Effect of embolization before stereotactic radiosurgery for brain arteriovenous malformations: a case-control study with propensity score matching.

OBJECTIVE: The aim of this study was to evaluate whether endovascular embolization prior to stereotactic radiosurgery (SRS) has a negative impact on nidus obliteration for patients with arteriovenous malformations (AVMs). METHODS: A total of 704 eligible patients with AVM who did not undergo prior surgery or radiotherapy were evaluated. Of these patients, 593 were treated with SRS only, and 111 were treated with embolization followed by SRS (E+SRS). Most patients in the E+SRS group (88%) underwent embolization with n-butyl-2-cyanoacrylate. In the comparison of radiosurgical outcomes between patients treated with SRS only and E+SRS, these groups were matched in a 1:1 ratio using propensity score matching to eliminate differences in basic characteristics. The primary outcome was to compare the nidus obliteration rates between the SRS-only and E+SRS groups. The secondary outcomes were the comparison of cumulative hemorrhage rates and the incidence of cyst formation or chronic encapsulated hematoma after SRS between these groups. RESULTS: In the unmatched cohorts, the actuarial 3-, 5-, and 8-year nidus obliteration rates after a single SRS session were 49.6%, 69.4%, and 74.1% in the SRS-only group, respectively, and 30.7%, 50.9%, and 68.6% in the E+SRS group, respectively (p = 0.001). In the matched cohort of 98 patients in each group, the rates were 47.1%, 62.0%, and 69.6% in the SRS-only group and 32.5%, 55.3%, and 75.0% in the E+SRS group, respectively (p = 0.24). There was no significant difference in either cumulative hemorrhage or the incidence of cyst formation or chronic encapsulated hematoma between the groups. CONCLUSIONS: Pre-SRS embolization did not affect nidus obliteration rates, cumulative hemorrhage rates, or the incidence of cyst formation or chronic encapsulated hematoma as late adverse radiation effects in patients with AVM treated with SRS.

Primary Dural Mucosa-associated Lymphoid Tissue Lymphoma Mimicking Falx Meningioma: A Case Report.

An 85-year-old woman presented with ataxia and deterioration of cognitive functions. She had no history of autoimmune diseases or viral infections. Magnetic resonance imaging showed a solitary mass lesion at the cerebral falx on contrast-enhanced T1-weighted imaging. Gross total resection of the lesion involving the dura mater was performed by bifrontal craniotomy. Histological examination showed diffuse infiltration of small lymphocytes and plasma cells. There was also some proliferation of large lymphocytes with folded nuclei, high-density chromatin, and inconspicuous nucleoli. The large atypical B lymphocytes did not demonstrate diffuse dense sheet findings. Meningothelial components were not detected. Immunohistochemistry was positive for pan B-cell antigens. The analysis of the kappa/lambda ratio indicated kappa immunoglobulin light chain-restricted B-cell proliferation. The final histopathological diagnosis was mucosa-associated lymphoid tissue lymphoma. Systemic screening examinations were then performed. Histological findings of the bone marrow showed normal findings without atypical lymphocytes. A chromosomal study of the bone marrow showed 46, XX. 18F fluoro-2-deoxyglucose positron emission tomography showed high accumulations at the left pterygoid muscle and the right transverse processes of the thoracic vertebrae, and mild accumulation at the right ilium bone, which indicated disseminated lesions. One year later, thickening of the dura mater was detected. Therefore, gamma knife surgery was performed. Two years later, she was alive without neurological deterioration, and magnetic resonance imaging showed no evidence of recurrence.

Intracranial Idiopathic Acute Epidural Hematoma Presenting with a Stroke-like Attack and Rapid Neurological Deterioration: A Case Report.

A 36-year-old woman presented with sudden onset of a right-sided headache that awoke her from sleep. She had no episodes of trauma or abuse. She was initially able to speak, but fell into a coma within an hour. The right pupil was dilated, with slow pupillary reflexes to light on both sides, and she showed left hemiparalysis. Computed tomography scan showed a right acute epidural hematoma, approximately 4 cm in thickness, and there were no findings of trauma such as skin wounds, subcutaneous hematomas, or skull fractures. In the emergency room, decompression of intracranial pressure by one burr hole was performed, and her dilated right pupil improved to normal size. She was then moved to the operating room, and hematoma removal was performed by craniotomy. Her blood pressure trended downward despite rapid blood transfusion and vasopressor therapy. There were no abnormal findings apparent intraoperatively, except for oozing from the whole surface of the dura mater and epidural space. Her consciousness improved postoperatively, and her left hemiparalysis improved within a few days. No causative diseases, risk factors, or vascular abnormalities were found on laboratory and radiological surveys. Two months postoperatively, the bone flap was removed because of infection. Eight months postoperatively, a cranioplasty using artificial skull was performed, and her postoperative course was uneventful. One year after the initial surgery, she has no neurological deficits, and there has been no recurrence of epidural hematoma.

Long-Term Risks of Hemorrhage and Adverse Radiation Effects of Stereotactic Radiosurgery for Brain Arteriovenous Malformations.

BACKGROUND: The information about long-term risks of hemorrhage and late adverse radiation effects (AREs) after stereotactic radiosurgery for brain arteriovenous malformations (AVMs) is lacking. OBJECTIVE: To evaluate the long-term risks of hemorrhage and late ARE rates in patients with AVM treated with Gamma Knife surgery (GKS). METHODS: We examined 1249 patients with AVM treated with GKS. The Spetzler-Martin grade was I in 313 patients (25%), II in 394 (32%), III in 458 (37%), and IV/V in 84 (7%). The median treatment volume was 2.5 cm3, and the median marginal dose was 20 Gy. RESULTS: The median follow-up period was 61 months. The 5- and 10-year nidus obliteration rates were 63% and 82%, respectively. The 5- and 10-year cumulative hemorrhage rates were 7% and 10%, respectively. The annual hemorrhage rate was 1.5% for the first 5 years post-GKS, which decreased to 0.5% thereafter. During the follow-up period, 42 symptomatic cyst formations/chronic encapsulated hematomas ([CFs/CEHs], 3%) and 3 radiation-induced tumors (0.2%) were observed. The 10- and 15-year cumulative CF/CEH rates were 3.7% and 9.4%, respectively. CONCLUSION: GKS is associated with reduced hemorrhage risk and high nidus obliteration rates in patients with AVM. The incidence of late AREs tended to increase over time. The most common ARE was CF/CEH, which can be safely removed; however, careful attention should be paid to the long-term development of fatal radiation-induced tumors.

Predictors of long-term tumor control after stereotactic radiosurgery for Koos grade 4 vestibular schwannomas.

PURPOSE: To evaluate the predictors of long-term tumor control following stereotactic radiosurgery (SRS) for Koos grade 4 vestibular schwannomas (VSs). METHODS: Overall, 203 sporadic VS patients with compression of the brainstem were treated with SRS. The median tumor volume was 6.7 cm3 (range, 2.0-28.9 cm3) and the median marginal dose was 12 Gy (range, 9-13.5 Gy). RESULTS: The median follow-up period was 152 months (range, 12-277 months). Tumor control (TC) rates at 3, 5, and 10 years were 89%, 85%, and 82%, respectively. Operation-free survival (OFS) rates at 3, 5, and 10 years were 92%, 85%, and 83%, respectively. Middle cerebellar peduncle (MCP) compression on pre-SRS magnetic resonance imaging scans was significant for both TC (p < 0.001, hazard ratio 1.332) and OFS (p < 0.001, hazard ratio 1.306). The 3-, 5-, and 10-year OFS rates were 98%, 94%, and 92% in the low-risk group (MCP compression < 9.8 mm and > 48 years old), and 58%, 25%, and 17% in high-risk group (MCP compression ≥ 9.8 mm and ≤ 48 years old), respectively. Ten patients (4.9%) developed delayed cyst-related complications. Eleven patients (5.4%) developed newly developed or worsened trigeminal neuralgia. No patient developed persistent facial palsy as an adverse radiation effect. A ventricular peritoneal shunt was required in six patients (3%) who developed hydrocephalus after SRS. CONCLUSION: SRS is an acceptable treatment option in selected patients with Koos grade 4 VSs. Risk group classification based on patient age and MCP compression is useful in decision-making of Koos grade 4 VSs.

Long-Term Outcomes of Sporadic Vestibular Schwannomas Treated with Recent Stereotactic Radiosurgery Techniques.

PURPOSE: Vestibular schwannomas (VSs) are benign; thus, understanding long-term tumor control and late adverse radiation effects of stereotactic radiosurgery (SRS) through current radiosurgical techniques is important to inform treatment decisions. Our aim was to clarify long-term tumor control rates and incidence of late adverse radiation effects in patients with VSs followed for 5 years or longer after SRS. METHODS AND MATERIALS: Altogether, 615 patients with VSs (excluding neurofibromatosis type 2 and partially treated tumors) followed for 5 years or longer after SRS using recent radiosurgical techniques were evaluated. All patients were treated at a margin dose of less than 14 Gy. All tumors were classified into 4 categories: type A (intracanalicular tumor, 87 patients [14%]), type B (cerebellopontine angle [CPA] tumor, 325 patients [53%]), type C (CPA tumor compressing the brain stem, 138 patients [22%]), and type D (CPA tumor compressing the brain stem with a deviation of the fourth ventricle, 65 patients [11%]). Median tumor volume was 2.0 cm3 and median marginal dose was 12 Gy. RESULTS: Median follow-up period was 158 months. Actuarial 5-, 10-, and 15-year or longer local control (LC) rates were 93%, 91%, and 89%, respectively. Tumor type (P < .001, hazard ratio 2.389) and number of prior surgeries (P = .007, hazard ratio 1.698) were significant for LC. Depending on the tumor type, the actuarial 10-year LC rates were 100%, 93%, 88%, and 70% in type A, B, C, and D tumors, respectively. No patient developed persistent facial palsy. Twenty patients (3.3%) developed delayed cysts. One patient developed malignant transformation (0.2%). CONCLUSIONS: SRS is a safe and effective treatment for VSs in the long term, excluding VSs compressing the brain stem with a deviation of the fourth ventricle. Delayed cysts such as cyst formation, enlarged preexisting cysts or extratumoral cysts, and malignant transformation should be considered possible causes of long-term treatment failures.

[A Case of Unilateral Multiple Cerebral Edema 4 Weeks after Coil Embolization].

Coil embolization for cerebral aneurysms can lead to various complications, such as aneurysm rupture and cerebral embolism. In recent years, foreign substance embolisms-caused by peeling off of coating materials from therapeutic devices-have been described. We report here a case of unilateral multiple cerebral edema four weeks after coil embolization. A 44-year-old woman presented with a subarachnoid hemorrhage from a right internal carotid-posterior communicating artery aneurysm, for which coil embolization was performed. Four weeks after the embolization, she developed numbness in the left side of her mouth and in her left upper extremity. Magnetic resonance images showed multiple edematous lesions in the right cerebral hemisphere. Subsequent treatment with steroids improved her symptoms and edematous cerebral lesions. Although definitive diagnosis by biopsy was not performed, her clinical course and imaging findings resembled a foreign substance embolism by hydrophilic coating. It is important to note that delayed cerebral edema due to foreign substance embolisms might occur after endovascular treatments.

Repeated Intracranial Hemorrhage After Delivery Induced by Coagulopathy Associated with Multiple Venous Malformations.

BACKGROUND: Venous malformations are classified as slow-flow vascular malformations. Coagulation abnormalities are known to be frequent among patients with venous malformations. We report a case of repeated intracranial hemorrhage after delivery, induced by coagulopathy associated with multiple venous malformations. CASE DESCRIPTION: A 28-year-old woman presented with left chronic subdural hematoma 1 month after successfully giving birth. She had a history of multiple venous malformations around the pubic region and hips. The hematoma was evacuated by burr hole surgery. Three hours later, her level of consciousness rapidly deteriorated and computed tomography showed acute epidural hematoma. The hematoma was removed immediately by craniotomy under general anesthesia. No bleeding points were apparent in the operative field. Continuous bleeding around the dura mater and subdural space were encountered, and hemostasis was not achieved by electrocoagulation. After using fresh frozen plasma, hemostasis was achieved. Level of consciousness and neurologic symptoms improved postoperatively. Magnetic resonance imaging revealed multiple venous malformations in bilateral lower extremities and the pelvis. Disseminated intravascular coagulopathy was diagnosed, and thrombomodulin and blood coagulation factor XIII were administered. She was discharged home without any neurologic deficits. CONCLUSIONS: The delivery activated localized intravascular coagulopathy in the venous malformations and induced chronic subdural hematoma. Surgical interventions then resulted in progression of the coagulopathy to disseminated intravascular coagulopathy, inducing acute epidural hematoma.

Long-Term Outcomes for Pediatric Patients with Brain Arteriovenous Malformations Treated with Gamma Knife Radiosurgery, Part 2: The Incidence of Cyst Formation, Encapsulated Hematoma, and Radiation-Induced Tumor.

OBJECTIVE: Long-term data about the incidence of late adverse radiation effects (AREs) in pediatric brain arteriovenous malformations (AVMs) treated with Gamma Knife radiosurgery (GKRS) are lacking. This study addresses the incidence of late AREs, including cyst formation (CF), chronic encapsulated hematoma (CEH), and radiation-induced tumor, in pediatric patients with AVM treated with GKRS. METHODS: This is a single-institutional study involving pediatric patients with AVM who underwent GKRS between 1991 and 2014. Among 201 pediatric patients with AVM (age ≤15 years), 189 who had at least 12 months of follow-up were assessed in this study. The median treatment volume was 2.2 cm3, and the median marginal dose was 20 Gy. RESULTS: The mean follow-up period was 136 months. During the follow-up period, symptomatic radiation-induced perilesional edema was found in 5 patients (3%), CFs in 7 patients (4%), CEHs in 7 patients (4%), and radiation-induced tumors in 2 patients (1%). The cumulative incidences of late AREs including CF, CEH, and radiation-induced tumor were 1.2% at 5 years, 5.2% at 8 years, 6.1% at 10 years, 7.2% at 15 years, and 17.0% at 20 years. In the multivariate analysis, treatment volume alone was a significant factor for late AREs (P < 0.001; hazard ratio, 1.111). CONCLUSIONS: GKRS is a reasonable treatment option for pediatric AVMs to prevent future intracranial hemorrhages, particularly in the eloquent regions. However, considerable attention should be paid to late AREs such as CFs, CEHs, and radiation-induced tumors because of longer life expectancy in pediatric patients.

Long-Term Outcomes for Pediatric Patients with Brain Arteriovenous Malformations Treated with Gamma Knife Radiosurgery, Part 1: Analysis of Nidus Obliteration Rates and Related Factors.

OBJECTIVE: Little is known about long-term outcomes for pediatric brain arteriovenous malformations (AVMs) treated with Gamma Knife radiosurgery (GKRS). This study investigated annual hemorrhage rates and nidus obliteration rates, and the factors affecting them, in pediatric AVMs treated with GKRS. METHODS: We examined 189 pediatric AVM patients (age ≤15 years) who underwent GKRS and had at least 12 months of follow-up. The Spetzler-Martin (S-M) grade was I in 29 patients (15%), II in 57 (30%), III in 82 (43%), IV in 16 (9%), and V in 5 (3%). The median treatment volume was 2.2 cm3, and the median marginal dose was 20 Gy. RESULTS: The mean follow-up period was 136 months. During a cumulative latency period to nidus obliteration of 813 years, 23 hemorrhages occurred, resulting in an annual post-GKRS hemorrhage rate of 2.8%. The cumulative hemorrhage rates after GKRS were 3.3%, 8.5%, and 11.9% at 3, 5, and 10 years, respectively. Higher S-M grade was significantly associated with intracranial hemorrhages during the latency period (P < 0.001). The actuarial nidus obliteration rates with repeated GKRS were 64% and 81% at 5 and 10 years, respectively. Absence of pre-GKRS embolization (P = 0.023) and higher marginal dose (P = 0.029) were significant factors predicting nidus obliteration. CONCLUSIONS: GKRS is a reasonable treatment option in pediatric AVMs to prevent future hemorrhages. Because higher S-M grade AVMs are more likely to hemorrhage during the latency period, a combined therapy with endovascular embolization should be considered to prevent AVM rupture.

Long-term hearing outcomes after gamma knife surgery in patients with vestibular schwannoma with hearing preservation: evaluation in 92 patients with serial audiograms.

The treatment strategy for patients with vestibular schwannoma (VS) is controversial, and data concerning the long-term hearing outcomes > 5 years after gamma knife surgery (GKS) are limited. The long-term hearing outcomes after GKS were evaluated in VS patients with hearing preservation. Ninety-two VS patients with a pure tone average (PTA) ≤ 50 dB were evaluated. The median age was 54 years; the median tumor volume was 1.5 cm3. The tumors were treated with a median margin dose of 12 Gy and a median mean cochlear dose of 4.0 Gy. At the time of GKS, 65 patients retained a PTA of 0-30 dB, and 27 had a PTA of 31-50 dB. The median follow-up period was 106 months. At the final follow-up, 2 (2%) developed tumor progression. During the median audiogram follow-up of 83 months, the PTA was ≤ 30 dB in 22 patients (24%) and 31-50 dB in 27 patients (29%); 43 patients (47%) worsened to a PTA > 50 dB. Hearing preservation rates were 66, 57, and 44% at 3, 5, and 10 years, respectively. In multivariate analysis, the mean cochlear dose (P < 0.001) and pre-GKS PTA (P = 0.045) were significant for hearing preservation. GKS was an effective treatment option for VS patients with a PTA ≤ 50 dB. As a lower cochlear dose and better pre-GKS PTA contributed to long-term hearing preservation, prophylactic GKS before hearing deterioration or tumor growth would be a treatment of choice if patients provided informed consent.

Pial arteriovenous fistula as a cause of bilateral thalamic hyperintensities--an unusual case report and review of the literature.

INTRODUCTION: Isolated bilateral thalamic congestion due to an arteriovenous malformation (AVM) is a rare entity. Few case reports of dural arteriovenous fistula associated with it have been reported in the literature. The association of pial arteriovenous fistula (pial AVF) with thalamic hyperintensities has never been described before. The pial AVF is a recently recognized lesion in which the multiple pial arterial feeders drain into a single venous channel without a nidus like in conventional AVM. In spite of being congenital in origin, these lesions may have expression in adulthood due to abrupt change in the venous drainage system. Successful management of pial AVF associated with bilateral thalamic hyperintensities is described here with review of the literature. CASE PRESENTATION: A 60-year-old man presented with rapidly progressive gait disturbance and cognitive decline. Magnetic resonance imaging (MRI) showed hyperintensities in the thalami on T2-weighted and fluid attenuated inversion recovery image. Digital subtraction angiography revealed a pial AVF near the splenium of corpus callosum. It had feeders from posterior choroidal arteries and drained into the vein of Galen through an abnormal mesencephalic vein. The stagnation and increase of pressure in the deep venous system led to congestion in the thalami. He was treated by partial transarterial embolization of the feeders followed by gamma knife therapy (GKT). The clinical symptoms and MRI improved rapidly after embolization and further reduction in shunt flow was observed after GKT. CONCLUSION: Strong suspicion of vascular malformation as a cause of bilateral thalamic hyperintensities helps in early detection. Such lesions like pial AVF presented here require active intervention by surgery or endovascular therapy. GKT is an important adjuvant in lesions refractory to either of them.

[Resistance to antiplatelet agents assessed by a point-of-care platelet function test and thromboembolic adverse events in neurointervention].

OBJECTIVE: To clarify the frequency of Japanese patients who are resistant to antiplatelet agents, and then clarify correlations between resistance and thromboembolic adverse events in neurointervention. METHODS: Blood samples were collected from 163 patients who were taking antiplatelet agents and received neurointervention, with 128 samples collected just before neurointervention. Residual platelet function was measured using a point-of-care platelet function test, VerifyNow®, and then the frequency of patients resistant to drugs (low-responders), correlations between resistance and thromboembolic events, and effects of adding cilostazol to clopidogrel administration were analyzed. Cut-off values were defined as 550 Aspirin Reaction Units (ARU), 230 P2Y12 Reaction Units (PRU), and 50%inhibition of P2Y12, respectively. RESULTS: Three of 105 patients (2.9%) taking aspirin at 100 mg/day were low-responders, whereas 48 (41.0%, as measured by PRU) or 80 (68.4%, as measured by %inhibition) of 117 patients taking clopidogrel at 75 mg/day were low-responders. Among the 19 patients taking cilostazol 200 mg/day in addition to clopidogrel 75 mg/day, platelet functions were significantly more strongly inhibited compared to patients taking clopidogrel alone (p=0.02 by PRU, p=0.005 by %inhibition). Thromboembolic adverse events occurred in 7 patients. Among these 7 patients, 6 who were taking aspirin were all responders to aspirin, while 4 of the 6 patients taking clopidogrel were low-responders to clopidogrel. In 69 patients who received aneurysmal transarterial embolization, 2 thromboembolic complications occurred among low-responders (p=0.09). CONCLUSION: Aspirin resistance is rare in Japanese individuals. With aneurysmal transarterial embolization, thromboembolic events tended to occur among clopidogrel low-responders. Addition of cilostazol may offer one method of overcoming clopidogrel resistance.

Magnetic resonance fluid dynamics for intracranial aneurysms--comparison with computed fluid dynamics.

BACKGROUND: Hemodynamics in intracranial aneurysms is thought to play an important role in their growth and rupture. Usual computed fluid dynamics (CFD) based on three-dimensional (3D) computed tomographic (CT) angiography requires a time-consuming process for analysis. Magnetic resonance fluid dynamics (MRFD) based on MR images is a new tool for analyzing flow dynamics and a promising method for obtaining such information more easily. We compared the data from MRFD and CFD and studied the clinical feasibility of MRFD. METHODS: A total of 15 aneurysms, including two ruptured ones, in 15 patients were investigated with MR imaging and 3D-CT angiography. The flow data of MRFD and CFD, 3D stream lines, flow velocity profile and wall shear stress (WSS) were extracted from the image reconstruction and were compared each other. RESULTS: Both flow dynamics images showed quite similar 3D flow pattern and WSS map. However, the calculated value of maximum WSS was quite different and there was no significant correlation. Further, in one ruptured case, CFD showed less visualization to evaluate the intra-aneurysmal flow. Interestingly, one delayed rupture case showed a particular flow pattern with abnormal secondary flow in the bottom of the aneurysm before rupture, which might suggest the specific finding of rupture risk. CONCLUSION: MRFD is a valuable and less invasive tool to evaluate aneurysmal fluid dynamics. It can be obtained from the usual MRI examination without contrast medium and exposure to radiation. Although there is a problem of consistency of the absolute value of WSS between MRFD and conventional CFD, it may be useful to predict the risk of enlargement or rupture of aneurysms based on the information of the similar distribution of WSS and flow patterns. The quantifiable analysis and establishment of a meaningful threshold for high risk should be further studied.