Stereotactic radiotherapy for the treatment of pituitary adenomas.

PURPOSE: The aim of this study was to retrospectively review local control and morbidity following stereotactic radiotherapy (SRT) for pituitary adenoma. METHODS: Between 1997 and 2004, 39 patients with pituitary adenomas received SRT. Median age was 56 years (range: 13 to 90 years). Thirty-three patients underwent incomplete transsphenoidal surgery prior to SRT and six had unresectable tumors. The largest tumor dimension varied from 1.7 to 6 cm (median: 3 cm). Tumor volume varied from 1.2 to 56 mL (median 10.5 mL). Thirty-five tumors were < or = 1 mm from the optic chiasm/nerve. Thirty-three tumors were non-functional. SRT was delivered by a dedicated linear accelerator (Novalis, Heimstetten, Germany). Beam collimation was achieved by a fixed circular collimator (five patients) or a micro-multileaf collimator (34 patients). Total dose varied from 4500 to 5040 cGy (median: 4860 cGy) and was prescribed at the 90 % isodose line. RESULTS: After a median follow-up of 32 months (range: 12 to 94 months), the local control rate was 100 %. Tumor size was stable in 26 patients and decreased in 13 patients. Hormone normalization did not occur following SRT. New endocrine deficiency occurred in six patients. No patient developed cranial nerve injury or second malignancy following treatment. CONCLUSIONS: SRT achieves a high rate of local control and a low rate of treatment-induced morbidity. SRT is applicable to pituitary adenomas in close proximity to the optic apparatus and tumors in excess of three centimeters in the greatest dimension. Further follow-up is necessary to establish the long-term outcome following SRT for pituitary adenomas.

Linear accelerator stereotactic radiosurgery for the treatment of gelastic seizures due to hypothalamic hamartoma.

PURPOSE: There are reports of successful gamma-knife stereotactic radiosurgery (SRS) for the treatment of gelastic seizures associated with a hypothalamic hamartoma. The authors reviewed the results of linear accelerator (LINAC) radiosurgery for patients with medically refractory gelastic seizures due to a sessile hypothalamic hamartoma. METHODS: Three patients with gelastic seizures received SRS between 2003 and 2004. All patients had associated partial complex and/or generalized seizures. One patient demonstrated aggressive behavior. Sessile hamartomas varying in diameter from 6 to 14 mm were identified by MRI. SRS was delivered to a single isocenter by a dedicated LINAC equipped with either a circular beam collimator or a micromultileaf collimator. Patients received 1500 to 1800 cGy prescribed at the 90 to 95 % isodose line. Seizure outcome was scored according to Engel's classification. RESULTS: Two patients became free of gelastic and partial complex/generalized seizures seven and nine months after radiosurgery. These patients remain free of seizures at 17 and 15 months, respectively, after treatment (Engle Class IA). One patient experienced a decline in gelastic seizure frequency nine months after treatment (Engle Class II) without significant reduction in aggressive behavior. Follow-up MRI demonstrated no change in the size or signal characteristics of any tumor. No patient developed post-treatment cranial neuropathy or hypothalamic-pituitary suppression. CONCLUSIONS: LINAC SRS represents a safe and effective therapeutic alternative for patients with medically refractory gelastic seizures due to unresectable hypothalamic hamartomas. Radiosurgery is associated with a latency of several months from treatment to reduction in seizure frequency. Further follow-up is required to establish the duration of seizure control following radiosurgery.

Dynamic arc radiosurgery field shaping: a comparison with static field conformal and noncoplanar circular arcs.

PURPOSE: Recent advances in field-shaping technology and linac multileaf collimator (MLC) integration have resulted in new approaches to performing stereotactic radiosurgery. We present a modeling study comparing the absolute dose distributions from three radiosurgery delivery techniques: a conventional approach utilizing noncoplanar circular arcs, a static field conformal approach, and a dynamic arc field-shaping approach. In the latter, the MLC leaves more in a continuous fashion, conforming to the beam's-eye-view projection of the target at every increment along the path of an arc. METHODS AND MATERIALS: For the analysis, we devised a simulated target consisting of three overlapping spheres. This was chosen because it offered a straightforward planning approach for all three techniques, primarily the multiple isocenter approach. In addition, three representative cases were selected from the prior radiosurgery experience. These range in increasing size, from 0.50 to 9.79 cm(3), and in complexity, requiring from 3 isocenters to 16 in the case of circular arcs. In each situation, the goals were twofold: (1) to cover the entire volume with as high an appropriate isodose level (90% in the case of the conformal and dynamic arc techniques, 50% in the case of circular collimators) while (2) minimizing the dose to normal brain and where applicable, any adjacent radiation-sensitive structures. Because of the latter requirement, a single isocenter circular arc approach was ruled out for the analysis. RESULTS: In the case of large or irregularly shaped lesions, the circular arc technique requires multiple isocenters, producing a high level of dose heterogeneity within the target volume. Both the static field and dynamic arc conformal techniques, as with all single isocenter approaches, produce a highly homogeneous dose throughout the target region. For a given large dose, peripheral dose is decreased as additional beams or arc degrees are added with either of the conformal approaches. Dose--volume histogram analysis evaluating the peripheral dose shows that, in many cases, dose to surrounding structures can be reduced through the use of a conformal static or dynamic arc approach over the conventional multiple isocenter, circular arc techniques. CONCLUSIONS: Dynamic arc shaping is an efficient and effective method for accurately delivering a homogeneous target dose while simultaneously minimizing peripheral dose in radiosurgery applications.

Staged bilateral pallidotomy for treatment of Parkinson disease.

OBJECT: Several investigators have described the motor benefits derived from performing unilateral stereotactic pallidotomy for the treatment of Parkinson disease (PD), but little is known about the efficacy and complication rates of bilateral procedures. The goal of this study was to assess both these factors in 12 patients. METHODS: Eleven patients with medically intractable PD underwent staged bilateral pallidotomy and one patient underwent a simultaneous bilateral procedure. Unilateral pallidotomy resulted in an improvement in the patients' Unified Parkinson Disease Rating Scale (UPDRS) total scores and motor subscores, Hoehn and Yahr stages, and Schwab and England Activities of Daily Living scores. There were no complications. The second procedures were performed 5 to 25 months after the first, and nearly complete 3-month follow-up data are available for eight of these patients. Staged bilateral pallidotomy did result in further improvements in some symptoms, but the patients proved to be less responsive to levodopa. In contrast to outcomes of the initial unilateral pallidotomy, there were significant complications. One patient suffered an acute stroke, two patients suffered delayed infarctions of the internal capsule, four patients had mild-to-moderate worsening of speech and increased drooling, and one patient complained of worsening memory. CONCLUSIONS: Bilateral pallidotomy results in modest benefits but is associated with an increased risk of complications.

Long-term methamphetamine-induced decreases of [(11)C]WIN 35,428 binding in striatum are reduced by GDNF: PET studies in the vervet monkey.

The effects of glial cell line-derived neurotrophic factor (GDNF) pretreatment on methamphetamine (METH)-induced striatal dopamine system deficits in the vervet monkey were characterized with [(11)C]WIN 35,428 (WIN)-positron emission tomography (PET). WIN, a cocaine analog that binds to the dopamine transporter (DAT), was used to provide an index of striatal dopamine terminal integrity. In two subjects, GDNF (200 microg/40 microl) was injected into the caudate and putamen unilaterally vs. saline contralaterally. After 1-2 weeks, + and -GDNF striatal WIN-PET binding values were equivalent as calculated by multiple time graphic analysis, suggestive of an absence of unilateral DAT up-regulation. Three other subjects (n = 3) received GDNF injections into the caudate and putamen unilaterally and one week later, were administered METH HCl (2 x 2 mg/kg; i.m., 24 hours apart; a neurotoxic dosage for this species). At 1 week post-METH, WIN-PET studies showed that mean WIN binding was decreased by 72% in the +GDNF and by 92% in the -GDNF striatum relative to pre-drug assessment values. Thus, GDNF pretreatment reduced the extent of METH-induced decreases in WIN binding. Subsequent WIN-PET studies (1.5-9-month range) showed a protracted recovery of WIN binding in each striatum, indicative of long-term but partially reversible METH neurotoxicity. Further, at each time point, WIN binding remained relatively higher in the +GDNF vs. -GDNF striatum. These results provide further evidence that the adult non-human primate brain remains responsive to exogenously administered GDNF and that this pharmacotherapy approach can counteract aspects of neurotoxic actions associated with methamphetamine.

Stereotactic pallidotomy in the treatment of Parkinson disease: an expert opinion.

The objective of this workshop was to provide recommendations on several issues involving pallidotomy for patients with medically intractable Parkinson disease to physicians, patients, and other health care providers. An international consortium of experts in neurology, neurosurgery, and neurophysiology who had extensive experience with pallidotomy were invited to the workshop. Participants were sent background materials from the scientific literature for review-based participant recommendations. A proposed agenda was circulated to all participants before the workshop, and the final agenda was based on their recommendations. Topics were introduced at the workshop by members of the organizing committee, followed by extensive group discussion. A draft of a consensus statement, based on the previous day's discussion, was circulated and further modifications were made. The final statement was agreed on by all members. The conclusions of the participants were: (1) Pallidotomy should be performed only at centers that have a team of physicians with substantial expertise and experience in the field. (2) Patients with disabling idiopathic Parkinson disease, without dementia, and who have exhausted medical therapy should be considered for pallidotomy. (3) All patients should be examined by means of standardized rating scales both preoperatively and postoperatively to ensure quality of care at each center. (4) Symptoms that respond best to pallidotomy include medication-induced dyskinesias, rigidity, and tremor, while balance, gait disorders, and hypophonia are generally less responsive to surgery. Benefits of pallidotomy appear to be long lasting. (5) Each institution's complication rate should be discussed before surgery.

Fractionated stereotactic radiotherapy: rationale and methods.

Stereotactic radiosurgery (SRS) has become a widely accepted technique for the treatment intracranial neoplasms. Combined with modern imaging modalities, SRS has established its efficacy in a variety of indications. From the outset, however, it was recognized that the delivery of a single large dose of radiation was essentially "bad biology made better by good physics." To achieve the accuracy required to compensate for this biological shortcoming, the application of SRS has required that a neurosurgical head frame of some sort be rigidly attached to the patients head. Historically, this prerequisite has, primarily for practical reasons, precluded the delivery of multiple fractions over multiple days. With recent improvements in immobilization and repeat fixation, the good biology of fractionated delivery has been realized. This technique, which has come to be known as stereotactic radiotherapy (SRT), has significantly expanded the efficacy of the technique through the use of accurate physical targeting coupled with the basic radiobiological principles gleaned from decades of clinical experience.

Motor, cognitive, and behavioral performance following unilateral ventroposterior pallidotomy for Parkinson disease.

OBJECTIVE: To evaluate the effects of ventroposterior pallidotomy on motor disability and on behavior and cognition in patients with medically intractable idiopathic Parkinson disease. DESIGN: Detailed motor testing both while receiving and discontinuing levodopa medication, posturography, and neurocognitive and behavioral assessments were performed before and 3 to 6 months after unilateral ventroposterior pallidotomy. SETTING: University-based movement disorder program. PATIENTS: Thirty-two patients without dementia with medically refractory idiopathic Parkinson disease were studied. MAIN OUTCOME MEASURES: Motor function and disability were measured using the Unified Parkinson's Disease Rating Scale, Hoehn and Yahr stage, and the Schwab and England Activities of Daily Living Scale. Dynamic balance was measured by sway (amplitude and velocity) using the Chattecx Balance System. Detailed cognitive and behavioral assessments were also performed both before and after surgery. RESULTS: Eighty-three percent of patients experienced improvement of their total Unified Parkinson's Disease Rating Scale score at 3 to 6 months after surgery. Significant improvements were also seen in the contralateral Unified Parkinson's Disease Rating Scale motor subscore (78%) as well as in the contralateral Unified Parkinson's Disease Rating Scale total score both during the on and off period (78% and 79%, respectively). The Hoehn and Yahr stage, Schwab and England Activities of Daily Living Scale score, and dynamic balance when standing on foam also improved following unilateral pallidotomy in many patients. Cognitive performance remained relatively unchanged following surgery with the exception of category fluency, which exhibited a modest decline (P < .04). A significant improvement in depression was found on the Beck Depression Inventory. CONCLUSIONS: Ventroposterior pallidotomy significantly improves motor performance and daily level of function in Parkinson disease. Cognition and behavior are not adversely affected in patients without dementia, and a cognitive screening battery is proposed.

Surgical outcomes in pure frontal lobe epilepsy and foci that mimic them.

In this study we examined 37 subjects with a diagnosis of intractable frontal lobe epilepsy (FLE) based on non-invasive pre-surgical evaluation. Twenty-six underwent chronic intracranial ictal recordings (CIR) with video monitoring; 20 of these went on to surgical resection. Eleven underwent surgery without CIR. Retrospectively, we determined that 19 had pure FLE, 12 had frontal plus extrafrontal epileptogenic zones, and six others did not have FLE. We analysed the whole group and individual categories to evaluate the determinants of surgical outcome. Sixty percent of the pure frontal group is seizure free with all having > or = 75% reduction. The frontal-plus group had only 10% seizure free with 70% having > or = 75% reduction. Being in the pure frontal group was associated with better outcomes than the 'frontal-plus' group (P < 0.05; chi-square). Subjects with FSIQ > or = 85, focal pathologies and 18FDG-PET scans which were normal or had focal abnormalities (P < or = 0.05, all, chi-square) were more likely to have excellent outcomes. MRI abnormalities, surface EEG, and location and size of resection were not predictive of surgical outcomes. Rasmussen's encephalitis, incomplete surgical strategies and bilateral foci were apparent in those with poor outcomes, and surgical size predicted post-operative deficits (chi-square; P < 0.001). We conclude that careful, hypothesis-driven implants and operating procedures can result in good surgical outcomes for frontal lobe epilepsy subjects even when lesions are not apparent on routine neuroimaging.

Multiple radiation-induced intracranial lesions after treatment for pituitary adenoma. Case report.

This 53-year-old man presented with a syncopal episode 31 years after undergoing craniotomy and external-beam radiation for a pituitary macroadenoma. A gadolinium-enhanced magnetic resonance (MR) image of the brain demonstrated a 2.5-cm enhancing mass in the right caudate region that had not been seen on previous studies. A stereotactically guided biopsy procedure was performed to obtain specimens from the mass, which were consistent with ependymoma. The MR image also revealed two additional lesions that appeared to be within the radiation fields: a right temporal meningioma and a left frontal cavernous malformation. A review of the literature found three previous reports in which ependymomas presented after radiation therapy.

Reduction of hippocampal-kindled seizure activity in rats by stereotactic radiosurgery.

Radiosurgery may provide an alternative therapy for intractable epilepsy by eliminating or modifying abnormally active pacemaker neurons in epileptic foci. In the present study, the effect of radiosurgery on rat hippocampal kindling was examined. Rats received daily hippocampal stimulus trains until they were fully kindled. They then underwent radiosurgery of the kindled focus, receiving a single-dose of 0-, 10-, or 40-Gy. The 40-Gy group demonstrated an acute decrease in seizure threshold (3-5 days). Three months after radiosurgery, the threshold for seizures increased and the duration of afterdischarges decreased in the 40-Gy radiosurgery group compared to controls. The changes to both seizure threshold and afterdischarge duration were not significant in the 10-Gy group. These data suggest that radiosurgery is an effective means of reducing the epileptogenic activity of seizure foci.

Monte Carlo treatment planning for stereotactic radiosurgery.

OBJECTIVES: In radiosurgery treatment planning there is general acceptance that the target volume can be assumed to be homogeneous and that corrections for variations in contour are unnecessary. Thus, dose algorithms employed in radiosurgery treatment planning are quite unsophisticated; in almost every case the algorithms are the simple product of tissue-maximum and off-axis ratios and an output factor. In small photon beams, however, the lack of side scatter equilibrium compromises these assumptions. METHODS: In this work we have employed Monte Carlo techniques in an attempt to obtain a more accurate representation of radiosurgical dose distributions. Specifically, the Monte Carlo system which we have devised traces the paths of primary and secondary radiation through a patient-specific anatomical representation defined by computed tomography data. In this manner the perturbation effects from external contour changes and internal tissue heterogeneities are accounted for completely. The ability to precisely mimic multi-beam multi-arc stereotactic delivery has been incorporated into our Monte Carlo treatment planning interface. RESULTS: Subsequent calculations show that substantial differences can exist when homogeneity is not assumed. Tissue heterogeneities produce a lateral broadening of the beam, resulting in a smaller volume contained within the higher isodose levels (80-90%) with a corresponding increase in the volume treated at the lower isodose levels (<50%). CONCLUSIONS: These results suggest that further investigation and refinement of radiosurgery dose algorithms is in order.

Thoracoscopic sympathectomy: techniques and outcomes.

Thoracic sympathectomy is an important option in the treatment of palmar hyperhidrosis and pain disorders. Earlier surgical procedures were highly invasive with known morbidity, acceptable outcome, and established recurrence rates that were the limitations to considering surgical treatment. Thoracoscopic sympathectomy is a minimally invasive procedure that allows detailed visualization of the sympathetic ganglia and minimal postoperative morbidity; however, outcome studies of this technique have been limited. The authors treated 39 patients with 60 thoracoscopic procedures, and the outcomes in this small series were equivalent to previously established open surgical techniques; however, operative moribidity rates, hospital stay, and time of return to normal activity were substantially reduced. Complications and recurrence of symptoms were also comparable to previous reports. Overall patient satisfaction and willingness to repeat the operative procedure ranged from 66 to 96% in all patients. Patients and physicians can consider minimally invasive thoracoscopic sympathectomy procedures as an option to treat sympathetically mediated disorders because of the procedure's reduced morbidity and at least equivalent outcome rates in comparison to other treatments.

A multimedia database system for thermal ablation therapy of brain tumors.

A prototype multimedia medical database is described for supporting thermal ablation therapy of brain tumors. Its design is motivated by the major need to manage and access multimedia information on the progress and reaction of tumors to various therapy protocols. The database links images to patient data in a way that permits the use to view and query medical information using alphanumeric, temporal, and feature-based predicates. Visualization programs permit the user to view or annotate the query results in various ways. These results support the wide variety of data types and presentation methods required by neuroradiologists to manage thermal ablation therapy data. The database satisfactorily meets the requirements defined by thermal ablation therapy. A similar approach is being undertaken for supporting different therapies of other types of tumors, thus showing the generality of our approach.

Longitudinal behavioral and 6-[18F]fluoro-L-DOPA-PET assessment in MPTP-hemiparkinsonian monkeys.

Biochemical and behavioral criteria were established to determine the long-term stability of a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced unilateral striatal dopamine deficiency in the vervet monkey. At time points over a 12-month period, post-MPTP striatal dopamine synthesis capacity was indexed with 6-[18F]fluoro-L-DOPA (FDOPA)-positron emission tomography. For the MPTP-treated subjects (n = 4), an intrasubject FDOPA influx rate constant (Ki) ratio method of right (lesioned) striatum/left (unlesioned) striatum values was used to assess changes in striatal activity. Striatal FDOPA Ki ratios differed less than 5% between studies conducted at 1-2, 5-7, and 9-11 months post-MPTP; these results indicated a stable MPTP-induced striatal lesion over this time period. At the 5-7 and 9-11 month time points, behavioral indices of the MPTP-induced deficits were obtained within a species-typical group setting. For three of the four subjects, persistent decrements in motoric, affiliative, and vigilance behavior were observed while the frequency of aggression toward group members was increased. At the 9-11 month time point, one subject showed a 30% improvement in the social measures, indicative of a partial recovery from the MPTP-induced behavioral decrements although its striatal FDOPAKi ratio remained unchanged. Thus, behavioral and noninvasive biochemical methods can provide complementary indices to assess individual differences in sensitivity to MPTP-induced deficits. Both types of data are required to determine lesion stability and, subsequently, the efficacy of interventions designed to restore normal function in this primate Parkinsonian model.

The safety and efficacy of chronically implanted subdural electrodes: a prospective study.

BACKGROUND: The popularity of subdural electrodes for the presurgical evaluation of patients with intractable seizures is increasing. However, few reports have prospectively dealt with their efficacy and safety. METHODS: We conducted a 5-year prospective study of patients evaluated by the California Comprehensive Epilepsy Program, who subsequently underwent subdural electrode implantation at one of two institutions. Efficacy was examined by ultimate outcome with regards to postsurgery resection seizure frequency. Fifty-five patients underwent 58 implant procedures and postresection outcomes were available in 47 patients. Safety was defined by the incidence of expected and unexpected complications, and neuropathologic examination of tissue specimens. RESULTS: The most common expected adverse effects during implant were fever < or = 102 degrees (41%), cerebrospinal fluid leakage (19%), headache (15%), and nausea (4%). There were no infections. Unexpected adverse events included fever > 102 degrees F (5%), migraine (5%), iatrogenic electrode dysfunction (5%), and temporalis muscle fibrosis (5%). The incidence of pathologic findings suggestive of foreign body reaction was 10%. There were no permanent sequelae. Surgical outcomes were excellent in all (> or = 75% seizure reduction) with 50% seizure free regardless of the focus. CONCLUSIONS: Subdural electrodes are a safe, easy, and efficacious tool for evaluating seizure foci prior to resective surgery. They should no longer be considered investigational devices.

Loin pain hematuria syndrome: pain relief with intrathecal morphine.

Loin pain hematuria syndrome (LPHS) is characterized by hematuria and incapacitating loin pain. The pain experienced with LPHS is, in general, extremely difficult to treat. Many surgical and pharmacologic therapies have been directed at LPHS pain without success. This report documents successful pain control in a patient with LPHS using long-term intrathecal morphine delivered via an implantable pump. Intrathecal narcotic therapy may provide pain relief for the chronic pain of LPHS.

Preliminary experience with MR-guided thermal ablation of brain tumors.

PURPOSE: To evaluate the feasibility of a technique of MR-guided stereotactic radio frequency ablation, which was developed as a minimally invasive treatment for brain tumors, and to determine MR characteristics and sequential evolution of radio frequency lesions created to ablate brain tumors. METHODS: Fourteen lesions in 12 patients with primary and metastatic brain tumors were treated with this technique and followed for up to 10 months. The stereotactic coordinates of the tumor and the angle of the radio frequency probe were calculated on MR imaging. The radio frequency lesion was generated in the awake patient by increasing the temperature to 80 degrees C within the tumor for 1 minute. This was repeated until the entire tumor volume was destroyed. MR imaging was performed before, during, and immediately after the radio frequency procedure, and sequential MR was obtained during clinical follow-up. RESULTS: MR imaging clearly showed well-defined radio frequency lesions and provided feedback for treatment planning. The radio frequency lesion boundary was well identified as a dark signal rim on T2-weighted images and showed ring enhancement on contrast-enhanced T1-weighted images. The sequential MR imaging showed the radio frequency lesions decreased in volume in all cases, suggesting focal control. CONCLUSION: Stereotactic MR-guided radio frequency brain tumor ablation is a feasible and promising technique that can be an attractive brain tumor treatment alternative. MR provided not only accurate tumor location but also visualization of feedback of thermal tissue changes that reflected therapeutic effect.

Thalamostriate artery aneurysm within the third ventricle. Case report.

The authors report the case of a 7-mm saccular aneurysm, located within the third ventricle and arising from the distal portion of a thalamostriate artery. The patient presented with an intraventricular hemorrhage and was treated via a frontotemporal craniotomy with translamina-terminalis approach for resection of the aneurysm. The etiology of the aneurysm was presumed to be idiopathic. Previously only one other third ventricular aneurysm has been reported. An intraventricular aneurysm arising from a perforating artery should therefore be considered as a rare cause of an intraventricular hemorrhage. Potential surgical approaches to third ventricular aneurysms are discussed.