Case of Cerebrospinal Fluid Leakage Nine Years after Pituitary Gamma Knife Surgery for Poststroke Thalamic Pain Syndrome.

Pituitary gamma knife surgery (GKS) is a treatment option for poststroke thalamic pain syndrome. Complications such as hypopituitarism, transient enuresis, and transient hyponatremia have been reported. However, cerebrospinal fluid (CSF) leakage has not yet been reported as a complication of pituitary GKS for poststroke thalamic pain syndrome. Herein, we report a case of delayed CSF rhinorrhea that developed 9 years after GKS for poststroke thalamic pain syndrome. A 64-year-old man presented to our hospital with bacterial meningitis and CSF rhinorrhea. Pituitary GKS for poststroke thalamic pain had been performed 9 years prior to his admission to our hospital. Computed tomography revealed pneumocephalus, fluid in the sphenoid and maxillary sinuses, and a partial bony defect of the sella turcica floor with communication between the paranasal and intracranial spaces. The CSF rhinorrhea resolved with bed rest and a lumbar CSF drain but recurred several days later. The patient underwent direct endoscopic surgical repair of the skull base. The sellar floor was covered with an autologous fascia graft harvested from the rectus sheath, and the sphenoid sinus was packed with abdominal fat grafts. The patient recovered, and the CSF rhinorrhea has not recurred for 2 years. Long-term follow-up is necessary after pituitary GKS, considering the complication of delayed CSF leakage.

Role of post-ischemic phase-dependent modulation of anti-inflammatory M2-type macrophages against rat brain damage.

Cerebral ischemia triggers inflammatory changes, and early complications and unfavorable outcomes of endovascular thrombectomy for brain occlusion promote the recruitment of various cell types to the ischemic area. Although anti-inflammatory M2-type macrophages are thought to exert protective effects against cerebral ischemia, little has been clarified regarding the significance of post-ischemic phase-dependent modulation of M2-type macrophages. To test our hypothesis that post-ischemic phase-dependent modulation of macrophages represents a potential therapy against ischemic brain damage, the effects on rats of an M2-type macrophage-specific activator, Gc-protein macrophage-activating factor (GcMAF), were compared with vehicle-treated control rats in the acute (day 0-6) or subacute (day 7-13) phase after ischemia induction. Acute-phase GcMAF treatment augmented both anti-inflammatory CD163+ M2-type- and pro-inflammatory CD16+ M1-type macrophages, resulting in no beneficial effects. Conversely, subacute-phase GcMAF injection increased only CD163+ M2-type macrophages accompanied by elevated mRNA levels of arginase-1 and interleukin-4. M2-type macrophages co-localized with CD36+ phagocytic cells led to clearance of the infarct area, which were abrogated by clodronate-liposomes. Expression of survival-related molecules on day 28 at the infarct border was augmented by GcMAF. These data provide new and important insights into the significance of M2-type macrophage-specific activation as post-ischemic phase-dependent therapy.

Transarterial Sinus Coiling for Dural Arteriovenous Fistula: Two Case Reports.

Objective: We report two cases of dural arteriovenous fistula (DAVF) treated by coil embolization of the affected sinus and fistula via a feeding artery instead of transvenous embolization (TVE) due to the difficulty of the transvenous approach. Case Presentation: An 82-year-old man was diagnosed with transverse sinus (TS) DAVF. A microcatheter was inserted into the isolated TS through the fistula via the middle meningeal artery (MMA), which was the feeding artery of the DAVF. The DAVF was occluded by coil embolization of the isolated sinus and fistula. A 79-year-old man was diagnosed with cavernous sinus (CS) DAVF. A microcatheter was inserted into the CS through the fistula via an accessory meningeal artery (AMA), which was the feeding artery of the DAVF. The DAVF was occluded by coil embolization of the affected sinus and fistula. Conclusion: These cases suggested that transarterial sinus coiling is one of the effective treatment options for DAVF.

[A Case Report of Subacute Thrombosis after Carotid Stenting Caused by Food Allergy].

An 89-year-old man underwent carotid artery stenting for symptomatic left internal carotid artery stenosis. His postoperative course was uneventful;however, on postoperative day 4, he developed a food allergy rash throughout his body after consuming sushi. He developed right hemiplegia and aphasia the following day, and magnetic resonance imaging revealed left internal carotid artery occlusion. Angiography revealed stent thrombosis, and endovascular thrombectomy achieved partial recanalization;however, right hemiplegia and aphasia persisted. Eosinophilia and increased platelet aggregation suggested allergic stent thrombosis(Kounis syndrome type 3).

[A Case Report of Endovascular Thrombectomy for Internal Carotid Artery Thromboembolism after Left Upper Lobectomy of Lung Cancer].

A 76-year-old man underwent a left upper lobectomy due to lung cancer. On postoperative day 3, he developed a cerebral infarction(NIHSS:17). MR and right carotid angiography demonstrated a right internal carotid artery occlusion. The patient underwent an endovascular thrombectomy without intravenous administration of recombinant tissue plasminogen activator. Complete recanalization was achieved and the symptoms almost disappeared except for a slight dysarthria. The patient subsequently continued cancer treatment by administration of edoxaban. Reports of cerebral emboli due to a thrombus migrating from the stump of the pulmonary vein after a left upper lobectomy are increasing. Several reports indicate that left upper lobectomy carries a high risk of thromboembolism. The current prospective study demonstrates that a mechanical thrombectomy can significantly improve both neurological and cognitive functions of patients after acute ischemic stroke. Endovascular neurosurgeons should prepare for and await an opportunity for thrombectomy for patients undergoing pulmonary resection.

[A Case Report of Basilar Artery Thromboembolism from Severe Stenosis of the Vertebral Artery Ostium].

We report a case of basilar artery embolism from the large thrombus of the right vertebral artery with severe stenosis of the vertebral artery ostium. Intravenous recombinant tissue plasminogen activator treatment and thrombectomy by catheter with reverse blood flow using a proximal subclavian artery blocking balloon(intentional subclavian artery steal phenomenon)were performed. A large thrombus along with other small thrombi were removed by an aspiration catheter. Additional stent placement was performed for residual vertebral artery stenosis, at ten days after the thrombectomy. Finally, the patient was discharged without any neurological deficits.

Treatment with the PPARγ Agonist Pioglitazone in the Early Post-ischemia Phase Inhibits Pro-inflammatory Responses and Promotes Neurogenesis Via the Activation of Innate- and Bone Marrow-Derived Stem Cells in Rats.

Neurogenesis is essential for a good post-stroke outcome. Exogenous stem cells are currently being tested to promote neurogenesis after stroke. Elsewhere, we demonstrated that treatment with the PPARγ agonist pioglitazone (PGZ) before cerebral ischemia induction reduced brain damage and activated survival-related genes in ovariectomized (OVX) rats. Here, we tested our hypothesis that post-ischemia treatment with PGZ inhibits brain damage and contributes to neurogenesis via activated stem cells. Bone marrow (BM) cells of 7-week-old Wistar female rats were replaced with BM cells from green fluorescent protein-transgenic (GFP+BM) rats. Three weeks later, they were ovariectomized (OVX/GFP+BM rats). We subjected 7-week-old Wistar male and 13-week-old OVX/GFP+BM rats to 90-min cerebral ischemia. Male and OVX/GFP+BM rats were divided into two groups, one was treated with PGZ (2.5 mg/kg/day) and the other served as the vehicle control (VC). In both male and OVX/GFP+BM rats, post-ischemia treatment with PGZ reduced neurological deficits and the infarct volume. In male rats, PGZ decreased the mRNA level of IL-6 and M1-like macrophages after 24 h. In OVX/GFP+BM rats, PGZ augmented the proliferation of resident stem cells in the subventricular zone (SVZ) and the recruitment of GFP+BM stem cells on days 7-14. Both types of proliferated stem cells migrated from the SVZ into the peri-infarct area. There, they differentiated into mature neurons, glia, and blood vessels in association with activated Akt, MAP2, and VEGF. Post-ischemia treatment with PGZ may offer a new avenue for stroke treatment through contribution to neuroprotection and neurogenesis.

Correction to: Treatment with the PPARγ Agonist Pioglitazone in the Early Post-ischemia Phase Inhibits Pro-inflammatory Responses and Promotes Neurogenesis Via the Activation of Innate- and Bone Marrow-Derived Stem Cells in Rats.

In the original publication of the article, the second author (Keiko T. Kitazato) was missing.

Site-specific elevation of interleukin-1ß and matrix metalloproteinase-9 in the Willis circle by hemodynamic changes is associated with rupture in a novel rat cerebral aneurysm model.

The pathogenesis of subarachnoid hemorrhage remains unclear. No models of cerebral aneurysms elicited solely by surgical procedures and diet have been established. Elsewhere we reported that only few rats in our original rat aneurysm model manifested rupture at the anterior and posterior Willis circle and that many harbored unruptured aneurysms at the anterior cerebral artery-olfactory artery bifurcation. This suggests that rupture was site-specific. To test our hypothesis that a site-specific response to hemodynamic changes is associated with aneurysmal rupture, we modified our original aneurysm model by altering the hemodynamics. During 90-day observation, the incidence of ruptured aneurysms at the anterior and posterior Willis circle was significantly increased and the high incidence of unruptured aneurysms at the anterior cerebral artery-olfactory artery persisted. This phenomenon was associated with an increase in the blood flow volume. Notably, the level of matrix metalloproteinase-9 associated with interleukin-1ß was augmented by the increase in the blood flow volume, suggesting that these molecules exacerbated the vulnerability of the aneurysmal wall. The current study first demonstrates that a site-specific increase in interleukin-1ß and matrix metalloproteinase-9 elicited by hemodynamic changes is associated with rupture. Our novel rat model of rupture may help to develop pharmaceutical approaches to prevent rupture.

The accumulation of brain water-free sodium is associated with ischemic damage independent of the blood pressure in female rats.

Estrogen deficiency worsens ischemic stroke outcomes. In ovariectomized (OVX(+)) rats fed a high-salt diet (HSD), an increase in the body Na(+)/water ratio, which characterizes water-free Na(+) accumulation, was associated with detrimental vascular effects independent of the blood pressure (BP). We hypothesized that an increase in brain water-free Na(+) accumulation is associated with ischemic brain damage in OVX(+)/HSD rats. To test our hypothesis we divided female Wistar rats into 4 groups, OVX(+) and OVX(-) rats fed HSD or a normal diet (ND), and subjected them to transient cerebral ischemia. The brain Na(+)/water ratio was increased even in OVX(+)/ND rats and augmented in OVX(+)/HSD rats. The increase in the brain Na(+)/water ratio was positively correlated with expansion of the cortical infarct volume without affecting the BP. Interestingly, OVX(+) was associated with the decreased expression of ATP1α3, a subtype of the Na(+) efflux pump. HSD increased the expression of brain Na(+) influx-related molecules and the mineralocorticoid receptor (MR). The pretreatment of OVX(+)/HSD rats with the MR antagonist eplerenone reduced brain water-free Na(+) accumulation, up-regulated ATP1α3, down-regulated MR, and reduced the cortical infarct volume. Our findings show that the increase in the brain Na(+)/water ratio elicited by estrogen deficiency or HSD is associated with ischemic brain damage BP-independently, suggesting the importance of regulating the accumulation of brain water-free Na(+). The up-regulation of ATP1α3 and the down-regulation of MR may provide a promising therapeutic strategy to attenuate ischemic brain damage in postmenopausal women.

PPARγ-Dependent and -Independent Inhibition of the HMGB1/TLR9 Pathway by Eicosapentaenoic Acid Attenuates Ischemic Brain Damage in Ovariectomized Rats.

High mobility group box 1 (HMGB1) elevation after cerebral ischemia activates inflammatory pathways via receptors such as the receptor for advanced glycation end products (RAGE) and toll-like receptors (TLRs) and leads to brain damage. Eicosapentaenoic acid (EPA), a peroxisome proliferator-activated receptor gamma (PPARγ) agonist, attenuates postischemic inflammation and brain damage in male animals. However, postischemic HMGB1 signaling and the effects of EPA on ovariectomized (OVX(+)) rats remain unclear. We hypothesized that EPA attenuates brain damage in OVX(+) rats via the inhibition of HMGB1 signaling in a PPARγ-dependent manner. Seven-week-old female Sprague-Dawley rats were divided into 3 groups; nonovariectomized (OVX(-)) rats and EPA-treated and EPA-untreated OVX(+) rats before cerebral ischemia induction. Another set of EPA-treated OVX(+) rats was injected with the PPARγ inhibitor GW9662. OVX(+) decreased the messenger RNA level of PPARγ and increased that of HMGB1, RAGE, TLR9, and tumor necrosis factor alpha (TNFα) in parallel with ischemic brain damage. EPA restored the PPARγ expression, downregulated the HMGB1 signal-related molecules, and attenuated the ischemic brain damage. Neither OVX(+) nor EPA affected the expression of TLR2 or TLR4. Interestingly, GW9662 partially abrogated the EPA-induced neuroprotection and the downregulation of RAGE and TLR9. In contrast, GW9662 did not affect HMGB1 or TNFα. These results suggest that EPA exerts PPARγ-dependent and PPARγ-independent effects on postischemic HMGB1/TLR9 pathway. The cortical infarct volume exacerbated by OVX(+) is associated with the upregulation of the HMGB1/TLR9 pathway. Suppression of this pathway may help to limit ischemic brain damage in postmenopausal women.

[Differential diagnosis of and therapy for anaplastic astroblastoma: case report and review of the literature].

Astroblastomas are rare glial tumors. We report a case of 33-year-old woman with high-grade astroblastoma with hypervascularity. She had a one-month history of right visual disturbance and papillar edema. MRI revealed a lobulated mass with cysts and flow voids in the right superficial frontal lobe, a phenomenon described as "bubbly appearance". Right carotid angiography demonstrated marked tumor stain and early venous filling. MR spectroscopy showed an increase in myoinositol and the choline/creatine ratio, and decreased N-acetyl aspartate. The lipid and lactate level was not increased. The well-circumscribed tumor was totally resected. Histological examination showed perivascular pseudorosettes and hyalinization of blood vessels with high cellularity, anaplastic nuclear features, focal necrosis, mitosis, and endothelial proliferation. Immunohistochemically, glial fibrillary acidic protein and S-100 protein were intensely positive and the MIB-1 labeling index was high(20%)in the tumor cells. Based on these findings, a diagnosis of high-grade astroblastoma was made. The patient received postoperative radiotherapy and chemotherapy with temozolomide and suffered no relapse in the course of 3 years after surgery. Characteristically, astroblastomas manifest a "bubbly appearance" and a lobulated mass on MRI scans. As these tumors tend to be hypervascular, angiograms are useful for designing the operative strategy. However, their low-or high grade is difficult to ascertain preoperatively based on MRI-, MRS-, and DSA findings. The standard therapy for high-grade astroblastoma is total resection and postoperative radiation therapy. As the incidence of tumor recurrence is high, we recommend additional chemotherapy with TMZ.