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BACKGROUND An intratumoral aneurysm encased within the associated intracranial tumor is rare, and hemorrhage caused by its rupture is even more rare. While urgent and adequate surgical treatment is important, the treatment can be difficult given the limited understanding of this rare condition. OBSERVATIONS A 69-year-old man who had undergone meningioma surgery 30 years prior presented with a disturbance in consciousness. Magnetic resonance imaging revealed massive intracerebral and subarachnoid hemorrhage. A round, partially calcified mass, which was diagnosed as recurrent meningioma, was also observed. Subsequent cerebral angiography revealed that the source of the hemorrhage was an intratumoral aneurysm in the dorsal internal carotid artery (ICA) encased within the recurrent meningioma. Urgent surgical ICA trapping and high-flow graft bypass were conducted. The postoperative course was uneventful, and he was referred to another hospital for rehabilitation. LESSONS This is the first case report of a ruptured intratumoral aneurysm being treated with urgent combined revascularization and parent artery trapping surgery. This surgical approach may be a feasible treatment option for such a challenging condition. Additionally, this case highlights the importance of diligent long-term follow-up after skull-base surgery, as minor intraoperative vascular wall injury may trigger the development and rupture of an intracerebral aneurysm.

Therapeutic hypothermia has consistently been shown to be a robust neuroprotectant in many labs studying different models of neurological disease. Although this therapy has shown great promise, there are still challenges at the clinical level that limit the ability to apply this routinely to each pathological condition. In order to overcome issues involved in hypothermia therapy, understanding of this attractive therapy is needed. We review methodological concerns surrounding therapeutic hypothermia, introduce the current status of therapeutic cooling in various acute brain insults, and review the literature surrounding the many underlying molecular mechanisms of hypothermic neuroprotection. Because recent work has shown that body temperature can be safely lowered using pharmacological approaches, this method may be an especially attractive option for many clinical applications. Since hypothermia can affect multiple aspects of brain pathophysiology, therapeutic hypothermia could also be considered a neuroprotection model in basic research, which would be used to identify potential therapeutic targets. We discuss how research in this area carries the potential to improve outcome from various acute neurological disorders.

Objectives This study aimed to assess the clinical usefulness of a direct aspiration first pass technique as a first-line strategy for mechanical thrombectomy in posterior circulation. Materials and methods We examined 34 consecutive patients treated with mechanical thrombectomy for acute vertebrobasilar artery occlusion. Procedural and clinical outcomes were assessed and compared between patients treated with a direct aspiration first pass technique first-line strategy (ADAPT group) and stent retriever system first-line strategy (stent retriever group). Results Overall, successful reperfusion, complete reperfusion, and first-pass effects were achieved in 94.1%, 61.8%, and 50% of patients with acute ischemic stroke in vertebra-basilar artery occlusion treated with mechanical thrombectomy, respectively. The ADAPT group required a significantly shorter procedural time (p=.015) and fewer attempts (p=.0498) to achieve successful recanalization than the stent retriever group. The ADAPT group also tended to show better recanalization rates and first-pass effects than the stent retriever group. The rates of favorable outcomes seemed to be better, although insignificant, in the ADAPT group than in the stent retriever group (52.2% vs. 27.3%, p=.217). However, a significant correlation between the time required for reperfusion and clinical outcome was detected, and this will serve as the rationale for encouraging a direct aspiration first pass technique as a first-line strategy in the acute vertebra-basilar artery. Conclusions The a direct aspiration first pass technique first-line strategy for mechanical thrombectomy in posterior circulation may achieve successful recanalization with fewer attempts and shorter durations than the stent retriever first-line strategy.

Background: Intracranial and central nervous system’s involvement with multiple myeloma (MM) is a clinically rare manifestation. Furthermore, the development of intracranial plasmacytoma without bone involvement is much rarer. Herein, we report the case of massive intracerebral hemorrhage form intracranial plasmacytoma that arose from the dura mater without bone involvement. Case Description: A 71-year-old woman, who had been diagnosed as MM and treated 2 years prior, developed sudden lethal intracerebral hemorrhage from the intracranial plasmacytoma. Massive hemorrhage was observed after a rapid tumor growth in the middle fossa. Immediate hematoma evacuation and tumor resection allowed the patient to avoid severe neurological deficits and lethal conditions. Conclusion: A close follow-up by neuroimaging studies is essential in cases of intracranial plasmacytoma in MM patients and early intervention with surgical resection or radiotherapy should be considered.

Electrocardiogram (ECG)-triggered angiography non-contrast-enhanced (TRANCE) imaging is useful for investigating peripheral vessel diseases; however, its efficacy for access route assessment in cerebral angiography has yet to be reported. Therefore we aimed to evaluate the efficacy of TRANCE imaging in the assessment of the access route before diagnostic subtraction angiography for cerebral vascular disorders.TRANCE imaging was performed in all patients undergoing catheter angiography for disease diagnosis at our institute between April 2014 and March 2015. This study included 31 patients (14 men, 17 women) and investigated potential changes in the planned puncture site before and during the procedure (including the reason for the change) as our main outcome.TRANCE was successfully conducted in all of the patients recruited. TRANCE images led to an alteration in the approach vessel for 5 cases. The mean procedure time for angiography was60 minutes. The median total number of catheters and guidewires used during catheter angiography was 1 (range: 1-3) and 1 (range: 1-2), respectively. There were no catheter angiography-related complications.TRANCE imaging before diagnostic angiography is useful because it allows detailed assessment of the access route. This practice may reduce procedure time, thus resulting in fewer complications.

Since the beneficial effect attained by mechanical thrombectomy (MT) seems to be worse in older than in the younger population, the establishment of an ideal and distinctive patient selection protocol in older is warranted. Herein, we modified our patient selection protocol based on age and premorbid independence in older adult patients.We retrospectively reviewed 141 consecutive patients with acute ischemic stroke who were treated with MT between 2015 and 2020. We started to restrict the indication of MT in very old patients (≥85-year-old) with severe premorbid functional independence (≥modified Rankin Scale [mRS] 3) in 2018. Clinical outcomes before the modification of protocol (period 1) were compared to after (period 2).Although there were no significant differences in median mRS at 90 days and the rates of favorable outcomes (mRS 0-2) between both periods, rates of poor outcomes (mRS 5, 6) significantly decreased (37.3% vs. 19.7%,Our modified patient selection protocol in older adults, not only limited by age but also premorbid function, improved the therapeutic outcome of MT. In rapidly aging society, further investigations facilitating a better understanding are necessary to establish an optimal patient selection protocol.

Objectives A direct first-pass aspiration technique (ADAPT) is an attractive interventional technique for mechanical thrombectomy (MT), which could achieve recanalization quickly and safely at a small amount of material resources. To clarify its usefulness, our ADAPT first-line strategy for middle cerebral artery (MCA)-mainstem occlusion was retrospectively analyzed. Materials and Methods We reviewed 54 consecutive patients who underwent MT for MCA-mainstem occlusion using ADAPT first-line strategy. A salvage procedure was concurrently conducted in cases that failed to achieve successful recanalization by ADAPT attempt alone. Procedural and clinical outcome were assessed in both ADAPT alone and Salvage groups. Further investigation was performed in cases that required salvage procedure to determine the reason, risk factors, and optimal procedure. Results Forty-one patients (75.9%) were able to achieve successful recanalization with ADAPT technique alone. In salvage group, the procedural time was longer, and rates of successful recanalization were lower than in ADAPT-alone group. No significant difference in the rates of favorable outcomes was observed. Among 13 patients who required salvage therapy, the major reason (eight cases) was intra-procedural “thrombus distal migration”. Failure of recanalization was seen in two cases due to “inaccessibility”. In patients who had “thrombus distal migration”, occlusion in the proximal portion was more frequently observed than in patients who did not (p = 0.032, 63.6% vs. 23.3%). Conclusions Our ADAPT first-line strategy for MCA-mainstem occlusion demonstrated favorable procedural and clinical outcomes, even in cases that required additional procedures. Further investigation and better understanding are required to refine this promising procedure.

Background: The development of cerebral infarction after transient ischemia is attributed to postischemic delayed hypoperfusion in the microvascular region. In the present study, we assessed the microvascular perfusion capacity of infused liposome-encapsulated hemoglobin (LEH) in a therapeutic approach for transient middle cerebral artery occlusion (tMCAO). Methods: Two-hour middle cerebral artery occlusion rats were immediately subjected to intra-arterial infusion of LEH (LEH group) or saline (vehicle group) or no treatment (control group), and then to recanalization. Neurological findings, infarct and edema progression, microvascular endothelial dysfunction, and inflammatory reactions were compared between the 3 groups after 24 hours of reperfusion. Microvascular perfusion in the early phase of reperfusion was evaluated by hemoglobin immunohistochemistry and transmission electron microscopy. Results: The LEH group achieved significantly better results in all items evaluated than the other groups. Hemoglobin immunohistochemistry revealed that the number of hemoglobin-positive microvessels was significantly greater in the LEH group than in the other groups (P < .01), with microvascular perfusion being more likely in narrow microvessels (≤ 5 µm in diameter). An electron microscopic examination revealed that microvessels in the control group were compressed and narrowed by swollen astrocyte end-feet, whereas those in the LEH group had a less deformed appearance and contained LEH particles and erythrocytes. Conclusion: The results of the present study demonstrated that the infusion of LEH reduced infarctions after tMCAO with more hemoglobin-positive and less deformed microvessels at the early phase of reperfusion, suggesting that the superiority of the microvascular perfusion of LEH mediates its neuroprotective effects.

BACKGROUND It is necessary and useful to obtain an experimental model which steadily and rapidly induces aneurysms for investigation of the pathogenesis of cerebral aneurysm. We attempted to examine whether intraperitoneal administration of β-aminopropionitrile fumarate (BAPN-F) with additional treatments of induced hypertension and hemodynamic stress could steadily and rapidly induce aneurysms in male rats. METHODS Seven-week-old male Sprague-Dawley rats pretreated with ligation of left common carotid and bilateral posterior renal arteries were administrated BAPN-F intraperitoneally. Induction rate and size of aneurysms was investigated with varying dose and duration of BAPN-F administration (low dose; 400 mg/kg/week for 4 or 8 weeks and high dose; 2800 mg/kg/week for 8 or 12 weeks). RESULTS Induction rate in the high-dose groups was significantly higher (p

Background and Purpose: Cofilin-actin rods are covalently linked aggregates of cofilin -1 and actin. Under ischemic conditions, these rods have been observed in neuronal processes, but their significance is unknown. Here, we explored a potential role of these rods in two different models of neuroprotection from experimental stroke—therapeutic hypothermia and the 70-kDa heat shock protein (Hsp70). Methods: Male C57/BL6 mice were subjected to distal middle cerebral artery occlusion (dMCAO), and treated with hypothermia. Cooling (31°C, 2hrs) was begun at the onset of dMCAO. A neuroprotective effect of hypothermia was validated by functional assessments and infarct volume measurement. Cofilin-actin rod formation was assessed by histological analysis at 4 and 24hrs after dMCAO. Its expression was analyzed in three different regions, infarct core (the center of the infarct), penumbra (area salvaged by intervention and a fixed distance from the midline), and ischemic borderzone (border of ischemic lesion). In addition, Hsp70-overexpressing transgenic (Tg) mice and Hsp70-deficient (Ko) mice were also subjected to dMCAO, and cofilin-actin rod expression was assessed in same manner. Results: As shown previously by our lab, both hypothermia and Hsp70 Tg mice had smaller lesion sizes and improved neurological outcomes compared to normothermic and wildtype (Wt) mice. Hsp70 Ko mice had larger lesion sizes and worsened neurological outcomes. Following dMCAO, cofilin-actin rods were increased, but were reduced by hypothermia in the ischemic core (24hrs, p Conclusions: Cofilin-actin rod formation was suppressed under conditions of improved neurological outcome, and increased under circumstances where outcome was worsened. This suggests that cofilin-actin rods may act to participate in or exacerbate ischemic pathology, and warrants further study as a potential therapeutic target.

Author(s): Kurisu, Kota; You, Jesung; Zheng, Zhen; Won, Seok Joon; Swanson, Raymond A; Yenari, Midori A | Abstract: BACKGROUND AND PURPOSE:Cofilin-actin rods are covalently linked aggregates of cofilin-1 and actin. Under ischemic conditions, these rods have been observed in neuronal dendrites and axons and may contribute to the loss of these processes. Hypothermia (Hypo) and the 70 kD inducible heat shock protein (Hsp70) are both known to improve outcomes after stroke, but the mechanisms are uncertain. Here, we evaluated the effect of these factors on cofilin-actin rod formation in a mouse model of stroke. MATERIALS AND METHODS:Mice were subjected to distal middle cerebral artery occlusion (dMCAO) and treated with Hypo using a paradigm previously shown to be neuroprotective. We similarly studied mice that overexpressed transgenic (Tg) or were deficient knockout (Ko) in the inducible 70 kDa heat shock protein (Hsp70), also previously shown to be protective by our group and others. Cofilin-actin rod formation was assessed by histological analysis at 4 and 24 h after dMCAO. Its expression was analyzed in three different regions, namely, infarct core (the center of the infarct), middle cerebral artery (MCA) borderzone (the edge of the brain regions supplied by the MCA), and the ischemic borderzone (border of ischemic lesion). Ischemic lesion size and neurological deficits were also assessed. RESULTS:Both Hypo-treated and Hsp70 Tg mice had smaller lesion sizes and improved neurological outcomes, whereas Hsp70 Ko mice had larger lesion sizes and worsened neurological outcomes. Cofilin-actin rods were increased after stroke, but were reduced by therapeutic Hypo and in Hsp70 Tg mice. In contrast, cofilin-actin rods were increased in ischemic brains of Hsp70 Ko mice. CONCLUSIONS:Cofilin-actin rod formation was suppressed under the conditions of neuroprotection and increased under circumstances where outcome was worsened. This suggests that cofilin-actin rods may act to participate in or exacerbate ischemic pathology and warrants further study as a potential therapeutic target.

The robust neuroprotective effects of transarterial regional hypothermia have been demonstrated in the typical transient middle cerebral artery occlusion (tMCAO) model, but have not yet been tested in other ischemic stroke models, even though clinical ischemic conditions are diverse. In order to clarify these effects in a different ischemic stroke model, we employed a rat model of permanent MCAO (pMCAO) with transient collateral hypoperfusion (tCHP), which was achieved by direct MCA ligation through craniotomy and 1-h bilateral common carotid artery occlusion at the beginning of pMCAO. The infusion of 20 ml/kg of 4 degrees C cold saline (CS) or 37 degrees C warm saline (WS) into the ipsilateral internal carotid artery (ICA) was performed for 15 min in intra- or post-tCHP. Neurological scores, infarct/edema volumes, and neuronal apoptosis and reactive gliosis were compared between the CS and WS groups and a non-infusion control group after 48 h of reperfusion. Although brain temperatures were only reduced by 2-3 degrees C for 15 min, the CS group had significantly better neurological scores, smaller infarct/edema volumes, and less penumbral neuronal apoptosis and reactive gliosis than the control and WS groups. The post-tCHP CS group exhibited prominent neuroprotective effects, even though infarct volumes and neuronal apoptosis were reduced less than those in the intra-tCHP CS group. In conclusion, we demonstrated the neuroprotective effects of transarterial regional hypothermia in an ischemic model of pMCAO with tCHP. Even though MCAO is persistent, cold infusion via the ICA is neuroprotective for the penumbra, suggesting the wider therapeutic application of this therapy.

Background Although transarterial regional hypothermia is an attractive alternative to general hypothermia, its efficacy and underlying mechanisms remain unclear. Objective To confirm transarterial regional hypothermia therapeutic effects on ischemia/reperfusion (I/R) injury and to elucidate the mechanisms responsible. Methods The therapeutic effects of transarterial regional hypothermia were initially investigated in 2-hour middle cerebral artery occlusion rats regionally infused with 10°C saline (cold saline group) or 37°C saline (warm saline group) and untreated rats (control group) just before the onset of 24 hours of reperfusion. The time course of infarct and edema progression, inflammatory reactions, microvascular morphological changes, and aquaporin-4 (AQP4) expression was analyzed after 0, 2, 6, and 24 hours of reperfusion. Results Cold saline infusion only lowered brain temperatures for 30 minutes but mediated strong neuroprotective effects with infarct volume reductions of less than one-third. The time-course analysis revealed the following sequence of ischemia/reperfusion injury-related events in the control group: upregulated expression of AQP4 (2 hours); microvascular narrowing resulting from swollen astrocytic end-feet (2-6 hours); infarct and edema progression, blood-brain barrier disruption, and upregulated expression of intracellular adhesion molecule-1 (6-24 hours); and the activation of other inflammatory reactions (24 hours). These sequential events were inhibited in the cold saline group. Conclusion Transarterial regional hypothermia initially inhibited the acute AQP4 surge and then attenuated microvascular narrowing, blood-brain barrier disruption, and activation of other inflammatory reactions, leading to strong neuroprotective effects. More direct and intensive cooling of the endothelium and its surroundings may contribute to these effects. Abbreviations AQP4, aquaporin-4BBB, blood-brain barrierIba1, ionized calcium-binding adapter molecule 1ICA, internal carotid arteryICAM-1, intracellular adhesion molecule-1I/R, ischemia/reperfusionMCAO, middle cerebral artery occlusionMMP-9, matrix metalloproteinase-9.

Regional cold perfusion and hemoglobin-based oxygen carrier administration both exert neuroprotective effects against cerebral ischemia reperfusion injury. We herein investigated whether the combination of these two therapies leads to stronger neuroprotective effects. Combination therapy was performed with the regional perfusion of cold HemoAct, a core-shell structured hemoglobin-albumin cluster, in a rat transient middle cerebral artery occlusion model. The effects of combination therapy, the intra-arterial administration of 10 °C HemoAct (10H) initiated at the onset of reperfusion, were compared with those of monotherapies, the intra-arterial administration of 10 °C saline (10S) and 37 °C HemoAct (37H), and an untreated control under the condition of 2-hour ischemia/24-hour reperfusion. The durability of therapeutic effects and the therapeutic time window of combination therapy were assessed based on comparisons with the 10H and control groups. Significantly better neurological findings and smaller infarct volumes were observed in the three treated (10S, 37H, and 10H) groups than in the control group. Among the 3 treated groups, only the 10H group showed significant improvements over the control group in the other items examined, including cerebral blood flow reduction, brain edema, and protein extravasation. The significant therapeutic effects of combination therapy on neurological disabilities and infarct volumes were confirmed at least until 7 days after reperfusion. Furthermore, combination therapy ameliorated neurological disabilities and hemorrhagic transformation in rats subjected to 4- and 5-hour ischemia/24-hour reperfusion. Since therapeutic effects may be expected until at least 5 h of complete ischemia and reperfusion, this combination therapy is a promising neuroprotective strategy against severe ischemic stroke.

Background and Purpose: We previously reported that triggering receptor expressed on myeloid cells-2 (TREM2) expression on microglia/macrophage activates its phagocytic function and promotes stroke recovery. Although its importance has been demonstrated, it is unclear whether there is a similar effect in females. Furthermore, TREM2 mutations have been linked to dementia. In the present study, we explored the influence of TREM2 deficiency in aged female mice subjected to middle cerebral artery occlusion (MCAO). We assessed histology, sensorimotor and cognitive functions along with post stroke immune responses. Methods: Age matched (≥8months) female TREM2 knockout (TREM2-KO) and Wild type (Wt) mice were subjected to permanent distal MCAO. Sensorimotor and cognitive (Y-maze test) functions and infarct size were assessed up to 14d after stroke (n=6/each). Microglial activation (isolectin B4, IB4 & CD68), phagocytosis (oil red O stain) and M1 (NO/iNOS) and M2 (arginase, Arg) markers 1,3,7 and 14d post MCAO. Results: At baseline, aged female mice lacking TREM2 had similar cognitive & sensorimotor function. However, post stroke, TREM2-KO females, compared to Wt, showed worsened cognitive (p Conclusions: Similar to male mice, TREM2 seems to have beneficial properties in female mice. TREM2 deficient female mice had larger infarct sizes and worsened neurological performance. Microglial responses also seemed to suggest that TREM2 promotes beneficial and/or recovery pathways.

A rare case of Mollaret meningitis characterized by four recurrent episodes of aseptic meningitis during a three-year period is reported. The patient showed a high fever and severe headache accompanied by a high level of cerebrospinal fluid (CSF) cytokines, such as interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha). The symptoms and high CSF cytokines were resolved immediately after introducing indomethacin treatment. Reactivation of the latent virus is considered to be the cause of this rare disease, and indomethacin is believed to inhibit the periodic abnormal generation of eicosanoid in the brain, resulting in a reduction in the fever and subsequent inflammation.

Triggering receptor expressed on myeloid cells-2 (TREM2) is an innate immune receptor that promotes phagocytosis by myeloid cells such as microglia and macrophages. We previously showed that TREM2 deficiency worsened outcomes from experimental stroke and impeded phagocytosis. However, myeloid cells participating in stroke pathology include both brain resident microglia and circulating macrophages. We now clarify whether TREM2 on brain microglia or circulating macrophages contribute to its beneficial role in ischemic stroke by generating bone marrow (BM) chimeric mice. BM chimera mice from TREM2 knockout (KO) or wild type (Wt) mice were used as donor and recipient mice. Mice were subjected to experimental stroke, and neurological function and infarct volume were assessed. Mice with intact TREM2 in brain microglia showed better neurological recovery and reduced infarct volumes, compared with mice lacking microglial TREM2. Myeloid cell activation and numbers of phagocytes were decreased in mice lacking brain TREM2, compared with mice with intact brain TREM2. These results suggest that TREM2 expression is important for post-stroke recovery, and that TREM2 expression on brain resident microglia is more essential to this recovery, than that of circulating macrophages. These findings might suggest a new therapeutic target for cerebrovascular diseases.

Background and Purpose— A hemoglobin-albumin cluster, 1 core of hemoglobin covalently bound with 3 shell albumins, designated as HemoAct was developed as a hemoglobin-based oxygen carrier. We aim to investigate neuroprotection by HemoAct in transient cerebral ischemia and elucidate its underlying mechanisms. Methods— Male rats were subjected to 2-hour transient middle cerebral artery occlusion and were then administered HemoAct transarterially at the onset of reperfusion. Neurological and pathological findings were examined after 24 hours of reperfusion to identify neuroprotection by HemoAct. Intermittent measurements of cortical blood flow and oxygen content were performed, and a histopathologic analysis was conducted on rats during the early phase of reperfusion to assess the therapeutic mechanism of HemoAct. In addition, the antioxidant effects of HemoAct were examined in hypoxia/reoxygenation-treated rat brain microvascular endothelial cells. Results— Neurological deterioration, infarct and edema development, and the activation of MMP-9 (matrix metalloprotease-9) and lipid peroxidation after 24 hours of reperfusion were significantly ameliorated by the HemoAct treatment. Reductions in blood flow and tissue partial oxygen pressure in the cortical penumbra after 6 hours of reperfusion were significantly ameliorated by the HemoAct treatment. The histopathologic analysis of the cortical penumbra revealed that HemoAct in HemoAct-treated rats showed superior microvascular perfusion with the mitigation of microvascular narrowing changes than autologous erythrocytes in nontreated rats. Although HemoAct extravasated into the ischemic core with serum protein, it did not induce an increase in serum extravasation or reactive oxygen species production in the ischemic core. In vitro experiments with rat brain microvascular endothelial cells revealed that HemoAct significantly suppressed cellular reactive oxygen species production in hypoxia/reoxygenation-treated cells, similar to albumin. Conclusions— HemoAct exerted robust neuroprotection in transient cerebral ischemia. Superior microvascular perfusion with an oxygen delivery capability and possible antioxidant effects appear to be the underlying neuroprotective mechanisms.

Although ultrasound (US) guidance for venous access is becoming the “standard of care” for preventing access site complications, its feasibility for arterial access has not been fully investigated, especially in the neuro-interventional population. We conducted the first prospective cohort study on US-guided femoral artery access during neuro-interventional procedure. This study included 64 consecutive patients who underwent US-guided femoral artery access through 66 arterial access sites for diagnostic and/or neuro-interventional purposes. The number of attempts required for both the sheath insertion and the success of anterior wall puncture were recorded. In addition, the occurrence of major complications and hematoma formation on the arterial access site examined by US were statistically analyzed. The median number of attempts was 1 (1–2) and first-pass success rate was 63.6%. Anterior wall puncture was achieved in 98.5%. In one case (1.5%), a pseudoaneurysm was observed. In all cases, US clearly depicted a common femoral artery (CFA) and its bifurcation. Post-procedural hematoma was detected in 13 cases (19.7%), most of which were “tiny” or “moderate” in size. Low body mass index and antiplatelet therapy were the independent risk factors for access site hematoma. The US-guided CFA access was feasible even in neuro-interventional procedure. The method was particularly helpful in the patients with un-palpable pulsation of femoral arteries. To prevent arterial access site hematoma, special care should be taken in patients with low body mass index and who are on antiplatelet therapy.

Background and Purpose: We previously reported that triggering receptor expressed on myeloid cells-2 (TREM2) expression promotes post-ischemic phagocytosis and leads to neurological recovery. However, the precise underlying mechanism is not fully understood yet. In present study, we aimed to clarify which pool of myeloid cells (brain resident microglia versus macrophage derived from circulation) are contributing to its beneficial role in post-ischemic recovery, with the usage of bone marrow (BM) chimeric mice. Methods: BM chimeric mice were created by BM transplanting BM from TREM2 knockout (KO) and wild type (Wt) mice into KO and Wt recipient mice. Thus, 4 groups (Wt (donor) to Wt (recipient), KO to Wt, Wt to KO, KO to KO; n=6/each) of BM chimeric mice were produced, then were subjected to dMCAO surgery. Neurological function was observed until 14 days after surgery. Infarct volume and immunohistological analysis (myeloid cell activation and infiltration: isolectin B4 (IB4) and CD11b; phagocytosis: oil red o and CD68; TREM2 expression) was also undergone. Results: Compared to mice lacking brain TREM2 (WT to KO and KO to KO), mice with intact TREM2 in brain microglia (KO to WT and WT to WT) showed better neurological recovery (p Conclusions: Although our results suggest TREM2 expression in both microglia and circulating macrophage were crucial for post-ischemic recovery, its beneficial effect was greater when TREM2 was present in brain resident microglia.

A rare case of Mollaret meningitis characterized by four recurrent episodes of aseptic meningitis during the 3-year periods were reported. The patient showed high fever and severe headache accompanied by high level of cerebrospinal fluid (CSF) cytokines such as interleukin-6 (IL-6) and tumor necrosis factor-alfa (TNF-a). The symptoms and high CSF cytokines were dramatically resolved immediately after inducing indomethacin treatment. Reactivation of the latent virus is considered to be the cause of this rare disease and indomethacin is estimated to inhibit periodic abnormal generation of eicosanoid in the brain resulting in reducing fever and subsequent inflammation.

Therapeutic hypothermia, or cooling of the body or brain for the purposes of preserving organ viability, is one of the most robust neuroprotectants at both the preclinical and clinical levels. Although therapeutic hypothermia has been shown to improve outcome from related clinical conditions, the significance in ischemic stroke is still under investigation. Numerous pre-clinical studies of therapeutic hypothermia has suggested optimal cooling conditions, such as depth, duration, and temporal therapeutic window for effective neuroprotection. Several studies have also explored mechanisms underlying the mechanisms of neuroprotection by therapeutic hypothermia. As such, it appears that cooling affects multiple aspects of brain pathophysiology, and regulates almost every pathway involved in the evolution of ischemic stroke. This multifaceted mechanism is thought to contribute to its strong neuroprotective effect. In order to carry out this therapy in optimal clinical settings, methodological and pathophysiological understanding is crucial. However, more investigation is still needed to better understand the underlying mechanisms of this intervention, and to overcome clinical barriers which seem to preclude the routine use therapeutic hypothermia in stroke. This article is part of the Special Issue entitled 'Cerebral Ischemia'.

Background: A hemoglobin-albumin cluster designated as “HemoAct” was developed as a red blood cell substitute. It is composed of one core hemoglobin center wrapped covalently by three albumin shells. Since its particle size with a diameter of 10 nm is far smaller than red blood cell, it is expected to maintain good perfusion in the cerebral microvessels, leading to neuroprotective effects on ischemia-reperfusion (I/R) injury. Purpose: We aim to examine whether HemoAct have neuroprotective effects in rat transient middle cerebral artery occlusion (tMCAO) model, without toxic effects of hemoglobin, by administering it though the recanalized artery just before the onset of reperfusion. Subjects and Methods: Male Sprague-Dawley rats were subjected to 2-hour tMCAO by suture occlusion and then divided into four groups with respective treatments: (1) control group; no infusion, (2) vehicle group; infusion of PBS as the solvent (3) 0.5х HemoAct group; infusion of one-half diluted HemoAct (4) HemoAct group; infusion of undiluted HemoAct. Physical and neurological states, infarct and edema volumes, reactive oxygen species (ROS) and protease immunoblot levels were compared between the four groups after 24 hours of reperfusion. Microvascular hemoglobin perfusion and morphological states were compared between the control and HemoAct groups with immunohistochemical technique. Results: No significant changes were observed in blood pressure, pH, and blood gas after HemoAct infusion. Neurological symptoms were significantly less severe in the HemoAct group than in the other groups. Infarct and edema volumes were significantly smaller in the 0.5х HemoAct group (27.1%/15.2%) and the HemoAct group (20.2%/14.1%) than in the control group (55.2%/26.4%) and the vehicle group (53.2%/27.1%). ROS (4-HNE) and protease (MMP-9) immunoblot levels were significantly reduced in HemoAct group compared with the control and vehicle groups. Microvascular hemoglobin perfusion was more and microvascular narrowing changes was less in the HemoAct group than in the control group. Conclusion: HemoAct exhibited strong neuroprotective effects on I/R injury without toxic effects of hemoglobin. Superior microvascular perfusion of HemoAct may be a possible neuroprotective mechanism.

An 86-year-old female presented with rare bilateral chronic subdural hematomas (CSHs) of the posterior fossae which were successfully treated by surgical intervention. She had experienced mild head trauma one month before admission. She was transferred to our hospital because of consciousness disturbance and tetraparesis. Magnetic resonance (MR) imaging showed simultaneous occurrence of supratentorial and infratentorial CSHs. We tried to evacuate the CSHs of the bilateral posterior fossae because brainstem compression was markedly severe. Through bilateral burr-hole trepanations, chocolate-colored fluid, not containing clotted components, gushed out under great pressure. Postoperative course was uneventful. MR imaging revealed that the CSHs of the posterior fossae had completely disappeared and brainstem compression had also improved. The patient's neurological deficits were immediately improved after the operation. The patient was discharged one month after the operation for further rehabilitation. Trepanation and evacuation of the hematoma through the posterior fossa might be one of the therapeutic options for posterior fossa CSH, which is similar to supratentorial CSH. However, we considered that the emergency of this rare entity and the method of anesthesia were quite different from supratentorial CSH.

A 68-year-old man presented with severe conscious disturbance caused by pituitary apoplexy resulting in massive intracerebral hemorrhage (ICH). He had been periodically followed up for asymptomatic pituitary adenoma at another hospital for 8 years. Neuroimaging examination revealed pituitary apoplexy and massive ICH located in the left frontal lobe, and the ICH was directly connected to the intratumoral hemorrhage. The diagnosis was massive ICH from pituitary apoplexy. The patient underwent emergent evacuation of hematoma and removal of the pituitary adenoma via bi-frontal craniotomy. Postoperatively, he continued to exhibit deep consciousness disturbance and died 1 month after the operation. Pituitary apoplexy is usually characterized by intra-tumoral hemorrhage. The treatment strategy for asymptomatic pituitary adenoma is still controversial. This case shows that we should always consider the risk of pituitary apoplexy manifesting as ICH which may cause a fatal outcome.

Systemic vascular diseases such as fibromuscular dysplasia, Ehlers-Danlos syndrome, Marfan syndrome, and Behçet's disease are known to cause spontaneous dissecting aneurysms of the cervical internal carotid artery. These diseases are generally associated with vascular fragility; therefore, invasive treatments are avoided in many cases of dissecting aneurysms, and a conservative approach is used for the primary disease. Surgical or intravascular treatment may be chosen when aneurysms are progressive or are associated with a high risk of hemorrhage; however, there is no consensus on which treatment is better. We report a case of a dissecting aneurysm of the cervical internal carotid artery in a patient with suspected Behçet's disease, which was treated using stent-assisted coil embolization. A man in his 40's, with suspected Behçet's disease, presented with an enlarged dissecting aneurysm of the right cervical internal carotid artery. The lesion was present for approximately 10 years. We performed stent-assisted coil embolization for the lesion. Post-surgery, no aneurysms were detected with carotid artery echography. Our case report suggests that stent-assisted coil embolization is a promising treatment for dissecting aneurysms of the cervical internal carotid artery. In addition, the procedure demonstrates the utility of carotid artery echograms for examining recanalization after stent-assisted coil embolization.

Crossed cerebellar diaschisis (CCD) is defined as functional mpairment due to decreased metabolism or blood flow in the cereellar hemisphere that is remote from, and contralateral to, the ausative supratentorial lesion. This widely known phenomenon is hought to be due to a transneuronal depression that is mediated y the corticopontocerebellar pathway. Crossed cerebellocerebral iaschisis (CCCD) is defined as the reverse of CCD, and has been uch less frequently described [1,2]. In fact, there are no reports n neuronal viability in CCCD. Here we report two cases in which e examined CCCD using 123I iomazenil single-photon emission omputed tomography (SPECT) in order to determine the neuronal iability.

Background and Purpose: We previously presented the robust neuroprotective effects of post-ischemic trans-arterial regional hypothermia therapy in I/R injury model rats (ISC 2014, San Diego). This treatment showed a significant suppression of infarct volume and inflammatory reaction at 24hrs after reperfusion. To characterize the neuroprotective effects in terms of microvascular integrity, we investigated microvascular morphological changes and inflammatory reactions by a time course analysis within 24hrs. Methods: At reperfusion onset, 2hr-MCAO rats were divided into cold saline group (10°C, 20ml/kg of trans-arterial infusion from the recanalized artery for 15mins), warm saline group (37°C, in the same manner as cold saline group), and control group (recanalization only). Microvascular morphological changes were examined by vWF Immunohistochemistry (IHC) and transmission electron microscopy (TEM), and inflammatory reactions were examined by Western blotting and IHC at the time point of 0hr, 2hrs, 6hrs, and 24hrs of reperfusion. Results: IHC analysis and TEM observation revealed that astrocyte end-feet swelling occurred at 2hrs and progressed to 6hrs, and microvascular narrowing due to the swelling occurred at 6hrs in control group. This microvascular morphological change was attenuated in cold saline group. While endothelial ICAM1 overexpression started at 6hrs in control group, MPO, MMP9, and Iba-1 overexpression occurred only at 24hrs in the same group. These inflammatory reactions were also inhibited in cold saline group. Conclusions: Post-ischemic trans-arterial regional hypothermia therapy attenuated astrocyte end-feet swelling from 2hrs and the swelling induced microvascular narrowing at 6hrs. The treatment also inhibited endothelial ICAM-1 overexpression at 6hrs, and subsequently inhibited inflammatory reactions at 24hrs. The maintenance of microvascular morphological and functional integrity may be the primary cause of the neuroprotective effects by the regional hypothermia.

An intradural arachnoid cyst is a relatively rare condition, occurring within the spinal subarachnoid space. We present the even-more rare case of an intradural arachnoid cyst associated with syringomyelia at the same spinal level. The patient was a 66-year-old man who presented with bilateral leg numbness and gait disturbance. Magnetic resonance imaging (MRI) revealed an intradural arachnoid cyst located dorsal to, and compressing, the thoracic spinal cord at the level of the 7th thoracic vertebra (Th 7). In addition, syringomyelia existed at the level of Th 8, slightly caudal to the intradural arachnoid cyst. We dissected the cyst but did not perform any surgical procedures for the syringomyelia. Post-operative MRI showed that the cyst had disappeared and the syringomyelia had spontaneously shrunk. The patient was discharged with improvement in his numbness and gait disturbance. There are a few case reports of intradural arachnoid cysts associated with syringomyelia, but recent evidence suggests that its occurrence is more common than previously thought. A combination of these two diseases is thought to be caused by blockage of cerebrospinal fluid (CSF) flow, which is also thought to cause adhesive arachnoiditis. For this reason, resection of the arachnoid cyst could improve the CSF flow and contribute to the shrinkage of syringomyelia. Furthermore, early treatment may correlate with improvement in radiological findings and neurological symptoms.

Background and Purpose: Although the neuroprotective effect of hypothermia on cerebral ischemia is well known, the clinical application of systemic hypothermia is limited because of management problems and complications. We examined whether focal hypothermia induced by post-ischemic intra-arterial infusion of cold saline attenuates cerebral ischemia reperfusion (I/R) injury in the rat transient middle cerebral artery occlusion (MCAO) model. Methods: Male Sprague-Dawley rats were subjected to 2-hour MCAO and then were divided into three groups: 1) cold saline group (n=7) infused with 10°C saline (20ml/kg) through the recanalized internal carotid artery for 15 minutes, 2) warm saline group (n=7) infused with 37°C warm saline in the same manner as the cold saline group, and 3) control group subjected to recanalization only (n=7). After 24-hour reperfusion, all rats were tested for neurological score and then sacrificed to examine infarction, brain edema, and Evans blue leakage. Results: In the cold saline group, brain temperature at basal ganglia rapidly decreased from 37.7±0.8°C to 35.4±0.7°C and remained significantly lower than pretreatment temperatures (p Conclusions: The results of the present study suggest that focal hypothermia induced by post-ischemic intra-arterial infusion of cold saline has a neuroprotective effect on I/R injury. This therapeutic strategy is promising because of its feasibility in the clinical situation of endovascular approach.

The prevalence of ivy sign on fluid-attenuated inversion recovery (FLAIR) imaging in patients with asymptomatic moyamoya disease is unclear. The aim of this study was to clarify the incidence of ivy sign in these patients, as well as the correlation between MRI and (15)O gas PET findings.A retrospective analysis including 16 consecutive patients with asymptomatic moyamoya disease enrolled between 2001 and 2010 in a single center. FLAIR imaging at the initial visit was categorized as ivy sign present, negative, or equivocal. Hemodynamic and metabolic parameters were quantified in 11 of 16 patients by (15)O-gas positron emission tomography, and the relationship between ivy sign and (15)O-gas PET parameters was analyzed. Cerebrovascular events within the follow-up period (54 ± 28 months) were also examined.Five of 16 asymptomatic moyamoya patients (31.3 %) had positive ivy sign (6/30 hemispheres, 20 %). In (15)O-gas PET examinations, 18 % of 22 hemispheres had elevated oxygen extraction fraction values that were significantly associated with positive ivy sign. Of these 16 asymptomatic moyamoya patients, six patients (37.5 %) underwent combined surgical revascularization. In this series, no patients experienced ischemic stroke, but one had intraventricular bleeding 1 year after surgery.Ivy sign on FLAIR imaging is still not rare in patients with moyamoya disease, even when asymptomatic. Although optimal management is still under debate, ivy sign may be an indicator of misery perfusion, and patients with asymptomatic moyamoya disease and ivy sign on FLAIR imaging will benefit from more careful follow-up.

An 86-year-old female presented with rare bilateral chronic subdural hematomas (CSHs) of the posterior fossae which were successfully treated by surgical intervention. She had experienced mild head trauma one month before admission. She was transferred to our hospital because of consciousness disturbance and tetraparesis. Magnetic resonance (MR) imaging showed simultaneous occurrence of supratentorial and infratentorial CSHs. We tried to evacuate the CSHs of the bilateral posterior fossae because brainstem compression was markedly severe. Through bilateral burr-hole trepanations, chocolate-colored fluid, not containing clotted components, gushed out under great pressure. Postoperative course was uneventful. MR imaging revealed that the CSHs of the posterior fossae had completely disappeared and brainstem compression had also improved. The patient's neurological deficits were immediately improved after the operation. The patient was discharged one month after the operation for further rehabilitation. Trepanation and evacuation of the hematoma through the posterior fossa might be one of the therapeutic options for posterior fossa CSH, which is similar to supratentorial CSH. However, we considered that the emergency of this rare entity and the method of anesthesia were quite different from supratentorial CSH.

Idiopathic syringomyelia not associated with Chiari malformation, tumor, nor tetherd cord syndrome has not been frequently reported. So the clinical significance and optimum treatment strategy for this disease remains unclear. We report a 37-year-old man who was diagnosed as having idiopathic syringomyelia and was treated successfully using implantation of a syringo-subarachnoid shunt. The patient suffered gradual worsening of sensory disturbance in the upper extremities, and Magnetic resonance imaging demonstrated a large syrinx located in the cervical spinal cord (C2-3), located mainly at the left anterior horn. We performed syringo-subarachnoid shunt for syringomyelia under partial hemilaminectomy. During the surgery, the spinal cord was markedly rotated and dorsal root entry had shifted to the midline because of the large syrinx. In order to perform myelotomy at the dorsal root entry zone, we needed additional drilling to the medial portion of the lamina. After this procedure, we were able to perform implantation of the syringo-subarachnoid shunt safely. After the operation, the syrinx collapsed immediately and no neurological deficit was observed. The patient was discharged 2 weeks after the operation. Idiopathic syringomyelia in which the syrinx has deviated to the anterior horn is rare. In those cases, we consider that sufficient hemilaminectomy for the midline should be performed.

Metastatic intraventricular tumor located in the choroid plexus is very rare. Only a few cases have been reported in the past. According to past reports, these tumors originated from lung, colon, and so on, but not from the bile duct. This is the first case report of choroid plexus metastasis from cholangiocellular carcinoma. A 57-year-old woman who had a history of cholagiocellular carcinoma, demonstrated intraventricular tumor. Although sufficient examination was performed, the tumor was difficult to diagnose as being a metastatic tumor or a choroid plexus carcinoma. Because of this, we performed endoscopic biopsy of the intraventricular tumor. However intraoperative findings were not helpful in distinguishing metastatic tumor and choroid plexus carcinoma. Postoperatively, histological examination was performed. However it was still difficult to differentiate this rare tumor from choroid plexus carcinoma by only hematoxylin and eosin stain. For further examination, Ber EP-4 stain was performed. Ber EP-4 showed strongly positive which indicates metastatic tumor. This method led us to make an appropriate diagnosis of this extremely rare tumor. We considered that in order to diagnose this rare tumor, appropriate histopathological examination, including immunohistopathological examination should be performed.

Congenital dermal sinuses, resulting from abnormal neurulation, are relatively uncommon and cause the patients to contract intraspinal infection. Sometimes, this intraspinal infection develops intramedurally abscess with severe neurological deficits. Therefore, a lack of awareness about this problem can result in fatal neurological sequelae. We report the case of a 1-year-old boy who had a lumbo-sacral dimple at birth without further evaluation. He presented repeated fever and rapidly progressive paraplegia. MRI showed a huge intraspinal and intramedullary abscess with dermoid, which was thought to be the result of a dermal sinus. Subsequently, he was transferred to our hospital and received immediate surgery. The patient underwent irrigation of purulent material in the intraspinal abscess including on intramedullary lesion, removal of dermoid tumor, and the resection of the dermal sinus. After that, he was treated with 8 weeks of antibiotic therapy. The patient remained paraplegia but made improvement. This patient illustrates the importance of the recognition and evaluation of skin markers. Prophylactic surgery is indicated to prevent dangerous and recurrent infections of the central nervous system.

We report a case of symptomatic subacute in-stent thrombosis after carotid artery angioplasty and stenting (CAS). The patient was a 72-year-old man who had severe asymptomatic right carotid artery stenosis. He received CAS with distal protection, and gained 100% opening of the right carotid artery. The administration of dual antiplatelet therapy (Aspirin 100 mg/day+Cilostazol 100 mg/day), which had been given since two weeks before the procedure, was continued afterwords. On the seventh day after the stent placement, the patient showed sudden onset of left hemiparesis and conjugated deviation of both eyes to the right side and followed by falling into a comatose state. Emergency angiography showed near occlusion of the right carotid artery, suggesting subacute in-stent thrombosis. In conjunction with the intravenous administration of tissue plasminogen activator (1300,000 IU), we performed additional stent placement on the stented portion of the ICA and gained full recanalization of the ICA about three hours after the onset of the symptoms. The patient showed rapid recovery and returned home with slight clumsiness of his right hand. Symptomatic subacute in-stent thrombosis after CAS is a rather rare complication. We discuss on the possible cause of this and stress the necessity of an additional emergency stenting to gain rapid recanalization.