentiate patients with ALS from healthy subjects with excellent accuracy. We validated the usefulness of the sign for differentiating patients with ALS from healthy subjects and investigated whether the "zebra sign" can be observed other neurodegenerative disorders with UMN involvement. The "zebra sign" on PADRE was assessed in 26 patients with ALS, 26 with multiple system atrophy (MSA) and 26 healthy controls, and the sign was observed in 50%, 23%, and no subjects, respectively. ALS patients with the "zebra sign" demonstrated a higher UMN burden score than those without the sign. The "zebra sign" on PADRE is not specific to ALS, also present in MSA, but might reflect the degeneration of the UMN within the motor cortex in neurodegenerative disorders.

Postoperative changes in the brain: Assessment with serial T2WI/FLAIR MR images in non-neoplastic patients.

The aim of the current study was to investigate the postoperative changes of high-signal lesions at the surgical margin on serial T2WI/FLAIR images in non-neoplastic patients. Seventy-one postoperative MR images in 27 patients (17 focal cortical dysplasia and 10 hippocampal sclerosis) who underwent surgery for intractable epilepsy were evaluated. T2WI/FLAIR-high-signal lesions in size and shape were visually assessed using a 3-point grading system. Associations of postoperative seizures or electroencephalography(EEG)spikes with advancing grade were also evaluated. As a result, follow-up showed enlarged T2WI/FLAIR-high-signal lesions in 6 of 27 patients (22%). The presence of post-operative seizures or EEG spikes was significantly associated with enlargement of the T2WI/FLAIR-high-signal lesion. Enlargement of the T2WI/FLAIR-high-signal lesion was observed in some non-neoplastic patients, and this finding might be correlated with remnant epileptogenesis.

Quantifying iron deposition in the cerebellar subtype of multiple system atrophy and spinocerebellar ataxia type 6 by quantitative susceptibility mapping.

We used quantitative susceptibility mapping (QSM) to assess the brain iron deposition in 28 patients with the cerebellar subtype of multiple system atrophy (MSA-C), nine patients with spinocerebellar ataxia type 6 (SCA6), and 23 healthy controls. Two reviewers independently measured the mean QSM values in brain structures including the putamen, globus pallidus, caudate nucleus, red nucleus, substantia nigra, and cerebellar dentate nucleus. A receiver operating characteristics (ROC) analysis was performed to assess the diagnostic usefulness of the QSM measurements. The QSM values in the substantia nigra were significantly higher in the MSA-C group compared to the HC group (p = .007). The QSM values in the cerebellar dentate nucleus were significantly higher in MSA-C than those in the SCA6 and HC groups (p < .001), and significantly lower in the SCA6 patients compared to the HCs (p = .027). The QSM values in the cerebellar dentate nucleus were correlated with disease duration in MSA-C, but inversely correlated with disease duration in SCA6. In the ROC analysis, the QSM values in the cerebellar dentate nucleus showed excellent accuracy for differentiating MSA-C from SCA6 (area under curve [AUC], 0.925), and good accuracy for differentiating MSA-C from healthy controls (AUC 0.834). QSM can identify increased susceptibility of the substantia nigra and cerebellar dentate nucleus in MSA-C patients. These results suggest that an increase in iron accumulation in the cerebellar dentate nucleus may be secondary to the neurodegeneration associated with MSA-C.

Voxel-based correlation of 18F-THK5351 accumulation and gray matter volume in the brain of cognitively normal older adults.

BACKGROUNDS: Although neurofibrillary tangles (NFTs) mainly accumulate in the medial temporal lobe with human aging, only a few imaging studies have investigated correlations between NFT accumulation and gray matter (GM) volume in cognitively normal older adults. Here, we investigated the correlations between 18F-THK5351 accumulation and GM volume at the voxel level. MATERIAL AND METHODS: We recruited 47 amyloid-negative, cognitively normal, older adults (65.0 ± 7.9 years, 26 women), who underwent structural magnetic resonance imaging, 11C-Pittsburgh compound-B and 18F-THK5351 PET scans, and neuropsychological assessment. The magnetic resonance and 18F-THK5351 PET images were spatially normalized using Statistical Parametric Mapping 12. Voxel-wise correlations between 18F-THK5351 accumulation and GM volume were evaluated using the Biological Parametric Mapping toolbox. RESULTS: A significant negative correlation (p < 0.001) between 18F-THK5351 accumulation and GM volume was detected in the bilateral medial temporal lobes. CONCLUSIONS: Voxel-wise correlation analysis revealed a significant negative correlation between 18F-THK5351 accumulation and GM volume in the medial temporal lobe in individuals without amyloid-ß deposits. These results may contribute to a better understanding of the pathophysiology of primary age-related tauopathy in human aging.

Psychiatric and neurodevelopmental aspects of Becker muscular dystrophy.

Little is known about the relationship between Becker Muscular Dystrophy (BMD) and mental disorders. This study aimed to clarify whether BMD is a risk factor for psychiatric diseases. We asked genetically or immunohistochemically confirmed BMD patients to participate in the study interview. Participants who consented to psychiatric tests underwent further assessments of intellectual, psychological, and neurodevelopmental disorders. In total, 76 (73%) of 105 BMD patients (median age, 37 years) completed the interview. Of these, 6 had developmental disorders (mental retardation, pervasive developmental disorder), 33/76 (43%) experienced bullying in school, 11 exhibited problematic behaviors such as cutting class and violent incidents, and 16 had psychiatric disorders (schizophrenia spectrum, 5; depressive spectrum, 4; stress-related disorders, 3; obsessive-compulsive and related disorders, 2; somatic symptom and related disorders, 2; bipolar and related disorders, 1). Mean IQ was normal, whereas 13/40 (32.5%) of participants were in a depressive state. High trait anxiety was found in 20/40 (50%) of patients, while 15/40 (38.5%) were in an anxious state. Review of MRI data from 14 participants revealed brain atrophy caused solely by BMD and unrelated to any other complication. Our findings suggest that BMD patients are at risk of developing psychiatric disorders. Physical handicap or bullying may influence their mental state, as many of them have high trait anxiety. Parents, teachers, and supporters should be mindful of the daily environment of BMD patients and provide support to help them cope with stress.

Disrupted cortico-ponto-cerebellar pathway in patients with hemimegalencephaly.

OBJECTIVE: Cerebellar dysmaturation and injury is associated with a wide range of neuromotor, neurocognitive and behavioral disorders as well as with preterm birth. We used diffusion tensor MR imaging to investigate a disruption in structural cortico-ponto-cerebellar (CPC) connectivity in children with infantile-onset severe epilepsy. METHODS: We performed CPC tract reconstructions in 24 hemimegalencephaly (HME) patients, 28 West syndrome (WS) of unknown etiology patients, and 25 pediatric disease control subjects without a history of epilepsy nor brain abnormality on MRI. To identify the CPC tract, we placed a seeding ROI separately in each right and left cerebral peduncle. We evaluated the distribution patterns of the CPC tracts to the cerebellum and their correlation with clinical findings. RESULTS: In control and WS of unknown etiology groups, both sides' CPC tracts descended to bilateral hemispheres in 20 (80.0%) and 21 (75.0%); mixed (bilateral on one side and unilateral on the other side) in five (20.0%) and five (17.9%); and unilateral in zero (0.0%) and two (7.1%), respectively. However, in the HME, both sides' CPC tracts descended to bilateral hemispheres in four (16.7%); mixed in 13 (54.1%); and unilateral in seven (29.2%). These CPC patterns differed significantly between the HME and other groups (p < 0.001). Among HME patients, those with a unilateral cerebellar distribution on both sides had significantly earlier seizure onset (p = 0.049) and more frequent seizures (p = 0.052) at a trend level compared to those with bilateral and mixed distributions. CONCLUSION: Disrupted CPC tracts were observed more frequently in HME patients than in WS of unknown etiology patients and controls, and they may be correlated with earlier seizure onset and more frequent seizures in HME patients. DTI is a useful and non-invasive method for speculating the pathology in the developing brain.

Analysis of susceptibility-weighted images of cortico-medullary junction.

OBJECTIVE: We qualitatively evaluated the differences among susceptibility-weighted (SWI), magnitude (MAG), and high pass filtered phase (PHA) images in depicting interlobar differences in the appearance of the signal of the corticomedullary junction (CMJ). We conducted quantitative evaluation to validate the qualitative results. MATERIALS AND METHODS: We obtained SWI images from 25 preoperative brain tumor patients (12 men, 13 women, aged 19 to 82 years, mean, 52 years). Two trained neuroradiologists evaluated MAG, PHA, and SWI images. Qualitative evaluation of the CMJ signal and quantitative calculation of the relative signal ratio (RSR) percentages between the CMJ and deep white matter (WM) were conducted at 3 different slice levels of the brain independently for 4 different lobes (frontal, parietal, temporal, and occipital) and compared among MAG, PHA, and SWI. The extent of the area of the CMJ signal was graded on a 4-point scale (Grade 3, >75%; Grade 2, 50 to 75%; Grade 1, 25 to 50%; Grade 0, <25%). Data were statistically analyzed using a nonparametric Friedman test. RESULTS: The Kappa coefficients between the qualitative and quantitative grades were 0.002 for MAG, 0.0047 for PHA, and 0.050 for SWI. Qualitatively, on the PHA images and SWI, grades of the occipital lobes were significantly higher than those of the other lobes (P < 0.005). Quantitatively, PHA images showed statistically significant interlobar differences in RSR percentage values of the CMJ (P = 0.025). CONCLUSION: Qualitatively, the appearance of the CMJ differed significantly among the different lobes of the brain on SWI and underlying PHA images but not on MAG images. Quantitatively, only PHA images showed significant interlobar differences in the RSR. PHA images are most sensitive to the CMJ signal contrast due to local paramagnetic iron content.

A neurodegeneration-specific gene-expression signature of acutely isolated microglia from an amyotrophic lateral sclerosis mouse model.

Microglia are resident immune cells of the CNS that are activated by infection, neuronal injury, and inflammation. Here, we utilize flow cytometry and deep RNA sequencing of acutely isolated spinal cord microglia to define their activation in vivo. Analysis of resting microglia identified 29 genes that distinguish microglia from other CNS cells and peripheral macrophages/monocytes. We then analyzed molecular changes in microglia during neurodegenerative disease activation using the SOD1(G93A) mouse model of amyotrophic lateral sclerosis (ALS). We found that SOD1(G93A) microglia are not derived from infiltrating monocytes, and that both potentially neuroprotective and toxic factors, including Alzheimer's disease genes, are concurrently upregulated. Mutant microglia differed from SOD1(WT), lipopolysaccharide-activated microglia, and M1/M2 macrophages, defining an ALS-specific phenotype. Concurrent messenger RNA/fluorescence-activated cell sorting analysis revealed posttranscriptional regulation of microglia surface receptors and T cell-associated changes in the transcriptome. These results provide insights into microglia biology and establish a resource for future studies of neuroinflammation.

"Hot cross bun" sign in multiple system atrophy with predominant cerebellar ataxia: a comparison between proton density-weighted imaging and T2-weighted imaging.

OBJECTIVE: To investigate whether proton density-weighted imaging can detect the "hot cross bun" sign in the pons in multiple system atrophy with predominant cerebellar ataxia significantly better than T2-weighted imaging at 3T. METHODS: Sixteen consecutive patients with multiple system atrophy with predominant cerebellar ataxia according to the Consensus Criteria were reviewed. Axial unenhanced proton density-weighted imaging and T2-weighted imaging were obtained using a dual-echo fast spin-echo sequence at 3T. Two neuroradiologists independently evaluated visualisation of the abnormal pontine signal using a 4-point visual grade from Grade 0 (no "hot cross bun" sign) to Grade 3 (prominent "hot cross bun" sign on two or more sequential slices). Differences in grade between proton density-weighted imaging and T2-weighted imaging were statistically analysed using the Wilcoxon signed-rank test. RESULTS: In 11 patients (69%), a higher grade was given for proton density-weighted imaging than T2-weighted imaging. In 1 patient (6%), grades were the same (Grade 3) on both images. In the remaining 4 patients (25%), signal abnormalities were not detected on either image (Grade 0). The "hot cross bun" sign was thus observed significantly better on proton density-weighted imaging than on T2-weighted imaging (P=0.001). CONCLUSIONS: The "hot cross bun" sign considered diagnostic for multiple system atrophy with predominant cerebellar ataxia is significantly better visualised on proton density-weighted imaging than on T2-weighted imaging at 3T.

Diffusion-weighted magnetic resonance imaging in autoimmune pancreatitis.

PURPOSE: The aim of this study was to investigate the usefulness of diffusion-weighted magnetic resonance imaging (DWI MRI) for the diagnosis and evaluation of autoimmune pancreatitis (AIP). MATERIALS AND METHODS: A total of 4 consecutive patients with AIP, 5 patients with chronic alcoholic pancreatitis (CP), and 13 patients without pancreatic disease (controls) were studied. DWI was performed in the axial plane with spin-echo echo-planar imaging single-shot sequence. Apparent diffusion coefficients (ADCs) were measured in circular regions of interest in the pancreas. In AIP patients, abdominal MRI was performed before, and 2-4 weeks after steroid treatment. Follow-up study was performed chronologically for up to 11 months in two patients. The correlation between ADCs of the pancreas and the immunoglobulin G4 (IgG4) index (serum IgG4 value/serum IgG4 value before steroid treatment) was evaluated. RESULTS: In the AIP patients, DWI of the pancreas showed high signal intensity, and the ADCs of the pancreas (mean +/- SD: 0.97 +/- 0.18 x 10(-3) mm(2)/s) were significantly lower than those in patients with CP (1.45 +/- 0.10 x 10(-3) mm(2)/s) or the controls (1.45 +/- 0.16 x 10(-3) mm(2)/s) (Mann-Whitney U-test, P < 0.05). In one AIP patient with focal swelling of the pancreas head that appeared to be a mass, DWI showed high signal intensity throughout the pancreas, indicating diffuse involvement. The ADCs of the pancreas and IgG4 index were significantly inversely correlated (Spearman's rank correlation coefficient, r (s) = -0.80, P < 0.05). CONCLUSION: Autoimmune pancreatitis showed high signal intensity on DWI, which improved after steroid treatment. ADCs reflected disease activity. Thus, diffusion-weighted MRI might be useful for diagnosing AIP, determining the affected area, and evaluating the effect of treatment.

Establishment and characterization of mammalian cell lines stably expressing human L-type amino acid transporters.

System L (SL), a basolateral amino acid transporter, transports large neutral amino acids (LNAAs) in a Na(+)-independent manner. Previously, we identified two isoforms of transporters: L-type amino acid transporter 1 (LAT1) and 2 (LAT2) and revealed their distinct substrate selectivity and transport properties. In this study, to establish more stable human LAT1 (hLAT1) and LAT2 (hLAT2) in vitro assay systems, we established mouse cell lines stably expressing hLAT1 (S2-LAT1) and hLAT2 (S2-LAT2). Real-time quantitative RT-PCR analysis revealed that S2-LAT1 and S2-LAT2 cells express hLAT1 and hLAT2 mRNAs at 20 - 1000-fold higher levels than those of endogenous mouse Lat1 and Lat2. S2-LAT1 and S2-LAT2 mediated [(14)C]L-leucine transport properties were measured and corresponded to results observed via Xenopus oocytes. Using these cells, the data demonstrate that hLAT1 and hLAT2 exhibit different characters in the acceptance of alpha-methyl amino acids and amino acid-related compounds with bulky side chains such as thyroid hormones and melphalan. S2-LAT1 and S2-LAT2 cells are expected to facilitate hLAT1 and hLAT2 substrate recognition research and contribute to drug development by providing an efficient assay system to screen for chemical compounds that interact with hLAT1 and hLAT2.