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.

Usefulness of medial temporal lobe atrophy visual rating scale in detecting Alzheimer's disease: Preliminary study.

BACKGROUND: The Korean version of Mini-Mental Status Examination (K-MMSE) and the Korean version of Addenbrooke Cognitive Examination (K-ACE) have been validated as quick neuropsychological tests for screening dementia in various clinical settings. Medial temporal atrophy (MTA) is an early pathological characteristic of Alzheimer's disease (AD). We aimed to assess the diagnostic validity of the fusion of the neuropsychological test and visual rating scale (VRS) of MTA in AD. MATERIALS AND METHODS: A total of fifty subjects (25 AD, 25 controls) were included. The neuropsychological tests used were the K-MMSE and the K-ACE. T1 axial imaging visual rating scale (VRS) was applied for assessing the grade of MTA. We calculated the fusion score with the difference of neuropsychological test and VRS of MTA. The receiver operating characteristics (ROC) curve was used to determine optimal cut-off score, sensitivity and specificity of the fusion scores in screening AD. RESULTS: No significant differences in age, gender and education were found between AD and control group. The values of K-MMSE, K-ACE, CDR, VRS and cognitive function test minus VRS were significantly lower in the AD group than control group. The AUC (Area under the curve), sensitivity and specificity for K-MMSE minus VRS were 0.857, 84% and 80% and for K-ACE minus VRS were 0.884, 80% and 88%, respectively. Those for K-MMSE only were 0.842, 76% and 72% and for K-ACE only were 0.868, 80% and 88%, respectively. CONCLUSIONS: The fusion of the neuropsychological test and VRS suggested clinical usefulness in their easy and superiority over neuropsychological test only. However, this study failed to find any difference. This may be because of small numbers in the study or because there is no true difference.

Validation of the Korean Addenbrooke's Cognitive Examination for diagnosing Alzheimer's dementia and mild cognitive impairment in the Korean elderly.

The Addenbrooke's Cognitive Examination (ACE) is a valid dementia-screening test that is a simple and effective instrument. We aimed to assess the diagnostic accuracy of the Korean version of the ACE (K-ACE) in a Korean population. A total of 115 subjects (50 with Alzheimer's dementia [AD], 26 with mild cognitive impairment [MCI], and 39 controls) who visited the Neurology Outpatient Clinic of Seoul Medical Center were included. The ACE was translated and modified to create the K-ACE. The sensitivity, specificity, area under the curve, reliability, and Verbal-Language/Orientation-Memory ratio were evaluated. The receiver-operating characteristic (ROC) curve was used to determine the optimal cutoff score in screening for dementia. The ROC curves showed the superiority of the K-ACE over the Korean Mini-Mental Status Examination in the diagnosis of AD and MCI. The optimal cutoff of the K-ACE for the identification of AD was 68/69, which had a sensitivity of 90% and a specificity of 84%. The K-ACE is a short, reliable, and valid neuropsychological test battery used to screen for dementia in the Korean elderly.

Testosterone relaxes rabbit seminal vesicle by calcium channel inhibition.

Recent studies have documented that testosterone relaxes several smooth muscles by modulating K(+) channel activities. Smooth muscles of seminal vesicles play a fundamental role in ejaculation, which might involve testosterone. This study was aimed to assess the role of testosterone in seminal vesicular motility by studying its effects on contractile agents and on the ion channels of single vesicular myocytes in a rabbit model. The contractile responses of circular smooth muscle strips of rabbit seminal vesicles to norepinephrine (10 microM), a high concentration of KCl (70 mM), and testosterone (10 microM) were observed. Single vesicular myocytes of rabbit were isolated using proteolytic enzymes including collagenase and papain. Inside-out, attached, and whole-cell configurations were examined using the patch clamp technique. The applications of 10 microM norepinephrine or 70 mM KCl induced tonic contractions, and 10 microM testosterone (pharmacological concentration) evoked dose-dependent relaxations of these precontracted strips. Various K(+) channel blockers, such as tetraethylammonium (TEA; 10 mM), iberiotoxin (0.1 microM), 4-aminopyridine (4-AP, 10 microM), or glibenclamide (10 microM) rarely affected these relaxations. Single channel data (of inside-out and attached configurations) of BK channel activity were also hardly affected by testosterone (10 microM). On the other hand, however, testosterone reduced L-type Ca(2+) currents significantly, and found to induce acute relaxation of seminal vesicular smooth muscle and this was mediated, at least in part, by Ca(2+) current inhibition in rabbit.

Heat shock protein 70 alters the endosome-lysosomal localization of huntingtin.

Huntington's disease is caused by CAG trinucleotide expansions in the gene encoding huntingtin. N- terminal fragments of huntingtin with polyglutamine produce aggregates in the endosome-lysosomal system, where proteolytic fragments of huntingtin is generated. Heat shock protein 70 (HSP70) prevents the formation of protein aggregates, but the effect of HSP70 on the huntingtin in the endosome-lysosomal system is unknown. This study was to determine whether HSP70 alters the distribution of huntingtin in endosome-lysosomal system. HSP70 expressing stable cells (NIH/3T3 or cerebral hybrid cell line A1) were generated, and mutant [(CAG)(100)] huntingtin was transiently overexpressed. Analysis of subcellular distribution by immunocytochemistry or proteolysis cleavage by Western blotting was performed. 18 CAG repeat wild type [WT; (CAG)(18)] huntingtin was used as a control. Cells with huntingtin showed patterns of endosome-lysosomal accumulation, from a "dispersed vacuole (DV)" type into a coalescent "perinuclear vacuole (PV)" type over time. In WT huntingtin, HSP70 increased the cells with the PV types that enhanced the proteolytic cleavage of huntingtin. However, HSP70 reduced cells of the DV and PV types expressing mutant huntingtin, that result in less proteolysis than that of control. In addition, intranuclear inclusions were formed only in mutant cells, which was not affected by HSP70. These results suggest that HSP70 alters the distribution of huntingtin in the endosome- lysosomal system, and that this contributes to huntingtin proteolysis.