A case of autoimmune encephalitis in a patient with a solitary intracranial plasmacytoma.

A 65-year-old woman presented with fever and abnormal behavior. Magnetic resonance imaging showed swelling of the left medial temporal lobe and an intracranial extra-axial occipital tumor. While her neurological symptoms improved after the administration of corticosteroid therapy under the suspicion of autoimmune encephalitis, the occipital tumor unexpectedly shrank, and the diagnosis of a solitary plasmacytoma was confirmed by biopsy. Additional examinations revealed elevated anti-glutamate receptor antibodies in the cerebrospinal fluid. The patient was diagnosed with autoimmune encephalitis concurrent with an intracranial solitary plasmacytoma. Central nervous system involvement can be considered a neurological complication in patients with a solitary plasmacytoma.

Blood levels of glial fibrillary acidic protein for predicting clinical progression to Alzheimer's disease in adults without dementia: a systematic review and meta-analysis protocol.

BACKGROUND: There is urgent clinical need to identify reliable prognostic biomarkers that predict the progression of dementia symptoms in individuals with early-phase Alzheimer's disease (AD) especially given the research on and predicted applications of amyloid-beta (Aß)-directed immunotherapies to remove Aß from the brain. Cross-sectional studies have reported higher levels of cerebrospinal fluid and blood glial fibrillary acidic protein (GFAP) in individuals with AD-associated dementia than in cognitively unimpaired individuals. Further, recent longitudinal studies have assessed the prognostic potential of baseline blood GFAP levels as a predictor of future cognitive decline in cognitively unimpaired individuals and in those with mild cognitive impairment (MCI) due to AD. In this systematic review and meta-analysis, we propose analyzing longitudinal studies on blood GFAP levels to predict future cognitive decline. METHODS: This study will include prospective and retrospective cohort studies that assessed blood GFAP levels as a prognostic factor and any prediction models that incorporated blood GFAP levels in cognitively unimpaired individuals or those with MCI. The primary outcome will be conversion to MCI or AD in cognitively unimpaired individuals or conversion to AD in individuals with MCI. Articles from PubMed and Embase will be extracted up to December 31, 2023, without language restrictions. An independent dual screening of abstracts and potentially eligible full-text reports will be conducted. Data will be dual-extracted using the CHeck list for critical appraisal, data extraction for systematic Reviews of prediction Modeling Studies (CHARMS)-prognostic factor, and CHARMS checklists, and we will dual-rate the risk of bias and applicability using the Quality In Prognosis Studies and Prediction Study Risk-of-Bias Assessment tools. We will qualitatively synthesize the study data, participants, index biomarkers, predictive model characteristics, and clinical outcomes. If appropriate, random-effects meta-analyses will be performed to obtain summary estimates. Finally, we will assess the body of evidence using the Grading of Recommendation, Assessment, Development, and Evaluation Approach. DISCUSSION: This systematic review and meta-analysis will comprehensively evaluate and synthesize existing evidence on blood GFAP levels for prognosticating presymptomatic individuals and those with MCI to help advance risk-stratified treatment strategies for early-phase AD. TRIAL REGISTRATION: PROSPERO CRD42023481200.

Comparison of consistency in centiloid scale among different analytical methods in amyloid PET: the CapAIBL, VIZCalc, and Amyquant methods.

OBJECTIVE: The Centiloid (CL) scale is a standardized measure for quantifying amyloid deposition in amyloid positron emission tomography (PET) imaging. We aimed to assess the agreement among 3 CL calculation methods: CapAIBL, VIZCalc, and Amyquant. METHODS: This study included 192 participants (mean age: 71.5 years, range: 50-87 years), comprising 55 with Alzheimer's disease, 65 with mild cognitive impairment, 13 with non-Alzheimer's dementia, and 59 cognitively normal participants. All the participants were assessed using the three CL calculation methods. Spearman's rank correlation, linear regression, Friedman tests, Wilcoxon signed-rank tests, and Bland-Altman analysis were employed to assess data correlations, linear associations, method differences, and systematic bias, respectively. RESULTS: Strong correlations (rho = 0.99, p < .001) were observed among the CL values calculated using the three methods. Scatter plots and regression lines visually confirmed these strong correlations and met the validation criteria. Despite the robust correlations, a significant difference in CL value between CapAIBL and Amyquant was observed (36.1 ± 39.7 vs. 34.9 ± 39.4; p < .001). In contrast, no significant differences were found between CapAIBL and VIZCalc or between VIZCalc and Amyquant. The Bland-Altman analysis showed no observable systematic bias between the methods. CONCLUSIONS: The study demonstrated strong agreement among the three methods for calculating CL values. Despite minor variations in the absolute values of the Centiloid scores obtained using these methods, the overall agreement suggests that they are interchangeable.

The influence of limbic-predominant age-related TDP-43 encephalopathy on argyrophilic grain disease: A voxel-based morphometry analysis of pathologically confirmed cases.

BACKGROUND: The influence of limbic-predominant age-related TAR DNA-binding protein of 43 kDa encephalopathy neuropathological change (LATE-NC) on structural alterations in argyrophilic grain disease (AGD) have not been documented. This study aimed to investigate the morphological impact of LATE-NC on AGD through voxel-based morphometry (VBM) technique. MATERIALS AND METHODS: Fifteen individuals with pathologically verified AGD, comprising 6 with LATE-NC (comorbid AGD [cAGD]) and 9 without LATE-NC (pure AGD [pAGD]), along with 10 healthy controls (HC) were enrolled. Whole-brain 3D-T1-weighted images were captured and preprocessed utilizing the Computational Anatomy Toolbox 12. VBM was employed to compare gray matter volume among (i) pAGD and HC, (ii) cAGD and HC, and (iii) pAGD and cAGD. RESULTS: In comparison to HC, the pAGD group exhibited slightly asymmetric gray matter volume loss, particularly in the ambient gyrus, amygdala, hippocampus, anterior cingulate gyrus, and insula. Alternatively, the cAGD group exhibited greater gray matter volume loss, with a predominant focus on the inferolateral regions encompassing the ambient gyrus, amygdala, hippocampus, and the inferior temporal area, including the anterior temporal pole. The atrophy of the bilateral anterior temporal pole and right inferior temporal gyrus persisted when contrasting the pAGD and cAGD groups. CONCLUSION: Comorbidity with LATE-NC is linked to different atrophic distribution, particularly affecting the inferolateral regions in AGD. Consequently, the consideration of comorbid LATE-NC is crucial in individuals with AGD exhibiting more widespread temporal atrophy.

Voxel-based Morphometry of Alzheimer's Disease Using a Localizer Image: A Comparative Study with Magnetization Prepared Rapid Acquisition with Gradient Echo.

PURPOSE: Magnetization prepared rapid acquisition with gradient echo (MPRAGE) sequence is a gold-standard technique for voxel-based morphometry (VBM) because of high spatial resolution and excellent tissue contrast, especially between gray matter (GM) and white matter (WM). Despite its benefits, MPRAGE exhibits distinct challenge for VBM in some patients with neurological disease because of long scan time and motion artifacts. Speedily acquired localizer images may alleviate this problem. This study aimed to evaluate the feasibility of VBM using 3D Fast Low Angle Shot image captured for localizer (L3DFLASH). METHODS: Consecutive 13 patients with pathologically confirmed Alzheimer's disease (AD) (82 ± 9 years) and 21 healthy controls (HC) (79 ± 4 years) were included in this study. Whole-brain L3DFLASH and MPRAGE were captured and preprocessed using the Computational Anatomy Toolbox 12 (CAT12). Agreement with MPRAGE was evaluated for L3DFLASH using regional normalized volume for segmented brain areas. In addition to brain volume difference on VBM and Bland-Altman analysis, atrophic pattern of AD on VBM was evaluated using L3DFLASH and MPRAGE. RESULTS: Acquisition time was 18 s for L3DFLASH and 288 s for MPRAGE. There was a slight systematic difference in all regional normalized volumes from L3DFLASH and MPRAGE. For the whole cohort, GM volume measured from MPRAGE was greater than that from L3DFLASH in most of the region on VBM. When AD and HC were compared, AD-related atrophic pattern was demonstrated in both L3DFLASH and MPRAGE on VBM, although the difference was noted in significant clusters between them. CONCLUSION: Although systematic difference was noted in regional brain volume measured from L3DFLASH and MPRAGE, AD-related atrophic pattern was preserved in L3DFLASH on VBM. VBM, using speedily acquired localizer image, may provide limited but useful information for evaluating brain atrophy.

Longitudinal Changes in Iron and Myelination Within Ischemic Lesions Associate With Neurological Outcomes: A Pilot Study.

BACKGROUND: Combined quantitative susceptibility mapping and R2* relaxometry can distinguish iron and myelin components in ischemic lesions. We aimed to investigate whether longitudinal changes in magnetic susceptibility and R2* values within ischemic lesions were associated with neurological outcomes. METHODS: In this single-center prospective study, we included patients, 20 to 90 years of age, who were consecutively admitted to the stroke care unit between August 2020 and March 2022 due to acute ischemic stroke. The participants underwent 2 instances of quantitative susceptibility mapping and R2* relaxometry scanning before and after stroke rehabilitation. We compared the changes in these quantitative measures across different subtypes of acute ischemic stroke. Multiple linear regression models were used to investigate the associations between the National Institutes of Health Stroke Scale scores and the mean magnetic susceptibility and R2* values in ischemic lesions. RESULTS: Among a total of 112 patients with acute ischemic stroke, 32 participants (aged 73.3±9.4 years; 20 men and 12 women) were evaluated. The median time from stroke onset to the first imaging was 5 days and that to the second imaging was 102 days. The changes in magnetic susceptibility values of branch atheromatous disease were higher than those of cardioembolism (mean difference, 0.018 [95% CI, 0.009-0.027] ppm; P<0.001) and lacunar (mean difference, 0.013 [95% CI, 0.005-0.020] ppm; P=0.004). Across all patients, the changes in National Institutes of Health Stroke Scale scores were associated with those of magnetic susceptibility values (coefficient, 0.311 [95% CI, 0.098-0.520]; P=0.017) but not with R2* values (coefficient, 0.114 [95% CI, -0.127 to 0.345]; P=0.291). CONCLUSIONS: The longitudinal changes in the magnetic susceptibility values within ischemic lesions were associated with neurological outcomes during the restorative stages poststroke in patients experiencing acute ischemic stroke. REGISTRATION: URL: https://www.umin.ac.jp/ctr/; Unique identifier: UMIN000050719.

Clinical course of pathologically confirmed corticobasal degeneration and corticobasal syndrome.

The clinical presentation of corticobasal degeneration is diverse, while the background pathology of corticobasal syndrome is also heterogeneous. Therefore, predicting the pathological background of corticobasal syndrome is extremely difficult. Herein, we investigated the clinical findings and course in patients with pathologically, genetically and biochemically verified corticobasal degeneration and corticobasal syndrome with background pathology to determine findings suggestive of background disorder. Thirty-two patients were identified as having corticobasal degeneration. The median intervals from the initial symptoms to the onset of key milestones were as follows: gait disturbance, 0.0 year; behavioural changes, 1.0 year; falls, 2.0 years; cognitive impairment, 2.0 years; speech impairment, 2.5 years; supranuclear gaze palsy, 3.0 years; urinary incontinence, 3.0 years; and dysphagia, 5.0 years. The median survival time was 7.0 years; 50% of corticobasal degeneration was diagnosed as corticobasal degeneration/corticobasal syndrome at the final presentation. Background pathologies of corticobasal syndrome (n = 48) included corticobasal degeneration (33.3%), progressive supranuclear palsy (29.2%) and Alzheimer's disease (12.5%). The common course of corticobasal syndrome was initial gait disturbance and early fall. In addition, corticobasal degeneration-corticobasal syndrome manifested behavioural change (2.5 years) and cognitive impairment (3.0 years), as the patient with progressive supranuclear palsy-corticobasal syndrome developed speech impairment (1.0 years) and supranuclear gaze palsy (6.0 years). The Alzheimer's disease-corticobasal syndrome patients showed cognitive impairment (1.0 years). The frequency of frozen gait at onset was higher in the corticobasal degeneration-corticobasal syndrome group than in the progressive supranuclear palsy-corticobasal syndrome group [P = 0.005, odds ratio (95% confidence interval): 31.67 (1.46-685.34)]. Dysarthria at presentation was higher in progressive supranuclear palsy-corticobasal syndrome than in corticobasal degeneration-corticobasal syndrome [P = 0.047, 6.75 (1.16-39.20)]. Pyramidal sign at presentation and personality change during the entire course were higher in Alzheimer's disease-corticobasal syndrome than in progressive supranuclear palsy-corticobasal syndrome [P = 0.011, 27.44 (1.25-601.61), and P = 0.013, 40.00 (1.98-807.14), respectively]. In corticobasal syndrome, decision tree analysis revealed that 'freezing at onset' or 'no dysarthria at presentation and age at onset under 66 years in the case without freezing at onset' predicted corticobasal degeneration pathology with a sensitivity of 81.3% and specificity of 84.4%. 'Dysarthria at presentation and age at onset over 61 years' suggested progressive supranuclear palsy pathology, and 'pyramidal sign at presentation and personality change during the entire course' implied Alzheimer's disease pathology. In conclusion, frozen gait at onset, dysarthria, personality change and pyramidal signs may be useful clinical signs for predicting background pathologies in corticobasal syndrome.

Asymmetric Cerebral Peduncle Atrophy: A Simple Diagnostic Clue for Distinguishing Frontotemporal Lobar Degeneration from Alzheimer's Disease.

BACKGROUND: Due to confusing clinicoradiological features such as amnestic symptoms and hippocampal atrophy in frontotemporal lobar degeneration (FTLD), antemortem differentiation between FTLD and Alzheimer's disease (AD) can be challenging. Although asymmetric atrophy of the cerebral peduncle is regarded as a representative imaging finding in some disorders of the FTLD spectrum, the utility of this finding has not been sufficiently evaluated for differentiating between FTLD and AD. OBJECTIVE: This study aimed to explore the diagnostic performance of asymmetric cerebral peduncle atrophy on axial magnetic resonance imaging as a simple radiological discriminator between FTLD and AD. METHODS: Seventeen patients with pathologically confirmed FTLD, including six with progressive supranuclear palsy, three with corticobasal degeneration, eight with TAR DNA-binding protein 43 (FTLD-TDP), and 11 with pathologically confirmed AD, were investigated. Quantitative indices representing the difference between the volumes of the bilateral cerebral peduncles (i.e., cerebral peduncular asymmetry index [CPAI]), the voxel-based specific regional analysis system for Alzheimer's disease (VSRAD) Z-score representing the degree of hippocampal atrophy, and semiquantitative visual analysis to evaluate the asymmetry of the cerebral peduncle (visual assessment of cerebral peduncular asymmetry: VACPA) were compared between the two groups. RESULTS: Contrary to the VSRAD Z-score, the CPAI and VACPA scores demonstrated higher diagnostic performance in differentiating patients with FTLD from those with AD (areas under the receiver operating characteristic curve of 0.88, 082, and 0.60, respectively). CONCLUSIONS: Quantitative and visual analytical techniques can differentiate between FTLD and AD. These simple methods may be useful in daily clinical practice.

Assessing white matter microstructural changes in idiopathic normal pressure hydrocephalus using voxel-based R2* relaxometry analysis.

Background: R2* relaxometry and quantitative susceptibility mapping can be combined to distinguish between microstructural changes and iron deposition in white matter. Here, we aimed to explore microstructural changes in the white matter associated with clinical presentations such as cognitive impairment in patients with idiopathic normal-pressure hydrocephalus (iNPH) using R2* relaxometry analysis in combination with quantitative susceptibility mapping. Methods: We evaluated 16 patients clinically diagnosed with possible or probable iNPH and 18 matched healthy controls (HC) who were chosen based on similarity in age and sex. R2* and quantitative susceptibility mapping were compared using voxel-wise and atlas-based one-way analysis of covariance (ANCOVA). Finally, partial correlation analyses were performed to assess the relationship between R2* and clinical presentations. Results: R2* was lower in some white matter regions, including the bilateral superior longitudinal fascicle and sagittal stratum, in the iNPH group compared to the HC group. The voxel-based quantitative susceptibility mapping results did not differ between the groups. The atlas-based group comparisons yielded negative mean susceptibility values in almost all brain regions, indicating no clear paramagnetic iron deposition in the white matter of any subject. R2* and cognitive performance scores between the left superior longitudinal fasciculus (SLF) and right sagittal stratum (SS) were positively correlated. In addition to that, R2* and gait disturbance scores between left SS were negatively correlated. Conclusion: Our analysis highlights the microstructural changes without iron deposition in the SLF and SS, and their association with cognitive impairment and gait disturbance in patients with iNPH.

Relationship between brain iron dynamics and blood-brain barrier function during childhood: a quantitative magnetic resonance imaging study.

BACKGROUND: Mounting evidence suggests that the blood-brain barrier (BBB) plays an important role in the regulation of brain iron homeostasis in normal brain development, but these imaging profiles remain to be elucidated. We aimed to establish a relationship between brain iron dynamics and BBB function during childhood using a combined quantitative magnetic resonance imaging (MRI) to depict both physiological systems along developmental trajectories. METHODS: In this single-center prospective study, consecutive outpatients, 2-180 months of age, who underwent brain MRI (3.0-T scanner; Ingenia; Philips) between January 2020 and January 2021, were included. Children with histories of preterm birth or birth defects, abnormalities on MRI, and diagnoses that included neurological diseases during follow-up examinations through December 2022 were excluded. In addition to clinical MRI, quantitative susceptibility mapping (QSM; iron deposition measure) and diffusion-prepared pseudo-continuous arterial spin labeling (DP-pCASL; BBB function measure) were acquired. Atlas-based analyses for QSM and DP-pCASL were performed to investigate developmental trajectories of regional brain iron deposition and BBB function and their relationships. RESULTS: A total of 78 children (mean age, 73.8 months ± 61.5 [SD]; 43 boys) were evaluated. Rapid magnetic susceptibility progression in the brain (Δsusceptibility value) was observed during the first two years (globus pallidus, 1.26 ± 0.18 [× 10- 3 ppm/month]; substantia nigra, 0.68 ± 0.16; thalamus, 0.15 ± 0.04). The scattergram between the Δsusceptibility value and the water exchange rate across the BBB (kw) divided by the cerebral blood flow was well fitted to the sigmoidal curve model, whose inflection point differed among each deep gray-matter nucleus (globus pallidus, 2.96-3.03 [mL/100 g]-1; substantia nigra, 3.12-3.15; thalamus, 3.64-3.67) in accordance with the regional heterogeneity of brain iron accumulation. CONCLUSIONS: The combined quantitative MRI study of QSM and DP-pCASL for pediatric brains demonstrated the relationship between brain iron dynamics and BBB function during childhood. TRIAL REGISTRATION: UMIN Clinical Trials Registry identifier: UMIN000039047, registered January 6, 2020.

[Changes in vessel wall magnetic resonance contrast-enhancement in a patient with multiple cerebral infarction due to meningovascular neurosyphilis].

A 46-year-old man with a history of generalized skin rash following physical contact with possible syphilis infection developed right upper and lower extremity ataxia and right lower extremity paresis. Brain magnetic resonance (MR) imaging revealed multiple areas of acute cerebral infarction mainly within the territories of the right superior cerebellar artery (SCA) and left anterior cerebral artery. The patient was diagnosed with meningovascular neurosyphilis based on positive results on syphilis testing of the serum and cerebrospinal fluid. MR angiography revealed decreased signal intensity in the proximal segment of the right SCA, and gadolinium-enhanced three-dimensional T1-weighted MR images showed an enhancement of the vessel wall in this segment of the artery. Signal intensity in the right SCA showed partial improvement following the completion of intravenous penicillin treatment, and contrast enhancement of the vessel wall disappeared simultaneously with clinical improvement. Alterations in cerebral vessel walls on contrast-enhanced MR imaging in cases of meningovascular neurosyphilis may reflect vascular inflammatory activity.

Voxel-Based and Surface-Based Morphometry Analysis in Patients with Pathologically Confirmed Argyrophilic Grain Disease and Alzheimer's Disease.

BACKGROUND: Due to clinicoradiological similarities, including amnestic cognitive impairment and limbic atrophy, differentiation of argyrophilic grain disease (AGD) from Alzheimer's disease (AD) is often challenging. Minimally invasive biomarkers, especially magnetic resonance imaging (MRI), are valuable in routine clinical practice. Although it is necessary to explore radiological clues, morphometry analyses using new automated analytical methods, including whole-brain voxel-based morphometry (VBM) and surface-based morphometry (SBM), have not been sufficiently investigated in patients with pathologically confirmed AGD and AD. OBJECTIVE: This study aimed to determine the volumetric differences in VBM and SBM analyses between patients with pathologically confirmed AGD and AD. METHODS: Eight patients with pathologically confirmed AGD with a lower Braak neurofibrillary tangle stage (

Contributions of blood-brain barrier imaging to neurovascular unit pathophysiology of Alzheimer's disease and related dementias.

The blood-brain barrier (BBB) plays important roles in the maintenance of brain homeostasis. Its main role includes three kinds of functions: (1) to protect the central nervous system from blood-borne toxins and pathogens; (2) to regulate the exchange of substances between the brain parenchyma and capillaries; and (3) to clear metabolic waste and other neurotoxic compounds from the central nervous system into meningeal lymphatics and systemic circulation. Physiologically, the BBB belongs to the glymphatic system and the intramural periarterial drainage pathway, both of which are involved in clearing interstitial solutes such as ß-amyloid proteins. Thus, the BBB is believed to contribute to preventing the onset and progression for Alzheimer's disease. Measurements of BBB function are essential toward a better understanding of Alzheimer's pathophysiology to establish novel imaging biomarkers and open new avenues of interventions for Alzheimer's disease and related dementias. The visualization techniques for capillary, cerebrospinal, and interstitial fluid dynamics around the neurovascular unit in living human brains have been enthusiastically developed. The purpose of this review is to summarize recent BBB imaging developments using advanced magnetic resonance imaging technologies in relation to Alzheimer's disease and related dementias. First, we give an overview of the relationship between Alzheimer's pathophysiology and BBB dysfunction. Second, we provide a brief description about the principles of non-contrast agent-based and contrast agent-based BBB imaging methodologies. Third, we summarize previous studies that have reported the findings of each BBB imaging method in individuals with the Alzheimer's disease continuum. Fourth, we introduce a wide range of Alzheimer's pathophysiology in relation to BBB imaging technologies to advance our understanding of the fluid dynamics around the BBB in both clinical and preclinical settings. Finally, we discuss the challenges of BBB imaging techniques and suggest future directions toward clinically useful imaging biomarkers for Alzheimer's disease and related dementias.

Concurrent cerebral infarction and intracranial tuberculoma induced by the carotid plaque complicated with miliary tuberculosis.

Cerebrovascular complications of central nervous system tuberculosis (TB) are predictors of poor prognosis and adverse outcomes. These complications are mainly intracranial arterial involvement, with occasional venous involvement. Here, we present a 67-year-old woman with concurrent cerebral infarction and intracranial tuberculoma induced by the carotid plaque complicated by miliary tuberculosis. Mycobacterium tuberculosis was observed on the luminal side of the carotid plaques in pathological specimens. Treatment with anti-TB drugs alone would likely not cure the patient, as M. tuberculosis would continue to disseminate. Endarterectomy could directly remove the embolic source, and a complete cure was achieved.

Early-onset Alzheimer Disease Associated With Neuromyelitis Optica Spectrum Disorder.

Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune demyelinating disease of the central nervous system. Although recent reports have noted that cognitive impairment is common in NMOSD, little longitudinal information is available on the trajectories of cognitive function in the disease. Here, we report a case of a 55-year-old woman with an 11-year history of NMOSD who visited our memory clinic for progressive memory loss. She was diagnosed with early-onset Alzheimer disease based on amyloid and tau positron emission tomography imaging biomarkers. This is the first report of early-onset Alzheimer disease in a patient with NMOSD. Complications of Alzheimer disease should be considered when patients with NMOSD exhibit rapid cognitive decline. More longitudinal studies of NMOSD with cognitive impairment are needed.

Diverse limbic comorbidities cause limbic and temporal atrophy in lewy body disease.

BACKGROUND: In contrast to Alzheimer's disease (AD)-related pathology, the influence of comorbid limbic-predominant age-related TDP-43 encephalopathy neuropathological change (LATE-NC) or argyrophilic grains (AG) on structural imaging in Lewy body disease (LBD) has seldom been evaluated. OBJECTIVE: This study aimed to investigate whether non-AD limbic comorbidities, including LATE-NC and AG, cause cortical atrophy in LBD. METHODS: Seventeen patients with pathologically confirmed LBD with lower Braak neurofibrillary tangle stage (

[Transient changes in food preference in a patient with cerebellar infarction].

A 44-year-old woman was admitted to our hospital due to dizziness and ataxia of the trunk and right upper limb. Brain MRI revealed an acute infarct lesion in the right posterior inferior cerebellar artery territory. In addition to the cognitive deterioration observed in the subacute phase, a change was noted in her food preference-from light-tasting, low-caloric Japanese cuisine, sugarless coffee, and hot drinks to strong-tasting, high-caloric Western cuisine, sugar-rich coffee, and iced drinks. Single-photon emission computed tomography showed hypoperfusion in the bilateral frontal lobes and right cerebellum. These cognitive and food preference-related changes were gradually restored over six months after the onset. The reduced cerebral blood flow in the bilateral frontal lobes also restored along with the clinical improvement, with the maximal changes in the bilateral subcallosal areas. This case suggests that changes in food preference can occur as a symptom of cerebellar infarction, possibly by the mechanism similar to cerebellar cognitive affective syndrome.

A preliminary study on predictors of treatment response to repetitive transcranial magnetic stimulation in patients with treatment-resistant depression in Japan.

BACKGROUND: Brain imaging studies have reported that the effect of repetitive transcranial magnetic stimulation (rTMS) is associated with the activities of the dorsolateral prefrontal cortex (DLPFC) and ventral medial prefrontal cortex (VMPFC). However, few studies have been conducted in Japanese patients. AIM: We aimed to identify brain regions associated with depressive symptom changes by measuring regional cerebral blood flow (rCBF) in the DLPFC and VMPFC before and after the high-frequency rTMS to the left DLPFC in Japanese patients with treatment-resistant depression. METHOD: Fourteen patients participated in the rTMS study and were assessed with the 17-item Hamilton depression rating scale (HAM-D17 ). Among them, 13 participants underwent magnetic resonance imaging scan of the brain using the arterial spin labeling method. The rCBF was calculated using the fine stereotactic region of interest template (FineSRT) program for automated analysis. We focused on eight regions reported in previous studies. RESULTS: Depression severity significantly decreased after 2 week (HAM-D17 :11.4 ± 2.8, P = 0.00027) and 4 week (HAM-D17 : 11.0 ± 3.7, P = 0.0023) of rTMS treatment. There was no significant change in rCBF at each region in the pre-post design. However, there was a significantly negative correlation between baseline rCBF in the right DLPFC and the improvement in HAM-D17 score (r = -0.559, P = 0.047). CONCLUSION: We obtained supportive evidence for the effectiveness of rTMS to the prefrontal cortex in treatment-resistant depression, which may be associated with reduced rCBF of the right DLPFC before initiation of rTMS.

Quantitative susceptibility mapping as an imaging biomarker for Alzheimer's disease: The expectations and limitations.

Alzheimer's disease (AD) is the most common type of dementia and a distressing diagnosis for individuals and caregivers. Researchers and clinical trials have mainly focused on ß-amyloid plaques, which are hypothesized to be one of the most important factors for neurodegeneration in AD. Meanwhile, recent clinicopathological and radiological studies have shown closer associations of tau pathology rather than ß-amyloid pathology with the onset and progression of Alzheimer's symptoms. Toward a biological definition of biomarker-based research framework for AD, the 2018 National Institute on Aging-Alzheimer's Association working group has updated the ATN classification system for stratifying disease status in accordance with relevant pathological biomarker profiles, such as cerebral ß-amyloid deposition, hyperphosphorylated tau, and neurodegeneration. In addition, altered iron metabolism has been considered to interact with abnormal proteins related to AD pathology thorough generating oxidative stress, as some prior histochemical and histopathological studies supported this iron-mediated pathomechanism. Quantitative susceptibility mapping (QSM) has recently become more popular as a non-invasive magnetic resonance technique to quantify local tissue susceptibility with high spatial resolution, which is sensitive to the presence of iron. The association of cerebral susceptibility values with other pathological biomarkers for AD has been investigated using various QSM techniques; however, direct evidence of these associations remains elusive. In this review, we first briefly describe the principles of QSM. Second, we focus on a large variety of QSM applications, ranging from common applications, such as cerebral iron deposition, to more recent applications, such as the assessment of impaired myelination, quantification of venous oxygen saturation, and measurement of blood- brain barrier function in clinical settings for AD. Third, we mention the relationships among QSM, established biomarkers, and cognitive performance in AD. Finally, we discuss the role of QSM as an imaging biomarker as well as the expectations and limitations of clinically useful diagnostic and therapeutic implications for AD.

Age-related increase of monoamine oxidase B in amyloid-negative cognitively unimpaired elderly subjects.

OBJECTIVE: Monoamine oxidase B (MAO-B) is highly abundant in reactive astrocytes and upregulated in neuroinflammatory processes. However, the age-related change of MAO-B in amyloid-negative cognitively unimpaired elderly subjects has not yet been sufficiently evaluated on positron emission tomography (PET). 18F-THK5351 is a radiotracer with high affinity to MAO-B, which may potentially serve as an imaging biomarker for detecting neuroinflammation. The purpose of this study was to investigate the age-related topographic change of 18F-THK5351 PET in amyloid-negative cognitively unimpaired elderly subjects. METHODS: The age-related change of 18F-THK5351 retention was evaluated on the visual analysis, voxel and region of interest (ROI)-based analyses using Statistical Parametric Mapping and PETSurfer tool of FreeSurfer in 31 amyloid-negative cognitively unimpaired elderly subjects. RESULTS: On visual inspection, elderly groups showed the spread of 18F-THK5351 accumulation from the medial to inferolateral temporal and basal frontal lobes, and cingulate gyrus. Additionally, voxel- and ROI-based analysis demonstrated the correlation between 18F-THK5351 accumulation and participants' age, especially in the inferior temporal lobes. CONCLUSIONS: This study demonstrated age-dependent increase of 18F-THK5351 retention in amyloid-negative cognitively unimpaired subjects, which suggests an increase in MAO-B positive reactive astrocytes with aging.