Björn Sommer

A Frameless Stereotactic Implantation Technique for Depth Electrodes in Refractory Epilepsy Using Intraoperative Magnetic Resonance Imaging.

OBJECTIVE Various complex techniques for depth electrode insertion in refractory epilepsy using preoperative imaging have been investigated. We evaluated a simple, accurate, cost-effective, and timesaving method using intraoperative magnetic resonance imaging (MRI). METHODS A neuronavigation-guided insertion tube attached to bone facilitated the placement of stereotactic percutaneous drill holes, bolt implantation, and frameless stereotactic insertion of depth electrodes. Image registration was carried out by head coil fiducials with trajectory planning and intraoperative electrode correction. RESULTS In 6 patients with refractory epilepsy (3 women and 3 men; mean age, 30.0 years; range, 20-37 years), 58 depth electrodes (9-11 per patient) were placed. The mean length of the inserted electrodes was 37.3 mm ± 8.8 (mean ± SD) (range, 22.1-84.4 mm). The overall target point accuracy was 3.2 mm ± 2.2 (range, 0-8.6 mm), which was significantly different from the overall entry point accuracy of 1.4 mm ± 1.2 (P < 0.0001). All electrodes functioned perfectly, enabling high-quality stereo-electroencephalography recordings over a period of 7.3 days ± 0.5 (range, 7-8 days). The mean implantation time for 9-11 electrodes per patient was 115 minutes ± 36.3 (range, 75-160 minutes; 12 minutes for 1 electrode on average) including the intraoperative MRI (T1 three-dimensional magnetization-prepared rapid acquisition gradient echo, T2, and diffusion tensor imaging). There was no hemorrhage, infection, or neurologic deficit related to the procedure. CONCLUSIONS Our frameless technique of depth electrode insertion using intraoperative MRI guidance is an accurate, reliable, cost-effective, and timesaving method for stereo-electroencephalography.

Inflammation, but not recruitment, of adipose tissue macrophages requires signalling through Mac-1 (CD11b/CD18) in diet-induced obesity (DIO)

Cell accumulation is a prerequisite for adipose tissue inflammation. The leukocyte integrin Mac-1 (CD11b/CD18, αMβ2) is a classic adhesion receptor critically regulating inflammatory cell recruitment. Here, we tested the hypothesis that a genetic deficiency and a therapeutic modulation of Mac-1 regulate adipose tissue inflammation in a mouse model of diet-induced obesity (DIO). C57Bl6/J mice genetically deficient (Mac-1-/-) or competent for Mac-1 (WT) consumed a high fat diet for 20 weeks. Surprisingly, Mac-1-/- mice presented with increased diet-induced weight gain, decreased insulin sensitivity in skeletal muscle and in the liver in insulin-clamps, insulin secretion deficiency and elevated glucose levels in fasting animals, and dyslipidaemia. Unexpectedly, accumulation of adipose tissue macrophages (ATMs) was unaffected, while gene expression indicated less inflamed adipose tissue and macrophages in Mac-1-/- mice. In contrast, inflammatory gene expression at distant locations, such as in skeletal muscle, was not changed. Treatment of ATMs with an agonistic anti-Mac-1 antibody, M1/70, induced pro-inflammatory genes in cell culture. In vivo, treatment with M1/70 induced a hyper-inflammatory phenotype with increased expression of IL-6 and MCP-1, whereas accumulation of ATMs did not change. Finally, inhibition of Mac-1s adhesive interaction to CD40L by the peptide inhibitor cM7 did not affect myeloid cell accumulation in adipose tissue. We present the surprising finding that adhesive properties of the leukocyte integrin Mac-1 are not required for macrophage accumulation in adipose tissue. Instead, Mac-1 modulates inflammatory gene expression in macrophages. These findings question the net effect of integrin blockade in cardio-metabolic disease.

Combined Laser-Doppler Flowmetry and Spectrophotometry: Feasibility Study of a Novel Device for Monitoring Local Cortical Microcirculation during Aneurysm Surgery.

Background Monitoring of cortical cerebral perfusion is essential, especially in neurovascular surgery. Study Aims To test a novel noninvasive laser‐Doppler flowmetry and spectrophotometry device for feasibility during elective cerebral aneurysm surgery. Material and Methods In this prospective single‐institution nonrandomized trial, we studied local cerebral microcirculation using the noninvasive laser‐Doppler spectrophotometer “Oxygen‐to‐see” (O2C) in 20 consecutive patients (15 female, 5 male; median age: 60.5 ± 11.7 years) who were operated on for incidental cerebral aneurysms. Capillary‐venous oxygenation (oxygen saturation [“SO2”]), postcapillary venous filling pressures (relative hemoglobin content [“rHb”]), blood cell velocity (“velo”), and blood flow (“flow”) were measured in 7‐mm tissue depth using a subdural fiberoptic probe. Results Representative recordings were acquired immediately after dural opening over a median time span of 88 ± 21.8 seconds (range: 60‐128 seconds) before surgical manipulation. Baseline values (median ± 2 standard deviations) of brain perfusion as measured with the O2C device were SO2, 39 ± 16.6%; rHb, 53 ± 18.6 arbitrary units (AU); velo, 60 ± 20.4 AU; and flow, 311 ± 72.8 AU. Placement of the self‐retaining retractor led to a decrease in SO2 of 17% ± 29% (p < .05) and flow of 10% ± 11% (p < .01); rHb increased by 18% ± 20% (p < .01), and velo remained unchanged. Retractor removal caused the opposite with an increased flow of 10% ± 7% (p < 0.001) and velo (3% ± 6%, p = 0.11), but a decrease in SO2 of 24% ± 33% (p = 0.09) and rHb of 12% ± 20% (p =0.18). No neurologic or surgical complications occurred. Conclusion Using this novel noninvasive system, we were able to measure local cerebral microcirculation during aneurysm surgery. Our data indicate that this device is able to detect changes during routine neurosurgical maneuvers. Thus it may be useful for early detection of cerebral microcirculatory disturbances.

Therapeutic challenges in a patient with POEMS syndrome and recurrent stroke: presentation of a case and review of the literature

POEMS syndrome includes the clinical features of polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy and skin changes. A severe complication of patients with this syndrome is ischemic stroke, which has been described only occasionally despite the hematologic abnormalities that may be associated with the disease. In the literature, only eight patients have been reported as suffering from multiple or recurrent strokes until now. We present a 54-year-old woman from Sri Lanka with POEMS syndrome who experienced recurrent ischemic strokes followed by an acute abdomen and global heart failure. On the basis of a literature review, we discuss current therapeutic approaches and their possible side effects.

Magnetoencephalography-guided surgery in frontal lobe epilepsy using neuronavigation and intraoperative MR imaging

BACKGROUND Especially in hidden lesions causing drug-resistant frontal lobe epilepsy (FLE), the localization of the epileptic zone EZ can be a challenge. Magnetoencephalography (MEG) can raise the chances for localization of the (EZ) in combination with electroencephalography (EEG). We investigated the impact of MEG-guided epilepsy surgery with the aid of neuronavigation and intraoperative MR imaging (iopMRI) on seizure outcome of FLE patients. METHODS Twenty-eight patients (15 females, 13 males; mean age 31.0±11.1 years) underwent surgery in our department. All patients underwent presurgical MEG monitoring (two-sensor Magnes II or whole head WH3600 MEG system; 4-D Neuroimaging, San Diego, CA, USA). Of those, six patients (group 1) with MRI-negative FLE were operated on before 2002 with intraoperative electrocorticography (ECoG) and invasive EEG mapping only. Eleven patients with MRI-negative FLE (group 2) and eleven with lesional FLE (group 3) underwent surgery using 1.5T-iopMRI and neuronavigation, including intraoperative visualization of the MEG localizations in 22 and functional MR imaging (for motor and speech areas) as well as DTI fiber tracking (for language and pyramidal tracts) in 13 patients. RESULTS In the first group, complete resection of the defined EZ including the MEG localization according to the latest postoperative MRI was achieved in four out of six patients. Groups two and three had complete removal of the MEG localizations in 20/22 (91%, 10 of 11 each). Intraoperative MRI revealed incomplete resection of the MEG localizations of four patients (12%; two in both groups), leading to successful re-resection. Transient and permanent neurological deficits alike occurred in 7.1%, surgery-associated complications in 11% of all patients. In the first group, excellent seizure outcome (Engel Class IA) was achieved in three (50%), in the second in 7 patients (61%) and third group in 8 patients (64%, two iopMRI-based re-resections). Mean follow-up was 70.3 months (from 12 to 284 months). CONCLUSION In our series, MEG-guided resection using neuronavigation and iopMR imaging led to promising seizure control rates. Even in non-lesional FLE, seizure control rates and the probability of complete resection of the MEG localizations was similar to lesional FLE using multimodal navigation.

Intraoperative Magnetic-Resonance Tomography and Neuronavigation During Resection of Focal Cortical Dysplasia Type II in Adult Epilepsy Surgery Offers Better Seizure Outcomes

OBJECTIVE Focal cortical dysplasia (FCD) is one important cause of drug-resistant epilepsy potentially curable by epilepsy surgery. We investigated the options of using neuronavigation and intraoperative magnetic-resonance tomographical imaging (MRI) to avoid residual epileptogenic tissue during resection of patients with FCD II to improve seizure outcome. METHODS Altogether, 24 patients with FCD II diagnosed by MRI (16 female, 8 male; mean age 34 ± 10 years) suffered from drug-resistant electroclinical and focal epilepsy for a mean of 20.7 ± 5 years. Surgery was performed with preoperative stereoelectroencephalography (in 15 patients), neuronavigation, and intraoperative 1.5T-iopMRI in all 24 investigated patients. RESULTS In 75% of patients (18/24), a complete resection was performed. In 89% (16/18) of completely resected patients, we documented an Engel I seizure outcome after a mean follow-up of 42 months. All incompletely resected patients had a worse outcome (Engel II-III, P < 0.0002). Patients with FCD IIB had also significant better seizure outcome compared with patients diagnosed as having FCD IIA (82% vs. 28%, P < 0.02). In 46% (11/24) of patients, intraoperative second-look surgeries due to residual lesions detected during the intraoperative MRI were performed. In these 11 patients, there were significant more completely seizure free patients (73% vs. 38% Engel IA), compared with 13 patients who finished surgery after the first intraoperative MRI (P < 0.05). CONCLUSIONS Excellent seizure outcome after surgery of patients with FCD II positively correlated with the amount of resection, histologic subtype, and the use of intraoperative MRI, especially when intraoperative second-look surgeries were performed.

Inflammatory Pathways Regulated by Tumor Necrosis Receptor–Associated Factor 1 Protect From Metabolic Consequences in Diet-Induced ObesityNovelty and Significance

Rationale: The coincidence of inflammation and metabolic derangements in obese adipose tissue has sparked the concept of met-inflammation. Previous observations, however, suggest that inflammatory pathways may not ultimately cause dysmetabolism. Objective: We have revisited the relationship between inflammation and metabolism by testing the role of TRAF (tumor necrosis receptor–associated factor)-1, an inhibitory adapter of inflammatory signaling of TNF (tumor necrosis factor)-&agr;, IL (interleukin)-1&bgr;, and TLRs (toll-like receptors). Methods and Results: Mice deficient for TRAF-1, which is expressed in obese adipocytes and adipose tissue lymphocytes, caused an expected hyperinflammatory phenotype in adipose tissue with enhanced adipokine and chemokine expression, increased leukocyte accumulation, and potentiated proinflammatory signaling in macrophages and adipocytes in a mouse model of diet-induced obesity. Unexpectedly, TRAF-1−/− mice were protected from metabolic derangements and adipocyte growth, failed to gain weight, and showed improved insulin resistance—an effect caused by increased lipid breakdown in adipocytes and UCP (uncoupling protein)-1–enabled thermogenesis. TRAF-1–dependent catabolic and proinflammatory cues were synergistically driven by &bgr;3-adrenergic and inflammatory signaling and required the presence of both TRAF-1–deficient adipocytes and macrophages. In human obesity, TRAF-1–dependent genes were upregulated. Conclusions: Enhancing TRAF-1–dependent inflammatory pathways in a gain-of-function approach protected from metabolic derangements in diet-induced obesity. These findings identify TRAF-1 as a regulator of dysmetabolism in mice and humans and question the pathogenic role of chronic inflammation in metabolism.

Intraoperative Vascular Neuromonitoring in Patients with Subarachnoid Hemorrhage: A Pilot Study Using Combined Laser-Doppler Spectrophotometry

BACKGROUND Intraoperative monitoring of cerebral microcirculation in patients with subarachnoid hemorrhage (SAH) may predict the postoperative neurologic outcome. In this pilot study, we examined the value of a novel noninvasive real-time measurement technique for detecting changes in local microcirculation. METHODS We used the O2C (Oxygen to see) laser-Doppler spectrophotometry system in 14 patients with Hunt & Hess grade 2-5 SAH who underwent microsurgical cerebral aneurysm clipping. A subdural probe recorded capillary venous oxygenation (SO2), relative hemoglobin concentration, blood cell velocity, and blood flow at a tissue depth of 7 mm. Data were recorded immediately before dural closure. We also recorded somatosensory evoked potentials (SEPs) with median and tibial nerve stimulation. Results were compared with neurologic performance, as measured on the modified Rankin Scale, at the day of discharge from the hospital and 12 months thereafter. RESULTS Patient functional outcomes after discharge and 12 months were correlated with pathological decreased flow and increased SO2 values. In 6 of 8 patients, microcirculatory monitoring parameters indicated ischemia during surgery, as shown by electrophysiological SEP changes and infarction detected on the postoperative computed tomography (CT) scan. Pathological SEP results correlated closely with infarct demarcation as seen on CT. CONCLUSIONS Our results indicate the potential benefit of intraoperative combined laser-Doppler flowmetry and spectrophotometry for predicting postoperative clinical outcomes in this small patient sample. Larger-cohort testing is needed to verify our findings and show the possible merits of this novel method.

A new functional classification system (FGA/B) with prognostic value for glioma patients

Despite advances in multimodal treatments, malignant gliomas remain characterized by a short survival time. Surgical treatment is accepted to be the first line of therapy, with recent studies revealing that maximal possible tumor reduction exerts significant impact on patient outcome. Consideration of tumor localization in relation to functionally eloquent brain areas has been gaining increasing importance. Despite existing assessment methods, the availability of a simple but reliable preoperative grading based on functional data would therefore prove to be indispensable for the prediction of postoperative outcome and hence for overall survival in glioma patients. We performed a clinical investigation comprising 322 patients with gliomas and developed a novel classification system of preoperative tumor status, which considers tumor operability based on two graduations (Friedlein Grading - FG): FGA with lesions at safe distance to eloquent regions which can be completely resected, and FGB referring to tumors which can only be partially resected or biopsied. Investigation of outcome revealed that FGA were characterized by a significantly longer overall survival time compared to FGB. We offer the opportunity to classify brain tumors in a dependable and reproducible manner. The FGA/B grading method provides high prognostic value with respect to overall survival time in relation to the extent of location-dependent tumor resection.

Long-term outcome after epilepsy surgery in older adults

PURPOSE The incidence of epilepsy in older adults is growing, as does the incidence of comorbidities. Therefore, when it comes to epilepsy surgery in medically intractable epilepsy, age is often seen as a limiting factor. To investigate the outcome after epilepsy surgery in a population of older adults, we compared the benefit for patients aged 50-59 years with those aged 60 years and older in respect of efficacy and safety. METHOD Patients aged ≥50 years with medically intractable epilepsy who underwent epilepsy surgery from 1990 to 2013 were selected from the database of a German epilepsy center. All of them received a standardised and detailed presurgical diagnostic evaluation. Follow-up included at least four scheduled visits with EEG, MRI and neuropsychological testing. Outcome was assessed using the Engel outcome scale. RESULTS 79 patients aged between 50 and 67 years were followed-up for a median of 4.7 years (2-16 years). 68% of patients were free of disabling seizures (Engel class I, ≥60 years: 75%) and 58% were seizure-free (Engel class IA, ≥60 years: 70%). 90% of our patients suffered from temporal lobe epilepsy (TLE), 9% from frontal lobe epilepsy (FLE) and one occipital lobe epilepsy (OLE). After surgery, 9% discontinued or tapered their medication. Permanent surgical complications occurred in 10% of cases and transient neurological deficits were seen in 11%. Older patients had a higher risk for postoperative hygroma (≥60 years 15%; <60 years 8%) and were more prone to postoperative memory deficits (≥60 years 45%), especially after resection of the dominant temporal lobe. Verbal and figural memory testing did not differ significantly between the groups. CONCLUSIONS The results support the view that in selected older patients, epilepsy surgery shows equal or even higher success rates as compared to younger patients. However, patients of older age may be at greater risk for postoperative hygroma and memory deficits, especially after dominant temporal lobe resections.