Double lesion MRgFUS thalamotomy for essential tremor: 4.5-year outcomes and framework for assessing loss of efficacy and tremor progression.

BACKGROUND: The essential tremor (ET) course to 54 months post-unilateral VIM/PSA magnetic resonance-guided focused ultrasound (MRgFUS) in the treated arm (TA) and non-treated arm (NTA) of 12 patients is reported. METHODS: Tremor severity was rated using Bain Findley spirography (BFS) scores in the TA and NTA. We divided follow-up into 'Early' (0-6 months) and 'Late' (6-54 months) phases, to minimise the effect of peri-lesion oedema resolution on the latter. RESULTS: The mean baseline BFS score was 6.2 in TA and 5.7 in the NTA. After unilateral VIM/PSA MRgFUS, mean BFS improved in TA at all subsequent time points (p < 0.001), with no significant differences between BFS scores at consecutive assessments or between 1 and 54 months, while the NTA BFS scores worsened between 12 and 24 months (p < 0.003). Three patients showed worsening of their TA BFS scores and an increasing NTA-TA BFS difference, indicating slower tremor worsening in TA compared to NTA, whilst one patient showed a greater rate of worsening in the TA compared to NTA BFS. CONCLUSION: After 54 months, the beneficial effect of MRgFUS is usually maintained with any worsening of BFS scores in TA slower than in NTA. Loss of treatment benefit is rare.

Tremor assessment scales before, during and after MRgFUS for essential tremor - results, recommendations and implications.

BACKGROUND: neurosurgical interventions such as MR-guided focused ultrasound (MRgFUS) are increasingly deployed for treatment of essential tremor. OBJECTIVE: to make recommendations for monitoring treatment effects during and after MRgFUS based on our investigation of correlations between different scales of tremor severity. METHODS: twenty-five clinical assessments were collected from thirteen patients before and after unilateral MRgFUS sequential lesioning of the thalamus and posterior subthalamic area for alleviating essential tremor. Scales included Bain Findley Spirography (BFS), Clinical Rating Scale for Tremor (CRST), Upper Extremity Total Tremor Score (UETTS) and Quality of Life of Essential Tremor (QUEST), and were documented at baseline, while lying in the scanner with stereotactic frame attached (BFS), and at 24-month follow-up. RESULTS: the four different scales of tremor severity all correlated significantly. BFS and CRST showed a strong correlation of 0.833 (p < 0.001). BFS, UETTS and CRST correlated moderately with QUEST (ρ = 0.575-0.721, p < 0.001). BFS and UETTS correlated significantly with all CRST subparts, with the strongest correlation between UETTS and CRST part C (ρ = 0.831, p < 0.001). Moreover, BFS drawn sitting upright in an outpatient setting correlated with spirals drawn in a supine position on the scanner bed with the stereotactic frame attached. CONCLUSION: we recommend a combination of BFS & UETTS for intraoperative assessment of awake essential tremor patients and BFS & QUEST for pre-operative and follow-up assessments, as these scale sets are quick and simple to collect and provide meaningful information whilst meeting the practical constraints of intraoperative assessment.

Deep learning for screening of interstitial lung disease patterns in high-resolution CT images.

AIM: To develop a screening tool for the detection of interstitial lung disease (ILD) patterns using a deep-learning method. MATERIALS AND METHODS: A fully convolutional network was used for semantic segmentation of several ILD patterns. Improved segmentation of ILD patterns was achieved using multi-scale feature extraction. Dilated convolution was used to maintain the resolution of feature maps and to enlarge the receptive field. The proposed method was evaluated on a publicly available ILD database (MedGIFT) and a private clinical research database. Several metrics, such as success rate, sensitivity, and false positives per section were used for quantitative evaluation of the proposed method. RESULTS: Sections with fibrosis and emphysema were detected with a similar success rate and sensitivity for both databases but the performance of detection was lower for consolidation compared to fibrosis and emphysema. CONCLUSION: Automatic identification of ILD patterns in a high-resolution computed tomography (CT) image was implemented using a deep-learning framework. Creation of a pre-trained model with natural images and subsequent transfer learning using a particular database gives acceptable results.

Thymic Atrophy: Experimental Studies and Therapeutic Interventions.

The thymus is essential for T cell development and maturation. It is extremely sensitive to atrophy, wherein loss in cellularity of the thymus and/or disruption of the thymic architecture occur. This may lead to lower naïve T cell output and limited TCR diversity. Thymic atrophy is often associated with ageing. What is less appreciated is that proper functioning of the thymus is critical for reduction in morbidity and mortality associated with various clinical conditions including infections and transplantation. Therefore, therapeutic interventions which possess thymopoietic potential and lower thymic atrophy are required. These treatments enhance thymic output, which is a vital factor in generating favourable outcomes in clinical conditions. In this review, experimental studies on thymic atrophy in rodents and clinical cases where the thymus atrophies are discussed. In addition, mechanisms leading to thymic atrophy during ageing as well as during various stress conditions are reviewed. Therapies such as zinc supplementation, IL7 administration, leptin treatment, keratinocyte growth factor administration and sex steroid ablation during thymic atrophy involving experiments in animals and various clinical scenarios are reviewed. Interventions that have been used across different scenarios to reduce the extent of thymic atrophy and enhance its output are discussed. This review aims to speculate on the roles of combination therapies, which by acting additively or synergistically may further alleviate thymic atrophy and boost its function, thereby strengthening cellular T cell responses.

The use of ultrasound in intracranial tumor surgery.

BACKGROUND: As an intraoperative imaging modality, ultrasound is a user-friendly and cost-effective real-time imaging technique. Despite this, it is still not routinely employed for brain tumor surgery. This may be due to the poor image quality in inexperienced hands, and the well-documented learning curve. However, with regular use, the operator issues are addressed, and intraoperative ultrasound can provide valuable real-time information. The aim of this review is to provide an understanding for neurosurgeons of the development and use of ultrasound in intracranial tumor surgery, and possible future advances. METHODS: A systematic search of the electronic databases Embase, Medline OvidSP, PubMed, Cochrane, and Google Scholar regarding the use of ultrasound in intracranial tumor surgery was undertaken. RESULTS AND DISCUSSION: Intraoperative ultrasound has been shown to be able to accurately account for brain shift and has potential for regular use in brain tumor surgery. Further developments in probe size, resolution, and image reconstruction techniques will ensure that intraoperative ultrasound is more accessible and attractive to the neuro-oncological surgeon. CONCLUSIONS: This review has summarized the development of ultrasound and its uses with particular reference to brain tumor surgery, detailing the ongoing challenges in this area.

The effect of pedunculopontine nucleus deep brain stimulation on postural sway and vestibular perception.

BACKGROUND AND PURPOSE: Deep brain stimulation (DBS) of the pedunculopontine nucleus (PPN) reduces the number of falls in patients with Parkinson's disease (PD). It was hypothesized that enhanced sensory processing contributes to this PPN-mediated gait improvement. METHODS: Four PD patients (and eight matched controls) with implanted bilateral PPN and subthalamic nucleus DBS electrodes were assessed on postural (with/without vision) and vestibular perceptual threshold tasks. RESULTS: Pedunculopontine nucleus ON stimulation (compared to OFF) lowered vestibular perceptual thresholds but there was a disproportionate increase in the normal sway increase on going from light to dark. CONCLUSIONS: The disproportionate increased sway with PPN stimulation in the dark may paradoxically improve balance function since mechanoreceptor signals rapidly adapt to continuous pressure stimulation from postural akinesia. Additionally, the PPN-mediated vestibular signal enhancement also improves the monitoring of postural sway. Overall, PPN stimulation may improve sensory feedback and hence balance performance.

Bedside saccadometry as an objective and quantitative measure of hemisphere-specific neurological function in patients undergoing cranial surgery.

Cranial surgery continues to carry a significant risk of neurological complications. New bedside tools that can objectively and quantitatively evaluate cerebral function may allow for earlier detection of such complications, more rapid initiation of therapy, and improved patient outcomes. We assessed the potential of saccadic eye movements as a measure of cerebral function in patients undergoing cranial surgery peri-operatively. Visually evoked saccades were measured in 20 patients before (-12 hours) and after (+2 and +5 days) undergoing cranial surgery. Hemisphere specific saccadic latencies were measured using a simple step-task and saccadic latency distributions were compared using the Kolmogorov-Smirnov test. Saccadic latency values were incorporated into an empirically validated mathematical model (Linear Approach to Threshold with Ergodic Rate [LATER] model) for further analysis (using Wilcoxon signed rank test). Thirteen males and seven females took part in our study (mean age 55 ± 4.9 years). Following cranial surgery, saccades initiated by the cerebral hemisphere on the operated side demonstrated significant deteriorations in function after 2 days (p < 0.01) that normalised after 5 days. Analysis using the LATER model confirmed these findings, highlighting decreased cerebral information processing as a potential mechanism for noted changes (p < 0.05). No patients suffered clinical complications after surgery. To conclude, bedside saccadometry can demonstrate hemisphere-specific changes after surgery in the absence of clinical symptoms. The LATER model confirms these findings and offers a mechanistic explanation for this change. Further work will be necessary to assess the practical validity of these changes in relation to clinical complications after surgery.

The sphericity deviation score: a quantitative radiologic outcome measure of Legg-Calvé Perthes disease applicable at the stage of healing and at skeletal maturity.

AIM: This study aimed to determine if a new measure of sphericity of the femoral head, the Sphericity Deviation Score (SDS), could be estimated reliably at the stage of healing of Legg-Calvé-Perthes disease (LCPD) and to determine if the SDS at the healing stage reflects the outcome at skeletal maturity. METHODS: The SDS was measured with image analysis software on radiographs of 120 children with unilateral LCPD at healing of the disease and at skeletal maturity. The reproducibility of measurement was assessed. SDS values for hips in different Stulberg classes were calculated. On the basis of SDS values at healing of 82 children, a logistic regression model was developed to determine the probability of a good outcome at skeletal maturity. The validity of the model was tested on another 38 children. RESULTS: The SDS values at the stage of healing and at skeletal maturity were comparable. The SDS values were lowest for Stulberg Class I hips and highest for Class IV and V hips. The validated regression model showed a very high probability of a good outcome (Stulberg Class I or II) at skeletal maturity if the SDS at the stage of healing was below 10. CONCLUSIONS: A reliable estimate of the outcome of LCPD at skeletal maturity can be made by computing the SDS as soon as the disease heals.

Exciton condensation and perfect Coulomb drag.

Coulomb drag is a process whereby the repulsive interactions between electrons in spatially separated conductors enable a current flowing in one of the conductors to induce a voltage drop in the other. If the second conductor is part of a closed circuit, a net current will flow in that circuit. The drag current is typically much smaller than the drive current owing to the heavy screening of the Coulomb interaction. There are, however, rare situations in which strong electronic correlations exist between the two conductors. For example, double quantum well systems can support exciton condensates, which consist of electrons in one well tightly bound to holes in the other. 'Perfect' drag is therefore expected; a steady transport current of electrons driven through one quantum well should be accompanied by an equal current of holes in the other. Here we demonstrate this effect, taking care to ensure that the electron-hole pairs dominate the transport and that tunnelling of charge between the quantum wells, which can readily compromise drag measurements, is negligible. We note that, from an electrical engineering perspective, perfect Coulomb drag is analogous to an electrical transformer that functions at zero frequency.

Arsenic(III) sorption on nanostructured cerium incorporated manganese oxide (NCMO): a physical insight into the mechanistic pathway.

Arsenic(III) sorption was investigated with nanostructured cerium incorporated manganese oxide (NCMO). The pH between 6.0 and 8.0 was optimized for the arsenic(III) sorption. Kinetics and equilibrium data (pH=7.0±0.2, T=303±1.6 K, and I=0.01 M) of arsenic(III) sorption by NCMO described, respectively, the pseudo-second order and the Freundlich isotherm equations well. The sorption process was somewhat complicated in nature and divided into two different segments, initially very fast sorption followed by slow intraparticle diffusion process. Sorption reaction of arsenic(III) on NCMO was endothermic (ΔH°=+13.46 kJ mol(-1)) and spontaneous (ΔG°=-24.75 to -30.15 kJ mol(-1) at T=283-323 K), which took place with increasing entropy (ΔS°=+0.14 kJ mol(-1)K(-1)) at solid-liquid interface. Energy of arsenic(III) sorption estimated by analyzing the equilibrium data using the D-R isotherm model was 15.4 kJ mol(-1), indicating the ion-exchange type mechanism. Raman, FT-IR, pH effect, desorption, etc. studies indicated that arsenic(III) was oxidized to arsenic(V) during the sorption process.

Photoionization of 2-pyridone and 2-hydroxypyridine.

We studied the photoionization of 2-pyridone and its tautomer, 2-hydroxypyridine by means of VUV synchrotron radiation coupled to a velocity map imaging electron/ion coincidence spectrometer. The photoionization efficiency (PIE) spectrum is composed of steps. The state energies of the [2-pyridone](+) cation in the X[combining tilde] ground and A excited electronic states, as well as of the [2-hydroxypyridine](+) cation in the electronic ground state, are determined. The slow photoelectron spectra (SPES) are dominated by the 0(0)(0) transitions to the corresponding electronic states together with several weaker bands corresponding to the population of the pure or combination vibrational bands of the cations. These vibrationally-resolved spectra compare very well with state-of-the-art calculations. Close to the ionization thresholds, the photoionization of these molecules is found to be mainly dominated by a direct process whereas the indirect route (autoionization) may contribute at higher energies.

Effect of prophylactic trochanteric epiphyseodesis in older children with Perthes' disease.

To evaluate the effect of prophylactic epiphyseodesis of the greater trochanter in Perthes' disease, 62 children with unilateral Perthes' disease who underwent trochanteric epiphyseodesis combined with varus osteotomy of the femur during the active stage of the disease (mean age at surgery: 8.4 y) and 20 controls were followed up until skeletal maturity. On radiographs taken at skeletal maturity, the articulo-trochanteric distance, the center-trochanteric distance, the length of the abductor lever arm, the neck-shaft angle, the radius of the femoral head, and the Reimer's migration index of normal and affected hips were measured. The shape of the femoral head was assessed according to the criteria of Mose. The range of hip motion, the strength of hip abduction, and limb lengths were measured and the Trendelenburg sign was elicited. The mean values of articulo-trochanteric distance and center-trochanteric distance were greater and the frequency of a positive Trendelenburg sign was less in children who had undergone trochanteric epiphyseodesis than in children who had no surgery (P<0.01). Trochanteric epiphyseodesis achieved optimal trochanteric growth arrest in 60% of operated children; the procedure was not effective in 30%, and in 10% of children there was overcorrection. Logistic regression analysis showed that the size of the femoral head at healing and the age at surgery were variables that significantly influenced the effectiveness of trochanteric growth arrest. At skeletal maturity, the mean shortening of the affected limb in operated children was 0.44 cm (SD 0.68 cm), whereas that of non-operated children was 0.86 cm (SD 0.78 cm) (P<0.05). The range of motion of the hip was excellent and there were no significant differences in the range of motion among children with optimal correction, under-correction, and overcorrection. A probability curve plotted on the basis of a logistic regression model suggests that effective trochanteric arrest may be achieved in a high proportion of children operated at or before 8.5 years of age and in half the children operated between the age of 8.5 years and 10 years. On the basis of this study, we recommend prophylactic epiphyseodesis of the greater trochanter as a means of minimizing trochanteric overgrowth and resultant Trendelenburg gait in older child with Perthes' disease.

The role of the subthalamic nucleus in response inhibition: evidence from deep brain stimulation for Parkinson's disease.

We measured reaction times during a stop-signal task while patients with Parkinson's disease were on and off unilateral deep brain stimulation (DBS) of the subthalamic nucleus (STN). While reaction times to a "go" stimulus improved, there was no change in reaction times to the "stop" stimulus (SSRTs). However, changes in SSRTs induced by DBS were highly dependent on baseline SSRTs (measured off stimulation), with the greatest improvements being achieved by those with particularly slow reaction times. We therefore selected only those patients whose baseline SSRTs were within the limits of a control sample (N=10). In this group, SSRTs became slower when DBS was on. This finding suggests a role for the STN in response inhibition, which can be interrupted by DBS, observable only when more general improvements in Parkinson's function are minimised. We also compared the effects of unilateral left and right sided stimulation. We found a greater increase in SSRTs after DBS of the left STN.

The pedunculopontine nucleus in Parkinson's disease: primate studies.

Gait freezing and poor balance are two of the most disabling symptoms of advanced Parkinson's disease (PD), and also of other untreatable progressive neurological disorders, such as multi-system atrophy (MSA) and progressive supranuclear palsy (PSP). In PD, these symptoms are currently inadequately managed by drugs and also the present surgical treatment of deep brain stimulation (DBS) of the sub-thalamic nucleus (STN) and the globus pallidus internus (GPi). The pedunculopontine nucleus (PPN) has been implicated in these symptoms. The PPN is in the upper brain stem. The major inhibitory input is from the GPi and substantia nigra reticulata (SNr), and bilateral output is to the substantia nigra compacta (SNc), thalamus and spinal cord. Stimulation of the PPN in the decerebrate rat, cat and dog induced gait-like movements. In autopsy studies in PD, MSA, PSP and the DYT-1 dystonic brain, the PPN is degenerate. Autoradiography of the MPTP-Parkinsonian primate shows excessive inhibition in the PPN. Lesions of the PPN in the normal primate induced PD-type bradykinesia, which was persistent with bilateral lesions. In the MPTP-primate model, microinjections of the gamma aminobutyric acid A (GABA) antagonist bicuculine into the PPN reversed Parkinsonian akinesia implying that stimulation of this region might have a therapeutic role in drug resistant PD. Low frequency (5-10Hz) stimulation of the PPN in the same model reversed akinesia independently of L-dopa; moreover, l-dopa and stimulation effects were additive, implying the involvement of non-dopaminergic pathways.

Milk trace elements in lactating cows environmentally exposed to higher level of lead and cadmium around different industrial units.

The present investigation was carried out to assess the trace mineral profile of milk from lactating cows reared around different industrial units and to examine the effect of blood and milk concentration of lead and cadmium on copper, cobalt, zinc and iron levels in milk. Respective blood and milk samples were collected from a total of 201 apparently healthy lactating cows above 3 years of age including 52 cows reared in areas supposed to be free from pollution. The highest milk lead (0.85+/-0.11 microg/ml) and cadmium (0.23+/-0.02 microg/ml) levels were recorded in lactating cows reared around lead-zinc smelter and steel manufacturing plant, respectively. Significantly (P<0.05) higher concentration of milk copper, cobalt, zinc and iron compared to control animals was recorded in cows around closed lead cum operational zinc smelter. Analysis of correlation between lead and other trace elements in milk from lactating cows with the blood lead level>0.20 microg/ml (n=79) revealed a significant negative correlations between milk iron and milk lead (r=-0.273, P=0.015). However, such trend was not recorded with blood lead level<0.20 microg/ml (n=122). The milk cobalt concentration was significantly correlated (r=0.365, P<0.001) with cadmium level in milk and the highest milk cadmium (>0.10 to 0.39 microg/ml) group had significantly (P<0.05) increased milk cobalt. It is concluded that increased blood and milk lead or cadmium level as a result of natural exposure of lactating cows to these environmental toxicants significantly influences trace minerals composition of milk and such alterations affect the milk quality and nutritional values.

Deep brain stimulation for neuropathic pain.

Deep brain stimulation (DBS) for pain was one of the earliest indications for the therapy. This study reports the outcome of DBS of the sensory thalamus and the periventricular and peri-aqueductal grey area (PVG/PAG) complex for different intractable neuropathic pain syndromes. Forty-seven patients (30 males and 17 females) were selected for surgery; they were suffering from any of the following types of pain: post-stroke neuropathic pain, phantom limb pain, post-herpetic neuralgia, anaesthesia dolorosa, brachial plexus injury and neuropathic pain secondary to neural damage from a variety of causes. Of the 47 patients selected for trial stimulation, 38 patients proceeded to permanent implantation. Patients suffering from post-stroke pain were the most likely to fail trial stimulation (33%), in contrast to individuals with phantom limb/post-brachial plexus injury pain and anaesthesia dolorosa, all of whom underwent permanent implantation. PVG stimulation alone was optimal in 17 patients (53%), whilst a combination of PVG and thalamic stimulation produced the greatest degree of analgesia in 11 patients (34%). Thalamic stimulation alone was optimal in 4 patients (13%). DBS of the PVG alone was associated with the highest degree of pain alleviation, with a mean improvement of 59% (p <0.001) and a > or =50% improvement in 66% of patients. Post-stroke pain responds in 70% of patients. We conclude that the outcomes of surgery appear to vary according to aetiology, but it would appear that the effects are best for phantom limb syndromes, head pain and anaesthesia dolorosa.

Tail hair as an indicator of environmental exposure of cows to lead and cadmium in different industrial areas.

This study examines the use of tail hair from cows as a possible biomarker of environmental exposure to lead and cadmium around different industrial areas. Respective blood and tail hair samples were collected from a total of 317 apparently healthy cows above 3 years of age. This includes 287 cows reared in industrial and urban areas and 30 cows from areas free from polluting sources. Significantly (P<0.05) higher lead and cadmium residues were recorded in hair from cows reared around lead-zinc smelter and closed lead cum operational zinc smelter. However, cows from those areas had significantly (P<0.05) higher blood lead but not cadmium concentration as compared to respective control value. Although mean blood lead concentration in cows around aluminum processing plant and urban cum small industrial areas and that of cadmium around steel processing plant were significantly (P<0.05) higher than respective control, the mean hair lead and cadmium content remained statistically (P>0.05) comparable to that of respective control values. The blood lead was significantly correlated with hair lead (r = 0.672, P<0.01) and cadmium (r = 0.309, P<0.05). There was a significant correlation between lead and cadmium concentration (r = 0.610, P<0.01) in hair and a nonsignificant correlation between blood and hair cadmium suggesting that cadmium accumulation in hair was influenced by blood and hair lead concentrations in cows environmentally exposed to lead.

Changes in plasma hormones profile and liver function in cows naturally exposed to lead and cadmium around different industrial areas.

The present study was carried out to assess the endocrine status and liver function in adult cows reared in polluted environment around different industrial units in India. The effect on endocrine system was examined by determination of plasma level of thyroid hormones, thyroxin (T4) (n=269) and triidothyronin (T3) (n=269), stress hormone cortisol (n=266), and reproductive hormones such as estradiol (n=84) and progesterone (n=84) in cows (>3 years) reared around different polluted industrial and non-polluted areas. The respective blood lead and cadmium concentration was also determined in all the cows. The mean plasma levels of both T3 and T4 were significantly (P<0.05) higher around lead zinc smelter (2.43+/-0.26 and 41.1+/-2.9nmol/L) and closed lead cum operational zinc smelter (1.81+/-0.16 and 42.4+/-6.2nmol/L), where the mean blood lead level (0.86+/-0.06 and 0.51+/-0.09mug/ml) was also significantly higher than that of cows (0.07+/-0.01mug/ml) from unpolluted areas. Regression analysis of data from 269 cows revealed a significant (P<0.01) positive correlation between the blood lead and plasma T3 (r=0.287) and T4 (r=0.173). The correlation between thyroidal hormones and the blood cadmium concentration (r=-0.079 and -0.48; P>0.05) was not significant. Plasma cortisol level had also a non-significant (P>0.05) correlation (r=-0.092) with blood lead level.However, the mean cortisol level (4.02+/-1.96nmol/L) of cows in phosphate rock mining areas was significantly (P<0.05) higher than that of controls (1.98+/-0.70nmol/L). The mean plasma estradiol level was significantly (P<0.05) higher in cows around closed lead cum operational zinc smelter (47.1+/-19.5pg/ml) than that of the control animals (21.8+/-3.9pg/ml) and in rest of the areas, the difference did not reach the statistical significance (P>0.05). The serum biochemical analysis in 36 cows around lead-zinc smelter with the highest mean blood lead level (0.86+/-0.06mug/ml) amongst all the industrial/urban areas surveyed, and in 15 animals from non-polluted areas revealed a significant positive correlation between blood lead and serum ALT (alanine transaminase) (r=0.688, P<0.01) and AST (aspartate transaminase) (r=0.390, P<0.01) and a negative correlation with serum total lipids (r=-0.337, P<0.05), total protein (r=-0.449, P<0.01) and albumin(r=-0.662, P<0.01). It is concluded from the study that the natural exposure to lead in polluted environments disturbs the endocrine profile and the higher blood lead level alters serum biochemical parameters indicative of liver functions.