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Biomedical subjects

M E Linskey

Publications and source records attributed to M E Linskey.

At least 19 recordsLinked to original sources

Pituicytoma: diagnostic features on selective carotid angiography and MR imaging.

We report a case of pituicytoma, a rare primary tumor of the neurohypophysis. A 64-year-old man presented with progressive visual complaints, bitemporal hemianopsia, and headache. Imaging studies revealed distinctive features of a mass lesion that thickened the pituitary stalk with a bilobed protrusion extending into the hypothalamus. Angiography demonstrated tumor vascular supply from the superior hypophyseal arteries representing the diencephalic branches of the internal carotid arteries. We discuss the imaging and pathology of this unusual tumor.

Astrocytoma↗

In situ cranioplasty with methylmethacrylate and wire lattice.

Most techniques of cranioplasty are expensive and require advance preparation if a custom-moulded prosthesis is to be used. Technical problems with cranioplasties using synthetic materials include sinking, elevation and rotation, while those with hydroxyapatite or bone graft cranioplasties include resorption and harvest site disfigurement. We report our technique of in situ cranioplasty using methylmethacrylate and a wire lattice that is fast, inexpensive and avoids these technical problems.

Bone Wires↗

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↗

Cranial nerve root entry zone primary cerebellopontine angle gliomas: a rare and poorly recognized subset of extraparenchymal tumors.

With the exception of patients with neurofibromatosis type II, pediatric extraparenchymal cerebellopontine angle (CPA) tumors of any sort are extremely rare. Most gliomas encountered in the CPA in either children or adults involve the CPA as exophytic extensions of primary brain stem and/or cerebellar tumors. We encountered an unusual case of a giant CPA pilocytic astrocytoma arising from the proximal trigeminal nerve, completely separate from the brain stem. A nine-year-old girl with no evidence for any neurocutaneous syndrome, presented with headaches, mild obstructive hydrocephalus, trigeminal hypesthesia and a subtle peripheral facial paresis. Pre-operative neuroimaging suggested a petroclival meningioma. The tumor was completely resected via a right pre-sigmoid, retro-labyrinthine, subtemporal, transtentorial ('petrosal') approach, using intraoperative neurophysiological monitoring, with minimal morbidity. This appears to be the first reported case of a pediatric primary CPA glioma and the seventh reported case of primary CPA glioma, overall. It represents the second reported case of a primary CPA pilocytic astrocytoma. Given the findings in this case and the six other cases of primary CPA gliomas reported in the literature, as well as the results of histological studies of normal cranial nerves, we hypothesize that the point of origin of these rare and unusual tumors is the root entry zone of the involved cranial nerves. The differential diagnosis of primary CPA tumors should be expanded to include cranial nerve root entry zone primary CPA gliomas.

Astrocytoma↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

Emergent middle cerebral artery embolectomy: a useful technique for cranial base surgery.

Given the poor natural history of untreated symptomatic acute middle cerebral artery occlusion, we have attempted emergent reperfusion in all three cases of acute embolic middle cerebral artery occlusion seen on our cranial base service over the last 10 years. One patient developed a massive stroke requiring a life-saving "strokectomy" within 48 hours, which left him permanently hemiplegic, hemianopic, and hemihypesthetic after a failed attempt at reperfusion by superselective endovascular injection of urokinase. The other two patients, who were aphasic and densely hemiparetic, underwent successful emergent embolectomy with reperfusion established within 5 and 12 hours, respectively. One of the two is now neurologically normal, and the second is left with a subtle monoparesis but is independent in activities of daily living. Since middle cerebral artery embolism in cranial base patients usually occurs in a closely monitored hospital setting, we are presented with a unique opportunity for early successful operative intervention. Principles for optimizing outcome include: early recognition and diagnosis, maximization of medical therapy during the diagnostic workup prior to embolectomy (induced hypertension, intravascular volume expansion, and pharmacologic cerebral metabolic demand reduction), confirmation that the involved region does not have absent blood flow by xenon/computed tomography, early operative intervention, and careful surgical technique.

Journal Article↗

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↗

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↗

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↗