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Eugene A. Bonaroti, Robert D. Rose, Douglas Kondziolka, Susan Baser, and L. Dade Lunsford

Posteroventral pallidotomy (PVP) has received renewed interest as an ablative procedure for the symptomatic treatment of Parkinson's disease. In previous reports, the proximity of the optic tract to the lesion target in the globus pallidus internus has resulted in the occurrence of visual field deficits in as much as 14% of patients. The authors have used intraoperative visual evoked potentials (VEPs) during PVP to reduce this risk. All procedures were performed in awake patients. Flash stimuli were delivered to each eye via fiberoptic sources. Baseline flash VEPs were recorded at O1/Cz (left visual cortex to vertex), Oz/Cz (midline visual cortex to vertex), and O2/Cz (right visual cortex to vertex) for OS, OU, and OD stimulation. Epochs were acquired before and after localization, after macroelectrode stimulation, after temporary thermal lesioning, and after permanent thermal lesioning. Forty-seven patients underwent a total of 59 procedures. Visual evoked potentials were recorded reproducibly in all patients. In 11 procedures, VEP changes were reported, including six amplitude changes (10-80%), six latency shifts (3-10 msec), and one report of “variability.” In four procedures, VEP changes prompted a change in target coordinates. One false-positive and one false-negative VEP change were encountered. The only confirmed visual deficit was a superior quadrantanopsia, present on formal fields, but clinically asymptomatic. The authors conclude that VEPs may be useful for procedures performed in the awake patient because of the lack of anesthetic-induced variability. The 1.7% visual morbidity reported here (one in 59 patients) compares favorably with other series using microelectrodes. Visual evoked potentials may be a useful monitoring technique to reduce the incidence of clinically significant visual morbidity during pallidotomy, especially during formal lesioning of the ventral pallidum adjacent to the optic tract.

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Douglas Kondziolka, Brian R. Subach, L. Dade Lunsford, David J. Bissonette, and John C. Flickinger

Surgeons perform stereotactic radiosurgery as the main alternative to acoustic tumor (vestibular schwannoma) resection. The goals of radiosurgery include preservation of neurological function and prevention of tumor growth. Longer-term outcomes are not well documented for patients with solitary tumors or those with neurofibromatosis Type 2 (NF2).

To define outcomes, the authors evaluated 462 consecutive patients with solitary acoustic tumors and 40 patients with NF2 (total of 45 tumors treated) who underwent radiosurgery between 1987 and 1998.

Serial imaging studies, clinical evaluations, and a patient survey were performed. The average tumor margin dose was 15 Gy, and the mean transverse tumor diameter was 22 mm. In patients with solitary tumors, prior resection had been performed in 111 patients (24%); 27 patients experienced tumor recurrence after a “total resection.”

The clinical tumor control rate (no resection required) was 98%. In non-NF2 patients followed for at least 5 years, 100 tumors (61.7%) were smaller, 53 (32.7%) remained unchanged in size, and nine (5.6%) were slightly larger. Resection was performed in four patients (2.4%). Neurological deficits after radiosurgery all occurred within the first 28 months. The rates of facial and trigeminal neuropathy varied with radiosurgery technique. In patients with NF2, 16 tumors were smaller, 28 remained unchanged, and one enlarged (overall 98% control rate at median 3-year follow up). Resection was performed in three patients (7%). Useful hearing was preserved in six (43%) of 14 NF2 patients who had useful hearing before radiosurgery.

Radiosurgery provided long-term tumor control associated with high rates of neurological function preservation. No further tumor surgery was necessary in 98% of patients with solitary tumors followed for a minimum of 5 years.

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Brian R. Subach, Douglas Kondziolka, L. Dade Lunsford, David J. Bissonette, John C. Flickinger, and Ann H. Maitz

Object

Stereotactically guided radiosurgery is one of the primary treatment modalities for patients with acoustic neuromas (vestibular schwannomas). The goal of radiosurgery is to arrest tumor growth while preserving neurological function. Patients with acoustic neuromas associated with neurofibromatosis Type 2 (NF2) represent a special challenge because of the risk of complete deafness. To better define the tumor control rate and long-term functional outcome, the authors reviewed their 10-year experience in treating these lesions.

Methods

Forty patients underwent stereotactic radiosurgery at the University of Pittsburgh, 35 of them for solitary tumors. The other five underwent staged procedures for bilateral lesions (10 tumors, 45 total). Thirteen patients (with 29% of tumors) had undergone a median of two prior resections. The mean tumor volume at radiosurgery was 4.8 ml and the mean tumor margin dose was 15 Gy (range 12–20 Gy).

The overall tumor control rate was 98%. During the median follow-up period of 36 months, 16 (36%) tumors regressed, 28 (62%) remained unchanged, and one (2%) grew. In the 10 patients for whom more than 5 years of clinical and neuroimaging follow-up results were available (median 92 months), five tumors were smaller and five remained unchanged. Surgical resection was performed in three patients (7%) after radiosurgery; only one showed radiographic evidence of progression. Useful hearing (Gardner-Robertson Class I or II) was preserved in six (43%) of 14 patients and this rate improved to 67% after modifications made in 1992. Normal facial nerve function (House-Brackmann Grade 1) was preserved in 25 (81%) of 31 patients. Normal trigeminal nerve function was preserved in 34 (94%) of 36 patients.

Conclusions

Stereotactically guided radiosurgery is a safe and effective treatment for patients with acoustic tumors in the setting of NF2. The rate of hearing preservation may be better with radiosurgery than with other available techniques.

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Douglas Kondziolka, Atul Patel, L. Dade Lunsford, and John C. Flickinger

Object

Multiple brain metastases are a common health problem, frequently found in patients with cancer. The prognosis, even after treatment with whole-brain radiation therapy (WBRT), is poor, with an average expected survival time of less than 6 months. Investigators at numerous centers have evaluated the role of stereotactic radiosurgery in retrospective case series of patients harboring solitary or multiple tumors. Tumor resection is used mainly for patients with large tumors that cause acute neurological syndromes. The authors conducted a randomized trial in which they compared radiosurgery combined with WBRT with WBRT alone.

Methods

Twenty-seven patients were randomized (14 to recieve WBRT alone and 13 to receive WBRT combined with radiosurgery). The rate of local failure at 1 year was 100% after WBRT alone but only 8% in patients in whom boost radiosurgery was performed. The median time to local failure was 6 months after WBRT alone (95% confidence interval (CI) 3.5–8.5) in comparison to 36 months (95% CI 15.6–57) after WBRT and radiosurgery (p = 0.0005). The median time to the development of any brain failure was improved in the combined modality group (p = 0.002). Survival was shown to be related to the extent of extracranial disease (p = 0.02).

Conclusions

Combined WBRT and radiosurgery for the treatment of patients with two to four brain metastases significantly improves control of brain disease. Whole-brain radiation therapy alone does not provide lasting and effective care when treating most patients. Surgical resection remains important for patients with large symptomatic tumors and in whom limited extracranial disease has been demonstrated.

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Douglas Kondziolka, Lawrence Wechsler, Elizabeth Tyler-Kabara, and Cristian Achim

Cellular therapy has been evaluated in small animals, subhuman primates, and now humans for the potential repair of brain injury due to stroke. Experimental striate stroke models have proven useful for the purpose of evaluating different treatment paradigms. Early clinical trials involving neuronal transplantation in patients suffering motor-related stroke in the basal ganglia region have begun.

This research will be described in this report.

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Douglas Kondziolka, L. Dade Lunsford, and John C. Flickinger

Management options for patients with vestibular schwannomas (acoustic neuromas) include observation, tumor resection, stereotactic radiosurgery, and fractionated radiotherapy. In this report the authors review their 15-year experience with radiosurgery and discuss indications and expectations in relation to the different approaches. They conducted a survey of neurosurgeons to determine management preferences in two different cases of intra- and extra-canalicular tumor presentations. Patient decisions must be based on quality information derived from peer-reviewed literature.

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Jason P. Sheehan, Douglas Kondziolka, John Flickinger, and L. Dade Lunsford

Object

Nonfunctioning pituitary adenomas comprise approximately 30% of all pituitary tumors. The purpose of this retrospective study was to evaluate the efficacy and role of gamma knife surgery (GKS) in the treatment of these lesions.

Methods

The authors conducted a review of cases in which GKS was performed at the University of Pittsburgh between 1987 and 2001. Forty-six patients with nonfunctioning pituitary adenomas and with at least 6 months of follow-up data were identified. In 41 of these patients some form of prior treatment such as transsphenoidal resection, craniotomy and resection, or conventional radiation therapy had been conducted. Five patients were deemed ineligible for microsurgery, and GKS served as the primary treatment modality. Endocrinological, ophthalmological, and radiological responses were evaluated. The mean radiation dose to the margin was 16 Gy.

In all patients with microadenomas and 91% of those with macroadenomas tumor control was demonstrated after radiosurgery. Gamma knife surgery had essentially equal efficacy in terms of achieving tumor control in cases of adenomas with cavernous sinus invasion and suprasellar extension. No new endocrinopathies were noted following radiosurgery. In two patients, however, tumor growth and decline in visual function occurred.

Conclusions

Gamma knife surgery is safe and effective in treating nonfunctioning pituitary adenomas. Radiosurgery may serve as a primary treatment modality in some or as a salvage treatment in others. Treatment must be tailored to meet the patient's symptoms, overall health, and tumor morphometry.

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Costas G. Hadjipanayis, Douglas Kondziolka, John C. Flickinger, and L. Dade Lunsford

Object

This study was conducted to examine the role of radiosurgery in the management of patients with recurrent or unresectable low-grade astrocytomas.

Methods

During a 13-year interval, 49 patients underwent stereotactic radiosurgery as part of multimodal treatment of their recurrent or unresectable low-grade astrocytomas. Thirty-seven of these patients (median age 14 years) harbored pilocytic astrocytomas and 12 patients harbored World Health Organization (WHO) Grade II fibrillary astrocytomas (median age 25 years). Tumors involved the brainstem in 22 cases, cerebellum in four, thalamus in six, temporal lobe in five, frontal lobe in four, and parietal lobe in three, as well as the hypothalamus, corpus callosum, insular cortex, optic tract, and third ventricle in one patient each. Each diagnosis was confirmed with the aid of stereotactic biopsy sampling in 17 patients, open biopsy sampling in five, partial resection in 13, and near-total resection in 14. Multimodal treatment included fractionated radiotherapy in 14 patients, stereotactic intracavitary irradiation in five, chemotherapy in two, cyst drainage in eight, ventriculoperitoneal shunt placement in five, and additional cytoreductive surgery in five. Tumor volumes ranged from 0.42 to 45.1 cm3. The median radiosurgical dose to the tumor margin was 15 Gy (range 9.6–22.5 Gy).

After radiosurgery, serial neuroimaging demonstrated complete tumor resolution in 11 patients, reduced tumor volume in 12, stable tumor volume in 10, and delayed tumor progression in 16. No procedure-related death was encountered. Forty-five of 49 patients are alive at a median follow-up period of 32 months after radiosurgery and 63 months after diagnosis. Sixteen patients participated in follow-up review for more than 60 months. Three patients died of local tumor progression.

Conclusions

Stereotactic radiosurgery is a potential alternative or adjunctive intervention in the management of selected patients with pilocytic or WHO Grade II fibrillary astrocytomas, usually performed for small-volume tumors in an attempt to avoid larger-field fractionated radiotherapy.

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Douglas Kondziolka and L. Dade Lunsford

Object

In the management of trigeminal neuralgia (TN), physicians seek rapid and long-lasting pain relief, together with preservation of trigeminal nerve function. Percutaneous retrogasserian glycerol rhizotomy (PRGR) offers distinct advantages over other available procedures. The aim of this report was to provide details of the PRGR procedure and its expected outcome.

Methods

The authors reviewed their experience with PRGR in 1174 patients to evaluate the procedural technique, results, and complications. Although it is clear that TN is not a static disorder but one characterized by remissions and recurrences, long-lasting pain relief was noted in 77% of patients, with 55% discontinuing all medications and 22% requiring some drug usage.

Conclusions

The authors discuss the role of PRGR in their practice, along with other procedures such as microvascular decompression and gamma knife surgery, for idiopathic or multiple sclerosis–related TN. They conclude that PRGR had distinct advantages over other procedures, which include eliminating the need for intraoperative confirmatory sensory testing, and a lower risk of facial sensory loss.

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Douglas Kondziolka and Lawrence Wechsler

✓ Stroke is a common cause of death and disability. The role of cellular transplantation to promote functional recovery has been explored. Preclinical studies first established the potential for cultured neuronal cells derived from a teratocarcinoma cell line to be tested for safety and efficacy in the treatment of human stroke. In animal models of stroke that caused reproducible learning and motor deficits, injection of neuronal cells resulted in a return of learning behavior retention time and motor function. In this report the authors review several current concepts for cellular repair, discuss important patient selection and surgical technique issues, and discuss plans for future experiments.