Lutz Weise

Intraoperative microelectrode recording for the delineation of subthalamic nucleus topography in Parkinson's disease

BACKGROUND The subthalamic nucleus (STN) as an effective target for deep brain stimulation (DBS) in advanced Parkinsons disease is functionally divided into the dorsolateral sensorimotor and the ventromedial limbic and associative parts. To implant electrodes for DBS close to the sensorimotor region is considered crucial for optimal motor benefit and for avoidance of potential cognitive and behavioral side effects. OBJECTIVE The aim of this study was to determine whether the functional segregation of the STN is associated with distinct and region-specific neuronal activity patterns and action potential properties obtained by intraoperative microelectrode recordings. METHODS In 12 Parkinsons disease patients, stepwise intraoperative microelectrode recordings were performed using five concentrically configured electrodes starting 10 mm above the calculated target point until the dorsal border of the substantia nigra. RESULTS Based on autocorrelogram analysis of a total of 329 single units, we found a higher occurrence of oscillatory (P < 0.01) and bursty (P = 0.058) spike pattern in the dorsal versus the ventral STN. In contrast the ventral region was characterized by irregular firing neurons (P < 0.01). There were no significant differences in firing frequency, coefficient of variance, asymmetry index as well as spike form, duration, and amplitude. CONCLUSIONS Among all parameters analyzed in the study, spike pattern is the only convenient electrophysiologic parameter for the differentiation of STN subregions in patients with Parkinsons disease. The autocorrelogram-based analysis of spike activity seems to be of certain value for the delineation of the dorsolateral STN and might therefore facilitate the precise electrode implantation for DBS.

Sustained focal antitumor activity of bevacizumab in recurrent glioblastoma

Objectives: To investigate the relevance of bevacizumab (BEV)-induced diffusion-restricted lesions and T1-hyperintense lesions in patients with recurrent glioblastoma. Methods: We prospectively screened 74 BEV-treated patients with recurrent glioblastoma for (1) diffusion-restricted lesions and/or, (2) lesions with a hyperintense signal on precontrast T1-weighted images. We further evaluated overall survival (OS), histopathology of the lesions, and patterns of progression. Results: Twenty-five of 74 patients (34%) developed T1-hyperintense lesions, whereas diffusion-restricted lesions could be detected in 35 of 74 patients (47%). In 21 of 74 patients (28%), the lesions displayed both features (“double-positive”). OS for patients with double-positive lesions was 13.0 months; patients with neither of these lesions had an OS of 6.6 months (p < 0.005). Histologic evaluation of double-positive lesions revealed extensive calcified necrosis in 4 of 4 patients. Notably, these double-positive lesions were rarely involved in further tumor progression. However, they were associated with an increase in distant recurrences at BEV failure. Conclusions: BEV-induced double-positive MRI lesions are a predictive imaging marker associated with a substantial survival benefit and with improved local control in patients with recurrent glioblastoma. Our data suggest that these lesions are the result of a sustained focal antitumor activity of BEV.

Does navigated transcranial stimulation increase the accuracy of tractography? A prospective clinical trial based on intraoperative motor evoked potential monitoring during deep brain stimulation.

BACKGROUND Tractography based on diffusion tensor imaging has become a popular tool for delineating white matter tracts for neurosurgical procedures. OBJECTIVE To explore whether navigated transcranial magnetic stimulation (nTMS) might increase the accuracy of fiber tracking. METHODS Tractography was performed according to both anatomic delineation of the motor cortex (n = 14) and nTMS results (n = 9). After implantation of the definitive electrode, stimulation via the electrode was performed, defining a stimulation threshold for eliciting motor evoked potentials recorded during deep brain stimulation surgery. Others have shown that of arm and leg muscles. This threshold was correlated with the shortest distance between the active electrode contact and both fiber tracks. Results were evaluated by correlation to motor evoked potential monitoring during deep brain stimulation, a surgical procedure causing hardly any brain shift. RESULTS Distances to fiber tracks clearly correlated with motor evoked potential thresholds. Tracks based on nTMS had a higher predictive value than tracks based on anatomic motor cortex definition (P < .001 and P = .005, respectively). However, target site, hemisphere, and active electrode contact did not influence this correlation. CONCLUSION The implementation of tractography based on nTMS increases the accuracy of fiber tracking. Moreover, this combination of methods has the potential to become a supplemental tool for guiding electrode implantation.

Correlation of Active Contact Positions with the Electrophysiological and Anatomical Subdivisions of the Subthalamic Nucleus in Deep Brain Stimulation

Background: The most effective contacts in subthalamic nucleus (STN) deep brain stimulation are reported to be dorsolateral, and suppression of synchronized oscillatory activity might be a mechanism of action. Objectives: To analyze the optimal contact position in regard to the anatomical and electrophysiological position and to determine whether oscillatory and bursty activity is more frequent around the active contact. Methods: In 21 patients, the clinically most effective contacts were analyzed according to their relative position to the anatomical and electrophysiological STN center, which was assessed by T2-weighted MRI and microrecording. In 12 out of 21 consecutive patients, autocorrelograms of the action potentials within the vicinity of the active contact were compared to the most ventromedial reference contact. Results: The isocenter of the anatomical and electrophysiological STN had a mean deviation of 0.8 mm (SD 1.45). Thirty-two out of 42 active contacts were found dorsal to the anatomical isocenter of the STN. None of the active contacts were ventral to the STN. Synchronized oscillatory or bursty activity was found in 67% of the patients within the vicinity of the active contact. In 64% of the patients, the ventromedial reference contact showed irregular activity. Conclusions: Synchronized activity in the autocorrelogram correlates with the most effective contact. The optimal localization of the finally stimulated contact is dorsal to the STN isocenter.

Diurnal Variation of Hypothalamic Function and Chronic Subthalamic Nucleus Stimulation in Parkinson's Disease

Background: Deep brain stimulation of the subthalamic nucleus (STN-DBS) improves quality of life in patients with advanced Parkinsons disease (PD), but is associated with neuropsychiatric side effects and weight gain in some individuals. The pathomechanisms of these phenomena are still unknown. Considering anatomical and functional connections of the STN with the hypothalamic-pituitary (HP) system, we prospectively investigated whether chronic STN-DBS alters HP functioning in 11 PD patients. Methods: Basal hormone levels of the HP-adrenal (HPA), HP-gonadal and HP-somatotropic axis were determined before surgery as well as 3 and 6 months after electrode implantation. In addition, 24-hour cortisol profiles and dexamethasone suppression tests were obtained. Postoperative hormone changes were correlated with individual neuropsychological test performance, psychiatric status and anthropometric measures. Results: While PD patients experienced weight gain (p = 0.025) at follow-up, most neuropsychological data and basal HP hormone levels did not change over time. HPA regulation and diurnal rhythmicity of cortisol remained intact in all patients. The 24-hour mean cortisol levels decreased 6 months after surgery (p = 0.002) correlating with improved postoperative depression (p = 0.02). Conclusions: Chronic application of high-frequency electrical stimuli in the STN was not associated with HP dysfunction in patients with advanced PD. The diurnal variability of peripheral cortisol secretion as one important element of the endogenous biological clock remained intact. Evening cortisol levels decreased after surgery reflecting a favorable regulation of the cortisol setpoint. STN-DBS can be considered safe from a neuroendocrine perspective, but the origin of unwanted side effects warrants further elucidation.

Intraoperative bleeding in stereotactic biopsies and its implication on postoperative management: can we predict CT findings?

Background: Stereotactic biopsies are procedures with a high diagnostic yield and a low but serious risk of hemorrhage. Postoperative management remains controversial. Objectives: To evaluate the predictive value of intraoperative bleeding and its implication on postoperative management. Methods: Cases of intraoperative bleeding were prospectively documented in a consecutive series comprising 303 patients. Categories were as follows: no bleeding, single drop, ≤10 drops and >10 drops. Incidence, size of hemorrhage and neurological deterioration were noted. Hemorrhage on routine postoperative CT scans was correlated with intraoperative findings, sample size, location and pathology. Results: A total of 93 patients (30.7%) showed intraoperative bleeding and 68 (22.4%) showed blood on postoperative CT. In 13 patients (4.3%) the diameter was >1 cm; 19 patients (6.3%) experienced neurological worsening, 9 (3.0%) having postoperative hemorrhage and 3 (1.0%) permanent neurological deficits. Bleeding was associated with postoperative hemorrhage (p < 0.0001). The negative predictive values to rule out any postoperative hemorrhage or hemorrhages >1 cm were 92 and 100%, respectively. Number of samples, location and pathology had no significant influence on postoperative hemorrhage. Conclusion: Stereotactic biopsies have a low risk of symptomatic hemorrhages. Intraoperative bleeding is a surveillance parameter of hemorrhage on CT. Therefore, routine postoperative CT may be restricted to patients who show intraoperative bleeding.

Confounding Factors in Diagnostics of MGMT Promoter Methylation Status in Glioblastomas in Stereotactic Biopsies

Background: In nonresectable glioblastoma (GBM), stereotactic biopsies are performed to retrieve tissue for diagnostic purposes. The analysis of O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation adds prognostic and predictive information. Objectives: The aim of the study was to detect confounding factors that limit the number of conclusive MGMT promoter methylation results. Methods: We analyzed 71 consecutive GBM patients undergoing stereotactic biopsy on whom MGMT analysis was performed by methylation-specific polymerase chain reaction. Specimens were correlated to imaging by coregistration and prospective documentation of biopsy localization. Our findings were validated in an additional 62 GBM stereotactic biopsies. Results: Our results demonstrate that the best MGMT promoter methylation results were obtained from samples (n = 71) taken in a tangential manner from tumor areas showing contrast enhancement in magnetic resonance imaging. In the additional validation series of 62 stereotactically biopsied GBM, we were able to increase the rate of conclusive MGMT promoter methylation results from 76.1 to 85.48% by strictly planning the route of biopsy in a tangential manner if possible. Conclusions: These results underline that within the contrast-enhanced tumor part, choosing the trajectory in a tangential manner increases the diagnostic yield for conclusive MGMT promoter methylation analyses in stereotactic biopsies as a basis for patient stratification and individualized therapy.

Impact of Stereotactic Biopsy in HIV Patients

OBJECTIVE During their disease a significant number of human immunodeficiency virus (HIV)-infected patients develop neurologic symptoms due to intracerebral pathologies. Entities commonly found are toxoplasmosis, lymphomas, or progressive multifocal leukoencephalopathy. In some patients, diagnosis is not feasible with imaging alone, requiring biopsy. The objective of this study was to evaluate the impact of stereotactic biopsy in HIV patients on adjustment of therapy. METHODS Between January 2004 and May 2015 at our clinic, 26 HIV-infected patients underwent stereotactic biopsy. Thin-layer magnetic resonance images were obtained and fused with computed tomography scans, taken with the stereotactic frame (Leksell) mounted. Biopsy material was evaluated pathologically and microbiologically. RESULTS Histologic analysis revealed B-cell lymphoma in 6 patients (23.1%) and progressive multifocal leukoencephalopathy in 2 patients (7.7%). Abscess and toxoplasmosis were found in 3 patients each (11.5% and 11.5%), and encephalitis occurred in 4 patients (15.4%). In 2 patients each (7.7%), vasculitis, metastasis, and glioblastoma were diagnosed. Further findings comprised non-Hodgkin lymphoma and Burkitt lymphoma in 1 patient each. After biopsy, treatment was significantly changed in 18 (69.2%) patients (P < 0.01). Antibiotic therapy was adjusted in 6 patients (23.1%), and chemotherapy in 3 patients (16.7%). Other changes included antibiotic/antiviral therapy to chemotherapy in 3 patients (16.7%), chemotherapy to radiation, cortisone to chemotherapy, and aciclovir to cortisone in 1 patient each. One patient with glioblastoma underwent resection, and another patient received radiation. One patient underwent palliative care. CONCLUSION Stereotactic biopsy in HIV-infected patients results in significant changes of therapy in more than two thirds of the patients.

Benefit of Stereotactic Procedures in a Series of 43 Children

Objectives: Stereotactic biopsies are procedures that enable neurosurgeons to obtain tissue samples of brain tumors located in eloquent areas with a low risk of perioperative complications. In this study, we examined stereotactic procedures (STX) in children. We focused on effectiveness, safety, and histopathological results to evaluate the benefits of the procedure. Methods: We performed a retrospective analysis of our prospective database and included 43 children aged less than 18 years who underwent STX between 1998 and May 2015. All MRIs were evaluated by a single, experienced neuroradiologist. For all biopsies, Leksell stereotactic frame was used and fixed to the children’s head with four pins. Entry and targetpoints were calculated by BrainLab navigation system. We assessed age, tumor localization, number of samples, histological diagnosis, and postoperative treatment. Results: Median age of the patients was 11 years (range 1-18 years), and median number of tissue samples taken was 12 (range 1 with mere puncture of a cyst to 36). Histopathological examination revealed a final diagnosis in all patients. 3 patients underwent puncture of a cyst. 27 patients had a postoperative imaging. Only in 3 patients, CT scan revealed blood in the area where the biopsy had been taken. All bleedings were small and without clinical sequelae. Conclusion: Stereotactic procedures are accurate and save surgeries to obtain tumor tissue from eloquent areas to base further therapy on. This not only applies to adults but also to children of all ages.

Stereotactic Biopsy of Pineal Lesions

BACKGROUND Stereotactic biopsies are carried out to obtain tumor tissue of unknown entity from cerebral lesions. Thus, tumor tissue can be examined, resulting in correct diagnosis and treatment. These procedures go in hand with high accuracy, high diagnostic yield, and low complication rates. OBJECTIVES The aim of this study is to evaluate the results and complications of stereotactic biopsies carried out for lesions of the pineal region. METHODS We performed a retrospective analysis of our prospective database and included 14 patients who underwent stereotactic biopsy of a pineal lesion between 2006 and February 2016. The Leksell stereotactic frame was used in all patients, and entry and target points were calculated using the BrainLab stereotactic system. We evaluated histopathologic results and postoperative complications such as hydrocephalus and hemorrhage. RESULTS Histopathologic diagnosis was established in all patients. On postoperative computed tomography, 7 patients (50%) showed a circumscribed blood collection at the site of biopsy. Six patients (42.8%) required a cerebrospinal fluid drain preoperatively. Two patients needed external ventricular drain postoperatively (14.2%). One of these patients showed a small hemorrhage area that caused the hydrocephalus. The other patient showed only postoperative swelling. Preoperatively, 2 patients (14.2%) already had a ventriculoperitoneal (VP) shunt, whereas postoperatively, another 4 patients (28.5%) needed a VP shunt. Thus, of the 14 patients, 6 (42.8%) required a VP shunt. CONCLUSIONS Because of their localization, pineal lesions may result in emergence of a hydrocephalus. Stereotactic biopsies in this area may increase this effect and, thus, even VP shunts are necessary in some patients.