Directional electrodes in deep brain stimulation: Results of a survey by the European Association of Neurosurgical Societies (EANS).

Introduction: Directional Leads (dLeads) represent a new technical tool in Deep Brain Stimulation (DBS), and a rapidly growing population of patients receive dLeads. Research question: The European Association of Neurosurgical Societies(EANS) functional neurosurgery Task Force on dLeads conducted a survey of DBS specialists in Europe to evaluate their use, applications, advantages, and disadvantages. Material and methods: EANS functional neurosurgery and European Society for Stereotactic and Functional Neurosurgery (ESSFN) members were asked to complete an online survey with 50 multiple-choice and open questions on their use of dLeads in clinical practice. Results: Forty-nine respondents from 16 countries participated in the survey (n = 38 neurosurgeons, n = 8 neurologists, n = 3 DBS nurses). Five had not used dLeads. All users reported that dLeads provided an advantage (n = 23 minor, n = 21 major). Most surgeons (n = 35) stated that trajectory planning does not differ when implanting dLeads or conventional leads. Most respondents selected dLeads for the ability to optimize stimulation parameters (n = 41). However, the majority (n = 24), regarded time-consuming programming as the main disadvantage of this technology. Innovations that were highly valued by most participants included full 3T MRI compatibility, remote programming, and closed loop technology. Discussion and conclusion: Directional leads are widely used by European DBS specialists. Despite challenges with programming time, users report that dLeads have had a positive impact and maintain an optimistic view of future technological advances.

Increased variance in second electrode accuracy during deep brain stimulation and its relationship to pneumocephalus, brain shift, and clinical outcomes: A retrospective cohort study.

•Overall electrode accuracy was 0.22+/-0.4 â€‹mm with only 3 (4%) electrodes out with 2 â€‹mm from the intended target.•Accuracy was significantly worse in the GPi versus the STN and on the second side implanted.•Inaccuracy occurred in the X (lateral) plane but was not related to pneumocephalus or brain shift.

Advanced magnetic resonance imaging and neuropsychological assessment for detecting brain injury in a prospective cohort of university amateur boxers.

BACKGROUND/AIM: The safety of amateur and professional boxing is a contentious issue. We hypothesised that advanced magnetic resonance imaging and neuropsychological testing could provide evidence of acute and early brain injury in amateur boxers. METHODS: We recruited 30 participants from a university amateur boxing club in a prospective cohort study. Magnetic resonance imaging (MRI) and neuropsychological testing was performed at three time points: prior to starting training; within 48 h following a first major competition to detect acute brain injury; and one year follow-up. A single MRI acquisition was made from control participants. Imaging analysis included cortical thickness measurements with Advanced Normalization Tools (ANTS) and FreeSurfer, voxel based morphometry (VBM), and Tract Based Spatial Statistics (TBSS). A computerized battery of neuropsychological tests was performed assessing attention, learning, memory and impulsivity. RESULTS: During the study period, one boxer developed seizures controlled with medication while another developed a chronic subdural hematoma requiring neurosurgical drainage. A total of 10 boxers contributed data at to the longitudinal assessment protocol. Reasons for withdrawal were: logistics (10), stopping boxing (7), withdrawal of consent (2), and development of a chronic subdural hematoma (1). No significant changes were detected using VBM, TBSS, cortical thickness measured with FreeSurfer or ANTS, either cross-sectionally at baseline, or longitudinally. Neuropsychological assessment of boxers found attention/concentration improved over time while planning and problem solving ability latency decreased after a bout but recovered after one year. CONCLUSION: While this neuroimaging and neuropsychological assessment protocol could not detect any evidence of brain injury, one boxer developed seizures and another developed a chronic sub-dural haematoma.

Trends in classification, referral and treatment and the effect on outcome of patients with glioma: a 20 year cohort.

This retrospective audit was conducted to examine the changes in patient characteristics, referral, treatment and outcome over a 20-year period in a large regional neuro-oncology centre, focusing on the impact of the changes in pathological classification of gliomas. Using the Edinburgh Cancer Centre (ECC) database all cases of glioma were identified and patient, tumour and treatment characteristics noted. Survival was calculated from date of surgery or, if no operation was performed, the date of referral. Comparison was made between four periods 1988-1992 (c1), 1993-1997(c2), 1998-2002(c3) and 2003-2007 (c4). During the 20 years, 1175 patients with a glioma were referred to ECC. The median age increased from 53 years to 57 years (p < 0.001) but the proportion without pathology remained unchanged (10%). The distribution of pathological grades changed over time Grade I-II: 24, 6, 6, and 6%, Grade III: 42, 27, 17, and 13% and Grade IV: 24, 61, 68, and 68% in c1, c2, c3 and c4, respectively (p < 0.001). Immediate RT was given to 68% (c1), 70% (c2), 78% (c3) and 79% (c4). Median interval from resection to RT reduced from 43 days (c1) to 36 days (c4) (p < 0.001). 5-year overall survival for patients with Grade III lesions increased: 21% (c1), 35% (c2), 37% (c3), 33% (c4) as did 1-year overall survival for Grade IV lesions: 18% (c1), 26% (c2), 29% (c3), 27% (c4)). This improvement probably reflects the change in pathological classification rather than a change in management. Proportional hazards analysis of grade IV 1993-2007 only (to reduce pathological variation) showed that younger age, frontal lesions, excision, higher RT dose had reduced hazard of death. Interval from surgery to RT had no impact on survival in this series.

A study in male and female 5-HT transporter knockout rats: an animal model for anxiety and depression disorders.

Human studies have shown that a reduction of 5-HT transporter (SERT) increases the vulnerability for anxiety and depression. Moreover, women are more vulnerable to develop depression and anxiety disorders than men. For that reason we hypothesized that homozygous 5-HT transporter knockout rat (SERT(-/-)) models, especially female, are valuable and reliable animal models for humans with an increased vulnerability for anxiety- and depression-related disorders. As rats are extensively used in neuroscience research, we used the unique 5-HT transporter knockout rat, that was recently generated using N-ethyl-N-nitrosurea (ENU) -driven mutagenesis, to test this hypothesis. Behavioral testing revealed that male and female SERT(-/-) rats spent less time in the center of the open field and spent less time on the open arm of the elevated plus maze compared with wild-type 5-HT transporter knockout rats (SERT(+/+)). In the novelty suppressed feeding test, only male SERT(-/-) rats showed a higher latency before starting to eat in a bright novel arena compared with SERT(+/+) controls. Both male and female SERT(-/-) rats showed a higher escape latency from their home cage than SERT(+/+) littermates. Moreover, SERT(-/-) rats were less mobile in the forced swim test, and sucrose consumption was reduced in SERT(-/-) rats relative to SERT(+/+) rats. Both effects were sex-independent. Neurochemically, basal extracellular 5-HT levels were elevated to a similar extent in male and female SERT(-/-) rats, which was not influenced by the selective 5-HT reuptake inhibitor citalopram. 5-HT immunostaining revealed no difference between SERT(+/+) and SERT(-/-) rats in the dorsal raphe nuclei, in both males and females. These findings demonstrate that SERT(-/-) rats show anxiety and depression-related behavior, independent of sex. Genetic inactivation of the SERT has apparently such a great impact on behavior, that hardly any differences are found between male and female rats. This knockout rat model may provide a valuable model to study anxiety- and depression-related disorders in male and female rats.

Follow-up and outcomes for resection of colorectal liver metastases in Edinburgh.

AIM: The aim of this study was to assess the value of a defined follow-up protocol for patients undergoing potentially curative hepatic resection for colorectal hepatic metastases. METHODS: A standard protocol for the duration of the study consisted of clinical assessment, serum carcinoembryonic antigen (CEA) and computed tomography. Patterns of recurrence, method and timing of diagnosis and outcome were recorded. RESULTS: One hundred and ninety-one patients underwent potentially curative resection from 1989 to 2004 of whom 103 developed recurrence. The median (inter-quartile range) follow-up was 24.4 (6.5-42.3) months. The median (IQR) time to recurrence and overall survival was 25.0 (10 -not yet reached) and 45.2 (21-123) months, respectively. Seventeen patients (8.9%) underwent further surgery with curative intent. Fifty-five patients (57.9%) had recurrence diagnosed at routine follow-up with 71% (44/62) being diagnosed by CEA and CT. The CEA was elevated in 85.7% (72/84 patients) at the time of diagnosis of recurrence. CONCLUSION: Although the detection of recurrent disease is common during follow-up after hepatic resection for colorectal metastases, few patients will be suitable for further intervention with curative intent. The exact nature of the follow-up protocol remains to be determined but if it is going to be performed it should be most intensive within the first 3 years.

Clinical associations of Dupuytren's disease.

Dupuytren's disease (DD) is a common progressive fibrotic condition affecting the palmar and digital fascia. Although its management is undertaken by hand surgeons, it is commonly seen by other doctors as an incidental finding. In many cases it is believed to be associated with other medical conditions, although the evidence for such associations is not always clear. This review considers the evidence behind these associations and discusses the aetiology of DD. By doing so, it is hoped that this review will permit a better understanding of the relevance of DD as a clinical sign.

Surgical resection and whole brain radiation therapy versus whole brain radiation therapy alone for single brain metastases.

BACKGROUND: The treatment of brain metastasis is generally palliative, with whole brain radiation therapy (WBRT), since the majority have uncontrollable systemic cancer. In certain circumstances, such as single brain metastases, death may be more likely from brain involvement than systemic disease. In this group, surgical resection has been proposed to relieve symptoms and prolong survival. OBJECTIVES: To assess the clinical effectiveness of surgical resection plus WBRT versus WBRT alone in the treatment of single brain metastasis. SEARCH STRATEGY: The Cochrane Cancer Network Specialised trials register (July 2003), Cochrane Central Register of Controlled Trials (CENTRAL) (Issue 1 2003), MEDLINE (1966 to July 2003), EMBASE (1980 to July 2003), CANCERLIT (1980 to July 2003), BIOSIS (1985 to July 2003) and SCIENCE CITATION INDEX (1981 to July 2003) were searched. References of identified studies were hand searched, as was the Journal of Neuro-Oncology over the previous 10 years and Neuro-Oncology over the past 2 years, including all conference abstracts. Specialists in neuro-oncology were also contacted. SELECTION CRITERIA: Randomized controlled trials (RCTs) comparing surgery and WBRT with WBRT alone, in patients with single brain metastasis. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed trial quality and extracted data. MAIN RESULTS: Three RCTs were identified, with 195 patients in total. No significant difference in survival was noted hazard ratio (HR) 0.74 (95% confidence interval (CI) 0.39 to 1.40, p = 0.35), although there was a high degree of heterogeneity between trials. One trial has shown surgery and WBRT to increase the duration of functionally independent survival (FIS) HR 0.42 (95% CI 0.22 to 0.80, p < 0.008). There is a trend for surgery and WBRT to reduce the number of deaths due to neurological cause odds ratio (OR) 0.57 (95% CI 0.29 to 1.10, p = 0.09). Adverse effects were not found to be statistically more common in any group. AUTHORS' CONCLUSIONS: Surgery and WBRT may improve FIS but not overall survival. There is a trend that it may reduce the proportion of deaths due to neurological cause. All these results were in a highly selected group of patients. Operating on metastases does not confer significantly more adverse effects.

Substance P receptor antagonist and clomipramine prevent stress-induced alterations in cerebral metabolites, cytogenesis in the dentate gyrus and hippocampal volume.

The neuropeptide substance P and its receptor, the neurokinin 1 receptor (NK(1)R) have been proposed as possible targets for new antidepressant therapies. The present study investigated the effect of the NK(1)R antagonist L-760,735 and the tricyclic antidepressant clomipramine in the chronic psychosocial stress paradigm of adult male tree shrews. Animals were subjected to a 7-day period of psychosocial stress before the onset of daily oral administration of L-760,735 (10 mg kg(-1) day(-1)) or clomipramine (50 mg kg(-1) day(-1)). The psychosocial stress continued throughout the treatment period of 28 days. Brain metabolite concentrations were determined in vivo by proton magnetic resonance spectroscopy. Cell proliferation in the dentate gyrus and hippocampal volume were measured post mortem. Stress significantly decreased in vivo concentrations of N-acetyl-aspartate (-14%), creatine and phosphocreatine (-15%) and choline-containing compounds (-15%). The proliferation rate of the granule precursor cells in the dentate gyrus was reduced (-45%), and hippocampal volume was decreased (-14%). The stress-induced changes of brain metabolites, hippocampal volume and dentate cytogenesis rate were prevented by concomitant drug administration. Elevated myo-inositol concentrations after both treatments hint to an astrocytic enhancement. These results suggest that-despite a different pharmacological profile-the NK(1)R antagonist L-760,735, a member of a novel class of antidepressant drugs, has comparable neurobiological efficacy to tricyclic antidepressants such as clomipramine.

The effect of home training with direct blood pressure biofeedback of hypertensives: a placebo-controlled study.

BACKGROUND: Home training in self-lowering of blood pressure using continuous blood pressure feedback has not previously been reported. Enhancement of laboratory-learned skills was hypothesized on the basis of outcomes from other intellectual, emotional and physical endeavours. OBJECTIVE: To examine the supplementary effect of home blood pressure biofeedback training. DESIGN: Thirty unmedicated, mild hypertensives participated in a randomized, double-blinded, modified contingency placebo-controlled study. METHOD: After suitable screening and baseline blood pressure measurements subjects undertook eight laboratory biofeedback sessions and then 12 home training sessions over 4 weeks using continuous finger blood pressure monitoring. RESULTS: In the laboratory those being administered active therapy (n=16) lowered systolic pressures by 5 +/- 5.4 mmHg compared with a lowering of 4 +/- 4.2 mmHg with placebo (NS). During the fourth week at home lowering for the active group (11 +/- 8 mmHg) was greater than that with placebo (4 +/- 6.2 mmHg, P=0.017). Arm-cuff blood pressures were not statistically different for groups and with time but that of the active group was lower by 9 +/- 15.4/7 +/- 10.2 mmHg, which is a clinically relevant change, after home biofeedback. CONCLUSIONS: The efficacy of self-lowering of systolic blood pressure in mild hypertensives by continuous feedback was enhanced by 6 mmHg with 4 weeks of practice at home. Standard arm-cuff blood pressure was reduced by a clinically relevant amount. The home environment proved cost effective for this 'high-tech' approach.

Effect of feedback signal and psychological characteristics on blood pressure self-manipulation capability.

Blood pressure presentation mode and personality are likely to influence biofeedback outcome. Thirty-six normotensive subjects were randomly assigned to visual or auditory continuous systolic feedback. "Distracting speech" and "broad band noise" were also superimposed and the effect on the biofeedback response was investigated. Psychological influence was also investigated. Systolic pressure reduction of 4 +/- 4.3 mmHg (visual, p = .04) and 5 +/- 5.5 mmHg (visual + auditory, p = .03) were achieved compared with auditory feedback (2 +/- 4.7 mmHg), which was less effective. The addition of noise or speech had no effect on the systolic response, but speech adversely affected diastolic reduction (p = .04). Mood (p = .003) was associated with systolic lowering, whereas increased trait anxiety (p = .06) and expectation (p = .03) had trends for opposite effects. Increased anger-hostility, state-anxiety, and expectation (p = .06) had links with systolic raising capability. We conclude that feedback modality and psychological characteristics have implications for studies investigating blood pressure manipulation capability.

Physiological influences on continuous finger and simultaneous intra-arterial blood pressure.

Because of the clinical and experimental utility of continuous finger blood pressure measurements and the need for accuracy, we tested the performance of a new hydraulic device in 22 consecutive hypertensive subjects during physiological and pharmacological interventions. Ipsilateral brachial intra-arterial pressure was monitored during rest, Valsalva's maneuver, static handgrip, and mental arithmetic and after sublingual glyceryl trinitrate. In excess of 40,000 blood pressure values were analyzed. Average bias (intra-arterial minus finger blood pressure) was 8.2 +/- 17.0 mm Hg (mean +/- SD, P = NS) for systolic and 2.8 +/- 10.4 mm Hg (P = NS) for diastolic pressure. Two-way ANOVA of biases with subject and task factors showed a subject effect (P < .001). Intersubject and intrasubject standard deviations of bias were 13.8 and 9.8 mm Hg systolic and 8.7 and 5.7 diastolic, respectively. Linear drift (millimeters of mercury per minute) of finger pressure was greater (P < .001) for systolic than diastolic pressure during static exercise and math and after glyceryl trinitrate. Coefficients of determination for blood pressure ranged from 0.4 +/- 0.3 to 0.8 +/- 0.3 during the tasks. We conclude that (1) noninvasive finger blood pressure faithfully follows intra-arterial changes but with clinically relevant offsets, (2) this technique is best suited for assessing pressure changes, (3) physiological and pharmacological interventions do not consistently affect finger pressure accuracy, (4) many reports of finger blood pressure measuring devices are based on direct readings obtained with inadequate system response characteristics, and (5) the tested instrument falls short of the standard requirements (bias < or = 5 +/- 8 mm Hg) for devices that measure intermittently.

Development of LYNX: a computer application for disease diagnosis and health monitoring in wild mammals, birds and reptiles.

IBM-compatible software has been developed so that quantitative and qualitative haematological and biochemical reference data for over 500 species of mammals, birds and reptiles can be made readily accessible to veterinary surgeons. The LYNX software makes it possible to retrieve these data at different taxonomic levels (species, genera, families, orders and classes) and to select data by age and sex. The data for each variable may be presented in the form of a reference range or as a frequency histogram. Notes describing the variations in blood cell morphology observed in healthy individuals of each species are included in the database. The user's own haematological and biochemical data can also be entered, stored and used.

Erythrocyte size, number and haemoglobin content in vertebrates.

Relationships between erythrocyte number, size and haemoglobin content were examined in 441 species (101 families) of mammals, birds and reptiles. Whereas the total number of red cells (RBC), the mean cell volume (MCV) and mean cell haemoglobin (MCH) showed much variation, the haemoglobin level (Hb), packed cell volume (PCV) and mean cell haemoglobin concentration (MCHC) were relatively constant in all adult mammals and birds but lower in reptiles. There was a strong positive correlation between MCV and MCH and a strong negative correlation between MCV and RBC across all species. Mammals had more, smaller erythrocytes per unit volume of blood than birds, which, in their turn, had more, smaller erythrocytes than reptiles. The findings confirm that the oxygen-carrying capacity of the blood is highly conserved in birds and mammals but is lower in exothermic groups such as reptiles. Although the significance of the observed species differences in RBC and MCV has yet to be explained, the findings have considerable evolutionary, physiological and diagnostic interest.

Haematology of clinically normal and sick captive reindeer (Rangifer tarandus).

A retrospective analysis of haematological values from clinically normal captive reindeer (Rangifer tarandus) showed that the red cell count, haemoglobin level, packed cell volume and lymphocyte count were higher and the erythrocyte sedimentation rate and eosinophil count were lower in juveniles than in adults. Newborn animals were anaemic compared with juveniles and adults and had high reticulocyte counts. The values from healthy reindeer were used to identify abnormal haematological variations in a number of sick animals. It was shown that reindeer exhibit similar haemopathological responses to those of other artiodactyla, with increases in the erythrocyte sedimentation rate and fibrinogen level being of particular diagnostic significance. Eosinophilia was the only abnormal haematological finding in individuals with subclinical infections of intestinal parasites.

Age-related changes in the haematology of female F344 rats.

As little comprehensive baseline data are available on age-related haematological changes in genetically-defined rat strains, the haematology of female F344 rats is described in animals sampled at 2, 4, 8, 20, 66 and 121 weeks of age. Values for Hb, RBC and PCV increased from 2 weeks of age to reach adult levels at 8 weeks, whereas MCV, MCH and reticulocyte counts were high initially but decreased to reach the adult range at 8 weeks. Between 66 and 121 weeks, reticulocyte counts were significantly increased and values for MCHC significantly decreased. Lymphocytes were the predominant white cell type in each age group. The absolute numbers of neutrophils and lymphocytes showed slight variations between 2 and 66 weeks and both cell types increased significantly between 66 and 121 weeks. Platelet counts showed no overall age-related trends. Fibrinogen values increased from 2 weeks of age to reach the adult level at 8 weeks. One animal of the 14 sampled at 121 weeks showed changes in the blood, liver and spleen consistent with a diagnosis of lymphoid leukaemia.

An analysis of the incidence of hyperfibrinogenaemia in birds with bacterial infections.

An analysis was carried out of fibrinogen values and heterophil counts in 87 blood samples from birds with a clinical diagnosis of bacterial infection. Increased fibrinogen levels were found in 63% and heterophilia in 56% of the cases. When a finding of either heterophilia or hyper-fibrinogenaemia was taken into account, the number of samples in which the diagnosis was confirmed was increased to 77%. It was concluded that fibrinogen estimation is a useful routine haematological screening test for birds.

Fibrinogen levels in mammals suffering from bacterial infections.

In a retrospective survey of fibrinogen levels and neutrophil counts in 388 blood samples from mammals suffering from bacterial infection, the combined results of the two tests provided positive confirmation of infection in a greater percentage of samples than did the results of either test alone. In Perissodactyla, Artiodactyla and Proboscidea, the fibrinogen level was abnormal more often than the neutrophil count. It was concluded that a fibrinogen estimation is a valuable addition to routine haematological screening procedures in mammals.

Haematological reference values for adult pumas, lions, tigers, leopards, jaguars and cheetahs.

Normal haematological values and fibrinogen levels were obtained from a number of healthy adult Felidae in the collection of the Zoological Society of London. The group comprised 29 pumas (Felis concolor), 32 lions (Panthera leo), 27 tigers (P tigris), 19 leopards (P pardus), 18 jaguars (P onca) and 22 cheetahs (Acinonyx jubatus). The values provided a basis for identifying abnormalities in the blood of sick individuals of these species and for undertaking interspecies comparisons.