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.

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.

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.

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.

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.

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.

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.

Principal components analysis of haematological data from F344 rats with bladder cancer fed N-(ethyl)-all-trans-retinamide.

Several multivariate statistical methods are available which can alleviate the problems of analysing the large volumes of data generated from toxicological experiments. One such technique, principal components analysis, provides a method for exploring the relationships between a number of variables (such as blood parameters) and for eliminating redundant data if strong correlations exist between the characters. It also provides a method for clustering individuals, which may reveal similarities between animals in a treatment group or highlight individual 'outliers'. The application of principal components analysis to a set of haematological data from a trial evaluating the efficacy of a synthetic retinoid against carcinogen-induced bladder cancer in the rat has clearly shown, in two bivariate plots, that while some animals in the carcinogen-treated groups were normal, others were anaemic and that animals fed the synthetic retinoid and killed at 1 year had a microcytic anaemia. A full exploration of the data using conventional univariate statistical analysis would have involved at least 28 graphic representations of the data, as well as the interpretation of more than 130 means and SDs. Principal components analysis provides a valuable additional tool for the statistical analysis and exploration of toxicological data, but it must be used in conjunction with univariate or other multivariate methods if hypothesis testing is required. The use of multivariate techniques in toxicology may best be assessed by their practical application to toxicological data, and this paper presents such an evaluation with the aim of encouraging further exploration of the usefulness of principal components analysis. The raw data on which most analyses have been carried out are given.

Clinical hematology of the common marmoset Callithrix jacchus.

Hematological studies have been carried out on a group of 96 common marmosets (Callithrix jacchus) on which full clinical histories were available. The group included both healthy and sick animals. Reference values for red-cell, white-cell, and platelet counts; hemoglobin levels; packed cell volumes; red- and white-cell absolute values; reticulocyte counts; and fibrinogen levels were calculated from results obtained in 43 clinically normal individuals. These reference values have been used to identify hematological abnormalities in sick animals so that relationships between the blood picture and the clinical findings could be defined. Leucopenia, raised platelet counts, and high fibrinogen levels were found in animals with bacterial infections and carried poor prognosis. Heinz bodies occurred in a significant number of the group as a whole, and were associated with a variety of hematological and clinical abnormalities. These findings illustrate the diagnostic and prognostic value of clinical hematology in C. jacchus.

Cotton-top tamarins (Saguinus oedipus oedipus): Hematologic reference values and hemopathologic responses.

Hematologic reference values have been established for captive adult cotton-top tamarins (Saguinus oedipus oedipus) by carrying out full blood counts and fibrinogen estimation on 43 clinically normal animals. Females were shown to have significantly lower hemoglobin levels, red cell counts and packed cell volumes, and higher reticulocyte counts than males. The reference values were used to identify abnormal changes in the blood of 13 clinical cases. Marked neutrophilia was found in animals with localized bacterial infections, and a degenerative left shift was recorded in an individual with streptococcal septicemia. Three cases of unexplained progressive muscle wasting showed Heinz body anemia and abnormal white cell changes. These hematologic responses have been compared where possible with those recorded in other species of Callithricidae.

Red-bellied tamarins (Saguinus labiatus): Hematologic reference values and hemopathologic responses.

Hematologic reference values have been established for captive adult red-bellied tamarins (Saguinus labiatus) by carrying out full blood counts and fibrinogen estimations on 25 clinically normal animals. The only significant sex difference detected was in the reticulocyte count which was higher in females than in males. The reference values were used to identify abnormal changes in the blood of nine clinical cases. Hypochromic anemia, neutrophilia, and raised fibrinogen levels were found in animals with self-inflicted injuries, dermatitis, and ileocecal intussusception. Target cells and jaundiced plasma were noted in a case of yersiniosis. Two animals in which generalized muscle wasting was the main abnormal clinical sign were severely anemic, and in one of these cases a significant number of Heinz bodies was present. The findings in these two animals were compared with those in common marmosets (Callithrix jacchus) with possible wasting marmoset syndrome.

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.

Normal haematological values of axis deer (Axis axis), Père David's deer (Elaphurus davidianus) and barasingha (Cervus duvauceli).

Full blood counts and fibrinogen estimations were carried out on a number of clinically normal adult axis deer (Axis axis), Père David's deer (Elaphus davidianus) and barasingha (Cervus duvauceli). Apart from the finding of higher total red cell counts and a lower mean red cell volume in axis deer than in Père David's deer and barasingha, there was little interspecies variation. Some individual Père David's deer showed eosinophilia, thought to be associated with subclinical intestinal nematode infestation. The findings should provide a useful reference base for monitoring health in these species.

Age related haematological changes in captive Barbary sheep (Ammotragus lervia).

Full blood counts were carried out on a number of clinically normal newborn, juvenile and adult Barbary sheep. Significant age related differences in the number and size of the red cells and in the absolute and relative numbers of neutrophils and lymphocytes were found. Fibrinogen levels and platelet counts were lowest in newborn animals. These differences could complicate the interpretation of haematological findings on sick Barbary sheep if not taken into account.

Haematological values in mouflon (Ovis musimon): influence of age, sex, season and vitamin E status.

Full blood counts, fibrinogen estimations and red cell osmotic fragility tests were carried out on a number of clinically normal captive mouflon (Ovis musimon) from various locations. Age related differences in red and white cell counts and sex related differences in red cell counts were demonstrated. There was also evidence for seasonal changes in red cell values in adult females. During this study, some mouflon were found to be deficient in vitamin E and were transferred to a vitamin E supplemented diet. Comparison of findings on vitamin E deficient and supplemented animals revealed no significant haematological differences.

Normal and clinical haematology in the yak (Bos grunniens).

Haematological examinations have been carried out on 21 clinically normal male and female adult yaks (Bos grunniens). Animals sedated with xylazine had significantly lower red cell counts, haemoglobin levels and packed cell volumes, fewer lymphocytes and higher monocyte counts than those bled while manually restrained. There were few significant sex differences. Several animals had eosinophilia associated with asymptomatic intestinal nematode infection. Haematological reference values were calculated for clinically normal, xylazine sedated and manually restrained yaks. These were used to identify haematological changes in 10 animals with various abnormal clinical signs. It was concluded that blood counts can provide valuable diagnostic information in this species.

Haematological findings in red-necked wallabies (Protemnodon rufogrisea) with necrobacillosis.

Results of blood counts on 17 red-necked wallabies (Protemnodon rufogrisea) with confirmed necrobacillosis have been compared with those of 36 clinically normal animals. The most common abnormality in infected animals was a raised fibrinogen level, found in all of the cases tested. Neutrophilia occurred in 10 individuals and neutrophil morphology was abnormal in 15. Some infected animals showed monocytosis, raised erythrocyte sedimentation rates, high platelet counts and changes in their red cells. The findings provide useful information about the response of the blood to severe bacterial infections in red-necked wallabies and demonstrate the potential diagnostic use of clinical haematology in this species.