Junliang Yuan

Serum Uric Acid is Independently Associated with Enlarged Perivascular Spaces

Enlarged perivascular spaces (EPVS) are reported to be associated with impaired cognitive function and sleep disorders. It is of clinical importance to understand the risk factors for EPVS. Hyperuricemia increases the risk of hypertension and endothelial dysfunction, which are well recognized to be associated with EPVS. Therefore, we postulated that serum uric acid (SUA) might be associated with EPVS. A total of 665 lacunar stroke patients were enrolled in this study. The SUA concentrations of patients with severe EPVS were much higher than those of patients with mild EPVS (for basal ganglia: 5.25 ± 1.40 mg/dl vs. 4.75 ± 1.40 mg/dl, p < 0.001; for white matter: 5.31 ± 1.41 mg/dl vs. 4.88 ± 1.37 mg/dl, p = 0.009). The percentage of subjects with severe EPVS tended to be higher in the highest quartile of SUA (chi-square test: P = 0.002 for basal ganglia and 0.006 for white matter). Spearman correlation analysis indicated that the SUA concentrations were positively correlated with the severity of EPVS (rho > 0, p < 0.05). Multivariate logistic regression analysis showed that high normal SUA was independently associated with a higher severity of EPVS. This finding suggests that high SUA levels might be an independent risk factor for EPVS in lacunar stroke patients.

Neurochemical correlates of cognitive dysfunction in patients with leukoaraiosis: a proton magnetic resonance spectroscopy study

Abstract Objectives: Leukoaraiosis (LA) is a common radiological finding in the elderly and may reflect cerebral small vessel disease (SVD). Although SVD has been identified as a major cause of vascular cognitive impairment or vascular dementia, the mechanisms for this association remain unclear. We therefore aimed to measure brain metabolites in LA using proton magnetic resonance spectroscopy (1H-MRS) as to determine the relationship between cognitive function and neurochemical white matter profile. Methods: We recruited 23 patients with LA and 23 age- and sex-matched healthy controls consecutively. Multi-voxel 1H-MRS was performed with a volume of interest located in centrum semiovale that contained mainly white matter voxels. Three main ratios of N-acetyl aspartate (NAA)/Cr, choline (Cho)/Cr and NAA/Cho were obtained. Spearman rank correlation coefficients were calculated between the cognitive function and the measured metabolite ratios. Results: We found significantly lower levels of NAA/Cho and NAA/Cr ratios in lesioned white matter in patients with LA than healthy controls (P<0·05). The ratios of NAA/Cho and NAA/Cr in normal appearing white matter (NAWM) were higher than lesioned white matter and lower than controls, but this difference was not significant (P>0·05). There was a positive relationship between Mini-Mental State Examination (MMSE) and NAA/Cho in NAWM (r = 0·417, P = 0·048), and also a positive relationship between MMSE and NAA/Cr in lesioned white matter (r = 0·551, P = 0·006) in patients with LA. A positive relationship between the Z scores of the executive function and NAA/Cho in lesioned white matter (r = 0·557, P = 0·006) was also found. Conclusion: The main finding of this study was a significant reduction in the ratios of NAA/Cr and NAA/Cho in lesioned white matter, which indicates a marker of neuronal loss or dysfunction in patients with LA, which was correlated with cognitive function. This relationship between cognitive function and metabolic changes suggests that 1H-MRS can be explored as a marker for cognitive dysfunction in patients with LA.

Higher ambulatory systolic blood pressure independently associated with enlarged perivascular spaces in basal ganglia

Abstract Backgrounds: Enlarged perivascular spaces (EPVS) have been identified as a marker of cerebral small vessel diseases (CSVD). Ambulatory blood pressure (ABP) is the strongest predictor of hypertension-related brain damage. However, the relationship between ABP levels and EPVS is unclear. Objectives: This study aimed to investigate the association between ABP levels and EPVS by 24-hour ambulatory blood pressure monitoring (ABPM). Methods: We prospectively recruited inpatients for physical examinations in our hospital from May 2013 to Jun 2016. 24-hour ABPM data and cranial magnetic resonance imaging information were collected. EPVS in basal ganglia (BG) and centrum semiovale (CSO) were identified and classified into three categories by the severity. White matter hyperintensities were scored by Fazekas scale. Spearman correlation analysis and multiple logistic regression analysis were used to determine the relationship between ABP levels and EPVS. Results: A total of 573 subjects were enrolled in this study. 24-hour, day and night systolic blood pressure (SBP) levels were positively related to higher numbers of EPVS in BG (24-hour SBP: r = 0.23, p < 0.01; day SBP: r = 0.25, p < 0.01; night SBP: r = 0.30, p < 0.01). The association was unchanged after controlling for confounders by multiple logistic regression analysis. 24-hour and day diastolic blood pressure (DBP) levels increased with an increasing degree of EPVS in CSO (p = 0.04 and 0.049, respectively). But the association disappeared after adjusting for confounders. Spearman correlation analysis indicated that ABP levels were not associated with higher numbers of EPVS in CSO (p > 0.05). DBP levels were not independently associated with the severity of EPVS in BG and CSO. Conclusion: Higher SBP levels were independently associated with EPVS in BG, but not in CSO, which supported EPVS in BG to be a marker of CSVD. Pathogenesis of EPVS in BG and CSO might be different.

Disconnections of Cortico-Subcortical Pathways Related to Cognitive Impairment in Patients with Leukoaraiosis: A Preliminary Diffusion Tensor Imaging Study

Background: We aimed to explore the relation between the microstructural integrity of white matter using the technique of diffusion tensor imaging (DTI) and changes of cognition in leukoaraiosis (LA). Methods: Fifty patients with LA and 50 age- and gender-matched controls were recruited consecutively. The average values of mean diffusivity (MD) and fractional anisotropy (FA) were quantified both within white matter lesions (WMLs) and normal-appearing white matter (NAWM) from the regions of interest (ROIs). Results: We found significantly decreased FA and increased MD in WMLs at the 5 ROIs than that in NAWM and controls (p < 0.05). The values of FA in NAWM were significantly lower at centrum semiovale and posterior periventricular white matter than those of controls (p < 0.05). The values of MD in NAWM were significantly higher at the anterior periventricular white matter and corpus callosum than those of controls (p < 0.05). The values of FA in NAWM located at anterior periventricular white matter correlated inversely with the Z scores of executive function (r = -0.420, p = 0.028). Conclusions: DTI may provide some important information about the cognitive dysfunction in patients with LA, which may largely attribute to the “disconnection” of cortico-subcortical pathways, with the evidence of reduced FA and increased MD.

Acute Disseminated Encephalomyelitis following Vaccination against Hepatitis B in a Child: A Case Report and Literature Review

Acute disseminated encephalomyelitis (ADEM) is an inflammatory demyelinating disease of the central nervous system, which has been associated with several vaccines such as rabies, diphtheria-tetanus-polio, smallpox, measles, mumps, rubella, Japanese B encephalitis, pertussis, influenza, and the Hog vaccine. Here, we presented a case of 12-year-old child who suffered from ADEM three weeks after hepatitis B vaccination. He was admitted to our hospital with symptoms of weakness of limbs, high fever, and alteration of consciousness. Some abnormalities were also found in CSF. Treatment with high-dose corticosteroids and intravenous immunoglobulin had significant effect, with marked improvement of the clinical symptoms and the results of CSF. The findings of MRI also detected some abnormal lesions located in both brain and spinal cord. The clinical features, the findings of CSF and MRI, and therapeutic effect may contribute to such diagnosis of ADEM.

Combined findings of FDG-PET and arterial spin labeling in sporadic Creutzfeldt-Jakob disease

ABSTRACT Sporadic Creutzfeldt-Jakob disease (sCJD) is a fatal progressive neurodegenerative disease. Multimodal approaches, including electroencephalogram, diffusion-weighted imaging (DWI) of brain MRI, and cerebrospinal fluid biomarkers, have been applied to increase the diagnostic accuracy of sCJD. Although previous studies suggested DWI could be the most useful modality for sCJD diagnosis, whether metabolism changes underlying in sCJD are still poorly understood. To the best of our knowledge, there are only one case using the technique of arterial spin labeling (ASL) to detection and follow-up of perfusion changes in CJD. Herein, we described a 71-year-old woman presented with progressive cognitive decline, behavioral and psychological symptoms for two months. The patient died one month later after her admission. As far as we know, this is the first report using the combination of fluorodeoxyglucose positron emission tomography and ASL to explore the metabolism changes in sCJD. Our case exemplifies the difficulty clinicians may face in the diagnosis of sCJD.

The comorbidity of acute ischemic stroke and splenic infarction resulting from essential thrombocythemia

Dear editors: Essential thrombocythemia (ET), as myeloproliferative neoplasm, is characterized by thrombotic or hemorrhagic complications with higher mortality, progression to myelofibrosis, and even transformation to acute leukemia [1]. The clinical features of thrombotic events in ET patients may vary, from mild disturbances to more severe complications. Up to now, ET has been increasing recognized to lead to some complications of systemic thrombus, including arterial (e.g., myocardial infarction, ischemic stroke, or a transient ischemic attack) or venous thrombosis (e.g., cerebral sinus and venous thrombosis or deep venous thrombosis) [2–4]. However, the hemostatic abnormalities and the underlying pathogenesis of the thrombosis in ET have been not well understood. As a result, the main indication for treatment of ET is to prevent thrombosis, if timely recognition, early correct diagnosis, and the prognosis of ET is relatively favorable [5]. However, the occurrence of acute ischemic stroke and multi-organ thrombosis overlapping syndrome in a same patient is quite so scarce. To the best of our knowledge, there was only one case concerning about acute onset of ischemic stroke and splenic infarction caused by ET in a same patient [6]. Herein, we reported a 63-year-old female, who developed acute ischemic stroke in left parietal lobe with restricted diffusion from magnetic resonance imaging (MRI) and splenic infarction simultaneously mainly due to ET. A 63-year-old woman was admitted to the Department of Neurology for acute onset of numbness and weakness in her right extremities for 2 days. ET was diagnosed 1 year ago, with the treatment of hydroxyurea. There was no history of stroke risk factors and family histories (e.g., hypertension, diabetes mellitus). On physical examination, there was mild numbness and weakness in her right extremities. Besides, splenomegaly was detected with the median spleen size of 8 cm below costal margin. Other physical examination showed no abnormalities. Laboratory data showed the platelet count was 448 × 10/L (reference range 100–300 × 10/L) and the JAK2V617F mutation was positive. Bone marrow biopsy revealed hypercellular marrow and megakaryopoiesis, which also supported the diagnosis of ET. The marrow fibrosis and Philadelphia chromosome were negative. The decreased levels of protein C and S were 56.3% (reference range 70– 140%) and 11% (reference range 60–130%), respectively. Other laboratory findings were normal. After her admission, brain MRI showed acute lacunar infarction located in left parietal lobe with restricted diffusion with the evidence of diffusion weighted imaging (DWI) and apparent diffusion coefficient (ADC) (Fig. 1a–d). Brain magnetic resonance angiography (Fig. 1e) and CT angiography indicated no abnormalities (Fig. 1f). Three days later, she developed the signs and symptoms of left abdominal pain, with intense pain at left hypochondrium and with high fever. Abdominal enhanced computed tomography (CT) revealed splenomegaly and multiple splenic infarctions without splenic artery occlusions (Fig. 2a-d). The X-ray of chest, electrocardiograph, cardiac ultrasound, transesophageal echocardiography, and the venous and arterial ultrasound of lower extremities were normal. At the admission, she was treated with aspirin (100 mg for oral treatment); however, there was not any response to the treatment of anti-platelet from the evidence of thromboelastogram. As a result, according to hypercoagulability, the low molecular weight heparin later with oral administration of warfarin Junliang Yuan and Yanhong Wu are co-first authors.

Assessment of Homocysteine as a Diagnostic and Early Prognostic Biomarker for Patients with Acute Lacunar Infarction

Background: Although increasing evidence has demonstrated that elevated homocysteine (Hcy) levels may be an important contributor for the development of cerebral infarction, rare studies focused on its diagnostic and early prognostic roles in acute lacunar infarction. Methods: A total of 197 patients with acute lacunar infarction and 192 to form the control group were prospectively recruited between January 2013 and February 2017. Early neurological deterioration was defined as an increase of ≥2 points in National Institutes of Health Stroke Scale or the decrease in Barthel index (BI) score at discharge. Results: Univariate and multivariate logistic regression analyses revealed that higher levels of fibrinogen and Hcy were independently clinical predictors associated with lacunar infarction. Receiver operating characteristic curves analysis demonstrated that the diagnosis value of Hcy was superior to fibrinogen, with the area under the curve of 0.881 and 0.688 respectively. Using the optimal cutoff value of 15.5 μmol/L of Hcy, a sensitivity of 65% and a specificity of 100% were achieved for predicting lacunar infarction. Hcy was only significantly related with BI reduction in the males (30.5 [15.5–65.5] vs. 18 [15–24], p = 0.034) in the univariate analysis but not in the females and the multivariate analysis. Conclusions: Serum Hcy may be an independent diagnostic and not an early prognostic biomarker for patients with acute lacunar infarction.

Correlation between prefrontal-striatal pathway impairment and cognitive impairment in patients with leukoaraiosis

Abstract Our study aimed to investigate the changes of white matter microstructure of cortico-subcortical pathways using diffusion tensor imaging (DTI), and to explore the relationship between abnormal parameters of DTI and cognitive function underlying in patients with leukoaraiosis (LA). A total of 42 patients with LA and 42 age- and sex-matched healthy controls were recruited from Beijing Chaoyang Hospital, Capital Medical University between January 2012 and December 2012. All the subjects underwent scans of conventional magnetic resonance imaging and DTI, and a comprehensive neuropsychological battery was utilized. The regions of interest (ROIs) were located at the white matter of centrum semiovale, anterior and posterior periventricular white matter, basal ganglia, corpus callosum. The averaged values of mean diffusivity (MD) and fractional anisotropy (FA) were quantified both within white matter lesions (WMLs) and normal appearing white matter (NAWM). A linear regression analysis was performed to assess the association between diffusion parameters and decline in cognitive domains. Patients with LA were associated with comprehensive cognitive function deficits. We found that significantly decreased FA and increased MD in WMLs at the 5 ROIs than that of NAWM and controls (P < .05). The values of FA in NAWM were significantly lower and MD in NAWM were significantly higher at centrum semiovale and posterior periventricular white matter than that of controls (P < .05). The values of FA in WMLs at anterior periventricular white matter were positively related to the performances of cognition in patients with LA (P < .05). The values of FA in NAWM located at anterior periventricular white matter were positively related to the score of Digit-symbol test (r = 0.446, P = .002). The values of FA in NAWM located at anterior periventricular white matter correlated inversely with the Z scores of executive function (r = −0.418, P = .03). In our study, patients with LA exhibited significant cognitive impairment especially in the domains of executive function. The technique of DTI revealed that the reduced FA and increased MD at the corresponding regions of cortico-subcortical pathways in patients with LA. DTI may be of great help for an early pathology of white matter microstructure underlying in patients with LA.

The Clinical Characteristics of Acute Cerebrovascular Accidents Resulting from Ovarian Hyperstimulation Syndrome

Background and Purpose: Ovarian hyperstimulation syndrome (OHSS) is a serious complication that occurs after the ovarian-induction treatment. Acute cerebrovascular accident is one of the most dangerous manifestations of the syndrome. However, the characteristics of stroke resulting from OHSS have so far not been well summarised in any study. Methods: We reported 2 cases of acute cerebrovascular accidents secondary to OHSS. And then we performed a literature search for reports on this type of stroke, and summarised their characteristics. Results: Thirty-six published cases of this type of stroke were reviewed. Thirty two out of 36 (88.9%) of the women were 35 years old or younger. Stroke in 28 out of 36 (77.8%) of these cases was caused by arterial thrombosis. In 17 out of 28 cases, the involved cerebral vascular branches were mainly middle cerebral artery (MCA) and internal carotid artery (ICA). The acute cerebrovascular accidents happened 7 and 9.25 days after embryo transplantation or 8 and 8.33 days after last human chorionic gonadotropin treatment respectively. The prognosis of patients was relatively good after anticoagulation and some supportive treatments. Conclusion: The MCA and ICA are easily involved in stroke resulting from OHSS. The young age may be a risk factor for developing stroke secondary to OHSS. Once thromboembolism develops, administering appropriate therapy is crucial.