Imaging the effective networks associated with cortical function through intracranial high‐frequency stimulation

Direct electrical stimulation (DES) is considered to be the gold standard for mapping cortical function. A careful mapping of the eloquent cortex is key to successful resective or ablative surgeries, with a minimal postoperative deficit, for treatment of drug‐resistant epilepsy. There is accumulating evidence suggesting that not only local, but also remote activations play an equally important role in evoking clinical effects. By introducing a new intracranial stimulation paradigm and signal analysis methodology allowing to disambiguate EEG responses from stimulation artifacts we highlight the spatial extent of the networks associated with clinical effects. Our study includes 26 patients that underwent stereoelectroencephalographic investigations for drug‐resistant epilepsy, having 337 depth electrodes with 4,351 contacts sampling most brain structures. The routine high‐frequency electrical stimulation protocol for eloquent cortex mapping was altered in a subtle way, by alternating the polarity of the biphasic pulses in a train, causing the splitting the spectral lines of the artifactual components, exposing the underlying tissue response. By performing a frequency‐domain analysis of the EEG responses during DES we were able to capture remote activations and highlight the effect''s network. By using standard intersubject averaging and a fine granularity HCP‐MMP parcellation, we were able to create local and distant connectivity maps for 614 stimulations evoking specific clinical effects. The clinical value of such maps is not only for a better understanding of the extent of the effects'' networks guiding the invasive exploration, but also for understanding the spatial patterns of seizure propagation given the timeline of the seizure semiology.     

Quality of life impairment in adult Moyamoya patients—preoperative neuropsychological assessment and correlation to MRI and H215O PET findings

Moyamoya angiopathy (MMA) related cerebral perfusion deficits or infarctions might influence quality of life (QoL). This study examines preoperative QoL in adult patients with MMA and correlates these with findings obtained via diagnostic imaging. Sixty-seven adult Moyamoya patients underwent preoperative neuropsychological testing including questionnaires to determine QoL, as well as psychiatric and depressive symptoms. The results were checked for correlation with territorial hypoperfusions seen in H₂¹⁵O PET with acetazolamide (ACZ) challenge (cerebrovascular reserve) and infarction patterns observed in MRI. Each vascular territory was analyzed separately and correlated with QoL. Physical role function was restricted in 41.0% of cases and emotional role function in 34.4% of cases (SF-36). Obsessive–compulsive disorder (39.3%) (SCL-90-R), psychoticism (34.4%) (SCL-90-R), and depression (32.7%) (BDI-II) were also very common. Psychoticism was significantly more frequent in cases where perfusion deficits in PET CT were observed in both MCA territories (left p?=?0.0124, right p?=?0.0145) and infarctions in MRI were present in the right MCA territory (p?=?0.0232). Depression was significantly associated with infarctions in the right MCA territory (SCL-90-R p?=?0.0174, BDI-II p?=?0.0246). Women were affected more frequently by depression (BDI-II, p?=?0.0234). Physical role function impairment was significantly associated with perfusion deficits in the left MCA territory (p?=?0.0178) and infarctions in the right MCA territory (p?=?0.0428). MMA leads to impairments in different areas of QoL. Approximately one-third of all adult MMA patients suffered from depression, with women being most affected. In addition to depression, presence of executive dysfunctions and mental disorders such as psychoticism, obsessive–compulsive disorder, and impaired physical and emotional role function affected QoL. These patients showed significantly more often infarctions and perfusion deficits in the right MCA territory. Long-term studies with follow-up results are necessary to clarify a possible beneficial impact of early surgical revascularization on QoL and depression in adult MMA patients.

     

Toll-like receptor 9 signaling mediates the anti-inflammatory effects of probiotics in murine experimental colitis

BACKGROUND & AIMS: We tested whether the attenuation of experimental colitis by live probiotic bacteria is due to their immunostimulatory DNA, whether toll-like receptor (TLR) signaling is required, and whether nonviable probiotics are effective. METHODS: Methylated and unmethylated genomic DNA isolated from probiotics (VSL-3), DNAse-treated probiotics and Escherichia coli (DH5 alpha) genomic DNA were administered intragastrically (i.g.) or subcutaneously (s.c.) to mice prior to the induction of colitis. Viable or gamma-irradiated probiotics were administered i.g. to wild-type mice and mice deficient in different TLR or in the adaptor protein MyD88, 10 days prior to administration of dextran sodium sulfate (DSS) to their drinking water and for 7 days thereafter. RESULTS: Intragastric and s.c. administration of probiotic and E. coli DNA ameliorated the severity of DSS-induced colitis, whereas methylated probiotic DNA, calf thymus DNA, and DNase-treated probiotics had no effect. The colitis severity was attenuated to the same extent by i.g. delivery of nonviable gamma-irradiated or viable probiotics. Mice deficient in MyD88 did not respond to gamma-irradiated probiotics. The severity of DSS-induced colitis in TLR2 and TLR4 deficient mice was significantly decreased by i.g. administration of gamma-irradiated probiotics, whereas, in TLR9-deficient mice, gamma-irradiated probiotics had no effect. CONCLUSIONS: The protective effects of probiotics are mediated by their own DNA rather than by their metabolites or ability to colonize the colon. TLR9 signaling is essential in mediating the anti-inflammatory effect of probiotics, and live microorganisms are not required to attenuate experimental colitis because nonviable probiotics are equally effective.     

Laparoscopic inguinal hernia repair: gold standard in bilateral hernia repair? Results of more than 2800 patients in comparison to literature

Background  

Advantages and disadvantages of open and endoscopic hernia surgery are still being discussed. Until now there has been no study that evaluated the advantages and disadvantages of bilateral hernia repair in a large number of patients.     

Metabolism and anticancer activity of the curcumin analogue, dimethoxycurcumin.

PURPOSE: The plant-derived compound curcumin has shown promising abilities as a cancer chemoprevention and chemotherapy agent in vitro and in vivo but exhibits poor bioavailability. Therefore, there is a need to investigate modified curcumin congeners for improved anticancer activity and pharmacokinetic properties. EXPERIMENTAL DESIGN: The synthetic curcumin analogue dimethoxycurcumin was compared with curcumin for ability to inhibit proliferation and apoptosis of human HCT116 colon cancer cells in vitro by estimating the GI(50) and LC(50) values and detecting the extent of apoptosis by flow cytometry analysis of the cell cycle. Metabolic stability and/or identification of metabolites were evaluated by recently developed mass spectrometric approaches after incubation with mouse and human liver microsomes and cancer cells in vitro. Additionally, circulating levels of dimethoxycurcumin and curcumin were determined in mice following i.p. administration. RESULTS: Dimethoxycurcumin is significantly more potent than curcumin in inhibiting proliferation and inducing apoptosis in HCT116 cells treated for 48 h. Nearly 100% of curcumin but <30% of dimethoxycurcumin was degraded in cells treated for 48 h, and incubation with liver microsomes confirmed the limited metabolism of dimethoxycurcumin. Both compounds were rapidly degraded in vivo but dimethoxycurcumin was more stable. CONCLUSIONS: Compared with curcumin, dimethoxycurcumin is (a) more stable in cultured cells, (b) more potent in the ability to kill cancer cells by apoptosis, (c) less extensively metabolized in microsomal systems, and (d) more stable in vivo. It is likely that the differential extent of apoptosis induced by curcumin and dimethoxycurcumin in vitro is associated with the metabolite profiling and/or the extent of stability.     

Survey of german clinical prescribing philosophies for hyperopia.

PURPOSE: We surveyed a group of German ophthalmologists to evaluate their prescribing philosophies for hyperopic refractive error in symptom-free children and to compare them with the two groups of U.S. pediatric ophthalmologists and U.S. pediatric optometrists as surveyed by Lyons et al. METHODS: Practitioners were selected from a list of ophthalmologists on the Internet. They were either in general practice in three cities in northern Bavaria or affiliated with large ophthalmology teaching hospitals in Wuerzburg and Erlangen. The survey questions of Lyons et al. were translated into German and mailed to 103 ophthalmologists. The data received from the German ophthalmologists were compared with those of the U.S. optometrists and ophthalmologists. RESULTS: A total of 45 surveys (44%) were returned to us and analyzed. In cases of asymptomatic bilateral hyperopia, German ophthalmologists did not prescribe significantly differently from U.S. optometrists at all patient age groups (p > or = 0.05), but they did differ significantly from U.S. ophthalmologists (p < 0.001). Prescribing fractional amounts of hyperopia or astigmatism was not a popular rule of thumb among the German ophthalmologists, and there was no statistical difference between the German and U.S. practitioners. German ophthalmologists would prescribe for anisometropia for all patient age groups in the same way as both U.S. optometrists and U.S. ophthalmologists. CONCLUSION: The prescribing philosophies of German ophthalmologists for pediatric patients did not differ from those of U.S. ophthalmologists and U.S. optometrists when prescribing for anisometropia; they did differ from those of U.S. ophthalmologists but not of those of the U.S. optometrists when prescribing for asymptomatic bilateral hyperopia.     

Caspase‐related apoptosis in chronic ischaemic microangiopathy following experimental vein occlusion in mini‐pigs

Purpose: Acute brain ischaemia (stroke) causes a central area of coagulation necrosis. Peripheral to it and after a few hours, apoptosis causes neurons throughout the entire area to die progressively. However, this sequence of events is related to the reperfusion of regenerated capillaries or collateral circulation, and is considered to be potentially salvageable. Similar findings have been reported in the retina after ischaemia?reperfusion injury in rats. In the present study, we intended to investigate whether delayed cell death is involved in neuronal injuries to the inner retina during chronic retinal ischaemia. Methods: Experimental branch retinal vein occlusion (BRVO) was induced in miniature pigs using indirect argon laser. The eyes were prelevated at 4, 24 and 48 hours and at 1 and 3 weeks following BRVO. The caspase inhibitor Z‐VAD was injected intravitreally 24 hours after BRVO. Affected retinas were examined 24 hours later for any protective effect from apoptotic cell death. Histological examination with cresyl violet staining and TUNEL (TdT‐mediated dUTP?biotin nick‐end labelling) was performed on the samples. Results: A progressive oedema of the nerve fibre, ganglion cell and inner plexiform layers, related to a widely diffused cell necrosis, was observed in the affected territory within 4–24 hours after BRVO. This was followed by a wave of apoptosis localized at the periphery of the affected territory, which peaked approximately 48 hours after BRVO and was associated with a diffuse oedema of the inner nuclear layer. A progressive atrophy of the inner retina was observed 1–3 weeks after BRVO. Injection of the caspase inhibitor Z‐VAD (24 hours after BRVO) decreased the amount of apoptotic cell bodies 48 hours after BRVO. Conclusions: This study shows that although necrosis is the predominant form of neuronal death in the early phase, massive delayed neuronal cell death caused by apoptosis occurs on a widespread basis as a result of chronic ischaemia after BRVO in the retina. Further studies are needed to evaluate the possibility of rescuing retinal neurons from death by neuroprotective treatments.     

Changes to visual acuity and the visual field in a case of meningioma operated at the anterior level

It's presented a midline meningioma of anterior level case which preoperative has an importance affectation of the visual acuity and visual field, and postoperative in dynamic is founded the important improvement of visual acuity and visual field. It's discussed visual field topography and atrophy optic pathophysiology. It's a neuro-ophthalmology case example, where the cooperation neurosurgery-ophthalmology permit medical solution and restored in social life of the patient.