Early Use of Statin in Patients Treated with Alteplase for Acute Ischemic Stroke.

Studies have reported that statin usage before stroke can increase the incidence of intracerebral hemorrhage after thrombolytic treatment. However, whether the administration of statin at an early stage of ischemic stroke increases hemorrhage occurrence is unknown. The aim of this study was to assess the effect of statin on neurological imaging and functional outcomes after intravenous alteplase treatment, within 24 h of acute ischemic stroke attack. A total of 119 consecutive acute ischemic stroke patients treated by intravenous alteplase were recruited, of which 71 patients (59.7 %) were given statin therapy within 24 h of stroke onset. The physiological parameters, including demography, vascular risk factors, and clinical characteristics were recorded. The occurrence of intracerebral hemorrhage (ICH), symptomatic intracerebral hemorrhage (sICH), 90-day functional outcomes, and mortality in the patients were further analyzed. There were 24 occurrences of ICH after alteplase treatment (20.2 %) and there was no difference when patients were treated with statin (p = 0.280). Multivariate logistic regression analysis showed no significant correlation between the administration of statin and the occurrence of ICH (p = 0.230) or sICH (p = 0.949). There was a trend toward better neurological function with higher statin dose. The use of statin in the early stage of ischemic stroke is safe and does not increase the risk of intracerebral hemorrhage after alteplase treatment, suggesting that a clinical trial of early statin treatment on a large scale following thrombolysis is needed for further evaluation.

The effect of double filtration plasmapheresis and corticosteroids on patients with anti-dipeptidyl-peptidase-like protein 6 encephalitis.

INTRODUCTION: Anti-dipeptidyl-peptidase-like protein 6 (DPPX) encephalitis is a rare condition with varied symptoms including gastrointestinal issues, weight loss, cognitive and mental dysfunction, and hyperexcitability of the central nervous system. METHODS: We studied five patients with anti-DPPX encephalitis who received immunotherapy, specifically DFPP, at our hospital. We analyzed their clinical symptoms, lab results, electrophysiological and imaging findings, and outcomes with immunotherapy. RESULTS: Patients presented with cognitive dysfunction, tremor, seizures, psychiatric disturbances, and cerebellar and brainstem dysfunction. Magnetic resonance imaging (MRI) showed brain abnormalities in one patient and elevated cerebrospinal fluid (CSF) protein levels in two patients. Antibodies against DPPX were detected in all patients and in CSF in two patients. One patient had antibodies against anti-CV2/contactin response mediator protein 5 (CRMP5). All patients responded well to DFPP and corticosteroids. CONCLUSION: DFPP may be an effective treatment for anti-DPPX encephalitis. Further research is needed to understand disease progression and evaluate immunotherapy efficacy.

Transcranial Doppler Ultrasonography as a Diagnostic Tool for Cerebrovascular Disorders.

Imaging techniques including transcranial Doppler (TCD), magnetic resonance imaging (MRI), computed tomography (CT), and cerebral angiography are available for cerebrovascular disease diagnosis. TCD is a less expensive, non-invasive, and practically simpler approach to diagnosing cerebrovascular disorders than the others. TCD is a commonly available and inexpensive diagnostic tool. However, owing to its large operator dependency, it has a narrow application area. Cerebrovascular disease indicates a group of disorders that alter the flow of blood in the brain. The brain's functions can be temporarily or permanently impaired as a result of this change in blood flow. Timely diagnosis and treatment can restore the brain-impaired functions, resulting in a much-improved prognosis for the patients. This review summarizes the basic principles underlying the TCD imaging technique and its utility as a diagnostic tool for cerebrovascular disease.

Silver Jubilee of Stroke Thrombolysis With Alteplase: Evolution of the Therapeutic Window.

In 1995, the results of a landmark clinical trial by National Institute of Neurological Disorders and Stroke (NINDS) made a paradigm shift in managing acute cerebral ischemic stroke (AIS) patients at critical care centers. The study demonstrated the efficacy of tissue-type plasminogen activator (tPA), alteplase in improving neurological and functional outcome in AIS patients when administered within 3 h of stroke onset. After about 12 years of efforts and the results of the ECASS-III trial, it was possible to expand the therapeutic window to 4.5 h, which still represents a major logistic issue, depriving many AIS patients from the benefits of tPA therapy. Constant efforts in this regards are directed toward either speeding up the patient recruitment for tPA therapy or expanding the current tPA window. Efficient protocols to reduce the door-to-needle time and advanced technologies like telestroke services and mobile stroke units are being deployed for early management of AIS patients. Studies have demonstrated benefit of thrombolysis guided by perfusion imaging in AIS patients at up to 9 h of stroke onset, signifying "tissue window." Several promising pharmacological and non-pharmacological approaches are being explored to mitigate the adverse effects of delayed tPA therapy, thus hoping to further expand the current tPA therapeutic window without compromising safety. With accumulation of scientific data, stroke organizations across the world are amending/updating the clinical recommendations of tPA, the only US-FDA approved drug for managing AIS patients. Alteplase has been a part of our neurocritical care and we intend to celebrate its silver jubilee by dedicating this review article discussing its journey so far and possible future evolution.

Diffusion tensor imaging changes correlate with cognition better than conventional MRI findings in patients with subcortical ischemic vascular disease.

BACKGROUND/AIMS: To investigate whether diffusion tensor imaging (DTI) is more sensitive than conventional MRI at detecting cognitive deterioration in patients with subcortical ischemic vascular disease (SIVD). METHODS: Forty-two SIVD patients had a diagnosis of no cognitive impairment (NCI), vascular cognitive impairment/no dementia or vascular dementia (VaD). Whole-brain DTI histography and routine MRI were performed on these participants. RESULTS: There were significant differences between cognitively impaired patients and NCI subjects in mean diffusivity and fractional anisotropy in either whole-brain white matter (WBWM) or in normal-appearing white matter (NAWM). All DTI indices within either WBWM or NAWM were found to be significantly correlated with both the attention-executive and memory measures in SIVD subjects. Lacune numbers and T2-weighted lesions correlated only with attention-executive measures, whereas hippocampal volumes correlated only weakly with memory measures. Whole-brain gray matter volumes correlated with Z scores for all cognitive domains but language. After VaD patients had been excluded from the analysis, cognitive measures remained significantly correlated with some of the DTI indices, but not with conventional MRI findings. CONCLUSIONS: Compared with conventional MRI, whole-brain DTI is a more reliable and sensitive technique for the early detection of cognitive impairment in SIVD patients.

Predictors of relapse in patients with medication overuse headache in Shanghai: A retrospective study with a 6-month follow-up.

Medication overuse headache (MOH) has a high relapse rate and disease heterogeneity. This study aimed to determine the predictors of MOH relapse in patients through a 6-month follow-up in Shanghai. In this retrospective study, patients diagnosed with MOH from June 2016 to June 2017 were recruited and followed up for 6 months after withdrawal treatment in Renji Hospital in Shanghai. Patients' information was obtained using headache questionnaires. Follow-up was conducted via telephone interview. Patients were divided into relapse group and no-relapse group according to the outcomes after 6 months. This study enrolled 124 outpatients with MOH at baseline. 102 patients completed the follow up and were analysis finally. Demographics and clinical characteristics were compared between the relapse (n = 39, 38.24%) and no-relapse (n = 63, 61.76%) group. Binary logistic regression analysis was performed, and two variables emerged as significant predictors of relapse before withdrawal; the headache frequency (day/month) was higher in the relapse group than in the no-relapse group [odds ratio (OR) 1.107, p = 0.008]. Furthermore, patients administered analgesics of ≥ 2 units per headache day had a higher risk of relapse [odds ratio (OR) 2.791, p = 0.038]. Headache frequency and analgesics units per headache day before withdrawal may be independent predictors of MOH relapse. Therefore, early identification of high-risk groups and enhancing patients' management could contribute to improving the prognosis of MOH.

The GluN2B subunit of N-methy-D-asparate receptor regulates the radial migration of cortical neurons in vivo.

The formation of layered structure of the mammalian neocortex requires a fine organized migration of post-mitotic neurons during early development. However, whether the radial migration is regulated by NMDA receptor and specific subunits remains contradictory and unknown. Here, we reported that in the developing rat cortex, migration of presumptive layer II/III neurons to their deserved destination was regulated by NMDA receptors with GluN2B but not GluN2A subunit. Using in utero electroporation of small interference RNA (siRNA) of distinct NMDA receptor subunits, we found that knockdown GluN1 and GluN2B subunits dramatically delayed the neuronal migration to proper layer II/III, while improperly stayed at lower layers or even the germinal regions, without changing the cell fate. In contrast, knockdown of GluN2A subunit did not impair the neuronal migration. Additionally, the ecotopic neurons by GluN2B RNAi developed to well dendritic differentiation, while the ones by GluN1 RNAi still kept morphology of migrating neurons. Therefore, GluN2B subunit of NMDA receptor plays an essential role in regulating proper neuronal migration and cortical lamination.

Meta-analysis of the association between polymorphisms of estrogen receptor α genes rs9340799 and rs2234693 and Alzheimer's disease: evidence from 23 articles.

OBJECTIVE: A meta-analysis was performed to better clarify the association between polymorphisms of estrogen receptor α genes rs9340799 and rs2234693 and risk of Alzheimer's disease (AD). METHODS: Pooled odds ratios (ORs) with 95% confidence intervals (CIs) from fixed and random effect models were calculated. Heterogeneity among studies was evaluated using the I(2). Meta-regression was used to explore the potential sources of between-study heterogeneity. RESULTS: A total of 23 studies about rs9340799 and 24 studies about rs2234693 were included in this meta-analysis. The combined evidence suggested that the x allele of rs9340799 had a significant protective effect on the risk of AD in codominant model (ORs = 0.893, 95%CIs = 0.822-0.970), especially for AD in Asia and sporadic AD (SAD). The p allele of rs2234693 was associated with decreased risk of AD in codominant model for patients with SAD. No publication bias was detected. CONCLUSIONS: This meta-analysis suggested that x allele of rs9340799 might have a protective effect on the risk of AD in Asia and in patients with SAD. In addition, the p allele of rs2234693 might decrease the risk of patients with SAD.