The silent loss of neuronavigation accuracy: a systematic retrospective analysis of factors influencing the mismatch of frameless stereotactic systems in cranial neurosurgery

BACKGROUND Neuronavigation has become an intrinsic part of preoperative surgical planning and surgical procedures. However, many surgeons have the impression that accuracy decreases during surgery. OBJECTIVE To quantify the decrease of neuronavigation accuracy and identify possible origins, we performed a retrospective quality-control study. METHODS Between April and July 2011, a neuronavigation system was used in conjunction with a specially prepared head holder in 55 consecutive patients. Two different neuronavigation systems were investigated separately. Coregistration was performed with laser-surface matching, paired-point matching using skin fiducials, anatomic landmarks, or bone screws. The initial target registration error (TRE1) was measured using the nasion as the anatomic landmark. Then, after draping and during surgery, the accuracy was checked at predefined procedural landmark steps (Mayfield measurement point and bone measurement point), and deviations were recorded. RESULTS After initial coregistration, the mean (SD) TRE1 was 2.9 (3.3) mm. The TRE1 was significantly dependent on patient positioning, lesion localization, type of neuroimaging, and coregistration method. The following procedures decreased neuronavigation accuracy: attachment of surgical drapes (DTRE2 = 2.7 [1.7] mm), skin retractor attachment (DTRE3 = 1.2 [1.0] mm), craniotomy (DTRE3 = 1.0 [1.4] mm), and Halo ring installation (DTRE3 = 0.5 [0.5] mm). Surgery duration was a significant factor also; the overall DTRE was 1.3 [1.5] mm after 30 minutes and increased to 4.4 [1.8] mm after 5.5 hours of surgery. CONCLUSION After registration, there is an ongoing loss of neuronavigation accuracy. The major factors were draping, attachment of skin retractors, and duration of surgery. Surgeons should be aware of this silent loss of accuracy when using neuronavigation.

White matter microstructure alterations of the medial forebrain bundle in melancholic depression

BACKGROUND The medial forebrain bundle (MFB) is a key structure of the reward system and connects the ventral tegmental area (VTA) with the nucleus accumbens (NAcc), the medial and lateral orbitofrontal cortex (mOFC, lOFC) and the dorsolateral prefrontal cortex (dlPFC). Previous diffusion tensor imaging (DTI) studies in major depressive disorder point to white matter alterations of regions which may be incorporated in the MFB. Therefore, it was the aim of our study to probe white matter integrity of the MFB using a DTI-based probabilistic fibre tracking approach. METHODS 22 patients with major depressive disorder (MDD) (12 melancholic-MDD patients, 10 non-melancholic-MDD patients) and 21 healthy controls underwent DTI scans. We used a bilateral probabilistic fibre tracking approach to extract pathways between the VTA and NACC, mOFC, lOFC, dlPFC respectively. Mean fractional anisotropy (FA) values were used to compare structural connectivity between groups. RESULTS Mean-FA did not differ between healthy controls and all MDD patients. Compared to healthy controls melancholic MDD-patients had reduced mean-FA in right VTA-lOFC and VTA-dlPFC connections. Furthermore, melancholic-MDD patients had lower mean-FA than non-melancholic MDD-patients in the right VTA-lOFC connection. Mean-FA of these pathways correlated negatively with depression scale rating scores. LIMITATIONS Due to the small sample size and heterogeneous age group comparisons between melancholic and non-melancholic MDD-patients should be regarded as preliminary. CONCLUSIONS Our results suggest that the melancholic subtype of MDD is characterized by white matter microstructure alterations of the MFB. White matter microstructure is associated with both depression severity and anhedonia.

Dental phobia is no contraindication for oral implant therapy

OBJECTIVES Dental phobia is a psychological disease and a possible contraindication for implant therapy. The study aimed to show that implant therapy in dental-phobic patients (DP, test group) after adequate psychological and dental pretreatment (PDPT) is successfully possible and results in a similar implant prognosis as in nonfearful patients (NF, control group). METHOD AND MATERIALS 15 DP with PDPT and 15 NF were treated with dental implants and were re-evaluated 2 to 4 years after denture-mounting regarding: alteration of dental anxiety (Hierarchical Anxiety Questionnaire [HAQ], Visual Analog Scale [VAS]), patient satisfaction and compliance, implant success, and peri-implant health. Statistical tests of non-inferiority DP versus NF were performed with Hodges-Lehmann estimators and respective one-sided 97.5% confidence intervals of Moses, and pairwise testings with Mann-Whitney test. RESULTS The DP test group rated its anxiety significantly lower at follow- up than at baseline (PHAQ < .001). However, at follow-up, anxiety was still higher in DP than in NF (PHAQ = .046; PVAS < .001). Implant success at follow-up was 100%. Oral health was equally good in DP and NF patients. At follow-up, all patients were satisfied with implant therapy, but compliance was better for NF (100%) than for DP (73% dental checkup; 67% dental hygienist). CONCLUSION Implant therapy can be successfully performed in DP patients with PDPT as phobia is not negatively influenced by the invasive implant therapy. However, motivation for professional maintenance programs remains challenging.

Ventral striatum gray matter density reduction in patients with schizophrenia and psychotic emotional dysregulation

INTRODUCTION: Substantial heterogeneity remains across studies investigating changes in gray matter in schizophrenia. Differences in methodology, heterogeneous symptom patterns and symptom trajectories may contribute to inconsistent findings. To address this problem, we recently proposed to group patients by symptom dimensions, which map on the language, the limbic and the motor systems. The aim of the present study was to investigate whether patients with prevalent symptoms of emotional dysregulation would show structural neuronal abnormalities in the limbic system. METHOD: 43 right-handed medicated patients with schizophrenia were assessed with the Bern Psychopathology Scale (BPS). The patients and a control group of 34 healthy individuals underwent structural imaging at a 3T MRI scanner. Whole brain voxel-based morphometry (VBM) was compared between patient subgroups with different severity of emotional dysregulation. Group comparisons (comparison between patients with severe emotional dysregulation, patients with mild emotional dysregulation, patients with no emotional dysregulation and healthy controls) were performed using a one way ANOVA and ANCOVA respectively. RESULTS: Patients with severe emotional dysregulation had significantly decreased gray matter density in a large cluster including the right ventral striatum and the head of the caudate compared to patients without emotional dysregulation. Comparing patients with severe emotional dysregulation and healthy controls, several clusters of significant decreased GM density were detected in patients, including the right ventral striatum, head of the caudate, left hippocampus, bilateral thalamus, dorsolateral prefrontal and orbitofrontal cortex. The significant effect in the ventral striatum was lost when patients with and without emotional dysregulation were pooled and compared with controls. DISCUSSION: Decreased gray matter density in a large cluster including the right ventral striatum was associated with severe symptoms of emotional dysregulation in patients with schizophrenia. The ventral striatum is an important part of the limbic system, and was indicated to be involved in the generation of incentive salience and psychotic symptoms. Only patients with severe emotional dysregulation had decreased gray matter in several brain structures associated with emotion and reward processing compared to healthy controls. The results support the hypothesis that grouping patients according to specific clinical symptoms matched to the limbic system allows identifying patient subgroups with structural abnormalities in the limbic network.

Efficiency of risk-based vs . random sampling for the monitoring of tetracycline residues in slaughtered calves in Switzerland

In all European Union countries, chemical residues are required to be routinely monitored in meat. Good farming and veterinary practice can prevent the contamination of meat with pharmaceutical substances, resulting in a low detection of drug residues through random sampling. An alternative approach is to target-monitor farms suspected of treating their animals with antimicrobials. The objective of this project was to assess, using a stochastic model, the efficiency of these two sampling strategies. The model integrated data on Swiss livestock as well as expert opinion and results from studies conducted in Switzerland. Risk-based sampling showed an increase in detection efficiency of up to 100% depending on the prevalence of contaminated herds. Sensitivity analysis of this model showed the importance of the accuracy of prior assumptions for conducting risk-based sampling. The resources gained by changing from random to risk-based sampling should be transferred to improving the quality of prior information.

Implementation status of error disclosure standards reported by Swiss hospitals

QUESTION UNDER STUDY To establish at what stage Swiss hospitals are in implementing an internal standard concerning communication with patients and families after an error that resulted in harm. METHODS Hospitals were identified via the Swiss Hospital Association's website. An anonymous questionnaire was sent during September and October 2011 to 379 hospitals in German, French or Italian. Hospitals were asked to specify their hospital type and the implementation status of an internal hospital standard that decrees that patients or their relatives are to be promptly informed about medical errors that result in harm. RESULTS Responses from a total of 205 hospitals were received, a response rate of 54%. Most responding hospitals (62%) had an error disclosure standard or planned to implement one within 12 months. The majority of responding university and acute care (75%) hospitals had introduced a disclosure standard or were planning to do so. In contrast, the majority of responding psychiatric, rehabilitation and specialty (53%) clinics had not introduced a standard. CONCLUSION It appears that Swiss hospitals are in a promising state in providing institutional support for practitioners disclosing medical errors to patients. This has been shown internationally to be one important factor in encouraging the disclosure of medical errors. However, many hospitals, in particular psychiatric, rehabilitation and specialty clinics, have not implemented an error disclosure policy. Further research is needed to explore the underlying reasons.

The cement prosthesis-like spacer: an intermediate halt on the road to healing.

BACKGROUND Periprosthetic infections remain a devastating problem in the field of joint arthroplasty. In the following study, the results of a two-stage treatment protocol for chronic periprosthetic infections using an intraoperatively molded cement prosthesis-like spacer (CPLS) are presented. METHODS Seventy-five patients with chronically infected knee prosthesis received a two-stage revision procedure with the newly developed CPLS between June 2006 and June 2011. Based on the microorganism involved, patients were grouped into either easy to treat (ETT) or difficult to treat (DTT) and treated accordingly. Range of motion (ROM) and the knee society score (KSS) were utilized for functional assessment. RESULTS Mean duration of the CPLS implant in the DTT group was 3.6 months (range 3-5 months) and in the ETT group 1.3 months (range 0.7-2.5 months). Reinfection rates of the final prosthesis were 9.6% in the ETT and 8.3% in the DTT group with no significant difference between both groups regarding ROM or KSS (P = 0.87, 0.64, resp.). CONCLUSION The results show that ETT patients do not necessitate the same treatment protocol as DTT patients to achieve the same goal, emphasizing the need to differentiate between therapeutic regimes. We also highlight the feasibility of CLPS in two-stage protocols.

Plasmodium berghei MAPK1 displays differential and dynamic subcellular localizations during liver stage development

Mitogen-activated protein kinases (MAPKs) regulate key signaling events in eukaryotic cells. In the genomes of protozoan Plasmodium parasites, the causative agents of malaria, two genes encoding kinases with significant homology to other eukaryotic MAPKs have been identified (mapk1, mapk2). In this work, we show that both genes are transcribed during Plasmodium berghei liver stage development, and analyze expression and subcellular localization of the PbMAPK1 protein in liver stage parasites. Live cell imaging of transgenic parasites expressing GFP-tagged PbMAPK1 revealed a nuclear localization of PbMAPK1 in the early schizont stage mediated by nuclear localization signals in the C-terminal domain. In contrast, a distinct localization of PbMAPK1 in comma/ring-shaped structures in proximity to the parasite's nuclei and the invaginating parasite membrane was observed during the cytomere stage of parasite development as well as in immature blood stage schizonts. The PbMAPK1 localization was found to be independent of integrity of a motif putatively involved in ATP binding, integrity of the putative activation motif and the presence of a predicted coiled-coil domain in the C-terminal domain. Although PbMAPK1 knock out parasites showed normal liver stage development, the kinase may still fulfill a dual function in both schizogony and merogony of liver stage parasites regulated by its dynamic and stage-dependent subcellular localization.

Magnetic resonance imaging and genetic investigation of a case of Rottweiler leukoencephalomyelopathy.

BACKGROUND Leukoencephalomyelopathy is an inherited neurodegenerative disorder that affects the white matter of the spinal cord and brain and is known to occur in the Rottweiler breed. Due to the lack of a genetic test for this disorder, post mortem neuropathological examinations are required to confirm the diagnosis. Leukoencephalopathy with brain stem and spinal cord involvement and elevated lactate levels is a rare, autosomal recessive disorder in humans that was recently described to have clinical features and magnetic resonance imaging (MRI) findings that are similar to the histopathologic lesions that define leukoencephalomyelopathy in Rottweilers. Leukoencephalopathy with brain stem and spinal cord involvement is caused by mutations in the DARS2 gene, which encodes a mitochondrial aspartyl-tRNA synthetase. The objective of this case report is to present the results of MRI and candidate gene analysis of a case of Rottweiler leukoencephalomyelopathy to investigate the hypothesis that leukoencephalomyelopathy in Rottweilers could serve as an animal model of human leukoencephalopathy with brain stem and spinal cord involvement. CASE PRESENTATION A two-and-a-half-year-old male purebred Rottweiler was evaluated for generalised progressive ataxia with hypermetria that was most evident in the thoracic limbs. MRI (T2-weighted) demonstrated well-circumscribed hyperintense signals within both lateral funiculi that extended from the level of the first to the sixth cervical vertebral body. A neurodegenerative disorder was suspected based on the progressive clinical course and MRI findings, and Rottweiler leukoencephalomyelopathy was subsequently confirmed via histopathology. The DARS2 gene was investigated as a causative candidate, but a sequence analysis failed to identify any disease-associated variants in the DNA sequence. CONCLUSION It was concluded that MRI may aid in the pre-mortem diagnosis of suspected cases of leukoencephalomyelopathy. Genes other than DARS2 may be involved in Rottweiler leukoencephalomyelopathy and may also be relevant in human leukoencephalopathy with brain stem and spinal cord involvement.

Clostridium perfringens beta-toxin induces necrostatin-inhibitable, calpain-dependent necrosis in primary porcine endothelial cells

Clostridium perfringens β-toxin (CPB) is a β-barrel pore-forming toxin and an essential virulence factor of C. perfringens type C strains, which cause fatal hemorrhagic enteritis in animals and humans. We have previously shown that CPB is bound to endothelial cells within the intestine of affected pigs and humans, and that CPB is highly toxic to primary porcine endothelial cells (pEC) in vitro. The objective of the present study was to investigate the type of cell death induced by CPB in these cells, and to study potential host cell mechanisms involved in this process. CPB rapidly induced lactate dehydrogenase (LDH) release, propidium iodide uptake, ATP depletion, potassium efflux, a marked rise in intracellular calcium [Ca(2+)]i, release of high-mobility group protein B1 (HMGB1), and caused ultrastructural changes characteristic of necrotic cell death. Despite a certain level of caspase-3 activation, no appreciable DNA fragmentation was detected. CPB-induced LDH release and propidium iodide uptake were inhibited by necrostatin-1 and the two dissimilar calpain inhibitors PD150606 and calpeptin. Likewise, inhibition of potassium efflux, chelation of intracellular calcium and treatment of pEC with cyclosporin A also significantly inhibited CPB-induced LDH release. Our results demonstrate that rCPB primarily induces necrotic cell death in pEC, and that necrotic cell death is not merely a passive event caused by toxin-induced membrane disruption, but is propagated by host cell-dependent biochemical pathways activated by the rise in intracellular calcium and inhibitable by necrostatin-1, consistent with the emerging concept of programmed necrosis ("necroptosis").

Investigation of potential causes for the development of porcine ear necrosis: different study designs--comparable results?

During the last years two studies for the investigation of the etiology of porcine ear necrosis were carried out at the Clinic for Swine of the University of Veterinary Medicine Vienna. In study 1, parameters, which are discussed in this context, were collected by veterinary practitioners by completing specially designed questionnaires in farms with symptoms of the porcine ear necrosis syndrome. In study 2, samples of piglets and feed were collected for laboratory analysis of the most important infectious agents as well as mycotoxins. In the present manuscript, the results of both projects were compared. Even if the selection criteria of both studies differed, the affected age class was comparable (5.5 to ten weeks of life in study 1 and six to ten weeks of life in study 2). The herd-specific prevalence of the porcine ear necrosis syndrome varied considerably with percentages between 2 and 10, respectively, to 100%. The evaluation of questionnaires in study 1 showed that 51% of the farms had problems with cannibalism. Particles of plant material, which were frequently seen on the histologic slides of study 2, could have got into the tissue by chewing the ears of the pen mates or cannibalism. Whereas in study 1 the negative effect of parameters as high pig density, suboptimal climate, missing enrichment material and bad quality of feed and water were considered, in study 2 all these factors were checked at sample collection and ruled out as precursor for cannibalism. In both studies bacterial agents proved to be a crucial co-factor for the expansion of the necroses to deeper tissue layers, whereas viral pathogens were classified less important. In both projects it was not possible to estimate the direct impact of infectious agents and mycotoxins as direct trigger of the necroses as well as their participation as co-factors or precursor in the sense of an immunosuppression or previous damage of blood vessels or tissue.

Current attitudes of bovine practitioners, claw-trimmers and farmers in Switzerland to pain and painful interventions in the feet in dairy cattle.

The attitudes of bovine practitioners, claw-trimmers and farmers towards painful therapeutic claw-trimming of dairy cattle were surveyed and differences between the respondents were assessed. A total of 77 farmers and 32 claw-trimmers were interviewed, and 137 bovine practitioners completed an equivalent online survey. No veterinary consultation for common painful interventions in the feet of cattle was reported by 52% of farmers (i.e. procedures in these herds were performed without local anaesthesia). Only ≈30% of practitioners always carried out such interventions under local anaesthesia and, in general, practitioners considered pain reduction to the lowest possible level less important than did farmers. Furthermore, 47% of practitioners and 33% of claw-trimmers, compared to only 11% of farmers, agreed with the statement that the cost of pain management was a major concern for farmers. There was a particular lack of awareness by farmers regarding the obligation to carry out painful therapeutic claw-trimming under analgesia and the application of local anaesthesia during the trimming of sole ulcers was considered reasonable by significantly fewer farmers (41.6%) and claw-trimmers (46.9%), than practitioners (78.6%). Overall, the attitudes of those involved in painful therapeutic claw-trimming contrasted with Swiss national legislation and with farmer opinion on the importance of reducing pain to the lowest level possible.

White matter pathway organization of the reward system is related to positive and negative symptoms in schizophrenia

The reward systemin schizophrenia has been linked to the emergence of delusions on the one hand and to negative symptoms such as affective flattening on the other hand. Previous Diffusion Tensor Imaging (DTI) studies reported white matter microstructure alterations of regions related to the reward system. The present study aimed at extending these findings by specifically investigating connection pathways of the reward system in schizophrenia. Therefore, 24 patients with schizophrenia and 22 healthy controls matched for age and gender underwent DTI-scans. Using a probabilistic fiber tracking approachwe bilaterally extracted pathways connecting the ventral tegmental area (VTA) with the nucleus accumbens (NAcc), themedial and lateral orbitofrontal cortices (mOFC, lOFC), the dorsolateral prefrontal cortex (dlPFC) and the amygdala; as well as pathways connecting NAcc with mOFC, lOFC, dlPFC and amygdala resulting in a total of 18 connections. Probability indices forming part of a bundle of interest (PIBI) were compared between groups using independent t-tests. In 6 connection pathways PIBI-valueswere increased in schizophrenia. In 3 of these pathways the spatial extension of connection pathways was decreased. In schizophrenia patients, there was a negative correlation of PIBI-values and PANSS negative scores in the left VTA–amygdala and in the left NAcc–mOFC connection. A sum score of delusions and hallucinations correlated positively with PIBI-values of the left amygdala–NAcc connection. Structural organization of specific segments ofwhite matter pathways of the reward systemin schizophrenia may contribute to the emergence of delusions and negative symptoms in schizophrenia.