Correlation between body composition and white matter hyperintensity in patients with acute ischemic stroke.

White matter hyperintensity (WMH) burden is associated with a higher risk of ischemic stroke. The relationship between WMH and obesity is somewhat controversial which might be interfered by different body composition such as skeletal muscle, fat and bone density. However, few researchers have evaluated the relationship between WMH burden and disaggregated body constituents in acute ischemic stroke (AIS) patients systematically. A total of 352 AIS patients were enrolled in this study. The subcutaneous adipose tissue, erector spinae muscle area and bone density were evaluated on the computed tomography scanning. The burden of WMH was evaluated using the Fazekas scale based on the fluid-attenuated inversion recovery sequence. The severity of overall WMH was defined as none-mild WMH (total Fazekas score 0-2) or moderate-severe WMH (total Fazekas score 3-6). Based on the severity of periventricular WMH (P-WMH) and deep WMH, patients were categorized into either a none-mild (Fazekas score 0-1) group or a moderate-severe (Fazekas score 2-3) group. We found that patients with moderate-severe WMH showed lower bone density and smaller erector spinae muscle area and subcutaneous adipose tissue than none-mild. The logistic regression analysis showed that the bone density was independently associated with moderate-severe overall WMH (odds radio = 0.98, 95% confidence interval, 0.972-0.992, P < .001) and similar results were found in the analyses according to P-WMH (odds radio = 0.98, 95% confidence interval, 0.972-0.992, P < .001). These findings suggest that among the AIS body composition, the bone density is independently associated with the severity of overall WMH and P-WMH.

Variability of blood pressure response to orthostatism and reproducibility of orthostatic hypotension in hospitalized patients with acute ischemic stroke.

OBJECTIVE: Orthostatic hypotension (OH) which diagnosis is based on the measurement of the blood pressure response to orthostatism (BPRO) is a common condition associated with adverse cerebrovascular and cognitive prognosis. It is likely that the single measurement might underestimate the true prevalence of OH. This study investigated the prevalence and reproducibility of the diagnosis of OH and related risk factors in hospitalized acute ischemic stroke (AIS) patients with multiple measurements. MATERIALS AND METHODS: This study was a prospective cohort analysis of consecutive AIS patients admitted to the hospital. A total of 211 patients were included. BPRO was assessed five times at the same time on different days. RESULTS: OH was found in 33 cases (15.6%) in the initial set of measurements of the first day. A cumulative diagnosis of OH after five BPRO tests was found in 75 cases (35.5%). The reproducibility of the diagnosis of OH was mild or poor. In patients with a cumulative diagnosis of OH, 29 (38.7%) patients had orthostatic hypertension (OHTN). In multivariate analysis, the Fazekas scale (odds radio = 1.28, 95% confidence interval (CI), 1.04-1.59, P = 0.023) and extracranial carotid stenosis (≥70%) (odds radio = 3.64, 95% CI, 1.19-11.13, P = 0.023) were independent risk factors for OH. CONCLUSION: The reproducibility of OH is poor and the concurrent appearance of OH and OHTN is common in hospitalized AIS patients. Multiple measurements should be taken in hospitalized AIS patients when screening for OH especially patients with higher Fazekas scale and extracranial carotid stenosis (≥70%).

Hemicranial postural headache as a first symptom of a spontaneous carotid cavernous fistula: A case report.

RATIONALE: Spontaneous carotid cavernous fistula (CCF) is rare, and the expression of headache caused by it can be variable. PATIENT CONCERNS: A case of a man hospitalized for high-intensity hemicranial headache which was aggravated by lying down and relieved when standing or sitting. The pain was of a pulsating character, localized on the right, behind the eye, followed by nausea and vomiting. He gradually appeared with ophthalmoplegia, decreased visual acuity and epistaxis. DIAGNOSIS: Digital subtraction angiogram (DSA) showed a pseudoaneurysm arising from the internal carotid artery (ICA) that projected anteriorly and medially into the sphenoid sinus with occluded fistula. INTERVENTIONS: The pseudoaneurysm was successfully treated with covered stent. OUTCOMES: The patient was then followed up clinically at the outpatient and seen in the outpatient clinic with no further episodes of nasal bleeding or new neurologic deficit. The vision loss and ophthalmoparesis were unchanged. LESSONS: Hemicranial postural headache may be the first and characteristic sign of spontaneous CCF.

Correlation of orthostatic hypotension with extracranial carotid and intracranial cerebral arteries atherosclerosis in patients with acute ischemic stroke under cerebral angiography.

OBJECTIVE: The clinical management of patients with acute ischemic stroke (AIS) is complicated by orthostatic hypotension, which might have close relationship with the atherosclerosis of cerebral arteries. The primary objectives were to evaluate the relationship of orthostatic hypotension with extracranial carotid arteries atherosclerosis (ECAS) and intracranial atherosclerosis (ICAS) in AIS patients. METHODS: This study was a prospective cohort analysis of consecutive AIS patients under cerebrovascular angiography. A total of 289 patients were included. orthostatic hypotension was defined as a systolic BP decline ≥20 mmHg or a diastolic BP decline ≥10 mmHg within 3 min of standing. Univariate and multivariate analysis were performed to investigate the association of the clinical variables with orthostatic hypotension. RESULTS: Orthostatic hypotension was identified in 80 (27.7%) of all patients. ECAS (≥70%) and ICAS (≥50%) was found in 39 (13.5%) and 71 (24.6%) respectively. In multivariate analysis, only diabetes mellitus (odds ratio = 2.00, 95% confidence interval, 1.12-3.58, P = 0.019) and ECAS (odds ratio = 1.97, 95% confidence interval, 1.54-2.51, P < 0.001) were independent risk factors for orthostatic hypotension. CONCLUSIONS: Orthostatic hypotension is a relatively common finding among patients with AIS. AIS patients should be screened for orthostatic hypotension, especially combined with severe ECAS and diabetes mellitus.

TOMM40 polymorphism is associated with resting-state functional MRI results in patients with Alzheimer's disease.

OBJECTIVE: Translocase of outer mitochondrial membrane 40 (TOMM40) encodes translocase of the outer mitochondrial membrane (TOM), which is associated with mitochondrial dysfunction in Alzheimer's disease (AD). TOMM40 rs157581-G has been reported to increase susceptibility to AD. However, the effect of TOMM40 rs157581-G in resting-state functional MRI (rs-fMRI) on AD has not been studied. Therefore, we aimed to investigate the role of TOMM40 rs157581-G on rs-fMRI results in AD patients. METHODS: Twenty-four AD patients were divided into two groups based on TOMM40 rs157581-G status, and clinical and imaging data were compared between the groups. RESULTS: TOMM40 rs157581-G carriers of AD showed decreased regional homogeneity in the left precuneus and decreased amplitude of low-frequency fluctuations in the bilateral temporal poles compared with noncarriers of AD. TOMM40 rs157581-G carriers of AD also showed increased functional connectivity between the right middle occipital gyrus and the left supramarginal gyrus and decreased connectivity between the left superior occipital gyrus and the right transverse temporal gyrus in comparison with TOMM40 rs157581-G noncarriers. CONCLUSION: We analyzed rs-fMRI characteristics of TOMM40 rs157581-G carriers of AD for the first time, which suggest that TOMM40 rs157581-G plays a harmful role in AD patients.

Multiple Visual Rating Scales Based on Structural MRI and a Novel Prediction Model Combining Visual Rating Scales and Age Stratification in the Diagnosis of Alzheimer's Disease in the Chinese Population.

Objective: To explore the value of multiple visual rating scales based on structural MRI in the diagnosis of Alzheimer's disease (AD) in the Chinese population. Materials and Methods: One hundred patients with AD and 100 age- and gender- matched cognitively normal controls were enrolled in this study. All the participants underwent neuropsychological tests and a structural MRI scan of the brain, among them, 42 AD cases and 47 cognitively normal controls also underwent 3D-T1 weighted sequence used for the analysis of voxel-based morphometry (VBM). The AD cases were divided into mild and moderate-severe groups according to the mini-mental state examination. Each participant was evaluated by two trained radiologists who were blind to the clinical information, according to the six visual rating scales, including for medial temporal lobe atrophy (MTA), posterior atrophy (PA), anterior temporal (AT), orbitofrontal (OF) cortex, anterior cingulate (AC), and fronto-insula (FI). Finally, we estimated the relationship between the visual rating scales and the volume of corresponding brain regions, using correlation analysis, and evaluated the specificity and sensitivity of every single scale and combination of multiple scales in the diagnosis of AD, using a receiver operating characteristic (ROC) curve and establishing a logistic regression model. Results: The optimal cutoff of all six visual rating scales for distinguishing AD cases from normal controls was 1.5. Using automated classification based on all six rating scales, the accuracy for distinguishing AD cases from healthy controls ranged from 0.68 to 0.80 (for mild AD) and 0.77-0.90 (for moderate-severe AD), respectively. A diagnostic prediction model with a combination of MTA and OF results was made as follows: Score = BMTA(score) + BOF(score) -1.58 (age < 65 years); Score = BMTA(score) + BOF(score) -4.09 (age ≥65 years). The model was superior to any single visual rating scale in the diagnosis of mild AD (P < 0.05). Conclusion: Each of the six visual rating scales could be applied to the diagnosis of moderate-severe AD alone in the Chinese population. A prediction model of the combined usage of MTA, OF, and age stratification for the early diagnosis of AD was preliminarily established.

Identification of CHCHD2 mutations in patients with Alzheimer's disease, amyotrophic lateral sclerosis and frontotemporal dementia in China.

Recently, the coiled­coil­helix­coiled­coil­helix domain 2 (CHCHD2) gene was identified as a possible causative gene for Parkinson's disease (PD). Three other neurodegenerative diseases, Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), share significant overlaps with PD in clinical phenotypes, pathological features and genetic heredities, and it is still unclear whether CHCHD2 variants could explain these three diseases. The present study screened all exons of the CHCHD2 gene in a total of 780 patients (511 AD, 181 ALS and 88 FTD) and 500 healthy controls from the Chinese Han population. Two missense variants, 5C>T (Pro2Leu) and 238A>G (Ile80Val), were identified in five unrelated patients with AD while no mutations were observed in patients with ALS or FTD. These mutations have been reported as low­frequency variants in the ExAC database with frequencies of 0.0075 and 0.000025. Pro2 Leu, however, was also detected in controls and was confirmed to have no significant association with the risk for AD; Ile80Val was not detected in any normal controls, suggesting that the CHCHD2 gene may be associated with AD in the Chinese Han population.

Mutations of CCNF gene is rare in patients with amyotrophic lateral sclerosis and frontotemporal dementia from Mainland China.

OBJECTIVE: Mutations of the cyclin F (CCNF) gene were recently identified to be associated with amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) in Western and Japanese populations. The rare protein-altering variants frequency is 0.6 to 3.3% in ALS and FTD from these diverse geographic populations while no systematic analysis of CCNF variants were conducted in the Chinese population. METHODS: We screened all exons of CCNF in a cohort of 269 cases (including 181 ALS and 88 FTD) from Mainland China using Sanger sequencing. RESULTS: A rare heterozygous variant (c.481G > A, p.G161R) was detected in a sporadic ALS case with a frequency of 0.6%, while no mutation was identified in patients with FTD. The same variant was also found in a sporadic ALS patient from America. CONCLUSIONS: Our result indicates that the mutation of CCNF is rare in patients with ALS and FTD from Mainland China.

The role of exosomes in the pathogenesis of Alzheimer' disease.

Exosomes are small vesicles secreted by most cell types including neurons that function in intercellular communication through transfer of their cargo or encapsulate and eliminate unnecessary cellular components and therefore have a broad impact on nerve development, activation and regeneration. In addition, exosomes have been observed to be involved in spreading pathological misfolded proteins, thereby leading to the onset and propagation of disease. Alzheimer disease (AD) is the most common form of dementia and characterized by two types of lesions: amyloid plaques and neurofibrillary tangles. Accumulating evidence has demonstrated that exosomes are associated with amyloid precursor (APP) and Tau proteins and play a controversial role in Alzheimer's disease process. In this review, we will discuss the role of exosomes in the metabolism and secretion of APP and Tau proteins and their subsequent impact on AD pathogenesis.

Identification of CHCHD10 Mutation in Chinese Patients with Alzheimer Disease.

CHCHD10 gene has been identified to be associated with frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS). Considering the clinical phenotype and pathology characterization were overlapped between FTD and Alzheimer disease (AD), and so far, no systematic analysis of CHCHD10 mutation was conducted in patients with AD in Asian population. Therefore, we screened of all exons in CHCHD10 in a cohort of 484 AD patients (60 with family history) from Mainland China. A heterozygous variant p.A35D (c.104C>A), previously reported in a patient with FTD in Italian population, was identified in a female patient with sporadic LOAD. The age at onset of mutation carrier was 86, presented as typical amnestic dementia. The mutation was found to be deleterious according to in silico predictions and excluded in 500 ethnically and geographically matched controls. Our finding revealed the clinical manifestations of variant p.A35D (c.104C>A) in a LOAD case and indicated that CHCHD10 mutation was presented in different types of dementia.

Mutational analysis of PRNP in Alzheimer's disease and frontotemporal dementia in China.

The prion protein (PRNP) gene is associated with prion diseases, whereas variants of the PRNP gene may also explain some cases of Alzheimer disease (AD) and frontotemporal dementia (FTD) in Caucasian populations. To determine the prevalence of the PRNP gene in patients with AD and FTD in China, we screened all exons of the PRNP gene in a cohort of 683 cases (606 AD and 77 FTD) in the Chinese Han population and we detected a novel missense mutation p.S17G in a late-onset AD (LOAD) patient. Furthermore, we analyzed the PRNP M/V polymorphism at codon 129, which was previously reported as a risk factor. However, there were no significant differences in genotype and allele frequency either in AD (OR = 0.75[0.378-1.49], P = 0.492), or FTD patients (OR = 2.046[0.265-15.783], P = 0.707). To our knowledge, this is the first study to reveal a correlation between the PRNP gene and Chinese AD and FTD patients in a large cohort. This study reports a novel p.S17G mutation in a clinically diagnosed LOAD patient, suggesting that the PRNP mutation is present in Chinese AD patients, whereas, M129V polymorphism is not a risk factor for AD or FTD in the Chinese Han population.