Subthalamic Nucleus Deep Brain Stimulation Restores Motor and Sensorimotor Cortical Neuronal Oscillatory Activity in the Free-Moving 6-Hydroxydopamine Lesion Rat Parkinson Model.

OBJECTIVES: Enhanced beta oscillations in cortical-basal ganglia (BG) thalamic circuitries have been linked to clinical symptoms of Parkinson's disease. Deep brain stimulation (DBS) of the subthalamic nucleus (STN) reduces beta band activity in BG regions, whereas little is known about activity in cortical regions. In this study, we investigated the effect of STN DBS on the spectral power of oscillatory activity in the motor cortex (MCtx) and sensorimotor cortex (SMCtx) by recording via an electrocorticogram (ECoG) array in free-moving 6-hydroxydopamine (6-OHDA) lesioned rats and sham-lesioned controls. MATERIALS AND METHODS: Male Sprague-Dawley rats (250-350 g) were injected either with 6-OHDA or with saline in the right medial forebrain bundle, under general anesthesia. A stimulation electrode was then implanted in the ipsilateral STN, and an ECoG array was placed subdurally above the MCtx and SMCtx areas. Six days after the second surgery, the free-moving rats were individually recorded in three conditions: 1) basal activity, 2) during STN DBS, and 3) directly after STN DBS. RESULTS: In 6-OHDA-lesioned rats (N = 8), the relative power of theta band activity was reduced, whereas activity of broad-range beta band (12-30 Hz) along with two different subbeta bands, that is, low (12-30 Hz) and high (20-30 Hz) beta band and gamma band, was higher in MCtx and SMCtx than in sham-lesioned controls (N = 7). This was, to some extent, reverted toward control level by STN DBS during and after stimulation. No major differences were found between contacts of the electrode grid or between MCtx and SMCtx. CONCLUSION: Loss of nigrostriatal dopamine leads to abnormal oscillatory activity in both MCtx and SMCtx, which is compensated by STN stimulation, suggesting that parkinsonism-related oscillations in the cortex and BG are linked through their anatomic connections.

Brain biopsy in patients with CLIPPERS syndrome: why and when.

CLIPPERS (chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids) is an inflammatory disorder of the central nervous system (CNS), predominantly involving the brainstem with a characteristic magnetic resonance imaging (MRI) appearance and clinical and radiological responsiveness to glucocorticosteroids. Yet diagnostic biomarkers are missing and other immune-mediated, (para-) infectious and malignant causes mimic CLIPPERS-like MRI presentations. We report the case of a 51-year-old male patient with CLIPPERS who repeatedly responded well to high-dose corticosteroids. After 7 months, however, treatment failed, and he had a biopsy-confirmed diagnosis of a CNS B-cell lymphoma. Clinical and MRI signs of CLIPPERS include a wide spectrum of differential diagnoses which often arise only later during the course of disease. Similar to the case presented here, delayed diagnosis and specific therapy may contribute to an unfavorable outcome. Hence, we propose that in the absence of other diagnostic markers, brain biopsy should be performed as early as possible in CLIPPERS patients.

Electric stimulation of the medial forebrain bundle influences sensorimotor gaiting in humans.

BACKGROUND: Prepulse inhibition (PPI) of the acoustic startle response, a measurement of sensorimotor gaiting, is modulated by monoaminergic, presumably dopaminergic neurotransmission. Disturbances of the dopaminergic system can cause deficient PPI as found in neuropsychiatric diseases. A target specific influence of deep brain stimulation (DBS) on PPI has been shown in animal models of neuropsychiatric disorders. In the present study, three patients with early dementia of Alzheimer type underwent DBS of the median forebrain bundle (MFB) in a compassionate use program to maintain cognitive abilities. This provided us the unique possibility to investigate the effects of different stimulation conditions of DBS of the MFB on PPI in humans. RESULTS: Separate analysis of each patient consistently showed a frequency dependent pattern with a DBS-induced increase of PPI at 60 Hz and unchanged PPI at 20 or 130 Hz, as compared to sham stimulation. CONCLUSIONS: Our data demonstrate that electrical stimulation of the MFB modulates PPI in a frequency-dependent manner. PPI measurement could serve as a potential marker for optimization of DBS settings independent of the patient or the examiner.

DBS of the PSA and the VIM in essential tremor: A randomized, double-blind, crossover trial.

OBJECTIVE: To evaluate deep brain stimulation (DBS) of the posterior subthalamic area (PSA) in essential tremor (ET) and compare it to the ventral intermediate nucleus of the thalamus (VIM) in terms of stimulation efficacy, efficiency, and side effects. METHODS: DBS leads were implanted such that contacts were placed in the VIM, on the intercommissural line, and in the PSA. Thirteen patients with ET entered a randomized, double-blind crossover phase and completed a 1-year follow-up. RESULTS: PSA-DBS significantly reduced tremor severity and improved quality of life. There were no relevant differences in quality and frequency of stimulation side effects between VIM and PSA, with a tendency toward greater tremor improvement with PSA stimulation. Clinical benefit was achieved at significantly lower stimulation amplitudes in the PSA. The majority of patients remained with PSA-DBS after 1 year. CONCLUSION: In accordance with previous retrospective investigations, our prospective data suggest that PSA-DBS is at least equally effective as but possibly more efficient than VIM-DBS. CLASSIFICATION OF EVIDENCE: This study provides Class I evidence that for patients with essential tremor, PSA-DBS is not significantly different from VIM-DBS in suppressing tremor, but clinical benefit from PSA-DBS is attained at lower stimulation amplitudes.

Deep brain stimulation of the posterior subthalamic area and the thalamus in patients with essential tremor: study protocol for a randomized controlled pilot trial.

BACKGROUND: Deep brain stimulation (DBS) of the ventral intermediate nucleus (VIM) of the thalamus is effective in medication refractory essential tremor (ET). In recent years, evidence has accumulated that the region ventral to the VIM, the posterior subthalamic area (PSA), might be an equally or even more effective target for electrode implantation. However, this evidence is primarily based on case series, cross-sectional observations, and retrospective data. METHODS/DESIGN: A prospective crossover pilot study investigating the effects of PSA stimulation in medication refractory ET patients was designed. In this study, bilateral electrodes are implanted such that at least one of the electrode contacts is located in the PSA and VIM, respectively. This implantation approach allows (1) a prospective double-blind investigation of the effects of PSA stimulation compared to baseline, as well as (2) a crossover comparison between VIM and PSA stimulation with respect to tremor suppression and side effect profiles. DISCUSSION: The results of this double-blinded, prospective study will allow a better understanding of the effects and side effects of PSA compared to VIM-DBS in patients with ET. TRIAL REGISTRATION: German Clinical Trials Register: DRKS00004235 . Registered on 4 July 2012.

Perimovement decrease of alpha/beta oscillations in the human nucleus accumbens.

The human nucleus accumbens is thought to play an important role in guiding future action selection via an evaluation of current action outcomes. Here we provide electrophysiological evidence for a more direct, i.e., online, role during action preparation. We recorded local field potentials from the nucleus accumbens in patients with epilepsy undergoing surgery for deep brain stimulation. We found a consistent decrease in the power of alpha/beta oscillations (10-30 Hz) before and around the time of movements. This perimovement alpha/beta desynchronization was observed in seven of eight patients and was present both before instructed movements in a serial reaction time task as well as before self-paced, deliberate choices in a decision making task. A similar beta decrease over sensorimotor cortex and in the subthalamic nucleus has been directly related to movement preparation and execution. Our results support the idea of a direct role of the human nucleus accumbens in action preparation and execution.

Lesion guided radiofrequency thermocoagulation (L-RFTC) for hypothalamic hamartomas, nodular heterotopias and cortical dysplasias: Review and perspective.

Lesion guided radiofrequency thermocoagulation (L-RFTC) via stereotactically inserted coagulation probes is a further development of stereotactic thermocoagulation thalamotomy and stereo-EEG guided RFTC. In this method epileptogenic lesions detected via magnetic resonance imaging (MRI) move to the center of coagulation planning. Two surgical strategies can be applied: lesion disconnection and lesion destruction. This focused review collects all data published until January 2016 on L-RFTC for the indications hypothalamic hamartoma, periventricular nodular heterotopia and focal cortical dysplasia and describes technical issues, surgical objectives and outcomes. Special attention is given to the aspect of presurgical MRI requirements.

Lesion guided stereotactic radiofrequency thermocoagulation for palliative, in selected cases curative epilepsy surgery.

INTRODUCTION: Resective epilepsy surgery is an established treatment option in patients with pharmacoresistant, lesion related epilepsy. Yet, if the presurgical work-up proves multi-focal organization of the epileptogenic zone, or the area of intended resection is close to eloquent brain areas, patients may decide against resections because of an unfavorable risk-benefit-ratio. We assess if lesion guided cortical stereotactic radiofrequency thermocoagulation (L-RFTC) is a potential surgical alternative in these patients. METHODS: We performed seven procedures of L-RFTC. Three patients had monofocal epilepsy arising close to eloquent structures; in four, invasive pre-surgical workup documented monofocal seizure onset but strong interictal epileptic activity also independent and distant from the seizure onset zone. L-RFTC was restricted to the lesional area (=seizure onset site). RESULTS: 12 to 37 months after RFTC worthwhile seizure improvement was achieved in 6 patients. One patient became seizure free following complete coagulation of a focal cortical dysplasia, two had had 1-2 auras under tapered but not under continued medication. In one patient only subclinical seizures persisted. In one patient hypermotor seizures were transformed into milder short tonic seizures and another one had a seizure reduction by 50%. Only one patient did not profit at all. One patient developed a persisting neurological deficit. SIGNIFICANCE: In patients with complex epileptogenic zones L-RFTC can lead to worthwhile seizure reduction. This qualifies this procedure as a palliative surgical technique with potential good risk-benefit ratio. In patients with small focal cortical dysplasias L-RFTC may even allow minimal-invasive surgery with curative intention.

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.

Lesion focused stereotactic thermo-coagulation of focal cortical dysplasia IIB: a new approach to epilepsy surgery?

PURPOSE: Over the last few decades, preferred epilepsy surgical approaches have developed from standard lobectomies to individually tailored resections. Yet, it remains uncertain how small surgical interventions can be without compromising the success of the surgery. Particularly in patients with epileptogenic lesions identified by magnetic resonance imaging (MRI), it is unresolved whether resection or destruction of the lesion suffices to eliminate the epileptogenic zone. We present a minimally invasive surgical approach that may provide insight into this issue. METHODS: Two patients with pharmacoresistant epilepsy due to focal cortical dysplasia type IIB demonstrated by 3 Tesla MRI were treated with lesion-focused stereotactic radio-frequency thermo-coagulation. In both patients, pathognomonic epileptic discharges were recorded from the lesion via a stimulation device prior to coagulation. In one patient, the suspected proximity of the lesion to the pyramidal tract was verified by eliciting motor evoked potentials from the depths of the lesion. RESULTS: Following complete and near complete lesion destruction, seizures (several per day or per week, respectively) ceased in patients A and B, with no seizures for 12 months and 5 months, respectively, at the time of this publication. Neither patient acquired persistent postoperative neurological deficits. CONCLUSION: The fact that seizure activity stopped after destruction of small bottom-of-sulcus dysplasias implies that in these cases, the epileptogenic zone and the epileptogenic lesion may overlap. If future studies can replicate this finding, focused lesion destruction could be a further development of individually tailored epilepsy surgery. The technique described here is especially suited for high-precision surgery close to eloquent brain structures.

Pallidal deep brain stimulation in patients with primary generalised or segmental dystonia: 5-year follow-up of a randomised trial.

BACKGROUND: Severe forms of primary dystonia are difficult to manage medically. We assessed the safety and efficacy of pallidal neurostimulation in patients with primary generalised or segmental dystonia prospectively followed up for 5 years in a controlled multicentre trial. METHODS: In the parent trial, 40 patients were randomly assigned to either sham neurostimulation or neurostimulation of the internal globus pallidus for a period of 3 months and thereafter all patients completed 6 months of active neurostimulation. 38 patients agreed to be followed up annually after the activation of neurostimulation, including assessments of dystonia severity, pain, disability, and quality of life. The primary endpoint of the 5-year follow-up study extension was the change in dystonia severity at 3 years and 5 years as assessed by open-label ratings of the Burke-Fahn-Marsden dystonia rating scale (BFMDRS) motor score compared with the preoperative baseline and the 6-month visit. The primary endpoint was analysed on an intention-to-treat basis. The original trial is registered with ClinicalTrials.gov (NCT00142259). FINDINGS: An intention-to-treat analysis including all patients from the parent trial showed significant improvements in dystonia severity at 3 years and 5 years compared with baseline, which corresponded to -20·8 points (SD 17·1; -47·9%; n=40) at 6 months; -26·5 points (19·7; -61·1%; n=31) at 3 years; and -25·1 points (21·3; -57·8%; n=32). The improvement from 6 months to 3 years (-5·7 points [SD 8·4]; -34%) was significant and sustained at the 5-year follow-up (-4·3 [10·4]). 49 new adverse events occurred between 6 months and 5 years. Dysarthria and transient worsening of dystonia were the most common non-serious adverse events. 21 adverse events were rated serious and were almost exclusively device related. One patient attempted suicide shortly after the 6-month visit during a depressive episode. All serious adverse events resolved without permanent sequelae. INTERPRETATION: 3 years and 5 years after surgery, pallidal neurostimulation continues to be an effective and relatively safe treatment option for patients with severe idiopathic dystonia. This long-term observation provides further evidence in favour of pallidal neurostimulation as a first-line treatment for patients with medically intractable, segmental, or generalised dystonia. FUNDING: Medtronic.

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.

Stereotactic brachytherapy of low-grade cerebral glioma after tumor resection.

The purpose of this study was to assess the impact of stereotactic brachytherapy (SBT) on survival time and outcome when applied after resection of low-grade glioma (LGG) of World Health Organization grade II. From January 1982 through December 2006 we treated 1024 patients who had glioma with stereotactic implantation of iodine-125 seeds and SBT in accordance with a prospective protocol. For the present analysis, we selected 95 of 277 patients with LGG, in whom SBT was applied to treat progressive (43 patients) or recurrent (52 patients) tumor after resection. At 24 months after seed implantation, the tumor response rate was 35.9%, and the tumor control rate was 97.3%. The median progression-free-survival (PFS) duration after SBT was 52.7 ± 7.1 months. Five-year and 10-year PFS probabilities were 43.4% and 10.7%, respectively. Malignant tumor transformation, the diagnosis "astrocytoma," and tumor volume >20 mL were significantly associated with reduced PFS. Tumor progression or relapse after SBT (53 of 95 patients) was treated with tumor resection, a second SBT, chemotherapy, and/or radiotherapy. The median overall survival duration (from the first diagnosis of LGG until the patient's last contact) was 245.0 ± 4.9 months. Patients still under observation after seed implantation had a median follow-up time of 156.4 ± 55.7 months. Perioperative transient morbidity was 1.1%, and the frequency of permanent morbidity caused by SBT was 3.3%. In conclusion, SBT of recurrent or progressive LGG after resection located in functionally critical brain areas has high local efficacy and comparably low morbidity. Referred to individually adopted glioma treatment concepts SBT provides a reasonably long PFS, thus improving overall survival. In selected patients, SBT can lead to delays in the application of chemotherapy and/or radiotherapy.

Stereotactic 125iodine brachytherapy for the treatment of singular brain metastases: closing a gap?

BACKGROUND: Brain metastases represent the most common intracranial tumors and are associated with very poor prognosis. OBJECTIVE: To investigate the feasibility, survival, and cerebral disease control of patients with singular brain metastases treated with stereotactic 125iodine brachytherapy (SBT), to identify prognostic factors, and to compare results with other local treatment methods. METHODS: Complications, survival (overall and separated by recursive partitioning analysis [RPA] classes), and local and distant disease control were evaluated retrospectively in 90 patients. Prognostic factors were identified by forming subgroups of patients based on age, Karnofsky Performance Status, status of extracranial disease, interval since initial diagnosis, absence/presence of prior whole-brain radiation therapy, localization, morphology, and tumor volume. RESULTS: There was no treatment-related mortality, and morbidity was transient and low (3.3%). Median survival was 8.5 months overall and 18.1 months for RPA class 1 patients. After 1 year, the actuarial incidence of local and distant cerebral relapse was 5.4% and 46.4%, respectively. Karnofsky Performance Status ≥ 70 (P < .002), stable systemic disease (P < .02), RPA class 1 (P < .02), and a prolonged (> 12 month) interval between initial diagnosis and SBT (P < .05) significantly improved survival. No significant influence of previous whole-brain radiation therapy on survival or cerebral disease relapse was found. CONCLUSION: SBT represents a safe, minimally invasive, and, compared with SRS and microsurgery, a similarly effective local treatment option in terms of survival and cerebral disease control. It allows histological (re-)evaluation and treatment within 1 stereotactic operation. Because it is less restricted by tumor localization or size, it greatly advances local treatment options, and on the basis of its favorable biological irradiation effect, SBT does not limit additional irradiation treatment in the event of disease relapse.

Comparison of stereotactic brachytherapy (125 iodine seeds) with stereotactic radiosurgery (LINAC) for the treatment of singular cerebral metastases.

PURPOSE: To compare stereotactic brachytherapy (SBT) with stereotactic radiosurgery (SRS) for treating singular cerebral metastases, regarding feasibility, complications, cerebral disease control, and survival. PATIENTS AND METHODS: For this retrospective, single-center study, all patients treated for newly diagnosed, untreated singular cerebral metastasis with SBT using (125)iodine seeds (cumulative tumor surface dose 50 Gy, applied for 42 days) were compared with patients receiving LINAC-based SRS for the same indication. Survival and actuarial local and distant disease control were evaluated using univariate Kaplan-Meier estimates and Cox regression. Results were compared using Student's t test and the χ2 test. RESULTS: A total of 142 patients treated with SRS were compared with 77 patients undergoing SBT. No significant differences were observed between epidemiological and disease-related features (p > 0.05), except a lower KPS (p < 0.007) and a larger tumor volume (p < 0.001) in the SBT group. Neither median survival (LINAC-SRS vs. SBT = 8.1 vs. 8.0 months, respectively) nor actuarial local/distant cerebral disease control after 12 months showed significant differences (93.6% vs. 96.7% / 42.4% vs. 46.4%). There was no treatment-related mortality and no permanent grade 3 or 4 CNS toxicity (RTOG/EORTC CNS toxicity criteria). CONCLUSION: For the treatment of singular cerebral metastasis, SBT represents a safe, minimally invasive, and effective local treatment option with results comparable to SRS regarding survival and cerebral disease control. Its advantage is that it allows histological (re-)evaluation and treatment within one stereotactic procedure and, compared to microneurosurgery, is almost unrestricted regarding tumor localization. Furthermore, larger metastases can be treated than with SRS. SBT, therefore, represents an alternative local treatment in selected cases.

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.

Methods to monitor gene therapy with molecular imaging.

Recent progress in scientific and clinical research has made gene therapy a promising option for efficient and targeted treatment of several inherited and acquired disorders. One of the most critical issues for ensuring success of gene-based therapies is the development of technologies for non-invasive monitoring of the distribution and kinetics of vector-mediated gene expression. In recent years many molecular imaging techniques for safe, repeated and high-resolution in vivo imaging of gene expression have been developed and successfully used in animals and humans. In this review molecular imaging techniques for monitoring of gene therapy are described and specific use of these methods in the different steps of a gene therapy protocol from gene delivery to assessment of therapy response is illustrated. Linking molecular imaging (MI) to gene therapy will eventually help to improve the efficacy and safety of current gene therapy protocols for human application and support future individualized patient treatment.

Thirty days complication rate following surgery performed for deep-brain-stimulation.

Serious adverse events (SAEs) during the first 30 postoperative days after stereotactic surgery for Deep-Brain-Stimulation performed in 1,183 patients were retrospectively collected from five German stereotactic centers. The mortality rate was 0.4% and causes for death were pneumonia, pulmonary embolism, hepatopathy, and a case of complicated multiple sclerosis. The permanent surgical morbidity rate was 1%. The most frequently observed SAEs were intracranial hemorrhage (2.2%) and pneumonia (0.6%). Skin infection occurred in 5 of 1,183 patients (0.4%). Surgical complications caused secondary AEs (e.g. pneumonia) preferentially in older patients and in patients treated for Parkinson's disease (PD). Complication rates did not differ among the five centers.