Daisuke Muta

Bilateral pallidal stimulation for idiopathic segmental axial dystonia advanced from meige syndrome refractory to bilateral thalamotomy

Meige syndrome is an adult‐onset dystonic movement disorder that predominantly involves facial muscles, while some patients with this syndrome develop spasmodic dysphonia and dystonia of the neck, trunk, arms, and legs. We report that all dystonic symptoms that had been refractory to both pharmacotherapy and bilateral thalamotomy were markedly alleviated by bilateral pallidal stimulation in a patient with segmental axial dystonia advanced from Meige syndrome.

Improvement of quality of life in patients surgically treated for asymptomatic unruptured intracranial aneurysms

Objective: To compare the preoperative and postoperative health-related quality of life (QOL) and psychological state of patients with asymptomatic unruptured intracranial aneurysms (ICAs) who underwent elective surgery. Methods: Out of 67 patients who underwent neck clipping of ICAs, we assessed the QOL of 61 patients using Short Form-36 (SF-36); their psychological state was rated on the Hospital Anxiety and Depression Scale (HADS) before, 3 months, and 1 and 3 years after treatment. Results: The preoperative mean scores for each of the eight SF-36 domains except bodily pain were significantly lower in the study population than in the reference population. 14 (20.9%) patients experienced surgical complications defined as neurological deterioration and/or abnormal CT findings within 30 days of the operation. Despite some complications, the QOL of all operated patients returned to the mean level of the reference population 3 years after treatment. At 3 months after surgery, the scores for psychosocial activities and general health perception were transiently below the preoperative levels. According to the HADS, the patients experienced mild anxiety before the operation; it disappeared by the third postoperative month. Conclusions: Preoperatively, patients with unruptured ICAs reported a significantly decreased QOL. It further declined transiently after elective surgery, but it returned to the mean level recorded for the reference population within 3 years. Our findings suggest that these patients derived significant QOL benefits from their surgery. Hence subjective QOL issues should be considered in deciding whether treatment-related risks and their natural history, such as their potential rupture, warrant surgery of asymptomatic unruptured ICAs.

Antitumor effect of humanized anti-interleukin-6 receptor antibody (tocilizumab) on glioma cell proliferation: Laboratory investigation

OBJECT Interleukin-6 (IL-6) is a pleiotropic cytokine that regulates diverse physiological functions, including cell proliferation and survival. Recent studies have shown that IL-6 expression is often elevated in response to several types of glioma. Although IL-6 is said to play an important role in glioma, the involvement of IL-6 signaling has been quite controversial. The aim of this study was to evaluate the involvement of IL-6 signaling in glioma and the inhibitory effect of IL-6 signaling on glioma tumor proliferation. METHODS The expression of IL-6 receptors (IL-6Rs) was evaluated in glioma tissues by means of immunohistochemical analysis, and the involvement of IL-6 signaling in glioblastoma multiforme (GBM) U87MG cell proliferation was also determined. In addition, to examine the inhibitory effect of IL-6 signaling on glioma cell proliferation, the authors investigated the effects of tocilizumab, the humanized anti-human IL-6R antibody in U87MG cells. RESULTS Increased immunoreactivity for IL-6R was predominantly found in the cytoplasm of endothelial cells in all GBM samples. Inhibition of IL-6 signaling by both IL-6- and IL-6R-specific small interfering RNA and AG490, a specific inhibitor of JAK2 phosphorylation, suppressed glioma cell proliferation. Furthermore, tocilizumab, a clinically developed humanized anti-human IL-6R antibody, exerted an antiproliferative effect on cells from the GBM cell line U87MG via the IL-6R-dependent JAK-STAT3 pathway. CONCLUSIONS The IL-6 signaling pathway plays an important role in glioma cell proliferation, and tocilizumab exerts an antitumor effect in U87MG glioma cells. These results may bring new insight into the molecular pathogenesis of glioma and may lead to a new therapeutic intervention.

Cavernous malformation of the optic chiasm: case report

We report a 14-year-old boy with cavernous malformation of the optic chiasm. He had a 2-year history of gradually worsening visual disturbance. Computed tomography (CT) and magnetic resonance imaging (MRI) revealed a suprasellar mass, findings compatible with craniopharyngioma. The mass was biopsied and histological examination confirmed cavernous malformation. On the second day after the biopsy, he suffered chiasmal apoplexy due to intratumoural haemorrhage, lost visual acuity and developed a field cut. Cavernous malformations arising from the optic nerve and chiasm are extremely rare; only 29 cases have been reported to date. Most patients manifested acute visual acuity and visual field disturbances. Although MRI findings of cavernous malformations in the brain parenchyma have been reported, MRI findings on the optic nerve and chiasm may not be completely diagnostic. Of the 29 documented patients, 16 underwent total resection of the lesion without exacerbation of their preoperative symptoms; in some cases, resection was complicated by risk of damage to the surrounding neural tissue. As patients may suffer intratumoural haemorrhage after biopsy or partial removal of the lesion, the advisability of surgical treatment of cavernous malformations of the optic nerve and chiasm must be considered carefully.

Prognostic value of isocitrate dehydrogenase 1, O6-methylguanine-DNA methyltransferase promoter methylation, and 1p19q co-deletion in Japanese malignant glioma patients

BackgroundTo determine the prognostic value of isocitrate dehydrogenase 1 (IDH1) mutation, O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation, and 1p/19q co-deletion in Japanese patients with malignant gliomas.MethodsWe studied 267 malignant gliomas, which included 171 glioblastomas (GBMs), 40 anaplastic astrocytomas (AAs), 30 anaplastic oligodendrogliomas (AOs), and 26 anaplastic oligoastrocytomas (AOAs). These malignant gliomas were divided into 2 groups (Group 1: GBM + AA, Group 2: AO + AOA) according to the presence of the oligodendroglioma component. We examined IDH1 mutation and MGMT promoter methylation in each group by direct sequencing and methylation-specific PCR, respectively. We further examined 1p/19q co-deletion in Group 2 by fluorescence in situ hybridization. Survival between groups was compared by Kaplan–Meier analysis.ResultsIn Group 1, patients with IDH1 mutations exhibited a significantly longer survival time than patients with wild-type IDH1. However, no significant difference was observed in Group 2, although patients with IDH1 mutations tended to show prolonged survival. For both Group 1 and Group 2, patients with MGMT methylation survived longer than those without this methylation. Further, patients with 1p/19q co-deletion showed significantly better outcome in Group 2.ConclusionsOur study confirms the utility of IDH1 mutations and MGMT methylation in predicting the prognosis of Group 1 patients (GBM + AA) and demonstrated that IDH1 mutations may serve as a more reliable prognostic factor for such patients. We also showed that MGMT methylation and 1p/19q co-deletion rather than IDH1 mutations were prognostic factors for Group 2 patients (AOA + AO). Our study suggests that patients survive longer if they have IDH1 mutations and undergo total resection. Further, irrespective of MGMT promoter methylation status, the prognosis of glioma patients can be improved if total resection is performed. Moreover, our study includes the largest number of Japanese patients with malignant gliomas that has been analyzed for these three markers. We believe that our findings will increase the awareness of oncologists in Japan of the value of these markers for predicting prognosis and designing appropriate therapeutic strategies for treating this highly fatal disease.

Prolonged Mean Transit Time Detected by Dynamic Susceptibility Contrast Magnetic Resonance Imaging Predicts Cerebrovascular Reserve Impairment in Patients with Moyamoya Disease

Background: Evaluating cerebrovascular reserve (CVR) is important for patients with moyamoya disease (MMD). 123I-iodoamphetamine single-photon emission CT (SPECT) with acetazolamide (ACZ) challenge is widely carried out, but using ACZ becomes problematic owing to its off-label use and its adverse effects. Here, we report the efficacy of dynamic susceptibility contrast MRI (DSC-MRI) for the evaluation of CVR in MMD patients. Methods: All 33 MMD patients underwent both SPECT and DSC-MRI at an interval of <10 days from each other (mean age 38.3 years). The region of interest (ROI) was the anterior cerebral artery (ACA) territory, middle cerebral artery (MCA) territory, basal ganglia and cerebellum hemisphere for cerebral blood flow (CBF), cerebral blood volume (CBV) and mean transit time (MTT) images. The ratios of the ROIs to the ipsilateral cerebellum were calculated for each parameter and evaluated. The CVR was calculated using images acquired by SPECT before and after ACZ administration. The ratios of DSC-MRI parameters and CVR were compared and evaluated for each ROI. Results: The MTT of the ACA and MCA territories significantly correlated with CVR (p < 0.0001). However, CBF and CBV had no correlation with CVR. The MTT ratio had a threshold of 1.966, with a sensitivity of 68.4% and a specificity of 91.5% for predicting decreased CVR (<10%). Conclusion: MTT had a negative correlation with CVR. DSC-MRI is easy, safe and useful for detecting decreased CVR and can be used as a standard examination in MMD patients care.

Superficial temporal artery-to-middle cerebral artery bypass surgery for middle cerebral artery stenosis in a patient with cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy

Cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy is a rare hereditary small vessel disease. Ischemic events are the main clinical manifestation of this condition. Here, we present a case in which superficial temporal artery-to-middle cerebral artery anastomosis was performed in a patient with cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy who developed cerebral infarctions caused by severe middle cerebral artery stenosis. Cerebral blood flow and cerebrovascular reactivity were effectively improved using double anastomoses. To our knowledge, surgical revascularization for patients with this condition has not yet been described in the literature. Superficial temporal artery-to-middle cerebral artery anastomosis is effective for patients with cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy who show marked regional cerebral hypoperfusion.

A new type of hyperplastic anterior choroidal artery

Hyperplastic anomaly of the anterior choroidal artery (hyperplastic AchA) and posterior communicating artery of duplicate origin (duplicated Pcom) are rare vessel anomalies. With some literature review, we here report three cases of hyperplastic AchA, one of which was considered a new type of hyperplastic AchA. This case was not categorized into Takahashi classification.