bluuebunny/crossref_metadata_2025 huggingface dataset:
Gamma knife surgery of brain cavernous hemangiomas
Authors: Liscák Roman , Vladyka Vilibald , Simonová Gabriela , Vymazal Josef , Novotny Josef
Published: May 2009

Object.The authors conducted a study to record more detailed information about the natural course and factors predictive of outcome following gamma knife surgery (GKS) for cavernous hemangiomas.

Methods.One hundred twelve patients with brain cavernous hemangiomas underwent GKS between 1993 and 2000. The median prescription dose was 16 Gy. One hundred seven patients were followed for a median of 48 months (range 6–114 months). The rebleeding rate was 1.6%, which is not significantly different with that prior to radiosurgery (2%). An increase in volume was observed in 1.8% of cases and a decrease in 45%. Perilesional edema was detected in 27% of patients, which, together with the rebleeding, caused a transient morbidity rate of 20.5% and permanent morbidity rate of 4.5%. Before radiosurgery 39% of patients suffered from epilepsy and this improved in 45% of them. Two patients with brainstem cavernous hemangiomas died due to rebleeding. Rebleeding was more frequent in female middle-aged patients with a history of bleeding, a larger lesion volume, and a prescription dose below 13 Gy. Edema after GKS occurred more frequently in patients who had surgery, a larger lesion volume, and in those in whom the prescription dose was more than 13 Gy.

Conclusions.Gamma knife surgery of cavernous hemangiomas can produce an acceptable rate of morbidity, which can be reduced by using a lower margin dose. Lesion regression was observed in many patients. Radiosurgery seems to remain a suitable treatment modality in carefully selected patients.
Progress in glaucoma treatment research: a nonrandomized prospective study of 102 patients with advanced refractory glaucoma treated by Leksell gamma knife irradiation
Authors: Vladyka Vilibald , Lis˘c˘ák R. , S˘imonová G. , Pilbauer J. , Hejduková I. , Novác˘ek L.
Published: May 2009

Object.The authors performed a study to characterize the effects of ciliary body gamma knife surgery (GKS) for advanced glaucoma.

Methods.In addition to a pilot project involving 14 patients, 88 other patients were treated. Four 8-mm isocenters were used. Blind eyes received 20 Gy to the 50% isodose. If there was preserved vision the dose was 15 Gy. The median follow up was 20 months (range 2–54 months).

Severe pain was present in 93% of patients with secondary glaucoma; after GKS it was substantially improved in 89% of cases. In primary open angle glaucoma, the pain was less frequent and severe. In more than half the patients it disappeared during a median latency of 6 weeks. The median intraocular pressure value was lowered in patients with secondary glaucoma (from 51.3–27 mm Hg). The same values for primary glaucoma were 25.3 and 16.1 mm Hg, respectively, after a median latency of 12 weeks. Twenty-seven of 40 patients with neovascular glaucoma showed a marked reduction of neovascularization after a median latency of 18 weeks. Treatment complications were slight. There was postoperative lacrimation in 61%. Two patients underwent postirradiation cataract extraction. Noninfectious keratitis was observed in two patients. Pharmacotherapy could be reduced in all patients and ceased in approximately one third. There has been no recurrence of the initial symptoms and no worsening of visual acuity.

Conclusions.Gamma knife surgery ameliorates the main symptoms in advanced glaucomas and precludes the need for eventual ocular enucleation.
Long-term results of Leksell gamma knife surgery for trigeminal schwannomas
Authors: Pan Li , Wang En-Min , Zhang Nan , Zhou Liang-Fu , Wang Bing-Jiang , Dong Ya-Fei , Dai Jia-Zhong , Cai Pei-Wu
Published: May 2009

Object. The authors evaluated the long-term efficacy of gamma knife surgery (GKS) in patients with trigeminal schwannomas.

Methods. Fifty-six patients, 31 women and 25 men (mean age 42 years), underwent GKS for trigeminal schwannomas. Fourteen had previously undergone surgery, and GKS was the primary treatment in the remaining 42 patients. The mean target volume was 8.7 cm3 (range 0.8–33 cm3); the mean maximum dose was 27 Gy (range 20–40 Gy); the mean tumor margin dose was 13.3 Gy (range 10–15 Gy); and the mean follow-up period was 68 months (range 27–114 months).

Disappearance of the tumor occurred in seven patients. An obvious decrease in tumor volume was observed in 41 patients, four tumors remained unchanged, and four tumors progressed at 5, 26, 30, and 60 months, respectively. One patient with disease progression died of tumor progression at 36 months after GKS. The tumor growth control rate in this group was 93% (52 of 56 cases).

Mild numbness or diplopia was relieved completely in 14 patients. Improvement of other neurological deficits was demonstrated in 25 patients. Trigeminal nerve dysfunction was either unchanged or slightly worse in 13 patients after GKS. Four patients experienced mild symptom deterioration related to tumor progression.

Conclusions. Radiosurgery proved to be an effective treatment for small- and medium-sized trigeminal schwannomas. Some larger tumors are also suitable for radiosurgery if there is no significant brainstem compression.
Radiosurgery for patients with recurrent small cell lung carcinoma metastatic to the brain: outcomes and prognostic factors
Authors: Sheehan Jason , Kondziolka Douglas , Flickinger John , Lunsford L. Dade
Published: May 2009

Object.Lung carcinoma is the leading cause of death from cancer. More than 50% of those with small cell lung cancer develop a brain metastasis. Corticosteroid agents, radiotherapy, and resection have been the mainstays of treatment. Nonetheless, median survival for patients with small cell lung carcinoma metastasis is approximately 4 to 5 months after cranial irradiation. In this study the authors examine the efficacy of gamma knife surgery for treating recurrent small cell lung carcinoma metastases to the brain following tumor growth in patients who have previously undergone radiation therapy, and they evaluate factors affecting survival.

Methods.A retrospective review of 27 patients (47 recurrent small cell lung cancer brain metastases) undergoing radiosurgery was performed. Clinical and radiographic data obtained during a 14-year treatment period were collected. Multivariate analysis was utilized to determine significant prognostic factors influencing survival.

The overall median survival was 18 months after the diagnosis of brain metastases. In multivariate analysis, factors significantly affecting survival included: 1) tumor volume (p = 0.0042); 2) preoperative Karnofsky Performance Scale score (p = 0.0035); and 3) time between initial lung cancer diagnosis and development of brain metastasis (p = 0.0127). Postradiosurgical imaging of the brain metastases revealed that 62% decreased, 19% remained stable, and 19% eventually increased in size. One patient later underwent a craniotomy and tumor resection for a tumor refractory to radiosurgery and radiation therapy. In three patients new brain metastases were demonstrating on follow-up imaging.

Conclusions.Stereotactic radiosurgery for recurrent small cell lung carcinoma metastases provided effective local tumor control in the majority of patients. Early detection of brain metastases, aggressive treatment of systemic disease, and a therapeutic strategy including radiosurgery can extend survival.
Gamma knife surgery of superficially located meningioma
Authors: Kim Dong Gyu , Kim Chi Heon , Chung Hyun-Tai , Paek Sun Ha , Jeong Sang Soon , Han Dae Hee , Jung Hee-Won
Published: May 2009

Object.The authors analyzed tumor control rates and complications in patients with superficially located meningiomas after gamma knife surgery (GKS).

Methods.Between 1998 and 2003, GKS was performed in 23 patients with 26 lesions in whom follow-up imaging for 1 year or more was available. The male/female ratio was 1:22. The mean age was 59 years. The median tumor volume was 4.7 cm3, and the mean margin dose was 16 Gy at the 50% isodose line. Peritumoral edema was revealed on magnetic resonance (MR) imaging in four patients before GKS. Magnetic resonance imaging and clinical examinations were performed every 6 months after GKS. The mean follow-up duration was 32 months.

The tumor shrank in eight cases, was stable in 17, and enlarged in one; thus 25 (95%) of 26 tumors were controlled. A peritumoral high signal on T2-weighted MR images was found in eight lesions and preexisting edema was aggravated in three lesions after GKS. Ten of these 11 patients complained of severe headache, and three patients experienced neurological deficits at the same time after a mean latency of 3 months; however, high signal was not demonstrated on imaging before 6 months on average. Steroid agents, when required, gave relief to all patients. The complication rate was 43% (10 of 23 cases). High signal disappeared in nine patients and decreased in the remaining two. High signal was associated with a high integral dose and a large tumor volume. Tumor shrinkage at the last follow-up examination was more prominent in the patients with symptomatic high signal (p = 0.03).

Conclusions.There was a good tumor control rate with a high complication rate. Longer follow up of more patients is needed. Adjusting the dose—volume relationship should be considered to reduce complications.
Ultrastructural changes in arteriovenous malformations after gamma knife surgery: an electron microscopic study
Authors: Szeifert György T. , Major Ottó , Kemeny Andras A.
Published: May 2009

Object.The authors analyzed morphological alterations at the subcellular level by undertaking transmission electron microscopy in arteriovenous malformations (AVMs) after gamma knife surgery (GKS).

Methods.Histological, immunohistochemical, and electron microscopic investigations were performed in a series of pathological specimens obtained in seven patients. The patients harbored cerebral AVMs that had been previously treated with GKS and had suffered subsequent bleeding 10 to 52 months after treatment.

Histological studies revealed spindle cell proliferation in the connective tissue stroma and in the subendothelial region of the irradiated AVM vessels. Electron microscopy demonstrated different ultrastructural characteristics of this spindle cell population. There were cells with a smooth-edged oval nuclei surrounded by massive bundles of collagen fibers in the extracellular matrix. Other cells with the same nuclear morphology contained abundant intracytoplasmic filaments. Nuclear deformation was connected to a fibrillary system developed within the cytoplasm, and peripheral attachment sites were related to an extracellular layer of basement membrane—like material arranged parallel to the cell border. Also present were cells containing well-developed cisterns of rough endoplasmic reticulum and dense bodies at the periphery of the cytoplasm with folded, irregular nuclei.

Conclusions.The ultrastructural and histological characteristics of the spindle cell population in the GKS-treated AVMs are similar to those designated as myofibroblasts in wound healing processes and pathological fibromatoses. Because similar cell modifications have not been demonstrated in control nonirradiated AVM specimens, these myofibroblasts may contribute to the shrinking process and final occlusion of AVMs after radiosurgery.
Linear accelerator radiosurgery for vestibular schwannoma: measuring tumor volume changes on serial three-dimensional spoiled gradient-echo magnetic resonance images
Authors: Okunaga Tomohiro , Matsuo Takayuki , Hayashi Nobuyuki , Hayashi Yukishige , Shabani Hamisi K. , Kaminogo Makio , Ochi Makoto , Nagata Izumi
Published: May 2009

Object

The authors report on a series of 46 patients harboring vestibular schwannomas (VSs) treated using linear accelerator (LINAC) radiosurgery and an analysis of serial magnetic resonance (MR) imaging data, specifically the changes in tumor volume.

Methods

Fifty-three consecutive patients underwent LINAC radiosurgery for VS between 1993 and 2002. Seven of these patients were lost to follow up. Three-dimensional (3D) spoiled gradient-echo (SPGR) MR imaging was performed at 3- to 4-month intervals after radiosurgery. Tumor volume was measured on Gd-enhanced MR images of each slice.

The median duration of follow-up MR imaging studies was 56.5 months (range 12–120 months). Follow-up imaging studies were conducted for longer than 1 year in 42 of 53 patients. Tumor volume changes were categorized into four types: enlargement (eight lesions [19%]), no change (two lesions [4.8%]), transient enlargement followed by shrinkage (19 lesions [45.2%]), and direct shrinkage (13 lesions [31%]). Two cases (4.8%) with twice the initial tumor volume required repeated radiosurgery. All cases of transient enlargement had subsequent shrinkage within 2 years after radiosurgery.

Nine (21.4%) of 42 patients demonstrated ventricular enlargement on MR images obtained after radiosurgery. Three patients (7.1%) required placement of a ventriculoperitoneal shunt because of symptomatic hydrocephalus, and another four cases (9.5%) spontaneously resolved.

Conclusions

Volume measurement on 3D-SPGR MR imaging was a suitable method to assess tumor changes. Volume changes beyond twofold or continuous enlargement for longer than 2 years after radiosurgery are key criteria in rating the effects of radiation. Some cases of hydrocephalus after radiosurgery resolved spontaneously and their rates of occurrence were similar to the typical incidence of hydrocephalus associated with VS.
Novel laser tissue-soldering technique for dural reconstruction
Authors: Gil Ziv , Shaham Amit , Vasilyev Tamar , Brosh Tamar , Forer Boaz , Katzir Abraham , Fliss Dan M.
Published: May 2009

Object

The goal of this study was to use a modified version of the CO2 laser—soldering system to develop a simple and reliable technique for the repair of dural defects after excision of brain tumors.

Methods

The authors used a CO2 fiber optic laser system that they had developed for heating, monitoring, and controlling tissue temperature in situ and in real time, thereby reducing damage to the brain parenchyma. They adapted the system for dural closure by using free fascial grafts in a porcine model. Measures for estimation of reconstruction quality included visual assessment under magnification and direct measurements of adhesive strength and cerebrospinal fluid leak (CSF) pressure.

Reliable soldering was achieved in 54 of 57 experiments, providing a 95% success rate. The average peak adhesive strength was 82 ± 3 mN/cm2. The measured leak pressure of the fascia—dura mater bond was 66 ± 5 mm Hg. Conventional suturing performed using Prolene stitches resulted in immediate CSF leakage from areas between the stitches and from the area of the needle hole itself.

Conclusions

Fascia—dura mater soldering using the CO2 laser is feasible and may support CSF pressure up to six times higher than normal intracranial pressure. Findings of this study may provide a basis for the development of new tools for dural reconstruction.
Encapsulated vascular endothelial growth factor—secreting cell grafts have neuroprotective and angiogenic effects on focal cerebral ischemia
Authors: Yano Akimasa , Shingo Tetsuro , Takeuchi Akira , Yasuhara Takao , Kobayashi Kazuki , Takahashi Kazuya , Muraoka Kenichiro , Matsui Toshihiro , Miyoshi Yasuyuki , Hamada Hirofumi , Date Isao
Published: May 2009

Object

The authors evaluated the neuroprotective and angiogenic effects of a continuous and low-dose infusion of vascular endothelial growth factor (VEGF)-165 on cerebral ischemia in rats.

Methods

The authors introduced VEGF complementary (c)DNA into baby hamster kidney (BHK) cells and established a cell line that produces human VEGF165 (BHK-VEGF). The BHK-VEGF cells and BHK cells that had been transfected with an expression vector that did not contain human VEGF165 cDNA (BHK-control) were encapsulated. Both capsules were implanted into rat striata. Six days after capsule implantation, the right middle cerebral artery (MCA) was occluded. Some animals were killed 24 hours after occlusion to measure the volume of the resulting infarct and to perform immunohistochemical studies. Other animals were used for subsequent behavioral studies 1, 7, and 14 days after MCA occlusion.

The encapsulated BHK-VEGF cell grafts significantly reduced the volume of the infarct and the number of apoptotic cells in the penumbral area when compared with the effect of the BHK-control cell capsule. In addition, angiogenesis and gliogenesis significantly increased in the region around the capsule in animals that received BHK-VEGF cell capsules without an increase in focal cerebral blood flow; this did not occur in animals that received the BHK-control cell capsule. In behavioral studies rats that received the BHK-VEGF cell capsule displayed significant recovery while participating in the accelerating rotarod test after stroke.

Conclusions

Continuous intracerebral administration of low-dose VEGF165 through encapsulated grafts of VEGF-producing cells produces neuroprotective and angiogenic effects. These effects improve subsequent motor function.
Thyrocervical trunk—external carotid artery bypass for positional cerebral ischemia due to common carotid artery occlusion
Authors: Melgar Miguel A. , Sahni Deshdeepak , Weinand Martin
Published: May 2009

✓ Medically refractory positional cerebral ischemia (PCI) and concomitant orthostatic hypotension associated with chronic common carotid artery (CCA) occlusion are rare. In this technical report, the authors describe an extracranial bypass in which the thyrocervical trunk was used as a donor vessel to treat three cases of CCA occlusion with PCI. Postoperatively, although orthostatic hypotension remained, ischemia-related symptoms resolved in all three patients and long-term graft patency was demonstrated. It is possible to treat cerebral ischemia due to CCA occlusion with extracranial bypass surgery. In these patients, the thyrocervical trunk proved to be a suitable donor vessel for the reconstitution of blood flow within the external carotid artery.
Gamma knife surgery for the treatment of intracranial metastases from breast cancer
Authors: Goyal Sharad , Prasad Dheerendra , Harrell Frank , Matsumoto Julie , Rich Tyvin , Steiner Ladislau
Published: May 2009

Object. The goal of this study was to evaluate the effectiveness and limitations of gamma knife surgery (GKS) in the treatment of intracranial breast carcinoma lesions.

Methods. A retrospective analysis of the GKS database at the University of Virginia Health System identified 43 patients with a total of 84 lesions who were treated between 1989 and 2000. All patients who received treatment were included in this study. Imaging studies were available in 35 patients with 67 treated lesions.

The overall duration of median survival was 13 months (95% confidence interval [CI] 7–16 months) after radiosurgery. A univariable Cox regression analysis revealed that a single lesion (p = 0.035), a high Karnofsky Performance Scale (KPS) score (p = 0.019), and a high Score Index for Radiosurgery (SIR) in Brain Metastases (p = 0.036) were associated with a significantly lengthened time to local treatment failure. The median duration of survival for patients grouped according to the SIR as low, middle, and high was 3, 8, and 21 months, respectively (p = 0.00033). A multivariable analysis showed that a high KPS score (p = 0.006), a high SIR (p = 0.014), and advanced age (0.038) were predictive of survival. The 1-, 2-, 3-, and 5-year survival rates were 49, 23, 12, and 2%, respectively.

The overall median time to local treatment failure was 10 months (95% CI 6–14 months) after GKS. A univariable analysis demonstrated that a single lesion, higher KPS score, and a higher SIR were associated with a significantly longer time until local treatment failure. A multivariable analysis showed that a higher KPS score and SIR and patients who had received chemotherapy were associated with a significantly longer time to local treatment failure.

Neuroimaging scores given for the enhancement pattern (ring-enhancing, heterogeneous, and homogeneous signal), amount of necrosis (none, < 50%, and > 50%), and mass effect (none, mild, moderate, and severe) of each treated lesion did not correlate with survival or local treatment failure.

Conclusions. The SIR and the KPS score are prognostic factors in patients whose intracranial breast cancer metastases are treated with GKS. The SIR, which includes the KPS score, patient age, systemic disease status, largest lesion volume, and number of lesions, can be used to identify those patients with breast cancer metastasis who would benefit from GKS better than KPS score alone. The contribution of whole-brain radiation therapy to GKS with regard to local tumor control or survival could not be identified.
Surgical management of the recurrence and regrowth of craniopharyngiomas
Authors: Minamida Yoshihiro , Mikami Takeshi , Hashi Kazuo , Houkin Kiyohiro
Published: May 2009

Object. The authors performed a retrospective analysis of a consecutive series of craniopharyngiomas and their recurrences, which were managed with surgery alone.

Methods. In the past 20 years, 37 consecutive patients with craniopharyngiomas underwent surgery without adjuvant radiotherapy. During that period there was a consistent strategy that surgical management was the first choice of treatment whenever possible.

Of these 37 patients, 11 experienced tumor recurrence (29.7%) during the mean follow-up period of 11.1 years. Of these 11 patients, seven experienced recurrence after neuroimaging-confirmed total removal, and four patients experienced recurrence after partial or incomplete removal. In these 11 patients, surgical removal was performed 17 times. Using a proper surgical approach (mainly a basal interhemispheric approach) and meticulous microsurgical techniques, total removal of the recurrent tumor was achieved in nine surgeries (52.9). The mortality and morbidity rates associated with these 17 surgeries were 0% and 9.1%, respectively. In most cases, visual function was preserved or improved and intellectual performance was also preserved.

Conclusions. Recurrence of craniopharyngioma can be safely managed by using meticulous contemporary microsurgical techniques without additional radiotherapy. The role of surgery and adjuvant radiotherapy for craniopharyngiomas may vary in the future, depending on innovations in treatment and technology. Nevertheless, surgery can be still a major therapeutic option in the management of recurrent craniopharyngiomas.
Association between elevated brain tissue glycerol levels and poor outcome following severe traumatic brain injury
Authors: Clausen Tobias , Alves Oscar Luis , Reinert Michael , Doppenberg Egon , Zauner Alois , Bullock Ross
Published: May 2009

Object. Glycerol is considered to be a marker of cell membrane degradation and thus cellular lysis. Recently, it has become feasible to measure via microdialysis cerebral extracellular fluid (ECF) glycerol concentrations at the patient's bedside. Therefore the aim of this study was to investigate the ECF concentration and time course of glycerol after severe traumatic brain injury (TBI) and its relationship to patient outcome and other monitoring parameters.

Methods. As soon as possible after injury for up to 4 days, 76 severely head-injured patients were monitored using a microdialysis probe (cerebral glycerol) and a Neurotrend sensor (brain tissue PO2) in uninjured brain tissue confirmed by computerized tomography scanning. The mean brain tissue glycerol concentration in all monitored patients decreased significantly from 206 ± 31 µmol/L on Day 1 to 9 ± 3 µmol/L on Day 4 after injury (p < 0.0001). Note, however, that there was no significant difference in the time course between patients with a favorable outcome (Glasgow Outcome Scale [GOS] Scores 4 and 5) and those with an unfavorable outcome (GOS Scores 1–3). Significantly increased glycerol concentrations were observed when brain tissue PO2 was less than 10 mm Hg or when cerebral perfusion pressure was less than 70 mm Hg.

Conclusions. Based on results in the present study one can infer that microdialysate glycerol is a marker of severe tissue damage, as seen immediately after brain injury or during profound tissue hypoxia. Given that brain tissue glycerol levels do not yet add new clinically significant information, however, routine monitoring of this parameter following traumatic brain injury needs further validation.
Predictive value of an early Glasgow Outcome Scale score: 15-month score changes
Authors: Miller Kelly J. , Schwab Karen A. , Warden Deborah L.
Published: May 2009

Object. Does an early Glasgow Outcome Scale (GOS) assessment provide a reliable indicator of later outcome in a patient with traumatic brain injury (TBI)? The authors examined the utility of the GOS during early treatment as a predictor of outcome score 15 months postinjury by analyzing outcome score change in a group of patients with closed head injuries.

Methods. Glasgow Outcome Scale scores assessed within 3 months of injury (baseline) were compared with scores obtained at 15 months postinjury in 121 patients, primarily young military personnel. Score changes between baseline and 8 months postinjury were also studied in a subgroup of 72 patients. The impact of initial injury severity (determined by the duration of unconsciousness) on score change was also explored. The GOS scores at three time points within the 15-month period—baseline (within 3 months of injury), 8, and 15 months postinjury—were examined to ascertain when the maximal GOS score had been reached.

Conclusions. Baseline GOS score was a reliable predictor of outcome in patients with an initial score of 5 (no disability) or 4 (mild disability), but not in patients with an initial score of 3 (severe disability). Patients who remained unconscious for more than 24 hours did not have significantly lower outcome scores than those who experienced loss of consciousness for less than 24 hours at 15 months postinjury. Interestingly, the duration of unconsciousness did not affect the likelihood of an improved score during the study period in patients with a GOS score of 3 or 4 at baseline. An updated evaluation conducted after the early phases of treatment is needed to provide a realistic prognosis of severe TBI.
Coexpression of erythropoietin and its receptor in endolymphatic sac tumors
Authors: Vogel Timothy W. A. , Vortmeyer Alexander O. , Lubensky Irina A. , Lee Youn-Soo , Furuta Makoto , Ikejiri Barbara , Kim H. Jeffrey , Lonser Russell R. , Oldfield Edward H. , Zhuang Zhengping
Published: May 2009

Object.Von Hippel—Lindau (VHL) disease is characterized by multiple tumors in specific organs. The cell of origin and the reason for the particular organ distribution of the tumors remains unknown. Endolymphatic sac tumor (ELST) is one of the lesions associated with VHL disease. Data from previous studies of VHL disease—associated hemangioblastomas (HBs) and renal cell carcinomas (RCCs) have indicated thatVHLgene deficiency causes coexpression of erythropoietin (Epo) and its receptor (Epo-R), which facilitates tumor growth.

Methods.The authors studied ELSTs from five patients with VHL germline mutations. Analysis of the five ELST samples revealed loss of the wild-type allele, consistent with Knudson's two-hit hypothesis for tumorigenesis. All five ELST specimens were characterized microscopically and by immunohistochemical analysis. Coexpression of Epo and Epo-R was found in all five tumors on immunohistochemical studies and confirmed through reverse transcription—polymerase chain reaction and Western blot analysis.

Conclusions.Expression of Epo appears to be a result ofVHLgene deficiency, whereas the simultaneous coexpression of Epo-R may reflect a developmental mechanism of tumorigenesis. Coexpression of Epo and Epo-R in ELSTs together with the morphological and genetic similarities of these lesions with other VHL disease—associated tumors indicates that VHL disease—associated tumors in different organs share common pathogenetic pathways.
Survival and differentiation of neural progenitor cells derived from embryonic stem cells and transplanted into ischemic brain
Authors: Takagi Yasushi , Nishimura Masaki , Morizane Asuka , Takahashi Jun , Nozaki Kazuhiko , Hayashi Junya , Hashimoto Nobuo
Published: May 2009

Object. Cell replacement therapy including the use of embryonic stem cells (ESCs) may represent a novel treatment for damage from stroke. In this study, the authors transplanted neural progenitor cells (NPCs) derived from ESCs into ischemic brain and analyzed their survival and differentiation.

Methods. Multipotential NPCs were generated from ESCs by using the stromal cell—derived inducing activity method. These cells could differentiate in vitro into neurons, glia, and oligodendrocytes, thus revealing them to be neural stem cells. The NPCs were then transplanted into ischemic brain. At 2 weeks postischemia, the transplanted cells occupied 18.8 ± 2.5% of the hemispheric area; by 4 weeks postischemia, 26.5 ± 4% of the hemisphere. At 4 weeks after transplantation, green fluorescent protein (GFP)—positive transplanted cells showed mature neuronal morphological features. The authors also investigated the expression of differentiation markers and various neurotransmitters. Transplanted cells were immunopositive for neuronal nuclei, β-tubulin-III, and glial fibrillary acidic protein. Of the GFP-positive cells, 33.3 ± 11.5% were positive for glutamate decarboxylase, 13.3 ± 5.8% for glutamate, 2.1 ± 2.5% for tyrosine hydroxylase, 1.8 ± 2% for serotonin, and 0.4 ± 0.2% for choline acetyltransferase.

Conclusions. The authors confirmed the survival and differentiation of ESC-derived NPCs transplanted into the ischemic brain. Surviving transplanted cells expressed several neural markers and neurotransmitters. These findings indicate that these cells can function in the brain.
Surface properties, more than size, limiting convective distribution of virus-sized particles and viruses in the central nervous system
Authors: Chen Michael Y. , Hoffer Alan , Morrison Paul F. , Hamilton John F. , Hughes Jeffrey , Schlageter Kurt S. , Lee Jeongwu , Kelly Brandon R. , Oldfield Edward H.
Published: May 2009

Object. Achieving distribution of gene-carrying vectors is a major barrier to the clinical application of gene therapy. Because of the blood—brain barrier, the distribution of genetic vectors to the central nervous system (CNS) is even more challenging than delivery to other tissues. Direct intraparenchymal microinfusion, a minimally invasive technique, uses bulk flow (convection) to distribute suspensions of macromolecules widely through the extracellular space (convection-enhanced delivery [CED]). Although acute injection into solid tissue is often used for delivery of oligonucleotides, viruses, and liposomes, and there is preliminary evidence that certain of these large particles can spread through the interstitial space of the brain by the use of convection, the use of CED for distribution of viruses in the brain has not been systematically examined. That is the goal of this study.

Methods. Investigators used a rodent model to examine the influence of size, osmolarity of buffering solutions, and surface coating on the volumetric distribution of virus-sized nanoparticles and viruses (adeno-associated viruses and adenoviruses) in the gray matter of the brain. The results demonstrate that channels in the extracellular space of gray matter in the brain are large enough to accommodate virus-sized particles and that the surface characteristics are critical determinants for distribution of viruses in the brain by convection.

Conclusions. These results indicate that convective distribution can be used to distribute therapeutic viral vectors in the CNS.
Endoscopic treatment of thalamic neuroepithelial cysts
Authors: Schmidt Kelly , Coimbra Caetano
Published: May 2009

✓ Thalamic neuroepithelial cysts are rare lesions of the central nervous system. Surgical management of these lesions has varied and yielded mixed results. The authors identified 10 reported cases in the literature, five of which involved symptomatic lesions. The authors present three unique cases of symptomatic thalamic neuroepithelial cysts associated with hydrocephalus, which were all successfully treated using endoscopic third ventriculostomy and fenestration of the cyst into the third ventricle.
Coronary AngioJet catheterization for the management of dural venous sinus thrombosis
Authors: Agner Celso , Deshaies Eric M. , Bernardini Gary L. , Popp A. John , Boulos Alan S.
Published: May 2009

✓ In most cases of deep venous sinus thrombosis, systemic anticoagulation represents the initial treatment of choice for preventing propagation of a clot in the dural sinuses. In patients with deep or extensive venous sinus thrombosis, a combination of treatment modalities may be required including systemic anticoagulation, selective venous thrombolysis, and mechanical thrombectomy. In the current study the authors report on a patient who presented with the acute onset of headache, vomiting, a depressed level of consciousness, and a left hemiparesis and in whom a right middle cerebral artery (MCA) territory ischemic stroke with hemorrhagic conversion was initially diagnosed. Results of diagnostic cerebral angiography demonstrated a patent right MCA and a deep venous sinus thrombosis involving most of the dural sinuses. Despite adequate systemic heparinization, the patient's neurological condition deteriorated and direct administration of alteplase into the transverse sinus in conjunction with mechanical clot disruption using a coronary AngioJet was required. Venous flow was successfully reestablished in the deep and superficial venous sinuses by using a 0.014-in exchange wire routed from the right common femoral vein through the sinuses and out the left common femoral vein. Excellent angiographic results were obtained, and the patient had recovered completely by the 7-month follow up.
The evolution of Harvey Cushing's surgical approach to pituitary tumors from transsphenoidal to transfrontal
Authors: Cohen-Gadol Aaron A. , Laws Edward R. , Spencer Dennis D. , De Salles Antonio A. F.
Published: May 2009

✓ The evolution of transsphenoidal surgery represents a special chapter in the progress of neurosurgery. Although Cushing initially advocated a transsphenoidal approach to pituitary tumors, he became disenchanted with this approach, ultimately favoring the subfrontal or “transfrontal” route late in his career. Other neurosurgeons followed Cushing's example, and the fate of transsphenoidal surgery entered a dark era in 1929. A review of Cushing's patients' records reveals that his abandonment of the transsphenoidal route was primarily related to the limitations of this approach in providing effective resection of large pituitary lesions—the symptomatic tumor recurrence rate after this procedure was substantial. Furthermore, given the preoperative uncertainty about the suprasellar extension of pituitary tumors prior to modern neuroimaging, the transfrontal route assured Cushing an adequate decompression of the optic chiasm. By 1927, Cushing's mastery of intracranial surgery was accompanied by the use of electrosurgical methods that enabled him to remove sellar lesions through the transfrontal route safely and with timely and effective restoration of visual loss. Transsphenoidal surgery remained relatively dormant, awaiting the efforts and enthusiasm of Norman Dott who bridged the gap between Cushing and Gerard Guiot, the surgeon who revitalized transsphenoidal adenomectomy for future generations of pituitary surgeons.
Serial diffusion-weighted magnetic resonance imaging in cases of glioma: distinguishing tumor recurrence from postresection injury
Authors: Smith Justin S. , Cha Soonmee , Mayo Mary Catherine , McDermott Michael W. , Parsa Andrew T. , Chang Susan M. , Dillon William P. , Berger Mitchel S.
Published: May 2009

Object

Diffusion-weighted magnetic resonance (MR) imaging is an invaluable tool in the diagnosis of acute stroke and other types of brain injury. Abnormalities in and around the resection cavity on diffusion-weighted imaging have been observed following surgery for infiltrating glioma. The purpose of this study was to investigate prospectively the incidence, time course, and ultimate outcome of these abnormalities.

Methods

Forty-four consecutive patients with newly diagnosed gliomas were prospectively observed using serial MR imaging including diffusion-weighted sequences. Clinical and surgical data were also collected. Immediately postoperatively neuroimaging identified 28 patients (64%) in whom areas of reduced diffusion appeared in or around the resection cavity (mean volume 8.2 ± 1.5 cm3). Complete resolution of this reduced diffusion was demonstrated within 90 days in 24 patients (86%). On subsequent neuroimages these areas demonstrated Gd enhancement as early as postoperative Day 15 and as late as Day 198 and ultimately took on the appearance of encephalomalacia in 26 (93%) of 28 cases. Postoperative reduced diffusion was not predicted by the clinical or surgical parameters that were assessed. No clinical deficits were attributable to the reduced diffusion.

Conclusions

An abnormality related to diffusion-weighted sequences on postoperative MR imaging can occur after resection of newly diagnosed gliomas. In this study the abnormality typically resolved and was replaced by contrast enhancement on follow-up imaging, ultimately demonstrating encephalomalacia on long-term follow up. Findings on neuroimaging during the period of enhancement could be confused with recurrent tumor and interpreted as early treatment failure. Based on the findings of this study the authors strongly suggest that the inclusion of diffusion-weighted sequences in postoperative MR imaging is essential, as is MR imaging immediately before radiation therapy to monitor disease progression. A new enhancement observed after glioma surgery should be interpreted in the context of the diffusion-weighted image obtained immediately postoperatively.
Pulmonary function after complete unilateral phrenic nerve transection
Authors: Xu Wen-Dong , Gu Yu-Dong , Liu Jing-Bo , Yu Cong , Zhang Cheng-Gang , Xu Jian-Guang
Published: May 2009

Object

The status of pulmonary function following phrenic nerve transfer surgery is still largely unknown because of the high degree of variability in the accessory phrenic nerve that may be involved. In the present study, pulmonary functions were assessed in patients before and after full-length phrenic nerve transfer surgery, in whom the phrenic nerve was severed at a location just before its entry into the diaphragm.

Methods

Fifteen patients (average age 27.4 years) with complete brachial plexus palsy underwent full-length phrenic nerve transfer. The phrenic nerve was harvested from the thoracic cavity by means of video-assisted thoracic surgery and then transferred to the musculocutaneous nerve. Postoperative pulmonary functions were retrospectively analyzed. Patients underwent follow-up evaluation for 42 to 48 months; four patients were eventually lost to follow up.

Although no patient experienced pulmonary problems following the surgery, all sustained varying degrees of diaphragmatic paralysis and elevation (for 1–1.5 intercostal spaces) on the surgically treated side as seen on chest x-ray films. Pulmonary functional parameters, including vital capacity, vital capacity in percentage of predicted values, residual volume, total lung capacity, forced vital capacity, and forced expiratory volume in 1 second, recovered to preoperative levels by 1 year postsurgery. In contrast, the postoperative maximal inspiratory pressure value was significantly decreased compared with the predicted values (average decrease ∼20%) in all of the patients, even at 4 years after the surgery.

Conclusions

In young patients with healthy lung function, unilateral phrenic nerve transection surgery can cause unilateral diaphragmatic paralysis and reduce the inspiration muscle force; however, most pulmonary function parameters gradually recover to preoperative levels within 1 year.
Tenascin-C—coated platinum coils for acceleration of organization of cavities and reduction of lumen size in a rat aneurysm model
Authors: Toma Naoki , Imanaka-Yoshida Kyoko , Takeuchi Taku , Matsushima Satoshi , Iwata Hiroo , Yoshida Toshimichi , Taki Waro
Published: May 2009

Object. Detachable platinum coils are widely used in the endovascular treatment of intracranial aneurysms. The use of coil placement produces a higher incidence of aneurysm recurrence compared with surgical clipping. To reduce the incidence of recurrence by promoting clot organization, the authors designed a platinum coil coated with tenascin-C (TNC), an extracellular matrix glycoprotein, and then histologically examined tissue responses.

Methods. Platinum coils were prepared by successive coatings with cationic polyethyleneimine and anionic heparin and then TNC or basic fibroblast growth factor (bFGF) was immobilized by affinity binding to the heparin. Six unmodified, six heparin-coated, six bFGF-coated, or eight TNC-coated platinum coils were inserted into ligated common carotid arteries (CCAs) of adult male rats, and CCA segments were harvested after 14 or 28 days.

The percentages of organized areas occupying the luminal cavity in unmodified, heparin-coated, bFGF-coated, and TNC-coated groups were 4.8 ± 4.6, 1.6 ± 1.1, 17.9 ± 10.7, and 93.4 ± 6.9%, respectively. In addition, the mean lumen size in the TNC-coated group (0.35 ± 0.23 mm2) was reduced to less than half that of the unmodified group (0.72 ± 0.21 mm2). Immunohistochemical analysis revealed that α—smooth muscle actin—positive cells were a major cellular component of the organized tissue within the TNC-coated coils but not in the bFGF group. Collagen fibrils in the organized areas were also much thicker and denser with TNC-coated coils than with bFGF-coated coils.

Conclusions. Placement of TNC-coated coils can remarkably accelerate organization of luminal cavities and reduce their volume, providing improved efficacy of these coils for endovascular embolization.
Differences in infarct evolution between lipopolysaccharide-induced tolerant and nontolerant conditions to focal cerebral ischemia
Authors: Furuya Kazuhide , Zhu Lidong , Kawahara Nobutaka , Abe Osamu , Kirino Takaaki
Published: May 2009

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 (lCBF) 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 lCBF 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.
In vitro and in vivo effects of probucol on hydrolysis of asymmetric dimethyl l-arginine and vasospasm in primates
Authors: Pluta Ryszard M. , Jung Carla S. , Harvey-White Judith , Whitehead Anne , Shilad Sabrina , Espey Michael G. , Oldfield Edward H.
Published: May 2009

Object. Increased cerebrospinal fluid (CSF) levels of asymmetric dimethyl l-arginine (ADMA), an endogenous inhibitor of endothelial nitric oxide synthase (eNOS), are associated with delayed vasospasm after subarachnoid hemorrhage (SAH); however, the source, cellular mechanisms, and pharmacological inhibition of ADMA production following SAH are unknown.

Methods. In an in vitro experiment involving human umbilical vein endothelial cells (HUVECs), the authors examined mechanisms potentially responsible for increased ADMA levels during vasospasm and investigated whether this increase can be inhibited pharmacologically. In a second study, an in vivo experiment, the authors used probucol, which effectively inhibited ADMA increase in HUVEC cultures in vitro, in a randomized double-blind placebo-controlled experiment in a primate model of delayed cerebral vasospasm after SAH.

Oxidized low-density lipids (OxLDLs; positive control; p < 0.02) and bilirubin oxidation products (BOXes; p < 0.01), but not oxyhemoglobin (p = 0.74), increased ADMA levels in HUVECs. Probucol inhibited changes in ADMA levels evoked by either OxLDLs (p < 0.001) or BOXes (p < 0.01). Comparable changes were observed in cell lysates. In vivo probucol (100 mg/kg by mouth daily) did not alter serum ADMA levels on Days 7, 14, and 21 after SAH compared with levels before SAH, and these levels were not different from those observed in the placebo group (p = 0.3). Despite achieving therapeutic levels in plasma and measurable levels in CSF, probucol neither prevented increased CSF ADMA levels nor the development of vasospasm after SAH. Increased CSF ADMA and decreased nitrite levels in both groups were strongly associated with the degree of delayed vasospasm after SAH (correlation coefficient [CC] 0.5, 95% confidence interval [CI] 0.19–0.72, p < 0.002 and CC −0.43, 95% CI −0.7 to < 0.05, p < 0.03, respectively).

Conclusions. Bilirubin oxidation products, but not oxyhemoglobin, increased ADMA levels in the HUVEC. Despite its in vitro ability to lower ADMA levels, probucol failed to inhibit increased CSF ADMA and decreased nitrite levels, and it did not prevent delayed vasospasm in a primate SAH model.
CSF Pulse Pressure and B Waves
Authors: Czosnyka Zofia , Czosnyka Marek , Pickard John D.
Published: May 2009

Abstract

Object. The appearance of numerous B waves during intracranial pressure (ICP) registration in patients with idiopathic adult hydrocephalus syndrome (IAHS) is considered to predict good outcome after shunt surgery. The aim of this study was to describe which physical parameters of the cerebrospinal fluid (CSF) system B-waves reflect and to find a method that could replace long-term B-wave analysis.

Methods. Ten patients with IAHS were subjected to long-term registration of ICP and a lumbar constant-pressure infusion test. The B-wave presence, CSF outflow resistance (Rout), and relative pulse pressure coefficient (RPPC) were assessed using computerized analysis. The RPPC was introduced as a parameter reflecting the joint effect of elastance and pulsatory volume changes on ICP and was determined by relating ICP pulse amplitudes to mean ICP.

Conclusions. The B-wave presence on ICP registration correlates strongly with RPPC (r = 0.91, p < 0.001, 10 patients) but not with CSF Rout. This correlation indicates that B waves—like RPPC—primarily reflect the ability of the CSF system to reallocate and store liquid rather than absorb it. The RPPC-assessing lumbar short-term CSF pulse pressure method could replace the intracranial long-term B-wave analysis.