Tsuyoshi Izumo

A nationwide survey on unilateral moyamoya disease in Japan

OBJECTIVE Moyamoya disease (MMD) is a unique occlusive disease of the bilateral internal carotid arteries; compensation for occlusion results in rich arterial collaterals at the base of the brain. The clinical features of unilateral MMD, confirmed by typical angiographic evidence of MMD unilaterally and normal or equivocal contralateral findings, are not well known. To identify the clinical features of unilateral MMD in Japan, a nationwide survey was conducted. PATIENTS AND METHODS The questionnaire was directly mailed to 241 departments that reported treating unilateral MMD patients in a primary survey. We ascertained the sex, age, family history, clinical manifestation, radiological findings, treatments, course of the disease, and daily activity of unilateral MMD patients. RESULTS A total of 114 departments replied to the questionnaire. The data of 203 patients (118 female and 85 male; female to male ratio 1.4:1) were registered and analyzed. The mean age was 40.2 years old with a peak occurring in the fifties. Twenty-one patients (10.7%) exhibited familial MMD. The clinical symptoms are motor weakness 57 (26.8%), headache 37 (17.4%), transient ischemic attack 35 (16.4%), and no symptom 30 (14.1%). The MMD types determined by imaging included ischemic type in 64 patients (32.5%), bleeding type in 51 (25.9%), and normal in 82 (41.6%). The development of moyamoya vessels was mild in 78 patients (43.9%) and most patients (81.1%) were accompanied with cerebral hypoperfusion. Medical treatment or vascular reconstruction was employed for more than half of the patients. CONCLUSION The clinical feature of unilateral MMD was revealed in this nationwide study. Unilateral MMD was predominant in adults and the development of moyamoya vessel was relatively less prevalent.

Cyst formation after linac-based radiosurgery for arteriovenous malformation: examination of predictive factors using magnetic resonance imaging.

OBJECTIVE Cyst formation is a well-known complication following radiosurgery for arteriovenous malformations (AVMs). In this retrospective study, the authors studied predictors for AVMs using magnetic resonance imaging (MRI) to assess the mechanism of cyst formation after linac-based radiosurgery (LBRS). METHODS From April 1993 to April 2008, LBRS was performed on 109 patients with cerebral AVMs at our institution. Six patients (5.5%) were diagnosed with cyst formation after LBRS, and 5 of them underwent regular MRI follow-up every 3-4 months for 2 years post-LBRS, and every 6-12 months thereafter. RESULTS Time from initial LBRS until cyst formation ranged from 8 months to 10.5 years. MRI showed contrast changes at the irradiated site and its periphery within a period of 4 months to 7 years after the initial LBRS. Moreover, the emergence of a high-intensity area (HIA) was observed on T2-weighted MRI (T2W-MRI) during the same period when changes were found on contrast-enhanced imaging. The emergence of a low-intensity area on T2W-MRI was observed prior to cyst formation or expansion, which was believed to be due to a subclinical hemorrhage near the irradiated region in all patients. Histological examination of the cyst nodule revealed hemosiderin deposits and microbleeding. CONCLUSIONS Future cyst formation was suggested by the emergence of subclinical hemorrhage (microbleeding) in an irradiated field after gadolinium-enhanced MRI showed contrast changes and T2W-MRI showed a HIA around the irradiated field. MRI follow-up should be conducted on a regular basis in such patients, even after a complete occlusion has been diagnosed.

Microsurgical Clipping for Recurrent Aneurysms After Initial Endovascular Coil Embolization

OBJECTIVE Surgical treatment for recurrent lesions of embolized aneurysms is difficult and challenging for many neurosurgeons because intra-aneurysmal coil masses are sometimes scarred to the wall of the aneurysm or adherent to adjacent vital structures. To assess the efficacy and safety of surgical treatment without coil removal for recurrent aneurysms after previous coil embolization, we retrospectively studied clinical results, angiographic results, and complications in patients treated with additional microsurgical clipping. METHODS From April 2003 to April 2013, 7 patients with recurrent previous embolized aneurysms underwent microsurgical treatment. RESULTS This series included 1 man and 6 women receiving endovascular coiling as the first-line treatment. One patients aneurysm was unruptured, whereas the other 6 were ruptured. The aneurysm locations were posterior communicating (n = 3), anterior communicating (n = 2), ophthalmic (n = 1), and posterior inferior cerebellar (n = 1). The initial sizes ranged from 3-11.5 mm in diameter (mean, 6.6 mm), and the aspect ratios were 1.2 to 3.4 (mean, 1.9). In these aneurysms, the initial coiling result was complete occlusion in 5 patients, and neck remnants in 2 patients. The mechanism underlying aneurysm recurrence was coil compaction in 3 aneurysms, aneurysm regrowth in 3 aneurysms, and fundal migration in 1 aneurysm. The median recurrence latency was 28.8 months (range, 0.7-115 months). Microsurgical clippings without coil removal were used in 6 patients; a parent artery occlusion under bypass protection was done in 1 case with a posterior inferior cerebellar aneurysm. Fenestrated clips in combination with another type of clip were successfully used for 4 of 6 patients who were treated with direct neck clipping. No postoperative morbidity was observed, and postoperative imaging studies revealed complete occlusion of the aneurysms in all cases. There were no recurrences of aneurysms during the follow-up period (mean, 44.7 months; range, 0.5-118 months). CONCLUSIONS The microsurgical clipping without coil removal for recurrent lesions of embolized aneurysms is effective and safe when it is technically feasible. The tandem clipping in combination with a fenestrated clip is a crucial method for direct neck clipping without coil removal for previously coiled recurrent aneurysms. For unclippable lesions, a parent artery occlusion under bypass protection should be taken into consideration.

De Novo Ivy Sign Indicates Postoperative Hyperperfusion in Moyamoya Disease

Background and Purpose— The ivy sign on fluid-attenuated inversion recovery MRI is a specific finding in moyamoya disease (MMD). This sign indicates decreased cerebral perfusion, dilated pial vasculature, and slow leptomeningeal collateral flow. This study aimed to clarify the characteristics of perioperative changes in the ivy sign in relation to cerebral hyperperfusion, which frequently occurs in MMD of unknown pathogenesis. Methods— This prospective study included patients with MMD who underwent superior temporal artery–middle cerebral artery single bypass. Fluid-attenuated inversion recovery MRI was performed to evaluate the appearance of the ivy sign in the ipsilateral hemisphere preoperatively and on postoperative days 2 and 30. The ivy sign was assessed in combination with perioperative symptoms and cerebral hemodynamics using single-photon emission computed tomography. Results— Of 42 consecutive patients (55 sides) who underwent bypass surgery, 32 (58.2%) showed an increase in the ivy sign (de novo ivy sign) on postoperative day 2; this had disappeared by day 30. Interestingly, these 32 patients had a significantly higher incidence of hyperperfusion on single-photon emission computed tomography and hyperperfusion syndrome, and there was no correlation between the de novo ivy sign and a preoperative ivy sign or the preoperative cerebral hemodynamics. In multivariate analysis, a de novo ivy sign was significantly correlated with postoperative hyperperfusion. Conclusions— In MMD, a de novo ivy sign could indicate postoperative hyperperfusion after bypass, which is not always correlated with preoperative hemodynamic impairment. Additional factors other than preoperative cerebral hemodynamics might be involved in postoperative hyperperfusion in MMD.

Linear accelerator-based radiosurgery alone for arteriovenous malformation: more than 12 years of observation.

PURPOSE Although radiosurgery is an accepted treatment method for intracranial arteriovenous malformations (AVMs), its long-term therapeutic effects have not been sufficiently evaluated, and many reports of long-term observations are from gamma-knife facilities. Furthermore, there are few reported results of treatment using only linear accelerator (LINAC)-based radiosurgery (LBRS). METHODS AND MATERIALS Over a period of more than 12 years, we followed the long-term results of LBRS treatment performed in 51 AVM patients. RESULTS The actuarial obliteration rates, after a single radiosurgery session, at 3, 5, 10, and 15 years were 46.9%, 54.0%, 64.4%, and 68.0%, respectively; when subsequent radiosurgeries were included, the rates were 46.9%, 61.3%, 74.2%, and 90.3%, respectively. Obliteration rates were significantly related to target volumes ≥4 cm(3), marginal doses ≥12 Gy, Spetzler-Martin grades (1 vs other), and AVM scores ≥1.5; multivariate analyses revealed a significant difference for target volumes ≥4 cm(3). The postprocedural actuarial symptomatic radiation injury rates, after a single radiation surgery session, at 5, 10, and 15 years were 12.3%, 16.8%, and 19.1%, respectively. Volumes ≥4 cm(3), location (lobular or other), AVM scores ≥1.5, and the number of radiosurgery were related to radiation injury incidence; multivariate analyses revealed significant differences associated with volumes ≥4 cm(3) and location (lobular or other). CONCLUSIONS Positive results can be obtained with LBRS when performed with a target volume ≤4 cm(3), an AVM score ≤1.5, and ≥12 Gy radiation. Bleeding and radiation injuries may appear even 10 years after treatment, necessitating long-term observation.

Effects of stereotactic radiosurgery on metastatic brain tumors of various histopathologies

Although reports have been published describing clinical results in a large series of patients with metastatic brain tumors treated by stereotactic radiosurgery (SRS), clinical neuropathological correlation has rarely been available. The present paper describes three autopsy cases and one surgical case treated with linear accelerator based radiosurgery. The cases comprised a lung cancer, a rectal cancer, an osteosarcoma, and a malignant melanoma. Histological sections of each tumor were analyzed by light microscopy based on the Ohosi and Shimosatos histopathological classification of the effects of radiation therapy. In three cases (pulmonary squamous cell carcinoma, rectal adenocarcinoma and osteosarcoma), a large area of the tumors consisted of coagulation necrosis and non‐viable tumor cells, while coagulation necrosis and non‐viable tumor cells comprised a very small part of the malignant melanoma. Histopathological type of the metastatic brain tumor may be one of the factors influencing outcome after SRS.

Acute stroke with major intracranial vessel occlusion: Characteristics of cardioembolism and atherosclerosis-related in situ stenosis/occlusion.

Acute ischemic stroke with major intracranial vessel occlusion is commonly due to cardioembolic or atherosclerosis-related in situ stenosis/occlusion, and immediate identification of these subtypes is important to establish the optimal treatment strategy. The aim of this study was to clarify the differences in clinical presentation, radiological findings, neurological temporal courses, and outcomes between these etiologies, which have not been fully evaluated. Consecutive emergency patients with acute ischemic stroke were retrospectively reviewed. Among them, patients with stroke with major intracranial vessel occlusion were analyzed with a focus on clinical and radiological findings, and a comparison was performed for those with cardioembolic or atherosclerosis-related in situ stenosis/occlusion. Of 1053 patients, 80 had stroke with acute major intracranial vessel occlusion (45 with cardioembolic and 35 with atherosclerosis-related in situ stenosis/occlusion). Interestingly, the susceptibility vessel sign (SVS) on T2-weighted MR angiography was more frequently detected in cardioembolic stroke (80.0%) than in atherosclerosis (in situ stenosis: 5.9%, chronic occlusion: 14.3%). Moreover, the proximal intra-arterial signal (IAS) on arterial spin labeling MRI and the distal IAS on fluid attenuated inversion recovery MRI was less frequently detected in chronic occlusion (27.3% and 50.0%, respectively) than in acute occlusion due to cardioembolic or in situ stenosis. Multivariate regression analysis showed that the SVS was significantly related to cardioembolism (adjusted odds ratio (OR): 21.68, P=0.004). Clinical characteristics of acute stroke with major intracranial vessel occlusion differ depending on the etiology. The SVS and proximal/distal IAS on MRI are useful to distinguish between cardioembolic and atherosclerotic-related in situ stenosis/occlusion.

Communication of inwardly projecting neovessels with the lumen contributes to symptomatic intraplaque hemorrhage in carotid artery stenosis.

OBJECT Recent studies have demonstrated that plaque morphology can contribute to identification of patients at high risk of carotid artery atherosclerosis as well as the degree of stenosis in those with carotid atherosclerosis. Neovascularization of carotid plaques is associated with plaque vulnerability. However, the mechanism of neovascularization in intraplaque hemorrhage (IPH) and its clinical contribution remain undetermined. In this study, the authors aimed to clarify the characteristics of neovessel appearance with a focus on inwardly projecting neovessels, which are reportedly important in plaque advancement. METHODS Consecutive patients with moderate to severe carotid atherosclerosis who underwent carotid endarterectomy were prospectively analyzed from 2010 to 2014. The neovessel appearance was categorized into 3 groups based on intraoperative indocyanine green (ICG) videoangiography: early appearance of neovessels from the endothelium (NVe), late appearance of neovessels from the vasa vasorum (NVv), and no appearance of vessels. Each neovessel pattern was evaluated with respect to clinical, radiological, and pathological findings including IPH, neovascularization, hemosiderin spots, and inflammation. RESULTS Of 57 patients, 13 exhibited NVe, 33 exhibited NVv, and 11 exhibited no neovessels. Overall, the interobserver and intraobserver reproducibilities of neovessel appearance were substantial for ICG videoangiography (κ=0.76) and at 7 days postoperatively (κ=0.76). There were no significant differences in baseline characteristics among the 3 groups, with the exception of a higher percentage of symptomatic presentations in patients with NVe (artery-to-artery embolic infarction in 61.5% and transient ischemic attack in 23.1%). Moreover, patients with NVe exhibited larger infarctions than did those with NVv (9675.0±5601.9 mm3 vs 2306.6±856.9 mm3, respectively; p=0.04). Pathologically, patients with NVe had more severe IPH (47.2±8.3 mm2 vs 19.8±5.2 mm2, respectively; p<0.01), hemosiderin spots (0.5±0.2 mm2 vs 0.2±0.1 mm2, respectively; p=0.04), neovessels (0.4±0.7 mm2 vs 0.1±0.4 mm2, respectively; p=0.11), and inflammation (1.0±1.1 mm2 vs 0.6±0.9 mm2, respectively; p=0.26) around the endothelium than did patients with NVv, and all of these parameters were correlated with hyperintensity on time-of-flight MRI. However, the neovessel and inflammation differences were nonsignificant. Interestingly, inflammation was significantly correlated with neovessel formation (r=0.43, p=0.0008), hemosiderin spots (r=0.62, p<0.0001), and IPH (r=0.349, p=0.0097), suggesting that inflammation may be a key factor in plaque vulnerability. CONCLUSIONS Communication of inwardly projecting neovessels with the lumen and inflammation synergistically contribute to IPH and symptomatic presentations in patients with carotid stenosis and are more specific than the vasa vasorum. This condition could be a new therapeutic target, and regression of luminal neovessel sprouting and inflammation may help to prevent IPH development and a symptomatic presentation.

Indication and Limitations of Endoscopic Extended Transsphenoidal Surgery for Craniopharyngioma

The transsphenoidal approach has been utilized in intrasellar craniopharyngioma surgeries. However, the advent of endoscopic extended transsphenoidal approach (EETSA) has expanded its indication to suprasellar craniopharyngiomas. We compared the indication and limitations of EETSA to those of uni-lateral basal interhemispheric approach (UBIHA), which presents similar indications for surgery. We analyzed 30 patients with tumors located below the foramen of Monro and the lateral boundary extending slightly beyond the internal carotid artery (UBIHA: N = 18; EETSA: N = 12). Postoperative magnetic resonance imaging (MRI) revealed gross total resection in 10 patients in the EETSA group (83.3%) and 12 in the UBIHA group (66.7%). Postoperative MRI in the EETSA group revealed residual tumor at the cavernous sinus in one patient, at the prepontine in one; in the UBIHA group, residual tumors were located in the retrochiasmatic area in two patients, infundibulum-hypothalamus in one, on the stalk in one, and in the intrasellar region in two. No intergroup differences were observed in the preservation of pituitary function and postoperative improvement of visual function. The extent of resection was better with EETSA than with UBIHA. EETSA is considered the first-line therapy because the distance between the optic chiasm and the superior border of the pituitary is large; the lateral extension does not go beyond the internal carotid artery; and the tumor does not extend inferiorly beyond the posterior clinoid process. However, in patients showing poorly developed sphenoid sinuses or pituitary stalks anterior to the tumor, surgery is difficult regardless of the selection criteria.

Long-term follow-up results of linear accelerator-based radiosurgery for vestibular schwannoma using serial three-dimensional spoiled gradient-echo MRI

We examined the characteristic changes in vestibular schwannoma (VS) volume after treatment with linear accelerator-based radiosurgery (LBRS) and the long-term therapeutic effects, by performing three-dimensional (3D) MRI evaluations of tumor volumes. We included 44 patients in whom tumor volume changes could be observed using 3D-spoiled gradient-echo MRI for at least 5 years. Examinations were performed every 3-4 months for the first 2 years after treatment and every 6-12 months thereafter. Enlargement or shrinkage was determined as a change of at least 20% from the volume at the time of treatment. The median observation period was 13.8 years (range, 5.5-19.5 years). The tumor control rates at 5 and 10 years after treatment and at the final MRI were 90.9%, 90.0%, and 88.6%, respectively. Tumor volume changes were categorized into the following four patterns: enlargement, five patients (11.4%); stable, three patients (6.8%); transient enlargement, 24 patients (54.5%); and direct shrinkage, 12 patients (27.3%). Bimodal peaks were observed in three of the 24 patients with transient enlargement. Tumor volume changes from 5 and 10 years post-LBRS to the final observation point were observed in 27 (64.2%) and 10 patients (33.3%), respectively. The long-term tumor volume changes observed after LBRS suggest that radiation exerts long-term effects on tumors. Furthermore, while transient enlargements in tumor volume were characteristic, true tumor enlargements should be characterized by increased volumes of more than two-fold and continued growth for at least 2 years.