Safety profile of clozapine: Analysis using national registry data in Japan.

Clozapine is the only effective antipsychotic drug used for the treatment of treatment-resistant schizophrenia. Although it has been shown that the frequency of clozapine use is very low in Japan, our previous study revealed that the number of clozapine prescriptions has been increasing in recent years, and that risk factors leading to discontinuation of clozapine were also identified as age ≥40 years, poor tolerability to olanzapine, previous treatment with clozapine, and white blood cell count <6000/mm3. The main cause for discontinuation of clozapine is the occurrence of a wide range of adverse events, including neutropenia/leukopenia and fatal cardiac disorders. In this study, we analyzed the physical details and backgrounds of patients with adverse events that led to clozapine discontinuation using a national registry database of more than 8000 Japanese patients. The physical adverse events that led to discontinuation of clozapine were neutropenia/leukopenia, glucose intolerance, cardiac disorders, gastrointestinal disorders, neuroleptic malignant syndrome, pleurisy, pulmonary embolism, sedation/somnolence, and seizures. Neutropenia/leukopenia had the highest incidence (5.0%). Neutropenia/leukopenia and cardiac disorders tended to occur early in the treatment period, indicating the need for careful monitoring for these adverse events in the early stages of clozapine treatment. Gastrointestinal disorders occurred over a long period of time, suggesting the need for careful observation during the maintenance period. The data obtained in our study will lead to the optimal and safe use of clozapine treatment.

Remote hemorrhage after burr-hole surgery for chronic subdural hematoma: A report of two cases.

BACKGROUND: The standard neurosurgical procedure for chronic subdural hematoma is a burr-hole surgery. Postoperative hemorrhage is one of the complications after burr-hole surgery. The hemorrhage generally occurs at the surgical site; however, remote hemorrhage is rare. Here, we report two cases of remote hemorrhage after burr-hole surgery for chronic subdural hematoma and discuss the possible mechanism underlying this rare complication. CASE DESCRIPTION: Two patients presented remote hemorrhages after burrhole surgery for chronic subdural hematoma. In the first case, hemorrhage occurred in the interhemispheric fissure and contralateral subdural space. In the second case, hemorrhage occurred in the subdural space of the posterior fossa. CONCLUSION: Postoperative remote hemorrhage is a rare complication, and it can occur after both craniotomy surgery and burr-hole surgery. Neurosurgeons should consider the possibility of this rare complication, and sufficient care should be taken to select the most appropriate surgical procedure to prevent remote hemorrhage.

Choroid plexus AVM with anomalous origin of the capsulothalamic artery: A case report.

Background and importance Traditionally, it has been believed that the plexal segment of the anterior choroidal artery (AChoA) can be sacrificed safely. Here, we present a case of choroid plexus arteriovenous malformation (AVM) in which the capsulothalamic artery originated from distal plexal segment of the AChoA. Clinical presentation A 45-year-old man was diagnosed with arteriovenous malformation involving the left inferior horn in screening MRI. Preceding stereotactic radiosurgery, transarterial target embolization was performed. In this procedure, 20% n-butyl-2-cyanoacrylate (NBCA) was successfully injected from the lateral plexal branch of the AChoA. After embolization, right homonymous hemianopsia developed due to cerebral infarction on the left optic radiation. This infarction was considered to be within the territory of the capsulothalamic artery. Conclusion This anomalous capsulothalamic artery might be formed by hemodynamic compromise of the brain surrounding AVM in early gestation. We must be aware of this unusual anatomical variation to avoid ischemic complication in embolization of the AChoA.

Fatal cerebral swelling immediately after cranioplasty: A case report.

BACKGROUND: Cranioplasty is a standard neurosurgical procedure which is performed after decompressive craniotomy. Fatal complications associated with this procedure are not well documented. Here, we report a case of fatal cerebral swelling after cranioplasty and discuss the possible mechanism of this complication. CASE DESCRIPTION: A 64-year-old man was admitted with the diagnosis of cerebral hemorrhage, and emergency surgery for hemorrhage removal and decompressive craniotomy were performed. One month after surgery, cranioplasty was performed using a titanium mesh plate. Sixteen hours after the surgery, the patient became comatose with bilateral dilated pupils followed by blood pressure lowering. Computed tomography of the brain showed bilateral massive cerebral edema. The titanium mesh plate was immediately removed, however, the patient's neurological condition did not recover and he died 7 days after the surgery. We speculated that the negative pressure difference and increase in cerebral blood flow after cranioplasty may have attributed to the fatal cerebral swelling. CONCLUSION: Fatal cerebral swelling after cranioplasty is a rare but devastating complication. Although it is rare, neurosurgeons should keep in mind that this fatal complication can follow cranioplasty.

Usefulness of interventional embolization of the middle meningeal artery for recurrent chronic subdural hematoma: Five cases and a review of the literature.

PURPOSE: Although several strategies against recurrent chronic subdural hematoma (CSDH) have been proposed, no consensus has been established. Recently, middle meningeal artery (MMA) embolization has been proposed as radical treatment for recurrent CSDH. We wanted to estimate the usefulness of MMA embolization for recurrent CSDH. METHODS: From February 2012 to June 2013, 110 patients with CSDH underwent single burr-hole surgery with irrigation and drainage. Among these patients, 13 showed recurrent hematoma formation and were retreated surgically. Furthermore, repeated recurrence of CSDH was observed in six patients. Five of these six patients underwent middle meningeal artery (MMA) embolization with polyvinyl alcohol particles. All five patients with interventional treatment were observed for four to 60 weeks. RESULTS: No more recurrence of CSDH was observed in any of the patients. During the follow-up period, no patients suffered from any side effects or complications from the interventional treatment. CONCLUSION: MMA embolization with careful attention paid to the procedure might be a treatment of choice for recurrent CSDH.

Adult classical glioblastoma with a BRAF V600E mutation.

The B-Raf proto-oncogene serine/threonine kinase (B-Raf) is a member of the Raf kinase family. The BRAF V600E mutation occurs frequently in certain brain tumors such as pleomorphic xanthoastrocytoma, ganglioglioma, and pilocytic astrocytoma, and less frequently in epithelioid and giant cell glioblastoma. BRAF V600E mutation in these cases has been canonically detected using Sanger sequencing or immunohistochemistry but not with next-generation sequencing (NGS). Moreover, to our knowledge, there is no detailed report of the BRAF V600E mutation in an adult glioblastoma with classical histologic features (c-GBM). Therefore, we performed NGS analysis to determine the mutational status of BRAF of 13 glioblastomas (GBMs) (11 primary and 2 secondary cases) and detected one tumor harboring the BRAF V600E mutation. We report here the detection of the BRAF V600E mutation in a patient with c-GBM and describe the patient's clinical course as well as the results of histopathological analysis.

Usefulness of 11C-methionine positron emission tomography for detecting intracranial ameloblastic carcinoma: A case report.

Ameloblastic carcinoma, secondary type, is an extremely rare odontogenic malignant tumor. The present study reports the case of a 58-year-old male with ameloblastic carcinoma that extended into the intracranial space close to the internal carotid artery. Surgical excision was performed, as headaches were being caused via compression by the mass. Small remnants of the tumor remained surrounding the internal carotid artery following surgical resection. Although the remnant tissue was not detected on magnetic resonance imaging or 18F-fluorodeoxyglucose (FDG)-positron emission tomography (PET), it was clearly visualized on 11C-methionine PET in the early post-operative follow-up period. No neurological deficits were exhibited during the follow-up period, and 11C-methionine PET was able to detect the remnant lesion distribution in the intracranial space. The current study presents a rare case of ameloblastic carcinoma that extended into the intracranial space. In addition, several diagnostic imaging tools were compared in order to determine the most suitable imaging modality. At present, the patient is continuing a therapeutic course of radiation and evident mass reduction has been observed. However, the therapeutic effects are currently under consideration. To the best of our knowledge, this is the first study on the effectiveness of using 11C-methionine PET for detecting ameloblastic carcinoma with intracranial extension.

[A case of the myelitis due to Toxocara canis infection complicated with cervical spondylosis].

A 59-year-old male had suffered from numbness of the hands for 7 months. With a diagnosis of cervical spondylosis, he had been treated conservatively at a nearby clinic. After he fell off his bicycle, the numbness intensified and limb weakness developed. Cervical MRI revealed spinal cord compression at the C4/5 and C5/6 levels due to cervical spondylosis with prominent edema in the spinal cord spreading from the C4 to C6 level. The edema was very serious. Therefore, we suspected that the traumatic spinal injury underlying the cervical spondylosis was complicated by another disease. Cervical spinal angiography revealed no apparent vascular disorder. Contrast enhanced MRI showed a small enhanced area in the spinal cord at the C5 level. Because of the rapid progression of gait disturbance, expansive laminoplasty was performed without further examination. Although remarkable amelioration of the symptoms was seen just after the surgery, the symptoms worsened again about 1 month later. The patient's clinical history was reconsidered, revealing that he likes raw bovine liver. Serological examination, because of suspicion of parasitic infection showed elevated titers of anti-Toxocara canis antibody in the serum and cerebrospinal fluid. Administration of albendazole improved the clinical symptoms, and normalized the serological and MRI findings. Myelitis due to T canis infection is a rare disease. For an early and accurate diagnosis, it is important to be fully aware of this disease and to include detailed information on food preferences and pet-keeping in the process of compiling a clinical history.

Histone deacetylase inhibitor, FK228, induces apoptosis and suppresses cell proliferation of human glioblastoma cells in vitro and in vivo.

We investigated the effects of FK228 on cell proliferation and apoptosis against human glioblastoma (GM) T98G, U251MG, and U87MG cells. Upon exposure to FK228, cell proliferation was inhibited, and apoptosis detected by the cleavage of CPP32 was induced. FK228 increased the expression levels of p21 (WAF-1) and of pro-apoptotic Bad protein in all GM cells. Furthermore, FK228 treatment also reduced the anti-apoptotic protein Bcl-xL in all GM cells and anti-apoptotic Bcl-2 in U87MG cells, thereby shifting the cellular equilibrium from life to death. An increased accumulation of histone H4 was detected in the p21 (WAF-1) promoter and the structural gene (exon 2) and the Bad structural gene (exon 2 and 3) upon treatment with FK228, as assessed by chromatin immunoprecipitation (ChIP) assay. Thus, the results indicated that an increased expression of p21 (WAF1) and Bad due to FK228 is regulated, at least in part, by the degree of acetylation of the gene-associated histone. We also found that FK228 inhibits cellular invasiveness and decreases MMP-2 activity. In addition, the growth of transplanted human GM m-3 cells into the subcutaneous tissue of hereditary athymic mice was significantly inhibited, and apoptosis was induced with FK228 treatment. The results suggested that FK228 might be useful in the treatment of human GM, although further studies will be needed.

[Clinical usefulness of multi-planar reconstruction images of three-dimensional computed tomographic angiography for internal carotid artery aneurysms].

The usefulness of multi-planar reconstruction (MPR) images of three-dimensional computed tomographic angiography (3D-CTA) for the diagnosis of internal carotid artery (ICA) aneurysms is described. Eleven unruptured ICA aneurysms including six cases of IC-cavernous aneurysm, two cases of IC-ophthalmic artery aneurysm, two cases of IC-posterior communicating artery aneurysm and one cases of IC-anterior choroidal artery aneurysm, were examined by magnetic resonance angiography (MRA), digital subtraction angiography (DSA), 3D-CTA and its MPR images. 3D-CTA and DSA were useful to identify the aneurysmal neck in small aneurysms, but it was difficult to identify the aneurysmal neck in small aneurysms by 3D-CTA-MPR images. DSA and MRA were not useful for identifying the aneurysmal neck in aneurysms more than 10 mm in diameter, as a precise viewing of the neck could not be found due to their large size. For large aneurysms, neither was 3D-CTA useful for identifying the aneurysmal neck when their large size and surrounding bony structures overlapped the aneurysmal neck. On the other hand, 3D-CTA-MPR was very useful for identifying the aneurysmal neck without overlapping by surrounding bony structures. 3D-CTA-MPR images clearly visualized the calcification of the wall. 3D-CTA-MPR images are obtained from 3D-CTA source images without any additional stress to the patients, and they are more useful for the diagnosis as well as demonstration of the aneurysmal neck particularly in more than large aneurysms.