Significance of Pupillary Findings in Decision Making and Outcomes of World Federation of Neurological Societies Grade V Subarachnoid Hemorrhage.

BACKGROUND: There is considerable debate regarding the definition of grade V subarachnoid hemorrhage (SAH). Recently, the Glasgow Coma Scale-Pupil (GCS-P) score was advocated for assessing traumatic brain injury. OBJECTIVE: To study the significance of pupillary findings and GCS-P in the management and outcomes of the World Federation of Neurological Societies (WFNS) grade V SAH. METHODS: We analyzed data obtained from a Japanese nationwide prospective registration study on the modified WFNS SAH grading system. Bilateral pupillary dilatation without reactivity was defined as pupil score 2, unilateral pupil dilation without reactivity as score 1, and no pupil dilatation with reactivity as score 0. The GCS-P score was calculated by subtracting the pupil score from the total GCS score. The characteristics and pupillary findings were examined in patients with each GCS score in WFNS grade V. RESULTS: Among 1638 patients, 472 (men/women = 161/311, age 67.0 ± 14.0 years) had a GCS score of ≤6 after initial resuscitation on arrival. Overall, lower GCS scores were associated with poorer neurological outcomes and higher mortality. Aneurysms were treated in 20.5%, 53.9%, and 67.5% of patients with pupil scores of 2, 1, and 0, respectively. Favorable outcomes (modified Rankin Scale 0-2) at 3 months occurred in 4.5%, 10.8%, and 21.4% in patients with pupil scores 2, 1, and 0, respectively ( P < .0001), and in 0%, 0%, 13.6%, 28.6%, 16.7%, and 18.8% of patients with GCS-P scores 1 to 6 ( P < .0001), respectively. CONCLUSION: Our study confirmed the significance of pupillary findings in decision making and outcomes of WFNS grade V SAH.

Different Risk Factors Between Cerebral Infarction and Symptomatic Cerebral Vasospasm in Patients with Aneurysmal Subarachnoid Hemorrhage.

OBJECTIVE: Cerebral infarction due to cerebral vasospasm (IVS) after aneurysmal subarachnoid hemorrhage is associated with poor outcomes and symptomatic cerebral vasospasm (SVS). However, the difference of risk factors between SVS and IVS was unclear to date. In this study, we aimed to elucidate the risk factors for SVS and IVS based on the registry study. METHODS: The modified World Federation of Neurosurgical Societies scale study comprises 1863 cases. Patients with aneurysmal subarachnoid hemorrhage who underwent radical treatment within 72 hours with a premorbid modified Rankin Scale score 0-2 as the inclusion criteria were retrospectively examined. The risk factors for SVS and IVS were analyzed using multivariable logistic regression analysis. RESULTS: Among them, 1090 patients who met the inclusion criteria were divided into 2 groups according to SVS and IVS; 273 (25%) patients with SVS and 92 (8.4%) with IVS. Age was not a risk factor for SVS, but for IVS, and Fisher scale was a risk factor for SVS, but not for IVS. CONCLUSIONS: The prevalence of IVS was not associated with the Fisher scale but with older age, suggesting possible factors other than SVS. Different associated factors between SVS and IVS were confirmed in this study.

Changes in Short-Term Outcomes After Discharge in Patients with Aneurysmal Subarachnoid Hemorrhage: A Multicenter, Prospective, Observational Study.

OBJECTIVE: The objective of the study was to clarify the prevalence of and factors associated with changes in patients' outcomes between discharge and 3 months after the onset of aneurysmal subarachnoid hemorrhage (aSAH). Additionally, the World Federation of Neurosurgical Societies (WFNS) and modified WFNS (mWFNS) scales were compared. METHODS: The data of curatively treated patients with aSAH, collected prospectively in the mWFNS scale study between January 2010 and December 2012, were analyzed retrospectively. The improvement or decline in the modified Rankin Scale (mRS) scores between discharge and 3 months after onset was determined. A multivariable logistic regression analysis was performed to identify factors, such as age and WFNS and mWFNS grades, associated with changes in the outcome. RESULTS: The mRS scores improved in 28.3% and declined in 2.5% of the patients. WFNS and mWFNS grades Ⅱ-V on admission were significantly associated with improved mRS scores at 3 months after onset. Older age (age: 65-74 years vs. age <65 years, odds ratio: 6.59, 95% confidence interval: 1.28-34.01; age ≥75 years vs. age <65 years, odds ratio: 17.67, 95% confidence interval: 2.11-148.26) and WFNS grade III were significantly associated with a decline in mRS scores at 3 months after onset. CONCLUSIONS: The optimal timing for postdischarge assessment of outcomes may be at 3 months after onset, especially in older patients with aSAH. The mWFNS scale is presumed to more accurately assess the outcomes of patients with aSAH than the WFNS scale, as demonstrated in this study.

Japanese Subarachnoid Aneurysm Trial of Neurosurgical Clipping versus Endovascular Coiling in 1863 Patients with Ruptured Intracranial Aneurysms.

This is a post hoc multivariate analysis of the modified World Federation of Neurosurgical Societies (WFNS) grading project, multicenter prospective observational study including 38 neurosurgical institutions across Japan. Japan Neurosurgical Society WFNS grading committee conducted a modified WFNS grading project as a nationwide prospective registry study. We investigate the clinical outcome of both surgical and endovascular interventions after aneurysmal subarachnoid hemorrhage (SAH) in Japan. A total of 792 patients received surgical intervention and 417 patients received endovascular treatment. Eight hundred patients were female, and 409 patients were male. The mean age was 61.5 ± 13.7 years. At 3 month follow-up, there was no statistically significant difference in good clinical outcome between surgical (68.2%) and endovascular (60.9%) group (odds ratio, 0.89; 95% confidence interval, 0.68-1.16; p = 0.381). Unfavorable outcome rate was 31.8% (238 patients) in the surgical group and 39.1% (154 patients) in the endovascular group. Male, elderly people, modified Rankin scale condition before onset, high-grade modified WFNS clinical grading scale, intracerebral hematoma, posttreatment normal pressure hydrocephalus, and neurological deficit due to symptomatic vasospasm were risk factors for the clinical outcome. Treatment modality was not a statistical factor for clinical outcomes. Surgical clipping has still a major role in the management of SAH in Japan. The present study was not a randomized controlled study, but clinical outcome is not influenced by treatment modalities.

Risk Factor for Poor Outcome in Elderly Patients with Aneurysmal Subarachnoid Hemorrhage Based on Post Hoc Analysis of the Modified WFNS Scale Study.

OBJECTIVE: There is currently no precise guide for the treatment and management of elderly patients with aneurysmal subarachnoid hemorrhage (aSAH). Thus, the aim of this study was to clarify the factors of poor outcome and mortality in elderly patients with aSAH. METHODS: In the modified World Federation of Neurosurgical Societies (mWFNS) scale study, 1124 patients were divided into 2 groups, elderly (age ≥65 years) and non-elderly (age <65 years), with aSAH investigated between October 2010 and March 2013 in Japan. The odds ratio (OR) and 95% confidence interval (CI) of each risk factor was calculated through multivariate logistic regression analysis for poor outcomes, as indicated by the modified Rankin Scale (mRS) score ≥3 and mortality at 3 months after onset in each group. RESULTS: Both groups demonstrated that the mWFNS scale was significant as a grade order risk factor for poor outcomes and mortality associated with disease. In the elderly group, risk factors for poor outcomes at 3 months after onset were older age (OR 1.10, 95% CI 1.06-1.14), male sex (OR 2.03, 95% CI 1.10-3.73), and severe cerebral vasospasm category (OR 10.13, 95% CI 4.30-23.87). Risk factors for mortality at 3 months after onset were older age (OR 1.06, 95% CI 1.01-1.11) and severe vasospasm category (OR 2.17, 95% CI 1.00-4.72). CONCLUSIONS: The mWFNS scale is a useful prognostic predictor for both non-elderly and elderly patients with aSAH. Elderly male patients with aSAH presenting with severe vasospasm should be managed more carefully.

RNA sequencing analysis revealed the induction of CCL3 expression in human intracranial aneurysms.

Intracranial aneurysm (IA) is a socially important disease as a major cause of subarachnoid hemorrhage. Recent experimental studies mainly using animal models have revealed a crucial role of macrophage-mediated chronic inflammatory responses in its pathogenesis. However, as findings from comprehensive analysis of unruptured human IAs are limited, factors regulating progression and rupture of IAs in humans remain unclear. Using surgically dissected human unruptured IA lesions and control arterial walls, gene expression profiles were obtained by RNA sequence analysis. RNA sequencing analysis was done with read count about 60~100 million which yielded 6~10 billion bases per sample. 79 over-expressed and 329 under-expressed genes in IA lesions were identified. Through Gene Ontology analysis, 'chemokine activity', 'defense response' and 'extracellular region' were picked up as over-represented terms which included CCL3 and CCL4 in common. Among these genes, quantitative RT-PCR analysis using another set of samples reproduced the above result. Finally, increase of CCL3 protein compared with that in control arterial walls was clarified in IA lesions. Findings of the present study again highlight importance of macrophage recruitment via CCL3 in the pathogenesis of IA progression.

State-of-art in surgical treatment of dissecting posterior circulation intracranial aneurysms.

Vertebrobasilar (VB) intracranial dissecting aneurysms (IDAs) pose difficult therapeutic issues and are especially among the most difficult to manage surgically. There are, however, some cases where selective aneurysm obliteration by endovascular approach is impossible or is associated with an unacceptable risk of morbidity. This is particularly true when the aneurysm is dissecting, giant, or has a large neck. In such cases, surgical treatment may be the only alternative. Optimal management of these lesions is therefore challenging and treatment decisions have to be made on a case-by-case basis. Ideal treatment should be a complete surgical excision of the lesion; however, this procedure might only be possible after distal and proximal vessel wall occlusion which might not be tolerated by the patient depending on the location of the aneurysm. Therefore, formulation of recommendations concerning the surgical strategy remains still difficult due to inconsistency of surgical outcomes. The literature describing surgical strategy of VB IDAs is varying in quality and content, and many studies deal with only a few patients. In the presented review, the authors summarize the current knowledge on the incidence, pathogenesis, clinical presentation, and diagnostic procedures with special emphasis on surgical treatment of IDAs in posterior circulation.

State-of-Art Surgical Treatment of Dissecting Anterior Circulation Intracranial Aneurysms.

Intracranial dissecting aneurysms (IDAs) are an important cause of subarachnoid hemorrhage, stroke, or compression of intracranial structures. Since the availability of endovascular treatment and the advantage of intraprocedural anticoagulation, an endovascular strategy has become the mainstay of their therapy. But in some cases selective aneurysm obliteration by the endovascular approach is impossible or associated with an unacceptable risk of morbidity. This is particularly true when the IDA is a blood blister-like aneurysm or when dissection affects peripheral branches of the internal carotid artery. The literature dealing with surgical treatment of IDAs in the anterior circulation is heterogeneous, and formulation of general recommendations concerning the surgical strategy remains difficult. The aim of this study was to conduct a systematic review of the current knowledge on incidence, pathogenesis, clinical presentation, and diagnostic procedures with a special emphasis on the surgical treatment of intracranial dissections of anterior circulation.

Dual-Image Videoangiography During Intracranial Microvascular Surgery.

OBJECTIVE: Indocyanine green videoangiography (ICG-VA) is a valuable tool to assess vessel and aneurysm patency during neurovascular surgical procedures. However, ICG-VA highlights vascular structures, which appear white over a black background. Anatomic relationships are sometimes difficult to understand at first glance. Dual-image videoangiography (DIVA) enables simultaneous visualization of light and near-infrared fluorescence images of ICG-VA. METHODS: The DIVA system was mounted on an OPMI Pentero Flow 800 intraoperative microscope. DIVA was used during microsurgical procedures on 5 patients who were operated for aneurysm clipping and superficial temporal artery-middle cerebral artery bypass. RESULTS: DIVA provides real-time simultaneous visualization of aneurysm and vessels and surrounding structures including brain, nerves, and surgical clips. Although visual contrast between vessels and background is higher with standard black-and-white imaging, DIVA makes it easier to understand anatomic relationships between intracranial structures. DIVA also provides better vision of the depth of field. CONCLUSIONS: DIVA has the potential to become a widely used intraoperative tool to check patency of intracranial vessels. It should be considered as an adjunct to standard ICG-VA for better understanding of vascular anatomy in relation to surrounding structures and can have an impact on decision making during surgery.

Modified World Federation of Neurosurgical Societies subarachnoid hemorrhage grading system.

OBJECT: A modified World Federation of Neurosurgical Societies scale (m-WFNS scale) for aneurysmal subarachnoid hemorrhage (SAH) recently has been proposed, in which patients with Glasgow Coma Scale (GCS) scores of 14 are assigned to grade II and those with GCS scores of 13 are assigned to grade III regardless of the presence of neurologic deficits. The study objective was to evaluate outcome predictability of the m-WFNS scale in a large cohort. METHODS: This was a multicenter prospective observational study conducted in Japan. A total of 1656 patients with SAH were registered during the 2.5-year study period, and the outcome predictability, using the Glasgow Outcome Scale (GOS) and modified Rankin Scale (mRS) scores at discharge and at 90 days after onset, was evaluated by comparing the m-WFNS with the original WFNS scale. We focused on whether significant differences in these scores were present between the neighboring grades. RESULTS: In the m-WFNS scale, significant difference between any neighboring grades was observed both in the mean GOS and mRS scores at 90 days except between grades III/IV. However, differences were not significant between grades II/III and between grades III/IV in the original WFNS scale. CONCLUSIONS: SAH-induced brain injury may be substantially severer in patients with GCS 13 than those with GCS 14, which may explain why grade III patients faired significantly worse than grade II patients by the modified WFNS scale. Although further validation is necessary, the m-WFNS scale has a potential of providing neurosurgeons with simpler and more reliable prognostication of patients with SAH.

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.

Contralateral approach to unruptured superior hypophyseal artery aneurysms.

OBJECTIVE: To evaluate the feasibility and limitations of the contralateral approach to unruptured superior hypophyseal artery (SHA) aneurysms. METHODS: Data regarding eight cases of superior hypophyseal artery aneurysms operated on by a contralateral pterional approach at our center from January 2008 to September 2010 were collected and evaluated retrospectively. Of these eight cases, six were male and two were female. The mean age was 57.1 years (range 28 years to 77 years). All the aneurysms were unruptured; five were on right side and three were on left side. The surgical technique and outcome of patients were reviewed. RESULTS: All aneurysms were successfully clipped without complication and patency of all superior hypophyseal arteries was preserved. Postoperative three-dimensional computed tomography angiography revealed residual aneurysm in only one case. None of the patients had deterioration of visual acuity or field after surgery. The contralateral pterional approach was found to be appropriate for fully exposing the aneurysmal dome and neck without retraction of the optic nerve or the carotid artery in five cases. Slight retraction of the optic nerve was required in two cases, and significant manipulation of the optic nerve was required in one case. CONCLUSIONS: The contralateral pterional approach for clipping of unruptured superior hypophyseal artery aneurysms is technically feasible and safe in a select group of patients where optimal results can be achieved without significant retraction of near by neurovascular structures.

The incorporation of neuroendoscopy in neurosurgical training programs.

Previously considered the domain of the otolaryngologists, the endoscopy is now a common part of the armamentarium of a neurosurgeon. Neuroendoscopy or endoscope-assisted microsurgery is now being used in almost all routine procedures performed in the neurosurgical operating room. Hands-on training has become essential to learn the basics of neuroendoscopy, even for neurosurgeons well accustomed to the use of microscopes. To decrease the slope of the learning curve of residents during their training and reduce complications of procedures, most neurosurgery training programs around the world have incorporated laboratory or dissection programs in their curricula. Preconference workshops held during annual meetings are also an excellent tool to aid in the transition of surgeons from being a resident under the umbrella of an attending neurosurgeon to being a neurosurgeon able to operate independently and with confidence. In this "tech-savvy era," various cadaver or synthetic models are readily available for endoscopy training in a virtually simulated environment. In accord with the results of a surveys conducted by individual groups and societies, the authors firmly believe that incorporation of endoscopy in the neurosurgical curriculum would add a new dimension to the existing protocol. There is an urgent need for dedicated endoscopy training programs similar to postresidency fellowships in addition to translational research and establishment of dedicated societies to formulate guidelines for such research and monitor its progress.

Stimulation-dependent intraspinal microtubules and synaptic failure in Alzheimer's disease: a review.

There are many microtubules in axons and dendritic shafts, but it has been thought that there were fewer microtubules in spines. Recently, there have been four reports that observed the intraspinal microtubules. Because microtubules originate from the centrosome, these four reports strongly suggest a stimulation-dependent connection between the nucleus and the stimulated postsynaptic membrane by microtubules. In contrast, several pieces of evidence suggest that spine elongation may be caused by the polymerization of intraspinal microtubules. This structural mechanism for spine elongation suggests, conversely, that the synapse loss or spine loss observed in Alzheimer's disease may be caused by the depolymerization of intraspinal microtubules. Based on this evidence, it is suggested that the impairment of intraspinal microtubules may cause spinal structural change and block the translocation of plasticity-related molecules between the stimulated postsynaptic membranes and the nucleus, resulting in the cognitive deficits of Alzheimer's disease.

Transvenous embolization in spontaneous direct carotid-cavernous fistula in childhood.

Carotid cavernous fistula (CCF) is an abnormal arteriovenous communication in the cavernous sinus. Direct CCF results from a tear in the intracavernous carotid artery. Typically, it has a high flow and usually presents with oculo-orbital venous congestive features such as exophthalmos, chemosis, and sometimes oculomotor or abducens cranial nerve palsy. Indirect CCF generally occurs spontaneously with subtle signs. We report a rare case of spontaneous direct CCF in childhood who did not have the usual history of craniofacial trauma or connective tissue disorder but presented with progressive chemosis and exophthalmos of the right eye. This report aims also to describe the safety and success of transvenous embolization with coils of the superior ophthalmic vein and cavernous sinus through the inferior petrosal sinus.

FLOW 800-assisted surgery for arteriovenous malformation.

FLOW 800 is software for analytical colour visualisation and objective evaluation of fluorescence video obtained by microscope-integrated intraoperative indocyanine green fluorescence angiography. A 56-year-old male underwent surgical excision of a large complex arteriovenous malformation (AVM) of the right parietal region. FLOW 800 software was used to identify feeding arteries, arterialised veins and passing vessels. Complete excision of the AVM was achieved, confirmed by FLOW 800 and postoperative digital subtraction angiography. The role of FLOW 800, its applications and limitations in AVM surgery are discussed.