Selective Transarterial Embolization for a Ruptured Persistent Trigeminal Artery Variant Aneurysm.

We report a male patient with a ruptured persistent primitive trigeminal artery variant aneurysm that resulted in a fistula with the cavernous sinus. He presented with left conjunctival hyperemia and exophthalmos. Cerebral angiography revealed a left direct carotid-cavernous fistula; however, a balloon occlusion test determined that the source was actually a ruptured aneurysm located on the trunk of a persistent primitive trigeminal artery. Endovascular trapping of the persistent primitive trigeminal artery was performed, which resulted in fistula occlusion and symptom resolution.

Erratum to "Crossing double stent retriever technique for refractory terminal internal carotid artery occlusion" [Radiology Case Reports 17 (2022) 1848-1852].

[This corrects the article DOI: 10.1016/j.radcr.2022.03.023.].

Carotid web arising in the common carotid artery and adjacent to a transverse process of the cervical spine: A case report.

BACKGROUND AND IMPORTANCE: A carotid web (CaW) is an intraluminal membrane-like filling defect typically located in the posterior wall of the proximal internal carotid artery and is increasingly recognized as a potential cause of embolic stroke. We herein reported a case of a CaW that has an unusual location at the CCA; furthermore, an elongated transverse process of the cervical spine was adjacent to the CaW at the CCA. CLINICAL PRESENTATION: An 87-year-old woman with a history of minor stroke underwent thorough radiological examinations of her CCA lesion. Radiological examinations, including duplex ultrasonography, digital subtraction angiography (DSA), computed tomography, and magnetic resonance angiography, revealed that the morphological characteristics of the lesion were compatible with those of a typical CaW except for its location at the CCA. Furthermore, three-dimensional DSA revealed that the lesion was adjacent to the transverse process of the sixth cervical spine (C6), suggesting mechanical damage by the spinal transverse process as a possible pathogenesis of this CaW. CONCLUSION: This is the rare case of a CaW located in the CCA, far from the carotid bulb. Arterial dissection due to mechanical damage by the spinal transverse process may be a possible causative mechanism of the CaW in the present case.

Acute internal carotid artery occlusion due to dissection of the paraclinoid segment: Diagnostic usefulness of angiographic findings during stent retriever deployment.

Intracranial artery dissection is an uncommon but possible cause of ischemic stroke, and is usually diagnosed based on imaging findings such as mural hematoma and dissection flap. However, it is challenging to recognize the underlying dissection in cases of acute large vessel occlusion. In this report, we present a case of acute internal carotid artery occlusion, in which the underlying dissection of the paraclinoid segment was found during the thrombectomy procedure. Two thrombectomy procedures failed to recanalize the acute internal carotid artery occlusion without removing any clot. Angiography performed during a Trevo stent retriever deployment in the first pass showed obscure contrast defects in the stent strut with temporary flow restoration. In the next pass, the appearance of the contrast defects changed and a parallel linear contrast appeared on the outside of the vessel wall. These angiographic findings were identified as mural hematoma and dissection flap, indicating dissection of the paraclinoid as the cause of the occlusion. During antiplatelet loading and preparation of a dedicated intracranial stent, the Trevo stent retriever was left deployed again at the occlusion site to maintain the blood flow. After permanent stenting with an Enterprise stent, angiography revealed complete recanalization. The patient recovered fully after the procedure. In the present case, stent retriever deployment revealed the hallmarks of dissection on angiography, such as mural hematoma, dissection flap, and temporal morphological changes, by restoring the blood flow temporarily. Such angiographic findings can provide useful information on the occlusion characteristics and real-time feedback for optimal treatment strategy.

Crossing double stent retriever technique for refractory terminal internal carotid artery occlusion.

Mechanical thrombectomy is highly effective for the recovery of acute ischemic stroke with large vessel occlusion. However, refractory occlusions are still encountered despite the use of currently available devices. In this article, we present a case of refractory terminal internal carotid artery occlusion treated with the "crossing double stent retriever technique." Two thrombectomy procedures with the combined technique using a stent retriever and aspiration catheter failed to recanalize the terminal internal carotid artery occlusion that involved the dominant anterior cerebral artery. We then applied the crossing double stent retriever technique as a rescue technique. Two microcatheters were advanced across the occlusion: one to the anterior cerebral artery and the other to the middle cerebral artery. First, a Trevo NXT 4 mm stent retriever was deployed from the anterior cerebral artery. Next, an additional Trevo NXT 4 mm stent retriever was deployed from the middle cerebral artery, and full immediate restoration of flow was achieved on angiography. Intraprocedural radiological images showed that the 2 microcatheters traversed different pathways, and the 2 stent retrievers completely covered the entire vessel with apparent in-stent clot sign. Both stent retrievers were then pulled back together, and a hard clot was retrieved. Subsequent angiography revealed complete recanalization. The crossing double stent retriever technique seems an effective rescue technique for treating refractory terminal internal carotid artery occlusion, especially with the anatomical feature of branching of the dominant anterior cerebral artery. This technique can facilitate the device-clot-vessel interaction by engaging the clot via 2 different device pathways.

PON1 Q192R is associated with high platelet reactivity with clopidogrel in patients undergoing elective neurointervention: A prospective single-center cohort study.

BACKGROUND AND PURPOSE: The impact of the paraoxonase-1 (PON1) polymorphism, Q192R, on platelet inhibition in response to clopidogrel remains controversial. We aimed to investigate the association between carrier status of PON1 Q192R and high platelet reactivity (HPR) with clopidogrel in patients undergoing elective neurointervention. METHODS: Post-clopidogrel platelet reactivity was measured using a VerifyNow® P2Y12 assay in P2Y12 reaction units (PRU) for consecutive patients before the treatment. Genotype testing was performed for PON1 Q192R and CYP2C19*2 and *3 (no function alleles), and *17. PRU was corrected on the basis of hematocrit. We investigated associations between factors including carrying ≥1 PON1 192R allele and HPR defined as original and corrected PRU ≥208. RESULTS: Of 475 patients (232 men, median age, 68 years), HPR by original and corrected PRU was observed in 259 and 199 patients (54.5% and 41.9%), respectively. Carriers of ≥1 PON1 192R allele more frequently had HPR by original and corrected PRU compared with non-carriers (91.5% vs 85.2%, P = 0.031 and 92.5% vs 85.9%, P = 0.026, respectively). In multivariate analyses, carrying ≥1 PON1 192R allele was associated with HPR by original (odds ratio [OR] 1.96, 95% confidence interval [CI] 1.03-3.76) and corrected PRU (OR 2.34, 95% CI 1.21-4.74) after adjustment for age, sex, treatment with antihypertensive medications, hematocrit, platelet count, total cholesterol, and carrying ≥1 CYP2C19 no function allele. CONCLUSIONS: Carrying ≥1 PON1 192R allele is associated with HPR by original and corrected PRU with clopidogrel in patients undergoing elective neurointervention, although alternative results related to other genetic polymorphisms cannot be excluded.

Platelet reactivity and hemorrhage risk in neurointerventional procedures under dual antiplatelet therapy.

BACKGROUND AND PURPOSE: Hemorrhagic complications during neurointerventional procedures have various etiologies and can result in severe morbidity and mortality. This study investigated the possible association between low platelet reactivity measured by the VerifyNow assay and increased hemorrhagic complications during elective neurointervention under dual antiplatelet therapy. METHODS: From May 2010 to April 2013 we recorded baseline characteristics, P2Y12 reaction units (PRU), and aspirin reaction units using VerifyNow. The primary endpoint was post-procedural hemorrhagic complications. RESULTS: A total of 279 patients were enrolled and 31 major hemorrhagic complications (11.1%) were identified. From receiver-operating characteristic curve analysis, PRU values could discriminate between patients with and without major hemorrhagic complications (area under the curve 0.63). Aspirin reaction unit values had no association with the primary outcome. The optimal cut-off for the primary outcome (PRU ≤175) was used to identify the low platelet reactivity group. The incidence of hemorrhagic complications was 20.0% in this group and 8.9% in the non-low platelet reactivity group. Multivariate analysis identified low platelet reactivity as an independent predictor for hemorrhagic complications. CONCLUSIONS: The risk of hemorrhagic complications during elective neurointervention including cerebral aneurysm coil embolization and carotid artery stenting under dual antiplatelet therapy is associated with the response to clopidogrel but not to aspirin. A PRU value of ≤175 discriminates between patients with and without hemorrhagic complications. Future prospective studies are required to validate whether a specific PRU value around 170-180 is predictive of hemorrhagic complications.

Rare complication characterized by late-onset transient neurological symptoms without hyperperfusion after carotid artery stenting: A report of three cases.

We experienced a rare complication after carotid artery stenting (CAS) characterized by transient neurological symptoms with no evidence of distal emboli or hyperperfusion. Using neuroimaging, we investigated the pathogenesis of the complication that occurred after CAS in three patients who developed neurological symptoms over a period of ten hours after CAS and improved within two days. None of the three patients showed signs of fresh infarctions on diffusion-weighted imaging or hyperperfusion on single-photon emission computed tomography. However, high signal intensity was observed in the leptomeningeal zone of the cerebral hemisphere on the stent side in all three patients and in the leptomeningeal zone of the contralateral anterior cerebral artery territory in one patient. These areas were assessed using fluid-attenuated inversion recovery (FLAIR) magnetic resonance imaging without gadolinium administration. The high signal intensity in the leptomeningeal zone disappeared as the symptoms improved. Based on the transient nature of the neurological disorders and the normalization of FLAIR imaging findings in these patients, the pathogenesis of this complication might have been vasogenic edema due to vasoparalysis of the local vessels caused by the hemodynamic changes occurring after CAS.

Rapid formation of cerebral microbleeds after carotid artery stenting.

BACKGROUND: Recent studies reported that cerebral microbleeds (CMBs), i.e. small areas of signal loss on T(2)*-weighted gradient-echo (GE) imaging, could develop rapidly after acute ischemic stroke. We hypothesized that CMBs rapidly emerge after carotid artery stenting (CAS). OBJECTIVE: We investigated the frequency of and predisposing factors for CMBs after CAS. METHODS: We retrospectively examined MRI before and after CAS in 88 consecutive patients (average age: 71.7 ± 7.2 years, average rates of carotid stenosis: 72.6 ± 12.8%) who underwent CAS for carotid artery stenosis between March 1, 2009, and September 30, 2010. We defined new CMBs as signal losses that newly appeared on the follow-up GE. We examined the association of new CMBs with demographics, risk factors, and baseline MBs. RESULTS: Among 88 patients, 18 (20.5%) had CMBs initially, and 7 (8.0%) developed new CMBs right after CAS. New CMBs appeared on the same side of CAS in all of the 7 patients. New CMBs appeared significantly more frequently in the CMB-positive group than in the CMB-negative one (22% vs. 4%, p = 0.03) on the pre-CAS MRI. Multivariate analysis also revealed that the presence of CMBs before CAS was an independent predictor of new development of CMBs after CAS (odds ratio: 8.09, 95% confidence interval: 1.39-47.1). CONCLUSION: CMBs can develop rapidly after CAS, especially in patients with pre-existing CMBs. Since the existence of CMBs prior to CAS suggests a latent vascular damage which is vulnerable to hemodynamic stress following CAS, particular attention should be paid to the prevention of intracerebral hemorrhage due to hyperperfusion after CAS.

Functional recovery of the murine brain ischemia model using human induced pluripotent stem cell-derived telencephalic progenitors.

Induced pluripotent stem (iPS) cells possess the properties of self-renewal and pluripotency, similar to embryonic stem cells. They are a good candidate as a source of suitable cells for cell replacement therapy. In this study, we transplanted human iPS cell-derived neural progenitors into an ischemic mouse brain. Human iPS cells were differentiated into neuronal progenitors by serum-free culture of embryoid body-like aggregates (SFEBs). Focal cerebral ischemia was induced by occluding the middle cerebral artery using the intraluminal filament technique. Donor cells were transplanted into the ischemic lateral striatum 1 week after ischemia induction. Cells survived at the transplantation site, with migration of a proportion of cells along the external capsule and corpus callosum. Cells that were positive for the basal telencephalon marker, Nkx2.1, migrated into the basal part of the telencephalon. The pallial telencephalon marker, Emx1, was detected in cells that had migrated into the pallial part of the telencephalon. SFEBs differentiated into various types of neurons, and a retrograde tracer labeling study showed that differentiated cells integrated into host neural circuitry. Behavioral recovery was significantly enhanced in the transplanted group. Our results suggest that human iPS cell-derived neuronal progenitors survive and migrate in the ischemic brain, and contribute toward functional recovery via neural circuit reconstitution.

Prolonged maturation culture favors a reduction in the tumorigenicity and the dopaminergic function of human ESC-derived neural cells in a primate model of Parkinson's disease.

For the safe clinical application of embryonic stem cells (ESCs) for neurological diseases, it is critical to evaluate the tumorigenicity and function of human ESC (hESC)-derived neural cells in primates. We have herein, for the first time, compared the growth and function of hESC-derived cells with different stages of neural differentiation implanted in the brains of primate models of Parkinson's disease. We herein show that residual undifferentiated cells expressing ESC markers present in the cell preparation can induce tumor formation in the monkey brain. In contrast, a cell preparation matured by 42-day culture with brain-derived neurotrophic factor/glial cell line-derived neurotrophic factor (BDNF/GDNF) treatment did not form tumors and survived as primarily dopaminergic (DA) neurons. In addition, the monkeys with such grafts showed behavioral improvement for at least 12 months. These results support the idea that hESCs, if appropriately matured, can serve as a source for DA neurons without forming any tumors in a primate brain.

Transplantation of telencephalic neural progenitors induced from embryonic stem cells into subacute phase of focal cerebral ischemia.

Cerebral ischemia causes neuronal death and disruption of neural circuits in the central nervous system. Various neurological disorders caused by cerebral infarction can severely impair quality of life and are potentially fatal. Functional recovery in the chronic stage mainly depends on physical treatment and rehabilitation. We aim to establish cell therapy for cerebral ischemia using embryonic stem (ES) cells, which have self-renewing and pluripotent capacities. We previously reported that the transplanted monkey and mouse ES cell-derived neural progenitors, by stromal cell-derived inducing activity method, could survive and differentiate into various types of neurons and glial cells, and form the neuronal network in basal ganglia. In this report, we induced the differentiation of the neural progenitors from mouse ES cells using the serum-free suspension culture method and confirmed the expression of various basal ganglial neuronal markers and neurotransmitter-related markers both in vitro and in vivo, which was thought to be suitable for replacing damaged striatum after middle cerebral artery occlusion. This is the first report that used selectively induced telencephalic neural progenitors into ischemia model. Furthermore, we purified the progenitors expressing the neural progenitor marker Sox1 by fluorescence-activated cell sorting and Sox1-positive neural progenitors prevented tumor formation in ischemic brain for 2 months. We also analyzed survival and differentiation of transplanted cells and functional recovery from ischemic damage.

Single and local blockade of interleukin-6 signaling promotes neuronal differentiation from transplanted embryonic stem cell-derived neural precursor cells.

Safe and efficient transplantation of embryonic stem (ES) cells to the brain requires that local inflammatory and immune responses to allogeneic grafts are inhibited. To investigate cytokines that affect graft cell survival and differentiation, we used stromal cell-derived inducing activity to induce the differentiation of neural progenitor cells (NPCs) from mouse ES cells and transplanted the NPCs into mouse brain. Examination of surrounding brain tissue revealed elevated expression levels of interleukin (IL)-1ß, IL-4, and IL-6 in response to NPC transplantation. Among these, only IL-6 reduced neuronal differentiation and promoted glial differentiation in vitro. When we added anti-IL-6 receptor antibodies to NPCs during transplantation, this single and local blockade of IL-6 signaling reduced the accumulation of host-derived leukocytes, including microglia. Furthermore, it also promoted neuronal differentiation and reduced glial differentiation from the grafted NPCs to an extent similar to that with systemic and continuous administration of cyclosporine A. These results suggest that local administration of anti-IL-6 receptor antibodies with NPCs may promote neuronal differentiation during the treatment of neurological diseases with cell replacement therapy.

Attenuation of neuronal degeneration in thioredoxin-1 overexpressing mice after mild focal ischemia.

Thioredoxin (Trx) is a 12-kDa protein ubiquitously expressed in all living cells that fulfills a variety of biological functions related to cell proliferation and apoptosis. It is characterized by the highly conserved reduction/oxidation (redox)-active site sequence Trp-Cys-Gly-Pro-Cys-Lys. Trx acts as a powerful antioxidant and plays an important role in maintaining critical protein thiols in the reduced state. Moreover, it has been shown to scavenge reactive oxygen species (ROS) and to protect against oxidative stress. We have reported that Trx-1 protects against neuronal damage during focal ischemia. However, the mechanisms underlying this protective effect and the effect of Trx-1 on neuronal apoptosis during ischemia have not been fully clarified. In this study, we analyzed the effect of Trx-1 overexpression against neuronal degeneration after a short duration of transient brain ischemia. Mild focal ischemia was reported to induce neuronal death through apoptosis. We employed Fluorojade-B staining to detect neuronal degeneration. In Trx transgenic mice, a smaller number of Fluorojade-B-positive neurons were detected after ischemia-reperfusion than in wild-type mice. In addition, we detected cleaved caspase-3- and TUNEL-positive cells, which indicated caspase-dependent apoptosis. Fewer caspase-3- and TUNEL-positive neurons were detected after ischemia-reperfusion in Trx transgenic mice than in wild-type mice. Furthermore, Akt signaling was reported to play a role in neuronal survival in Trx-1 overexpressing mice. After ischemia-reperfusion, Western blot and immunohistochemical analysis indicated that phosphorylation of Akt was enhanced in Trx transgenic mice after ischemia-reperfusion. Intraventricular injection of LY294002,which is a phosphoinositide 3-kinase (PI3K), vanished the neuroprotective effect in Trx-1 transgenic mice. These results indicate that Trx-1 overexpression protects neurons from apoptosis after ischemia-reperfusion.

Chronic venous congestion following embolization of spinal dural arteriovenous fistula.

The authors present a case of spinal dural arteriovenous fistula with fluctuations in symptoms following embolization. Superselective injection of 33% N-butyl cyanoacrylate into the feeding vessel resulted in the complete occlusion of the fistula with traversal of the nidus. The subsequent venous congestion was progressive and treatable with anti-thrombin therapy. Extended medication with dual antiplatelet therapy was required because dose reduction to aspirin monotherapy worsened symptoms. In this case, it took > 2 months for the patient's symptoms to stabilize. The duration of progressive venous thrombosis after embolization of a spinal dural arteriovenous fistula is not well known, nor is the most adequate treatment. Although it is presumed that prevention of venous thrombosis is best achieved with anticoagulation, dual antiplatelet therapy can be a substitute for patients with poor compliance.

Tissue inhibitor of metalloproteinases protect blood-brain barrier disruption in focal cerebral ischemia.

Enhanced matrix metalloproteinases (MMPs) can cause vasogenic edema and hemorrhagic transformation after cerebral ischemia, and affect the extent of ischemic injury. We hypothesized that the endogenous MMP inhibitors, tissue inhibitor of MMPs (TIMPs), were essential to protect against blood-brain barrier (BBB) disruption after ischemia by regulating the activities of MMPs. We confirmed the transition of MMP-2 and MMP-9, and the TIMPs family after 30 mins of middle cerebral artery occlusion, and elucidated the function of TIMP-1 and TIMP-2 in focal ischemia, using TIMP-1(-/-) and TIMP-2(-/-) mice. TIMP-1 mRNA expression was gradually increased until 24 h after reperfusion. In TIMP-1(-/-) mice, MMP-9 protein expression and gelatinolytic activity were significantly more augmented after cerebral ischemia than those in WT mice, and were accompanied by exacerbated BBB disruption, neuronal apoptosis, and ischemic injury. In contrast, TIMP-2 gene deletion mice exhibited no significant difference in MMP expressions and the degree of ischemic injury despite an increased Evans blue leakage. These results suggest that TIMP-1 inhibits MMP-9 activity and can play a neuroprotective role in cerebral ischemia.

Immune or inflammatory response by the host brain suppresses neuronal differentiation of transplanted ES cell-derived neural precursor cells.

Embryonic stem (ES) cells are a promising donor source for transplantation therapy, but several problems must be solved before they can be clinically useful. One of these is the host immune reaction to allogeneic grafts. In this article, we examine the effect of the host immune reaction on survival and differentiation of grafted ES cell-derived neural precursor cells (NPCs). We induced NPCs from mouse ES cells by stromal cell-derived inducing activity and then transplanted them into mouse brains with or without administering the immunosuppressant cyclosporine A (CsA). Two and 8 weeks following transplantation, the accumulation of host-derived microglia/macrophages and lymphocytes was observed around the graft. This effect was reduced by CsA treatment, although no significant difference in graft volume was observed. These data suggest that an immune response occurs in allografts of ES cell-derived NPCs. Intriguingly, however, the ratio of neurons to astrocytes in the graft was higher in immunosuppressed mice. Because inflammatory or immune cells produce various cytokines, we examined the effect of IL-1beta, IL-6, IFN-gamma, and TNF-alpha on the differentiation of NPCs in vitro. Only IL-6 promoted glial cell fate, and this effect could be reversed by the addition of an IL-6 neutralizing antibody. These results suggest that allogeneic ES cell-derived NPCs can cause an immune response by the host brain, but it is not strong enough to reject the graft. More important, activated microglia and lymphocytes can suppress neuronal differentiation of grafted NPCs in vivo by producing cytokines such as IL-6.

[Treatment of a ruptured giant internal carotid artery pseudoaneurysm following transsphenoidal surgery: case report and literature review].

We report here a case of giant internal carotid artery (ICA) pseudoaneurysm as a complication of transsphenoidal surgery. This 50-year-old acromegalic male presented to our clinic with a status of hypovolemic shock due to serious epistaxis. Neuroradiological examinations at his admission revealed a giant aneurysm in the right cavernous portion projecting into the sphenoid sinus. Eight years before this presentation, he had undergone a transsphenoidal surgery for growth hormone producing pituitary tumor at the other clinic. Then intraoperative arterial bleeding was reported, probably as a result of carotid injury. His medical history and radiological findings suggested that his epistaxis resulted from a rupture of the iatrogenic pseudoaneurysm which had gradually grown after the ICA injury at the previous surgery over 8 years. Emergent coil embolization using Guglielmi detachable coils (GDCs) resulted in a successful homeostasis. Major part of the aneurysm dome was obliterated via the intervention, however small part of the aneurysm neck was unable to be obliterated due to a technical difficulty. His postoperative course was favorable, but he suffered from a recurrence of serious epitaxis 4 weeks after the embolization. Emergent angiography suggested a rupture of the un-obliterated aneurysm neck remnant. Thus, trapping of the aneurysm combined with high flow bypass was necessitated. Relevant literatures are reviewed, and possible therapeutic strategies for this rare lesion are discussed.

Expansive duraplasty for the treatment of spinal extradural arachnoid cysts: case report.

The authors report the case of a 25-year-old man with a thoracolumbar extradural arachnoid cyst who underwent expansive duraplasty. Symptoms, preoperative magnetic resonance imaging features, and intraoperative findings suggested the involvement of entrapment neuropathy in the manifestation of symptoms. To the authors' knowledge, this case represents the first evidence that expansive duraplasty can achieve complete resolution of the symptoms in a patient with a spinal extradural arachnoid cyst. The results indicate that duraplasty may be an alternative option in cases in which complete resection of the lesion is difficult and widening of the dural sac is necessary at surgery.

[A case of bow hunter's stroke treated with endovascular surgery].

Bow hunter's stroke results from vertebrobasilar insufficiency due to a mechanical occlusion or stenosis of the vertebral artery caused by head rotation. We report here a case of bow hunter's stroke that was successfully treated with endovascular surgery. A 69-year-old male complained of intractable vertigo when he rotated his head to the right side. Neuroradiological studies proved that the symptom was attributed to the mechanical severe stenosis of the left vertebral artery at the C1-C2 level on head rotation, in addition to the atherosclerotic stenosis at the origin of the right vertebral artery. Two different treatments were considered, including direct surgeries to prevent the mechanical stenosis of the left vertebral artery, and an endovascular dilatation of the atherosclerotic stenosis of the right vertebral artery. Endovascular surgery with a stenting technique, which was thought to be less invasive, was undertaken and resulted in a complete relief of the patient's symptom. To our knowledge, this is the first report to have shown the efficacy of endovascular surgery on this uncommon disease.