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Objective Muscle atrophy is observed in a subset of patients with chronic inflammatory demyelinating polyneuropathy (CIDP). Its manifestation is associated with a poor functional prognosis and poor response to immunomodulatory therapies. We evaluated muscle atrophy in patients with CIDP using a bioelectrical impedance analysis (BIA). Methods We enrolled 12 patients with CIDP for a BIA of muscle atrophy. Of these 12 patients, 10 were diagnosed with typical CIDP, 1 with multifocal acquired demyelinating sensory and motor neuropathy, and 1 with distal acquired demyelinating symmetric neuropathy. All 12 patients underwent a series of assessments and evaluations, including a BIA and computed tomography (CT). A correlation was found between the skeletal muscle mass determined by the BIA and that found using CT of the muscles. Results The BIA provided values for each patient's skeletal muscle mass index (SMI) ranging from 4.1 to 8.1 kg/m

Objective About 30%–50% of patients with amyotrophic lateral sclerosis (ALS) show cognitive impairment ranging from mild dysexecutive syndrome to frontotemporal dementia. We aimed to develop a brief cognitive test, convenient auditory-based language and executive function test (CABLET), for rapid detection of cognitive impairment in ALS, with reduced load on motor function. Method The CABLET comprises two tests using auditory verbal stimuli: Test 1, assessing word repetition and lexical judgment, and Test 2, evaluating verbal short-term memory and semantics knowledge. The administration time of Test 1 and Test 2 was 1 and 3–5 min, respectively. Overall, 61 patients with ALS and 46 age-, sex-, and education-matched healthy controls participated in this study. All participants underwent existing neuropsychological tests and the CABLET. We investigated the applicability of the CABLET to detect ALS with cognitive impairment (ALSci) from normal cognition. Results Receiver operating characteristic analyses showed that both the CABLET total and Test 2 had good diagnostic accuracy (area under the curve [AUC]: total = 0.894, Test 2 = 0.893). Test 2 had the highest sensitivity (100% sensitivity and 71.4% specificity). No significant difference existed in the AUC between the analyses with and without age, education, and disease severity as covariates. Correlations were observed between the CABLET and established neuropsychological tests, supporting its good convergent validity. Conclusions Our findings indicated that the CABLET could be useful in identifying ALSci quickly without adjusting for confounding factors. Further validation is required to evaluate it in larger groups and compare with ALS-specific cognitive screen.

IgG4-related inflammatory pseudotumor is a feature of IgG4-related disease and develops in various organs. Intracranial IgG4-related inflammatory pseudotumor is rare, and data on the clinical course and response to treatment are insufficient in the literature. We herein report a patient with IgG4-related inflammatory pseudotumor who had magnetic resonance imaging findings similar to meningioma. Tumorectomy was discontinued because of the intraoperative rapid diagnosis, which revealed the infiltration of lymphocytes and plasma cells. She received oral prednisolone therapy for IgG4-related inflammatory pseudotumor, and the tumor size had significantly decreased after six months of treatment.

A 32-year-old man, who visited Japan from the Philippines in 2020, was diagnosed with rabies, the first reported case in Japan since 2006. This is the fourth imported case of rabies since 1957; one case in 1970 was imported from Nepal and two in 2006 were imported from the Philippines.

Progressive multifocal leukoencephalopathy (PML) is a demyelinating disease of the central nervous system caused by reactivation of the JC virus under an immunosuppressed state. This condition carries a high risk of cryptococcal meningitis. We herein report a 65-year-old woman who simultaneously developed PML and cryptococcal meningitis and presented with bilateral sixth nerve palsy. She had been treated with methotrexate and infliximab for rheumatoid arthritis. Her symptoms improved with antifungal drug treatment and discontinuation of immunosuppression therapy. Although concurrent PML and cryptococcal meningitis is rare, it should be considered in immunosuppressed patients.

Background: The clinicopathological continuity between amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD) is well known. Although ALS demonstrates language symptoms similar to FTLD, including semantic dementia, word reading impairments in ALS have not been well studied. “Jukujikun” are Kanji-written words with irregular pronunciation comparable to “exception words” and useful for detecting semantic deficits in Japan. We conducted a cross-sectional study to investigate Jukujikun reading impairments and related network changes in ALS. Methods: We enrolled 71 ALS patients and 69 healthy controls (HCs). Age-, sex-, and education matched HCs were recruited from another cohort study concurrently with patient registration. We examined neuropsychological factors including low frequency Jukujikun reading. We performed resting-state functional magnetic resonance imaging with voxel-based graph analysis on a subset of participants who agreed. Findings: Low frequency Jukujikun score was decreased in ALS (15·0[11·0–19·0](median[25–75 percentile])) compared with HCs (19·0[17·3–20·0]) (p

Background The clinicopathological continuity between amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD) is well known. Although ALS demonstrates language symptoms similar to FTLD, including semantic dementia, word reading impairments in ALS have not been well studied. “Jukujikun” are Kanji-written words with irregular pronunciation comparable to “exception words” and useful for detecting semantic deficits in Japan. We conducted a cross-sectional study to investigate Jukujikun reading impairments and related network changes in ALS. Methods We enrolled 71 ALS patients and 69 healthy controls (HCs). Age-, sex-, and education matched HCs were recruited from another cohort study concurrently with patient registration. We examined neuropsychological factors including low frequency Jukujikun reading. We performed resting-state functional magnetic resonance imaging with voxel-based graph analysis on a subset of participants who agreed. Findings Low frequency Jukujikun score was decreased in ALS (15·0[11·0–19·0](median[25–75 percentile])) compared with HCs (19·0[17·3–20·0]) (p

Healthy aging is associated with structural and functional changes in the brain even in individuals who are free of neurodegenerative diseases. Using resting state functional magnetic resonance imaging data from a carefully selected cohort of participants, we examined cross sectional changes in the functional organization of several large-scale brain networks over the adult lifespan and its potential association with general cognitive performance. Converging results from multiple analyses at the voxel, node, and network levels showed widespread reorganization of functional brain networks with increasing age. Specifically, the primary processing (visual and sensorimotor) and visuospatial (dorsal attention) networks showed diminished network integrity, while the so-called core neurocognitive (executive control, salience, and default mode) and basal ganglia networks exhibited relatively preserved between-network connections. The visuospatial and precuneus networks also showed significantly more widespread increased connectivity with other networks. Graph analysis suggested that this reorganization progressed towards a more integrated network topology. General cognitive performance, assessed by Addenbrooke’s Cognitive Examination-Revised total score, was positively correlated with between-network connectivity among the core neurocognitive and basal ganglia networks and the integrity of the primary processing and visuospatial networks. Mediation analyses further indicated that the observed association between aging and relative decline in cognitive performance could be mediated by changes in relevant functional connectivity measures. Overall, these findings provided further evidence supporting widespread age-related brain network reorganization and its potential association with general cognitive performance during healthy aging.

We aimed to elucidate the effect of cerebellar degeneration in relation to cognition in multiple system atrophy (MSA). Thirty-two patients diagnosed with probable MSA and 32 age- and gender-matched healthy controls (HCs) were enrolled. We conducted voxel-based morphometry (VBM) for anatomical images and independent component analysis (ICA), dual-regression analysis, and seed-based analysis for functional images with voxel-wise gray matter correction. In the MSA group, a widespread cerebellar volume loss was observed. ICA and dual-regression analysis showed lower functional connectivity (FC) in the left executive control and salience networks in regions located in the cerebellum. Seed-based analysis using the identified cerebellar regions as seeds showed extensive disruptions in cerebello-cerebral networks. Global cognitive scores correlated with the FC values between the right lobules VI/crus I and the medial prefrontal/anterior cingulate cortices and between the same region and the amygdala/parahippocampal gyrus. Our study indicates that cerebellar degeneration in MSA causes segregation of cerebellar-cerebral networks. Furthermore, the cognitive deficits in MSA may be driven by decreased cerebello-prefrontal and cerebello-amygdaloid functional connections.

Recent studies have demonstrated that connector hubs, regions considered critical for the flow of information across neural systems, are mostly involved in neurodegenerative dementia. Considering that aging can significantly affect the brain’s intrinsic connectivity, identifying aging’s impact on these regions’ overall connection strength is important to differentiate changes associated with healthy aging from neurodegenerative disorders. Using resting state functional magnetic resonance imaging data from a carefully selected cohort of 175 healthy volunteers aging from 21 to 86 years old, we computed an intrinsic connectivity contrast (ICC) metric, which quantifies a region’s overall connectivity strength, for whole brain, short-range, and long-range connections and examined age-related changes of this metric over the adult lifespan. We have identified a limited number of hub regions with ICC values that showed significant negative relationship with age. These include the medial precentral/midcingulate gyri and insula with both their short-range and long-range (and thus whole-brain) ICC values negatively associated with age, and the angular, middle frontal, and posterior cingulate gyri with their long-range ICC values mainly involved. Seed-based connectivity analyses further confirmed that these regions are connector hubs with connectivity profile that strongly overlapped with multiple large-scale brain networks. General cognitive performance was not associated with these hubs’ ICC values. These findings suggest that even healthy aging could negatively impact the efficiency of regions critical for facilitating information transfer among different functional brain networks. The extent of the regions involved, however, was limited.

Misfolded and aggregated tau and amyloid β (Aβ) proteins are the pathological hallmarks of Alzheimer's disease (AD). These aberrant proteins lose their physiological roles, acquire neurotoxicity, and propagate across neural systems. Despite the growing understanding of the molecular pathophysiology, the relationship among molecular alterations, pathological changes, and dementia onset and progression remain to be elucidated. Connectivity is an exclusive characteristic of the brain, and the integrity and segregation of the functional and anatomical networks are crucial for normal functioning. Interestingly, a lot of magnetic resonance imaging (MRI) studies have demonstrated successive structural and functional disconnection among brain regions supporting the idea that AD is a disconnection syndrome. Recent several studies using the combination of cutting-edge Aβ and tau PET tracers integrated by data-driven statistical methods, resting-state functional MRI, and diffusion tensor imaging have shed light on the spatial distribution pattern of tau retention as well the relationship between tau retention and functional/structural network disruption in AD. Regional retention of tau PET traces is associated with gray matter changes, structural network disruption, and cognitive function tests. The tau retention will mainly spread along with cognition-related resting state networks and be more common in the network hubs which exhibit many strong interconnections with other regions within the network as well as without the networks. Mainly, precuneus and posterior cingulate gyrus are commonly involved and can be the critical nodes associated with clinically manifested dementia from the normal cognitive state.

Introduction Parkinson's disease (PD) shows a variety of visual deficits including visuoperceptual disturbances, however, the neural basis remains unclear. We aimed to clarify clinical and neural features of visuoperceptual disturbances in PD. Methods The visuospatial/perceptual abilities of ninety-six participants (48 patients with PD and 48 healthy controls) were evaluated using the subtest part 1 and 5–8 of the Visual Object and Space Perception battery (VOSP), cube/pentagon copying and clock drawing tasks. Resting-state fMRI images were acquired and analyzed the differences between PD with incomplete letters below the cut-off and above for intranetwork (primary/medial/higher visual networks) and interregional functional connectivity changes, and spectral dynamic causal modeling was performed to examine the causality. Results In the PD group, position discrimination and incomplete letter scores were significantly decreased among VOSP subtests, the latter having the largest effect size. The incomplete letter scores correlated with the position discrimination while not with the dot counting, number location and cube analysis, cube/pentagon copying or clock drawing. The group with the incomplete letter scores below the cut-off had regions with decreased functional connectivity surrounding the calcarine sulcus in the primary visual network. These regions had decreased interregional functional connectivity with bilateral lingual gyri and cunei but increased with the thalamus. In this group, effective connectivity from the lingual gyrus to the calcarine sulcus was significantly decreased. Conclusion The incomplete letters may be sensitive to detect visuoperceptual disturbances in PD. Decreased connectivity in the ventral visual feedback pathway may contribute to these deficits., Highlights • PD patients may exhibit impaired identification of incomplete letters. • Incomplete letters are sensitive to detect visuoperceptual deficits in PD. • Incomplete letters were not associated with visuoconstruction abilities. • Decreased connectivity in visual feedback pathway may contribute to the deficits.

Highlights • Some epilepsy associated with Mowat-Wilson syndrome (MWS) is resistant to anti-seizure drugs. • Occasionally, determining the best combination of therapeutic anti-seizure drugs for the management of MWS is challenging. • In the management of MWS, keeping the patient seizure-free warrants close monitoring. • Adult MWS patients may be prone to develop recurrent intractable status epilepticus., Mowat-Wilson syndrome (MWS) is a rare genetic disorder characterized by intellectual disability, distinctive facial features, epilepsy, and multiple anomalies caused by heterozygous loss-of-function mutations in the zinc finger E-box-binding homeobox-2 gene (ZEB2). Treatment choice is very important as patients with MWS because patients sometimes develop drug-resistant epilepsy. Here, we report the case of a 45-year-old male patient with MWS who developed drug-resistant status epilepticus after a 26-years seizure-free period while taking multiple anti-seizure medications. He showed a characteristic magnetic resonance imaging finding with a focal lesion in his left thalamic pulvinar nucleus, a finding not previously reported in status epilepticus with MWS. We succeeded in controlling seizures in the patient after trying multiple new antiseizure drug combinations. These findings indicate that patients with MWS may develop drug-resistant status epilepticus with age, even after a long-term seizure-free period, which can be managed with anti-seizure medication. Therefore, careful monitoring of seizures is important for the treatment of people with MWS, even in patients who have not experienced seizures for a long time.

Objective. Painful ophthalmoplegia includes nonspecific magnetic resonance imaging (MRI) manifestations and various clinical features including orbital pain and cranial nerve palsies. Treatment for painful ophthalmoplegia remains controversial. The aim of this report was to describe detailed clinical features, MRI findings, treatments, and prognosis of patients with painful ophthalmoplegia. Patients and Methods. We retrospectively investigated four cases of patients with painful ophthalmoplegia diagnosed using the International Classification of Headache Disorders, 3rd edition. Results. All patients experienced unilateral orbital pain and oculomotor nerve palsy with diplopia but no vision loss. One of the four patients was diagnosed with Tolosa–Hunt syndrome based on the appearance of a granulomatous inflammation of the cavernous sinus on MRI. No specific lesions were detected on brain MRI for the other three patients; therefore, their headaches were attributed to ischaemic ocular motor nerve palsy. In all patients, a high-intensity ring appearance around the ipsilateral optic nerve was observed on MRI. Steroid therapy was administered to these patients, and good prognoses were anticipated. Conclusion. These results indicate that prednisolone is a useful treatment for painful ophthalmoplegia that displays ipsilateral hyperintense ring lesions around the optic nerve on MRI, regardless of the presence of granulomatous inflammation of the cavernous sinus.

The aging brain undergoes structural changes even in very healthy individuals. Quantifying these changes could help disentangle pathologic changes from those associated with the normal human aging process. Using longitudinal magnetic resonance imaging (MRI) data from 227 carefully selected healthy human cohort with age ranging from 50 to 80 years old at baseline scan, we quantified age-related volumetric changes in the brain of healthy human older adults. Longitudinally, the rates of tissue loss in total gray matter (GM) and white matter (WM) were 2497.5 and 2579.8 mm3per year, respectively. Across the whole brain, the rates of GM decline varied with regions in the frontal and parietal lobes having faster rates of decline, whereas some regions in the occipital and temporal lobes appeared relatively preserved. In contrast, cross-sectional changes were mainly observed in the temporal-occipital regions. Similar longitudinal atrophic changes were also observed in subcortical regions including thalamus, hippocampus, putamen, and caudate, whereas the pallidum showed an increasing volume with age. Overall, regions maturing late in development (frontal, parietal) are more vulnerable to longitudinal decline, whereas those that fully mature in the early stage (temporal, occipital) are mainly affected by cross-sectional changes in healthy older cohort. This may suggest that, for a successful healthy aging, the former needs to be maximally developed at an earlier age to compensate for the longitudinal decline later in life and the latter to remain relatively preserved even in old age, consistent with both concepts of reserve and brain maintenance.

Older age is thought to be a risk factor for cognitive impairment in amyotrophic lateral sclerosis (ALS). However, very few clinical studies have investigated this relationship using sufficient numbers of healthy controls that correspond to each generation. The purpose of this study was to determine the age-related changes of Addenbrooke's Cognitive Examination-Revised (ACE-R) score in ALS patients by comparing healthy controls of various ages.131 ALS patients (86 males, 45 females; mean age: 64.8 ± 10.2; mean education: 12.5 ± 2.7) and 151 age-, gender-, and education-matched healthy controls were enrolled. We applied ACE-R, which could evaluate not only global cognition but five cognitive subdomains that included orientation/attention, memory, verbal fluency, language, and visuospatial ability.ALS patients had significantly lower total and subdomain scores of ACE-R than healthy controls. Multiple regression analysis suggested that age at examination and age at onset had significant influence on ACE-R scores. When we divided ALS patients and healthy controls into 4 groups according to age at examination for ALS, total and each subdomain scores were significantly lower with age, particularly in the older-middle and the oldest group (66.31 years or more) of ALS compared with healthy controls. Locally weighted scatterplot smoothing analysis supported that these reductions of ACE-R total and subdomain scores in ALS patients were more accelerated by approximately 60 years as compared with healthy controls.ALS patients showed accelerated age-related ACE-R score reduction beyond normal ageing processes.

White matter (WM) fiber bundles change dynamically with age. These changes could be driven by alterations in axonal diameter, axonal density, and myelin content. In this study, we applied a novel fixel‐based analysis (FBA) framework to examine these changes throughout the adult lifespan. Using diffusion‐weighted images from a cohort of 293 healthy volunteers (89 males/204 females) from ages 21 to 86 years old, we performed FBA to analyze age‐related changes in microscopic fiber density (FD) and macroscopic fiber morphology (fiber cross section [FC]). Our results showed significant and widespread age‐related alterations in FD and FC across the whole brain. Interestingly, some fiber bundles such as the anterior thalamic radiation, corpus callosum, and superior longitudinal fasciculus only showed significant negative relationship with age in FD values, but not in FC. On the other hand, some segments of the cerebello‐thalamo‐cortical pathway only showed significant negative relationship with age in FC, but not in FD. Analysis at the tract‐level also showed that major fiber tract groups predominantly distributed in the frontal lobe (cingulum, forceps minor) exhibited greater vulnerability to the aging process than the others. Differences in FC and the combined measure of FD and cross section values observed between sexes were mostly driven by differences in brain sizes although male participants tended to exhibit steeper negative linear relationship with age in FD as compared to female participants. Overall, these findings provide further insights into the structural changes the brain's WM undergoes due to the aging process., In this study, we investigated age‐related changes in white matter fiber density (FD) and morphology (fiber cross section [FC]) across the adult lifespan. Our results showed significant and widespread age‐related alterations in FD and FC across the whole brain. The observed changes were nonuniform across white matter with some fibers exhibiting higher vulnerability than the others.

Background: The clinicopathological continuity between amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD) is well known. Although patients with ALS demonstrate similar language symptoms to patients with FTLD, including semantic dementia, word reading impairments in ALS have not been well studied. "Jukujikun" are kanji-written words with irregular pronunciation that applies to "exception words" and are useful for detecting semantic deficits in Japan. We investigated Jukujikun reading impairments and related changes in resting-state networks in patients with ALS. Methods: We enrolled 140 participants, including 71 ALS patients and 69 healthy controls. We examined demographic and comprehensive neuropsychological factors, including Jukujikun. We also performed resting-state functional magnetic resonance imaging with voxel-based graph analysis on a subset of participants who agreed to participate in the imaging study to investigate the hub regions and related networks associated with Jukujikun impairments in ALS. Findings: Fifty-two percent of ALS patients (N=37) exhibited a significantly reduced score in Jukujikun reading compared with controls. We classified those patients as ALS with positive Jukujikun deficit (ALS-JD+) and the other patients as ALS with negative deficit (ALS-JD-). Resting-state network analysis showed significantly decreased degree centrality in the right fusiform/lingual gyrus and increased degree centrality in the left inferior/middle temporal gyrus in ALS-JD+ compared with ALS-JD- and controls. Seed-based analysis also revealed that the hub dysfunction in the right fusiform/lingual gyrus depended on decreased connectivity with regions associated with visual word perception, semantic processing, and speech. On the other hand, the observed increased degree centrality in the left inferior/middle temporal gyrus was derived from regions related to semantic processing. Interpretation Dysfunction of the "hub" in the right fusiform/lingual gyrus can affect semantic deficit in ALS. Considering neuropsychological symptoms as network impairments is vital for understanding various diseases. Funding MHLW and MEXT, Japan. Funding Statement: MHLW and MEXT, Japan. Declaration of Interests: The authors declare no competing interests. Ethics Approval Statement: The study conformed to the Ethical Guidelines for Medical and Health Research Involving Human Subjects endorsed by the Japanese government. The study protocol was approved by the Ethics Review Committee of the Nagoya University Graduate School of Medicine, and written informed consent was obtained from all participants.

Misfolded and aggregated tau and amyloid β (Aβ) proteins are the pathological hallmarks of Alzheimer's disease (AD). These aberrant proteins lose their physiological roles, acquire neurotoxicity, and propagate across neural systems. Despite the growing understanding of the molecular pathophysiology, the relationship among molecular alterations, pathological changes, and dementia onset and progression remain to be elucidated. Connectivity is an exclusive characteristic of the brain, and the integrity and segregation of the functional and anatomical networks are crucial for normal functioning. Interestingly, a lot of magnetic resonance imaging (MRI) studies have demonstrated successive structural and functional disconnection among brain regions supporting the idea that AD is a disconnection syndrome. Recent several studies using the combination of cutting-edge Aβ and tau PET tracers integrated by data-driven statistical methods, resting-state functional MRI, and diffusion tensor imaging have shed light on the spatial distribution pattern of tau retention as well the relationship between tau retention and functional/structural network disruption in AD. Regional retention of tau PET traces is associated with gray matter changes, structural network disruption, and cognitive function tests. The tau retention will mainly spread along with cognition-related resting state networks and be more common in the network hubs which exhibit many strong interconnections with other regions within the network as well as without the networks. Mainly, precuneus and posterior cingulate gyrus are commonly involved and can be the critical nodes associated with clinically manifested dementia from the normal cognitive state.

Background: Imaging studies in Alzheimer's disease (AD) have yet to answer the underlying questions concerning the relationship among tau retention, neuroinflammation, network disruption and cognitive decline. We compared the spatial retention patterns of 18F-THK5351 and resting state network (RSN) disruption in patients with early AD and healthy controls. Methods: We enrolled 23 11C-Pittsburgh compound B (PiB)-positive patients with early AD and 24 11C-PiB-negative participants as healthy controls. All participants underwent resting state functional MRI and 18F-THK5351 PET scans. We used scaled subprofile modeling/principal component analysis (SSM/PCA) to reduce the complexity of multivariate data and to identify patterns that exhibited the largest statistical effects (variances) in THK5351 concentration in AD and healthy controls. Findings: SSM/PCA identified a significant spatial THK5351 pattern composed by mainly three clusters including precuneus/posterior cingulate cortex (PCC), right and left dorsolateral prefrontal cortex (DLPFC) which accounted for 23.6% of the total subject voxel variance of the data and had 82.6% sensitivity and 79.1% specificity in discriminating AD from healthy controls. There was a significant relationship between the intensity of the 18F-THK5351 covariation pattern and cognitive scores in AD. The spatial patterns of 18F-THK5351 uptake showed significant similarity with intrinsic functional connectivity, especially in the PCC network. Seed-based connectivity analysis from the PCC showed significant decrease in connectivity over widespread brain regions in AD patients. An evaluation of an autopsied AD patient with Braak V showed that 18F-THK5351 retention corresponded to tau deposition, monoamine oxidase-B (MAO-B) and astrogliosis in the precuneus/PCC. Interpretation: We identified an AD-specific spatial pattern of 18F-THK5351 retention in the precuneus/PCC, an important connectivity hub region in the brain. Disruption of the functional connections of this important network hub may play an important role in developing dementia in AD.

Cerebral Amyloid Angiopathy-related inflammation (CAA-ri) is a distinct subtype of CAA characterized by rapidly progressive cognitive decline, focal deficits, seizures, and headache. It is characterized by vasculitis associated with cerebral amyloid deposition. Differential diagnosis may be challenging due to overlapping symptoms and lack of clear imaging criteria, although CCA-ri is usually responsive to immunosuppressive therapy. We describe an 81-year-old female diagnosed with CAA-ri by Magnetic Resonance Imaging (MRI). Fluid-Attenuated Inversion Recovery (FLAIR) imaging revealed hyperintense lesions in the bilateral temporal and occipital areas, and T2*-weighted gradient echo (T2*-GRE) imaging demonstrated multiple cortical and subcortical hypointensities in the same areas. Furthermore, the findings of T2*-GRE were confirmed by Susceptibility-Weighted Imaging (SWI). In cases of encephalopathy, CAA-ri should be considered in the differential diagnosis, and the presence of microbleeds should be examined using T2*-GRE and (or) SWI MRI.

Cognitive deficits in Parkinson’s disease (PD) are heterogeneous entities, but a relationship between the heterogeneity of cognitive deficits and resting-state network (RSN) changes remains elusive. In this study, we examined five sub-domain scores according to Addenbrooke’s Cognitive Examination-Revised (ACE-R) for the cognitive evaluation and classification of 72 non-demented patients with PD. Twenty-eight patients were classified as PD with normal cognition (PD-NC). The remaining 44 were subdivided into the following 2 groups using a hierarchical cluster analysis: 20 with a predominant decrease in memory (PD with amnestic cognitive deficits: PD-A) and 24 with good memory who exhibited a decrease in other sub-domains (PD with non-amnestic cognitive deficits: PD-NA). We used an independent component analysis of RS-fMRI data to investigate the inter-group differences of RSN. Compared to the controls, the PD-A showed lower FC within the ventral default mode network (vDMN) and the visuospatial network. On the other hand, the PD-NA showed lower FC within the visual networks and the cerebellum–brainstem network. Significant differences in the FC within the vDMN and cerebellum–brainstem network were observed between the PD-A and PD-NA, which provided a good discrimination between PD-A and PD-NA using a support vector machine. Distinct patterns of cognitive deficits correspond to different RSN changes.

This study aims to elucidate age-related intrinsic brain volume changes over the adult lifespan using an unbiased data-driven structural brain parcellation. Anatomical brain images from a cohort of 293 healthy volunteers ranging in age from 21 to 86 years were analyzed using independent component analysis (ICA). ICA-based parcellation identified 192 component images, of which 174 (90.6%) showed a significant negative correlation with age and with some components being more vulnerable to aging effects than others. Seven components demonstrated a convex slope with aging; 3 components had an inverted U-shaped trajectory, and 4 had a U-shaped trajectory. Linear combination of 86 components provided reliable prediction of chronological age with a mean absolute prediction error of approximately 7.2 years. Structural co-variation analysis showed strong interhemispheric, short-distance positive correlations and long-distance, inter-lobar negative correlations. Estimated network measures either exhibited a U- or an inverted U-shaped relationship with age, with the vertex occurring at approximately 45-50 years. Overall, these findings could contribute to our knowledge about healthy brain aging and could help provide a framework to distinguish the normal aging processes from that associated with age-related neurodegenerative diseases.

Objective Previous studies have indicated that type-1 and type-2 interleukin-1 (IL-1) receptors (IL-1R1 and IL-1R2) play important roles in periodontitis progression. We investigated the association between periodontitis and polymorphisms in the IL-1R1 and IL-1R2 genes ( IL1R1 and IL1R2 ). Design We searched for genetic variants in IL1R1 and IL1R2 in 24 Japanese patients with aggressive periodontitis (AgP) and 24 periodontally healthy controls. Thirty-eight single nucleotide polymorphisms (SNPs) were identified within genomic regions containing all exons and relevant exon-intron boundaries in IL1R1 and IL1R2 . Possible associations of each gene locus with AgP were investigated in 119 AgP patients and 102 periodontally healthy controls using allelotypes, genotypes, and haplotypes. Results Significant differences were noted in the frequencies of 3 SNPs in IL1R2 (rs3819370, rs3218974 and rs3218977) for AgPs and controls ( p = 0.012, p = 0.008, and p = 0.038, respectively), after adjustment for gender and smoking status in the additive model ( p = 0.016, p = 0.007, and p = 0.027, respectively) and 2 haplotypes ( p = 0.010 and p = 0.011, respectively) constructed from 2 SNPs (rs3819370 and rs3218974) that showed the lowest p -values after adjustment of covariates in additive models. Conclusion A genetic susceptibility locus for AgP may lie within or close to the IL1R2 locus. Further studies in other populations are necessary to confirm these results.

The dental follicle is a mesenchymal tissue that surrounds the developing tooth germ. During tooth root formation, periodontal components, viz., cementum, periodontal ligament (PDL), and alveolar bone, are created by dental follicle progenitors. Here, we report the presence of PDL progenitors in mouse dental follicle (MDF) cells. MDF cells were obtained from mouse incisor tooth germs and immortalized by the expression of a mutant human papilloma virus type 16 E6 gene lacking the PDZ-domain-binding motif. MDF cells expressing the mutant E6 gene (MDF( E6-EGFP ) cells) had an extended life span, beyond 150 population doublings (PD). In contrast, normal MDF cells failed to proliferate beyond 10 PD. MDF( E6-EGFP ) cells expressed tendon/ligament phenotype-related genes such as Scleraxis (Scx), growth and differentiation factor-5, EphA4, Six-1, and type I collagen. In addition, the expression of periostin was observed. To elucidate the differentiation capacity of MDF( E6-EGFP ) cells in vivo, the cells were transplanted into severe combined immunodeficiency mice. At 4 weeks, MDF( E6-EGFP ) cell transplants had the capacity to generate a PDL-like tissue that expressed periostin, Scx, and type XII collagen and the fibrillar assembly of type I collagen. Our findings suggest that MDF( E6-EGFP ) cells can act as PDL progenitors, and that these cells may be a useful research tool for studying PDL formation and for developing regeneration therapies.

A cementoblast progenitor cell line designated BCPb8 was successfully isolated from dental follicle cells immortalized with Bmi-1 and hTERT. BCPb8 showed the potential to differentiate into cementoblasts on implantation into immunodeficient mice. BCPb8 was confirmed to be the first established cementoblast progenitor cell line and will provide a useful model for investigating cementogenesis. Introduction: The dental follicle is the mesenchymal tissue surrounding the developing tooth germ. During tooth root development, progenitor cells present in the dental follicle are believed to play a central role in the formation of periodontal components (cementum, periodontal ligament, and alveolar bone). However, little more is known about the biology of these progenitors. Previously, we observed that cultured bovine dental follicle cells (BDFCs) contained putative cementoblast progenitors. To further analyze the biology of these cells, we attempted to isolate cementoblast progenitors from immortalized BDFC through expression of the polycomb group protein, Bmi-1, and human telomerase reverse transcriptase (hTERT). Materials and Methods: BDFCs were transduced with replication-deficient retroviruses carrying human Bmi-1(LXSN-Bmi-1), and hTERT (LXSH-hTERT) for immortalization. Single cell clones were established from immortalized BDFC, and differentiation into cementoblasts was assessed by implantation into immunodeficient mice. Results and Conclusion: BDFCs expressing Bmi-1 and hTERT showed an extended life span - 90 population doublings more than normal BDFCs - and still contained cells with the potential to differentiate into cementoblasts on implantation into immunodeficient mice. From these cells, we established a clonal cell line, designated BCPb8, which formed cementum-like tissue that was reactive to the anti-cementum-specific monoclonal antibody 3G9 and expressed mRNA for bone sialoprotein, osteocalcin, osteopontin, and type I collagen on implantation. Thus, by using Bmi-1 and hTERT, we succeeded in immortalizing cementoblast progenitor cells from BDFC without affecting differentiation potential. The BCPb8 cell line is the first immortalized clonal cell line of cementoblast progenitors and could be a useful tool not only to study cementogenesis but also to develop regeneration therapy for patients with periodontitis.

Paraneoplastic limbic encephalitis is a rare neurological disorder that frequently precedes the detection of malignancy. We report the case of a 68-year-old male with small-cell lung cancer who developed paraneoplastic limbic encephalitis associated with presence of the anti-Hu antibody, after achieving complete remission of the tumor by chemotherapy. The patient visited our hospital because of progressive sensory disturbance of the distal extremities at 65 years of age. Though paraneoplastic sensory neuropathy was suspected, we could not find any tumor and he did not improve with steroids or immunoglobulin therapy. Chest computed tomography (CT) revealed large mediastinal lymphadenopathy. He was subsequently diagnosed with small cell lung cancer at one year and three months after the neurological symptoms occurred. As his serum analysis was positive for the anti-Hu antibody, we diagnosed paraneoplastic sensory neuropathy. The lung cancer disappeared with chemotherapy, but he had developed short-term memory loss six months later. Brain fluid attenuated inversion recovery (FLAIR) imaging showed an abnormal high-intensity lesion in the left medial temporal lobe including the hippocampus. We therefore made the diagnosis of paraneoplastic limbic encephalitis following subacute sensory neuropathy associated with the anti-Hu antibody. To our knowledge, this is the first report of a patient presenting with paraneoplastic neurological syndrome in which limbic encephalitis developed after tumor disappearance. So we must recognize the possibility of neurological symptoms occurring during remission. As the mechanism of pathogenesis, delayed neuronal cell damage due to immune responses against the tumor is implicated.

Matrix remodeling is regulated by matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs). Periostin, originally identified in a mouse osteoblastic library, plays a role in cell adhesion and migration and in mechanical stress-induced matrix remodeling. In this study, we analyzed and compared the distribution patterns of TIMP-2 and periostin during mouse mandible development. Immunohistochemical staining for TIMP-2 and periostin was carried out on serial cryosections obtained from mice at embryonic days 13-16, postnatal day 2 (P2), P35, and 12 weeks of age. TIMP-2 and periostin exhibited a strikingly similar protein distribution during mandible development. From bud to early bell stages of molars, TIMP-2 and periostin were highly expressed on the lingual and anterior sides of the basement membrane and on the adjacent jaw mesenchyme. In pre- and postnatal incisors, the basement membrane of the apical loop and dental follicle was immunostained for TIMP-2 and periostin. At postnatal stages, TIMP-2 and periostin were prominently confined to the extracellular matrix (ECM) of gingival tissues, periodontal ligaments, and tendons (all recipients of mechanical strain). However, periostin was solely detected in the lower portion of the inner root sheath of hair follicles. Gingiva of P2 cultured in anti-TIMP-2 antibody-conditioned medium showed markedly reduced staining of periostin. We suggest that TIMP-2 and periostin are co-distributed on ECM exposed to mechanical forces and coordinately function as ECM modulators.

This paper studies on a new eignespace method which employs autoassociative networks for object recognition. Five layered autoassociative network is available to obtain a manifold on the minimum square error hypersurface which approximates a distribution of learning sample. Recognition experiments were performed to show that the manifold of rotating object is obtained by learning and the objects, such as a mouse and a stapler, are correctly recognized by the autoassociative networks. It is also shown that the accuracy of approximating closed manifold and the accuracy of recognition are improved by emploing multiple autoassociative networks each of which is trained by a partition of the learning sample.The property and the advantage of the five layered autoassociative network are demonstrated by a comparative study with the nearest neighbor method and the eigenspace method.