[18F]-THK5351 PET Imaging in Patients With Semantic Variant Primary Progressive Aphasia.

BACKGROUND: Semantic variant primary progressive aphasia (svPPA) has been associated with a variety of proteinopathies, mainly transactive response DNA-binding protein, but also with tau and ß-amyloid. Recently selective tau tracers for positron emission tomography (PET) have been developed to determine the presence of cerebral tau deposits in vivo. Here, we investigated the topographical distribution of THK5351 in svPPA patients. MATERIALS AND METHODS: Five svPPA patients, 14 Alzheimer's disease patients, and 15 age-matched normal controls underwent [F]-THK5351 PET scans, magnetic resonance imaging, and detailed neuropsychological tests. [F]-fluorodeoxyglucose PET was obtained in 3 svPPA patients, whereas the remaining 2 underwent amyloid PET using [F]-flutemetamol. Tau distribution among the 3 groups was compared using regions of interest-based and voxel-based statistical analyses. RESULTS: In svPPA patients, [F]-THK5351 retention was elevated in the anteroinferior and lateral temporal cortices compared with the normal controls group (left>right), and in the left inferior and temporal polar region compared with Alzheimer's disease patients. [F]-THK5351 retention inversely correlated with glucose metabolism, whereas regional THK retention correlated with clinical severity. [F]-flutemetamol scans were negative for ß-amyloid. CONCLUSIONS: These findings show that [F]-THK5351 retention may be detected in cortical regions correlating with svPPA pathology.

Topical anti-inflammatory and anti-oxidative effects of porcine placenta extracts on 2,4-dinitrochlorobenzene-induced contact dermatitis.

BACKGROUND: The placenta is a reservoir enriched with growth factors, hormones, cytokines and minerals. While several beneficial effects of placenta extracts on wound healing, anti-aging and anti-inflammatory responses have been reported, relatively limited mechanistic exploration has been conducted to date. Here, we provide compelling evidence of anti-inflammatory and anti-oxidative activities of porcine placenta extracts (PPE) against contact dermatitis in vivo. METHODS: A contact dermatitis mouse model was established by sensitizing the dorsal skin of BALB/c mice using the contact allergen, 2,4-dinitrochlorobenzene (DNCB), and molecular consequences of topical application of PPE were investigated. PPEs were pre-sterilized via γ-irradiation, which is a milder but more effective way of sterilizing biomolecules relative to the conventional autoclaving method. RESULTS: DNCB-induced skin lesions displayed clear contact dermatitis-like symptoms and topical application of PPE dramatically alleviated both local and systemic inflammatory responses. Inflammatory epidermal thickening was completely abrogated and allergen-specific serum IgE levels significantly reduced in the presence of PPE. Moreover, anti-oxidative activities of PPE were observed both in vitro and in vivo, which may lead to attenuation of inflammatory responses. Prolonged treatment with PPE strongly inhibited production of DNCB-induced reactive oxygen species (ROS) and subsequently prevented oxidative degradation of hyaluronic acid (HA), which triggers innate inflammatory responses. CONCLUSION: Our findings supply valuable insights into the mechanisms underlying the anti-inflammatory effects of PPE and provide a functional basis for the clinical application of PPE in inflammatory diseases.

Air Quality, Biomarker Levels, and Health Effects on Staff in Korean Restaurants and Pubs Before and After a Smoking Ban.

INTRODUCTION: The Korean government implemented a smoking ban at square floor area of ≥150 m(2), rather than <150 m(2), restaurants and pubs from July 2013. This study examined the effects of the smoking regulations in restaurants and pubs in terms of the air quality, biomarker levels and health effects on staff. METHODS: Particulate matter smaller than 2.5 µm (PM2.5) was measured in 146 facilities before and 1 month after the ban. The urinary cotinine and 4-(methylnitrosamino)-1-(3-pyridyl)-1- butanol (NNAL) levels were measured in 101 staff members at 77 facilities before and 1 month after the ban. We also measured self-reported respiratory and sensory symptoms on both phases. RESULTS: Of the 146 facilities, 121 facilities were included in the PM2.5 analysis. In ≥150 m(2) pubs, the indoor PM2.5 concentration was significantly reduced after the ban (p < .05). While the urinary cotinine concentrations of the staff in all facilities were not changed after the ban, the total NNAL concentrations of the staff in ≥150 m(2) pubs were significantly reduced after the ban (p < .05). The health effects on staff show that only sensory symptoms significantly improved in ≥150 m(2) facilities after the ban (p < .05). CONCLUSIONS: The smoking ban significantly reduced the levels of PM2.5 and total NNAL concentrations in ≥150 m(2) pubs and improved sensory health among staff in ≥150 m(2) facilities. The results of this study can be useful in supporting an expansion of the smoking ban in all indoor places, including <150 m(2) restaurants and pubs.

Response to rivastigmine transdermal patch or memantine plus rivastigmine patch is affected by apolipoprotein E genotype in Alzheimer patients.

BACKGROUND/AIMS: The apolipoprotein E (APOE) genotype in response to pharmacological treatments in patients with Alzheimer's disease (AD) remains a matter of controversy. This analysis investigated the effect of the APOE genotype on the clinical response to rivastigmine transdermal patch monotherapy or memantine plus rivastigmine patch in patients with mild to moderate AD. METHODS: Two hundred and six (n = 206) patients with probable AD and Mini-Mental State Examination (MMSE) scores of 10-20 were randomized to rivastigmine patch monotherapy or memantine plus rivastigmine patch for 24 weeks. Of the 206 patients with probable AD, 146 patients who consented to genetic testing for APOE were included and assessed for this subgroup study. RESULTS: There were no significant differences on MMSE, NPI, ADAS-cog, ADCS-ADL, CDR-SB, NPI and FAB between rivastigmine patch monotherapy and memantine plus rivastigmine patch according to the APOE genotype. However, patients with moderately severe AD (MMSE ≤15) who were APOE ε4 carriers showed higher responder rates on ADCS-ADL with memantine plus rivastigmine patch compared to rivastigmine patch monotherapy. CONCLUSION: Moderately severe AD patients with the APOE ε4 allele may respond more favorably to memantine plus rivastigmine patch than ε4 noncarriers.

Heat-processed ginseng enhances the cognitive function in patients with moderately severe Alzheimer's disease.

OBJECTIVES: Ginseng has been reported to improve cognitive function in animals and in healthy and cognitively impaired individuals. In this study, we investigated the efficacy of a heat-processed form of ginseng that contains more potent ginsenosides than raw ginseng in the treatment of cognitive impairment in patients with moderately severe Alzheimer's disease (AD). METHODS: Forty patients with AD were randomized into one of three different dose groups or the control group as follows: 1.5 g/day (n = 10), 3 g/day (n = 10), and 4.5 g/day (n = 10) groups, or control (n = 10). The Alzheimer's Disease Assessment Scale (ADAS) and Mini-Mental State Examination (MMSE) were used to assess cognitive function for 24 weeks. RESULTS: The treatment groups showed significant improvement on the MMSE and ADAS. Patients with higher dose group (4.5 g/day) showed improvements in ADAS cognitive, ADAS non-cognitive, and MMSE score as early as at 12 weeks, which sustained for 24-week follow-up. DISCUSSION: These results demonstrate the potential efficacy of a heat-processed form of ginseng on cognitive function and behavioral symptoms in patients with moderately severe AD.

Familial Takayasu's arteritis in female siblings.

Takayasu's arteritis (TA) is a rare chronic vasculitis of the aorta and its main branches. Infectious agents or autoimmunity are thought to influence the pathophysiology. Ethnic preponderance in East Asia and usually affects young Asian women suggesting a possible role of genetic factor in the etiology. We present a rare case of familial TA in female siblings with the involvement of the main branches of aortic arch and renal arteries described by three-dimensional computed tomography (3D-CT). This case is rare familial TA in female siblings with CT angiography, which is feasible in diagnosis and informative for the stage of TA.

The New Diagnosis-Related Group Reimbursement System and Laboratory Test Quality in Korea: Analysis of External Quality Assessment Results.

Korea introduced a new diagnosis-related group (NDRG), which is a mixed-bundle reimbursement system. We evaluated the effects of NDRGs on laboratory test quality by analyzing data over three years (2016-2018) from the Korean Association of External Quality Assessment Service (KEQAS). A total of 42 NDRG-participating hospitals (CASE), 84 non-participating similar size-hospitals (CON-1), and 42 tertiary hospitals (CON-2) were included. We assumed the proportion of KEQAS results with a larger than 2 standard deviation index (SDI) to be a bad laboratory quality marker (BLQM). CASE BLQMs were lower than CON-1 BLQMs for more than 2 years in alkaline phosphatase (ALP), alanine aminotransferase (ALT), chloride, glucose, sodium, and total protein, and higher in creatinine. CASE BLQMs were higher than CON-2 BLQMs for more than 2 years in ALP, chloride, creatinine, glucose, lactate dehydrogenase (LDH), phosphorus, potassium, sodium, total calcium, total cholesterol, triglyceride, and uric acid. Mean SDIs for general chemistry tests were not significantly different depending on NDRG participation. However, the NDRG is currently a pilot program that compensates the amount of each institution's reimbursement based on the fee-for-service system, and most participants were public hospitals. Thus, the effects of NDRGs on laboratory test quality should be re-evaluated after the NDRG program has stabilized and more private hospitals are participating.

White matter hyperintensities and cognitive dysfunction in Alzheimer disease.

The effect of white matter lesions in magnetic resonance imaging or vascular atherosclerosis on cognitive function is not fully understood in Alzheimer disease (AD). In this investigation, we examined the influence of white matter lesions on cognitive decline in AD. A total of 142 patients with AD (44 men, mean age 65.7 + 7.6 years; mean education period 7.8 + 5.0 years) were included. Patients were divided into 4 groups based on the severities of white matter hyperintensities (WMH) in brain magnetic resonance images (MRI) using Fazekas scale. Cognitive functions were determined using the Korean version of the Mini-Mental State Examination (K-MMSE) and the Clinical Dementia Rating (CDR) scale before acetylcholinesterase inhibitors were administered. Of the 142 patients, 30% (43/142) had no white matter signal abnormality (grade 0). Fourteen percentage (20/142) were grade 1, 42% (59/142) grade 2, and 14% (20/142) were grade 3. Mean K-MMSE scores declined as MRI grades increased to grade 2 and 3 compared to grade 0 (P < .01). Clinical Dementia Ratings were also aggravated by MRI grade. These results remained significant after adjusting for compounding factors affecting cognitive functions; sex, age, number of years in full-time education, hypertension, diabetes, hypercholesterolemia, smoking, and atrial fibrillation. The presence of WMHs were associated with score of MMSE and CDR impairment in patients with AD. These features could be a correctable factor hastening cognitive decline in AD.

Relationships between [¹8F]-THK5351 Retention and Language Functions in Primary Progressive Aphasia.

BACKGROUND AND PURPOSE: There are three distinct subtypes of primary progressive aphasia (PPA): the nonfluent/agrammatic variant (nfvPPA), the semantic variant (svPPA), and the logopenic variant (lvPPA). We sought to characterize the pattern of [¹8F]-THK5351 retention across all three subtypes and determine the topography of [¹8F]-THK5351 retention correlated with each neurolinguistic score. METHODS: We enrolled 50 participants, comprising 13 PPA patients (3 nfvPPA, 5 svPPA, and 5 lvPPA) and 37 subjects with normal cognition (NC) who underwent 3.0-tesla magnetic resonance imaging, [¹8F]-THK5351 positron-emission tomography scans, and detailed neuropsychological tests. The PPA patients additionally participated in extensive neurolinguistic tests. Voxel-wise and region-of-interest-based analyses were performed to analyze [¹8F]-THK5351 retention. RESULTS: The nfvPPA patients exhibited higher [¹8F]-THK5351 retention in the the left inferior frontal and precentral gyri. In svPPA patients, [¹8F]-THK5351 retention was elevated in the anteroinferior and lateral temporal cortices compared to the NC group (left>right). The lvPPA patients exhibited predominant [¹8F]-THK5351 retention in the inferior parietal, lateral temporal, and dorsolateral prefrontal cortices, and the precuneus (left>right). [¹8F]-THK5351 retention in the left inferior frontal area was associated with lower fluency scores. Comprehension was correlated with [¹8F]-THK5351 retention in the left temporal cortices. Repetition was associated with [¹8F]-THK5351 retention in the left inferior parietal and posterior temporal areas, while naming difficulty was correlated with retention in the left fusiform and temporal cortices. CONCLUSIONS: The pattern of [¹8F]-THK5351 retention was well matched with clinical and radiological findings for each PPA subtype, in agreement with the anatomical and functional location of each language domain.

The efficacy of combined estrogen and buspirone treatment in olivopontocerebellar atrophy.

BACKGROUND: Olivopontocerebellar atrophy (OPCA) is a chronic neurodegenerative disease with symptoms of cerebellar ataxia, parkinsonism, autonomic disturbances and ophthalmoplegia. Buspirone, a 5-HT1(A) agonist could constitute a symptomatic improvement in cerebellar dysfunction whereas estrogen has been investigated for neuroprotection. We conducted an open-labeled pilot trial to assess the efficacy of estrogen with buspirone treatment. PATIENTS AND METHODS: Eighteen patients (7 male and 11 female) with OPCA were randomized into the buspirone (15 mg/day, n=9), or the combined treatment group (estrogen, 0.625 mg/d plus buspirone, n=9). For the clinical rating, International Cooperative Ataxia Rating Scale (ICARS) was used and dysarthria, gaze evoked nystagmus, finger to nose, pronation-supination alternating movement, knee-tibia test, and gait speed were evaluated for 12 months. RESULTS: Buspirone-treated group showed improvements in finger to nose and pronation-supination alternating movement test (p=0.046 and p=0.025, respectively). The combination group (Estrogen+buspirone), however, showed no improvement in cerebellar sub-scales compared to the baseline. CONCLUSIONS: Buspirone treatment showed feasible efficacies for OPCA, while the combined treatment of estrogen and buspirone failed to improve, suggesting estrogen may not have further benefit in cerebellar dysfunction.

Neuro-Behcet's disease mimicking multiple brain tumors: diffusion-weighted MR study and literature review.

A 47-year-old man with Behcet's disease presented with a five day history of right side weakness and dysarthria. Ten years ago, he was diagnosed as Behcet's disease. Since then, he was treated with low dose steroids. T1-weighted magnetic resonance images with gadolinium injection revealed ring enhancing lesions with internal hypointensities at the left side of the pons and at the left parietal cortex suggesting multiple metastatic tumors. Diffusion-weighted image and ADC map revealed central hyperintensity on diffusion with low ADC values at both lesions. The histopathology of stereotactic biopsy specimen showed frequent perivascular lymphocytic cuffings, focal necrotic lesions and reactive gliosis. The most common neuropathologic findings in neuro-Behcet's disease are focal necrotic lesions, but the location in cerebral cortex has not been reported before. Long term steroid therapy and antibiotics were administered and the patient recovered gradually. Neuro-Behcet's disease could be presented as brain tumor like lesion, and stereotactic biopsy should be considered in such situation.

The effects of bilateral subthalamic nucleus deep brain stimulation (STN DBS) on cognition in Parkinson disease.

The effects of subthalamic nucleus (STN) stimulation on cognition and mood have not been well established. The authors estimated cognitive and mood effects of bilateral subthalamic nucleus deep brain stimulation (STN DBS) in patients with Parkinson's disease (PD) at 6 months and 1 year postoperatively. Forty-six patients were recruited from the Movement Disorder Center at Seoul National University Hospital. Neuropsychologic tests were performed three times, before, 6 months after, and 1 year after surgery. Mean patient age was 58 and mean education duration 8 years. Eighteen of the 46 patients were men. The instruments used for assessing cognitive functions were; the Mini-Mental Status Examination (MMSE), the Trail Making Test (TMT), the Korean Boston Naming Test (K-BNT), the Rey-Kim Memory Battery, the Grooved pegboard test, the Stroop test, a fluency test, the Wisconsin Card Sorting test (WCST), and the Beck depression inventory (BDI). Of these tests, the verbal memory test, the Stroop test, and the fluency test showed statistically significant changes. The verbal memory test using the Rey-Kim memory battery showed a decline in delayed recall and recognition at 6 months and 1 year postoperatively, whereas nonverbal memory showed no meaningful change. In terms of frontal lobe function tests, Stroop test and fluency test findings were found to be aggravated at 6 months and this continued at 1 year postoperatively. Previous studies have consistently reported a reduction in verbal fluency and improvements in self-reported symptoms of depression after STN DBS. However, in the present study, Beck depression inventory (B.D.I.) was not significantly changed. Other tests, namely, MMSE, TMT, K-BNT, Grooved pegboard test, and the WCST also failed to show significant changes. Of the baseline characteristics, age at onset, number of years in full-time education, and L-dopa equivalent dosage were found to be correlated with a postoperative decline in neuropsychological test results. The correlation of motor improvement and cognitive deterioration was not significant, which suggests that the stimulation effect is rather confined to the motor-related part in the STN. In conclusion, bilateral STN DBS in Parkinson's disease did not lead to a significant global deterioration in cognitive function. However, our findings suggest that it has minor detrimental long-term impacts on memory and frontal lobe function.

Panax ginseng enhances cognitive performance in Alzheimer disease.

Recent experimental evidences suggest protective and trophic effects of ginseng in the memory function of Alzheimer disease (AD). Thus, we investigated the clinical efficacy of Panax ginseng in the cognitive performance of AD patients in an open-label study. Consecutive AD patients were randomly assigned to the ginseng (n=58) or the control group (n=39), and the ginseng group was treated with Panax ginseng powder (4.5 g/d) for 12 weeks. Cognitive performances were monitored using the mini-mental state examination (MMSE) and Alzheimer disease assessment scale (ADAS) during 12 weeks of the ginseng treatment and at 12 weeks after the ginseng discontinuation. MMSE and ADAS scales showed no baseline difference between the groups. After ginseng treatment, the cognitive subscale of ADAS and the MMSE score began to show improvements and continued up to 12 weeks (P=0.029 and P=0.009 vs. baseline, respectively). After discontinuing ginseng, the improved ADAS and MMSE scores declined to the levels of the control group. These results suggest that Panax ginseng is clinically effective in the cognitive performance of AD patients.

Reliability of semiology description.

OBJECTIVE: Seizure semiology is important for classifying patients' epilepsy. Physicians usually get most of the seizure information from observers though there have been few reports on the reliability of the observers' description. This study aims at determining the reliability of observers' description of the semiology. METHODS: We included 92 patients who had their habitual seizures recorded during video-EEG monitoring. We compared the semiology described by the observers with that recorded on the videotape, and reviewed which characteristics of the observers affected the reliability of their reported data. RESULTS: The classification of seizures and the individual components of the semiology based only on the observer-description was somewhat discordant compared with the findings from the videotape (correct classification, 85%). The descriptions of some ictal behaviors such as oroalimentary automatism, tonic/dystonic limb posturing, and head versions were relatively accurate, but those of motionless staring and hand automatism were less accurate. The specified directions by the observers were relatively correct. The accuracy of the description was related to the educational level of the observers. CONCLUSIONS: Much of the information described by well-educated observers is reliable. However, every physician should keep in mind the limitations of this information and use this information cautiously.

18F-THK5351 PET Imaging in Nonfluent-Agrammatic Variant Primary Progressive Aphasia.

BACKGROUND AND PURPOSE: To analyze 18F-THK5351 positron emission tomography (PET) scans of patients with clinically diagnosed nonfluent/agrammatic variant primary progressive aphasia (navPPA). METHODS: Thirty-one participants, including those with Alzheimer's disease (AD, n=13), navPPA (n=3), and those with normal control (NC, n=15) who completed 3 Tesla magnetic resonance imaging, 18F-THK5351 PET scans, and detailed neuropsychological tests, were included. Voxel-based and region of interest (ROI)-based analyses were performed to evaluate retention of 18F-THK5351 in navPPA patients. RESULTS: In ROI-based analysis, patients with navPPA had higher levels of THK retention in the Broca's area, bilateral inferior frontal lobes, bilateral precentral gyri, and bilateral basal ganglia. Patients with navPPA showed higher levels of THK retention in bilateral frontal lobes (mainly left side) compared than NC in voxel-wise analysis. CONCLUSIONS: In our study, THK retention in navPPA patients was mainly distributed at the frontal region which was well correlated with functional-radiological distribution of navPPA. Our results suggest that tau PET imaging could be a supportive tool for diagnosis of navPPA in combination with a clinical history.

Neurological Complications during Treatment of Middle East Respiratory Syndrome.

BACKGROUND AND PURPOSE: Middle East respiratory syndrome (MERS) has a high mortality rate and pandemic potential. However, the neurological manifestations of MERS have rarely been reported since it first emerged in 2012. METHODS: We evaluated four patients with laboratory-confirmed MERS coronavirus (CoV) infections who showed neurological complications during MERS treatment. These 4 patients were from a cohort of 23 patients who were treated at a single designated hospital during the 2015 outbreak in the Republic of Korea. The clinical presentations, laboratory findings, and prognoses are described. RESULTS: Four of the 23 admitted MERS patients reported neurological symptoms during or after MERS-CoV treatment. The potential diagnoses in these four cases included Bickerstaff's encephalitis overlapping with Guillain-Barré syndrome, intensive-care-unit-acquired weakness, or other toxic or infectious neuropathies. Neurological complications did not appear concomitantly with respiratory symptoms, instead being delayed by 2-3 weeks. CONCLUSIONS: Neuromuscular complications are not rare during MERS treatment, and they may have previously been underdiagnosed. Understanding the neurological manifestations is important in an infectious disease such as MERS, because these symptoms are rarely evaluated thoroughly during treatment, and they may interfere with the prognosis or require treatment modification.

Effect of Korean Red Ginseng on Cognitive Function and Quantitative EEG in Patients with Alzheimer's Disease: A Preliminary Study.

BACKGROUND: Korean red ginseng (KRG) has a nootropic effect. This study assessed the efficacy of KRG on cognitive function and quantitative electroencephalography (EEG) in patients with Alzheimer's disease (AD). METHODS: Fourteen patients with AD (mean age, 74.93 years; 11 women and 3 men) were recruited and treated with KRG (4.5 g per day) for 12 weeks. Cognitive function was assessed by the Korean Mini-Mental State Examination (K-MMSE) and the Frontal Assessment Battery (FAB). EEG performed before and after treatment were analyzed with quantitative spectral analysis. RESULTS: The FAB score improved significantly after 12 weeks of treatment. In the relative power spectrum analysis performed according to responsiveness, alpha power increased significantly in the right temporal area of the responders. The increments of relative alpha power in the right temporal, parietal, and occipital areas were significantly higher in the responders than the nonresponders. CONCLUSIONS: This study indicates the efficacy of KRG on frontal lobe function in AD, related to increasing relative alpha power.