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M E Linskey

Publications and source records attributed to M E Linskey.

At least 19 recordsLinked to original sources
PubMed2000

Multi-agent cytostatic treatment of 'low-grade' gliomas.

The rationale and current supporting evidence for a complementary, multi-agent, low-toxicity, chronic, cytostatic therapeutic approach to treating patients with gliomas is presented in detail. This strategy would involve the simultaneous treatment of patients with DNA/chromosomal stabilizing agent(s), anti-angiogenesis agent(s), and anti- invasion agent(s), with or without the addition of a low-toxicity antiproliferation agent. Oral agents would be the ideal for this chronic, potentially life-long, therapeutic approach. The most logical target group would be patients with newly diagnosed "low-grade" gliomas rather than those with more malignant (usually recurrent) gliomas.

Angiogenesis Inhibitors↗
PubMed2000

Gamma knife radiosurgery as a primary treatment for prolactinomas.

OBJECT: The purpose of this study was to estimate the efficacy of gamma knife radiosurgery (GKS) in controlling tumor growth and endocrinopathy associated with prolactinomas. METHODS: Between 1993 and 1997, 164 of 469 patients with pituitary adenomas treated by GKS harbored prolactinomas. The dose to the tumor margin ranged from 9 to 35 Gy (mean 31.2 Gy), and the visual pathways were exposed to a dose of less than 10 Gy. The mean tumor diameter was 13.4 mm. The mean follow-up time for 128 cases was 33.2 months (range 6-72 months). Tumor control was observed in all but two patients who underwent surgery 18 and 36 months, respectively, after GKS. Clinical cure was achieved in 67 cases. Clinical improvement was noted with a decrease in the hyperprolactinemia after GKS. Nonetheless, in 31 (29%) of 108 patients who were followed for more than 2 years no improvement in serum prolactin levels was demonstrated, although this could be normalized by bromocriptine administration after treatment. Nine infertile women became pregnant 2 to 13 months after GKS and all gave birth to normal children. There was no visual deterioration related to GKS. Five women experienced premature menopause. In these patients there was subtotal disappearance of the tumor and an empty sella developed. CONCLUSIONS: Gamma knife radiosurgery as a primary treatment for prolactinomas can be safe and effective both for controlling tumor growth and for normalization of prolactin hypersecretion. A higher margin dose (> or = 30 Gy) seemed to be associated with a better clinical outcome. Gamma knife radiosurgery may make prolactinomas more sensitive to the bromocriptine.

Humans↗
PubMed1997

Glial ontogeny and glial neoplasia: the search for closure.

The last ten years have seen rapid progress in both our understanding of the normal progression and control of gliogenesis and in the laboratory techniques necessary to sustain and study most glial cell types, including progenitor cells of both type-1 astrocyte (T1A) and oligodendrocyte-type-2 astrocyte (T2A) lineage. These studies have direct relevance for the lineage analysis of human gliomas, optimizing in vitro glioma models, and suggesting potentially fertile new grounds for glioma biology research. We do not yet known whether malignant transformation occurs only in mature glia that then 'de-differentiate' into cells with glial precursor phenotypes and behavior characteristics, whether neoplastic transformation occurs in O-2A progenitor cells, or whether both mechanisms may occur in different patients. However, preliminary results suggest that astrocytomas can arise from two different glial lineages, that oligodendrogliomas and mixed oligo-astrocytomas arise exclusively from the O-2A lineage, and that medulloblastomas may also have a connection with the O-2A lineage. An ontogeny-based glioma classification system may lead to better prognostic patient data and better predict patient response to treatment than currently available classification systems. Available data from the study of developmental glial biology raises serious doubts about the fidelity and relevance of in vitro glioma models that rely on culture media supplemented with animal serum and suggest that relying on chemically-defined media conditioned by astrocytes may be the better research strategy. Findings from the study of normal gliogenesis also suggest that growth factors are likely to act as much more than simple mitogens in glioma biology. Potentially fertile areas of research for glioma biology include studying the cooperative effect of multiple growth factors, potential growth factor effects as survival factors, inhibitors of differentiation, and differentiation inducers, and studying potential positive humoral feedback loops between glioma cells and normal glial cells, as well as normal non-glial cells, within and surrounding each glioma.

Animals↗
PubMed1995

Glial differentiation: a review with implications for new directions in neuro-oncology.

Major advances in cell culture techniques, immunology, and molecular biology during the last 10 years have led to significant progress in understanding the process of normal glial differentiation. This article summarizes our current understanding of the cellular and molecular basis of glial differentiation based on data obtained in cell culture and reviews current hypotheses regarding the transcriptional control of the gene switching that controls differentiation. Understanding normal glial differentiation has potentially far-reaching implications for developing new forms of treatment for patients with glial neoplasms. If oncogenesis truly involves a blockage or a short circuiting of the differentiation process in adult glial progenitor cells, or if it results from dedifferentiation of previously mature cells, then a clear understanding of differentiation may provide a key to understanding and potentially curtailing malignancy. Differentiation agents represent a relatively new class of drugs that effect cellular gene transcription at the nuclear level, probably through alterations in chromatin configuration and/or differential gene induction. These exciting new agents may provide a means of preventing the dedifferentiation of low-grade gliomas or inducing malignant glioma cells to differentiate with minimal toxicity. In the future, genetic therapy has the potential of more specifically rectifying the defect in genetic control that led to oncogenesis in any given tumor.

Adult↗
PubMed1994

Stereotactic localization and removal of a bullet in the third ventricle causing obstructive hydrocephalus after a cerebral gunshot wound: case report.

A bullet, lodged in the pineal-posterior region of the third ventricle and causing obstructive hydrocephalus, was removed without damage to critical adjacent vascular structures using stereotactic localization followed by laser-guided stereotactic craniotomy. Stereotactic techniques provided precise target localization and allowed dissection to be restricted to the previously injured missile track, thus avoiding any additional morbidity from the surgical procedure.

Adult↗
PubMed1994

Microvascular decompression for trigeminal neuralgia caused by vertebrobasilar compression.

Thirty-one (2%) of 1404 consecutive patients with typical trigeminal neuralgia who underwent microvascular decompression between 1972 and 1993 were found to have vascular compression by the vertebral artery (VA) or the basilar artery (BA). Compared to the remaining 1373 patients, this subgroup was older (mean age 62 vs. 55 years, p < 0.001), was predominantly male (68% vs. 39%, p < 0.002), demonstrated left-sided predominance (65% vs. 39%, p < 0.002), was more likely to be hypertensive (65% vs. 18%, p < 0.001), and was more likely to have ipsilateral hemifacial spasm (16% vs. 0.6%, p < 0.001). The trigeminal nerve was compressed by the VA in 18 cases (the VA alone in three and the VA plus other vessels in 15), the BA in 12 cases (the BA alone in four and the BA plus other vessels in eight), and the vertebrobasilar junction in one case. Twenty-nine of the 31 patients underwent vascular decompression of the trigeminal nerve, one had a complete trigeminal root section, and one underwent partial root section with vascular decompression of the remaining nerve. All 31 patients were pain-free, off medication immediately after surgery, and this pain-free, medication-free status was maintained at 1 year after surgery in 96% of cases, at 3 years in 92%, and at 10 years in 86%, based on life-table analysis. Minor trigeminal hypesthesia/hypalgesia was present preoperatively in 52%. New or worsened minor hypesthesia/hypalgesia developed in 41% of patients, while transient diplopia as well as hearing loss developed in 23% and 13% in the overall series, respectively. No patient developed major trigeminal sensory loss or masseter weakness after vascular decompression alone. There was no operative mortality. Vascular decompression is an effective treatment for patients with trigeminal neuralgia who have vertebrobasilar compression of the trigeminal nerve. Patients should be warned that decompression of a tortuous vertebrobasilar system carries a higher risk of mild trigeminal dysfunction, diplopia, and hearing loss than standard microvascular decompression.

Age Factors↗
PubMed1994

Stroke risk after abrupt internal carotid artery sacrifice: accuracy of preoperative assessment with balloon test occlusion and stable xenon-enhanced CT.

PURPOSE: To evaluate stable xenon-enhanced CT cerebral blood flow with balloon test occlusion as a predictor of stroke risk in internal carotid artery sacrifice. METHODS: Abrupt internal carotid artery occlusion was performed by surgical or endovascular means below the origin of the ophthalmic artery in 31 normotensive patients who were assessed preoperatively by a 15-minute clinical balloon test occlusion followed by an internal carotid artery-occluded xenon CT cerebral blood flow study. RESULTS: One patient, who passed the clinical test occlusion but exhibited regions of cerebral blood flow less than 30 mL/100 g per minute on the occlusion xenon CT cerebral blood flow study went on to have a fatal stroke corresponding exactly to the region of reduced blood flow. Thirty patients passed both components of the preoperative stroke-risk assessment. Neuroimaging demonstrated possible flow-related infarctions, which subsequently developed in three patients. Two patients were asymptomatic, and one patient was left with a mild residual hemiparesis. CONCLUSIONS: Our protocol provided a statistically significant reduction in subsequent infarction rate and infarction-related death rate when compared with a control group of normotensive abrupt internal carotid artery occlusion patients who did not undergo any preoperative stroke-risk assessment (reported in the literature). The estimated false-negative rate for our preoperative assessment protocol ranged from 3.3% to 10% depending on the assessment of the cause of the three potentially flow-related infarctions. Although life-threatening major vascular territory infarctions have been avoided, our protocol is less sensitive to changes predicting smaller, often minimally symptomatic, vascular border zone infarctions and does not predict postoperative thromboembolic strokes.

Adolescent↗
PubMed1993

Cranial nerve length predicts the risk of delayed facial and trigeminal neuropathies after acoustic tumor stereotactic radiosurgery.

PURPOSE: To test the hypothesis that length of cranial nerve irradiated is a major factor predicting the risk of cranial nerve injury following radiosurgery and to identify any other significant related treatment factors. METHODS AND MATERIALS: Ninety-two patients (93 acoustic tumors) were treated with a 201 source Cobalt-60 gamma unit from 1987 to 1990 and prospectively followed. The range of minimum tumor dose was 12-20 Gy and maximum dose 24-50 Gy. Univariate and multivariate analyses were used to evaluate any correlations between tumor measurements and treatment factors, with the development of trigeminal and facial neuropathies following radiosurgery. RESULTS: The risks of trigeminal and facial neuropathy following radiosurgery were associated with the pon-petrous distance and mid porous transverse tumor diameters respectively (anatomically related to the irradiated length of cranial nerves V and VII respectively) in both univariate (p = .002 for V and p = .026 for VII) and multivariate (p = .004 for V and p = .055 for VII) analyses. Tumor volume, other tumor measurements, maximum dose, minimum tumor dose, and tumor dose inhomogeneity were not significantly related to either trigeminal or facial neuropathy in univariate and multivariate analyses. CONCLUSION: Within a minimum tumor dose range of 12-20 Gy, the incidence of delayed trigeminal or facial neuropathy depended more on the estimated length of nerve irradiated than the tumor dose or tumor volume. In the future, the risk of delayed facial or trigeminal cranial neuropathy may be reduced significantly by performing radiosurgery when the tumor still has both a small mid-porous transverse diameter and a small pons-petrous distance.

Facial Neuralgia↗
PubMed1993

Gamma knife radiosurgery for acoustic tumors: multivariate analysis of four year results.

In order to evaluate the results of radiosurgery for acoustic tumors and to identify optimum treatment parameters, an analysis of tumor control, as well as incidences of hearing loss, facial and trigeminal neuropathies was undertaken. Between August 1987 and August 1991, 134 patients with 136 acoustic tumors received stereotactic gamma knife radiosurgery at the University of Pittsburgh. Median follow-up was 24 months (range: 6-56 months). Tumor volumes ranged from 0.10 to 17.00 cm3 (median = 2.75 cm3). From one to ten isocenters were utilized per tumor treated (median = 3). Minimum tumor doses varied from 12 to 20 Gy (median = 17 Gy). The 4-year actuarial tumor control rate was 89.2 +/- 6.0%. Some degree of hearing (by pure tone audiometry) was preserved in 71.0 +/- 4.4% of patients. The actuarial rates for preservation of either pretreatment hearing level or useful hearing were 34.4 +/- 6.6% and 35.1 +/- 97% respectively. Respectively, the actuarial incidences of postradiosurgery facial and trigeminal neuropathies were 29.0 +/- 4.4% and 32.9 +/- 4.5%, respectively. No significant factors affecting tumor control were identified. Multivariate analysis identified a significantly increased risk of hearing loss in patients with neurofibromatosis (p = 0.0003) as well as decreased risks of facial and trigeminal neuropathies with both decreasing tumor diameter (p = 0.001) and increasing number of isocenters treated (p = 0.003). Radiosurgery is a safe and effective treatment for acoustic neuromas with acceptable morbidity that may be lowered by the use of multiple isocenter treatment techniques and by earlier treatment of small tumors.

Adolescent↗
PubMed1993

The radiobiology of human acoustic schwannoma xenografts after stereotactic radiosurgery evaluated in the subrenal capsule of athymic mice.

An experimental model with xenograft transplantation into the subrenal capsule of athymic (nude) mice was used to evaluate the early response of human acoustic schwannomas to stereotactic radiosurgery. After xenograft placement, 45 mice underwent radiosurgery with single doses of 10, 20, or 40 Gy using a 201-source 60Co gamma unit (4-mm collimator, single isocenter, 80% isodose line). The 45 radiosurgery-treated xenografts were compared with 15 untreated xenografts and 15 xenografts in mice that underwent "sham radiosurgery." All five study groups were matched for the following pretreatment variables: patient of origin, animal weight, average xenograft diameter, and percentage of xenograft surface vascularity. Immediately prior to sacrifice of the mice all xenografts were evaluated in situ to determine the average tumor diameter, tumor volume, and percentage of surface vascularity. Mice were sacrificed 2 weeks, 1 month, or 3 months after radiosurgery. Blinded histological review was performed by an independent neuropathologist. Tumor volume was reduced 33.6% after 2 weeks (p = 0.023) and 45% after 3 months (p = 0.018) in the 40-Gy radiosurgery group. Tumor volume was reduced by 46.2% after 1 month (p = 0.0002) and 35.2% after 3 months (p = 0.032) in the 20-Gy radiosurgery group. An average volume reduction of 16.4% was observed after 3 months (p = 0.17) in the 10-Gy radiosurgery group. At 3 months after surgery, tumor surface vascularity was reduced by an average of 19.7% (p = 0.043) in the 40-Gy radiosurgery group and 5.8% (p = 0.12) in the 20-Gy radiosurgery group and was unchanged in the 10-Gy radiosurgery group and both control groups. Histological examination demonstrated a higher incidence of hemosiderin deposits (p = 0.026) and vascular mural hyalinization (p = 0.032) in radiosurgery xenografts versus control. The subrenal capsule xenograft in nude mice was an excellent model for studying the in vivo radiobiology of acoustic schwannomas after radiosurgery. Both cellular and vascular effects could be assessed serially in situ and the model was stable even 4 months after transplantation. Additional studies investigating radiobiology over periods better approximating the time course of clinical neuroimaging changes (6 to 12 months) are warranted.

Animals↗
PubMed1992

Cavernous sinus hemangiomas: a series, a review, and an hypothesis.

Cavernous sinus hemangiomas represent 3% of all benign cavernous sinus tumors. They are dangerous tumors because of the risk of excessive bleeding, but they are easier to dissect from surrounding structures than meningiomas because of the presence of a pseudocapsule. Three cases where total excision was achieved with minimal blood loss, without stroke, and with preservation of cranial nerve function in 2 cases are reported, and 50 cases from the literature are reviewed. Hemangiomas can be distinguished preoperatively from over one-half of meningiomas by their marked hyperintensity on T2-weighted magnetic resonance imaging. They arise within the cavernous sinus and extend laterally by dissecting between the two layers of dura lining the floor of the middle fossa. Cranial nerves III, IV, and V remained stretched over the tumor surface within the overlying dura, whereas cranial nerve VI is found within the tumor and is the most difficult cranial nerve to preserve. Principles for successful and safe excision include preoperative assessment of the safety of temporary or permanent carotid artery occlusion, obtaining early proximal carotid artery control, carefully developing the plane between the dura and the tumor pseudocapsule, early devascularization of the tumor, and avoiding "piecemeal" tumor resection. A few cases demonstrated tumor shrinkage with radiation therapy which should be considered for patients with incomplete tumor excision or who are too ill to undergo surgery.

Brain Neoplasms↗
PubMed1992

Tumor control after stereotactic radiosurgery in neurofibromatosis patients with bilateral acoustic tumors.

During a 4-year interval, 17 patients with bilateral acoustic tumors (vestibular schwannomas) underwent unilateral stereotactic radiosurgery using a multisource gamma unit; 2 patients underwent radiosurgery of both tumors in separate sessions. Eleven patients with unoperated contralateral tumors served as concurrent controls to compare the effects of radiosurgery with the natural history of acoustic tumors. After radiosurgery, the tumor control and regression rates were 89.5 and 21.1%, respectively (median neuroimaging follow-up, 1.4 years; range, 0.3-3.9). The tumor regression rate increased to 40% for patients evaluated at least 12 months after radiosurgery. In comparison to the unoperated contralateral tumors, stereotactic radiosurgery achieved tumor control, as assessed by the ultimate change in tumor size at follow-up (P, 0.012), the change in tumor size over time (P, 0.006), and tumor growth rates (P, 0.003). This study provided convincing evidence that tumor stabilization after radiosurgery (as assessed by neuroimaging) truly represented tumor control. The incidence of delayed facial neuropathy after radiosurgery compared favorably with the incidence reported after microsurgical removal. Some hearing was preserved in one-third of the patients who had preoperative hearing, including three patients who were contralaterally deaf. Stereotactic radiosurgery should be considered as a primary surgical modality for many patients with neurofibromatosis Type II.

Adolescent↗
PubMed1992

Emergency embolectomy for embolic occlusion of the middle cerebral artery after internal carotid artery balloon test occlusion. Case report.

Balloon test occlusion of the internal carotid artery (ICA) is useful in preoperatively assessing the risk of temporary occlusion or permanent sacrifice of the carotid artery. The incidence of symptomatic complications from this procedure is 1.7%. The case is reported of a 57-year-old woman in whom a balloon test occlusion of the left ICA was attempted. She developed a left ICA dissection/occlusion with subsequent embolization to the left middle cerebral artery, leading to right-sided hemiplegia and expressive aphasia. She was successfully treated by an emergency embolectomy followed by surgical repair of the left ICA, with an excellent outcome. This case represents the most serious complication encountered by the authors in more than 300 balloon test occlusions. Means of avoiding this complication during balloon test occlusion as well as the important factors in managing this problem are emphasized.

Carotid Artery, Internal↗
PubMed1992

Stereotactic radiosurgery in the treatment of patients with acoustic tumors.

Stereotactic radiosurgery is performed under local anesthesia, and most patients can be discharged from the hospital within 24 hours of treatment. All patients in our series returned to their preoperative level of employment or function within 5 to 7 days of treatment, and this functional level was maintained over the period of follow-up. "Tumor control" was achieved in 96% of patients during an average follow-up of 1.7 years. Tumor shrinkage occurred in 45% of patients who had at least 1.5 years of follow-up. Useful hearing preservation rates were 50% at 6 months and 30% 1 year after treatment. New delayed facial or trigeminal neuropathy occurred in 34% and 32% of patients, respectively, with a median onset of 5 to 6 months after treatment. The vast majority of cranial neuropathies were partial at onset and tended to improve over time. Other complications included tumor growth (4%), communicating hydrocephalus (4%), and transient adjacent brain parenchymal changes best seen on T2-weighted MRI (9%). Stereotactic radiosurgery is an important alternative treatment for carefully selected patients with acoustic tumors. Indications for treatment include sufficient medical problems to pose excessive surgical risk, advanced age, the presence of bilateral acoustic tumors or contralateral deafness, recurrent tumor despite surgical resection, or refusal to undergo microsurgery. Radiosurgery is contraindicated in patients with symptomatic brain stem or cerebellar compression from a large acoustic tumor. Previous posterior fossa radiotherapy is a relative contraindication that must be considered on a patient to patient basis. Stereotactic radiosurgery should be viewed as an additional weapon in our arsenal for combating acoustic tumors rather than feared as a potential replacement for surgical excision. The strategic role of stereotactic radiosurgery in the overall treatment of patients with acoustic tumors will continue to be refined as longer-term, carefully assessed results become available.

Adolescent↗
PubMed1992

Stereotactic radiosurgery for acoustic tumors.

Stereotactic radiosurgery is an important alternative treatment for carefully selected patients with acoustic tumors. We perform radiosurgery under local anesthesia, and 91% of our patients have been discharged from the hospital within 24 hours after treatment. All returned to their preoperative level of function or employment within 5 to 7 days after treatment. Our current tumor control rate is 97%, but reduction in tumor size, judged by strict, objective criteria, was achieved in only 23%. Our actuarial rate of useful hearing preservation after radiosurgery is 38% at 1 year. Three tumors increased in size after treatment. Only one of the three demonstrated increased mass effect on surrounding brain structures by neuroimaging criteria. No increase has led to worsened clinical symptoms or has required surgical excision at this point in follow-up. The 1-year rates for developing new facial or trigeminal neuropathies after radiosurgery were 30% and 33%, respectively. Cranial neuropathies had a delayed onset, with the median onset occurring after 5 to 6 months. The vast majority were partial at onset, and most improved over time. Communicating hydrocephalus requiring ventriculoperitoneal shunts developed after radiosurgery in four patients. Eight patients developed increased signal within adjacent brain parenchyma on T2-weighted MR imaging, consistent with edema or blood-brain barrier breakdown. It is unlikely that stereotactic radiosurgery using the gamma knife will obviate the need for microsurgical removal performed by skilled and experienced microsurgeons. However, radiosurgery is a safe and effective treatment for patients whose medical problems make surgery unacceptably dangerous, those with bilateral tumors or a tumor in their only hearing ear, those who have recurrent tumor despite surgical resection, or patients who refuse microsurgical excision.

Adolescent↗
PubMed1991

Radiosurgery of acoustic neurinomas.

Eighty-five patients with acoustic neurinomas underwent stereotactic radiosurgery with the gamma unit at the University of Pittsburgh (Pittsburgh, PA) during its first 30 months of operation. Neuroimaging studies performed in 40 patients with more than 1 year follow-up showed that tumors were smaller in 22 (55%), unchanged in 17 (43%), and larger in one (2%). The 2-year actuarial rates for preservation of useful hearing and any hearing were 46% and 62%, respectively. Previously undetected neuropathies of the trigeminal (n = 12) and facial nerves (n = 14) occurred 1 week to 1 year after radiosurgery (median, 7 and 6 months, respectively), and improved at median intervals of 13 and 8 months, respectively, after onset. Hearing loss was significantly associated with increasing average tumor diameter (P = 0.04). No deterioration of any cranial nerve function has yet developed in seven patients with average tumor diameters less than 10 mm. Radiosurgery is an important treatment alternative for selected acoustic neurinoma patients.

Adolescent↗