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Douglas Kondziolka

Publications and source records attributed to Douglas Kondziolka.

At least 19 recordsLinked to original sources
PubMed2006

Gamma knife radiosurgery for refractory epilepsy caused by hypothalamic hamartomas.

BACKGROUND: Hypothalamic hamartomas are associated with precocious puberty and chronic epilepsy characterized by gelastic seizures. The seizure disorder is usually refractory to most antiepileptic drugs. Gamma knife surgery has emerged as an alternative to microsurgical removal or radiofrequency ablation to improve seizure control. We present our experience with radiosurgery in 4 patients afflicted by this disorder. METHODS: Using gamma knife radiosurgery, 4 patients with intractable gelastic seizures and complex epilepsy were managed. Patient age varied from 5 to 29 years. The duration of symptoms was 4-28 years. A conformal radiosurgery plan was designed with a mean of 4.25 isocenters to cover the hamartoma at the 50% isodose line. A mean margin dose of 17.5 Gy was used. The clinical outcome was evaluated with the Engel scale. RESULTS: No complication occurred. After a median follow-up of 22 months, 3 patients had shown some improvement, with 2 attaining Engel class II status. CONCLUSION: Gamma knife surgery is a promising alternative to microsurgical removal for patients with refractory epilepsy caused by hypothalamic hamartomas.

Adolescent↗
PubMed2006

Cerebral metastases pathology after radiosurgery: a multicenter study.

BACKGROUND: To the authors' knowledge, comprehensive human pathologic investigations that explore fundamental radiosurgical effects on metastatic brain tumors are sparse in the literature. The objective of this study was to analyze histopathologic findings in a set of clinically recurrent cerebral metastases after patients underwent stereotactic radiosurgery (SRS). METHODS: In a series of 7500 patients who underwent radiosurgery, 2020 patients (27%) harbored cerebral metastases. Eighteen of 2020 patients (0.9%) underwent subsequent craniotomy for tumor removal anywhere from 1 month to 59 months after they received high-dose irradiation. Histologic and immunohistochemical investigations were performed on the surgically resected tissue specimens. These specimens were within the radiosurgical treatment volume of the metastatic tumor. RESULTS: Light microscopy revealed 3 basic categories of histologic responses: acute-type, subacute-type, and chronic-type tissue reactions. A moderate-to-intense inflammatory cell reaction was seen in the tissue responses of well controlled neoplasms (i.e., in patients who had neoplasms that required craniotomy for recurrent disease > 5 months after SRS), whereas the inflammatory reaction was missing or sparse in poorly controlled neoplasms (patients who required craniotomy for recurrent disease < 5 months after SRS). This reaction was seen within the irradiated tumor volume and not in the peritumoral area nor in areas remote from the radiosurgical treatment volume. Immunohistochemical characterization demonstrated the presence of prominent CD68-positive macrophage and CD3-positive T-lymphocyte populations. A progressively severe vasculopathy also was observed with increasing time after radiosurgery. CONCLUSIONS: Although causality has not been established, a brisk inflammatory response and more severe vasculopathy were observed in lesions in which recurrences were more delayed.

Adult↗
PubMed2006

Cell transplantation for ischemic stroke.

Cell replacement therapy has been evaluated as a regenerative strategy for patients with fixed neurologic deficits after ischemic stroke. Animal models have identified specific cell lines which lead to regeneration and improvement in behavior and motor function after implantation into areas of ischemic injury. This has led to the development of pilot studies in humans, which have mainly investigated the safety and pilot efficacy of such approaches with promising early results. As research in this area progresses, further prospective trials are necessary not only to demonstrate clinical efficacy but also to understand the mechanisms underlying the early positive experiences, to select appropriate patients for cell replacement therapy, and to elucidate the optimal timing and mode of cell delivery.

Animals↗
PubMed2006

Prospective staged volume radiosurgery for large arteriovenous malformations: indications and outcomes in otherwise untreatable patients.

OBJECTIVE: The obliteration response of an arteriovenous malformation (AVM) to radiosurgery is strongly dependent on dose and volume. For larger volumes, the dose must be reduced for safety, but this compromises obliteration. In 1992, we prospectively began to stage anatomic components in order to deliver higher single doses to symptomatic AVMs >15 ml in volume. METHODS: During a 17-year interval at the University of Pittsburgh, 1040 patients underwent radiosurgery for a brain AVM. Out of 135 patients who had multiple procedures, 37 patients underwent prospectively staged volume radiosurgery for symptomatic otherwise unmanageable larger malformations. Twenty-eight patients who were managed before 2002 were included in this study to achieve sufficient follow-up in assessing the outcomes. The median age was 37 years (range, 13-57 yr). Thirteen patients had previous hemorrhages and 13 patients had attempted embolization. Separate anatomic volumes were irradiated at 3 to 8 months (median, 5 mo) intervals. The median initial AVM volume was 24.9 ml (range, 10.2-57.7 ml). Twenty-six patients had two stages and two had three-stage radiosurgery. Seven patients had repeat radiosurgery after a median interval of 63 months. The median target volume was 12.3 ml. (range, 4.2-20.8 ml.) at Stage I and 11.5 ml. (range, 2.8-22 ml.) at Stage II. The median margin dose was 16 Gy at both stages. Median follow-up after the last stage of radiosurgery was 50 months (range, 3-159 mo). RESULTS: Four patients (14%) sustained a hemorrhage after radiosurgery; two died and two patients recovered with mild permanent neurological deficits. Worsened neurological deficits developed in one patient. Seizure control was improved in three patients, was stable in eight patients and worsened in two. Magnetic resonance imaging showed T2 prolongation in four patients (14%). Out of 28 patients, 21 had follow-up more than 36 months. Out of 21 patients, seven underwent repeat radiosurgery and none of them had enough follow- up. Of 14 patients followed for more than 36 months, seven (50%) had total, four (29%) near total, and three (21%) had moderate AVM obliteration. CONCLUSIONS: Prospective staged volume radiosurgery provided imaging defined volumetric reduction or closure in a series of large AVMs unsuitable for any other therapy. After 5 years, this early experience suggests that AVM related symptoms can be stabilized and anticipated bleed rates can be reduced.

Adolescent↗
PubMed2005

Long-term survivors after gamma knife radiosurgery for brain metastases.

BACKGROUND: Stereotactic radiosurgery, with or without whole-brain radiation therapy, has become a valued management choice for patients with brain metastases, although their median survival remains limited. In patients who receive successful extracranial cancer care, patients who have controlled intracranial disease are living longer. The authors evaluated all brain metastasis in patients who lived for > or = 4 years after radiosurgery to determine clinical and treatment patterns potentially responsible for their outcome. METHODS: Six hundred seventy-seven patients with brain metastases underwent 781 radiosurgery procedures between 1988 and 2000. Data from the entire series were reviewed; and, if patients had > or = 4 years of survival, then they were evaluated for information on brain and extracranial treatment, symptoms, imaging responses, need for further care, and management morbidity. These long-term survivors were compared with a cohort who lived for < 3 months after radiosurgery (n = 100 patients). RESULTS: Forty-four patients (6.5%) survived for > 4 years after radiosurgery (mean, 69 mos with 16 patients still alive). The mean age at radiosurgery was 53 years (maximum age, 72 yrs), and the median Karnofsky performance score (KPS) was 90. The lung (n = 15 patients), breast (n = 9 patients), kidney (n = 7 patients), and skin (melanoma; n = 6 patients) were the most frequent primary sites. Two or more organ sites outside the brain were involved in 18 patients (41%), the primary tumor plus lymph nodes were involved in 10 patients (23%), only the primary tumor was involved in 9 patients (20%), and only brain disease was involved in 7 patients (16%), indicating that extended survival was possible even in patients with multiorgan disease. Serial imaging of 133 tumors showed that 99 tumors were smaller (74%), 22 tumors were unchanged (17%), and 12 tumors were larger (9%). Four patients had a permanent neurologic deficit after brain tumor management, and six patients underwent a resection after radiosurgery. Compared with the patients who had limited survival (< 3 mos), long-term survivors had a higher initial KPS (P = 0.01), fewer brain metastases (P = 0.04), and less extracranial disease (P < 0.00005). CONCLUSIONS: Although the expected survival of patients with brain metastases may be limited, selected patients with effective intracranial and extracranial care for malignant disease can have prolonged, good-quality survival. The extent of extracranial disease at the time of radiosurgery was predictive of outcome, but this does not necessarily mean that patients cannot live for years if treatment is effective.

Adult↗
PubMed2005

Stereotactic radiosurgery for four or more intracranial metastases.

PURPOSE: To evaluate the outcomes after a single stereotactic radiosurgery procedure for the care of patients with 4 or more intracranial metastases. METHODS AND MATERIALS: Two hundred five patients with primary malignancies, including non-small-cell lung carcinoma (42%), breast carcinoma (23%), melanoma (17%), renal cell carcinoma (6%), colon cancer (3%), and others (10%) underwent gamma knife radiosurgery for 4 or more intracranial metastases at one time. The median number of brain metastases was 5 (range, 4-18) with a median total treatment volume of 6.8 cc (range, 0.6-51.0 cc). Radiosurgery was used as sole management (17% of patients), or in combination with whole brain radiotherapy (46%) or after failure of whole brain radiotherapy (38%). The median marginal radiosurgery dose was 16 Gy (range, 12-20 Gy). The mean follow-up was 8 months. RESULTS: The median overall survival after radiosurgery for all patients was 8 months. The 1-year local control rate was 71%, and the median time to progressive/new brain metastases was 9 months. Using the Radiation Therapy Oncology Group recursive partitioning analysis (RPA) classification system, the median overall survivals for RPA classes I, II, and III were 18, 9, and 3 months, respectively (p < 0.00001). Multivariate analysis revealed total treatment volume, age, RPA classification, and marginal dose as significant prognostic factors. The number of metastases was not statistically significant (p = 0.333). CONCLUSION: Radiosurgery seems to provide survival benefit for patients with 4 or more intracranial metastases. Because total treatment volume was the most significant predictor of survival, the total volume of brain metastases, rather than the number of metastases, should be considered in identifying appropriate radiosurgery candidates.

Adolescent↗
PubMed2005

The impact of whole-brain radiation therapy on the long-term control and morbidity of patients surviving more than one year after gamma knife radiosurgery for brain metastases.

PURPOSE: To better analyze how whole-brain radiotherapy (WBXRT) affects long-term tumor control and toxicity from the initial stereotactic radiosurgery (SRS) for brain metastases, we studied these outcomes in patients who had survived at least 1 year from SRS. METHODS AND MATERIALS: We evaluated the results of gamma knife radiosurgery for 160 brain metastases in 110 patients who were followed for a median of 18 months (range, 12-122 months) after SRS. Eighty-two patients had a solitary brain metastasis and 28 patients had multiple metastases. Seventy patients (116 tumors) were treated with initial radiosurgery and WBXRT, whereas 40 patients (44 lesions) initially received radiosurgery alone. Median treatment volume was 1.9 cc in the entire group, 2.3 cc in the WBXRT group, and 1.6 cc in the SRS alone group. Median tumor dose was 16 Gy (range, 12-21 Gy). RESULTS: At 1, 3, and 5 years, local tumor control was 84.1% +/- 5.5%, 68.6% +/- 8.7%, and 68.6% +/- 8.7% with SRS alone compared with 93.1% +/- 2.4%, 87.7% +/- 4.9%, and 65.7% +/- 10.2%. with concurrent WBXRT and SRS (p = 0.0228, univariate). We found that WBXRT improved local control in patient subsets tumor volume > or =2 cc, peripheral dose < or =16 Gy, single metastases, nonradioresistant tumors, and lung cancer metastases (p = 0.0069, 0.0080, 0.0083, 0.0184, and 0.0348). Distal intracranial failure developed at 1, 3, and 5 years in 26.0% +/- 7.1%, 74.5% +/- 9.4%, and 74.5% +/- 9.4% with SRS alone compared with 20.7% +/- 4.9%, 49.0% +/- 8.7%, and 61.8% +/- 12.8% with concurrent WBXRT and SRS (p = 0.0657). We found a trend for improved distal intracranial control with WBXRT for only nonradioresistant tumors (p = 0.054). Postradiosurgery complications developed in 2.8% +/- 1.2% and 10.7% +/- 3.5% at 1 and 3-5 years and was unaffected by WBXRT (p = 0.7721). WBXRT did not improve survival in the entire series (p = 0.5027) or in any subsets. CONCLUSIONS: In this retrospective study of 1-year survivors of SRS for brain metastases, the addition of concurrent WBXRT to SRS was associated with an improved local control rate in patient subsets with tumor volume > or =2 cc, peripheral dose < or =16 Gy, single metastases, nonradioresistant tumors, and specifically lung cancer metastases. A trend was noted for improved distal intracranial control for patients having nonradioresistant tumors. Distant intracranial relapse >1 year posttreatment is a significant problem with or without initial WBXRT.

Adolescent↗
PubMed2005

Individualized treatment of pediatric craniopharyngiomas.

OBJECTIVE: The treatment of children with craniopharyngiomas should be individualized because of their heterogeneous clinical and radiographic characteristics. We performed this study to correlate the clinical and radiographic features at the time of presentation with the multimodality treatments the children received. METHODS: Medical records were reviewed for children with craniopharyngiomas who presented to the Children's Hospital of Pittsburgh for their initial management between 1983 and 2004. Children were treated with microsurgical tumor resections (27), intracavitary irradiation with phosphorus 32 (32P) (12), and with gamma knife stereotactic radiosurgery (GKSR) (5). CONCLUSIONS: There were no deaths in any treatment group. Gross total resections were thought to be performed in 18 patients and were confirmed by imaging in 13 of the 18 patients. The primary operative morbidities were hormonal and visual. Every child needed at least two replacement hormones and most had panhypopituitarism. Vision worsened postoperatively in 5 of 27 children. There was no operative morbidity or mortality from 32P. After 32P treatment, one child required a later cyst aspiration and one required a craniotomy for progressive cyst enlargement. There was no morbidity or mortality from GKSR, which achieved tumor stabilization or shrinkage in 4 of 5 cases. Resections, 32P, and GKSR are complimentary treatment modalities for children with craniopharyngiomas. Their indications and outcomes differ, but all should be available in the treatment armamentarium.

Adolescent↗
PubMed2005

Percutaneous retrogasserian glycerol rhizotomy for trigeminal neuralgia: technique and expectations.

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.

Glycerol↗
PubMed2005

The characterization of tumor apoptosis after experimental radiosurgery.

We sought to evaluate whether radiosurgery induces apoptosis in an experimental glioma model and to elucidate the time course of this radiobiologic phenomenon. Fischer 344 rats harboring established intracranial 9L gliosarcomas underwent radiosurgery (n = 42) or no radiosurgery (n = 45). Animals were sacrificed at 3, 6, 12, 24, 48, 72 h, and 1 or 2 weeks after treatment and in situ tumor apoptosis was assessed by specific staining. Tumor apoptosis was noted to be statistically higher in radiosurgery-treated animals relative to controls at the 6-, 24-, and 48-hour time points following radiosurgery. Radiosurgery induces apoptosis in the rat intracranial 9L gliosarcoma in a time-dependent fashion. The time course of this radiobiologic phenomenon begins at approximately 6 h following radiosurgery, continues up to 48 h, and begins to decline by 72 h.

Animals↗
PubMed2005

Radiosurgery for dural arteriovenous fistulas.

OBJECTIVE: Dural arteriovenous fistulas (DAVFs) comprise 10% to 15% of all arteriovenous malformations. Recent studies have demonstrated promising results when radiosurgery is used for DAVFs. We retrospectively analyzed our patients with DAVFs who received stereotactic radiosurgery with or without embolization. METHODS: Between 1991 and 2002, 18 patients with 23 angiographically confirmed symptomatic DAVFs underwent gamma knife radiosurgery, either alone (n = 8) or in combination with embolization (n = 10). A retrospective chart review was performed to identify DAVF location, venous drainage pattern, radiosurgery dosimetry, clinical outcomes, and imaging results. The series included 9 men and 9 women with a mean age of 65 (range 50-89) years. Nine patients received particulate, coil, and/or absolute ethanol embolization before radiosurgery, and 1 patient received particulate embolization after radiosurgery. The mean duration of clinical follow-up was 43 (range 2-116) months. The mean margin radiosurgery dose was 20 (range 15-30) Gy. RESULTS: Nine patients had complete resolution of their presenting symptoms, and 9 patients had resolution of all but 1 of their presenting symptoms. Angiographic follow-up (mean 46 months) was performed on 8 patients demonstrating complete obliteration in all the cases. Seven patients evaluated by magnetic resonance angiography or computed tomography angiography showed no evidence of DAVF (4 patients) or decreased DAVF size (3 patients). After radiosurgery, 1 patient developed a temporary hemiparesis. Two permanent neurological deficits occurred after embolization before radiosurgery. No patient had an intracranial hemorrhage after treatment. CONCLUSION: Stereotactic radiosurgery provides effective long-term relief of symptoms in selected patients with DAVFs.

Aged↗
PubMed2005

Indications for resection and radiosurgery for brain metastases.

PURPOSE OF REVIEW: This review is focused on indications for resection, stereotactic radiosurgery, and fractionated radiotherapy for patients with single or multiple brain metastases. Our purpose is to summarize the indications and effect of these management approaches. RECENT FINDINGS: Brain metastases are a frequent challenge in patients with extracranial solid cancers. More than 40% of patients with cancer will develop metastases to the brain. While some patients present with large lesions and symptoms related to mass effect, many are diagnosed when asymptomatic tumors are found on screening studies. The main options for patients with brain metastases are whole brain radiation therapy, surgical resection, and stereotactic radiosurgery. Much information regarding outcomes, survival, management morbidity, and quality of life is available. Randomized, class III clinical trials demonstrate that multimodal therapy is important for both life quality and extended survival. A better understanding of the current therapeutic options should result in improvements in patient care. SUMMARY: This is a review of the literature from May 2004 to June 2005 with special attention on publications related to effect on quality of life with different procedures and therapies.

Brain Neoplasms↗
PubMed2005

Radiosurgery with or without whole-brain radiotherapy for brain metastases: the patients' perspective regarding complications.

INTRODUCTION: When cancer spreads to the brain, patients and their families report a much reduced quality of life. Whole-brain radiation therapy (WBRT) and/or radiosurgery (RS) are mainstays of management for patients with metastatic brain cancer. Despite the ubiquity of this problem, little is known about the patients' perspective regarding management-related complications. To assess the patients' perspective regarding current therapeutic options, we retrospectively surveyed 200 consecutive patients who underwent radiosurgery with or without WBRT. METHODS AND MATERIALS: The survey consisted of 10 questions that sought information on quality of life, employment status, side effects (hair loss, fatigue, memory, concentration, mood, or employment), activity level, and satisfaction. RESULTS: We tabulated 104 responses (52%). WBRT was used in 69% (72 of 104); all patients had radiosurgery. After WBRT, the following were noted: hair loss (88%; total regrowth in 24%), excess fatigue (95%), problems with short-term memory (72%), long-term memory (33%), concentration (61%), and depression (54%). Sixty-three percent of patients who had WBRT thought they had side effects after treatment compared with 34% who had radiosurgery only (P <0.001). Only 5% of RS patients reported fatigue. Seventy-six percent and 56% of respondents considered RS or WBRT, respectively, a good treatment of them (P = 0.25). Only 26 patients (27%) were employed at the time of treatment and 16 remained employed (62%). Eighteen percent believed that WBRT delayed other cancer treatments. CONCLUSIONS: Patients with brain metastases often report complications of their disease or its treatment. Side effects are most pronounced in those who received WBRT. Radiosurgery had fewer reported side effects and was believed by more patients or families to be effective. Further study of clinical outcomes and quality of life is important to guide our management of patients with these common brain tumors.

Adult↗
PubMed2005

Stereotactic radiosurgery for pituitary adenomas: an intermediate review of its safety, efficacy, and role in the neurosurgical treatment armamentarium.

OBJECT: Pituitary adenomas are very common neoplasms, constituting between 10 and 20% of all primary brain tumors. Historically, the treatment armamentarium for pituitary adenomas has included medical management, microsurgery, and fractionated radiotherapy. More recently, radiosurgery has emerged as a viable treatment option. The goal of this research was to define more fully the efficacy, safety, and role of radiosurgery in the treatment of pituitary adenomas. METHODS: Medical literature databases were searched for articles pertaining to pituitary adenomas and stereotactic radiosurgery. Each study was examined to determine the number of patients, radiosurgical parameters (for example, maximal dose and tumor margin dose), duration of follow-up review, tumor growth control rate, complications, and rate of hormone normalization in the case of functioning adenomas. A total of 35 peer-reviewed studies involving 1621 patients were examined. Radiosurgery resulted in the control of tumor size in approximately 90% of treated patients. The reported rates of hormone normalization for functioning adenomas varied substantially. This was due in part to widespread differences in endocrinological criteria used for the postradiosurgical assessment. The risks of hypopituitarism, radiation-induced neoplasia, and cerebral vasculopathy associated with radiosurgery appeared lower than those for fractionated radiation therapy. Nevertheless, further observation will be required to understand the true probabilities. The incidence of other serious complications following radiosurgery was quite low. CONCLUSIONS: Although microsurgery remains the primary treatment modality in most cases, stereotactic radiosurgery offers both safe and effective treatment for recurrent or residual pituitary adenomas. In rare instances, radiosurgery may be the best initial treatment for patients with pituitary adenomas. Further refinements in the radiosurgical technique will likely lead to improved outcomes.

Adenoma↗
PubMed2005

Gamma knife surgery for glomus jugulare tumors: an intermediate report on efficacy and safety.

OBJECT: Glomus jugulare tumors are rare tumors that commonly involve the middle ear, temporal bone, and lower cranial nerves. Resection, embolization, and radiation therapy have been the mainstays of treatment. Despite these therapies, tumor control can be difficult to achieve particularly without undo risk of patient morbidity or mortality. The authors examine the safety and efficacy of gamma knife surgery (GKS) for glomus jugulare tumors. METHODS: A retrospective review was undertaken of the results obtained in eight patients who underwent GKS for recurrent, residual, or unresectable glomus jugulare tumors. The median radiosurgical dose to the tumor margin was 15 Gy (range 12-18 Gy). The median clinical follow-up period was 28 months, and the median period for radiological follow up was 32 months. All eight patients demonstrated neurological stability or improvement. No cranial nerve palsies arose or deteriorated after GKS. In the seven patients in whom radiographic follow up was obtained, the tumor size decreased in four and remained stable in three. CONCLUSIONS: Gamma knife surgery would seem to afford effective local tumor control and preserves neurological function in patients with glomus jugulare tumors. If long-term results with GKS are equally efficacious, the role of stereotactic radiosurgery will expand.

Adult↗
PubMed2005

Radiosurgery for patients with recurrent small cell lung carcinoma metastatic to the brain: outcomes and prognostic factors.

OBJECT: Lung carcinoma is the leading cause of death from cancer. More than 50% of those with small cell lung cancer develop a brain metastasis. Corticosteroid agents, radiotherapy, and resection have been the mainstays of treatment. Nonetheless, median survival for patients with small cell lung carcinoma metastasis is approximately 4 to 5 months after cranial irradiation. In this study the authors examine the efficacy of gamma knife surgery for treating recurrent small cell lung carcinoma metastases to the brain following tumor growth in patients who have previously undergone radiation therapy, and they evaluate factors affecting survival. METHODS: A retrospective review of 27 patients (47 recurrent small cell lung cancer brain metastases) undergoing radiosurgery was performed. Clinical and radiographic data obtained during a 14-year treatment period were collected. Multivariate analysis was utilized to determine significant prognostic factors influencing survival. The overall median survival was 18 months after the diagnosis of brain metastases. In multivariate analysis, factors significantly affecting survival included: 1) tumor volume (p = 0.0042); 2) preoperative Karnofsky Performance Scale score (p = 0.0035); and 3) time between initial lung cancer diagnosis and development of brain metastasis (p = 0.0127). Postradiosurgical imaging of the brain metastases revealed that 62% decreased, 19% remained stable, and 19% eventually increased in size. One patient later underwent a craniotomy and tumor resection for a tumor refractory to radiosurgery and radiation therapy. In three patients new brain metastases were demonstrating on follow-up imaging. CONCLUSIONS: Stereotactic radiosurgery for recurrent small cell lung carcinoma metastases provided effective local tumor control in the majority of patients. Early detection of brain metastases, aggressive treatment of systemic disease, and a therapeutic strategy including radiosurgery can extend survival.

Adult↗
PubMed2005

Neurotransplantation for patients with subcortical motor stroke: a phase 2 randomized trial.

OBJECT: No definitive treatment exists to restore lost brain function following a stroke. Transplantation of cultured neuronal cells has been shown to be safe and effective in animal models of stroke and safe in a Phase 1 human trial. In the present study the authors tested the usefulness of human neuron transplantation followed by participation in a 2-month stroke rehabilitation program compared with rehabilitation alone in patients with substantial fixed motor deficits associated with a basal ganglia stroke. METHODS: Human neuronal cells (LBS-Neurons; Layton BioScience, Inc.) were delivered frozen and then thawed and formulated on the morning of surgery. The entry criteria in this randomized, observer-blinded trial of 18 patients included age between 18 and 75 years, completed stroke duration of 1 to 6 years, presence of a fixed motor deficit that was stable for at least 2 months, and no contraindications to stereotactic surgery. Patients were randomized at two centers to receive either 5 or 10 million implanted cells in 25 sites (seven patients per group) followed by participation in a stroke rehabilitation program, or to serve as a nonsurgical control group (rehabilitation only; four patients). The surgical techniques used were the same at both centers. All patients underwent extensive pre- and postoperative motor testing and imaging. Patients received cyclosporine A for 1 week before and 6 months after surgery. The primary efficacy measure was a change in the European Stroke Scale (ESS) motor score at 6 months. Secondary outcomes included Fugl-Meyer, Action Research Arm Test, and Stroke Impact Scale scores, as well as the results of other motor tests. Nine strokes were ischemic in origin and nine were hemorrhagic. All 14 patients who underwent surgery (ages 40-70 years) underwent uncomplicated surgeries. Serial evaluations (maximum duration 24 months) demonstrated no cell-related adverse serological or imaging-defined effects. One patient suffered a single seizure, another had a syncopal event, and in another there was burr-hole drainage of an asymptomatic chronic subdural hematoma. Four of seven patients who received 5 million cells (mean improvement 6.9 points) and two of seven who received 10 million cells had improved ESS scores at 6 months; however, there was no significant change in the ESS motor score in patients who received cell implants (p = 0.756) compared with control or baseline values (p = 0.06). Compared with baseline, wrist movement and hand movement scores recorded on the Fugl-Meyer Stroke Assessment instrument were not improved (p = 0.06). The Action Research Arm Test gross hand-movement scores improved compared with control (p = 0.017) and baseline (p = 0.001) values. On the Stroke Impact Scale, the 6-month daily activities score changed compared with baseline (p = 0.045) but not control (p = 0.056) scores, and the Everyday Memory test score improved in comparison with baseline (p = 0.004) values. CONCLUSIONS: Human neuronal cells can be produced in culture and implanted stereotactically into the brains of patients with motor deficits due to stroke. Although a measurable improvement was noted in some patients and this translated into improved activities of daily living in some patients as well, this study did not find evidence of a significant benefit in motor function as determined by the primary outcome measure. This experimental trial indicates the safety and feasibility of neuron transplantation for patients with motor stroke.

Adult↗