Nitro-fatty acids suppress ischemic ventricular arrhythmias by preserving calcium homeostasis.

Nitro-fatty acids are electrophilic anti-inflammatory mediators which are generated during myocardial ischemic injury. Whether these species exert anti-arrhythmic effects in the acute phase of myocardial ischemia has not been investigated so far. Herein, we demonstrate that pretreatment of mice with 9- and 10-nitro-octadec-9-enoic acid (nitro-oleic acid, NO2-OA) significantly reduced the susceptibility to develop acute ventricular tachycardia (VT). Accordingly, epicardial mapping revealed a markedly enhanced homogeneity in ventricular conduction. NO2-OA treatment of isolated cardiomyocytes lowered the number of spontaneous contractions upon adrenergic isoproterenol stimulation and nearly abolished ryanodine receptor type 2 (RyR2)-dependent sarcoplasmic Ca2+ leak. NO2-OA also significantly reduced RyR2-phosphorylation by inhibition of increased CaMKII activity. Thus, NO2-OA might be a novel pharmacological option for the prevention of VT development.

Development of evidence-based quality indicators for deep brain stimulation in patients with Parkinson's disease and first year experience of implementation of a nation-wide registry.

INTRODUCTION: Deep Brain Stimulation (DBS) is a complex, invasive and cost-intensive therapy that requires a high level of expertise. To date, data on quality of DBS in clinical routine in the German health care system are lacking. METHODS: The development of evidence-based QIs for DBS in PD patients was performed following a standardized process by a multidisciplinary board between 2014 and 2016. The process was initiated by the German Parkinson Society and followed international recommendations for developing QIs including: a systematic literature search; an appraisal of the published evidence; a consensus-based selection of the QI set; and a pilot study to assess the feasibility in implementing the QIs in clinical routine. RESULTS: A set of 28 QIs for determining the quality of DBS in PD was established by the board covering different dimensions of health care quality (structure, process, and outcome) in different treatment phases of DBS care (pre-operative, peri-operative, and post-operative). Implementation in clinical practice was tested in a pilot study comprising three hospitals delivering DBS care. The feasibility of the QI set was evaluated positively by the participating physicians and hospitals. Mean time to document one patient was 25 min. The German-wide implementation of the defined indicator set within a dedicated quality registry (QualiPa) started in June 2016. CONCLUSION: QIs are a necessary requirement to monitor hospital performance in DBS care. The evidence-based approach to develop the proposed indicator set is expected to assure transparency, acceptance and long-term applicability of the QI set in Germany.

Deep Brain Stimulation Surgery without Sedation.

BACKGROUND: Sedatives and opioids used during deep brain stimulation (DBS) surgery interfere with optimal target localization and add to side effects and risks, and thus should be minimized. OBJECTIVE: To retrospectively test the actual need for sedatives and opioids when cranial nerve blocks and specific therapeutic communication are applied. METHODS: In a case series, 64 consecutive patients treated with a strong rapport, constant contact, non-verbal communication and hypnotic suggestions, such as dissociation to a "safe place," reframing of disturbing noises and self-confirmation, were compared to 22 preceding patients under standard general anaesthesia or conscious sedation. RESULTS: With introduction of the protocol the need for sedation dropped from 100% in the control group to 5%, and from a mean dose of 444 mg to 40 mg in 3 patients. Remifentanil originally used in 100% of the patients in an average dose of 813 µg was reduced in the study group to 104 µg in 31% of patients. There were no haemodynamic reactions indicative of stress during incision, trepanation, electrode insertion and closure. CONCLUSION: With adequate therapeutic communication, patients do not require sedation and no or only low-dose opioid treatment during DBS surgery, leaving patients fully awake and competent during surgery and testing.

The risk of hypotension and seizures in patients receiving prophylactic anti-epileptic drugs for supratentorial craniotomy.

BACKGROUND: Perioperative seizure prophylaxis with antiepileptic drugs (AED) has been advocated in patients undergoing supratentorial craniotomy. The practice remains controversial. The reasoning presupposes that the possibility of an adverse drug reaction from the AED is lower than the probability of harm from a seizure. Even short periods of hypotension during the operation can lead to acute kidney and myocardial injury. We retrospectively evaluated cardiovascular effects and tolerability of levetiracetam (LEV) alone, LEV and lacosamid (LCM) as compared to phenytoin (PHT). METHODS: After IRB approval, the charts of individuals who underwent craniotomy from April 2007 to September 2011 were reviewed. Those receiving PHT were compared to those receiving LEV alone and LEV/LCM. The patient data included demographic, indication and procedure related data. The cumulative dose of norepinephrine (NET), atropine (ATR) and the change in systolic blood pressure during and after the administration of the AED were analyzed. RESULTS: Five hundred thirty-eight patients were screened of which 122 were included for analysis. 40 patients with primary or secondary supratentorial brain tumors received LEV (19 female, 21 male; mean age 56 years), 41 patients received LEV/ LCM (16 female, 25 male; mean age 56 years) and 41 patients received PHT (15 female, 26 male; mean age 50 years). The commonest indications for craniotomy were glioblastoma (N.=14 vs. N.=12 vs. N.=15), meningiomas (N.=9 vs. N.=7 vs. N.=10), low-grade gliomas (N.=6 vs. N.=13 vs. N.=6) and brain metastases (N.=5 vs. N.=4 vs. N.=5). 1 LEV/LCM patient (2%) and 4 PHT patients (4.5%) had a seizure despite prophylaxis. Possible side effects were observed in 2 patients associated with PHT. During anesthesia there was a significant drop in systolic blood pressure in the PHT group after administration of the AED perioperatively when compared to LEV (P=0.001) and LEV/LCM (P≤0.0001) respectively. The mean cumulative doses of NET and ATR over the course of the operation did not differ significantly. CONCLUSIONS: LEV alone and in combination with LCM for patients without and with symptomatic epilepsy as seizure prophylaxis provides a safe and feasible alternative to PHT. PHT was associated with an unfavorable drop in blood pressure during anesthesia and more adverse reactions.

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.

Educational attainment and motor burden in advanced Parkinson's disease - The emerging role of education in motor reserve.

OBJECTIVE: To explore the relationship of motor burden and educational attainment in patients with advanced stage PD. MATERIALS AND METHODS: We included 102 consecutive patients who underwent a complete evaluation for DBS surgery, including detailed neuropsychological testing and UPDRSIII in a standardized Levodopa challenge. Years of education (YoE) were calculated as the highest grade attained in secondary school plus years for post-secondary training. RESULTS: The OFF medication UPDRS-III score was associated with YoE (p=0.006; t=-2.82) and age (p=0.007; t=-2.75) in our multivariable linear regression model even while including disease duration (p=0.8; t=0.21), presence of mild cognitive impairment (MCI) (p=0.9; t=0.16) or current IQ (p=0.2; t=1.25) as additional covariables. In a subgroup of 60 patients two years after DBS, the ON/ON UPDRS score was associated with YoE (p=0.01; t=-2.42) and diagnosis of PD dementia (p=0.05, t=1.95), while age (p=0.08, t=1.75), disease duration (p=0.6t=0.48) and LEDD (p=0.3; t=1.05) showed no significant association to ON/ON UPDRS score. CONCLUSIONS: We found an inverse correlation between years of education and lower (better) UPDRS -III motor score after adjusting for important covariables. Education may lead to an increased ability to compensate disturbances in basal ganglia circuits affecting not only for cognitive, but also for motor aspects of PD. Thus, educational attainment may play an important role in the concept of motor reserve.

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.

Myeloperoxidase Mediates Postischemic Arrhythmogenic Ventricular Remodeling.

RATIONALE: Ventricular arrhythmias remain the leading cause of death in patients suffering myocardial ischemia. Myeloperoxidase, a heme enzyme released by polymorphonuclear neutrophils, accumulates within ischemic myocardium and has been linked to adverse left ventricular remodeling. OBJECTIVE: To reveal the role of myeloperoxidase for the development of ventricular arrhythmias. METHODS AND RESULTS: In different murine models of myocardial ischemia, myeloperoxidase deficiency profoundly decreased vulnerability for ventricular tachycardia on programmed right ventricular and burst stimulation and spontaneously as assessed by ECG telemetry after isoproterenol injection. Experiments using CD11b/CD18 integrin-deficient (CD11b-/-) mice and intravenous myeloperoxidase infusion revealed that neutrophil infiltration is a prerequisite for myocardial myeloperoxidase accumulation. Ventricles from myeloperoxidase-deficient (Mpo-/-) mice showed less pronounced slowing and decreased heterogeneity of electric conduction in the peri-infarct zone than wild-type mice. Expression of the redox-sensitive gap junctional protein Cx43 (Connexin 43) was reduced in the peri-infarct area of wild-type compared with Mpo-/- mice. In isolated wild-type cardiomyocytes, Cx43 protein content decreased on myeloperoxidase/H2O2 incubation. Mapping of induced pluripotent stem cell-derived cardiomyocyte networks and in vivo investigations linked Cx43 breakdown to myeloperoxidase-dependent activation of matrix metalloproteinase 7. Moreover, Mpo-/- mice showed decreased ventricular postischemic fibrosis reflecting reduced accumulation of myofibroblasts. Ex vivo, myeloperoxidase was demonstrated to induce fibroblast-to-myofibroblast transdifferentiation by activation of p38 mitogen-activated protein kinases resulting in upregulated collagen generation. In support of our experimental findings, baseline myeloperoxidase plasma levels were independently associated with a history of ventricular arrhythmias, sudden cardiac death, or implantable cardioverter-defibrillator implantation in a cohort of 2622 stable patients with an ejection fraction >35% undergoing elective diagnostic cardiac evaluation. CONCLUSIONS: Myeloperoxidase emerges as a crucial mediator of postischemic myocardial remodeling and may evolve as a novel pharmacological target for secondary disease prevention after myocardial ischemia.

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.

Distance between Active Electrode Contacts and Dentatorubrothalamic Tract in Patients with Habituation of Stimulation Effect of Deep Brain Stimulation in Essential Tremor.

Background Some patients under thalamic deep brain stimulation (DBS) for essential tremor (ET) experience habituation of tremor reduction. The nucleus ventralis intermedius (Vim) is the current main target side for ET in DBS. However, the dentatorubrothalamic tract (DRTT) is considered the relevant structure to stimulate. We investigated the distance between the active contact of the DBS electrode and the DRTT and compared this distance in patients with habituation of tremor reduction and good responders. Material and Methods In this retrospective study, we performed deterministic fiber tracking of the DRTT in 6 patients (12 hemispheres) with ET who underwent DBS in the Vim. We subsequently measured the distance between the active contact of the electrode and the ipsilateral DRTT in both hemispheres. The clinical tremor response of those 6 patients was analyzed accordingly. Results The distance between the active contact and the DRTT in patients with better and constant clinical tremor reduction was shorter (mean distance: 2.9 ± 2.2 mm standard deviation [SD]) than in patients who showed habituation of their response (mean distance: 6.1 ± 3.9 mm SD). After re-placement of a thalamic electrode inside the DRTT in one patient who experienced unsatisfying tremor reduction due to habituation of stimulation, the tremor alleviation was significant and persistent at a 13-month follow-up. Conclusion This retrospective analysis suggests that recurrence of ET tremor under chronic DBS might be associated with a larger distance between the DRTT and the active lead contact, in comparison with the smaller distances in patients with persistently good tremor control.

Intravenous lacosamide in clinical practice-Results from an independent registry.

PURPOSE: This non-interventional study was conducted to evaluate the efficacy and tolerability of intravenous lacosamide (LCM-iv) under routine conditions in daily clinical practice as a prospective registry. METHODS: Patients with any type of seizure or epilepsy syndrome were recruited in 16 neurological and neuropediatric centers in Germany if the treating physician decided to administer LCM-iv for any reason. Observation time per patient was 10 days with daily documentation of LCM-iv administration, type and frequency of seizures, currently used drugs and doses, and adverse events. Treatment efficacy, tolerability, and handling of LCM-iv were assessed using a five-step scale. RESULTS: In 119 patients treating physicians classified epilepsies as focal in 66.1% and generalized in 17.4% (16.5% unclassifiable). Most common etiologies of seizures were tumors (36.1%) and cerebrovascular diseases (21.8%). Reasons for LCM-iv treatment included preparation for surgery (25.2%), convulsive (24.4%) and non-convulsive (18.5%) status epilepticus (SE), series of seizures (16.0%), gastrointestinal causes (5.9%), and acute seizures (4.2%). The median dose of LCM-iv was 300mg per day. In 45 of 64 patients (70.3%) with SE or series of seizures, epileptic activity ceased during observation time. Five patients showed abnormalities in ECG prior to the infusion and one patient afterwards, but during infusion no abnormalities were reported. Treating physicians rated efficacy and tolerability as very good or good in 77.6% and 93.1% of patients, respectively. CONCLUSIONS: This large and independent multicenter registry on the use of LCM-iv in clinical practice demonstrates that LCM-iv is well-tolerated and highly efficacious when given in emergency situations, including patients experiencing SE. It is advisable to perform an electrocardiogram prior to LCM-iv administration.

Urgent discectomy: Clinical features and neurological outcome.

BACKGROUND: To evaluate the clinical features and outcome of patients with progressive neurological deficits due to disc herniation who were treated surgically within 24 h. METHODS: We conducted a retrospective analysis of consecutive patients who were admitted between 2004 and 2013 via the Emergency Department. Records were screened for presenting symptoms, neurological status at admission, discharge, and 6-week follow-up. RESULTS: About 72 of 526 patients underwent surgery within 24 h. Magnetic resonance imaging showed lumbar disc herniation in 72 patients. The most common presenting symptoms included radiculopathy (n = 69), the Lasègue sign (n = 60), sensory deficits (n = 57), or motor deficits (n = 47). In addition, 11 patients experienced perineal numbness and 12 had bowel and bladder dysfunction. At discharge, motor and sensory deficits and bowel and bladder dysfunction had improved significantly (P < 0.001, P = 0.029, and P = 0.015, respectively). CONCLUSION: Motor deficits, sensory deficits, and cauda equina dysfunction were significantly improved immediately after urgent surgery. After 6 weeks, motor and sensory deficits were also significantly improved compared to the neurological status at discharge. Thus, we advocate immediate surgery of disc herniation in patients with acute onset of motor deficits, perineal numbness, or bladder or bowel dysfunction indicative of cauda equina syndrome.

47 patients with FLNA associated periventricular nodular heterotopia.

BACKGROUND: Heterozygous loss of function mutations within the Filamin A gene in Xq28 are the most frequent cause of bilateral neuronal periventricular nodular heterotopia (PVNH). Most affected females are reported to initially present with difficult to treat seizures at variable age of onset. Psychomotor development and cognition may be normal or mildly to moderately impaired. Distinct associated extracerebral findings have been observed and may help to establish the diagnosis including patent ductus arteriosus Botalli, progressive dystrophic cardiac valve disease and aortic dissection, chronic obstructive lung disease or chronic constipation. Genotype-phenotype correlations could not yet be established. METHODS: Sanger sequencing and MLPA was performed for a large cohort of 47 patients with Filamin A associated PVNH (age range 1 to 65 years). For 34 patients more detailed clinical information was available from a structured questionnaire and medical charts on family history, development, epileptologic findings, neurological examination, cognition and associated clinical findings. Available detailed cerebral MR imaging was assessed for 20 patients. RESULTS: Thirty-nine different FLNA mutations were observed, they are mainly truncating (37/39) and distributed throughout the entire coding region. No obvious correlation between the number and extend of PVNH and the severity of the individual clinical manifestation was observed. 10 of the mutation carriers so far are without seizures at a median age of 19.7 years. 22 of 24 patients with available educational data were able to attend regular school and obtain professional education according to age. CONCLUSIONS: We report the clinical and mutation spectrum as well as MR imaging for a large cohort of 47 patients with Filamin A associated PVNH including two adult males. Our data are reassuring in regard to psychomotor and cognitive development, which is within normal range for the majority of patients. However, a concerning median diagnostic latency of 17 to 20 years was noted between seizure onset and the genetic diagnosis, intensely delaying appropriate medical surveillance for potentially life threatening cardiovascular complications as well as genetic risk assessment and counseling prior to family planning for this X-linked dominant inherited disorder with high perinatal lethality in hemizygous males.

Deep Brain Stimulation for Obsessive Compulsive Disorder Reduces Symptoms of Irritable Bowel Syndrome in a Single Patient.

Irritable bowel syndrome (IBS) is a frequent gastrointestinal disorder that is difficult to treat. We describe findings from evaluation of a woman (55 years old) with obsessive compulsive disorder, which was treated with bilateral deep brain stimulation in the anterior limb of the internal capsule, and IBS. After the brain stimulation treatment she reported substantial relief of her IBS symptoms. This reduction depended on specific stimulation parameters, was reproducible over time, and was not directly associated with improvements in obsessive compulsive disorder symptoms. These observations indicate a specific effect of deep brain stimulation on IBS. This observation confirms involvement of specific brain structures in the pathophysiology of IBS and shows that symptoms can be reduced through modulation of neuronal activity in the central nervous system. Further studies of the effects of brain stimulation on IBS are required.

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.

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.

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.

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.

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.