Shunsuke Nakae

Clinical characteristics and risk factors of chronic subdural haematoma associated with clipping of unruptured cerebral aneurysms

Chronic subdural haematoma (CSDH) is an uncommon but potentially serious complication of clipping unruptured cerebral aneurysms. We conducted a study to identify the patients who are at risk of developing postoperative CSDH. The data from 713 consecutive patients who underwent clipping of unruptured anterior circulation aneurysms were reviewed, and risk factors correlated with CSDH were identified by multivariate regression analysis of demographic variables. Fifteen patients (2.1%) developed CSDH after the surgery. Advanced age (odds ratio [OR] 1.151, 95% confidence interval [CI] 1.051-1.261) and male gender (OR 3.167, 95% CI 1.028-9.751) were correlated with CSDH. Subsequently, all 713 patients were quadrichotomized on the basis of gender and age, with 70 years as the cut-off value for age. The frequency of CSDH in men <70 years of age was 1.3% and that in men ≥70 years of age was 15.1%, with risk of CSDH was significantly higher in the older men (OR 13.39; 95% CI: 3.42-52.44). The frequency of CSDH in women <70 years of age was 0.6% and that in women ≥70 years of age was 3.7%. As in men, the risk of CSDH was significantly higher in the older women (OR 6.69, 95% CI 1.10-40.73). The interval between the aneurysm clipping and CSDH development was 0.5-6 months, suggesting that clinical observation should be continued up to 6 months after surgery. Although prognosis for patients with a postoperative CSDH complication is generally favourable, the risk of CSDH should be taken into account when considering elective clipping of unruptured aneurysms in patients ≥70 years of age.

World Health Organization grade II-III astrocytomas consist of genetically distinct tumor lineages.

Recent investigations revealed genetic analysis provides important information in management of gliomas, and we previously reported grade II–III gliomas could be classified into clinically relevant subgroups based on the DNA copy number aberrations (CNAs). To develop more precise genetic subgrouping, we investigated the correlation between CNAs and mutational status of the gene encoding isocitrate dehydrogenase (IDH) of those tumors. We analyzed the IDH status and CNAs of 174 adult supratentorial gliomas of astrocytic or oligodendroglial origin by PCR‐based direct sequencing and comparative genomic hybridization, respectively. We analyzed the relationship between genetic subclassification and clinical features. We found the most frequent aberrations in IDH mutant tumors were the combined whole arm‐loss of 1p and 19q (1p/19q codeletion) followed by gain on chromosome arm 7q (+7q). The gain of whole chromosome 7 (+7) and loss of 10q (−10q) were detected in IDH wild‐type tumors. Kaplan–Meier estimates for progression‐free survival showed that the tumors with mutant IDH, −1p/19q, or +7q (in the absence of +7p) survived longer than tumors with wild‐type IDH, +7, or −10q. As tumors with +7 (IDH wild‐type) showed a more aggressive clinical nature, they are probably not a subtype that developed from the slowly progressive tumors with +7q (IDH mutant). Thus, tumors with a gain on chromosome 7 (mostly astrocytic) comprise multiple lineages, and such differences in their biological nature should be taken into consideration during their clinical management.

PCR-Based Simple Subgrouping Is Validated for Classification of Gliomas and Defines Negative Prognostic Copy Number Aberrations in IDH Mutant Gliomas

Genetic subgrouping of gliomas has been emphasized recently, particularly after the finding of isocitrate dehydrogenase 1 (IDH1) mutations. In a previous study, we investigated whole-chromosome copy number aberrations (CNAs) of gliomas and have described genetic subgrouping based on CNAs and IDH1 mutations. Subsequently, we classified gliomas using simple polymerase chain reaction (PCR)-based methods to improve the availability of genetic subgrouping. We selected IDH1/2 and TP53 as markers and analyzed 237 adult supratentorial gliomas using Sanger sequencing. Using these markers, we classified gliomas into three subgroups that were strongly associated with patient prognoses. These included IDH mutant gliomas without TP53 mutations, IDH mutant gliomas with TP53 mutations, and IDH wild-type gliomas. IDH mutant gliomas without TP53 mutations, which mostly corresponded to gliomas carrying 1p19q co-deletions, showed lower recurrence rates than the other 2 groups. In the other high-recurrence groups, the median progression-free survival (PFS) and overall survival (OS) of patients with IDH mutant gliomas with TP53 mutations were significantly longer than those of patients with IDH wild-type gliomas. Notably, most IDH mutant gliomas with TP53 mutations had at least one of the CNAs +7q, +8q, −9p, and −11p. Moreover, IDH mutant gliomas with at least one of these CNAs had a significantly worse prognosis than did other IDH mutant gliomas. PCR-based mutation analyses of IDH and TP53 were sufficient for simple genetic diagnosis of glioma that were strongly associated with prognosis of patients and enabled us to detect negative CNAs in IDH mutant gliomas.

Improvement in patient outcomes following endovascular treatment of WFNS grade V subarachnoid haemorrhage from 2000 to 2014

Patient outcomes following grade V subarachnoid haemorrhage (SAH) have been dismal, although they may have improved following recent technological advances in endovascular treatment (EVT). A single-centre, retrospective study was conducted to evaluate whether outcomes have improved from 2000 to 2014 for patients with World Federation of Neurosurgical Societies (WFNS) grade V SAH. Coiling has been the preferred first-line treatment for grade V SAH patients in our institution since 2000. Patients who underwent EVT (n=115) were grouped on the basis of their hospital admission year: 2000-2004 (n=44), 2005-2009 (n=37) and 2010-2014 (n=34). Patient demographics, outcomes and in-hospital mortality rates were compared between the groups. Patient outcomes at discharge were evaluated using the Glasgow Outcome Scale (GOS), with GOS scores of 4-5 defined as favourable outcomes. There were no significant intergroup differences in patient demographics. In addition, there were no significant differences in the frequencies of favourable outcomes (14% in 2000-2004, 16% in 2005-2009 and 26% in 2010-2014). Mortality rates were 52% in 2000-2004, 43% in 2005-2009 and 24% in 2010-2014, with a significantly lower mortality rate in 2010-2014 than in 2000-2004 (p=0.01). Both perioperative rebleeding and delayed cerebral ischaemia decreased over time; however, multivariate regression analysis showed that the former contributed more to the decrease in mortality. Age was the only variable associated with favourable outcomes. The results of this study indicate that EVT is an appropriate therapeutic option for grade V SAH patients. However, multi-centre, prospective trials are required to provide evidence-based verification of the efficacy of EVT.

Early rebleeding in patients with subarachnoid haemorrhage under intensive blood pressure management.

The objective of this study was to report the frequency and clinical characteristics of early rebleeding in subarachnoid haemorrhage (SAH) patients who underwent intensive blood pressure (BP) management. Patients with aneurysmal SAH frequently present to the emergency department (ED) with elevated BP. Intensive BP management has been recommended to lower the risk of early rebleeding. However, few studies have reported the frequency of early rebleeding in SAH patients undergoing BP management. In our institution, SAH patients with systolic BP (SBP)>140 mmHg received continuous intravenous nicardipine to maintain their SBP within 120±20 mmHg after diagnosis. An attempt to implement intensive BP management was made on 309 consecutive SAH patients who presented to our ED within 48 hours of SAH onset. Overall, 24 (7.8%) of the 309 patients sustained early rebleeding. Fifteen patients sustained early rebleeding before the implementation of BP management, and the other nine sustained early rebleeding after the implementation of BP management. Therefore, the frequency of early rebleeding under BP management was 3.1% (9/294). When the 309 patients were dichotomised using ED SBP of 140 mmHg as a cut off (SBP>140 mmHg; n=239 versus SBP⩽140 mmHg; n=70), the latter counter-intuitively exhibited a significantly higher frequency of early rebleeding (5.9% versus 14.2%; p=0.04). This relatively low frequency of early rebleeding under BP management may be acceptable. However, early rebleeding is not eradicated even with strict BP control as factors other than elevated BP are involved. ED SBP within the target range (SBP⩽140 mmHg) does not negate the risk of early rebleeding. Other treatment options that reduce the risk should also be explored.

Prediction of genetic subgroups in adult supra tentorial gliomas by pre- and intraoperative parameters

Recent progress in neuro-oncology has validated the significance of genetic diagnosis in gliomas. We previously investigated IDH1/2 and TP53 mutations via Sanger sequencing for adult supratentorial gliomas and reported that PCR-based sequence analysis classified gliomas into three genetic subgroups that have a strong association with patient prognosis: IDH mutant gliomas without TP53 mutations, IDH and TP53 mutant gliomas, and IDH wild-type gliomas. Furthermore, this analysis had a strong association with patient prognosis. To predict genetic subgroups prior to initial surgery, we retrospectively investigated preoperative radiological data using CT and MRI, including MR spectroscopy (MRS), and evaluated positive 5-aminolevulinic acid (5-ALA) fluorescence as an intraoperative factor. We subsequently compared these factors to differentiate each genetic subgroup. Multiple factors such as age at diagnosis, tumor location, gadolinium enhancement, 5-ALA fluorescence, and several tumor metabolites according to MRS, such as myo-inositol (myo-inositol/total choline) or lipid20, were statistically significant factors for differentiating IDH mutant and wild-type, suggesting that these two subtypes have totally distinct characteristics. In contrast, only calcification, laterality, and lipid13 (lipid13/total Choline) were statistically significant parameters for differentiating TP53 wild-type and mutant in IDH mutant gliomas. In this study, we detected several pre- and intraoperative factors that enabled us to predict genetic subgroups for adult supratentorial gliomas and clarified that lipid13 quantified by MRS is the key tumor metabolite that differentiates TP53 wild-type and mutant in IDH mutant gliomas. These results suggested that each genetic subtype in gliomas selects the distinct lipid synthesis pathways in the process of tumorigenesis.

Application of time-spatial labeling inversion pulse magnetic resonance imaging in the diagnosis of spontaneous intracranial hypotension due to high-flow cerebrospinal fluid leakage at C1-2

Background: Spontaneous intracranial hypotension (SIH) due to cerebrospinal fluid (CSF) leakage at C1-2 poses diagnostic and therapeutic challenges to spine surgeons. Although computed tomography (CT) myelography has been the diagnostic imaging modality of choice for identifying the CSF leakage point, extradural CSF collection at C1-2 on conventional CT myelography or magnetic resonance imaging (MRI) may often be a false localizing sign. Case Description: The present study reports the successful application of time-spatial labeling inversion pulse (T-SLIP) MRI, which enabled the precise identification of the CSF leakage point at C1-2 in a 28-year-old woman with intractable SIH. After identifying the leakage point using both CT myelography and T-SLIP MRI, surgery was performed to seal the CSF leak. Intraoperatively, a pouch suggestive of an extradural arachnoid cyst around the left C2 nerve root was found, which was repaired by packing the pouch with muscle and fibrin glue. Clinical improvement was observed shortly after surgery, and postoperative imaging revealed the disappearance of the CSF leakage. Conclusions: T-SLIP MRI may provide useful information on the flow dynamics of CSF in SIH patients due to high-flow leakage. However, further experience is required to assess its sensitivity and specificity as an imaging modality for identifying CSF leakage points.

The outcomes of early aneurysm repair in World Federation of Neurosurgical Societies grade V subarachnoid haemorrhage patients with emphasis on those presenting with a Glasgow Coma Scale score of 3

Grade V subarachnoid haemorrhage (SAH) patients may be dichotomised into those with temporary deterioration and those with irreversible injury, and only the former have a chance of favourable outcomes by aneurysm obliteration. One method of differentiating the two conditions is to wait and observe potential recovery for 12-48hours. However, early rebleeding and non-convulsive seizures may occur during this period. In our institution, grade V SAH patients receive immediate treatment (general anaesthesia induction and aneurysm obliteration within 24hours of onset) to minimise those risks. We focused on therapeutic outcomes in SAH patients presenting with a Glasgow Coma Scale score of 3 (GCS-3). Between January 2006 and December 2013, 82 GCS-3 SAH patients were admitted, among whom 51 (62%) underwent immediate aneurysm obliteration. Their outcomes 90days after onset were evaluated with the Glasgow Outcome Scale, with either good recovery or moderate disability regarded as favourable outcomes. Multivariate logistic regression analysis was performed to identify variables correlated with favourable outcomes. Among the 51 patients, 11 (22%) had favourable 90-day outcomes. Age (odds ratio [OR], 0.838; 95% confidence interval [CI], 0.733-0.959; p=0.010) and intact pupillary light reflex (OR, 21.939; 95% CI, 1.465-328.576; p=0.025) were correlated with favourable outcomes. By contrast, neither intact respiratory pattern nor isocoric pupils was correlated with favourable outcomes. The current results indicate that vigorous intervention may be worth attempting in young GCS-3 SAH patients with intact pupillary light reflex. It remains unclear, however, whether the seemingly high frequency of favourable outcomes was truly due to reduction in early rebleeding or seizures.

Relative Vasodilatory Change in Seizure-induced Crossed Cerebellar Diaschisis

A 75-year-old man was referred to our hospital following a generalized seizure. Brain MRI showed high-intensity areas (HIAs) in the right temporo-occipital lobes, right thalamus (Picture A) and left cerebellar hemisphere (Picture B) on diffusion-weighted images (DWI). Magnetic resonance angiography (MRA) findings, which were obtained simultaneously (Picture C), were compared with the MRA findings of an examination that had been performed two years previously for a health check-up (Picture D). The comparison revealed that the cortical branches of the right middle cerebral artery were depicted more numerously, whereas those of the left side were depicted less numerously. Although rare, crossed cerebellar diaschisis may occur after a prolonged generalized seizure (1). Ipsilateral cortical HIA coupled with contralateral cerebellar HIA is a characteristic finding on DWI. The HIA corresponds to the hyperperfused areas on cerebral blood flow studies (2), reflecting a high metabolic demand around the epileptic focus. These MRA findings suggest that such seizure-induced hyperperfusion may be a consequence of relative vasodilation/vasoconstriction of the cortical arteries.

Novel Application of Time-Spatial Labeling Inversion Pulse Magnetic Resonance Imaging for Diagnosis of External Hydrocephalus

BACKGROUND Although a subdural fluid collection frequently is observed, diagnostic methods that differentiate between the subdural collection caused by external hydrocephalus and that caused by subdural hygroma have not been established. Here, we report a case of external hydrocephalus caused by Gliadel-induced eosinophilic meningitis that has been previously reported in only 1 case and can be diagnosed by time-spatial labeling inversion pulse magnetic resonance imaging (time-SLIP MRI). CASE DESCRIPTION A tumor located in the left temporal was detected incidentally in an 81-year-old man by examination of a head injury. The tumor was surgically resected and diagnosed as a high-grade glioma during the surgery; Gliadel wafers subsequently were implanted. Three weeks after the resection, the patient showed disturbed consciousness, and computed tomography revealed a subdural fluid collection. The out-flow of cerebrospinal through the resection cavity was detected by time-SLIP MRI. Cerebrospinal tests indicated high white blood cell counts and high protein levels, with more than 90% of the white blood cell count comprising eosinophils. Therefore, we suspected that the subdural fluid collection was caused by external hydrocephalus because of Gliadel-induced eosinophilic meningitis. We surgically removed the Gliadel wafers and subsequently performed a surgery to insert a ventriculoperitoneal shunt. Histologic examination indicated eosinophilic accumulation around the Gliadel wafers. The patients symptoms improved after the insertion of a ventriculoperitoneal shunt. CONCLUSIONS In the present case, time-SLIP MRI was a useful and noninvasive method for diagnosing external hydrocephalus which was caused by eosinophilic meningitis because of Gliadel-induced eosinophilic meningitis.