Nobuyuki Takeshige

The Efficacy of Edaravone (Radicut), a Free Radical Scavenger, for Cardiovascular Disease

Edaravone was originally developed as a potent free radical scavenger, and has been widely used to treat acute ischemic stroke in Japan since 2001. Free radicals play an important role in the pathogenesis of a variety of diseases, such as cardiovascular diseases and stroke. Therefore, free radicals may be targets for therapeutic intervention in these diseases. Edaravone shows protective effects on ischemic insults and inflammation in the heart, vessel, and brain in experimental studies. As well as scavenging free radicals, edaravone has anti-apoptotic, anti-necrotic, and anti-cytokine effects in cardiovascular diseases and stroke. Edaravone has preventive effects on myocardial injury following ischemia and reperfusion in patients with acute myocardial infarction. Edaravone may represent a new therapeutic intervention for endothelial dysfunction in the setting of atherosclerosis, heart failure, diabetes, or hypertension, because these diseases result from oxidative stress and/or cytokine-induced apoptosis. This review evaluates the potential of edaravone for treatment of cardiovascular disease, and covers clinical and experimental studies conducted between 1984 and 2013. We propose that edaravone, which scavenges free radicals, may offer a novel option for treatment of cardiovascular diseases. However, additional clinical studies are necessary to verify the efficacy of edaravone.

Leakage Sign for Primary Intracerebral Hemorrhage A Novel Predictor of Hematoma Growth

Background and Purpose— Recent studies of intracerebral hemorrhage treatments have highlighted the need to identify reliable predictors of hematoma expansion. Several studies have suggested that the spot sign on computed tomographic angiography (CTA) is a sensitive radiological predictor of hematoma expansion in the acute phase. However, the spot sign has low sensitivity for hematoma expansion. In this study, we evaluated the usefulness of a novel predictive method, called the leakage sign. Methods— We performed CTA for 80 consecutive patients presenting with spontaneous intracerebral hemorrhage. Two scans were completed: CTA phase and delayed phase (5 minutes after the CTA phase). By comparing the CTA phase images, we set a region of interest with a 10-mm diameter and calculated the Hounsfield units. We defined a positive leakage sign as a >10% increase in Hounsfield units in the region of interest. Additionally, hematoma expansion was determined on plain computed tomography at 24 hours in patients who did not undergo emergent surgery. Results— Positive spot signs and leakage signs were present in 18 (22%) patients and 35 (43%) patients, respectively. The leakage sign had higher sensitivity (93.3%) and specificity (88.9%) for hematoma expansion than the spot sign. The leakage sign, but not the spot sign, was significantly related with poor outcomes (severely disabled, vegetative state, and death) in all of the patients (P=0.03) and in patients with a hemorrhage in the putamen (P=0.0016). Conclusions— The results indicate that the leakage sign is a useful and sensitive method to predict hematoma expansion.

Beneficial Effects of the Free Radical Scavenger Edaravone (Radicut) in Neurologic Diseases

Free radicals play major roles in the pathogenesis of many diseases, including neurologic diseases, making them an attractive target for therapeutic intervention. Several free radical scavengers have been developed, and some have progressed to clinical trials for the treatment of ischemic stroke. One such scavenger, edaravone is currently used to treat patients who present within 24 h of an attack. Edaravone can diffuse into many affected organs. Edaravone also exerts protective effects against brain and spinal cord injuries. Beyond its direct free radical scavenging effect, edaravone has anti-apoptotic and anti-inflammatory effects in various diseases. Here, we critically review the literature on experimental animal model and clinical studies of edaravone efficacy, and examine whether it should be considered a candidate for worldwide development. Edaravone has proven safe during 10 years of use as a free radical scavenger to treat ischemic stroke. In addition to ischemic stroke treatment, animal data suggest that edaravone may be an effective treatment option for several neurologic diseases, but additional clinical trials are necessary to verify its efficacy.

Primary meningeal melanocytoma of the sellar region: review of the literature and differential diagnosis with special reference to angiographical features

PurposePrimary intracranial melanocytomas are rare neoplasms, especially in the sellar region. Intracranial melanocytoma is usually a dural-based tumor, fed by dural arterial branches in a manner similar to meningioma. Primary sellar melanocytoma may be misdiagnosed as hemorrhagic pituitary macroadenoma, spindle cell oncocytoma, and intrasellar meningioma. These tumors differ in some radiological respects, but are difficult to differentiate preoperatively.MethodsOnly five cases of primary sellar/suprasellar melanocytic tumors, excluding melanomas have been reported thus far. In this paper, we report an instructive new case of a 31-year-old woman presenting with a 2-year history of amenorrhea and an intrasellar mass with suprasellar extension, suggestive of hemorrhagic pituitary adenoma.ResultsTranssphenoidal surgical excision was difficult due to extensive bleeding from the lesion, and at the time, the tumor could not be diagnosed histopathologically. Six years later, we operated again because of tumor regrowth. Angiography revealed a hypervascular tumor, which was fed from the dorsal sellar floor. We had difficulty resecting the tumor, but achieved total removal. Our case had typical radiographic characteristics of melanocytoma, revealed by both magnetic resonance imaging and angiography. However, it was difficult to reach a final diagnosis. Further histopathological examination, including immunohistochemical and ultrastructural studies, was helpful for diagnosis of melanocytoma.ConclusionsPrimary sellar melanocytic tumors are derived from melanocytes in the meningeal lining of the sellar floor or in the diaphragm sellae, based on both embryological assumptions and the clinical findings of our case. We discuss the problems of differential diagnosis and management of primary sellar melanocytic tumors.

Rare case of a rapidly enlarging symptomatic arachnoid cyst of the posterior fossa in an infant: A case report and review of the literature

Background: Intracranial arachnoid cysts are space-occupying lesions that typically remain stable or decrease in size over time. Cysts in infants younger than 1 year of age are remarkably different from those in older children and adults in terms of cyst localization and enlargement. Arachnoid cysts of the posterior fossa (PFACs) are very rare in infants and do not typically grow or present with clinical symptoms, such that surgical treatment is generally considered to be unnecessary. Here, we describe an extremely rare case of an infant with a rapidly enlarging symptomatic PFAC that was successfully treated with surgery. Case Description: A 4-month-old boy presented with increasing head circumference and a rapidly enlarging arachnoid cyst in the left posterior fossa with ventriculomegaly, which was documented using serial imaging over the preceding 2 months. We performed a microscopic resection of the cyst membrane to remove the mass effect as soon as possible and facilitate normal development. To confirm dural closure and prevent cerebrospinal fluid leakage, we also performed short-term (7 days) percutaneous long-tunneled external ventricle drainage after the surgery. Magnetic resonance imaging over a 4-year follow-up period revealed adequate reduction of the ventricle and cyst. The patient no longer exhibited progressive macrocrania and showed normal development. Conclusion: To our knowledge, this is the second successful case of surgical treatment of an enlarging symptomatic PFAC in an infant. Our surgical strategy for the treatment of this rare case can serve as a guide for surgeons in similar future cases.

Estimation of elevated intracranial pressure in infants with hydroce-phalus by using transcranial Doppler velocimetry with fontanel compression

For infants with acute progressive hydrocephalus, invasive drainage of cerebrospinal fluid (CSF) is performed until a ventriculo-peritoneal shunt can be inserted. Surrogate markers of intracranial pressure (ICP) may help optimise the timing of invasive procedures. To assess whether RI with/without fontanel compression helps distinguish between infants with normal (<5 cmH2O), mild (5–11 cmH2O), and moderate (>11 cmH2O) ICP elevation, 74 ICP measures before/after CSF removal and 148 related Doppler measures of the middle cerebral artery were assessed. Higher RI was associated with fontanel compression, elevated ICP, and their interaction (all p < 0.001). Without compression, differences in RI were observed between normal and moderate (p < 0.001) and between mild and moderate ICP elevation (p = 0.033). With compression, differences in RI were observed for all pairwise comparisons among normal, mild, and moderate ICP elevation (all p < 0.001). Without compression, areas under the receiver-operating characteristic curve for prediction of mild and moderate ICP elevation were 0.664 (95% confidence interval (CI), 0.538–0.791; p = 0.020) and 0.727 (95% CI, 0.582–0.872; p = 0.004), respectively, which improved to 0.806 (95% CI, 0.703–0.910; p < 0.001) and 0.814 (95% CI, 0.707–0.921; p < 0.001), respectively, with compression. RI with fontanel compression provides improved discrimination of infants with absent, mild, and moderate ICP elevation.