Computer-aided detection improves brain metastasis identification on non-enhanced CT in less experienced radiologists.

BACKGROUND: Brain metastases (BMs) are the most common intracranial tumors causing neurological complications associated with significant morbidity and mortality. PURPOSE: To evaluate the effect of computer-aided detection (CAD) on the performance of observers in detecting BMs on non-enhanced computed tomography (NECT). MATERIAL AND METHODS: Three less experienced and three experienced radiologists interpreted 30 NECT scans with 89 BMs in 25 cases to detect BMs with and without the assistance of CAD. The observers' sensitivity, number of false positives (FPs), positive predictive value (PPV), and reading time with and without CAD were compared using paired t-tests. The sensitivity of CAD and the observers were compared using a one-sample t-test. RESULTS: With CAD, less experienced radiologists' sensitivity significantly increased from 27.7% ± 4.6% to 32.6% ± 4.8% (P = 0.007), while the experienced radiologists' sensitivity did not show a significant difference (from 33.3% ± 3.5% to 31.9% ± 3.7%; P = 0.54). There was no significant difference between conditions with CAD and without CAD for FPs (less experienced radiologists: 23.0 ± 10.4 and 25.0 ± 9.3; P = 0.32; experienced radiologists: 18.3 ± 7.4 and 17.3 ± 6.7; P = 0.76) and PPVs (less experienced radiologists: 57.9% ± 8.3% and 50.9% ± 7.0%; P = 0.14; experienced radiologists: 61.8% ± 12.7% and 64.0% ± 12.1%; P = 0.69). There were no significant differences in reading time with and without CAD (85.0 ± 45.6 s and 73.7 ± 36.7 s; P = 0.09). The sensitivity of CAD was 47.2% (with a PPV of 8.9%), which was significantly higher than that of any radiologist (P < 0.001). CONCLUSION: CAD improved BM detection sensitivity on NECT without increasing FPs or reading time among less experienced radiologists, but this was not the case among experienced radiologists.

Cerebral toxoplasmosis complicating lymphoplasmacytic lymphoma in partial remission.

Toxoplasma gondii can develop toxoplasmic encephalitis (TE) in immunodeficient conditions such as AIDS and after organ transplantation. While some cases of TE with malignant lymphoma were reported, these cases occurred immediately after chemotherapy or when their diseases were active. Here we report the first Case of TE that occurred in patient who was in partial remission (PR) of lymphoplasmacytic lymphoma (LPL) for two years. A 76-year-old man was referred to our institute because of disturbance of consciousness, right arm weakness and paresthesia. A computed tomography (CT) scan detected multiple nodules in his brain. Magnetic resonance imaging (MRI) of the head detected multiple gadolinium-enhancing parenchymal lesions with hyperintense signals on T2-and diffusion-weighted images, located in both cerebral and cerebellar hemispheres. Blood test and cerebrospinal fluid (CSF) findings were unremarkable. His rapidly deteriorating consciousness precluded a chance of brain biopsy. Considering the limited efficacy of antimicrobials and the imaging findings that could be compatible with the diagnosis of malignant lymphoma, we suspected central nerve system (CNS) recurrence of LPL. Although chemotherapy was initiated, he died of respiratory failure just after chemotherapy. A pathological autopsy showed his cause of death was TE. To our knowledge, this is the first case of TE in long-term PR of malignant lymphoma. TE should be suspected when patients with malignant lymphoma present unexplained neurologic symptoms regardless of their treatment efficacy of lymphoma. (226/250 words).

Effect of high-dose delivery on the attachment of meningiomas in Gamma Knife surgery: a retrospective study.

BACKGROUND: Meningiomas have vascular supply from the tumor attachment on the dura mater. Gamma Knife radiosurgery (GKS) is known to have a vascular obliterating effect. This study aims to determine the benefits of high-dose irradiation to the tumor attachment compared to conventional dose planning in the long-term control of tumor growth with GKS. METHODS: Two different dose plannings were retrospectively compared in 75 patients with meningioma treated with GKS as a primary treatment. Forty-three patients were irradiated over 20 Gy to the tumor attachment. The remaining 32 patients were treated with conventional-dose planning. Tumor growth control, reduction of enhancement on the gadolinium-enhanced magnetic resonance imaging (MRI), and neurological status were retrospectively assessed. RESULTS: The maximum dose on the tumor attachment was significantly higher in the high-dose group (23 Gy) than in the conventional group (16 Gy). The tumor margin was irradiated with the median of the 50% isodose line in both groups. The prescription doses resulted in 14 Gy and 12 Gy, respectively. The tumor control rate achieved 91% in both groups during the median follow-up period of 54 months. A decrease of enhancement on follow-up MRI was noted in one patient in each group. Kaplan-Meier analysis revealed no statistical difference in the progression-free survival between the two groups. The number of patients with improved neurological status showed no statistical difference. CONCLUSIONS: No obvious benefit of high-dose irradiation to the tumor attachment and margin was found in tumor control and neurological status in the long term.

Structural connectivity changes in the cerebral pain matrix in burning mouth syndrome: a multi-shell, multi-tissue-constrained spherical deconvolution model analysis.

PURPOSE: Burning mouth syndrome (BMS) is a chronic intraoral pain syndrome. Previous studies have attempted to determine the brain connectivity features in BMS using functional and structural magnetic resonance imaging. However, no study has investigated the structural connectivity using multi-shell, multi-tissue-constrained spherical deconvolution (MSMT-CSD), anatomically constrained tractography (ACT), and spherical deconvolution informed filtering of tractograms (SIFT). Therefore, this study aimed to assess the differences in brain structural connectivity of patients with BMS and healthy controls using probabilistic tractography with these methods, and graph analysis. METHODS: Fourteen patients with BMS and 11 age- and sex-matched healthy volunteers underwent 3-T magnetic resonance imaging. MSMT-CSD-based probabilistic structural connectivity was computed using the second-order integration over fiber orientation distributions algorithm based on nodes set in 84 anatomical cortical regions with ACT and SIFT. A t-test was performed for comparisons between the BMS and healthy control brain networks. RESULTS: The betweenness centrality was significantly higher in the left insula, right amygdala, and right lateral orbitofrontal cortex and significantly lower in the right inferotemporal cortex in the BMS group than that in healthy controls. However, no significant difference was found in the clustering coefficient, node degree, and small-worldness between the two groups. CONCLUSION: Graph analysis of brain probabilistic structural connectivity, based on diffusion imaging using an MSMT-CSD model with ACT and SIFT, revealed alterations in the regions comprising the pain matrix and medial pain ascending pathway. These results highlight the emotional-affective profile of BMS, which is a type of chronic pain syndrome.

Serial MRI alterations of pediatric patients with beta-propeller protein associated neurodegeneration (BPAN).

BACKGROUND AND PURPOSE: Beta-propeller protein-associated neurodegeneration (BPAN) is one subtype of neurodegeneration with brain iron accumulation. It is difficult to diagnose BPAN due to the non-specificity of their clinical findings and neuroimaging in early childhood. We experienced four pediatric patients with serial brain MRI and evaluated the alteration of the findings through their course. METHODS: We retrospectively reviewed the clinical findings and 21 MRI findings of the four patients with genetically confirmed pediatric BPAN. We also performed a quantitative MR assessment using the quantitative susceptibility mapping (QSM) values of the globus pallidus (GP), substantia nigra (SN), and deep cerebellar nuclei (DCN) compared to 10 age-matched disease controls. RESULTS: Only one patient was suspected of BPAN based on imaging findings before the genetic diagnosis was made. The other three patients could not be suspected until their Whole-exome sequencings (WES) done. In all four cases, no abnormal signals were noted in the GP and SN at the initial brain MRI, but hypointensities were observed after the ages of 4-7 years on T2-weighted images and after the ages of 2-7 years on susceptibility-weighted images. In three patients, T2 hyperintensity in the bilateral DCN was persistently observed throughout the observational period. Three patients showed transient T2 hyperintensity and swelling in the GP, SN and/or DCN during the episodes of pyrexia and seizures. The other findings included cerebral and cerebellar atrophy, thinning of the corpus callosum, and delayed myelination. The QSM values of the GP and SN were significantly higher in the patients compared to the controls (P=0.005, respectively), but that of the DCN did not differ significantly (P=0.16). CONCLUSION: Brain MRI is a useful method to establish the early diagnosis of BPAN.

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.

Single-stage total resection of giant dumbbell-shaped hypoglossal schwannoma: a case report.

Extensive large dumbbell-shaped hypoglossal schwannoma is extremely rare, and total resection is nearly impossible. We present a case of a 61-year-old male with a giant-size hypoglossal schwannoma with moderate tongue atrophy. The tumor extended from the enlarged hypoglossal canal to the brainstem intradurally and the high cervical region extradurally. Through the extreme lateral infrajugular transcondylar (ELITE) skull base approach, the tumor was totally removed in a single-stage operation. Single-stage total resection is feasible by an experienced skull base team utilizing transcondylar skull base techniques and high cervical dissection.

Atypical Fast-Slow Atrioventricular Nodal Reentrant Tachycardia Incorporating a "Superior" Slow Pathway: A Distinct Supraventricular Tachyarrhythmia.

BACKGROUND: The existence of an atypical fast-slow (F/S) atrioventricular nodal reentrant tachycardia (AVNRT) including a superior (sup) pathway with slow conductive properties and an atrial exit near the His bundle has not been confirmed. METHODS AND RESULTS: We studied 6 women and 2 men (age, 74 ± 7 years) with sup-F/S-AVNRT who underwent successful radiofrequency ablation near the His bundle. Programmed ventricular stimulation induced retrograde conduction over a superior SP with an earliest atrial activation near the His bundle, a mean shortest spike-atrial interval of 378 ± 119 milliseconds, and decremental properties in all patients. sup-F/S-AVNRT was characterized by a long-RP interval; a retrograde atrial activation sequence during tachycardia identical to that over a sup-SP during ventricular pacing; ventriculoatrial dissociation during ventricular overdrive pacing of the tachycardia in 5 patients or atrioventricular block occurring during tachycardia in 3 patients, excluding atrioventricular reentrant tachycardia; termination of the tachycardia by ATP; and a V-A-V activation sequence immediately after ventricular induction or entrainment of the tachycardia, including dual atrial responses in 2 patients. Elimination or modification of retrograde conduction over the sup-SP by ablation near the right perinodal region or from the noncoronary cusp of Valsalva eliminated and confirmed the diagnosis of AVNRT in 4 patients each. CONCLUSIONS: sup-F/S-AVNRT is a distinct supraventricular tachycardia, incorporating an SP located above the Koch triangle as the retrograde limb, that can be eliminated by radiofrequency ablation.

Long-term outcomes of microvascular decompression and Gamma Knife surgery for trigeminal neuralgia: a retrospective comparison study.

BACKGROUND: There is still no clear guideline for surgical treatment for patients with medically refractory trigeminal neuralgia (TN). When it comes to which surgical treatment to choose, microvascular decompression (MVD) or Gamma Knife surgery (GKS), we should know the long-term outcome of each treatment. METHODS: We analyzed 179 patients undergoing MVD and 52 patients undergoing GKS followed for 1 year or longer. We evaluated the patient's neurological status including pain relief, complications and recurrence. Results were assessed with Barrow Neurological Institute (BNI) pain intensity and facial numbness scores. Overall outcomes were compared between the two groups based on pain relief and complications. RESULTS: BNI pain intensity and facial numbness scores at the final visit were significantly lower in the MVD group than in the GKS group (P < 0.001, P = 0.04, respectively). Overall outcomes were superior following MVD than following GKS (P < 0.001). Following whichever treatment, there were initially high rates of pain-free status "without medication": 96.6% in the MVD group and 96.2% in the GKS group. However, 6.1% in the MVD group and 51.9% in the GKS group fell into a "with medication" state within median periods of 1.83 and 3.92 years, respectively (P < 0.001). Kaplan-Meier analysis revealed that pain recurred more often and later in the GKS group than in the MVD group (P < 0.001). CONCLUSIONS: Considering the long-term outcomes, MVD should be chosen as the initial surgical treatment for patients with medically refractory TN.

Diagnosis and management for trigeminal neuralgia caused solely by venous compression.

BACKGROUND: Trigeminal neuralgia (TN) caused solely by venous compression is uncommon. An appropriate vein management protocol for microvascular decompression (MVD) has not been established. We evaluated the management of veins for TN solely due to venous involvement. METHOD: We analyzed 31 patients with TN in whom only veins were manipulated during MVD. The culprit veins smaller in diameter than the vein of the cerebellopontine fissure (VCPF) were coagulated and divided in 20 patients (divided group), while transposition was performed for larger veins in the remaining 11 patients (non-divided group). Postoperative outcomes were assessed by Barrow Neurological Institute (BNI) pain intensity score and BNI facial numbness score. RESULTS: Preoperative contrast-enhanced T1 spoiled gradient recalled (SPGR) imaging exhibited higher detection rates for veins (93.5%) than non-contrast fast imaging employing a steady-state acquisition image (74.2%). The transverse pontine vein (TPV) was the most frequently involved vessel. All the divided veins were small TPVs except one. The non-divided group included seven cases of large TPVs and four involving the main trunk of the superior petrosal vein or its large tributaries. The median follow-up duration was 33 months. Pain relief was achieved immediately after the surgery in 28 (90.3%) and within a month in the remaining 3 (9.7%) patients. Numbness was present in seven (22.6%) patients at the final follow-up. Recurrence was observed in only two (10.0%) patients in the divided group compared with four (36.4%) patients in the non-divided group. Comparison at the final follow-up revealed that the divided group had superior outcome compared to the non-divided group. CONCLUSIONS: Contrast-enhanced T1 SPGR imaging is crucial to detect small veins in the preoperative diagnosis. Division of the culprit veins is recommended if the diameter is smaller than the VCPF as it provides a better outcome and lower recurrence rate than transposition.

Activation of mTOR signaling pathway is secondary to neuronal excitability in a mouse model of mesio-temporal lobe epilepsy.

Recent studies in animal models have suggested that the mammalian target of rapamycin (mTOR) signaling pathway is involved in several features of mesio-temporal lobe epilepsy (MTLE), and that its inhibition could have therapeutic interests. However, it remains controversial whether mTOR activation is the cause or the consequence of MTLE. We previously showed in a mouse model of MTLE associated with hippocampal sclerosis that increased neuronal excitability and brain-derived neurotrophic factor (BDNF) overexpression contribute to the development of morphological features of this form of epilepsy. Here, we addressed whether mTOR activation promotes MTLE epileptogenesis via increasing neuronal excitability and/or BDNF expression or rather mediates neuroplasticity associated with hippocampal sclerosis. In mice injected intrahippocampally with kainate (1 nmol), we showed a biphasic increase of phospho-S6 (p-S6) ribosomal protein expression, the downstream product of the mTOR signaling pathway, in the dispersed granule cell layer (GCL) of the dentate gyrus with a second phase lasting up to 6 months. Chronic treatment with rapamycin suppressed p-S6 expression, granule cell dispersion and mossy fiber sprouting, but did not reduce cell loss, BDNF overexpression, glutamic acid decarboxylase (GAD)67 expression or the development of hippocampal paroxysmal discharges. Neuronal inhibition by midazolam (2 × 10 mg/kg, i.p.) abolished the increased expression of p-S6 in the dispersed GCL. Our data suggest that activation of the mTOR signaling pathway results from the increased neuronal excitation that develops in the GCL and may contribute to MTLE morphological changes. However, these data do not support the role of this pathway in the development of MTLE or its inhibition as a therapy for this form of epilepsy.

Usefulness of immunohistochemical studies in diagnosing metachronous gallbladder and small intestinal metastases from lung cancer with gastrointestinal hemorrhage: a case report.

Isolated metachronous gastrointestinal metastases from advanced-stage lung cancer are rarely diagnosed on the basis of symptoms and resected. In this report, we present a case of resectable metachronous gallbladder and small intestinal metastases of lung cancer. An 86-year-old woman was treated for lung cancer with resection of the right inferior lobe. Five months after the surgery, she was re-admitted because of melena and anemia. Ultrasonography showed a gallbladder tumor with gastrointestinal hemorrhage, and laparoscopic-assisted cholecystectomy was subsequently performed. However, 2 months after this event, the patient presented again with melena and anemia and was diagnosed with a small intestinal tumor. Therefore, laparoscopic-assisted partial resection of the small intestine was performed. Immunohistochemical staining for thyroid transcription factor-1 and cytokeratin 7 confirmed that the two resected tumors were metachronous metastases of the primary lung cancer. The patient died of liver metastases 5 months after the last surgery. Our experience with this case suggests that surgical resection might not be curative but palliative for patients with isolated gallbladder and small intestinal metastases diagnosed on the basis of melena that is resistant to conservative treatment.

Asymmetric nature of two subunits of RAD18, a RING-type ubiquitin ligase E3, in the human RAD6A-RAD18 ternary complex.

RAD18, a RING-type ubiquitin ligase (E3) that plays an essential role in post-replication repair, possesses distinct domains named RING, UBZ, SAP and the RAD6-binding domain (R6BD) and forms a dimer. RAD6, an ubiquitin-conjugating enzyme (E2), stably associates with R6BD in the C-terminal portion. In this study, we established a method to distinguish between the two subunits of RAD18 by introduction of different tags, and analyzed mutant complexes. Our results, surprisingly, demonstrate that RAD6A and RAD18 form a ternary complex, RAD6A-(RAD18)(2) and the presence of only one R6BD in the two RAD18 subunits is sufficient for ternary complex formation and the ligase activity. Interestingly, ligase activity of a mutant dimer lacking both R6BDs is not restored even with large amounts of RAD6A added in solution, suggesting a requirement for precise juxtaposition via interaction with R6BD. We further show that mutations in both subunits of either RING or SAP, but not UBZ, strongly reduce ligase activity, although inactivation in only one of two subunits is without effect. These results suggest an asymmetric nature of the two RAD18 subunits in the complex.

En bloc transfer of polyubiquitin chains to PCNA in vitro is mediated by two different human E2-E3 pairs.

Post-replication DNA repair in eukaryotes is regulated by ubiquitination of proliferating cell nuclear antigen (PCNA). Monoubiquitination catalyzed by RAD6-RAD18 (an E2-E3 complex) stimulates translesion DNA synthesis, whereas polyubiquitination, promoted by additional factors such as MMS2-UBC13 (a UEV-E2 complex) and HLTF (an E3 ligase), leads to template switching in humans. Here, using an in vitro ubiquitination reaction system reconstituted with purified human proteins, we demonstrated that PCNA is polyubiquitinated predominantly via en bloc transfer of a pre-formed ubiquitin (Ub) chain rather than by extension of the Ub chain on monoubiquitinated PCNA. Our results support a model in which HLTF forms a thiol-linked Ub chain on UBC13 (UBC13∼Ubn) and then transfers the chain to RAD6∼Ub, forming RAD6∼Ubn+1. The resultant Ub chain is subsequently transferred to PCNA by RAD18. Thus, template switching may be promoted under certain circumstances in which both RAD18 and HLTF are coordinately recruited to sites of stalled replication.

Early effect of dutasteride added to alpha-1 blocker therapy for patients with lower urinary tract symptoms associated with benign prostatic hyperplasia.

OBJECTIVE: To investigate the hypothesis that 5-alpha-reductase inhibitors exert early ameliorative effects on voiding and storage symptoms in men with lower urinary tract symptom-associated benign prostatic hyperplasia. METHODS: This was a prospective study involving the participation of eight outpatient clinics in Chiba Prefecture, Japan. The patients received dutasteride (0.5 mg) once daily orally for 24 weeks as an add-on to their ongoing therapy with an alpha-1 blocker. The study patients recorded their urinary symptoms every day for 14 days after starting dutasteride. The International Prostate Symptom Score, prostate volume, uroflowmetry results, and residual urine volume were checked at 3 and 6 months after starting dutasteride. RESULTS: A total of eighty-eight patients participated in the present study; 74 were eligible for analysis of the early effects of dutasteride. The median age was 69.6 years (range 54-89), the median prostate volume was 50.3 mL (range 24.7-103.3) and the median International Prostate Symptom Score was 17.6 (range 8-35). The proportion of patients with International Prostate Symptom Score improvements (≥3 points, or ≥25%) or 3 points or more decreased International Prostate Symptom Score were defined effective, 37 (50.0%) and 47 (63.5%) experienced improvement at 1 month after administration, respectively. CONCLUSION: This is the first prospective clinical study to show the early beneficial effects of 5-alpha-reductase inhibitors for lower urinary tract symptom-associated benign prostatic hyperplasia. Patients with severe symptoms were found to be responsive to dutasteride. The influence of the placebo effect was not denied. Further study is necessary.

Successful ablation of atypical atrioventricular nodal reentrant tachycardia from a noncoronary sinus of Valsalva.

An 81-year-old man with long RP narrow QRS tachycardia underwent catheter ablation. Ventricular pacing reset the atrial cycle over a retrograde slow pathway, followed by termination of the tachycardia without atrial capture, confirming the diagnosis of fast-slow atrioventricular nodal reentrant tachycardia (AVNRT). The earliest atrial activation during tachycardia was found in the noncoronary sinus of Valsalva, where the first delivery of radiofrequency energy terminated and eliminated the inducibility of the tachycardia, by retrograde conduction block over the slow pathway. This is the first report of a fast-slow AVNRT, with successful ablation of the slow pathway from a noncoronary sinus of Valsalva.

White and Gray Matter Abnormality in Burning Mouth Syndrome Evaluated with Diffusion Tensor Imaging and Neurite Orientation Dispersion and Density Imaging.

PURPOSE: Burning mouth syndrome (BMS) is defined by a burning sensation or pain in the tongue or other oral sites despite the presence of normal mucosa on inspection. Both psychiatric and neuroimaging investigations have examined BMS; however, there have been no analyses using the neurite orientation dispersion and density imaging (NODDI) model, which provides detailed information of intra- and extracellular microstructures. Therefore, we performed voxel-wise analyses using both NODDI and diffusion tensor imaging (DTI) models and compared the results to better comprehend the pathology of BMS. METHODS: Fourteen patients with BMS and 11 age- and sex-matched healthy control subjects were prospectively scanned using a 3T-MRI machine using 2-shell diffusion imaging. Diffusion tensor metrics (fractional anisotropy [FA], mean diffusivity [MD], axial diffusivity [AD], and radial diffusivity [RD]) and neurite orientation and dispersion index metrics (intracellular volume fraction [ICVF], isotropic volume fraction [ISO], and orientation dispersion index [ODI]) were retrieved from diffusion MRI data. These data were analyzed using tract-based spatial statistics (TBSS) and gray matter-based spatial statistics (GBSS). RESULTS: TBSS analysis showed that patients with BMS had significantly higher FA and ICVF and lower MD and RD than the healthy control subjects (family-wise error [FWE] corrected P < 0.05). Changes in ICVF, MD, and RD were observed in widespread white matter areas. Fairly small areas with different FA were included. GBSS analysis showed that patients with BMS had significantly higher ISO and lower MD and RD than the healthy control subjects (FWE-corrected P < 0.05), mainly limited to the amygdala. CONCLUSION: The increased ICVF in the BMS group may represent myelination and/or astrocytic hypertrophy, and microstructural changes in the amygdala in GBSS analysis indicate the emotional-affective profile of BMS.

Genotype-relevant neuroimaging features in low-grade epilepsy-associated tumors.

Introduction: Low-grade epilepsy-associated tumors are the second most common histopathological diagnoses in cases of drug-resistant focal epilepsy. However, the connection between neuroimaging features and genetic alterations in these tumors is unclear, prompting an investigation into genotype-relevant neuroimaging characteristics. Methods: This study retrospectively analyzed neuroimaging and surgical specimens from 46 epilepsy patients with low-grade epilepsy-associated neuroepithelial tumors that had genetic mutations identified through panel sequencing to investigate their relationship to genotypes. Results: Three distinct neuroimaging groups were established: Group 1 had indistinct borders and iso T1-weighted and slightly high or high T2-weighted signal intensities without a diffuse mass effect, associated with 93.8% sensitivity and 100% specificity to BRAF V600E mutations; Group 2 exhibited sharp borders and very or slightly low T1-weighted and very high T2-weighted signal intensities with a diffuse mass effect and 100% sensitivity and specificity for FGFR1 mutations; and Group 3 displayed various characteristics. Histopathological diagnoses including diffuse low-grade glioma and ganglioglioma showed no clear association with genotypes. Notably, postoperative seizure-free rates were higher in Group 1 tumors (BRAF V600E) than in Group 2 tumors (FGFR1). Discussion: These findings suggest that tumor genotype may be predicted by neuroimaging before surgery, providing insights for personalized treatment approaches.

Multimodal imaging analyses in neuromyelitis optica spectrum disorder with or without visual disturbance.

BACKGROUND AND PURPOSE: Neuromyelitis optica spectrum disorder is a demyelinating and inflammatory affliction that often leads to visual disturbance. Various imaging techniques, including free-water imaging, have been used to determine neuroinflammation and degeneration. Therefore, this study aimed at determining multimodal imaging differences between patients with neuromyelitis optica spectrum disorder, especially those with visual disturbance, and healthy controls. MATERIALS AND METHODS: Eighty-five neuromyelitis optica spectrum disorder patients and 89 age- and sex-matched healthy controls underwent 3-T magnetic resonance imaging (MRI). We analyzed adjusted brain-predicted age difference, voxel-based morphometry, and free-water-corrected diffusion tensor imaging (DTI) by tract-based spatial statistics in each patient group (MRI-positive/negative neuromyelitis optica spectrum disorder patients with or without a history of visual disturbance) compared with the healthy control group. RESULTS: MRI-positive neuromyelitis optica spectrum disorder patients exhibited reduced volumes of the bilateral thalamus. Tract-based spatial statistics showed diffuse white matter abnormalities in all DTI metrics in MRI-positive neuromyelitis optica spectrum disorder patients with a history of visual disturbance. In MRI-negative neuromyelitis optica spectrum disorder patients with a history of visual disturbance, voxel-based morphometry showed volume reduction of bilateral thalami and optic radiations, and tract-based spatial statistics revealed significantly lower free-water-corrected fractional anisotropy and higher mean diffusivity in the posterior dominant distributions, including the optic nerve radiation. CONCLUSION: Free-water-corrected DTI and voxel-based morphometry analyses may reflect symptoms of visual disturbance in neuromyelitis optica spectrum disorder.

Phosphorylation by aurora kinase A induces Mdm2-mediated destabilization and inhibition of p53.

Aurora kinase A (also called STK15 and BTAK) is overexpressed in many human cancers. Ectopic overexpression of aurora kinase A in mammalian cells induces centrosome amplification, chromosome instability and oncogenic transformation, a phenotype characteristic of loss-of-function mutations of p53. Here we show that aurora kinase A phosphorylates p53 at Ser315, leading to its ubiquitination by Mdm2 and proteolysis. p53 is not degraded in the presence of inactive aurora kinase A or ubiquitination-defective Mdm2. Destabilization of p53 by aurora kinase A is abrogated in the presence of mutant Mdm2 that is unable to bind p53 and after repression of Mdm2 by RNA interference. Silencing of aurora kinase A results in less phosphorylation of p53 at Ser315, greater stability of p53 and cell-cycle arrest at G2-M. Cells depleted of aurora kinase A are more sensitive to cisplatin-induced apoptosis, and elevated expression of aurora kinase A abolishes this response. In a sample of bladder tumors with wild-type p53, elevated expression of aurora kinase A was correlated with low p53 concentration. We conclude that aurora kinase A is a key regulatory component of the p53 pathway and that overexpression of aurora kinase A leads to increased degradation of p53, causing downregulation of checkpoint-response pathways and facilitating oncogenic transformation of cells.