✓ In the past 10 years, the authors performed microsurgical evacuation of hypertensive intracerebral hematoma in 100 cases during the ultra-early stage (within 7 hours) after the apoplectic attack. Operative indications were the presence of obvious hemiplegia and disturbed consciousness (from stupor to semicoma). Functional outcomes at 6 months postoperatively were as follows: 15 patients had returned to a full social life, 35 were capable of self-care at home, 33 required partial care at home, two were bedridden and in a vegetative state, and seven had died.
Mitsuo Kaneko, Keisei Tanaka, Tsutomu Shimada, Kengo Sato and Kenichi Uemura
Kazuhiko Nishino, Hitoshi Hasegawa, Kenichi Morita, Masafumi Fukuda, Yasushi Ito, Yukihiko Fujii and Mitsuya Sato
Arteriovenous malformations (AVMs) in the cerebellopontine angle cistern (CPAC) are specific lesions that can cause neurovascular compression syndromes as well as intracranial hemorrhage. Although case reports describing the CPAC AVMs, especially those presenting with trigeminal neuralgia (TN), have been accumulating by degrees, the pathophysiology of CPAC AVMs remains obscure. The authors' purpose in the present study was to evaluate the clinical and radiographic features of CPAC AVMs as well as the treatment options.
This study defined a CPAC AVM as a small AVM predominantly located in the CPAC with minimal extension into the pial surface of the brainstem and closely associated with cranial nerves. All patients with CPAC AVMs treated in the authors' affiliated hospitals over a 16-year period were retrospectively identified. Clinical charts, imaging studies, and treatment options were evaluated.
Ten patients (6 men and 4 women), ranging in age from 56 to 77 years (mean 65.6 years), were diagnosed with CPAC AVMs according to the authors' definition. Six patients presented with hemorrhage, 3 with TN, and the remaining patient developed a hemorrhage subsequent to TN. Seven AVMs were associated with the trigeminal nerve (Group V), and 3 with the facial-vestibulocochlear nerve complex (Group VII–VIII). All patients in Group VII–VIII presented with the hemorrhage instead of hemifacial spasm. Regarding angioarchitecture, the intrinsic pontine arteries provided the blood supply for all CPAC AVMs in Group V. In addition, 5 of 7 AVMs with hemorrhagic episodes accompanied flow-related aneurysms, although no aneurysm was detected in patients with TN alone. With respect to treatment, all patients with hemorrhagic presentation underwent Gamma Knife surgery (GKS), resulting in favorable outcomes except for 1 patient who experienced rebleeding after GKS, which was caused by the repeated rupture of a feeder aneurysm. The AVMs causing TN were managed with surgery, GKS, or a combination, according to the nidus-nerve relationship. All patients eventually obtained pain relief.
Clinical symptoms caused by CPAC AVMs occur at an older age compared with AVMs in other locations; CPAC AVMs also have distinctive angioarchitectures according to their location in the CPAC. Although GKS is likely to be an effective treatment option for the CPAC AVMs with hemorrhagic presentations, it seems ideal to obliterate the flow-related aneurysms before performing GKS, although this is frequently challenging. For CPAC AVMs with TN, it is important to evaluate the nidus-nerve relationship before treatment, and GKS is especially useful for patients who do not require urgent pain relief.
Kenichi Sato, Hidefumi Jokura, Reizo Shirane, Tetsuya Akabane, Hiroshi Karibe and Takashi Yoshimoto
Susumu Ito, Ken'ichi Sekido, Hiroshi Kanno, Hironobu Sato, Masaaki Tanaka, Kazuo Yamaguchi and Isao Yamamoto
Object. The goal of this study was to elucidate the genotype—phenotype relationship in syndromic craniosynostoses by analyzing the mutations of the fibroblast growth factor receptor (FGFR) gene and its clinical manifestations in patients, particularly those in atypical cases.
Methods. Twenty patients with craniosynostoses unrelated to Apert syndrome were enrolled in this study. The phenotypes indicated the following syndromes: 12 patients with unrelated Crouzon syndrome, including nine sporadic and three familial cases; two with sporadic Pfeiffer syndrome; and one with Antley—Bixler syndrome. The Crouzon phenotype was subdivided into three clinical forms: regular, top, and bottom ones. Two patients who demonstrated craniofacial anomalies and bilateral elbow joint contractures were categorized as having an unspecified craniosynostosis. Three cases of unclassifiable cloverleaf skull malformation were also analyzed.
Methods. Fourteen mutations of the FGFR2 gene were identified in these patients; seven of the 10 cysteine-related mutations were substitutions of codon 342 in the third immunoglobulin-like domain of this gene. The phenotypes of these seven cases were three of regular Crouzon, two of unspecified craniosynostosis, and one each of top Crouzon and unclassifiable cloverleaf skull malformation. In addition, four of the seven patients were found to have the same genotype (Cys342Arg). The phenotypes of these patients, however, were quite variable, ranging from regular Crouzon to unclassifiable cloverleaf skull malformation.
Conclusions. The phenotypes of patients with craniosynostoses unrelated to Apert syndrome proved quite variable, even in cases in which patients demonstrated the same genotype. In view of the phenotypic diversity evident in cases in which the same mutation in the FGFR2 gene is present, it is possible that other disease-modifying genetic factors exist to control the abnormal gain-of-function that accompanies FGFR signaling.
Lei Zhang, Eiji Sato, Kenichi Amagasaki, Atsuhito Nakao and Hirofumi Naganuma
Malignant glioma cells secrete and activate transforming growth factor–β (TGFβ) and are resistant to growth inhibition by that factor. Nevertheless, the mechanism underlying this effect remains poorly understood. In this study, the mechanism of the resistance to growth inhibition induced by TGFβ was investigated.
The authors examined the expression of downstream components of the TGFβ receptor, including Smad2, Smad3, Smad4, and Smad7, and the effect of TGFβ1 treatment on the phosphorylation of Smad2 and the nuclear translocation of Smad2 and Smad3 by using 10 glioma cell lines and the A549 cell line, which is sensitive to TGFβ-mediated growth inhibition. The expression of two transcriptional corepressor proteins, SnoN and Ski, and the effect of TGFβ1 treatment on the expression of the SnoN protein and the cell cycle regulators p21, p15, cyclin-dependent kinase–4 (CDK4), and cyclin D1 were also examined.
Expression of the Smad2 and Smad3 proteins was lower in the glioma cell lines than in the A549 cell line and in normal astrocytes. In particular, Smad3 expression was low or very low in nine of the 10 malignant glioma cell lines. Expression of Smad4 was low in four glioma cell lines, and expression of the Smad7 protein was similar when compared with protein expression in the A549 cell line and in normal astrocytes. The levels of Smad2 phosphorylation after TGFβ1 treatment were lower in glioma cell lines than in the A549 cell line, except for one glioma cell line. Seven of the 10 glioma cell lines exhibited lower levels of nuclear translocation of Smad2 and Smad3, and two cell lines that expressed very low levels of Smad3 protein showed no nuclear translocation. All glioma cell lines expressed the SnoN protein and its expression was unaltered by treatment with TGFβ1. Three glioma cell lines expressed high levels of the Ski protein. The expression of the p21cip1, p15INK4B, CDK4, and cyclin D1 proteins was not altered by TGFβ1 treatment, except in one cell line that displayed a slight increase in p21 protein. Overall, the expression of the Smad2 and Smad3 proteins was low in the glioma cell lines, the phosphorylation and nuclear translocation of Smad2 and Smad3 were impaired, and the TGFβ receptor signal did not affect the expression of the SnoN, p21, p15, cyclin D1, and CDK4 proteins.
These results suggest that the ability to resist TGFβ-mediated growth inhibition in malignant glioma cells is due to abnormalities in the TGFβ signaling pathway.
Kenichi Sato, Toshiki Endo, Kuniyasu Niizuma, Miki Fujimura, Takashi Inoue, Hiroaki Shimizu and Teiji Tominaga
Dural arteriovenous fistulas (DAVFs) and perimedullary arteriovenous fistulas (PAVFs) are uncommonly associated in the craniocervical junction. The purpose of this study was to describe the clinical and angiographic characteristics of such concurrent lesions.
Authors reviewed 9 cases with a coexistent DAVF and PAVF at the craniocervical junction. Clinical presentation, angiographic characteristics, intraoperative findings, and treatment outcomes were assessed.
All patients (male/female ratio 5:4; mean age 66.3 years) presented with subarachnoid hemorrhage. Angiography revealed that 8 patients had both a DAVF and PAVF on the same side, whereas 1 patient had 3 arteriovenous fistulas, 1 DAVF, and 1 PAVF on the right side and 1 DAVF on the left side. All of the fistulas shared dilated perimedullary veins (anterior spinal vein, 7 cases; anterolateral spinal vein, 2 cases) as a main drainage route. The shared drainage route was rostrally directed in 8 of 9 cases. Eight patients exhibited an arterial aneurysm on the distal side of the feeding arteries to the PAVF, and the aneurysm in each case was intraoperatively confirmed as a bleeding point. One patient had ruptured venous ectasia at the perimedullary fistulous point. All patients underwent direct surgery via a posterolateral approach. No recurrence was observed in the 4 patients who underwent postoperative angiography, and no rebleeding event was recorded among any of the 9 patients during the follow-up period (mean 38.4 months).
The similarity of the angioarchitecture and the close anatomical relationship between DAVF and PAVF at the craniocervical junction suggested that these lesions are pathogenetically linked. The pathophysiological mechanism and anatomical features of these lesions represent a unique vascular anomaly that should be recognized angiographically to plan a therapeutic strategy.
Hidenori Endo, Yasushi Matsumoto, Ryushi Kondo, Kenichi Sato, Miki Fujimura, Takashi Inoue, Hiroaki Shimizu, Akira Takahashi and Teiji Tominaga
Internal coil trapping is a treatment method used to prevent rebleeding from a ruptured intracranial vertebral artery dissection (VAD). Postoperative medullary infarctions have been reported as a complication of this treatment strategy. The aim of this study was to determine the relationship between a postoperative medullary infarction and the clinical outcomes for patients with ruptured VADs treated with internal coil trapping during the acute stage of a subarachnoid hemorrhage (SAH).
A retrospective study identified 38 patients who presented between 2006 and 2011 with ruptured VADs and underwent internal coil trapping during the acute stage of SAH. The SAH was identified on CT scanning, and the diagnosis for VAD was rendered by cerebral angiography. Under general anesthesia, the dissection was packed with coils, beginning at the distal end and proceeding proximally. When VAD involved the origin of the posterior inferior cerebellar artery (PICA) with a large cerebellar territory, an occipital artery (OA)–PICA anastomosis was created prior to internal coil trapping. The pre- and postoperative radiological findings, clinical course, and outcomes were analyzed.
The internal coil trapping was completed within 24 hours after admission. An OA-PICA anastomosis followed by internal coil trapping was performed in 5 patients. Postoperative rebleeding did not occur in any patient during a mean follow-up period of 16 months. The postoperative MRI studies showed medullary infarctions in 18 patients (47%). The mean length of the trapped VAD for the infarction group (15.7 ± 6.0 mm) was significantly longer than that of the noninfarction group (11.5 ± 4.3 mm) (p = 0.019). Three of the 5 patients treated with OA-PICA anastomosis had postoperative medullary infarction. The clinical outcomes at 6 months were favorable (modified Rankin Scale Scores 0–2) for 23 patients (60.5%) and unfavorable (modified Rankin Scale Scores 3–6) for 15 patients (39.5%). Of the 18 patients with postoperative medullary infarctions, the outcomes were favorable for 6 patients (33.3%) and unfavorable for 12 patients (66.7%). A logistic regression analysis predicted the following independent risk factors for unfavorable outcomes: postoperative medullary infarctions (OR 21.287 [95% CI 2.622–498.242], p = 0.003); preoperative rebleeding episodes (OR 7.450 [95% CI 1.140–71.138], p = 0.036); and a history of diabetes mellitus (OR 45.456 [95% CI 1.993–5287.595], p = 0.013).
A postoperative medullary infarction was associated with unfavorable outcomes after internal coil trapping for ruptured VADs. Coil occlusion of the long segment of the VA led to medullary infarction, and an OA-PICA bypass did not prevent medullary infarction. A VA-sparing procedure, such as flow diversion by stenting, is an alternative treatment in the future, if this approach is demonstrated to effectively prevent rebleeding.
Alaa Elkordy, Hidenori Endo, Kenichi Sato, Yasushi Matsumoto, Ryushi Kondo, Kuniyasu Niizuma, Toshiki Endo, Miki Fujimura and Teiji Tominaga
The anterior and posterior choroidal arteries are often recruited to supply arteriovenous malformations (AVMs) involving important paraventricular structures, such as the basal ganglia, internal capsule, optic radiation, lateral geniculate body, and medial temporal lobe. Endovascular embolization through these arteries is theoretically dangerous because they supply eloquent territories, are of small caliber, and lack collaterals. This study aimed to investigate the safety and efficacy of embolization through these arteries.
This study retrospectively reviewed 13 patients with cerebral AVMs who underwent endovascular embolization through the choroidal arteries between 2006 and 2014. Embolization was performed as a palliative procedure before open surgery or Gamma Knife radiosurgery. Computed tomography and MRI were performed the day after embolization to assess any surgical complications. The incidence and type of complications and their association with clinical outcomes were analyzed.
Decreased blood flow was achieved in all patients after embolization. Postoperative CT detected no hemorrhagic complications. In contrast, postoperative MRI detected that 4 of the 13 patients (30.7%) developed infarctions: 3 patients after embolization through the anterior choroidal artery, and 1 patient after embolization through the lateral posterior choroidal artery. Two of the 4 patients in whom embolization was from the cisternal segment of the anterior choroidal artery (proximal to the plexal point) developed symptomatic infarction of the posterior limb of the internal capsule, 1 of whom developed morbidity (7.7%). The treatment-related mortality rate was 0%. Additional treatment was performed in 12 patients: open surgery in 9 and Gamma Knife radiosurgery in 3 patients. Complete obliteration was confirmed by angiography at the last follow-up in 10 patients. Recurrent bleeding from the AVMs did not occur in any of the cases during the follow-up period.
Ischemic complications are possible following the embolization of cerebral AVMs through the choroidal artery, even with modern neurointerventional devices and techniques. Although further study is needed, embolization through the choroidal artery may be an appropriate treatment option when the risk of surgery or radiosurgery is considered to outweigh the risk of embolization.