New directions in bioabsorbable technology

2002 ◽  
Vol 97 (4) ◽  
pp. 481-489 ◽  
Author(s):  
Stephen M. Warren ◽  
Marc H. Hedrick ◽  
Karl Sylvester ◽  
Michael T. Longaker ◽  
Constance M. Chen
Keyword(s):  
Interdisciplinary Approach ◽  
Patient Specific ◽  
Therapeutic Gene ◽  
Content Type ◽  
Tissue Constructs ◽  
New Directions ◽  
Material Sciences ◽  
Specific Tissue ◽  
Tissue Restoration ◽  
Fine Print

✓ Generating replacement tissues requires an interdisciplinary approach that combines developmental, cell, and molecular biology with biochemistry, immunology, engineering, medicine, and the material sciences. Because basic cues for tissue engineering may be derived from endogenous models, investigators are learning how to imitate nature. Endogenous models may provide the biological blueprints for tissue restoration, but there is still much to learn. Interdisciplinary barriers must be overcome to create composite, vascularized, patient-specific tissue constructs for replacement and repair. Although multistep, multicomponent tissue fabrication requires an amalgamation of ideas, the following review is limited to the new directions in bioabsorbable technology. The review highlights novel bioabsorbable design and therapeutic (gene, protein, and cell-based) strategies currently being developed to solve common spine-related problems.

Cervical spinal cord delivery of a rabies G protein pseudotyped lentiviral vector in the SOD-1 transgenic mouse

2004 ◽  
Vol 1 (1) ◽  
pp. 128-136 ◽  
Author(s):  
Kiana Tanase ◽  
Qingshan Teng ◽  
Ajit A. Krishnaney ◽  
James K. Liu ◽  
Mary E. Garrity-Moses ◽  
...  
Keyword(s):  
Gene Expression ◽  
Spinal Cord ◽  
Transgenic Mice ◽  
Lentiviral Vector ◽  
Cervical Spinal Cord ◽  
Wild Type ◽  
Therapeutic Gene ◽  
Content Type ◽  
Fine Print

Object. Lentiviral vectors may constitute a vehicle for long-term therapeutic gene expression in the spinal cord. In amyotrophic lateral sclerosis, spinal cord sclerosis and altered axonal transport pose barriers to therapeutic gene distribution. In the present study the authors characterize gene expression distribution and the behavioral impact of the rabies G (RabG) protein pseudotyped lentiviral vector EIAV.LacZ through cervical spinal cord injection in control and Cu/Zn superoxide dismutase—1 (SOD-1) transgenic mice. Methods. Seven-week-old SOD-1 transgenic mice and their wild-type littermates underwent exposure of the cervicomedullary junction and microinjection of RabG.EIAV.LacZ or vehicle. The Basso-Beattie-Bresnahan locomotor score, grip strength meter, and Rotarod assays were used to assess the effects of disease progression, spinal cord microinjection, and lentiviral gene expression. Spinal cords were removed when the mice were in the terminal stage of the disease. The distribution of LacZ gene expression was histologically evaluated and quantified. Direct cervical spinal cord microinjection of RabG.EIAV.LacZ results in extensive central nervous system uptake in SOD-1 transgenic mice; these findings were statistically similar to those in wild-type mice (p > 0.05). Gene expression lasts for the duration of the animal's survival (132 days). The SOD-1 mutation does not prevent retrograde axonal transport of the vector. Three behavioral assays were used to demonstrate that long-term gene expression does not alter sensorimotor function. In comparison with normative data, vector injection and transgene expression do not accelerate disease progression. Conclusions. Direct spinal cord injection of RabG.EIAV vectors represents a feasible method for delivering therapeutic genes to upper cervical spinal cord and brainstem motor neurons. Distribution is not affected by the SOD-1 mutation or disease phenotype.

A patient-specific computer model to predict outcomes of the balloon occlusion test

2004 ◽  
Vol 101 (6) ◽  
pp. 977-988 ◽  
Author(s):  
Fady T. Charbel ◽  
Meide Zhao ◽  
Sepideh Amin-Hanjani ◽  
William Hoffman ◽  
Xinjian Du ◽  
...  
Keyword(s):  
Blood Flow ◽  
Cerebral Artery ◽  
Phase Contrast ◽  
Mr Angiography ◽  
Balloon Occlusion ◽  
Patient Specific ◽  
Flow Modeling ◽  
Content Type ◽  
Blood Flow Modeling ◽  
Fine Print

Object. Balloon occlusion tests (BOTs) are performed to identify patients who are at risk for ischemia and stroke following permanent internal carotid artery (ICA) occlusion. The object of this work was to determine whether patient-specific blood flow modeling can be used to identify patients in whom the BOT would not be tolerated. Methods. The test was performed in 16 patients who underwent BOT with continuous neurological and electroencephalographic monitoring, followed by a hypotensive challenge. During hypotension a tracer was injected so that single-photon emission tomography (SPECT) scans could be obtained. Each individual brain circulation was modeled using information gained from phase-contrast magnetic resonance (MR) angiography and digital subtraction (DS) angiography, and the predicted effect of the BOT was evaluated. Six patients did not tolerate the BOT; in these patients, decreases in middle cerebral artery (M1 segment) blood flow of 41 ± 27% (mean ± standard deviation), anterior cerebral artery (A3 segment) flow of 56 ± 33%, and posterior cerebral artery (P2 segment) flow of 4 ± 13% ipsilateral to the site of occlusion were found with modeling; these changes were significantly greater than the percentage of changes measured in the contralateral hemisphere (p < 0.05). Ten patients who tolerated the BOT well had calculated decreases in ipsilateral flows of only 9 ± 6% for the M1 segment, 12 ± 40% for the A3 segment, and 17 ± 21% for the P2 segment during BOT modeling. Conclusions. A decrease in blood flow in both the ipsilateral M1 and A3 segments that was greater than 20%, calculated by flow modeling of the BOT, was 100% sensitive and 100% specific in identifying patients who could not tolerate the BOT. Blood flow modeling, coupled with DS angiography and noninvasive phase-contrast MR angiography measurements to make calculations patient specific, can be used to identify patients who have an elevated risk of ischemia during the BOT.

Temporary arterial occlusion in the repair of ruptured intracranial aneurysms: an analysis of risk factors for stroke

2002 ◽  
Vol 97 (4) ◽  
pp. 836-842 ◽  
Author(s):  
Richard Ferch ◽  
Alberto Pasqualin ◽  
Giampietro Pinna ◽  
Franco Chioffi ◽  
Albino Bricolo
Keyword(s):  
Risk Factors ◽  
Stroke Risk ◽  
Surgical Repair ◽  
Univariate Analysis ◽  
Arterial Occlusion ◽  
Patient Specific ◽  
Clinical Grade ◽  
Vessel Occlusion ◽  
Content Type ◽  
Fine Print

Object. This study was performed to further elucidate technical and patient-specific risk factors for perioperative stroke in patients undergoing temporary arterial occlusion during the surgical repair of their aneurysms. Methods. One hundred twelve consecutive patients in whom temporary arterial occlusion was performed during surgical repair of an aneurysm were retrospectively analyzed. Confounding factors (inadvertent permanent vessel occlusion and retraction injury) were identified in six cases (5%) and these were excluded from further analysis. The demographics for the remaining 106 patients were analyzed with respect to age, neurological status, aneurysm characteristics, intraoperative rupture, duration of temporary occlusion, and number of occlusive episodes; end points considered were outcome at 3-month follow up and symptomatic and radiological stroke. Conclusions. Overall 17% of patients experienced symptomatic stroke and 26% had radiological evidence of stroke attributable to temporary arterial occlusion. A longer duration of clip placement, older patient age, a poor clinical grade (Hunt and Hess Grades IV–V), early surgery, and the use of single prolonged clip placement rather than repeated shorter episodes were associated with a higher risk of stroke based on univariate analysis. Intraoperative aneurysm rupture did not affect stroke risk. On multivariate analysis, only poorer clinical grade (p = 0.001) and increasing age (p = 0.04) were significantly associated with symptomatic stroke risk.

Evaluation of gamma thalamotomy for parkinsonian and other tremors: survival of neurons adjacent to the thalamic lesion after gamma thalamotomy

2000 ◽  
Vol 93 (supplement_3) ◽  
pp. 120-127 ◽  
Author(s):  
Chihiro Ohye ◽  
Tohru Shibazaki ◽  
Junji Ishihara ◽  
Jie Zhang
Keyword(s):  
Tissue Reaction ◽  
Vascular Lesions ◽  
Thalamic Lesion ◽  
Mr Images ◽  
Unsatisfactory Result ◽  
Content Type ◽  
Rhythmic Discharge ◽  
Latent Interval ◽  
Fine Print

Object. The effects of gamma thalamotomy for parkinsonian and other kinds of tremor were evaluated. Methods. Thirty-six thalamotomies were performed in 31 patients by using a 4-mm collimator. The maximum dose was 150 Gy in the initial six cases, which was reduced to 130 Gy thereafter. The longest follow-up period was 6 years. The target was determined on T2-weighted and proton magnetic resonance (MR) images. The point chosen was in the lateral-most part of the thalamic ventralis intermedius nucleus. This is in keeping with open thalamotomy as practiced at the authors' institution. In 15 cases, gamma thalamotomy was the first surgical procedure. In other cases, previous therapeutic or vascular lesions were visible to facilitate targeting. Two types of tissue reaction were onserved on MR imaging: a simple oval shape and a complex irregular shape. Neither of these changes affected the clinical course. In the majority of cases, the tremor subsided after a latent interval of approximately 1 year after irradiation. The earliest response was demonstrated at 3 months. In five cases the tremor remained. In four of these cases, a second radiation session was administered. One of these four patients as well as another patient with an unsatisfactory result underwent open thalamotomy with microrecording. In both cases, depth recording adjacent to the necrotic area revealed normal neuronal activity, including the rhythmic discharge of tremor. Minor coagulation was performed and resulted in immediate and complete arrest of the remaining tremor. Conclusions. Gamma thalamotomy for Parkinson's disease seems to be an alternative useful method in selected cases.

Gamma knife radiosurgery as a single treatment modality for large cerebral arteriovenous malformations

2000 ◽  
Vol 93 (supplement_3) ◽  
pp. 113-119 ◽  
Author(s):  
D. Hung-Chi Pan ◽  
Wan-Yuo Guo ◽  
Wen-Yuh Chung ◽  
Cheng-Ying Shiau ◽  
Yue-Cune Chang ◽  
...  
Keyword(s):  
Gamma Knife ◽  
Arteriovenous Malformations ◽  
Radiation Treatment ◽  
Gamma Knife Radiosurgery ◽  
Consecutive Series ◽  
Content Type ◽  
Obliteration Rate ◽  
Complete Obliteration ◽  
Fine Print

Object. A consecutive series of 240 patients with arteriovenous malformations (AVMs) treated by gamma knife radiosurgery (GKS) between March 1993 and March 1999 was evaluated to assess the efficacy and safety of radiosurgery for cerebral AVMs larger than 10 cm3 in volume. Methods. Seventy-six patients (32%) had AVM nidus volumes of more than 10 cm3. During radiosurgery, targeting and delineation of AVM nidi were based on integrated stereotactic magnetic resonance (MR) imaging and x-ray angiography. The radiation treatment was performed using multiple small isocenters to improve conformity of the treatment volume. The mean dose inside the nidus was kept between 20 Gy and 24 Gy. The margin dose ranged between 15 to 18 Gy placed at the 55 to 60% isodose centers. Follow up ranged from 12 to 73 months. There was complete obliteration in 24 patients with an AVM volume of more than 10 cm3 and in 91 patients with an AVM volume of less than 10 cm3. The latency for complete obliteration in larger-volume AVMs was significantly longer. In Kaplan—Meier analysis, the complete obliteration rate in 40 months was 77% in AVMs with volumes between 10 to 15 cm3, as compared with 25% for AVMs with a volume of more than 15 cm3. In the latter, the obliteration rate had increased to 58% at 50 months. The follow-up MR images revealed that large-volume AVMs had higher incidences of postradiosurgical edema, petechiae, and hemorrhage. The bleeding rate before cure was 9.2% (seven of 76) for AVMs with a volume exceeding 10 cm3, and 1.8% (three of 164) for AVMs with a volume less than 10 cm3. Although focal edema was more frequently found in large AVMs, most of the cases were reversible. Permanent neurological complications were found in 3.9% (three of 76) of the patients with an AVM volume of more than 10 cm3, 3.8% (three of 80) of those with AVM volume of 3 to 10 cm3, and 2.4% (two of 84) of those with an AVM volume less than 3 cm3. These differences in complications rate were not significant. Conclusions. Recent improvement of radiosurgery in conjunction with stereotactic MR targeting and multiplanar dose planning has permitted the treatment of larger AVMs. It is suggested that gamma knife radiosurgery is effective for treating AVMs as large as 30 cm3 in volume with an acceptable risk.

Factors related to complete occlusion of arteriovenous malformations after gamma knife radiosurgery

2000 ◽  
Vol 93 (supplement_3) ◽  
pp. 96-101 ◽  
Author(s):  
Jong Hee Chang ◽  
Jin Woo Chang ◽  
Yong Gou Park ◽  
Sang Sup Chung
Keyword(s):  
Gamma Knife ◽  
Arteriovenous Malformations ◽  
Gamma Knife Radiosurgery ◽  
Maximum Diameter ◽  
Content Type ◽  
Complete Occlusion ◽  
Factors Associated ◽  
Martin Grade ◽  
Fine Print

Object. The authors sought to evaluate the effects of gamma knife radiosurgery (GKS) on cerebral arteriovenous malformations (AVMs) and the factors associated with complete occlusion. Methods. A total of 301 radiosurgical procedures for 277 cerebral AVMs were performed between December 1988 and December 1999. Two hundred seventy-eight lesions in 254 patients who were treated with GKS from May 1992 to December 1999 were analyzed. Several clinical and radiological parameters were evaluated. Conclusions. The total obliteration rate for the cases with an adequate radiological follow up of more than 2 years was 78.9%. In multivariate analysis, maximum diameter, angiographically delineated shape of the AVM nidus, and the number of draining veins significantly influenced the result of radiosurgery. In addition, margin radiation dose, Spetzler—Martin grade, and the flow pattern of the AVM nidus also had some influence on the outcome. In addition to the size, topography, and radiosurgical parameters of AVMs, it would seem to be necessary to consider the angioarchitectural and hemodynamic aspects to select proper candidates for radiosurgery.

Stereotactic radiosurgery versus stereotactic radiotherapy for patients with vestibular schwannoma: a Leksell Gamma Knife Society 2000 debate

2000 ◽  
Vol 93 (supplement_3) ◽  
pp. 90-92 ◽  
Author(s):  
Mark E. Linskey
Keyword(s):  
Gamma Knife ◽  
Stereotactic Radiotherapy ◽  
Three Dimensional ◽  
Late Recurrence ◽  
Vestibular Schwannomas ◽  
Tumor Control ◽  
Complication Rates ◽  
Content Type ◽  
Single Fraction ◽  
Fine Print

✓ By definition, the term “radiosurgery” refers to the delivery of a therapeutic radiation dose in a single fraction, not simply the use of stereotaxy. Multiple-fraction delivery is better termed “stereotactic radiotherapy.” There are compelling radiobiological principles supporting the biological superiority of single-fraction radiation for achieving an optimal therapeutic response for the slowly proliferating, late-responding, tissue of a schwannoma. It is axiomatic that complication avoidance requires precise three-dimensional conformality between treatment and tumor volumes. This degree of conformality can only be achieved through complex multiisocenter planning. Alternative radiosurgery devices are generally limited to delivering one to four isocenters in a single treatment session. Although they can reproduce dose plans similar in conformality to early gamma knife dose plans by using a similar number of isocenters, they cannot reproduce the conformality of modern gamma knife plans based on magnetic resonance image—targeted localization and five to 30 isocenters. A disturbing trend is developing in which institutions without nongamma knife radiosurgery (GKS) centers are championing and/or shifting to hypofractionated stereotactic radiotherapy for vestibular schwannomas. This trend appears to be driven by a desire to reduce complication rates to compete with modern GKS results by using complex multiisocenter planning. Aggressive advertising and marketing from some of these centers even paradoxically suggests biological superiority of hypofractionation approaches over single-dose radiosurgery for vestibular schwannomas. At the same time these centers continue to use the term radiosurgery to describe their hypofractionated radiotherapy approach in an apparent effort to benefit from a GKS “halo effect.” It must be reemphasized that as neurosurgeons our primary duty is to achieve permanent tumor control for our patients and not to eliminate complications at the expense of potential late recurrence. The answer to minimizing complications while maintaining maximum tumor control is improved conformality of radiosurgery dose planning and not resorting to homeopathic radiosurgery doses or hypofractionation radiotherapy schemes.

Gamma knife radiosurgery in the management of cavernous sinus meningiomas

2000 ◽  
Vol 93 (supplement_3) ◽  
pp. 68-73 ◽  
Author(s):  
Pierre-Hugues Roche ◽  
Jean Régis ◽  
Henry Dufour ◽  
Henri-Dominique Fournier ◽  
Christine Delsanti ◽  
...  
Keyword(s):  
Mr Imaging ◽  
Tumor Growth ◽  
Gamma Knife ◽  
Cavernous Sinus ◽  
Gamma Knife Radiosurgery ◽  
Surgical Removal ◽  
Content Type ◽  
Cavernous Sinus Meningioma ◽  
The Mean ◽  
Fine Print

Object. The authors sought to assess the functional tolerance and tumor control rate of cavernous sinus meningiomas treated by gamma knife radiosurgery (GKS). Methods. Between July 1992 and October 1998, 92 patients harboring benign cavernous sinus meningiomas underwent GKS. The present study is concerned with the first 80 consecutive patients (63 women and 17 men). Gamma knife radiosurgery was performed as an alternative to surgical removal in 50 cases and as an adjuvant to microsurgery in 30 cases. The mean patient age was 49 years (range 6–71 years). The mean tumor volume was 5.8 cm3 (range 0.9–18.6 cm3). On magnetic resonance (MR) imaging the tumor was confined in 66 cases and extensive in 14 cases. The mean prescription dose was 28 Gy (range 12–50 Gy), delivered with an average of eight isocenters (range two–18). The median peripheral isodose was 50% (range 30–70%). Patients were evaluated at 6 months, and at 1, 2, 3, 5, and 7 years after GKS. The median follow-up period was 30.5 months (range 12–79 months). Tumor stabilization after GKS was noted in 51 patients, tumor shrinkage in 25 patients, and enlargement in four patients requiring surgical removal in two cases. The 5-year actuarial progression-free survival was 92.8%. No new oculomotor deficit was observed. Among the 54 patients with oculomotor nerve deficits, 15 improved, eight recovered, and one worsened. Among the 13 patients with trigeminal neuralgia, one worsened (contemporary of tumor growing), five remained unchanged, four improved, and three recovered. In a patient with a remnant surrounding the optic nerve and preoperative low vision (3/10) the decision was to treat the lesion and deliberately sacrifice the residual visual acuity. Only one transient unexpected optic neuropathy has been observed. One case of delayed intracavernous carotid artery occlusion occurred 3 months after GKS, without permanent deficit. Another patient presented with partial complex seizures 18 months after GKS. All cases of tumor growth and neurological deficits observed after GKS occurred before the use of GammaPlan. Since the initiation of systematic use of stereotactic MR imaging and computer-assisted modern dose planning, no more side effects or cases of tumor growth have occurred. Conclusions. Gamma knife radiosurgery was found to be an effective low morbidity—related tool for the treatment of cavernous sinus meningioma. In a significant number of patients, oculomotor functional restoration was observed. The treatment appears to be an alternative to surgical removal of confined enclosed cavernous sinus meningioma and should be proposed as an adjuvant to surgery in case of extensive meningiomas.

Gamma knife radiosurgery for craniopharyngiomas

2000 ◽  
Vol 93 (supplement_3) ◽  
pp. 47-56 ◽  
Author(s):  
Wen-Yuh Chung ◽  
David Hung-Chi Pan ◽  
Cheng-Ying Shiau ◽  
Wan-Yuo Guo ◽  
Ling-Wei Wang
Keyword(s):  
Clinical Outcome ◽  
Gamma Knife ◽  
Tumor Volume ◽  
Gamma Knife Radiosurgery ◽  
Tumor Control ◽  
Content Type ◽  
Stereotactic Aspiration ◽  
Cystic Component ◽  
The Mean ◽  
Fine Print

Object. The goal of this study was to elucidate the role of gamma knife radiosurgery (GKS) and adjuvant stereotactic procedures by assessing the outcome of 31 consecutive patients harboring craniopharyngiomas treated between March 1993 and December 1999. Methods. There were 31 consecutive patients with craniopharyngiomas: 18 were men and 13 were women. The mean age was 32 years (range 3–69 years). The mean tumor volume was 9 cm3 (range 0.3–28 cm3). The prescription dose to the tumor margin varied from 9.5 to 16 Gy. The visual pathways received 8 Gy or less. Three patients underwent stereotactic aspiration to decompress the cystic component before GKS. The tumor response was classified by percentage reduction of tumor volume as calculated based on magnetic resonance imaging studies. Clinical outcome was evaluated according to improvement and dependence on replacement therapy. An initial postoperative volume increase with enlargement of a cystic component was found in three patients. They were treated by adjuvant stereotactic aspiration and/or Ommaya reservoir implantation. Tumor control was achieved in 87% of patients and 84% had fair to excellent clinical outcome in an average follow-up period of 36 months. Treatment failure due to uncontrolled tumor progression was seen in four patients at 26, 33, 49, and 55 months, respectively, after GKS. Only one patient was found to have a mildly restricted visual field; no additional endocrinological impairment or neurological deterioration could be attributed to the treatment. There was no treatment-related mortality. Conclusions. Multimodality management of patients with craniopharyngiomas seemed to provide a better quality of patient survival and greater long-term tumor control. It is suggested that GKS accompanied by adjuvant stereotactic procedures should be used as an alternative in treating recurrent or residual craniopharyngiomas if further microsurgical excision cannot promise a cure.

Combined stereotactic split-course fractionated gamma knife radiosurgery and conventional radiation therapy for unfavorable gliomas: a phase I study

2000 ◽  
Vol 93 (supplement_3) ◽  
pp. 37-41 ◽  
Author(s):  
William F. Regine ◽  
Roy A. Patchell ◽  
James M. Strottmann ◽  
Ali Meigooni ◽  
Michael Sanders ◽  
...  
Keyword(s):  
Radiation Therapy ◽  
Disease Progression ◽  
Gamma Knife ◽  
Gamma Knife Radiosurgery ◽  
External Beam Radiation ◽  
Low Grade ◽  
Beam Radiation ◽  
Content Type ◽  
Group B ◽  
Fine Print

Object. This investigation was performed to determine the tolerance and toxicities of split-course fractionated gamma knife radiosurgery (FSRS) given in combination with conventional external-beam radiation therapy (CEBRT). Methods. Eighteen patients with previously unirradiated, gliomas treated between March 1995 and January 2000 form the substrate of this report. These included 11 patients with malignant gliomas, six with low-grade gliomas, and one with a recurrent glioma. They were stratified into three groups according to tumor volume (TV). Fifteen were treated using the initial FSRS dose schedule and form the subject of this report. Group A (four patients), had TV of 5 cm3 or less (7 Gy twice pre- and twice post-CEBRT); Group B (six patients), TV greater than 5 cm3 but less than or equal to 15 cm3 (7 Gy twice pre-CEBRT and once post-CEBRT); and Group C (five patients), TV greater than 15 cm3 but less than or equal to 30 cm3 (7 Gy once pre- and once post-CEBRT). All patients received CEBRT to 59.4 Gy in 1.8-Gy fractions. Dose escalation was planned, provided the level of toxicity was acceptable. All patients were able to complete CEBRT without interruption or experiencing disease progression. Unacceptable toxicity was observed in two Grade 4/Group B patients and two Grade 4/Group C patients. Eight patients required reoperation. In three (38%) there was necrosis without evidence of tumor. Neuroimaging studies were available for evaluation in 14 patients. Two had a partial (≥ 50%) reduction in volume and nine had a minor (> 20%) reduction in size. The median follow-up period was 15 months (range 9–60 months). Six patients remained alive for 3 to 60 months. Conclusions. The imaging responses and the ability of these patients with intracranial gliomas to complete therapy without interruption or experiencing disease progression is encouraging. Excessive toxicity derived from combined FSRS and CEBRT treatment, as evaluated thus far in this study, was seen in patients with Group B and C lesions at the 7-Gy dose level. Evaluation of this novel treatment strategy with dose modification is ongoing.

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