Prediction model for 3-year rupture risk of unruptured cerebral aneurysms in Japanese patients.

OBJECTIVE: To build a prediction model that estimates the 3-year rupture risk of unruptured saccular cerebral aneurysms. METHODS: Survival analysis was done using each aneurysm as the unit for analysis. Derivation data were from the Unruptured Cerebral Aneurysm Study (UCAS) in Japan. It consists of patients with unruptured cerebral aneurysms enrolled between 2000 and 2004 at neurosurgical departments at tertiary care hospitals in Japan. The model was presented as a scoring system, and aneurysms were classified into 4 risk grades by predicted 3-year rupture risk: I, < 1%; II, 1 to 3%; III, 3 to 9%, and IV, >9%. The discrimination property and calibration plot of the model were evaluated with external validation data. They were a combination of 3 Japanese cohort studies: UCAS II, the Small Unruptured Intracranial Aneurysm Verification study, and the study at Jikei University School of Medicine. RESULTS: The derivation data include 6,606 unruptured cerebral aneurysms in 5,651 patients. During the 11,482 aneurysm-year follow-up period, 107 ruptures were observed. The predictors chosen for the scoring system were patient age, sex, and hypertension, along with aneurysm size, location, and the presence of a daughter sac. The 3-year risk of rupture ranged from <1% to >15% depending on the individual characteristics of patients and aneurysms. External validation indicated good discrimination and calibration properties. INTERPRETATION: A simple scoring system that only needs easily available patient and aneurysmal information was constructed. This can be used in clinical decision making regarding management of unruptured cerebral aneurysms.

The natural course of unruptured cerebral aneurysms in a Japanese cohort.

BACKGROUND: The natural history of unruptured cerebral aneurysms has not been clearly defined. METHODS: From January 2001 through April 2004, we enrolled patients with newly identified, unruptured cerebral aneurysms in Japan. Information on the rupture of aneurysms, deaths, and the results of periodic follow-up examinations were recorded. We included 5720 patients 20 years of age or older (mean age, 62.5 years; 68% women) who had saccular aneurysms that were 3 mm or more in the largest dimension and who initially presented with no more than a slight disability. RESULTS: Of the 6697 aneurysms studied, 91% were discovered incidentally. Most aneurysms were in the middle cerebral arteries (36%) and the internal carotid arteries (34%). The mean (±SD) size of the aneurysms was 5.7±3.6 mm. During a follow-up period that included 11,660 aneurysm-years, ruptures were documented in 111 patients, with an annual rate of rupture of 0.95% (95% confidence interval [CI], 0.79 to 1.15). The risk of rupture increased with increasing size of the aneurysm. With aneurysms that were 3 to 4 mm in size as the reference, the hazard ratios for size categories were as follows: 5 to 6 mm, 1.13 (95% CI, 0.58 to 2.22); 7 to 9 mm, 3.35 (95% CI, 1.87 to 6.00); 10 to 24 mm, 9.09 (95% CI, 5.25 to 15.74); and 25 mm or larger, 76.26 (95% CI, 32.76 to 177.54). As compared with aneurysms in the middle cerebral arteries, those in the posterior and anterior communicating arteries were more likely to rupture (hazard ratio, 1.90 [95% CI, 1.12 to 3.21] and 2.02 [95% CI, 1.13 to 3.58], respectively). Aneurysms with a daughter sac (an irregular protrusion of the wall of the aneurysm) were also more likely to rupture (hazard ratio, 1.63; 95% CI, 1.08 to 2.48). CONCLUSIONS: This study showed that the natural course of unruptured cerebral aneurysms varies according to the size, location, and shape of the aneurysm. (Funded by the Ministry of Health, Labor, and Welfare in Japan and others; UCAS Japan UMIN-CTR number, C000000418.).

Symptomatic T2 vertebral hemangioma in a pregnant woman treated by one stage combination surgery; posterior stabilization and anterior subtotal tumor resection. Case report.

A 27-year-old woman presented with vertebral hemangioma manifesting as sudden onset of paraplegia, and bladder and bowel dysfunction during pregnancy. Magnetic resonance imaging revealed a mass lesion that had infiltrated into the entire T2 vertebral body and expanded to the vertebral canal. Laminectomy from T1 to T3 and biopsy of the lesion were performed. Biopsy confirmed the diagnosis of vertebral hemangioma, but laminectomy resulted in no neurological changes. The patient was transferred to our hospital, where radical treatment comprising embolization of the feeding arteries, posterior stabilization of the vertebrae, and anterior excision of the tumor was performed. Symptoms resolved gradually but steadily, and she made a full recovery by 18 months postoperatively. Radical operation might be extremely effective for extradural vertebral hemangioma, even in the delayed phase or in the presence of severe neurological deficit.

Deficiency of chemokine receptor CCR1 causes osteopenia due to impaired functions of osteoclasts and osteoblasts.

Chemokines are characterized by the homing activity of leukocytes to targeted inflammation sites. Recent research indicates that chemokines play more divergent roles in various phases of pathogenesis as well as immune reactions. The chemokine receptor, CCR1, and its ligands are thought to be involved in inflammatory bone destruction, but their physiological roles in the bone metabolism in vivo have not yet been elucidated. In the present study, we investigated the roles of CCR1 in bone metabolism using CCR1-deficient mice. Ccr1(-/-) mice have fewer and thinner trabecular bones and low mineral bone density in cancellous bones. The lack of CCR1 affects the differentiation and function of osteoblasts. Runx2, Atf4, Osteopontin, and Osteonectin were significantly up-regulated in Ccr1(-/-) mice despite sustained expression of Osterix and reduced expression of Osteocalcin, suggesting a lower potential for differentiation into mature osteoblasts. In addition, mineralized nodule formation was markedly disrupted in cultured osteoblastic cells isolated from Ccr1(-/-) mice. Osteoclastogenesis induced from cultured Ccr1(-/-) bone marrow cells yielded fewer and smaller osteoclasts due to the abrogated cell-fusion. Ccr1(-/-) osteoclasts exerted no osteolytic activity concomitant with reduced expressions of Rank and its downstream targets, implying that the defective osteoclastogenesis is involved in the bone phenotype in Ccr1(-/-) mice. The co-culture of wild-type osteoclast precursors with Ccr1(-/-) osteoblasts failed to facilitate osteoclastogenesis. This finding is most likely due to a reduction in Rankl expression. These observations suggest that the axis of CCR1 and its ligands are likely to be involved in cross-talk between osteoclasts and osteoblasts by modulating the RANK-RANKL-mediated interaction.

Induction of striatal neurogenesis and generation of region-specific functional mature neurons after ischemia by growth factors. Laboratory investigation.

OBJECT: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Endoscopic microneurosurgery: usefulness and cost-effectiveness in the consecutive experience of 210 patients.

OBJECTIVE: Indications, usefulness, and cost-effectiveness of the endoscope in routine microneurosurgery are not clear. To delineate such aspects, we assessed our experience of endoscopic application and additional cost to use an endoscope. METHODS: Endoscopes were used in 210 patients with cranial base and cisternal pathological features in the previous 7 years. Lesions were located in the extradural cranial base in 78 patients and in the cistern in 132 patients. Rigid lens endoscopes 2.7 to 4 mm in width, 11 to 20 cm in length, and 0 to 70 degrees in angle were used. RESULTS: Endoscopes were used for primary or a significant part of the surgery in 64% of the extradural cranial base procedures. Although endoscopes were used only for visual assistance in 82% of cisternal pathological features, significant benefit was noted in 9% and was not different from cranial base lesions. Eleven patients may have had complications if the endoscope had not been used, and 10 procedures would have been impossible without endoscopic use. Therefore, the number of patients need to treat to experience significant benefits by endoscope was 10. Endoscopic equipment costs an additional US $326 per patient and, hence, significant benefit was the equivalent of US $3260. No permanent complications resulted from the use of the endoscope. CONCLUSION: The endoscope can be applied safely in routine microsurgery with specific equipment and has proven useful in 1 of 10 patients. To perform more effective procedures using endoscopes, we need to develop specially designed instruments usable through a narrow corridor and in an angled field.

Region-specific proliferative response of neural progenitors to exogenous stimulation by growth factors following ischemia.

The most effective way to augment neural progenitor proliferation after ischemia is still unknown. We administered various agents into the rat cerebral ventricle after transient global ischemia and compared the neural progenitor response in the anterior subventricular zone (aSVZ), dentate gyrus subgranular zone, posterior periventricle, and hypothalamus. We demonstrated that cocktail administration of epidermal growth factor (EGF) and fibroblast growth factor-2 (FGF-2) remarkably increased the numbers of neural progenitors in all four regions examined. The addition of Notch ligand DLL4 to the cocktail elicited the largest progenitor response in the aSVZ and hypothalamus. Our results suggest that EGF and FGF-2, combined with DLL4, represent the universally applicable regimen for the expansion of the neural progenitor pool following ischemia.

Endoscopy-guided removal of spontaneous intracerebral hemorrhage: comparison with computer tomography-guided stereotactic evacuation.

BACKGROUND AND PURPOSE: Spontaneous intracerebral hemorrhage (ICH) continues to be a major medical and socioeconomic problem. While the surgical procedure failed to show benefits over functional outcome, a less invasive and quicker surgical decompression might improve the outcome. The authors introduced endoscopy-guided evacuation in managing ICH and reports the benefits over the conventional method. MATERIALS AND METHODS: Twenty-seven cases underwent endoscopic evacuation of ICH (Group E). The clinical features and outcomes were compared to the retrospective data of 20 cases who underwent computer tomography (CT)-guided stereotactic removal of ICH (Group C). Confidence level less than 0.05 was considered statistically significant. RESULTS: While the clinical features of the two groups were not significantly different except for the ICH volume, outcomes were better in all aspects in Group E. The patients in Group E required shorter operative time (72 min vs 102 min, p < 0.01) with better hematoma evacuation (95.5% vs 75%, p < 0.01), shorter stay in the intensive care unit (ICU; 4.2 days vs 6.9 days, p < 0.01) and less frequent CT scanning (6.4 times vs 8.6 times, p < 0.01) compared to the patients in Group C. Neurological outcome improved significantly in Group E 1 week after surgery (p < 0.01), but not in Group C. Glasgow outcome scale at 6 months were better in Group E than in Group C (p < 0.05). Nine patients (33%) showed good recovery at 6 months postoperatively after endoscopic evacuation of ICH. CONCLUSION: Endoscopic hematoma evacuation provided the quick, adequate decompression of ICH. The outcomes were better than the CT-guided hematoma removal. Further study is necessary to evaluate the real benefit of this surgical procedure over the functional outcome of ICH.

Lymphoplasmacyte-rich meningioma with atypical invasive nature.

A 12-year-old boy presented with a lymphoplasmacyte-rich (LPR) meningioma in the posterior fossa. The tumor was subtotally removed. Histological examination showed the tumor had invaded the normal brain tissue despite its benign grade in the World Health Organization classification. The Ki-67 staining index using MIB-1 monoclonal antibody was relatively high. (18)F-2-fluoro-2-deoxy-D-glucose positron emission tomography revealed high uptake in the tumor. These findings indicate the atypical nature of LPR meningioma.

Functional identification of the primary motor area by corticospinal tractography.

OBJECTIVE: For quick and stable identification of the primary motor area (PMA), diffusion tensor imaging (DTI) data were acquired and corticospinal tractography was mathematically visualized. METHODS: Data sets of DTI, anatomic magnetic resonance imaging, and functional magnetic resonance imaging with finger-tapping tasks were acquired during the same investigation in 30 patients with a brain lesion affecting the motor system. Off-line processing of DTI data was performed to visualize the corticospinal tract, placing a seed area in the cerebral peduncle of the midbrain, where the corticospinal tract is densely concentrated. Somatosensory evoked magnetic fields and intraoperative cortical somatosensory evoked potentials were recorded with electrical stimulation of the median nerve to confirm the results of the corticospinal tractography. RESULTS: Functional magnetic resonance imaging and somatosensory evoked magnetic fields failed to identify the PMA in eight patients (16.7%) and one patient (3.8%) investigated, respectively, because of cortical dysfunctions caused by brain lesions. DTI data were acquired within 3 minutes without patient tasks. Using the appropriate seed area and fractional anisotropy, corticospinal tractography successfully indicated the PMA location in all patients. The suspected PMA and central sulcus locations were confirmed by the cortical somatosensory evoked potentials. CONCLUSION: Corticospinal tractography enables identification of the PMA and is beneficial, particularly for patients who present with dysfunction of the PMA.

Sarcomatous transformation of clival chordoma after charged-particle radiotherapy. Report of two cases.

Skull base chordomas containing a sarcomatous component are extremely rare. Here the authors report two new cases in which a recurrent tumor with a sarcomatous component appeared after the patient had undergone charged-particle radiotherapy. Histological examinations performed in Case 1 revealed some retention of epithelial features in the sarcomatous component, whereas no such regions were observed in Case 2. Both patients had rapidly deteriorating clinical courses and died within 6 months after diagnosis of the recurrent tumor. The authors discuss the significance of the histological subtypes of these tumors for long-term prognosis and their pathogenetic mechanisms in relation to radiotherapy. Although these sarcomatous transformations are rare in conventional chordomas, a careful histological examination and thorough follow-up imaging studies are crucial when treating patients with such lesions.

Intracerebroventricular delivery of dominant negative prion protein in a mouse model of iatrogenic Creutzfeldt-Jakob disease after dura graft transplantation.

We have developed a novel procedure in which a small collagen sheet (3 mm x 3 mm) absorbing prion-infected brain homogenates was transplanted onto the brain surface of highly prion-susceptible transgenic mice (Tg(MoPrP)4053/FVB), as an animal model of iatrogenic Creutzfeldt-Jakob disease (iCJD) caused by prion-contaminated cadaveric dura graft transplantation. Using the iCJD model, we further investigated the in vivo efficacy of dominant negative recombinant prion protein with lysine substitution at mouse codon 218 (rPrP-Q218K), which is known to inhibit prion replication in vitro (H. Kishida, Y. Sakasegawa, K. Watanabe, Y. Yamakawa, M. Nishijima, Y. Kuroiwa, N.S. Hachiya, K. Kaneko, Non-glycosylphosphatidylinositol (GPI)-anchored recombinant prion protein with dominant-negative mutation inhibits PrPSc replication in vitro, Amyloid, vol. 11, 2004, pp. 14-20.). Following 7-day intracerebroventricular administration of the rPrP-Q218K via an indwelling catheter connected to the implanted osmotic pump, the median incubation period of Tg(MoPrP)4053/FVB was prolonged considerably from 117 days to 131 days (p=0.016, log-rank test) in the rPrP-Q218K-treated group, even after a lengthy latency period of as long as 30 days by starting the rPrP-Q218K injection. Whether wild-type rPrP, other mutant rPrPs, or the combination of rPrP-Q218K with other anti-prion compounds might extend the survival period in that condition must be further investigated.

p53 potentiates hippocampal neuronal death caused by global ischemia.

Although p53 controls cell death after various stresses, its role in neuronal death after brain ischemia is poorly understood. To address this issue, we subjected p53-deficient (p53-/- and p53+/-) mice (backcrossed for 12 generations with C57BL/6 mice) and wild-type mice (p53+/+) to transient global ischemia by the three-vessel occlusion method. Despite similar severity of ischemia, as shown by anoxic depolarization and cortical blood flow, neuronal death in the hippocampal cornus ammonis (CA)1 region was much more extensive in p53+/+ than in p53-/- mice (surviving neuronal count, 9.3%+/-3.0% versus 61.3%+/-34.0% of nonischemic p53+/+ controls, respectively, P<0.0037). In p53+/- mice, a similar trend was also observed, though not statistically significant (43.5% of nonischemic p53+/+ controls). In p53+/+ mice, p53-like immunoreactivity in hippocampal CA1 neurons was enhanced at 12 h after ischemia, and messenger ribonucleic acid for Bax, a direct downstream target of p53, was also increased. These results indicate that p53 potentiates ischemic neuronal death in vivo and suggest that this molecule could be a therapeutic target in neuronal death after cerebral ischemia.

Endoscopic microneurosurgery: usefulness and cost-effectiveness in the consecutive experience of 210 patients.

OBJECTIVE: Indications, usefulness, and cost-effectiveness of the endoscope in routine microneurosurgery are not clear. To delineate such aspects, we assessed our experience of endoscopic application and additional cost to use an endoscope. METHODS: Endoscopes were used in 210 patients with cranial base and cisternal pathological features in the previous 7 years. Lesions were located in the extradural cranial base in 78 patients and in the cistern in 132 patients. Rigid lens endoscopes 2.7 to 4 mm in width, 11 to 20 cm in length, and 0 to 70 degrees in angle were used. RESULTS: Endoscopes were used for primary or a significant part of the surgery in 64% of the extradural cranial base procedures. Although endoscopes were used only for visual assistance in 82% of cisternal pathological features, significant benefit was noted in 9% and was not different from cranial base lesions. Eleven patients may have had complications if the endoscope had not been used, and 10 procedures would have been impossible without endoscopic use. Therefore, the number of patients need to treat to experience significant benefits by endoscope was 10. Endoscopic equipment costs an additional 326 US dollars per patient and, hence, significant benefit was the equivalent of 3260 US dollars. No permanent complications resulted from the use of the endoscope. CONCLUSION: The endoscope can be applied safely in routine microsurgery with specific equipment and has proven useful in 1 of 10 patients. To perform more effective procedures using endoscopes, we need to develop specially designed instruments usable through a narrow corridor and in an angled field.

Differences in infarct evolution between lipopolysaccharide-induced tolerant and nontolerant conditions to focal cerebral ischemia.

OBJECT: Although brain tissue may be protected by previous preconditioning, the temporal evolution of infarcts in such preconditioned brain tissue during focal cerebral ischemia is largely unknown. Therefore, in this study the authors engaged in long-term observation with magnetic resonance (MR) imaging to clarify the difference in lesion evolution between tolerant and nontolerant conditions. METHODS: Bacterial lipopolysaccharide (LPS; 0.9 mg/kg) was administered intravenously to induce cross-ischemic tolerance. Focal cerebral ischemia was induced 72 hours later in spontaneously hypertensive rats. Serial brain MR images were obtained 6 hours, 24 hours, 4 days, 7 days, and 14 days after ischemia by using a 7.05-tesla unit. Lesion-reducing effects were evident 6 hours after ischemia in the LPS group. Preconditioning with LPS does not merely delay but prevents ischemic cell death by reducing lesion size. Lesion reduction was a sustained effect noted up to 14 days after ischemia. Reduction of local cerebral blood flow (ICBF) in the periinfarct area was significantly inhibited in the LPS group, which was correlated with endothelial nitric oxide synthase (eNOS) expression. CONCLUSIONS: Significant preservation of ICBF in the periinfarct area, which is relevant to sustained upregulation of eNOS, could be a candidate for the long-term inhibiting effect on infarct evolution in the LPS-induced tolerant state.

Subdural hematoma associated with dural metastasis--case report--.

A 56-year-old female presented with acute subdural hematoma associated with dural metastasis. The patient had been treated for breast cancer with disseminated bone and lung metastases. Evacuation of the hematoma with local management of the tumor and bleeding successfully improved her neurological condition and she underwent postoperative radiotherapy. This condition is especially associated with dural metastasis from adenocarcinoma (most frequently stomach cancer) and the clinical outcome depends on the general condition of the patient and the status of the coagulation disorders. If the tumors are multiple, as in this case, extreme caution should be paid to recurrent bleeding in the ipsilateral or contralateral side.

Radiation-induced spinal cord cavernous malformation. Case report.

The authors report a case of a 16-year-old girl who presented with progressive gait difficulty 8 years after undergoing spinal radiation therapy for spinal astrocytoma. Magnetic resonance imaging revealed intramedullary multicentric cavity formation in the T4-10 area. Extensive subtotal resection was performed and a pathological examination of the excised tissue demonstrated cavernous malformation with radiation-induced degeneration in the surrounding vessels. This is believed to be the third case of de novo formation of an intramedullary cavernous malformation following spinal radiation therapy.

Intracranial extracerebral glioneuronal heterotopia. Case report and review of the literature.

The authors report a case of intracranial extracerebral glioneuronal heterotopia (IEGH) in an infant. Glioneuronal heterotopias are rare congenital disorders that arise in the head, face, spine, and thoracic cavity. They consist of nodular accumulations of neuronal and glial cells that have developed abnormally, ranging in size from small lesions to large masses. Among heterotopias, IEGHs are relatively rare. They cause various clinical symptoms, depending on their size and location. The neuroimaging studies, histological examinations, and intraoperative findings presented provide insight into the pathogenesis of this disorder. The findings support the separation and detachment theory, which proposes that IEGHs originate from a third telencephalon that erroneously forms between the 4th and 6th week of embryogenesis. More detailed case reports are necessary to understand fully the pathogenesis of IEGHs.

Aberrant vertebral artery course in a case of Chiari malformation and occipitoatlantal assimilation. Case report.

tThe authors report an unusual case of a patient with combined vertebral artery and Chiari malformation anomalies. Unless such anomalies are properly recognized prior to decompression and fusion, this condition can have grave surgical consequences. The diagnostic and surgery-related implications of such anomalous codiseases are discussed.

Microsurgical robotic system for the deep surgical field: development of a prototype and feasibility studies in animal and cadaveric models.

OBJECT: To enhance the surgeon's dexterity and maneuverability in the deep surgical field, the authors developed a master-slave microsurgical robotic system. This concept and the results of preliminary experiments are reported in this paper. METHODS: The system has a master control unit, which conveys motion commands in six degrees of freedom (X, Y, and Z directions; rotation; tip flexion; and grasping) to two arms. The slave manipulator has a hanging base with an additional six degrees of freedom; it holds a motorized operating unit with two manipulators (5 mm in diameter, 18 cm in length). The accuracy of the prototype in both shallow and deep surgical fields was compared with routine freehand microsurgery. Closure of a partial arteriotomy and complete end-to-end anastomosis of the carotid artery (CA) in the deep operative field were performed in 20 Wistar rats. Three routine surgical procedures were also performed in cadavers. The accuracy of pointing with the nondominant hand in the deep surgical field was significantly improved through the use of robotics. The authors successfully closed the partial arteriotomy and completely anastomosed the rat CAs in the deep surgical field. The time needed for stitching was significantly shortened over the course of the first 10 rat experiments. The robotic instruments also moved satisfactorily in cadavers, but the manipulators still need to be smaller to fit into the narrow intracranial space. CONCLUSIONS: Computer-controlled surgical manipulation will be an important tool for neurosurgery, and preliminary experiments involving this robotic system demonstrate its promising maneuverability.