Keisuke Maruyama, Masahiro Shin, Masao Tago, Hiroki Kurita, Nobutaka Kawahara, Akio Morita and Nobuhito Saito
Appropriate management of hemorrhage after Gamma Knife surgery (GKS) for arteriovenous malformations (AVMs) of the brain is poorly understood, although a certain proportion of patients suffer from hemorrhage.
Among 500 patients observed for 1 to 183 months (median 70 months) after GKS, 32 patients (6.4%) suffered a hemorrhage. Hemorrhage developed even after angiographically documented obliteration of the AVM in five (2%) of 250 patients followed for 1 to 133 months (median 75 months) post-GKS. These patients had been treated according to their pathological condition. Treatment of these patients and their outcomes were retrospectively reviewed. As a management strategy in patients with preobliteration hemorrhage, the intracerebral hematoma and the AVM nidus were removed in four patients, and chronic encapsulated hematoma was removed in three. Among 11 patients who were conservatively treated, AVMs were ultimately obliterated in five, including three patients who underwent repeated GKS. Intracerebral hematoma from angiographically documented obliterated AVMs was radically resected in two patients, including one who also underwent aspiration of an accompanying symptomatic cyst. Intraoperative bleeding was easily controlled in these patients. Outcomes after hemorrhage, measured with the modified Rankin Scale, were significantly better in patients with postobliteration hemorrhage than in those with preobliteration hemorrhage (p < 0.05).
Various types of hemorrhagic complications after GKS for AVMs can be properly managed based on an understanding of each pathological condition. Although a small risk of bleeding remains after angiographically demonstrated obliteration, surgery for such AVMs is safe, and the patient outcomes are more favorable. Radical resection to prevent further hemorrhage is recommended for ruptured AVMs after obliteration because such AVMs can cause repeated hemorrhages.
Nobutaka Kawahara, Tomio Sasaki, Takahiro Asakage, Kazunari Nakao, Masashi Sugasawa, Hirotaka Asato, Isao Koshima and Nobuhito Saito
Primary temporal bone malignancy is a rare form of tumor for which the therapeutic strategy remains controversial. In this study, the authors reviewed their experience with radical temporal bone resection (TBR) of such lesions and analyzed the long-term results to provide treatment recommendations.
Between 1994 and 2006, 17 patients (10 men and 7 women) underwent total or subtotal TBR for primary temporal bone malignancies. Tumors were graded according to the University of Pittsburgh system. The effects of surgical margins and tumor extensions on patient survival were analyzed using the Kaplan–Meier method.
All tumors, except 1, were graded T4 (most advanced). Subtotal TBR was performed in 14 patients, and total TBR was performed in 3. The surgical margin was tumor negative in 10 patients and tumor positive in 7. For large tumors extending into the infratemporal fossa or encroaching on the jugular foramen, orbitozygomatic (3 patients) and posterior transjugular (4 patients) approaches were combined with the standard approach, and en bloc resection with a negative margin was achieved in all cases but 1. The follow-up time ranged from 0.3–11.6 years (mean 3.3 years). The 5-year recurrence-free and disease-specific survival rates were 67.5 and 60.1%, respectively. When a negative surgical margin was achieved, the survival rates improved to 100 and 89%, respectively.
The neurosurgical skull base technique could improve the probability of en bloc resection with a tumor-free margin for extensive temporal bone malignancies, which would cure a subset of patients. The active participation of neurosurgeons would improve patient care in this field.
Gakushi Yoshikawa, Toshihiko Momiyama, Soichi Oya, Keisuke Takai, Jun-ichi Tanaka, Shigeki Higashiyama, Nobuhito Saito, Takaaki Kirino and Nobutaka Kawahara
The capacity to replace lost neurons after insults is retained by several regions of adult mammalian brains. However, it is unknown how many neurons actually replace and mature into region-specific functional neurons to restore lost brain function. In this paper, the authors asked whether neuronal regeneration could be achieved efficaciously by growth factor treatment using a global ischemia model in rats, and they analyzed neuronal long-term maturation processes.
Rat global ischemia using a modified 4-vessel occlusion model was used to induce consistent ischemic neuronal injury in the dorsolateral striatum. To potentiate the proliferative response of neural progenitors, epidermal growth factor and fibroblast growth factor–2 were infused intraventricularly for 7 days from Day 2 after ischemia. Six weeks after ischemia, the number of neurons was counted in the defined dorsolateral striatum. To label the proliferating neural progenitors for tracing studies, 5-bromo-2′-deoxyuridine (BrdU; 150 mg/kg, twice a day) was injected intraperitoneally from Days 5 to 7, and immunohistochemical studies were conducted to explore the maturation of these progenitors. Migration of the progenitors was further studied by enhanced green fluorescent protein retrovirus injection. The effect of an antimitotic drug (cytosine arabinoside) on the neuronal count was also evaluated for contribution to regeneration. To see electrophysiological changes, treated rats were subjected to slice studies by whole-cell recordings. Finally, the effect of neural regeneration was assessed by motor performance by using the staircase test.
Following epidermal growth factor and fibroblast growth factor–2 infusion into the lateral ventricles for 7 days beginning on Day 2, when severe neuronal loss in the adult striatum was confirmed (2.3% of normal controls), a significant increase of striatal neurons was observed at 6 weeks (~ 15% of normal controls) compared with vehicle controls (~ 5% of normal controls). Immunohistochemical studies by BrdU and enhanced green fluorescent protein retrovirus injection disclosed proliferation of neural progenitors in the subventricular zone and their migration to the ischemic striatum. By BrdU tracing study, NeuN- and BrdU-positive new neurons significantly increased at 6 and 12 weeks following the treatment. These accounted for 4.6 and 11.0% of the total neurons present, respectively. Antimitotic treatment demonstrated an approximately 66% reduction in neurons at 6 weeks. Further long-term studies showed dynamic changes of site-specific maturation among various neuronal subtypes even after 6 weeks. Electrophysiological properties of these newly appeared neurons underwent changes that conform to neonatal development. These regenerative changes were accompanied by a functional improvement of overall behavioral performance.
Treatment by growth factors significantly contributed to regeneration of mature striatal neurons after ischemia by endogenous neural progenitors, which was accompanied by electrophysiological maturation and improved motor performance. Recognition and improved understanding of these underlying dynamic processes will contribute to the development of novel and efficient regenerative therapies for brain injuries.