Safety for cervical corpectomy and diskectomy: univariate and multivariate analysis on predictors for prolonged ICU stay after anterior spinal fusion.

AIM: Cervical anterior spinal fusion (ASF) with corpectomy has risks of catastrophic acute complications such as airway obstruction requiring re-intubation. Our team has adopted a management plan for all cervical corpectomy patients to be admitted to the intensive care unit (ICU) after the operations for overnight observation. Some of these patients were kept intubated after the operations and transferred to the ICU. This study aims to review the outcome of this practice and to identify independent predictors associated with a prolonged ICU stay. METHODS: We reviewed consecutive patients with cervical ASF from January 2010 to June 2018. The primary outcome was the ICU length of stay. Univariate and multivariate analyses were conducted to identify independent risk factors associated with a prolonged ICU stay. In total, 103 patients had ASF during the study period. ICU length of stay for elective ASF was 1.01 day (SD 0.373 days) and was significantly shorter than that for emergency ASF (13.29 days, SD 12.57 days) (p < 0.001). 79.6% (82/103) of the ASF patients were extubated in the operating theatre after surgery. Significantly more corpectomy patients (33.3%) versus ACDF patients (15.1%) were kept intubated to the ICU after the operation (p = 0.037). None required reintubation in the ICU. 90.9% (80/88) of the elective ASF can be discharged from the ICU within 24 hours and only 3.41% (3/88) of the elective ASF had prolonged post-operative stay in the ICU (≥48 hours). RESULTS: For prolonged postoperative ICU stay (≥48 hours), ICU admission airway status of ASF patients who were either extubated in the OT or kept intubated to ICU had no significant association (p = 0.903). Univariate and multivariate analysis had identified emergency admissions (p = 0.043) and the presence of postoperative neurological deficits (p = 0.031) as independent predictors associated with a prolonged postoperative ICU stay. CONCLUSION: In conclusion, cervical corpectomy and ASF were safe with minimal acute complications.

Elderly population have a decreased aneurysmal subarachnoid hemorrhage incidence rate than Middle aged population: a descriptive analysis of 8,144 cases in mainland China.

PURPOSE: Rupture of an intracranial aneurysm is a life-threatening acute cerebrovascular event. The purpose of this study was to investigate whether aneurysmal subarachnoid haemorrhage (SAH) incidence rate is higher or lower in elderly population than in middle aged population. MATERIALS AND METHODS: Aneurysmal SAH cases were collected retrospectively from the archives of 21 hospitals in Mainland China. All the cases were collected from September 2016 and backward consecutively for a period of time up to 8 years. SAH was initially diagnosed by brain computed tomography (CT). CT angiography (CTA) or digital subtraction angiography (DSA) was followed and SAH was confirmed to be due to cerebral aneurysm rupture. For cases when multiple bleeding occurred, the age of the first SAH was used in this study. The total incidence from all hospitals at each age group were summed together for females and males respectively; then adjusted by the total population number at each age group for females and males which was from the 2010 population census of the People's Republic of China. RESULTS: In total there were 8,144 cases of intracranial aneurysmal SAH, with 4,861 females and 3,283 males. For females the relative aneurysmal SAH incidence rate started to decrease after around 65 years old, while for males the relative aneurysmal SAH incidence rate started to decrease after around 53 years old. CONCLUSION: Our data tentatively suggest elderly patients may be at a reduced risk of rupture compared with patients who are younger while have similar other risk factors.

High-dose simvastatin for aneurysmal subarachnoid hemorrhage: multicenter randomized controlled double-blinded clinical trial.

BACKGROUND AND PURPOSE: Experimental evidence has indicated the benefits of simvastatin for the treatment of subarachnoid hemorrhage. Two randomized placebo-controlled pilot trials that used the highest clinically approved dose of simvastatin (80 mg daily) gave positive results despite the fact that a lower dose of simvastatin (40 mg daily) did not improve clinical outcomes. We hypothesized that a high dose of 80 mg of simvastatin daily for 3 weeks would reduce the incidence of delayed ischemic deficits after subarachnoid hemorrhage compared with a lower dose (40 mg of simvastatin daily) and lead to improved clinical outcomes. METHODS: The study design was a randomized controlled double-blinded clinical trial. Patients with aneurysmal subarachnoid hemorrhage (presenting within 96 hours of the ictus) from 6 neurosurgical centers were recruited for 3 years. The primary outcome measure was the presence of delayed ischemic deficits, and secondary outcome measures included a modified Rankin disability score at 3 months and an analysis of cost-effectiveness. RESULTS: No difference was observed between the groups treated with the higher dose or the lower dose of simvastatin in the incidence of delayed ischemic deficits (27% versus 24%; odds ratio, 1.2; 95% confidence interval, 0.7-2.0; P=0.586) or in the rate of favorable outcomes (modified Rankin Scale score, 0-2) at 3 months (73% versus 72%; odds ratio, 1.1; 95% confidence interval, 0.6-1.9; P=0.770). CONCLUSIONS: High-dose simvastatin treatment should not be prescribed routinely for aneurysmal subarachnoid hemorrhage. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT01077206.

Early Magnesium Treatment After Aneurysmal Subarachnoid Hemorrhage: Individual Patient Data Meta-Analysis.

BACKGROUND AND PURPOSE: Delayed cerebral ischemia (DCI) is an important cause of poor outcome after aneurysmal subarachnoid hemorrhage (SAH). Trials of magnesium treatment starting <4 days after symptom onset found no effect on poor outcome or DCI in SAH. Earlier installment of treatment might be more effective, but individual trials had not enough power for such a subanalysis. We performed an individual patient data meta-analysis to study whether magnesium is effective when given within different time frames within 24 hours after the SAH. METHODS: Patients were divided into categories according to the delay between symptom onset and start of the study medication: <6, 6 to 12, 12 to 24, and >24 hours. We calculated adjusted risk ratios with corresponding 95% confidence intervals for magnesium versus placebo treatment for poor outcome and DCI. RESULTS: We included 5 trials totaling 1981 patients; 83 patients started treatment<6 hours. For poor outcome, the adjusted risk ratios of magnesium treatment for start <6 hours were 1.44 (95% confidence interval, 0.83-2.51); for 6 to 12 hours 1.03 (0.65-1.63), for 12 to 24 hours 0.84 (0.65-1.09), and for >24 hours 1.06 (0.87-1.31), and for DCI, <6 hours 1.76 (0.68-4.58), for 6 to 12 hours 2.09 (0.99-4.39), for 12 to 24 hours 0.80 (0.56-1.16), and for >24 hours 1.08 (0.88-1.32). CONCLUSIONS: This meta-analysis suggests no beneficial effect of magnesium treatment on poor outcome or DCI when started early after SAH onset. Although the number of patients was small and a beneficial effect cannot be definitively excluded, we found no justification for a new trial with early magnesium treatment after SAH.

Characteristics of rat lumbar vertebral body bone mineral density and differential segmental responses to sex hormone deficiency: a clinical multidetector computed tomography study.

OBJECTIVE: To investigate sex hormone deficiency related osteoporosis and efficacy of different therapies. METHODS: Orchiectomized and ovariectomized rat models are used to investigate sex hormone deficiency related osteoporosis and efficacy of different therapies. A rat vertebral body can be longitudinally divided into central portion, which contain more trabecular bone, and para-endplate portions which contain more compact bone. In matured male and female Wistar and Sprague-Dawley rat lumbar spines, we investigated baseline bone mineral density (BMD) characteristics and the differential segmental responses in bone loss within the lumbar vertebral body post gonadal surgery with clinical multidetector computed tomography. RESULTS: Para-endplate sections had a higher BMD than central sections. The cephalad para-endplate sections had a higher BMD than the caudad para-endplate sections. Eight weeks after gonadal removal, there was more bone loss in central sections than para-endplate sections. The relative difference of bone loss between para-endplate and central sections was more apparent in male rats than in female rats. There was more bone loss in caudad sections than cephalad sections; this lead to a further increase of BMD difference between caudad para-endplate sections and cephalad para-endplate sections post gonadal surgery. CONCLUSION: The approach described in this study provided a consistent way to study BMD change within predominantly compact bone portion and trabecular bone portion of the vertebral body.

Intravenous magnesium sulphate for aneurysmal subarachnoid hemorrhage: an updated systemic review and meta-analysis.

INTRODUCTION: Previous meta-analyses of magnesium sulphate infusion in the treatment of aneurysmal subarachnoid hemorrhage (SAH) have become outdated due to recently published clinical trials. Our aim was thus to perform an up-to-date systemic review and meta-analysis of published data on the use of magnesium sulphate infusion in aneurysmal SAH patients. METHODS: A systemic review and meta-analysis of the literature was carried out on published randomized controlled clinical trials that investigated the efficacy of magnesium sulphate infusion in aneurysmal SAH patients. The results were analyzed with regard to delayed cerebral ischemia (DCI), delayed cerebral infarction, and favorable neurological outcomes at three and six months. The risks of bias were assessed using the Jadad criteria, with a Jadad score >3 indicating a lower such risk. Meta-analyses are presented in terms of relative risk (RR) with 95% confidence intervals (CIs). RESULTS: Six eligible studies with 875 patients were reviewed. The pooled RR for DCI was 0.87 (95% CI, 0.36 to 2.09; P = 0.75). That for delayed cerebral infarction was 0.58 (95% CI, 0.35 to 0.97; P = 0.04), although this result did not persist if only randomized clinical trials with a lower risk of bias were included (RR 0.61, 95% CI, 0.31 to 1.22; P = 0.17). The pooled RR for a favorable outcome at three months was 1.14 (95% CI, 0.99 to 1.31; P = 0.07), and that for a favorable outcome at six months was 1.08 (95% CI, 0.94 to 1.24; P = 0.29). CONCLUSIONS: The present findings do not lend support to a beneficial effect of magnesium sulphate infusion on delayed cerebral infarction. The reduction in DCI and improvement in the clinical outcomes of aneurysmal SAH patients following magnesium sulphate infusion observed in previous pilot studies are not confirmed, although a beneficial effect cannot be ruled out because of sample size limitation.

Intravenous magnesium sulphate for aneurysmal subarachnoid hemorrhage (IMASH): a randomized, double-blinded, placebo-controlled, multicenter phase III trial.

BACKGROUND AND PURPOSE: Pilot clinical trials using magnesium sulfate in patients with acute aneurysmal subarachnoid hemorrhage have reported trends toward improvement in clinical outcomes. This Phase III study aimed to compare intravenous magnesium sulfate infusion with saline placebo among such patients. METHODS: We recruited patients with aneurysmal subarachnoid hemorrhage within 48 hours of onset from 10 participating centers. The patients were randomly assigned to magnesium sulfate infusion titrated to a serum magnesium concentration twice the baseline concentration or saline placebo for 10 to 14 days. Patients and assessors were blinded to treatment allocation. The study is registered at www.strokecenter.org/trials (as Intravenous Magnesium Sulphate for Aneurysmal Subarachnoid Hemorrhage [IMASH]) and www.ClinicalTrials.gov (NCT00124150). RESULTS: Of the 327 patients recruited, 169 were randomized to receive treatment with intravenous magnesium sulfate and 158 to receive saline (placebo). The proportions of patients with a favorable outcome at 6 months (Extended Glasgow Outcome Scale 5 to 8) were similar, 64% in the magnesium sulfate group and 63% in the saline group (OR, 1.0; 95% CI, 0.7 to 1.6). Secondary outcome analyses (modified Rankin Scale, Barthel Index, Short Form 36, and clinical vasospasm) also showed no significant differences between the 2 groups. Predefined subgroups included age, admission World Federation of Neurological Surgeons grade, pre-existing hypertension, intracerebral hematoma, intraventricular hemorrhage, location of aneurysm, size of aneurysm, and mode of aneurysm treatment. In none of the subgroups did the magnesium sulfate group show a better outcome at 6 months. CONCLUSIONS: The results do not support a clinical benefit of intravenous magnesium sulfate infusion over placebo infusion in patients with acute aneurysmal subarachnoid hemorrhage.

Plasma magnesium concentrations and clinical outcomes in aneurysmal subarachnoid hemorrhage patients: post hoc analysis of intravenous magnesium sulphate for aneurysmal subarachnoid hemorrhage trial.

BACKGROUND AND PURPOSE: Conflicting data have been obtained on optimal plasma magnesium concentrations for clinical outcomes in patients with aneurysmal subarachnoid hemorrhage. METHODS: Adults (aged 18 years or older) who had acute aneurysmal subarachnoid hemorrhage diagnosed were randomly assigned to receive either an intravenous MgSO(4) infusion (80 mmol in 500 mL normal saline per day) or a placebo (500 mL normal saline per day) for up to 14 days. Post hoc multivariable binary logistic regression analyses were performed by dividing mean plasma magnesium concentrations into 4 quartiles according to treatment group and then comparing with the lowest quartiles. RESULTS: The worst clinical outcomes at 6 months were seen in MgSO(4) group patients, with mean plasma magnesium concentrations in the fourth quartile, and in placebo group patients, with mean such concentrations in the third and fourth quartiles. CONCLUSIONS: No evidence was found to suggest that a higher mean plasma magnesium concentration improves clinical outcomes. On the contrary, we found an association between high plasma magnesium concentration and worse clinical outcomes.

Antibiotics-impregnated ventricular catheter versus systemic antibiotics for prevention of nosocomial CSF and non-CSF infections: a prospective randomised clinical trial.

BACKGROUND: In recent years, cranial ventricular catheters impregnated with antimicrobial agents have become available. Theoretically, they provide antibiotic prophylaxis locally without the associated complications of opportunistic nosocomial infections. This study aims to compare antibiotic impregnated catheters with conventional catheters coupled with systemic antibiotics. METHODS: Patients undergoing emergency neurosurgical operations were recruited. Patients were randomly assigned to antibiotic impregnated catheters (Bactiseal, Codman, Johnson & Johnson, Raynham, MA, USA) or conventional catheters coupled with systemic antibiotics. RESULTS: 184 neurosurgical patients were enrolled between April 2004 and December 2008. Mean duration of ventricular catheter was 10 days for both groups. The proportion of patients with nosocomial infection was not significantly different: 57% (51/90) in the Bactiseal group and 51% (48/94) in the conventional group (OR 1.3, 0.7 to 2.2). There were also no differences in secondary outcome measures (CSF infection, intensive care unit stay, acute hospital stay and functional outcome) between the two groups. CONCLUSIONS: Antibiotic impregnated catheters are as effective as systemic antibiotics in the prevention of CSF infection and their corresponding nosocomial infection rates are not significantly different. The study is registered at http://www.ClinicalTrials.gov (NCT00286104).

Clinical study on cognitive dysfunction after spontaneous subarachnoid haemorrhage: patient profiles and relationship to cholinergic dysfunction.

PURPOSE: We aimed to explore the cognitive profiles of subarachnoid haemorrhage patients who returned to the community, along with the associated risk factors. METHODS: We recruited 40 Chinese patients with spontaneous subarachnoid haemorrhage 7-27 months after the initial presentation. They had all been discharged to their homes or to care homes for the elderly. For cognitive assessment, we employed the Cognitive Subscale of the Alzheimer Disease Assessment Scale (ADAS-cog) for global cognitive function, the Frontal Assessment Battery (FAB) for frontal lobe function, and the Rivermead Behavioural Memory Test (RBMT) for everyday memory function. RESULTS: An ADAS-cog of more than 21/85 (poor global cognitive function) was noted in 14 (35%) patients. A FAB of less than 12/18 (poor frontal lobe function) was noted in 13 (27.5%) patients. An RBMT score of less than 15/26 (poor everyday memory function) was noted in 17 (43.6%) patients. Poor cognitive function was found to be associated with chronic hydrocephalus (in terms of FAB), with clinical vasospasm (in terms of RBMT), and with cerebral infarction (in terms of RBMT). CONCLUSIONS: Poor cognitive function was common and occurred in up to 43.6% of the patients, with the verbal and behavioural memory aspects predominantly affected. We did not find a significant association between cholinergic dysfunction and cognitive dysfunction. Organization of future drug trials and cognitive rehabilitation should take into account the association between frontal lobe dysfunction and chronic hydrocephalus.

The effect of hypermagnesemic treatment on cerebrospinal fluid magnesium level in patients with aneurysmal subarachnoid hemorrhage.

Preliminary evidence has suggested that magnesium sulfate infusion reduces delayed ischemic neurological deficit and improves clinical outcome after aneurysmal subarachnoid hemorrhage. However, little is known about its site of action in vivo. We studied 22 aneurysmal subarachnoid hemorrhage patients with or without magnesium sulfate infusion for 10-14 days. Thirteen patients had external ventricular drains inserted for hydrocephalus and daily cerebrospinal fluid magnesium levels were measured. For patients given magnesium sulfate infusion, the aim was to raise the plasma magnesium level to double the baseline level. We found that the magnesium sulfate infusion bought an 11% to 21% increase in cerebrospinal fluid magnesium. The elevation of cerebrospinal fluid magnesium was sustained for at least nine days. Whether this mild elevation in cerebrospinal fluid magnesium level was adequate for neuroprotection awaits the results of ongoing clinical trials.

Ischemic events after carotid interventions in relationship to baseline cerebrovascular reactivity.

BACKGROUND: We aimed to investigate whether baseline cerebrovascular reactivity could predict subsequent ischemic event after intervention and identify the patient group for more aggressive medical and interventional management paradigms. METHODS: Patients with more than 70% cervical carotid stenosis (from ultrasonography) were reviewed. Patients, who had baseline cerebrovascular reactivity test before intervention and had either carotid endarterectomy (CEA) or carotid angioplasty and stenting (CAS) performed, were recruited for analysis. Transcranial Doppler ultrasonography was used to examine the reactivity of the middle cerebral artery in response to 5% carbon dioxide in oxygen. The mean follow up period was 66 months. FINDINGS: Twenty-six patients had symptomatic carotid stenosis and ten patients had asymptomatic carotid stenosis. There were four subsequent ischemic events during follow up. None of the nine patients with impaired baseline ipsilateral cerebrovascular reactivity had subsequent ischemic event. CONCLUSIONS: In this current study, impaired baseline cerebrovascular reactivity did not predict the subsequent stroke risk after carotid intervention. Cerebrovascular reactivity testing may not serve as an indicator for aggressive medical and surgical treatments.

Changes of cognitive functioning following mild traumatic brain injury over a 3-month period.

PRIMARY OBJECTIVE: To examine the cognitive functioning in patients with complicated mild traumatic brain injury immediately post-injury and at 1 and 3 months post-injury. RESEARCH DESIGN, METHODS, AND PROCEDURES: Between-group comparisons were adopted for this study. Specifically, both patients and healthy controls were administered neuropsychological assessments measuring attention, memory and executive functions at three time points. RESULTS: Findings indicate that patients performed significantly more poorly in information processing and divided attention, sustained attention, verbal recognition and verbal fluency immediately post-injury. While the information processing and divided attention of mild TBI patients improved at 1 month and returned to normal at 3 months post-injury, their sustained attention remained significantly poorer over the 3-month period. CONCLUSIONS: Findings suggest that attention dysfunction is noticeable immediately following a mild TBI. Different attention functions appear to recover at a different pace over time, suggesting that the condition may have a differential impact on the different sub-types of attention.

Treatment of profuse epistaxis in patients irradiated for nasopharyngeal carcinoma.

BACKGROUND: Profuse epistaxis in patients with nasopharyngeal carcinoma (NPC) previously treated with radiotherapy (RT) can be life threatening. Surgical means to prevent rebleeding may at times be difficult and unsuccessful. We aim to investigate the characteristics of this group of patients and our experience of endovascular embolization technique in the management of epistaxis in this group of patients. METHODS: A retrospective review of all nasopharyngeal carcinoma patients presented with profuse epistaxis during follow up after radiotherapy was carried out in a regional neurosurgical centre in Hong Kong. Seventeen patients were included for the analysis within the recent 6-year period. The age of patients was 55.5 +/- 8.358 years (mean +/- standard deviation). The sex ratio was 5:1 (M : F). Diagnostic catheter angiography was carried out in all 17 patients. Endovascular embolization was carried out in 11 patients with the joint decision of the otolaryngologist and neurointerventionist in charge . RESULTS: Four patients underwent main trunk occlusion for internal carotid pseudoaneurysm. Seven patients underwent embolization of branches of external carotid artery. One patient required another session of external carotid artery embolization 1 month later. There was one inpatient death because of pneumonia and hepatic encephalopathy. With our protocol, there were only two patients (11.7%) with delayed rebleed at 2 and 5 months, respectively. Both patients had advanced diseases and died. CONCLUSION: In irradiated patients with nasopharyngeal carcinoma presenting with profuse epistaxis, angiography had a high yield of pseudoaneurysm or hypervascularity and these lesions could be safely managed through endovascular embolization.

The effect of intravenous magnesium sulfate infusion on serum levels of sodium and potassium in patients with aneurysmal subarachnoid hemorrhage.

Abnormal serum sodium levels are frequently observed among patients with aneurysmal subarachnoid hemorrhage (SAH) and may worsen cerebral edema or mass effect. Low serum potassium levels (hypokalemia) are also common among patients with aneurysmal SAH and are associated with prolonged QT interval and ventricular arrhythmia. Recent meta-analysis suggests that MgSO4 infusion improves the clinical outcome in patients after aneurysmal SAH; however, MgSO4 infusion may theoretically exacerbate electrolyte disturbance. We retrospectively reviewed the prospectively collected demographic and laboratory data of 100 patients after aneurysmal subarachnoid SAH in a neurosurgical center in Hong Kong. 51 patients had daily magnesium sulfate infusion for 14 days (Group 1) and 49 patients were managed similarly, without magnesium sulfate infusion (Group 2). Days of hypernatremia (mean+/-SD) were 2.0+/-2.7 for group 1 and 2.0+/-2.5 for group 2, p = 0.999; days of hyponatremia (mean+/-SD) were 2.7+/-3.1 for group 1 and 2.0+/-2.9 for group 2, p = 0.230; days of hypokalemia (mean+/-SD) were 4.5+/-3.1 for group 1 and 4.5+/-3.2 for group 2, p = 0.819. Hyperkalemia was uncommon in both groups. There was also no statistically significant difference between the two groups when the data were re-analyzed as severe hyponatremia, severe hypokalemia and severe hyperkalemia. Magnesium sulfate infusion was safe and did not seem to exacerbate the duration of electrolyte disturbance associated with aneurysmal subarachnoid hemorrhage.

MicroRNA-182 Regulates Neurite Outgrowth Involving the PTEN/AKT Pathway.

MicroRNAs are implicated in neuronal development and maturation. Neuronal maturation, including axon outgrowth and dendrite tree formation, is regulated by complex mechanisms and related to several neurodevelopmental disorders. We demonstrated that one neuron-enriched microRNA, microRNA-182 (miR-182), played a significant role in regulating neuronal axon outgrowth and dendrite tree formation. Overexpression of miR-182 promoted axon outgrowth and complexity of the dendrite tree while also increasing the expression of neurofilament-M and neurofilament-L, which provide structural support for neurite outgrowth. However, a reduction of miR-182 inhibited neurite outgrowth. Furthermore, we showed that miR-182 activated the AKT pathway by increasing AKT phosphorylation on S473 and T308 and inhibiting PTEN activity by increasing phosphorylation on S380. Inhibition of AKT activity with the PI3-K inhibitor LY294002 could downregulate AKT and PTEN phosphorylation and suppress axon outgrowth. In addition, we showed that BCAT2 might be the target of miR-182 that takes part in the regulation of neuronal maturation; blockage of endogenous BCAT2 promotes axon outgrowth and AKT activity. These observations indicate that miR-182 regulates axon outgrowth and dendrite maturation involving activation of the PTEN/AKT pathway.

Interactome and reciprocal activation of pathways in topical mesenchymal stem cells and the recipient cerebral cortex following traumatic brain injury.

In this study, GFP-MSCs were topically applied to the surface of cerebral cortex within 1 hour of experimental TBI. No treatment was given to the control group. Three days after topical application, the MSCs homed to the injured parenchyma and improved the neurological function. Topical MSCs triggered earlier astrocytosis and reactive microglia. TBI penumbra and hippocampus had higher cellular proliferation. Apoptosis was suppressed at hippocampus at 1 week and reduced neuronal damaged was found in the penumbral at day 14 apoptosis. Proteolytic neuronal injury biomarkers (alphaII-spectrin breakdown products, SBDPs) and glial cell injury biomarker, glial fibrillary acidic protein (GFAP)-breakdown product (GBDPs) in injured cortex were also attenuated by MSCs. In the penumbra, six genes related to axongenesis (Erbb2); growth factors (Artn, Ptn); cytokine (IL3); cell cycle (Hdac4); and notch signaling (Hes1) were up-regulated three days after MSC transplant. Transcriptome analysis demonstrated that 7,943 genes were differentially expressed and 94 signaling pathways were activated in the topical MSCs transplanted onto the cortex of brain injured rats with TBI. In conclusion, topical application offers a direct and efficient delivery of MSCs to the brain.

Magnesium therapy within 48 hours of an aneurysmal subarachnoid hemorrhage: neuro-panacea.

Whereas advances in neurosurgical treatment and intensive care management improve the results from many of the devastating complications associated with aneurysmal subarachnoid hemorrhage, cerebral vasospasm remains a major cause of neurological morbidity and mortality. Experimental studies suggested that MgSO(4) inhibits excitatory amino acid release, blocks N-methyl-D-aspartate (NMDA) receptors and prevents calcium entry into the cell. Magnesium also increases red blood cell deformability. These changes may reduce the occurrence of cerebral vasospasm and minimize neuronal injury during episodes of cerebral vasospasm. Our group is currently hosting the intravenous magnesium sulfate to improve outcome after aneurysmal subarachnoid hemorrhage (IMASH) trial, which is a randomized, placebo-controlled, double-blinded, multicentered trial to evaluate the effect of magnesium sulfate infusion on the clinical outcome of patients with aneurysmal subarachnoid hemorrhage since 2002. The pilot result showed a trend towards decreased clinical vasospasm and better patient outcome. Magnesium sulfate infusion may prove to be an effective and inexpensive way to reduce the morbidity and mortality associated with aneurysmal subarachnoid hemorrhage, which is a major breakthrough in the current management.

Intravenous magnesium sulfate after aneurysmal subarachnoid hemorrhage: a prospective randomized pilot study.

We performed a randomized, double-blind, pilot study on magnesium sulfate (MgSO4) infusion for aneurysmal subarachnoid hemorrhage (SAH).Sixty patients with SAH were randomly allocated to receive either MgSO4 80 mmol/day or saline infusion for 14 days. Patients also received intravenous nimodipine. Episodes of vasospasm were treated with hypertensive and hypervolemic therapy. Neurologic status was assessed 6 months after hemorrhage using the Barthel index and Glasgow Outcome Scale. Incidences of cardiac and pulmonary complications were also recorded. Patient characteristics, severity of SAH, and surgical treatment did not differ between groups. The incidence of symptomatic vasospasm decreased from 43% in the saline group to 23% in patients receiving MgSO4 infusion, but it did not reach statistical significance, P=0.06. For patients who had transcranial Doppler-detected vasospasm, defined as mean flow velocity >120 cm/s and a Lindegaard index >3, the duration was shorter in the magnesium group compared with controls (P<0.01). There was, however, no difference between groups in functional recovery or Glasgow Outcome Scale score. The incidence of adverse events such as brain swelling, hydrocephalus, and nosocomial infection was also similar in patients receiving MgSO4 or saline. In this small pilot study, MgSO4 infusion for aneurysmal SAH is feasible. On the basis of the preliminary data, a larger study recruiting approximately 800 patients is required to test for a possible neuroprotective effect of magnesium after SAH.

Pattern of recurrence and factors associated with cerebrospinal fluid dissemination of glioblastoma in Chinese patients.

BACKGROUND: Pattern of recurrence of glioblastoma (GBM) seems to have undergone some shifts from distant metastasis as a rarity to a higher proportion, including disease disseminated via cerebrospinal fluid (CSF) pathway. There is still no report on the pattern of recurrence for Chinese population. Here, we evaluated the pattern of recurrence of GBM in Chinese patients along with factors that could affect the distribution of recurrence. METHODS: Medical records of GBM patients with definite recurrence were reviewed. Local recurrence was defined as tumor regrowth within the preoperative abnormal signals on magnetic resonance imaging (MRI) T2 sequence. New recurrence was a new lesion away from the preoperative T2 abnormalities. New recurrence in contact with CSF pathways was registered as new CSF dissemination. Progress-free survival (PFS) and survival after progress were compared using the Kaplan-Meier survival curves. Potential risk factors for new CSF dissemination were assessed using univariate models followed by multivariate analysis. RESULTS: Thirty-six patients were proven to have recurrence; 22 local and 14 new recurrences. Among the 14 patients, 11 had new CSF dissemination. Median PFS for local, new parenchymal recurrence, and new CSF dissemination were 5.5 months, 9.9 months, and 12.1 months, whereas survival after progress were 6.1 months, 5.7 months, and 16.9 months, respectively. The ventricular entry during surgery and the completion of concomitant chemoradiotherapy were risk factors for new CSF dissemination. O6-methylguanine-DNA methyltransferase methylation was associated with the development of CSF dissemination. CONCLUSION: The majority of recurrence remained local (22/36, 61%). However, CSF dissemination was up to 30% (11/36). PFS for patients with CSF dissemination was the longest, and paradoxically survival after progress was the shortest. Ventricular entry should be avoided. Whole craniospinal MRI surveillance should be included for these patients.