Effects of Neurofeedback on Cognitive Function, Productive Activity, and Quality of Life in Patients With Traumatic Brain Injury: A Randomized Controlled Trial.

BACKGROUND: Cognitive impairment is common in patients with traumatic brain injury (TBI). Studies that have examined the effectiveness of neurofeedback (NFB) on cognitive function following TBI have had poor study designs and small sample sizes. OBJECTIVES: This randomized controlled trial assessed the effects of low-resolution tomography Z-score NFB (LZNFB) and theta/beta NFB on cognitive impairment, return to productive activity, and quality of life in patients with TBI. METHODS: We randomly assigned 87 patients with TBI with cognitive impairment to LZNFB, theta/beta NFB, or usual care (UC) groups. Patients in both NFB groups received weekly 60-minute treatment for 10 weeks, and those in the control group received UC and telephone interviews for 10 weeks. The primary outcome was cognitive function as measured by performance on cognitive tasks; the secondary outcomes included productive activity and quality of life based on the Community Integration Questionnaire-revised (CIQ-R) and the Quality of Life after Brain Injury (QOLIBRI), respectively, at baseline and immediately after the last intervention. RESULTS: The LZNFB group exhibited significantly greater improvements in immediate recall, delayed recall, recognition memory, and selective attention compared with the UC group; the theta/beta NFB group exhibited improvements in only immediate memory and selective attention (P < .05). The total CIQ-R scores of the LZNFB group after treatment were significantly improved than those of the UC group were. CONCLUSION: Consecutive LZNFB achieved therapeutic effects in memory, attention, and productive activity, whereas theta/beta NFB improved memory and attention in patients with TBI.This trial was prospectively registered at ClinicalTrial.gov (registration number: NCT03515317; https://clinicaltrials.gov/ct2/show/NCT03515317).

Does a negative correlation of heme oxygenase-1 with hematoma thickness in chronic subdural hematomas affect neovascularization and microvascular leakage? A retrospective study with preliminary validation.

OBJECTIVE: Chronic subdural hematoma (CSDH) is a common neurological disease among elderly adults. The progression of CSDH is an angiogenic process, involving inflammatory mediators that affect vascular permeability, microvascular leakage, and hematoma thickness. The authors aimed to identify biomarkers associated with angiogenesis and vascular permeability that might influence midline shift and hematoma thickness. METHODS: Medical records and laboratory data of consecutive patients who underwent surgery for CSDH were analyzed. Collected data were basic demographic data, CSDH classification, CSDH thickness, midline shift, heme oxygenase-1 (HO-1) levels in hematomas, and common laboratory markers. Linear regression analysis was used to evaluate the relationship of CSDH thickness with characteristic variables. The chick chorioallantoic membrane (CAM) assay was used to test the angiogenic potency of identified variables in ex ovo culture of chick embryos. RESULTS: In total, 93 patients with CSDH (71.0% male) with a mean age of 71.0 years were included. The mean CSDH thickness and midline shift were 19.7 and 9.8 mm, respectively. The mean levels of HO-1, ferritin, total bilirubin, white blood cells, segmented neutrophils, lymphocytes, platelets, international normalized ratio, and partial thromboplastin time were 36 ng/mL, 14.8 µg/mL, 10.5 mg/dL, 10.3 × 103 cells/µL, 69%, 21.7%, 221.1 × 109 cells/µL, 1.0, and 27.8 seconds, respectively. Pearson correlation analysis revealed that CSDH thickness was positively correlated with midline shift distance (r = 0.218, p < 0.05) but negatively correlated with HO-1 concentration (r = -0.364, p < 0.01) and ferritin level (r = -0.222, p < 0.05). Multivariate linear regression analysis revealed that HO-1 was an independent predictor of CSDH thickness (ß = -0.084, p = 0.006). The angiogenic potency of HO-1 in hematoma fluid was tested with the chick CAM assay; topical addition of CSDH fluid with low HO-1 levels promoted neovascularization and microvascular leakage. Addition of HO-1 in a rescue experiment inhibited CSDH fluid-mediated angiogenesis and microvascular leakage. CONCLUSIONS: HO-1 is an independent risk factor in CSDH hematomas and is negatively correlated with CSDH thickness. HO-1 may play a role in the pathophysiology and development of CSDH, possibly by preventing neovascularization and reducing capillary fragility and hyperpermeability.

Dental Pulp Stem Cell-Derived Conditioned Medium Alleviates Subarachnoid Hemorrhage-Induced Microcirculation Impairment by Promoting M2 Microglia Polarization and Reducing Astrocyte Swelling.

Aneurysmal subarachnoid hemorrhage (SAH) can cause severe neurological deficits and high mortality. Early brain edema following SAH contributes to the initiation of microcirculation impairment and may further lead to delayed ischemic neurologic deficit (DIND). This study aimed to investigate whether dental pulp stem cell conditioned medium (DPSC-CM) ameliorates SAH-induced microcirculation impairment and the underlying mechanisms. SAH was induced via intrathecal injection of fresh autologous blood in Wistar male adult rat. DPSC-CM or DPSC-CM + insulin growth factor-1 (IGF-1) antibody was randomly administered by intrathecal route 5 min after SAH induction. To evaluate the underlying mechanisms of DPSC-CM in the treatment of SAH, primary rat astrocyte and microglia co-cultures were challenged with hemolysate or SAH-patient CSF in the presence or absence of DPSC-CM. The results showed that in vivo, DPSC-CM treatment decreased the brain water content, improved microcirculation impairment and enhanced functional recovery at 24 h post-SAH. DPSC-CM treatment also alleviated the expressions of water channel protein aquaporin-4 (AQP4) and pro-inflammatory cytokines, and enhanced the expressions of anti-inflammatory factors in the cortical region. However, all the beneficial effects of DPSC-CM were abrogated after treatment with IGF-1 neutralizing antibody. The in vitro results further showed that DPSC-CM treatment reduced hemolysate/SAH-patient CSF-induced astrocyte swelling and promoted M2 microglia polarization, partially through IGF-1/AKT signaling. The data suggested that DPSC-CM significantly reduced brain edema and rescued microcirculation impairment with concomitant anti-inflammatory benefits after SAH, and may potentially be developed into a novel therapeutic strategy for SAH.

Three-Dimensional Angioarchitecture of Rete Middle Cerebral Artery Anomalies and the Clinical Significance.

PURPOSE: Rete middle cerebral artery (MCA) anomaly is characterized by a web-like network of arteries involving the first MCA segment (M1) and a normal downstream MCA. The detailed composition of this anomaly and the hemodynamic impacts on cerebral perfusion are rarely addressed. The purpose of this study was to elucidate the anatomical and hemodynamic perspectives of the rete MCA anomaly. METHODS: From August 2020 to December 2021, 4 rete MCA anomalies were identified at Shuang Ho hospital. Clinical information, perfusion magnetic resonance (MR) imaging, and angiographic images were collected. Detailed angioarchitecture, including types of arterial feeders and extent of rete involvement, were analyzed based on three-dimensional volume-rendering reconstruction images obtained from the catheter-based angiographies. RESULTS: Despite their variable clinical presentations (two hemorrhage, one ischemia, and one asymptomatic), all cases shared common angiographic findings as follows: (1) the internal carotid artery did not connect directly to the rete, (2) the anterior choroidal artery (AChA) was the artery constantly supplying the rete and (3) there was a watershed zone shift toward MCA territory. The perfusion MR cerebral blood flow map was symmetric in all studied cases. CONCLUSION: The AChA is an artery constantly supplying the rete, which suggests that the angioarchitectural features associated with this anomaly may be the result of both congenital and acquired compensatory processes. Cerebral perfusion remains preserved at the lesion side, despite angiographic evidence of watershed zone shift. These findings will be important for making better clinical judgments about this condition.

Label-Free Cholesteric Liquid Crystal Biosensing Chips for Heme Oxygenase-1 Detection within Cerebrospinal Fluid as an Effective Outcome Indicator for Spontaneous Subarachnoid Hemorrhage.

A novel device for cholesteric liquid crystal (LC; CLC)-based biosensing chips for detecting heme oxygenase (HO)-1 within the cerebrospinal fluid (CSF) was invented. In the CLC device, the reorientation of the LCs was strongly influenced by the alignment layer surface and adjacent LCs. When the substrate was coated with the alignment layer, the CLCs oriented homeotropically in a focal conic state. Once HO-1 was immobilized onto the orientation sheet-coated substrate, the CLC changed from a focal conic state to a bright planar state by disrupting the CLCs. The concentration of HO-1 within CSF was shown to be an effective outcome indicator for patients with a spontaneous subarachnoid hemorrhage. We showed that the CLC immunoassaying can be used to measure HO-1 with a lower detection limit of about 10 ng/mL. The linear range was 10 ng/mL to 1 mg/mL. An easy-to-use, rapid-detection, and label-free CLC immunoassay device is proposed.

Comparative efficacy of prophylactic anticonvulsant drugs following traumatic brain injury: A systematic review and network meta-analysis of randomized controlled trials.

We systematically compared the effects of prophylactic anticonvulsant drug use in patients with traumatic brain injury. We searched four electronic databases from their inception until July 13, 2021. Two researchers independently screened, appraised, and extracted the included studies. Network meta-analysis using multivariate random effects and a frequentist framework was adopted for data analysis. The risk of bias of each study was assessed using the Cochrane risk of bias tool, and confidence in evidence was assessed through confidence in network meta-analysis (CINeMA). A total of 11 randomized controlled trials involving 2,450 participants and six different treatments (i.e., placebo, carbamazepine, phenytoin, levetiracetam, valproate, and magnesium sulfate) were included. We found that anticonvulsant drugs as a whole significantly reduced early posttraumatic seizures (PTS) but not late PTS compared with placebo (odd ratios [ORs] = 0.42 and 0.82, 95% confidence intervals [CIs] = 0.21-0.82 and 0.47-1.43). For the findings of network meta-analysis, we observed that phenytoin (ORs = 0.43 and 0.71; 95% CIs = 0.18-1.01 and 0.23-2.20), levetiracetam (ORs = 0.56 and 1.58; 95% CIs = 0.12-2.55 and 0.03-84.42), and carbamazepine (ORs = 0.29 and 0.64; 95% CIs = 0.07-1.18 and 0.08-5.28) were more likely to reduce early and late PTS compared with placebo; however, the treatment effects were not significant. Sensitivity analysis, after excluding a study enrolling only children, revealed that phenytoin had a significant effect in preventing early PTS (OR = 0.33; 95% CI = 0.14-0.78). Our findings indicate that no antiepileptic drug had an effect on early or late PTS superior to that of another; however, the sensitivity analysis revealed that phenytoin might prevent early PTS. Additional studies with large sample sizes and a rigorous design are required to obtain high-quality evidence on prophylactic anticonvulsant drug use in patients with traumatic brain injury.

Label-Free, Color-Indicating, Polarizer-Free Dye-Doped Liquid Crystal Microfluidic Polydimethylsiloxane Biosensing Chips for Detecting Albumin.

We reveal a novel design for dye-doped liquid crystal (DDLC) microfluidic biosensing chips in the polydimethylsiloxane material. With this design chip, the orientation of DDLCs was affected by the interface between the walls of the channels and DDLCs. When the inside of a channel was coated with an N,N-dimethyl-n-octadecyl-3-aminopropyltrimethoxysilyl chloride (DMOAP) alignment layer, the DDLCs oriented homeotropically in a homeotropic (H) state under cross-polarized microscopy. After immobilization of antigens with antibodies on the alignment layer-coated microchannel walls, the optical intensity of the DDLC change from the dark H state to the bright planar (P) state. Using pressure-driven flow, the binding of antigens/antibodies to the DDLCs could be detected in an experimental sequential order. The microfluidic DDLCs were tested by detecting bovine serum albumin (BSA) and its immune-responses of antigens/antibodies. We proved that this immunoassay chip was able to detect BSA antigens/antibodies pairs with the detection limit about 0.5 µg/mL. The novel DDLC chip was shown to be a simple, multi-detection device, and label-free microfluidic chips are presented.

The Roles of Neurotrophins in Traumatic Brain Injury.

Neurotrophins are a collection of structurally and functionally related proteins. They play important roles in many aspects of neural development, survival, and plasticity. Traumatic brain injury (TBI) leads to different levels of central nervous tissue destruction and cellular repair through various compensatory mechanisms promoted by the injured brain. Many studies have shown that neurotrophins are key modulators of neuroinflammation, apoptosis, blood-brain barrier permeability, memory capacity, and neurite regeneration. The expression of neurotrophins following TBI is affected by the severity of injury, genetic polymorphism, and different post-traumatic time points. Emerging research is focused on the potential therapeutic applications of neurotrophins in managing TBI. We conducted a comprehensive review by organizing the studies that demonstrate the role of neurotrophins in the management of TBI.

Progressive multifocal leukoencephalopathy in a renal transplant patient.

End-stage renal disease (ESRD) has a major impact on health and affects more than 600,000 people in the USA. The current mainstay treatments include dialysis and kidney transplantation (KT), and patients who have received KT have a higher quality of life and a lower mortality risk than those on chronic dialysis. Therefore, KT is considered the more preferred treatment modality for patients with ESRD. However, even though KT results in a higher long-term survival rate, the use of immunosuppressants is associated with various complications, including opportunistic infections and malignancies, which may lead to a higher risk of death in the first year after transplantation. Progressive multifocal leukoencephalopathy (PML) is a rare complication following KT, with an incidence of 0.027% in KT recipients. We present a case of PML following immunosuppressant therapy in a patient who received KT.

Local hemostatic matrix for endoscope-assisted removal of intracerebral hemorrhage is safe and effective.

BACKGROUND/PURPOSE: Minimally invasive endoscope-assisted (MIE) evacuation of spontaneous intracerebral hemorrhage (ICH) is simple and effective, but the limited working space may hinder meticulous hemostasis and might lead to rebleeding. Management of intraoperative hemorrhage is therefore a critical issue of this study. This study presents experience in the treatment of patients with various types of ICH by MIE evacuation followed by direct local injection of FloSeal Hemostatic Matrix (Baxter Healthcare Corp, Fremont, CA, USA) for hemostasis. METHODS: The retrospective nonrandomized clinical and radiology-based analysis enrolled 42 patients treated with MIE evacuation of ICH followed by direct local injection of FloSeal Hemostatic Matrix. Rebleeding, morbidity, and mortality were the primary endpoints. The percentage of hematoma evacuated was calculated from the pre- and postoperative brain computed tomography (CT) scans. Extended Glasgow Outcome Scale (GOSE) was evaluated at 6 months postoperatively. RESULTS: Forty-two ICH patients were included in this study, among these, 23 patients were putaminal hemorrhage, 16 were thalamic ICH, and the other three were subcortical type. Surgery-related mortality was 2.4%. The average percentage of hematoma evacuated was 80.8%, and the rebleeding rate was 4.8%. The mean operative time was 102.7 minutes and the average blood loss was 84.9 mL. The mean postoperative GOSE score was 4.55 at 6-months' follow-up. CONCLUSION: This study shows that local application of FloSeal Hemostatic Matrix is safe and effective for hemostasis during MIE evacuation of ICH. In our experience, this shortens the operation time, especially in cases with intraoperative bleeding. A large, prospective, randomized trial is needed to confirm the findings.