Endogenous calcitonin gene-related peptide in cerebrospinal fluid and early quality of life and mental health after good-grade spontaneous subarachnoid hemorrhage-a feasibility series.

The vasodilatory calcitonin gene-related peptide (CGRP) is excessively released after spontaneous subarachnoid hemorrhage (sSAH) and modulates psycho-behavioral function. In this pilot study, we prospectively analyzed the treatment-specific differences in the secretion of endogenous CGRP into cerebrospinal fluid (CSF) during the acute stage after good-grade sSAH and its impact on self-reported health-related quality of life (hrQoL). Twenty-six consecutive patients (f:m = 13:8; mean age 50.6 years) with good-grade sSAH were enrolled (drop out 19% (n = 5)): 35% (n = 9) underwent endovascular aneurysm occlusion, 23% (n = 6) microsurgery, and 23% (n = 6) of the patients with perimesencephalic SAH received standardized intensive medical care. An external ventricular drain was inserted within 72 h after the onset of bleeding. CSF was drawn daily from day 1-10. CGRP levels were determined via competitive enzyme immunoassay and calculated as "area under the curve" (AUC). All patients underwent a hrQoL self-report assessment (36-Item Short Form Health Survey (SF-36), ICD-10-Symptom-Rating questionnaire (ISR)) after the onset of sSAH (t1: day 11-35) and at the 6-month follow-up (t2). AUC CGRP (total mean ± SD, 5.7 ± 1.8 ng/ml/24 h) was excessively released into CSF after sSAH. AUC CGRP levels did not differ significantly when dichotomizing the aSAH (5.63 ± 1.77) and pSAH group (5.68 ± 2.08). aSAH patients revealed a higher symptom burden in the ISR supplementary item score (p = 0.021). Multiple logistic regression analyses corroborated increased mean levels of AUC CGRP in CSF at t1 as an independent prognostic factor for a significantly higher symptom burden in most ISR scores (compulsive-obsessive syndrome (OR 5.741, p = 0.018), anxiety (OR 7.748, p = 0.021), depression (OR 2.740, p = 0.005), the supplementary items (OR 2.392, p = 0.004)) and for a poorer performance in the SF-36 physical component summary score (OR 0.177, p = 0.001). In contrast, at t2, CSF AUC CGRP concentrations no longer correlated with hrQoL. To the best of our knowledge, this study is the first to correlate the levels of endogenous CSF CGRP with hrQoL outcome in good-grade sSAH patients. Excessive CGRP release into CSF may have a negative short-term impact on hrQoL and emotional health like anxiety and depression. While subacutely after sSAH, higher CSF levels of the vasodilator CGRP are supposed to be protective against vasospasm-associated cerebral ischemia, from a psychopathological point of view, our results suggest an involvement of CSF CGRP in the dysregulation of higher integrated behavior.

Deep brain stimulation: Connectivity profile for bradykinesia alleviation.

OBJECTIVE: Subthalamic deep brain stimulation may alleviate bradykinesia in Parkinson patients. Research suggests that this stimulation effect may be mediated by brain networks like the corticocerebellar loop. This study investigated the connectivity between stimulation sites and cortical and subcortical structures to identify connections for effective stimulation. METHODS: We retrospectively investigated 21 patients with Parkinson disease with bilateral subthalamic deep brain stimulation. Stimulation effectiveness in reducing bradykinesia, tremor, and rigidity was evaluated for each electrode contact in brain hemispheres contralateral to the affected hemibody. Dysarthric side effects were also examined. Probabilistic tractography based on diffusion-weighted imaging was performed in individual patient-specific brains using electrode contacts as seeds. Connectivity profiles of contacts with effective and noneffective stimulation were compared. RESULTS: Connectivity profiles of effective and noneffective contacts differed. Moreover, the connectivity profile for bradykinesia differed from that for rigidity, tremor, or dysarthria. Regarding bradykinesia, effective contacts were significantly more often connected with the ipsilateral superior cerebellar peduncle and the ipsilateral dentate nucleus, which correspond to the ipsilateral portion of the cerebellothalamocortical pathway. Rigidity was mitigated by stimulation of ascending brainstem and intralaminar thalamic connections. Tremor alleviation was related to connections with the internal capsule (anterior limb) and the pallidum. Dysarthric side effects were associated with connections to the supplementary motor area and the decussating cerebellothalamocortical pathway. INTERPRETATION: Whereas bradykinesia seems to be mitigated by stimulation of the ascending, ipsilateral cerebellothalamocortical pathway, stimulation of the descending corticopontocerebellar pathway may be ineffective. Rigidity, tremor, and dysarthric side effects seem to be influenced by different neural networks. ANN NEUROL 2019;85:852-864.

Long-Term Follow-Up of Cerebral Amyloid Angiopathy-Associated Intracranial Hemorrhage Reveals a High Prevalence of Atrial Fibrillation.

GOAL: Cerebral amyloid angiopathy (CAA) is the second-most common cause of nontraumatic intracerebral hemorrhages (ICH), surpassed only by uncontrolled hypertension. We characterized the percentage, risk factors, and comorbidities of patients suffering from CAA-related ICH in relation to long-term outcomes. MATERIAL AND METHODS: We performed retrospective analyses and clinical follow-ups of individuals suffering from ICH who were directly admitted to neurosurgery between 2002 and 2016. FINDINGS: Seventy-four of 174 (42%) spontaneous nontraumatic lobar ICH cases leastwise satisfied the modified Boston criteria definition for at least "possible CAA." Females suffered a higher risk of CAA-caused ICH (42 of 74, 56.8%, P= .035). Atrial fibrillation as a major comorbidity was observed in 19 patients (25.7%). Recovery (decrease of modified Rankin scale [mRS]) was highest during hospitalization in the acute clinic. One-year mortality was as follows: 14 of 25 patients (56%) with probable CAA without supporting pathology, 6 of 18, and 8 of 31 patients with supporting pathology and possible CAA, respectively. Only 10 of 74 (13.6%) had favorable long-term outcomes (mRS ≤2). Increasing numbers of lobar hemorrhages, low initial Glasgow Coma Scale, and subarachnoid hemorrhage were significantly associated with poor survivability, whereas statins, antithrombotic agents, an intraventricular hemorrhage, and midline shift played seemingly minor roles. CONCLUSIONS: Symptomatic ICH is a serious stage in CAA progression with high mortality. The high incidence of concurrent atrial fibrillation in these patients may support data on more widespread vascular pathology in CAA.

Deep brain stimulation: custom-made silicone-coated pulse-generator implantation after allergic reaction to generator compounds.

Deep brain stimulation for Parkinson's disease has become an established treatment option in recent years. The method and its application in clinical practice has proved to be safe and effective. Nevertheless, procedure-related and hardware-related complications occur. We present a rare case of a patient with an allergic reaction to the impulse generator. The patient suffered from delayed wound-healing deficits with several wound revisions and generator repositionings. After diagnosis of an allergic reaction to components of the generator, a custom-made silicon-coated model was implanted. Hereafter, no wound healing-deficit occurred throughout long-term follow-up. Allergic reaction to hardware components may lead to wound-healing deficits. In such cases, custom-made silicon-coated models may be an effective treatment option.

Probabilistic vs. deterministic fiber tracking and the influence of different seed regions to delineate cerebellar-thalamic fibers in deep brain stimulation.

This study compared tractography approaches for identifying cerebellar-thalamic fiber bundles relevant to planning target sites for deep brain stimulation (DBS). In particular, probabilistic and deterministic tracking of the dentate-rubro-thalamic tract (DRTT) and differences between the spatial courses of the DRTT and the cerebello-thalamo-cortical (CTC) tract were compared. Six patients with movement disorders were examined by magnetic resonance imaging (MRI), including two sets of diffusion-weighted images (12 and 64 directions). Probabilistic and deterministic tractography was applied on each diffusion-weighted dataset to delineate the DRTT. Results were compared with regard to their sensitivity in revealing the DRTT and additional fiber tracts and processing time. Two sets of regions-of-interests (ROIs) guided deterministic tractography of the DRTT or the CTC, respectively. Tract distances to an atlas-based reference target were compared. Probabilistic fiber tracking with 64 orientations detected the DRTT in all twelve hemispheres. Deterministic tracking detected the DRTT in nine (12 directions) and in only two (64 directions) hemispheres. Probabilistic tracking was more sensitive in detecting additional fibers (e.g. ansa lenticularis and medial forebrain bundle) than deterministic tracking. Probabilistic tracking lasted substantially longer than deterministic. Deterministic tracking was more sensitive in detecting the CTC than the DRTT. CTC tracts were located adjacent but consistently more posterior to DRTT tracts. These results suggest that probabilistic tracking is more sensitive and robust in detecting the DRTT but harder to implement than deterministic approaches. Although sensitivity of deterministic tracking is higher for the CTC than the DRTT, targets for DBS based on these tracts likely differ.

Evaluation of robot-guided minimally invasive implantation of 2067 pedicle screws.

Objective Recent studies have investigated the role of spinal image guidance for pedicle screw placement. Many authors have observed an elevated placement accuracy and overall improvement of outcome measures. This study assessed a bi-institutional experience following introduction of the Renaissance miniature robot for spinal image guidance in Europe. Methods The medical records and radiographs of all patients who underwent robot-guided implantation of spinal instrumentation using the novel system (between October 2011 and March 2015 in Mainz and February 2014 and February 2016 in Regensburg) were reviewed to determine the efficacy and safety of the newly introduced robotic system. Screw position accuracy, complications, exposure durations to intraoperative radiation, and reoperation rate were assessed. Results Of the 413 surgeries that used robotic guidance, 406 were via a minimally invasive approach. In 7 cases the surgeon switched to conventional screw placement, using a midline approach, due to referencing problems. A total of 2067 screws were implanted using robotic guidance, and 1857 screws were evaluated by postoperative CT. Of the 1857 screws, 1799 (96.9%) were classified as having an acceptable or good position, whereas 38 screws (2%) showed deviations of 3-6 mm and 20 screws (1.1%) had deviations > 6 mm. Nine misplaced screws, implanted in 7 patients, required revision surgery, yielding a screw revision rate of 0.48% of the screws and 7 of 406 (1.7%) of the patients. The mean ± SD per-patient intraoperative fluoroscopy exposure was 114.4 (± 72.5) seconds for 5.1 screws on average and any further procedure required. Perioperative and direct postoperative complications included hemorrhage (2 patients, 0.49%) and wound infections necessitating surgical revision (20 patients, 4.9%). Conclusions The hexapod miniature robotic device proved to be a safe and robust instrument in all situations, including those in which patients were treated on an emergency basis. Placement accuracy was high; peri- and early postoperative complication rates were found to be lower than rates published in other series of percutaneous screw placement techniques. Intraoperative radiation exposure was found to be comparable to published values for other minimally invasive and conventional approaches.

Fluorescein sodium-guided resection of cerebral metastases-an update.

BACKGROUND: Cerebral metastasis (CM) is the most common malignancy affecting the brain. In patients eligible for surgery, complete tumor removal is the most important predictor of overall survival and neurological outcome. The emergence of surgical microscopes fitted with a fluorescein-specific filter have facilitated fluorescein-guided microsurgery and identification of tumor tissue. In 2012, we started evaluating fluorescein (FL) with the dedicated microscope filter in cerebral metastases (CM). After describing the treatment results of our first 30 patients, we now retrospectively report on 95 patients. METHODS: Ninety-five patients with CM of different primary cancers were included (47 women, 48 men, mean age, 60 years, range, 25-85 years); 5 mg/kg bodyweight of FL was intravenously injected at induction of anesthesia. A YELLOW 560-nm filter (Pentero 900, ZEISS Meditec, Germany) was used for microsurgical tumor resection and resection control. The extent of resection (EOR) was assessed by means of early postoperative contrast-enhanced MRI and the grade of fluorescent staining as described in the surgical reports. Furthermore, we evaluated information on neurological outcome and surgical complications as well as any adverse events. RESULTS: Ninety patients (95%) showed bright fluorescent staining that markedly enhanced tumor visibility. Five patients (5%); three with adenocarcinoma of the lung, one with melanoma of the skin, and one with renal cell carcinoma) showed insufficient FL staining. Thirteen patients (14%) showed residual tumor tissue on the postoperative MRI. Additionally, the MRI of three patients did not confirm complete resection beyond doubt. Thus, gross-total resection had been achieved in 83% (n = 79) of patients. No adverse events were registered during the postoperative course. CONCLUSIONS: FL and the YELLOW 560-nm filter are safe and feasible tools for increasing the EOR in patients with CM. Further prospective evaluation of the FL-guided technique in CM-surgery is in planning.

Underutilization of deep brain stimulation for Parkinson's disease? A survey on possible clinical reasons.

BACKGROUND: Only 10% of the up to 15% of patients with advanced Parkinson's disease (PD) eligible for deep brain stimulation (DBS) are referred to specialized centers. This survey evaluated the reasons for the reluctance of patients and referring physicians regarding DBS. METHODS: Two different questionnaires containing multiple choice and open verbalized questions were developed, one for neurologists and one for patients with PD. The first questionnaire was sent to 87 neurologists in private practice in the catchment area of the authors' medical center, the second to patient support groups in the same region with the help of the German Parkinson Association. RESULTS: Of the addressed neurologists, 56.3% completed the questionnaire; 61.2% of them estimated the risk of intracerebral hemorrhage as the most severe complication at 4.3% on average; 30.6% were concerned about patients developing mood changes or depression after DBS. Only 16.3% felt unable to care for patients after DBS; 61.2% already had personal experience with patients after DBS and reported good clinical outcome in 90.0% of patients. Although 87.8% claimed to know the specific criteria for DBS, only 40.8% could actively describe them. Only 14.0% could state each of the three main criteria. Of the 46 patients, 88.1% completing the questionnaire had obtained information on DBS from regional patient organizations and 54.8% also from a physician; 44.7% assumed the risk of severe complications to be ≥5.0%. Not being satisfied with their medical treatment was reported by 22.2%, of whom more than 70% considered DBS a further treatment option. CONCLUSIONS: The latter numbers indicate that treating neurologists tend to overestimate the reluctance of their patients to undergo DBS. Therefore, education of patients and neurologists should be improved and give more realistic figures on the actual outcomes and frequencies of possible complications.

Fluorescein sodium-guided surgery of parotid gland tumors as a technical advance.

BACKGROUND: Complete tumor removal and preservation of the facial nerve are essential in parotid gland surgery. A technical adjunct that potentially enhances the contrast between the facial nerve and the adherent tumor tissue and allows to identify residual tumor tissue could be Fluorescein Sodium. METHODS: Retrospective chart analysis on 7 patients with benign parotid gland lesions that were operated using Fluorescein Sodium intravenously and the application of the YELLOW 560 nm filter of the operating microscope. Safety and feasibility were evaluated. RESULTS: All tumors showed fluorescence and the rating ´contrast-enhancing´ was assigned in all cases. In 2 patients, satellite nodules were identified and resected meaning that the fluorescence staining of the tumor margins was significantly better than under white light. CONCLUSION: The use of Fluorescein Sodium in parotidectomy is promising. In two cases residual tumor was detected that would have been left behind under white light. Further research in parotid gland surgery and other head and neck tumor procedures is warranted.

DTI-based deterministic fibre tracking of the medial forebrain bundle.

BACKGROUND: Deep brain stimulation (DBS) of the medial forebrain bundle (MFB) was reported to reduce symptoms in psychiatric disorders. The aim of our study was to find standardised parameters for diffusion tensor imaging (DTI) based fibre tracking to reliably visualise the MFB. METHODS: Twenty-two cerebral hemispheres in 11 patients were investigated. Three different regions of interest (ROIs) were defined as seed regions for fibre tracking: the ipsilateral and contralateral superior cerebellar peduncle (SCP) and the nucleus raphe dorsalis (NRD). From each seed region the fibres were followed separately through the ventral tegmental area (VTA = second ROI) and their further courses and volumina were documented and compared. Minimal fibre length was set at 30 mm and the FA threshold at 0.12. RESULTS: The fibre tracts starting in seed regions in the ipsilateral SCP and the NRD follow a similar course along the lateral wall of the third ventricle (hypothalamus) and the anterior limb of the internal capsule (ALIC) to inferior fronto-medial brain areas. These fibres are in accordance with the course of the MFB as described in various anatomical atlases. Consistently, a branch leaves the main fibre tract laterally to take a course through the capsula externa to the temporo-parietal cortex. Fibre tracts starting from the contralateral SCP follow a more superior and lateral course, including the dentato-rubro-thalamic and the pyramidal tract. CONCLUSIONS: Deterministic fibre tracking with standardised ROIs provides constant and reproducible delineations of the medial forebrain bundle. Its visualisation might help to adjust targeting in DBS for psychiatric disorders.

Fluorescein sodium-guided resection of cerebral metastases­experience with the first 30 patients.

BACKGROUND: Surgical resection is a key element of the multidisciplinary treatment of cerebral metastases (CMs). Recent studies have highlighted the importance of complete resection of CMs for improving recurrence-free and overall survival rates. This study presents the first data on the use of fluorescein sodium (FL) under the dedicated surgical microscope filter YELLOW 560 nm (Zeiss Meditec, Germany) in patients with CM. METHODS: Thirty patients with CMs of different primary cancers were included (15 females, 15 males; mean age 61.1 years); 200 mg of FL was intravenously injected directly before CM resection. A YELLOW 560 nm filter was used for microsurgical tumor resection and resection control. Surgical reports were evaluated regarding the degree of fluorescent staining, postoperative MRIs regarding the extent of resection [gadolinium (Gd)-enhanced T1-weighted sequence] and the postoperative courses regarding any adverse effects. RESULTS: Most patients (90.0%, n = 27) showed bright fluorescent staining, which markedly enhanced tumor visibility. Three patients (10.0%) (two with adenocarcinoma of the lung and one with melanoma of the skin) showed no or only insufficient FL staining. Another three patients (10.0%) showed residual tumor tissue in the postoperative MRI examination. In two other patients, radiographic examination could not exclude the possibility of very small areas of residual tumor tissue. Thus, gross-total resection was achieved in 83.3% (n = 25) of patients. No adverse effects were registered over the postoperative course. CONCLUSIONS: FL and the YELLOW 560 nm filter are safe and practical tools for the resection of CM, but further prospective research is needed to confirm that this advanced technique will improve the quality of CM resection.

Continuous intra-arterial nimodipine infusion in patients with severe refractory cerebral vasospasm after aneurysmal subarachnoid hemorrhage: a feasibility study and outcome results.

BACKGROUND: Severe cerebral vasospasm is a major cause of death and disability in patients with aneurysmal subarachnoid hemorrhage. No causative treatment is yet available and hypertensive hypervolemic therapy (HHT) is often insufficient to avoid delayed cerebral ischemia and neurological deficits. We compared patients receiving continuous intra-arterial infusion of the calcium-antagonist nimodipine with a historical group treated with HHT and oral nimodipine alone. METHODS: Between 0.5 and 1.2 mg/h of nimodipine were continuously administered by intra-arterial infusion via microcatheters either into the internal carotid or vertebral artery or both, depending on the areas of vasospasm. The effect was controlled via multimodal neuromonitoring and transcranial Doppler sonography. Outcome was determined by means of the Glasgow Outcome Scale at discharge and 6 months after the hemorrhage and compared to a historical control group. RESULTS: Twenty-one patients received 28 intra-arterial nimodipine infusions. Six months after discharge, the occurrence of cerebral infarctions was significantly lower (42.6 %) in the nimodipine group than in the control group (75.0 %). This result was reflected by a significantly higher proportion (76.0 %) of patients with good outcome in the nimodipine-treated group, when compared to 10.0 % good outcome in the control group. Median GOS was 4 in the nimodipine group and 2 in the control group (p = 0.001). CONCLUSIONS: Continuous intra-arterial nimodipine infusion is an effective treatment for patients with severe cerebral vasospasm who fail to respond to HHT and oral nimodipine alone. Key to the effective administration of continuous intra-arterial nimodipine is multimodal neuromonitoring and the individual adaptation of dosage and time of infusion for each patient.

Deep brain stimulation for essential tremor: targeting the dentato-rubro-thalamic tract?

OBJECTIVE: The aim of our study was to evaluate the influence of the stimulation site relative to the dentato-rubro-thalamic tract (DRTT) on the alleviation of tremor in deep brain stimulation. METHODS: Ten DRTTs in five patients were investigated using preoperative diffusion tensor imaging (DTI). Regions of interest for fiber tracking were located in the cerebellar dentate nucleus, the superior cerebellar peduncle and the contralateral red nucleus. The position and distance of all intraoperative stimulation sites to the DRTT were measured and correlated to the amount of tremor reduction. RESULTS: Nine of 10 DRTTs could be identified using DTI-based fiber tracking. Better tremor reduction was achieved in locations in or posterior and lateral to the DRTT than in medial and anterior positions (p = 0.001). Stimulation sites inferior to and in the DRTT achieved better results than locations superior to the DRTT (p < 0.05). The vicinity of the stimulation site to the DRTT did not correlate with tremor alleviation. DISCUSSION: In deep brain stimulation targeting for thalamic stimulation sites is limited to statistical, atlas-based coordinates. Diffusion tensor imaging and fiber tracking was used to visualize the dentato-rubro-thalamic tract as a potential, individualized target structure. However, we could not demonstrate that contacts closer to the DRTT provided better clinical effects than distant contacts, in any given direction. DTI sequences with a higher number of read-out directions, probabilistic fiber tracking and three Tesla MRI scanners may lead to different results in the depiction of the chosen fiber tract and may provide a better correlation with stimulation effects. CONCLUSIONS: The results do not provide sufficient evidence to define the DRTT as a new DBS-target for tremor. Further investigations on different fiber tracts, DTI sequences, and fiber tracking algorithms are mandatory.

Skull base meningiomas: neurological outcome after microsurgical resection.

Microsurgical resection is the primary treatment of skull base meningiomas. Maximal resection provides the best tumor control rates but can be associated with high surgical morbidity. To understand the relation between extent of resection (EOR) and functional outcome we have analyzed the neurological improvement and recurrence rate in a large consecutive series of skull base meningioma patients. In addition, we defined anatomical and biological factors predictive for recurrence and overall outcome. We investigated 226 skull base meningioma patients receiving tumor resection in our institution. The most frequent location was the medial sphenoid ridge (29.6 %). EOR was rated according to the Simpson scale. Overall performance was measured by the Karnofsky performance score (KPS); neurological deficits were quantified using the Medical Research Council Neurological Severity Score (MRC-NPS). Complete resection was achieved in 62.8 % and the EOR was significantly correlated to tumor location. The morbidity and mortality rate was 32.1 and 2.7 % respectively, new permanent neurological deficits occurred in 3.5 % of all patients. From all patients with focal neurological deficits, 60.1 % experienced significant improvement. Both the MRC-NPS and the KPS significantly improved from the preoperative status to discharge, however the improvement rate was dependent on the tumor location. Recurrence rate was 15.5 %; tumor size, bone- and venous sinus infiltration, WHO grade, poor EOR but not MIB-1 labeling index were independent factors predictive for recurrence. Microsurgical resection of skull base meningiomas improves neurological impairment in the majority of patients. Specific risk factors for recurrence require consideration for postoperative management.

Deep brain stimulation in Parkinson's disease: motor effects relative to the MRI-defined STN.

This study aims to evaluate the improvements of cardinal motor symptoms depending on the stimulation site relative to a standardized, reconstructed three-dimensional MRI-defined subthalamic nucleus (STN.) This retrospective, clinical study includes 22 patients with idiopathic Parkinson's disease, who consecutively underwent bilateral subthalamic nucleus stimulation. Intraoperative microelectrode recording and clinical testing were performed. The location of the best stimulation site, found intraoperatively, and the positions of the active electrode contacts 12 months after the operation were correlated to a standardized, reconstructed three-dimensional MRI-defined STN. Further, the impact of the stimulation site on rigidity, tremor and akinesia was analysed. Significant improvement of the contralateral akinesia was observed if the intraoperative stimulation site was located more lateral and superior in the MRI-STN. Furthermore, active electrode contacts located superior to or in the superior part of the MRI-STN had a significantly better effect on the tremor of the contralateral hand than in other locations inside the STN. For rigidity and akinesia, these correlations were statistically not significant. Although we found significantly better results for tremor suppression in superior and lateral aspects of the STN, for overall clinical improvement, several patients fared better with randomly distributed stimulation sites in medial, posterior or inferior parts of the MRI-defined STN. Locations of stimulation sites with the best improvements of motor symptoms were distributed randomly throughout the whole MRI-defined STN, indicating that MRI-based targeting alone is not sufficient, but intraoperative clinical testing is necessary to determine the optimal stimulation site for each individual patient.

The variability of atlas-based targets in relation to surrounding major fibre tracts in thalamic deep brain stimulation.

BACKGROUND: In essential tremor (ET), the main target for deep brain stimulation (DBS) is the thalamic ventralis intermedius nucleus (Vim). This target cannot be identified on conventional magnetic resonance imaging (MRI). Therefore, targeting depends on probabilistic coordinates derived from stereotactic atlases. The goal of our study was to investigate the variability of atlas-based Vim targets in relation to surrounding major fibre tracts. METHODS: With the MRI and computed tomography (CT) scan data of ten patients who underwent DBS, we planned atlas based Vim targets in both hemispheres. We also performed deterministic fibre-tracking with diffusion tensor imaging (DTI) of the dentato-rubro-thalamic tract (DRTT), pyramidal tract (PT) and lemniscus medialis (LM) in all 20 hemispheres. Subsequently, we measured the distance from the atlas-based Vim target to each tract along the medial/lateral (x-coordinate), anterior/posterior (y-coordinate) and superior/inferior axis (z-coordinate). RESULTS: Seventeen out of 20 DRTTs could be depicted with our standardised DTI/fibre-tracking parameters. The PT and the LM could be displayed in all 20 hemispheres. The atlas-based Vim target was found inside the DRTT in 11 (concerning the x-coordinate) and 10 hemispheres (concerning the z-coordinate). Regarding the anterior/posterior direction, the target was posterior to the DRTT in 11 cases. In 19 hemispheres the Vim target was located medial and superior to the PT and in 17 hemispheres posterior to it. Concerning the LM, the Vim target was found inside the LM in 16 (regarding the x-coordinate) and in 14 cases (regarding the z-coordinate). In eight cases it was located inside and in 12 cases anterior to the LM concerning the y-coordinate. CONCLUSIONS: We found a considerable variability of the location of atlas-based target points of the ventralis intermedius nucleus in relation to neighbouring major fibre tracts in individual patients. These results suggest that individualised targeting to structures not directly visible on conventional MRI is necessary.

Fatal hemorrhagic stroke in a Caucasian girl with moyamoya disease.

INTRODUCTION: Moyamoya disease (MMD) is an extremely rare neurovascular disorder in Caucasian children. To the best of our knowledge, the aggressive variant including hemorrhagic malignant stroke and consecutive global ischemia has not been reported for this population before. CASE REPORT: We present the case of an 11-year-old girl with sudden neurological deterioration due to intracerebral hemorrhage with early irruption into the ventricular system. MMD with extensive neovascularization was diagnosed by means of computed tomography and magnetic resonance imaging. Despite immediate ventricular drainage, intracranial pressure increased above the mean arterial pressure resulting in malignant bi-hemispheric ischemia. The girl died within 53 h after admission to hospital. DISCUSSION: Intracerebral hemorrhage in young patients is often attributed to vascular malformation. This case shows that MMD may constitute a potential diagnosis in the case of sudden neurological deterioration and loss of consciousness, even in previously healthy children.

Awake craniotomies without any sedation: the awake-awake-awake technique.

BACKGROUND: Temporary anaesthesia or analgosedation used for awake craniotomies carry substantial risks like hemodynamic instabilities, airway obstruction, hypoventilation, nausea and vomiting, agitation, and interference with test performances. We tested the actual need for sedatives and opioids in 50 patients undergoing awake craniotomy for brain tumour resection in eloquent or motoric brain areas when cranial nerve blocks, permanent presence of a contact person, and therapeutic communication are provided. METHODS: Therapeutic communication was based on the assumption that patients in such an extreme medical situation enter a natural trance-like state with elevated suggestibility. The anaesthesiologist acted as a continuous guide, using a strong rapport, nonverbal communication, hypnotic suggestions, such as dissociation to a "safe place", and the reframing of disturbing noises, while simultaneously avoiding negative suggestions. Analgesics or sedatives were at hand according to the principle "as much as necessary, but not more than needed". RESULTS: No sedation was necessary for any of the patients besides for the treatment of seizures. Only two-thirds of the patients requested remifentanil, with a mean dosage of 96 µg before the end of tumour resection and a total of 156 µg. Hemodynamic reactions indicative of stress were mainly seen during nerve blockades and neurological testing. Postoperative vigilance tests showed equal or higher scores than preoperative tests. CONCLUSIONS: The main challenges for patients undergoing awake craniotomies include anxiety and fears, terrifying noises and surroundings, immobility, loss of control, and the feeling of helplessness and being left alone. In such situations, psychological support might be more helpful than the pharmacological approach. With adequate therapeutic communication, patients do not require any sedation and no or only low-dose opioid treatment during awake craniotomies, leaving patients fully awake and competent during the entire surgical procedure without stress. This approach can be termed "awake-awake-awake-technique".

The influence of intraoperative microelectrode recordings and clinical testing on the location of final stimulation sites in deep brain stimulation for Parkinson's disease.

BACKGROUND: The goal of our study was to investigate the influence of intraoperative microelectrode recordings and clinical testing on the location of the final stimulation site in deep brain stimulation in Parkinson's disease. METHODS: In 22 patients with Parkinson's disease we compared magnetic resonance imaging (MRI)-based and atlas-based targets with the adjusted stimulation sites after intraoperative, multitrack microelectrode recording (MER) and intraoperative and postoperative clinical testing. The investigation included 176 target/stimulation sites in 44 subthalamic nuclei (STNs), which were related to a standardised three-dimensional, MRI-defined STN. RESULTS: Atlas-based targets were positioned more superior and more medial than the MRI-based targets, which were located in the centre of the MRI-STN. The optimal stimulation sites, found intraoperatively after MER and clinical testing, were located more lateral and slightly more superior than both planned targets. In the majority of the cases the location of the active contact was the most superior and most lateral of all target sites. The differences in the distributions of those four targets reached statistical significance. However, final active contacts were distributed throughout the MRI-defined STN and its immediate surroundings. CONCLUSIONS: The adoption of microelectrode recordings and extensive clinical testing allows the adjustment of anatomical targeting even to unexpected stimulation sites in and around the MRI-defined STN.

Sodium fluorescein-guided resection under the YELLOW 560 nm surgical microscope filter in malignant brain tumor surgery--a feasibility study.

OBJECTIVE: In glioma surgery, the extent of resection (EOR) is one important predictor of progression-free survival. In 2006, fluorescence-guided surgery using 5-aminolevulinic acid (5-ALA) was shown to improve the EOR in malignant gliomas. However, the use of 5-ALA is complex and causes certain side effects. Sodium fluorescein (FL) is a fluorescent dye that is used for angiography in ophthalmic surgery. FL accumulates in areas of the disturbed blood-brain barrier and can be visualized under a 560-nm wavelength fluorescent light source (YELLOW 560 nm, Carl Zeiss Meditec, Oberkochen, Germany). Here, we present the first experiences with low-dose FL and YELLOW 560 nm in 35 patients with malignant brain tumors. PATIENTS AND METHOD: A total of 200 mg of FL (3-4 mg/kg bodyweight) was administered in 35 patients during craniotomy as an off-label use between May and August 2012. We retrospectively analyzed the histology, pre-treatment, clinical parameters pre- and postoperatively and occurrence of any adverse effects. The feasibility and efficacy ('helpful,' 'not helpful') of FL under YELLOW 560 nm (demarcation of the tumor margin) was assessed by the responsible neurosurgeon (n = 5) for each surgical procedure. RESULTS: Twenty-six patients had gliomas (1 WHO grade I, 3 WHO grade II, 5 WHO grade III, 17 WHO grade IV), 5 patients had cerebral metastases, 2 had non-malignant astrogliosis and 2 had post-radiation necrosis. The fluorescence signal was detected in all patients immediately after the FL administration. FL application was classified as 'helpful' in 28 patients, implying improved visualization of the tumor margins. The intensity of the fluorescence signal seemed to be correlated to the histology and was strongly dependent on the pre-treatment status. We did not record any allergic reactions or any other adverse effects. CONCLUSION: The use of FL for the resection of brain tumors is safe and feasible. Presumably, the visualization of the tumor margin depends on the histopathology and on the pre-treatment status. A randomized evaluation of FL under the YELLOW 560 nm filter is planned to prospectively analyze the extent of resection in patients with malignant brain tumors.