Combination of Single- and Paired-Pulse Somatosensory Evoked Potentials in Ischemic Monitoring: Preliminary Investigation in Carotid Endarterectomy.

Introduction Severe ischemia induces cerebral excitability imbalance before completion of infarct. To investigate the clinical availability of this imbalance with ischemic monitoring, paired-pulse somatosensory evoked potentials (SEPs) were performed in conjunction with conventional SEPs during carotid endarterectomy. Methods For carotid endarterectomy patients with hemodynamic deficits of the middle cerebral artery area (n = 34), the excitability imbalances (Q) were measured by paired-pulse SEPs, wherein the second response (A2) was divided by the first (A1; Q = A2/A1). Regional cerebral saturation (rSO2) was also measured. Occlusion was performed twice using shunting. Results Each carotid occlusion induced a significant decrease in mean A1 and rSO2, and an increase in mean Q values (p < 0.001), which returned to the baseline level after occlusion. While neuronal imbalances were mostly transient, persistently increased Q values were observed in four cases (11.8%), all indicating postoperative abnormalities in diffusion-weighted magnetic resonance imaging (100%). Meanwhile, A1 detected the postoperative abnormality in only one case (25%). Preoperative Q values at the time of surgery were significantly higher in symptomatic patients having the upper limb deficits than those without (p < 0.01), indicating persistent or permanent imbalances. Conclusion Paired-pulse SEPs reliably identified transient, persistent or permanent neuronal imbalances, depending on the ischemic severity. These preliminary results indicated that paired-pulse SEPs, in combination with conventional SEPs (A1), may offer better ischemic monitoring.

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.

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.

Cannabinoid Receptor Type 2 Agonist Attenuates Acute Neurogenic Pulmonary Edema by Preventing Neutrophil Migration after Subarachnoid Hemorrhage in Rats.

We evaluated whether JWH133, a selective cannabinoid type 2 receptor (CB2R) agonist, prevented neurogenic pulmonary edema (NPE) after subarachnoid hemorrhage (SAH) by attenuating inflammation. Adult male rats were assigned to six groups: sham-operated, SAH with vehicle, SAH with JWH133 (0.3, 1.0, or 3.0 mg/kg) treatment 1 h after surgery, and SAH with JWH133 (1.0 mg/kg) at 1 h with a selective CB2R antagonist, SR144528 (3.0 mg/kg). The perforation model of SAH was performed and pulmonary wet-to-dry weight ratio was evaluated 24 and 72 h after surgery. Western blot analyses and immunohistochemistry were evaluated 24 h after surgery. JWH133 (1.0 mg/kg) significantly and most strongly improved lung edema 24 h after SAH. SR144528 administration significantly reversed the effects of JWH133 (1.0 mg/kg). SAH-induced increasing levels of myeloperoxidase (MPO) and decreasing levels of a tight junction (TJ) protein, junctional adhesion molecule (JAM)-A, were ameliorated by JWH133 (1.0 mg/kg) administration 24 h after SAH. Immunohistochemical assessment also confirmed substantial leukocyte infiltration in the outside of vessels in SAH, which were attenuated by JWH133 (1.0 mg/kg) injection. CB2R agonist ameliorated lung permeability by inhibiting leukocyte trafficking and protecting tight junction proteins in the lung of NPE after SAH.

Subarachnoid Hemorrhage-Triggered Acute Hypotension Is Associated with Left Ventricular Cardiomyocyte Apoptosis in a Rat Model.

Whether hypotension that occurs due to neurogenic stunned myocardium after subarachnoid hemorrhage (SAH) is associated with cardiomyocyte apoptotic cell death remains unknown. In this study, 18 male rats were subjected to sham or the endovascular perforation model of SAH surgery. Based on the mean arterial pressure (MAP) after SAH, rats were separated into SAH with hypotension (SAH hypotension) or SAH with blood pressure preservation (SAH BP preservation) groups. All animals were euthanized 2 h after the surgical procedure. Hearts were removed and separated transversely into base and apex parts, then Western blot analyses and immunohistochemistry were performed only in the apex part. One rat died as a result of severe SAH and two rats with mild SAH were excluded. We analyzed data from 15 rats that were divided into three groups: sham, SAH hypotension, and SAH BP preservation (n = 5, each). There was a significantly higher cleaved caspase-3/caspase-3 ratio in the SAH hypotension group compared with sham and the SAH BP preservation group. Cardiomyocyte apoptosis was demonstrated in the SAH rats. This is the first experimental report that describes SAH-induced neurogenic stunned myocardium with ensuing hypotension may result from the acute apoptotic cardiomyocyte cell death in the left ventricle.

Primary intraosseous meningioma in the calvaria: morphological feature changes on magnetic resonance images over several years.

Primary intraosseous meningiomas (PIMs) are rare, and their pathogenesis remains unclear. We report the case of a sizable PIM in the calvaria that progressively enlarged over several years and presented temporal changes in the morphological features on magnetic resonance images. Along with discussing the case, we further emphasize the potential pitfalls of diagnosing a PIM in the calvaria.

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.

Cannabinoid receptor type 2 agonist attenuates apoptosis by activation of phosphorylated CREB-Bcl-2 pathway after subarachnoid hemorrhage in rats.

Early brain injury (EBI) which comprises of vasogenic edema and apoptotic cell death is an important component of subarachnoid hemorrhage (SAH) pathophysiology. This study evaluated whether cannabinoid receptor type 2 (CB2R) agonist, JWH133, attenuates EBI after SAH and whether CB2R stimulation reduces pro-apoptotic caspase-3 via up-regulation of cAMP response element-binding protein (CREB)-Bcl-2 signaling pathway. Male Sprague-Dawley rats (n=123) were subjected to SAH by endovascular perforation. Rats received vehicle or JWH133 at 1h after SAH. Neurological deficits and brain water content were evaluated at 24h after SAH. Western blot was performed to quantify phosphorylated CREB (pCREB), Bcl-2, and cleaved caspase-3 levels. Neuronal cell death was evaluated with terminal deoxynucleotidyl transferase-mediated uridine 5'-triphosphate-biotin nick end-labeling staining. Additionally, CREB siRNA was administered to manipulate the proposed pathway. JWH133 (1.0mg/kg) improved neurological deficits and reduced brain water content in left hemisphere 24h after SAH. JWH133 significantly increased activated CREB (pCREB) and Bcl-2 levels and significantly decreased cleaved caspase-3 levels in left hemisphere 24h after SAH. CREB siRNA reversed the effects of treatment. TUNEL positive neurons in the cortex were reduced with JWH133 treatment. Thus, CB2R stimulation attenuated EBI after SAH possibly through activation of pCREB-Bcl-2 pathway.

Cannabinoid type 2 receptor stimulation attenuates brain edema by reducing cerebral leukocyte infiltration following subarachnoid hemorrhage in rats.

Early brain injury (EBI), following subarachnoid hemorrhage (SAH), comprises blood-brain barrier (BBB) disruption and consequent edema formation. Peripheral leukocytes can infiltrate the injured brain, thereby aggravating BBB leakage and neuroinflammation. Thus, anti-inflammatory pharmacotherapies may ameliorate EBI and provide neuroprotection after SAH. Cannabinoid type 2 receptor (CB2R) agonism has been shown to reduce neuroinflammation; however, the precise protective mechanisms remain to be elucidated. This study aimed to evaluate whether the selective CB2R agonist, JWH133 can ameliorate EBI by reducing brain-infiltrated leukocytes after SAH. Adult male Sprague-Dawley rats were randomly assigned to the following groups: sham-operated, SAH with vehicle, SAH with JWH133 (1.0mg/kg), or SAH with a co-administration of JWH133 and selective CB2R antagonist SR144528 (3.0mg/kg). SAH was induced by endovascular perforation, and JWH133 was administered 1h after surgery. Neurological deficits, brain water content, Evans blue dye extravasation, and Western blot assays were evaluated at 24h after surgery. JWH133 improved neurological scores and reduced brain water content; however, SR144528 reversed these treatment effects. JWH133 reduced Evans blue dye extravasation after SAH. Furthermore, JWH133 treatment significantly increased TGF-ß1 expression and prevented an SAH-induced increase in E-selectin and myeloperoxidase. Lastly, SAH resulted in a decreased expression of the tight junction protein zonula occludens-1 (ZO-1); however, JWH133 treatment increased the ZO-1 expression. We suggest that CB2R stimulation attenuates neurological outcome and brain edema, by suppressing leukocyte infiltration into the brain through TGF-ß1 up-regulation and E-selectin reduction, resulting in protection of the BBB after SAH.

Multiple intracranial nodules associated with rheumatoid arthritis: case report.

A 71-year-old woman with active rheumatoid arthritis (RA) was referred to our department because of multiple intracranial nodules. On admission, the RA disease activity was very high even after the treatment of methotrexate in other hospital. She underwent open biopsy to confirm a histopathological diagnosis of the intracranial lesions. Surgical specimen mainly consisted of necrosis surrounded by epithelioid cells. The masses were reduced spontaneously in size without additional treatment. Eleven month later, the lesions were relapsed. She underwent treatment with corticosteroid, and the lesions were remarkably regressed. The clinical course and histological examination were compatible with rheumatoid nodule (RN). Intracranial RN is extremely rare and its clinical course is not completely understood. In active RA patients, RNs should be considered, and histological diagnosis is inevitable for following suitable treatment.

Severe subarachnoid hemorrhage associated with cerebral venous thrombosis in early pregnancy: a case report.

BACKGROUND: Cerebral venous thrombosis (CVT) rarely induces subarachnoid hemorrhage (SAH). During late pregnancy and puerperium, CVT is an uncommon but important cause of stroke. However, severe SAH resulting from CVT is extremely rare during early pregnancy. OBJECTIVE: We report on a rare case of severe SAH due to CVT, and discuss the potential pitfalls of CVT diagnosis in early pregnancy. CASE REPORT: A 32-year-old pregnant woman (9th week of pregnancy) presented with slight head dullness. Initial magnetic resonance imaging (MRI) revealed focal, abnormal signal intensity in the left thalamus. Nine days later, the patient developed a generalized seizure and severe SAH was detected with computed tomography (CT) scan. MRI and cerebral angiography revealed a completely thrombosed superior sagittal sinus, vein of Galen, straight sinus, and right transverse sinus. Transvaginal sonography indicated a missed abortion. The day after admission, the patient presented again with a progressive loss of consciousness and signs of herniation. The patient underwent emergency decompressive craniotomy, followed by intrauterine curettage. Two months later, she made an excellent recovery except for a slight visual field defect. CONCLUSIONS: A rare case of severe SAH due to CVT is reported, with emphasis on the potential pitfalls of CVT diagnosis in early pregnancy.

Early brain injury, an evolving frontier in subarachnoid hemorrhage research.

Subarachnoid hemorrhage (SAH), predominantly caused by a ruptured aneurysm, is a devastating neurological disease that has a morbidity and mortality rate higher than 50%. Most of the traditional in vivo research has focused on the pathophysiological or morphological changes of large-arteries after intracisternal blood injection. This was due to a widely held assumption that delayed vasospasm following SAH was the major cause of delayed cerebral ischemia and poor outcome. However, the results of the CONSCIOUS-1 trial implicated some other pathophysiological factors, independent of angiographic vasospasm, in contributing to the poor clinical outcome. The term early brain injury (EBI) has been coined and describes the immediate injury to the brain after SAH, before onset of delayed vasospasm. During the EBI period, a ruptured aneurysm brings on many physiological derangements such as increasing intracranial pressure (ICP), decreased cerebral blood flow (CBF), and global cerebral ischemia. These events initiate secondary injuries such as blood-brain barrier disruption, inflammation, and oxidative cascades that all ultimately lead to cell death. Given the fact that the reversal of vasospasm does not appear to improve patient outcome, it could be argued that the treatment of EBI may successfully attenuate some of the devastating secondary injuries and improve the outcome of patients with SAH. In this review, we provide an overview of the major advances in EBI after SAH research.

Hyperbaric oxygen preconditioning attenuates hyperglycemia-enhanced hemorrhagic transformation by inhibiting matrix metalloproteinases in focal cerebral ischemia in rats.

Hyperglycemia dramatically aggravates brain infarct and hemorrhagic transformation (HT) after ischemic stroke. Oxidative stress and matrix metalloproteinases (MMPs) play an important role in the pathophysiology of HT. Hyperbaric oxygen preconditioning (HBO-PC) has been proved to decrease oxidative stress and has been demonstrated to be neuroprotective in experimental stroke models. The present study determined whether HBO-PC would ameliorate HT by a pre-ischemic increase of reactive oxygen species (ROS) generation, and a suppression of MMP-2 and MMP-9 in hyperglycemic middle cerebral artery occlusion (MCAO) rats. Rats were pretreated with HBO (100% O2, 2.5 atmosphere absolutes) 1 h daily for 5 days before MCAO. Acute hyperglycemia was induced by an injection of 50% dextrose. Neurological deficits, infarction volume and hemorrhagic volume were assessed 24 h and 7 days after ischemia. ROS scavenger n-acetyl cysteine (NAC), hypoxia-inducible factor-1α (HIF-1α), inhibitor 2-methoxyestradiol (2ME2) and activator cobalt chloride (CoCl2), and MMP inhibitor SB-3CT were administrated for mechanism study. The activity of MMP-2 and MMP-9, and the expression HIF-1α were measured. HBO-PC improved neurological deficits, and reduced hemorrhagic volume; the expression of HIF-1α was significantly decreased, and the activity of MMP-2 and MMP-9 was reduced by HBO-PC compared with vehicle group. Our results suggested that HBO-PC attenuated HT via decreasing HIF-1α and its downstream MMP-2 and MMP-9 in hyperglycemic MCAO rats.

Delayed hyperbaric oxygen therapy induces cell proliferation through stabilization of cAMP responsive element binding protein in the rat model of MCAo-induced ischemic brain injury.

Treatments that could extend the therapeutic window of opportunity for stroke patients are urgently needed. Early administration of hyperbaric oxygen therapy (HBOT) has been proven neuroprotective in the middle cerebral artery occlusion (MCAo) in rodents. Our aim was to determine: 1) whether delayed HBOT after permanent MCAo (pMCAo) can still convey neuroprotection and restorative cell proliferation, and 2) whether these beneficial effects rely on HBO-induced activation of protein phosphatase-1γ (PP1-γ) leading to a decreased phosphorylation and ubiquitination of CREB and hence its stabilization. The experiments were performed in one hundred thirty-two male Sprague-Dawley rats with the body weight ranging from 240 to 270 g. Permanent MCAo was induced with the intraluminal filament occluding the right middle cerebral artery (MCA). In the first experiment, HBOT (2.5 ATA, 1h daily for 10 days) was started 48 h after pMCAo. Neurobehavioral deficits and infarct size as well as cyclic AMP response element-binding protein (CREB) expression and BrdU-DAB staining in the hippocampus and the peri-infarct region were evaluated on day 14 and day 28 post-MCAo. In the second experiment, HBOT (2.5 ATA, 1h) was started 3h after pMCAo. The effects of CREB siRNA or PP1-γ siRNA on HBO-induced infarct size alterations and target protein expression were studied. HBOT started with 48 h delay reduced infarct size, ameliorated neurobehavioral deficits and increased protein expression of CREB, resulting in increased cell proliferations in the hippocampus and peri-infarct region, on day 14 and day 28 post-MCAo. In the acute experiment pMCAo resulted in cerebral infarction and functional deterioration and reduced brain expression of PP1-γ, which led to increased phosphorylation and ubiquitination of CREB 24h after MCAo. However HBOT administered 3h after ischemia reversed these molecular events and resulted in CREB stabilization, infarct size reduction and neurobehavioral improvement. Gene silencing with CREB siRNA or PP1-γ siRNA reduced acute beneficial effects of HBO. In conclusion, delayed daily HBOT presented as potent neuroprotectant in pMCAo rats, increased CREB expression and signaling activity, and bolstered regenerative type cell proliferation in the injured brain. As shown in the acute experiment these effects of HBO were likely to be mediated by reducing ubiquitin-dependent CREB degradation owing to HBO-induced activation of PP1γ.

Hyperbaric oxygen preconditioning attenuates hyperglycemia enhanced hemorrhagic transformation after transient MCAO in rats.

BACKGROUND: Hemorrhagic transformation (HT) can be a devastating complication of ischemic stroke. Hyperbaric oxygen preconditioning (HBO-PC) has been shown to improve blood-brain barrier (BBB) permeability in stroke models. The purpose of this study is to examine whether HBO-PC attenuates HT after focal cerebral ischemia, and to investigate whether the mechanism of HBO-PC against HT includes up-regulation of antioxidants in hyperglycemic rats. METHODS: Male Sprague-Dawley rats (280-320 g) were divided into the following groups: sham, middle cerebral artery occlusion (MCAO) for 2 h, and MCAO treated with HBO-PC. HBO-PC was conducted giving 100% oxygen at 2.5 atm absolute (ATA), for 1 h at every 24 h interval for 5 days. At 24 h after the last session of HBO-PC, rats received an injection of 50% glucose (6 ml/kg intraperitoneally) and were subjected to MCAO 15 min later. At 24 h after MCAO, neurological behavior tests, infarct volume, blood-brain barrier permeability, and hemoglobin content were measured to evaluate the effect of HBO-PC. Western blot analysis of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) was evaluated at multiple time-points before and after MCAO. RESULTS: HBO-PC improved neurological behavior test, and reduced infarction volume, HT and Evans blue extravasation in the ipsilateral hemisphere at 24 h after MCAO. Western blot analysis failed to demonstrate up-regulation of Nrf2 in HBO-PC group before and after MCAO. Paradoxically, HBO-PC decreased HO-1 expression at 24 h after MCAO, as compared with htMCAO group. CONCLUSIONS: HBO-PC improved neurological deficits, infarction volume, BBB disruption, and HT after focal cerebral ischemia. However, its mechanism against focal cerebral ischemia and HT may not include activation of Nrf2 and subsequent HO-1 expression.

Inhibition of Rho kinase by hydroxyfasudil attenuates brain edema after subarachnoid hemorrhage in rats.

The blood-brain barrier (BBB) disruption and brain edema are important pathophysiologies of early brain injury after subarachnoid hemorrhage (SAH). This study is to evaluate whether Rho kinase (Rock) enhances BBB permeability via disruption of tight junction proteins during early brain injury. Adult male rats were assigned to five groups; Sham-operated, SAH treated with saline, a Rock inhibitor hydroxyfasudil (HF) (10 mg/kg) treatment at 0.5 h after SAH, HF treatment at 0.5 and 6 h (10 mg/kg, each) after SAH, and another Rock inhibitor Y27632 (10 mg/kg) treatment at 0.5 h after SAH. The perforation model of SAH was performed and neurological score and brain water content were evaluated 24 and 72 h after surgery. Evans blue extravasation, Rock activity assay, and western blotting analyses were evaluated 24 h after surgery. Treatment of HF significantly improved neurological scores 24 h after SAH. Single treatment with HF and Y27632, and two treatments with HF reduced brain water content in the ipsilateral hemisphere. HF reduced Evans blue extravasation in the ipsilateral hemisphere after SAH. Rock activity increased 24 h after SAH, and HF reversed the activity. SAH significantly decreased the levels of tight junction proteins, occludin and zonula occludens-1 (ZO-1), and HF preserved the levels of occluding and ZO-1 in ipsilateral hemisphere. In conclusion, HF attenuated BBB permeability after SAH, possibly by protection of tight junction proteins.

Rapid progression of rhabdoid components of a composite high-grade glioma and rhabdoid tumor in the occipital lobe of an adult.

We report a very unusual case of a composite high-grade glioma and rhabdoid tumor in an adult. A 22-year-old woman presented with scintillating scotoma due to a solid tumor with surrounding brain edema in the right occipital lobe. The tumor was grossly resected. Histological examinations showed that the tumor was mainly composed of INI1-positive high-grade glioma tissue containing an INI1-negative rhabdoid component. She received radiation therapy and chemotherapy. Three months after the surgery, she again complained of visual disturbances, and tumor recurrence within the resection cavity was noted. A second operation was performed. The findings of histological examinations of the surgical specimen obtained during the second surgery were completely different from those of the specimen obtained during the initial surgery. Only the rhabdoid component showed remarkable proliferation and did not express INI1. Diffuse dissemination along the craniospinal axis eventually progressed, and she died 5 months after the initial diagnosis. We suggest that the inactivation of the INI1 gene affects potent proliferation activity and resistance to both chemotherapy and radiation therapy.

Focal leptomeningeal metastasis following curative surgery for lung cancer: case report.

A 58-year-old woman presented with 4 lesions of pulmonary adenocarcinoma which were curatively resected. No adjuvant therapy was needed because the lesions were all in the early stage. Magnetic resonance (MR) imaging of the brain, taken 10 months after the curative surgery, disclosed focal enhancement along the right central sulcus. Cerebrospinal fluid examination was normal. The lesion remained stable for 16 months, then began to spread out. She underwent open biopsy and the histological diagnosis was leptomeningeal metastasis from adenocarcinoma. She was treated with gefitinib at first because the lesion expressed epidermal growth factor receptor domain mutation. However, the lesion continued to enlarge, so she underwent whole cranial irradiation which was not effective. She died 2 years 10 months after the first detection of the metastasis. Early histological diagnosis is important even though the MR imaging lesion is not likely to be metastasis after curative surgery of the primary lesions.