Persistent or permanent atrial fibrillation is associated with severe cardioembolic stroke in patients with non-valvular atrial fibrillation.

BACKGROUND: Little is known about the difference in the severity of cardioembolic (CE) stroke between patients with paroxysmal atrial fibrillation (PAF) and persistent/permanent AF (PerAF). We assessed stroke severity in patients with CE stroke divided by the type of AF. METHODS: Three hundred and fifty-eight consecutive patients with CE stroke within 48 h of onset and with a modified Rankin Scale (mRS) score ≤ 1 before onset were studied. We compared basic characteristics, stroke severity, and functional outcome between patients with PAF (n = 127) and PerAF (n = 231). RESULTS: Patients with PerAF were more likely to take oral anticoagulants (OACs) than those with PAF (37% vs. 13%, P <  0.0001), even though still underuse of OAC in both patients. Regarding stroke severity on admission, patients with PerAF exhibited a tendency toward a higher score on the National Institutes of Health Stroke Scale (NIHSS) compared with patients with PAF (12 [5-20] vs. 9 [4-18]; P = 0.12). Mortality and mRS score at discharge were higher in the PerAF than in the PAF group (13% vs. 4%; P = 0.005, and 3 [1-5] vs. 2 [1-4]; P = 0.01, respectively). Multivariate analyses confirmed that PerAF was a significant determinant of severe stroke (NIHSS score > 8) on admission (odds ratio [OR] to PAF = 1.80; 95% confidence interval [CI] 1.08-2.98; P = 0.02) and of an mRS score ≥ 3 at discharge (OR = 2.07; 95% CI 1.24-3.46; P = 0.006). Patients with PerAF had three times more internal carotid artery occlusion evaluated by magnetic resonance angiography, which indicated a more severe cerebral embolism compared with patients with PAF. CONCLUSIONS: We found underuse of OAC in high risk AF patients with CE stroke. PerAF is significantly associated with severe stroke on admission and an unfavorable functional outcome at discharge in Japanese patients with CE stroke.

[Temporal Profiles of Neuroimaging Features of Non-haemorrhagic and Non-ischemic Vertebral Artery Dissections for Conservative Treatment].

Most patients with non-hemorrhagic and non-ischemic vertebral artery dissections(VADs)are likely to recover with good outcomes. In contrast, some cases of uneventful outcomes have also been reported. Therefore, whether surgical treatment or prolonged follow-up should be utilized for each case remains controversial. In this study, we retrospectively investigated the radiological features and changes in non-hemorrhagic and non-ischemic VADs during the follow-up period. We reviewed the medical records of 15 consecutive patients with VADs without hemorrhage or ischemic lesions diagnosed between 2008 and 2017; all patients reported severe occipital headache. All hemorrhagic and ischemic lesions were categorized into morphological types according to the initial radiological findings. The following morphological types of dissections were observed: six cases, pearl and string type; six cases, dilatation type; two cases, stenosis type; and one case, occlusion type. We observed morphological aggravation in four cases, and among them, three underwent surgical interventions. Seven patients recovered during the follow-up period, and five of them showed marked radiological changes within 2 months. One patient died fromethe clinical onset. Therefore, careful follow-up radiological imaging is presumably necessary for patients with non-hemorrhagic and non-ischemic VADs, within at least 2 months of the clinical onset because of the tendency of VADs for rapid morphological changes during that period.

Unruptured Saccular Aneurysm Arising from the Fenestrated A1 Segment of the Anterior Cerebral Artery: Report of 2 Cases.

Some cases of aneurysms originating from the fenestrated A1 segment of the anterior cerebral artery (ACA) have been reported, but the pitfalls of the surgical procedure have not been well determined. We herein report 2 cases of a saccular aneurysm arising from the fenestrated A1 segment. Case 1 was a 72-year-old man incidentally diagnosed with an unruptured left ACA aneurysm on magnetic resonance imaging (MRI). Cerebral angiography revealed a saccular aneurysm arising from the proximal end of the left A1 segment. He underwent surgical clipping via the left pterional approach. The aneurysm originated from the proximal bifurcation of the fenestrated left A1 segment. A fenestrated ring clip was applied to obliterate the aneurysmal neck and one small fenestrated trunk, preserving the other fenestrated trunk and perforators around the fenestration. Case 2 was a 73-year-old man incidentally diagnosed with an unruptured ACA aneurysm on MRI. Cerebral angiography revealed a saccular aneurysm arising from the proximal end of the fenestrated left A1 segment. He underwent surgical clipping via the interhemispheric approach. The aneurysm originated from the proximal bifurcation of the fenestrated left A1 segment. A fenestrated ring clip was applied to obliterate the aneurysmal neck and one hypoplastic fenestrated trunk, preserving the other fenestrated trunk and perforators around the aneurysm. Detailed intraoperative evaluations of the anatomical structure and hemodynamics around the fenestration are important. The intentional obliteration of a fenestrated trunk and application of fenestrated clips need to be considered in difficult cases in order to expose the aneurysmal neck.

Expression of CD133 as a Putative Prognostic Biomarker to Predict Intracranial Dissemination of Primary Spinal Cord Astrocytoma.

OBJECTIVE: Spinal cord astrocytoma with intracranial dissemination carries a poor prognosis. The mechanisms leading to dissemination remain to be elucidated. A stem cell marker, CD133, was reported to predict recurrence patterns in intracranial glioblastoma. We evaluated the significance of CD133 as a putative prognostic biomarker to predict intracranial dissemination in spinal cord astrocytoma. METHODS: This study included 14 consecutive patients with primary spinal cord astrocytoma treated from 1998 to 2014. Six of the patients were women and the patients' ages ranged from 12 to 75 years. Seven and 6 patients underwent open biopsy and partial resection of the tumors, respectively. After confirmation of the histologic diagnoses, all patients were treated with postoperative radiotherapy, chemotherapy, or a combination of both. To identify factors predictive of intracranial dissemination, we analyzed their clinical data including Ki-67 labeling index, and CD133 expression. RESULTS: Intracranial dissemination was observed in 6 of 14 patients. All 6 patients died during the follow-up period. Of the 8 patients without intracranial dissemination, 5 survived (P = 0.02). Median survival for the patients with intracranial dissemination was 22.7 months. CD133 expression was significantly higher in patients with intracranial dissemination (P = 0.04), whereas other variables did not indicate the dissemination. CONCLUSIONS: The expression of CD133 can be an efficient biomarker to predict intracranial dissemination in spinal cord astrocytoma. Recognition of high CD133 expression in surgical specimens and early detection of intracranial dissemination is important for the clinical management of spinal cord astrocytoma.

Microvascular decompression for intractable singultus.

Intractable singultus due to cerebrovascular disease is very rare. We report a case of intractable singultus that improved after microvascular decompression and present a literature review. The patient was a 58-year-old man with a 30-year history of persistent singultus. Its frequency and duration gradually increased and it was resistant to multiple medical treatments. Microvascular decompression to relieve pressure on the anterolateral surface of the lower medulla oblongata from the vertebral artery resulted in the resolution of singultus. Patients with intractable idiopathic singultus who fail to respond to medical therapy need to be considered for the evaluation of cerebrovascular diseases and microvascular decompression.

A Dissecting Aneurysm of the Distal Medial Lenticulostriate Artery: Case Report.

BACKGROUND: Medial lenticulostriate artery (MLSA) aneurysms are rare; to our knowledge, only 2 cases without an association with moyamoya disease have been documented. We treated a ruptured dissecting aneurysm of the distal MLSA surgically using a tube retractor. CASE DESCRIPTION: A 66-year-old woman suffered a sudden-onset disturbance in consciousness. Computed tomography showed diffuse subarachnoid hemorrhage and a dense intraventricular hematoma associated with acute hydrocephalus. She underwent emergent ventricular drainage. Angiography revealed a 3-mm distal MLSA aneurysm. On repeat angiographs, the aneurysm had not disappeared. Because the stenotic, narrow structure of the proximal portion of the MLSA disallowed the endovascular approach, we performed direct surgery via the transventricular approach using a tube retractor. The aneurysm on the intraventricular surface of the anterior horn of the lateral ventricle adjacent to the caudate nucleus was exposed. We resected the aneurysm under transcranial motor-evoked potential monitoring because neck clipping would have endangered the patency of the MLSA. Her postoperative course was uneventful. The pathologic diagnosis was ruptured dissecting aneurysm. CONCLUSIONS: There is no definitive strategy to treat distal MLSA aneurysms. Our experience illustrates that natural healing of the vessel wall cannot be expected in all cases. Therefore, less-invasive direct surgical as well as endovascular treatment should not be ruled out in patients with ruptured distal MLSA aneurysms.

Peri-tumoral leakage during intra-tumoral convection-enhanced delivery has implications for efficacy of peri-tumoral infusion before removal of tumor.

In cases of malignant brain tumors, infiltrating tumor cells that exist at the tumor-surrounding brain tissue always escape from cytoreductive surgery and, protected by blood-brain barrier (BBB), survive the adjuvant chemoradiotherapy, eventually leading to tumor recurrence. Local interstitial delivery of chemotherapeutic agents is a promising strategy to target these cells. During our effort to develop effective drug delivery methods by intra-tumoral infusion of chemotherapeutic agents, we found consistent pattern of leakage from the tumor. Here we describe our findings and propose promising strategy to cover the brain tissue surrounding the tumor with therapeutic agents by means of convection-enhanced delivery. First, the intracranial tumor isograft model was used to define patterns of leakage from tumor mass after intra-tumoral infusion of the chemotherapeutic agents. Liposomal doxorubicin, although first distributed inside the tumor, distributed diffusely into the surrounding normal brain once the leakage happen. Trypan blue dye was used to evaluate the distribution pattern of peri-tumoral infusions. When infused intra- or peri-tumorally, infusates distributed robustly into the tumor border. Subsequently, volume of distributions with different infusion scheduling; including intra-tumoral infusion, peri-tumoral infusion after tumor resection, peri-tumoral infusion without tumor removal with or without systemic infusion of steroids, were compared with Evans-blue dye. Peri-tumoral infusion without tumor removal resulted in maximum volume of distribution. Prior use of steroids further increased the volume of distribution. Local interstitial drug delivery targeting tumor surrounding brain tissue before tumor removal should be more effective when targeting the invading cells.

Safety and feasibility of convection-enhanced delivery of nimustine hydrochloride co-infused with free gadolinium for real-time monitoring in the primate brain.

OBJECTIVES: Convection-enhanced delivery (CED) has been developed as an effective drug-delivery strategy for brain tumors. Ideally, direct visualization of the tissue distribution of drugs infused by CED would assure successful delivery of therapeutic agents to the brain tumor while minimizing exposure of the normal brain tissue. We previously showed the anti-tumor efficacy of nimustine hydrochloride (ACNU) delivered via CED against a rodent intracranial xenografted tumor model. Here, we developed a method to monitor the drug distribution using a non-human primate brain. METHODS: CED of a mixture of ACNU with gadodiamide was performed using three non-human primates under real-time magnetic resonance imaging monitoring. Animals were clinically observed for any toxicity after infusion. Two months later, their brains were subjected to histological examination for the evaluation of local toxicity. Another one animal was euthanized immediately after CED of a mixture of ACNU, gadodiamide, and Evans blue dye to evaluate the concordance between ACNU and gadodiamide distributions. The harvested brain was cut into blocks and the ACNU content was measured. RESULTS AND DISCUSSION: Real-time magnetic resonance imaging monitoring of co-infused gadodiamide confirmed the success of the infusion maneuver. In the monkey that also received Evans blue, the distribution of Evans blue was similar to that of gadodiamide and paralleled the measured ACNU content, suggesting concordance between ACNU and gadodiamide distributions. Histological examination revealed minimum tissue damage with the infusion of ACNU at 1 mg/ml, determined as a safe dose in our previous rodent study. CED of ACNU can be co-administered with gadodiamide to ensure successful infusion and monitor the distribution volume.

Local convection-enhanced delivery of chemotherapeutic agent transiently opens blood-brain barrier and improves efficacy of systemic chemotherapy in intracranial xenograft tumor model.

Recently, local chemotherapy proved its efficacy against malignant gliomas. Under the hypothesis that local delivery of chemotherapeutic agents into the brain parenchyma induce opening of the blood-brain barrier (BBB), we evaluated the opening of BBB after convection-enhanced delivery of nimustine hydrochloride into the brain parenchyma. Local convection-enhanced delivery of nimustine hydrochloride transiently opened the BBB from about 7-12 days after delivery in normal rodent brain. Systemic chemotherapy during this period of BBB disruption had synergistic effects resulting in prolonged survival of tumor-bearing rats. The present strategy may provide a new approach for glioma chemotherapy.

Early detection of venous thromboembolism in patients with neuroepithelial tumor: efficacy of screening with serum D-dimer measurements and Doppler ultrasonography.

The efficacy of combined serum D-dimer level measurement and Doppler ultrasonography of the lower extremity was investigated for screening of venous thromboembolism (VTE) in patients with neuroepithelial tumor. Eighty-one patients with neuroepithelial tumor were prospectively studied. All patients underwent measurement of serum D-dimer levels and Doppler ultrasonography of the lower extremity. The serum D-dimer level was measured every week, and Doppler ultrasonography was performed two and two weeks after surgery, then every two weeks until discharge, or every two weeks for patients who did not undergo surgery. If the serum D-dimer level increased over 10.0 µg/ml, Doppler ultrasonography or computed tomography was performed to detect VTE. VTE occurred in 12 (14.8%) patients (seven males and five females; age 34-75, mean 59.0 years). Only one patient was symptomatic, whereas 11 patients identified by the screening were without symptoms. Five patients were treated with anticoagulant therapy, one with prophylactic inferior vena cava filter placement with anticoagulant therapy, and the other six were closely followed up without medication. No patient died of pulmonary embolism. Serial Doppler ultrasonography showed thrombus regression or organization and no thrombus extension. The maximum serum D-dimer value was significantly higher in patients with VTE than in those without VTE (mean 14.5 vs. 3.46 µg/ml, P < 0.001). The D-dimer cutoff value of 5.4 µg/ml could be used to identify VTE with 83% sensitivity and 84% specificity. The combination of sequential serum D-dimer measurement and Doppler ultrasonography of the lower extremity is an efficient and non-invasive procedure for identifying asymptomatic VTE in patients with neuroepithelial tumor.

Analysis of IDH1 and IDH2 mutations in Japanese glioma patients.

A recent study reported on mutations in the active site of the isocitrate dehydrogenase 1 (IDH1) gene in several types of gliomas. All mutations detected resulted in an amino acid exchange at position 132. We analyzed the genomic region spanning wild-type R132 of IDH1 by direct sequencing in 125 glial tumors. A total of 39 IDH1 mutations were observed. Mutations of the IDH2 gene, homologous to IDH1, were often detected in gliomas without IDH1 mutations. In the present study, R172 mutation of the IDH2 gene was detected in one anaplastic astrocytoma. IDH1 or IDH2 mutations were frequently in oligodendrogliomas (67%), anaplastic astrocytomas (62%), anaplastic oligoastrocytomas (75%), anaplastic oligodendrogliomas (50%), secondary glioblastomas (67%), gangliogliomas (38%), and anaplastic gangliogliomas (60%). Primary glioblastomas were characterized by a low frequency of mutations (5%) at amino acid position 132 of IDH1. Mutations of the IDH1 or IDH2 genes were significantly associated with improved outcome in patients with anaplastic astrocytomas. Our data suggest that IDH1 or IDH2 mutation plays a role in early tumor progression of several types of glioma and might arise from a common glial precursor. The infrequency of IDH1 mutation in primary glioblastomas revealed that these subtypes are genetically distinct entities from other glial tumors.

[Primary yolk sac tumor in the cerebellar vermis. Case report].

A 2-year-old boy presented with gait disturbance and limb ataxia. T1-weighted magnetic resonance (MR) imaging with gadolinium-diethylenetriaminepenta-acetic acid administration showed a heterogeneously enhanced mass lesion with a cystic component in the cerebellar vermis. The minimum apparent diffusion coefficient value of the lesion was 1.96 x 10(-3) mm2/sec, and 1H-MR spectroscopy showed elevated choline and lipid peaks, and decreased N-acetyl aspartate peak. The tumor was totally resected, and the histological diagnosis was yolk sac tumor. Consistent with this diagnosis, a-fetoprotein levels in the serum and cerebrospinal fluid were 7094 ng/m/ and 22.3 ng/m/, respectively. 18F-fluorodeoxyglucose-positron emission tomography, and thoracic, abdominal, and pelvic computed tomography showed no abnormal lesions, excluding the possibility of metastatic yolk sac tumor from an extracranial lesion. The patient received chemotherapy consisting of ifosfamide, cisplatin, and etoposide, and had not relapsed at 6 months after resection. Germ cell tumors rarely develop in the posterior fossa. This case suggests that yolk sac tumor could develop in the cerebellar vermis.