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Objectives: This study was designed and conducted to compare the neurological and neuropsychological functions of depressed patients with and without suicidal thoughts. Methods: This research is a case-comparative study. A group of depressed patients visited NAJA Imam Sajjad Hospital between early August and late October 2016. According to the Morgan table, 66 individuals (33 with suicidal thoughts and 33 without) were selected for comparison with controlled variables in this examination. The Beck Depression Inventory (BDI), Neurological Evaluation Scale, and Wechsler Memory Scale (for neuropsychological function) were administered to all the participants. Data were analyzed using one-way analysis of variance (ANOVA), Scheffe follow-up test, and SPSS version 22 software. Results: The findings indicated that the group of depressed patients with suicidal thoughts showed poorer scores in neurological functions compared to the control group (P = 0.01). Furthermore, the control group scored higher than the depressed group with suicidal thoughts on the Wechsler Memory Scale (P = 0.05). Conclusions: The results suggest that depressed patients with suicidal thoughts exhibit worse performance in both neurological and neuropsychological functions compared to the non-suicidal group. [ABSTRACT FROM AUTHOR]

Central neurocytomas (CNs) usually occur in young adults, and the clinical characteristics and surgical outcomes of patients in different age groups may be different. This study was undertaken to compare the clinical and long-term treatment outcomes of patients with CNs in younger and older adult age groups. Eighty consecutive adults with CNs were included, with a mean presentation age of 28.4 ± 7.6 years (range: 19–66 years). Thirty (37.5%) patients were <27 years old, and they tended to manifest with multiple symptoms (P = 0.002), increased intracranial pressure (ICP) symptoms (P = 0.036), an acute clinical course (P = 0.037), worse preoperative neurologic function (P = 0.023), and a larger lesion size and volume (P = 0.004 and 0.007, respectively) than their older age counterparts (≧27 years). An older onset age (P = 0.005) or age ≧27 years (P = 0.014) and worsened Karnofsky Performance Status (KPS) scale (P = 0.040) immediately after microsurgery were associated with unimproved long-term outcomes. CNs in younger adult patients behave differently from those in the older age group. Surgery can halt neurologic deterioration and ensure satisfactory outcomes. [ABSTRACT FROM AUTHOR]

Motor disturbances predominantly characterize hypoxic-ischemic encephalopathy (HIE). Among its intervention methods, environmental enrichment (EE) is strictly considered a form of sensory intervention. However, limited research uses EE as a single sensory input intervention to validate outcomes postintervention. A Sprague–Dawley rat model subjected to left common carotid artery ligation and exposure to oxygen-hypoxic conditions is used in this study. EE was achieved by enhancing the recreational and stress-relief items within the cage, increasing the duration of sunlight, colorful items exposure, and introducing background music. JZL184 (JZL) was administered as neuroprotective drugs. EE was performed 21 days postoperatively and the rats were randomly assigned to the standard environment and EE groups, the two groups were redivided into control, JZL, and vehicle injection subgroups. The Western blotting and behavior test indicated that EE and JZL injections were efficacious in promoting cognitive function in rats following HIE. In addition, the motor function performance in the EE-alone intervention group and the JZL-alone group after HIE was significantly improved compared with the control group. The combined EE and JZL intervention group exhibited even more pronounced improvements in these performances. EE may enhance motor function through sensory input different from the direct neuroprotective effect of pharmacological treatment. NEW & NOTEWORTHY: Rarely does literature assess motor function, even though it is common after hypoxia ischemic encephalopathy (HIE). Previously used environmental enrichment (EE) components have not been solely used as sensory inputs. Physical factors were minimized in our study to observe the effects of purely sensory inputs. [ABSTRACT FROM AUTHOR]

Background We assess the effects of standard decompressive craniectomy with stepwise decompression of the intracranial compartment on the postoperative neurologic function, hemodynamics, and Glasgow Outcome Scale (GOS) score of patients with severe traumatic brain injury (sTBI). Methods One hundred sTBI patients admitted from July 2017 to February 2019 were enrolled and randomly divided into step and standard groups (n = 50) using a random number table. The standard group received traditional standard decompression during surgery, while the step group underwent multistep decompression during surgery. Heart rate (HR), systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean arterial pressure (MAP) were measured immediately after surgery (T0), 3 hours after surgery (T1), 6 hours after surgery (T2), and 12 hours after surgery (T3). The postoperative Glasgow Coma Scale (GCS) score, neurologic function deficit score, and GOS score were evaluated. Results After treatment, the excellent/good rate of neurologic function improvement and GCS and GOS scores of the step group significantly exceeded those of the standard group (p < 0.05). Compared with the standard group, the HR, SBP, DBP, and MAP decreased significantly in the step group at T1, T2, and T3 (p < 0.05). Conclusion Standard decompressive craniectomy under multistep decompression can markedly improve the neurologic function, hemodynamics, and prognosis of patients. [ABSTRACT FROM AUTHOR]

The current animal models of stroke primarily model a single intracerebral hemorrhage (ICH) attack, and there is a lack of a reliable model of recurrent ICH. In this study, we established 16-month-old C57BL/6 male mouse models of ICH by injecting collagenase VII-S into the left striatum. Twenty-one days later, we injected collagenase VII-S into the right striatum to simulate recurrent ICH. Our results showed that mice subjected to bilateral striatal hemorrhage had poorer neurological function at the early stage of hemorrhage, delayed recovery in locomotor function, motor coordination, and movement speed, and more obvious emotional and cognitive dysfunction than mice subjected to unilateral striatal hemorrhage. These findings indicate that mouse models of bilateral striatal hemorrhage can well simulate clinically common recurrent ICH. These models should be used as a novel tool for investigating the pathogenesis and treatment targets of recurrent ICH.

Microglia, the main immune effector cells in the central nervous system, play a dual role in the function/structure of the blood–brain barrier (BBB) and brain health. During and soon after a cerebral ischemic injury, microglia produce neurotrophic factors and neurotoxins that can impact on the injury itself and pathology progression. At the same time, microglia undergo polarization to M1 or M2 pro- vs. anti-inflammatory subtypes that also help drive the outcome of the injury process. Thus, agents that can mitigate cerebral ischemic injury progression, promote protective functions of microglia, and help maintain BBB and overall brain health/host neurologic function after a cerebral ischemic event would be of great use in clinical settings. Protective effects from gallic acid (GA) in cerebral ischemia/re-perfusion-induced injury to the BBB and other sites in the brain have not yet been assessed. To address this, a middle cerebral artery occlusion (MCAO) method was used to establish an experimental ischemic stroke model in mice. Mice were placed in sham operation (Sham), model (MCAO), MCAO + GA (50 mg/kg), MCAO + GA (100 mg/kg), or MCAO + GA (150 mg/kg) groups. At various times post-stroke, cerebral infarct volume and host neurological function were evaluated. In addition, qRT-PCR, Western blotting, and ELISA were used to evaluate the expression and tissue content of microglia-related factors. The results showed GA treatment protected the integrity of the BBB, significantly reduced brain edema, and helped lead to improved neurological function scores in the MCAO mice. Whether these changes were due to that GA attenuated cerebral ischemia/re-perfusion-induced activation of microglial cells overall, in part, by inhibiting their polarization to the M1 subtype, is uncertain. Taking these outcomes together, for now it is reasonable to suggest that use of GA either as a prophylactic or immediately in the event of a cerebral ischemic event/stroke could help to promote neuronal survival and allow for a more likely of host neurological function over time.

Purpose: Indication for surgical decompression in metastatic spinal cord compression (MSCC) is often based on prognostic scores such as the modified Bauer score (mBs), with favorable prognosis suggestive of surgery and poor prognosis of non-surgical management. This study aimed to clarify if (1) surgery may directly affect overall survival (OS) aside from short-term neurologic outcome, (2) explore whether selected patient subgroups with poor mBs might still benefit from surgery, and (3) gauge putative adverse effects of surgery on short-term oncologic outcomes. Methods: Single-center propensity score analyses with inverse-probability-of-treatment-weights (IPTW) of OS and short-term neurologic outcomes in MSCC patients treated with or without surgery between 2007 and 2020. Results: Among 398 patients with MSCC, 194 (49%) underwent surgery. During a median follow-up of 5.8 years, 355 patients (89%) died. MBs was the most important predictor for spine surgery (p < 0.0001) and the strongest predictor of favorable OS (p < 0.0001). Surgery was associated with improved OS after accounting for selection bias with the IPTW method (p = 0.021) and emerged as the strongest determinant of short-term neurological improvement (p < 0.0001). Exploratory analyses delineated a subgroup of patients with an mBs of 1 point who still benefited from surgery, and surgery did not result in a higher risk of short-term oncologic disease progression. Conclusion: This propensity score analysis corroborates the concept that spine surgery for MSCC associates with more favorable neurological and OS outcomes. Selected patients with poor prognosis might also benefit from surgery, suggesting that even those with low mBs may be considered for this intervention. [ABSTRACT FROM AUTHOR]

Modulators of the sphingosine-1-phosphate receptor (S1PR) have been proposed as a promising strategy for treating stroke. However, the detailed mechanisms and the potential translational value of S1PR modulators for intracerebral hemorrhage (ICH) therapy warrant exploration. Using collagenase VII-S-induced ICH in the left striatum of mice, we investigated the effects of siponimod on cellular and molecular immunoinflammatory responses in the hemorrhagic brain in the presence or absence of anti-CD3 monoclonal antibodies (Abs). We also assessed the severity of short- and long-term brain injury and evaluated the efficacy of siponimod in long-term neurologic function. Siponimod treatment significantly decreased brain lesion volume and brain water content on day 3 and the volume of the residual lesion and brain atrophy on day 28. It also inhibited neuronal degeneration on day 3 and improved long-term neurologic function. These protective effects may be associated with a reduction in the expression of lymphotactin (XCL1) and T-helper 1 (Th1)-type cytokines (interleukin 1β and interferon-γ). It may also be associated with inhibition of neutrophil and lymphocyte infiltration and alleviation of T lymphocyte activation in perihematomal tissues on day 3. However, siponimod did not affect the infiltration of natural killer cells (NK) or the activation of CD3-negative immunocytes in perihematomal tissues. Furthermore, it did not influence the activation or proliferation of microglia or astrocytes around the hematoma on day 3. Siponimod appears to have a profound impact on infiltration and activation of T lymphocytes after ICH. The effects of neutralized anti-CD3 Abs-induced T-lymphocyte tolerance on siponimod immunomodulation further confirmed that siponimod alleviated the cellular and molecular Th1 response in the hemorrhagic brain. This study provides preclinical evidence that encourages future investigation of immunomodulators, including siponimod, which target the lymphocyte-related immunoinflammatory reaction in ICH therapy. [ABSTRACT FROM AUTHOR]

Study Design: Multi-center, prospective, observational cohort. Objective: To compare myelopathic vs. non-myelopathic ambulatory patients in short- and long-term neurologic function, operative treatment, and patient-reported outcomes. Methods: Pediatric deformity patients from 16 centers were enrolled with the following inclusion criteria: aged 10-21 years-old, a Cobb angle ≥100° in either the coronal or sagittal plane or any sized deformity with a planned 3-column osteotomy, and community ambulators. Patients were dichotomized into 2 groups: myelopathic (abnormal preoperative neurologic exam with signs/symptoms of myelopathy) and non-myelopathic (no clinical signs/symptoms of myelopathy). Results: Of 311 patients with an average age of 14.7 ± 2.8 years, 29 (9.3%) were myelopathic and 282 (90.7%) were non-myelopathic. There was no difference in age (P = 0.18), gender (P = 0.09), and Risser Stage (P = 0.06), while more patients in the non-myelopathic group had previous surgery (16.1% vs. 3.9%; P = 0.03). Mean lower extremity motor score (LEMS) in myelopathic patients increased significantly compared to baseline at every postoperative visit: Baseline: 40.7 ± 9.9; Immediate postop: 46.0 ± 7.1, P = 0.02; 1-year: 48.2 ± 3.7, P < 0.001; 2-year: 48.2 ± 7.7, P < 0.001). The non-myelopathic group had significantly higher LEMS immediately postoperative (P = 0.0007), but by 1-year postoperative, there was no difference in LEMS between groups (non-myelopathic: 49.3 ± 3.6, myelopathic: 48.2 ± 3.7, P = 0.10) and was maintained at 2-years postoperative (non-myelopathic: 49.2 ± 3.3, myelopathic: 48.2 ± 5.7, P = 0.09). Both groups improved significantly in all SRS domains compared to preoperative, with no difference in scores in the domains for pain (P = 0.12), self-image (P = 0.08), and satisfaction (P = 0.83) at latest follow-up. Conclusion: In severe spinal deformity pediatric patients presenting with preoperative myelopathy undergoing spinal reconstructive surgery, myelopathic patients can expect significant improvement in neurologic function postoperatively. At 1-year and 2-year postoperative, neurologic function was no different between groups. While non-myelopathic patients had significantly higher postoperative outcomes in SRS mental-health, function, and total-score, both groups had significantly improved outcomes in every SRS domain compared to preoperative. [ABSTRACT FROM AUTHOR]

Microglia, the main immune effector cells in the central nervous system, play a dual role in the function/structure of the blood–brain barrier (BBB) and brain health. During and soon after a cerebral ischemic injury, microglia produce neurotrophic factors and neurotoxins that can impact on the injury itself and pathology progression. At the same time, microglia undergo polarization to M1 or M2 pro- vs. anti-inflammatory subtypes that also help drive the outcome of the injury process. Thus, agents that can mitigate cerebral ischemic injury progression, promote protective functions of microglia, and help maintain BBB and overall brain health/host neurologic function after a cerebral ischemic event would be of great use in clinical settings. Protective effects from gallic acid (GA) in cerebral ischemia/re-perfusion-induced injury to the BBB and other sites in the brain have not yet been assessed. To address this, a middle cerebral artery occlusion (MCAO) method was used to establish an experimental ischemic stroke model in mice. Mice were placed in sham operation (Sham), model (MCAO), MCAO + GA (50 mg/kg), MCAO + GA (100 mg/kg), or MCAO + GA (150 mg/kg) groups. At various times post-stroke, cerebral infarct volume and host neurological function were evaluated. In addition, qRT-PCR, Western blotting, and ELISA were used to evaluate the expression and tissue content of microglia-related factors. The results showed GA treatment protected the integrity of the BBB, significantly reduced brain edema, and helped lead to improved neurological function scores in the MCAO mice. Whether these changes were due to that GA attenuated cerebral ischemia/re-perfusion-induced activation of microglial cells overall, in part, by inhibiting their polarization to the M1 subtype, is uncertain. Taking these outcomes together, for now it is reasonable to suggest that use of GA either as a prophylactic or immediately in the event of a cerebral ischemic event/stroke could help to promote neuronal survival and allow for a more likely of host neurological function over time. [ABSTRACT FROM AUTHOR]

Asphyxial cardiac arrest (ACA) survivors face lasting neurological disability from hypoxic ischemic brain injury. Sex differences in long-term outcomes after cardiac arrest (CA) are grossly understudied and underreported. We used rigorous targeted temperature management (TTM) to understand its influence on survival and lasting sex-specific neurological and neuropathological outcomes in a rodent ACA model. Adult male and female rats underwent either sham or 5-minute no-flow ACA with 18 hours TTM at either ∼37°C (normothermia) or ∼36°C (mild hypothermia). Survival, temperature, and body weight (BW) were recorded over the 14-day study duration. All rats underwent neurological deficit score (NDS) assessment on days 1-3 and day 14. Hippocampal pathology was assessed for cell death, degenerating neurons, and microglia on day 14. Although ACA females were less likely to achieve return of spontaneous circulation (ROSC), post-ROSC physiology and biochemical profiles were similar between sexes. ACA females had significantly greater 14-day survival, NDS, and BW recovery than ACA males at normothermia (56% vs. 29%). TTM at 36°C versus 37°C improved 14-day survival in males, producing similar survival in male (63%) versus female (50%). There were no sex or temperature effects on CA1 histopathology. We conclude that at normothermic conditions, sex differences favoring females were observed after ACA in survival, NDS, and BW recovery. We achieved a clinically relevant ACA model using TTM at 36°C to improve long-term survival. This model can be used to more fully characterize sex differences in long-term outcomes and test novel acute and chronic therapies.

BackgroundAcupuncture has proved effective in reducing inflammatory cytokine levels. However, it is still unclear about its improvement on the neurologic function and activities of daily living as well as over all clinical efficacy in patients with acute ischemic stroke.ObjectiveTo explore the effects of acupuncture as an adjuvant therapy for intravenous thrombolytic treatment on peripheral inflammatory cytokines and neurologic function in acute ischemic stroke patients.MethodsAcute ischemic stroke patients who were treated in Hai'an Traditional Chinese Medicine Hospital from March 2018 to March 2021 were selected, and divided into a control group (intravenous thrombolytic treatment with urokinase and ulinastatin) and an acupuncture group (intravenous thrombolytic treatment with urokinase and ulinastatin and acupuncture) by the order of admission. The treatment for both groups lasted for four consecutive weeks. The levels of peripheral CRP, TNF-α, IL-1β, IL-6, and IL-8 were compared at baseline, two and four weeks of treatment between the groups. Activities of Daily Living Scale (ADL) and NIH Stroke Scale (NIHSS) were used to assess pre- and post-treatment activities of daily living and neurologic function, respectively. Clinical efficacy was evaluated.ResultsA total of 324 patients were included, equally divided into control and acupuncture groups. Both groups had no significant differences in sex ratio, mean age, time interval between symptom onset, the first medical visit, incidence of hypertension, diabetes mellitus and hyperlipidemia (P>0.05) . The levels of peripheral CRP, TNF-α, IL-1β, IL-6 and IL-8 demonstrated no significant intergroup differences at baseline (P>0.05) , but they decreased more obviously at two and four weeks of treatment in the acupuncture group (P0.05) , but ADL score increased and NIHSS score decreased significantly in acupuncture group at four weeks of treatment (P

Aim: Our aim was to determine the association of cardiopulmonary resuscitation (CPR) for in hospital cardiac arrest (IHCA) with quality of life after discharge.Methods: We performed a systematic review using available databases for studies that measured any quality-of-life or functional outcome both before and after CPR for IHCA. All screening and data abstraction was performed in duplicate.Results: We screened 10,927 records and included 24 papers representing 20 unique studies. Fifteen studies measured Cerebral Performance Category. Survival ranged from 11.8% to 39.5%. The risk of impaired cerebral function after discharged ranged from -16.1% (lower risk) to 44.7% increased risk of poor cerebral function after surviving to discharge. Four studies measured discharge to an institutional environment finding that the risk was increased by 18.2-72.2% among survivors. One study measured EQ-5D and found no difference pre and post CPR. One study measured performance of activities of daily living finding that survivors needed assistance with more activities after discharge.Conclusion: Our review is limited by the lack of adjustment for confounders, including the baseline level of each outcome, in all included studies. Therefore, although risk for most outcomes was increased after discharge vs pre-admission we cannot be certain if this is a causal relationship. [ABSTRACT FROM AUTHOR]

Yunpeng Cui,1 Xuedong Shi,1 Chunwei Li,2 Chuan Mi,1 Bing Wang,1 Yuanxing Pan,1 Yunfei Lin1 1Department of Orthopaedics, Peking University First Hospital, Beijing, People’s Republic of China; 2Department of Neurosurgery, Peking University First Hospital, Beijing, People’s Republic of ChinaCorrespondence: Xuedong ShiDepartment of Orthopedic, Peking University First Hospital, No. 7 Xishiku Street, Xicheng District, Beijing, 100032, People’s Republic of ChinaTel +86 10-83575660Email pku_ortho@163.comObjective: This study aimed to investigate the effect of timing of surgery on neurological recovery for patients with metastatic spinal cord compression (MSCC).Methods: According to the timing of surgery, 75 patients with incomplete paraplegia caused by MSCC were assigned to 3 groups: within 3 days (group A), between 4 days and 7 days (group B), and after 7 days (group C). T-test, one-way ANOVA, Mann–Whitney U-test, and Chi-square test were used to evaluate the difference in the improvement of American Spinal Injury Association Impairment Scale (AIS) and ambulatory status, the incidence of perioperative complications, surgical site infection, and the length of hospital stay between 3 groups.Results: Patients with incomplete paraplegia treated in our department had an average of 17.4± 1.8 days delayed and most occurred before hospitalization (4.0± 0.4 vs 13.2± 1.8, P< 0.001). There was no significant difference in the AIS improvement between patients with different pre-op AIS. The timing of surgery was significantly correlated with AIS improvement (correlation coefficient=− 0.257, P=0.019). Sub-analysis showed that patients who underwent surgery within 7 days (group A and group B) had significantly better AIS improvement compared with group C (improved at least 1 grade, P=0.043; improved more than 1 grade, P=0.039) and the surgery timing was more important for patients with AIS B and C. The timing of surgery was significantly correlated with the length of hospital stay (correlation coefficient=0.335, P=0.003). Patients of group C had the longest length of hospital stay (P=0.002). The incidence of perioperative complications and surgical site infection did not differ significantly between the 3 groups.Conclusion: Delay surgery was common in incomplete paraplegia patients with MSCC. Patients with AIS B and C who underwent surgery within 7 days had better AIS improvement.Keywords: timing of surgery, metastatic spinal cord compression, incomplete paraplegia, neurologic function

Extracorporeal membrane oxygenation (ECMO) is a superior life support technology, commonly employed in critical patients with severe respiratory or hemodynamic failure to provide effective respiratory and circulatory support, which is especially recommended for the treatment of critical neonates. However, the vascular management of neonates with veno-arterial extracorporeal membrane oxygenation (VA-ECMO) is still under controversy. Reconstruction or ligation for the right common carotid artery (RCCA) after ECMO is inconclusive. This review summarized the existed studies on hemodynamics and neurological function after vascular ligation or reconstruction hoping to provide better strategies for vessel management in newborns after ECMO. After reconstruction, the right cerebral blood flow can increase immediately, and the normal blood supply can be restored rapidly. But the reconstructed vessel may be occluded and stenotic in long-term follow-ups. Ligation may cause lateralization damage, but there could be no significant effect owing to the establishment of collateral circulation. The completion of the circle of Willis, the congenital anomalies of cerebral or cervical vasculature, the duration of ECMO, and the vascular condition at the site of arterial catheterization should be assessed carefully before making the decision. It is also necessary to follow up on the reconstructed vessel sustainability, and the association between cerebral hemodynamics and neurological function requires further large-scale multi-center studies.

Abstract Background To investigate the clinical efficacy and therapeutic value of posterior decompression reduction, bone grafting fusion, and internal fixation for treatment of symptomatic old thoracolumbar fractures. Method Retrospective analysis was conducted for 14 patients (9 men, 5 women; average age 40.1 years) with old thoracolumbar fractures who underwent posterior operation. American Spinal Injury Association (ASIA) scores were used to evaluate neurologic function. Vertebral body height, Cobb angle in the sagittal plane, spinal canal volume ratio (%) and bone graft fusion were analyzed by radiography and computed tomography on different follow-up times. Results Mean follow-up was 27.1 months (23–36 months). Of three patients with ASIA grade A, 2 had improved postoperative urination and defecation, although no classification change. Preoperative ASIA score for eight patients with incomplete injury was grade B; four patients recovered to grade C at final follow-up. Preoperative ASIA score was C in three patients, increased to D in two patients and returned to normal E in one patient. Preoperative results showed average injured vertebra height loss rate decreased from 50.4 to 8.9%; average Cobb angle on the sagittal plane recovered from 39.6 to 6.9°; and the average spinal canal volume ratio recovered from 33.8 to 5.9%. Bony fusion was achieved; local lumbago and leg pain were relieved to some extent. No patients exhibited loosening of the fracture treated by internal fixation, pseudoarthrosis, or other related serious complications. Conclusion Treatment of old thoracolumbar fractures by posterior decompression reduction, bone grafting fusion, and internal fixation can relieve spinal cord compression, improve neurologic function of some patients (ASIA grades B–C), effectively relieve pain, correct deformity, restore biomechanical stability, and significantly improve quality of life.

Background: Although relatively infrequent, neurological injury is a much dreaded complication in spine surgery and has the potential to result in serious postoperative motor and sensory deficits. As a result of these surgical challenges, intraoperative neuromonitoring (IONM) has gained favorable grounds in facilitating maximal tumor resection andminimizing neurologicmorbidity. Aim and Objectives: to review the efficacy of intraoperative neurophysiological monitoring (IONM) on post operative outcomes preventing neurological injury, predicting post operative neurological deficit and its effect on intraoperative surgeon's decision making, and to know if it is beneficial or not in intramedullary spinal cord tumors surgeries in adults. Subjects and Methods: This was observational studies and non randomized controlled studies. our patients were followed up according to this schedule (immediate post operative, first day, three days, first month, three months, six months, one year post operative) and the assessment were done by using Oxford grading system. Result: Regarding neurological status by clinical examination at last follow up, Improved in 72, transient worsening in no cases, no change in 12 cases and progression in 17 cases, Conclusion. Conclusion: our systematic review of the literature indicates that there is strong evidence that multimodality neuromonitoring is sensitive and specific for detecting intraoperative neurologic injury during spine surgery. Although the level of evidence supporting the conclusion that intraoperative neuromonitoring reduces the rate of new or worsening neurologic deficits is low, the available evidence does consistently support this conclusion. [ABSTRACT FROM AUTHOR]

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Background: To explore the effects of predictive nursing intervention among patients with acute stroke. Methods: One hundred and sixty participants were included. They were hospitalized in the Department of Neurology of a third-level first-class hospital in Changsha, Hunan Province, from January to August 2019. They were categorized into control group and intervention group by random number table, with 80 patients in each group. General nursing for patients in Neurology Department was offered to the control group. On the basis of general nursing, predictive nursing intervention was offered to the intervention group. The effectiveness of predictive nursing intervention were evaluated by disparity in neurologic function, movement function, daily life ability and sleep quality before intervention and 2 weeks after intervention. The neurologic function, movement function, daily life ability and sleep quality were evaluated by National Institute of Health acute stroke scale (NIHSS), Fugl-Meyer scale, Barthel indicator, and Pittsburgh sleep quality indicator (PSQI), respectively. Results: There was no significant difference in gender, age, complications and treatment methods between two groups. There was no significant difference in the scores of NIHSS, Fugl-Meyer scale, Barthel indicator, and PSQI before intervention. The scores of NIHSS and PSQI were significantly lower in the intervention group than those in the control group, and the scores of Fugl-Meyer scale and Barthel indicator were significantly higher in the intervention group than those in the control group (P

Background: Targeted temperature management (TTM) improves neurologic outcome after cardiac arrest. However, better neurologic prognostication is needed.Objective: The purpose of this study was to test the hypothesis that noninvasive recording of skin sympathetic nerve activity (SKNA) and its association with heart rate (HR) during TTM may serve as a biomarker of neurologic status.Methods: SKNA recordings were analyzed from 29 patients undergoing TTM. Patients were grouped based on Clinical Performance Category (CPC) score into group 1 (CPC 1-2) representing a good neurologic outcome and group 2 (CPC 3-5) representing a poor neurologic outcome.Results: Of the 29 study participants, 18 (62%) were deemed to have poor neurologic outcome. At all timepoints, low average skin sympathetic nerve activity (aSKNA) was associated with poor neurologic outcome (odds ratio 22.69; P = .002) and remained significant (P = .03) even when adjusting for presenting clinical factors. The changes in aSKNA and HR during warming in group 1 were significantly correlated (ρ = 0.49; P <.001), even when adjusting for corresponding temperature and mean arterial pressure measurements (P = .017), whereas this correlation was not observed in group 2. Corresponding to high aSKNA, there was increased nerve burst activity during warming in group 1 compared to group 2 (0.739 ± 0.451 vs 0.176 ± 0.231; P = .013).Conclusion: Neurologic recovery was retrospectively associated with SKNA. Patients undergoing TTM who did not achieve neurologic recovery were associated with low SKNA and lacked a significant correlation between SKNA and HR. These preliminary results indicate that SKNA may potentially be a useful biomarker to predict neurologic status in patients undergoing TTM. [ABSTRACT FROM AUTHOR]

Background: To investigate the clinical efficacy and therapeutic value of posterior decompression reduction, bone grafting fusion, and internal fixation for treatment of symptomatic old thoracolumbar fractures.Method: Retrospective analysis was conducted for 14 patients (9 men, 5 women; average age 40.1 years) with old thoracolumbar fractures who underwent posterior operation. American Spinal Injury Association (ASIA) scores were used to evaluate neurologic function. Vertebral body height, Cobb angle in the sagittal plane, spinal canal volume ratio (%) and bone graft fusion were analyzed by radiography and computed tomography on different follow-up times.Results: Mean follow-up was 27.1 months (23-36 months). Of three patients with ASIA grade A, 2 had improved postoperative urination and defecation, although no classification change. Preoperative ASIA score for eight patients with incomplete injury was grade B; four patients recovered to grade C at final follow-up. Preoperative ASIA score was C in three patients, increased to D in two patients and returned to normal E in one patient. Preoperative results showed average injured vertebra height loss rate decreased from 50.4 to 8.9%; average Cobb angle on the sagittal plane recovered from 39.6 to 6.9°; and the average spinal canal volume ratio recovered from 33.8 to 5.9%. Bony fusion was achieved; local lumbago and leg pain were relieved to some extent. No patients exhibited loosening of the fracture treated by internal fixation, pseudoarthrosis, or other related serious complications.Conclusion: Treatment of old thoracolumbar fractures by posterior decompression reduction, bone grafting fusion, and internal fixation can relieve spinal cord compression, improve neurologic function of some patients (ASIA grades B-C), effectively relieve pain, correct deformity, restore biomechanical stability, and significantly improve quality of life. [ABSTRACT FROM AUTHOR]

Intradural extramedullary spinal cord tumors (ID-EMSCT) make up 40% of all spinal neoplasms. Resection of these tumors is mostly conducted using intraoperative neuromonitoring (IONM). However, the literature shows heterogenous data on its added value for ID-EMSCT. The aim of this study is to define sensitivity and specificity of IONM in ID-EMSCT resection and to study possible correlations between preoperative, intraoperative, and postoperative variables and neurologic outcomes after ID-EMSCT resection. Data of patients undergoing ID-EMSCT surgeries with IONM from January 2012 until July 2019 were examined. Using neurologic status 6 weeks and 1 year postoperatively, sensitivity and specificity for IONM were calculated. IONM test results and neurologic outcomes were paired to preoperative, intraoperative, and postoperative parameters. Data of 78 patients were analyzed. 6 weeks postoperatively, 14.10% of patients had worse neurologic status, decreasing to 9.84% 1 year postoperatively. Multimodal IONM showed a sensitivity of 0.73 (95% confidence interval [CI], 0.39–0.94) and a specificity of 0.78 (95% CI, 0.66–0.87) after 6 weeks, and a sensitivity of 1.00 (95% CI, 0.54–1.00) and a specificity of 0.71 (95% CI, 0.57–0.82) after 1 year. IONM yielded high to perfect sensitivity and high specificity. However, IONM signals did not always determine the extent of resection, and false-positive results did not always result in incomplete tumor resections, because of surgeons overruling IONM. Therefore, IONM cannot fully replace clinical judgment and other perioperative information. [ABSTRACT FROM AUTHOR]

Rami A El Shafie,1,2 Karina Böhm,1,2 Dorothea Weber,3 Kristin Lang,1,2 Fabian Schlaich,1,2 Sebastian Adeberg,1,2 Angela Paul,1,2,4 Matthias F Haefner,1,2 Sonja Katayama,1,2 Florian Sterzing,1,2,5 Juliane Hörner-Rieber,1,2 Sarah Löw,6 Klaus Herfarth,1,2,4 Jürgen Debus,1,2,4,7 Stefan Rieken,1,2,4 Denise Bernhardt1,2 1Department of Radiation Oncology, Heidelberg University Hospital, Heidelberg 69120, Germany; 2National Center for Radiation Oncology (NCRO), Heidelberg Institute for Radiation Oncology (HIRO), Heidelberg 69120, Germany; 3Institute of Medical Biometry and Informatics (IMBI), Heidelberg University Hospital, Heidelberg 69120, Germany; 4Heavy Ion Therapy Center (HIT), Heidelberg University Hospital, Heidelberg 69120, Germany; 5Department of Radiation Oncology, Klinikum Kempten, Kempten 87439, Germany; 6Department of Neurology, University Hospital of Heidelberg, Heidelberg 69120, Germany; 7German Cancer Research Center (DKFZ), Heidelberg 69120, Germany Background: Leptomeningeal carcinomatosis (LC) is a severe complication of metastatic tumor spread to the central nervous system. Prognosis is dismal with a median overall survival (OS) of ~10–15 weeks. Treatment options include radiotherapy (RT) to involved sites, systemic chemo- or targeted therapy, intrathecal chemotherapy and best supportive care with dexamethasone. Craniospinal irradiation (CSI) is a more aggressive radiotherapeutic approach, for which very limited data exists. Here, we report on our 10-year experience with palliative CSI of selected patients with LC. Patients and methods: Twenty-five patients received CSI for the treatment of LC at our institution between 2008 and 2018. Patients were selected individually for CSI based on clinical performance, presenting symptoms and estimated benefit. Median patient age was 53 years (IQR: 45–59), and breast cancer was the most common primary. Additional brain metastases were found in 18 patients (72.0%). RT was delivered at a TomoTherapy machine, using helical intensity-modulated radiotherapy (IMRT). The most commonly prescribed dose was 36 Gy in 20 fractions, corresponding to a median biologically equivalent dose of 40.8 Gy (IQR: 39.0– 2.5). Clinical performance and neurologic function were assessed before and in response to therapy, and deficits were retrospectively quantified on the 5-point neurologic function scale (NFS). A Cox proportional hazards model with univariate and multivariate analyses was fitted for survival.Results: Twenty-one patients died and four were alive at the time of analysis. Median OS from LC diagnosis was 19.3 weeks (IQR: 9.3–34.0, 95% CI: 11.0–32.0). In univariate analysis, a Karnofsky performance scale index (KPI) ≥70% (P=0.001), age ≤55 years at LC diagnosis (P=0.022), cerebrospinal fluid (CSF) protein

This paper used magnetic resonance diffusion kurtosis imaging to observe the acute cerebral infarction model of mice, and studied the imaging changes of ischemic penumbra after perfusion of model for rat middle cerebral artery occlusion experiment, and combined with the physiologic changes of mice. The damage of neurons was evaluated by the evolution of N-methyl-D-aspartate receptors to provide a corresponding imaging basis for the diagnosis and treatment of ischemic penumbra. The research shows that the diffusivity value decreases with time, and the diffusion kurtosis increases with time. The difference in diffusivity between different parts of the same time point and the same part of the same point (except the edge relative to the normal area) is statistically different. Learning significance was set at P < 0.05. The expression of N-methyl-D-aspartate receptor 2A in tissue homogenate increased overall, and expression in synaptic membrane, synaptic membrane, and light membrane decreased. The expression of N-methyl-D-aspartate acid receptor 2B in tissue homogenate, synaptic membrane, and light cell membrane decreased, and it increased first and then decreased in the synaptic membrane. The studies confirmed that magnetic resonance imaging has a certain clinical diagnostic value for the penumbra evolution mechanism and neuronal injury of acute cerebral infarction, which deserves further study. [ABSTRACT FROM AUTHOR]

Background: Patients with intracranial tumors are more sensitive to anesthetics than the general population and are therefore more susceptible to postoperative neurologic and neurocognitive dysfunction. Sevoflurane or propofol combined with remifentanil are widely used general anesthetic regimens for craniotomy, with neither regimen shown to be superior to the other in terms of neuroprotective efficacy and anesthesia quality. There is no evidence regarding the variable effects on postoperative neurologic and neurocognitive functional outcome under these two general anesthetic regimens. This trial will compare inhalational sevoflurane or intravenous propofol combined with remifentanil anesthesia in patients with supratentorial gliomas and test the hypothesis that postoperative neurologic function is equally affected between the two regimens. Methods: This is a prospective, single-center, randomized parallel arm equivalent clinical trial, which is approved by China Ethics Committee of Registering Clinical Trials (ChiECRCT-20,160,051). Patients with supratentorial gliomas diagnosed by magnetic resonance imaging will be eligible for the trial. Written informed consent will be obtained before randomly assigning each subject to either the sevoflurane-remifentanil or propofol-remifentanil group for anesthesia maintenance to achieve an equal-desired depth of anesthesia. Intraoperative intervention and monitoring will follow a standard anesthetic management protocol. All of the physiological parameters and other medications administered during the intervention will be recorded. The primary outcome will be neurologic function change assessed by National Institute of Health Stroke Scale (NIHSS) within 4 h after general anesthesia when observer's assessment of alertness/sedation (OAA/S) reaches 4. Secondary outcomes will include NIHSS and modified NIHSS change 1 and 2 days after general anesthesia, hemodynamic stability, intraoperative brain relaxation, quality of anesthesia emergence, quality of anesthesia recovery, postoperative cognitive function, postoperative pain, postoperative neurologic complications, as well as perioperative medical expense. Discussion: This randomized equivalency trial will primarily compare the impacts of sevoflurane-remifentanil and propofol-remifentanil anesthesia on short-term postoperative neurologic function in patients with supratentorial gliomas undergoing craniotomy. The exclusion criteria are strict to ensure that the groups are comparable in all aspects. Repeated and routine neurologic evaluations after operation are always important to evaluate neurosurgical patients' recovery and any newly presenting complications. The results of this trial would help specifically to interpret anesthetic residual effects on postoperative outcomes, and perhaps would help the anesthesiologist to select the optimal anesthetic regimen to minimize its impact on neurologic function in this specific patient population. Trial registration: The study was registered and approved by the Chinese Clinical Trial Registry (Chinese Clinical Trial Registry, ChiCTR-IOR-16009177). Principle investigator: Nan Lin (email address: linnan127@gmail.com) and Ruquan Han (email address: hanrq666@aliyun.com) Date of Registration: September 8th, 2016. Country of recruitment: China. [ABSTRACT FROM AUTHOR]

Introduction: Stereotactic radiosurgery (SRS) is an emerging treatment for patients with multiple brain metastases (BM). The present work compares the SRS of multiple brain metastases with whole-brain radiotherapy (WBRT). Methods: We performed a matched-pair analysis for 128 patients with multiple BM treated with either SRS or WBRT over a 5-year period. Patients were matched pairwise for seven potential prognostic factors. A mixed Cox Proportional Hazards model with univariate and multivariate analysis was fitted for overall survival (OS). Distant intracranial progression-free survival (icPFS) and local control were assessed using a Fine and Gray subdistribution hazard model and considering death as competing event. Results: Patients undergoing SRS had a median of 4 BM (range 3–16). 1-year local control of individual BM following SRS was 91.7%. Median OS in the SRS subgroup was 15.7 months (IQR 9.7–36.4) versus 8.0 months (interquartile range, IQR 3.8–18.0) in the WBRT subgroup (HR 2.25, 95% CI [1.5; 3.5], p < 0.001). Median icPFS was 8.6 (IQR 3.4–18.0) versus 22.4 (IQR 5.6–28.6) months, respectively (HR for WBRT 0.41, 95% CI [0.24; 0.71], p = 0.001). Following SRS, synchronous BM diagnosis (HR 2.51, 95% CI [1.30; 4.70], p = 0.004), higher initial number of BM (HR 1.21, 95% CI [1.10; 1.40], p = 0.002) and lung cancer histology (HR 2.05, 95% CI [1.10; 3.80], p = 0.024) negatively impacted survival. Excellent clinical performance (KPI 90%) was a positive prognosticator (HR 0.38, 95% CI [0.20; 0.72], p = 0.003), as was extracerebral tumor control (HR 0.48, 95% CI [0.24; 0.97], p = 0.040). Higher initial (HR 1.19, 95% CI [1.00; 1.40], p < 0.013) and total number of BM (HR 1.23, 95% CI [1.10; 1.40], p < 0.001) were prognostic for shorter icPFS. Conclusion: This is the first matched-pair analysis to compare SRS alone versus WBRT alone for multiple BM. OS was prolonged in the SRS subgroup and generally favorable in the entire cohort. Our results suggest SRS as a feasible and effective treatment for patients with multiple BM. [ABSTRACT FROM AUTHOR]

Aims: To compare the efficacy of ginkgolide in the treatment of Chinese patients with ischemic stroke between pre-marketing and post-marketing studies. Methods: This is a re-analysis of a pre-marketing (phase II/III, multicenter, double-blind, parallel-controlled; February 2005 to September 2005) and post-marketing (phase IV, multicenter, open, single-arm registration; April 2013 to June 2014) studies. The intervention groups received intravenous ginkgolide (10 mL daily, 14 days). Primary outcome was an improvement of National Institute of Health Stroke Scale (NIHSS) and modified Rankin Scale (mRS) scores after 14 days. Results: In pre- and post-marketing studies, NIHSS and mRS scores all improved, compared to that of baseline (P < 0.001) in acute phase. Those factors significantly associated with △NIHSS after 14 days of therapy with ginkgolide were grouping (pre-marketing vs. post-marketing; OR 2.169, 95%CI = 1.462–3.216, P < 0.001), male (OR = 1.532, 95%CI = 1.152–2.037, P = 0.003), enrollment within 30 days after onset (OR = 1.915, 95%CI = 1.452–2.526, P < 0.001) and NIHSS score more than 8 points at baseline (OR = 15.140, 95%CI = 11.436–20.045, P < 0.001) after adjustment. Ginkgolide had a greater effect on patients in a relatively acute phase (time of onset to enrollment ≤30 days) and moderate-severe stroke (baseline NIHSS>8 points). Incidences of adverse reactions in the pre-marketing and post-marketing studies were 0.46% and 5.28%, respectively (P < 0.001). Conclusion: Intravenous ginkgolide may improve the outcome of acute ischemic stroke. Differences in effect between pre-marketing and post-marketing studies may be associated with gender, time of onset to enrollment and severity of stroke. [ABSTRACT FROM AUTHOR]

Extracorporeal membrane oxygenation (ECMO) as a rescue strategy during cardiopulmonary resuscitation (ECPR) is increasingly being used for nonresponders to conventional cardiopulmonary resuscitation. To identify patients most likely to benefit from ECPR, the authors investigated predictors of hospital discharge with good neurologic function. Retrospective cohort analysis. Single institution academic medical center. Patients who underwent ECPR. Venoarterial ECMO initiation for witnessed refractory cardiac arrest from 2009–2019. Baseline characteristics and post-ECMO outcomes were compared between patients who had good versus poor neurologic function at discharge. Good neurologic function was defined as a cerebral performance category 1 to 2, whereas poor neurologic function was defined as a cerebral performance category 3 to 5. Of 54 patients, 13 (24%) were discharged with good neurologic function and 41 (76%) had poor neurologic function (n = 38 in-hospital deaths; n = 3 discharged with severe disability.) Survivors with good neurologic function were younger (41 v 61 y; p = 0.03), more likely to arrest because of pulmonary embolism (46% v 10%; p = 0.01), and more likely to receive concurrent Impella (Abiomed, Danvers, MA) placement while on ECMO (38% v 12%; p = 0.03.) Young age was the most important predictor of good neurologic function (odds ratio 0.92 [0.87-0.97]; p = 0.004), with a threshold for improved survival around 60 years. For all patients, survival to discharge was 30%; however, among survivors with good neurologic function, 5-year survival was 100%. ECPR is associated with high rates of neurologic morbidity and mortality. However, in select patients, it may be an acceptable option with favorable long-term survival. Additional studies are indicated to further define the appropriate selection criteria for ECPR implementation. [ABSTRACT FROM AUTHOR]

Aims: Inflammation is associated with vascular events. We aimed to investigate the relationship between high-sensitivity C-reactive protein (hsCRP) levels with and without intracranial arterial stenosis (ICAS) and the prognosis of patients with minor stroke or transient ischemic attack., Methods: We used data from the Clopidogrel in High-Risk Patients with Acute Nondisabling Cerebrovascular Events trial (derivation cohort) and the Third China National Stroke Registry (validation cohort). Patients were divided into four groups according to the dichotomy of hsCRP level and ICAS status. The primary outcome was new ischemic stroke within 90 days, and the secondary outcome was dependence or death (Modified Rankin Scale score of 3-6) at 90 days. The associations between hsCRP level with and without ICAS and risk of outcomes were analyzed using multivariate Cox regression and logistic regression models., Results: In the derivation cohort, compared with patients with nonelevated hsCRP levels and no ICAS, those with both elevated hsCRP levels and ICAS had increased risk of recurrent stroke (adjusted hazard ratio [HR], 2.62; 95% confidence interval [CI], 1.28-5.34; p=0.008) and dependence or death (adjusted odds ratio [OR], 7.58; 95% CI, 1.30-44.13; p=0.02). Consistent relationships of elevated hsCRP levels and presence of ICAS with recurrent stroke (adjusted HR, 1.67; 95% CI, 1.13-2.45; p=0.009) and dependence or death (adjusted OR, 1.87; 95% CI, 1.23-2.84; p=0.003) were observed in the validation cohort., Conclusion: Concomitant presence of increased hsCRP levels and ICAS was associated with increased risk of stroke recurrence and dependence or death in patients with minor ischemic stroke or transient ischemic attack.

Objective: To analyze the effect of bovine serum protein extract combined with tianma gouteng drink on the nerve function recovery and hemorheology of patients with acute cerebral infarction. Methods: Ninety patients with acute cerebral infarction treated in our hospital from October 2015 to October 2018 were selected as the study subjects, they were randomly divided into two groups. The control group was treated with bovine serum protein extract alone, while the experimental group was treated with tianma gouteng drink on the basis of control group. The total effective rate, changes of neurological impairment score, daily living ability score and hemorheology index before and at 20 days after treatment and the occurrence of adverse reactions during treatment were compared between the two groups. Results: After treatment, the total effective rate of experimental group was 95.56%, which was significantly higher than that of the control group(77.78%, P<0.05). The scores of National Institutes of Health Stroke Scale(NIHSS) and Activities of Daily Living(ADL) in both groups after treatment were significantly higher than those before treatment, which were significantly higher than those in the control group(P<0.05). After treatment, the whole blood high tangential viscosity, whole blood low tangential viscosity,erythrocyte specific volume, platelet aggregation rate and fibrinogen in both groups were significantly lower than before treatment, and the above indexes in the experimental group were significantly lower than those in the control group(P<0.05). Conclusion: Bovine serum protein extrac combined with tianma gouteng drink is more effective than bovine serum protein extrac alone in the treatment of acute cerebral infarction. It can more effectively promote the recovery of neurological function, improve the hemorheology and quality of life [ABSTRACT FROM AUTHOR]

• HIF-1α and MMP-9 expression are increased and positively correlated following CSCI. • HIF-1α and MMP-9 expression were negatively correlated with BBB score following CSCI. • Decreased expression of HIF-1α and MMP-9 may contribute to functional recovery following CSCI. The molecular mechanisms underlying cervical spondylotic myelopathy (CSM) are poorly understood. To assess the correlation between HIF-1α, MMP-9 and functional recovery following chronic cervical spinal cord compression (CSCI). Rats in the sham group underwent C5 semi-laminectomy, while a water-absorbable polyurethane polymer was implanted into the C6 epidural space in the chronic CSCI group. Basso, Beattie and Bresnahan score and somatosensory evoked potentials were used to evaluate neurological function. Hematoxylin and eosin staining was performed to assess pathological changes in the spinal cord, while immunohistochemical analysis was used to examine HIF-1α and MMP-9 expression on days 7, 28, 42 and 70 post-surgery. Normal rats were only used for HE staining. The BBB score was significantly reduced on day 28 following CSCI, while SEPs exhibited decreased amplitude and increased latency. In chronic CSCI group, the BBB score and SEPs significantly improved on day 70 compared with day 28. HE staining revealed different level of spinal cord edema after chronic CSCI. Compared with the sham group, immunohistochemical analyses revealed that HIF-1α- and MMP-9-positive cells were increased on day 7 and peaked on day 28. HIF-1α and MMP-9 expression were demonstrated to be significantly positively correlated, whereas HIF-1α expression and BBB score were significantly negatively correlated, as well MMP-9 expression and BBB score. HIF-1α and MMP-9 expression are increased following chronic spinal cord compression and are positively correlated with one another. Decreased expression of HIF-1α and MMP-9 may contribute to functional recovery following CSCI. This expression pattern of HIF-1α and MMP-9 may give a new perspective on the molecular mechanisms of CSM. [ABSTRACT FROM AUTHOR]

Introduction: The purpose of this article is to report our institution's 10-year experience on palliative radiotherapy for the treatment of leptomeningeal carcinomatosis (LC), assessing survival, neurologic outcome, and prognostic factors.Patients and methods: We retrospectively analyzed 110 patients who received palliative radiotherapy for LC between 2008 and 2018. The most common histologies were breast cancer (n = 43, 39.1%) and non-small cell lung cancer (NSCLC) (n = 31, 28.2%). Radiotherapy was administered as whole-brain radiotherapy (WBRT) (n = 51, 46.4%), focal spinal RT (n = 11, 10.0%) or both (n = 47, 42.7%). Twenty-five patients (22.7%) were selected for craniospinal irradiation. Clinical performance and neurologic function were quantified on the neurologic function scale (NFS) before and in response to therapy. A Cox Proportional Hazards model with univariate and multivariate analysis was fitted for survival.Results: Ninety-eight patients (89.1%) died and 12 (10.9%) were alive at the time of analysis. Median OS from LC diagnosis and from the beginning of RT was 13.9 weeks (IQR: 7.1–34.0) and 9.9 weeks (IQR: 5.3–26.3), respectively. In univariate analysis, prognostic of longer OS were a Karnofsky performance scale index (KPI) of ≥70% (HR 0.20, 95%-CI: [0.13; 0.32], p < 0.001), initially moderate neurological deficits (NFS ≤2) (HR 0.32, 95% CI: [0.19; 0.52], p < 0.001), symptom response to RT (HR 0.41, 95%-CI: [0.26; 0.67], p < 0.001) and the administration of systemic therapy (HR 0.51, 95%-CI: [0.33; 0.78], p = 0.002). Prognostic of inferior OS were high-grade myelosuppression (HR 1.78, 95% CI: [1.06; 3.00], p = 0.03) and serum LDH levels >500 U/l (HR 3.62, 95% CI: [1.76; 7.44], p < 0.001). Clinical performance, symptom response and serum LDH stayed independently prognostic for survival in multivariate analysis. RT was well-tolerated and except for grade III myelosuppression in 19 cases (17.3%), no high-grade acute toxicities were observed. Neurologic symptom stabilization was achieved in 83 cases (75.5%) and a sizeable improvement in 39 cases (35.5%).Conclusion: Radiotherapy is a well-tolerated and efficacious means of providing symptom palliation for patients with LC, delaying neurologic deterioration while probably not directly influencing survival. Prognostic factors such as clinical performance, neurologic response and serum LDH can be used for patient stratification to facilitate treatment decisions.

Antiretroviral (ART) drugs has previously been associated with lipodystrophic syndrome, metabolic consequences, and neuropsychiatric complications. ART drugs include three main classes of protease inhibitors (PIs), nucleoside analog reverse transcriptase inhibitors (NRTIs), and non-nucleoside reverse transcriptase inhibitors (NNRTIs). Our previous work demonstrated that a high risk of hyperlipidemia was observed in HIV-1-infected patients who received ART drugs in Taiwan. Patients receiving ART drugs containing either Abacavir/Lamivudine (Aba/Lam; NRTI/NRTI), Lamivudine/Zidovudine (Lam/Zido; NRTI/NRTI), or Lopinavir/Ritonavir (Lop/Rit; PI) have the highest risk of hyperlipidemia. The aim of this study was to investigate the effects of Aba/Lam (NRTI/NRTI), Lam/Zido (NRTI/NRTI), and Lop/Rit (PI) on metabolic and neurologic functions in mice. Groups of C57BL/6 mice were administered Aba/Lam, Lam/Zido, or Lop/Rit, orally, once daily for a period of 4 weeks. The mice were then extensively tested for metabolic and neurologic parameters. In addition, the effect of Aba/Lam, Lam/Zido, and Lop/Rit on lipid metabolism was assessed in HepG2 hepatocytes and during the 3T3-L1 preadipocyte differentiation. Administration with Aba/Lam caused cognitive and motor impairments in mice, as well as their metabolic imbalances, including alterations in leptin serum levels. Administration with Lop/Rit also caused cognitive and motor impairments in mice, as well as their metabolic imbalances, including alterations in serum levels of total cholesterol, and HDL-c. Treatment of mice with Aba/Lam and Lop/Rit enhanced the lipid accumulation in the liver, and the decrease in AMP-activated protein kinase (AMPK) phosphorylation and/or its downstream target acetyl-CoA carboxylase (ACC) protein expression. In HepG2 hepatocytes, Aba/Lam, Lam/Zido, and Lop/Rit also enhanced the lipid accumulation and decreased phosphorylated AMPK and ACC proteins. In 3T3-L1 pre-adipocyte differentiation, Aba/Lam and Lop/Rit reduced adipogenesis by decreasing expression of transcription factor CEBPb, implicating the lipodystrophic syndrome. Our results demonstrate that daily oral administration of Aba/Lam and Lop/Rit may produce cognitive, motor, and metabolic impairments in mice, regardless of HIV-1 infection.

Background: Leptomeningeal carcinomatosis (LC) is a severe complication of metastatic tumor spread to the central nervous system. Prognosis is dismal with a median overall survival (OS) of ~10–15 weeks. Treatment options include radiotherapy (RT) to involved sites, systemic chemo- or targeted therapy, intrathecal chemotherapy and best supportive care with dexamethasone. Craniospinal irradiation (CSI) is a more aggressive radiotherapeutic approach, for which very limited data exists. Here, we report on our 10-year experience with palliative CSI of selected patients with LC. Patients and methods: Twenty-five patients received CSI for the treatment of LC at our institution between 2008 and 2018. Patients were selected individually for CSI based on clinical performance, presenting symptoms and estimated benefit. Median patient age was 53 years (IQR: 45–59), and breast cancer was the most common primary. Additional brain metastases were found in 18 patients (72.0%). RT was delivered at a TomoTherapy machine, using helical intensity-modulated radiotherapy (IMRT). The most commonly prescribed dose was 36 Gy in 20 fractions, corresponding to a median biologically equivalent dose of 40.8 Gy (IQR: 39.0– 2.5). Clinical performance and neurologic function were assessed before and in response to therapy, and deficits were retrospectively quantified on the 5-point neurologic function scale (NFS). A Cox proportional hazards model with univariate and multivariate analyses was fitted for survival. Results: Twenty-one patients died and four were alive at the time of analysis. Median OS from LC diagnosis was 19.3 weeks (IQR: 9.3–34.0, 95% CI: 11.0–32.0). In univariate analysis, a Karnofsky performance scale index (KPI) ≥70% (P=0.001), age ≤55 years at LC diagnosis (P=0.022), cerebrospinal fluid (CSF) protein <100 mg/dL (P=0.018) and no more than mild or moderate neurologic deficits (NFS ≤2; P=0.007) were predictive of longer OS. So were the neurologic response to treatment (P=0.018) and the application of systemic therapy after RT completion (P=0.029). The presence of CSF flow obstruction was predictive of shorter OS (P=0.026). In multivariate analysis, age at LC diagnosis (P=0.018), KPI (P<0.001) and neurologic response (P=0.037) remained as independent prognostic factors for longer OS. Treatment-associated toxicity was manageable andmostly grades I and II according to the Common Terminology Criteria for Adverse Events v4.0. Eight patients (32%) developed grade III myelosuppression. Neurologic symptom stabilization could be achieved in 40.0% and a sizeable improvement in 28.0% of all patients. Conclusion: CSI for the treatment of LC is feasible and may have therapeutic value in carefully selected patients, alleviating symptoms or delaying neurologic deterioration. OS after CSI was comparable to the rates described in current literature for patients with LC. The use of modern irradiation techniques such as helical IMRT is warranted to limit toxicity. Patient selection should take into account prognostic factors such as age, clinical performance, neurologic function and the availability of systemic treatment options. [ABSTRACT FROM AUTHOR]

During the 2010 Deepwater Horizon (DWH) disaster, oil spill response and cleanup (OSRC) workers were exposed to toxic volatile components of crude oil. Few studies have examined exposure to individual volatile hydrocarbon chemicals below occupational exposure limits in relation to neurologic function among OSRC workers. To investigate the association of several spill-related chemicals (benzene, toluene, ethylbenzene, xylene, n-hexane, i.e., BTEX-H) and total petroleum hydrocarbons (THC) with neurologic function among DWH spill workers enrolled in the Gulf Long-term Follow-up Study. Cumulative exposure to THC and BTEX-H across the oil spill cleanup period were estimated using a job-exposure matrix that linked air measurement data to detailed self-reported DWH OSRC work histories. We ascertained quantitative neurologic function data via a comprehensive test battery at a clinical examination that occurred 4–6 years after the DWH disaster. We used multivariable linear regression and modified Poisson regression to evaluate relationships of exposures (quartiles (Q)) with 4 neurologic function measures. We examined modification of the associations by age at enrollment (<50 vs. ≥50 years). We did not find evidence of adverse neurologic effects from crude oil exposures among the overall study population. However, among workers ≥50 years of age, several individual chemical exposures were associated with poorer vibrotactile acuity of the great toe, with statistically significant effects observed in Q3 or Q4 of exposures (range of log mean difference in Q4 across exposures: 0.13–0.26 μm). We also observed suggestive adverse associations among those ≥ age 50 years for tests of postural stability and single-leg stance, although most effect estimates did not reach thresholds of statistical significance (p < 0.05). Higher exposures to volatile components of crude oil were associated with modest deficits in neurologic function among OSRC workers who were age 50 years or older at study enrollment. • The Deepwater Horizon oil spill workers were exposed to crude oil chemicals. • Exposures to BTEX and n-hexane were elevated, but below occupational limits. • Neurologic function was assessed via a battery of four tests at a clinical exam. • The clinical exam occurred 4–6 years after the spill. • Exposures were linked to worse neurologic function among workers ≥50 years of age. [ABSTRACT FROM AUTHOR]

Recent studies have shown that microglia/macrophages and astrocytes can mediate synaptic phagocytosis through the MER proto-oncokinase in developmental or stroke models, but it is unclear whether the same mechanism is also active in traumatic brain injury. In this study, we established a mouse model of traumatic brain injury and found that both microglia/macrophages and astrocytes phagocytosed synapses and expression of the MER proto-oncokinase increased 14 days after injury. Specific knockout of MER in microglia/macrophages or astrocytes markedly reduced injury volume and greatly improved neurobehavioral function. In addition, in both microglia/macrophages-specific and astrocytes-specific MER knock-out mice, the number of microglia/macrophage and astrocyte phagocytosing synapses was markedly decreased, and the total number of dendritic spines was increased. Our study suggested that MER proto-oncokinase expression in microglia/macrophages and astrocytes may play an important role in synaptic phagocytosis, and inhibiting this process could be a new strategy for treating traumatic brain injury., Competing Interests: None