Molecular Biomarkers Affecting Moyamoya Disease.

Although the pathogenetic pathway of moyamoya disease (MMD) remains unknown, studies have indicated that variations in the RING finger protein RNF 213 is the strongest susceptible gene of MMD. In addition to the polymorphism of this gene, many circulating angiogenetic factors such as growth factors, vascular progenitor cells, inflammatory and immune mediators, angiogenesis related cytokines, as well as circulating proteins promoting intimal hyperplasia, excessive collateral formation, smooth muscle migration and atypical migration may also play critical roles in producing this disease. Identification of these circulating molecules biomarkers may be used for the early detection of this disease. In this chapter, how the hypothesized pathophysiology of these factors affect MMD and the interactive modulation between them are summarized.

Risk, Predictive, and Preventive Factors for Noninfectious Ventriculitis and External Ventricular Drain Infection.

BACKGROUND: External ventricular drain (EVD) is used for monitoring intracranial pressure or diverting cerebrospinal fluid. However, confirmation of an infection is not immediate and requires obtaining culture results, often leading to the excessive use of antibiotics. This study aimed to compare noninfectious ventriculitis and EVD infection in terms of the risk factors, predictors, prognosis, and effectiveness of care bundle interventions. METHODS: This retrospective study was conducted at a medical center with 1,006 beds in northern Taiwan between January 2018 and July 2022. Standard EVD insertion protocols and care bundles have been implemented since 2018, along with the initiation of chlorhexidine. RESULTS: In total, 742 EVD cases were identified. Noninfectious ventriculitis typically presents with fever approximately 8 days following EVD placement, whereas EVD infection typically manifests as fever after 20 days. Aneurysmal subarachnoid hemorrhage was strongly associated with the development of noninfectious ventriculitis (adjusted odds ratio [OR] 2.6, 95% confidence interval [CI] 1.5-4.4). Alcoholism (adjusted OR 3.5, 95% CI 1.1-12.3) and arteriovenous malformation (adjusted OR 13.1, 95% CI 2.9-58.2) significantly increased the risk of EVD infection. The EVD infection rate significantly decreased from 3.6% (14 of 446) to 1.0% (3 of 219) (p = 0.03) after the implementation of chlorhexidine gluconate bathing. CONCLUSIONS: Aneurysmal subarachnoid hemorrhage or fever with neuroinflammation within 2 weeks of EVD placement is indicative of a higher likelihood of noninfectious ventriculitis. Conversely, patients with arteriovenous malformation, alcoholism, or fever with neuroinflammation occurring after more than 3 weeks of EVD placement are more likely to necessitate antibiotic treatment for EVD infection. Chlorhexidine gluconate bathing decreases EVD infection.

Endothelial Dysfunction in Neurodegenerative Diseases.

The cerebral vascular system stringently regulates cerebral blood flow (CBF). The components of the blood-brain barrier (BBB) protect the brain from pathogenic infections and harmful substances, efflux waste, and exchange substances; however, diseases develop in cases of blood vessel injuries and BBB dysregulation. Vascular pathology is concurrent with the mechanisms underlying aging, Alzheimer's disease (AD), and vascular dementia (VaD), which suggests its involvement in these mechanisms. Therefore, in the present study, we reviewed the role of vascular dysfunction in aging and neurodegenerative diseases, particularly AD and VaD. During the development of the aforementioned diseases, changes occur in the cerebral blood vessel morphology and local cells, which, in turn, alter CBF, fluid dynamics, and vascular integrity. Chronic vascular inflammation and blood vessel dysregulation further exacerbate vascular dysfunction. Multitudinous pathogenic processes affect the cerebrovascular system, whose dysfunction causes cognitive impairment. Knowledge regarding the pathophysiology of vascular dysfunction in neurodegenerative diseases and the underlying molecular mechanisms may lead to the discovery of clinically relevant vascular biomarkers, which may facilitate vascular imaging for disease prevention and treatment.

Continuous lumbar drainage after aneurysmal subarachnoid hemorrhage decreased malondialdehyde in cerebrospinal fluid and improved outcome.

PURPOSE: The use of a continuous lumbar drain (LD) for the treatment of aneurysmal subarachnoid hemorrhage (aSAH), and malondialdehyde (MDA), a marker of oxidative stress, is correlated with clinical outcome. This study aimed to investigate the relationship between LD placement and MDA level after aSAH. METHODS: Patients with modified Fisher's grade III and IV aSAH who underwent early aneurysm obliteration were enrolled. Cerebrospinal fluid (CSF) was obtained on day 7 after aSAH in non-LD group. In LD group, the LD was inserted on day 3 after aSAH for continuous CSF drainage. The levels of intrathecal hemoglobin, total bilirubin, ferritin, and MDA were measured. RESULTS: There were 41 patients in non-LD group (age: 58.7 ± 13.7 years; female: 61.0%) and 48 patients in LD group (age: 58.3 ± 10.4 years; female: 79.2%). There were more favorable outcomes (Glasgow Outcome Scale ≥4) at 3 months after aSAH in LD group (p = 0.0042). The intrathecal hemoglobin, total bilirubin, ferritin, and MDA levels at day 7 after aSAH were all significantly lower in LD group. An older age (>60 years) (p = 0.0293), higher MDA level in the CSF (p = 0.0208), and delayed ischemic neurological deficit (p = 0.0451) were independent factors associated with unfavorable outcomes. LD placement was associated with a decreased intrathecal MDA level on day 7 after aSAH (p < 0.001). CONCLUSION: The intrathecal MDA level at day 7 after aSAH can be an effective outcome indicator in modified Fisher's grade III/IV aSAH. Continuous CSF drainage via a LD can decrease the intrathecal MDA level and improve the functional outcome.

Three-Dimensional Angioarchitecture of Rete Middle Cerebral Artery Anomalies and the Clinical Significance.

PURPOSE: Rete middle cerebral artery (MCA) anomaly is characterized by a web-like network of arteries involving the first MCA segment (M1) and a normal downstream MCA. The detailed composition of this anomaly and the hemodynamic impacts on cerebral perfusion are rarely addressed. The purpose of this study was to elucidate the anatomical and hemodynamic perspectives of the rete MCA anomaly. METHODS: From August 2020 to December 2021, 4 rete MCA anomalies were identified at Shuang Ho hospital. Clinical information, perfusion magnetic resonance (MR) imaging, and angiographic images were collected. Detailed angioarchitecture, including types of arterial feeders and extent of rete involvement, were analyzed based on three-dimensional volume-rendering reconstruction images obtained from the catheter-based angiographies. RESULTS: Despite their variable clinical presentations (two hemorrhage, one ischemia, and one asymptomatic), all cases shared common angiographic findings as follows: (1) the internal carotid artery did not connect directly to the rete, (2) the anterior choroidal artery (AChA) was the artery constantly supplying the rete and (3) there was a watershed zone shift toward MCA territory. The perfusion MR cerebral blood flow map was symmetric in all studied cases. CONCLUSION: The AChA is an artery constantly supplying the rete, which suggests that the angioarchitectural features associated with this anomaly may be the result of both congenital and acquired compensatory processes. Cerebral perfusion remains preserved at the lesion side, despite angiographic evidence of watershed zone shift. These findings will be important for making better clinical judgments about this condition.

HDACi protects against vascular cognitive impairment from CCH injury via induction of BDNF-related AMPA receptor activation.

We previously showed a hydroxamic acid-based histone deacetylase inhibitor (HDACi), compound 13, provides neuroprotection against chronic cerebral hypoperfusion (CCH) both in vitro under oxygen-glucose deprivation (OGD) conditions and in vivo under bilateral common carotid artery occlusion (BCCAO) conditions. Intriguingly, the protective effect of this HDACi is via H3K14 or H4K5 acetylation-mediated differential BDNF isoform activation. BDNF is involved in cell proliferation and differentiation in development, synaptic plasticity and in learning and memory related with receptors or synaptic proteins. B6 mice underwent BCCAO and were randomized into 4 groups; a sham without BCCAO (sham), BCCAO mice injected with DMSO (DMSO), mice injected with HDACi-compound 13 (compound 13) and mice injected with suberoylanilide hydroxamic acid (SAHA). The cortex and hippocampus of mice were harvested at 3 months after BCCAO, and levels of BDNF, AMPA receptor and dopamine receptors (D1, D2 and D3) were studied using Western blotting analysis or immunohistochemistry. We found that the AMPA receptor plays a key role in the molecular mechanism of this process by modulating HDAC. This protective effect of HDACi may be through BDNF; therefore, activation of this downstream signalling molecule, for example by AMPA receptors, could be a therapeutic target or intervention applied under CCH conditions.

Pathological Circulating Factors in Moyamoya Disease.

Moyamoya disease (MMD) is a cerebrovascular disease that presents with vascular stenosis and a hazy network of collateral formations in angiography. However, the detailed pathogenic pathway remains unknown. Studies have indicated that in addition to variations in the of genetic factor RNF213, unusual circulating angiogenetic factors observed in patients with MMD may play a critical role in producing "Moyamoya vessels". Circulating angiogenetic factors, such as growth factors, vascular progenitor cells, cytokines, inflammatory factors, and other circulating proteins, could promote intimal hyperplasia in vessels and excessive collateral formation with defect structures through endothelial hyperplasia, smooth muscle migration, and atypical neovascularization. This study summarizes the hypothesized pathophysiology of how these circulating factors affect MMD and the interactive modulation between them.

HDAC inhibitor protects chronic cerebral hypoperfusion and oxygen-glucose deprivation injuries via H3K14 and H4K5 acetylation-mediated BDNF expression.

Vascular dementia (VaD) is the second most common cause of dementia, but the treatment is still lacking. Although many studies have reported that histone deacetylase inhibitors (HDACis) confer protective effects against ischemic and hypoxic injuries, their role in VaD is still uncertain. Previous studies shown, one HDACi protected against cognitive decline in animals with chronic cerebral hypoperfusion (CCH). However, the underlying mechanisms remain elusive. In this study, we tested several 10,11-dihydro-5H-dibenzo[b,f]azepine hydroxamates, which act as HDACis in the CCH model (in vivo), and SH-SY5Y (neuroblastoma cells) with oxygen-glucose deprivation (OGD, in vitro). We identified a compound 13, which exhibited the best cell viability under OGD. The compound 13 could increase, in part, the protein levels of brain-derived neurotrophic factor (BDNF). It increased acetylation status on lysine 14 residue of histone 3 (H3K14) and lysine 5 of histone 4 (H4K5). We further clarified which promoters (I, II, III, IV or IX) could be affected by histone acetylation altered by compound 13. The results of chromatin immunoprecipitation and Q-PCR analysis indicate that an increase in H3K14 acetylation leads to an increase in the expression of BDNF promoter II, while an increase in H4K5 acetylation results in an increase in the activity of BDNF promoter II and III. Afterwards, these cause an increase in the expression of BDNF exon II, III and coding exon IX. In summary, the HDACi compound 13 may increase BDNF specific isoforms expression to rescue the ischemic and hypoxic injuries through changes of acetylation on histones.

Protective effects of 10,11-dihydro-5H-dibenzo[b,f]azepine hydroxamates on vascular cognitive impairment.

A series of 10,11-dihydro-5H-dibenzo [b,f]azepine hydroxamates (4-15) were synthesized, behaving as histone deacetylase inhibitors, and examined for their influence on vascular cognitive impairment (VCI), which correlated with dementia. The results revealed that (E)-3-(4-(((3-(3-chloro-10,11-dihydro-5H-dibenzo [b,f]azepin-5-yl)propyl)amino)methyl)phenyl)-N-hydroxy-acrylamide (13) increases cerebral blood flow (CBF), attenuates cognitive impairment, and improves hippocampal atrophy in in vivo study. It is also able to increase the level of histone acetylation (H3K14 or H4K5) in the cortex and hippocampus of chronic cerebral hypoperfusion (CCH) mice; as a result, it could be a potential HDAC inhibitor for the treatment of vascular cognitive impairment.

Impaired microcirculation after subarachnoid hemorrhage in an in vivo animal model.

The influence of aneurysmal subarachnoid hemorrhage (SAH) on brain microcirculation has not yet been systematically investigated. We established an animal model to examine (1) the brain surface microcirculation (2) the influences of cerebrospinal fluid (CSF) from aneurysmal SAH on the brain surface microcirculation. A rat SAH model was induced by injection of autologous arterial blood into the cisterna magnum, and the brain surface microcirculation was evaluated by a capillary videoscope with craniotomy at the fronto-parietal region. CSF from SAH rats and SAH patients was applied on the brain surface of naïve rats to assess the resulting microcirculatory changes. In the SAH rats, diffuse constriction of cortical arterioles within 24 hours of SAH was observed. Similar patterns of microcirculation impairment were induced on normal rat brain surfaces via application of CSF from SAH rats and SAH patients. Furthermore, the proportion of subjects with arteriolar vasoconstriction was significantly higher in the group of SAH patients with delayed ischemic neurological deficits (DIND) than in those without DIND (p < 0.001). This study demonstrated impaired microcirculation on brain surface arterioles in a rat model of SAH. CSF from SAH rats and patients was responsible for impairment of brain surface microcirculation.

Prediction of Shunt Dependency After Intracerebral Hemorrhage and Intraventricular Hemorrhage.

BACKGROUND: Spontaneous intracerebral hemorrhage is a disease with high morbidity and mortality. Extension of the hemorrhage into the ventricles is associated with the development of acute hydrocephalus and a poor outcome. Although it can be managed by external ventricular drainage (EVD), a subset of these patients require placement of permanent ventricular shunts. This study aimed to examine the factors on admission that can predict shunt dependency after EVD management. METHODS: Seventy-two patients who underwent EVD were included in this study. Seventeen of these patients underwent placement of a ventriculoperitoneal shunt. Variables analyzed included age, intraventricular hemorrhage (IVH) score, bicaudate index, acute hydrocephalus, initial Glasgow Coma Scale scores, and blood volume in each ventricle. RESULTS: In univariate analysis, IVH score (p = 0.020), bicaudate index (p < 0.001), blood volume in lateral ventricles (p = 0.025), blood volume in the fourth ventricle (p = 0.038), and the ratio of blood volume in lateral ventricles to that in third and fourth ventricles (p = 0.003) were significantly associated with persistent hydrocephalus. The best multiple logistic regression model included blood volume parameters and bicaudate index as predictors with the area under a receiver operating characteristic curve of 0.849. The variance inflation factor (VIF) showed that collinearity was not found among predictors. Patients diagnosed with acute hydrocephalus had less blood volume in the lateral ventricles (OR = 0.910) and had more blood volume in the third ventricle (OR = 3.174) and fourth ventricle (OR = 2.126). CONCLUSIONS: These findings may promote more aggressive monitoring and earlier interventions for persistent hydrocephalus after intraventricular hemorrhage in patients at risk.

Cerebrospinal fluid high mobility group box 1 is associated with neuronal death in subarachnoid hemorrhage.

We aim to determine the cerebrospinal fluid levels of high mobility group box 1 in subarachnoid hemorrhage patients and to investigate the involvement of the receptor for advanced glycation end products and high mobility group box 1 in the pathogenesis of post-subarachnoid hemorrhage neuronal death. The study included 40 patients (mean age, 59 ± 19 years) with Fisher's grade ≥ III aneurysmal subarachnoid hemorrhage. Cerebrospinal fluid was collected on the seventh day post-hemorrhage. Receptor for advanced glycation end products expression was examined in rat brain tissue following subarachnoid hemorrhage and in cultured neurons exposed to post-subarachnoid hemorrhage cerebrospinal fluid. Therapeutic effects of the recombinant soluble form of RAGE on subarachnoid hemorrhage models were also investigated. The results indicated that a higher level of cerebrospinal fluid high mobility group box 1 was independently associated with unfavorable outcome at three months post-subarachnoid hemorrhage (OR = 1.061, 95% CI: 1.005-1.121). Expression of RAGE increased in post-subarachnoid hemorrhage rat brain cells and in cultured neuron with stimulation of post-subarachnoid hemorrhage cerebrospinal fluid. Administration of recombinant soluble form of RAGE significantly reduced the number of positive TUNEL staining cells in subarachnoid hemorrhage rat and improved cell viability in post-subarachnoid hemorrhage cerebrospinal fluid-treated cultured neurons. Thus, the level of cerebrospinal fluid high mobility group box 1 can be a prognostic indicator for patients with Fisher's grade ≥ III aneurysmal subarachnoid hemorrhage and that treatment with soluble form of RAGE is a novel approach for subarachnoid hemorrhage.

Multiplexed methylation profiles of tumor suppressor genes and clinical outcome in oligodendroglial tumors.

Aberrant methylation has been associated with transcriptional inactivation of tumor-related genes in a wide spectrum of human neoplasms. The influence of DNA methylation in oligodendroglial tumors is not fully understood. Genomic DNA was isolated from 61 oligodendroglial tumors for analysis of methylation using methylation-specific multiplex ligation-dependent probe amplification assay (MS-MLPA). We correlated methylation status with clinicopathological findings and outcome. The genes found to be most frequently methylated in oligodendroglial tumors were RASSF1A (80.3%), CASP8 (70.5%), and CDKN2A (52.5%). Kaplan-Meier survival curve analysis demonstrated longer duration of progression-free survival in patients with 19q loss, aged less than 38 years, and with a proliferative index of less than 5%. Methylation of the ESR1 promoter is significantly associated with shorter duration of overall survival and progression-free survival, and that methylation of IGSF4 and RASSF1A is significantly associated with shorter duration of progression-free survival. However, none of the methylation status of ESR1, IGSF4, and RASSF1A was of prognostic value for survival in a multivariate Cox model. A number of novel and interesting epigenetic alterations were identified in this study. The findings highlight the importance of methylation profiles in oligodendroglial tumors and their possible involvement in tumorigenesis.

Intrathecal lactate predicting hydrocephalus after aneurysmal subarachnoid hemorrhage.

BACKGROUND: Evidence shows possible benefits from continuous drainage by lumbar drain after aneurysmal subarachnoid hemorrhage (SAH). Under the hypothesis that compartmentalization occurs between the ventricle and subarachnoid space after massive SAH, this study aimed to evaluate the biochemical differences between ventricular and intrathecal cerebrospinal fluid (CSF) and assess the role of CSF lactate in shunt-dependent hydrocephalus (SDHC) after aneurysmal SAH. MATERIALS AND METHODS: Patients with modified Fisher grade III/IV aneurysmal SAH who underwent early obliteration were evaluated. Intrathecal and intraventricular CSF were obtained on day 7 post-SAH to measure their biochemical composition in terms of total protein, glucose, ferritin, and lactate. The associations of SDHC with the clinical parameters and CSF data were analyzed. RESULTS: There were 28 patients (mean age, 55.4 y; males, 46.6%), including 18 (64.3%) with SDHC. Intrathecal CSF had significantly higher levels of total protein, ferritin, hemoglobin, and lactate but lower glucose level than intraventricular CSF (all P < 0.0001). By multivariate analysis of clinical and CSF parameters, elevated intrathecal CSF lactate (P = 0.036) and the presence of intraventricular hemorrhage (P = 0.05) were independent factors associated with SDHC. Moreover, intrathecal lactate >5.5 µM effectively predicted the occurrence of SDHC (odds ratio: 32, 95% confidence interval: 3.8-270.8; P = 0.0015). CONCLUSIONS: By compartmentalization of the subarachnoid space after SAH, intrathecal lactate level is a useful predictive parameter for long-term SDHC in patients with aneurysmal SAH patients.

Predicting long-term outcome after traumatic brain injury using repeated measurements of Glasgow Coma Scale and data mining methods.

Previous studies have identified some clinical parameters for predicting long-term functional recovery and mortality after traumatic brain injury (TBI). Here, data mining methods were combined with serial Glasgow Coma Scale (GCS) scores and clinical and laboratory parameters to predict 6-month functional outcome and mortality in patients with TBI. Data of consecutive adult patients presenting at a trauma center with moderate-to-severe head injury were retrospectively analyzed. Clinical parameters including serial GCS measurements at emergency department, 7th day, and 14th day and laboratory data were included for analysis (n = 115). We employed artificial neural network (ANN), naïve Bayes (NB), decision tree, and logistic regression to predict mortality and functional outcomes at 6 months after TBI. Favorable functional outcome was achieved by 34.8% of the patients, and overall 6-month mortality was 25.2%. For 6-month functional outcome prediction, ANN was the best model, with an area under the receiver operating characteristic curve (AUC) of 96.13%, sensitivity of 83.50%, and specificity of 89.73%. The best predictive model for mortality was NB with AUC of 91.14%, sensitivity of 81.17%, and specificity of 90.65%. Sensitivity analysis demonstrated GCS measurements on the 7th and 14th day and difference between emergency room and 14th day GCS score as the most influential attributes both in mortality and functional outcome prediction models. Analysis of serial GCS measurements using data mining methods provided additional predictive information in relation to 6-month mortality and functional outcome in patients with moderate-to-severe TBI.

Acquired Chiari malformation type I associated with a supratentorial fistulous arteriovenous malformation: a case report.

A case of acquired Chiari malformation type I with frontal fistulous arteriovenous malformation (AVM) is presented, and the pathophysiology is discussed. The tonsillar herniation and hydrocephalus both resolved after AVM was excised. This case provides some insight into the complex hemodynamic change exerted by the fistulous AVM and the mechanism of the development of acquired Chiari malformation type I.

Prognostic value of intrathecal heme oxygenase-1 concentration in patients with Fisher Grade III aneurysmal subarachnoid hemorrhage.

OBJECT: Experimental studies have demonstrated the crucial role of posthemorrhagic erythrocyte catabolism in the pathogenesis of subarachnoid hemorrhage (SAH). The authors of this study aimed to investigate the prognostic value of a series of CSF biomarkers linked to heme metabolism in SAH patients. METHODS: Patients with Fisher Grade III aneurysmal SAH undergoing early aneurysm obliteration were enrolled. The levels of heme oxygenase-1 (HO-1), oxyhemoglobin, ferritin, and bilirubin in intrathecal CSF were measured on the 7th day posthemorrhage. The associations of functional outcome with clinical and CSF parameters were analyzed. RESULTS: The study included 41 patients (mean age 59 ± 14 years; 16 male, 25 female), 17 (41.5%) of whom had an unfavorable outcome (Glasgow Outcome Scale score ≤ 3) 3 months after SAH. In terms of the clinical data, age > 60 years, admission World Federation of Neurosurgical Societies Grade ≥ III, and the presence of acute hydrocephalus were independent factors associated with an unfavorable outcome. After adjusting for clinical parameters, a higher level of HO-1 appeared to be the most significant CSF parameter related to an unfavorable outcome among all tested CSF molecules (OR 0.934, 95% CI 0.883-0.989, p = 0.018). Further analysis using a generalized additive model identified a cutoff HO-1 value of 81.2 µM, with higher values predicting unfavorable outcome (82.4% accuracy). CONCLUSIONS: The authors propose that the level of intrathecal CSF HO-1 at Day 7 post-SAH can be an effective outcome indicator in patients with Fisher Grade III aneurysmal SAH.

Genetic and epigenetic alterations in primary-progressive paired oligodendroglial tumors.

The aim of the present study was to identify genetic and epigenetic alterations involved in the progression of oligodendroglial tumors. We characterized 21 paired, World Health Organization (WHO) grade II and III oligodendroglial tumors from patients who received craniotomies for the partial or complete resection of primary and secondary oligodendroglial tumors. Tumor DNA was analyzed for alterations in selected genetic loci (1p36, 9p22, 10q23-24, 17p13, 19q13, 22q12), isocitrate dehydrogenase 1 (IDH1), isocitrate dehydrogenase 2 (IDH2) and the CpG island methylation status of critical tumor-related genes (MGMT, P16, DAPK, PTEN, RASSF1A, Rb1). Alterations of these markers were common early in the tumorigenesis. In the primary tumors we identified 12 patients (57.1%) with 1p36 deletions, 17 (81.0%) with 19q13 deletions, 9 (42.9%) with 1p36/19q13 codeletions, 11 (52.3%) with 9p22 deletions, and 12 (57.1%) with IDH1 mutation. Epigenetic analysis detected promoter methylation of the MGMT, P16, DAPK, PTEN, RASSF1A, and Rb1 genes in 38.1%, 19.0%, 38.1%, 33.3%, 66.7%, and 14.3% of primary tumors, respectively. After progression, additional losses of 1p, 9p, 10q, 17p, 19q and 22q were observed in 3 (14.3%), 1 (4.8%), 3 (14.3%), 2 (9.5%), 1 (4.8%) and 3 (14.3%) cases, respectively. Additional methylations of the MGMT, P16, DAPK, PTEN, RASSF1A, and RB1 promoters was observed in 4 (19.0%), 2 (9.5%), 0 (0%), 6 (28.6%), 2(9.5%) and 3 (14.3%) cases, respectively. The status of IDH1 mutation remained unchanged in all tumors after progression. The primary tumors of three patients with subsequent progression to high-grade astrocytomas, all had 9p deletion, intact 1p, intact 10q and unmethylated MGMT. Whether this may represent a molecular signature of patients at-risk for the development of aggressive astrocytomas needs further investigation.

Single-Incision laparoscopic surgery (SILS) for ventriculoperitoneal shunt placement.

BACKGROUND: Single-incision laparoscopic surgery (SILS) may facilitate safer shunt placement and lower distal obstruction rate than is seen in conventional surgery. OBJECTIVE: We reviewed our 2-year experience in SILS for ventriculoperitoneal shunt placement to evaluate its usefulness and safety.Materials and Methods In this retrospective study, we enrolled patients older than 18 years with dilated ventricle and syndromes of hydrocephalus. A total of 31 patients underwent 31 primary ventriculoperitoneal shunt placement surgery and two underwent revision surgery. All the procedures were performed by the SILS technique. RESULTS: The entire duration of ventriculoperitoneal shunt implantation ranged from 45 to 80 minutes, with mean operation time of 65 ± 15.3 minutes. No major laparoscopy-related complications were noted. Shunt infection, peritonitis, and distal catheter malfunction occurred in one case (3.2%), proximal malfunction in one case (3.2%), and subcutaneous emphysema occurred in two cases (6.4%). The emphysema resolved within 2 days. Cosmetic results were "very good to good" in 17 patients (54.8%) and "satisfactory" in 14 patients (45.2%). The abdominal scars in most cases were nearly invisible. CONCLUSION: SILS is a safe and effective technique for ventriculoperitoneal shunt placement and can be accomplished with no higher risk of shunt infection and distal malfunction. Without an additional port, SILS allows good visualization of the peritoneal cavity to avoid major intra-abdominal complications. Only one 6-mm incision at the umbilicus area is required and is almost invisible after wound healing.