Therapeutics potentiating microglial p21-Nrf2 axis can rescue neurodegeneration caused by neuroinflammation.

Neurodegenerative disorders are caused by progressive neuronal loss, and there is no complete treatment available yet. Neuroinflammation is a common feature across neurodegenerative disorders and implicated in the progression of neurodegeneration. Dysregulated activation of microglia causes neuroinflammation and has been highlighted as a treatment target in therapeutic strategies. Here, we identified novel therapeutic candidate ALGERNON2 (altered generation of neurons 2) and demonstrate that ALGERNON2 suppressed the production of proinflammatory cytokines and rescued neurodegeneration in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced Parkinson's disease model. ALGERNON2 stabilized cyclinD1/p21 complex, leading to up-regulation of nuclear factor erythroid 2-related factor 2 (Nrf2), which contributes to antioxidative and anti-inflammatory responses. Notably, ALGERNON2 enhanced neuronal survival in other neuroinflammatory conditions such as the transplantation of induced pluripotent stem cell-derived dopaminergic neurons into murine brains. In conclusion, we present that the microglial potentiation of the p21-Nrf2 pathway can contribute to neuronal survival and provide novel therapeutic potential for neuroinflammation-triggered neurodegeneration.

Stenting for chronic total occlusion of the proximal subclavian artery.

SUMMARY: We report the results of 26 patients who underwent stent deployment for chronic total occlusion of proximal subclavian artery. From January 1998 to October 2005, 26 patients (18 male; mean age, 62.7 years, range 22 to 83 years), 28 lesions, underwent 29 procedures of stenting for chronic total occlusion of the proximal subclavian artery.Twenty-three patients had symptoms of claudication in their arm, no patients had subclavian steal syndrome.A brachial approach was used in 21 procedures, a femoral approach was used in five procedures, and combined femoral-brachial approach was required in three procedures. Primary stent deployment was success in 24 lesions (85.7%), and secondary procedure was success in one patient, totally 25 lesions (89.3%) were successfully treated by stenting. Procedure related complication occurred in four cases, including stent migration without symptoms in two procedures, hemianopsia on next day in a case, and TIA on unclear reason in one case. Permanent morbidity rate is 3.4% in procedure. Target lesion re-treatment required in three lesions, caused by subacute thrombosis, in-stent-restenosis, and dissection of the vessel by stent edge. The cases of subacute thrombosis and in-stent-restenosis were treated by re-PTA, and the case of dissection was treated by additional stenting. Secondary patency was 100%. We conclude that stenting for chronic total occlusion of subclavian arteries appears feasible and safe.

Revascularization procedure mainly by suction thrombectomy for acute cervical carotid occlusion.

SUMMARY: In many cases, the prognosis for acute cervical carotid artery occlusion is poor. However, a standard treatment for the acute stage is not yet established. We report here the results of eight consecutive patients (mean age 71.5 years old) in which revascularization mainly by suction thrombectomy was performed under proximal protection during the acute phase. The occlusion sites were the intracranial internal carotid artery in five patients, tandem lesions of the internal carotid origin and intracranial vessel in two patients, and the common carotid artery in one patient. In addition, the subjects who received the treatment had an extent of infarction in MRI/DWI that was 1/3 or less of the internal carotid artery territory. The mean time from the onset to treatment commencement was 7.25 hours (2-28 hours). For the endovascular treatment, a guiding catheter with a balloon was used for proximal protection of the carotid artery. Revascularization was performed mainly by suction thrombectomy, and if a stenosed lesion was observed, PTA/stenting was added. Local fibrinolysis was not performed in combination with the above procedure. The treatment results were complete recanalization in three patients and partial recanalization in three patients. However, recanalization was not achieved in two patients. No hyperfusion syndrome or hemorrhagic infarction was observed postoperatively. All four patients in whom thrombi were successfully aspirated had occlusions proximal to the ophthalmic artery branch. In three of these four patients, complete recanalization was achieved. The revascularization procedure using suction thrombectomy under proximal protection was considered effective against the acute cervical carotid occlusions, in particular, those proximal to the ophthalmic artery branch.

Percutaneous transluminal angioplasty and stenting for chronic total occlusion of intracranial carotid artery: a case report.

SUMMARY: Chronic total occlusion of cerebrovascular lesions is regarded as a contraindication to revascularization. We describe a case of chronic total occlusion of intracranial internal carotid artery that iwass successfully recanalized by endovascular treatment. A 72-year-old man who presented with slight right hemiparesis was proved to have chronic total occlusion of the left intracranial internal carotid artery. Percutaneous transluminal angioplasty/stenting was achieved using reversal of flow with the Parodi Anti-Embolic System. The present case indicates that percutaneous transluminal angioplasty/stenting can be an effective therapeutic option in selected patients with chronic total occlusion of cerebrovascular lesions.

Computed Tomography Angiography of Carotid Stent. Comparison of Various Self-expandable Stent in a Phantom Model.

SUMMARY: We evaluated Computed Tomography Angiography (CTA) of four different self-expandable stents in phantom model. Three stents ware made of nitinol and one was made of cobaltbased alloy. Each stent placed in plastic injector, filled with diluted iodinated contrast material, and placed on a plastic case filled with saline. CTA was performed on a four-detector CT scanner (detector collimation, 0.5mm: helical pitch 3.5). Axial and longitudinal reconstructions of CT imaging were compared with the instent attenuation. Three nitinol stents showed few artifact, and cobalt-based alloy stent was appeared artificial narrowing. In conclusion, CTA is useful for follow-up examination after carotid artery stenting (CAS) as a less invasive evaluation method.

Simulation Study of Distal Balloon Protection Systems during Carotid Artery Stenting.

SUMMARY: The purpose of our experimental study was to assess the pitfalls of distal balloon protection systems and to learn any technique tips to increase safety. Silicone carotid artery models were connected to a circulatory system to simulate arterial flow. A distal balloon protection device, PercuSurge GuardWire Plus (GWP, Medtronic Vascular) was delivered to the internal carotid artery (ICA), then was inflated to occlude ICA flow temporarily. A debris aspiration catheter (Export catheter) was delivered just proximal to the GuardWire Plus balloon coaxially, in order to introduce and diffuse particulate debris (20-500micro meter in diameter) in the ICA stump. Then, after debris in the stump was aspirated, the GWP balloon was deflated. We recorded all the processes of our simulation experiments on a digital video and observed the movements of debris during these experiments. Exp 1) We simulated the movements of debris in the ICA stump when the GWP balloon was gradually deflated to produce a crevice between the balloon and vessel wall, simulating accidental movement of the GWP balloon during the procedure. Exp 2) In order to assess the optimal placement of the tip of aspiration catheter, the debris in the ICA stump was aspirated from three different sites(from just below the GuardWire balloon, from 2cm below it, and from 5cm below it). Exp 1) When the crevice appeared between GuardWire balloon and silicone tube, simulated debris began to concentrate just below the balloon. Then, some debris migrated distally from the crevice, and another part crowded in the crevice so that was impossible to aspirate and migrated in the end. Exp. 2) Debris aspiration was most effective from immediately below the GuardWire balloon, and the aspiration ability declined as the distance between the balloon and aspiration catheter became longer. According to our simulation studies, when the GWP balloon was moved accidentally during CAS procedures, or when the aspiration catheter was not delivered all the way to the GuardWire Plus balloon, distal embolization might still occur, even under protection.

[Combined endovascular stent implantation and coil embolization for the treatment of a vertebro-basilar fusiform aneurysm: technical case report].

We describe a case of the combined application of endovascular stent implantation and Guglielmi detachable coil packing for the treatment of a vertebro-basilar fusiform aneurysm and review the literature on stent placement to treat cerebral aneurysms. A 70-year-old female presented with an acute headache from subarachnoid hemorrhage. A fusiform aneurysm with a broad-based neck and dome, measuring 15 mm, involving the union of the vertebral arteries and the proximal basilar artery was demonstrated on cerebral angiography. The aneurysm was judged to be inoperable and treated conservatively. Twelve days later the patient was transferred to our hospital for endovascular therapy. An intravascular stent (MultiLink) was placed across the base of the aneurysm through the right vertebral artery. After this, coil placement in the aneurysm around the stent was performed via a microcatheter guided from the left vertebral artery. After that a microcatheter was guided from the right vertebral artery through the interstices of the stent into the aneurysm, and additional coils were placed. Final angiography showed subtotal occlusion of the aneurysm and excellent blood flow of the parent artery through the stent. There were no new neurological deficits. Neither rerupture nor ischemic event has occurred. The use of stents provides another treatment for managing the difficult entity of intracranial aneurysms.

Postoperative changes in paraspinal muscle thickness after various lumbar back surgery procedures.

Damage to the paraspinal muscle after various lumbar back surgery procedures was evaluated by measuring the paraspinal muscle thickness preoperatively and postoperatively in 89 patients, 61 males and 28 females. There were 42 single interlaminar level procedures (SL group), 13 multiple interlaminar level procedures (ML group), and 34 posterolateral fusion procedures (PLF group). Changes in paraspinal muscle thickness were evaluated at more than 10 months after surgery, because muscle swelling continued as long as 10 months after surgery, and then reduced as the edema subsided. Postoperative serum creatine phosphokinase (CPK) level on postoperative day 2 was also measured. The decrease of paraspinal muscle thickness was significantly larger in the PLF group than in the SL group (-12.9% and -2.7%, respectively, p < 0.02). There was no significant correlation between postoperative serum CPK level and decrease of paraspinal muscle thickness. However, the postoperative elevation of serum CPK level was significantly higher in the PLF group than in the SL and ML groups (979 +/- 114 vs. 292 +/- 45 and 410 +/- 44 IU/l, respectively, p < 0.001). In conclusion, posterolateral fusion is the most invasive procedure of the paraspinal muscles in various lumbar back surgery procedures. Paraspinal muscle damage during lumbar back surgery may be one of the most important factors that causes atrophy of the muscles.

Embolic Complications of Endovascular Surgery for Cerebrovascular Diseases. Evaluation with Diffusion-Weighted MR Imaging.

SUMMARY: The purpose of this study was to evaluate asymptomatic embolisms during cerebral endovascular surgery for cerebrovascular diseases with diffusion-weighted magnetic resonance imaging (DWI) which allowed sensitive and early detection of cerebral ischemic lesions. 71 patients who underwent a total of 74 cerebral endovascular procedures were subjected to DWI screening study. MR imaging was performed on a 1.5T system by using single-shot SE echo-planar imaging (EPI) with b value of 1100 seconds per mm(2) in pre- and post-treatment periods (between day 2 and 5 after procedures). In 38 (51.3%) of 74 procedures, new high intensity lesions, as recent infarctions related to procedures, were detected on post-procedural DWI. In 18 Of the patients (47.4%), symptomatic infarctions occurred and resulted in TIAs (n = 4), RINDs (n = 8), minor strokes (n = 6) and no major strokes and no death. 20 (52.6%) of the recent infarctions detected by DWI were asymptomatic lesions.Most of the asymptomatic ischemic lesions were likely to be distributed in watershed border areas. On the other hand, symptomatic lesions tended to be distributed in cortical and/or perforator regions and to be multiple. Thus, DWI is a useful method that can detect neurologically silent and asymptomatic ischemic lesions. It can be used to help to evaluate the safety and efficacy of neurovascular intervention.

Dorsally sequestrated thoracic disc herniation--case report.

A 53-year-old male presented with a rare dorsally sequestrated thoracic disc herniation manifesting as acute low back pain and weakness. He had no history of trauma. Magnetic resonance (MR) imaging demonstrated a mass at T10-11 intervertebral level connected with the T-10 disc. Axial MR imaging showed the mass had surrounded and compressed the dural sac from the lateral and dorsal sites. MR imaging with gadolinium-diethylenetriaminepenta-acetic acid showed slight rim enhancement of the lesion. Computed tomography detected no abnormal calcification. The diagnosis was thoracic disc herniation. Laminectomy resulted in rapid and satisfactory recovery. The histological diagnosis was thoracic disc herniation. MR imaging was very effective for the diagnosis based on the connection between the mass and the disc space. The differential diagnosis includes metastatic epidural tumor, epidural hematoma, and epidural abscess.

[Endovascular surgery for untreated ruptured aneurysm with symptomatic vasospasm].

It is difficult to treat ruptured aneurysms with symptomatic vasospasm. Although direct surgery for such cases is associated with poor outcomes, conservative therapy has the risk of both rerupture and infarction. In two cases of ruptured aneurysms with symptomatic vasospasm, we performed aneurysmal coil embolization with Guglielmi electrodetatchable coils (GDC). At the same time we performed percutaneous transluminal angioplasty (PTA) with papaverine infusion. In both cases, rerupture did not occur and PTA was effective angiographically. A good outcome was achieved in case 1. However, broad cerebral infarction occurred in case 2, in which the patient had shown severe symptomatic vasospasm on admission. In advanced cases, such as in case 2, the outcome is poor. The aneurysm may not be able to be approached before PTA because of severe vasospasm. In such cases, PTA must be performed carefully to avoid aneurysmal rerupture. Intraarterial papaverine infusion is safer than PTA for severe spasm in distal vessels. However the efficacy of papaverine is known to be transient in many cases. It is often difficult to determine the exact relationship between branches and the aneurysm in the presence of vasospasm. In such cases, we recommend that the rupture point be packed and that the aneurysmal neck remain unpacked. After vasospasm is cured and good general condition has been recovered, direct surgery can be performed. In summary, endovascular surgery is an effective option for treatment of ruptured aneurysm with symptomatic vasospasm.

[A malignant rhabdoid tumor appearing simultaneously in the kidney and the brain of an infant: case report].

A 6-month-old female was admitted to the hospital with bad temper and decreased sucking power. CT scans revealed tumors in her right kidney and left cerebellum. The patient underwent right radical nephrectomy to excise the kidney tumor. The pathological diagnosis was malignant rhabdoid tumor (MRT). Seven days later, the patient underwent left suboccipital craniectomy for total excision of the cerebellar tumor. The cerebellar tumor existed extraaxially, and consisted of a solid mass lesion and a cystic lesion. Histological examination revealed that it was also a malignant rhabdoid tumor. A follow-up CT, 1.5 months after surgery, revealed a recurrence of the kidney tumor and metastasis to the chest wall and lung. The patient received 16.9 Gy radiotherapy to the abdominal tumor and chemotherapy with etoposide, carboplatin, and ifosfamide. However, she died of respiratory insufficiency 4 months after surgery, though neither recurrence nor metastasis was found in the brain. Nor was there evidence of leptomeningeal dissemination. MRT is a highly malignant tumor that occurs most frequently in the kidney. However, it can also occur in other tissues, including the brain. This tumor occurs most commonly in children under 2 years of age. There is a 3:2 male predominance. The median length of overall survival of MRT in the brain is 6 months. MRT contains nests or sheets of rhabdoid cells. A typical rhabdoid cell has an eccentric round nucleus with a prominent nucleolus and a plump cell body. MRT is composed entirely or partly of rhabdoid cells. Many MRTs have other components, such as PNET areas, mesenchymal area, and epithelial areas. For this reason, they are sometimes called atypical teratoid/rhabdoid tumors. MRTs in the brain contain fewer rhabdoid cell areas than MRT in the kidney. This makes diagnosing MRT in the brain more difficult. A careful search of the entire specimen for variations in pattern and cell type, along with application of immunohistochemical methods is the most useful method of obtaining a diagnosis. In our case, the cerebellar tumor consisted of rhabdoid cell areas, mesenchymal areas, and PNET areas. The cerebellar tumor contained fewer rhabdoid cell areas than the kidney tumor. However, the rhabdoid cell areas in the cerebellar tumor were almost the same as those in the kidney tumor. Furthermore, immunohistochemical staining was positive for vimentin and keratin in the rhabdoid cell areas. Therefore, we were able to make a diagnosis of MRT. It is possible that some of the previously reported cases diagnosed as CNS PNET were actually MRT in the brain, especially if the cases were associated with MRT in the kidney.