Transthyretin attenuates TDP-43 proteinopathy by autophagy activation via ATF4 in FTLD-TDP.

TAR DNA-binding protein-43 (TDP-43) proteinopathies are accompanied by the pathological hallmark of cytoplasmic inclusions in the neurodegenerative diseases, including frontal temporal lobar degeneration-TDP and amyotrophic lateral sclerosis. We found that transthyretin accumulates with TDP-43 cytoplasmic inclusions in frontal temporal lobar degeneration-TDP human patients and transgenic mice, in which transthyretin exhibits dramatic expression decline in elderly mice. The upregulation of transthyretin expression was demonstrated to facilitate the clearance of cytoplasmic TDP-43 inclusions through autophagy, in which transthyretin induces autophagy upregulation via ATF4. Of interest, transthyretin upregulated ATF4 expression and promoted ATF4 nuclear import, presenting physical interaction. Neuronal expression of transthyretin in frontal temporal lobar degeneration-TDP mice restored autophagy function and facilitated early soluble TDP-43 aggregates for autophagosome targeting, ameliorating neuropathology and behavioural deficits. Thus, transthyretin conducted two-way regulations by either inducing autophagy activation or escorting TDP-43 aggregates targeted autophagosomes, suggesting that transthyretin is a potential modulator therapy for neurological disorders caused by TDP-43 proteinopathy.

Outcomes of surgery and subsequent therapy for central nervous system oligoprogression in EGFR-mutated NSCLC patients.

BACKGROUND: Oligoprogression is an emerging issue in patients with epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC). However, the surgical treatment for central nervous system (CNS) oligoprogression is not widely discussed. We investigated the outcomes of craniotomy with adjuvant whole-brain radiotherapy (WBRT) and subsequent therapies for CNS oligoprogression in patients with EGFR-mutated NSCLC. METHODS: NSCLC patients with CNS oligoprogression were identified from a tertiary medical center. The outcomes of surgery with adjuvant WBRT or WBRT alone were analyzed, along with other variables. Overall survival and progression-free survival were analyzed using the log-rank test as the primary and secondary endpoints. A COX regression model was used to identify the possible prognostic factors. RESULTS: Thirty-seven patients with CNS oligoprogression who underwent surgery or WBRT were included in the study after reviewing 728 patients. Twenty-one patients underwent surgery with adjuvant WBRT, and 16 received WBRT alone. The median overall survival for surgery and WBRT alone groups was 43 (95% CI 17-69) and 22 (95% CI 15-29) months, respectively. Female sex was a positive prognostic factor for overall survival (OR 0.19, 95% CI 0.06-0.57). Patients who continued previous tyrosine kinase inhibitors (OR 3.48, 95% CI 1.06-11.4) and induced oligoprogression (OR 3.35, 95% CI 1.18-9.52) were associated with worse overall survival. Smoking history (OR 4.27, 95% CI 1.54-11.8) and induced oligoprogression (OR 5.53, 95% CI 2.1-14.7) were associated with worse progression-free survival. CONCLUSIONS: Surgery combined with adjuvant WBRT is a feasible treatment modality for CNS oligoprogression in patients with EGFR-mutated NSCLC. Changing the systemic-targeted therapy after local treatments may be associated with improved overall survival.

Evaluation of the safety, radiographic and resident training results of thoracic pedicle screws placement using resection of the transverse process.

OBJECTIVE: This study aimed at the evaluation and assessment of a simple method, the transverse process resection (TPR) technique, for freehand thoracic pedicle screw placement and the learning curve for trainee surgeons. METHODS: In the TPR technique, the tip of the thoracic transverse process (TP) is removed to create an entry point in the cancellous bone of the TP, and the thoracic pedicle is cannulated from the TP. We retrospectively evaluated the safety and radiographic results of the TPR technique and compared with that of conventional pedicle screws. The training performance of seven neurosurgical residents with TPR techniques were evaluated. RESULTS: Among 46 patients, a total of 322 thoracic screws were analyzed, including 178 screws placed using the TPR technique and 144 screws using the conventional straight-forward (SF) technique. TPR screws had greater medial angulations in all levels from T2 to T12 compared to SF screws (p < 0.001). The incidence of pedicle breach was lower in the TPR screws compared to SF screws (6.2% vs. 21.5%, p < 0.001), especially for screws placed by residents (6.7% vs. 29.6%, p < 0.001). Residents had improved performance following a cadaveric training course on the TPR technique (p = 0.001). CONCLUSION: This study demonstrated the safety of the TPR technique for thoracic pedicle screw placement and its short learning curve for trainee surgeons.

Significant effects of late evening snack on liver functions in patients with liver cirrhosis: A meta-analysis of randomized controlled trials.

BACKGROUND AND AIM: Reducing post-absorptive (fasting) phase by eating late evening snacks (LESs) is a potential intervention to improve substrate utilization and reverse sarcopenia. This study analyzed the results of published randomized controlled trials and controlled clinical trials to evaluate the effects of LES on liver function of patients with cirrhosis. METHODS: A meta-analysis was conducted. The search strategy included electronic database searches, and 300 articles were searched. Eight of these articles provided qualified data for pooling and analysis. Outcomes assessments included serum albumin, total bilirubin, alanine aminotransferase, prothrombin time, and aspartate aminotransferase, complications of cirrhosis, severity of liver disease, and blood glucose levels. RESULTS: Our analysis included eight studies comprising 341 patients (167 in LES groups and 174 in control groups). The results showed that LES intervention helped to maintain liver reserves. These eight studies demonstrated that LES intervention had significant effects for liver biochemical parameters on albumin, ammonia, and prothrombin time, with respective effect sizes of 0.233, -0.425, and -0.589; liver enzymes include aspartate aminotransferase and alanine aminotransferase, with respective effect sizes of -0.320 and -0.284. Studies on clinical signs of liver dysfunction showed lower occurrence rates of ascites and hepatic encephalopathy than in the control group. LES had no significant effect on Child-Pugh score. CONCLUSIONS: The overall results of the meta-analysis indicated that having LES can improve liver function reserve for patients with liver cirrhosis, with or without hepatocellular carcinoma. LES is a promising intervention for reversing anabolic resistance and the sarcopenia of cirrhosis, resulting in an improved quality of life for patients with cirrhosis.

High Fat Diet Suppresses Peroxisome Proliferator-Activated Receptors and Reduces Dopaminergic Neurons in the Substantia Nigra.

Although several epidemiologic and animal studies have revealed correlations between obesity and neurodegenerative disorders, such as Parkinson disease (PD), the underlying pathological mechanisms of obesity-induced PD remain unclear. Our study aimed to assess the effect of diet-induced obesity on the brain dopaminergic pathway. For five months, starting from weaning, we gave C57BL/6 mice a high-fat diet (HFD) to generate an obese mouse model and investigate whether the diet reprogrammed the midbrain dopaminergic system. Tyrosine hydroxylase staining showed that the HFD resulted in fewer dopaminergic neurons in the substantia nigra (SN), but not the striatum. It also induced neuroinflammation, with increased astrogliosis in the SN and striatum. Dendritic spine density in the SN of HFD-exposed mice decreased, which suggested that prolonged HFD altered dopaminergic neuroplasticity. All three peroxisome proliferator-activated receptor (PPAR) subtype (PPAR-α, PPAR-ß/δ, PPAR-γ) levels were significantly reduced in the SN and the ventral tegmental area of HFD mice when compared to those in controls. This study showed that a prolonged HFD induced neuroinflammation, suppressed PPAR levels, caused degeneration of midbrain dopaminergic neurons, and resulted in symptoms reminiscent of human PD. To our knowledge, this is the first study documenting the effects of an HFD on PPARs in dopaminergic neurons.

Factors Influencing Family Surrogates' Intention with Regard to Do-Not-Resuscitate Directive for Patients with Dementia.

Objective: To investigate the prevalence of family surrogates' do-not-resuscitate (DNR) intention for patients with dementia (PwD), and factors influencing family surrogates' decisions. Methods: This is a descriptive and cross-sectional study. Patients with dementia and their family surrogates from Dementia Outpatient Clinic of a teaching hospital in southern Taiwan were included. Data were collected using chart review and questionnaire survey. Influential factors were analyzed using multiple logistic regression. Results: One hundred and forty of the 223 participants (62.8%) have intention to sign DNR consents for their dementia relatives. Factors influencing the intention were: (1) Comorbid with musculoskeletal diseases or diabetes (p < .05); (2) psychological symptoms of repetitive wording and behavior (p < .05); (3) spouse (p < .05) and lineal relatives (p < .01); (4) previous discussion between families and patient about DNR directive (p = .001); (5) believers of Taiwan folk belief (Buddhism or Taoism) (p < .05). Conclusions: Advanced dementia patients cannot express intention about their end-of-life care and depend on family surrogates to decide for them. Our study showed that spouse and direct relatives, comorbidities of musculoskeletal disease or diabetes, psychological symptoms of repetitive wording and behavior, previous discussion about patients' intention, and believers of Taiwan folk belief are all positive influencing factors for surrogates to consent DNR directive for patients. Our findings are important in promoting DNR directive for PwD. Clinical implications: Our results may help to promote DNR decisions for dementia patients, especially in Chinese populations.

Memantine Attenuates Delayed Vasospasm after Experimental Subarachnoid Hemorrhage via Modulating Endothelial Nitric Oxide Synthase.

Delayed cerebral vasospasm is an important pathological feature of subarachnoid hemorrhage (SAH). The cause of vasospasm is multifactorial. Impairs nitric oxide availability and endothelial nitric oxide synthase (eNOS) dysfunction has been reported to underlie vasospasm. Memantine, a low-affinity uncompetitive N-methyl-d-aspartate (NMDA) blocker has been proven to reduce early brain injury after SAH. This study investigated the effect of memantine on attenuation of vasospasm and restoring eNOS functionality. Male Sprague-Dawley rats weighing 350-450 g were randomly divided into three weight-matched groups, sham surgery, SAH + vehicle, and SAH + memantine groups. The effects of memantine on SAH were evaluated by assessing the severity of vasospasm and the expression of eNOS. Memantine effectively ameliorated cerebral vasospasm by restoring eNOS functionality. Memantine can prevent vasospasm in experimental SAH. Treatment strategies may help combat SAH-induced vasospasm in the future.

Decompressive Craniectomy versus Craniotomy for Acute Subdural Hematoma: Updated meta-analysis of real-world clinical outcome after RESCUE-ASDH trial.

INTRODUCTION: The RESCUE-ASDH trial found that disability and quality-of-life outcomes were similar between craniotomy and decompressive craniectomy for traumatic acute subdural hematoma, contrasting previous literature. This meta-analysis aims to validate the applicability of RESCUE-ASDH results using real-world data in acute subdural hematoma patients. METHODS: We searched Chocrane, Embase, and MEDLINE for relevant articles reporting clinical outcomes of craniotomy and decompressive craniectomy. Meta-analysis utilized R software with the restricted maximum likelihood method for random-effects meta-analyses, presenting odds ratios and 95% confidence intervals with Hartung-Knapp-Sidik-Jonkman adjustment for heterogeneity. RESULTS: Besides RESCUE-ASDH, 5 retrospective studies were included, spanning 2006-2016. A total of 961 patients with traumatic ASDH were included in this study (Craniotomy = 467; Decompressive craniotomy = 494). The pooled analysis of retrospective studies showed no significant difference in poor clinical outcomes between the two groups (OR 0.59, 95% CI, 0.32 to 1.10). These findings align with the RESCUE-ASDH trial (OR 0.84, 95% CI, 0.58 to 1.23). Mortality rate was significant higher in patients undergoing craniectomy in pooled result of retrospective studies (OR 0.59, 95% CI, 0.32 to 1.10). In RESCUE-ASDH trial, reoperation rate was higher in the craniotomy group, but the pooled result of retrospective did not show significant difference between the craniotomy and craniectomy group. CONCLUSIONS: This real-world evidence confirms the RESCUE-ASDH trial results. Both craniotomy and decompressive craniectomy yielded similar disability and quality-of-life outcomes for traumatic acute subdural hematoma patients. LEVEL OF EVIDENCE: Level 2, Systematic and meta-analysis.

Systematic Review and Meta-analysis of Radial or Femoral Access for Carotid Stenting.

PURPOSE: There is a growing interest in performing coronary artery and neurovascular interventions via the radial artery; however, few studies have examined the outcomes of transradial carotid stenting. Therefore, our study aimed to compare cerebrovascular outcomes and crossover rates in carotid stenting between transradial and traditional transfemoral approaches. METHODS: A systematic review was performed by searching three electronic databases from inception to June 2022 in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. In addition, random effect meta-analysis was used to pool the odds ratios (ORs) for stroke, transient ischemic attack, major adverse cardiac events, death, major vascular access site complications, and procedure crossover rates between the transradial and transfemoral approaches. RESULTS: A total of 6 studies were included involving a total of n = 567 transradial and n = 6176 transfemoral procedures. The ORs for stroke, transient ischemic attack, and major adverse cardiac events were 1.43 (95% confidence interval, CI 0.72-2.86, I2 = 0), 0.51 (95% CI 0.17-1.54, I2 = 0), and 1.08 (95% CI 0.62-1.86, I2 = 0), respectively. Neither the major vascular access site complication rate (OR 1.11, 95% CI 0.32-3.87, I2 = 0) nor crossover rate (OR 3.94, 95% CI 0.62-25.11, I2 = 57%) showed statistically significant differences between the two approaches. CONCLUSION: The modest quality of the data suggested comparable procedural outcomes between the transradial and transfemoral approaches when performing carotid stenting; however, high level evidence regarding postoperative brain images and risk of stroke in transradial carotid stenting are lacking. Therefore, it is reasonable for interventionists to weigh up the risks of neurological events and potential benefits, including fewer access site complications, before choosing the radial or femoral arteries as access sites. Future large-scale randomized controlled trials are imperative.

Inhibition of Bcl-6 Expression Ameliorates Asthmatic Characteristics in Mice.

OBJECTIVE: The function of Bcl-6 in T follicular helper (Tfh) cell maturation is indispensable, and Tfh cells play a pivotal role in asthma. This study investigated the impact of Bcl-6 on asthmatic traits. METHODS: The microscopic pathological alterations, airway resistance (AR), and lung compliance (LC) were determined in asthmatic mice and Bcl-6 interference mice. The surface molecular markers of Tfh cells and the Bcl-6 mRNA and protein expression were determined by flow cytometry, RT-qPCR, and Western blotting, respectively. The relationships between the Tfh cell ratio and the IgE and IgG1 concentrations in peripheral blood mononuclear cells (PBMCs) and bronchoalveolar lavage fluid (BALF) were determined. RESULTS: Asthmatic inflammatory changes were observed in the lung tissue and were attenuated by Bcl-6 siRNA and dexamethasone (DXM). Asthmatic mice exhibited an increased AR and a decreased LC, while Bcl-6 siRNA or DXM mitigated these changes. The percentages of Tfh cells and eosinophils were significantly increased in the asthmatic mice, and they significantly decreased after Bcl-6 inhibition or DXM treatment. RT-qPCR and Western blotting analyses revealed that the Bcl-6 expression level in PBMCs was significantly higher in asthmatic mice, and it decreased following Bcl-6 inhibition or DXM treatment. The IgE expression in the serum and BALF and the B cell expression in PBMCs exhibited a similar trend. In asthmatic mice, the ratio of Tfh cells in the peripheral blood showed a strong positive correlation with the IgE levels in the serum and BALF, but not with the IgG1 levels. CONCLUSION: The amelioration of airway inflammation and airway hyper-responsiveness is achieved through Bcl-6 suppression, which effectively hinders Tfh cell differentiation, ultimately resulting in a concurrent reduction in IgE production.

Surgical excision and radiotherapy for brain metastasis from colorectal cancer: How frailty and comorbidity indices influence outcome.

The incidence of brain metastasis (BM) from colorectal cancer (CRC) is increasing. This study aims to identify the clinical prognosticators and evaluate the prognostic validity of common comorbidity indices in patients with BM from CRC. This retrospective single-center study analyzed 93 patients with BM from CRC who received surgical excision and/or radiotherapy. The clinical characteristics and prognostic indices including the 5-item modified frailty index (mFI-5) and prognostic nutritional index (PNI) were calculated from the collected patient data and analyzed. In this study, 66 (71.0%), 10 (10.8%), and 17 (18.3%) patients received whole-brain radiotherapy (WBRT) alone, surgery alone, and surgery plus WBRT, respectively. The median survival of all patients was 3.98 months (IQR: 1.74-7.99). The 2- and 3-year survival rates were 7.4% and 3.7%, respectively. Controlled primary tumor (p = 0.048), solitary BM (p = 0.001), surgery + radiation (p < 0.001), and greater PNI (p = 0.001) were independent predictors of favorable survival. In surgically treated patients, uncontrolled primary tumor (p = 0.006), presence of multiple BM (p < 0.001), and MFI-5 ≥ 2 (p = 0.038) were independent prognosticators. For patients who received WBRT, the presence of two (p = 0.004) or multiple (p < 0.001) BM and PNI (p < 0.001) were independent survival predictors MFI-5, multiple BM, and the status of the primary tumor were independent prognosticators for patients who underwent surgery for CRCBM. For patients who received WBRT, the PNI and the number of BM were independent survival predictors.

Simple coiling of middle meningeal artery embolization for chronic subdural hematoma: An inverse probability of treatment weighting matched cohort study.

BACKGROUND: Middle meningeal artery embolization (MMAE) for chronic subdural hematoma (CSDH) has gained much attention in recent years. However, unintended embolization may occur when employing liquid embolic agents or particles. We present our clinical experience in simple coiling of MMAE to manage CSDH. METHODS: Patients underwent either surgical evacuation or MMAE with simple coiling for CSDH were reviewed. Clinical and radiographic outcomes were assessed at admission, 1-month, and 6-month intervals. Two treatment groups were matched with inverse probability of treatment weighting. RESULTS: One hundred twelve patients were included, with 27 patients in MMAE group and 87 patients in surgery group. In MMAE group, significant reductions were observed in hematoma width (admission vs. 1-month, 2.04 [1.44-2.60] cm vs. 0.62 [0.37-0.95] cm, p < 0.001). The adjusted odds ratio (aOR) of surgical rescue rate (0.77 95%CI 0.13-4.47, p = 0.77), hematoma reduction (>50%) (0.21 95%CI 0.04-1.07, p = 0.06), and midline shift improvement rate (3.22, 95%CI 0.84-12.4, p = 0.09) had no substantial disparities between two groups at 1-month follow-up. In addition, no significant difference was noted between two groups in terms of hematoma reduction (>50%) at 6-month follow-up (aOR 1.09 95%CI 0.32-3.70, p = 0.89). No procedure-related complications were found in MMA embolization group. CONCLUSION: Simple coiling for MMA had comparable outcomes with surgical evacuation for CSDH. Our findings suggest that simple coiling can be an alternative choice for liquid agents or particles in MMA embolization for CSDH with acceptable safety.

Comparison of equivolume, equiosmolar solutions of mannitol and hypertonic saline with or without furosemide on brain water content in normal rats.

BACKGROUND: Mannitol and hypertonic saline (HS) are used by clinicians to reduce brain water and intracranial pressure and have been evaluated in a variety of experimental and clinical protocols. Administering equivolume, equiosmolar solutions in healthy animals could help produce fundamental data on water translocation in uninjured tissue. Furthermore, the role of furosemide as an adjunct to osmotherapy remains unclear. METHODS: Two hundred twenty isoflurane-anesthetized rats were assigned randomly to receive equivolume normal saline, 4.2% HS (1,368 mOsm/L 25% mannitol (1,375 mOsm/L), normal saline plus furosemide (8 mg/kg), or 4.2% HS plus furosemide (8 mg/kg) over 45 min. Rats were killed at 1, 2, 3, and 5 h after completion of the primary infusion. Outcome measurements included body weight; urinary output; serum and urinary osmolarity and electrolytes; and brain, lung, skeletal muscle, and small bowel water content. RESULTS: In the mannitol group, the mean water content of brain tissue during the experiment was 78.0% (99.3% CI, 77.9-78.2%), compared to results from the normal saline (79.3% [99.3% CI, 79.1-79.5%]) and HS (78.8% [99.3% CI, 78.6-78.9%]) groups (P < 0.001), whereas HS plus furosemide yielded 78.0% (99.3% CI, 77.8-78.2%) (P = 0.917). After reaching a nadir at 1 h, brain water content increased at similar rates for mannitol (0.27%/h [99.3% CI, 0.14-0.40%/h]) and HS (0.27%/h [99.3% CI, 0.17-0.37%/h]) groups (P = 0.968). CONCLUSIONS: When compared to equivolume, equiosmolar administration of HS, mannitol reduced brain water content to a greater extent over the entire course of the 5-h experiment. When furosemide was added to HS, the brain-dehydrating effect could not be distinguished from that of mannitol.

Long course hyperbaric oxygen stimulates neurogenesis and attenuates inflammation after ischemic stroke.

Several studies have provided evidence with regard to the neuroprotection benefits of hyperbaric oxygen (HBO) therapy in cases of stroke, and HBO also promotes bone marrow stem cells (BMSCs) proliferation and mobilization. This study investigates the influence of HBO therapy on the migration of BMSCs, neurogenesis, gliosis, and inflammation after stroke. Rats that sustained transient middle cerebral artery occlusion (MCAO) were treated with HBO three weeks or two days. The results were examined using a behavior test (modified neurological severity score, mNSS) and immunostaining to evaluate the effects of HBO therapy on migration of BMSCs, neurogenesis, and gliosis, and expression of neurotrophic factors was also evaluated. There was a lower mNSS score in the three-week HBO group when compared with the two-day HBO group. Mobilization of BMSCs to an ischemic area was more improved in long course HBO treatments, suggesting the duration of therapy is crucial for promoting the homing of BMSCs to ischemic brain by HBO therapies. HBO also can stimulate expression of trophic factors and improve neurogenesis and gliosis. These effects may help in neuronal repair after ischemic stroke, and increasing the course of HBO therapy might enhance therapeutic effects on ischemic stroke.

Endovascular treatment in bilateral cavernous sinus dural arteriovenous fistulas: a systematic review and meta-analysis.

Few studies have discussed the disease nature and treatment outcomes for bilateral cavernous sinus dural arteriovenous fistula (CSDAVF). This study aimed to investigate the clinical features and treatment outcomes of bilateral CSDAVF. Embase, Medline, and Cochrane library were searched for studies that specified the outcomes of bilateral CSDAVF from inception to April 2022. The classification, clinical presentation, angiographic feature, surgical approach, and treatment outcomes were collected. Meta-analysis was performed using the random effects model. Eight studies reporting 97 patients were included. The clinical presentation was mainly orbital (n = 80), cavernous (n = 52) and cerebral (n = 5) symptoms. The most approached surgical route was inferior petrosal sinus (n = 80), followed by superior orbital vein (n = 10), and alternative approach (n = 7). Clinical symptoms of 88% of the patients (95% CI 80-93%, I2 = 0%) were cured, and 82% (95% CI 70-90%, I2 = 7%) had angiographic complete obliteration of fistulas during follow up. The overall complication rate was 18% (95% CI 11-27%, I2 = 0%). Therefore, endovascular treatment is an effective treatment for bilateral CSDAVF regarding clinical or angiographic outcomes. However, detailed evaluation of preoperative images and comprehensive surgical planning of the approach route are mandatory owing to complexity of the lesions.

Quantification of vessel separation using the carotid-jugular angle to predict the nerve origin of neck peripheral nerve sheath tumours: a pooled analysis of cases from the literature and a single-center cohort.

BACKGROUND: Postoperative nerve palsy is a major complication following resection of neck peripheral nerve sheath tumours (PNSTs). Accurate preoperative identification of the nerve origin (NO) can improve surgical outcomes and patient counselling. MATERIAL AND METHODS: This study was a retrospective cohort and quantitative analysis of the literature. The authors introduced a parameter, the carotid-jugular angle (CJA), to differentiate the NO. A literature review of neck PNST cases from 2010 to 2022 was conducted. The CJA was measured from eligible imaging data, and quantitative analysis was performed to evaluate the ability of the CJA to predict the NO. External validation was performed using a single-centre cohort from 2008 to 2021. RESULTS: In total, 17 patients from our single-centre cohort and 88 patients from the literature were analyzed. Among them, 53, 45, and 7 patients had sympathetic, vagus, and cervical nerve PNSTs, respectively. Vagus nerve tumours had the largest CJA, followed by sympathetic tumours, whereas cervical nerve tumours had the smallest CJA ( P <0.001). Multivariate logistic regression identified a larger CJA as a predictor of vagus NO ( P <0.001), and receiver operating characteristic (ROC) analysis showed an area under the curve (AUC) of 0.907 (0.831-0.951) for the CJA to predict vagus NO ( P <0.001). External validation showed an AUC of 0.928 (0.727-0.988) ( P <0.001). Compared with the AUC of the previously proposed qualitative method (AUC=0.764, 0.673-0.839), that of the CJA was greater ( P =0.011). The cut-off value identified to predict vagus NO was greater than or equal to 100°. Receiver operating characteristic analysis showed an AUC of 0.909 (0.837-0.956) for the CJA to predict cervical NO ( P <0.001), with a cut-off value less than 38.5°. CONCLUSIONS: A CJA greater than or equal to 100° predicted a vagus NO and a CJA less than 100° predicted a non-vagus NO. Moreover, a CJA less than 38.5 was associated with an increased likelihood of cervical NO.

Population based study on patients with traumatic brain injury suggests increased risk of dementia.

OBJECTIVE: The relationship between traumatic brain injury (TBI) and the risk of dementia remains controversial. This population based study was designed to estimate and compare the risk of dementia in TBI and non-TBI individuals during the 5 year period after TBI. METHODS: This study was a retrospective cohort study. Data were obtained from the Longitudinal Health Insurance Database 2000. We included 44,925 patients receiving ambulatory or hospital care and 224,625 non-TBI patients; patients were matched for sex, age and year of index use of healthcare. Patients <15 years of age and those admitted to the intensive care unit were excluded. Each individual was studied for 5 years to identify the subsequent development of dementia. Data were analysed by Cox proportional hazard regression. RESULTS: During the 5 year follow-up period, 1196 TBI (2.66%) and 224,625 non-TBI patients (1.53%) patients developed dementia. During the 5 year follow-up period, TBI was independently associated with a 1.68 (range 1.57-1.80) times greater risk of dementia after adjusting for sociodemographic characteristics and selected comorbidities. CONCLUSIONS: The findings of this study suggest an increased risk of dementia among individuals with TBI. We suggest the need for more intensive medical monitoring and health education in individuals with TBI.

Short-Term Cortical Electrical Stimulation during the Acute Stage of Traumatic Brain Injury Improves Functional Recovery.

Functional restoration is an important issue in the treatment of traumatic brain injury (TBI). Various electrical stimulation devices and protocols have been applied in preclinical studies and have shown therapeutic potential for brain trauma. Short-term invasive cortical electrical stimulation during the acute stage of TBI might be a feasible adjuvant therapy for patients with moderate-to-severe brain injury receiving neurosurgical treatment in the intensive care unit. However, the therapeutic effects of short-term multisession cortical electrical stimulation for brain trauma are not clear. This study explored the therapeutic effects of acute-stage short-term cortical electrical stimulation on TBI. We conducted seven sessions of one-hour cortical electrical stimulation from day 0 to day 6 in rats after brain trauma by controlled cortical impact and then evaluated the functional outcome and histopathological changes. Our data showed that short-term cortical electrical stimulation improved motor coordination, short-term memory, and learning ability and attenuated neurological severity after brain trauma. Lesion volume, apoptosis, and gliosis after brain trauma were reduced, and trauma-induced neurogenesis in the hippocampus for the innate neural reparative response was increased. Our study demonstrated that short-term cortical electrical stimulation applied in the acute stage of traumatic brain injury is a potential adjuvant therapy to improve the recovery of neurological deficits.

Somatosensory Cortical Electrical Stimulation After Reperfusion Attenuates Ischemia/Reperfusion Injury of Rat Brain.

Objective: Ischemic stroke is an important cause of death and disability worldwide. Early reperfusion by thrombolysis or thrombectomy has improved the outcome of acute ischemic stroke. However, the therapeutic window for reperfusion therapy is narrow, and adjuvant therapy for neuroprotection is demanded. Electrical stimulation (ES) has been reported to be neuroprotective in many neurological diseases. In this study, the neuroprotective effect of early somatosensory cortical ES in the acute stage of ischemia/reperfusion injury was evaluated. Methods: In this study, the rat model of transient middle cerebral artery occlusion was used to explore the neuroprotective effect and underlying mechanisms of direct primary somatosensory (S1) cortex ES with an electric current of 20 Hz, 2 ms biphasic pulse, 100 µA for 30 min, starting at 30 min after reperfusion. Results: These results showed that S1 cortical ES after reperfusion decreased infarction volume and improved functional outcome. The number of activated microglia, astrocytes, and cleaved caspase-3 positive neurons after ischemia/reperfusion injury were reduced, demonstrating that S1 cortical ES alleviates inflammation and apoptosis. Brain-derived neurotrophic factor (BDNF) and phosphoinositide 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) signaling pathway were upregulated in the penumbra area, suggesting that BDNF/TrkB signals and their downstream PI3K/Akt signaling pathway play roles in ES-related neuroprotection. Conclusion: This study demonstrates that somatosensory cortical ES soon after reperfusion can attenuate ischemia/reperfusion injury and is a promising adjuvant therapy for thrombolytic treatment after acute ischemic stroke. Advanced techniques and devices for high-definition transcranial direct current stimulation still deserve further development in this regard.