Risk factors of postoperative trigeminal neuropathy in surgical treatment of trigeminal schwannomas.

OBJECTIVE: Trigeminal schwannomas are rare benign tumors originating from the Schwann cells of the trigeminal nerve. Despite the common occurrence of trigeminal neuropathy in trigeminal schwannomas, a detailed analysis has not yet been performed because of the rarity of this disease. This study aimed to analyze trigeminal neuropathy in trigeminal schwannoma resection and identify the risk factors for postoperative worsening of trigeminal neuropathy. METHODS: A retrospective analysis of 86 surgical cases was performed at our institution between 1975 and 2018. Obtained parameters included age, sex, diagnosis, reoperation, tumor size, tumor location, presence or absence of cysts, surgical approach, degree of tumor removal, and pre/postoperative trigeminal neuropathy. Uni- and multivariate analyses were performed to identify the risk factors for worsening postoperative sensory disturbances. RESULTS: Of 83 patients, 58.1% had preoperative trigeminal neuropathy. Postoperative sensory disturbance occurred in 27.9%, with worsening in two cases and de novo symptoms in 22 cases. Regarding risk factors for worsening postoperative sensory disturbances, older age, smaller tumor size, middle and posterior (MP) type, gross total removal (GTR), and anterior transpetrosal approach were identified in the univariate analysis, while MP type and GTR were identified in the multivariate analysis. CONCLUSIONS: This study analyzed trigeminal neuropathy in trigeminal schwannomas in detail and identified tumor location and removal rate as risk factors for worsening postoperative sensory disturbances. Treatment strategies to reduce the risk of trigeminal neuropathy should be considered.

[Durable remission with lenalidomide in a patient with early relapse of adult T-cell leukemia/lymphoma after cord blood transplantation].

A 62-year-old woman with adult T-cell leukemia/lymphoma (ATL) received umbilical cord blood transplantation (CBT) in first complete remission. However, relapse of ATL was detected on day 74 post-transplantation, as evidenced by the rapid growth of lymphoma cells in peripheral blood and an increase in soluble interleukin-2 receptor (sIL2R) levels. Discontinuation of immunosuppressant therapy alone did not improve ATL findings, but treatment with lenalidomide caused lymphoma cells to disappear from the peripheral blood and sIL2R levels to return to normal. Pancytopenia was observed as a lenalidomide-associated adverse effect, but lymphocyte counts were not reduced. The patient was judged to be in complete remission based on results of Southern blot analysis and human T-cell leukemia virus 1 (HTLV-1)-infected cell analysis using flow cytometry (HAS-Flow). Flow cytometric analysis of peripheral blood and FISH analysis of X and Y chromosomes revealed that the therapeutic effect of lenalidomide was associated with an increase in the number of donor-derived peripheral natural killer cells. ATL relapse was not observed at 13 months into lenalidomide treatment. Our results suggest that lenalidomide is an effective option for the treatment of post-transplant relapsed ATL.

[Molecular Mechanisms of Pituitary Tumorigenesis].

Scientific advances have improved our understanding of the molecular pathological mechanisms underlying pituitary tumorigenesis, allowing us to analyze tumors in a more precise manner and to identify the tumors that have a greater risk of aggressive behavior at an earlier stage. Based on these molecular pathological findings, the classification of pituitary tumors has been revised over the last two decades to better describe their biological and clinical behavior and to identify prognostic markers of aggressiveness and poor prognosis. Understanding pituitary tumors at the molecular level has enabled increasingly targeted treatments with safety and efficacy validated in randomized trials. This paper reviews recent advances in the study of pituitary tumors, particularly pituitary endocrine tumors, and craniopharyngiomas, and describes potential therapies for pituitary tumors.

Intergenerational concordance of brain structure between depressed mothers and their never-depressed daughters.

AIM: Parents have significant genetic and environmental influences, which are known as intergenerational effects, on the cognition, behavior, and brain of their offspring. These intergenerational effects are observed in patients with mood disorders, with a particularly strong association of depression between mothers and daughters. The main purpose of our study was to investigate female-specific intergenerational transmission patterns in the human brain among patients with depression and their never-depressed offspring. METHODS: We recruited 78 participants from 34 families, which included remitted parents with a history of depression and their never-depressed biological offspring. We used source-based and surface-based morphometry analyses of magnetic resonance imaging data to examine the degree of associations in brain structure between four types of parent-offspring dyads (i.e. mother-daughter, mother-son, father-daughter, and father-son). RESULTS: Using independent component analysis, we found a significant positive correlation of gray matter structure between exclusively the mother-daughter dyads within brain regions located in the default mode and central executive networks, such as the bilateral anterior cingulate cortex, posterior cingulate cortex, precuneus, middle frontal gyrus, middle temporal gyrus, superior parietal lobule, and left angular gyrus. These similar observations were not identified in other three parent-offspring dyads. CONCLUSIONS: The current study provides biological evidence for greater vulnerability of daughters, but not sons, in developing depression whose mothers have a history of depression. Our findings extend our knowledge on the pathophysiology of major psychiatric conditions that show sex biases and may contribute to the development of novel interventions targeting high-risk individuals.

Endoscopic Endonasal Reconstruction Using a Pedicled Middle Turbinate Flap for Spontaneous Cerebrospinal Fluid Rhinorrhea.

ABSTRACT: Although endoscopic skull-base reconstruction protocols to reduce cerebrospinal fluid (CSF) leakage are reported, the most effective management strategies have not been determined. We describe the successful repair of a spontaneous CSF leak using a vascularized middle turbinate flap (MTF) via an endonasal endoscopic approach and also discuss the effective reconstruction with other available pedicled flaps. An 11-year-old girl had a 5-month history of intermittent CSF rhinorrhea. Endoscopic endonasal skull base reconstruction was performed using the pedicled MTF technique, which sufficiently covered the unilateral cribriform plate and ethmoidal fovea including suspicious leakage site. Middle turbinate flaps may be good for repairing spontaneous CSF leaks, which commonly have small, low-flow CSF fistulas around a cribriform plate. As spontaneous CSF leaks are known to have a higher recurrence rate, MTF may be advantageous because more of the normal structures are retained.

Quantitative Analysis of Mobile Proteins in Normal Brain Tissue by Amide Proton Transfer Imaging: Age Dependence and Sex Differences.

PURPOSE: The aims of this study were to evaluate the relationship between age change and amide proton transfer (APT) signal in each region of the whole brain and to derive the standard value of APT signal in each brain region of normal adults. MATERIALS AND METHODS: Using the mDIXON 3-dimensional-APT sequence of the fast spin echo method, an APT image was obtained. In total, 60 patients (mean age, 49.8 ± 16.9 years) with no abnormal findings on magnetic resonance imaging data were included. For image analysis, registration parameters were created using the FMRIB Software Library 5.0.11, and then a region of interest was set in the Montreal Neurological Institute structural atlas for analysis. Statistical analyses were performed using the age-dependent and sex differences in APT signals from each brain region. RESULTS: No significant correlation was seen between APT signal and age and sex in all brain regions. CONCLUSION: Under the APT imaging parameter conditions used in this study, local brain APT signals in healthy adults are independent of age and sex.

Correction to: Clinical and histopathological analyses of VEGF receptors peptide vaccine in patients with primary glioblastoma - a case series.

Following publication of the original article [1], the authors reported an error in the author group.

Clinical and histopathological analyses of VEGF receptors peptide vaccine in patients with primary glioblastoma - a case series.

BACKGROUND: The expression of vascular endothelial growth factor (VEGF)-A/ VAGF receptors (VEGFRs) signaling plays a pivotal role in the tumor angiogenesis and the development of the immunosuppressive tumor microenvironment in glioblastomas. We have previously conducted exploratory clinical studies investigating VEGFRs peptide vaccination with and without multiple glioma oncoantigens in patients with recurrent high-grade gliomas. Recently, an exploratory clinical investigation of VEGFRs peptide vaccination was conducted in patients with progressive neurofibromatosis type 2. Those studies suggested that cytotoxic T lymphocytes (CTLs) induced by the vaccination can directly kill a wide variety of cells associated with tumor growth, including tumor vessels, tumor cells, and immunosuppressive cells expressing VEGFR1 and/or 2. In the present study, synergistic activity of the combination of VEGFRs peptide vaccination with chemotherapy was evaluated. METHODS: We performed the first clinical trial to assess VEGFR1 and 2 vaccination along with temozolomide (TMZ) -based chemoradiotherapy for the patients with primary glioblastomas. Furthermore, histopathological changes after the vaccination were evaluated using paired pre- and post- vaccination specimens. RESULTS: The disappearance of radiographically enhanced lesion was observed in 2 patients after the vaccination, including one in which the methylation of the O6-methylguanine-DNA methyltransferase (MGMT) promoter was not observed. The histopathological findings of pre- and post-vaccination specimens demonstrated that tumor vessels showed negative or slight VEGFRs expressions after the vaccination and most endothelial cells were covered with PDGFR-ß-positive pericytes. Notably, CTLs induced by VEGFRs peptide vaccination attacked not only tumor vessels but also tumor cells and regulatory T cells expressing VEGFRs even in recurrent tumors. CONCLUSIONS: VEGFR1 and 2 vaccination may have a preliminary synergistic effect when administered with TMZ. The limitation of the present study was the paucity of the number of the samples. Further studies involving more patients are warranted to confirm the findings of this study. TRIAL REGISTRATION: This study was registered as UMIN000013381 (University Hospital Medical Information Network-Clinical Trial Registry: UMIN-CTR) on 5 March, 2014 and with the Japan Registry of Clinical Trials (jRCT) as jRCTs031180170 on 1 March, 2019.

MRI evaluation of motor function recovery by rTMS and intensive occupational therapy and changes in the activity of motor cortex.

Purpose/aim: An intervention that combines low-frequency repetitive transcranial magnetic stimulation and intensive occupational therapy can improve brain function in post-stroke patients with motor paralysis. The purpose of the present study is examined motor function recovery by repetitive transcranial magnetic stimulation and intensive occupational therapy and changes in the activity of motor cortex based on magnetic resonance imaging data.Materials and methods: In total, we assessed 30 patients with post-stroke upper extremity paralysis who were hospitalized for 12 sessions of low-frequency repetitive transcranial magnetic stimulation over the lesion-free hemisphere plus daily occupational therapy for 15 days. Imaging analysis was performed using 3-dimensional T1-weighted image and functional magnetic resonance imaging. Hemispheric dominance was assessed by functional magnetic resonance imaging using the laterality index. In addition, Seed-based functional connectivity analysis was used to evaluate functional connectivity between the precentral gyrus of the affected side and other areas.Results: A positive correlation was found between laterality index before intervention and the Brunnstrom recovery stage for hand/fingers (p < 0.05). The intervention resulted in significantly higher functional connectivity between the precentral gyrus of the affected side and that of the healthy side (false discovery rate corrected p < 0.05).Conclusions: We clarified that the recovery of motor function by intervention with low-frequency repetitive transcranial magnetic stimulation and occupational therapy and the increase of functional connectivity between the precentral gyrus on the affected side and the healthy side are related. These results facilitate prognostic predictions and evidence-based medical care.

Ventricular volumetry and free-water corrected diffusion tensor imaging of the anterior thalamic radiation in idiopathic normal pressure hydrocephalus.

BACKGROUND AND PURPOSE: The pathophysiology of idiopathic normal pressure hydrocephalus (iNPH) has not been completely clarified. We investigated the brain structure in iNPH using automatic ventricular volumetry, single-tensor diffusion tensor imaging (DTI) and bi-tensor free-water (FW) imaging analyses while focusing on cognitive impairments before and after lumboperitoneal shunt surgery. MATERIALS AND METHODS: This retrospective study included 12 iNPH patients with structural magnetic resonance imaging (MRI) and diffusion MRI (dMRI) on a 3T-MRI scanner who underwent neuropsychological assessments before and after shunting and 8 healthy controls. Ventricular volumetry was conducted on structural MRI datasets using FreeSurfer. Ventricular volume was compared pre- and postoperatively. Correlation analyses were performed between ventricular volume or volume change and neuropsychological scores or score change. Tract-based spatial statistics were performed using dMRI datasets for group analyses between iNPH and controls and between pre- and post-surgery iNPH patients and for correlation analyses using neuropsychological scores. Tract-specific analyses were performed in the anterior thalamic radiation (ATR), followed by comparison and correlation analyses. RESULTS: The third ventricular volume was significantly decreased after shunting; its volume reduction negatively correlated with a neuropsychological improvement. Compared with controls, iNPH patients had lower fractional anisotropy and higher axial, radial, and mean diffusivities, and FW in the periventricular white matter including ATR, resulting in no difference in FW-corrected indices. Single-tensor DTI indices partially correlated with neuropsychological improvements, while FW-corrected indices had no correlations. CONCLUSION: Third ventricle enlargement is possibly linked to cognitive impairment and FW imaging possibly provides better white matter characterization in iNPH.

Unraveling Specific Brain Microstructural Damage in Moyamoya Disease Using Diffusion Magnetic Resonance Imaging and Positron Emission Tomography.

BACKGROUND AND PURPOSE: Chronic ischemia may induce brain microstructural damage and lead to neurocognitive dysfunction in patients with Moyamoya disease (MMD). We applied neurite orientation dispersion and density imaging (NODDI) and 15O-gas positron emission tomography (PET) to elucidate the specific ischemic brain microstructural damage of MMD in the cortex and the white matter. MATERIALS AND METHODS: Thirty-one patients (16-63years old, 9 males) and 20 age- and sex-matched normal controls were enrolled in this study. NODDI evaluates quantitative parameters reflecting neurite and axonal density, network complexity and the interstitial fluid in all participants. Of 31 patients, 12 newly diagnosed patients were evaluated with PET, also. We evaluated correlations between the microstructural parameters of NODDI and the hemodynamic and metabolic parameters of PET, the relationship between NODDI and clinical severity of each hemisphere (Normal, Asymtpomatic, Symptomatic, and Infarcted) as well as neurocognitive performance. RESULTS: All NODDI parameters significantly correlated with PET parameters (absolute r = 0.46-0.83, P ≤ .048) and clinical severity (P < .001), suggesting that neurite and axonal density and network complexity decreased, and the interstitial fluid increased, as the ischemic burden became severe. NODDI parameters reflecting neurite and axonal density and network complexity significantly correlated with neurocognitive profiles (r = 0.36-0.64, P ≤ .048), but the interstitial fluid component did not. CONCLUSIONS: Chronic ischemia in patients with MMD may induce decreased neurite and axonal density, simplified network complexity, and may lead to neurocognitive dysfunction. The increased interstitial fluid accompanying hemodynamic impairment may not be identical to the decreased neurite density and might be driven by another mechanism.

[Acute myeloid leukemia with sudden onset bilateral lower extremity paralysis caused by disseminated mucormycosis following unrelated bone marrow transplantation].

A 63-year-old woman was admitted to our hospital with relapsed acute myeloid leukemia. On day10 after reinduction therapy, she became febrile. Computed tomography on day15 revealed right upper lobe consolidation. Because the ß-D glucan and Aspergillus galactomannan antigen tests were negative, we considered pulmonary mucormycosis as a breakthrough infection under voriconazole administration. Liposomal amphotericin B was initiated, and the patient underwent unrelated bone marrow transplantation although not in complete remission. She developed right shoulder pain on day1, and her pneumonia worsened on day3. She reported right lower extremity paralysis on day15, and developed bilateral lower extremity motor and sensory paralysis the next day. T2-enhanced magnetic resonance imaging revealed hyperdense lesions in the spinal cord at Th11. Transverse myelitis was diagnosed, and she underwent antiviral therapy. After engraftment, she died of pneumonia on day24. Postmortem examination revealed disseminated mucormycosis involving the lungs, liver, diaphragm, blood vessels, and dura matter of the spinal cord; it also revealed that the sudden bilateral lower extremity paralysis was caused by disseminated mucormycosis. This case stresses the possibility of mucormycosis, particularly in prolonged neutropenic patients with pain, fever, and focal neurological findings.

Microstructural Damage in Normal-Appearing Brain Parenchyma and Neurocognitive Dysfunction in Adult Moyamoya Disease.

Background and Purpose -Microstructural damage in the brain induced by chronic ischemia is suggested to play a pivotal role in the neurocognitive dysfunction of adults with Moyamoya disease (MMD). We investigated specific changes in the brain microstructure and their correlations with neurocognitive dysfunction in patients with MMD using a multishell diffusion magnetic resonance imaging technique called neurite orientation dispersion and density imaging. Methods- We evaluated 26 patients with MMD (16-63 years old, 20 females) and 20 age- and sex-matched normal volunteers using neurite orientation dispersion and density imaging and neuropsychological batteries. Neurite orientation dispersion and density imaging calculates 2 parameters: the intracellular volume fraction (Vic), which reflects the axon density in the white matter and dendrite density in the cortex, and the orientation dispersion index (OD), which reflects the network complexity. The microstructural damage and its correlation with neurocognitive performance were evaluated by performing a whole-brain analysis using SPM12 and correlation analysis with regional values. Results- Patients with MMD had significantly lower Vic in the white matter and a lower OD mainly in the cortex than those of the controls ( P<0.001, family-wise error corrected). Of all neuropsychological scores, Processing Speed Index (PS) exhibited the strongest correlation with Vic in the white matter ( P<0.001, family-wise error corrected). The Vic and OD values for regions with group differences, including both temporoparietal and frontal areas, correlated with neurocognitive performance (absolute r=0.37-0.64; P<0.01). Conclusions- Chronic ischemia in MMD may decrease the axon density in the white matter and dendrite density in the cortex (Vic) and simplify network complexity (OD), leading to neurocognitive dysfunction. Processing Speed Index may be the most sensitive index used to evaluate the ischemic burden, and the posterior part of the brain may play an important role in neurocognitive function. Clinical Trial Registration- URL: http://www.umin.ac.jp/ctr/ . Unique identifier: UMIN000023082.

Diffusion Tensor Imaging Evaluation of Neural Network Development in Patients Undergoing Therapeutic Repetitive Transcranial Magnetic Stimulation following Stroke.

We aimed to investigate plastic changes in cerebral white matter structures using diffusion tensor imaging following a 15-day stroke rehabilitation program. We compared the detection of cerebral plasticity between generalized fractional anisotropy (GFA), a novel tool for investigating white matter structures, and fractional anisotropy (FA). Low-frequency repetitive transcranial magnetic stimulation (LF-rTMS) of 2400 pulses applied to the nonlesional hemisphere and 240 min intensive occupation therapy (OT) daily over 15 days. Motor function was evaluated using the Fugl-Meyer assessment (FMA) and Wolf Motor Function Test (WMFT). Patients underwent diffusion tensor magnetic resonance imaging (MRI) on admission and discharge, from which bilateral FA and GFA values in Brodmann area (BA) 4 and BA6 were calculated. Motor function improved following treatment (p < 0.001). Treatment increased GFA values for both the lesioned and nonlesioned BA4 (p < 0.05, p < 0.001, resp.). Changes in GFA value for BA4 of the lesioned hemisphere were significantly inversely correlated with changes in WMFT scores (R2 = 0.363, p < 0.05). Our findings indicate that the GFA may have a potentially more useful ability than FA to detect changes in white matter structures in areas of fiber intersection for any such future investigations.

Vertebrobasilar Dolichoectasia Causing Symptomatic Hydrocephalus Due to Third Ventricular Compression.

Vertebrobasilar dolichoectasia sometimes presents with symptoms related to mass effect like cranial nerve palsies, or with ischemia or hemorrhage. Symptomatic hydrocephalus as a complication of vertebrobasilar dolichoectasia is extremely uncommon. Furthermore, there are few cases of vertebrobasilar dolichoectasia, in which cerebrospinal fluid flow disorder mechanisms are clearly demonstrated in neuroimaging findings. Here, we describe a patient with vertebrobasilar dolichoectasia who presented with symptomatic hydrocephalus due to direct compression against the third ventricle, which was immediately relieved by ventriculoperitoneal shunt. This patient exhibited a progressive clinical course of acute hydrocephalus; however, a subclinical ventricular dilatation may have been present before the onset. Therefore, a careful follow-up is warranted to treat symptomatic hydrocephalus that may develop in patients with vertebrobasilar dolichoectasia.

Gray Matter Abnormalities in Idiopathic Parkinson's Disease: Evaluation by Diffusional Kurtosis Imaging and Neurite Orientation Dispersion and Density Imaging.

Mapping gray matter (GM) pathology in Parkinson's disease (PD) with conventional MRI is challenging, and the need for more sensitive brain imaging techniques is essential to facilitate early diagnosis and assessment of disease severity. GM microstructure was assessed with GM-based spatial statistics applied to diffusion kurtosis imaging (DKI) and neurite orientation dispersion imaging (NODDI) in 30 participants with PD and 28 age- and gender-matched controls. These were compared with currently used assessment methods such as diffusion tensor imaging (DTI), voxel-based morphometry (VBM), and surface-based cortical thickness analysis. Linear discriminant analysis (LDA) was also used to test whether subject diagnosis could be predicted based on a linear combination of regional diffusion metrics. Significant differences in GM microstructure were observed in the striatum and the frontal, temporal, limbic, and paralimbic areas in PD patients using DKI and NODDI. Significant correlations between motor deficits and GM microstructure were also noted in these areas. Traditional VBM and surface-based cortical thickness analyses failed to detect any GM differences. LDA indicated that mean kurtosis (MK) and intra cellular volume fraction (ICVF) were the most accurate predictors of diagnostic status. In conclusion, DKI and NODDI can detect cerebral GM abnormalities in PD in a more sensitive manner when compared with conventional methods. Hence, these methods may be useful for the diagnosis of PD and assessment of motor deficits. Hum Brain Mapp 38:3704-3722, 2017. © 2017 Wiley Periodicals, Inc.

Glymphatic system dysfunction in mood disorders: Evaluation by diffusion magnetic resonance imaging.

The glymphatic system, an expansive cerebral waste-disposal network, harbors myriad enigmatic facets necessitating elucidation of their nexus with diverse pathologies. Murine investigations have revealed a relationship between the glymphatic system and affective disorders. This study aimed to illuminate the interplay between bipolar disorder and the glymphatic system. Fifty-eight individuals afflicted with bipolar disorder were identified through meticulous psychiatric assessment. These individuals were juxtaposed with a cohort of 66 comparably aged and sex-matched, mentally stable subjects. Subsequent analysis entailed the application of covariance analysis to evaluate along with the perivascular space (ALPS) index, a novel magnetic resonance imaging method for assessing brain interstitial fluid dynamics via diffusion tensor imaging within the bipolar and control cohorts. We also evaluated the correlation between the ALPS index and clinical parameters, which included the Hamilton Depression scale scores, disease duration, and other clinical assessments. Moreover, partial correlation analyses, incorporating age and sex as covariates, were performed to investigate the relationships between the ALPS index and clinical measures within the two cohorts. A noteworthy adverse correlation was observed between the ALPS index and illness duration. A free-water imaging analysis revealed a substantial elevation in the free-water index within the white-matter tracts, prominently centered on the corpus callosum, within the bipolar cohort relative to that in the control group. In analogous cerebral regions, a conspicuous affirmative correlation was observed between the free-water-corrected radial diffusivity and depression rating scales. Our results showed that the protracted course of bipolar disorder concomitantly exacerbated glymphatic system dysregulation.

The Role of Genetic Analysis in Distinguishing Multifocal and Multicentric Glioblastomas: An Illustrative Case.

Introduction: Glioblastomas can manifest as multiple, simultaneous, noncontiguous lesions. We genetically analyzed multiple glioblastomas and discuss their etiological origins in this report. Case Presentation: We present the case of a 47-year-old woman who presented with memory impairment and left partial paralysis. Radiographic imaging revealed three apparently noncontiguous lesions in the right temporal and parietal lobes extending into the corpus callosum, leading to diagnosis of multicentric glioblastomas. All three lesions were excised. Genetic analysis of the lesions revealed a TERT promoter C228T mutation, a roughly equivalent amplification of EGFR, and homozygous deletion of CDKN2A/B exclusively in the two contrast-enhanced lesions. Additionally, the contrast-enhanced lesions exhibited the same two-base pair mutations of PTEN, whereas the non-enhanced lesion showed a partially distinct 13-base pair mutation. The other genetic characteristics were consistent. Rather than each having arisen de novo, we believe that they had developed by infiltration and are therefore best classified as multifocal glioblastomas. Conclusion: Our findings underscore anew the possibility of infiltration by glioblastomas, even within regions devoid of signal alterations on T2-weighted images or fluid-attenuated inversion recovery images. Genetic analysis can play a crucial role in differentiating whether multiple glioblastomas are multifocal or multicentric.