First autopsy analysis of a neovascularized arterial network induced by indirect bypass surgery for moyamoya disease: case report.

The object of this study was to analyze the pathology of collateral vessels newly induced by indirect bypass surgery for moyamoya disease (MMD). An autopsy analysis was conducted on a 39-year-old woman with MMD who had died of a brainstem infarction. The patient had undergone bilateral indirect bypass surgeries 22 years earlier. Sufficient revascularization via bilateral external carotid arterial systems was confirmed by cerebral angiography before her death. Macroscopic observation of the operative areas revealed countless meandering vessels on the internal surface of the dura mater connected with small vessels on the brain surface and in the subpial brain tissue. Notably, microscopic analysis of these vessels revealed the characteristic 3-layer structure of an arterial wall. This autopsy analysis was the first to confirm that indirect bypass surgery had induced the formation of a new arterial network (arteriogenesis) and that this network had been maintained for more than 20 years to compensate for the chronic cerebral ischemia caused by the MMD.

INVESTIGATIVE RESEARCH PROJECTS RELATED TO THE TOHOKU EARTHQUAKE (THE GREAT EAST JAPAN EARTHQUAKE) CONDUCTED IN FUKUSHIMA.

BACKGROUNDS: On March 11(th) 2011, the Tohoku region of Japan was struck by catastrophic disasters. Thousands of people were killed due to a magnitude 9.0 earthquake and its subsequent tsunami. Furthermore, a serious nuclear crisis occurred in Fukushima Prefecture as a result of the disasters, and an emergency evacuation was ordered to people living near the nuclear power plants. There was a lot of anxiety regarding lost families as well as the influences of radioactivity on the health of people and their children. Based on these urgent and uncertain situations, a number of research projects were developed at many institutes both inside and outside Fukushima. METHODS: We herein report the investigative research projects related to the Tohoku Earthquake (The Great East Japan Earthquake) conducted after the disasters. The research projects were reviewed by the Institutional Review Board in Fukushima Medical University during the two years following the disasters. The research projects conducted in universities other than Fukushima Medical University were also examined using questionnaire analysis. RESULTS: Among the research projects conducted in Fukushima Medical University (n=424), 7% (n=32) were disaster-related investigative research. The mean duration planned to pursue the projects was 25.5 months. Among these projects, those focusing on the health of Fukushima citizens were most common (n=9), followed by the influence of chronic exposure of radiation on chronic inflammatory disorders (n=6), and the mental health of Fukushima citizens (n=5). They were carefully reviewed for the purpose, suitability, and necessity from ethical as well as scientific viewpoints. The majority of the research projects focused on the effects of the Tohoku Earthquake and/or chronic exposure to low-dose radioactivity on the health of children and pregnant women, as well as on various disorders, such as mental health and chronic inflammatory diseases. On the other hand, among 58 projects we collected from 22 institutes in prefectures other than Fukushima, mental health-related projects were the most common (n=18), followed by radiation exposure-related projects (n=10). CONCLUSIONS: Many of these projects are ongoing, and in particular, long term follow-up regarding the health of the residents of Fukushima Prefecture, especially children and pregnant women, is necessary.

Extended orbital exenteration for sinonasal malignancy with orbital apex extension: surgical technique and clinical analysis.

OBJECT: The majority of sinonasal malignancies present with advanced disease, and cure rates are generally poor. Surgical extirpation remains the mainstay of treatment. In cases of sinonasal malignancy with orbital apex extension, gross-total tumor resection requires orbital exenteration and bony skull base resection around the orbital apex to provide sufficient margins. In this retrospective study, the authors describe their surgical strategy in and technique for orbital exenteration with orbital apex resection in patients at Tokyo Medical and Dental University who had sinonasal malignancy with orbital apex extension. They also analyzed the clinical features of and the results in these patients. METHODS: Between February 2001 and August 2012 at the authors' institution, sinonasal malignancy with orbital apex extension was treated using craniofacial tumor resection with orbital exenteration including skull base bone around the orbital apex. The authors describe this technique and analyze the surgical indications, extent of resection, primary tumor location, outcome, pathological findings, and neoadjuvant and adjuvant therapies of the patients who underwent the technique. RESULTS: The patients consisted of 12 men and 3 women with a mean age of 47.7 years (range 14-79 years). The longest postoperative follow-up was 9.5 years, and the shortest was 0.67 year (mean 3.0 years). Tumor originated at the ethmoid sinus in 6 patients (40%), maxillary sinus in 5 (33%), nasal cavity in 2 (13%), and orbital cavity and maxillary bone in 1 patient each (7%). Histological analysis of tumor specimens revealed squamous cell carcinoma in 9 patients (60%), rhabdomyosarcoma in 2 (13%), and small cell carcinoma, mucoepidermoid carcinoma, adenoid cystic carcinoma, and Ewing sarcoma in 1 patient each (7%). Two patients experienced recurrences at 1 and 5 months after treatment; these patients died at 5 and 10 months after surgery, respectively. Estimated 5-year recurrence-free survival (RFS) was 86.7%, and estimated 5-year overall survival (OS) was 86.2%; there was no perioperative mortality. None of the patients had new neurological deficits as a result of the surgery, but 5 patients suffered infectious complications from the graft transplanted into the cavity after resection. There were no other perioperative complications. CONCLUSIONS: These authors are the first to describe a technique for extended orbital exenteration with orbital apex skull base resection. The technique provided sufficient margins for gross-total resection of the sinonasal malignancy with orbital apex extension. The estimated 5-year OS and RFS rates were high, and the perioperative complication rate was acceptably low, demonstrating the safety and efficacy of this technique.

Validation and evaluation of the volumetric measurement of cerebellopontine angle cistern as a prognostic factor of microvascular decompression for primary trigeminal neuralgia.

BACKGROUND: The aim of this study was to analyze the prognostic factors of trigeminal neuralgia (TN) after microvascular decompression (MVD), and to evaluate the volumetric parameters of the cerebellopontine angle (CPA) cistern as a pathogenic factor and imaging predictor. METHODS: This retrospective study included 70 patients with primary TN treated with pure MVD, followed up for at least 1 year and evaluated by high-resolution MR imaging. The volume of the CPA cistern was calculated bilaterally, and the "Cistern Deviation Index" was defined to represent degree of deviation of the CPA cistern. Clinical data and volumetric parameters were compared between patients with TN and age- and sex-matched controls without TN, and between the recurrent and non-recurrent patients. RESULTS: The transposition procedure had a better outcome than the interposition procedure (P < 0.001). There was a significant difference in the volume of CPA cistern between the affected and unaffected side (152.1 ± 50.1 vs. 179.9 ± 63.7 mm(3), P < 0.001) in patients with TN, while no significant difference between the right and left side (158.7 ± 44.6 vs. 163.1 ± 49.8 mm(3), P = 0.162) in controls. The Cistern Deviation Index was significantly larger in controls than in patients with TN (P = 0.048), and in the non-recurrent patients than in recurrent patients (P = 0.040). CONCLUSION: We demonstrated that the volumetric parameters of the CPA cistern are a marker for understanding the pathogenesis of TN and useful for predicting the recurrence after MVD. The Cistern Deviation Index might contribute to deciding the surgical approach.

Practical clinical use of dynamic susceptibility contrast magnetic resonance imaging for the surgical treatment of moyamoya disease.

BACKGROUND: Precise evaluation of hemodynamic stress is important for the treatment of moyamoya disease (MMD). OBJECTIVE: To explore whether dynamic susceptibility contrast magnetic resonance imaging could predict the effects and risk of indirect bypass surgery on MMD. METHODS: Clinical data of patients with MMD who were evaluated preoperatively and postoperatively with dynamic susceptibility contrast magnetic resonance imaging and digital subtraction angiography were evaluated retrospectively. Indirect bypass surgery was performed on 115 hemispheres of 69 patients (mean age, 15 years; range, 3-54 years). We examined the correlations of ischemic events and revascularization with the mean transit time (MTT) delay to cerebellum. RESULTS: The hemispheres that caused the ischemic events (responsible hemisphere) had a significantly longer preoperative MTT delay than the nonresponsible hemispheres (2.66 ± 1.34 vs 1.57 ± 1.09 seconds). The postoperative MTT delay fell significantly in the patients whose symptoms disappeared (preoperative, 2.61 ± 1.35 seconds; postoperative, 1.35 ± 0.96 seconds). Perioperative infarction occurred in 4 hemispheres (3.5%), and the MTT delay was significantly longer in those hemispheres than in the others (3.97 ± 1.20 vs 2.38 ± 1.34 seconds). The MTT delay was significantly longer in patients with higher angiographic stages. Indirect bypass surgery ameliorated the MTT delay to the same degree in adults and children. Digital subtraction angiography revealed that the induced revascularization was far superior in areas with longer MTT delays. CONCLUSION: Dynamic susceptibility contrast magnetic resonance imaging proved to be a useful clinical imaging method for patients with MMD. It may be helpful for selecting candidates for MMD intervention and for predicting the effects and risks of surgery. ABBREVIATIONS: DSC-MRI, dynamic susceptibility contrast magnetic resonance imagingMMD, moyamoya diseaseMTT, mean transit timeROI, region of interest.

Successful coil embolization of a ruptured basilar artery aneurysm in a child with leukemia: a case report.

Ruptured intracranial aneurysms are rare in the pediatric population compared to adults. This has incited considerable discussion on how to treat children with this condition. Here, we report a child with a ruptured saccular basilar artery aneurysm that was successfully treated with coil embolization. A 12-year-old boy with acute lymphoblastic leukemia and accompanying abdominal candidiasis after chemotherapy suddenly complained of a severe headache and suffered consciousness disturbance moments later. Computed tomography scans and cerebral angiography demonstrated acute hydrocephalus and subarachnoid hemorrhage caused by saccular basilar artery aneurysm rupture. External ventricular drainage was performed immediately. Because the patient was in severe condition and did not show remarkable signs of central nervous system infection in cerebrospinal fluid studies, we applied endovascular treatment for the ruptured saccular basilar artery aneurysm, which was successfully occluded with coils. The patient recovered without new neurological deficits after ventriculoperitoneal shunting. Recent reports indicate that both endovascular and microsurgical techniques can be used to effectively treat ruptured cerebral aneurysms in pediatric patients. A minimally invasive endovascular treatment was effective in the present case, but long-term follow-up will be necessary to confirm the efficiency of endovascular treatment for children with ruptured saccular basilar artery aneurysms.

Expansion of CD133-positive glioma cells in recurrent de novo glioblastomas after radiotherapy and chemotherapy.

OBJECT: Recent evidence suggests that a glioma stem cell subpopulation may determine the biological behavior of tumors, including resistance to therapy. To investigate this hypothesis, the authors examined varying grades of gliomas for stem cell marker expressions and histopathological changes between primary and recurrent tumors. METHODS: Tumor samples were collected during surgery from 70 patients with varying grades of gliomas (Grade II in 12 patients, Grade III in 16, and Grade IV in 42) prior to any adjuvant treatment. The samples were subjected to immunohistochemistry for MIB-1, factor VIII, GFAP, and stem cell markers (CD133 and nestin). Histopathological changes were compared between primary and recurrent tumors in 31 patients after radiation treatment and chemotherapy, including high-dose irradiation with additional stereotactic radiosurgery. RESULTS: CD133 expression on glioma cells was confined to de novo glioblastomas but was not observed in lower-grade gliomas. In de novo glioblastomas, the mean percentage of CD133-positive glioma cells in sections obtained at recurrence was 12.2% ± 10.3%, which was significantly higher than that obtained at the primary surgery (1.08% ± 1.78%). CD133 and Ki 67 dual-positive glioma cells were significantly increased in recurrent de novo glioblastomas as compared with those in primary tumors (14.5% ± 6.67% vs 2.16% ± 2.60%, respectively). In contrast, secondary glioblastomas rarely expressed CD133 antigen even after malignant progression following radiotherapy and chemotherapy. CONCLUSIONS: The authors' results indicate that CD133-positive glioma stem cells could survive, change to a proliferative cancer stem cell phenotype, and cause recurrence in cases with de novo glioblastomas after radiotherapy and chemotherapy.

Chronic subdural hematoma - an up-to-date concept.

Chronic subdural hematoma (CSDH) is prevalent among elderly populations worldwide, and its mysterious pathogenesis has been discussed in the literature for decades. The issues remaining to be solved in regard to CSDH include the initiating events; the bleeding into the subdural space and the formation of the outer and inner membranes, its development; increase and liquefaction of hematoma, the optimal treatments, and the natural history. The pathophysiology is becoming more clear due to recent findings from computed tomography studies and human models of CSDH. In this work, we review previous studies on CSDH and present a new integrated concept about the development of this common condition after head injuries.

Clinical features of familial juvenile cases of moyamoya disease: analysis of patients treated in a single institute over a 28-year period.

OBJECT: The authors compared the clinical features between familial and sporadic cases of moyamoya disease (MMD) by retrospectively analyzing data on patients with MMD registered in the database of Tokyo Medical and Dental University over a period of 28 years. METHODS: In total, 383 patients with hospital records at Tokyo Medical and Dental University from 1980 to 2007 were registered into the database. The data on all of these patients were retrospectively reviewed to clarify the occurrence of familial cases. Clinical features of child or adolescent patients (< 20 years of age) with MMD were compared between familial and sporadic cases in a subgroup of patients who were registered after 1995, initially diagnosed using MR angiography, and assessed using an intelligence scale. RESULTS: Familial occurrence was observed in 59 patients (15.4%) in 40 pedigrees. The clinical features of juvenile patients were analyzed in 124 patients, 22 (17.7%) of whom had familial histories. In comparison with the sporadic cases, patients with familial histories were significantly younger at onset (4.7 vs 6.6 years old), had significantly more cortical infarction (59.1% vs 25.5%), and had significantly more stenoocclusive lesions in the posterior cerebral artery (45.4% vs 24.5%). The rate of patients with intellectual disturbance (intelligence quotient < 75) was significantly larger in the familial cases (47.4%) than in the sporadic cases (17.8%). CONCLUSIONS: This survey of the clinical features of familial MMD suggests that patients with familial MMD had a more serious clinical course in childhood than the sporadic MMD cases.

Combined extradural subtemporal and anterior transpetrosal approach to tumors located in the interpeduncular fossa and the upper clivus.

BACKGROUND: Central skull base lesions in the interpeduncular fossa and the upper clival regions can be challenging to access because of their location anterior to the brainstem. We have modified the anterior transpetrosal approach by combination with the extradural subtemporal route to increase the surgical corridor. METHODS: Thirty-seven patients underwent surgical treatment via the anterior transpetrosal approach from 2002 to 2012. The combined surgical approach was primarily applied when the tumors arose from the upper clival portion and extended to the interpeduncular fossa. The combined approach was used in seven of these patients, comprising four patients with petroclival meningiomas, one patient with sphenoclival meningiomas, one patient with trigeminal schwannoma, and one patient with an epidermoid cyst extending from the interpeduncular fossa to the prepontine cistern. RESULTS: The combined approach permitted excellent visualization of the interpeduncular fossa in addition to the upper clivus and the lateral aspect of the brain stem. Mobilization of the temporal lobe by the entire epidural dissection of the lateral wall of the cavernous sinus facilitates access via the subtemporal route. The transient symptom of the temporal lobe in the dominant site may be the only drawback for this combined approach, although it may disappear immediately after the surgery. CONCLUSION: The present approach combines Dolenc's approach and Kawase's approach, providing a wide exposure to lesions of the interpeduncular fossa and the clivus.

Three-dimensional quantification of susceptibility artifacts from various metals in magnetic resonance images.

Susceptibility artifacts generated in magnetic resonance (MR) images were quantitatively evaluated for various metals using a three-dimensional (3-D) artifact rendering to demonstrate the correlation between magnetic susceptibility and artifact volume. Ten metals (stainless steel, Co-Cr alloy, Nb, Ti, Zr, Mo, Al, Sn, Cu and Ag) were prepared, and their magnetic susceptibilities measured using a magnetic balance. Each metal was embedded in a Ni-doped agarose gel phantom and the MR images of the metal-containing phantoms were taken using 1.5 and 3.0 T MR scanners under both fast spin echo and gradient echo conditions. 3-D renderings of the artifacts were constructed from the images and the artifact volumes were calculated for each metal. The artifact volumes of metals decreased with decreasing magnetic susceptibility, with the exception of Ag. Although Sn possesses the lowest absolute magnetic susceptibility (1.8×10(-6)), the artifact volume from Cu (-7.8×10(-6)) was smaller than that of Sn. This is because the magnetic susceptibility of Cu was close to that of the agarose gel phantom (-7.3×10(-6)). Since the difference in magnetic susceptibility between the agarose and Sn is close to that between the agarose and Ag (-17.5×10(-6)), their artifact volumes were almost the same, although they formed artifacts that were reversed in all three dimensions.

Cerebral ischemia model using mongolian gerbils-comparison between unilateral and bilateral carotid occlusion models.

We permanently occluded unilaterally and/or bilaterally the carotid arteries of anesthetized Mongolian gerbils (60-80 g) and compared the two models. In the former, stroke-positive animals were selected by calculating the stroke index score of the conscious animals. Selection was not made in the latter. We measured the rCBF of the cerebral cortex, hippocampus, and diencephalon using the (3)H-nicotine scintillation method; analyzed the EEG using the wave-form recognition method (Fujimori); measured ATP, PCr (phosphocreatine), lactate, and glucose content in the cerebral hemisphere using the Lowry method; and measured infarct size on HE-stained coronal sections. All parameter values were uniform in the gerbils of the unilateral model, whereas great variation was observed in the right and left cerebral cortex, hippocampus, and diencephalon in the bilateral occlusion model. Therefore, we have discarded the bilateral model and used the stroke-positive unilateral model only.By changing the length of time of the unilateral carotid occlusions and intervals, we found that two 10-min unilateral carotid occlusions with a 5-h interval between them achieved a threshold ischemic insult in gerbils, which produced uniform cortical focal infarctions that evolved in the maturing DSNN on the coronal surface sectioned at the chiasmatic level (Face A). This model showed a marked reduction in the occurrence of ischemic epilepsy and death.

A selective adenosine A2A receptor antagonist ameliorated hyperlocomotion in an animal model of lateral fluid percussion brain injury.

Increased concentration of extracellular adenosine after brain injury is supposed to be one of the causes of secondary brain damage. The purpose of the present study is to examine whether or not administration of adenosine A2A receptor antagonist may be efficacious in ameliorating neurological symptoms by blocking secondary brain damage through cascades initiated by adenosine A2a receptor.Mongolian gerbils were divided into four groups: the trauma-medication (T-M), trauma-saline (T-S), sham-medication (S-M), and sham-saline (S-S) groups. Trauma groups received lateral fluid percussion injury. Medication groups received i.p. injection of SCH58261 (selective adenosine A2A receptor antagonist) until the fifth post-injury day. Open-field locomotion test and grabbing test were conducted before and 1, 3, 5, 7, and 9 days after injury.The total distance of movement in the T-S group was significantly greater than in the other three groups at all time points. In the T-M group, administration of SCH58261 significantly blocked hyperlocomotion, which was observed in the T-S group. There was no significant difference in the total distance among the T-M, S-M, and S-S groups. In the grabbing test, grabbing time was significantly increased in the T-S group 3, 5, 7, and 9 days after the operation. SCH58261 also improved grabbing time in the T-M group.Adenosine A2A antagonist successfully suppressed the trauma-induced hyperlocomotion, presumably by blocking secondary brain damage.

PET molecular imaging to investigate higher brain dysfunction in patients with neurotrauma.

INTRODUCTION: Many neurotrauma patients suffer from higher brain dysfunction even when focal brain damage is not detected with MRI. We performed functional imaging with positron emission tomography (PET) to clarify the relationship between the functional deficit and symptoms of such patients. METHODS: Patients who complain of higher brain dysfunction without apparent morphological cortical damage were recruited. Thirteen patients underwent PET study to image glucose metabolism by (18)F-FDG, and central benzodiazepine receptor (cBZD-R) by (11)C-flumazenil, together with measurement of cognition. RESULTS: Diffuse axonal injury (DAI) patients have a significant decrease in glucose metabolism and cBZD-R distribution in the cingulated cortex than normal controls. Score of cognition test was variable among patients. The degree of decreased glucose metabolism and cBZD-R in the dominant hemisphere corresponded well to the severity of cognitive disturbance. Patients with a milder type of diffuse brain injury (i.e., cerebral concussion) also showed abnormal glucose metabolism and cBZD-R distribution when they suffered from cognitive deficit. CONCLUSION: PET molecular imaging was useful for depicting the cortical dysfunction of neurotrauma patients even when morphological change was not apparent. This method may be promising in clarifying the pathophysiology of higher brain dysfunction of patients with neurotrauma, but without morphological abnormality.

Transcranial direct current stimulation improves swallowing function in stroke patients.

BACKGROUND: Poststroke dysphagia can persist, leading to many complications. OBJECTIVE: We investigated whether noninvasive brain stimulation to the pharyngeal motor cortex combined with intensive swallowing therapy can improve dysphagia. METHODS: A total of 20 patients who had dysphagia for at least 1 month after stroke were randomly assigned to receive 10 sessions lasting 20 minutes each of either 1-mA anodal transcranial direct current stimulation (tDCS) or a sham procedure to the ipsilesional pharyngeal motor cortex, along with simultaneous conventional swallowing therapies. We evaluated swallowing function with the dysphagia outcome and severity scale (DOSS) before, immediately after, and 1 month after the last session. RESULTS: Anodal tDCS resulted in an improvement of 1.4 points in DOSS (P = .006) immediately after the last session and 2.8 points (P = .004) 1 month after the last session. The sham tDCS group improved 0.5 points (P = .059) after the last session and 1.2 points (P = .026) 1 month after the final session. The improvements in the anodal tDCS group were significantly greater than those in the sham tDCS group (P = .029 after the last session, and P = .007 1 month after the last session). CONCLUSIONS: Anodal tDCS to the ipsilesional hemisphere and simultaneous peripheral sensorimotor activities significantly improved swallowing function as assessed by the DOSS.

Chronic encapsulated expanding hematoma in nonfunctioning pituitary adenoma.

The diagnosis and treatment of pituitary macroadenomas with entire hematoma fluid accumulation are problematic. Such lesions are often difficult to completely resect, and recurrence is not uncommon. We present five cases of pituitary macroadenomas entirely composed of hematoma fluid and investigated their histopathology to clarify the mechanism of the hematoma fluid accumulation. Five patients with pituitary adenoma and significant intra-tumor hematoma underwent transsphenoidal resection and were retrospectively reviewed for their clinical status, findings on magnetic resonance imaging (MRI), intraoperative findings, and histopathology. The specific surgical techniques used to address these cases were also reviewed. All patients were diagnosed with nonfunctioning pituitary adenomas by histopathological examination. MRI showed all tumors extended to the cavernous sinus. Histopathology showed tumor tissues were located between the thick granulation tissue and the pseudocapsule of the tumor. The thick granulation tissues were composed of collagenous layers, neovascular vessels, and necrotic red blood cells, indicating repeat hemorrhage from the granulation tissues. The boundary between adenoma and normal pituitary gland was identified during surgical removal in four patients and was not identified in the other patient who showed a recurrence 2 years later. Clinical and histopathological findings indicate hematoma fluid accumulation in the present cases is caused by repeat hemorrhage from the reactive granulation tissues and can be regarded as a chronic encapsulated expanding hematoma. In these cases, the boundary between adenoma and normal pituitary gland should be identified before puncturing the hematoma fluid to minimize the risk of tumor recurrence.

Long-term follow-up of surgically treated juvenile patients with Moyamoya disease.

OBJECT: Surgical revascularization is considered an effective treatment for juvenile patients with moyamoya disease (MMD). Yet the long-term outcome in surgically treated patients still needs to be clarified. More than 30 years have passed since the authors' department started intensively treating pediatric patients with MMD using indirect anastomosis techniques. In this study the authors surveyed the current status of these patients. METHODS: Activities of daily living (ADLs) were surveyed and present clinical status was assessed based on the modified Rankin scale (mRS). Cerebrovascular events subsequent to surgical treatment were also recorded. RESULTS: Since 1979, 208 patients younger than 19 years of age with MMD were surgically treated and followed up for > 3 years. Data were available on 172 patients (83%), who had been followed up for a mean of 14.3 years (range 3-32 years). Activity of daily living outcomes were as follows: 138 patients (80.2%) had mRS scores of 0-2, 29 (16.9%) a score of 3, 1 (0.6%) a score of 4, 1 (0.6%) a score of 5, and 3 (1.7%) a score of 6. Cerebrovascular events occurred 8 or more years after surgery in 6 patients (3.4%), that is, 6 hemorrhages and 3 infarctions. The cumulative risk of late-onset stroke at 10, 20, and 30 years after surgical intervention was 0.8%, 6.3%, and 10.0%, respectively. CONCLUSIONS: This long-term survey demonstrated that most surgically treated pediatric patients with MMD maintain good ADL outcomes. However, a significant number of new cerebrovascular events occurred more than 10 years after the initial surgery. Additional follow-up will help to identify which events may occur during the adult years of patients treated as children.

Circulatory characteristics of normovolemia and normotension therapy after subarachnoid hemorrhage, focusing on pulmonary edema.

BACKGROUND AND PURPOSE: Cardiopulmonary complications are common after subarachnoid hemorrhage (SAH), and include pulmonary edema (PE). The purpose of this study was to investigate circulatory characteristics of normovolemia and normotension therapy after SAH using pulse contour analysis, and to reveal the mechanisms of PE after SAH. METHODS: Pulse contour analysis was performed from day 3 until day 12 after the onset of SAH in 49 patients. RESULTS: Global end-diastolic volume index (GEDI) was normal, although net water balance was estimated to be negative and central venous pressure (CVP) was low in all patients. Seven patients (14 %) suffered from pulmonary edema. Cardiac function index (CFI) and global ejection fraction (GEF) were lower in patients with pulmonary edema (PE group) than in patients without PE (non-PE group) throughout the study period (CFI, P≤0.0119; GEF, P≤0.0348). The PE group showed higher GEDI from days 7 to 10, and higher extravascular lung water index (ELWI) throughout the entire study period compared to the non-PE group (GEDI, P≤0.0094; ELWI, P≤0.0077). CONCLUSIONS: The appropriate preload was kept despite negative net water balance and low CVP. PE after SAH was biphasic, with cardiogenic PE caused by low cardiac contractility immediately after SAH, and hydrostatic PE caused by low cardiac contractility and hypervolemia on and after day 7 of SAH. Pulse contour analysis was useful to monitor this unique circulatory change and effective for detecting cardiopulmonary complications after SAH.

The RASSF3 candidate tumor suppressor induces apoptosis and G1-S cell-cycle arrest via p53.

RASSF3 is the smallest member of the RASSF family of proteins that function as tumor suppressors. Unlike other members of this important family, the mechanisms through which RASSF3 suppresses tumor formation remain unknown. Here, we show that RASSF3 expression induces p53-dependent apoptosis and its depletion attenuates DNA damage-induced apoptosis. We found that RASSF3-induced apoptosis depended upon p53 expression. Exogenous expression of RASSF3 induced G(1)-S arrest, which was also p53 dependent. In contrast, loss of RASSF3 promoted cell-cycle progression, abrogated UVB- and VP-16-induced G(1)-S arrest, decreased p53 protein and target gene expression, and prevented DNA repair. RASSF3 was shown to directly interact with and facilitate the ubiquitination of MDM2, the E3 ligase that targets p53 for degradation, thereby increasing p53 stabilization. Together, our findings show the tumor suppressor activity of RASSF3, which occurs through p53 stabilization and regulation of apoptosis and the cell cycle.

[Slowly progressive expanding hematoma in the Basal Ganglia: a report of 3 cases and a literature review].

We demonstrate and discuss slowly progressive expanding hematoma (SPEH) in the basal ganglia, which expands over 2 weeks. To our knowledge, there have been only 5 cases of sudden-onset SPEH of the basal ganglia. To this, we add 3 cases admitted our hospitals because of putaminal hemorrhage within 1.5 hours of onset. All hematomas exhibited "2 components of hematoma sign" on initial CT scans, which we termed the "TCH sign" characterized as an anterolateral fluid portion and a posteromedial solid portion. Follow-up CT scans revealed gradual expansion of the fluid component of the hematoma without rebleeding for the subacute phase. Two cases were treated surgically. The first case, a 47-year-old man, underwent ultrasonically guided hematoma aspiration on day 17 and the second case, a 37-year-old man, underwent hematoma removal by craniotomy on day 23 after onset. Their postoperative courses were uneventful. The third case, a 57-year-old man, improved without surgical treatment and the hematoma dissolved completely within 2 months. To an extent, the TCH sign on a CT scan can be related to SPEH. We reviewed previous reports, including those an chronic expanding intracerebral hematomas and chronic encapsulated intracerebral hematomas, and concluded that it requires approximately 1 month for encapsulation of the hematoma to emerge. We suggest a possible progressive mechanism of SPEH. At first, the hematoma is divided into a fluid and a solid portion. Local generation of osmotically active molecules by clot degradation may allow intravascular fluid to escape into the fluid portion of the hematoma. Edema fluid with leakage via the disrupted blood-brain barrier may also aggravate the fluid portion of the hematoma. The continuing inflammatory response leads to the emergence of a hematoma capsule similar to the membrane observed in cases of chronic subdural hematoma, followed by the secondary causes of hematoma expansion. We discuss feasible timing and surgical treatment methods.