Occipital Nerve Stimulation in Chronic Migraine: The Relationship Between Perceived Sensory Quality, Perceived Sensory Location, and Clinical Efficacy-A Prospective, Observational, Non-Interventional Study.

INTRODUCTION: Occipital nerve stimulation (ONS) is used to treat therapy-resistant chronic migraine. Clinical use has resulted in a wide intraindividual and interindividual variation of clinical efficacy. The aim of this study was to analyze a potential relationship between sociodemographic variables, headache parameters, perceived sensory quality, perceived sensory location, as well as clinical efficacy. METHODS: Thirty-two subjects (21.9% male, mean age 45.77 years) suffering from chronic migraine refractory to other treatment and therefore treated with ONS were included in this study. We used a computer-based imaging method for mapping the ONS-induced perceived sensory location, the perceived spatial sensory field size, as well as the perceived sensory quality in a long-term course over 21 months in weekly time intervals. Additionally, the effect of ONS on the migraine headache was documented weekly by the participants using a verbal rating scale. Over the observation period, a total of 808 individual weekly data sets were recorded and a potential relationship between ONS-induced perceptions and headache parameters could be analyzed. RESULTS: We found that 48.9% of stimulation intervals were reported as effective by patients. Women displayed a significantly higher responder rate than men. The reported effectiveness did not differ depending on age, the average number of migraine days per month, the MIDAS score, or the duration of the migraine disorder prior to ONS treatment. Implantation with trial period led to significantly lower responder rates than without the trial period. The most frequently perceived sensory quality of "tingling" was found significantly more frequently in non-responders than in responders. Responders displayed significantly lower pleasantness scores for their reported perceptions than non-responders. Sensations that were spatially perceived above the line connecting the external acoustic meati with the external occipital protuberance (MOP line) led to patients reporting a positive clinical effect significantly more frequently than sensations spatially perceived below the MOP line. Spatially small fields of sensory perception were correlated with a higher responder rate than those covering broader areas. CONCLUSIONS: The ONS-induced sensory location, the size of the spatial sensory field, as well as the sensory quality are significantly correlated with the reported clinical effectiveness. The results suggest that besides surgical technique, the individual and continuous programming of the stimulation parameters is clinically relevant in increasing the therapeutic effectiveness.

Screening for Platelet Dysfunction and Use of Prophylactic Tranexamic Acid in Patients Undergoing Deep Brain Stimulation: A Retrospective Analysis of Incidence and Outcome of Intracranial Hemorrhage.

INTRODUCTION: The rate of intracranial hemorrhage (ICH) after deep brain stimulation (DBS) is between 1.5 and 6.1%, with prolonged deficits occurring in 0.4-2.5% of the patients. This retrospective study investigates whether the prophylactic administration of tranexamic acid (TA) to patients with abnormal platelet function detected preoperatively by platelet function analyzer (PFA) lowered the risk for an ICH event. METHODS: We performed a systematic review of the medical records of 485 consecutively admitted patients who underwent bilateral DBS surgery in a single-center university hospital setting between 2009 and 2018. The cohort was split into two groups. In one group, preoperative PFA screening was performed (n = 156, patients recruited from 2014 to 2018), and TA was administered if platelet function was abnormal. No preoperative PFA was performed in the second group (n = 359, patients recruited from 2009 to 2013). Both cohorts were analyzed for the occurrence of ICH, defined by (i) detection of ICH in routine postoperative magnetic resonance/computed tomography imaging or (ii) in non-routine imaging for the onset of new neurological symptoms. RESULTS: Fourteen of the 156 screened patients (9%) showed reproducible PFA-100 closure abnormalities (3 with von Willebrand disease, 11 with no identifiable cause of platelet dysfunction). Two of the 156 patients (1.3%) in this cohort revealed an ICH on imaging, 1 of whom (0.6%) exhibited a prolonged neurological deficit as a result of ICH. In the cohort without platelet testing, 11 of the 329 patients (3.3%) demonstrated ICH on imaging, of whom 5 (1.5%) suffered from a prolonged neurological deficit. CONCLUSION: In this retrospective study, the screening and the administration of TA appeared to lower the risk of an ICH by 1.8%. One patient with von Willebrand disease suffered an ICH despite TA treatment. A prospective study is needed to clarify the impact of platelet testing and TA administration on the of incidence ICH.

Do Adaptors Shorten the Battery Life of Nonrechargeable Generators for Deep Brain Stimulation?

OBJECTIVE: Generators implanted for deep brain stimulation must be replaced after several years. If a Kinetra generator is replaced by the Activa-PC, an adaptor will be required to attach it to the original extension cables. On the basis of our clinical impression that the battery life of the Active-PC generator was shorter when an adaptor was used, we performed this retrospective study. METHODS: We determined the battery lifetimes of deep brain stimulation generators that had been implanted in our department. The inclusion criterion was the initial implantation of a Kinetra generator that was later replaced by an Activa-PC with adaptor, which itself was subsequently also replaced. These patients were compared with an Activa-PC control group without an adaptor but identical with regard to number of battery exchanges, disease, and target. RESULTS: There were 28 patients in the study group and 14 in the control group. Battery lifetime of the Activa-PC with adaptor (32.4 ± 7.7 months) was significantly shorter than that of the Kinetra (53.5 ± 15.7 months, P = 0.000006). The battery life of Activa-PC without an adaptor (35.3 ± 8.2 months) did not differ significantly from that of the Activa-PC with an adaptor (P = 0.333). CONCLUSIONS: The battery lifetime in a replacement Activa-PC is shorter than that in the original Kinetra generator. Adaptors have no significant effect on battery life. Patients should be informed that the battery in their new generator must be checked more frequently than before.

Fear of disease progression in adult ambulatory patients with brain cancer: prevalence and clinical correlates.

BACKGROUND: Fear of progression (FoP) is frequent in patients with cancer and of high clinical relevance. Despite the often devastating prognosis of brain cancer, FoP has not yet been assessed in neurooncological patients. OBJECTIVE: The aim of this study was thus the assessment of FoP and its clinical correlates. METHODS: In an ambulatory setting, 42 patients with a primary brain tumour completed the Fear of Progression questionnaire FoP-Q-12. Clinical correlates of FoP were assessed via a variety of measures, including patients' physical state (Karnofsky Performance Status, KPS), cancer-related psychosocial distress (Distress Thermometer, DT), anxiety (General Anxiety Disorder Scale, GAD-7), depression (Patient Health Questionnaire, PHQ-9), Quality of Life (Short Form Health Survey, SF-8), and unmet supportive care needs (Supportive Care Needs Survey, SCNS). RESULTS: Eighteen patients (42%) suffered from high FoP (i.e. scored ≥ 34 in the FoP-Q-12). According to the 12 items of the FoP-Q-12, the greatest fears were worrying about what would happen to their family and being afraid of severe medical treatments. No sociodemographic variables (e.g. age, gender) or medical tumour characteristics (e.g. tumour malignancy, first or recurrent tumour) were related to FoP. Patients with more severe physical symptoms reported higher FoP. Patients with higher FoP were more anxious, more depressed, reported lower Quality of Life, and suffered from more unmet supportive care needs. CONCLUSION: Our results demonstrate that FoP is frequent and of high clinical relevance for neurooncological patients. Its assessment is not sufficiently covered by instruments for assessment of other areas of psychological morbidity (e.g. general anxiety). Moreover, FoP cannot be predicted by objective characteristics of the patients and disease. Thus, the routine screening for FoP is recommended in neurooncological patients. Clinicians should bear in mind that patients with high FoP are likely to suffer from high emotional distress and unmet supportive care needs and initiate treatment accordingly.

Assessment of preoperative anxiety in neurosurgical patients: Comparison of widely used measures and recommendations for clinic and research.

OBJECTIVE: Preoperative anxiety is frequent in neurosurgical patients and of high clinical relevance (e. g., associated with anestesiological requirements and surgery outcome). Little however is known about the quality of instruments for assessment of preoperative anxiety in this specific patient group and setting. This paper therefore focused on the psychometric properties of widely used questionnaires. Aim of this study was thus to enable both the clinician and the researcher to select appropriate instruments for assessment of surgery-related anxiety. PATIENTS AND METHODS: The following instruments for assessment of preoperative anxiety were administered in a pseudo-randomized order one day prior to surgery in sample of 158 neurosurgical patients: The State Trait Operation Anxiety Inventory (STOA) - state scale, the Amsterdam Preoperative Anxiety and Information Scale (APAIS), and the one-item visual analogue scale (VAS). The questionnaires were psychometrically tested according to classical test theory (validity, reliability, diagnostic accuracy). RESULTS: Construct validity was supported in all applied measures (convergent and divergent validity, known-group comparisons). For the STOA state, we found a one factor scale structure and thus no support for the proposed subscales covering cognitive and affective anxiety. The proposed scale structure of the APAIS, measuring anxiety and information requirement, was replicated. Internal consistency as indicator for reliability of the STOA and the APAIS was excellent (Cronbach's alpha = 0.937/0.868). All instruments showed adequate diagnostic accuracy with the most favourable results of the STOA. CONCLUSIONS: All instruments included in this study can be recommended for assessment of surgery-related anxiety in neurosurgical patients with regard to their psychometric properties. Each instrument offers distinct advantages. Thus, clinicians and researchers can base their individual choice on specific aims and available resources.

Breaking Bad News to Patients with Intracranial Tumors: The Patients' Perspective.

OBJECTIVE: Bad news refers to information that subjectively impedes a patient's future prospects. Patients with intracranial tumors potentially face numerous pieces of bad news. This study assessed the patients' perspective regarding the content of bad news, patients' preferences for the communication of bad news, and clinical consequences of mismatch of patients' communication preferences. METHODS: We included 42 patients with an intracranial tumor shortly after neurosurgical tumor removal. Patients' preferences for communication of bad news was assessed via the Measure of Patients' Preferences Scale. Various areas of patients' psychosocial well-being were included (e.g., depression or quality of life). RESULTS: At this early stage of the disease trajectory, patients with a brain tumor had already received on average 2.2 (standard deviation, 1.38; range, 0-6) pieces of bad news. For most patients, these pieces included receiving the initial diagnosis. Patients reported a multitude of communication preferences, some highly specific for patients with brain tumors. On average, 30% of these preferences were not matched with the physicians' behavior. Communication mismatch was associated with lower patient satisfaction regarding information but no other areas of psychosocial well-being. CONCLUSIONS: Communicating bad news to the patient with a brain tumor in a way that is appreciated by the patient is a complex and demanding endeavor for the treating physician. Meeting patients' needs not only requires the skills regarding the communication of cancer-related news but also accounting for the specific needs ascribable to the neurologic features of the disease (e.g., regarding neuropsychological impairment or neurosurgical treatment).

A missing piece? Neuropsychiatric functioning in untreated patients with tumors within the cerebellopontine angle.

PURPOSE: To date, little is known about neuropsychiatric symptoms in patients with tumors within the cerebellopontine angle (CPA). These, however, might be of clinical relevance. Aim of this study was thus to assess possible impairment in cognition, elevation in mood symptoms, and fatigue in this specific patient group. METHODS: Forty-five patients with an untreated CPA tumor (27 vestibularis schwannoma, 18 meningioma) were tested within a cross-sectional observational study in a single institution prior to neurosurgical treatment. Patients were administered a multifaceted battery comprising of widely-used tests for assessment of neuropsychiatric functioning. RESULTS: The majority of the included patients (69%) showed neurocognitive impairment, most frequently in the areas of attention and visuo-motor speed (e.g., alertness) (62%) as well as visuo-construction (44%). Impaired structural integrity of the brain stem was accompanied by more serious neurocognitive deficits. About one-third of the sample reported clinically relevant depression and/or anxiety and an even higher proportion (48%) described high levels of fatigue. Cognitive and affective symptoms as well as fatigue contributed significantly to patients' Quality of Life, indicating the clinical relevance of neuropsychiatric symptoms in patients with CPA tumors. CONCLUSIONS: Although patients with untreated CPA tumors often suffer from devastating and prominent physical symptoms, neuropsychiatric problems are also frequent. Including these aspects in the routine clinical assessment and initiating treatment accordingly might thus improve clinical management of the patients and improve Quality of Life.

Surgery-Related Coping in Surgery Patients with Intracranial Tumors.

BACKGROUND: Neurosurgical brain tumor removal poses a unique threat for patients while also minimizing instrumental control. Thus, psychological processes used by patients to cope with surgery-related anxiety are of utmost importance. This is the first study to assess both nature and effectiveness of surgery-related coping efforts in neuro-oncological patients. METHODS: We included 70 inpatients with an intracranial tumor before neurosurgical treatment. For assessment of patients' coping efforts, we used the Coping with Surgical Stress Scale, which includes the 5 subscales: Rumination, Optimism and Trust, Turning to Social and Religious Resources, Threat Avoidance, and Information Seeking. The extent of operation-specific anxiety was assessed via the State-Trait-Operational-Anxiety Inventory. Effectiveness of coping efforts was assessed via relations to other areas of psychosocial well-being (e.g., depression or health-related quality of life). RESULTS: All patients reported using a variety of coping strategies, most frequently from the area of Optimism and Trust, which was associated with less surgery-related anxiety and better emotional well-being. By contrast, Rumination was positively correlated with surgery-related anxiety and psychiatric morbidity. Mediator analyses supported a model in which surgery-related anxiety initiates coping efforts, which then distinctively mediates the influence of patients' anxiety on psychosocial well-being. CONCLUSIONS: Neuro-oncologic patients undertake considerable psychological effort to cope with surgery-related anxiety. The majority of patients use coping strategies facilitating emotional adjustment. A minority of patients, however, report extensive rumination, which negatively influences psychosocial well-being. Our results stress the importance of the doctor-patient relationship and offer implications for targeted interventions.

Complications of Impulse Generator Exchange Surgery for Deep Brain Stimulation: A Single-Center, Retrospective Study.

BACKGROUND: Nonrechargeable deep brain stimulation impulse generators (IGs) with low or empty battery status require surgical IG exchange several years after initial implantation. The aim of this study was to investigate complication rates after IG exchange surgery and identify risk factors. METHODS: We retrospectively analyzed complications following IG exchange surgery from 2008 to 2015 in our department. Medical records of all patients who underwent IG exchange surgery were systematically reviewed. The shortest follow-up time was 19 months. RESULTS: From 2008 to 2015, 438 IGs were exchanged in 319 patients. Overall complication rate was 8.90%. Infection developed in 12 patients (2.74%). Six patients (1.37%) experienced local wound erosions. Hardware malfunctions were present in 11 patients (2.51%), and local hemorrhage was observed in 3 cases (0.68%). Repeated fixation of the IG was required in 2 patients (0.46%). Traction of the connecting cables necessitated surgical revision in 2 patients (0.46%). In 2 cases (0.46%), the IG was placed abdominally or exchanged for a smaller device owing to patient discomfort resulting from the initial positioning. One 80-year-old patient (0.23%) had severely worsening heart failure and died 4 days after IG exchange surgery. CONCLUSIONS: IG exchange surgery, although often considered a minor surgery, was associated with a complication rate of approximately 9% in our center. Patients and physicians should understand the complication rates associated with IG exchange surgery because this information might facilitate selection of a rechargeable IG.

Spatial and Cellular Expression Patterns of Erythropoietin-Receptor and Erythropoietin during a 42-Day Post-Lesional Time Course after Graded Thoracic Spinal Cord Impact Lesions in the Rat.

Erythropoietin (Epo) exhibits promising neuroregenerative potential for spinal cord injury (SCI), and might be involved in other long-term sequelae, such as neuropathic pain development. The current studies investigated the time courses and spatial and cellular patterns of Epo and erythropoietin receptor (EpoR) expression along the spinal axis after graded SCI. Male Long Evans rats received 100 kdyn, 150 kdyn, and 200 kdyn thoracic (T9) contusions from an Infinite Horizon impactor. Sham controls received laminectomies. Anatomical and quantitative immunohistochemical analyses of the EpoR/Epo expression along the whole spinal axis were performed 7, 15, and 42 postoperative days (DPO) after the lesioning. Cellular expression was investigated by double- and triple-labeling for EpoR/Epo with cellular markers and proliferating cells in subgroups of 5-bromo-2-deoxyuridine pre-treated animals. Prolonged EpoR/Epo-expression was confirmed by real-time reverse transcriptase polymerase chain reaction (RT-PCR). Quantified EpoR/Epo immunoreactivities in pain-related spinal cord regions and ventrolateral white matter (VLWM) were correlated with the mechanical sensitivity thresholds and locomotor function of the respective animals. EpoR and Epo were constitutively expressed in the ventral horn neurons and vascular and glial cells in the dorsal columns (DC) and the VLWM. After SCI, in addition to expression in the lesion core, EpoR/Epo immunoreactivities exhibited significant time- and lesion grade-dependent induction in the DC and VLWM along the spinal axis. EpoR and Epo immunoreactive cells were co-stained with markers for astroglial, neural precursor cell and vascular markers. In the VLWM, EpoR- and Epo-positive proliferating cells were co-stained with glial fibrillary acidic protein (GFAP) and nestin. The DC EpoR/Epo immunoreactivities exhibited linear relationships with the behavioral correlates of post-lesional chronic pain development at DPO 42. SCI leads to long-lasting multicellular EpoR/Epo induction beyond the lesion core in the spinal cord regions that are involved in central pain development and regenerative processes. Our studies provide a time frame to investigate the effects of Epo application on motor function or pain development, especially in the later time course after lesioning.

Comparison of the Battery Life of Nonrechargeable Generators for Deep Brain Stimulation.

OBJECTIVE: Nonrechargeable deep brain stimulation (DBS) generators must be replaced when the battery capacity is exhausted. Battery life depends on many factors and differs between generator models. A new nonrechargeable generator model replaced the previous model in 2008. Our clinical impression is that the earlier model had a longer battery life than the new one. We conducted this study to substantiate this. METHODS: We determined the battery life of every DBS generator that had been implanted between 2005 and 2012 in our department for the treatment of Parkinson's disease, and compared the battery lives of the both devices. We calculated the current used by estimating the total electrical energy delivered (TEED) based on the stimulation parameters in use one year after electrode implantation. RESULTS: One hundred ninety-two patients were included in the study; 105 with the old and 86 with the new model generators. The mean battery life in the older model was significantly longer (5.44 ± 0.20 years) than that in the new model (4.44 ± 0.17 years) (p = 0.023). The mean TEED without impedance was 219.9 ± 121.5 mW * Ω in the older model and 145.1 ± 72.7 mW * Ω in the new one, which indicated significantly lower stimulation parameters in the new model (p = 0.00038). CONCLUSION: The battery life of the new model was significantly shorter than that of the previous model. A lower battery capacity is the most likely reason, since current consumption was similar in both groups.

Cellular Profiles and Molecular Mediators of Lesion Cascades in the Placode in Human Open Spinal Neural Tube Defects.

Myelomeningoceles (mmc) are clinically challenging CNS malformations. Although improvement in their management has been achieved with respect to antenatal diagnosis, prevention, and fetal surgery, the cellular mechanisms of damage in the neural placode are poorly understood. We aimed to identify cellular and molecular factors in lesion amplifying cascades in mmc placodes. Seventeen mmc specimens obtained during reconstructive surgery that harbored sufficient neuroepithelial tissue were investigated. Normal adult and stillborn spinal cord tissue served as controls. Placodes exhibited similar cellular profiles with consistent neuronal marker expression, elevated GFAP-/vimentin immunoreactivity in all, and CD3/CD11b/CD68-immunolabeling in some cases. Increased expression of pro-inflammatory (tumor necrosis factor, interleukin-1ß [Il-1ß]/IL-1 receptor type 1 [IL-R1]) and neuroprotective erythropoietin/erythropoietin receptor (Epo/EpoR) cytokines was detected by immunohistochemistry, double-fluorescence labeling, and real-time RT-PCR. In all cases, there was a multi-cellular induction of IL-1ß and IL1-R1. EpoR and Epo immunoreactivity was elevated in some cases with neuronal expression patterns. Epo was further co-expressed with HIF-1/-2α, which paralleled Epo induction in the corresponding placodes. These observations confirm the induction of cellular and molecular alterations in human mmc placodes that resemble the secondary lesion cascades induced by spinal cord injury. The pro-inflammatory and neuroprotective cytokine expression in mmc placodes may represent new targets for the treatment of open neural tube defects.

The sensory-motor profile awake-A new tool for pre-, intra-, and postoperative assessment of sensory-motor function.

OBJECTIVES: Awake craniotomy is a well-established procedure in surgery of intracranial tumors in eloquent areas. However, sufficiently standardized instruments for the assessment of sensory-motor function before, during and after the operation are currently lacking, despite their importance for evaluation of operative outcome. PATIENTS AND METHODS: To address this issue, we designed a standardized assessment tool (the "sensory-motor profile awake scale"; SMP-a). The final scale consists of three motor sections (face, arm and leg) assessing both gross and fine motor skills and one sensory section. It differentiates between six grades of impairment and its tasks are applicable for intraoperative continuous monitoring of sensory-motor functions and supporting processes. We analyzed the data of 17 patients with intracranial tumors eligible for awake craniotomy who were preoperatively assessed with the SMP-a. In addition, we present an exemplary case. RESULTS: Our data support the assumption that the SMP-a is feasible in patients eligible for awake craniotomy, even in patients with symptoms of mild aphasia or more severe sensory-motor deficits caused by tumor recurrence. The exemplary case demonstrates the feasibility of repeated measures with the SMP-a in a tumor patient, including the adaption of tasks to the individual requirements of an intraoperative setting. CONCLUSION: This exploratory study suggests that the SMP-a might be a feasible rating scale in patients with intracranial tumors. The flexibility of the scale enables individual adaption, but preserves the standardized scoring system to allow comparison between assessment dates, patients and, hopefully in the future, institutions. However, future studies are mandatory to provide data on the instrument's diagnostic properties with respect to feasibility, objectivity, validity and reliability.

Deep brain stimulation for dystonia: review of the literature.

Deep brain stimulation (DBS) has become one of the major therapy options for movement disorders including dystonia. This article should give a review of the current literature from a neurosurgical perspective. Since dystonia is a rare disease, only few studies on larger cohorts have been published, and very few randomized controlled studies are avaialable in the international literature. Our experiences gained treating 134 patients with various types of dystonia, between 1999 and 2015, will serve a guide to interpret the current literature. Symptoms of dystonia are due to a variety of medical conditions. A careful and extensive neurological evaluation is mandatory before medical and surgical treatment options are considered, since the clinical benefits of more aggressive treatment e.g. by DBS depend to a large extent on the etiology of the disease. Diagnostic steps should include also magnetic resonance imaging (MRI) and possibly genetic evaluation. Therapy consists of physiotherapy, medical therapy including botulinum toxin injections in focal dystonia and DBS. This neurosurgical therapy is considered a highly effective therapy in well selected patients, which should be discussed, depending on the etiology, early in the patient's career. Patients with primary dystonia will benefit the most from DBS to the ventromediolateral part of the globus pallidus internus (GPi) with acceptable low complication rates; in order to optimize longterm results in these groups of patient, they will require an interdisciplinary individualized approach both pre- and postoperatively as well as longterm care adjusting to their needs.

Cognitive screening in patients with intracranial tumors: validation of the BCSE.

This study presents the first validation of the Brief Cognitive Status Exam (BCSE) against two other screening tools for cognitive impairment in patients with intracranial tumors. 58 patients and 22 matched healthy controls completed the BCSE, the Mini Mental State Examination (MMSE) and the Montreal Cognitive Assessment (MoCA). Patients were additionally tested with a comprehensive neuropsychological battery. Based on this assessment, they were classified as cognitively impaired or unimpaired on five cognitive domains. Analyses revealed a comparable feasibility of the BCSE relative to the MoCA and the MMSE, but a smaller range of assessed functions (e.g., no correlation with the domain visual-spatial functions). The ability to separate patients and healthy controls was extremely poor for BCSE and MMSE (sensitivity of 38.6 % and less), but moderate for MoCA (sensitivity 68.97 %). Detection of cognitive impairment in patients was worst with BCSE (sensitivity 37 %; MoCA 92.9 %, MMSE 44.4 %) as compared to neuropsychological testing. Moreover, prediction of cognitive outcome was also worst for the BCSE (AUC = .713, NPV = 50 %). An optimal cut-off of 50.5 increased the results slightly. In summary, the BCSE showed good feasibility but no sufficient results in separating healthy individuals from patients or detecting cognitive impairment in patients. Consequently, as a screening measure, we would recommend the MoCA instead of the BCSE. However, since even the MoCA failed to detect cognitive impairment, our study supports the view that reliable results could only be obtained with a comprehensive neuropsychological battery.

Down regulation of Akirin-2 increases chemosensitivity in human glioblastomas more efficiently than Twist-1.

The Twist-1 transcription factor and its interacting protein Akirin-2 regulate apoptosis. We found that in glioblastomas, highly malignant brain tumors, Akirin-2 and Twist-1 were expressed in glial fibrillary acidic protein positive tumor regions as well as in tumor endothelial cells and infiltrating macrophages / microglia. Temozolomide (TMZ) induced the expression of both molecules, partly shifting their nuclear to cytosolic localization. The knock-down (kd) of Akirin-2 increased the activity of cleaved (c)Caspase-3/-7, the amounts of cCaspases-3, -7 and cPARP-1 and resulted in an increased number of apoptotic cells after TMZ exposure. Glioblastoma cells containing decreased amounts of Akirin-2 after kd contained increased amounts of cCaspase-3 as determined by the ImageStreamx Mark II technology. For Twist-1, similar results were obtained with the exception that the combination of TMZ treatment and Twist-1 kd failed to significantly reduce chemoresistance compared with controls. This could be attributed to a cell population containing only slightly increased cCaspase-3 together with decreased Twist-1 levels, which was clearly larger than the respective population observed under Akirin-2 kd. Our results showed that, compared with Twist-1, Akirin-2 is the more promising target for RNAi strategies antagonizing Twist-1/Akirin-2 facilitated glioblastoma cell survival.

Imaging sensory effects of occipital nerve stimulation: a new computer-based method in neuromodulation.

BACKGROUND: Within the last years, occipital nerve stimulation (ONS) has proven to be an important method in the treatment of severe therapy-resistant neurological pain disorders. The correspondence between lead placement as well as possible stimulation parameters and the resulting stimulation effects remains unclear. OBJECTIVE: The method aims to directly relate the neuromodulatory mechanisms with the clinical treatment results, to achieve insight in the mode of action of neuromodulation, to identify the most effective stimulation sets and to optimize individual treatment effects. METHODS: We describe a new computer-based imaging method for mapping the spatial, cognitive and affective sensory effects of ONS. The procedure allows a quantitative and qualitative analysis of the relationship between lead positioning, the stimulation settings as well as the sensory and clinical stimulation effects. CONCLUSION: A regular mapping of stimulation and sensory parameters allows a coordinated monitoring. The stimulation results can be reviewed and compared with regards to clinical effectiveness.

Visualization of small veins with susceptibility-weighted imaging for stereotactic trajectory planning in deep brain stimulation.

Intracerebral hemorrhage (ICH) is the most significant complication of Deep Brain Stimulation (DBS). To prevent ICH, stereotactic contrast enhanced T1-weighted images are used to visualize vessels as source of hemorrhage. Susceptibility-Weighted Imaging (SWI) is an MRI sequence with improved visualization of susceptibility differences between tissues, particularly sensitive for brain veins. The aim of this prospective study was to analyze the utility of SWI compared to contrast enhanced stereotactic T1-weighted images for trajectory planning of DBS. Preoperative SWI was performed in 33 patients undergoing DBS and was compared to the T1-weighted images. Vessels identified only with SWI in relation to the bilateral planned trajectory were analyzed. In all patients vessels were depicted on SWI only within the planned trajectory (range 1-4 vessels, for each trajectory, mean: 2.4). In 6 patients vessels were identified on SWI adjacent to the target (up to 5mm distal from target). In 11 patients SWI visualized additional cortical veins adjacent to the entry point of the trajectory. The apparent diameter of these vessels ranged between 0.8 and 2.1mm (mean: 1.2mm). Postoperative MRI was compared with preoperative SWI and revealed in two patients small (<3 mm) T2 hyperintense lesions along electrodes without correlation with visualized veins. SWI facilitates the visualization of small veins superior to T1-weighted images. However, cerebral veins within the trajectory were not found to be a significant source of ICH after DBS. Potential sources of ICH are mesencephal veins at the endpoint of electrodes which can cause fatal hemorrhage and are visualized with SWI reliably.

Functional magnetic resonance imaging of motor and language for preoperative planning of neurosurgical procedures adjacent to functional areas.

OBJECTIVE: Functional magnetic resonance imaging (fMRI) for motor and language mapping is used for presurgical planning. This study aimed to evaluate the value of fMRI in clinical routine for preoperative planning of brain surgery adjacent to functional brain areas. METHODS: Thirty-seven consecutive patients with brain lesions adjacent to sensomotor and/or language functional areas underwent fMRI prior to planned brain surgery on a 3T MRI scanner for identification of motor in all and language functional areas in 29 patients. Analysis software installed on the MRI console was used for rapid image analysis and direct visualization. All fMRI results were analyzed according to the use for preoperative planning. RESULTS: fMRI data analysis and visualization was possible in less than 10min. In 35 patients fMRI of motor cortex and in 25 patients fMRI of language could be performed due to the patient's compliance. In 34 patients motor activity could be clearly identified in the precentral gyrus. The dominant hemisphere could be identified clearly in 22 cases. In 18 patients direct anatomical correlation of the activity maps to the speech area of Broca and/or Wernicke could be made. Resection surgery was performed in all patients. 11 patients underwent awake surgery with intraoperative cortical stimulation. CONCLUSION: fMRI for clinical routine is a reliable and rapid method for identification of functional brain areas prior to brain surgery adjacent to functional areas. This method allows direct monitoring of the data quality and visualization without being time consuming. Knowledge about the relation of functional areas to the brain lesions improves the preoperative planning, the operation strategy and decision making with patients.