HbA1c (Glycated Hemoglobin) Levels and Clinical Outcome Post-Mechanical Thrombectomy in Patients With Large Vessel Occlusion.

Background and Purpose- We analyzed the relationship between HbA1c (glycated hemoglobin) levels and clinical outcomes in patients with large vessel occlusion treated with mechanical thrombectomy (MT). Methods- A total of 534 patients with acute ischemic stroke (AIS) treated with MT were enrolled in this prospective cohort study. The primary outcome measured was the modified Rankin Scale score at 3 months, according to HbA1c level. High HbA1c levels were defined as a plasma level of HbA1c >6.5%. Favorable outcomes were defined as functional independence, with modified Rankin Scale scores of 0 to 2. Secondary functional outcomes included mortality, early clinical outcomes, and intracranial hemorrhage. Results- The number of patients with a favorable outcome was significantly lower in patients with HbA1c >6.5% than in those with HbA1c ≤6.5% (28.8% versus 42.1%; P=0.006). In multivariate analysis, high HbA1c levels (especially >7.0% HbA1c) were significantly associated with poor functional outcomes 3 months after AIS in patients with large vessel occlusion treated with MT. High HbA1c was also significantly associated with increased mortality and worse early clinical outcomes after AIS in patients treated with MT. Subgroup analyses showed that HbA1c >6.5% was associated with significantly lower odds of functional independence at 3 months after AIS, when comparing the recanalized group with nonrecanalized patients. Conclusions- These results suggest that high HbA1c level is an independent predictor of a poor outcome at 3 months after AIS in patients with large vessel occlusion treated with MT, particularly in those with recanalization, and may augment the risk of mortality and early clinical worsening after AIS.

Impact of Microbleeds on Outcome Following Recanalization in Patients With Acute Ischemic Stroke.

Background and Purpose- We analyzed the association between cerebral microbleeds (CMBs) and clinical outcome in acute ischemic stroke patients and especially in a subgroup of patients with successful recanalization. Methods- A total of 1532 acute ischemic stroke patients treated with intravenous thrombolysis or mechanical thrombectomy were enrolled in this prospective cohort study. The primary outcome was measured using the modified Rankin Scale at 3 months, according to the CMB status based on magnetic resonance imaging at admission. Favorable outcome was defined as functional independence with modified Rankin Scale scores of 0 to 2. Secondary outcomes included the occurrence of symptomatic intracranial hemorrhage. Results- There was no statistically significant association between the presence of CMB and favorable outcome at 3 months when considering all patients (44.3% versus 37.6%; P=0.121). In patients with recanalization, the number of patients with favorable outcomes was significantly higher in the CMB-negative than in the CMB-positive group (57.0% versus 36.0%; P<0.001). In the final multivariate analysis, the presence of CMB, and in particular high CMB burden (≥5), and lobar location, were significantly associated with less favorable 3-month outcomes (odds ratio=0.57; 95% CI, 0.33-0.97; P=0.038) and symptomatic intracranial hemorrhage (odds ratio=3.21; 95% CI, 1.37-7.49; P=0.007) in patients with recanalization. In the analysis of subgroups, a statistically significant interaction was found between CMB presence and recanalization in predicting functional outcomes at 3 months. Conclusions- These results indicate that the presence of CMBs, and especially high burden and lobar location, are independent predictors of poor 3-month clinical outcomes and may increase symptomatic intracranial hemorrhage risk in acute ischemic stroke patients with recanalization. Our findings suggest that CMBs lead to more unfavorable effects in patients with recanalization after large vessel occlusion than in those without recanalization.

Acute stress causes rapid synaptic insertion of Ca2+ -permeable AMPA receptors to facilitate long-term potentiation in the hippocampus.

The neuroendocrine response to episodes of acute stress is crucial for survival whereas the prolonged response to chronic stress can be detrimental. Learning and memory are particularly susceptible to stress with cognitive deficits being well characterized consequences of chronic stress. Although there is good evidence that acute stress can enhance cognitive performance, the mechanism(s) for this are unclear. We find that hippocampal slices, either prepared from rats following 30 min restraint stress or directly exposed to glucocorticoids, exhibit an N-methyl-d-aspartic acid receptor-independent form of long-term potentiation. We demonstrate that the mechanism involves an NMDA receptor and PKA-dependent insertion of Ca2+ -permeable AMPA receptors into synapses. These then trigger the additional NMDA receptor-independent form of LTP during high frequency stimulation.

ATN Classification and Clinical Progression of the Amyloid-Negative Group in Alzheimer's Disease Neuroimaging Initiative Participants.

Alzheimer's disease has recently been classified using three biological markers (amyloid [A], tau [T], and neurodegeneration [N]) to help elucidate its progression. We aimed to investigate whether there were differences between cognitive function and the clinical dementia symptoms over time relative to the ATN classification in the amyloid-negative group. In the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort, 310 participants who underwent all the tests required for ATN classification were enrolled. The cognitive function score differences (Alzheimer's Disease Assessment Scale-Cognitive Subscale 13 [ADAS-Cog 13], Clinical Dementia Rating Sum of Boxes [CDR-SOB], and Mini-Mental State Examination [MMSE]) between the groups were analyzed using the analysis of covariance and score changes over time with a linear mixed-effects model. In the cross-sectional analysis, ADAS-Cog 13 scores were higher for A-T-N+ and A-T+N+ than for A-T-N- (p<0.001) and A-T+N- (p<0.001). In the longitudinal analysis, CDR-SOB scores for A-T+N+ deteriorated faster than A-T-N- (p<0.001), A-T+N- (p<0.001) and A-T-N+ (p<0.001). Hippocampal atrophy progressed faster in A-T-N+ (p<0.001) and A-T+N+ (p=0.02) than in A-T-N-. Through this study, we discovered that even in individuals classified as amyloid negative, neurodegeneration with tau deposition exacerbates cognitive decline and worsens clinical symptoms, underscoring the need for continuous monitoring and observation.

Outcome of mechanical thrombectomy with Solitaire stent as first-line intra-arterial treatment in intracranial internal carotid artery occlusion.

INTRODUCTION: Acute stroke from occlusion of the intracranial internal carotid artery (ICA) is associated with a poor clinical outcome despite a thrombolytic treatment. The purpose of this study was to evaluate the outcome of mechanical thrombectomy using the Solitaire stent for the treatment of acute stroke patients with intracranial ICA occlusion. METHODS: A total of 104 consecutive patients with acute stroke were treated with mechanical thrombectomy using the Solitaire stent as a first-line intra-arterial treatment. We retrospectively reviewed data from 26 of these patients who presented with acute stroke attributable to intracranial ICA occlusion. Rescue treatments in cases of failed Solitaire thrombectomy included intra-arterial urokinase, angioplasty, and forced suction thrombectomy. Successful recanalization was defined as thrombolysis in cerebral ischemia grades 2b to 3. Outcome measure was the modified Rankin Scale (mRS) score of 0-2 at 3 months. RESULTS: Successful recanalization was achieved in 77% (20/26) of patients. Recanalization was achieved with the Solitaire stent alone in 69% (18/26) of patients. Ten patients (39%) had a good clinical outcome (mRS score of 0-2) at 3 months. There was a good outcome in 50% of patients (10/20) with recanalization and no good outcome in patients (0/6) without recanalization (P = 0.027). None of eight patients who received rescue treatments showed a good outcome. No symptomatic intracerebral hemorrhage occurred. Mortality was 8% (2/26) at 3 months. CONCLUSION: Mechanical thrombectomy using the Solitaire stent can achieve a high rate of successful recanalization and a very low rate of symptomatic hemorrhage and thus improve a clinical outcome in patients with acute intracranial ICA occlusion.

Effect of Education on Discriminability of Montreal Cognitive Assessment Compared to Mini-Mental State Examination.

Background and Purpose: The Montreal Cognitive Assessment (MoCA) has been known as a screening test for detecting mild cognitive impairment (MCI) better than Mini-Mental State Examination (MMSE). However, in previous domestic studies, no significant difference was found in the discriminability between MoCA and MMSE. Researchers have suggested that this might be because older Koreans are less educated than older Westerners. This study was conducted to examine the effect of education on the discriminability of MoCA compared to the MMSE. Methods: Participants were 123 cognitively normal elderly, 118 with vascular MCI, 108 with amnestic MCI, 121 with vascular dementia, and 113 with dementia of the Alzheimer's type. The Korean-MoCA (K-MoCA) and Korean-MMSE (K-MMSE) were administered. Multiple regression analyses and receiver operating characteristic (ROC) curve analyses were performed. Results: In all participants, education significantly affected both K-MoCA and K-MMSE scores along with age. The effect of education was re-examined by subgroup analysis after dividing subjects according to the level of education. Effect of education on K-MoCA and K-MMSE was only shown in the group with <9 years of education. ROC curve analyses revealed that the discriminability of K-MoCA to differentiate between vascular MCI and normal elderly was significantly higher than that of K-MMSE. When re-examining subgroups divided by education level, however, this higher discriminability of K-MoCA disappeared in the group with <9 years of education. Conclusions: These results indicate no difference in discriminating cognitive deficits between K-MoCA and K-MMSE in Korean elderly with <9 years of education.

Comparison of automated quantification of amyloid deposition between PMOD and Heuron.

Several programs are widely used for clinical and research purposes to automatically quantify the degree of amyloid deposition in the brain using positron emission tomography (PET) images. Given that very few studies have investigated the use of Heuron, a PET image quantification software approved for clinical use, this study aimed to compare amyloid deposition values quantified from 18F-flutemetamol PET images using PMOD and Heuron. Amyloid PET data obtained from 408 patients were analysed using each quantitative program; moreover, the standardized uptake value ratios (SUVRs) of target areas were obtained by dividing the standardized uptake value (SUV) of the target region by the SUV of cerebellar grey matter as a reference. Compared with PMOD, Heuron yielded significantly higher SUVRs for all target areas (paired sample t-test, p < 0.001), except for the PC/PCC (p = 0.986). However, the Bland-Altman plot analysis indicated that the two quantitative methods may be used interchangeably. Moreover, receiver operating characteristic curve analysis revealed no significant between-method difference in the performance of the SUVRs in evaluating the visual positivity of amyloid deposits (p = 0.948). In conclusion, Heuron and PMOD have comparable performance in quantifying the degree of amyloid deposits in PET images.

Early clinical implications of microalbuminuria in patients with acute ischaemic stroke.

BACKGROUND: Microalbuminuria is thought to be independently associated with an increased risk of, and mortality from, stroke. However, no studies have shown whether microalbuminuria is associated with the early clinical outcomes of acute ischaemic stroke. Therefore we investigated whether this. We also looked at radiological outcomes in stroke patients with microalbuminuria. METHODS: This was a retrospective study of patients with ischaemic stroke (within 72 h of symptom onset) who had been consecutively admitted to the Cerebrovascular Center at Chonnam National University Hospital between May 2010 and February 2011. Early clinical outcomes were assessed by early neurological deterioration (END) and modified Rankin Scale score >2 at discharge. In addition, early radiological outcomes were assessed from haemorrhagic transformation (HT) and lesion changes on follow-up diffusion-weighted imaging. We categorised a urine albumin/creatinine ratio of ≤30 mg albumin/g creatinine as normal and 30-300 mg albumin/g creatinine as microalbuminuria. RESULTS: 139 of 361 patients (38.5%) had microalbuminuria. In multivariate analysis, microalbuminuria was independently associated with END and HT. Furthermore, there were significant relationships between urinary albumin/creatinine ratio and white matter hyperintensity (WMH) grades (31.78 mg albumin/g creatinine for no WMH, 48.41 for grade 1, 64.29 for grade 2, and 44.16 for grade 3; p=0.004) and the types of HT (37.43 mg albumin/g creatinine for no HT, 71.41 for HI, and 131.63 for PH; p<0.001). CONCLUSION: In the early phase of ischaemic stroke, patients with microalbuminuria were associated with worse clinical and radiological outcomes (END, HT and lesion changes on follow-up diffusion-weighted imaging) than those without.

DeepParcellation: A novel deep learning method for robust brain magnetic resonance imaging parcellation in older East Asians.

Accurate parcellation of cortical regions is crucial for distinguishing morphometric changes in aged brains, particularly in degenerative brain diseases. Normal aging and neurodegeneration precipitate brain structural changes, leading to distinct tissue contrast and shape in people aged >60 years. Manual parcellation by trained radiologists can yield a highly accurate outline of the brain; however, analyzing large datasets is laborious and expensive. Alternatively, newly-developed computational models can quickly and accurately conduct brain parcellation, although thus far only for the brains of Caucasian individuals. To develop a computational model for the brain parcellation of older East Asians, we trained magnetic resonance images of dimensions 256 × 256 × 256 on 5,035 brains of older East Asians (Gwangju Alzheimer's and Related Dementia) and 2,535 brains of Caucasians. The novel N-way strategy combining three memory reduction techniques inception blocks, dilated convolutions, and attention gates was adopted for our model to overcome the intrinsic memory requirement problem. Our method proved to be compatible with the commonly used parcellation model for Caucasians and showed higher similarity and robust reliability in older aged and East Asian groups. In addition, several brain regions showing the superiority of the parcellation suggest that DeepParcellation has a great potential for applications in neurodegenerative diseases such as Alzheimer's disease.

Directional asymmetries of saccadic hypometria in patients with early Parkinson's disease and unilateral symptoms.

BACKGROUND: Saccade may be abnormal in Parkinson's disease (PD), but there have been no systematic studies on directional asymmetries of horizontal saccades in early PD. The aims of this study were to determine the saccadic abnormalities and their directional asymmetries. METHODS: We recorded visually guided horizontal prosaccades with random (random amplitudes and irregular time intervals) and regular (fixed amplitude and regular time interval) paradigms using video-oculography in 44 patients with unilateral symptoms and signs from early PD and in 26 controls. RESULTS: PD patients showed decreased saccadic amplitude compared to the controls, especially during regular paradigm while the saccadic latency did not differ between the groups. Patients with unilateral PD tended to show more severe saccadic hypometria toward the symptomatic side during the regu- lar paradigm, compared to normal control. CONCLUSION: Even in early PD patients, saccadic accuracy may be abnormal. Asymmetries in saccadic hypometria are more likely to be detected during the anticipatable saccadic paradigm, which could be a useful adjunct in the diagnosis of early-stage PD.

White matter hyperintensity as a factor associated with delayed mood disorders in patients with acute ischemic stroke.

BACKGROUND: Mood disorder is a frequent complication of stroke. Comorbid depressive and anxiety disorders are very common, indicating that it is advisable to assess both disorders at the same time. The aim of the present study was to examine the prevalence of post-stroke depression (PSD) and poststroke anxiety (PSA) at baseline and to evaluate factors related to delayed PSD and PSA at 3 months after stroke onset. METHODS: This was a prospectively registered and retrospectively analyzed study of patients with acute ischemic stroke between January 2009 and March 2010. Patients included in this study were interviewed in order to evaluate their Hospital Anxiety and Depression Scale (HADS) scores. In this study, each depression and anxiety score was dichotomized into 'nondepressive and nonanxious' (HADS-D and HADS-A ≤7) and 'depressive and anxious' (HADS-D and HADS-A >7). Multiple logistic regression analysis was used to evaluate the independent factors of depressive and anxious symptoms 3 months after stroke onset. RESULTS: Of the 133 patients, 47.4% were 'depressive' and 56.4% were 'anxious' at baseline. The depressive and anxious groups had a significantly higher frequency of severe white matter hyperintensity (WMH) than the nondepressive and nonanxious groups (p < 0.05). The independent factors of PSD and PSA at 3 months were deep white matter hyperintensities (DWMH) and modified Rankin scale 0 to 1 at 3 months. CONCLUSION: In conclusions, the results of our study demonstrated that delayed depression and anxiety after ischemic stroke were related to the severity of DWMH and unfavorable outcomes at 3 months, regardless of anti-anxiety treatment. Our results suggested that WMH might be associated with pathomechanism of delayed depression and anxiety.

Validity of the Montreal Cognitive Assessment (MoCA) Index Scores: a Comparison with the Cognitive Domain Scores of the Seoul Neuropsychological Screening Battery (SNSB).

BACKGROUND AND PURPOSE: A new approach was proposed to score the Montreal Cognitive Assessment (MoCA) index scores for 6 cognitive domains: orientation (OIS), attention (AIS), language (LIS), visuospatial function (VIS), memory (MIS), and executive function (EIS). This study investigated whether the MoCA index scores represent the functions of each cognitive domain by examining the correlations with the corresponding cognitive domain scores derived from conventional neuropsychological tests included in the Seoul Neuropsychological Screening Battery, 2nd Edition (SNSB-II). METHODS: The participants were 104 amnestic mild cognitive impairment (aMCI), 74 vascular mild cognitive impairment (VaMCI), 73 dementia of the Alzheimer's type (DAT), and 41 vascular dementia (VaD) patients. All participants were administered the Korean-MoCA and SNSB-II. RESULTS: Like the MoCA total score, the MoCA-OIS, MoCA-VIS, and MoCA-MIS showed differences between aMCI and AD groups and between VaMCI and VaD groups. The MoCA-AIS, MoCA-LIS, and MoCA-EIS showed significant differences between VaMCI and VaD groups, but no difference between aMCI and DAT groups. In the aMCI and VaMCI groups, all index scores of the MoCA showed significant correlations with the corresponding cognitive domain scores of the SNSB-II. Except for MoCA-MIS, the MoCA-AIS, MoCA-LIS, MoCA-VIS, and MoCA-EIS also showed significant correlations with the corresponding domain scores of the SNSB-II in the DAT and VaD groups. CONCLUSIONS: These results indicate that all MoCA index scores, except for MoCA-MIS, which does not reflect the severity of memory impairment in dementia patients, provide highly valid information on the function of each cognitive domain in patients with mild cognitive impairment and dementia.

Lesion patterns of small deep infarcts have different clinical and imaging characteristics.

BACKGROUND: The mechanisms underlying small deep infarcts in the subcortical area are unknown. This study used coronal diffusion-weighted imaging (DWI) to investigate clinical and radiological findings in patients with small deep infarcts. METHODS: This was a retrospective study of consecutively admitted patients with small deep infarcts in the subcortical area. We divided the patients into two groups as follows: (1) those with isolated lesion (IL) defined as an IL in the parenchyma by coronal DWI (group A), and (2) those with linear lesion (LL), defined as a LL extending to the basal surface on coronal DWI (group B). RESULTS: A total of 86 patients were included in this study, with 43 patients in each group. Neurological decline and ipsilateral MCA stenosis were observed more frequently in group B than in group A. Fluid-attenuated inversion recovery (FLAIR) signals showed that white-matter hyperintensity was more severe in group A than in group B (p = 0.015). CONCLUSIONS: This study suggests that LL patterns of small deep infarcts may result in a higher rate of neurological decline and ipsilateral MCA stenosis than IL patterns.

The CBV-ASPECT Score as a predictor of fatal stroke in a hyperacute state.

BACKGROUND: Many parameters of multimodal computed tomography (CT) have been assessed to predict clinical outcome and recanalization after thrombolysis. However, an early predictor of fatal stroke has not been clearly identified. Therefore, this study was conducted to identify early predictors related to fatal stroke. METHODS: We retrospectively analyzed subjects with acute ischemic stroke within 6 h of onset between March 2007 and January 2009. Early fatal stroke was defined as death or coma within 1 week of the initial ischemic stroke. Multimodal CT images were scored according to previous studies, such as the Alberta Stroke Program Early CT Score (ASPECTS), collateral score (CS) and clot burden score (CBS). RESULTS: A total of 68 patients were analyzed in this study. Twenty-two patients (32.4%) fell into a coma or died within 1 week of the initial stroke. Patients with fatal stroke had a lower CS, CBS and ASPECTS in the cerebral blood volume (CBV) and time-to-peak maps than those with nonfatal stroke. The initial NIHSS score, CBV-ASPECTS, age and diabetes mellitus were associated with fatal infarct in multivariate logistic regression analysis. CONCLUSIONS: Our study demonstrated that initially low CBV-ASPECTS on perfusion CT could predict early fatal stroke and that a CBV-ASPECTS threshold of <4 with a modest sensitivity and specificity could be considered as an early predictor of fatal stroke.

A case of recurrent neuro-Behçet's disease after tooth extraction.

We report a 39-yr-old man with neuro-Behçet's disease (NBD) in remission who developed left-sided ataxia with a sensory deficit about 10 days after tooth extraction. Several years ago, he experienced a similar episode of relapse after tooth extraction. Brain magnetic resonance imaging showed a newly developed right thalamic lesion. In cerebrospinal fluid, lymphocyte-dominant pleocytosis and mild elevation of IgG were found. Immunologic factors may be important in the pathogenesis of NBD because of the time delay between tooth extraction and relapse. Careful observation and prevention are needed before dental procedures in patients with NBD.

Classification and Graphical Analysis of Alzheimer's Disease and Its Prodromal Stage Using Multimodal Features From Structural, Diffusion, and Functional Neuroimaging Data and the APOE Genotype.

Graphical, voxel, and region-based analysis has become a popular approach to studying neurodegenerative disorders such as Alzheimer's disease (AD) and its prodromal stage [mild cognitive impairment (MCI)]. These methods have been used previously for classification or discrimination of AD in subjects in a prodromal stage called stable MCI (MCIs), which does not convert to AD but remains stable over a period of time, and converting MCI (MCIc), which converts to AD, but the results reported across similar studies are often inconsistent. Furthermore, the classification accuracy for MCIs vs. MCIc is limited. In this study, we propose combining different neuroimaging modalities (sMRI, FDG-PET, AV45-PET, DTI, and rs-fMRI) with the apolipoprotein-E genotype to form a multimodal system for the discrimination of AD, and to increase the classification accuracy. Initially, we used two well-known analyses to extract features from each neuroimage for the discrimination of AD: whole-brain parcelation analysis (or region-based analysis), and voxel-wise analysis (or voxel-based morphometry). We also investigated graphical analysis (nodal and group) for all six binary classification groups (AD vs. HC, MCIs vs. MCIc, AD vs. MCIc, AD vs. MCIs, HC vs. MCIc, and HC vs. MCIs). Data for a total of 129 subjects (33 AD, 30 MCIs, 31 MCIc, and 35 HCs) for each imaging modality were obtained from the Alzheimer's Disease Neuroimaging Initiative (ADNI) homepage. These data also include two APOE genotype data points for the subjects. Moreover, we used the 2-mm AICHA atlas with the NiftyReg registration toolbox to extract 384 brain regions from each PET (FDG and AV45) and sMRI image. For the rs-fMRI images, we used the DPARSF toolbox in MATLAB for the automatic extraction of data and the results for REHO, ALFF, and fALFF. We also used the pyClusterROI script for the automatic parcelation of each rs-fMRI image into 200 brain regions. For the DTI images, we used the FSL (Version 6.0) toolbox for the extraction of fractional anisotropy (FA) images to calculate a tract-based spatial statistic. Moreover, we used the PANDA toolbox to obtain 50 white-matter-region-parcellated FA images on the basis of the 2-mm JHU-ICBM-labeled template atlas. To integrate the different modalities and different complementary information into one form, and to optimize the classifier, we used the multiple kernel learning (MKL) framework. The obtained results indicated that our multimodal approach yields a significant improvement in accuracy over any single modality alone. The areas under the curve obtained by the proposed method were 97.78, 96.94, 95.56, 96.25, 96.67, and 96.59% for AD vs. HC, MCIs vs. MCIc, AD vs. MCIc, AD vs. MCIs, HC vs. MCIc, and HC vs. MCIs binary classification, respectively. Our proposed multimodal method improved the classification result for MCIs vs. MCIc groups compared with the unimodal classification results. Our study found that the (left/right) precentral region was present in all six binary classification groups (this region can be considered the most significant region). Furthermore, using nodal network topology, we found that FDG, AV45-PET, and rs-fMRI were the most important neuroimages, and showed many affected regions relative to other modalities. We also compared our results with recently published results.

MRI-Based Multimodal Approach to the Assessment of Clinical Symptom Severity of Obsessive-Compulsive Disorder.

OBJECTIVE: This study assessed the associations of the abnormal brain activation and functional connectivity (FC) during memory processing and brain volume alteration in conjunction with psychiatric symptom severity in patients with obsessive-compulsive disorder (OCD). METHODS: Twenty-OCD patients and 20-healthy controls (HC) underwent T1-weighted and functional imaging underlying explicit memory task. RESULTS: In memory encoding, OCD patients showed higher activities in right/left (Rt./Lt.) inferior temporal gyrus (ITG), medial prefrontal cortex (MPFC), dorsolateral prefrontal cortex (DLPFC) and anterior cingulate cortex (ACC), compared with HC. In task-based FC, caudate (Cd) was positively connected with DLPFC and ITG in OCD, while HC showed different connectivities of Cd-ACC and Rt.-Lt. ITG. In memory retrieval, only Cd was activated in OCD patients. Cd was positively connected with DLPFC and vmPFC in OCD, but negatively connected between same brain areas in HC. OCD patients showed increased gray matter (GM) volumes of cerebellum, DLPFC, orbitofrontal cortex (OFC), hippocampus, Cd and ITG, and concurrently, increased white matter volumes of DLPFC. In OCD patients, GM volumes of Cd and OFC were positively correlated with HAMA and Y-BOCS. Functional activity changes of Cd in OCD were positively correlated with Y-BOCS. CONCLUSION: Our findings support to accessing clinical symptom and its severity linked by brain structural deformation and functional abnormality in OCD patients.

A pilot study of brain morphometry following donepezil treatment in mild cognitive impairment: volume changes of cortical/subcortical regions and hippocampal subfields.

The efficacy of donepezil is well known for improving the cognitive performance in patients with mild cognitive impairment (MCI) and Alzheimer's disease (AD). Most of the recent neuroimaging studies focusing on the brain morphometry have dealt with the targeted brain structures, and thus it remains unknown how donepezil treatment influences the volume change over the whole brain areas including the cortical and subcortical regions and hippocampal subfields in particular. This study aimed to evaluate overall gray matter (GM) volume changes after donepezil treatment in MCI, which is a prodromal phase of AD, using voxel-based morphometry. Patients with MCI underwent the magnetic resonance imaging (MRI) before and after 6-month donepezil treatment. The cognitive function for MCI was evaluated using the questionnaires of the Korean version of the mini-mental state examination (K-MMSE) and Alzheimer's disease assessment scale-cognitive subscale (ADAS-Cog). Compared with healthy controls, patients with MCI showed significantly lower GM volumes in the hippocampus and its subfields, specifically in the right subiculum and left cornu ammonis (CA3). The average scores of K-MMSE in patients with MCI improved by 8% after donepezil treatment. Treated patients showed significantly higher GM volumes in the putamen, globus pailldus, and inferior frontal gyrus after donepezil treatment (p < 0.001). However, whole hippocampal volume in the patients decreased by 0.6% after 6-month treatment, and the rate of volume change in the left hippocampus was negatively correlated with the period of treatment. These findings will be useful for screening and tracking MCI, as well as understanding of the pathogenesis of MCI in connection with brain morphometric change.

Early outcome of combined thrombolysis based on the mismatch on perfusion CT.

BACKGROUND: Possible factors associated with early outcome after thrombolysis are the recanalization time and the status of tissue. We assessed whether combined intravenous (IV) and intra-arterial (IA) thrombolysis performed according to the status of tissue based on perfusion computed tomography (PCT) is beneficial for the early outcome in patients with acute ischemic stroke. METHODS: To improve the recanalization time, we assumed that combined IA thrombolysis after IV thrombolysis would be beneficial. Eligible patients for combined thrombolysis were selected according to the status of tissue based on PCT. Recanalization was defined as Thrombolysis in Myocardial Infarction (TIMI) grade 2 or 3. 'Good functional outcome' was defined as a Modified Rankin Scale (mRS) score of 2 or less at discharge. RESULTS: Eighteen patients (11 men) underwent combined IV/IA thrombolysis. The recanalization rate after combined IV/IA thrombolysis was 88.9% (TIMI 2, 4; TIMI 3, 12). A good functional outcome at discharge was noted in 12 patients (66.7%). The incidence of symptomatic intracranial hemorrhage was 5.6% (1/18). CONCLUSIONS: The results of this study suggest that combined IV/IA thrombolysis based on the presence of mismatches on PCT might have a relatively high rate of recanalization and a favorable early outcome. In addition, the incidence of symptomatic intracranial hemorrhage was acceptable.

Gene-to-gene interaction between sodium channel-related genes in determining the risk of antiepileptic drug resistance.

The pathogenesis of antiepileptic drug (AED) resistance is multifactorial. However, most candidate gene association studies typically assess the effects of candidate genes independently of each other, which is partly because of the limitations of the parametric-statistical methods for detecting the gene-to-gene interactions. A total of 200 patients with drug-resistant epilepsy and 200 patients with drug-responsive epilepsy were genotyped for 3 representative the single nucleotide polymorphisms (SNPs) of the voltage-gated sodium channel genes (SCN1A, SCN1B, and SCN2A) by polymerase chain reaction and direct sequencing analysis. Besides the typical parametric statistical method, a new statistical method (multifactor dimensionality reduction [MDR]) was used to determine whether gene-to-gene interactions increase the risk of AED resistance. None of the individual genotypes or alleles tested in the present study showed a significant association with AED resistance, regardless of their theoretical functional value. With the MDR method, of three possible 2-locus genotype combinations, the combination of SCN2A-PM with SCN1B-PM was the best model for predicting susceptibility to AED resistance, with a p value of 0.0547. MDR, as an analysis paradigm for investigating multi-locus effects in complex disorders, may be a useful statistical method for determining the role of gene-to-gene interactions in the pathogenesis of AED resistance.