Comparison of Two Analytical Platforms in Cerebrospinal Fluid Biomarkers for the Classification of Alzheimer's Disease Spectrum with Amyloid PET Imaging.

BACKGROUND: Cerebrospinal fluid (CSF) amyloid-ß1-42 (Aß1-42), total tau protein (t-Tau), and phosphorylated Tau (p-Tau) are ATN biomarkers for Alzheimer's disease (AD) and reflect pathogenic changes in the brain. CSF biomarkers of AD are considered for inclusion in the diagnostic criteria for research and clinical purposes to reduce the uncertainty of clinical diagnosis and to distinguish among AD stages. OBJECTIVE: This study aims to compare two commercially available analytical platforms with respect to accuracy and the potential for early diagnosis of AD. METHODS: A total of 211 CSF samples from healthy control (HC) and AD subjects were analyzed using two analytical platforms, INNOTEST ELISA and INNOBIA AlzBio3 xMAP kits. The accuracy of diagnosis and AUC values distinguishing study groups were compared between the two analytical platforms. RESULTS: The absolute values for Aß1-42, t-Tau, and p-Tau181 levels differed between the two platforms. The Aß1-42 levels decreased, while t-Tau and p-Tau levels increased according to the AD stages. The AUC of Aß1-42 and t-Tau, which distinguish the early stages of AD (preclinical and prodromal AD), were similar between the two platforms, whereas there were significant differences in p-Tau AUC values. CSF p-Tau using the INNOBIA was highly accurate for distinguishing both preclinical AD (AUC = 0.826, cut-off score≥38.89) and prodromal AD (AUC = 0.862, cut-off score≥41.88) from HC. CONCLUSION: The accuracy of CSF p-Tau levels in the preclinical and prodromal AD is higher for the INNOBIA than the INNOTEST, and the early stage AD can be accurately distinguished from HC.

Cerebrospinal Fluid Biomarkers for the Diagnosis of Prodromal Alzheimer's Disease in Amnestic Mild Cognitive Impairment.

BACKGROUND/AIMS: Disease-modifying therapy for Alzheimer's disease (AD) has led to a need for biomarkers to identify prodromal AD and very early stage of AD dementia. We aimed to identify the cutoff values of cerebrospinal fluid (CSF) biomarkers for detecting prodromal AD. METHODS: We assessed 56 patients with amnestic mild cognitive impairment (aMCI) who underwent lumbar puncture. Additionally, 87 healthy elderly individuals and 34 patients with AD dementia served as controls. Positron emission tomography was performed using florbetaben as a probe. We analyzed the concentration of Aß1-42, total tau protein (t-Tau), and tau protein phosphorylated at threonine 181 (p-Tau181) in CSF with INNOTEST enzyme-linked immunosorbent assay. RESULTS: For the detection of prodromal AD in patients with aMCI, the cutoff values of CSF Aß1-42, t-Tau, and p-Tau181 were 749.5 pg/mL, 225.6 pg/mL, and 43.5 pg/mL, respectively. To discriminate prodromal AD in patients with aMCI, the t-Tau/Aß1-42 and -p-Tau181/Aß1-42 ratios defined cutoff values at 0.298 and 0.059, respectively. CONCLUSIONS: CSF biomarkers are very useful tools for the differential diagnosis of prodromal AD in aMCI patients. The concentration of CSF biomarkers is well correlated with the stages of the AD spectrum.

Histologic features of acute thrombi retrieved from stroke patients during mechanical reperfusion therapy.

BACKGROUND: The histologic features of thrombus may differ according to the stroke subtypes. However, in acute reperfusion therapy, fibrin-specific thrombolytics are used based on the assumption that all thrombi are alike. AIMS: The histologic characteristics of thrombi were compared between patients with different stroke etiologies. METHODS: Between April 2010 and March 2012, we analyzed thrombi retrieved from acute stroke patients during mechanical thrombectomy. All thrombi were analyzed using component-specific stains such as Martius scarlet blue for fibrins and immunostaining with CD42b antibody for platelets. The stroke subtypes were determined based on the Trial of ORG 10172 in Acute Stroke Treatment classification. RESULTS: Among 36 patients, 22 were diagnosed with cardioembolism, 8 with atherothrombosis, and 6 with undetermined etiology. In arteriogenic thrombi, red blood cells were most abundant (56.9 ± 12.2%), and the platelets covered the fibrin layers or were localized at the edge or periphery of the thrombus. In cardiogenic thrombi, fibrin was most abundant (39.5 ± 13.5%), and platelets were clustered within the rich fibrin. Red blood cells proportion was greater in arteriogenic thrombi than in cardiogenic thrombi (p < 0.001), whereas fibrin proportion was greater in cardiogenic thrombi than in arteriogenic thrombi (p = 0.003). Of six patients with undetermined etiology, the thrombi in five showed histologic features and composition similar to that of cardiogenic thrombi. CONCLUSIONS: Acute thrombi showed different histologic features according to the stroke etiology. The distribution of platelets and proportion of red blood cells and fibrin were major distinguishing factors between stroke subtypes.

Interaction between Sleep-Disordered Breathing and Acute Ischemic Stroke.

BACKGROUND AND PURPOSE: Sleep-disordered breathing (SDB) is suggested to be strongly associated with ischemic strokes. Risk factors, stroke subtypes, stroke lesion distribution, and the outcome of SDB in stroke patients remain unclear in Korea. METHODS: We prospectively studied 293 patients (159 men, 134 women; age 68.4±10.5) with acute ischemic stroke. Cardiovascular risk factors, stroke severity, sleep-related stroke onset, distribution of stroke lesions, and 3-month score on the modified Rankin Scale (mRS) were assessed. Stroke severity was assessed by the US National Institutes of Health Stroke Scale (NIHSS) and the mRS. The apnea-hypopnea index (AHI) was determined 6.3±2.2 days after stroke onset with the Apnea Link portable sleep apnea monitoring device. RESULTS: The prevalence of SDB (defined as an AHI of ≥10) was 63.1% (111 men, 74 women). Those in the SDB group were older, had higher NIHSS and mRS scores, greater bulbar weakness, and a higher incidence of sleep-associated stroke onset. Among risk-factor profiles, alcohol consumption and atrial fibrillation were significantly related to SDB. The stroke outcome was worse in patients with SDB than in those without SDB. The lesion location and specific stroke syndrome were not correlated with SDB. CONCLUSIONS: SDB is very common in acute cerebral infarction. Different risk-factor profiles and sleep-related stroke onsets suggest SDB as a cause of ischemic stroke. The higher NIHSS score and greater bulbar involvement in the SDB group seem to show the influence of ischemic stroke on the increased SDB prevalence.

Marital status of people with epilepsy in Korea.

A multicentre face-to-face interview was conducted to identify factors contributing to the marital status of people with epilepsy (PWE) in Korea. The marriage rate of PWEs was only 80% and the divorce rate was more than double that in the general population. Among the single subjects, 34% replied that they were unmarried because of epilepsy, and 76% of divorced PWEs replied that epilepsy was the cause of the divorce. The factors affecting the single and divorced status in PWEs included gender, an earlier onset of seizure and seizure onset before marriage. Not informing the spouse of the disease before marriage for fear of discrimination was not related to disadvantage in marriage negotiation or to divorce. Social stigmatization of epilepsy continues and impacts on the marital status of PWEs in Korea. However, there is no correlation between the perceived and the enacted stigmas of epilepsy.

Arteriovenous malformation with an occlusive feeding artery coexisting with unilateral moyamoya disease.

BACKGROUND: Arteriovenous malformations (AVMs) with vascular abnormalities, including aneurysms, have been reported frequently. However, the coexistence of AVM and unilateral moyamoya disease is rare. We report herein an AVM patient who presented with acute ischemic stroke with unilateral moyamoya disease and occlusion of the feeding artery. CASE REPORT: A-41-year old man was admitted with sudden dysarthria and facial palsy. Brain computed tomography and magnetic resonance imaging revealed an acute infarction adjacent to a large AVM in the right frontal lobe. Cerebral angiography revealed occlusions of the proximal right middle cerebral and proximal anterior cerebral arteries, which were the main feeders of the AVM. Innumerable telangiectatic moyamoya-type vessels between branches of the anterior cerebral artery and dilated lenticulostriate arteries on the occluded middle cerebral artery were detected. However, a nidus of the AVM was still opacified through the distal right callosomarginal artery, which was supplied by the remaining anterior cerebral artery and leptomeningeal collaterals from the posterior cerebral artery. CONCLUSIONS: While AVM accompanied by unilateral moyamoya disease is rare, our case suggests an association between these two dissimilar vascular diseases.

Nitric oxide modulation of the spontaneous firing of rat medial vestibular nuclear neurons.

Modulation of the spontaneous activity of rat medial vestibular nuclear neurons by nitric oxide was investigated using the whole-cell patch-clamp technique. The spike frequency was increased by sodium nitroprusside (SNP), a nitric oxide liberating agent, and it was also increased by another nitric oxide liberating agent, sodium-nitroso-N-acetylpenicillamine. L-Arginine, the substrate of nitric oxide synthase, increased the firing of the neurons. The increased SNP-induced firing was inhibited by 1H-[1,2,4]oxadiazolo[4,3-a]quinozalin-1-one (ODQ), a specific inhibitor of guanylate cyclase. These results suggest that nitric oxide increases the neuronal excitability of the neurons by a cGMP-dependent mechanism.