Miller-Fisher Syndrome With Initial Manifestation of Rhinolalia Aperta: A Case Report and Literature Review.

Rhinolalia aperta (hypernasal speech) is rarely reported in patients with Miller-Fisher syndrome (MFS). Here, we report a patient with MFS who presented with rhinolalia aperta. A 35-year-old man with a history of alcohol abuse and hepatic cirrhosis presented with a three-day acute hypernasal voice change and numbness of both hands/thighs. After admission, the exam also revealed palatal hypomobility, decreased bilateral hand/thigh sensation, ataxic gait, dysmetria, areflexia, and bilateral abducens palsy. Serum immunoglobulin G (IgG) anti-GQ1b antibody titer was elevated (1:6400). A five-day intravenous IgG was administered with a robust clinical response. Oropharyngeal involvement in MFS can initially manifest with isolated hypernasal speech.

Cholecystokinin attenuates ß-cell apoptosis in both mouse and human islets.

Loss of functional pancreatic ß-cell mass and increased ß-cell apoptosis are fundamental to the pathophysiology of type 1 and type 2 diabetes. Pancreatic islet transplantation has the potential to cure type 1 diabetes but is often ineffective due to the death of the islet graft within the first few years after transplant. Therapeutic strategies to directly target pancreatic ß-cell survival are needed to prevent and treat diabetes and to improve islet transplant outcomes. Reducing ß-cell apoptosis is also a therapeutic strategy for type 2 diabetes. Cholecystokinin (CCK) is a peptide hormone typically produced in the gut after food intake, with positive effects on obesity and glucose metabolism in mouse models and human subjects. We have previously shown that pancreatic islets also produce CCK. The production of CCK within the islet promotes ß-cell survival in rodent models of diabetes and aging. We demonstrate a direct effect of CCK to reduce cytokine-mediated apoptosis in a ß-cell line and in isolated mouse islets in a receptor-dependent manner. However, whether CCK can protect human ß-cells was previously unknown. Here, we report that CCK can also reduce cytokine-mediated apoptosis in isolated human islets and CCK treatment in vivo decreases ß-cell apoptosis in human islets transplanted into the kidney capsule of diabetic NOD/SCID mice. Collectively, these data identify CCK as a novel therapy that can directly promote ß-cell survival in human islets and has therapeutic potential to preserve ß-cell mass in diabetes and as an adjunct therapy after transplant.

Survey on Acceptance of Passive Technology Monitoring for Early Detection of Cognitive Impairment.

INTRODUCTION: Digital biomarkers may act as a tool for early detection of changes in cognition. It is important to understand public perception of technologies focused on monitoring cognition to better guide the design of these tools and inform patients appropriately about the associated risks and benefits. Health care systems may also play a role in the clinical, legal, and financial implications of such technologies. OBJECTIVE: To evaluate public opinion on the use of passive technology for monitoring cognition. METHODS: This was a one-time, Internet-based survey conducted in English and Spanish. RESULTS: Within the English survey distributed in the USA (n = 173), 58.1% of respondents would be highly likely to agree to passive monitoring of cognition via a smartphone application. Thirty-eight percent of those with a higher degree of experience with technology were likely to agree to monitoring versus 20% of those with less experience with technology (p = 0.003). Sixty-two percent of non-health-care professionals were likely to agree to monitoring versus 45% of health-care workers (p = 0.012). There were significant concerns regarding privacy (p < 0.01). We compared the surveys answered in Spanish in Costa Rica via logistic regression (n = 43, total n = 216), adjusting for age, education level, health-care profession, owning a smartphone, experience with technology, and perception of cognitive decline. Costa Rican/Spanish-speaking respondents were 7 times more likely to select a high probability of agreeing to such a technology (p < 0.01). English-speaking respondents from the USA were 5 times more likely to be concerned about the impact on health insurance (p = 0.001) and life insurance (p = 0.01). CONCLUSIONS: Understanding public perception and ethical implications should guide the design of digital biomarkers for cognition. Privacy and the health-care system in which the participants take part are 2 major factors to be considered. It is the responsibility of researchers to convey the ethical and legal implications of cognition monitoring.

Cytomorphologic features of small cell carcinoma of lung in effusion fluid using a liquid-based cytology technique.

BACKGROUND: Liquid-based cytology (LBC) testing induces morphologic changes due to the use of specific fixatives and preparation techniques, and the cytologies of effusions determined in this manner differ morphologically from those of conventional cytopreparation (CCP) smear methods. We compared the cytologic features of pulmonary small cell carcinoma in effusion fluid using CCP and LBC preparations. METHODS: Fifty-three malignant effusion specimens from 36 patients with small cell carcinoma were examined, including 41 LBCs from 27 patients and 12 CCPs from 9 patients. RESULTS: LBC and CCP preparations preserved the typical features of small cell carcinoma, that is, nuclear molding, very high nuclear to cytoplasmic ratio and granular chromatin. The architectural patterns involved small cohesive clusters and chains with nuclear molding, tight three-dimensional clusters, or single cell dispersion were preserved in both preparations. Oval nuclei (83.3% vs 26.8%, P < .001) and a discernable rim of cytoplasm (66.7% vs 26.8%, P = .043) were more frequently identified in CCPs, whereas cellular degeneration and dry artifact were more frequent in LBC preparations (73.2% vs 8.3%, P < .001). LBC had a tendency to show frequent nuclear size variation (51.2% vs 25.0%) than CCP. CONCLUSION: LBC tends to show more degeneration and dry artifact with exaggerated irregular nuclear shape and nuclear size variation and scanty cytoplasm than CCP. Cytopathologists should be familiar with the cytomorphologic spectrum of this tumor in CCP and LBC prepared effusions.

Cholinesterase Inhibitors May Not Benefit Mild Cognitive Impairment and Mild Alzheimer Disease Dementia.

INTRODUCTION: We investigated whether cholinesterase inhibitors (ChEIs) benefit cognitive outcomes in mild cognitive impairment due to Alzheimer disease (MCI-AD) and in mild AD dementia (ADdem). METHODS: Data from 2242 individuals, clinically diagnosed with MCI-AD [Clinical Dementia Rating (CDR), 0 or 0.5] or with mild ADdem (CDR, 0.5 or 1), were available from the National Alzheimer's Coordinating Center's (NACC) Uniform Data Set (UDS). General linear mixed models were used to examine the annual change in the CDR Sum of Boxes (CDR-SB) and in neuropsychological performance. We compared slopes before and after ChEI initiation among ChEI users, and also compared the change in scores of ChEI users versus nonusers. RESULTS: Thirty-four percent of 944 MCI-AD and 72% of 1298 ADdem participants were ChEI users. Cognitive decline was greater after ChEI initiation in MCI-AD and ADdem groups (eg, MCI-AD, CDR-SB: 0.03 points/y before initiation; 0.61 points/y after initiation, P<0.0001). Both MCI-AD and ADdem groups had faster decline after ChEI initiation than nonusers (eg, MCI-AD, CDR-SB: 0.61 points/y, ChEI users; 0.24 points/y, nonusers, P<0.0001). DISCUSSION: This study suggests that ChEI use may not improve the cognitive course in MCI-AD and mild ADdem.

Oligomeric forms of amyloid-ß protein in plasma as a potential blood-based biomarker for Alzheimer's disease.

BACKGROUND: Soluble amyloid-ß (Aß) oligomers are the major toxic substances associated with the pathology of Alzheimer's disease (AD). The ability to measure Aß oligomer levels in the blood would provide simple and minimally invasive tools for AD diagnostics. In the present study, the recently developed Multimer Detection System (MDS) for AD, a new enzyme-linked immunosorbent assay for measuring Aß oligomers selectively, was used to detect Aß oligomers in the plasma of patients with AD and healthy control individuals. METHODS: Twenty-four patients with AD and 37 cognitively normal control individuals underwent extensive clinical evaluations as follows: blood sampling; detailed neuropsychological tests; brain magnetic resonance imaging; cerebrospinal fluid (CSF) measurement of Aß42, phosphorylated tau protein (pTau), and total tau protein (tTau); and 11C-Pittsburgh compound B (PIB) positron emission tomography. Pearson's correlation analyses between the estimations of Aß oligomer levels by MDS and other conventional AD biomarkers (CSF Aß42, pTau, and tTau, as well as PIB standardized uptake value ratio [PIB SUVR]) were conducted. ROC analyses were used to compare the diagnostic performance of each biomarker. RESULTS: The plasma levels of Aß oligomers by MDS were higher in patients with AD than in normal control individuals, and they correlated well with conventional AD biomarkers (levels of Aß oligomers by MDS vs. CSF Aß42, r = -0.443; PIB SUVR, r = 0.430; CSF pTau, r = 0.530; CSF tTau, r = 0.604). The sensitivity and specificity of detecting plasma Aß oligomers by MDS for differentiating AD from the normal controls were 78.3% and 86.5%, respectively. The AUC for plasma Aß oligomers by MDS was 0.844, which was not significantly different from the AUC of other biomarkers (p = 0.250). CONCLUSIONS: Plasma levels of Aß oligomers could be assessed using MDS, which might be a simple, noninvasive, and accessible assay for evaluating brain amyloid deposition related to AD pathology.

Thyroid Fine-Needle Aspiration Cytology Practice in Korea.

We reviewed the current status of thyroid fine-needle aspiration cytology (FNAC) in Korea. Thyroid aspiration biopsy was first introduced in Korea in 1977. Currently, radiologists aspirate the thyroid nodule under the guidance of ultrasonography, and cytologic interpretation is only legally approved when a cytopathologist makes the diagnosis. In 2008, eight thyroid-related societies came together to form the Korean Thyroid Association. The Korean Society for Cytopathology and the endocrine pathology study group of the Korean Society for Pathologists have been updating the cytologic diagnostic guidelines. The Bethesda System for Reporting Thyroid Cytopathology was first introduced in 2009, and has been used by up to 94% of institutions by 2016. The average diagnosis rates are as follows for each category: I (12.4%), II (57.9%), III (10.4%), IV (2.9%), V (3.7%), and VI (12.7%). The malignancy rates in surgical cases are as follows for each category: I (28.7%), II (27.8%), III (50.6%), IV (52.3%), V (90.7%), and VI (100.0%). Liquid-based cytology has been used since 2010, and it was utilized by 68% of institutions in 2016. The categorization of thyroid lesions into "atypia of undetermined significance" or "follicular lesion of undetermined significance" is necessary to draw consensus in our society. Immunocytochemistry for galectin-3 and BRAF is used. Additionally, a molecular test for BRAF in thyroid FNACs is actively used. Core biopsies were performed in only 44% of institutions. Even the institutions that perform core biopsies only perform them for less than 3% of all FNACs. However, only 5% of institutions performed core biopsies up to three times more than FNAC.

Supernumerary phantom limb in a patient with basal ganglia hemorrhage - a case report and review of the literature.

BACKGROUND: Supernumerary phantom limb (SPL) is a rare neurologic phenomenon, in which a patient misperceives an extra limb in addition to the original set of limbs. We report a case of SPL in a patient with a right basal ganglia hemorrhage and review the previous literature about this peculiar phenomenon. CASE PRESENTATION: Two days after the event of a right basal ganglia hemorrhage, a 78-year-old male reported a phantom arm protruding from his left shoulder. He could not see or touch the phantom arm but he felt the presence of an addition arm lateral to his paretic arm. Pain or sensory discomfort were absent in either the paretic arm or the phantom arm. He stated that he could intentionally move the phantom arm independent of his paretic arm. The examination showed that the passive movement of his paretic arm did not elicit any movement of his phantom arm. We diagnosed the SPL as a complication of the hypertensive basal ganglia hemorrhage and treated him with anti-hypertensive medications. His phantom arm persisted for 3 weeks, and it gradually faded away. CONCLUSION: SPL had been reported as a rare complication of various types of cerebral lesions. Right hemispheric lesions were most frequently associated with the SPL. Considering the intentional movement of the phantom arm, we deduced that the SPL might result from the impairment of the sensory feedback system for both internal body image and motor movement.

Validation of the Korean Version of the Lewy Body Composite Risk Score (K-LBCRS).

The Lewy body composite risk score (LBCRS) is a useful clinical screening tool to help determine whether the dementia is related to Lewy body pathology. The purpose of this study is to verify reliability, validity, and diagnostic usefulness of Korean version of LBCRS (K-LBCRS). CDR-sum of boxes, Mini-Mental State Examination, and standardized scales related to cognition, mood, behavior, and motor function were administered to a total of 107 subjects, including 30 dementia with Lewy bodies (DLB), 54 Alzheimer's disease (AD), and 23 cognitively normal elderly people and their collateral informants. Internal consistency of the K-LBCRS was good with Cronbach's alpha of 0.85, and concurrent validity was also satisfactory, with K-LBCRS correlating highly with CDR-SB and other scales. The test-retest reliability was very high with a Pearson correlation coefficient of 0.97. The mean scores of K-LBCRS were significantly different among three groups, with DLB (6.2±2.4), AD (1.4±1.3), and controls (0.3±0.6). We identified a cut-off score of 3 as best to differentiate between DLB and AD, having AUC of 0.97 (95% CI 0.94-1.00), sensitivity 97%, specificity 83%, positive predictive value 76%, negative predictive value 98%, which is the same score suggested in the original study. This study shows K-LBCRS as a new useful screening tool for Korean DLB patients in clinical settings.

Analysis of Cerebrospinal Fluid and [11C]PIB PET Biomarkers for Alzheimer's Disease with Updated Protocols.

BACKGROUND: Recently, a Korean research group suggested a consensus protocol, based on the Alzheimer's Disease Neuroimaging Initiative study protocol but with modifications for minimizing the confounding factors, for the evaluation of cerebrospinal fluid (CSF) biomarkers. OBJECTIVE: Here, we analyzed fluid and imaging biomarkers of Alzheimer's disease (AD) in Korean population. We used the updated protocol to propose a more accurate CSF biomarker value for the diagnosis of AD. METHODS: Twenty-seven patients with AD and 30 cognitively normal controls (NC) were enrolled. CSF was collected from 55 subjects (patients with AD = 26, NC = 29) following the Korea consensus protocol. CSF biomarkers were measured using the INNO-BIA AlzBio3 immunoassay, and Pittsburgh compound B (PIB) positron emission tomography (PET) scans were also performed. RESULTS: The cutoff values of CSF amyloid beta 1-42 (Aß42), total tau (t-Tau), and phosphorylated tau (p-Tau) proteins were 357.1 pg/ml, 83.35 pg/ml, and 38.00 pg/ml, respectively. The cutoff values of CSF t-Tau/Aß42 and p-Tau/Aß42 ratio- were 0.210 (sensitivity 100%, specificity 86.21%) and 0.1350 (sensitivity 88.46%, specificity of 92.86%). The concordance rate with PIB-PET was higher using the CSF t-Tau/Aß42 ratio (κ= 0.849, CI 0.71-0.99) than CSF Aß42 alone (κ= 0.703, CI 0.51-0.89). CONCLUSIONS: Here, we improved controversial factors associated with the previous CSF study protocol and suggested a new cutoff value for the diagnosis of AD. Our results showed good diagnostic performance for differentiation of AD. Thus, we expect our findings could be a cornerstone in the establishment and clinical application of biomarkers for AD diagnosis.

Early onset of puberty in an obese boy with Klinefelter syndrome.

Klinefelter syndrome (KS) is one of the most common disease entities characterized by X-chromosomal aberration causing the primary hypogonadism in adult men. Patients with KS seem to be typically characterized by tall, slender bodies with delayed puberty and hypergonadotropic hypogonadism. However, it has been known that they have a broad spectrum of phenotype ranging from almost normal external appearances to typical phenotype. Only 25% KS Patients are ever diagnosed because KS remains unrecognized. Also, boys with KS have an onset of pubertal development within the normal range, not delayed onset of puberty. Adolescents with KS are generally diagnosed as having the lack of pubertal progress. Early detection of KS can be difficult without awareness. We report an unusual case of early onset of puberty in obese boy with KS who presented with a unilateral non-hormone secreting testicular teratoma.

Brain Atrophy of Secondary REM-Sleep Behavior Disorder in Neurodegenerative Disease.

BACKGROUND: Rapid eye movement sleep behavior disorder (RBD) may present as an early manifestation of an evolving neurodegenerative disorder with alpha-synucleinopathy. OBJECTIVE: We investigated that dementia with RBD might show distinctive cortical atrophic patterns. METHODS: A total of 31 patients with idiopathic Parkinson's disease (IPD), 23 with clinically probable Alzheimer's disease (AD), and 36 healthy controls participated in this study. Patients with AD and IPD were divided into two groups according to results of polysomnography and rated with a validated Korean version of the RBD screening questionnaire (RBDSQ-K), which covers the clinical features of RBD. Voxel-based morphometry was adapted for detection of regional brain atrophy among groups of subjects. RESULTS: Scores on RBDSQ-K were higher in the IPD group (3.54 ± 2.8) than in any other group (AD, 2.94 ± 2.4; healthy controls, 2.31 ± 1.9). Atrophic changes according to RBDSQ-K scores were characteristically in the posterior part of the brain and brain stem, including the hypothalamus and posterior temporal region including the hippocampus and bilateral occipital lobe. AD patients with RBD showed more specialized atrophic patterns distributed in the posterior and inferior parts of the brain including the bilateral temporal and occipital cortices compared to groups without RBD. The IPD group with RBD showed right temporal cortical atrophic changes. CONCLUSION: The group of patients with neurodegenerative diseases and RBD showed distinctive brain atrophy patterns, especially in the posterior and inferior cortices. These results suggest that patients diagnosed with clinically probable AD or IPD might have mixed pathologies including α-synucleinopathy.

Neuro-Behçet's Disease Presenting as Hypertrophic Pachymeningitis.

A 25-year-old man presented with blurred vision and chronic headache. His brain MRI revealed bilateral frontal pachymeningeal enhancement with leptomeningeal enhancement. The patient had experienced recurrent oral ulcer and had anterior uveitis and papulopustules skin lesion. We diagnosed him with hypertrophic pachymeningitis (HP) associated with neuro-Behçet's disease (NBD). There have been few reports describing HP in patients with NBD. We report a case of NBD presenting as HP.

Fusion protein of retinol-binding protein and albumin domain III reduces liver fibrosis.

Activated hepatic stellate cells (HSCs) play a key role in liver fibrosis, and inactivating HSCs has been considered a promising therapeutic approach. We previously showed that albumin and its derivative designed for stellate cell-targeting, retinol-binding protein-albumin domain III fusion protein (referred to as R-III), inactivate cultured HSCs. Here, we investigated the mechanism of action of albumin/R-III in HSCs and examined the anti-fibrotic potential of R-III in vivo. R-III treatment and albumin expression downregulated retinoic acid (RA) signaling which was involved in HSC activation. RA receptor agonist and retinaldehyde dehydrogenase overexpression abolished the anti-fibrotic effect of R-III and albumin, respectively. R-III uptake into cultured HSCs was significantly decreased by siRNA-STRA6, and injected R-III was localized predominantly in HSCs in liver. Importantly, R-III administration reduced CCl4- and bile duct ligation-induced liver fibrosis. R-III also exhibited a preventive effect against CCl4-inducd liver fibrosis. These findings suggest that the anti-fibrotic effect of albumin/R-III is, at least in part, mediated by downregulation of RA signaling and that R-III is a good candidate as a novel anti-fibrotic drug.

Primary prevention of Alzheimer's disease: is it an attainable goal?

Alzheimer's disease (AD) is the leading cause of dementia, and the most prevalent neurodegenerative disease in the elderly. The prevalence of AD is predicted to rise as life expectancy grows across populations. The exact cause of this devastating disease is still unknown; however, it is an aging-related multi-factorial disorder, and growing evidence supports the contribution of modifiable environmental factors to unmodifiable factors such as gene and ageing itself. The recent advancement of methodologies and techniques for early diagnosis of AD facilitates the investigation of strategies to reduce the risk for AD progression in the earliest stages of the disease. Pharmacological attempts at curing, halting or modifying it have, by and large, been unsuccessful, and no breakthrough is seen in the near future. However, a lot of elements that seem to contribute to the disease such as risk factors have been identified, mainly from epidemiological and basic research studies. Many of these are amenable to lifestyle modification. Therefore, prevention in the preclinical stage is likely the most effective way to decrease the incidence of this age-associated dreadful neurodegenerative condition, and its associated burden for individuals and society. We provide an overview of modifiable risk factors for AD along with the supporting evidence.

A case report of testicular sparganosis misdiagnosed as testicular tumor.

Sparganosis is a parasitic infestation of human by plerocercoid larvae. Sparganum is usually reported to be found in the subcutaneous tissues as well as other organs, including scrotum. However, testicular sparganosis is extremely rare, because of strong capsule of tunica albuginea. An urban-living 54-yr-old Korean man presented with left scrotal pain for 6 yr. Both testes look normal physically. Ultrasonography revealed poorly defined, heterogeneous mass with increased echogenicity in the left testis. This case was misdiagnosed as testicular tumor and underwent orchiectomy, but was diagnosed as testicular sparganosis by histopathology. Sparganosis should be included for differential diagnosis of testis tumor in countries where sparganosis is prevalent.

Adult onset Leigh syndrome with mitochondrial DNA 8344 A>G mutation.

We report a pedigree of adult-onset Leigh syndrome (LS) with mitochondrial mutation 8344 A>G. A 38-year-old woman presented with optic neuropathy, weakness and cognitive impairment. Family history of optic neuropathy and systemic involvement was suggestive of mitochondrial encephalopathy. Genetic and radiologic studies showed m.8344 A>G mutation with characteristics of LS. To our knowledge this is the first case of adult-onset LS demonstrating the m.8344 A>G mutation.