Jigang Chen

Vascular endothelial growth factor is neuroprotective against ischemic brain injury by inhibiting scavenger receptor A expression on microglia

Vascular endothelial growth factor (VEGF) is a secreted mitogen associated with angiogenesis. VEGF has long been thought to be a potent neurotrophic factor for the survival of spinal cord neurons. However, the role of VEGF in the regulation of ischemic brain injury remains unclear. In this study, rats were subjected to MCAO (middle cerebral artery occlusion) followed by intraperitoneal injection of VEGF165 (10 mg/kg) immediately after surgery and once daily until the day 10. The expression of target genes was assayed using qPCR, western blot and immunofluorescence to investigate the role of VEGF165 in regulating ischemic brain injury. We found that VEGF165 significantly inhibited MCAO‐induced up‐regulation of Scavenger receptor class A (SR‐A) on microglia in a VEGFR1‐dependent manner. VEGF165 inhibited lipopolysaccharide (LPS)‐induced expression of proinflammatory cytokines IL‐1β, tumor necrosis factor alpha (TNF‐α) and iNOS in microglia. More importantly, the role of VEGF165 in inhibiting neuroinflammation is partially abolished by SR‐A over‐expression. SR‐A further reduced the protective effect of VEGF165 in ischemic brain injury. These data suggest that VEGF165 suppresses neuroinflammation and ischemic brain injury by inhibiting SR‐A expression, thus offering a new target for prevention of ischemic brain injury.

Decompressive craniectomy in the management of intracranial hypertension after traumatic brain injury: a systematic review and meta-analysis

We aim to perform a systematic review and meta-analysis to examine the prognostic value of decompressive craniectomy (DC) in patients with traumatic intracranial hypertension. PubMed, EMBASE, Cochrane Controlled Trials Register, Web of Science, http://clinicaltrials.gov/ were searched for eligible studies. Ten studies were included in the systematic review, with four randomized controlled trials involved in the meta-analysis, where compared with medical therapies, DC could significantly reduce mortality rate [risk ratio (RR), 0.59; 95% confidence interval (CI), 0.47–0.74, P < 0.001], lower intracranial pressure (ICP) [mean difference (MD), −2.12 mmHg; 95% CI, −2.81 to −1.43, P < 0.001], decrease the length of ICU stay (MD, −4.63 days; 95% CI, −6.62 to −2.65, P < 0.001) and hospital stay (MD, −14.39 days; 95% CI, −26.00 to −2.78, P = 0.02), but increase complications rate (RR, 1.94; 95% CI, 1.31–2.87, P < 0.001). No significant difference was detected for Glasgow Outcome Scale at six months (RR, 0.85; 95% CI, 0.61–1.18, P = 0.33), while in subgroup analysis, early DC would possibly result in improved prognosis (P = 0.04). Results from observational studies supported pooled results except prolonged length of ICU and hospital stay. Conclusively, DC seemed to effectively lower ICP, reduce mortality rate but increase complications rate, while its benefit on functional outcomes was not statistically significant.

Effects of Intensive Blood Pressure Reduction on Acute Intracerebral Hemorrhage: A Systematic Review and Meta-analysis

Current opinions about the effect of intensive blood pressure (BP) reduction for acute intracerebral hemorrhage (ICH) are inconsistent. We performed a meta-analysis to evaluate the efficacy and safety of intensive BP reduction for acute ICH by analyzing data from several recent randomized controlled trials (RCTs). There were six eligible studies that met the inclusion criteria, for a total of 4,385 acute ICH patients in this meta-analysis. After analyzing these data, we found differences between intensive and standard BP lowering treatment groups in total mortality rates, unfavorable outcomes, hematoma expansion, neurologic deterioration, and severe hypotension were not significant. Moreover, compared with the standard treatment, the rate of renal adverse event in intensive treatment group was significantly higher. The intensive treatment approach was recommended in the following situations: (1) longer prehospital duration; (2) lower National Institute of Health stroke scale (NIHSS) score; (3) no hypertension history.

Management of Penetrating Skull Base Injury: A Single Institutional Experience and Review of the Literature

Background Penetrating skull base injury (PSBI) is uncommon among head injuries, presenting unique diagnostic and therapeutic challenges. Although many cases of PSBIs have been reported, comprehensive understanding of its initial diagnosis, management, and outcome is still unavailable. Materials and Methods A retrospective review was performed for patients treated in neurosurgical department of Changzheng Hospital for PSBIs. Presurgical three-dimensional (3D) Slicer-assisted reconstructions were conducted for each patient. Then we reviewed previous literature about all the published cases of PSBIs worldwide and discussed their common features. Results A total of 5 patients suffering PSBIs were identified. Penetrating points as well as the surrounding neurovascular structures were clearly visualized, assisting in the presurgical planning of optimal surgical approach and avoiding unexpected vascular injury. Four patients underwent craniotomy with foreign bodies removed successfully and 1 patient received conservative treatment. All of them presented good outcomes after proper management. Conclusion Careful physical examination and radiological evaluation are essential before operation, and angiography is recommended for those with suspected vascular injuries. 3D modeling with 3D Slicer is practicable and reliable, facilitating the diagnosis and presurgical planning. Treatment decision should be made upon the comprehensive evaluation of patients clinicoradiological features and characteristics of foreign bodies.

Dorsum sellae and bilateral temporal bone fracture associated with bilateral abducens and facial nerve palsy: letter to the editor

Dear Editor: Cranial base fractures are common after head injuries, yet fractures involving the dorsum sellae and both sides of the temporal bone are scarcely seen [4, 8]. Cranial base fractures are usually complicated by cranial nerve injuries. However, bilateral traumatic abducens nerve palsy is a very rare clinical condition [7]; bilateral abducens nerve palsy associated with bilateral facial nerve palsy is even rarer and has not been well described in the literature. We recently treated a case of bilateral abducens and facial nerve palsy in a head trauma patient with fractures of the dorsum sellae and bilateral temporal bones. The patient is a 22-year-old male whose head was crushed by an iron pipe while working. He was alert with a GCS score of 15 points when emergency services arrived minutes later. Then he was admitted to the local hospital, and an ordinary head CT scan was performed, which showed pneumocephalus on the left side of the brain. A complete neurologic examination was performed 3 days later by the neurosurgeon, confirming bilateral abducens and facial nerve palsy (Fig. 1). No signs of other types of injuries were seen. A course of steroids and antibiotics was given to minimize the neurologic edema and avoid intracranial infection. Twenty days later the patient was transferred to our hospital since there was no functional improvement of the injured nerves. We performed a high-resolution head CT scan, which demonstrated a fracture of the dorsum sellae. This fracture allowed the dorsum sellae to rotate anticlockwise by approximately 30° from the bottom view. Also a longitudinal fracture of the left temporal bone and oblique fracture of the right one were confirmed (Fig. 1). The patient rejected facial nerve exploration surgery and was transferred to a recovery center for further treatment. Six months later he had almost recovered from the bilateral abducens palsy, although there was no fundamental improvement of the bilateral facial nerve function. Only a few cases of traumatic bilateral abducens nerve palsy have been reported in the literature [6]. The course of the abducens nerve from the brain stem to the lateral rectus muscle is long and delicate. After piercing the dura matter at the dorsum sellae through a rigid hole, the nerve passes under Gruber’s ligament, a thickening of the dura matter between the petrous bone and posterior clinoidal process. The triangular space defined by the apex of the petrous bone, the posterior clinoidal process of the dorsum sellae and Gruber’s ligament are known as Dorellos canal [5]. Inside Dorellos canal, the abducens nerve is tightly and intimately attached to the endosteal dura of the petrous apex and Gruber’s ligament by connective tissue. Thus, the compression or stretch near Dorellos canal can result in abducens nerve spasms and palsy since the nerve’s rigid fixation does not allow any protective flexibility [2]. In our case, the rotation of the dorsum sellae can lead to the compression of one Dorello canal and stretch of the opposite one simultaneously. Thus, the bilateral abducens nerves are injured at the same time. Treatment of post-traumatic bilateral abducens nerve palsy is usually conservative since its spontaneous recovery rate can be as high as 73 % [3]. Jigang Chen and Danfeng Zhang contributed equally to this work and are considered first authors.

Efficacy and Safety of Cerebrolysin for Acute Ischemic Stroke: A Meta-Analysis of Randomized Controlled Trials

Cerebrolysin was reported to be effective in the neurological improvement of patients with acute ischemic stroke (AIS) in experimental models, while data from clinical trials were inconsistent. We performed a meta-analysis to explore the efficacy and safety of cerebrolysin for AIS. PubMed, EMBASE, and Cochrane Library were searched for randomized controlled trials, which intervened within 72 hours after the stroke onset. We investigated the efficacy and safety outcomes, respectively. Risk ratios and mean differences were pooled with fixed-effects model or random-effects model. Seven studies were identified, involving 1779 patients with AIS. The summary results failed to demonstrate significant superiority of cerebrolysin in the assessment of efficacy outcomes of mRS and BI. Similarly, administration of cerebrolysin had neutral effects on safety outcomes compared with placebo, including mortality and SAE. However, the number of included studies was small, especially in the analysis of efficacy outcomes, which might cause publication bias and inaccurate between-studies variance in the meta-analysis. Conclusively, although it seemed to be safe, routine use of cerebrolysin to improve the long-term rehabilitation after stroke could not be supported by available evidence.

Peak Neutrophil-to-Lymphocyte Ratio Correlates with Clinical Outcomes in Patients with Severe Traumatic Brain Injury

BackgroundStudies suggested that the neutrophil-to-lymphocyte ratio (NLR) was associated with unfavorable outcomes in different diseases such as intracerebral hemorrhage, cardiovascular problem, cancer, and severe traumatic brain injury (sTBI). We aimed to evaluate the relationship between peak NLR and 1-year outcomes in patients with sTBI.MethodsWe retrospectively reviewed the clinical data of patients with sTBI who were treated in our department between January 2013 and January 2017. NLRs between day 1 and day 12 after admission as well as other related indicators were collected. The relationship between peak NLR and 1-year outcomes was analyzed. Factors associated with larger peak NLR were also explored.ResultsA total of 316 patients were included, and 81.3% (257/316) experienced unfavorable outcomes. Peak NLR was identified as an independent predictor for unfavorable outcomes after sTBI in multivariable logistic regression analysis (odds ratio, 1.086; 95% confidence interval, 1.037–1.137; P < 0.001). Its predictive value was confirmed by receiver operating characteristic analysis (area under curve = 0.775; P < 0.001). The day 1 NLR as well as admission Glasgow Coma Scale score was independently correlated with increased peak NLR.ConclusionPeak NLR was associated with the clinical prognosis after sTBI and was a promising predictor for 1-year outcomes.

Heterogeneity Signs on Noncontrast Computed Tomography Predict Hematoma Expansion after Intracerebral Hemorrhage: A Meta-Analysis

Background and Purpose Hematoma expansion (HE) is related to clinical deterioration after intracerebral hemorrhage (ICH) and noncontrast computed tomography (NCCT) signs are indicated as predictors for HE but with inconsistent conclusions. We aim to clarify the correlations of NCCT heterogeneity signs with HE by meta-analysis of related studies. Methods PubMed, Embase, and Cochrane library were searched for eligible studies exploring the relationships between NCCT heterogeneity signs (hypodensity, mixed density, swirl sign, blend sign, and black hole sign) and HE. Poor outcome and mortality were considered as secondary outcomes. Odds ratio (OR) and its 95% confidence intervals (CIs) were selected as the effect size and combined using random effects model. Results Fourteen studies were included, involving 3240 participants and 435 HEs. The summary results suggested statistically significant correlations of heterogeneity signs with HE (OR, 5.17; 95% CI, 3.72–7.19, P < 0.001), poor outcome (OR, 3.60; 95% CI, 1.98–6.54, P < 0.001), and mortality (OR, 4.64; 95%, 2.96–7.27, P < 0.001). Conclusions Our findings suggested that hematoma heterogeneity signs on NCCT were positively associated with the increased risk of HE, poor outcome, and mortality rate in ICH.

Cerebral venous sinus thrombosis complicated with acute development of dural arteriovenous fistula: A case report

Development of dural arteriovenous fistula (dAVF) after cerebral venous sinus thrombosis (CVST) was very uncommon and for all these reported cases, the dAVF was a chronic complication. We present a case of acute development of dAVF after CVST. A 40-year-old female was admitted into our department with 2days headache and vomiting for 9h. Head computed tomography (CT) scan showed only scattered minor hematomas over the right frontal lobe. Blood test indicated an elevated D-dimer. The patient experienced transient paralysis (Todds paralysis) after intermittent focal epilepsy from day 3, which progressed into sustained epilepsy on day 6. Magnetic resonance imaging (MRI) on day 7 confirmed the thrombosis of the superior sagittal sinus and a large area of infarction and edema in the left frontal and parietal lobe. She was then treated with heparin and warfarin. Cerebral angiography on day 9 demonstrated a dAVF which was classified as Borden Type II and fed by the left occipital artery. Subsequently, endovascular occlusion of the fistula was conducted and the patient recovered well with only slight right limbs weakness at 1year follow up.

Functional Recovery of Cranial Nerves in Patients with Traumatic Orbital Apex Syndrome

Objective Traumatic orbital apex syndrome (TOAS) is a rare disease characterized by the damage of cranial nerves (CNs) II, III, IV, and VI. The aim of our study was to analyze the functional recovery of CNs in TOAS and discuss the management of these patients. Methods We retrospectively reviewed 28 patients with TOAS treated in the Department of Neurosurgery, Shanghai Changzheng Hospital from February 2006 to February 2016. Functional recovery of CNs was evaluated based on extraocular muscle movement and visual perception. Follow-up duration was at least 6 months. Results There were 26 males and 2 females with a mean age of 35.3 years. The most common cause of TOAS was traffic accident. CN IV suffered the lightest injury among CNs III, IV, and VI. CN II achieved obvious improvement at 3-month follow-up, while other CNs enjoyed evident improvement at 6-month follow-up. There was no significant difference between conservative treatment and surgical decompression. Conclusion CNs passing through orbital apex region might recover to different degrees several months after proper management. Clinical decision should be individualized and surgical decompression could be considered with evidence of fracture, hematoma, or deformation.