Endovascular embolization of spontaneous massive hemorrhage of a facial plexiform neurofibroma: case report and literature review.

BACKGROUND: As a subtype of neurofibromatosis, the plexiform neurofibroma is a benign, autosomally inherited disorder and predisposed to tumour formation. However, life-threatening haemorrhage into facial plexiform neurofibroma is extremely rare. CASE INFORMATION: In the current study, we showed a facial plexiform neurofibroma case with massive haemorrhage in the cranio-maxillofacial region. An emergent selective angiography of the external carotid artery was performed to identify the offending artery, which was then selectively occluded by the combination of detachable coils and Onyx-34. Thus, the minimally invasive drainage surgery was successfully performed to evacuate the haematoma. CONCLUSION: We believe the endovascular embolization achieved its purpose by providing an initial salvage strategy for stopping active haemorrhage in plexiform neurofibroma, allowing surgeons to perform open surgery with lower complications rate.

Invention of a non-invasive intracranial pressure (ICP) monitoring system - an enlightenment from a hydrocephalus study.

BACKGROUND: Mechanical obstruction is the most common cause of shunt failure for hydrocephalic patients. However, the diagnosis is extremely challenging and often requires invasive testing methods. Thus, a simple and non-invasive technique is in urgent need to predict the intracranial pressure (ICP) of hydrocephalic patients during their post-surgical follow-up, which could help neurosurgeons to determine the conditions of the shunt system. MATERIALS AND METHODS: Two groups of patients were enrolled in the current study. In group I, patients were enrolled as they were diagnosed with high ICP hydrocephalus and received shunt surgery. The shunt valve pressures were taken for their post-surgical ICP. Meanwhile, the participants of group II exhibited abnormally increased lumbar puncture opening pressure (LPOP; from 180 to 400 mmH2O). Both the ICP and LPOP were used to match with their corresponding tympanic membrane temperature (TMT). RESULTS: When patients' ICP were in the normal range (group I, from 50 to 180 mmH2O), the TMT correlated with ICP in a linear regression model (R2 = 0.59, p < 0.001). Interestingly, when patients exhibited above-normal ICP (LPOP was from 180 to 400 mmH2O), their TMT fit well with the ICP in a third-order polynomial regression (R2 = 0.88). When the ICP was 287.98 mmH2O, the TMT approached the vertex, which was 38.54 °C. Based on this TMT-ICP algorithm, we invented a non-invasive ICP monitor system. Interestingly, a tight linear correlation was detected between the ICP data drawn from the non-invasive device and Codman ICP monitoring system (R2 = 0.93, p < 0.01). CONCLUSIONS: We believe the TMT-ICP algorithm (the Y-Jiang model) could be used for preliminary prediction of shunt malfunction as well as monitoring ICP changes.

Crosstalk between soluble PDGF-BB and PDGFRß promotes astrocytic activation and synaptic recovery in the hippocampus after subarachnoid hemorrhage.

Platelet-derived growth factor receptor ß (PDGFRß) dynamically changes after brain injury, possibly mediating the neuroprotective role of soluble homodimers of the platelet-derived growth factor ß subunit (PDGF-BB) that is secreted by microcirculation cells. The aim of this study was to determine whether binding of PDGF-BB to astrocytic PDGFRß enhanced crosstalk among the various components of the neurovascular unit, leading to synaptic recovery after subarachnoid hemorrhage (SAH). The soluble PDGF-BB from the cerebrospinal fluid (CSF) of patients with SAH was measured. The relationship between PDGF-BB treatment and astrocytic PDGFRß signaling was further explored in vivo and in vitro in experimental SAH models. Compared with the levels in the control samples, the PDGF-BB protein levels in the CSF of patients with SAH were significantly increased. After the generation of experimental SAH, astrocyte activation markers were markedly induced by the binding of PDGF-BB to astrocytic PDGFRß, accompanied by improved levels of synaptic recovery and cognitive function. Soluble PDGF-BB and astrocytic PDGFRß signaling are essential for the neuroprotective effect in the hippocampus and the coculture system in vitro after SAH that otherwise leads to cognitive dysfunction and neuronal damage.-Zhou, X., Wu, Q., Lu, Y., Zhang, X., Lv, S., Shao, J., Zhou, Y., Chen, J., Hou, L., Huang, C., Zhang, X. Crosstalk between soluble PDGF-BB and PDGFRß promotes astrocytic activation and synaptic recovery in the hippocampus after subarachnoid hemorrhage.

miR-448-3p controls intracranial aneurysm by regulating KLF5 expression.

microRNAs (miRNAs) control several processes known to be involved in progression of aneurysm. Here, intracranial aneurysms (IAs) were surgically induced in Sprague-Dawley rats, and we found that miR-448-3p was downregulated and KLF5 was upregulated in IA rats. We identified Klf5 as a direct target of miR-448-3p in smooth muscle cells (SMCs). In addition, aneurysms size and the lumen area of the aneurysms were smaller 4 weeks after IA induction in the miR-448-3p-treated group. miR-448-3p treatment protected the wall thickness ratio and suppressed macrophage infiltration after IA induction. IAs caused a significant increase in KLF5 expression and were alleviated by miR-448-3p. Moreover, the anti-inflammatory effect of miR-448-3p was verified in lipopolysaccharide -stimulated RAW 264.7 macrophage cells. The expression levels of KLF5, MMP2, and MMP9 levels were elevated by LPS, and were attenuated by miR-448-3p. These data suggest that miR-448-3p plays the inhibitory role in IA progression, indicating that miR-448-3p overexpression is crucial for preventing the development of IA through downregulation of macrophage-mediated inflammation.

Individualized endovascular treatment of high-grade traumatic vertebral artery injury.

BACKGROUND: Traumatic vertebral artery injury (TVAI) is associated with craniocervical trauma that can lead to potentially fatal posterior circulation stroke. It presents a clinical challenge since it is hard to detect and there are no widely accepted guidelines on diagnosis and management. High-grade TVAI is more difficult to treat and no consensus has been reached yet. METHODS: We performed a single-center, long-term, therapeutic study involving 272 patients with craniocervical injury, eleven of which were diagnosed with high-grade TVAI. Individualized endovascular treatments were performed on these patients based upon the hemodynamic and morphological characteristics of the injured vertebral artery. Postoperative angiography was conducted at 2 weeks, 3 months and 6 months, and then annually after intervention. RESULTS: Ten vertebral pseudoaneurysms and one arteriovenous fistula (AVF) were confirmed by postoperative angiography. All the participants' neurological deficit symptoms disappeared or were significantly alleviated gradually, and no new symptoms were found after endovascular treatment. Follow-up angiography of the patients with pseudoaneurysms showed a normally shaped vertebral artery with no stenosis or aneurysms; the angiographic result of the patient with the AVF presented successful embolization in the proximal vertebral artery fistula with no progression or new stenosis. Their modified Rankin Scale (mRS) scores were also satisfactory. CONCLUSIONS: Application of individualized endovascular therapy in high-grade TVAI is safe, technically feasible and clinically effective, but there is no comparison between endovascular management and other management approaches because randomized trials cannot be carried out currently.

Cholesterol levels and risk of hemorrhagic stroke: a systematic review and meta-analysis.

BACKGROUND AND PURPOSE: Cholesterol levels are inconsistently associated with the risk of hemorrhagic stroke. The purpose of this study is to assess their relationships using a meta-analytic approach. METHODS: We searched PubMed and Embase for pertinent articles published in English. Only prospective studies that reported effect estimates with 95% confidential intervals (CIs) of hemorrhagic stroke for ≥3 categories of cholesterol levels, for high and low comparison, or for per 1 mmol/L increment of cholesterol concentrations were included. We used the random-effects model to pool the study-specific results. RESULTS: Twenty-three prospective studies were included, totaling 1 430 141 participants with 7960 (5.6%) hemorrhagic strokes. In high versus low analysis, the summary relative risk of hemorrhagic stroke was 0.69 (95% CI, 0.59-0.81) for total cholesterol, 0.98 (95% CI, 0.80-1.19) for high-density lipoprotein cholesterol, and 0.62 (95% CI, 0.41-0.92) for low-density lipoprotein cholesterol. In dose-response analysis, the summary relative risk of hemorrhagic stroke for 1 mmol/L increment of total cholesterol was 0.85 (95% CI, 0.80-0.91), for high-density lipoprotein cholesterol was 1.11 (95% CI, 0.99-1.25), and for low-density lipoprotein cholesterol was 0.90 (95% CI, 0.77-1.05). The pooled relative risk for intracerebral hemorrhage was 1.17 (95% CI, 1.02-1.35) for high-density lipoprotein cholesterol. CONCLUSIONS: Total cholesterol level is inversely associated with risk of hemorrhagic stroke. Higher level of low-density lipoprotein cholesterol seems to be associated with lower risk of hemorrhagic stroke. High-density lipoprotein cholesterol level seems to be positively associated with risk of intracerebral hemorrhage.

Clinical review: Efficacy of antimicrobial-impregnated catheters in external ventricular drainage - a systematic review and meta-analysis.

To assess the efficacy of antimicrobial-impregnated catheters in preventing catheter-related infections during external ventricular drainage (EVD), we performed a meta-analysis and systematic review. We systematically searched Medline, Embase, and the Cochrane Library. All randomized controlled trials (RCTs) and nonrandomized prospective studies (NPSs) related to antimicrobial-impregnated EVD catheters were included. The primary outcome was the rate of cerebrospinal fluid infection (CFI). The secondary outcomes included the rate of time-dependent CFI and catheter bacterial colonization. We further performed subgroup analysis, meta-regression analysis, and microbial spectrum analysis. Four RCTs and four NPSs were included. The overall rate of CFIs was 3.6% in the antimicrobial-impregnated catheter group and 13.7% in the standard catheter group. The pooled data demonstrated that antimicrobial-impregnated catheters were superior to standard catheters in lowering the rate of CFIs (odds ratio (OR) = 0.25, 95% confidence interval (CI) = 0.12 to 0.52, P <0.05). In survival analysis, the 20-day infection rate was significantly reduced with the use of antimicrobial-impregnated catheters (hazard ratio = 0.52, 95% CI = 0.29 to 0.95, P <0.05). Furthermore, a significantly decreased rate of catheter bacterial colonization was noticed for antimicrobial-impregnated catheters (OR = 0.37, 95% CI = 0.21 to 0.64, P <0.05). In subgroup analyses, although significant results remained for RCTs and NPSs, a subgroup difference was revealed (P <0.05). Compared with standard catheters, a significantly lower rate of CFIs was noticed for clindamycin/rifampin-impregnated catheters (OR = 0.27, 95% CI = 0.10 to 0.73, P <0.05) and for minocycline/rifampin-impregnated catheters (OR = 0.11, 95% CI = 0.06 to 0.21, P <0.05). However, no statistical significance was found when compared with silver-impregnated catheters (OR = 0.33, 95% CI = 0.07 to 1.69, P = 0.18). In microbial spectrum analysis, antimicrobial-impregnated catheters were shown to have a lower rate of Gram-positive bacterial infection, particularly the coagulase-negative Staphylococcus. In conclusion, the use of antimicrobial-impregnated EVD catheters could be beneficial for the prevention of CFI and catheter bacterial colonization. Although antibiotic-coated catheters seem to be effective, no sufficient evidence supports the efficacy of silver-impregnated catheters.

Introduction of a Novel, Continuous, Noninvasive Estimation of Intracranial Pressure and Cerebral Perfusion Pressure Based on Tympanic Membrane Temperature.

OBJECTIVE: Hydrocephalus is a common but potentially life-threatening condition. However, valve malfunction makes further diagnosis difficult. Thus, we tried to develop a noninvasive method to detect the hydrocephalus intracranial pressure (ICP) during routine follow-up. METHODS: In group I, the patient was recruited because a spinal tap test was necessary for either disease diagnosis or treatment. In group II, patients were diagnosed with high ICP hydrocephalus and received shunt surgery. The tympanic membrane temperatures (TMTs) were recorded and plotted against the spinal tap pressure (STP) and shunt valve pressures. RESULTS: All patients in group I showed an above-normal STP (from 180 to 400 mm H2O). The STP presents with an inverted U-shaped curve when it is plotted against TMT (R2 = 0.9). When the STP was 286.1 mm H2O, the TMT approached its peak value, which was 38.61°C (101.5°F). However, when ICP was in the normal range (50-200 mm H2O), the TMT correlated with ICP in a linear regression model (R2 = 0.69; P < 0.001). In addition, the cerebral perfusion pressure (CPP) was calculated and plotted against TMT. The TMT-CPP was also shown as a parabola (R2 = 0.74). Based on the TMT-ICP algorithm, we invented a noninvasive ICP monitor system, which performs in a manner comparable to the Codman ICP Transducer (R2 = 0.9; P < 0.01). CONCLUSIONS: Both Y-Jiang TMT-ICP and TMT-CPP algorithms are useful to monitor the shunt outcomes and identify potential shunt failure. More importantly, these algorithms open the possibility for the rational acquisition of ICP and CPP noninvasively.

Histone Demethylase KDM4A Inhibition Represses Neuroinflammation and Improves Functional Recovery in Ischemic Stroke.

BACKGROUND: Epigenetic regulation concerning histone lysine methylation and demethylation play a crucial role in cerebral ischemic injury. Dysregulation of histone methylation modifiers has been identified in cerebral ischemia. However, the function and the underlying mechanisms of histone demethylase KDM4A on neuroinflammation and functional recovery in ischemic stroke remains unclear. METHODS: In the present study, the rat model of transient middle cerebral artery occlusion (MCAO) was established, and the expression level of KDM4A was assessed in brain tissues. KDM4A inhibition was carried out by intrathecal injection with Lv-shKDM4A, and then pro-inflammatory cytokines and neurological functional tests were assessed. RESULTS: We demonstrated that rats subjected to MCAO showed a markedly increased expression of KDM4A, pro-inflammatory cytokines IL-1ß and TNF-α, and vascular endothelial growth factor (VEGF), whereas KDM4A inhibition repressed the expression of IL-1ß, TNF-α and VEGF both in MCAO and oxygen-glucose deprivation (OGD) models. Furthermore, KDM4A inhibition showed a marked improvement in spatial learning and sensorimotor function, as suggested by mNSS and foot-fault test, respectively. Mechanistically, KDM4A inhibition repressed NF-κB signaling activation in microglia as indicated by decreased expression and nuclear translocation of p65 in vitro and in vivo. The effects of KDM4A overexpression on exacerbating neuroinflammation was inhibited by additional treatment of NF-κB inhibitor (JSH-23). CONCLUSION: The current results demonstrated KDM4A inhibition improves functional recovery in ischemic stroke by repressing NF-κB activation and subsequent neuroinflammation.

Intracranial haemophilic pseudotumor associated with factor VIII deficiency.

Haemophilic pseudotumor is a rare complication of haemophilia occurring in 1-2% of patients and is more frequently located is in the long bones of the lower extremities and in the pelvis. We present the first case of an intracranial haemophilic pseudotumor in a patient with factor VIII deficiency.

Expression of ubiquitin-conjugating enzyme E2C/UbcH10 in astrocytic tumors.

UbcH10 is one of the key regulators of cell cycle progression through the mitotic spindle assembly checkpoint pathway. Recently, aberrantly high UbcH10 expression has been demonstrated in a variety of malignancies. However, its role in astrocytic carcinogenesis is not well defined. This study investigated the splice pattern of the UbcH10 gene and its expression status in astrocytomas of different grades. Consequently, UbcH10 splice variant 1 (GenBank accession nos. NM_007019) was detected in astrocytomas and normal brain tissues by RT-PCR and sequence analysis. Expression levels of UbcH10 mRNA were elevated in high- versus low-grade astrocytomas (64.33+/-60.98 vs 8.36+/-8.15, respectively; p=0.000) or normal controls (64.33+/-60.98 vs 1.00+/-1.57, respectively; p=0.000), as determined by quantitative real time PCR analysis. Similarly, immunohistochemistry study showed increased UbcH10 labelling index in high-grade astrocytomas versus low-grade tumors (10.53+/-5.79% vs 4.23+/-2.85%, respectively; p=0.000) or normal controls (10.53+/-5.79% vs 0.0+/-0.0%, respectively; p=0.000) and, a positive correlation between UbcH10 immunoreactivity and Ki-67 immunostaining was also noted (Spearman r=0.63, p<0.001). These data suggest that overexpression of UbcH10 may serve as one important molecular mechanism that underlies the astrocytic carcinogenesis.

3-Dimensional rotational angiography for the treatment of spinal cord vascular malformations.

BACKGROUND: This study was conducted to evaluate the effect of 3D-RA on the treatment of SCVMs. METHODS: Twelve patients with SCVM were retrospectively reviewed for details of 2D and 3D-RA findings. Pretherapeutic 2D and 3D-RA angiograms were compared with respect to 4 critical categories of parameters: (1) the exact anatomic location, size, and extent; (2) the definitive diagnosis; (3) the precise angioarchitectural configuration; and (4) the contribution to further intervention. RESULTS: Overall, 2D and 3D-RA were equally effective in demonstrating the exact anatomic location, size, and extent, and establishing the definitive diagnosis of SCVM in all 12 cases. 3-Dimensional rotational angiography demonstrated precise angioarchitectural configuration in 8 (8/12) cases, facilitated treatment in 6 (6/12) cases, and modified therapeutic strategies in 2 (2/12) cases via information not available from 2D-DSA images. Both 2D and 3D-RA contributed equally to the therapeutic intervention in 4 (4/12) patients. No complications occurred as a result of 3D-RA. CONCLUSIONS: 3-Dimensional rotational angiography may enhance our ability to treat SCVMs with complex angioarchitecture and is an ideal addition to conventional 2D angiography in the management of these vascular lesions.

SIRT3 Expression Decreases with Reactive Oxygen Species Generation in Rat Cortical Neurons during Early Brain Injury Induced by Experimental Subarachnoid Hemorrhage.

Sirtuin3 (SIRT3) is an important protein deacetylase which predominantly presents in mitochondria and exhibits broad bioactivities including regulating energy metabolism and counteracting inflammatory effect. Since inflammatory cascade was proved to be critical for pathological damage following subarachnoid hemorrhage (SAH), we investigated the overall expression and cell-specific distribution of SIRT3 in the cerebral cortex of Sprague-Dawley rats with experimental SAH induced by internal carotid perforation. Results suggested that SIRT3 was expressed abundantly in neurons and endothelia but rarely in gliocytes in normal cerebral cortex. After experimental SAH, mRNA and protein expressions of SIRT3 decreased significantly as early as 8 hours and dropped to the minimum value at 24 h after SAH. By contrast, SOD2 expression increased slowly as early as 12 hours after experimental SAH, rose up sharply at the following 12 hours, and then was maintained at a higher level. In conclusion, attenuated SIRT3 expression in cortical neurons was associated closely with enhanced reactive oxygen species generation and cellular apoptosis, implying that SIRT3 might play an important neuroprotective role during early brain injury following SAH.

Hemiparesis in carotid cavernous fistulas (CCFs): a case report and review of the literature.

Carotid-cavernous fistulas (CCFs) are abnormal arteriovenous anastamoses between the carotid artery and the cavernous sinus. These fistulas may be classified by cause (spontaneous or traumatic), flow velocity (high or low), or pathogenesis (direct or indirect). The most commonly adopted classification is that described by Barrow based on arterial supply. Traumatic CCFs are almost always direct shunts between the internal carotid artery (ICA) and the cavernous sinus. General features of CCFs, which may be apparent with any lesion, including bruit, headache, loss of vision, altered mental status and neurological deficits. Some fistulae may present primarily with hemorrhage before any evaluation can be performed. However, hemiparesis has been rarely observed. Only a literature review of Murata et al reported a case of hemiparesis caused by posttraumatic CCF, in which the fistula resulted in venous hypertension and subsequent brainstem congestion. While in our case, cerebral infarction was caused by total steal of the blood flow. The patient recovered after occlusion of the fistula with a detachable balloon.

Analysis of the embolization spinal dural arteriovenous fistula and surgical treatments on 52 cases of the patients.

BACKGROUND: Spinal dural arteriovenous fistula (SDAVF) highly threatens people's life and health. Effective methods for the diagnosis and treatment of the disease are badly needed in clinical application. OBJECTIVE: The objective of the present study was to sum up the diagnosis and treatment method of SDAVF to improve the diagnosis and treatment effect of the disease. METHODS: The epidemiological data, imaging data, therapeutic methods and postoperative follow-up data of 52 cases of patients with SDAVF received in our hospital in recent 6 years were collected and retrospectively analyzed. RESULTS: There were 43 male patients and 9 female patients with ages of 39-77 years and average age of 59.6 years. The course of disease was 1 to 48 months with an average disease course of 14.4 months. All the patients had syndromes of lower limb numbness, pain, weakness and other sensory and movement disorders mostly accompanied with defecation dysfunction. Magnetic resonance imaging (MRI) results demonstrated that spinal cord abnormalities were found in spinal cord, which could be diagnosed by digital subtraction angiography (DSA) examination. There were 40 cases received surgical treatment and there was no recurrence in the follow-up. There were 12 patients received embolotherapy, of whom 3 patients were operated the second time and 2 patients had embolization again. After 0.5-6 years of follow-up, postoperative symptoms of the 40 patients were improved in different degrees. The modified Aminoff-Logue function scoring was significantly decreased after treatment. CONCLUSION: SDAVF is the easily diagnosed and delayed spinal cord vascular lesions in clinical applications. The diagnosis relies mainly on MRI and DSA examinations. The surgical treatment effect is good and is not easily relapsed. The trauma of the interventional embolization treatment is small, but the recurrence rate is high.

Endoscopic transmaxillary transMüller's muscle approach for decompression of superior orbital fissure: a cadaveric study with illustrative case.

BACKGROUND: In an effort to avoid the damage and inconvenience associated with transcranial approaches, we developed an endoscopic transmaxillary transMüller's muscle approach for decompression of the superior orbital fissure (SOF). METHODS: The endoscopic transmaxillary transMüller's muscle route was performed in ten cadaveric heads. We measured important anatomic landmarks, and angles radiographically. This approach was initially attempted in one patient with traumatic superior orbital fissure syndrome (tSOFS). RESULTS: A maxillary antrostomy was carried out with a buccal sulcus incision. The sinus ostium and the course of infraorbital nerve were used as endoscopic anatomic landmarks. Then the inferior orbital fissure was drilled out, followed by separating the Müller's muscle. The periorbita were peeled off from the lateral wall, followed by the endoscope going along the periorbital space, until the lateral aspect of the SOF could be visualized. Decompression was successfully performed in all specimens. The initial clinical application justified this approach. The patient had an uneventful postoperative course and satisfactory recovery. CONCLUSION: This approach offers sufficient endoscopic visualization and reliable decompression of SOF. It avoids the need for brain retraction, temporalis muscle manipulation, or any external incision, and appears to be able to deliver satisfying aesthetic results as well as favourable functional recovery.

Nutritional support for patients sustaining traumatic brain injury: a systematic review and meta-analysis of prospective studies.

BACKGROUND: In traumatic brain injury (TBI), the appropriate timing and route of feeding, and the efficacy of immune-enhancing formulae have not been well established. We performed this meta-analysis aiming to compare the effects of different nutritional support modalities on clinical outcomes of TBI patients. METHODS: We systematically searched Pubmed, Embase, and the Cochrane Library until October, 2012. All randomized controlled trials (RCTs) and non-randomized prospective studies (NPSs) that compared the effects of different routes, timings, or formulae of feeding on outcomes in TBI patients were selected. The primary outcomes included mortality and poor outcome. The secondary outcomes included the length of hospital stay, the length of ventilation days, and the rate of infectious or feeding-related complications. FINDINGS: 13 RCTs and 3 NPSs were included. The pooled data demonstrated that, compared with delayed feeding, early feeding was associated with a significant reduction in the rate of mortality (relative risk [RR] = 0.35; 95% CI, 0.24-0.50), poor outcome (RR = 0.70; 95% CI, 0.54-0.91), and infectious complications (RR = 0.77; 95% CI, 0.59-0.99). Compared with enteral nutrition, parenteral nutrition showed a slight trend of reduction in the rate of mortality (RR = 0.61; 95% CI, 0.34-1.09), poor outcome (RR = 0.73; 95% CI, 0.51-1.04), and infectious complications (RR = 0.89; 95% CI, 0.66-1.22), whereas without statistical significances. The immune-enhancing formula was associated with a significant reduction in infection rate compared with the standard formula (RR = 0.54; 95% CI, 0.35-0.82). Small-bowel feeding was found to be with a decreasing rate of pneumonia compared with nasogastric feeding (RR = 0.41; 95% CI, 0.22-0.76). CONCLUSION: After TBI, early initiation of nutrition is recommended. It appears that parenteral nutrition is superior to enteral nutrition in improving outcomes. Our results lend support to the use of small-bowel feeding and immune-enhancing formulae in reducing infectious complications.

Efficacy of modafinil on fatigue and excessive daytime sleepiness associated with neurological disorders: a systematic review and meta-analysis.

BACKGROUND: Modafinil is a novel wake-promoting agent approved by the FDA ameliorating excessive daytime sleepiness (EDS) in three disorders: narcolepsy, shift work sleep disorder and obstructive sleep apnea. Existing trials of modafinil for fatigue and EDS associated with neurological disorders provided inconsistent results. This meta-analysis was aimed to assess drug safety and effects of modafinil on fatigue and EDS associated with neurological disorders. METHODS: A comprehensive literature review was conducted in order to identify published studies assessing the effects of modafinil on fatigue and EDS associated with neurological disorders. Primary outcomes included fatigue and EDS. Secondary outcomes included depression and adverse effects. FINDINGS: Ten randomized controlled trials were identified including 4 studies of Parkinson's disease (PD), 3 of multiple sclerosis (MS), 2 of traumatic brain injury (TBI) and 1 of post-polio syndrome (PPS). A total of 535 patients were enrolled. Our results suggested a therapeutic effect of modafinil on fatigue in TBI (MD -0.82 95% CI -1.54 - -0.11 p=0.02, I(2)=0%), while a beneficial effect of modafinil on fatigue was not confirmed in the pooled studies of PD or MS. Treatment results demonstrated a clear beneficial effect of modafinil on EDS in patients with PD (MD -2.45 95% CI -4.00 - -0.91 p=0.002 I(2)=14%), but not with MS and TBI. No difference was seen between modafinil and placebo treatments in patients with PPS. Modafinil seemed to have no therapeutic effect on depression. Adverse events were similar between modafinil and placebo groups except that more patients were found with insomnia and nausea in modafinil group. CONCLUSIONS: Existing trials of modafinil for fatigue and EDS associated with PD, MS, TBI and PPS provided inconsistent results. The majority of the studies had small sample sizes. Modafinil is not yet sufficient to be recommended for these medical conditions until solid data are available.

Effect of clazosentan in patients with aneurysmal subarachnoid hemorrhage: a meta-analysis of randomized controlled trials.

BACKGROUND: Cerebral vasospasm is the most important potentially treatable cause of mortality and morbidity following aneurysmal subarachnoid hemorrhage (aSAH). Clazosentan, a selective endothelinreceptor antagonist, has been suggested to help reduce the incidence of vasospasm in patients with aSAH. However, the results were controversial in previous trials. This meta-analysis attempts to assess the effect of clazosentan in patients with aSAH. METHODOLOGY/PRINCIPAL FINDINGS: We systematically searched Pubmed, Embase, and the Cochrane Library from their inception until June, 2012. All randomized controlled trials (RCTs) related to the effect of clazosentan in aSAH were included. The primary outcomes included the incidence of angiographic vasospasm, new cerebral infarction (NCI), delayed ischemic neurological deficits (DIND), and vasospasm-related morbidity/mortality (M/M); the second outcomes included the occurrence of rescue therapy, all-cause-mortality, and poor outcome. 4 RCTs were included with a total of 2156 patients. The risk of angiographic vasospasm (relative risk [RR] =0.58; 95% CI, 0.48 to 0.71), DIND (RR=0.76; 95% CI, 0.62 to 0.92), and vasospasm-related M/M (RR=0.80; 95% CI, 0.67 to 0.96) were statistically significantly reduced in the clazosentan group. Patients treated with clazosentan had a reduced occurrence of rescue therapy (RR=0.62; 95% CI, 0.49 to 0.79). However, no statistically significant effects were observed in NCI (RR=0.74; 95% CI, 0.52 to 1.04), mortality (RR=1.03; 95% CI, 0.71 to 1.49), and poor outcome (RR=1.12; 95% CI, 0.96 to 1.30). CONCLUSIONS/SIGNIFICANCE: Our pooling data supports that clazosentan is probably effective in preventing the occurrence of angiographic vasospasm, vasospasm-related DIND, vasospasm related M/M, and rescue therapy. However, no evidence lends significant supports to the benefits of clazosentan in decreasing the occurrence of NCI, mortality or improving the functional outcome.

Acute paraplegia following embolization of spinal dural arteriovenous fistula.

Embolization therapy has been used as the initial treatment for spinal dural arteriovenous fistula (SDAVF) only for certain patients or in certain medical institutions due to its minimal invasiveness, but the recurrence of embolization remains a clinical challenge. The recurrent patient usually exhibits a gradual onset of symptoms and progressive deterioration of neurological function. Developing paraplegia several hours after embolization is commonly seen in patients with venous thrombosis-related complications, for which anticoagulation therapy is often administered. This article reports on a SDAVF patient who had weakness of both lower extremities before embolization and developed complete paraplegia several hours after embolization therapy, later confirmed by angiography as fistula recurrence. The symptoms were relieved gradually after second embolization. The pathophysiology of this patient is also discussed.