Axons of the adult central nervous system are capable of only limited regrowth after injury, and an unfavorable environment plays a major role in the lack of regeneration. Some of the axon growth inhibitory effects are associated with myelin. Identification of the myelin-derived inhibitors has led to a spurt in our knowledge about the molecular mechanisms. The neurotrophin receptor p75, which has long been known as a receptor for neurotrophins that promote survival and differentiation, transduces the signal from all of the myelin-derived inhibitors found to date. p75NTR has the ability to elicit bi-directional signals, which result in the inhibition as well as the promotion of the neurite outgrowth. p75NTR, in response to myelin-derived inhibitors, elicits activation of Rho, one of the key regulators of actin cytoskeleton. Activation of Rho is required for axon growth inhibition in vitro as well as in vivo. These findings establish Rho as a key player in inhibiting the regeneration of the central nervous system, and launched a new wave of studies aimed at promoting regeneration of injured axons by modulating this inhibitory pathway.
In patients with ruptured dissecting aneurysms requiring occlusion of the posterior inferior cerebellar artery (PICA), revascularization of this artery should be performed. We present a novel technique for revascularization of the PICA. After a segment of the superficial temporal artery (STA) was harvested, the aneurysm was treated by trapping followed by placement of a vertebral artery-PICA bypass using the STA as an interposed graft. When the length of the proximal PICA was inadequate, the distal end of the STA was anastomosed to the proximal PICA in an end-to-side fashion. When the length of the proximal PICA was adequate, the STA was anastomosed to the proximal PICA in an end-to-end fashion. In either case, the proximal end of the STA was anastomosed to the vertebral artery in an end-to-side fashion. This procedure was used in 7 patients whose dissecting aneurysms involved the PICA. Although 1 patient developed partial laterally medullary syndrome, follow-up evaluation revealed graft patency in all patients. Although our procedure requires harvesting of a STA graft and 2 anastomoses, it facilitates anterograde flow to the PICA territory. It also involves minimal mobilization of brain stem perforators and the proximal PICA.
We propose a treatment for a ruptured dissecting aneurysm involving a posterior inferior cerebellar artery (PICA). The ruptured vertebral artery dissecting aneurysm is considered easy to re-bleed, so that, trapping or proximal occlusion of the aneurysm should be carried out in the acute period following subarachnoid hemorrhage. In a case with PICA originating from the aneurysm might result in cerebellar infarction. To avoid cerebellar ischemic complication, we perform occipital artery for PICA anastomosis at the time of trapping surgery.
We retrospectively investigated the clinical and angiographic follow-up results of intracranial vertebral artery (VA) dissection initially presented without subarachnoid hemorrhage (SAH) to clarify its management. Forty-one patients with VA dissection initially presenting without SAH were studied. Initial angiography revealed pearl and string sign in 18, double lumen sign in 4, aneurysmal dilatation with double lumen in 2, only aneurysmal dilatation in 6, occlusion in 7, and string-like stenosis in 4. Twenty patients, including 6 with subsequent SAH, underwent endovascular treatment (parent artery occlusion in 16 and stent-assisted coil embolization in 4). The other 21 patients were treated conservatively. The intervals between the onset and SAH were 1 day (2 patients), 3 days (2 patients), 14 days (1 patient) and 51 months (1 patient). One of the 16 patients treated by parent artery occlusion suffered from ischemic complications. Stent-assisted coil embolization was safely performed in all of the 4 patients. Follow-up angiography of the 37 patients showed deterioration in 14, complete resolution or improvement in 9, and no change in 14. Thirty-seven patients achieved good recovery, and 4 patients remained moderately disabled due to the initial ischemic attack. Although the natural history of unruptured VA dissection is still unknown, endovascular treatment should be considered for patients with a relatively large or growing aneurysmal dilatation because prognosis of the patients with subsequent SAH is poor.
We sought to clarify the clinical features, natural history, and optimal treatment for patients suffering from non-hemorrhagic cerebral arterial dissection. Fifty-four males and 14 females were enrolled in this study, and the mean age was 55.1 years. We analyzed the clinical manifestations, angiographical findings and treatment. Fifty-two patients (76.5%) presented with cerebral ischemia, 7 (10.3%) with headache, 4 (5.9%) with neck mass, and 2 (2.9%) for routine brain check-up, and 3 (4.4%) with other disease entities. Of the 68 patients, modified Rankin Scales on admission were 0-2 in 55 (80.8%) patients. In 50 (73.5%) patients, the arterial dissection was observed in the vertebro-basilar system and in 18 (26.5%) arterial dissection was observed in the carotid systems. Initial angiography revealed the pearl and string sign (PSS) in 30 lesions, which was the most common findings, and tapered occlusion, the second most common one, was observed in 15 lesions. Follow-up angiography revealed that 15 patients (22.7%) were improving on the dissected arteries, but the other 14 patients (20.1%) were progressing. We conservatively treated all the patients in the acute stage, but 7 (10.1%) patients showed symptomatic aggravations. Six out of the 7 exhibited cerebral ischemic symptoms, and 3 of these 6 patients suffered from cerebral embolism due to dissecting aneurysm at the cervical internal carotid arteries. Among the remaining 3 patients, 2 had enlarged cerebral infarction due to progressive arterial stenosis; 1 had perforating arterial infarction. Another suffered from subarachnoid hemorrhage followed by cerebral infarction. Nine patients underwent surgeries. Of the 9 patients, we performed trapping of the dissecting aneurysms in 4 patients due to a tendency of aneurysmal enlargement after being confirmed by a follow-up angiography. To prevent further cerebral embolism, a dissecting aneurysm in 1 patient at the cervical internal carotid arterial portion was treated surgically by resection. STA-SCA bypass surgery was performed in 4 patients for hemodynamic stress due to the bilateral vertebral arterial dissection. Clinical outcomes of the 68 patients at discharge were excellent or good in 40 patients (58.8%). Although most patients suffering from non-hemorrhagic cerebral arterial dissection recover well by conservative treatments, some cases require surgical treatment if they are complicated by enlargement of the aneurysms, cerebral ischemia due to dissecting aneurysms at the cervical carotid arteries, or hemodynamic stress due to the bilateral vertebral arterial dissection.
We reviewed 55 unruptured dissecting aneurysms treated in Nagoya University and its affiliated hospitals over the last 7 years, and investigated the indications and pitfalls of such endovascular treatments. Among 55 aneurysms, 38 were endovascularly treated. The aneurysms were located on the vertebral artery (VA) in 47, the anterior cerebral artery in 3, middle cerebral artery in 1, and the posterior cerebral artery (PCA) in 4. As for the clinical presentation, ischemic symptoms was found in 22 cases, and headaches without neurological symptoms occurred in 27 patients. Five patients had bilateral lesions, including 3 aneurysms with 1 ruptured on the contralateral side. Thirty aneurysms were treated with endovascular trapping. A worsening of ischemic symptoms by trapping of VA was experienced in 5 cases in which the posterior inferior cerebellar artery (PICA) was hypoplastic or the aneurysm located far from the PICA origin. Two of 14 patients during the follow-up period showed complete thrombosis with parent artery occlusion, and 1 aneurysm underwent a spontaneous reduction in size. No aneurysms recurred or ruptured after endovascular trapping. According to our analysis, endovascular treatments proved very useful in avoiding the rupture of dissecting aneurysms. However, dissecting aneurysms of VA with hypoplastic PICA should be carefully performed. The aneurysms with the tendency for spontaneous regression should be followed up without surgical sacrifice of the parent artery. A targeted treatment strategy is needed against unruptured lesions following multiple dissections with SAH as well as parent artery stenosis at the dissection site.
Basilar artery occlusion (BA occlusion) is a catastrophic event and a neurologic emergency that requires a rapid diagnosis and therapy. High mortality of patients treated only with nonthrombolytic methods has been reported several times in the literature. We treated a series of 9 patients with BA occlusion that underwent intra-arterial thrombolysis over a period of 9 years (1995-2004). Ultra-early MRI, including diffusion weighted imaging (DWI) and MR angiography were performed in 6 patients. We retrospectively investigated MRI findings, clinical outcome and indication of thrombolysis in BA occlusion. Initial clinical status was critical in all cases. Five patients had atrial fibrillation. The DWI was performed 60 to 210 minutes after onset and showed different patterns of ischemic lesions. In 3 patients, no signs of high intensity areas in the brain stem could be identified. The remaining demonstrated multiple lesions involving the brain stem. The clinical outcome was unfavorable (SD, veg, dead) in the 3 patients with residual lesion in brain stem in spite of successful recanalization. We present the clinical outcomes of 6 patients with BA occlusion, focusing especially on ultra-early MRI findings. These results suggest that success is possible in patients with no signs of high-intensity areas in the brain stem in spite of its poorer condition before treatment if reperfusion was achieved with thrombolysis.
We evaluated neuropsychological function and MR images in patients with asymptomatic cerebral aneurysms in order to improve the results of surgical treatment. Consecutive operations (n=53) on 51 patients since 2000 were included in this study. Direct surgery (DS) was performed in 37 operations on 35 patients, and intravascular surgery (IVS) was performed in 16 operations on 16 patients. IVS was selected for patients with large-sized or posterior circulation aneurysms. MR imaging was conducted 1 week after surgery and WAIS-R examination was done 1 month and 1 year after surgery. In the DS group, abnormal neurological findings were recognized postoperatively in 27% of surgeries. Among them, visual disturbance was permanent in 5% of surgeries, all of which were surgeries for paraclinoid internal carotid artery aneurysms. WAIS-R results deteriorated in 26% of surgeries at 1 month and in 4% of surgeries at 1 year after surgery. MR images at 1 week after surgery revealed brain damage in 38% of surgeries and subdural fluid collection in 18% of surgeries. Of patients with anterior communicating artery aneurysms, 33% showed abnormal neurological findings, 33% showed deterioration of WAIS-R results, although almost all these findings were transient, and 58% showed brain damage upon evaluation of MR images at 1 week after surgery. In the IVS group, abnormal neurological findings were recognized postoperatively in 19% of patients, and hemiparesis was permanent in 6% of patients. Cerebral infarction was observed in 31% of patients on MR images at 1 week after surgery. Of patients with partially thrombosed aneurysms, 75% showed cerebral infarction and 50% showed abnormal neurological findings transiently. To improve surgical results, selection of treatment or surgical approaches should be strictly based on evaluation of postoperative MR images and neuropsychological function, as well as on neurological findings and outcome. Results of DS were not satisfactory in patients with anterior communicating artery or paraclinoid internal carotid artery aneurysms, and results of IVS were discontented in patients with partially thrombosed aneurysms.
We investigated the indications for endovascular treatment of unruptured cerebral aneurysms based on the natural history reported in ISUIA and our treatment results. At Nagoya University hospital and affiliated hospitals over 7 years we treated or attempted embolization for 383 unruptured aneurysms, including 301 asymptomatic and 82 symptomatic ones. Among them, 326 were treated with embolization and 57 were left untreated due to the high risks involved. Ruptures during the follow-up occurred in 2 symptomatic cases without treatment. We experienced 28 technical complications including 9 hemorrhagic, 14 ischemic and 4 others at the intra- and perioperative stage, in addition to 14 recanalizations at the delayed stage. The rate of morbidity associated with procedure was 4.0%. There was a high risk of hemorrhagic complications from a tiny anterior communicating artery aneurysm and ischemic complications in the middle cerebral, basilar-tip, and vertebral dissecting aneurysms with a hypoplastic posterior inferior cerebellar artery. As for the symptomatic aneurysms, although 72 patients had a good outcome, symptoms due to mass effects did not improve in 19 cases and worsened in 7. Particularly large paraclinoid aneurysms with visual symptoms showed a reduced possibility of symptom improvement. Although embolization has proved highly effective for the treatment of unruptured aneurysms, the treatment decision should take into account the relevant guidelines, including those for surgical option and observation.
Abbreviations: ISUIA: International Study of Unruptured Intracranial Aneurysms
We report 7 cases presenting with double aneurysms originated from the junction of the internal carotid artery-posterior communicating artery and the ipsilateral internal carotid artery-anterior choroidal artery. It was equivocal in the preoperative angiogram whether 2 adjacent aneurysms were adherent or not. Meticulous dissection of the aneurysms and preservation of blood flow in the parent artery and its branches are required in direct surgery.
We retrospectively evaluated the relationship between the collateral pathway defined 3D Time-of Flight Magnetic Resonance Angiogram (MRA) and intraoperative cerebral ischemia. As the collateral pathway, ACA collateral and PCA collateral were defined and analyzed. Intraoperative cerebral ischemia was assessed by the continuously monitored electroencephalographic (EEG) change. Internal shunt was inserted routinely. Carotid stump pressure (CSP) was measured through the inserted shunt on all cases. In the cases except for contralateral carotid occlusion (n=100), incomplete pattern on both ACA collateral and PCA collateral was significantly related to the EEG change and CSP≤25 mmHg (p=0.003, p<0.0001, respectively). Individual evaluations showed the state of ACA collateral was significantly related to the EEG change and CSP≤25 mmHg (p=0.0025, p<0.0001, respectively). Conversely, the state of PCA collateral was not significantly related to them. Therefore, ACA collateral was a major pathway on carotid clamping except for the contralateral carotid occlusion case. Contralateral carotid occlusion (n=10) was significantly related to the EEG change and CSP≤25 mmHg (p<0.0001, p=0.0007, respectively), but no specific pattern of the collateral pathway related to them was found. Incomplete pattern on ACA collateral and contralateral carotid occlusion might predict intraoperative cerebral ischemia.