Novel method of intraoperative ocular movement monitoring using a piezoelectric device: experimental study of ocular motor nerve activating piezoelectric potentials (OMNAPP) and clinical application for skull base surgeries.

Intraoperative monitoring systems that utilize various evoked potentials for the detection and/or preservation of cranial nerves have become increasingly common due to recent technical and commercial developments, particularly during skull base surgeries. We established a novel system for the intraoperative monitoring of the extraocular motor nerves (eOMNs) using a piezoelectric device capable of detecting imperceptible vibrations induced by ocular movement, with sensors placed on the eyelids alone. We first evaluated the efficacy and reliability of this device for the intraoperative monitoring of eOMNs in two Beagle dogs. Based on the results, we then determined the appropriate stimulation parameters for use in human surgical cases involving removal of various skull base tumors. Animal experiments revealed that a 0.4 mA monopolar electrical stimulation was required to elicit significant responses and that these responses were not inferior to those obtained via the electrooculogram/electromyogram. Significant responses were also detected in preliminary clinical investigations in human patients, following both direct and indirect monopolar electrical stimulation of the oculomotor and abducens nerves, although obtaining responses from the trochlear nerve was difficult. Intraoperative monitoring using a piezoelectric device provides a simple and reliable method for detecting eOMNs, especially the oculomotor and abducens nerves. This monitoring system can be adapted to various surgeries for skull base tumor.

Double pituitary adenomas associated with persistent trigeminal artery: a rare case report and the review of literature.

Multiple pituitary adenomas are rare. We present a quite unique case of double pituitary adenomas associated with persistent trigeminal artery (PTA) treated by endoscopic surgery. To the best of our knowledge, this is the first report in the literature. A 64-year-old woman was referred to our hospital for suspicion of acromegaly. Preoperative magnetic resonance imaging revealed two separate intrasellar masses with intrasellar vascular structure. Right cerebral angiography showed medial-type PTA. The patient underwent endoscopic transsphenoidal surgery and both tumors were resected completely. Postoperative immunohistopathologic examination revealed two histologic types of adenoma: the first tumor was positive for growth hormone (GH), while the second was considered nonfunctioning. Postoperatively, the patient's serum levels of GH and insulin-like growth factor-1 returned to normal. We observed an extremely rare case of double pituitary adenomas associated with PTA. Preoperative neuroimaging and modern endoscopic surgery are valuable to confirm diagnosis of double pituitary adenomas and identify anatomical localization of PTA.

[Head Injuries due to Ladder-related Falls].

We examined the clinical characteristics and outcomes of patients who had fallen from ladders and statistically analyzed the prognostic factors, highlighting the impact of the coexistence of head injuries on their prognoses. The clinical records of patients who had experienced ladder-related falls who were admitted to the Advanced Emergency Medical Service Center at Kurume University Hospital between April 2013 and August 2015 were retrospectively reviewed. A total of 86 patients were enrolled. The mean patient age was 69.2 years, and 82 patients were male. The median fall height was 2.55 m. Sixty patients fell during non-professional use of the ladder. Forty-four patients experienced some type of head injury. Although the older patients had more frequent complications with head injuries, the height of the fall was not related statistically. The group of patients with head injuries exhibited trends of older age, lower Glasgow Coma Scale scores, higher Injury Severity Score, and poorer outcomes than those of the group of patients without head injuries. Multivariate analysis showed that head injury and non-professional use were independent risk factors for poor outcomes. Our results revealed that ladder-related falls with head injury can occur when older people are working at home, even if they have fallen from a low height. Especially when older men work with the ladder at home, local community-based education and guidance for the prevention of ladder-related fall injuries are needed.

Primary meningeal melanocytoma of the sellar region: review of the literature and differential diagnosis with special reference to angiographical features.

PURPOSE: Primary intracranial melanocytomas are rare neoplasms, especially in the sellar region. Intracranial melanocytoma is usually a dural-based tumor, fed by dural arterial branches in a manner similar to meningioma. Primary sellar melanocytoma may be misdiagnosed as hemorrhagic pituitary macroadenoma, spindle cell oncocytoma, and intrasellar meningioma. These tumors differ in some radiological respects, but are difficult to differentiate preoperatively. METHODS: Only five cases of primary sellar/suprasellar melanocytic tumors, excluding melanomas have been reported thus far. In this paper, we report an instructive new case of a 31-year-old woman presenting with a 2-year history of amenorrhea and an intrasellar mass with suprasellar extension, suggestive of hemorrhagic pituitary adenoma. RESULTS: Transsphenoidal surgical excision was difficult due to extensive bleeding from the lesion, and at the time, the tumor could not be diagnosed histopathologically. Six years later, we operated again because of tumor regrowth. Angiography revealed a hypervascular tumor, which was fed from the dorsal sellar floor. We had difficulty resecting the tumor, but achieved total removal. Our case had typical radiographic characteristics of melanocytoma, revealed by both magnetic resonance imaging and angiography. However, it was difficult to reach a final diagnosis. Further histopathological examination, including immunohistochemical and ultrastructural studies, was helpful for diagnosis of melanocytoma. CONCLUSIONS: Primary sellar melanocytic tumors are derived from melanocytes in the meningeal lining of the sellar floor or in the diaphragm sellae, based on both embryological assumptions and the clinical findings of our case. We discuss the problems of differential diagnosis and management of primary sellar melanocytic tumors.

The eagle jugular syndrome as the cause of delayed intracranial hemorrhage after microvascular decompression for hemifacial spasm: A case report.

BACKGROUND: Eagle syndrome is a rare disorder whereby an elongated styloid process (ESP) causes not only some otolaryngological symptoms, but also cerebrovascular events caused by compression of the carotid artery. In recent years a syndrome, denominated as Eagle jugular syndrome, involving internal jugular vein (IJV) compression caused by an ESP has been proposed as a variation of Eagle syndrome. Clinical impact of the Eagle jugular syndrome on neurosurgical procedures has not been reported yet. CASE DESCRIPTION: We present a case of a 68-year-old woman who underwent microvascular decompression for hemifacial spasm of the left side and developed delayed intracranial hemorrhage on postoperative day 3. We also demonstrate that this patient developed ipsilateral IJV stenosis between an ESP and the muscle bundle of the rectus capitis lateralis with antero-flexion neck position, which would induce venous congestion in addition to surgical disruption of emissary vein. CONCLUSION: This case is the first report demonstrating the association of an ESP with postoperative delayed intracranial hemorrhage. Our report elucidates the importance of the awareness among neurosurgeons of considering the ESP as an important bony anomaly, especially when planning for posterior fossa surgery.

Endoscopic Endonasal Removal of Primary/Recurrent Meningiomas in the Medial Optic Canal: Surgical Technique and Long-Term Visual Outcome.

BACKGROUND: Tuberculum sellae meningiomas frequently extend into the optic canals, which leads to a progressive longitudinal visual loss. Therefore, in addition to tumor removal, unroofing and exploration inside the optic canal are important procedures. OBJECTIVE: To perform endoscopic endonasal tumor removal with optic canal decompression for small primary or recurrent meningiomas associated with a progressive visual loss at the inferior-medial optic canal, which corresponded to a blind corner in the ipsilateral pterional/subfrontal approach. METHODS: We retrospectively reviewed 2 cases of primary meningiomas that arose in the inferior-medial optic canal and 4 recurrent cases from the remnant inside the medial optic canal that had previously undergone craniotomy for tuberculum sellae meningiomas, and were treated by the endoscopic endonasal approach. RESULTS: All tumors were detectable and could be removed without manipulation of the affected optic nerve. The average maximum diameter of the tumor was 8.4 mm (range: 5-12 mm). Two patients who had a long history of progressive visual disturbance and papillary atrophy did not recover from severe visual disturbances postoperatively. However, others showed considerable improvement, maintaining postoperative visual function during follow-up. There were no postoperative complications. CONCLUSION: Endoscopic endonasal approach has several advantages for meningiomas in the medial optic canal and associated with progressive visual disturbance. In surgery of tuberculum sellae meningiomas, optic canal decompression and exploration inside the optic canal are important procedures to avoid symptomatic recurrence, which may be facilitated by the endoscopic endonasal approach. Papillary atrophy and duration of visual deterioration are predictive factors for postoperative visual outcomes.

Expression of GLUT1 in Pseudopalisaded and Perivascular Tumor Cells Is an Independent Prognostic Factor for Patients With Glioblastomas.

Glioblastomas are highly aggressive brain tumors with a particularly poor prognosis. Glucose transporter-1 (GLUT1/SLC2A1), a uniporter that is expressed by various carcinomas and may be involved in malignant neoplasm glycometabolism, may also be related to prognosis in glioblastomas. GLUT1 is essential to central nervous system glycometabolism. To clarify the exact role of GLUT1 in glioblastoma, we assessed the expression and localization of GLUT1 in patient samples by immunohistochemistry and in situ RNA hybridization. This revealed that GLUT1 was mainly expressed on perivascular and pseudopalisaded tumor cell membranes. All samples expressed GLUT1 to some degree, with 30.8% showing stronger staining. On the basis of these data, samples were divided into high and low expression groups, although SLC2A1 mRNA expression was also higher in the high GLUT1 expression group. Kaplan-Meier survival curves revealed that high GLUT1 expression associated with lower overall survival (log-rank test, p = 0.001) and worse patient prognoses (p = 0.001). Finally, MIB-1 staining was stronger in high GLUT1 expression samples (p = 0.0004), suggesting a link with proliferation. We therefore hypothesize that GLUT1 expression in glioblastomas may enhance glycolysis, affecting patient prognosis. Examination of GLUT1 in patients with glioblastomas may provide a new prognostic tool to improve outcome.

Impact of combination therapy with repeat surgery and temozolomide for recurrent or progressive glioblastoma multiforme: a prospective trial.

BACKGROUND: The purpose of this study is to evaluate the feasibility of repeat surgery combination with postoperative TMZ for adults with recurrent or progressive GBMs. METHODS: Of 35 patients who had diagnoses of GBM between 2002 and 2005, 7 (20%) underwent second surgeries and TMZ for recurrent or progressive disease. We examined the case histories of these 7 patients and determined the location of tumor and extent of their surgical procedures. Using the KPS, we assessed each patient's neurologic state before and after initial and repeat surgery. We calculated survival times from time of initial surgery and compared actual survival with statistically predicted survival times for each patient. RESULTS: Median survival rates were higher than predicted: The statistical risk estimate for median survival time after repeat surgery for these patients was 9 months; the actual survival time from initial operation until time of death averaged 15.1 months. The neurologic status before and after second surgery also averaged 76 points on KPS. Survival time did not depend on removing the entire tumor at initial and second surgery. CONCLUSION: Combination with repeat surgery and TMZ improved overall survival of these GBM patients.

[A rare case of intracranial meningioma with intratumoral metastatic breast cancers].

We report an uncommon case of breast cancer metastasis to an intracranial meningioma. A 47-year-old female was admitted to our hospital due to general convulsion. She had undergone a radical operation for left breast cancer 4 years refore, and received postoperative adjuvant therapies. MRI revealed a solid well-circumscribed tumor in the right frontal convexity. The patient underwent tumor resection successfully. The pathological examination revealed ductal carcinoma in the tissue of a transitional meningioma. Tumor-to tumor metastasis is a rare event. Literature review and discussion of such an uncommon occurrence was presented.

[Case of meningioma with extracranial extension through the internal jugular vein].

We report a case of posterior fossa meningioma extending into the cervical jugular vein, which was successfully resected. A 57-year old male with ataxia and mild hypogeusia was admitted to our hospital. MRI demonstrated a well-circumscribed large posterior fossa mass with extracranial extension through the internal jugular vein. Two-staged surgical treatment was then performed. The mass in the posterior fossa was removed at the first operation. The tumor was invading into the sigmoid sinus which was filled with tumor. The second operation for extracranial mass was performed 1 month later. Transcervically, the internal jugular vein obstructed by tumor was successfully removed. The post-operative course was uneventful and histopathological examination revealed the fibrous meningioma in the posterior fossa, but the intravenous portion of the tumor showed more atypical findings. Such a case is quite uncommon and the mechanism of tumor extension with different histological features is discussed.

Nontraumatic aneurysm rupture following an endoscopic third ventriculostomy and ventricular drainage: Case report of a rare complication.

BACKGROUND: Although endoscopic third ventriculostomy is a safe procedure, the authors report a case of aneurysmal subarachnoid hemorrhage as an unusual and serious complication of an endoscopic third ventriculostomy and ventricular drainage. CASE DESCRIPTION: A 60-year-old male presented with obstructive hydrocephalus caused by midbrain tumors was admitted to our hospital. Endoscopic third ventriculostomy and external ventricular drainage were successfully performed. Two days after the operation, he became comatose, and a computed tomography (CT) scan revealed a diffuse subarachnoid hemorrhage. Emergency cerebral angiogram showed an aneurysm of the left internal carotid artery. Endovascular coil embolization of the ruptured aneurysm was then performed. CONCLUSION: The rupture of the aneurysm may have been induced by excessive cerebrospinal fluid drainage after the endoscopic third ventriculostomy. Planning for intracranial endoscopic procedures should consider that rupture of an unknown previously unruptured aneurysm is a possible complication.

[A successfully treated case of a ruptured anterior wall aneurysm of the internal carotid artery (C2) which changed in form from blister-like to saccular type].

We successfully treated a case of ruptured anterior wall aneurysm of the ICA (C2) which changed in form from blister-like to saccular type. A 46-year-old woman developed subarachnoid hemorrhage on July 12, 2002. Cerebral angiogram demonstrated a blister-like aneurysm located in the left C2 portion of the internal carotid artery, but which didn't affect the arterial branches. Because of the risk of premature rupture during early surgery, delayed surgery was scheduled and the patient underwent serial study of the aneurysm. During 2 weeks of follow-up, the shape and size of the aneurysm changed in form blister-like to an enlarged saccular type aneurysm. On the day 18th, a left episubcombined approach, after insertion of a balloon catheter into the cervical ICA, was attempted and the aneurysm projecting antero-medially under the left carotid artery was exposed. The aneurysm had a distinct neck and its wall was not fragile. There was no macroscopic evidence of dissection of the ICA and the aneurysm was successfully clipped by conventional manipulation. Because of the difficulty in determining by angiographic evidence alone, whether an anterior wall aneurysm is a blister type or saccular type, careful follow-up is needed and if the shape or size changes, immediate appropriate treatment becomes mandatory. Intraoperative observation will determine the final diagnosis, as in this uncommon case.

Secondary prevention of stroke: Pleiotropic effects of optimal oral pharmacotherapy.

Stroke is a major cause of mortality and disability worldwide. During the past three decades, major advances have occurred in secondary prevention, which have demonstrated the broader potential for the prevention of stroke. Risk factors for stroke include previous stroke or transient ischemic attack, hypertension, high blood cholesterol and diabetes. Proven secondary prevention strategies are anti-platelet agents, antihypertensive drugs, statins and glycemic control. In the present review, we evaluated the secondary prevention of stroke in light of clinical studies and discuss new pleiotropic effects beyond the original effects and emerging clinical evidence, with a focus on the effect of optimal oral pharmacotherapy.

Beyond free radical scavenging: Beneficial effects of edaravone (Radicut) in various diseases (Review).

Free radicals play an important role in the pathogenesis of a variety of diseases; thus, they are an attractive target for therapeutic intervention in these diseases. Compounds capable of scavenging free radicals have been developed for this purpose and some, developed for the treatment of cerebral ischemic stroke, have progressed to clinical trials. One such scavenger, edaravone, is used to treat patients within 24 h of stroke. Edaravone, which can diffuse into many disease-affected organs, also shows protective effects in the heart, lung, intestine, liver, pancreas, kidney, bladder and testis. As well as scavenging free radicals, edaravone has anti-apoptotic, anti-necrotic and anti-cytokine effects in various diseases. Here, we critically review the literature on its clinical efficacy and examine whether edaravone should be considered a candidate for worldwide development, focusing on its effects on diseases other than cerebral infarction. Edaravone has been safely used as a free radical scavenger for more than 10 years; we propose that edaravone may offer a novel treatment option for several diseases.

Beyond neurological disease: new targets for edaravone (Review).

Free radicals play major roles in the pathogenesis of tissue damage in many diseases and clinical conditions, and the removal of free radicals may offer a treatment option. Several modulators of free radical scavenger pathways have been developed and some have progressed to clinical trials. One such agent, edaravone, was approved in 2001 in Japan for the treatment of cerebral infarction. It has since been shown that edaravone can diffuse into many organs and, in addition to its effects on hydroxyl radical removal, edaravone modulates inflammatory processes, matrix metalloproteinase levels, nitric oxide production, apoptotic cell death, and necrotic cell death. Edaravone also exerts protective effects in a number of animal models of disease and tissue damage, including models of myocardial, lung, intestinal, liver, pancreatic and renal injury. Together with the proven safety of edaravone following 9 years of use as a modulator of free radical scavenging pathways in neurological disease, these additional effects of edaravone suggest that it may offer a novel treatment for several non-neurological diseases and clinical conditions in humans.

HMGB1 as a therapeutic target in spinal cord injury: A hypothesis for novel therapy development.

Historically, clinical outcomes following spinal cord injury (SCI) have been dismal. Severe SCI leads to devastating neurological deficits, and there is no treatment available that restores the injury-induced loss of function to a degree that an independent life can be guaranteed. To address all the issues associated with SCI, a multidisciplinary approach is required, as it is unlikely that a single approach, such as surgical intervention, pharmacotherapy or cellular transplantation, will suffice. High mobility group box 1 (HMGB1) is an inflammatory cytokine. Various studies have shown that HMGB1 plays a critical role in SCI and that inhibition of HMGB1 release may be a novel therapeutic target for SCI and may support spinal cord repair. In addition, HMGB1 has been associated with graft rejection in the early phase. Therefore, HMGB1 may be a promising therapeutic target for SCI transplant patients. We hypothesize that inhibition of HMGB1 release rescues patients with SCI. Taken together, our findings suggest that anti-HMGB1 monoclonal antibodies or short hairpin RNA-mediated HMGB1 could be administered for spinal cord repair in SCI patients.

Potential of edaravone for neuroprotection in neurologic diseases that do not involve cerebral infarction.

Edaravone was originally developed as a potent free radical scavenger and has been widely used to treat cerebral infarction in Japan since 2001. Several free radical scavengers have been developed and some of them have progressed to clinical trials for the treatment of cerebral infarction. One such scavenger, edaravone, has been approved by the regulatory authority in Japan for the treatment of patients with cerebral infarction. Of particular interest is the ability of edaravone to diffuse into the central nervous system in various neurologic diseases. Aside from its hydroxyl radical scavenging effect, edaravone has been found to have beneficial effects on inflammation, matrix metalloproteinases, nitric oxide production and apoptotic cell death. Concordantly, edaravone has been found to have neuroprotective effects in a number of animal models of disease, including stroke, spinal cord injury, traumatic brain injury, neurodegenerative diseases and brain tumors. The proven safety of edaravone following 9 years of use as a free radical scavenger suggests that it may have potential for development into an effective treatment of multiple neurologic conditions in humans.

Edaravone: a new therapeutic approach for the treatment of acute stroke.

Acute stroke, including acute ischemic stroke (AIS) and acute hemorrhagic stroke, (AHS) is a common medical problem with particular relevance to the demographic changes in industrialized societies. In recent years, treatments for AIS have emerged, including thrombolysis with tissue plasminogen activator (t-PA). Although t-PA is the most effective currently available therapy, it is limited by a narrow therapeutic time window and side effects, and only 3% of all AIS patients receive thrombolysis. Edaravone was originally developed as a potent free radical scavenger and, since 2001, has been widely used to treat AIS in Japan. It was shown that edaravone extended the narrow therapeutic time window of t-PA in rats. The therapeutic time window is very important for the treatment of AIS, and early edaravone treatment is more effective. Thus, more AIS patients might be rescued by administering edaravone with t-PA. Meanwhile, edaravone attenuates AHS-induced brain edema, neurologic deficits and oxidative injury in rats. Although edaravone treatment is currently only indicated for AIS, it does offer neuroprotective effects against AHS in rats. Therefore, we hypothesize that early administration of edaravone can rescue AHS patients as well as AIS patients. Taken together, our findings suggest that edaravone should be immediately administered on suspicion of acute stroke, including AIS and AHS.

Sensitivity and usefulness of anti-phosphohistone-H3 antibody immunostaining for counting mitotic figures in meningioma cases.

According to current World Health Organization (WHO) criteria, counting mitotic figures (MF), which is equal to the mitotic index (MI), on paraffin sections stained with hematoxylin and eosin (HE) is one of the recognized classification methods for meningiomas. However, it is not always easy to find the area of highest mitotic activity, and there are different perspectives among pathologists with regard to differentiating MF from non-MF, i.e., which are apoptotic figures and which are crushed or distorted cells. Moreover, there is an issue of overgrading in meningiomas with preoperative feeder embolization. Recently, anti-phosphohistone-H3 (PHH3) antibody has been reported as a mitosis-specific marker for meningioma grading. In this study, we attempted PHH3 immunostaining for our meningioma cases and verified not only the sensitivity of PHH3 immunostaining but also that of its usefulness in grading meningiomas. Forty-five initial histologically confirmed meningiomas (37 benign, 7 atypical, and 1 anaplastic) were reviewed according to current WHO criteria based on counting MF on HE-stained slides. PHH3-immunostained MF were counted in the same way, and the MIB-1 labeling index (LI) was calculated for each sample. PHH3-labeled MF were easily identified and permitted rapid recognition of the areas of highest mitotic activity. As a result, significant increase of PHH3 mitotic index (PHH3-MI) in comparison with HE mitotic index (HE-MI) and strong correlations with HE-MI to PHH3-MI as well as PHH3-MI to MIB-1 LI were demonstrated. Furthermore, no significant differences of PHH3-MI between cases with and without feeder embolization were demonstrated. As such, PHH3 may be a sensitive and useful marker for meningioma grading as based on the MF.