Ischemic stroke patients with low DWI ASPECTS scores require puncture to recanalization within 30 min for large vessel occlusion.

BACKGROUND: The clinical benefits of faster recanalization in acute large vessel occlusion are well recognized, but the optimal procedure time remains uncertain. The aim of this study was to identify patient characteristics that necessitate puncture-to-recanalization (P-R) time within 30 min to achieve favorable outcome. METHODS: We evaluated the patients from a prospective, multicenter, observational registry of acute ischemic stroke patients. The study included patients who underwent endovascular therapy for ICA or MCA M1 occlusion and achieved successful recanalization. Patients were categorized into subgroups based on pre-treatment characteristics and the frequency of favorable outcomes was compared between P-R time < 30 min and ≥ 30 min. Interaction terms were incorporated into the models to assess the correlation between each patient characteristic and P-R time. RESULTS: A total of 1053 patients were included in the study. Univariate analysis within each subgroup revealed a significant association between P-R < 30 min and favorable outcomes in patients with DWI ASPECTS ≤6, age > 85 and NIHSS ≥16. In the multivariable analysis, NIHSS, age, time from symptom recognition to puncture, and DWI ASPECTS were significant independent predictors of favorable outcomes. Notably, only DWI ASPECTS exhibited interaction terms with P-R < 30 min. The multivariable analysis indicated that P-R < 30 min was an independent predictor for favorable outcome in DWI ASPECTS ≤6 group, whereas not in DWI ≥7. CONCLUSIONS: P-R time < 30 min is predictive of favorable outcomes; however, the effect depends on DWI ASPECTS. Target P-R time < 30 min is appropriate for patients with DWI ASPECTS ≤6.

Increased door-to-puncture time during off-duty hours results in poor treatment outcomes for acute ischemic stroke: A subanalysis of the K-NET registry.

BACKGROUND: For patients who undergo endovascular treatment for acute ischemic stroke, the total time for treatment may increase during off-duty hours leading to worse outcomes. The present study compared endovascular treatment outcomes for on-duty and off-duty hours and examined factors that could be responsible for the prolonged treatment of patients in a multicenter registry. METHODS: The study group comprised 1571 patients listed in the multicenter stroke registry (K-NET) who had undergone endovascular treatment between January 2018 and June 2020. The modified Rankin Scale (mRS), evaluated at 90 days after stroke onset, was utilized as the primary outcome. Patients were divided into on-duty and off-duty patients based on admission time. Multivariate logistic regression analysis was used to identify the independent factors that increased the time from admission to puncture during the off-duty period. RESULTS: The mean mRS score at 90 days after stroke onset was 2.9, similar in both on-duty and off-duty patients, with no significant difference (p = 0.77); however, significant differences were observed in time from door-to-puncture (74.7 vs. 88.8, p < 0.01). Additionally, the mRS score at 90 days worsened significantly for door-to-puncture time >60 min in the off-duty period. Multivariate logistic regression analysis revealed that a low National Institute of Health Stroke Scale (NIHSS) score, high pre-mRS score, posterior circulation, and diabetes were independent indicators of door-to-puncture time >60 min during the off-duty period. CONCLUSION: Door-to-puncture time >60 min during off-duty hours was associated with poor outcomes related to low NIHSS, high pre-mRS, posterior circulation, and diabetes.

Retroperitoneal hematoma: A rare complication of percutaneous pedicle screw in an osteoporotic patient.

Background: Percutaneous pedicle screw (PPS) placement is an established technique for minimally invasive surgery. However, life-threatening hematomas may occur in osteoporotic patients undergoing percutaneous screw placement. Case Description: An 80-year-old female with an osteoporotic T10 chance fracture developed a life-threatening hematoma following a T8-L3 posterior fusion performed with PPS. Prompt angiography diagnosed a life-threatening hematoma attributed to laceration of the left third lumbar artery occurring following pedicle screw (PS) placement into an osteoporotically fractured left L3 transverse process. This was immediately and successfully embolized. Conclusion: An 80-year-old female with multiple lumbar osteoporotic fractures developed a life-threatening hematoma during a T8-L3 PS fusion. When the lumbar computed tomography angiography diagnosed a laceration of the left L3 lumbar artery, immediate transarterial embolization proved life-saving.

Optimal Treatment of C3 Lamina in Cervical Laminoplasty.

STUDY DESIGN: Results of C4-C6 laminoplasty with C3 laminectomy and C3-C6 laminoplasty were compared retrospectively. OBJECTIVES: To clarify the difference between C3 laminectomy and C3 laminoplasty in cervical laminoplasty. SUMMARY OF BACKGROUND DATA: Intraoperative damage to the semispinalis cervicis has been shown to lead to postoperative axial symptoms and reduced range of motion (ROM). To prevent this event, C3 laminectomy in cervical laminoplasty is considered superior to C3 laminoplasty. METHODS: A total of 36 patients were included in this study: 20 patients (GroupA) of C3 laminectomy, C4-C6 laminoplasty compared with 16 patients (GroupB) of C3-C6 laminoplasty. We collected patient's background data, operative time, Japanese Orthopaedic Association (JOA) score, VAS score, and radiologic findings such as C2-C7 Cobb angle, ROM, C2 inter-spinous angle, and use of postoperative PRN medication were compared. RESULTS: There was no statistically significant difference in the C2-C7 Cobb angles between the 2 groups before and after surgery (P = 0.315). In ROM, there was a 17.7% decrease from 31.5 preoperatively to 25.9 postoperatively in Group A, and a 6.1% decrease from 29.3 preoperatively to 27.5 postoperatively in Group B. There was no statistically significant difference in ROM (P = 0.683). Postoperative neck pain (VAS) was significantly lower in Group A than in Group B both at 1 week (P = 0.015) and 1 month (P = 0.035) after surgery. The C2 inter-spinous angle was statistically significantly smaller in Group A than in Group B (P = 0.004). Clinical outcomes and surgical outcomes did not differ significantly between groups. CONCLUSIONS: If the C2 interspinous angle is wide and intraoperative semispinalis capitis damage can be minimized, it is worth trying C3 laminoplasty, but if the C2 inter-spinous angle is narrow, C3 laminectomy is recommended from the beginning.

"Dual Internal Shunts Technique" for Carotid Endarterectomy with Carotid Vertebral Anastomosis: Technical Note.

In revascularization of internal carotid stenosis with carotid vertebrobasilar anastomoses, attention should be paid not only to the anterior circulation but also to the posterior circulation cerebral infarction. A 74-year-old man was referred for treatment of carotid artery stenosis; NASCET 75% stenosis in the right internal carotid artery and acute cerebral infarction were confirmed. Occlusion of the left subclavian artery and vascular anastomosis between the right external carotid artery and the vertebral artery were indicated, such that the right external carotid artery may maintain blood flow to the vertebrobasilar artery. Therefore, dual shunts were used for the common and internal carotid arteries and the common and external carotid arteries to maintain blood flow during carotid endarterectomy. Management of the dual shunts is difficult due to the instable parallel placement of the common carotid artery shunt balloons. To solve this problem, the "dual internal shunts technique" was performed. The first shunt was inserted into the external and common carotid arteries, and the second into the internal and common carotid arteries. The shunt balloon on the common carotid artery side was placed distal to the first shunt balloon so that the dual balloons were placed in a tandem position. The proximal balloon was subsequently deflated gradually to improve flow in both shunts. The procedure is technically easy and safe.

Efficacy and safety of thrombectomy for acute ischaemic stroke in patients with pre-stroke mRS scores of 2-3: Real-world evaluation from an open-label, prospective, multicentre, observational study.

BACKGROUND: This study assessed the efficacy and safety of thrombectomy for acute ischaemic stroke in a population with pre-stroke modified Rankin scale (mRS) scores of 2-3 using real-world data. METHODS: Our sample set included 2313 consecutive patients enrolled in the Kanagawa Registry of Intravenous and Endovascular Treatment of Acute Ischemic Stroke registry between January 2018 and June 2020 in 40 stroke centres in Kanagawa Prefecture, Japan. Patients treated with intravenous tissue plasminogen activator (t-PA), thrombectomy, or both were included. Patients with pre-stroke mRS scores of 4-5 and those treated only with intra-arterial thrombolysis were excluded. The primary outcome of this study was an mRS score of 0-3 at 90 days after onset to assess the efficacy of thrombectomy for pre-stroke disabled individuals. We performed multivariate logistic regression analyses to investigate independent factors for a 90-day mRS score of 0-3. We also performed nearest-neighbour within-calliper matching between thrombectomy and t-PA only. RESULTS: After excluding patients meeting the exclusion criteria, we analysed data of 2136 consecutive patients, of which 315 (14.7%) had pre-stroke disabilities (mRS score 2-3). A 90-day mRS score of 0-3 was achieved by 33.3% of patients with pre-stroke mRS scores of 2-3. According to multivariate analysis, the National Institutes of Health Stroke Scale (NIHSS) score was an independent factor. Furthermore, after propensity-score matching, thrombectomy showed considerable superiority for achieving a 90-day mRS score of 0-3. CONCLUSION: Intravenous t-PA and especially thrombectomy were safe and effective for the population with pre-stroke disabilities, particularly for patients with low NIHSS scores.

Detection of Atrial Fibrillation Using Insertable Cardiac Monitors in Patients With Cryptogenic Stroke in Japan (the LOOK Study): Protocol for a Prospective Multicenter Observational Study.

BACKGROUND: Paroxysmal atrial fibrillation (AF) is a probable cause of cryptogenic stroke (CS), and its detection and treatment are important for the secondary prevention of stroke. Insertable cardiac monitors (ICMs) are clinically effective in screening for AF and are superior to conventional short-term cardiac monitoring. Japanese guidelines for determining clinical indications for ICMs in CS are stricter than those in Western countries. Differences between Japanese and Western guidelines may impact the detection rate and prediction of AF via ICMs in patients with CS. Available data on Japanese patients are limited to small retrospective studies. Furthermore, additional information about AF detection, including the number of episodes, cumulative episode duration, anticoagulation initiation (type and dose of regimen and time of initiation), rate of catheter ablation, role of atrial cardiomyopathy, and stroke recurrence (time of recurrence and cause of the recurrent event), was not provided in the vast majority of previously published studies. OBJECTIVE: In this study, we aim to identify the proportion and timing of AF detection and risk stratification criteria in patients with CS in real-world settings in Japan. METHODS: This is a multicenter, prospective, observational study that aims to use ICMs to evaluate the proportion, timing, and characteristics of AF detection in patients diagnosed with CS. We will investigate the first detection of AF within the initial 6, 12, and 24 months of follow-up after ICM implantation. Patient characteristics, laboratory data, atrial cardiomyopathy markers, serial magnetic resonance imaging findings at baseline, 6, 12, and 24 months after ICM implantation, electrocardiogram readings, transesophageal echocardiography findings, cognitive status, stroke recurrence, and functional outcomes will be compared between patients with AF and patients without AF. Furthermore, we will obtain additional information regarding the number of AF episodes, duration of cumulative AF episodes, and time of anticoagulation initiation. RESULTS: Study recruitment began in February 2020, and thus far, 213 patients have provided written informed consent and are currently in the follow-up phase. The last recruited participant (May 2021) will have completed the 24-month follow-up in May 2023. The main results are expected to be submitted for publication in 2023. CONCLUSIONS: The findings of this study will help identify AF markers and generate a risk scoring system with a novel and superior screening algorithm for occult AF detection while identifying candidates for ICM implantation and aiding the development of diagnostic criteria for CS in Japan. TRIAL REGISTRATION: UMIN Clinical Trial Registry UMIN000039809; https://tinyurl.com/3jaewe6a. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/39307.

[Three cases of mechanical thrombectomy in patients over 100 years old].

BACKGROUND: While several cases involving mechanical thrombectomy in patients >90 years old have been reported, only 1 case involving a patient >100 years old has been described. We herein report 3 cases of mechanical thrombectomy performed in patients >100 years old, along with a review of the literature.Case 1: A 102-year-old woman with a National Institute of Health Stroke Scale (NIHSS) score of 20 and diffusion weighted imaging (DWI)-Alberta Stroke Program Early Computed Tomography Score (ASPECTS) of 8 points showed M1 occlusion. She was treated with tissue plasminogen activator followed by mechanical thrombectomy. Recanalization of thrombosis in cerebral infarction (TICI)-3 was obtained at 1 pass. After 90 days, her modified Rankin Scale (mRS) was 2, and she returned to living independently.Case 2: A 104-year-old woman with a NIHSS score of 13 and DWI-ASPECTS of 9 points showed M1 occlusion, so mechanical thrombectomy was performed. Recanalization of TICI-3 was obtained. She was admitted with an mRS of 5.Case 3: A 101-year-old woman with an NIHSS score of 8 and DWI-ASPECTS of 10 points showed right internal carotid artery occlusion, so mechanical thrombectomy was performed. Direct puncture of the right common carotid artery was performed due to access difficulties. Recanalization of TICI-3 was obtained. She was admitted with an mRS of 5. CONCLUSION: In all cases, occlusion access using techniques such as direct carotid puncture was possible, but two of the three patients had an mRS of 5, resulting in a poor prognosis. The indication for treatment in patients >100 years old should be carefully considered.

Primary results of mechanical thrombectomy for acute ischemic stroke: The K-NET registry in the Japanese metropolitan area.

BACKGROUND: Endovascular treatment (EVT) for acute large vessel occlusion has proven to be effective in randomized controlled trials. We conducted a prospective cohort study to evaluate the real-world efficacy of EVT in a metropolitan area with a large number of comprehensive stroke centers and to compare it with the results of other registries and randomized controlled trials (RCTs). METHODS: We analyzed the Kanagawa Intravenous and Endovascular Treatment of Acute Ischemic Stroke registry, a prospective, multicenter observational study of patients treated by EVT and/or intravenous tissue-type plasminogen activator (tPA). Of the 2488 patients enrolled from January 2018 to June 2020, 1764 patients treated with EVT were included. The primary outcome was a good outcome, which was defined as a modified Rankin Scale (mRS) of 0-2 at 90 days. Secondary analysis included predicting a good outcome using multivariate logistic regression analysis. RESULTS: The median age was 77 years, and the median National Institute of Health Stroke Scale (NIHSS) score was 18. Pretreatment mRS score 0-2 was 87%, and direct transport was 92%. The rate of occlusion in anterior circulation was 90.3%. Successful recanalization was observed in 88.7%. The median time from onset to recanalization was 193 min. Good outcomes at 90 days were 43.3% in anterior circulation and 41.9% in posterior circulation. Overall mortality was 12.6%. Significant predictors for a good outcome were as follows: age, male, direct transfer, NIHSS score, Alberta Stroke Program Early Computed Tomography Score, intravenous tPA, and successful recanalization. CONCLUSION: EVT in routine clinical use in a metropolitan area showed comparable good outcomes and lower mortality compared to previous studies, despite the high proportion of patients with older age, pretreatment mRS score of >2, posterior circulation occlusion, and higher NIHSS. Those results may have been associated with more direct transport and faster onset-to-recanalization times.

Closure of a dural defect as a cause of superficial siderosis: does early dural repair lead to a better outcome? Illustrative case.

BACKGROUND: Superficial hemosiderosis (SS) of the central nervous system is a rare condition that is caused by chronic, repeated hemorrhage into the subarachnoid space. The subsequent deposition of hemosiderin in the brain and spinal cord causes neurological deterioration. In this report, the authors describe a repair procedure for SS associated with a dural defect in the thoracic spine. OBSERVATIONS: A 75-year-old man presented with tinnitus symptoms that began about 1 year prior. Subsequently, his hearing loss progressed, and he gradually became unsteady on walking. Magnetic resonance imaging (MRI) of the head showed diffuse hemosiderin deposition on the surface of the cerebellum. Thoracic MRI showed ventral cerebrospinal fluid leakage of T2-7, and computed tomography myelography showed leakage of contrast medium that appeared to be a dural defect. Dural closure was successful, and MRI showed decreased fluid collection ventral to the dura. The patient's symptoms of wobbliness on walking and tinnitus improved dramatically from the postoperative period. LESSONS: Dural abnormalities of the spine must always be considered as one of the causes of SS. Early dural closure is an effective means of preventing the progression of symptoms.

A Surgical Case of Bow Hunter's Syndrome Diagnosed by Cervical Rotational MRA.

Bow hunter's syndrome is an ischemic manifestation of vertebrobasilar artery (VA) insufficiency due to stenosis or occlusion of the contralateral VA at the bony elements of the atlas and axis during neck rotation. In early reports, VA stenosis at the craniovertebral junction was the main cause, but later, symptoms due to VA occlusion at the middle and lower cervical vertebrae were also included in this pathology. Although the confirmed diagnosis is usually determined by dynamic digital subtraction angiography (DSA), we have experienced a method of minimally invasive MR angiogram (MRA) that provides the same diagnostic value as DSA and would like to present it here. The patient was a 61-year-old man who had been visiting the outpatient clinic for cervical spondylosis due to neck pain for 9 months. When he rotated his neck to the left side, dizziness and syncope appeared. Initial MRA in the neutral position did not show any steno-occlusive changes in the vertebrobasilar artery. In our hospital, repeated MRA with the neck rotated 45 degrees to the left demonstrated ipsilateral left VA severe stenosis. Subsequent DSA showed the same findings, with occlusion of the left VA. CT of the cervical spine revealed a ventral C3/4 osteophyte within the foramen. Based on these findings, instability at the C3-4 during head rotation was considered the cause of the vertebrobasilar insufficiency. The patient underwent anterior discectomy and fusion (ACDF) at the C3/4 level using a cylindrical titanium cage. Immediately after the surgery, the patient's symptoms improved dramatically and did not appear even when the neck were fully rotated to the left. More than 5 years have passed since the surgery, and the patient is still in good health.

Dysphagia after occipital cervical fusion for retro-odontoid pseudotumor with ossification of the anterior longitudinal ligament.

Background: Ossification of the anterior longitudinal ligament (OALL) of the cervical spine is a relatively rare disease. If patients present with dysphagia, hoarseness, and/or dyspnea, they may require surgery. Case Description: Over a 7-month period, a 55-year-old female with a history of cerebral palsy developed a progressive quadriparesis accompanied by diffuse sensory loss (i.e., clumsiness of the hand/legs and gait disturbance). The cervical spine X-rays showed atlanto-axial subluxation with instability, while the cervical MRI demonstrated "pseudotumor in the retro-odontoid" region. Following an occipital cervical fusion (C0-C2) surgery, her quadriparesis resolved. Nevertheless, she had persistent dysphagia that worsened over 6 months. Video fluoroscopy revealed severe mechanical stenosis of the pharynx, which was attributed to OALL extending from the C3-C6 levels. Following OALL resection through a right anterior approach utilizing diamond burrs and an ultrasonic bone curette, the dysphagia rapidly resolved. Conclusion: We report a rare case of retro-odontoid pseudotumor successfully treated with a posterior C0-C2 cervical fusion. Additional symptomatic C3-C6 OALL, responsible for progressive dysphagia, was later managed with focal anterior OALL resection.

Repeated-Manual Aspiration with Maximum Pressure (r-MAX): A New Technique of Mechanical Thrombectomy Using Syringe Aspiration.

Objective: We report a new contact aspiration technique using syringe aspiration called repeated-manual aspiration with maximum pressure (r-MAX). Case Presentation: From January 2020 to May 2021, 18 patients underwent mechanical thrombectomy with r-MAX for occlusion of the internal carotid artery, the first division of the middle cerebral artery (M1), and basilar artery occlusion. In this method, the aspiration catheter is first guided to the occlusion site, and then, two VacLok syringes are connected to the aspiration catheter. Next, the three-way stopcock is released in one direction. After 15 seconds, the direction of the three-way stopcock is switched. In the meantime, negative pressure is reapplied through the syringe, and the direction of the three-way stopcock is switched again. After reapplying negative pressure through the syringe and switching the three-way stopcock two more times, the aspiration catheter is removed. First-pass thrombolysis in cerebral infarction (TICI) scale 3 recanalization was achieved in 11 out of 18 patients (61.1%). In all, 11 patients (61.1%) achieved modified Rankin Scale scores of 0-2 at 90 days. Asymptomatic hemorrhage was observed in two patients (11.1%), and no patients had symptomatic hemorrhage. Conclusion: The r-MAX technique using syringe aspiration can be employed as one of the methods of contact aspiration.

Spinal subarachnoid hemorrhage after percutaneous kyphoplasty: a case report and literature review.

Background: Spinal intradural (subdural and subarachnoid) hematoma following percutaneous kyphoplasty is an extremely rare complication. In this report, we describe a case of subarachnoid hemorrhage with delayed paralysis after kyphoplasty and review the literature on similar cases to describe the complications of kyphoplasty and vertebroplasty (VP). Case Description: An 80-year-old man underwent percutaneous kyphoplasty at a local hospital an osteoporotic vertebral fracture (OVF) at the T12 and L1 level. On the second day after kyphoplasty for T12 OVF, he developed paralysis of the lower limbs. At his initial visit to our clinic, he had a complete loss of sensation below T11 and complete paralysis of both lower extremities. Thoracolumbar magnetic resonance imaging revealed an intradural hematoma on the ventral side of the spinal cord, in the spinal canal from T5 to T12, compressing the spinal cord. Thoracolumbar computed tomography showed a fracture line in the medial cortex of the right pedicle at T12 and a tract from the spinal canal to the vertebral body. An emergency posterior decompression from T11 to L1 was performed. A small hole was found on the right side of the pedicle at T12, and tear of the nerve and subarachnoid hematoma were observed in the vicinity of the T11 nerve root. The subarachnoid hematomas were removed. Postoperatively, the neurological symptoms improved rapidly. Eventually, he was able to walk and was transferred for rehabilitation. Conclusions: Percutaneous surgery through the pedicle might cause hematoma and bone cement leakage into the spinal canal. This can be a serious complication: hence prevention is important.

COVID-19 Countermeasures in Acute Stroke.

The impact of coronavirus disease 2019 (COVID-19) is continuing, and the most important issue facing medical staff is how to provide medical care while preventing nosocomial infections. Since acute stroke treatment, particularly mechanical thrombectomy, is urgent, infection protection measures may not always be followed, which increases the risk of infection exposure. The measures and methods for patient screening, transport, zoning, and use of personal protective equipment (PPE) employed to prevent nosocomial infections of COVID-19 at our facility are described herein.

Hybrid procedure combining clip on wrapping and stent placement for ruptured supraclinoid blood blister-like aneurysm of the internal carotid artery.

Blood blister-like aneurysms of the supraclinoid portion of the internal carotid artery are rare, fragile, and thin-walled lesions with a higher rate of rebleeding. Our case underwent a hybrid procedure combining direct surgical and endovascular approach.

[A Case of Juvenile Cerebral Infarction due to Reversible Cerebral Vasoconstriction Syndrome].

A 19-year-old woman had a thunderclap headache, followed by left hemiparesis and left homonymous hemianopsia. Laboratory tests showed no signs of infection and immunological test results were unremarkable. MRI revealed a cerebral infarction in the right posterior cerebral artery territory, and digital subtraction angiography(DSA)showed right posterior cerebral artery stenosis on day 2. The first follow-up DSA demonstrated an irregular, bead-like appearance on day 9, but the stenotic lesion returned to normal on day 21. Reversible cerebral vasoconstriction syndrome should be suspected in cases of rapid resolution of symptoms.

Consequences of preoperative evaluation of patterns of drainage of the cavernous sinus in patients treated using the anterior transpetrosal approach.

Extradural procedures in an anterior transpetrosal approach (ATPA) may interrupt the route of drainage from the superficial middle cerebral veins (SMCVs) and the cavernous sinus (CS) to the pterygoid venous plexus at the temporal skull base. Patterns of drainage of the SMCV and the CS and the results of surgery were examined in 12 patients with petroclival lesions treated using the ATPA between 2000 and 2008. The angiographic patterns of drainage of the SMCV were examined in 22 sides of the 12 patients. The SMCV drained into the sphenoparietal sinus in 12 sides, the sphenobasal veins in 4 sides, and the cortical veins in 6 sides. The patterns of drainage of the CS were examined on 12 sides in which the SMCV drained into the sphenoparietal sinus. The CS drained into the inferior petrosal sinus (IPS) in 7 sides and equally into the pterygoid plexus and IPS in 3 sides. The CS drained mainly into the pterygoid plexus in 2 sides of 2 patients, who both suffered temporal lobe swelling postoperatively. The pattern of venous drainage of the CS must be considered in planning surgical approaches to petroclival lesions. In patients with a well-developed pterygoid plexus, surgical interruption of this drainage route may be a cause of injury of the temporal lobe.

Malignant transformation of supratentorial clear cell ependymoma.

Recurrence of clear cell ependymoma is not a rare condition, but malignant transformation of clear cell ependymoma has not yet been well presented. The authors report a 44-year-old man who presented with progressive right hemiparesis. A brain tumor in the left frontal premotor area was removed and an initial pathological diagnosis of oligodendroglioma was made. The tumor recurred 4 months later, and reoperation of the tumor and adjuvant local radiotherapy were performed. The patient subsequently underwent surgical removal of recurrent tumors on another four occasions (6 times in total) during a period of 11 years and finally died of the original disease. Histopathological studies of all surgical and autopsy specimens were carried out. The first and second surgical specimens did not contain any ependymal rosettes or pseudorosettes, and thus a diagnosis of oligodendroglioma was made. However, the third surgical specimen showed pseudorosettes. At this time, the tumor had an ultrastructural appearance compatible with ependymoma. Thereafter, the recurrent tumors showed anaplastic features such as nuclear pleomorphisms and necrosis with pseudopallisading. The autopsy specimens resembled a feature of glioblastoma but the tumor was sharply demarcated from the surrounding parenchyma.

Induction of autophagic cell death and radiosensitization by the pharmacological inhibition of nuclear factor-kappa B activation in human glioma cell lines.

OBJECT: The intrinsic radioresistance of certain cancer cells may be closely associated with the constitutive activation of nuclear factor-kappa B (NF-kappaB) activity, which may lead to protection from apoptosis. Recently, nonapoptotic cell death, or autophagy, has been revealed as a novel response of cancer cells to ionizing radiation. In the present study, the authors analyzed the effect of pitavastatin as a potential inhibitor of NF-kappaB activation on the radiosensitivity of A172, U87, and U251 human glioma cell lines. METHODS: The pharmacological inhibition of NF-kappaB activation was achieved using pitavastatin, an inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase. Growth and radiosensitivity assays were performed using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Hoechst 33258 staining, supravital acridine orange staining, and electron microscopy were performed utilizing 3 glioma cell lines with or without pitavastatin pretreatment to identify apoptosis or autophagy after irradiation. RESULTS: The growth of these 3 glioma cell lines was not significantly inhibited by pitavastatin at a concentration of up to 1 microM. Treatment with 0.1 microM of pitavastatin enhanced radiation-induced cell death in all glioma cell lines, with different sensitivity. Apoptosis did not occur in any pretreated or untreated (no pitavastatin) cell line following irradiation. Instead, autophagic cell changes were observed regardless of the radiosensitivity of the cell line. An inhibitor of autophagy, 3-methyladenine suppressed the cytotoxic effect of irradiation with pitavastatin, indicating that autophagy is a result of an antitumor mechanism. Using the most radiosensitive A172 cell line, the intracellular localization of p50, a representative subunit of NF-kappaB, was evaluated through immunoblotting and immunofluorescence studies. The NF-kappaB of A172 cells was immediately activated and translocated from the cytosol to the nucleus in response to irradiation. Pitavastatin inhibited this activation and translocation of NF-kappaB. CONCLUSIONS: Autophagic cell death rather than apoptosis is a possible mechanism of radiation-induced and pitavastatin-enhanced cell damage, and radiosensitization by the pharmacological inhibition of NF-kappaB activation may be a novel therapeutic strategy for malignant gliomas.