Stereotactic radiosurgery and radiotherapy for brainstem metastases: An international multicenter analysis.

Brainstem metastases (BSM) present a significant neuro-oncological challenge, resulting in profound neurological deficits and poor survival outcomes. Stereotactic radiosurgery (SRS) and fractionated stereotactic radiotherapy (FSRT) offer promising therapeutic avenues for BSM despite their precarious location. This international multicenter study investigates the efficacy and safety of SRS and FSRT in 136 patients with 144 BSM treated at nine institutions from 2005 to 2022. The median radiographic and clinical follow-up periods were 6.8 and 9.4 months, respectively. Predominantly, patients with BSM were managed with SRS (69.4%). The median prescription dose and isodose line for SRS were 18 Gy and 65%, respectively, while for FSRT, the median prescription dose was 21 Gy with a median isodose line of 70%. The 12-, 24-, and 36-month local control (LC) rates were 82.9%, 71.4%, and 61.2%, respectively. Corresponding overall survival rates at these time points were 61.1%, 34.7%, and 19.3%. In the multivariable Cox regression analysis for LC, only the minimum biologically effective dose was significantly associated with LC, favoring higher doses for improved control (in Gy, hazard ratio [HR]: 0.86, p < .01). Regarding overall survival, good performance status (Karnofsky performance status, ≥90%; HR: 0.43, p < .01) and prior whole brain radiotherapy (HR: 2.52, p < .01) emerged as associated factors. In 14 BSM (9.7%), treatment-related adverse events were noted, with a total of five (3.4%) radiation necrosis. SRS and FSRT for BSM exhibit efficacy and safety, making them suitable treatment options for affected patients.

Rescuing Infected Deep Brain Stimulation Therapies in Severely Affected Patients.

(1) Background: Infections in deep brain stimulation (DBS) hardware, while an undesired complication of DBS surgeries, can be effectively addressed. Minor infections are typically treated with wound revision and IV antibiotics. However, when visible hardware infection occurs, most centers opt for complete removal, leaving the patient in a preoperative state and necessitating post-removal care. To avoid the need for such care, a novel technique was developed. (2) Methods: The electrodes are placed at the exact same spot and then led to the contralateral side. new extensions and a new generator contralateral to the infection as well. Subsequently, the infected system is removed. This case series includes six patients. (3) Results: The average duration of DBS system implantation before the second surgery was 272 days. Only one system had to be removed after 18 months due to reoccurring infection; the others remained unaffected. Laboratory alterations and pathogens were identified in only half of the patients. (4) Conclusions: The described surgical technique proves to be safe, well tolerated, and serves as a viable alternative to complete system removal. Importantly, it effectively prevents the need of post-removal care for patients.

The Role of Stereotactic Radiosurgery in the Management of Foramen Magnum Meningiomas-A Multicenter Analysis and Review of the Literature.

BACKGROUND: Foramen magnum meningiomas (FMMs) represent a considerable neurosurgical challenge given their location and potential morbidity. Stereotactic radiosurgery (SRS) is an established non-invasive treatment modality for various benign and malignant brain tumors. However, reports on single-session or multisession SRS for the management and treatment of FMMs are exceedingly rare. We report the largest FMM SRS series to date and describe our multicenter treatment experience utilizing robotic radiosurgery. METHODS: Patients who underwent SRS between 2005 and 2020 as a treatment for a FMM at six different centers were eligible for analysis. RESULTS: Sixty-two patients met the inclusion criteria. The median follow-up was 28.9 months. The median prescription dose and isodose line were 14 Gy and 70%, respectively. Single-session SRS accounted for 81% of treatments. The remaining patients received three to five fractions, with doses ranging from 19.5 to 25 Gy. Ten (16%) patients were treated for a tumor recurrence after surgery, and thirteen (21%) underwent adjuvant treatment. The remaining 39 FMMs (63%) received SRS as their primary treatment. For patients with an upfront surgical resection, histopathological examination revealed 22 World Health Organization grade I tumors and one grade II FMM. The median tumor volume was 2.6 cubic centimeters. No local failures were observed throughout the available follow-up, including patients with a follow-up ≥ five years (16 patients), leading to an overall local control of 100%. Tumor volume significantly decreased after treatment, with a median volume reduction of 21% at the last available follow-up (p < 0.01). The one-, three-, and five-year progression-free survival were 100%, 96.6%, and 93.0%, respectively. Most patients showed stable (47%) or improved (21%) neurological deficits at the last follow-up. No high-grade adverse events were observed. CONCLUSIONS: SRS is an effective and safe treatment modality for FMMs. Despite the paucity of available data and previous reports, SRS should be considered for selected patients, especially those with subtotal tumor resections, recurrences, and patients not suitable for surgery.

Neurostimulator-induced ECG artefacts: A systematic analysis.

OBJECTIVES: Deep brain stimulation (DBS) is known to interfere with electrocardiographic (ECG) examinations. In emergency situations, such electrical interferences can not only thwart ECG diagnostics, but even induce an ECG pattern that causes the emergency medical service to initiate inadequate or even harmful therapy. Aim of this prospective study was to evaluate factors influencing ECG interpretation in DBS and to evaluate the susceptibility of ECG criteria 'frequency', 'rhythm', 'regularity', 'QRS-configuration', and 'ST-segment' on neurostimulation. PATIENTS AND METHODS: In 33 DBS patients (17 male, 16 female, mean age 64 years), limb-, 12 channel-, Nehb, and adhesive paddle-lead ECG were performed in activated (n = 33) and deactivated (n = 31) stimulation mode during outpatient follow-up examinations. The examinations were carried out using three different ECG devices (two portable emergency ECG-monitor/defibrillation/pacer-devices, one stationary hospital device), resulting in 4096 ECG leads. Statistics have been based on regression analyses and on a maximum likelihood estimation regression model. RESULTS: Monopolar settings were found to be a relevant factor interfering significantly more often with ECG recording than bipolar parameters (p < 0.0001). Due to recurring movement artefacts, deactivation of bipolar stimulation might even significantly worsen ECG quality (p < 0.0001). Interpretability of 'rhythm' (ß = -0.088, p = 0.03) and 'frequency' (ß = -0.110, p = 0.02) revealed significant negative correlation to the applied neurostimulation voltage. Nehb lead yielded in highest ECG interpretability. CONCLUSION: Bipolar neurostimulation mode barely affected the ECGs; furthermore, the suppression of motion artefacts by neurostimulation can improve ECG quality. If monopolar neurostimulation is required, at least, stimulation voltage should be as low as possible to obtain good stimulation results.

Robotic Radiosurgery for Persistent Postoperative Acromegaly in Patients with Cavernous Sinus-Invading Pituitary Adenomas-A Multicenter Experience.

BACKGROUND: The rates of incomplete surgical resection for pituitary macroadenomas with cavernous sinus invasion are high. In growth hormone-producing adenomas, there is a considerable risk for persistent acromegaly. Thus, effective treatment options are needed to limit patient morbidity and mortality. This multicenter study assesses the efficacy and safety of robotic radiosurgery (RRS) for patients with cavernous sinus-invading adenomas with persistent acromegaly. METHODS: Patients who underwent RRS with CyberKnife for postoperative acromegaly were eligible. RESULTS: Fifty patients were included. At a median follow-up of 57 months, the local control was 100%. The pretreatment insulin-like growth factor 1 (IGF-1) levels and indexes were 381 ng/mL and 1.49, respectively. The median dose and prescription isodose were 18 Gy and 70%, respectively. Six months after RRS, and at the last follow-up, the IGF-1 levels and indexes were 277 ng/mL and 1.14, as well as 196 ng/mL and 0.83, respectively (p = 0.0001 and p = 0.0002). The IGF-1 index was a predictor for biochemical remission (p = 0.04). Nine patients achieved biochemical remission and 24 patients showed biochemical disease control. Three patients developed a new hypopituitarism. CONCLUSIONS: RRS is an effective treatment for this challenging patient population. IGF-1 levels are decreasing after treatment and most patients experience biochemical disease control or remission.

Image-guided robotic radiosurgery for glomus jugulare tumors-Multicenter experience and review of the literature.

BACKGROUND: Glomus jugulare tumors (GJTs) are challenging to treat due to their vascularization and location. This analysis evaluates the effectiveness and safety of image-guided robotic radiosurgery (RRS) for GJTs in a multicenter study and reviews the existing radiosurgical literature. METHODS: We analyzed outcome data from 101 patients to evaluate local control (LC), changes in pretreatment deficits, and toxicity. Moreover, radiosurgical studies for GJTs have been reviewed. RESULTS: After a median follow-up of 35 months, the overall LC was 99%. Eighty-eight patients were treated with a single dose, 13 received up to 5 fractions. The median tumor volume was 5.6 cc; the median treatment dose for single-session treatments is 16 Gy, and for multisession treatments is 21 Gy. Fifty-six percentage of patients experienced symptom improvement or recovered entirely. CONCLUSIONS: RRS is an effective primary and secondary treatment option for GJTs. The available literature suggests that radiosurgery is a treatment option for most GJTs.

A Submammarian Approach for Cosmetically Improved Implantation of Deep Brain Stimulation Generators.

BACKGROUND: Deep brain stimulation (DBS) indications include movement disorders, psychiatric affections, or epilepsy in which patients risk social isolation heightened by abnormal motions or behavioral patterns. Further stigmatization after DBS surgery from head shaving, visible scarring, or disfigurement from bulky lead insertion points should be avoided. OBJECTIVE: We present a cosmetically optimized, adapted submammarian approach for DBS neurostimulator implantation that leaves the décolletage untouched. METHODS: Over 24 months, 61 patients suffering from Parkinson disease, dystonia, or tremor underwent DBS surgery. The modified, submammarian approach was compared with the conventional infraclavicular approach regarding clinical outcome, complications, and limitations over a 5-year follow-up. RESULTS: Neurostimulators were implanted in a paraumbilical (n = 20) or infraclavicular position (n = 41; Parkinson disease, n = 27; dystonia, n = 9; tremor, n = 5), the latter using a standard (n = 16), modified juxta-axillary (n = 6), or submammarian approach (n = 19; 18 women, 1 man with significant gynecomastia). After 12 months, there was no significant difference in the infection rate and one event of rebleeding in each group. Overall, operation time was longer (+20 minutes) for the submammarian versus standard, infraclavicular approach, but acceptable. Neurostimulator replacement was, necessary within 5 years due to advanced battery discharge (n = 32). Battery replacement was easily achieved using the submammarian approach (n = 14), again with increased surgical time (+20 minutes), and iatrogenic damage to extensions was avoidable. CONCLUSIONS: A submammarian approach might be an alternative for infraclavicular implantation of DBS neurostimulators, particularly in female patients in the context of cosmetically optimized surgery. Patients' self-perception and self-esteem may be strengthened, potentially enabling them to better cope with disease.

Progressive gait ataxia following deep brain stimulation for essential tremor: adverse effect or lack of efficacy?

Thalamic deep brain stimulation is a mainstay treatment for severe and drug-refractory essential tremor, but postoperative management may be complicated in some patients by a progressive cerebellar syndrome including gait ataxia, dysmetria, worsening of intention tremor and dysarthria. Typically, this syndrome manifests several months after an initially effective therapy and necessitates frequent adjustments in stimulation parameters. There is an ongoing debate as to whether progressive ataxia reflects a delayed therapeutic failure due to disease progression or an adverse effect related to repeated increases of stimulation intensity. In this study we used a multimodal approach comparing clinical stimulation responses, modelling of volume of tissue activated and metabolic brain maps in essential tremor patients with and without progressive ataxia to disentangle a disease-related from a stimulation-induced aetiology. Ten subjects with stable and effective bilateral thalamic stimulation were stratified according to the presence (five subjects) of severe chronic-progressive gait ataxia. We quantified stimulated brain areas and identified the stimulation-induced brain metabolic changes by multiple 18 F-fluorodeoxyglucose positron emission tomography performed with and without active neurostimulation. Three days after deactivating thalamic stimulation and following an initial rebound of symptom severity, gait ataxia had dramatically improved in all affected patients, while tremor had worsened to the presurgical severity, thus indicating a stimulation rather than disease-related phenomenon. Models of the volume of tissue activated revealed a more ventrocaudal stimulation in the (sub)thalamic area of patients with progressive gait ataxia. Metabolic maps of both patient groups differed by an increased glucose uptake in the cerebellar nodule of patients with gait ataxia. Our data suggest that chronic progressive gait ataxia in essential tremor is a reversible cerebellar syndrome caused by a maladaptive response to neurostimulation of the (sub)thalamic area. The metabolic signature of progressive gait ataxia is an activation of the cerebellar nodule, which may be caused by inadvertent current spread and antidromic stimulation of a cerebellar outflow pathway originating in the vermis. An anatomical candidate could be the ascending limb of the uncinate tract in the subthalamic area. Adjustments in programming and precise placement of the electrode may prevent this adverse effect and help fine-tuning deep brain stimulation to ameliorate tremor without negative cerebellar signs.

Stereotactic intracavitary brachytherapy with P-32 for cystic craniopharyngiomas in children.

PURPOSE: Although microsurgery remains the first-line treatment, gross total resection of cystic craniopharyngeomas (CP) is associated with significant morbidity and mortality and the addition of external irradiation to subtotal resection proves to achieve similar tumor control. However, concern regarding long-term morbidity associated with external irradiation in children still remains. With this retrospective analysis, the authors emphasize intracavitary brachytherapy using phosphorus-32 (P-32) as a treatment option for children with cystic CP. PATIENTS AND METHODS: Between 1992 and 2009, 17 children (median age 15.4 years; range 7-18 years) with cystic CP underwent intracavitary brachytherapy using P-32. Eleven patients were treated for recurrent tumor cysts; 6 patients were treated primarily. MR imaging revealed solitary cysts in 7 patients; 10 patients had mixed solid-cystic lesions (median tumor volume 11.1 ml; range 0.5-78.9 ml). The median follow-up time was 61.9 months (range 16.9-196.6 months). RESULTS: Local cyst control could be achieved in 14 patients (82 %). Three patients showed progression of the treated cystic formation (in-field progression) after a median time of 8.3 months (range 5.3-10.3 months), which led to subsequent interventions. The development of new, defined cysts and progression of solid tumor parts (out-of-field progression) occurred in 5 patients and led to additional interventions in 4 cases. There was neither surgery-related permanent morbidity nor mortality in this study. The overall progression-free survival was 75, 63, and 52 % after 1, 3, and 5 years, respectively. CONCLUSION: Intracavitary brachytherapy using P-32 represents a safe and effective treatment option for children harboring cystic CP, even as primary treatment. However, P-32 does not clearly affect growth of solid tumor parts or the development of new cystic formations.

Intracavitary brachytherapy using stereotactically applied phosphorus-32 colloid for treatment of cystic craniopharyngiomas in 53 patients.

This paper summarizes outcomes of a single-center study of intracavitary brachytherapy (IBT) with stereotactically applied phosphorus-32 ((32)P) colloid for treatment of cystic craniopharyngiomas. We assessed its efficacy and safety, on the basis of clinical and radiological outcomes in one of the largest reported patient series. Between 1992 and 2011, 53 patients were treated with IBT, 14 without previous treatment and 39 who had previously been treated for recurrent cysts. Intervention was performed by applying 200 Gy to the internal cyst wall (median volume 6.1 ml). Median clinical and radiological follow-up were 60.2 and 53.0 months, respectively. Actuarial tumor cyst control was 86.0 ± 5.3 % at 12, 24, and 60 months. Actuarial out-of-field control (development of new cysts or progression of solid tumor parts) was 90.9 ± 4.3, 84.0 ± 5.6, and 54.5 ± 8.8 % after 12, 24, and 60 months, respectively. Corresponding actuarial overall progression-free survival was 79.4 ± 6.1, 72.4 ± 6.8, and 45.6 ± 8.7 % at 12, 24, and 60 months, respectively. Visual function improved for 12 patients (23.5 %), remained unchanged for 34 patients (66.7 %), and worsened for five patients (9.8 %), correlating with tumor progression in each case. Endocrinological deterioration occurred for ten patients (19.6 %); for nine patients this was a result of tumor progression or after tumor resection and for one it was attributed to irradiation. Within six months of IBT seven patients (13.7 %) experienced transient neurological deficits and two patients (3.9 %) deteriorated permanently (hemiparesis and third nerve palsy). Stereotactically applied (32)P is highly efficacious for control of cystic components of craniopharyngiomas and is associated with a low risk of permanent morbidity. The procedure does not, however affect the development of new cysts or the progression of solid tumor parts.

Stereotactic brachytherapy with iodine-125 seeds for the treatment of inoperable low-grade gliomas in children: long-term outcome.

PURPOSE: Resection is generally considered the gold standard for treatment of low-grade (WHO grades I and II) gliomas (LGGs) in childhood. However, approximately 30% to 50% of these tumors are inoperable because of their localization in highly eloquent brain areas. A few reports have suggested stereotactic brachytherapy (SBT) with implantation of iodine-125 ((125)I) seeds as a safe and effective local treatment alternative. This single-center study provides a summary of the long-term outcome after SBT in one of the largest reported patient series. PATIENTS AND METHODS: All pediatric patients treated with SBT ((125)I seeds; cumulative therapeutic dose 50-65 Gy within 9 months) by our group for LGG with follow-up of more than 6 months were included. Clinical and radiologic outcome, time to progression, and overall survival were evaluated. Prognostic factors (age, sex, Karnofsky performance score, tumor volume, and histology) for survival and disease progression were investigated. RESULTS: In all, 147 of 160 pediatric patients treated with SBT (from 1982 through 2009) were analyzed in detail. Procedure-related mortality was zero, and the 30-day morbidity was transient and low (5.4%). Survival rates at 5 and 10 years were 93%, and 82%, respectively, with no significant difference between WHO grades I and II tumors (median follow-up, 67.1 ± 57.7 months). Twenty-one (14.8%) of 147 patients presented with tumor relapse. The remaining 126 patients revealed complete response in 24.6%, partial response in 31.0%, and stable disease in 29.6%. Neurologic status improved (57.8%) or remained stable (23.0%). None of the evaluated factors had significant impact on the study's end points except tumor volume more than 15 mL, which caused significantly higher rates of tumor recurrence (P < .05). CONCLUSION: We demonstrate that SBT represents a safe, minimally invasive, and highly effective local treatment option for pediatric patients with inoperable LGG WHO grades I and II.

Is a patient controller for Parkinson's disease patients with subthalamic nucleus deep brain stimulation reasonable?

BACKGROUND: A patient controller (PC) is an optional device for patients with deep brain stimulation (DBS) to have limited control of their stimulator system. OBJECTIVES: We investigated the impact of a PC on DBS safety, most notably the handling/prevention of unexpected DBS failure in patients with Parkinson's disease (PD). METHODS: PD patients with subthalamic DBS were educated in the use of a PC. After a first impulse generator (IPG) replacement, data on the use of the PC were obtained from the patients' records and by a patient questionnaire. RESULTS: A total of 27 patients with IPG replacements after 4.4 ± 0.8 years (118.8 patient-years) were included. Thirteen patients transiently used the PC to optimize stimulation amplitudes. Eighteen patients reported events when they used the PC to ensure DBS being on. No accidental switch off by environmental electromagnetism was confirmed. In contrast, 4 patients accidentally turned the IPG off with the PC. Sixteen patients regularly checked the IPG battery but only 1 patient noted a low battery status before quarterly control visits. Of the 27 patients, 26 had anticipated and only 1 an unanticipated IPG replacement. CONCLUSIONS: A PC is not needed for patient safety. However, in some patients, a PC is helpful to optimize stimulation amplitudes and to increase the patients' own perception of safety.

Pineal parenchymal tumors. Management with interstitial iodine-125 radiosurgery.

PURPOSE: To evaluate the efficacy of interstitial radiosurgery (IRS) for pineal parenchymal tumors (PPTs). PATIENTS AND METHODS: 18 consecutively admitted patients (twelve male and six female, age range 6-68 years, median age 34 years) with PPTs (eight pineocytomas, ten malignant PPTs) were treated at the authors' institution with IRS using stereotactically guided iodine-125 seed implantation ((125)I-IRS) as either primary or salvage therapy. The cumulative tumor surface dose ranged from 40 to 64 Gy. Adjuvant radiotherapy of the whole brain or the craniospine was done in patients with grade III and grade IV PPT. The median follow-up period was 57.4 months (range 6-134 months). RESULTS: Overall actuarial 5- and 8-year survival rates after IRS were 100% and 86% for pineocytomas, and the overall actuarial 5-year survival rate was 78% for high-grade PPTs. Follow-up magnetic resonance imaging showed complete remission in 72% (13/18) and partial remission in 28% (5/18) of the cases. One patient developed an out-of-field relapse 4 years after partial remission of a pineocytoma, which had already been treated with IRS. There was no treatment-related mortality. Treatment-related morbidity occurred in two patients only. CONCLUSION: This study indicates that stereotactic (125)I-IRS for the management of PPTs is quite efficient and safe. Due to the low rate of side effects, IRS may develop into an attractive alternative to microsurgery in de novo diagnosed pineocytomas. In malignant PPTs, IRS may be routinely applied in a multimodality treatment schedule supplementary to conventional irradiation.

Secondary failure after ten years of pallidal neurostimulation in a patient with advanced Parkinson's disease.

Deep-brain stimulation of the subthalamic nucleus and internal globus pallidus are both surgical options in advanced Parkinson's disease. The best target is still debated with data suggesting better motor outcome in subthalamic stimulation but higher rates of psychiatric problems. Failure of pallidal stimulation within the first 2 years has been described. Here, we report a patient with good response to pallidal neurostimulation who developed a secondary failure after 10 years of treatment which was successfully reversed by reimplanting the electrodes into the subthalamic nucleus. This case suggests that a controlled comparison of treatment efficacy of pallidal and subthalamic neurostimulation may require a very long follow-up period to yield reliable results.

Ten Hertz thalamus stimulation increases tremor activity in the subthalamic nucleus in a patient with Parkinson's disease.

OBJECTIVE: In patients with Parkinson's disease (PD) the effect of thalamic stimulation on tremor pathophysiology remains largely unclear. By recording local field potentials (LFPs) in the subthalamic nucleus (STN) while stimulating the nucleus ventralis intermedius thalami (VIM), information of the stimulation effects should be gained. METHODS: We had the unique opportunity to intraoperatively record LFPs of the STN in a patient with PD while stimulating the VIM. VIM electrodes had been implanted 9 years previously because of tremor. Due to worsening of clinical symptoms an implantation of STN electrodes had become necessary. RESULTS: High frequency stimulation in the VIM lowered the power of the tremor frequency band (4-7Hz) in the STN. In contrast, 10Hz VIM stimulation elevated the power of the tremor frequency band as well as STN-EMG coupling. CONCLUSIONS: The effect of high frequency stimulation may explain the improvement of tremor in patients who are treated with VIM deep brain stimulation. The power elevation during 10Hz stimulation suggests that the pathological cerebral and cerebral-muscular communication in PD is mainly driven at 10Hz. SIGNIFICANCE: The direct cerebral recordings support the view that a 10Hz network is a pathophysiological key mechanism in the generation of motor deficits in PD.

Frequency-dependent reciprocal modulation of verbal fluency and motor functions in subthalamic deep brain stimulation.

BACKGROUND: High-frequency deep brain stimulation (DBS) of the subthalamic nucleus (STN) improves motor functions in those with Parkinson disease but may worsen frontal functions such as verbal fluency (VF). In contrast, low-frequency DBS leads to deterioration of motor functions. It is not known whether low-frequency STN DBS also has an effect on frontal functions. OBJECTIVE: To examine whether low-frequency STN DBS in contrast to high-frequency STN DBS has a positive effect on frontal functions on the basis of VF test results. DESIGN: A double-blind randomized crossover experiment to compare performance in 4 VF subtests and motor performance at 10 Hz, 130 Hz, and no stimulation. SETTING: University hospitals in Düsseldorf and Cologne, Germany. PATIENTS: Twelve patients with Parkinson disease 3 months or more after bilateral electrode implantation into the STN. MAIN OUTCOME MEASURE: Mean number of words in VF at different stimulation frequencies. RESULTS: The VF was significantly better at 10 Hz (48.3 words) compared with 130 Hz and showed a nonsignificant trend toward worsening at 130 Hz (42.3 words) compared with no stimulation (43.8 words). These results were consistent across all subtests. CONCLUSIONS: The study provides evidence of a beneficial effect of low-frequency (10 Hz) STN DBS on VF, which may be caused by activating neural pathways projecting to the frontal cortex. In addition, the study reproduces the negative effect of therapeutic high-frequency STN DBS on VF. The study results provide evidence for a frequency-dependent modulation of cognitive circuits involving the STN.

Linear accelerator radiosurgery for pituitary macroadenomas: a 7-year follow-up study.

BACKGROUND: A prospective study was conducted to assess the efficacy and side effects of linear accelerator (LINAC)-based radiosurgery (RS) performed with a reduced dose of therapeutic radiation for patients with surgically inaccessible pituitary macroadenomas. METHODS: From August 1990 through January 2004, 175 patients with pituitary macroadenomas were treated with LINAC-RS according to a prospective protocol. To minimize the risk for radiation-induced damage of the pituitary function, the therapeutic dose to be applied was limited to 20 grays. RESULTS: Among 175 patients, 142 patients who had a minimum follow-up of 12 months (mean +/- standard deviation, 81.9 +/- 37.2 months) were included in the current study. The local tumor control rate was 96.5%, and the tumor response rate was 32.4%. The mean time (+/- standard deviation) from LINAC-RS to normalization of pathologic hormone secretion was 36.2 +/- 24.0 months. The probability for normalization was 34.3% at 3 years and 51.1% at 5 years. The frequency of endocrine cure (defined as the normalization of hormone secretion without specific medication intake) was 35.2% (mean +/- standard deviation time to cure, 42.1 +/- 25.0 months). Patients with Cushing disease had a statistically significant greater chance of achieving a cure (P = .001). Side effects of LINAC-RS were deterioration of anterior pituitary function (12.3%), radiation-induced tissue damage (2.8%), and radiation-induced neuropathy (1.4%). CONCLUSIONS: LINAC-RS using a lower therapeutic radiation dose achieved local tumor control and normalization or cure of hormone secretion comparable to the results achieved with gamma-knife RS. Compared with the latter, the time to normalization or endocrine cure was delayed, most probably as a result of dose reduction. However, the lower therapeutic radiation dose did not prevent radiation-induced damage of pituitary function completely.

Accuracy and conformity of stereotactically guided interstitial brain tumour therapy using I-125 seeds.

OBJECTIVE: To assess the accuracy of the stereotactic implantation procedure of catheters containing I-125 seeds in brain tumours and investigate the effect of catheter deviations on the dose distribution in patients. METHODS: A randomised sample (n = 37) of all patients treated with I-125 seeds in our department between 6/1994 and 2/2002 was examined. Intraoperative X-ray images were used to measure deviations of implanted I-125 seed catheters from their planned positions and the influence on dose conformity, tumour surface dose and dose burden of surrounding healthy brain tissue was determined. RESULTS: The mean spatial target point deviation was 2.0 mm (maximum 4.1 mm, SD 0.9 mm) and in 54.1% of the cases, reduction of the planned dose was greater than 5%. Target point deviations less than 1.5 mm have only minor influence on surface dose and conformity. Results indicated that in 10.8% of the cases the realized dose distribution showed a 'slight deviation', according to the guideline criteria for external radiosurgery of the Radiation Therapy Oncology Group. In 89.2% of the patients the applied dose conformed to the target volume. CONCLUSIONS: Stereotactically guided interstitial irradiation with I-125 seeds can be used to treat brain tumours and metastases with high conformity comparable to radiosurgery. The observed deviations of the stereotactically implanted I-125 seed catheters from their planned target points were smaller when compared to frameless procedures. In order to maintain the required spatial accuracy of 1.5 mm in interstitial therapy using I-125 seeds, it appears necessary to optimise stereotactic instruments further.

Ten-Hertz stimulation of subthalamic nucleus deteriorates motor symptoms in Parkinson's disease.

Recently, a pathological oscillatory network at 10 Hz including several motor areas was described in patients with idiopathic Parkinson's disease (PD). In 7 PD patients, we tested the clinical effect of subthalamic nucleus (STN) stimulation at varying frequencies 1 to 3 years after implantation of electrodes. STN stimulation at 10 Hz induced significant worsening of motor symptoms, especially akinesia, compared with no stimulation and therapeutic stimulation (> or =130 Hz). This finding indicates the clinical relevance of pathological 10 Hz synchronization in PD.

Subthalamic nucleus stimulation restores glucose metabolism in associative and limbic cortices and in cerebellum: evidence from a FDG-PET study in advanced Parkinson's disease.

Deep brain stimulation of the subthalamic nucleus (STN-DBS) is a highly effective surgical treatment in patients with advanced Parkinson's disease (PD). Because the STN has been shown to represent an important relay station not only in motor basal ganglia circuits, the modification of brain areas also involved in non-motor functioning can be expected by this intervention. To determine the impact of STN-DBS upon the regional cerebral metabolic rate of glucose (rCMRGlc), we performed positron emission tomography (PET) with 18-fluorodeoxyglucose (FDG) in eight patients with advanced PD before surgery as well as in the DBS on- and off-conditions 4 months after electrode implantation and in ten age-matched healthy controls. Before surgery, PD patients showed widespread bilateral reductions of cortical rCMRGlc versus controls but a hypermetabolic state in the left rostral cerebellum. In the STN-DBS on-condition, clusters of significantly increased rCMRGlc were found in both lower thalami reaching down to the midbrain area and remote from the stimulation site in the right frontal cortex, temporal cortex, and parietal cortex, whereas rCMRGlc significantly decreased in the left rostral cerebellum. Therefore, STN-DBS was found to suppress cerebellar hypermetabolism and to partly restore physiologic glucose consumption in limbic and associative projection territories of the basal ganglia. These data suggest an activating effect of DBS upon its target structures and confirm a central role of the STN in motor as well as associative, limbic, and cerebellar basal ganglia circuits.