Hak Young Rhee

Regional cerebral perfusion in patients with Alzheimer’s disease and mild cognitive impairment: effect of APOE Epsilon4 allele

IntroductionThe objective of this study was to evaluate the effect of apolipoprotein E (APOE) epsilon 4 allele on regional cerebral perfusion (rCBF) changes using arterial spin labeling (ASL) magnetic resonance imaging (MRI) in subjects who are carriers or noncarriers of this risk factor for Alzheimer disease (AD).MethodsTwenty-five subjects with AD, 25 with amnestic mild cognitive impairment (MCI) and 25 cognitively normal (CN) subjects underwent isotropic volumetric T1-weighted imaging and pulsed ASL MRI. All subjects were divided into carrier or noncarriers of the epsilon4 allele. Voxel-based statistical analyses were performed among groups on rCBF by ANOVA tests. In each subject group, we also evaluated the rCBF change between carrier and noncarrier groups.ResultsrCBF was significantly reduced in AD subjects compared to other subjects. In CN and AD subjects, rCBF in the carrier group was significantly reduced in several areas of the brain compared with that of the noncarrier group. In the carrier group, rCBF was significantly increased in the right parahippocampal gyrus, the bilateral cingulate gyri and the right posterior cingulate on the MCI group in addition to the right superior frontal gyrus in the AD group.ConclusionrCBF in the CN and AD groups were significantly reduced in the subjects with the carriers of the epsilon4 allele, which is a risk factor for Alzheimer’s disease. In addition, rCBF in the MCI group was significantly increased in subjects who were carriers. Therefore, rCBF can be used as a biomarker to show disease progression in areas of the brain of MCI subjects.

Regional white matter hyperintensities in normal aging, single domain amnestic mild cognitive impairment, and mild Alzheimer’s disease

Few studies have examined white matter hyperintensities (WMH) along the cognitive continuum between single-domain amnestic mild cognitive impairment (sd-aMCI) and Alzheimers disease (AD). The aims of our study were to explore relationships between the extent and location of WMH and disease severity along the cognitive continuum and to determine whether differences in the distribution of WMH could be predictive of specific patterns of cognitive impairment. We compared cognitive function, vascular risk factors, and regional (frontal lobe, parieto-occipital [PO] lobe, temporal lobe, periventricular [PV] white matter and deep white matter) WMH volume in 37 patients with mild AD, 23 patients with sd-aMCI, and 24 age-matched and education-matched normal controls. A quantitative volumetric method was applied to measure WMH burden. Total and regional WMH burdens, except for those in the temporal lobe, were significantly correlated with age (p<0.01). We found a trend toward increasing WMH volume with disease severity, higher in AD than in sd-aMCI and lowest in the controls. Total WMH volume was associated with the global cognitive test score. In multiple linear regression analysis, PV WMH volume, but not deep WMH volume, strongly predicted performances on the Controlled Oral Word Association test and the Color Word Stroop test after adjusting for important demographic variables. Only PO WMH volume was a significant predictor of a cognitive test score when frontal and temporal WMH volumes were simultaneously entered into the regression model. The extent and distribution of WMH, especially in the PV and PO regions, were associated with disease severity and reduced cognition.

Microstructural Change of the Brain in Chronic Obstructive Pulmonary Disease: A Voxel-Based Investigation by MRI

Abstract Background: Cognitive deficit is a common problem in patients with chronic obstructive pulmonary disease (COPD). The aim of this study was to prospectively evaluate if MRI can demonstrate microstructural volume loss and the diffusion anisotropic change in subjects with COPD, compared with cognitively normal (CN) subjects. Methods: Six subjects with severe COPD, 13 with moderate COPD, and 12 CN subjects underwent isotropic volumetric T1-weighted imaging and diffusion tensor imaging (DTI). Voxel-based statistical analyses among groups were performed on brain volumes, fractional anisotropy (FA) and trace. Cognitive function tests were performed in all subjects, and the Cognitive function tests (CFT) scores were compared among the three groups. Results: No significant regional difference in volume was found in both the severe and moderate COPD groups relative to the CN group. Comparing between severe COPD and CN, FA was reduced in both the cerebral cortices, and in frontoparietal periventricular white matter. The trace value of the severe COPD group was significantly higher in the cerebral cortices, and in frontoparietal periventricular white matter, than that of the CN group. The severe COPD group showed significantly lower scores in the language-related, visuospatial, and frontal executive functions compared to those of the CN and moderate COPD group. Conclusion: This study demonstrated that COPD could affect the axonal integrity in multiple brain regions, and change in DTI might be related with the severity of the COPD.

Texture analyses of quantitative susceptibility maps to differentiate Alzheimer's disease from cognitive normal and mild cognitive impairment

PURPOSE Although a number of studies have focused on finding anatomical regions in which iron concentrations are high, no study has been conducted to examine the overall variations in susceptibility maps of Alzheimers disease (AD). The objective of this study, therefore, was to differentiate AD from cognitive normal (CN) and mild cognitive impairment (MCI) using a texture analysis of quantitative susceptibility maps (QSMs). METHODS The study was approved by the local institutional review board, and informed consent was obtained from all subjects. In each participant group-CN, MCI, and AD-18 elderly subjects were enrolled. A fully first-order flow-compensated 3D gradient-echo sequence was run to obtain axial magnitudes and phase images and to produce QSM data. Sagittal structural 3D T1-weighted (3DT1W) images were also obtained with the magnetization-prepared rapid acquisition of gradient-echo sequence to obtain brain tissue images. The first- and second-order texture parameters of the QSMs and 3DT1W images were obtained to evaluate group differences using a one-way analysis of covariance. RESULTS For the first-order QSM analysis, mean, standard deviation, and covariance of signal intensity separated the subject groups (F = 5.191, p = 0.009). For the second-order analysis, angular second moment, contrast, and correlation separated the subject groups (F = 6.896, p = 0.002). Finally, a receiver operating characteristic curve analysis differentiated MCI from CN in white matter on the QSMs (z = 3.092, p = 0.0020). CONCLUSIONS This was the first study to evaluate the textures of QSM in AD, which overcame the limitations of voxel-based analyses. The QSM texture analysis successfully distinguished both AD and MCI from CN and outperformed the voxel-based analysis using 3DT1-weighed images in separating MCI from CN. The first-order textures were more efficient in differentiating MCI from CN than did the second-order.

Glutamine and Glutamate Complex, as Measured by Functional Magnetic Resonance Spectroscopy, Alters During Face-Name Association Task in Patients with Mild Cognitive Impairment and Alzheimer’s Disease

BACKGROUND The metabolite response during a memory task in Alzheimers disease (AD) patients is unknown. OBJECTIVE To investigate the metabolite changes in subjects with AD, amnestic mild cognitive impairment (aMCI), and cognitively normal (CN) elderly during a memory task using functional magnetic resonance spectroscopy (fMRS). METHODS This study involved 23 young normal controls (YC), 24 CN elderly, 24 aMCI, and 24 mild and probable AD individuals. fMRS data were acquired at the precuneus and posterior cingulate brain regions during a face-name association task. Statistical analyses of quantified metabolites were performed to evaluate differences of the metabolite values between the stimulation conditions and among the four subject groups. Receiver operating curve analysis was performed to evaluate whether the metabolic changes after functional activations can differentiate the subject groups. RESULT Glutamine and glutamate complex (Glx) was statistically significantly different between the fixation and repeat conditions in aMCI (p = 0.0492) as well as between the fixation and the novel conditions in the AD (p = 0.0412) group. The total N-acetylaspartate (tNAA) was statistically significantly different among the four subject groups in the fixation condition (DF = 3, F = 7.673, p <  0.001), the novel condition (DF = 3, F = 6.945, p <  0.001), and the repeat condition (DF = 3, F = 7.127, p <  0.001). tNAA, tCr, and mIns could be used to differentiate CN from aMCI. Furthermore, tNAA, tCr, Glx, and Glu could also differentiate CN from AD, and aMCI from AD. CONCLUSION Glx was altered during a stimulation that may be used to evaluate neuronal dysfunction in a demented patient. tNAA and tCr were reduced in patients with AD.

Quantitative susceptibility mapping to evaluate the early stage of Alzheimer's disease☆

The objective of this study was to evaluate susceptibility changes caused by iron accumulation in cognitive normal (CN) elderly, those with amnestic mild cognitive impairment (aMCI), and those with early state AD, and to compare the findings with gray matter volume (GMV) changes caused by neuronal loss. The participants included 19 elderly CN, 19 aMCI, and 19 AD subjects. The voxel-based quantitative susceptibility map (QSM) and GMV in the brain were calculated and the differences of those insides were compared among the three groups. The differences of the QSM data and GMVs among the three groups were investigated by voxel-based and region of interest (ROI)-based comparisons using a one-way analysis of covariance (ANCOVA) test with the gender and age as covariates. Finally, a receiver-operating-characteristic (ROC) curve analysis was performed. The voxel-based results showed that QSM demonstrated more areas with significant difference between the CN and AD groups compared to GMV. GMVs were decreased, but QSM values were increased in aMCI and AD groups compared with the CN group. QSM better differentiated aMCI from CN than GMV in the precuneus and allocortex regions. In the accumulation regions of iron and amyloid β, QSM can be used to differentiate between CN and aMCI groups, indicating a useful an auxiliary imaging for early diagnosis of AD.

Paraganglioma of the filum terminale presenting with normal pressure hydrocephalus

We describe a patient with an intraspinal paraganglioma who presented with normal pressure hydrocephalus. A 70-year-old man presented with a 6-month history of gait disturbance and cognitive dysfunction. Computed tomography of the brain and magnetic resonance imaging of the spine revealed communicating hydrocephalus and a spinal mass at the T12-L1 level which proved to be a paraganglioma of the filum terminale. Radioisotope cisternography revealed a severe delay in cerebrospinal fluid circulation. Symptoms related to communicating hydrocephalus resolved after tumor resection.

Cerebral Air Embolism as a Result of Inducing Pneumoperitoneum After Bilobectomy

A 62-year-old man with lung cancer underwent a right lower bilobectomy of the lung. After resection, we insufflated air through the diaphragm into the peritoneal cavity, and sudden cardiac arrest developed in the patient. A large number of air bubbles were aspirated from the heart and great vessels, and the patient recovered after resuscitation. However, he remained with a left sensory deficit, a left homonymous hemianopia, and left hemiparesis. A brain computed tomographic scan revealed an acute ischemic lesion in the right parieto-occipital area. Our case shows that an air embolism is a possible complication of artificial intraoperative pneumoperitoneum after pulmonary resection.

Neurosyphilis combined with acute anterior thalamic infarction.

Dear Editor, A 65-year-old right-handed man with 9 years of education was brought to our memory disorder clinic by his wife, who reported that over the past 6 months, the patient had experienced personality changes such as apathy, abulia, and emotional lability. The patient’s wife recalled him having fairly goodmemory; however, his memory had deteriorated dramatically over the prior 2 weeks. He could not remember the names of familiar people, and presented with reduced verbal fluency and word-finding difficulty. His medical history was otherwise unremarkable. On neurological examination, his mini-mental state examination (MMSE) score was 19/30 (four points lost on time and one point lost on place orientation, three points lost on attention and calculation, and three points lost on delayed recall). The cranial nerves were intact, including normal pupillary responses to light and convergence. Motor examination revealed normal muscle strength and tone, and deep tendon reflexes were also normal. Babinski sign was not elicited. Sensory examination results were normal for all modalities. Neuropsychological tests revealed global cognitive impairment, particularly delayed recall of verbal and visual memory, language, and frontal/executive functions. However, digit span function and immediate memory recall was relatively preserved (Table 1). Rapidly progressive dementia (RPD) was suspected, and a laboratory and imaging diagnostic workup was performed. Extensive serology and hematological tests including complete blood count, blood chemistry, vitamin B12/folate, and thyroid function tests were normal except for positive rapid plasma reagin (RPR) and Treponema pallidum hemagglutination assays (TPHA). Human immunodeficiency virus (HIV) tests were negative, and no early signs of primary (chancre) or secondary (rash) syphilis were identified in the patient’s history. Apolipoprotein E genotype was ε3/ε3. Cerebrospinal fluid (CSF) analysis demonstrated a clear color with 57 cells/mm (94% lymphocytes), 170 mg/dl protein, 62.6 mg/ dl glucose (serum glucose 107 mg/dl), positive venereal disease research laboratory (VDRL 1:4) and RPR (1:8), and fluorescent treponemal antibody absorption (FTA-ABS) immunoglobulin G. Serum and CSF adenosine deaminase were within normal range. Brain magnetic resonance imaging (MRI) demonstrated focal hyperintensities in the left anterior thalamus and right basal ganglia on diffusion-weighted imaging. The above lesions were confirmed to be acute ischemic cerebral infarctions based on low signal intensity on the apparent diffusion coefficient map and hyperintensity on fluid-attenuated inversion recovery (FLAIR) sequencing. Magnetic resonance angiography (MRA) of the brain revealed mild atherosclerotic lesions in bilateral posterior cerebral arteries. In addition, a chronic focal cerebral infarction at the left corona radiata was seen on FLAIR, sugges t ing a s i lent infarc t ion (Fig . 1) . Electroencephalography revealed generalized, intermittent, slow activity, predominantly in the right hemisphere, without epileptiform discharges. A diagnosis of neurosyphilis was made, and the patient was treated with 4 × 10 units of penicillin G administrated intravenously six times daily for 14 days. Because the patient exhibited acute ischemic stroke with mild intracranial * Key-Chung Park kcpark@khu.ac.kr

Treatment of Propriospinal Myoclonus at Sleep Onset

Dear Editor, Propriospinal myoclonus (PSM) is characterized by jerks arising in axial muscles that spread to more caudal and rostral segments along propriospinal pathways. PSM at sleep onset is a subtype of PSM that occurs during the sleep–awake transition and causes severe sleep-onset insomnia.1 Previous case reports have focused on the etiology and mechanism of PSM, but have not evaluated treatment responses objectively. Moreover, most treatments have only employed clonazepam.1 We present a patient with PSM at sleep onset who improved after treatment with clonazepam and add-on levetiracetam. The improvement was confirmed by serial video polysomnography (VPSG).