Atorvastatin combined with dexamethasone in chronic subdural haematoma (ATOCH II): study protocol for a randomized controlled trial.

BACKGROUND: Chronic subdural haematoma (CSDH) is a common condition in the elderly that often requires neurosurgical management. For small CSDH, evidence has emerged that statins may reduce haematoma volume and improve outcomes, presumably by reducing local inflammation and promoting vascular repair. We wish to extend this evidence in a study that aims to determine the efficacy and safety of atorvastatin combined with low-dose dexamethasone in patients with CSDH. METHODS: The second ATorvastatin On Chronic subdural Hematoma (ATOCH-II) study is a multi-centre, randomized, placebo-controlled, double-blind trial which aims to enrol 240 adult patients with a conservative therapeutic indication for CSDH, randomly allocated to standard treatment with atorvastatin 20 mg combined with low-dose dexamethasone (or matching placebos) daily for 28 days, and with 152 days of follow-up. The primary outcome is a composite good outcome defined by any reduction from baseline in haematoma volume and survival free of surgery at 28 days. Secondary outcomes include functional outcome on the modified Rankin scale (mRS) and modified Barthel Index at 28 days, surgical transition and reduction in haematoma volumes at 14, 28 and 90 days. DISCUSSION: This multi-centre clinical trial aims to provide high-quality evidence on the efficacy and safety of the combined treatment of atorvastatin and low-dose dexamethasone to reduce inflammation and enhance angiogenesis in CSDH. TRIAL REGISTRATION: ChiCTR, ChiCTR1900021659 . Registered on 3 March 2019, http://www.chictr.org.cn/showproj.aspx?proj=36157 .

Using a New Landmark of the Most External Point in the Embolization of Distal Anterior Choroidal Aneurysms: A Report of Two Cases.

There are landmarks on the course of the anterior choroidal artery (AChoA), such as the original point (OP) and the plexal point (PP), as documented in previous articles. In these previous articles, the AChoA was the terminal branch of the internal carotid artery (ICA), which had two segments throughout its course. The first cisternal segment began from the origin and ended at the point where the artery reached the choroidal fissure (the PP). The second segment consisted of one or more branches, which passed through the choroidal fissure and entered the choroid plexus. However, we found another angiographic landmark, named the most external point (MEP), along the course of the AChoA in the anteroposterior (AP) view. There was a sharp turn at the outermost limit of the course of the AChoA, and then the AChoA progressed inward and upward. We defined the outermost limit as the MEP of the AChoA. This study describes two rare cases of distal AChoA aneurysms associated with arteriovenous malformation (AVM) and Moyamoya disease that developed intraventricular hemorrhage, and we used the parent artery occlusion (PAO) technique to embolize the distal AChoA lesions at the MEP. The patients recovered well without any neurological complications.

Use of a compact high-definition two-dimensional exoscope in surgical treatment of large vestibular schwannoma.

BACKGROUND: Extra-corporeal video telescope operating monitor system provides a necessary instrument to perform high-precision neurosurgical procedures that could substitute or supplement the traditional surgical microscope. The present study was designed to evaluate a compact high-definition two-dimensional exoscope system for assisting in surgical removal of large vestibular schwannoma (VS), as an alternative to a binocular surgical microscope. METHODS: Patients with Koos grade 3 and grade 4 VS undergoing surgery were enrolled in this prospective cohort study between January 2013 and June 2018. The demographics and tumor characteristics (size, Koos grade, composition [cystic or solid mass]) were matched between the two groups of patients. The following outcome measurements were compared between the two groups: duration of surgery, volume of blood loss, extent of tumor resection, number of operating field adjustments, pre- and post-operative facial and cochlear nerve function evaluated at 3 months post-surgery, complications and surgeons' comfortability. RESULTS: A total of 81 patients received tumor resection through the retrosigmoid approach under either an exoscope (cases, n = 39) or a surgical microscope (control, n = 42). Patients in the two groups had comparable tumor location (P = 0.439), Koos grading (P = 0.867), and composition (P = 0.891). While no significant differences in the duration of surgery (P = 0.172), extent of tumor resection (P = 0.858), facial function (P = 0.838), and hearing ability (P = 1.000), patients operated on under an exoscope had less blood loss (P = 0.036) and a fewer field adjustments (P < 0.001). Both primary and assistant surgeons reported a high level of comfort operating under the exoscope (P = 0.001 and P < 0.001, respectively). CONCLUSIONS: The compact high-definition two-dimensional exoscope system provides a safe and efficient means to assist in removing large VSs, as compared to a surgical microscope. After the acquaintance with a visual perception through a dynamic hint and stereoscopically viewing corresponding to the motion parallax, the exoscope system provided a comfortable, high-resolution visualization without compromising operational efficiency and patient safety.

Risk factors for corticosteroid insufficiency during the sub-acute phase of acute traumatic brain injury.

Hypothalamic-pituitary-adrenal axis dysfunction may lead to the occurrence of critical illness-related corticosteroid insufficiency. Critical illness-related corticosteroid insufficiency can easily occur after traumatic brain injury, but few studies have examined this occurrence. A multicenter, prospective, cohort study was performed to evaluate the function of the hypothalamic-pituitary-adrenal axis and the incidence of critical illness-related corticosteroid insufficiency during the sub-acute phase of traumatic brain injury. One hundred and forty patients with acute traumatic brain injury were enrolled from the neurosurgical departments of three tertiary-level hospitals in China, and the critical illness-related corticosteroid insufficiency incidence, critical-illness-related corticosteroid insufficiency-related risk factors, complications, and 28-day mortality among these patients was recorded. Critical illness-related corticosteroid insufficiency was diagnosed in patients with plasma total cortisol levels less than 10 µg/dL (275.9 nM) on post-injury day 4 or when serum cortisol was insufficiently suppressed (less than 50%) during a dexamethasone suppression test on post-injury day 5. The results demonstrated that critical illness-related corticosteroid insufficiency occurred during the sub-acute phase of traumatic brain injury in 5.6% of patients with mild injury, 22.5% of patients with moderate injury, and 52.2% of patients with severe injury. Traumatic brain injury-induced critical illness-related corticosteroid insufficiency was strongly correlated to injury severity during the sub-acute stage of traumatic brain injury. Traumatic brain injury patients with critical illness-related corticosteroid insufficiency frequently presented with hemorrhagic cerebral contusions, diffuse axonal injury, brain herniation, and hypotension. Differences in the incidence of hospital-acquired pneumonia, gastrointestinal bleeding, and 28-day mortality were observed between patients with and without critical illness-related corticosteroid insufficiency during the sub-acute phase of traumatic brain injury. Hypotension, brain-injury severity, and the types of traumatic brain injury were independent risk factors for traumatic brain injury-induced critical illness-related corticosteroid insufficiency. These findings indicate that critical illness-related corticosteroid insufficiency is common during the sub-acute phase of traumatic brain injury and is strongly associated with poor prognosis. The dexamethasone suppression test is a practical assay for the evaluation of hypothalamic-pituitary-adrenal axis function and for the diagnosis of critical illness-related corticosteroid insufficiency in patients with traumatic brain injury, especially those with hypotension, hemorrhagic cerebral contusions, diffuse axonal injury, and brain herniation. Sub-acute infection of acute traumatic brain injury may be an important factor associated with the occurrence and development of critical illness-related corticosteroid insufficiency. This study protocol was approved by the Ethics Committee of General Hospital of Tianjin Medical University, China in December 2011 (approval No. 201189).

Electrical stimulation improved cognitive deficits associated with traumatic brain injury in rats.

Introduction: Cognitive deficits associated with traumatic brain injury (TBI) reduce patient quality of life. However, to date, there have been no effective treatments for TBI-associated cognitive deficits. In this study, we aimed to determine whether electrical stimulation (ES) improves cognitive deficits in TBI rats. Methods: Rats were randomly divided into three groups: the Sham control group, electrical stimulation group (ES group), and No electrical stimulation control group (N-ES group). Following fluid percussion injury, the rats in the ES group received ES treatment for 3 weeks. Potent cognitive function-relevant factors, including the escape latency, time percentage in the goal quadrant, and numbers of CD34+ cells, von Willebrand Factor+ (vWF +) vessels, and circulating endothelial progenitor cells (EPCs), were subsequently assessed using the Morris water maze (MWM) test, immunohistochemical staining, and flow cytometry. Results: Compared with the rats in the N-ES group, the rats in the ES group exhibited a shorter escape latency on day 3 (p = .025), day 4 (p = .011), and day 5 (p = .003), as well as a higher time percentage in the goal quadrant (p = .025) in the MWM test. After 3 weeks of ES, there were increased numbers of CD34+ cells (p = .008) and vWF + vessels (p = .000) in the hippocampus of injured brain tissue in the ES group compared with those in the N-ES group. Moreover, ES also significantly increased the number of EPCs in the peripheral blood from days 3 to 21 after TBI in the ES group (p < .05). Conclusions: Taken together, these findings suggest that ES may improve cognitive deficits induced by TBI, and this protective effect may be a result, in part, of enhanced angiogenesis, which may be attributed to the increased mobilization of EPCs in peripheral blood.

Cold water swimming pretreatment reduces cognitive deficits in a rat model of traumatic brain injury.

A moderate stress such as cold water swimming can raise the tolerance of the body to potentially injurious events. However, little is known about the mechanism of beneficial effects induced by moderate stress. In this study, we used a classic rat model of traumatic brain injury to test the hypothesis that cold water swimming preconditioning improved the recovery of cognitive functions and explored the mechanisms. Results showed that after traumatic brain injury, pre-conditioned rats (cold water swimming for 3 minutes at 4°C) spent a significantly higher percent of times in the goal quadrant of cold water swim, and escape latencies were shorter than for non-pretreated rats. The number of circulating endothelial progenitor cells was significantly higher in pre-conditioned rats than those without pretreatment at 0, 3, 6 and 24 hours after traumatic brain injury. Immunohistochemical staining and Von Willebrand factor staining demonstrated that the number of CD34+ stem cells and new blood vessels in the injured hippocampus tissue increased significantly in pre-conditioned rats. These data suggest that pretreatment with cold water swimming could promote the proliferation of endothelial progenitor cells and angiogenesis in the peripheral blood and hippocampus. It also ameliorated cognitive deficits caused by experimental traumatic brain injury.

Effect of ATorvastatin On Chronic subdural Hematoma (ATOCH): a study protocol for a randomized controlled trial.

BACKGROUND: Chronic subdural hematoma (CSDH) is a common disease that is more prevalent in older people. Surgical intervention is a safe treatment of choice. However, the recurrence rate is relatively high and the outcome is not always satisfactory among surgically treated patients. It is believed that aberrant angiogenesis and intracapsular inflammation contribute to the development of CSDH. Atorvastatin is reported to promote angiogenesis and suppress inflammation. We have recently shown that atorvastatin is effective to non-surgically reduce and eliminate CSDH with minimal side effects. Here, we report a clinical research trial protocol that is designed to evaluate the therapeutic effects of atorvastatin on CSDH. METHODS/DESIGN: We have designed a multi-center, randomized, placebo-controlled, double blind clinical trial for evaluating the efficacy of oral atorvastatin in reducing CSDH. We have so far recruited 96 patients with CT-confirmed or MRI-confirmed CSDHs from 16 medical centers in China. These patients were originally recruited for the Oriental Neurosurgical Evidence-based Study Team (ONET) study. After informed consent is provided, patients are randomized to receive either atorvastatin (oral 20 mg/night for 8 weeks) or placebo (dextrin for 8 weeks); and followed for 16 weeks after the treatment. The primary outcome is the change in hematoma volume at the end of 8-week treatment. Secondary outcomes include: changes in 1) the hematoma volume at the 4(th), 12(th), and 24(th) weeks; 2) Markwalder's Grading Scale and Glasgow Coma Scale (MGS-GCS); 3) Glasgow Outcome Score (GOS) and 4) Activities of Daily Life-the Barthel Index scale (ADL-BI). Safety will be assessed during the study by monitoring adverse events, laboratory tests, electrocardiography (ECG), measurements of vital signs (temperature, pulse, and blood pressure) and body weight. DISCUSSION: Results of this trial will provide critical information regarding whether atorvastatin is an effective and safe alternative to surgical treatment of CSDH. TRIAL REGISTRATION: ClinicalTrials.gov Identifier--NCT02024373 The date of trial registration: 7 August 2013.

[Intraoperative magnetic resonance imaging-guided functional neuronavigation plus intraoperative neurophysiological monitoring for microsurgical resection of lesions involving hand motor area].

OBJECTIVE: To explore the methods and applications of intraoperative magnetic resonance imaging (iMRI)-guided functional neuronavigation plus intraoperative neurophysiological monitoring (IONM) for microsurgical resection of lesions involving hand motor area. METHODS: A total of 16 patients with brain lesions adjacent to hand motor area were recruited from January 2011 to April 2012. All of them underwent neuronavigator-assisted microsurgery. Also IONM was conducted to further map hand motor area and epileptogenic focus. High-field iMRI was employed to update the anatomical and functional imaging date and verify the extent of lesion resection. RESULTS: Brain shifting during the functional neuronavigation was corrected by iMRI in 5 patients. Finally, total lesion resection was achieved in 13 cases and subtotal resection in 3 cases. At Months 3-12 post-operation, hand motor function improved (n = 10) or remained unchanged (n = 6). None of them had persistent neurological deficit. The postoperative seizure improvement achieved Enge II level or above in 9 cases of brain lesions complicated with secondary epilepsy. CONCLUSION: Intraoperative MRI, functional neuronavigation and neurophysiological monitoring technique are complementary in microsurgery of brain lesions involving hand motor area. Combined use of these techniques can obtain precise location of lesions and hand motor functional structures and allow a maximum resection of lesion and minimization of postoperative neurological deficits.

[Application of high-field intraoperative magnetic resonance imaging in stereotactic aspiration and drainage of hypertensive hematomas].

OBJECTIVE: To explore the application values of high-field intraoperative magnetic resonance imaging (MRI) in stereotactic aspiration and drainage of hypertensive hematomas. METHODS: During a period of August 2011 to January 2012, 11 patients with hypertensive hemorrhage were examined preoperatively by conventional MRI and diffusion tensor imaging (DTI) with 1.5T intraoperative MRI system (Signa HDi, GE, USA) at Tianjin Medical University General Hospital. The anatomic relationship of corticospinal tract (CST) and hematoma was used for the operative planning with the neuronavigation planning workstation (iPlan Cranial 3.0 software, BrainLab, Germany) for 3D reconstruction. During stereotactic surgery, intraoperative MRI scan was performed. According to the clearance rate of hematomas, the operators decided to finish the operation or update the operative planning to continue hematoma removal. All patients were reexamined by conventional MRI and DTI at Week 3 postoperation. Then comparative analysis was performed for the preoperative and postoperative integrity of CST. RESULTS: No death or severe complications occurred. All patients showed improvement of motor function and the postoperative integrity of CST. CONCLUSION: The intracranial condition may be monitored effectively by intraoperative MRI throughout surgery so as to increase the rate of hematoma removal and reduce the postoperative complications.

Primary granulomatous hypophysitis: a case report and literature review.

Primary granulomatous hypophysitis (PGH) is a rarely occurred inflammatory disease of unknown etiology. We retrospective review a case of PGH treated by microsurgical transsphenoidal approach and review the appropriately documented cases of PGH collected from the literatures. The patient was a 56-year-old female who presented with 4 months history of headache and 2 months history of polyuria and polydipsia. Clinic examination did not find remarkable neurological signs, except endocrinological abnormalities of secondary hypothyroidism and hypocorticalism. MRI revealed a symmetric sellar mass, which was isointensity as gray matter on T1-weighted and T2-weighted images with heterogeneous enhancement. The mass was partially resected via transsphenoidal approach. Histological assessment revealed a non-necrotizing granulomatous lesion with chronic inflammation. Although the resection was limited, repeatedly MRI scanning in 3 months following surgery revealed almost normal pituitary soft tissue without evidence of the lesion. Searching in PubMed, we found 21 papers published from 1985 to 2009 and 37 patients with PGH were reported. In order to identify the clinical and radiological presentation, treatment strategy, and prognosis of PGH, we analyzed these 38 cases together. The results indicate that the clinical presentations and radiological signs are helpful for the diagnosis of PGH. The outcome of surgery for PGH is favorable for immediate mass reduction and histological diagnosis, but hormone replacement is required in most cases and long-term follow up is very important.

[Stereotactic resection of small intracerebral lesions in motor cortex using blood oxygen level depended functional magnetic resonance imaging and diffusion tensor imaging fusion guidance].

OBJECTIVE: To explore the effect of stereotactic resection of small intracerebral lesions located in the motor cortex using blood oxygen level depended functional magnetic resonance imaging (BOLD-fMRI) and diffusion tensor imaging (DTI) fusion guidance. METHODS: Fifteen patients with lesions in posterior frontal lobe to anterior central gyrus, 1.5-3 cm in diameter, underwent combined three-dimensional (3D) enhancement MRI with BOLD-fMRI, and DTI. Computer procedure was used to perform the images fusion to show directly the lesions, motor cortex, and corticospinal tract, and to confirm their position relationship and design the operative approach so as to guide the stereotactic resection of the small intracerebral lesions. RESULTS: The images fusion demonstrated that the motor cortex and corticospinal tract were located in the lateral-posterior side of the lesions, and were both compressed, reformatted and displaced. Total removal of the lesions under microscope was achieved in 12 cases, and subtotal removal in 3 cases. Histological examination showed 3 cases of meningeoma, 3 cases of astrocytoma of grade II, 2 cases of astrocytoma of grade III, 2 cases of abscess, and 2 cases of cavernous angioma. No complication was found postoperatively. CONCLUSION: Mutual complementarity can be achieved by combining 3D-enhancement MRI, BOLD-fMRI, and DTI. Stereotactic resection of the small intracerebral lesions is safe, accurate and effective under the images fusion guidance.