[Cryptococcus Neoformans Var. Gattii meningoencephalitis with cryptococcoma in an immunocompetent patient successfully treated by surgical resection].

Cryptococcosis is a fungal infection, which mainly invades the lungs and central nervous system. In Japan, most cases of cryptococcosis are caused by Cryptococcus neoformans(C. neoformans). Until now, only three cases which the infectious agent was Cryptococcus neoformans var. gattii(C. gattii)have been reported. As compared with cryptococcosis caused by C. neoformans, which is often observed in immunocompromised hosts, cryptococcosis caused by C. gattii occurs predominantly in immunocompetent hosts and is resistant to antifungal drugs. Here, we report a case of refractory cerebral cryptococcoma that was successfully treated by surgical resection of the lesions. A 33-year-old man with no medical history complained of headache, hearing disturbance, and irritability. Pulmonary CT showed a nodular lesion in the left lung. Cerebrospinal fluid examination with Indian ink indicated cryptococcal meningitis, and PCR confirmed infection with C. gattii. C. gattii is usually seen in the tropics and subtropics. Since this patient imported trees and soils from abroad to feed stag beetles, parasite or fungal infection was, as such, suspected. Although he received 2 years of intravenous and intraventricular antifungal treatment, brain cryptococcomas were formed and gradually increased. Because of the refractory clinical course, the patient underwent surgical resection of the cerebral lesions. With continuation of antifungal drugs for 6 months after the surgeries, Cryptococcus could not be cultured from cerebrospinal fluid, and no lesions were seen on MR images. If cerebral cryptococcosis responds poorly to antifungal agents, surgical treatment of the cerebral lesion should be considered.

"Loop-like formation" in the cortical venous reflux of dural arteriovenous fistula with intracranial hemorrhage.

BACKGROUND AND PURPOSE: Cortical venous reflux (CVR) in dural arteriovenous fistulas (AVFs) is a well-known risk factor for intracranial hemorrhage. However, the impact of the angiographic characteristics of CVR on the risk of intracranial hemorrhage remains unclear. This study retrospectively reviewed the angioarchitectural features of CVR to assess their influence on the risk of intracranial hemorrhage in dural AVFs. PATIENTS AND METHODS: We retrospectively evaluated 68 consecutive patients with dural AVFs treated at our hospital between September 2001 and February 2010. In all cases, the angioarchitectural features of CVR were analyzed using cerebral angiography with a special focus on the venous drainage pattern of dural AVFs. "Loop-like formation" was defined as at least one CVR forming a curvature and connection adjacent to the original arteriovenous shunt point. RESULTS: Ten dural AVF patients (14.7%) presented with intracranial hemorrhage. All ten dural AVFs with intracranial hemorrhage showed CVR with a "loop-like formation" on angiography. This association was found to be statistically significant (P<0.0001). CONCLUSION: "Loop-like formation" in CVR may be a risk factor for intracranial hemorrhage resulting from dural AVF. This angioarchitectural feature of venous drainage may be a useful prognostic indicator, and hence should be a point of focus during treatment decisions.

[Cluster-like headache cause by cavernous sinus dural arteriovenous fistula, cured by transvenous embolization: a case report].

We report a unique case of cavernous sinus(CS)-dural arteriovenous fistula(dAVF)with cluster headache-like ophthalmalgia without chemosis and exophthalmos, that was successfully treated by transvenous embolization. A 25-year-old man presented with severe right cluster headache-like ophthalmalgia and could not get complete relief of symptoms by medical treatment. MRI showed a hyper-intensity signal in the right cavernous sinus and cerebral angiography revealed Barrow type D cavernous sinus dural arteriovenous fistula, which is thought to be the cause of ophthalmalgia. Percutaneous transvenous embolization of the anterior part of the right CS and superior ophthalmic vein was performed and complete obliteration of dAVF was obtained followed by complete cure of cluster headache-like ophthalmalgia. We can detect neither the recurrence of dAVF on MRI nor any clinical symptom after 23 months of the treatment. This is the first clinical presentation of cluster headache-like ophthalmalgia caused by CS dAVF and it emphasizes the unique and important potential relationship between them.

Small unruptured intracranial aneurysm verification study: SUAVe study, Japan.

BACKGROUND AND PURPOSE: The natural history and optimal management of incidentally found small unruptured aneurysms <5 mm in size remain unclear. A prospective study was conducted to determine the optimal management for incidentally found small unruptured aneurysms. METHODS: From September 2000 to January, 2004, 540 aneurysms (446 patients) were registered. Four hundred forty-eight unruptured aneurysms <5 mm in size (374 patients) have been followed up for a mean of 41.0 months (1306.5 person-years) to date. We calculated the average annual rupture rate of small unruptured aneurysms and also investigated risk factors that contribute to rupture and enlargement of these aneurysms. RESULTS: The average annual risks of rupture associated with small unruptured aneurysms were 0.54% overall, 0.34% for single aneurysms, and 0.95% for multiple aneurysms. Patient <50 years of age (P=0.046; hazard ratio, 5.23; 95% CI, 1.03 to 26.52), aneurysm diameter of >or=4.0 mm (P=0.023; hazard ratio, 5.86; 95% CI, 1.27 to 26.95), hypertension (P=0.023; hazard ratio, 7.93; 95% CI, 1.33 to 47.42), and aneurysm multiplicity (P=0.0048; hazard ratio, 4.87; 95% CI, 1.62 to 14.65) were found to be significant predictive factors for rupture of small aneurysms. CONCLUSIONS: The annual rupture rate associated with small unruptured aneurysms is quite low. Careful attention should be paid to the treatment indications for single-type unruptured aneurysms <5 mm. If the patient is <50 years of age, has hypertension, and multiple aneurysms with diameters of >or=4 mm, treatment should be considered to prevent future aneurysmal rupture.

Platelet-derived growth factor-induced severe and chronic vasoconstriction of cerebral arteries: proposed growth factor explanation of cerebral vasospasm.

OBJECTIVE: After subarachnoid hemorrhage (SAH), platelet-derived growth factor-BB (PDGF-BB) is secreted in and around the cerebral arteries. To clarify the role of PDGF-BB in the development of vasospasm after SAH, we determined whether PDGF-BB alone can cause long-lasting vasoconstriction of a severity similar to that of vasospasm. In addition, the anti-vasospastic effect of trapidil, an antagonist of PDGF-BB function, was investigated. METHODS: We infused recombinant PDGF-BB (10 microg/mL saline as the vehicle) (n = 14) into the subarachnoid space of rabbits and analyzed alterations in the caliber of the basilar artery using repeated angiography. To study the role of PDGF-BB on the development of vasospasm, trapidil was administered continuously starting 1 hour after SAH, on day 0 (0.63-1.25 mg/kg /h or vehicle) for 47 hours (n = 24), or after the full development of cerebral vasospasm on day 2 (3.0 mg/kg/h or vehicle) for 0.5 hours (n = 17), and alterations in the caliber of the basilar artery were monitored. RESULTS: PDGF-BB caused long-lasting vasoconstriction, with maximum constriction of 56% (P < .001) of the control value (= 100%) on day 2, resembling vasospasm seen after SAH. Prolonged administration of intravenous trapidil, starting soon after SAH, prevented the development of vasospasm in a dose-dependent manner (P < .05, .01, or .001). Intravenous or intra-arterial administration of trapidil significantly dilated vasospasm (P < .01) on day 2, at least transiently. CONCLUSION: PDGF-BB, a growth factor synthesized in the subarachnoid space after SAH, can cause severe and long-lasting vasoconstriction. Significant prevention and resolution of vasospasm can be achieved by the PDGF-BB antagonist trapidil. We propose that excessive production of PDGF-BB, essentially aiming to repair injured arteries, causes cerebral vasospasm. Although the half-life of trapidil in serum may be shorter than that of PDGFG-BB-derived spasmogenic signaling, trapidil is a candidate drug for constructing a new therapeutic modality for preventing and resolving vasospasm.

[A case of A3-A3 bypass and proximal clipping for a ruptured left A1 dissecting aneurysm].

A 58-year-old woman was admitted to our hospital with sudden onset of headache. CT and angiogram revealed subarachnoid hemorrhage due to a dissecting aneurysm at the left A1 segment. ACoA was not identified. We performed proximal clipping with A3-A3 bypass for preventing the recurrence of the hemorrhage and for reducing ischemia in the territory of the left ACA. After the operation, CT revealed the infarctions in the corpus callosum, the left medial frontal lobe and the genu of the internal capsule. But the postoperative angiogram demonstrated no aneurysm and the opacification of the recurrent artery of Heubner and the part of perforating branches. A3-A3 bypass was patent. The patient experienced a good recovery without recurrence of bleeding.

Endovascular trapping for vertebral artery fusiform aneurysm in a patient with idiopathic thrombocytopenic purpura.

A 56-year-old woman with adult idiopathic thrombocytopenic purpura (ITP) diagnosed 17 years previously presented with a fusiform aneurysm manifesting as chronic headache. She had suffered no major hemorrhagic complications, although her platelet counts were between 3.0 x 10(9)/l and 50.0 x 10(9)/l. Magnetic resonance angiography identified a fusiform aneurysm of the right vertebral artery. Endovascular trapping after high-dose gammaglobulin with steroid therapy was performed. The patient received antiplatelet therapy to prevent thromboembolic events. The parent artery and aneurysm were completely occluded with no hemorrhagic complications. Endovascular treatment is considered safe in patients with ITP, although careful periprocedural management of platelet count is required.

Clinical predictors of transient ischemic attack, stroke, or death within 30 days of carotid artery stent placement with distal balloon protection.

PURPOSE: Carotid artery stent placement has been accepted as an effective alternative to carotid endarterectomy (CEA), especially in patients at high risk in the setting of CEA. The purpose of this study was to determine potential clinical risk factors for the development of postprocedural neurologic deficits after carotid artery stent placement. MATERIALS AND METHODS: The clinical characteristics of 58 patients (49 men, nine women; 41 at high risk with CEA, 17 at low risk; median age, 70 years) who underwent carotid artery stent placement with distal balloon protection for 65 hemispheres/arteries (31 asymptomatic lesions and 34 symptomatic lesions) and the combined 30-day complication rates (transient ischemic attack [TIA], minor stroke, major stroke, or death) were analyzed. RESULTS: Six patients (9.0%) experienced a TIA and one patient (1.5%) had a major stroke (1.5%) within 30 days of the procedure. There were no deaths, so the overall 30-day combined stroke and death rate was 1.5%. The chi(2) test revealed that advanced age (>75 years) was a significant clinical predictor of 30-day combined neurologic complications and major adverse effects (P < .01). In addition, a symptomatic lesion was marginally associated with the 30-day incidence of neurologic ischemia on the ipsilateral side (P = .049). CONCLUSIONS: Our data suggest that carotid artery stent placement with distal balloon protection can be performed with similar periprocedural complication rates as CEA. CEA should be the first-line treatment in the management of patients older than 75 years of age.

Repeated application of an electric field increases BDNF in the brain, enhances spatial learning, and induces infarct tolerance.

Development of a safe method to increase brain-derived neurotrophic factor (BDNF) in the brain is expected to have utility in enhancing learning and memory, in protecting the brain, and in suppressing appetite. We investigated the effects of whole-body exposure to high voltage electric potential (HELP), which generates an electric field and current density in the body, on BDNF levels in the brain, spatial learning, or resistance to cerebral infarction development after focal ischemia. Adult mice (C57BL/6J) were exposed to 3.5 kV, or 5.8 kV for 5 h a day, making indirect contact with the ground via room air, over 1, 3, 6 or 12 consecutive weeks. After treatment, BDNF levels, performances in the Morris water maze task (MWM), or development of infarct lesion after focal ischemia was analyzed. Treatment with 3.5 kV for 1, 3, 6 or 12 weeks, or with 5.8 kV for 1, 3 or 12 weeks increased BDNF levels in the cortex (P<0.05, one-way ANOVA). Every HELP treatment differentially improved escape latency in the MWM, compared with the corresponding untreated controls (P<0.05, one-way ANOVA). Treatment with 3.5 kV for 6 or 12 weeks, but not with 5.8 kV protected the brain suppressing cerebral infarction development (P<0.05). The HELP treatment with 3.5 kV for 6 or 12 weeks improves spatial learning, gently suppressing body weight gain, and protects the brain against cerebral infarction.

Surgical applications to arteriovenous malformations involving the brainstem.

OBJECTIVE: To evaluate possible applications of microsurgical extirpation to arteriovenous malformations (AVMs) involving the brainstem. METHODS: We retrospectively reviewed clinical records of 25 patients with AVMs involving brainstems who were admitted to our institute from 1984 to 2004. We defined a brainstem AVM as an AVM in which some part was located within the brainstem. The main location of the nidus was classified into ventral midbrain (n = 3), dorsal midbrain (n = 10), pons (n = 5), cerebellopontine angle (n = 6), and medulla oblongata (n = 1). Bleeding risks from the AVMs were calculated, and applied treatment modalities, respectability, and clinical outcomes were analyzed. RESULTS: The annual bleeding and rebleeding risks of brainstem AVMs were 15.1 and 14.2%, respectively. Total resection was successfully performed in 0 out of 3, 6 out of 10, 2 out of 5, 6 out of 6, and 0 out of 1 in each of the groups, respectively. Stereotactic radiosurgery was applied as a main treatment modality in three patients (two ventral midbrain AVMs and one pontine AVM), and after microsurgery in one patient with a medulla oblongata AVM. Microsurgery-related permanent neurological complications were observed in five patients (one postoperative bleeding, one hemiparesis, three hearing deterioration, one abducens nerve palsy). During a follow-up period of 8 years (range, 8 mo-15 yr), one patient with an untreated pontine AVM died owing to hemorrhage and one patient with a subtotally resected dorsal midbrain AVM died owing to an unknown etiology 4 years later. CONCLUSION: Surgical resection can be applied with considerable, but acceptable, morbidity and mortality in some groups of brainstem AVMs with hemorrhagic presentation, particularly dorsal midbrain and cerebellopontine angle types, in which most parts of the nidus located sub- or extrapially.

Induced spreading depression activates persistent neurogenesis in the subventricular zone, generating cells with markers for divided and early committed neurons in the caudate putamen and cortex.

BACKGROUND AND PURPOSE: Status epilepticus and cerebral ischemia stimulate persistent neurogenesis in the adult brain, but both conditions cause neuronal damage. We determined whether spreading depression, a common epiphenomenon of these conditions, stimulates persistent neurogenesis. METHODS: We analyzed the effect of KCl-induced spreading depression on persistent neurogenesis and the spatio-temporal distribution of cells exhibiting immunohistochemical markers for divided and early committed neurons (new neurons) in the adult rat brain. RESULTS: After induction of spreading depression for 48 hours, the density of mitotic cells, divided cells, and new neurons in the subventricular zone increased at days 1 to 3, days 3 to 6, and day 6, respectively (P<0.05). The divided cell density in the rostral migratory stream and the stream size increased at day 12 (P<0.001). Vehicle (saline) infusion or induction of spreading depression for 4 hours only did not increase the divided cell density, but the latter increased new neuron density in the subventricular zone (P<0.001). Double-labeled new neuron-like cells also appeared in the caudate putamen or cortex in ectopic fashion at day 3, with dramatic increases at days 6 and 12. Administration of the NMDA receptor antagonist, MK-801, which inhibits the propagation of spreading depression, abolished the increase in new neurons in the subventricular zone and the appearance of ectopic new neuron-like cells after 48-hour KCl infusion. There was no neuronal damage, as evidenced by mature neuron density, neurite density, and apoptotic cell appearance after spreading depression for 48 hours. CONCLUSIONS: Spreading depression has the potential to stimulate persistent neurogenesis or to produce ectopic new neuron-like cells.

Postoperative evaluation of microsurgical resection for cavernous malformations of the brainstem.

OBJECT: The aim of this study was to propose criteria to determine whether complete resection of cavernous malformations in the brainstem had been achieved. METHODS: The authors retrospectively analyzed data in 10 patients harboring a single cavernous malformation who had presented with hemorrhagic symptoms and had been followed up for longer than 2 years postsurgery. The study population consisted of five male and five female patients ranging in age from 13 to 57 years (mean 36.8 years). When preoperative magnetic resonance (MR) images demonstrated the lesion as a homogeneous hyperintense mass, the surgery was defined as complete or incomplete based on intraoperative findings. When preoperative MR images revealed other findings, complete resection was determined according to whether postoperative MR imaging results demonstrated lesions distinct from the peripheral hemosiderin rim. Among the 13 operations in this series, nine resulted in complete resection and were associated with no postoperative clinical relapse of hemorrhage, whereas four operations resulted in incomplete resection and were correlated with postoperative recurrent hemorrhage. The seven patients in whom the outcome of the initial operation was complete demonstrated good neurological recovery in the long-term follow-up period, whereas the three patients in whom the outcome of the initial surgery was judged to be incomplete showed inadequate neurological recovery due to recurrent hemorrhage. CONCLUSIONS: The criteria proposed in this study to evaluate surgical treatment may be a reliable means of predicting the recurrence of hemorrhage postoperatively.

Spreading depression induces long-lasting brain protection against infarcted lesion development via BDNF gene-dependent mechanism.

Preconditioning the rat brain with spreading depression for 48 h induces potent ischemic tolerance (infarct tolerance) after an interval of 12-15 days, consequently reducing the infarcted lesion size in the acute phase following focal cerebral ischemia. However, persistence of the morphological and functional neuroprotection has not yet been proven. We tested whether tolerance-derived neuroprotection against focal cerebral ischemia persists or merely delays the progress of cerebral infarction. Prolonged spreading depression was induced in mice by placing a depolarized focus with intracerebral microinfusion of KCl for 24 h; after intervals of 3, 6, 9 or 12 days, temporary focal ischemia was imposed. In the analysis of the infarcted lesion volume 24 h after ischemia, groups with 6 or 9 day interval demonstrated significantly smaller lesion volume compared to time-matched vehicle control group (P=0.002). Significant reduction in cerebral infarction was also observed at the chronic phase, namely 14 days after ischemia (33% reduction) (P=0.021) accompanied with less severe neurological deficits (38% reduction) (P=0.020). Using this technique, we also investigated if the mice with targeted disruption of a single BDNF allele (heterozygous BDNF-deficient mice) can gain the same potency of tolerance as the wild mice. In the result on infarcted lesion volumes following temporary focal ischemia, potent tolerance developed in the wild type (35% reduction) (P=0.007) but not in the heterozygous BDNF-deficient mice (<19% reduction) (P=0.155), indicating that BDNF expression level following spreading depression is contributing to infarct tolerance development.

[Consensus and controversy in the treatment of ischemic cerebrovascular diseases].

Surgical and endovascular revascularization for ischemic cerebrovascular diseases (CVD) should be strictly indicated based on medical treatment. In this report, we describe current consensus and controversy in the treatment of ischemic CVD, and perspectives. 1) Local intra-arterial fibrinolytic therapy for acute cerebral embolism; intra-venous t-PA can be beneficial when given within 3 hours of stroke onset (NINDS), but many patients present later after stroke onset and alternative treatments are needed. Despite an increased frequency intracranial hemorrhage, treatment with intra-arterial proUK within 6 hours for MCA occlusion significantly improved clinical outcome at 90 days (mRS 40% >25%, PROACT-II). MELT-Japan are going now and waiting for results. 2) Carotid stenting; Carotid angioplasty and stenting (CAS) has been proposed as an alternative to carotid endarterectomy (CEA) in those considered at high risk for CEA. SAPPHIRE study confirmed CAS is an excellent option for patients with coexisting coronary artery disease, congestive heart failure, and other comorbid conditions that make them poor candidates for CEA. Now, CREST in USA and CSSA in Europe are going for randomized trial compared with CEA and CAS in any risk for CEA patients. 3) Stenting for intracranial arteries; Stroke rates in patients with symptomatic intracranial stenosis may be high on medical therapy. Although there is no clinical evidence and appropriate devices for intracranial vessels, it seems to be a potentially effective in the future.

Evaluation of MCAO stroke models in normotensive rats: standardized neocortical infarction by the 3VO technique.

The temporary three-vessel occlusion (3VO) technique with a surgical approach for middle cerebral artery (MCA) produces consistent cerebral infarction in the neocortex in normotensive rats. The intraluminal thread-occlusion technique with an endovascular approach targeting the MCA occlusion (MCAO) is more widely used since it does not require complicated intracranial procedures. The aim of this study was to review the methods/models for MCAO stroke in normotensive rats and to evaluate a 3VO stroke model that provides consistent degrees and variance of cortical stroke injury for additional discussion. First, we analyzed a model with modified temporary 3VO technique requiring less complicated procedures than the temporary 3VO model, i.e., temporary occlusion of the bilateral common carotid arteries (CCAs) superimposed on a permanent occlusion of the MCA, in Sprague-Dawley rats or C57BL/6J mice. In the microvascular tissue (cerebral) perfusion study, significant reductions in regional cerebral perfusion during the 3VO accompanied a rapid return to baseline after release of the CCAs, showing that the technique induces temporary focal ischemia. The average sizes and variances of the neocortical infarction in this model, together with those in the other normotensive rat models caused by the 3VO technique in the literature, indicated a standard size and variance of infarcted lesion in the control groups relative to the specific ischemic period. However, stroke injuries in the neocortex induced by the thread occlusion technique showed greater variability with less consistent lesion sizes. Inclusion/exclusion criteria to avoid inappropriate cases with too mild (no/faint infarction) or too great (huge/fatal infarction) severity in the ischemic injury may differ between laboratories in the thread occlusion model.