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Background: The amyloid-β oligomers, consisting of 10–20 monomers (AβO10–20), have strong neurotoxicity and are associated with cognitive impairment in Alzheimer’s disease (AD). However, their role in patients with idiopathic normal pressure hydrocephalus (iNPH) is poorly understood. Objective: We hypothesized that cerebrospinal fluid (CSF) AβO10–20 accumulates in patients with iNPH, and its clearance after CSF shunting contributes to neurological improvement. We measured CSF AβO10–20 levels before and after CSF shunting in iNPH patients evaluating their diagnostic and prognostic role. Methods: We evaluated two iNPH cohorts: “evaluation” (cohort-1) with 32 patients and “validation” (cohort-2) with 13 patients. Comparison cohorts included: 27 neurologically healthy controls (HCs), and 16 AD, 15 Parkinson’s disease (PD), and 14 progressive supranuclear palsy (PSP) patients. We assessed for all cohorts CSF AβO10–20 levels and their comprehensive clinical data. iNPH cohort-1 pre-shunting data were compared with those of comparison cohorts, using cohort-2 for validation. Next, we compared cohort-1’s clinical and CSF data: 1) before and after CSF shunting, and 2) increased versus decreased AβO10–20 levels at baseline, 1 and 3 years after shunting. Results: Cohort-1 had higher CSF AβO10–20 levels than the HCs, PD, and PSP cohorts. This result was validated with data from cohort-2. CSF AβO10–20 levels differentiated cohort-1 from the PD and PSP groups, with an area under receiver operating characteristic curve of 0.94. AβO10–20 levels in cohort-1 decreased after CSF shunting. Patients with AβO10–20 decrease showed better cognitive outcome than those without. Conclusion: AβO10–20 accumulates in patients with iNPH and is eliminated by CSF shunting. AβO10–20 can be an applicable diagnostic and prognostic biomarker.

Background Individuals with Sturge-Weber syndrome (SWS) often expereince intractable epilepsy and cognitive decline. We hypothesized that the extent of the leptomeningeal capillary malformation (LCM) may correlate with the severity of neurological impairment due to SWS. We tested the hypothesis in a cross-sectional study of seizure severity and electroencephalographic (EEG) findings and a retrospective cohort study for surgical indications related to the extent of the LCM. Methods We enrolled 112 patients and classified them according to LCM distribution: (1) bilateral, (2) hemispheric, (3) multilobar, and (4) single lobe. Age at seizure onset, seizure semiology and frequency, and EEG findings were compared. Surgical indications were evaluated for each group by Fisher exact test, and predictors for surgery were evaluated by univariate and multivariate analyses. Therapeutic efficacy was evaluated by the SWS-Neurological Score (SWS-NS). Results The bilateral and hemispheric groups had early seizure onset (4.0 months old and 3.0 months old), frequent seizures (88.9% and 80.6% had more than one per month), focal-to-bilateral tonic-clonic seizures (88.9% and 74.2%), and status epilepticus (100% and 87.1%). The groups’ EEG findings did not differ substantially. Surgical indications were present in 77.8% of the bilateral, 88.1% of the hemispheric, and 46.8% of the multilobar groups. Seizure more than once per month was a predictor of surgical treatment. Seizure subscore improved postoperatively in the hemispheric and multilobar groups. Even after surgical treatment, the bilateral and hemispheric groups exhibited higher SWS-NSs than members of the other groups. Conclusion Our study demonstrated a strong association between extensive LCM and epilepsy severity. Surgical intervention improved seizure outcome in patients with SWS with large LCMs.

OBJECTIVEImproved outcomes in patients with subarachnoid hemorrhage (SAH) treated at high-volume centers have been reported. The authors sought to examine whether hospital case volume and comprehensive stroke center (CSC) capabilities affect outcomes in patients treated with clipping or coiling for SAH.METHODSThe authors conducted a nationwide retrospective cohort study in 27,490 SAH patients who underwent clipping or coiling in 621 institutions between 2010 and 2015 and whose data were collected from the Japanese nationwide J-ASPECT Diagnosis Procedure Combination database. The CSC capabilities of each hospital were assessed by use of a validated scoring system based on answers to a previously reported 25-item questionnaire (CSC score 1–25 points). Hospitals were classified into quartiles based on CSC scores and case volumes of clipping or coiling for SAH.RESULTSOverall, the absolute risk reductions associated with high versus low case volumes and high versus low CSC scores were relatively small. Nevertheless, in patients who underwent clipping, a high case volume (> 14 cases/yr) was significantly associated with reduced in-hospital mortality (Q1 as control, Q4 OR 0.71, 95% CI 0.55–0.90) but not with short-term poor outcome. In patients who underwent coiling, a high case volume (> 9 cases/yr) was associated with reduced in-hospital mortality (Q4 OR 0.69, 95% CI 0.53–0.90) and short-term poor outcomes (Q3 [> 5 cases/yr] OR 0.75, 95% CI 0.59–0.96 vs Q4 OR 0.65, 95% CI 0.51–0.82). A high CSC score (> 19 points) was significantly associated with reduced in-hospital mortality for clipping (OR 0.68, 95% CI 0.54–0.86) but not coiling treatment. There was no association between CSC capabilities and short-term poor outcomes.CONCLUSIONSThe effects of case volume and CSC capabilities on in-hospital mortality and short-term functional outcomes in SAH patients differed between patients undergoing clipping and those undergoing coiling. In the modern endovascular era, better outcomes of clipping may be achieved in facilities with high CSC capabilities.

Objectives Comorbidities of idiopathic normal pressure hydrocephalus (iNPH), such as Alzheimer's disease (AD) and Parkinson's spectrum (PS) disorder, can affect the long-term prognosis of cerebrospinal fluid (CSF) shunting. Therefore, it is important to be able to predict comorbidities in the early stage of the disease. This study aimed to predict the comorbidities of iNPH using neuropsychological tests and cognitive performance evaluation. Materials & methods Forty-nine patients with possible iNPH were divided into three groups: iNPH without AD or PS comorbidity (group-1), iNPH with AD comorbidity (group-2), and iNPH with PS comorbidity (group-3), according to CSF biomarkers such as phosphorylated tau and dopamine transporter imaging. Scores on the new EU-iNPH-scale, which is based on 4 neuropsychological tests (Rey Auditory Verbal Learning Test, Grooved Pegboard test, Stroop colour-naming test and interference test), were compared for each group. In addition, the scores before and 12 months after CSF shunting for each group were compared. Results EU-iNPH-scale using 4 neuropsychological tests could distinguish group-1 from group-2 or group-3 by area under the curve values of 0.787 and 0.851, respectively. Patients in group-1 showed a remarkable increase in memory and learning ability after surgery. Group-2 performed significantly poorer than group-1 patients on memory testing, but otherwise showed improvements in most of the neuropsychological tests. Group-3 performed significantly worse than group-1 patients-especially on Stroop tests-but showed post-surgery improvement on only the Stroop colour-naming test. Conclusions The 4 neuropsychological tests of the EU-iNPH-scale can help predict iNPH comorbidities and evaluate the prognosis of CSF shunting.

Background and purpose The pathophysiology of idiopathic normal pressure hydrocephalus (iNPH) has not been completely clarified. We investigated the brain structure in iNPH using automatic ventricular volumetry, single-tensor diffusion tensor imaging (DTI) and bi-tensor free-water (FW) imaging analyses while focusing on cognitive impairments before and after lumboperitoneal shunt surgery. Materials and methods This retrospective study included 12 iNPH patients with structural magnetic resonance imaging (MRI) and diffusion MRI (dMRI) on a 3T-MRI scanner who underwent neuropsychological assessments before and after shunting and 8 healthy controls. Ventricular volumetry was conducted on structural MRI datasets using FreeSurfer. Ventricular volume was compared pre- and postoperatively. Correlation analyses were performed between ventricular volume or volume change and neuropsychological scores or score change. Tract-based spatial statistics were performed using dMRI datasets for group analyses between iNPH and controls and between pre- and post-surgery iNPH patients and for correlation analyses using neuropsychological scores. Tract-specific analyses were performed in the anterior thalamic radiation (ATR), followed by comparison and correlation analyses. Results The third ventricular volume was significantly decreased after shunting; its volume reduction negatively correlated with a neuropsychological improvement. Compared with controls, iNPH patients had lower fractional anisotropy and higher axial, radial, and mean diffusivities, and FW in the periventricular white matter including ATR, resulting in no difference in FW-corrected indices. Single-tensor DTI indices partially correlated with neuropsychological improvements, while FW-corrected indices had no correlations. Conclusion Third ventricle enlargement is possibly linked to cognitive impairment and FW imaging possibly provides better white matter characterization in iNPH.

Clipping of paraclinoid aneurysm is still challenging because of poor visual morbidity. The extradural temporopolar approach was applied to clip paraclinoid aneurysms, with the expectation of reducing visual morbidity. Factors related to poor visual morbidity were evaluated, to assess the results for clipping of paraclinoid aneurysms.A series of 40 unruptured paraclinoid aneurysms in 38 patients were clipped via extradural temporopolar approach. Preoperative and postoperative states of visual cognitive function and radiological outcomes were investigated. Aneurysms were classified into dorsal type or non-dorsal type, and small (9 mm) or not-small (≥9 mm), respectively, to identify factors correlated with visual morbidity.Complete clipping rate was 90.0% without any recurrence (mean: 5.2 years). Visual morbidity was unexpectedly high at 28.9%, including 2.7% of blindness immediately after the operation, and 23.7% and 2.7% at the final examination (mean: 3.6 years). Multivariate analysis showed aneurysm size was significantly correlated with worse visual outcome. Visual morbidity was 13.3% and 11.1% for dorsal and the non-dorsal small aneurysms, respectively, and all these cases showed visual field defect limited to the nasal quadrant without decreased visual acuity. In contrast, the non-dorsal not-small aneurysms showed significantly worse visual morbidity (60%) with decreased visual acuity.Clipping via extradural temporopolar approach can achieve durable treatment for small unruptured paraclinoid aneurysms with acceptable visual morbidity. Visual morbidity of the not-small non-dorsal type, however, was poor. The indications for clipping of paraclinoid aneurysm should be limited to small aneurysms, especially the dorsal type in young patients.

Background Atlantoaxial transarticular screw fixation (TASF) is a procedure that involves inserting screws vertically into the articular processes of C1 and C2. However, this procedure is associated with a risk of injury to surrounding structures including the vertebral artery, carotid artery, pharynx, and spinal cord by misinserting K-wires or screws. This study was performed to evaluate the risk of TASF using 3-dimensional navigation-guided drilling and screw insertion tract creation. Methods Three patients underwent the surgical procedure using a navigation system guided by intraoperative computed tomography. The insertion tract of the screw was created using the navigation system to avoid penetration of the C1 anterior arch or damage to the vertebral artery. A blunt-tipped guide wire was used, which was safe to advance to the cortex of the anterior arch of C1. Results There were no complications or instrument failures in any of the surgeries. In each case, the total radiation dose delivered was 5.31–7.02 mGy, and total radiation exposure time was 55.6–106.8 seconds. Bone fusion was achieved in all cases. Conclusions TASF using a navigation system for drilling is useful for accurate placement of K-wire and preventing damage of the vital structures, lowering the risk of the procedure.

Stent-assisted coiling is recognized as effective to induce progressive occlusion and prevent recurrence of aneurysm. The long-term effects of stent-assisted coiling of sidewall-type and terminal-type aneurysms were comparatively analyzed focusing on the different hemodynamic characteristics.Retrospective analysis included a total of 120 unruptured aneurysms in 116 consecutive patients who underwent stent-assisted coiling and completed 2-year follow-up. The stent systems, baseline characteristics, and postcoiling occlusion status of sidewall-type and terminal-type aneurysms were assessed.Sidewall-type aneurysms had a significantly larger dome size (P = 0.02) and greater diameter of the parent vessel (P0.001) than terminal-type aneurysms. Initial occlusion status of the aneurysms was significantly maintained for 2 years in both sidewall-type and terminal-type aneurysms as follows: sidewall-type aneurysms showed that complete occlusion (CO), neck remnants (NRs), and body filling (BF) immediately posttreatment were significantly correlated with CO (P0.05), NRs (P 0.01), and BF (P0.05) at 2-year follow-up, respectively, and terminal-type aneurysms showed that CO, NRs, and BF immediately posttreatment were significantly correlated with CO (P0.05), NRs (P0.05), and BF (P 0.05) at 2-year follow-up, respectively. In addition, sidewall-type aneurysms with CO immediately posttreatment were significantly correlated with non-NRs (P0.01) and non-BF (P 0.01) at 2-year follow-up.Stent-assisted coiling allows higher coil packing for sidewall-type aneurysms, but the indication should be carefully considered for terminal-type aneurysms.

Background Patients with idiopathic normal-pressure hydrocephalus (iNPH) are typically older adults with multiple comorbidities that are associated with a reduction in the efficacy of iNPH treatment via cerebrospinal fluid (CSF) shunt placement. Objective The present study aimed to investigate the effectiveness of CSF shunt for iNPH using data from a nationwide epidemiological survey in Japan. Methods We examined 1,423 patients (581 women) aged ≥60 years (median age [25%-75%]: 77 [73-80] years) who were diagnosed with iNPH following a hospital visit in 2012. Patients who experienced an improvement of at least one modified Rankin Scale (mRS) grade after the CSF shunt were classified as "improvement" while the remaining patients were classified as "non-improvement." The efficacy of the shunt intervention (n = 842) was analyzed using a binomial logistic regression analysis. Results An analysis of risk factors associated with shunt placement in patients with mRS grade 2 revealed an association between comorbid chronic ischemic lesions (odds ratio [OR], 2.28; 95% confidence interval [CI], 1.11-4.67; p = 0.025) and cervical spondylosis (OR, 3.62; 95% CI, 1.15-11.34; p = 0.027). Patients with mRS grade 3 at study entry had an association with comorbid Alzheimer's disease (OR, 3.02; 95% CI, 1.44-6.31; p = 0.003). Conclusions The results presented here showed that any age-related risk is minimal and should not be cause for rejection of surgical treatment options. Clinical decisions regarding CSF shunt should be individualized to each patient, with adequate consideration of the relative risks and benefits, including maximizing a healthy life expectancy.

INTRODUCTION Patients with craniosynostosis with shortened occipitofrontal diameter are mainly treated with posterior cranial vault distraction osteogenesis (PVDO) in our institution. If further intracranial volume (ICV) expansion is needed, additional treatment with frontal orbital advancement (FOA) is done. On the contrary, frontal orbital remodeling (FOR) is done for better aesthetic results. In this study, post-treatment ICV changes in patients with craniosynostosis treated with these methods have been investigated. METHODS Patients who underwent FOA or FOR in addition to PVDO at Juntendo University Hospital between 2011 and 2017 were reviewed for patient characteristics and pre/postoperative ICV measurements using 3-dimensional computed tomography scans. RESULTS Nine patients aged from 5 months to 6 years 8 months at the time of PVDO were included. For PVDO, the ICV change was 113 to 328 mL, and the enlargement ratio of ICV was 109% to 152%. Two patients were further operated with FOA while the remaining 7 with FOR. With FOA, ICV change was 73 to 138 mL, while enlargement ratio of ICV was 107% to 114%. With FOR, ICV change was 3 to 45 mL (mean 20 mL), while enlargement ratio of ICV was 100% to 103%. CONCLUSION The PVDO is our first line of treatment for ICV expansion and posterior cranial fossa decompression in patients with severe craniosynostosis. The FOA is performed if extra ICV increase is necessary. This approach seems to enable larger ICV expansions compared with other conventional methods. The FOR should be reserved for patients in whom adequate ICV levels are achieved with PVDO yet additional frontal reshaping is necessary.

Purpose Antiplatelet therapy initiated before flow diverter placement is effective for the prevention of ischemic complications. However, the effectiveness of oral anticoagulant treatment is unclear. This retrospective study evaluated the complications and obliteration rates after flow diverter placement in patients taking anticoagulants. Methods A total of 155 cases were treated by Pipeline Flex placement for unruptured large and giant cerebral aneurysms in our hospital between October 2015 and June 2019. The groups of 8 patients taking anticoagulants before operation and 147 patients not taking anticoagulants were compared. Results Clopidogrel oral dose ( P = 0.002) was significantly lower in the anticoagulant group. Delayed aneurysm rupture ( P = 0.002) and additional treatment ( P = 0.009) rates were significantly higher and complete obliteration rate ( P = 0.011) was lower in the anticoagulant group. Conclusions Additional oral anticoagulant administration before flow diverter placement does not reduce ischemic complications compared to dual antiplatelet therapy, but does increase hemorrhagic complications, especially delayed aneurysm rupture. Complete obliteration of the cerebral aneurysm is difficult to achieve in patients taking anticoagulants.

Brain extraction represents an important step in numerous neuroimaging analyses. The brain extraction tool (BET)2 is a widely used deformable model-based approach for extraction of intracranial volume (ICV). The aim of this study is to estimate the ICV extraction accuracy using synthetic MR(SyMRI) method and BET2 in healthy adult participants and patients with Sturge-Weber Syndrome (SWS), including infants. 'Quantification of relaxation times and proton density by multi-echo acquisition of saturation recovery with turbo-spin-echo readout' (QRAPMASTER) with a 3.0 T magnetic resonance image (MRI) system was used for data acquisition. Statistical evaluations were performed with linear regression analysis and the Jaccard similarity coefficient (J). ICV extraction accuracy with synthetic MR method is found to be higher than BET2, for both aged healthy participants and SWS.

Background Alzheimer's disease (AD) pathology in idiopathic normal pressure hydrocephalus (iNPH) contributes to poor shunt responses. Amyloid-β 1- 42 (Aβ42) toxic conformer was recently identified with features of rapid oligomerization, strong neurotoxicity and synaptotoxicity. Objective This observational study points to Aβ42 toxic conformer as a biomarker for AD pathology and for poor postoperative prognosis in patients with iNPH. Methods The first cohort consisted of patients with AD (n = 17) and iNPH (n = 17), and cognitively normal individuals (CN, n = 12). The second cohort, consisted of 51 patients with iNPH, was divided into two groups according to phosphorylated Tau (pTau) level (low- and high-pTau groups); the low-pTau group was further subdivided according to one-year postoperative change in Aβ42 toxic conformer ratio (%) [Aβ42 toxic conformer/Aβ42×100] (decreased- and increased-conformer subgroups). Enzyme-linked immunosorbent assay was used to measure pTau, Aβ42, and Aβ42 toxic conformer in cerebrospinal fluid. Outcomes were evaluated using neuropsychological tests one- and two-years postoperatively. Results In the first cohort, Aβ42 toxic conformer ratio in the iNPH group (10.8%) was significantly higher than that in the CN group (6.3%) and significantly lower than that in the AD group (17.2%). In the second cohort, the high-pTau group showed cognitive decline two-years postoperatively compared to baseline. However, the low-pTau group showed favorable outcomes one-year postoperatively; furthermore, the increased-conformer subgroup showed cognitive decline two-years postoperatively while the decreased-conformer subgroup maintained the improvement. Conclusions Change in Aβ42 toxic conformer ratio predicts long-term cognitive outcome in iNPH, even in the low-pTau group.

Idiopathic normal pressure hydrocephalus (iNPH) is a dementia-inducing disorder. Primary cause of iNPH is speculated to be a reduction of cerebrospinal fluid (CSF) absorption, which secondarily induces hydrocephalus, compression of brain, and reduction of CSF production. Patients are treated by surgically inserting a shunt to deliver excess CSF to the abdominal cavity. The prognosis for cognitive improvement after shunt surgery has been difficult to predict. We therefore investigated various CSF proteins, hoping to find a biomarker predictive of cognitive performance one to two years after shunt surgery. CSF proteins of 34 iNPH and 15 non-iNPH patients were analysed by Western blotting, revealing two glycan isoforms of transferrin (Tf); 'brain-type' Tf with N-acetylglucosaminylated glycans and 'serum-type' Tf with α2, 6-sialylated glycans. Brain-type Tf levels decreased in iNPH but rapidly returned to normal levels within 1-3 months after shunt surgery. This change was positively correlated with recovery from dementia, per Mini-Mental State Examination and Frontal Assessment Battery scores at 11.8 ± 7.7 months post-operation, suggesting that brain-type Tf is a prognostic marker for recovery from dementia after shunt surgery for iNPH. Histochemical staining with anti-Tf antibody and an N-acetylglucosamine-binding lectin suggests that brain-type Tf is secreted from choroid plexus, CSF-producing tissue.

Background Treating idiopathic normal pressure hydrocephalus (iNPH) with lumboperitoneal shunts (LPSs) may cause cerebrospinal fluid (CSF) overdrainage. Objective To investigate whether LPSs, including gravitational "add-on" and programmable pressure valves (PPVs/+GVs), reduce complications and improve outcomes. Methods We compared PPVs/+small lumen abdominal catheters (SLs) to PPVs/+GVs using different opening pressures for supine and standing positions. We analyzed 115 patients with iNPH in 2 consequent cohorts: 48 patients receiving LPSs with PPVs/+SLs and 67 patients receiving LPSs with PPVs/+GVs. The modified Rankin Scale (mRS), Japan iNPH grading scale, Mini Mental State Examination, Frontal Assessment Battery, and CSF biomarkers were evaluated. Results Comparisons of postoperative clinical factors in 64 patients in the PPV/+SL and PPV/+GV groups using 1:1 propensity score matching revealed differences in the mean (±standard deviation) postoperative mRS (2.65 ± 1.07 vs 2.16 ± 1.02, P = .049) and gait disturbance scores (1.97 ± 1.03 vs 1.39 ± 0.92, P = .011). Thus, outcomes improved in the LPS group with the GV. Serious and nonserious adverse event rates for the PPV/+SL and PPV/+GV groups were 22.9% and 19.4% (P = .647) and 38% and 17.9% (P = .018), respectively, indicating higher rates of subdural collections for the PPV/+SL group. Conclusion This is the first study to examine LPS treatment for iNPH using a GV in tandem with a PPV. Our results suggest that the CSF shunt flow volume is restricted in the standing position and maintained in the supine position, thus improving iNPH symptoms. This may reduce intracranial CSF hypotension-related complications.

BACKGROUND Treatments for unruptured anterior communicating artery (AcomA) aneurysm have relatively high morbidity. OBJECTIVE To assess the lateral supraorbital keyhole approach for safe and complete clipping of unruptured AcomA aneurysm and evaluate the long-term clinical and radiological outcomes, including cognitive and depressive status. METHODS A total of 63 patients (aged 41-79 yr, mean 64 yr) with relatively small AcomA aneurysms clipped via the lateral supraorbital approach were retrospectively analyzed among the 105 AcomA aneurysms treated by clipping from 2005 to 2014. Neurological and cognitive functions were examined by several scales, including the modified Rankin Scale (mRS) and Mini-Mental Status Examination. The depressive state was assessed using the Beck Depression Inventory and Hamilton Depression Scale. The state of clipping was assessed 1 yr and then every few years after the operation by 3-dimensional computed tomography angiography. RESULTS Complete neck clipping was confirmed in 62 aneurysms (98.4%). Perioperative complications occurred in 5 patients (5/63; mild frontalis muscle weakness in 3, anosmia in 1, and meningitis in 1). The mean clinical follow-up period was 5.2 ± 2.1 yr. No patient showed an mRS score more than 2 and all were completely independent in daily life. The depression scores were significantly improved after surgery. The overall mortality was 0% and overall morbidity (mRS score > 2 or Mini-Mental Status Examination score < 24) was 1.6%. All completely clipped aneurysms did not show any recurrence during the mean follow-up period of 4.9 ± 2.1 yr. CONCLUSION Lateral supraorbital keyhole approach to clip relatively small unruptured AcomA aneurysm promises less invasive and durable treatment.

OBJECTIVEAdvanced age is known to be associated with a poor prognosis after surgical clipping of unruptured intracranial aneurysms (UIAs). Keyhole clipping techniques have been introduced for less invasive treatment of UIAs. In this study, the authors compared the complications and clinical and radiological outcomes after keyhole clipping between nonfrail elderly patients (≥ 70 years) and nonelderly patients.METHODSKeyhole clipping (either supraorbital or pterional) was performed to treat 260 cases of relatively small (≤ 10 mm) anterior circulation UIAs. There were 62 cases in the nonfrail elderly group (mean age 72.9 ± 2.6 years [± SD]) and 198 cases in the nonelderly group (mean age 59.5 ± 7.6 years). The authors evaluated mortality and morbidity (modified Rankin Scale score > 2 or Mini–Mental State Examination [MMSE] score < 24) at 3 months and 1 year after the operation, the general cognitive function by MMSE at 3 months and 1 year, anxiety and depression by the Beck Depression Inventory (BDI) and Hamilton Rating Scale for Depression (HAM-D) at 3 months, and radiological abnormalities and recurrence at 1 year.RESULTSBasic characteristics including comorbidities, frailty, and BDI and HAM-D scores were not significantly different between the 2 groups, whereas the MMSE score was slightly but significantly lower in the elderly group. Aneurysm location, largest diameter, type of keyhole surgery, neck clipping rate, and hospitalization period were not significantly different between the 2 groups. The incidence of chronic subdural hematoma was not significantly higher in the elderly group than in the nonelderly group (8.1% vs 4.5%, p = 0.332); rates of other complications including stroke and epilepsy were not significantly different. Lacunar infarction occurred in 3.2% of the elderly group and 3.0% of the nonelderly group. No patient in the elderly group required re-treatment or demonstrated recurrence of clipped aneurysms. The MMSE score at 3 months significantly improved in the nonelderly group but did not change in the elderly group. The BDI and HAM-D scores at 3 months were significantly improved in both groups. No patient died in either group. The morbidity at 3 months and 1 year in the elderly group (1.6% and 4.8%, respectively) was not significantly different from that in the nonelderly group (2.0% and 1.5%, respectively).CONCLUSIONSKeyhole clipping for nonfrail elderly patients with relatively small anterior circulation UIAs did not significantly increase the complication, mortality, or morbidity rate; hospitalization period; or aneurysm recurrence compared with nonelderly patients, and it was associated with improvement in anxiety and depression. Keyhole clipping to treat UIAs in the nonfrail elderly is an effective and long-lasting treatment.

The symptoms of idiopathic normal pressure hydrocephalus (iNPH) can be improved by shunt surgery, but prediction of treatment outcome is not established. We investigated changes of the corticospinal tract (CST) in iNPH before and after shunt surgery by using diffusion microstructural imaging, which infers more specific tissue properties than conventional diffusion tensor imaging. Two biophysical models were used: neurite orientation dispersion and density imaging (NODDI) and white matter tract integrity (WMTI). In both methods, the orientational coherence within the CSTs was higher in patients than in controls, and some normalization occurred after the surgery in patients, indicating axon stretching and recovery. The estimated axon density was lower in patients than in controls but remained unchanged after the surgery, suggesting its potential as a marker for irreversible neuronal damage. In a Monte-Carlo simulation that represented model axons as undulating cylinders, both NODDI and WMTI separated the effects of axon density and undulation. Thus, diffusion MRI may distinguish between reversible and irreversible microstructural changes in iNPH. Our findings constitute a step towards a quantitative image biomarker that reflects pathological process and treatment outcomes of iNPH., Highlights • NODDI and WMTI provide markers of reversible and irreversible changes in iNPH. • Measures of axon orientation indicated recovery from stretching after surgery. • Axon density remained low after surgery, suggesting chronic neuronal damage. • Axon stretching in simulations differentially affected diffusion metrics.

OBJECTIVEJapan has been reported to have the highest (and increasing) incidence of subarachnoid hemorrhage (SAH) in the world. However, there has never been a report on the nationwide incidence rate and recent trends for SAH in Japan. In this register-based study, the authors aimed to clarify the estimated nationwide SAH incidence rate and the recent trend in SAH incidence in Japan and the reasons for any changes in this trend.METHODSThe authors compiled data from the Japanese Ministry of Health, Labour and Welfare and from the records of the Japan Neurosurgical Society. They reviewed the age-standardized nationwide SAH mortality rate, the estimated age-standardized SAH incidence rate according to the age-standardized SAH mortality rate, and the estimated crude SAH incidence rate, including the 95% confidence intervals, from 2003 to 2015. The trends in the number of treatments for unruptured and ruptured cerebral aneurysms, as well as the prevalence of hypertension, current smoking status, and use of cholesterol-lowering drugs, were assessed. The estimated treatment rate for unruptured cerebral aneurysms (UCAs) was also calculated along with the 95% confidence interval.RESULTSThe estimated age-standardized nationwide SAH incidence rate significantly declined from 31.34 cases (95% CI 31.32–31.34) to 27.63 (95% CI 27.59–27.63; decrease by 11.8%) per 100,000 person-years. This decline was based on the 2010 population as the reference from 2003 through 2015 and a case-fatality rate of SAH that was assumed to decrease by 1% annually from 44% in 2003 to 32% in 2015. According to sensitivity analysis, the change rate of the estimated age-standardized SAH incidence rate ranged from −56.69% to 23.27%, with a mean of −30.91% (SD 20.52%), and there were decline trends in 92% of all trends. The estimated nationwide crude SAH incidence rate also showed a significant decline from 23.79 (95% CI 23.78–23.79) to 20.25 (95% CI 20.24–20.25; decrease by 14.9%) per 100,000 person-years. The trend in treatment numbers for UCAs increased significantly (p < 0.0001) from 2003 through 2015; however, the estimated treatment rate for UCAs was only 0.19 (95% CI 0.19–0.20) to 0.51 (95% CI 0.50–0.51) among all UCA patients. The prevalence of hypertension (males, p = 0.0003; females, p < 0.0001) and current smoking status (males, p < 0.0001; females, p = 0.0002) declined significantly from 2003 through 2015, while the use of cholesterol-lowering drugs increased significantly (males, p < 0.0001; females, p = 0.0005) during the same period.CONCLUSIONSThe estimated nationwide SAH incidence rate in Japan was higher than rates in other countries, although it has declined recently. An improving lifestyle may have contributed to the declining rate of SAH incidence in Japan.

Chronic subdural hematoma (CSDH) has a reported postoperative recurrence rate of 3–20% and the optimal therapeutic strategy remains controversial. Recently, in Japan, Goreisan (Kampo medicine) was used for preventing postoperative CSDH recurrence. Therefore, this study aimed to explore if Goreisan is effective against specific CSDH types by evaluating its effects on postoperative CSDH recurrence and reoperation rates based on its natural history and internal structure on CT images. This retrospective, single-center, cohort study was conducted at the Tokyo Metropolitan Hiroo Hospital. After applying the inclusion/exclusion criteria, data from 107 patients (70 men and 37 women; mean age, 77.1 ± 10.9 years), admitted for CSDH from January 2013 to December 2018, were included in the Goreisan group, whereas those of 122 patients (84 men and 38 women; mean age, 73.9 ± 13.3 years), admitted for CSDH from January 2007 to December 2012, were included in the control group. This corresponded to 114 lesions, with 14 reoperation lesions, in the Goreisan group and 108 lesions, with 16 reoperation lesions, in the control group. Lesions were categorized as homogeneous, laminar, separated, or trabecular type, and patients with homogeneous type lesions in the Goreisan group were approximately 50% less likely to undergo reoperation compared with those in the control group (7.3% versus 14%; odds ratio = 0.51; 95% confidence interval = 0.12–2.11). Thus, the homogeneous type CSDH was the most responsive to Goreisan, whereas the separated type was the least responsive. Therefore, selecting treatment strategies for preventing CSDH recurrence on CSDH type may contribute toward reducing reoperation rates.

Background We aimed to develop quality indicators (QIs) related to primary and comprehensive stroke care and examine the feasibility of their measurement using the existing Diagnosis Procedure Combination (DPC) database. Methods and results We conducted a systematic review of domestic and international studies using the modified Delphi method. Feasibility of measuring the QI adherence rates was examined using a DPC-based nationwide stroke database (396,350 patients admitted during 2013-2015 to 558 hospitals participating in the J-ASPECT study). Associations between adherence rates of these QIs and hospital characteristics were analyzed using hierarchical logistic regression analysis. We developed 17 and 12 measures as QIs for primary and comprehensive stroke care, respectively. We found that measurement of the adherence rates of the developed QIs using the existing DPC database was feasible for the 6 QIs (primary stroke care: early and discharge antithrombotic drugs, mean 54.6% and 58.7%; discharge anticoagulation for atrial fibrillation, 64.4%; discharge antihypertensive agents, 51.7%; comprehensive stroke care: fasudil hydrochloride or ozagrel sodium for vasospasm prevention, 86.9%; death complications of diagnostic neuroangiography, 0.4%). We found wide inter-hospital variation in QI adherence rates based on hospital characteristics. Conclusions We developed QIs for primary and comprehensive stroke care. The DPC database may allow efficient data collection at low cost and decreased burden to evaluate the developed QIs.

Temporal lobe epilepsy with amygdala enlargement (TLE-AE) has been considered a subtype of TLE. We evaluated the epileptogenic zone in patients with TLE-AE, who underwent intracranial video-EEG (ivEEG) and/or intraoperative electrocorticography (ioECoG) as well as epilepsy surgery. Eleven patients with TLE-AE were enrolled and investigated based on seizure profile, volumetric MRI, the Wechsler Memory Scale-Revised (WMS-R), the location of seizure onset zone (SOZ) and irritative zone (IZ) based on ivEEG (n=8), the location of interictal epileptiform discharges (IEDs) based on ioECoG (11), surgical procedure, and seizure outcome. The mean age at seizure onset was 34.9 years (range: 23-57). The mean duration of seizures was 5.0 years (range: 1-10). The number of AEDs was 2.3 (range: 1-5). The mean seizure frequency was nine per month (range: 1-30/month). All patients presented with focal impaired awareness seizures with (n=9) and without (2) secondary generalized convulsions. Volumetric MRI analysis showed unilateral enlarged amygdala with statistical significance (p0.01). None of the patients' hippocampi had any abnormality based on MRI. Pre-operative mean verbal, visual, and delayed recall scores based on the WMS-R were over 100. The SOZ and IZ were identified in both the amygdala and hippocampus in seven patients and in only the amygdala in one patient based on ivEEG. IEDs were identified in the hippocampus in six patients and in both the amygdala and hippocampus in four patients based on ioECoG. All 11 patients underwent anterior temporal lobectomy, including amygdala resection, with multiple hippocampal transections (dominant hemisphere: seven patients) and resection (non-dominant hemisphere: three patients). Nine (81.8%) of 11 patients achieved seizure freedom with a mean follow-up of 26 months (range: 12-47). Post-operative WMS-R results did not show any significant deterioration, with a mean follow-up of 15 months (range: 12-24). The resected amygdala showed no histopathological abnormality. The epileptogenic zone of TLE-AE involves both the amygdala and hippocampus. ivEEG may be needed to explore the SOZ in normal hippocampus in addition to enlarged amygdala. Amygdala resection and multiple hippocampal transections may control the epileptogenic limbic system and save memory function in patients with TLE-AE.

The epidemiology of patients with traumatic brain injury (TBI) has changed dramatically over recent decades as a result of rapid advances in aging societies. We assessed the influence of age on outcomes of patients with TBI and sought to identify prognostic factors for in-hospital mortality of TBI among elderly patients.Using a nationwide database, we analyzed data from 5651 patients with TBI. Univariate analysis was conducted to compare patient demographics, neurologic status on admission, radiologic findings, systemic complication rates, length of hospital stay, in-hospital mortality, and home discharge rates between elderly and nonelderly groups. Multivariable analysis was conducted to determine prognostic factors for in-hospital mortality among elderly patients.Overall in-hospital mortality was significantly higher in elderly patients (12.8% vs. 19.3%; P0.001). In-hospital mortality of elderly patients with mild TBI increased significantly at7 days after admission, whereas that of elderly patients with moderate or severe TBI was significantly higher immediately after admission. Age (odds ratio [OR], 1.62; P = 0.024), male sex (OR, 1.30; P = 0.004), Japan Coma Scale score on admission (OR, 5.95, P0.001), and incidence of acute subdural hematoma (OR, 1.89; P0.001) were associated with in-hospital mortality in elderly patients with TBI.Elderly patients with TBI showed significantly higher in-hospital mortality. Delayed increases in in-hospital mortality were observed among elderly patients with mild TBI. Level of consciousness on admission was the strongest predictor of in-hospital mortality among elderly patients.

BACKGROUND AND PURPOSE: The flow-diverter device has been established as a treatment procedure for large unruptured intracranial aneurysms. The purpose of this study was to compare the usefulness of Silent MR angiography and time-of-flight MRA to assess the parent artery and the embolization state of the aneurysm after a flow-diverter placement. MATERIALS AND METHODS: Seventy-eight large, unruptured internal carotid aneurysms in 78 patients were the subjects of this study. After 6 months of treatment, they underwent follow-up digital subtraction angiography, Silent MRA, and TOF-MRA, performed simultaneously. All images were independently reviewed by 2 neurosurgeons and 1 radiologist and rated on a 4-point scale from 1 (not visible) to 4 (excellent) to evaluate the parent artery. The aneurysmal embolization status was assessed with 2 ratings: complete or incomplete occlusion. RESULTS: The mean scores of Silent MRA and TOF-MRA regarding the parent artery were 3.18 ± 0.72 and 2.31 ± 0.86, respectively, showing a significantly better score with Silent MRA (P < .01). In the assessment of the embolization of aneurysms on Silent MRA and TOF-MRA compared with DSA, the percentages of agreement were 91.0% and 80.8%, respectively. CONCLUSIONS: Silent MRA is superior for visualizing blood flow images inside flow-diverter devices compared with TOF-MRA. Furthermore, Silent MRA enables the assessment of aneurysmal embolization status. Silent MRA is useful for assessing the status of large and giant unruptured internal carotid aneurysms after flow-diverter placement.

Purpose We aimed to analyse the patency rate of the anterior choroidal artery, and presented imaging and neurological findings, after deployment of a flow diverter in the anterior choroidal artery in the treatment of patients with intracranial aneurysms. Methods Among the 139 patients who underwent a flow diverter deployment from December 2012 to September 2017 in our hospital, there were 21 patients (15.1%) for whom their anterior choroidal artery was covered for the procedure with a flow diverter. The patients' age, sex, size of aneurysm and the presence or absence of an anterior choroidal artery occlusion, neurological findings and postoperative infarction in the anterior choroidal artery region were analysed retrospectively. Results The mean age of the six male and 15 female patients was 61.5 years (range 32–77 years). The mean maximal diameter of the aneurysms was 16.4 mm (range 10.0–29.4 mm). The anterior choroidal artery was patent in all 21 patients; however, a haemodynamic alteration in the anterior choroidal artery was detected in one patient. Postoperatively, hemiparesis was observed in two patients (9.5%) and a visual field defect in one patient (4.8%), both of which were the symptoms of infarction of the cortical branch of the middle cerebral artery or retinal artery ischaemia. However, no patients had symptoms due to ischaemia of the anterior choroidal artery confirmed with magnetic resonance imaging. Conclusions In all patients who underwent flow diverter deployment, the anterior choroidal artery was patent and no ischaemia was detected in the imaging or evidenced by neurological findings. Therefore, flow diverter deployment in the anterior choroidal artery was considered to be a safe procedure.

To evaluate diffusional changes of the corticospinal tract (CST) in patients with idiopathic normal pressure hydrocephalus (iNPH) by neurite orientation dispersion and density imaging (NODDI). Nineteen patients with iNPH and 12 healthy controls were included. Diffusion MRI data for NODDI were acquired with a 3-T system, using 32 motion-probing gradient directions with six b-values (from 0 to 2500 s/mm2). The orientation dispersion index (ODI), intra-cellular volume fraction (Vic), and isotropic volume fraction (Viso) of the CST were calculated by tract-specific analysis in patients and controls. We also measured the fractional anisotropy (FA) and apparent diffusion coefficient (ADC). The ODI of the CST (0.087 ± 0.024 vs. 0.183 ± 0.051, P

Purpose We retrospectively evaluated the diagnostic value of 18 F-2-fluorodeoxy-d-glucose positron emission tomography (FDG-PET) with statistical analysis for the foci detection and predictive utility for postsurgical seizure outcome of patients with mesial temporal lobe epilepsy (mTLE). Method We evaluated 40 patients who were diagnosed mTLE and underwent selective amygdalohippocampectomy (SAH) or anterior temporal lobectomy (ATL) in our institute. Preoperative interictal FDG-PET with statistical analysis using three-dimensional stereotactic surface projection (3D-SSP) was detected with several clinical data including seizure semiology, MRI, scalp electroencephalography, surgical procedure with SAH or ATL and postsurgical outcome. The region of interest (ROI) was defined on ⿿Hippocampus & Amygdala⿿, ⿿Parahippocampal gyrus & Uncus⿿, ⿿T1 & T2⿿, and ⿿T3 & Fusiform gyrus⿿. We obtained the ratio of hypometabolism difference (RHD) by 3D-SSP, and evaluated the relation among hypometabolic extent, surgical outcome and surgical procedure. Result The RHD in each ROIs ipsilateral to operative side was significantly higher than that of contralateral side in good outcome group. Hypometabolism of ⿿Hippocampus & Amygdala⿿ was most reliable prognostic factor. Patients of discordant with presurgical examinations hardly showed obvious lateralized hypometabolism. Nevertheless, when they have significantly high RHD in mesial temporal lobe, good surgical outcome was expected. There was not significant difference of RHD distribution between SAH and ATL in good outcome group. Conclusion Significant hypometabolism in mesial temporal lobe on FDG-PET with 3D-SSP is useful to predict good surgical outcome for patients with mTLE, particularly in discordant patients with hypometabolism in mesial temporal structure. However, FDG-PET is not indicative of surgical procedure.

Posterior cranial vault distraction is considered to be more effective for increasing intracranial volume than fronto-orbital advancement or anterior cranial vault expansion, but the changes in intracranial volumes after posterior cranial vault distraction remain unclear. The changes in intracranial volume were investigated in patients of premature craniosynostosis treated by this technique. Seven patients, 3 boys and 4 girls aged from 5 months to 3 years 3 months (mean 23 months) at operation, with craniosynostosis underwent posterior cranial vault distraction at Juntendo University Hospital from 2011 to 2014. Patient characteristics, length of distraction, and pre- and postoperative computed tomography findings were reviewed. Total intracranial volume, including the supratentorial space and posterior cranial fossa, was measured using the workstation functions on three-dimensional computed tomography scans. Posterior distraction was performed without severe complications except in 2 patients requiring additional surgeries. The distraction length was 22.3 to 39 mm (mean 31 mm), the intracranial volume change was 144 to 281 mL (mean 192 mL), and the enlargement ratio of intracranial volume was 113% to 134% (mean 121%). The present quantitative analysis of intracranial volume change after posterior distraction showed greater increases in intracranial volume compared with previous reports. Furthermore, intracranial volumes in our patients became nearly normal and were maintained for the follow-up period (maximum 13 months). Posterior cranial vault distraction is very effective to increase cranial volume, so may be the first choice of treatment in patients of craniosynostosis.

Two transferrin (Tf) glycan-isoforms were previously found in cerebrospinal fluid (CSF); one appears to be derived from serum (Tf-2) and the other from choroid plexus, a CSF-producing tissue (Tf-1). To analyse metabolic differences associated with the two isoforms, their ratio (Tf-2/Tf-1) was defined as the Tf index. Here we report that Tf indices of patients with tauopathies including Alzheimer's disease (2.29 + 0.64) were similar to those of neurological controls (2.07 + 0.87) (P = 0.147). In contrast, Tf indices with Parkinson's disease (PD, 3.38 ± 1.87) and multiple system atrophy (MSA, 3.15 ± 1.72) were higher than those of the controls (2.07 ± 0.87), the P-values being < 0.001 and 0.024, respectively. Tf indices of PD and MSA did not appear to be normally distributed. Indeed, detrended normal Quantile-Quantile plot analysis revealed the presence of an independent subgroup showing higher Tf indices in PD and MSA. The subgroup of PD showed higher levels of CSF α-synuclein (38.3 ± 17.8 ng/ml) than the rest (25.3 ± 11.3 ng/ml, P = 0.012). These results suggest that PD (and MSA) includes two subgroups, which show different metabolism of CSF transferrin and α-synuclein.

Extensive molecular analyses of ependymal tumors have revealed that supratentorial and posterior fossa ependymomas have distinct molecular profiles and are likely to be different diseases. The presence of C11orf95-RELA fusion genes in a subset of supratentorial ependymomas (ST-EPN) indicated the existence of molecular subgroups. However, the pathogenesis of RELA fusion-negative ependymomas remains elusive. To investigate the molecular pathogenesis of these tumors and validate the molecular classification of ependymal tumors, we conducted thorough molecular analyses of 113 locally diagnosed ependymal tumors from 107 patients in the Japan Pediatric Molecular Neuro-Oncology Group. All tumors were histopathologically reviewed and 12 tumors were re-classified as non-ependymomas. A combination of RT-PCR, FISH, and RNA sequencing identified RELA fusion in 19 of 29 histologically verified ST-EPN cases, whereas another case was diagnosed as ependymoma RELA fusion-positive via the methylation classifier (68.9%). Among the 9 RELA fusion-negative ST-EPN cases, either the YAP1 fusion, BCOR tandem duplication, EP300-BCORL1 fusion, or FOXO1-STK24 fusion was detected in single cases. Methylation classification did not identify a consistent molecular class within this group. Genome-wide methylation profiling successfully sub-classified posterior fossa ependymoma (PF-EPN) into PF-EPN-A (PFA) and PF-EPN-B (PFB). A multivariate analysis using Cox regression confirmed that PFA was the sole molecular marker which was independently associated with patient survival. A clinically applicable pyrosequencing assay was developed to determine the PFB subgroup with 100% specificity using the methylation status of 3 genes, CRIP1, DRD4 and LBX2. Our results emphasized the significance of molecular classification in the diagnosis of ependymomas. RELA fusion-negative ST-EPN appear to be a heterogeneous group of tumors that do not fall into any of the existing molecular subgroups and are unlikely to form a single category. Electronic supplementary material The online version of this article (10.1186/s40478-018-0630-1) contains supplementary material, which is available to authorized users.

Flow diverters (FDs) have been developed for intracranial aneurysms difficult to treat with conventional endovascular therapy and surgical clipping. We reviewed 94 patients with 100 large or giant unruptured internal carotid artery (ICA) aneurysms treated with Pipeline embolization device (PED) embolization from December 2012 to June 2017 at Juntendo University Hospital. The patients' mean age was 63.4 years (range, 19-88), and there were 90 women 89.4%. Aneurysm locations were: C4 (45), C3 (4), and C2 (51) in ICA segments. Mean aneurysm size and neck width were 16.9 ± 6.8 mm and 8.3 ± 4.4 mm, respectively, in 40 symptomatic and 60 asymptomatic aneurysms. Follow-up catheter angiographies of 85 patients with 90 aneurysms showed no filling in 62 aneurysms (68.9%), entry remnant in 16 (17.8%), subtotal filling in 11 (12.2), and total filling in 1 (1.1%) with a mean follow-up of 10.2 ± 5.6 months. In-stent stenosis occurred in 1 patient and parent artery occlusion in 2 during follow-up. Hemorrhagic complications occurred in 4 (4.3%): delayed aneurysm rupture (2) and intraparenchymal hemorrhage (2). Ischemic complications with neurological symptoms occurred in 2 (2.1%): very delayed device occlusion (1) and intraprocedural distal embolism (1). Eighteen patients (45%) showed improvement in pre-existing cranial nerve dysfunction because of the aneurysm's mass effect, 3 patients (7.5%) worsened. One patient died of systemic organ failure unassociated with the procedure. Morbidity and mortality rates were 4.3% and 1.1%, respectively. PED embolization for unruptured large and giant ICA aneurysms is safe and efficacious. Physicians should be observant of characteristic risks associated with FD therapy.

Background Experiencing a ventriculoperitoneal (VP) shunt complication is a major obstacle in the management of hydrocephalus. Degradation of a shunt catheter associated with surrounding tissue calcification could be 1 reason for a difference in facture rates. Furthermore, tissue reactions around cerebrospinal fluid shunts may be a sign of bacterial shunt infection, which is not uncommon. Case Description A 31-year-old man was living with a ventriculoperitoneal shunt since childhood. Consequently, his cerebrospinal fluid absorption was supposed to be modified by the shunt. Shunt malfunction later occurred concomitant with symptoms of headache and repeated vomiting. He had undergone shunt revision a year before presentation, but examination revealed that a new, extremely rare calcified lesion had formed in the aponeurosis of the abdomen, compressing the shunt tube. We removed it and replaced the shunt tube, thus relieving his symptoms. Conclusions We treated a rare case of shunt dysfunction caused by calcification of the aponeurosis coinciding with significant weight gain over the course of a year. To the best of our knowledge, this is the first report to describe a case of shunt malfunction caused by calcification of the aponeurosis.

Objective To describe microsurgical anatomy of the rhomboid lip (RL) and to consider its role by presenting histology and clinical cases. Methods We examined 10 (20 sides) formalin-fixed adult human cadaveric heads injected with colored silicone. A total of 20 RLs were examined posteriorly. We examined the expansion of the RL in the cerebellopontine cistern. We assessed the relationship between the RL and choroid plexus and the RL and cranial nerve IX and classified the RL. We also observed these relationships in clinical cases during surgeries and examined histologic assessments of the RL. Results The RL was divided into 3 types, non-extension type, lateral extension type, and jugular foramen type, according to the relationship between the RL and choroid plexus. There were many variations of the extension of the RL. The jugular foramen type was rare. Conclusions Histologically, the RL is the remnant of the fourth ventricle covered with ependymal cells. Knowledge of the detailed anatomy and proper dissection of the RL may help surgeons to obtain good visualization of structures around the foramen of Luschka.

Background Fusion genes driving tumourigenesis have drawn the attention of researchers and oncologists. Despite the importance of such molecular alterations, there are no comprehensive reproducible methods for detecting fusion genes. Materials and methods Nineteen paediatric brain tumours of five types, namely pilocytic astrocytoma, oligodendroglioma, anaplastic astrocytoma, glioblastoma and, ganglioglioma, were examined to detect fusion genes using a pyrosequencing-based method following RNA isolation, cDNA synthesis and real-time polymerase chain reaction. Results Our method successfully detected KIAA1549-v-raf murine sarcoma viral oncogene homolog B1 (BRAF) fusion in 14 out of 19 patients suffering from five types of paediatric brain tumours providing information on fusion breakpoints within 2 h. Conclusion A comprehensive method for detecting fusion genes in paediatric brain tumours was evaluated. This method identified KIAA1549-BRAF fusion variants quickly. Our results may help researchers interested in the role of fusion genes in tumourigenesis.

The aim of this study was to quantitatively evaluate the function of the cranial diploic and spinal epidural veins as cerebrospinal fluid (CSF) drainage pathways by measuring lipocalin-type prostaglandin D synthase (PGDS) and cystatin C (CysC) dissolved in the blood of these veins. This was a prospective study involving 51 consecutive patients, 31 males and 20 females, who underwent 41 cranial and 10 spinal surgeries. Intraoperatively, peripheral venous blood and diploic venous blood, or peripheral venous blood and spinal epidural venous blood samples were simultaneously collected and immediately centrifuged. For all samples, dissolved albumin (for reference), PGDS and CysC were measured using an enzyme-linked immunosorbent assay. The diploic vein/peripheral vein ratios in five cranial locations and epidural vein/peripheral vein ratios were calculated and statistically evaluated for the three biomarkers. For PGDS, the diploic vein/peripheral vein ratio was significantly increased in the frontal (P = 0.011), temporal (P = 0.028), parietal (P = 0.046) and skull base (P = 0.039), while it did not reach statistical significance for CysC. For patients older than 45 years, the diploic vein/peripheral vein ratio for PGDS was significantly decreased in the frontal region (P = 0.028), and the epidural vein/peripheral vein ratio for CysC was significantly decreased (P = 0.014). These results show that the diploic veins constitute CSF drainage pathways with heterogeneous functional intensity at different cranial locations. Compared with the diploic veins, spinal epidural veins seem to drain less CSF. The cranial diploic and spinal epidural veins may jointly function as an alternative, age-related trans-dural CSF drainage system.

Despite extensive investigations, the process of development of chronic subdural hematoma (CSDH) is not known. The present study aims to investigate CSDH by measuring biomarkers in it, gas analysis, and immunohistochemical examination. A total of 42 patients with symptomatic CSDH who underwent burr-hole drainage were enrolled. Intraoperatively, hematoma fluid and peripheral venous blood (PVCSDH) were simultaneously collected. As controls, peripheral venous blood (PVControl) and intracranial cerebrospinal fluid (CSF) were collected from other subjects during other surgeries. CatK, lipocalin-type prostaglandin D synthase (PGDS), and cystatin C (CysC) present in these specimens were measured using enzyme-linked immunosorbent assay. Data obtained were statistically analyzed after age correction. In 15 patients, gas analysis was performed for CSDH and PVCSDH. Furthermore, immunohistochemical examination for the outer membrane was performed for four patients. CatK, PGDS, and CysC levels were markedly elevated in the CSF and CSDH. CatK levels in PVCSDH were significantly higher than in PVControl (P

Background To implement personalized medicine, we established a large-scale patient cohort, BioBank Japan, in 2003. BioBank Japan contains DNA, serum, and clinical information derived from approximately 200,000 patients with 47 diseases. Serum and clinical information were collected annually until 2012. Methods We analyzed clinical information of participants at enrollment, including age, sex, body mass index, hypertension, and smoking and drinking status, across 47 diseases, and compared the results with the Japanese database on Patient Survey and National Health and Nutrition Survey. We conducted multivariate logistic regression analysis, adjusting for sex and age, to assess the association between family history and disease development. Results Distribution of age at enrollment reflected the typical age of disease onset. Analysis of the clinical information revealed strong associations between smoking and chronic obstructive pulmonary disease, drinking and esophageal cancer, high body mass index and metabolic disease, and hypertension and cardiovascular disease. Logistic regression analysis showed that individuals with a family history of keloid exhibited a higher odds ratio than those without a family history, highlighting the strong impact of host genetic factor(s) on disease onset. Conclusions Cross-sectional analysis of the clinical information of participants at enrollment revealed characteristics of the present cohort. Analysis of family history revealed the impact of host genetic factors on each disease. BioBank Japan, by publicly distributing DNA, serum, and clinical information, could be a fundamental infrastructure for the implementation of personalized medicine., Highlights • The BioBank Japan Project (BBJ) annually collected clinical information. • Analysis of the clinical information at enrollment characterized the BBJ cohort. • Analysis of family history revealed impacts of host genetic factors on the diseases.

Objectives There have been no nationwide epidemiological studies of idiopathic normal pressure hydrocephalus (iNPH) in Japan. Therefore, a nationwide epidemiologic survey of iNPH was performed to determine the number of cases and clinical characteristics by sex and diagnostic level. Methods The first survey examined the numbers of cases that met the diagnostic criteria of iNPH and those who underwent shunt operations in 2012. The second survey gathered patients' details to clarify their clinical background characteristics. Results The estimated number of cases meeting the diagnostic criteria in 2012 was 12,900, with 6,700 undergoing shunt operations. The estimated crude prevalence was 10.2/100,000 persons. The age of onset was in the 70s in more than 50% of both men and women. Significantly higher (p

Background: Patients presenting with the classical idiopathic normal pressure hydrocephalus (iNPH) triad often show additional parkinsonian spectrum signs. Accurate differential diagnosis strongly influences the long-term outcome of cerebrospinal fluid (CSF) shunting. Objective: The aim of this study was to find potential CSF microRNA (miRNA) biomarkers for NPH mimics with parkinsonian syndromes that can reliably distinguish them from iNPH patients. Methods: Two cohorts of 81 patients (cohort 1, n = 55; cohort 2, n = 26) with possible iNPH who were treated in two centers between January 2011 and May 2014 were studied. In both cohorts, CSF samples were obtained from patients clinically diagnosed with iNPH (n = 21 and n = 10, respectively), possible iNPH with parkinsonian spectrum (PS) (n = 18, n = 10, respectively), possible iNPH with Alzheimer’s disease (AD) (n = 16), and non-affected elderly individuals (NC) (n = 6). A three-step qRT-PCR analysis of the CSF samples was performed to detect miRNAs that were differentially expressed in the groups. Results: The expression of hsa-miR-4274 in CSF was decreased in both cohorts of PS group patients (cohort 1: p

Background and purpose We report the results of endosaccular coil embolization of asymptomatic unruptured intracranial aneurysms (UIAs) in elderly patients (≥65 years). Materials There were 375 elderly patients with 400 asymptomatic UIAs. Patients were divided into two groups: group A included patients aged 65–74 years and group B patients aged ≥75 years. Results Endovascular procedures were completed in 97.8% of patients. Immediate anatomical outcomes showed complete occlusion in 53.7%, residual neck in 18.9%, and residual aneurysm in 27.4%. Anatomical follow-ups (mean 36.3±28.1 months) were unchanged in 55.7%, improved in 22.6%, minor recurrence in 11.5%, and major recurrence in 10.2%. Procedure related complications occurred in 31 patients (8.3%). 15 patients had ischemic and 10 hemorrhagic complications. Retreatments were performed in 16 patients (4.3%). Among 366 patients technically completed, 363 (99.2%) showed a favorable clinical outcome (modified Rankin Scale (mRS) score 0 at 30 days. The latest clinical follow-up outcomes showed: mRS score 0 in 362 patients; mRS score 1 in one; mRS score 3 in one; mRS score 4 in one; and mRS score 5 in one patient. Permanent morbidity and mortality rates were 1.1% and 0%, respectively. There were no statistically significant differences in gender, comorbidities, aneurysm size, neck width, dome-to-neck ratio, immediate anatomical outcomes, anatomical follow-up outcomes, or procedure related complications between the groups. Conclusions Endosaccular coil embolization is safe and feasible for elderly patients with asymptomatic UIAs. Old age itself should not be a contraindication.

BACKGROUND AND PURPOSE: Studies have suggested that arachnoid villi or granulations found in the walls of the cranial dural sinuses, olfactory mucosa, and cranial nerve sheaths function as outlets for intracranial CSF. However, their role as CSF outlets has not yet been verified. Here we show that arachnoid protrusions and contiguous diploic veins provide an alternative drainage route for intracranial CSF. MATERIALS AND METHODS: Four hundred patients with intact skull, dura mater, and dural sinuses underwent MR imaging to explore arachnoids protruding into the skull and diploic veins. Patients with symptoms of increased intracranial pressure or intracranial hypotension were excluded. For 15 patients undergoing craniotomy, both peripheral and diploic venous blood was collected. Albumin and the CSF-specific biomarkers were measured by enzyme-linked immunosorbent assay. RESULTS: With MR imaging, arachnoid protrusions into the skull and contiguous diploic veins were consistently identified throughout the cranium with their characteristic appearance depending on the cranial region. In addition, elevated amounts of prostaglandin D synthase and cystatin C were confirmed in diploic veins compared with peripheral venous blood. CONCLUSIONS: Diploic veins are distributed ubiquitously throughout the cranium. A portion of the intracranial CSF may be drained through arachnoid protrusions and contiguous diploic veins.

Purpose To examine the effects of conservative and surgical treatments for nocturnal leg cramps in patients with lumbar spinal stenosis (LSS). Nocturnal leg cramps is frequently observed in patients with peripheral neuropathy. However, there have been few reports on the relationship between nocturnal leg cramps and LSS, and it remains unknown whether conservative or surgical intervention has an impact on leg cramps in patients with LSS. Materials and Methods The subjects were 130 LSS patients with low back and leg pain. Conservative treatment such as exercise, medication, and epidural block was used in 66 patients and surgical treatment such as decompression or decompression and fusion was performed in 64 patients. Pain scores and frequency of nocturnal leg cramps were evaluated based on self-reported questionnaires completed before and 3 months after treatment. Results The severity of low back and leg pain was higher and the incidence of nocturnal leg cramps was significantly higher before treatment in the surgically treated group compared with the conservatively treated group. Pain scores improved in both groups after the intervention. The incidence of nocturnal leg cramps was significantly improved by surgical treatment (p=0.027), but not by conservative treatment (p=0.122). Conclusion The findings of this prospective study indicate that the prevalence of nocturnal leg cramps is associated with LSS and severity of symptoms. Pain symptoms were improved by conservative or surgical treatment, but only surgery improved nocturnal leg cramps in patients with LSS. Thus, these results indicate that the prevalence of nocturnal leg cramps is associated with spinal nerve compression by LSS.

Primary spinal extradural Ewing’s sarcoma (PSEES) or primitive neuroectodermal tumor (PNET) is uncommon. The present study summarizes the magnetic resonance (MR) imaging appearance of PSEES. Literature search from 1994 to 2012 with our representative case presentation. Twenty-one patients, 12 males and 9 females, aged 3 weeks to 44 years, were identified. The thoracic spine was most frequently affected, followed by the cervical, cervicothoracic, and thoracolumbar spine. Superior–inferior extension of lesions was three vertebral levels in 7, two in 7, five in 4, four in 1, one in 1 and unknown in 1. PSEESs appeared isointense in 9 cases, hypointense in 2, hyperintense in 1, and no description in 9 on T1-weighted imaging, while hyperintense in 6, hypointense in 3, heterogeneous in 1, and no description in 11 on T2-weighted imaging. Varying enhancement was noted in 13 cases (62 %), with no description of contrast study in the other 8 cases. Dumbbell-shaped configuration of PSEES was found in 5 cases, foraminal widening in 4, and erosions or scalloping of the adjacent vertebral bodies in 4. The MR imaging appearance of PSEESs is indistinguishable from other tumors. PSEES should be assumed as the differential diagnosis of spinal extradural tumors in pediatric, adolescent, and young adult patients, and prompt surgical exploration should be performed.

Eosinophilic meningitis is defined as the presence of 10 eosinophils/mm(3) in the cerebrospinal fluid (CSF) or eosinophils accounting for more than 10% of CSF leukocytes. A 76-year-old man who developed cognitive dysfunction and consciousness disturbance had eosinophilic meningitis (his CSF contained 19.0% eosinophils). Because the etiology was unknown, we performed a brain biopsy. The pathological findings showed inflammatory infiltration in the small-sized arteries of the meninges. The patient was ultimately diagnosed as having primary angiitis of the central nervous system (PACNS). Eosinophilic meningitis occurring in a patient with PACNS is extremely rare, and this is the first report of this condition in Japan.

Objective Almost two-thirds of patients with Sturge-Weber syndrome (SWS) have epilepsy, and half of them require surgery for it. However, it is well known that scalp electroencephalography (EEG) does not demonstrate unequivocal epileptic discharges in patients with SWS. Therefore, we analyzed interictal and ictal discharges from intracranial subdural EEG recordings in patients treated surgically for SWS to elucidate epileptogenicity in this disorder. Methods Five intractable epileptic patients with SWS who were implanted with subdural electrodes for presurgical evaluation were enrolled in this study. We examined the following seizure parameters: seizure onset zone (SOZ), propagation speed of seizure discharges, and seizure duration by visual inspection. Additionally, power spectrogram analysis on some frequency bands at SOZ was performed from 60 s before the visually detected seizure onset using the EEG Complex Demodulation Method (CDM). Results We obtained 21 seizures from five patients for evaluation, and all seizures initiated from the cortex under the leptomeningeal angioma. Most of the patients presented with motionless staring and respiratory distress as seizure symptoms. The average seizure propagation speed and duration were 3.1 ± 3.6 cm/min and 19.4 ± 33.6 min, respectively. Significant power spectrogram changes at the SOZ were detected at 10–30 Hz from 15 s before seizure onset, and at 30–80 Hz from 5 s before seizure onset. Significance In patients with SWS, seizures initiate from the cortex under the leptomeningeal angioma, and seizure propagation is slow and persists for a longer period. CDM indicated beta to low gamma-ranged seizure discharges starting from shortly before the visually detected seizure onset. Our ECoG findings indicate that ischemia is a principal mechanism underlying ictogenesis and epileptogenesis in SWS.

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Purpose: Diffusional kurtosis imaging (DKI) is an emerging technique that describes diffusion of water molecules in terms of deviation from Gaussian distribution. This study investigated correlations between DKI metrics and cognitive function in patients with idiopathic normal pressure hydrocephalus (iNPH). Materials and Methods: DKI was performed in 29 iNPH patients and 14 age-matched controls. Mini-mental state examination (MMSE), frontal assessment battery (FAB), and trail making test A (TMT-A) were used as cognitive measures. Tract-based spatial statistics (TBSS) analyses were performed to investigate the between-group differences and correlations with the cognitive measures of the diffusion metrics, including mean kurtosis (MK), fractional anisotropy (FA), apparent diffusion coefficient (ADC), axial diffusivity (AD), and radial diffusivity (RD). Results: In iNPH patients, FA and MK identified positive correlations with cognitive function in similar regions, predominantly in the frontal lobes (P < 0.05, corrected for multiple comparisons). The frontoparietal subcortical white matter showed significant correlations with FAB and TMT-A across more extensive areas in MK analyses than in FA. ADC, AD, and RD analyses showed no significant correlations with MMSE and FAB, while negative correlation with TMT-A was observed in the limited portion of the frontal deep white matter. Conclusion: Both FA and MK correlated well with cognitive impairment in iNPH. The observed differences between FA and MK results suggest DKI may play a complementary role to conventional FA and ADC analyses, especially for evaluation of the subcortical white matter.

Little is known about genetic risk factors for idiopathic normal pressure hydrocephalus (iNPH). We examined whether a copy number loss in intron 2 of the SFMBT1 gene could be a genetic risk for shunt-responsive, definite iNPH. Quantitative and digital PCR analyses revealed that 26.0% of shunt-responsive definite iNPH patients (n = 50) had such a genetic change, as compared with 4.2% of the healthy elderly (n = 191) (OR = 7.94, 95%CI: 2.82-23.79, p = 1.8 x 10-5) and 6.3% of patients with Parkinson's disease (n = 32) (OR = 5.18, 95%CI: 1.1-50.8, p = 0.038). The present study demonstrates that a copy number loss within intron 2 of the SFMBT1 gene may be a genetic risk factor for shunt-responsive definite iNPH.

Idiopathic normal pressure hydrocephalus (iNPH) is an elderly dementia caused by abnormal metabolism in the cerebrospinal fluid (CSF). The tap test is the current basis for confirming iNPH, but it shows very low sensitivity, indicating that many patients who might be cured by a shunt operation will be missed. On sodium dodecyl sulfate-polyacrylamide gel electrophoresis, we found two transferrin isoforms: one had a unique N-glycan (Tf-1) whereas the other had N-glycan similar to that of serum transferrin (Tf-2). Glycan analyses revealed that Tf-1 had branching (biantennary) asialo- and agalacto-complex type N-glycans (N-acetylglucosamine [GlcNAc]-terminated glycans), which carried bisecting β1,4-N-acetylglucosamine and core α1,6-fucose. To examine glycoform whether changes in iNPH, we introduced the Tf-2/Tf-1 ratio as a diagnostic index, which minimized blot-to-blot variations in measurement. The Tf-2/Tf-1 ratios of iNPH patients are significantly higher than those of controls (p = 0.0019) and Alzheimer's patients (p = 0.0010). This suggests that the Tf-2/Tf-1 ratio could distinguish iNPH from Alzheimer's disease, and possibly other dementias. In conclusion, glycoform analysis has diagnostic potential in neurological diseases.