Short-term clinical and radiographic outcomes of chemonucleolysis with condoliase for painful lumbar disc herniation and analysis regarding intradiscal injection area.

Percutaneous chemonucleolysis with condoliase has been available for painful lumbar disc herniation since 2018 in Japan. This study investigated clinical and radiographic outcomes three months after the administration because the secondary surgical removal is most required during this period for the insufficient pain relief, and analyzed whether the differences of intradiscal injection areas affected the clinical outcomes. We retrospectively investigated 47 consecutive patients (males, 31; median age, 40 years) three months after the administration. Clinical outcomes were evaluated using the Japanese Orthopaedic Association Back Pain Questionnaire (JOABPEQ), a visual analog scale (VAS) score for low back pain, and VAS scores for pains and numbness in the lower limbs. Radiographic outcomes were analyzed in 41 patients, using parameters such as mid-sagittal disc height and maximal protrusion length of herniation on MRI preoperatively and at the final follow-up. Postoperative median evaluation period was 90 days. The effective rate of low back pain based on the pain-related disorders at baseline and the last follow-up in the JOABPEQ reached 79.5%. The postoperative proportion of VAS scores recovery ≥ 2 points and ≥ 50% for pains in the lower limbs were 80.9% and 66.0%, respectively, revealing satisfactory effectiveness. Preoperative median mid-sagittal disc height significantly reduced from 9.5 to 7.6 mm postoperatively. There were no significant differences in pain relief in the lower limbs by injection areas in the center and the dorsal 1/3rd near the herniation of nucleus pulposus. Chemonucleolysis with condoliase revealed satisfactory short-term outcomes after the administration regardless of intradiscal injection areas.

Longest survival by the combination of radiation-therapy and resection in patient with metastatic spinal paragangliomas from primary-neck lesion with succinate dehydrogenase subunit B (SDHB) mutation.

Metastatic paraganglioma (MPG) of the spine is a rare condition, with no established management. Herein, we report the longest survival case of a primary neck tumor that caused spinal MPG with a succinate dehydrogenase subunit B (SDHB) mutation (c.470delT, p.L157X) which could have promoted its malignancy. This male patient initially presented with a left neck PG which was diagnosed by a biopsy when he was 54 years-old. Simultaneously performed additional examinations revealed the spinal metastatic tumors on the T5-7 vertebrae and L3 vertebra-sacrum. These primary neck and metastatic spinal tumors' growths were once suppressed under the radiation therapy. Nineteen years later, he developed acute progressive paraparesis due to a mass located at the T2-3 level, tightly compressing the spinal cord, and protruding into the left thoracic cavity. We resected the maximum possible area of tumor in the spinal canal, confirmed MPG by histological examination, and then, we administered radiation therapy of 40 Gy in 20 fractions. Eventually, the patient was able to walk unaided with no evidential tumor recurrence for 3 years after treatment. Generally, clinical feature of MPG with SDHB mutation from abdominal lesion is thought to be poor prognosis. However, our case suggests the possibility of long-term control of spinal MPG with the adequate combination of radiation therapy and resection if metastatic lesions from primary-neck lesion with an SDHB mutation are remained to spine.

5-Aminolevulinic Acid: Pitfalls of Fluorescence-guided Resection for Malignant Gliomas and Application for Malignant Glioma Therapy.

5-Aminolevulinic acid (ALA) has been widely used as an intravital fluorescence marker in the fluorescence-guided resection of malignant gliomas. Although not a photosensitizer itself, 5-ALA is a prodrug that accumulates protoporphyrin IX (PpIX) in the mitochondria of glioma cells; PpIX acts as a photosensitizer. Fluorescence-guided resection for malignant gliomas has some pitfalls. Moreover, 5-ALA is not merely a fluorescence marker but has potential as a mitochondria-targeting drug for malignant glioma therapy. In this article, we review the literature related to 5-ALA, discuss the pitfalls of fluorescence-guided resection using 5-ALA for malignant gliomas, and describe the application of 5-ALA for malignant glioma therapy with personal opinions.

Importance of Finding Embolic Sources for Patients with Embolic Stroke of Undetermined Source.

OBJECTIVE: The concept of embolic stroke of undetermined source refers to cryptogenic strokes caused by either major or minor risks. Although antiplatelet treatments are most often used for secondary prevention of embolic stroke of undetermined source, optimal strategies remain unclear. To determine the ideal treatment strategy for secondary prevention, we investigated embolic sources among patients with embolic stroke of undetermined source. METHODS: The study included 292 consecutive patients (135 men, 157 women; mean age: 74.3 ± 11.6 years) diagnosed with cerebral infarction, 27 of whom were diagnosed with embolic stroke of undetermined source (9.2%; 14 men, 13 women; mean age: 70.7 ± 11.5 years). These 27 patients were examined using contrast-enhanced whole-body computed tomography, transesophageal echocardiography, and Holter electrocardiography. We evaluated whether antiplatelet or anticoagulant treatment was preferred based on the embolic source. RESULTS: Embolic sources among patients with embolic stroke of undetermined source included valve calcification (11.1%), left ventricle diastolic dysfunction (18.5%), cancer-associated stroke (25.9%), covert atrial fibrillation (7.4%), aortic arch atherosclerotic plaques (11.1%), paradoxical embolism (3.7%), and sick sinus syndrome (3.7%). Embolic sources remained unidentified in 5 patients (18.5%). Our analysis revealed that 21 of the 27 patients (77.8%) with embolic stroke of undetermined source required anticoagulant therapy for secondary prevention. CONCLUSION: Although aspirin is the most commonly used antithrombotic drug for embolic stroke of undetermined source, our results suggest that some patients require anticoagulant therapy. Determining embolic sources is important for selecting the appropriate treatment options for this patient population.

Characteristics of Bone Destruction in Cranial Vault Lymphoma Compared with Other Skull Tumors.

Cranial vault lymphomas are rare and challenging to diagnose. We present herein two cases of cranial vault lymphoma. The first patient was a 72-year-old woman who presented with a large mass in the parietal bone found incidentally following a head injury. The second patient was a 63-year-old man who presented with an occipital subcutaneous mass associated with visual disturbance and occipital headaches. The diagnosis of a malignant tumor in the second patient was straightforward due to his symptoms and considerable bone destruction, but the first patient was more difficult to diagnose due to a lack of symptoms and only slight bone destruction detected by computed tomography (CT). Both were histophathologically diagnosed with diffuse large B cell lymphoma (DLBCL) in the cranial vault. We also investigated the clinical features, including initial symptoms and patterns of bone destruction, in 23 patients with other types of skull tumors. This comparison showed that cranial vault lymphomas cause large masses on the scalp and lead to characteristic incomplete bone destruction, indicating that cranial bone is destroyed very slowly despite the expanding subcutaneous mass. This feature is unique compared with other benign and malignant skull tumors. In addition, cranial vault lymphoma can be confirmed via bone window CT.

[Takotsubo Cardiomyopathy and Neurogenic Pulmonary Edema Following Fibrinolytic Therapy for Embolic Stroke:A Case Report].

A 79-year-old man presented with left hemiparesis and disturbance of consciousness. Brain magnetic resonance(MR)imaging revealed an infarction in the right insular cortex. MR angiography showed a defect in the inferior trunk of the right middle cerebral artery. The patient was treated with alteplase about 2.5 h after onset. Immediately after the intravenous alteplase administration, the hemiparesis improved. However, his respiratory condition unexpectedly worsened 10 h after onset. Chest radiography demonstrated an infiltrative shadow in both lung fields. Transthoracic echocardiogram showed a dysfunction in the left ventricle and no contraction at the apex of the heart, consistent with a type of cardiomyopathy, known as takotsubo cardiomyopathy(TCM). Gradually, the patient's respiratory and cardiac function improved. Here, we describe a very rare case of TCM and neurogenic pulmonary edema(NPE)following an acute cerebral infarction, which was treated with alteplase intravenous administration. TCM and NPE have a poor prognosis, therefore diagnosis, management, and treatment in the acute phase is required.

[Factor Xa Inhibitor for the Treatment of Cerebral Venous Thrombosis with Intracerebral Hemorrhage during Anticoagulation Therapy:A Case Report].

A 46-year-old man presented with headache, right hemiparesis, and motor aphasia. A diagnosis of cerebral venous thrombosis with subarachnoid hemorrhage was made. We started intravenous administration of unfractionated heparin. After 6 days in hospital, the right hemiparesis and motor aphasia worsened, and brain computed tomographic(CT)images demonstrated intracerebral hemorrhage in the left parietal lobe. Therefore, we switched treatment from heparin to apixaban. His condition improved and a brain magnetic resonance(MR)venogram after 7 days in hospital showed recanalization of the cerebral veins. He was discharged with no apparent neurological defects 33 days after onset and his modified Rankin Scale score was 1. In cases of progressive cerebral venous thrombosis with intracerebral hemorrhage, during anticoagulation, it is necessary to achieve recanalization of the occluded cerebral vein rapidly without spreading the intracerebral hemorrhage. Factor Xa inhibitors, especially apixaban, may be another option for treating cerebral venous thrombosis with intracerebral hemorrhage.

Pilocytic astrocytoma presenting with atypical features on magnetic resonance imaging.

Pilocytic astrocytoma, which is classified as a grade I astrocytic tumor by the World Health Organization, is the most common type of glioma in children and young adults. Pilocytic astrocytoma generally appears as a well-circumscribed, contrast-enhancing lesion, frequently with cystic components on magnetic resonance imaging (MRI). However, it has been reported that the MRI appearance of pilocytic astrocytoma may be similar to that of high-grade gliomas in some cases. We here report on 6 cases of pilocytic astrocytoma with atypical MRI findings, including small cyst formation, heterogeneously enhancing tumor nodules, irregularly enhancing tumor nodules, and enhancing tumor nodules with internal hemorrhage. All tumors were successfully resected, and the histological diagnoses were pilocytic astrocytoma. When the tumor is located near a cerebral cistern or ventricle, the risk of leptomeningeal dissemination is increased. Furthermore, partial resection has also been associated with a higher risk of recurrence and leptomeningeal dissemination. To date, all but one patient are alive and recurrence-free. Because the preoperative diagnosis influences the decision on the extent of resection and because of the high risk of leptomeningeal dissemination associated with these tumors, careful and correct diagnosis by MRI is important.

Preoperative radiological evaluation and surgical strategy for the preservation of visual acuity in patients with skull base meningiomas--two case reports.

Two women aged 48 and 73 years, respectively, presented with unilateral visual disturbance. On admission, magnetic resonance imaging (MRI) showed an extraaxial mass in the parasellar region. Contrast-enhanced fast imaging with steady-state acquisition (CE-FIESTA) showed that the optic nerves were compressed and encased by the tumors. At an early stage of surgery, we performed decompression of the optic nerves to avoid optic nerve injury. Both the patients were relieved of visual disturbances without any postoperative neurological deficit. In conclusion, CE-FIESTA is a useful diagnostic tool for preoperative evaluation of the optic nerves in patients with skull base meningiomas. Decompression of the optic nerves should be performed at an early stage of surgery in meningioma patients presenting with visual disturbance.

Surgical treatment for a ruptured true posterior communicating artery aneurysm arising on the fetal-type posterior communicating artery--two case reports and review of the literature.

Only a small number of aneurysms arising on the posterior communicating artery itself (true Pcom aneurysm) have been reported. We report two cases of ruptured true Pcom aneurysms with some characteristic features of true Pcom aneurysm. A 43 year old man suffering from subarachnoid hemorrhage (SAH) had an aneurysm arising on the fetal-type Pcom artery itself, and underwent surgery for clipping. Most of the aneurysm was buried in the temporal lobe, so retraction of the temporal lobe was mandatory. During the retraction, premature rupture was encountered. After tentative dome clipping and the control of bleeding, complete clipping was achieved. Another patient, a 71 year old woman presenting with consciousness disturbance due to SAH, had an aneurysm on the fetal-type Pcom artery itself, and underwent surgery for clipping. It has been generally considered that hemodynamic factor plays an important role in the formation, the growth, and the rupture of the cerebral aneurysm. This factor is especially significant in true Pcom aneurysm formation and rupture. According to the literature, a combination of fetal type Pcom and formation of the true Pcom aneurysm has been reported in most cases (81.8%). Most of the aneurysm can be buried in the temporal lobe, and the retraction of the temporal lobe during the dissection of the neck would be necessary, which causes premature rupture of the true Pcom aneurysm. In the surgery for a true Pcom aneurysm, we should be aware of possible premature rupture when temporal lobe retraction is necessary.

Brain ischemia due to direct vascular compression associate with rapid enlargement of unruptured middle cerebral artery aneurysm: A case report.

BACKGROUND: Acute cerebral infarction is a rare complication resulting from an unruptured cerebral aneurysm (UCA). There is presently no consensus on the optimal strategy for the management of UCAs with cerebral infarctions. CASE DESCRIPTION: A 53-year-old man presented with transient dysarthria and left hemiparesis. Magnetic resonance imaging (MRI) demonstrated the presence of a 7 mm UCA originating from the middle cerebral artery bifurcation, and diffusion-weighted imaging showed no evidence of cerebral infarction. One month later, his transient left hemiparesis recurred, and the patient was admitted to our hospital. Computed tomography angiography showed enlargement of the aneurysm. His left hemiparesis worsened 3 days later. MRI showed cerebral infarction in the area of perforating arteries and further enlargement of the aneurysm with surrounding parenchymal edema. Therefore, the rupture risk was considered to be rarely high and dome clipping was performed immediately. Postoperatively, his neurological status improved without any recurrent brain ischemia. CONCLUSION: We report a rare case of a rapidly enlarging aneurysm that presented with cerebral infarction. This is the first report describing aneurysmal sac enlargement that can lead to perforating artery obstruction and brain ischemia. The case illustrates the importance of performing close follow-up examinations to confirm findings that suggest a high rupture risk.

Preliminary Results on Radiological Hypermobility at Upper Adjacent Disc Level in Posterior Lumbar Interbody Fusion Compared to Advanced Dynamic Stabilization.

Whether posterior lumbar interbody fusion (PLIF) is effective in patients older than 55 years remains questionable because of the high prevalence of adjacent segment disease. We retrospectively investigated early clinical outcomes and radiological changes at upper adjacent disc (UAD) level in such age-group patients who underwent advanced dynamic stabilization (ADS) or PLIF. ADS or PLIF were performed in patients with grade 1 spondylolisthesis or disc degeneration complicated by apparent vacuum phenomenon. All patients suffered from neurological symptoms in lower limbs with/without low back pain. In all, 16 patients (six females; mean age, 69.0 ± 8.5 years) who underwent ADS and 14 patients (seven females; mean age, 67.8 ± 9.3 years) who underwent PLIF were followed-up, and preoperative and postoperative final disc height (DH) and range of motion (ROM) were investigated retrospectively using dynamic radiography at the operated and UAD levels. Clinical data of patients who underwent ADS and PLIF were as follows: postoperative follow-up, 459.3 ± 263.5 and 507.7 ± 288.3 days; preoperative Japanese Orthopaedic Association (JOA) score, 14.4 ± 4.1 and 13.4 ± 4.5; and recovery rate of JOA score, 67.5 ± 18.5 and 50.1 ± 23.4%, respectively. Recovery rate of JOA score in ADS group was significantly high compared to PLIF group (P = 0.044). At UAD level, ROM decreased from 4.7 ± 2.9° preoperatively to 3.6 ± 2.6° postoperatively in the ADS group and increased from 3.4 ± 4.1° preoperatively to 5.6 ± 2.8° postoperatively with significant hypermobility (P = 0.020) in the PLIF group. ADS has the advantage in clinical outcomes even in the postoperative early stage, avoiding the early hypermobility at UAD level, compared to PLIF in patients older than 55 years.

Facet Joint- and Nuchal Ligament-Sparing Laminectomy is Not Inferior to Conventional Open-Door Laminoplasty from Clinical and Radiologic Perspectives.

OBJECTIVE: To investigate the noninferiority of facet joint- and nuchal ligament-sparing laminectomy (FNL) compared with conventional open-door laminoplasty. METHODS: This retrospective study analyzed 31 patients who underwent FNL (7 women; median age, 71 years) and 29 patients who underwent laminoplasty (9 women; median age, 61 years) with cervical myelopathy due to degenerative cervical spine diseases. The surgical concept in laminectomy was to spare the facet joints and nuchal ligament, providing laminectomy with deviation to the side of dominant symptoms. In both groups, recovery rate of Japanese Orthopaedic Association (JOA) score, mean decompression ratio (decompressed width/distance between outermost edges of the lateral mass on computed tomography ×100) at decompressed laminas, and pre- and postoperative final cervical Cobb angle and cervical sagittal vertical axis were mainly examined. RESULTS: Clinical and radiologic median data with interquartile range for patients who underwent FNL and laminoplasty were as follows: postoperative follow-up, 783.0 days (535.0-1128.0 days) and 731.0 days (524.0-1213.5 days); preoperative JOA score (full score 17), 13.0 (9.5-15.0) and 13.0 (10.0-14.0); recovery rate of JOA score, 72.2% (33.3-100.0%) and 50.0% (31.0-75.0%); and mean decompression ratio, 41.9% (40.0-43.6%) and 51.6% (48.9-55.4%), respectively. The FNL group showed a comparable recovery rate of JOA score to the laminoplasty group, despite the significantly smaller mean decompression ratio (P < 0.001). Furthermore, no significant differences in pre- or postoperative median cervical Cobb angle or sagittal vertical axis were observed between groups. CONCLUSIONS: FNL was not inferior to conventional open-door laminoplasty in terms of clinical or radiologic outcomes, reducing the detachment of muscle from each lamina.

Takotsubo Cardiomyopathy and Neurogenic Pulmonary Edema After Carotid Endarterectomy.

BACKGROUND: Takotsubo cardiomyopathy (TCM) and neurogenic pulmonary edema (NPE) are rare complications of an acute ischemic stroke. In particular, TCM and NPE following carotid endarterectomy (CEA) are extremely rare. In general, TCM- and NPE-associated ischemic strokes are caused by excess catecholamine release after sympathetic nervous stimulation following stroke onset, but the mechanism triggering this stimulation is still unknown. CASE DESCRIPTION: An 88-year-old man underwent left CEA for symptomatic carotid artery stenosis (North American Symptomatic Carotid Endarterectomy Trial, 65%). After the surgery, his respiratory condition rapidly worsened, and chest radiography revealed an infiltrative shadow on both lung fields. Transthoracic echocardiography revealed left ventricular dysfunction, suggesting TCM. Postoperative magnetic resonance imaging revealed a small infarction in the left anterior insular cortex. Eventually, his respiratory and cardiac functions gradually improved. He was finally discharged on his own from the hospital on postoperative day 9. CONCLUSIONS: We described a very rare case of TCM and NPE following CEA. The mechanisms of TCM and NPE involve excess catecholamine release after sympathetic nervous stimulation. Our findings suggest that surgery-associated transient ischemia and reperfusion injury to the left insular cortex stimulate sympathetic nerves.

5-Aminolevulinic Acid Suppresses Prostaglandin E2 Production by Murine Macrophages and Enhances Macrophage Cytotoxicity Against Glioma.

BACKGROUND: 5-Aminolevulinic acid (5-ALA) induces the accumulation of a large amount of protoporphyrin IX (PpIX) in tumors, which has been used in the treatment of several cancers. 5-ALA is commonly used for fluorescence-guided tumor resection in clinical neurosurgery and for photodynamic therapy based on the generation of cytotoxic oxygen. OBJECTIVE: The purpose of this study was to identify the mechanisms of 5-ALA-induced immune response in macrophages in malignant glioma. METHODS: Intracellular levels of 5-ALA-induced PpIX in C3H/HeN murine peritoneal macrophages were measured by the median fluorescence intensity using flow cytometry and confocal laser scanning microscopy. Macrophages were cultured in vitro with or without 0.5 mM 5-ALA, 0.1 µg/mL lipopolysaccharide, and 20% glioma-conditioned medium. Levels of immunosuppressive prostaglandin E2 (PGE2), interleukin-10, and transforming growth factor ß were measured using enzyme immunoassay in the culture supernatant. In addition, macrophages and RSV-M mouse glioma cells were co-cultured in vitro with cell culture inserts with or without 5-ALA (0.1 and 0.5 mM) and lipopolysaccharide (0.1 µg/mL). RESULTS: We found that 5-ALA-induced PpIX accumulated in macrophages and significantly suppressed PGE2 production and expression of both cyclooxygenase-2 and microsomal prostaglandin E synthase-1. 5-ALA treatment also suppressed PGE2 production by glioma-conditioned medium. 5-ALA suppressed RSV-M glioma cell proliferation in a concentration-dependent manner. CONCLUSIONS: These results indicate that 5-ALA suppressed PGE2 production by macrophages via the downregulation of cyclooxygenase-2 and microsomal prostaglandin E synthase-1 expression levels. This is a novel mechanism to induce effective immune response against glioma in macrophages.

Giant Cerebral Aneurysm in a Patient with Cowden Syndrome Treated with Surgical Clipping.

BACKGROUND: Cowden syndrome is characterized by multiple hamartomas and accompanied by a germline mutation of the phosphatase and tensin homolog gene. Cowden syndrome has been described to be associated with vascular anomalies such as arteriovenous malformation and developmental venous anomalies with high frequency. However, the association of cerebral aneurysms with this syndrome has not been reported yet. CASE DESCRIPTION: A 39-year-old Japanese man presented with a subarachnoid hemorrhage due to a ruptured giant fusiform middle cerebral artery aneurysm. We diagnosed him with Cowden syndrome by clinical presentations as outlined in the National Comprehensive Cancer Network's criteria. As the ruptured fusiform aneurysm involved a middle cerebral artery bifurcation, we prepared for extracranial-intracranial bypass surgery. We successfully performed a surgical clipping using multiple tandem clipping techniques and suction decompression techniques. Bypass surgery was not performed as reconstruction of the M2 trunks was successfully completed. CONCLUSIONS: We present this rare case that potentially indicates an association between cerebral aneurysms and Cowden syndrome. Because vascular anomalies are not included in the diagnostic criteria for Cowden syndrome, intracranial vascular anomalies may be underestimated. We therefore recommended a careful search of vascular diseases, including cerebral aneurysms, in cases of Cowden syndrome.

Vessel wall magnetic resonance imaging findings and surgical treatment in nilotinib-associated cerebrovascular disease: A case report.

Nilotinib, a second-generation tyrosine kinase inhibitor, is considered as one of the most effective drugs for the treatment of chronic myeloid leukemia (CML); however, the use of nilotinib has been reported to be associated with vascular adverse events, such as peripheral arterial occlusive disease and ischemic heart disease. Moreover, there are few reports on cerebral vascular disease associated with nilotinib use. We herein describe the case of a 55-year-old male patient with CML, who presented with cerebral infarction and severe cerebrovascular stenosis that developed during nilotinib treatment. The patient was diagnosed with cerebral infarction and severe stenosis of the intracranial arteries associated with nilotinib use. Vessel wall magnetic resonance imaging (VW-MRI) revealed diffuse concentric thickening of the vessel wall, unlike ordinary patterns of atherosclerosis. The patient underwent direct revascularization (superficial temporal artery to middle cerebral artery bypass) and was successfully treated without recurrence. Based on this rare case, VW-MRI may be used to detect the morphological changes of the intracranial arteries that are associated with nilotinib use. Moreover, surgical revascularization may improve the prognosis of nilotinib-associated cerebrovascular diseases, such as severe stenosis or occlusion of the main trunk of the cerebral arteries, that cause brain ischemia.

Intraoperative monitoring of motor-evoked potential for parenchymal brain tumor removal: An analysis of false-negative cases.

Transcranial motor-evoked potential (tc-MEP) monitoring is unreliable for brain tumor removal due to its low sensitivity. According to previous literature, this is because transcranial stimulation seems to reach the deep pyramidal tract beyond the operation point and may thus yield false-negative results, where, although MEP recording is stable, postoperative motor deficits are encountered. Therefore, we aimed to analyze the causes for the false-negative results and investigate whether decreasing the stimulation intensity better reflects the operation point and can improve the sensitivity during parenchymal brain tumor removal. We assessed 122 patients with parenchymal brain and intraventricular tumors, who underwent surgery under tc-MEP monitoring in our hospital between 2011 and 2014. In these patients, the stimulation intensity was fixed at 200 mA. We detected 11 false-negative cases, while the sensitivity of tc-MEP monitoring was 33.9% and the specificity was 99.0%. Between 2015 and 2016, we examined 68 patients with parenchymal brain tumors, in whom the stimulation intensity was reduced to an average of 136.5 mA. Only one case was false-negative, while the sensitivity increased to 83.3% and the specificity was 98.4%. From these results, we conclude that the intensity of tc-MEP stimulation should be minimal to precisely reflect the damage to the operated location. Tc-MEP can be an easy and reliable monitor in brain tumor surgery when used at proper, lower intensity.

5-Aminolevulinic acid enhances mitochondrial stress upon ionizing irradiation exposure and increases delayed production of reactive oxygen species and cell death in glioma cells.

5-Aminolevulinic acid (5-ALA) can accumulate protoporphyrin IX (PpIX) in tumour cell mitochondria and is well known for its utility in fluorescence-guided resection of malignant gliomas as a live molecular marker. Previously, we and other authors demonstrated that 5-ALA has a radiosensitizing effect for tumours. In the present study, we aimed to investigate the mechanism underlying the radiosensitizing effect of 5-ALA by focusing on glioma cell mitochondria. Using an enhancer (ciprofloxacin) of 5-ALA-induced PpIX accumulation, we evaluated the influence of ionizing irradiation (IR) and delayed reactive oxygen species (ROS) production 12 h after IR by colony-forming assay and flow cytometry (FCM) with different amounts of PpIX accumulation. The mitochondrial mass and mitochondrial electron transport chain (mtETC) activity were evaluated by FCM and western blot analysis. Cell death and delayed ROS production after IR in glioma cells were increased in proportion to 5-ALA-induced PpIX accumulation. Delayed ROS production enhanced by 5-ALA localized to the glioma cell mitochondria. Mitochondrial mass and mitochondrial complex III activity, among mtETC factors, were also increased 12 h after IR in glioma cells in proportion to 5-ALA-induced PpIX accumulation with some variation. These results suggest that 5-ALA enhances IR-induced mitochondrial oxidative stress and leads to increased cell death with mitochondrial changes, thereby acting as a targeting mitochondrial drug, and so­called radiosensitizer in glioma cells.

Clinical features and surgical management of intracranial meningiomas in the elderly.

Meningioma accounts for ~25% of all primary intracranial neoplasms and the incidence increases with age. Prvios population-based studies demonstrated that the annual incidence of intracranial meningiomas was 1.2-3.1/100,000 population. In particular, the incidence of this disease among the elderly is high. Recently, increased life expectancy and greater use of diagnostic radiological imaging led to an increased incidence in the diagnosis of intracranial meningiomas, both symptomatic and asymptomatic, in the elderly. Thus, neurosurgeons may be increasingly confronted with the management of intracranial meningiomas in the elderly. In practice, it is often difficult for physicians to determine whether traditional surgical resection is the optimal management strategy for intracranial meningiomas in the elderly. However, reported clinical studies about the outcome of surgical resection of intracranial meningiomas in the elderly are limited. Increased risk of mortality and morbidity associated with surgical treatment for intracranial meningiomas in the elderly compared with younger patients have been controversial. In the present study, the clinical features of intracranial meningiomas in 70 consecutive intracranial meningioma patients that underwent surgical treatment at the affiliated hospital of University of Occupational and Environmental Health between 2007 and 2013 were assessed. In addition, patient selection and surgical management of intracranial meningioma in elderly patients was discussed. Preoperative factors, including symptoms, tumor location, tumor size, Karnofsky Performance Scale (KPS) score and American Society of Anesthesiology (ASA) score, and postoperative factors, including pathological diagnosis, tumor proliferation index (Ki-67), resection rate (Simpson grade), length of hospital stay and discharge destination were retrospectively analyzed in patients aged ≥75 years (n=16; elderly group) and <75 years (n=54; younger group). Outcomes were assessed 6 months after surgery. Multivariate logistic regression revealed that tumor resection rate (Simpson grade III-V) was an important predictor of surgical complications (odds ratio, 5.662; 95% confidence interval, 1.323-24.236; P=0.0194). Perioperative morbidity was not correlated with age (>75 years), tumor location, tumor size, KPS score or ASA score. Thus, the present study indicated that age is not associated with surgical outcome in elderly meningioma patients. Regardless of patient age, the decision to perform surgical resection should be made on an individual basis wherein tumor characteristics and the general health of the patient are considered.