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1.
Alzheimer Dis Assoc Disord ; 36(4): 365-367, 2022.
Article in English | MEDLINE | ID: mdl-35288519

ABSTRACT

Primary progressive apraxia of speech (PPAOS), a rare neurodedegenerative disorder, can be subdivided into predominant phonetic or prosodic type. Pure prosodic type of PPAOS as an isolated disorder has been hardly found. We present 2 cases of patients with pure prosodic PPAOS who initially were misdiagnosed as nonfluent variant of primary progressive aphasia and later turned out to be corticobasal syndrome. A 65-year-old woman and a 72-year-old man were referred to our speech-language clinic under the clinical impression of nonfluent variant of primary progressive aphasia. The neurological examinations revealed no definite abnormalities except for slow and effortful speech with the production of simple sentences. However, their receptive and expressive language abilities were normal. Their brain magnetic resonance imaging was unremarkable. We initially entertained the diagnosis of pure prosodic type of PPAOS. During several years of follow up, they gradually developed extrapyramidal symptoms which are compatible with corticobasal syndrome. The characteristics of the patients and the results of neuroimaging studies are discussed.


Subject(s)
Aphasia, Primary Progressive , Apraxias , Corticobasal Degeneration , Primary Progressive Nonfluent Aphasia , Male , Female , Humans , Aged , Aphasia, Broca , Speech , Aphasia, Primary Progressive/diagnosis , Apraxias/diagnosis , Primary Progressive Nonfluent Aphasia/diagnosis
2.
Eur J Neurol ; 28(5): 1520-1527, 2021 05.
Article in English | MEDLINE | ID: mdl-33559375

ABSTRACT

BACKGROUND AND PURPOSE: As part of network-specific neurodegeneration, changes in cerebellar gray matter (GM) volume and impaired cerebello-cerebral functional networks have been reported in Alzheimer disease (AD). Compared with healthy controls, a volume loss in the cerebellum has been observed in patients with continuum of AD. However, little is known about the anatomical or functional changes in patients with clinical AD but no brain amyloidosis. We aimed to identify the relationship between cerebellar volume and dementia conversion of amyloid-negative mild cognitive impairment (MCI). METHODS: This study was a retrospective cohort study of patients over the age 50 years with amyloid-negative amnestic MCI who visited the memory clinic of Asan Medical Center with no less than a 36-month follow-up period. All subjects underwent detailed neuropsychological tests, 3 T brain magnetic resonance imaging scans including three-dimensional T1 imaging, and fluorine-18[F18 ]-florbetaben amyloid positron emission tomography scans. A spatially unbiased atlas template of the cerebellum and brainstem was used for analyzing cerebellar GM volume. RESULTS: During the 36 months of follow-up, 39 of 107 (36.4%) patients converted to dementia from amnestic MCI. The converter group had more severe impairments in all visual memory tasks. In terms of volumetric analysis, reduced crus I/II volume adjusted with total intracranial volume, and age was observed in the converter group. CONCLUSIONS: Significant cerebellar GM atrophy involving the bilateral crus I/II may be a novel imaging biomarker for predicting dementia progression in amyloid-negative amnestic MCI patients.


Subject(s)
Alzheimer Disease , Amyloidosis , Cognitive Dysfunction , Biomarkers , Cerebellum , Cognitive Dysfunction/diagnostic imaging , Disease Progression , Humans , Magnetic Resonance Imaging , Middle Aged , Neuropsychological Tests , Positron-Emission Tomography , Retrospective Studies
3.
Dement Geriatr Cogn Disord ; 50(6): 585-591, 2021.
Article in English | MEDLINE | ID: mdl-35240660

ABSTRACT

INTRODUCTION: Action verbal fluency (AVF) task, a word fluency test, involves language and executive function and is known to be sensitive to fronto-striatal degeneration. However, the ability may also decrease qualitatively as well as quantitatively in normal aging. The objective of this study is to investigate the age-related quantitative and qualitative differences in AVF of Korean adults. METHODS: We analyzed data from 78 participants of 40 young (mean age = 28.9) and 38 older adults (mean age = 67.7). The correct responses in the AVF task were measured for quantitative analysis. Qualitatively, the mean number of arguments required by each verb was calculated for syntactic analysis. For semantic analysis, we subclassified verbs according to their characteristics (e.g., moment vs. non-moment verbs/active vs. non-active verbs) and calculated the ratio for comparison. The results of AVF were also compared to those of semantic/phonemic fluency and the Korean version of the Montreal Cognitive Assessment (MoCA-K). RESULTS: The older group showed quantitatively lower performance in AVF than the young group (p < 0.01). The result of the AVF task significantly correlated (p < 0.01) with both semantic/phonemic fluency and the MoCA-K. Also, the older group produced syntactically more simple verbs than the counterpart (p < 0.01). In the semantic analysis, the older group produced fewer moment verbs (p < 0.05) but more non-moment verbs (p < 0.05) than the young group. There was no difference in active or non-active verbs between two groups. CONCLUSION: These results indicated that the ability of AVF declines with age not only quantitatively but also qualitatively in relation to their cognitive changes.


Subject(s)
Language , Semantics , Aged , Aging , Asian People , Executive Function , Humans
4.
Dement Geriatr Cogn Disord ; 50(3): 289-295, 2021.
Article in English | MEDLINE | ID: mdl-34518459

ABSTRACT

BACKGROUND: Donepezil 23 mg is considered for Alzheimer's disease (AD) to optimize cognitive benefits; however, increased adverse events (AEs) can negatively influence drug adherence. We investigated whether body weight (BW) differs based on the presence of AEs, and which baseline factors were relevant to the safety of high-dose donepezil. METHODS: This study was a post hoc analysis of a multicenter randomized trial between 2014 and 2016. We included patients with moderate to severe AD treated with 10 mg/day of donepezil, and the daily dose was escalated to 23 mg with/without dose titration. Dose titration indicates 15 mg/day of donepezil before escalation or 10 mg and 23 mg/day on alternate days before escalation during the first 4 weeks. The patients were divided into 2 groups based on occurrence of AEs of special interest (AESIs) to compare baseline characteristics. We also assessed relationships between BW and AESIs. RESULTS: Among the 160 participants in the safety population, the baseline BWs differed between the AESI (+) (n = 67) and AESI (-) (n = 93) groups. Baseline BW was inversely correlated with the occurrence of AESIs (p = 0.020), and this relationship was prominent in the no-dose titration group (p = 0.009) but absent in the dose-titration groups (p > 0.05). CONCLUSIONS: BW is the most important factor that correlated with cholinergic AEs. Hence, stepwise dose titration should be considered, particularly in patients with low BW, to minimize the inverse relationship between BW and the occurrence of AEs ("Clinicaltrials.gov" No. NCT02550665 registered on September 15, 2015).


Subject(s)
Alzheimer Disease , Alzheimer Disease/drug therapy , Body Weight , Cholinesterase Inhibitors/adverse effects , Donepezil/adverse effects , Dose-Response Relationship, Drug , Double-Blind Method , Humans , Indans/adverse effects , Piperidines/adverse effects , Treatment Outcome
5.
Alzheimer Dis Assoc Disord ; 35(4): 298-305, 2021.
Article in English | MEDLINE | ID: mdl-34132669

ABSTRACT

BACKGROUND: Around 15% to 20% of patients with clinically probable Alzheimer disease have been found to have no significant Alzheimer pathology on amyloid positron emission tomography. A previous study showed that conversion to dementia from amyloid-negative mild cognitive impairment (MCI) was observed in up to 11% of patients, drawing attention to this condition. OBJECT: We gathered the detailed neuropsychological and neuroimaging data of this population to elucidate factors for conversion to dementia from amyloid-negative amnestic MCI. METHODS: This study was a single-institutional, retrospective cohort study of amyloid-negative MCI patients over age 50 with at least 36 months of follow-up. All subjects underwent detailed neuropsychological testing, 3 tesla brain magnetic resonance imaging), and fluorine-18(18F)-florbetaben amyloid positron emission tomography scans. RESULTS: During the follow-up period, 39 of 107 (36.4%) patients converted to dementia from amnestic MCI. The converter group had more severe impairment in all visual memory tasks. The volumetric analysis revealed that the converter group had significantly reduced total hippocampal volume on the right side, gray matter volume in the right lateral temporal, lingual gyri, and occipital pole. CONCLUSION: Our study showed that reduced gray matter volume related to visual memory processing may predict clinical progression in this amyloid-negative MCI population.


Subject(s)
Alzheimer Disease , Cognitive Dysfunction , Cognitive Dysfunction/diagnosis , Disease Progression , Humans , Magnetic Resonance Imaging , Middle Aged , Neuropsychological Tests , Positron-Emission Tomography , Retrospective Studies , Visual Pathways
6.
Eur Neurol ; 78(1-2): 15-21, 2017.
Article in English | MEDLINE | ID: mdl-28538224

ABSTRACT

BACKGROUND: The underlying mechanism of transcortical sensory aphasia (TSA) caused by lesions occurring in the left frontal lobe remains unclear. We attempted to investigate the mechanism with the use of functional MRI (fMRI). METHODS: We studied 2 patients with TSA after a left frontal infarction identified by diffusion-weighted MRI. As control subjects, a patient with transcortical motor aphasia and a healthy normal adult were chosen. The Korean version of Western Aphasia Battery was performed initially and at 3 months post stroke. We performed fMRI using verb generation and sentence completion tasks. Resting-state fMRI (rs-fMRI) was also obtained for network-level analysis initially and at 3 months post stroke. RESULTS: The results of diffusion- and perfusion-weighted MRI revealed no diffusion-perfusion mismatch. Initial fMRI in patients with TSA showed no reversed inter-/intrahemispheric activation patterns. rs-fMRI showed significantly decreased resting-state functional connectivity in the language network in patients with TSA compared with the control subjects. Follow-up rs-fMRI studies showed improvement in functional connectivity along with the recovery of patients' language function. CONCLUSION: Our data showed that the auditory comprehension deficits in patients with frontal lobe infarcts is attributed to difficulty accessing the posterior language area due to functional disconnection between language centers in the acute stage of stroke.


Subject(s)
Aphasia, Wernicke/pathology , Cerebral Infarction/pathology , Frontal Lobe/pathology , Neural Pathways/pathology , Aged , Aphasia, Wernicke/diagnostic imaging , Aphasia, Wernicke/etiology , Cerebral Infarction/complications , Cerebral Infarction/diagnostic imaging , Diffusion Tensor Imaging , Female , Follow-Up Studies , Frontal Lobe/diagnostic imaging , Humans , Language Tests , Magnetic Resonance Imaging , Male , Neural Pathways/diagnostic imaging , Stroke/complications , Stroke/diagnostic imaging , Stroke/pathology
8.
Neurocase ; 20(1): 46-52, 2014.
Article in English | MEDLINE | ID: mdl-23058062

ABSTRACT

Agrammatic primary progressive aphasia (PPA-G) has been known to be associated with focal brain atrophy involving the left posterior frontal and anterior insular regions. However, aphasia can also rarely result from right hemispheric lesions in right-handed patients, so-called crossed aphasia in dextrals (CAD). We report two right-handed patients with PPA-G whose 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET) showed hypometabolism predominantly in the right hemisphere, implicating "crossed PPA-G."


Subject(s)
Brain/pathology , Functional Laterality , Primary Progressive Nonfluent Aphasia/diagnosis , Aged , Female , Humans , Male , Middle Aged
9.
Neurol Sci ; 35(3): 357-63, 2014 Mar.
Article in English | MEDLINE | ID: mdl-23975521

ABSTRACT

Gait freezing and speech disturbance are disabling axial features of Parkinson's disease (PD). However, the pathogenesis of these features remains unclear. We investigated the relation between changes in gait freezing and speech disturbance using visual and auditory cues in PD. 18 PD patients, comprising of 9 patients with freezing (PDGF) and 9 without gait freezing were studied. Patients performed a 7-m back-and-forth walk in a baseline state and with visual and auditory cues. Gait velocity, stride length and cadence were evaluated using a three-dimensional gait analysis system. For speech evaluation, patients read ten sentences in a baseline state and with visual and auditory cues. The time delay of speech initiation, speech rate and the number of repetitions per sentence were quantified. In PDGF patients, the increase in gait velocity positively correlated with the decrease in the time delay of the speech initiation. Also, the increase in the gait velocity and cadence positively correlated with the decrease in the number of repetitions per sentence. The increase in the stride length positively correlated with the increase in speech rate. Lastly, the increase in stride length positively correlated with the decrease in the number of repetitions per sentence. These findings suggest that there is a common pathomechanism of gait freezing and speech disturbance in PD.


Subject(s)
Gait Disorders, Neurologic/etiology , Parkinson Disease/complications , Speech Disorders/etiology , Disability Evaluation , Female , Gait Disorders, Neurologic/diagnosis , Humans , Linear Models , Male , Neurologic Examination , Speech Disorders/diagnosis , Statistics, Nonparametric
10.
J Stroke ; 24(1): 108-117, 2022 Jan.
Article in English | MEDLINE | ID: mdl-35135064

ABSTRACT

BACKGROUND AND PURPOSE: This study aimed to investigate the applicability of deep learning (DL) model using diffusion-weighted imaging (DWI) data to predict the severity of aphasia at an early stage in acute stroke patients. METHODS: We retrospectively analyzed consecutive patients with aphasia caused by acute ischemic stroke in the left middle cerebral artery territory, who visited Asan Medical Center between 2011 and 2013. To implement the DL model to predict the severity of post-stroke aphasia, we designed a deep feed-forward network and utilized the lesion occupying ratio from DWI data and established clinical variables to estimate the aphasia quotient (AQ) score (range, 0 to 100) of the Korean version of the Western Aphasia Battery. To evaluate the performance of the DL model, we analyzed Cohen's weighted kappa with linear weights for the categorized AQ score (0-25, very severe; 26-50, severe; 51-75, moderate; ≥76, mild) and Pearson's correlation coefficient for continuous values. RESULTS: We identified 225 post-stroke aphasia patients, of whom 176 were included and analyzed. For the categorized AQ score, Cohen's weighted kappa coefficient was 0.59 (95% confidence interval [CI], 0.42 to 0.76; P<0.001). For continuous AQ score, the correlation coefficient between true AQ scores and model-estimated values was 0.72 (95% CI, 0.55 to 0.83; P<0.001). CONCLUSIONS: DL approaches using DWI data may be feasible and useful for estimating the severity of aphasia in the early stage of stroke.

11.
Dement Geriatr Cogn Dis Extra ; 11(2): 172-180, 2021.
Article in English | MEDLINE | ID: mdl-34249074

ABSTRACT

INTRODUCTION: False memory, observed as intrusion errors or false positives (FPs), is prevalent in patients with Alzheimer's disease, but has yet to be thoroughly investigated in patients with amnestic mild cognitive impairment (a-MCI) with Alzheimer's disease pathology (ADP). We analyzed false versus veridical memory in individuals with a-MCI and measured the utility of false memory for ADP discrimination. METHODS: Patients with a-MCI who received neuropsychological testing and amyloid PET were included. Patients were categorized into "with" and "without ADP" groups according to PET results. Memory tests assessed veridical and false memory, and the verity of patient responses was analyzed. A logistic regression model was used to evaluate false memory efficiency in discriminating ADP, and the sensitivity and specificity at the optimal level were estimated using the receiver-operating characteristic curve. RESULTS: Thirty-seven ADP and 46 non-ADP patients were enrolled. The ADP group made more FPs in the recognition tests, and their response verity was significantly lower in every delayed memory test. No group difference, however, was observed in the veridical memory. The logistic regression analysis demonstrated that as the FPs increased, the risk of ADP increased 1.31 and 1.36 times in the verbal and visual recognition tests, respectively. The discriminatory accuracy of the FPs was estimated "low" to "moderate" in the visual and verbal recognition, respectively, with an optimal cutoff above 2.5. CONCLUSION: Increased false memory was the only feature to discriminate ADP from non-ADP in individuals with a-MCI. Further studies regarding false memory and its mechanism are warranted.

12.
Parkinsonism Relat Disord ; 88: 96-101, 2021 07.
Article in English | MEDLINE | ID: mdl-34166866

ABSTRACT

INTRODUCTION: Apraxia is a core clinical feature of corticobasal syndrome (CBS). Among the subtypes of apraxia, ideomotor and imitation apraxia are frequently found in CBS. However, little is known about the brain networks that are characteristic of each apraxia subtype or their clinical implication. In this study, we used 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) to explore the specific patterns of glucose hypometabolism that are characteristic of apraxia subtypes by focusing on ideomotor and imitation apraxia. METHODS: We compared the areas of glucose hypometabolism in the brains of 52 patients with CBS and 13 healthy controls, both as a whole and according to apraxia subtypes. In addition, we investigated the relationship between the apraxia subtypes and the clinical phenotype of CBS. RESULTS: In patients with CBS, common hypometabolism was observed in the frontal gyrus, precentral gyrus and caudate regardless of apraxia subtypes. In particular, ideomotor apraxia was associated with hypometabolism in the angular gyrus, while imitation apraxia was associated with hypometabolism in the posterior part including the postcentral gyrus, precuneus, and posterior cingulate gyrus. Patients who showed both ideomotor and imitation apraxia were more likely to show the typical features of CBS and progressive supranuclear palsy compared with patients showing only one type of apraxia. CONCLUSION: Group comparison analysis using FDG-PET revealed distinct pathways of ideomotor and imitation apraxia in CBS. These findings add to our understanding of the brain networks underlying apraxia in association with the clinical features of CBS.


Subject(s)
Apraxias/physiopathology , Caudate Nucleus/physiopathology , Cerebral Cortex/physiopathology , Corticobasal Degeneration/physiopathology , Imitative Behavior , Nerve Net/physiopathology , Aged , Apraxia, Ideomotor/diagnostic imaging , Apraxia, Ideomotor/etiology , Apraxia, Ideomotor/metabolism , Apraxia, Ideomotor/physiopathology , Apraxias/diagnostic imaging , Apraxias/etiology , Apraxias/metabolism , Caudate Nucleus/diagnostic imaging , Caudate Nucleus/metabolism , Cerebral Cortex/diagnostic imaging , Cerebral Cortex/metabolism , Corticobasal Degeneration/complications , Corticobasal Degeneration/diagnostic imaging , Corticobasal Degeneration/metabolism , Female , Fluorodeoxyglucose F18 , Humans , Male , Middle Aged , Nerve Net/diagnostic imaging , Nerve Net/metabolism , Positron-Emission Tomography
13.
Eur Neurol ; 74(1-2): 84-5, 2015.
Article in English | MEDLINE | ID: mdl-26303121
14.
J Mov Disord ; 12(3): 152-160, 2019 Sep.
Article in English | MEDLINE | ID: mdl-31556260

ABSTRACT

Oro-pharyngeal dysphagia is a common symptom in patients with Parkinson's disease (PD) and related disorders, even in their early stage of diseases. Dysphagia in these patients has been underdiagnosed, probably due to poor the self-awareness of the conditions and the underuse of validated tools and objective instruments for assessment. The early detection and intervention of dysphagia are closely related to improving the quality of life and decreasing the mortality rate in these patients. The purpose of this paper is to give an overview of the characteristics of dysphagia, including the epidemiology, pathophysiology, and clinical symptomatology, in patients with PD compared with other parkinsonian disorders and movement disorders. The management of dysphagia and future research directions related to these disorders are also discussed.

15.
Int J Cancer ; 123(12): 2808-15, 2008 Dec 15.
Article in English | MEDLINE | ID: mdl-18803288

ABSTRACT

To elucidate the pathogenesis of hepatocellular carcinoma (HCC) and develop useful prognosis predictors, it is necessary to identify biologically relevant genomic alterations in HCC. In our study, we defined recurrently altered regions (RARs) common to many cases of HCCs, which may contain tumor-related genes, using whole-genome array-CGH and explored their associations with the clinicopathologic features. Gene set enrichment analysis was performed to investigate functional implication of RARs. On an average, 23.1% of the total probes were altered per case. Mean numbers of altered probes are significantly higher in high-grade, bigger and microvascular invasion (MVI) positive tumors. In total, 32 RARs (14 gains and 18 losses) were defined and 4 most frequent RARs are gains in 1q21.1-q32.1 (64.5%), 1q32.1-q44 (59.2%), 8q11.21-q24.3 (48.7%) and a loss in 17p13.3-p12 (51.3%). Through focusing on RARs, we identified genes and functional pathways likely to be involved in hepatocarcinogenesis. Among genes in the recurrently gained regions on 1q, expression of KIF14 and TPM3 was significantly increased, suggesting their oncogenic potential in HCC. Some RARs showed the significant associations with the clinical features. Especially, the recurrent loss in 9p24.2-p21.1 and gain in 8q11.21-q24.3 are associated with the high tumor grade and MVI, respectively. Functional analysis showed that cytokine receptor binding and defense response to virus pathways are significantly enriched in high grade-related RARs. Taken together, our results and the strategy of analysis will help to elucidate pathogenesis of HCC and to develop biomarkers for predicting behaviors of HCC.


Subject(s)
Carcinoma, Hepatocellular/genetics , Carcinoma, Hepatocellular/pathology , Chromosomes, Human, Pair 8 , Liver Neoplasms/genetics , Liver Neoplasms/pathology , Neoplasm Recurrence, Local/genetics , Biomarkers, Tumor/analysis , Blotting, Western , Carcinoma, Hepatocellular/chemistry , Cell Line, Tumor , Chromosome Deletion , Chromosomes, Human, Pair 1 , Humans , Kinesins/analysis , Liver Neoplasms/chemistry , Mutagenesis, Insertional , Oncogene Proteins/analysis , Polymerase Chain Reaction , Tropomyosin/analysis
16.
J Geriatr Psychiatry Neurol ; 21(2): 104-10, 2008 Jun.
Article in English | MEDLINE | ID: mdl-18474719

ABSTRACT

The Montreal Cognitive Assessment (MoCA) is a brief cognitive screening tool with high sensitivity for screening patients with mild cognitive impairment (MCI). The authors examined the validity and reliability of the Korean version of the MoCA (MoCA-K) in elderly outpatients. The MoCA-K, a Korean version of the Mini-Mental State Examination (MMSE), Clinical Dementia Rating (CDR) scale, and neuropsychological batteries were administered to 196 elderly persons (mild Alzheimer's disease [AD] = 44, MCI = 37, normal controls [NC] = 115). MoCA-K scores were highly correlated with those of MMSE and CDR. Using a cutoff score of 22/23, the MoCA-K had an excellent sensitivity of 89% and a good specificity of 84% for screening MCI. Internal consistency and test-retest reliability were good. The results obtained show that the MoCA-K is brief, reliable, and suitable for use as a screening tool to screen MCI patients in elderly outpatient clinic settings.


Subject(s)
Cognition Disorders/diagnosis , Cross-Cultural Comparison , Mass Screening/statistics & numerical data , Neuropsychological Tests/statistics & numerical data , Outpatient Clinics, Hospital , Aged , Alzheimer Disease/diagnosis , Alzheimer Disease/psychology , Cognition Disorders/psychology , Disease Progression , Educational Status , Female , Humans , Korea , Male , Mental Status Schedule/statistics & numerical data , Middle Aged , Psychometrics/statistics & numerical data , Reference Values , Reproducibility of Results , Risk Assessment , Translating
17.
J Nucl Med ; 48(2): 194-200, 2007 Feb.
Article in English | MEDLINE | ID: mdl-17268014

ABSTRACT

UNLABELLED: This study examined the relationship between the severity of aphasia and regional cerebral perfusion on brain SPECT using statistical parametric mapping (SPM) and a statistical probabilistic anatomic map (SPAM) in patients with a striatocapsular infarction (SCI) along with the other clinical and imaging findings. METHODS: The subjects were 16 right-handed Korean-speaking patients with a left SCI who underwent 99mTc-ethylcyteinate dimer (99mTc-ECD) SPECT (8.1 +/- 4.8 d [mean +/- SD] after onset). MRI showed that no patient had any abnormality in the cerebral cortex (6.8 +/- 6.0 d after onset). The aphasia quotient (AQ), which is a measure of the severity of aphasia, was obtained by using the Korean version of the Western Aphasia Battery (5.3 +/- 3.9 d after onset). For quantitative evaluation of cerebral perfusion, the asymmetry indices (AIs) for subcortical and cortical areas were calculated using SPM and SPAM. The infarct size was measured using MRI. RESULTS: Aphasia occurred in 15 (2 global, 7 transcortical, and 6 anomic aphasia) of the 16 patients. Left cerebral cortical hypoperfusion was observed in all 15 patients with subcortical aphasia. Aphasia was more severe in 6 patients with extensive cerebral cortical hypoperfusion than in the remaining 10 patients (AQ = 41.8 +/- 25.2 points vs. 84.2 +/- 7.7 points [mean +/- SD], P = 0.001). There was an association between the AQ and age (rho = -0.665), infarct size (rho = -0.594), AIs of the frontal cortex (rho = -0.653), temporal cortex (rho = -0.782), parietal cortex (rho = -0.694), whole cerebral cortex (rho = -0.768), and the cerebellar cortex (rho = 0.765). Voxel-based SPM analysis showed a significant positive correlation between the AQ and the perfusion of the left temporal cortex and the right cerebellum. CONCLUSION: The severity of subcortical aphasia after a left SCI without cortical abnormalities on MRI is associated with the extent and severity of the left cerebral cortical hypoperfusion on brain perfusion SPECT performed during the subacute stage, particularly in the left temporal cortex. Quantitative brain perfusion SPECT using SPM and SPAM can help in evaluating subcortical aphasia in a SCI because it provides functional information that cannot be obtained by morphologic imaging.


Subject(s)
Aphasia/diagnostic imaging , Aphasia/etiology , Cerebral Infarction/complications , Cerebral Infarction/diagnostic imaging , Cerebrovascular Circulation/physiology , Aged , Aged, 80 and over , Aging/physiology , Aphasia/psychology , Brain Mapping , Cerebral Infarction/physiopathology , Female , Humans , Image Processing, Computer-Assisted , Magnetic Resonance Angiography , Magnetic Resonance Imaging , Male , Middle Aged , Models, Statistical , Neostriatum/diagnostic imaging , Neuropsychological Tests , Tomography, Emission-Computed, Single-Photon
18.
Clin Cancer Res ; 11(23): 8235-42, 2005 Dec 01.
Article in English | MEDLINE | ID: mdl-16322280

ABSTRACT

PURPOSE: Although many genomic alterations have been observed in lung cancer, their clinicopathologic significance has not been thoroughly investigated. This study screened the genomic aberrations across the whole genome of non-small cell lung cancer cells with high-resolution and investigated their clinicopathologic implications. EXPERIMENTAL DESIGN: One-megabase resolution array comparative genomic hybridization was applied to 29 squamous cell carcinomas and 21 adenocarcinomas of the lung. Tumor and normal tissues were microdissected and the extracted DNA was used directly for hybridization without genomic amplification. The recurrent genomic alterations were analyzed for their association with the clinicopathologic features of lung cancer. RESULTS: Overall, 36 amplicons, 3 homozygous deletions, and 17 minimally altered regions common to many lung cancers were identified. Among them, genomic changes on 13q21, 1p32, Xq, and Yp were found to be significantly associated with clinical features such as age, stage, and disease recurrence. Kaplan-Meier survival analysis revealed that genomic changes on 10p, 16q, 9p, 13q, 6p21, and 19q13 were associated with poor survival. Multivariate analysis showed that alterations on 6p21, 7p, 9q, and 9p remained as independent predictors of poor outcome. In addition, significant correlations were observed for three pairs of minimally altered regions (19q13 and 6p21, 19p13 and 19q13, and 8p12 and 8q11), which indicated their possible collaborative roles. CONCLUSIONS: These results show that our approach is robust for high-resolution mapping of genomic alterations. The novel genomic alterations identified in this study, along with their clinicopathologic implications, would be useful to elucidate the molecular mechanisms of lung cancer and to identify reliable biomarkers for clinical application.


Subject(s)
Carcinoma, Non-Small-Cell Lung/genetics , Chromosome Aberrations , Chromosomes, Human/genetics , DNA, Neoplasm/genetics , Genome , Lung Neoplasms/genetics , Carcinoma, Non-Small-Cell Lung/mortality , Chromosome Mapping , Homozygote , Humans , Lung Neoplasms/mortality , Microarray Analysis , Middle Aged , Nucleic Acid Hybridization/genetics , Survival Rate
19.
Clin Cancer Res ; 8(7): 2311-22, 2002 Jul.
Article in English | MEDLINE | ID: mdl-12114436

ABSTRACT

PURPOSE: Colorectal cancers harbor one of two distinct alterations, unilateral chromosomal loss as evidenced by a loss of heterozygosity (LOH) and microsatellite instability (MSI), as represented by the widespread insertion or deletion of simple repeat nucleotides. We investigated the relationships between the clinicopathological features and microsatellite alterations (LOH and MSI) of 168 colorectal cancers. EXPERIMENTAL DESIGN: The concerted and individual effects of various chromosomal losses on survival were comparatively analyzed using a reference panel of 40 microsatellite markers in eight cancer-related chromosomes, 3p, 4p, 5q, 8p, 9p, 13q, 17p, and 18q. RESULTS: Of the 168 colorectal cancers tested, 29 (17%) with high-frequency MSI were associated with good survival (P < 0.05). The extent of LOH detected in 139 (83%) cases without MSI was classified as low level involving three or fewer arms (35%), moderate level involving four arms (22%), or high level involving five or more arms (43%). High-level loss correlated with earlier onset, lymphatic invasion, and rectal location, whereas low-level loss was more common in proximal colon and stages I and II (P < 0.05). The survival curve and multivariate analysis identified high- and low-level chromosomal loss as the most significant predictor of poor and good survival, respectively (log-rank test, P < 0.0001), in patients with stage II (hazard ratio, 6.27; 95% confidence interval, 1.99-19.7; P = 0.0017) and those with stage III (hazard ratio, 10.89; 95% confidence interval, 2.54-46.77; P = 0.0013). Moderate chromosomal loss showed dual prognostic values associated with favorable stage II and unfavorable stage III. Single chromosomal losses tended to play a role as a part of the concerted chromosomal function. CONCLUSION: The classification of colorectal cancer based on chromosomal loss and MSI provides a prognostic index that reflects tumor pathobiology.


Subject(s)
Chromosomes, Human/genetics , Colorectal Neoplasms/classification , Colorectal Neoplasms/genetics , Microsatellite Repeats/genetics , Alleles , Antineoplastic Agents/therapeutic use , Chromosome Deletion , Colorectal Neoplasms/pathology , DNA, Neoplasm/analysis , Female , Humans , Male , Middle Aged , Neoplasm Staging , Prognosis , Retrospective Studies , Risk Factors , Survival Rate
20.
Clin Neuropharmacol ; 38(2): 47-51, 2015.
Article in English | MEDLINE | ID: mdl-25768850

ABSTRACT

OBJECTIVE: As the fiberoptic gastroscopy using midazolam is being in widespread use, the exact nature of midazolam on memory should be clarified. We intended to examine whether midazolam causes selective anterograde amnesia and what impact it has on other aspects of memory and general cognitive function. METHODS: We recruited healthy subjects undergoing fiberoptic gastroscopy under conscious sedation. At baseline, history taking for retrograde amnesia and the Korean version of the Montreal Cognitive Assessment were performed. A man's name and address were given immediately after intravenous midazolam administration. After gastroscopy, the subjects were asked to recall those items. By the time they had fully recovered consciousness, the same test was repeated along with the Korean version of the Montreal Cognitive Assessment and a test for retrograde amnesia. RESULTS: A total of 30 subjects were enrolled in this study. Subjects with high-dose midazolam showed lower scores in the immediate and delayed recall of "a man's name and address" compared with those with low-dose midazolam. The midazolam dose was inversely correlated with the delayed recall scores of "a man's name and address." On full recovery of consciousness, the subjects did not exhibit any of anterograde or retrograde amnesia. CONCLUSIONS: These findings suggest that midazolam causes transient selective anterograde amnesia in a dose-dependent manner.


Subject(s)
Conscious Sedation , Hypnotics and Sedatives/administration & dosage , Memory Disorders/chemically induced , Midazolam/administration & dosage , Adult , Aged , Dose-Response Relationship, Drug , Female , Gastroscopy , Humans , Male , Memory Disorders/diagnosis , Middle Aged , Neuropsychological Tests , Prospective Studies , Statistics as Topic , Young Adult
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