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Purpose: This study identified the factors affecting cerebral microbleed (CMBs) development. Moreover, their effects on intelligence and memory and association with stroke in patients with germinoma who had long-term follow-up were evaluated., Methods: This study included 64 patients with germinoma who were histologically and clinically diagnosed with and treated for germinoma. These patients were evaluated cross-sectionally, with a focus on CMBs on susceptibility-weighted magnetic resonance imaging (SWI), brain atrophy assessed through volumetric analysis, and intelligence and memory., Results: The follow-up period was from 32 to 412 (median: 175.5) months. In total, 43 (67%) patients had 509 CMBs and 21 did not have CMBs. Moderate correlations were observed between the number of CMBs and time from initial treatments and recurrence was found to be a risk factor for CMB development. Increased temporal CMBs had a marginal effect on the processing speed and visual memory, whereas brain atrophy had a statistically significant effect on verbal, visual, and general memory and a marginal effect on processing speed. Before SWI acquisition and during the follow-up periods, eight strokes occurred in four patients. All of these patients had ≥ 15 CMBs on SWI before stroke onset. Meanwhile, 33 patients with < 14 CMBs or 21 patients without CMBs did not experience stroke., Conclusion: Patients with a longer time from treatment initiation had a higher number of CMBs, and recurrence was a significant risk factor for CMB development. Furthermore, brain atrophy had a stronger effect on memory than CMBs. Increased CMBs predict the stroke onset., (© 2024. The Author(s).)

Introduction: Pareidolia, a form of visual illusions phenomenologically similar to complex visual hallucinations, is a phenomenon that is associated with visual hallucinations in dementia with Lewy bodies (DLB). This study aimed to identify commonalities and differences in behavioral and neural correlates between pareidolic illusions and visual hallucinations in DLB., Methods: Forty-three patients with DLB underwent the scene pareidolia test, which evokes and measures pareidolic illusions, and standardized neuropsychological and behavioral assessments. Regional cerebral blood flow (rCBF) was measured by single-photon emission computed tomography. Factor analysis was performed to assess the relationships among pareidolic illusions, cognitive functions, and behavioral symptoms. Partial least squares correlation analysis was used to investigate the relationship between these symptoms and rCBF., Results: Factor analysis yielded three behavior factors: the first factor (hallucinations/fluctuations) consisted of pareidolic illusions, visual hallucinations, and fluctuating cognition; the second factor (general cognitive function) consisted of general cognitive function and working memory; and the third factor (visual processing) consisted of visual processing and pareidolic illusions. Partial least squares correlation analysis identified two brain-behavior correlation patterns: (1) rCBF reduction in the frontal and perisylvian/periventricular regions was associated with lower general cognitive function and lower visual processing; and (2) rCBF reduction in the bilateral occipitotemporal cortex was associated with more severe hallucinations/fluctuations and lower visual processing., Conclusions: At the behavioral level, pareidolic illusions are associated with visual hallucinations, fluctuating cognition, and visual processing in DLB. At the neural level, pareidolic illusions may arise from the synergistic effects of global neuropathological changes and occipitotemporal cortical dysfunctions., Competing Interests: Declaration of competing interest Nothing to report., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

This study investigated the effectiveness and safety of low-dose salvage craniospinal irradiation (CSI) for recurrent germinoma. We retrospectively reviewed long-term tumor control and late adverse effects in 15 recurrent germinoma patients treated at our hospital between 1983 and 2019. Following the first recurrence of germinoma, seven were treated with 24-30 Gy of salvage CSI, three underwent non-CSI, and five were treated with only chemotherapy. CSI achieved a significantly better recurrence-free survival rate after the first recurrence compared to other strategies (100% vs 33%, p < 0.001: log-rank test). To evaluate the safety of salvage CSI, we assessed the outcomes at the final follow-up of seven patients who received salvage CSI at first recurrence and three patients who received salvage CSI at second recurrence. The median follow-up period was 220 months after initial treatment. Five patients who received 40-50 Gy of radiation therapy or underwent multiple radiation therapy before salvage CSI were classified into Group A, whereas five patients treated with platinum-based chemotherapy and 24-32 Gy of radiation therapy to the primary site, whole ventricle, or whole brain were classified into Group B. In Group A, one had endocrine dysfunction and the other had visual dysfunction. None were socially independent. Meanwhile, in Group B, no endocrine or visual dysfunction was found, and three patients were socially independent. Salvage CSI achieved excellent tumor control in recurrent germinoma and was safe in patients initially treated with low-dose radiation therapy and chemotherapy., (© The Author(s) 2023. Published by Oxford University Press on behalf of The Japanese Radiation Research Society and Japanese Society for Radiation Oncology.)

This study was aiming at investigating the extent of neuronal damage in cases of traumatic brain injury (TBI) with diffuse axonal injury (DAI) using 123 I-iomazenil(IMZ) SPECT and MRI. We compared the findings in 31 patients with TBI without any major focal brain lesions and 25 age-matched normal controls. Subjects underwent 123 I-IMZ SPECT and MRI, and also assessment by cognitive function tests. The partial volume effect of 123 I-IMZ SPECT was corrected using MRI. In the patients with TBI, decreased spatial concentration of 123 I-IMZ binding was detected in the medial frontal/orbitofrontal cortex, posterior cingulate gyrus, cuneus, precuneus, and superior region of the cerebellum. ROC analysis of 123 I-IMZ SPECT for the detection of neuronal injury showed a high diagnostic ability of 123 I-IMZ binding density for TBI in these areas. The decreased 123 I-IMZ uptake density in the cuneus and precuneus was associated with cognitive decline after the injury. In the patients with TBI, brain atrophy was detected in the frontal lobe, anterior temporal and parietal cortex, corpus callosum, and posterior part of the cerebellum. Evaluation of the neuronal integrity by 123 I-IMZ SPECT and MRI provides important information for the diagnosis and pathological interpretation in cases of TBI with DAI.

The differentiation between major histological types of lung cancer, such as adenocarcinoma (ADC), squamous cell carcinoma (SCC), and small-cell lung cancer (SCLC) is of crucial importance for determining optimum cancer treatment. Hematoxylin and Eosin (H&E)-stained slides of small transbronchial lung biopsy (TBLB) are one of the primary sources for making a diagnosis; however, a subset of cases present a challenge for pathologists to diagnose from H&E-stained slides alone, and these either require further immunohistochemistry or are deferred to surgical resection for definitive diagnosis. We trained a deep learning model to classify H&E-stained Whole Slide Images of TBLB specimens into ADC, SCC, SCLC, and non-neoplastic using a training set of 579 WSIs. The trained model was capable of classifying an independent test set of 83 challenging indeterminate cases with a receiver operator curve area under the curve (AUC) of 0.99. We further evaluated the model on four independent test sets-one TBLB and three surgical, with combined total of 2407 WSIs-demonstrating highly promising results with AUCs ranging from 0.94 to 0.99.

Objective: This study aimed to examine echolalia and its related symptoms and brain lesions in primary progressive aphasia (PPA)., Methods: Forty-five patients with PPA were included: 19 nonfluent/agrammatic variant PPA (nfvPPA), 5 semantic variant PPA, 7 logopenic variant PPA, and 14 unclassified PPA patients. We detected echolalia in unstructured conversations. An evaluation of language function and the presence of parkinsonism, grasp reflex, imitation behaviour, and disinhibition were assessed. We also measured regional cerebral blood flow (rCBF) using single-photon emission computed tomography., Results: Echolalia was observed in 12 nfvPPA and 2 unclassified PPA patients. All patients showed mitigated echolalia. We compared nfvPPA patients with echolalia (echolalia group) to those without echolalia (non-echolalia group). The median age of the echolalia group was significantly lower than that of the non-echolalia group, and the echolalia group showed a significantly worse auditory comprehension performance than the non-echolalia group. In contrast, the performance of repetition tasks was not different between the two groups. The prevalence of imitation behaviour in the echolalia group was significantly higher than that in the non-echolalia group. The rCBFs in the bilateral pre-supplementary motor area and bilateral middle cingulate cortex in the echolalia group were significantly lower than those in the non-echolalia group., Conclusions: These findings suggest that echolalia is characteristic of nfvPPA patients with impaired comprehension. Reduced inhibition of the medial frontal cortex with release activity of the anterior perisylvian area account for the emergence of echolalia., (© 2020 European Academy of Neurology.)

Primary progressive aphasia (PPA) is a neurological syndrome characterized by progressive language impairment. Various neurodegenerative disorders cause PPA. Dementia with Lewy bodies (DLB) is one known cause of PPA, and little is known about this association. Almost all published cases of PPA associated with DLB are the logopenic variant of PPA. Here, we describe the novel case of a patient with DLB presenting clinical features of the semantic variant PPA (svPPA). A 75-year-old woman was referred to our hospital with a 2-year history of progressive anomia and amnesia. Two months before admission, she had been experiencing visual hallucinations, and at the age of 60 years, she had venous infarction in the left temporal lobe, which she recovered from without any residual symptoms. Upon admission to our hospital, she displayed anomia, impaired single-word comprehension, and surface dyslexia with preserved repetition and speech production. These symptoms met the criteria for the diagnosis of svPPA. 123 I-ioflupane single-photon emission computed tomography and 123 I-meta-iodobenzylguanidine myocardial scintigraphy indicated DLB. Thus, she was administered donepezil, and this dramatically improved her symptoms. We hypothesize that the combination of DLB with the previous asymptomatic venous thrombosis in the left temporal lobe may have contributed to the "svPPA" in this patient. In conclusion, we show that PPA associated with DLB could be treated with donepezil, and we suggest that donepezil should be pursued as a treatment option for PPA., Competing Interests: None., (© 2021 The Authors.)

Signet ring cell carcinoma (SRCC) of the stomach is a rare type of cancer with a slowly rising incidence. It tends to be more difficult to detect by pathologists, mainly due to its cellular morphology and diffuse invasion manner, and it has poor prognosis when detected at an advanced stage. Computational pathology tools that can assist pathologists in detecting SRCC would be of a massive benefit. In this paper, we trained deep learning models using transfer learning, fully-supervised learning, and weakly-supervised learning to predict SRCC in Whole Slide Images (WSIs) using a training set of 1,765 WSIs. We evaluated the models on two different test sets (n = 999, n = 455). The best model achieved a ROC-AUC of at least 0.99 on all two test sets, setting a top baseline performance for SRCC WSI classification.

The development of retinal blood vessels has extensively been used as a model to study vascular pattern formation. To date, various quantitative measurements, such as size distribution have been performed, but the relationship between pattern formation mechanisms and these measurements remains unclear. In the present study, we first focus on the islands (small regions subdivided by the capillary network). We quantitatively measured the island size distribution in the retinal vascular network and found that it tended to exhibit an exponential distribution. We were able to recapitulate this distribution pattern in a theoretical model by implementing the stochastic disappearance of vessel segments around arteries could reproduce the observed exponential distribution of islands. Second, we observed that the diameter distribution of the retinal artery segment obeyed a power law. We theoretically showed that an equal bifurcation branch pattern and Murray's law could reproduce this pattern. This study demonstrates the utility of examining size distribution for understanding the mechanisms of vascular pattern formation., Competing Interests: The authors have declared that no competing interests exist.

Lung cancer is one of the major causes of cancer-related deaths in many countries around the world, and its histopathological diagnosis is crucial for deciding on optimum treatment strategies. Recently, Artificial Intelligence (AI) deep learning models have been widely shown to be useful in various medical fields, particularly image and pathological diagnoses; however, AI models for the pathological diagnosis of pulmonary lesions that have been validated on large-scale test sets are yet to be seen. We trained a Convolution Neural Network (CNN) based on the EfficientNet-B3 architecture, using transfer learning and weakly-supervised learning, to predict carcinoma in Whole Slide Images (WSIs) using a training dataset of 3,554 WSIs. We obtained highly promising results for differentiating between lung carcinoma and non-neoplastic with high Receiver Operator Curve (ROC) area under the curves (AUCs) on four independent test sets (ROC AUCs of 0.975, 0.974, 0.988, and 0.981, respectively). Development and validation of algorithms such as ours are important initial steps in the development of software suites that could be adopted in routine pathological practices and potentially help reduce the burden on pathologists.

•Pathological basis of primary progressive aphasia is heterogeneous.•Logopenic primary progressive aphasia can precede dementia with Lewy bodies (DLB).•Cholinesterase inhibitor can improve logopenic aphasia with DLB., (© 2020 The Author(s).)

Histopathological classification of gastric and colonic epithelial tumours is one of the routine pathological diagnosis tasks for pathologists. Computational pathology techniques based on Artificial intelligence (AI) would be of high benefit in easing the ever increasing workloads on pathologists, especially in regions that have shortages in access to pathological diagnosis services. In this study, we trained convolutional neural networks (CNNs) and recurrent neural networks (RNNs) on biopsy histopathology whole-slide images (WSIs) of stomach and colon. The models were trained to classify WSI into adenocarcinoma, adenoma, and non-neoplastic. We evaluated our models on three independent test sets each, achieving area under the curves (AUCs) up to 0.97 and 0.99 for gastric adenocarcinoma and adenoma, respectively, and 0.96 and 0.99 for colonic adenocarcinoma and adenoma respectively. The results demonstrate the generalisation ability of our models and the high promising potential of deployment in a practical histopathological diagnostic workflow system.

Background and Purpose: We previously reported the usefulness of iodine-123 metaiodobenzylguanidine ( 123 I-MIBG) myocardial scintigraphy for differentiation of dementia with Lewy bodies (DLB) from Alzheimer's disease (AD) in a cross-sectional multicentre study. The aim of this study was, by using reassessed diagnosis after 3-year follow-up, to evaluate the diagnostic accuracy of 123 I-MIBG scintigraphy in differentiation of probable DLB from probable AD., Methods: We undertook 3-year follow-up of 133 patients with probable or possible DLB or probable AD who had undergone 123 I-MIBG myocardial scintigraphy at baseline. An independent consensus panel made final diagnosis at 3-year follow-up. Based on the final diagnosis, we re-evaluated the diagnostic accuracy of 123 I-MIBG scintigraphy performed at baseline., Results: Sixty-five patients completed 3-year follow-up assessment. The final diagnoses were probable DLB (n=30), possible DLB (n=3) and probably AD (n=31), and depression (n=1). With a receiver operating characteristic curve analysis of heart-to-mediastinum (H/M) ratios for differentiating probable DLB from probable AD, the sensitivity/specificity were 0.77/0.94 for early images using 2.51 as the threshold of early H/M ratio, and 0.77/0.97 for delayed images using 2.20 as the threshold of delayed H/M ratio. Five of six patients who were diagnosed with possible DLB at baseline and with probable DLB at follow-up had low H/M ratio at baseline., Conclusions: Our follow-up study confirmed high correlation between abnormal cardiac sympathetic activity evaluated with 123 I-MIBG myocardial scintigraphy at baseline and the clinical diagnosis of probable DLB at 3-year follow-up. Its diagnostic usefulness in early stage of DLB was suggested., Trial Registration Number: UMIN00003419., Competing Interests: Competing interests: HeA, TAr and KW received honoraria for sponsored lectures from Fujifilm RI Pharma. TAs and SY received honoraria for sponsored lectures and research grant from Fujifilm RI Pharma Co and Nihon Medi-Physics. HF, SN, SO, JT and MYo received honoraria for sponsored lectures from Fujifilm RI Pharma and Nihon Medi-Physics. HH and KUt received honoraria for sponsored lectures from Nihon Medi-Physics. EI received honoraria for consultancies, sponsored lectures and presiding at lecture meetings from Nihon Medi-Physics. OI received honoraria for sponsored lectures and travel costs from Nihon Medi-Physics. KKo received honoraria for sponsored lectures, writing and editing from Fujifilm RI Pharma, and honoraria for sponsored lectures from Nihon Medi-Physics. HM received honoraria for sponsored lectures and travel costs from Fujifilm RI Pharma and Nihon Medi-Physics. KNakaj has collaborative research works with Fujifilm RI Pharma and received research funds for joint research and honoraria for lectures and writing. KNakas received sponsored scholarship and honoraria for presiding at meetings from Fujifilm RI Pharma and honoraria for presiding at lecture meetings from Nihon Medi-Physics. EM received research grant from Fujifilm RI Pharma and honoraria for sponsored lectures from Nihon Medi-Physics and Fujifilm RI Pharma. TT received honoraria for sponsored lectures and presiding at lecture meetings from Nihon Medi-Physics. KUr received research grant from Fujifilm RI Pharma and honoraria for sponsored lectures from Nihon Medi-Physics. MYa received honoraria for sponsored lectures and research grant from Fujifilm RI Pharma. JY received sponsored scholarship, honoraria for sponsored lectures and travel costs from Fujifilm RI Pharma, and honoraria for sponsored lectures and research grant from Nihon Medi-Physics. JK, HiA, EI, KKa, KM, YM, HN, YN, MS, AT and YW declare that they have no conflicts of interest., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Background: There is increasing evidence for predictive coding theories of psychosis, which state that hallucinations arise from abnormal perceptual priors or biases. However, psychological processes that foster abnormal priors/biases in patients suffering hallucinations have been largely unexplored. The widely recognized relationship between affective disorders and psychosis suggests a role for mood and emotion., Methods: Thirty-six patients with dementia with Lewy bodies (DLB), a representative condition associated with psychosis of neurological origin, and 12 patients with Alzheimer's disease (AD) were enrolled. After an experimental mood induction, the participants underwent the pareidolia test, in which visual hallucination-like illusions were evoked and measured., Results: In DLB patients, the number of pareidolic illusions was doubled under negative mood compared to that under neutral mood. In AD patients, there was no significant difference in the number of pareidolic responses between negative and neutral mood conditions. A signal detection theory analysis demonstrated that the observed affective modulation of pareidolic illusions was mediated through heightened perceptual bias, not sensory deterioration., Conclusions: The current findings demonstrated that abnormal perceptual priors in psychotic false perception have an affective nature, which we suggest are a type of cognitive feeling that arises in association with perception and cognition., Competing Interests: The authors have declared that no competing interests exist.

Agrammatism is one of the core clinical features of non-fluent/agrammatic variant primary progressive aphasia, and it has traditionally been considered the hallmark of non-fluent aphasia in Western countries. However, agrammatic speech may remain undetected in Japanese patients because of the agglutinative structure of the language and high flexibility in word order. In the present study, we aimed to analyze agrammatism in the speech production of Japanese patients with aphasia due to neurodegenerative disease using an anagram test generated by our laboratory. Four patients were recruited from the dementia clinic at Tohoku University Hospital between December 2014 and August 2015: two patients with non-fluent/agrammatic variant primary progressive aphasia, one with semantic variant primary progressive aphasia, and one with probable Alzheimer's disease experiencing episodic memory impairment accompanied by transcortical sensory aphasia. All patients underwent thorough neurological and neuropsychological testing before performing a Japanese anagram task based on the Northwestern Anagram Test. Our findings indicated that the two patients with non-fluent/agrammatic variant primary progressive aphasia exhibited poorer performance on the anagram task than the remaining two patients. Therefore, the anagram test used in the present study may aid in detecting output aspects of agrammatism in Japanese patients with aphasia, although future studies are required to develop a standardized version of test., (© 2018 Japanese Psychogeriatric Society.)

Pareidolias are visual illusions of meaningful objects, such as faces and animals, that arise from ambiguous forms embedded in visual scenes. Pareidolias and visual hallucinations have been suggested to have a common underlying neural mechanism in patients with dementia with Lewy bodies (DLB). The aim of the present study was to find an externally observable physiological indicator of pareidolias. Using a pareidolia test developed by Uchiyama and colleagues, we evoked pareidolias in patients with DLB and recorded the resultant changes in the diameters of their pupil. The time frequencies of changes in pupil diameters preceding pareidolic utterances and correct utterances by the patients, as well as correct utterances by healthy control participants, were analyzed by a fast Fourier transform program. The power at time frequencies of 0-0.46 Hz was found to be greatest preceding pareidolic utterances in patients with DLB, followed by that preceding correct utterances in control participants, followed by that preceding correct utterances in patients with DLB. When the changes in power preceding the utterance were greater than the median value of correct utterances by the control group, the frequency of pareidolic utterances was significantly greater than that of correct utterances and when the changes were the same as or lower than the median value, the frequency of correct utterances was significantly greater than that of pareidolic utterances. Greater changes in power preceding the utterance at time frequencies of 0-0.46 Hz may thus be an externally observable physiological indicator of the occurrence of pareidolias.

Background: The aim of this study was to elucidate changes in cerebral white matter after shunt surgery in idiopathic normal pressure hydrocephalus (INPH) using diffusion tensor imaging (DTI)., Methods: Twenty-eight consecutive INPH patients whose symptoms were followed for 1 year after shunt placement and 10 healthy control (HC) subjects were enrolled. Twenty of the initial 28 INPH patients were shunt-responsive (SR) and the other 8 patients were non-responsive (SNR). The cerebral white matter integrity was detected by assessing fractional anisotropy (FA) and mean diffusivity (MD). The mean hemispheric DTI indices and the ventricular sizes were calculated, and a map of these DTI indices was created for each subject. The DTI maps were analysed to compare preshunt INPH with HC and preshunt INPH with 1 year after shunt placement in each INPH group, using tract-based spatial statistics. We restricted analyses to the left hemisphere because of shunt valve artefacts., Results: The ventricles became significantly smaller after shunt placement both in the SR and SNR groups. In addition, there was a significant interaction between clinical improvement after shunt and decrease in ventricular size. Although the hemispheric DTI indices were not significantly changed after shunt placement, there was a significant interaction between clinical improvement and increase in hemispheric MD. Compared with the HC group, FA in the corpus callosum and in the subcortical white matter of the convexity and the occipital cortex was significantly lower in SR at baseline, whereas MD in the periventricular and peri-Sylvian white matter was significantly higher in the SR group. Compared with the pre-operative images, the post-operative FA was only decreased in the corona radiata and only in the SR group. There were no significant regions in which DTI indices were altered after shunt placement in the SNR group., Conclusions: Brain white matter regions in which FA was decreased after shunt placement were in the corona radiata between the lateral ventricles and the Sylvian fissures. This finding was observed only in shunt-responsive INPH patients and might reflect the plasticity of the brain for mechanical pressure changes from the cerebrospinal fluid system.

Background and Purpose: Although neuroimaging plays an important role in the diagnosis of idiopathic normal pressure hydrocephalus, its predictive value for response to shunt surgery has not been established. The purpose of the current study was to identify neuroimaging markers that predict the shunt response of idiopathic normal pressure hydrocephalus., Materials and Methods: Sixty patients with idiopathic normal pressure hydrocephalus underwent presurgical brain MR imaging and clinical evaluation before and 1 year after shunt surgery. The assessed MR imaging features included the Evans index, high-convexity tightness, Sylvian fissure dilation, callosal angle, focal enlargement of the cortical sulci, bumps in the lateral ventricular roof, and deep white matter and periventricular hyperintensities. The idiopathic normal pressure hydrocephalus grading scale total score was used as a primary clinical outcome measure. We used measures for individual symptoms (ie, the idiopathic normal pressure hydrocephalus grading scale subdomain scores, such as gait, cognitive, and urinary scores), the Timed Up and Go test, and the Mini-Mental State Examination as secondary clinical outcome measures. The relationships between presurgical neuroimaging features and postoperative clinical changes were investigated by using simple linear regression analysis. To identify the set of presurgical MR imaging features that best predict surgical outcomes, we performed multiple linear regression analysis by using a bidirectional stepwise method., Results: Simple linear regression analyses demonstrated that presurgical high-convexity tightness, callosal angle, and Sylvian fissure dilation were significantly associated with the 1-year changes in the clinical symptoms. A multiple linear regression analysis demonstrated that presurgical high-convexity tightness alone predicted the improvement of the clinical symptoms 1 year after surgery., Conclusions: High-convexity tightness is a neuroimaging feature predictive of shunt response in idiopathic normal pressure hydrocephalus., (© 2016 by American Journal of Neuroradiology.)

Background: Visual hallucinations are a core clinical feature of dementia with Lewy bodies (DLB), and this symptom is important in the differential diagnosis and prediction of treatment response. The pareidolia test is a tool that evokes visual hallucination-like illusions, and these illusions may be a surrogate marker of visual hallucinations in DLB. We created a simplified version of the pareidolia test and examined its validity and reliability to establish the clinical utility of this test., Methods: The pareidolia test was administered to 52 patients with DLB, 52 patients with Alzheimer's disease (AD) and 20 healthy controls (HCs). We assessed the test-retest/inter-rater reliability using the intra-class correlation coefficient (ICC) and the concurrent validity using the Neuropsychiatric Inventory (NPI) hallucinations score as a reference. A receiver operating characteristic (ROC) analysis was used to evaluate the sensitivity and specificity of the pareidolia test to differentiate DLB from AD and HCs., Results: The pareidolia test required approximately 15 minutes to administer, exhibited good test-retest/inter-rater reliability (ICC of 0.82), and moderately correlated with the NPI hallucinations score (rs = 0.42). Using an optimal cut-off score set according to the ROC analysis, and the pareidolia test differentiated DLB from AD with a sensitivity of 81% and a specificity of 92%., Conclusions: Our study suggests that the simplified version of the pareidolia test is a valid and reliable surrogate marker of visual hallucinations in DLB.

Background: Abnormal cardiac uptake of 123I-metaiodobenzylguanidine (123I-MIBG) is a diagnostic marker of Lewy body diseases (LBDs), e.g., Parkinson's disease (PD) and dementia with Lewy bodies (DLB). Planar imaging is generally used to assess cardiac sympathetic dysfunction in 123I-MIBG scintigraphy; however, its clinical utility requires further improvement. We hypothesized that the co-registration of single-photon emission tomography (SPECT) and computed tomography (CT) images would improve the diagnostic accuracy of 123I-MIBG cardiac scintigraphy for LBDs. This study sought to evaluate the effects of SPECT/CT imaging on 123I-MIBG cardiac scintigraphy for diagnosing LBDs., Methods: We retrospectively investigated data of 54 patients (consecutive 18 patients in each PD, DLB, and idiopathic normal pressure hydrocephalus [iNPH] groups) who underwent 123I-MIBG cardiac scintigraphy (planar and SPECT/CT) because of suspected LBDs at the Tohoku University hospital from June 2012 to June 2015. We compared the diagnostic accuracies of the conventional planar 123I-MIBG method and SPECT/CT methods (manual and semi-automatic)., Results: In the conventional planar analysis, 123I-MIBG uptake decreased only in the DLB group compared with the iNPH group. In contrast, the SPECT/CT analysis revealed significantly lower 123I-MIBG uptake in both the PD and DLB groups compared with the iNPH group. Furthermore, a receiver operating characteristic analysis revealed that both the manual and semi-automatic SPECT/CT methods were superior to the conventional planar method in differentiating the 3 disorders., Conclusions: SPECT/CT 123I-MIBG cardiac scintigraphy can detect mild cardiac sympathetic dysfunction in LDBs. Our results suggest that the SPECT/CT technique improves diagnostic accuracy for LBDs.

Relapsing polychondritis (RP) is a rare inflammatory disorder of the cartilagenous structures, and it sometimes involves the central nervous system. Encephalitis associated with RP causes a wide variety of symptoms according to the affected sites. We herein report the first case of 72-year-old right-handed man who developed acute meningoencephalitis associated with RP involving the corpus callous. After immunosuppressive therapy, his symptoms dramatically improved, but difficulty in performing bimanual movements with occasional diagonistic dyspraxia in his right hand remained. Because callosal signs are easily missed, especially in acute settings, it would be useful to know that RP can sometimes cause callosal disconnection syndrome.

Background: Comorbidity of idiopathic normal pressure hydrocephalus and neurodegenerative diseases presents a diagnostic challenge. The aim of this study was to elucidate the clinical features of iNPH patients who are possibly comorbid with Lewy body diseases., Methods: In this study, we retrospectively analyzed the records of consecutive 127 patients with definite idiopathic normal pressure hydrocephalus. (123)I-Metaiodobenzylguanidine myocardial scintigraphy was undertaken to 21 patients with idiopathic normal pressure hydrocephalus because of suspicion for comorbid Lewy body diseases., Results: As a result, 7 of the 21 patients with idiopathic normal pressure hydrocephalus exhibited cardiac sympathetic abnormality. Idiopathic normal pressure hydrocephalus patients with cardiac sympathetic dysfunction had the constellation of clinical findings, such as younger onset, less severe urinary dysfunction, kinesie paradoxale, and cogwheel rigidity., Conclusions: Our results suggested that comorbidity of idiopathic normal pressure hydrocephalus and Lewy body diseases are not rare condition and careful screening for potentially-curative surgery is important especially in atypical cases., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Objectives: In previous studies, patients with idiopathic normal-pressure hydrocephalus (iNPH) occasionally showed Alzheimer's pathology in frontal lobe cortical biopsy during cerebrospinal fluid shunt surgery or intracranial pressure monitoring. In clinical practice, the differential diagnosis of iNPH from Alzheimer's disease (AD) can be problematic, particularly because some iNPH cases exhibit AD comorbidity. In this study, we evaluated amyloid deposition in the brains of patients with iNPH before shunt surgery, and investigated the association between brain amyloid deposits and clinical improvement following the surgery., Materials & Methods: Amyloid imaging was performed in patients with iNPH or AD and also in healthy control subjects by using positron emission tomography (PET) and a radiolabeled pharmaceutical compound, (11)C-BF227. Using the cerebellar hemispheres as reference regions, the standard uptake value ratio (SUVR) of the neocortex was estimated and used as an index for amyloid deposition. In patients with iNPH, clinical symptoms were assessed before shunt surgery and 3 months after surgery., Results: Five of the 10 patients with iNPH had neocortical SUVRs that were as high as those of AD subjects, whereas the SUVRs of the 5 patients were as low as those of healthy controls. A significant inverse correlation between neocortical SUVRs and cognitive improvements after shunt surgery was observed in iNPH., Conclusions: The amount of amyloid deposits ranges widely in the brains of patients with iNPH and is associated with the degree of cognitive improvement after shunt surgery., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Background and Purpose: Dementia with Lewy bodies (DLB) needs to be distinguished from Alzheimer's disease (AD) because of important differences in patient management and outcome. Severe cardiac sympathetic degeneration occurs in DLB, but not in AD, offering a potential system for a biological diagnostic marker. The primary aim of this study was to investigate the diagnostic accuracy, in the ante-mortem differentiation of probable DLB from probable AD, of cardiac imaging with the ligand 123I-meta-iodobenzylguanidine (MIBG) which binds to the noradrenaline reuptake site, in the first multicenter study., Methods: We performed a multicenter study in which we used 123I-MIBG scans to assess 133 patients with clinical diagnoses of probable (n = 61) or possible (n = 26) DLB or probable AD (n = 46) established by a consensus panel. Three readers, unaware of the clinical diagnosis, classified the images as either normal or abnormal by visual inspection. The heart-to-mediastinum ratios of 123I-MIBG uptake were also calculated using an automated region-of-interest based system., Results: Using the heart-to-mediastinum ratio calculated with the automated system, the sensitivity was 68.9% and the specificity was 89.1% to differentiate probable DLB from probable AD in both early and delayed images. By visual assessment, the sensitivity and specificity were 68.9% and 87.0%, respectively. In a subpopulation of patients with mild dementia (MMSE ≥ 22, n = 47), the sensitivity and specificity were 77.4% and 93.8%, respectively, with the delayed heart-to-mediastinum ratio., Conclusions: Our first multicenter study confirmed the high correlation between abnormal cardiac sympathetic activity evaluated with 123I-MIBG myocardial scintigraphy and a clinical diagnosis of probable DLB. The diagnostic accuracy is sufficiently high for this technique to be clinically useful in distinguishing DLB from AD, especially in patients with mild dementia.

By definition, visual illusions and hallucinations differ in whether the perceived objects exist in reality. A recent study challenged this dichotomy, in which pareidolias, a type of complex visual illusion involving ambiguous forms being perceived as meaningful objects, are very common and phenomenologically similar to visual hallucinations in dementia with Lewy bodies (DLB). We hypothesise that a common psychological mechanism exists between pareidolias and visual hallucinations in DLB that confers meaning upon meaningless visual information. Furthermore, we believe that these two types of visual misperceptions have a common underlying neural mechanism, namely, cholinergic insufficiency. The current study investigated pareidolic illusions using meaningless visual noise stimuli (the noise pareidolia test) in 34 patients with DLB, 34 patients with Alzheimer׳s disease and 28 healthy controls. Fifteen patients with DLB were administered the noise pareidolia test twice, before and after donepezil treatment. Three major findings were discovered: (1) DLB patients saw meaningful illusory images (pareidolias) in meaningless visual stimuli, (2) the number of pareidolic responses correlated with the severity of visual hallucinations, and (3) cholinergic enhancement reduced both the number of pareidolias and the severity of visual hallucinations in patients with DLB. These findings suggest that a common underlying psychological and neural mechanism exists between pareidolias and visual hallucinations in DLB., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

We retrospectively analyzed 15 years experience of awake surgeries for neuroepithelial tumors in Tohoku University. Awake surgeries mostly for language mapping were performed for 42 of 681 newly diagnosed cases (6.2%) and 59 of 985 surgeries including for recurrence (6.0%). When the same histologies and locations as cases resected under awake condition are selected from the parent population treated by radical resection, awake surgeries were most frequently performed for 14 of 55 newly diagnosed cases (25.5%) and 14 of 62 surgeries (22.6%) with grade II gliomas. In the results, 8 of 59 surgeries (13.6%) could not achieve complete language monitoring until the final stage of tumor resection, considered as failed awake surgery. Gross total resection was accomplished in 20 of 42 newly diagnosed cases (47.6%) and 32 of 59 surgeries (54.2%). Mortality rate was 0%. Late severe deficits were observed in 2 of 42 newly diagnosed cases (4.8%) and 3 of 59 surgeries (5.1%). Negative language mapping cases did not suffer severe deficits in both early and late stages. In contrast, high incidence of severe deficits, 3 as early and 2 as late of 8 cases, were identified with failed awake surgery. The overall survival of patients treated by awake surgery compared favorably with those treated without stimulation mapping and with stimulation mapping under general anesthesia. Awake surgery may contribute to improve the outcome of gliomas near eloquent areas by maximizing the tumor resection and minimizing the surgical morbidity.

The aim of this study was to validate the Japanese version of the Addenbrooke's Cognitive Examination-Revised (ACE-R) [Mori: Japanese Edition of Hodges JR's Cognitive Assessment for Clinicians, 2010] designed to detect dementia, and to compare its diagnostic accuracy with that of the Mini-Mental State Examination. The ACE-R was administered to 85 healthy individuals and 126 patients with dementia. The reliability assessment revealed a strong correlation in both groups. The internal consistency was excellent (α-coefficient = 0.88). Correlation with the Clinical Dementia Rating sum of boxes score was significant (r(s) = -0.61, p < 0.001). The area under the curve was 0.98 for the ACE-R and 0.96 for the Mini-Mental State Examination. The cut-off score of 80 showed a sensitivity of 94% and a specificity of 94%. Like the original ACE-R and the versions designed for other languages, the Japanese version of the ACE-R is a reliable and valid test for the detection of dementia.

We investigated the effects of aging and Alzheimer's disease (AD) on item and associative recognition memory. Three groups of participants (younger adults, elderly adults, and AD patients) studied photographs of common objects that were located on either the left or the right side of a black computer screen inside either a red or a blue square. In a subsequent old/new recognition memory test, the participants were presented with four kinds of stimuli: "intact" stimuli, which were presented as they were during the study phase; "location-altered" stimuli, which were presented in a different location; "color-altered" stimuli, which were presented with a different surrounding color; and "new" stimuli, which consisted of photographs that had not been presented during the study phase. Compared with younger adults, the older adults showed equivalent performance in simple item recognition but worse performance in discriminating location-altered and color-altered stimuli. Compared with older adults, the AD patients showed equivalent performance in discriminating color-altered stimuli but worse performance in simple item recognition and the discrimination of location-altered stimuli. We speculate that distinct structural and functional changes in specific brain regions that are caused by aging and AD are responsible for the different patterns of memory impairment.

The aim of this study was to characterise the white matter damage involved in idiopathic normal pressure hydrocephalus (INPH) using diffusion tensor imaging (DTI) and the relationship between this damage and clinical presentation. Twenty patients with INPH, 20 patients with Alzheimer's disease and 20 patients with idiopathic Parkinson's disease (as disease control groups) were enrolled in this study. Mean diffusivity (MD) and fractional anisotropy (FA) were determined using DTI, and these measures were analysed to compare the INPH group with the control groups and with certain clinical correlates. On average, the supratentorial white matter presented higher MD and lower FA in the INPH group than in the control groups. In the INPH group, the mean hemispheric FA correlated with some of the clinical measures, whereas the mean hemispheric MD did not. On a voxel-based statistical map, white matter involvement with high MD was localised to the periventricular regions, and white matter involvement with low FA was localised to the corpus callosum and the subcortical regions. The total scores on the Frontal Assessment Battery were correlated with the FA in the frontal and parietal subcortical white matter, and an index of gait disturbance was correlated with the FA in the anterior limb of the left internal capsule and under the left supplementary motor area. DTI revealed the presence of white matter involvement in INPH. Whereas white matter regions with high MD were not related to symptom manifestation, those with low FA were related to motor and cognitive dysfunction in INPH.

Recent evidence suggests that patients with Alzheimer's disease (AD), as compared with normal individuals, exhibit increased false recognition by stimulus repetition in the Deese-Roediger-McDermott (DRM) task or associative recognition memory tasks, probably due to impaired recollection-based monitoring. However, because of possible alternative explanations for the findings of these previous studies, the evidence for impaired recollection-based monitoring in AD patients remains inconclusive. In this study, we employed stimulus repetition in old/new recognition judgments of single-item picture memory without a factor of association between the stimuli and examined whether AD patients showed increased false item recognition as compared with healthy controls. AD patients and healthy controls studied single-item pictures presented either once or three times. They were later asked to make an old/new recognition judgment in response to (a) Same pictures, pictures identical to those seen at encoding, (b) Similar lures, novel pictures similar to but not identical to those seen at encoding, and (c) Dissimilar lures, novel pictures not similar to those seen at encoding. For Same pictures, repeated presentation of stimuli increased the proportion of "old" responses in both groups. For Similar lures, repeated presentation of stimuli increased the rate of "old" responses in AD patients but not in control subjects. The results of the present study clearly demonstrated elevated false recognition by stimulus repetition in single-item recognition in AD patients. The present findings strongly support the view that AD patients are impaired in their ability to use item-specific recollection in order to avoid false recognition., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Gait disturbance is the most common symptom in idiopathic normal-pressure hydrocephalus (iNPH). However, its pathophysiology in iNPH has not been clarified. Some researchers have hypothesized that the mesencephalic locomotor region, which is a functionally defined area in the brainstem playing an important role in locomotion, is involved in the development of gait disturbance in iNPH. The purpose of the study was to investigate whether the midbrain is involved in the manifestation of gait disturbance in iNPH. Twenty-one iNPH patients who showed clinical improvements after shunt surgery were studied. Brain magnetic resonance imaging (MRI) was performed and clinical symptoms were assessed before and 1 year after surgery. Gait disturbance was assessed by the Timed Up and Go test and gait subcategory of the iNPH Grading Scale, a validated assessment tool for iNPH symptoms. Anteroposterior, left-to-right diameter and cross-sectional areas of the midbrain were measured at the inferior collicular level of axial images in MRI. The diameters and cross-sectional area of the midbrain at baseline did not show significant correlation with gait assessments at baseline (Spearman's correlation). The midbrain measurement did not show significant difference between the baseline and postoperative values (paired t test), and its change rates did not show significant correlation with the change (rates) of the gait assessments. In this study there were no findings to suggest involvement of the midbrain in the manifestation of gait disturbance in iNPH. The hypothesis that the mesencephalic locomotor region is involved in the manifestation of gait disturbance in iNPH needs to be reconsidered.

Background/aims: Frontal lobe dysfunction is believed to be a primary cognitive symptom in idiopathic normal pressure hydrocephalus (iNPH); however, the neuropsychology of this disorder remains to be fully investigated. The objective of this study was to delineate a comprehensive profile of cognitive dysfunction in iNPH and evaluate the effects of cerebrospinal fluid (CSF) shunt surgery on cognitive dysfunction., Methods: A total of 32 iNPH patients underwent neuropsychological testing of memory, attention, language, executive function, and visuoperceptual and visuospatial abilities. Of these 32 patients, 26 were reevaluated approximately 1 year following CSF shunt surgery. The same battery of tests was performed on 32 patients with Alzheimer's disease (AD) and 30 healthy elderly controls., Results: The iNPH patients displayed baseline deficits in attention, executive function, memory, and visuoperceptual and visuospatial functions. Impairments of attention, executive function, and visuoperceptual and visuospatial abilities in iNPH patients were more severe than in those with AD, whereas the degree of memory impairment was comparable to that in AD patients. A significant improvement in executive function was observed following shunt surgery., Conclusion: Patients with iNPH are impaired in various aspects of cognition involving both 'frontal' executive functions and 'posterior cortical' functions. Shunt treatment can ameliorate executive dysfunction.

Objectives: To investigate volumetric changes of the brain and cerebrospinal fluid (CSF) spaces after shunt surgery in shunt-responsive idiopathic normal-pressure hydrocephalus (iNPH), and correlations between the changes and postoperative clinical improvements., Methods: Twenty-one patients with shunt-responsive iNPH were studied. Magnetic resonance imaging (MRI) of the brain was performed before and 1year after surgery, and clinical symptoms were assessed by the iNPH Grading Scale, a validated assessment tool of the triad of iNPH, the Modified Rankin Scale, the Timed Up and Go Test, and neuropsychological tests including the Mini-Mental State Examination. The volumes of the left cerebral hemisphere, infratentorial brain, ventricles, and suprasylvian and infrasylvian subarachnoid CSF spaces were measured using an MRI-based volumetric technique., Results: The volumes of the cerebral hemisphere and infratentorial brain did not change significantly after shunt surgery (p=0.231, 0.109, respectively). The volumes of the ventricles and infrasylvian subarachnoid CSF spaces were significantly decreased (p<0.0001, <0.05, respectively), with a mean change rate of -26.1% and -4.5%, respectively. The volumes of the suprasylvian subarachnoid CSF spaces increased significantly (p<0.0001), with a mean change rate of 43.5%. The decrease in ventricular volumes was significantly correlated with clinical improvement., (2010 Elsevier B.V. All rights reserved.)

The negative motor area and anterior and posterior language areas were localized by intraoperative electrical cortical stimulation under the awake condition to evaluate the clinical significance of these areas. Thirty-seven awake craniotomies with language mapping were performed in 36 patients with brain tumors. The negative motor area was determined in 17 cases, and the anterior and posterior language areas were found in 12 and 6 cases, respectively. The negative motor area was located in the precentral gyrus inferior to the orofacial motor area in 16 cases, and in the inferior frontal gyrus anterior to the orofacial motor area in one case. Both the negative motor area and the anterior language area were determined in 8 cases. Anterior language areas in these 8 cases were located anterior and/or inferior to the negative motor areas. The negative motor area is an easily determined, important landmark for intraoperative language mapping.

Significant neuropsychologic sequelae were induced by total removal of craniopharyngioma via a frontobasal interhemispheric approach. A 50-year-old right-handed man developed severe amnesic syndrome and collecting behavior after total removal of a craniopharyngioma. He had very poor results on tests of learning, recall, and recognition for both verbal and nonverbal tasks. Magnetic resonance imaging revealed damage to the bilateral mammillary bodies and fornices, and N-isopropyl-p-[23I]iodoamphetamine single photon emission computed tomography showed decreased cerebral blood flow in the bilateral frontal lobes, predominantly in the right, and regions around the third ventricle. The present case suggests that damage to the brain structures surrounding the third ventricle associated with surgery for craniopharyngioma may result in amnesic syndrome and collecting behavior. Generally, the frontobasal interhemispheric approach is the optimum choice for the removal of craniopharyngioma without significant sequelae related to the surgical method, but the risk of neuropsychologic disturbances must be kept in mind.

There has been a controversy as to the contribution of the frontal lobe to human memory function. We describe a 49-year-old right-handed patient with memory disturbance following a left medial frontal subcortical hematoma. Her amnesia was characterized by (1) predominant anterograde amnesia, (2) difficulty in both voluntary recall and recognition tasks, (3) a great number of false-alarm responses in a recognition task, and (4) no confabulation. An MRI demonstrated that her lesion was restricted to the left medial frontal area and anterior cingulate gyrus. This case represents a rare instance of amnesia following damage to the frontal lobe. We speculated that the unique feature of her memory impairment resulted from combined lesions in the medial frontal subcortical white matter and anterior cingulate gyrus. It seems that Papez's circuite participated in the development of these symptoms.

We report a 69-year-old left-handed man, who developed alexia after a right medial occipito-temporal lobe infarction. On admission to the rehabilitation department two months after the onset, neurological examination showed left hemianopia, left hemiparesis, decreased deep sensation on the left side, and alexia. A brain MRI demonstrated infarcts in the right medial occipito-temporal lobe and the splenium of the corpus callosum. Detailed neuropsychological examination was performed two months after the onset. The patient was alert and cooperative. His speech was fluent with some word-finding difficulty. Comprehension for spoken materials, repetition, and naming abilities were all preserved. Systematic examination for reading revealed that reading aloud was disturbed in both kanji and kana words. Reading comprehension was significantly better for kanji words than kana words. First, we examined the effects of number of characters in a word. The number of characters in a word didn't affect his reading performance. Second, his performance on reading aloud of usual kanji words was compared with that of kanji words representing idioms. A kanji idiom is different from usual kanji words, in which pronunciation of each character is selected from several options. Reading aloud kanji idioms was significantly better than usual kanji words. In addition, reaction time to complete reading a word was much shorter for kanji idioms than usual kanji. An analysis of qualitative features of errors revealed that most errors in kanji idiom reading were semantically similar to the correct answers, while many errors in usual kanji word reading were classified into "don't know" responses. These findings suggested that a kanji idiom was tightly connected to its pronunciation, which resulted in his much better performance for kanji idiom reading. Overlearning of a unique relationship between a kanji idiom and its pronunciation might modify neuronal organization for reading.

Patients with jargon aphasia generally have fluent speech with poor comprehension. However, outstanding jargons may appear in non-fluent aphasics. We report a 69-year-old left-handed woman with non-fluent jargon aphasia due to lesions in the right frontoparietal area. Features of her speech included non-fluent meaningless sequences of syllables, i. e., phonetic jargon, which was obvious in all the tasks including spontaneous speech, repetition, naming and reading. Her utterance was sparse, but not effortful or anarthric. She understood most of spoken single words, but was confused by complex sentences. Brain CTs revealed acute lesions affecting the inferior and middle frontal gyri, insular cortex, precentral and postcentral gyri, and a part of the angular gyrus in the right hemisphere. Old infarcts were also noted in the right frontal pole and prefrontal area. The unique feature of her language impairment suggested somewhat deviated lateralization and localization of her language function.