Heeyoung Kang

Effects of Medial Temporal Atrophy and White Matter Hyperintensities on the Cognitive Functions in Patients with Alzheimer’s Disease

Aims: We conducted this study to investigate the independent association of medial temporal atrophy (MTA) and white matter hyperintensities (WMH) with cognitive impairments of Alzheimer’s disease (AD) patients and the interaction between MTA and WMH. Methods: From 13 centers, a total of 216 AD patients were consecutively recruited and their MTA and WMH were visually rated. We evaluated the association of MTA and WMH with the various cognitive domains, and the interaction between MTA and WMH. Results: MTA independently correlated with scores of the Mini-Mental State Examination (MMSE), Clinical Dementia Rating scale (CDR), delayed recalls of the Seoul Verbal Learning Test (SVLT), the Boston Naming Test (BNT), and Word Fluency. WMH independently correlated with MMSE, CDR, Digit Span, and Stroop word reading, but not with delayed recall. There were interactions of WMH and MTA on CDR (p = 0.004), SVLT (p = 0.023), BNT (p = 0.002) and the semantic Word Fluency (p = 0.007). Conclusion: MTA and WMH independently affected cognitive deficits in AD patients, with somewhat different patterns where MTA was associated mostly with memory and language, while WMH were associated with attention and frontal executive functions. This study also showed interactions between MTA and WMH on some cognitive deficits and dementia severity, suggesting that they synergistically contribute to cognitive impairment in AD.

Emergency carotid artery stenting in patients with acute ischemic stroke due to occlusion or stenosis of the proximal internal carotid artery: a single-center experience

Background The feasibility, safety and effectiveness of emergency carotid artery stenting (eCAS) in patients with acute ischemic stroke (AIS) due to proximal internal carotid artery (ICA) stenosis or occlusion are still controversial. In this study we analyzed our experience with eCAS in patients with AIS. Methods Twenty-two eCAS procedures for proximal ICA stenosis or occlusion were performed in 22 patients at our institution between January 2011 and November 2013. The mean time from stroke symptom onset to presentation was 204 min (range 50–630 min) and the mean initial score on the National Institutes of Health Stroke Scale (NIHSS) was 12.55 (range 5–23). Ten patients had total occlusion of the proximal ICA and the remaining 12 patients had near total occlusion or severe stenosis (mean degree 90.7%, range 80–100%). Eleven patients also had tandem occlusion on the more distal intracranial arteries. Results Successful stent insertion was achieved in all patients and additional thrombectomy using a Solitaire stent or Penumbra aspiration catheter achieved a Thrombolysis In Cerebral Infarction grade of more than 2a in all patients with distal tandem occlusion. Procedure-related complications occurred in one patient (cerebral hyperperfusion syndrome) who recovered successfully. The mean NIHSS score at discharge was 3.55 (range 0–18). The mean modified Rankin Scale score at 3 months was 1±1.67 (range 0–6). Conclusions eCAS in patients with AIS due to proximal ICA stenosis or occlusion appears to be a technically feasible and effective method for achieving good clinical outcomes.

Comparison of Solitaire thrombectomy and Penumbra suction thrombectomy in patients with acute ischemic stroke caused by basilar artery occlusion

Background and purpose Acute ischemic stroke (AIS) caused by basilar artery occlusion (BAO) is a very severe neurological disease with a high mortality rate and poor clinical outcomes. In this study, we compared our experience of mechanical thrombectomy using the Solitaire stent (Solitaire thrombectomy) and manual aspiration thrombectomy using the Penumbra reperfusion catheter (Penumbra suction thrombectomy) in patients with AIS caused by BAO. Materials and methods Between March 2011 and December 2011, 13 patients received Solitaire thrombectomy. In January 2012, the Korean Food and Drug Administration banned the use of the Solitaire stent as a thrombectomy device, and a further 18 patients received Penumbra suction thrombectomy until December 2013. We compared parameters between patients treated with each device. Results Successful recanalization rates (Thrombolysis in Cerebral Infarction (TICI) score ≥2b: 84.6% vs 100%, p=0.168) and clinical outcomes (judged by the modified Rankin Scale scores recorded at 3 months: 3.6±2.6 vs 3.2±2.6, p=0.726) were not significantly different between the two groups. However, complete recanalization rates (TICI score of 3: 23.1% vs 72.2%, p=0.015) and total procedure times (101.9±41.4 vs 62.3±34.8 min, p=0.044) were significantly higher, and shorter, respectively, in patients treated by Penumbra suction thrombectomy. Conclusions The two thrombectomy devices were associated with similar recanalization rates and clinical outcomes in patients with AIS caused by BAO. However, Penumbra suction thrombectomy seemed to allow more rapid and complete recanalization than Solitaire thrombectomy.

Carotid artery stenting in patients with near occlusion: a single-center experience and comparison with recent studies.

OBJECTIVE The optimal management strategy for carotid artery near occlusion is still controversial. Nevertheless, prior studies about carotid artery stenting in patients with near occlusion reported both technically and clinically inspiring results. To define the effectiveness, safety, and clinical outcomes of carotid artery stenting in patients with near occlusion, we analyzed our experiences and compared with recent studies. METHODS We performed 24 carotid artery stenting procedures in 24 patients with near occlusion between January 2010 and July 2012. The patient group comprised 20 men (83.3%) and four women (16.7%) with a mean age of 69.5 years (range, 53-85 years). Eighteen patients had prior stroke or transient ischemic attack (75%), and six patients were asymptomatic (25%). RESULTS Successful stent insertion was achieved in 23 of 24 patients (95.8%). Cerebral hyperperfusion syndrome and post-procedural vascular events occurred in four patients, and all of these developed within 24h after the procedure (17.4%; two: hyperperfusion syndrome, two: acute myocardial infarction). The mean follow-up period after carotid artery stenting was 16.7±9.2 months (range, 6-32 months). No stroke related to carotid artery stenting or significant restenosis of the inserted stent developed during the follow-up period. CONCLUSIONS Carotid artery stenting in patients with near occlusion seems to be a technically feasible and effective method to prevent stroke recurrence. But hyperperfusion syndrome and post-procedural vascular event rates may be high, as shown in this study.

MRI in Tolosa‐Hunt Syndrome Associated With Facial Nerve Palsy

A 44‐year‐old woman developed a severe right frontotemporal headache, retro‐orbital pain, and, later, diplopia owing to right sixth nerve palsy. The brain MRI demonstrated strong enhancement of the right cavernous sinus. The sixth nerve palsy and headache improved with steroid therapy after 6 weeks. At that time, she suffered right peripheral facial nerve palsy. Enhancement of the distal canalicular and labyrinthic segment of the right facial nerve was found on contrast‐enhanced MRI. To our knowledge, this is a very rare case of Tolosa‐Hunt syndrome with facial nerve palsy, with simultaneous enhancement of the cavernous sinus and facial nerve on contrast‐enhanced MRI.

Caloric restriction improves diabetes-induced cognitive deficits by attenuating neurogranin-associated calcium signaling in high-fat diet-fed mice.

Diabetes-induced cognitive decline has been recognized in human patients of type 2 diabetes mellitus and mouse model of obesity, but the underlying mechanisms or therapeutic targets are not clearly identified. We investigated the effect of caloric restriction on diabetes-induced memory deficits and searched a molecular mechanism of caloric restriction-mediated neuroprotection. C57BL/6 mice were fed a high-fat diet for 40 weeks and RNA-seq analysis was performed in the hippocampus of high-fat diet-fed mice. To investigate caloric restriction effect on differential expression of genes, mice were fed high-fat diet for 20 weeks and continued on high-fat diet or subjected to caloric restriction (2 g/day) for 12 weeks. High-fat diet-fed mice exhibited insulin resistance, glial activation, blood–brain barrier leakage, and memory deficits, in that we identified neurogranin, a down-regulated gene in high-fat diet-fed mice using RNA-seq analysis; neurogranin regulates Ca2+/calmodulin-dependent synaptic function. Caloric restriction increased insulin sensitivity, reduced high-fat diet-induced blood–brain barrier leakage and glial activation, and improved memory deficit. Furthermore, caloric restriction reversed high-fat diet-induced expression of neurogranin and the activation of Ca2+/calmodulin-dependent protein kinase II and calpain as well as the downstream effectors. Our results suggest that neurogranin is an important factor of high-fat diet-induced memory deficits on which caloric restriction has a therapeutic effect by regulating neurogranin-associated calcium signaling.

Neuropsychological Correlates of the Proportional Impact of White Matter Hyperintensities on Mild to Moderate Dementia: The MRI 300 Study

Background: White matter hyperintensities (WMH) increase cognitive impairment in patients with dementia. Objective: We investigated the impact of WMH on the neuropsychological profiles in patients with mild to moderate dementia. Methods: We consecutively recruited newly diagnosed patients with mild to moderate dementia across South Korea for 1 year. The participants completed neuropsychological tests, magnetic resonance imaging, and structured neurological evaluations. The patients were divided into 3 categories, i.e. minimal, moderate, and severe WMH groups, according to the proportional degree of WMH. Results: 289 patients were recruited; 140 (48.3%) for the minimal WMH group, 99 (34.2%) for the moderate group, and 50 (17.5%) for the severe group. Both advanced age and low general cognitive level were significant contributors to WMH in patients with dementia. After adjusting for age, the neuropsychological correlates of the proportional impact of WMH were frontal executive, language, and attention profiles. However, the only significant neuropsychological correlate was the recognition memory profile after adjusting for both age and general cognitive level simultaneously. Conclusion: The results suggest that the most significant neuropsychological profile impacting the burden of WMH in patients with mild to moderate dementia was the recognition memory profile, regardless of age and general cognitive function.

Teaching NeuroImages: Glossopharyngeal neuralgia with syncope Heart rate and blood pressure change

A 53-year-old man was admitted for recurrent syncope. For 2 years he had experienced a severe paroxysmal stabbing pain in the left oropharynx, starting at the submandibular area and then radiating to …

Efficacy and tolerability of rivastigmine patch therapy in patients with mild-to-moderate Alzheimer’s dementia associated with minimal and moderate ischemic white matter hyperintensities: A multicenter prospective open-label clinical trial

Background and objective Studies investigating the impact of white matter hyperintensities (WMHs) on the response of acetylcholinesterase inhibitors in patients with Alzheimer’s disease (AD) have presented inconsistent results. We aimed to compare the effects of the rivastigmine patch between patients with AD with minimal WMHs and those with moderate WMHs. Methods Three hundred patients with mild to moderate AD were enrolled in this multicenter prospective open-label study and divided into two groups. Group 1 comprised patients with AD with minimal WMHs and group 2 comprised those with moderate WMHs. The patients were treated with a rivastigmine patch for 24 weeks. Efficacy measures were obtained at baseline and after 24 weeks. The primary endpoint was the change in the AD Assessment Scale-Cognitive subscale (ADAS-Cog) from the baseline to the end of the study. Results Of the 300 patients, there were 206 patients in group 1 and 94 patients in group 2. The intention-to-treat group comprised 198 patients (group 1, n = 136; group 2, n = 46) during the 24-week study period. Demographic factors did not differ between group 1 and group 2. There were no significant differences in change in ADAS-cog between group 1 (-0.62±5.70) and group 2 (-0.23±5.98) after the 24-week rivastigmine patch therapy (p = 0.378). The patients in group 1 had a 0.63-point improvement from baseline on the Frontal Assessment Battery, while group 2 had a 0.16-point decline compared to baseline at the end of the study (p = 0.037). The rates of adverse events (AEs) (42.6 vs. 40.3%) and discontinuation due to AEs (10.3% vs. 4.3%) did not differ between the groups. Conclusions Although the efficacy and tolerability of rivastigmine patch therapy were not associated with WMH severity in patients with AD, some improvement in frontal function was observed in those with minimal WMHs. Trial registration ClinicalTrials.gov NCT01380288

Location of Irritative Zone in Epileptic Brains of Schizencephalic Patients

Although many schizencephaly patients suffer from epilepsy, the relationship between schizencephalic lesions and epileptic foci remains unclear. Previous studies have shown that schizencephalic lesions may be associated with, rather than contain, epileptogenic zones. Thus, the purpose of this study was to investigate the current source distribution (CSD) of epileptiform discharges in schizencephalic patients and to correlate this activity with existing structural lesions. A consecutive series of 30 schizencephalic patients who were diagnosed using brain magnetic resonance imaging (MRI) were selected retrospectively and prospectively. Of the original 30 subjects selected, 13 had epilepsy, and 6 of these patients exhibited schizencephaly, epilepsy, and interictal spikes on electroencephalograms (EEG) and were enrolled in the present study investigating the current source analysis of interictal spikes. The CSDs of the initial rising phases and the peak points of the interictal spikes were obtained using standardized low-resolution brain electromagnetic tomography (LORETA). Five patients exhibited a single focus of interictal spikes, while 1 patient showed 2 foci. Relative to the structural brain lesions, 5 patients displayed extrinsically localized CSDs, while 1 patient showed a partially intrinsically localized CSD. The present findings demonstrate that the CSDs of interictal spikes in schizencephalic patients are in general anatomically distinct from the cerebral schizencephalic lesions and that these lesions may display an extrinsic epileptogenicity.