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BACKGROUND: Although deep brain stimulation (DBS) of the subthalamic nucleus (STN) is a highly effective therapeutic intervention in severe Parkinson's disease, its mechanism of action remains unclear. One possibility is that DBS suppresses local pathologically synchronised oscillatory activity. METHODS: To explore this, the authors recorded from DBS electrodes implanted in the STN of 16 patients with Parkinson's disease during simultaneous stimulation (pulse width 60 μs; frequency 130 Hz) of the same target using a specially designed amplifier. The authors analysed data from 25 sides. RESULTS: The authors found that DBS progressively suppressed peaks in local field potential activity at frequencies between 11 and 30 Hz as voltage was increased beyond a stimulation threshold of 1.5 V. Median peak power had fallen to 54% of baseline values by a stimulation intensity of 3.0 V. CONCLUSION: The findings suggest that DBS can suppress pathological 11-30 Hz activity in the vicinity of stimulation in patients with Parkinson's disease. This suppression occurs at stimulation voltages that are clinically effective.

The burning question surrounding the use of Brain-Machine Interface (BMI) devices is not merely whether they should be used, but how widely they should be used, especially in view of some ethical implications that arise concerning the social and legal aspects of human life. As technology advances, it can be exploited to affect the quality of life. Since the effects of BMIs can be both positive and negative, it is imperative to address the issue of the ethics surrounding them. This paper presents the ways in which BMIs can be used and focuses on the ethical concerns to which neuroscience is thus exposed. The argument put forward supports the use of BMIs solely for purposes of medical treatment, and invites the legal framing of this.

Cerebral neoplasms are uncommon in pregnancy but should be considered in any pregnant woman with new onset neurological symptoms and signs. We report a case of cerebellar haemangioblastoma presenting in pregnancy and discuss the clinical presentation, diagnosis, surgical management and medical literature surrounding the condition.

Background/Aims: Stereotactic postoperative imaging is essential for verification of the position of electrodes implanted for deep brain stimulation (DBS). MRI offers superior visualisation of the DBS targets relative to CT, but previous adverse incidents have heightened concerns about risks of postoperative MRI. Preoperative MRI fused with postoperative CT offers an alternative method for evaluating electrode position, but before this method can be clinically applied, the image registration accuracy must be established. The purpose of this study was to quantitatively assess the accuracy of three different image registration and fusion methods. Methods: Preoperative stereotactic MRI and postoperative stereotactic CT were acquired from 20 patients under- going DBS surgery (35 electrodes in total). The postoperative CT was registered and fused with the preoperative MRI, using three different registration algorithms. The position of each electrode tip was determined in stereotactic coordinates both in the (unfused) postoperative CT and the fused CT/MRI. The difference in tip position between the CT and fused CT/MRI was used to evaluate the registration accuracy. Results: The mean error along the lateral, anteroposterior, and vertical axes was 0.5, 0.5, and 1 mm, respectively. Conclusions: CT/MRI fusion provides a safe, practical technique for postoperative identification of DBS electrodes.

Depth recordings in patients with Parkinson's disease (PD) have demonstrated exaggerated local field potential (LFP) activity at frequencies between 10 and 30 Hz in the subthalamic nucleus (STN). This activity is modulated prior to single phasic movements, possibly as part of the feedforward organization of incipient voluntary movement, and after single phasic movements, as a consequence of afferent feedback processes. Here we test the hypothesis that this activity is also modulated during repetitive movements, reflecting a role in ongoing performance. Accordingly, we recorded LFP activity from the contralateral STN of seven patients with PD withdrawn from anti-parkinsonian medication while they performed repetitive index finger to thumb taps. Cross-correlograms of LFP activity at different frequencies in the 10-30 Hz band with finger position showed that LFP activity was modulated in amplitude by finger tapping. The modulation was higher at the beginning of each recording when tapping performance was better, and diminished as tapping became more bradykinetic over time. The best modulations were seen over those frequencies that were maximal in the power spectrum of the corresponding LFP, and for a given side were most marked at the contact pair that exhibited the highest power at these frequencies. In conclusion, subthalamic activity in the 10-30-Hz band is amplitude modulated during movement. This process fails as bradykinesia increases.

International audience; We have examined dopaminergic cell survival after alteration of the subthalamic nucleus (STN) in methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated monkeys. The STN was lesioned with kainic acid (B series) or underwent deep brain stimulation (DBS) at high frequency (C series). In another series, MPTP-treated and non-MPTP-treated monkeys had no STN alteration (intact animals; A series). Animals were treated with MPTP either after (B1, C1) or before (B2, C2) STN alteration. We also explored the long-term ( approximately 7 months) effect of DBS in non-MPTP-treated monkeys (D series). Brains were aldehyde-fixed and processed for routine Nissl staining and tyrosine hydroxylase immunocytochemistry. Our results showed that there were significantly more (20-24%) dopaminergic cells in the substantia nigra pars compacta (SNc) of the MPTP-treated monkeys that had STN alteration, either with kainic acid lesion or DBS, compared to the non-MPTP-treated monkeys (intact animals). We suggest that this saving or neuroprotection was due to a reduction in glutamate excitotoxicity, as a result of the loss or reduction of the STN input to the SNc. Our results also showed that SNc cell number in the B1 and C1 series were very similar to those in the B2 and C2 series. In the cases that had long-term DBS of the STN (D series), there was no adverse impact on SNc cell number. In summary, these results indicated that STN alteration offered neuroprotection to dopaminergic cells that would normally die as part of the disease process.

International audience; Dopamine active transporter (DAT) single photon emission computerised tomography (SPECT) is considered a useful and practical technique for early diagnosis of Parkinson's disease (PD) and assessment of its progression. The application of this technique, particularly as a surrogate marker for therapeutic and neuroprotective trials in Parkinsonism, however, is dependent on pathological validation. In the absence of human studies, we used 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) primate models of Parkinsonism to verify correlation between the SPECT, immunohistochemical and behavioural data. The DAT SPECT data correlated strongly and significantly with the substantia nigra pars compacta tyrosine hydroxylase and Nissl cell counts as well as the behavioural scores. Within the limitations of small numbers inherent to such studies, this data provides the first attempt at pathological validation of SPECT in primates.

INTRODUCTION: Altered mitochondrial metabolism is a hallmark of glioblastoma (GBM). Previous work in our group using next generation sequencing of GBM cell line mitochondrial DNAs (mtDNAs), combined with 3D structural protein analysis, identified 42 non-synonymous mutations, including 8 within the MT-CYB subunit of complex III (CIII) of the mitochondrial respiratory chain (MRC). Four MT-CYB mutations were predicted to impact on function and concomitant measurement of the MRC enzyme activities in a cohort of GBM cell lines revealed their potential structure-function relationships. METHOD: A cohort of 5 adult GBM cell lines were grown at 37°C and 5% CO2 and 25% O2 until 80% confluent. The cells were treated to allow access of ligands to the inner mitochondrial membrane so that relative activities of complex I, II, linked II/III and IV could be determined spectrophotometrically. RESULTS: Although diverse MRC activity profiles were seen between GBM cell lines, a relationship between CII/CIII activity and the MT-CYB mutation F18L was observed which correlated with structural predictions. GBM cell lines containing F18L, exhibited statistically elevated CII/CIII activity (p > 0.0001) relative to a non-neoplastic control cell line. CONCLUSION: We show a link between a single mtDNA mutation and altered mitochondrial metabolism in GBM which highlights the predictive power of our combined approach. F18L is a germ-line mutation occurring in ∼30% of GBM-patients, raising the possibility that some patients are predisposed to alterations in mitochondrial function. F18L thus provides a target for diagnostic/prognostic research and the development of patient-specific therapeutics.

INTRODUCTION: CD15, a cell adhesion molecule which is overexpressed in various cancers, is thought to be a key player in non-central nervous system (CNS) metastasis. However, the role of CD15 in brain metastasis is largely unexplored. CD15, a trisaccharide adhesion molecule, is over-expressed in non-CNS metastatic cancers. The role of CD15/CD62E interaction in lung to brain metastasis is still unexplored. The aim of this study is to therefore provide a better understanding of CD15/CD62E interaction and its role in adhesion in brain metastasis. METHOD: Expression of CD62E and CD15 were evaluated in brain microvascular endothelial cells (hCMEC/D3), primary (A549 and COR-L105) and metastatic NSCLC cells (NCI-H1299, SEBTA-001 and SEBTA-005) using flow cytometry (FC), immunocytochemistry (ICC) and Western blotting (WB). Adhesion assays under static conditions and physiological flow (shear stress 2.5 dyn/cm2) conditions were conducted. Immunoblocking of CD15 was performed to investigate its role in adhesion. RESULTS: Low levels of CD15 was seen on hCMEC/D3 (19.69%) compared to metastatic NSCLC cells (NCI-H1299: 79%, SEBTA-001: 54% and SEBTA-005: 39%) and primary NSCLC (COR-L105: 31% and A549: 23%) cells (P < 0.001). CD62E expression was high in hCMEC/D3 cells activated with TNF-α. Metastatic NSCLC adhered most strongly to hCMEC/D3 compared to primary NSCLC cells. CD15 immunoblocking blunted this adhesion under static and shear stress conditions (p < 0.001), confirming the correlation between CD15 and cerebral metastasis. CONCLUSION: This study enhances understanding of lung cancer cell-brain endothelial adhesion and suggests that CD15 may play a role in adhesion in concert with TNF-α activation of its binding partner CD62E.

Glioblastoma multiforme (GBM) is the most common adult primary brain tumor. It is highly malignant with 2-year survival of just 27.2% following diagnosis. Treatment is hampered by its unique underlying biology, including differential inter- and intra-tumor responses to therapy. Impaired mitochondrial function is a common feature of cancer cells in comparison to healthy cells. However, the precise contribution of single mitochondrial DNA (mtDNA) mutations to this impairment, and consequently to the development, progression and chemosensitivity of GBM remains poorly described. To address this we have developed a novel integrated approach where we have: (1) obtained complete mitochondrial genomes from multiple GBM samples, (2) employed 3D structural mapping and analysis to predict the function of non-synonymous mtDNA-encoded complex III and IV mutations; (3) measured oxidative phosphorylation (OXPHOS) enzyme complex activities of GBM cell lines. Finally, to circumvent the current inability to genetically transform human mtDNA, we have employed humanized yeast technology to decipher the specific impact of single key mtDNA mutations on cellular growth and OXPHOS complex activity. Over 200 mutations were identified in 42 GBM-mtDNAs using next generation sequencing. This included 9 functional candidates in complexes III and IV, with highly variable mutation loads, which were predicted to affect corresponding enzyme activity. Most were GBM-specific and not found in the general population, two were present in the germ-line and 43% of tumors carried at least one functional candidate. Preliminary spectrophotometric measurements indicate a striking diversity of OXPHOS enzyme complex activity profiles between the GBM cell lines. One cell line exhibited a combined increase in complex I, II, linked II/III and IV activity compared to control. In 5 GBM cell lines, all complex I activities were altered (either elevated or reduced) and all complex IV activities were altered (mostly decreased), while the remaining cell line exhibited decreases in both complex I and IV activity combined with an increase in linked complex II/III activity. Analysis of yeast cells that were genetically transformed to contain a single mutation that mimics the most prevalent functional candidate identified in GBM to date: F18L, revealed an alteration of complex III activity (quinol-cytochrome c reduction) probably caused by a modification of the substrate quinol binding. Using our approach, we show for the first time that a single GBM-associated mtDNA mutation can have a direct effect on mitochondrial function, raising the possibility that small mitogenomic elements could contribute to the heterogeneous biology of GBM. This study paves the way for the systematic study of other functional candidates using humanized yeast technology, as well as other studies that explore their contribution to GBM cell behavior and drug sensitivity. Citation Format: Rhiannon E. Lloyd, Kathleen Keatley, Anais Laleve, Samantha C. Higgins, Stavros Polyzoidis, Keyoumars Ashkan, Helen L. Fillmore, Simon J. Heales, John E. McGeehan, Iain Hargreaves, Brigitte Meunier, Geoffrey J. Pilkington. A novel integrated approach for deciphering the mitochondrial mutation enigma in glioblastoma. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3042. doi:10.1158/1538-7445.AM2015-3042

Objective To determine the effect of globus pallidus internus (GPi) deep brain stimulation (DBS) on motor cortex plasticity in patients with primary generalised dystonia. Methods We studied 10 patients with primary generalised dystonia (5 DYT1+, 5 idiopathic, 5 female, mean age 42) following GPi DBS and 10 healthy subjects. Motor cortex plasticity was assessed using transcranial magnetic stimulation (TMS) paired associative stimulation (PAS) of motor cortex and median nerve, a method which has been shown in healthy subjects to produce LTP-like effects. Thresholds and TMS intensity to produce a resting motor evoked potential (MEP) of 1 mV were determined. Resting MEP amplitude and stimulus response curves were recorded before and after PAS. Patients were recorded ON and OFF DBS in separate sessions. Results The mean TMS intensity to produce a resting MEP of 1 mV was 54% of maximum stimulator output when OFF and 52% ON DBS. Fifteen minutes after PAS the resting MEP amplitude increased in patients OFF DBS and in control subjects whereas it decreased in patients ON DBS. Similarly, after PAS, the mean amplitude of the stimulus response curve increased OFF DBS, but this effect was abolished with DBS ON. Furthermore, patients who had the largest clinical response to chronic DBS also had the largest difference in the effect of PAS with DBS ON vs. OFF. Conclusions After PAS, patients with primary generalised dystonia showed a similar pattern of increased motor cortex excitability as healthy subjects when GPi DBS was OFF but not with GPi DBS ON. These results suggest that GPi DBS may reduce LTP-like motor cortex plasticity, which could contribute to its mechanism of action in dystonia.

Hypophyseal tuberculomas are exceptionally rare. We report two patients with sellar tuberculoma but with no evidence of concurrent extrasellar disease. Although the lesion is often mistaken for adenoma, there are characteristic radiological features: intense enhancement on contrast CT and thickening of the pituitary stalk on MRI in 86% of cases. Accurate diagnosis is important because pituitary tuberculoma is curable.

International audience; We explore the patterns of cell loss in the pedunculopontine tegmental nucleus (PpT), a major locomotor and muscle tone suppression centre of the brainstem, in two animal models of Parkinson disease, namely MPTP (methyl-4-phenyl-1,2,3,6-tetrahydropyridine)-treated monkeys and 6-hydroxydopamine(6OHDA)-lesioned rats. Although there have been many studies documenting the loss of dopaminergic cells from the substantia nigra in these animal models, there has been little, if any, documentation of a loss of cells in the PpT. Results were obtained from macaque monkeys (Macaca fascicularis) and Sprague-Dawley rats. For the monkey series, animals were injected intramuscularly with MPTP (0.2 mg/kg) for 8 days consecutively and then allowed to survive for 21 days thereafter. Each monkey underwent behavioural assessment for parkinsonian symptoms. For the rat series, 6OHDA was injected into the midbrain using stereotactic coordinates. Rats were then allowed to survive for either 7, 14, 28, or 84 days thereafter. Monkey and rat brains were aldehyde-fixed and processed for routine tyrosine hydroxylase (TH; to label nigral dopaminergic cells) and nitric oxide synthase (NOs; to label PpT cholinergic cells) immunocytochemistry. In monkeys, the morphology, distribution and number of NOs(+) cells in the controls and MPTP-treated cases were very similar. In fact, in terms of number, there was only a 1% difference in the mean cell number between the controls and MPTP-treated cases. A comparable pattern was evident in 6OHDA-lesioned rats; there was no substantial difference in morphology, distribution and number of NOs(+) cells on the 6OHDA-lesioned cases when compared to the controls at each of the survival periods post-surgery. In summary, we show no loss of the large cholinergic/NOs(+) cells in the PpT in two animal models of Parkinson disease. This is in contrast to the heavy loss of these cells reported by previous findings in idiopathic Parkinson disease in patients.

International audience; We explore the patterns of survival among dopaminergic cells of the midbrain in MPTP-treated macaque monkeys and 6OHDA-lesioned Sprague-Dawley rats. For the monkeys, animals were injected intramuscularly with MPTP for 8 days consecutively and then allowed to survive for 21 days. For the rats, 6OHDA was injected into the midbrain and then allowed to survive for either 7, 28 or 84 days. Brains were processed for tyrosine hydroxylase (TH) and calbindin immunocytochemistry to label populations in the ventral and dorsal tiers of midbrain dopaminergic cells. In monkeys, while there was a decrease in the TH+ cell number in the ventral tier of MPTP-treated cases (65%), there was an overall increase (22%) in the TH+ and calbindin+ cell number in the dorsal tier. Double labelling studies indicate that approximately 50% of TH+ cells of the dorsal tier contain calbindin also. In rats, there was a decrease in TH+ cell number in the ventral tier of 6OHDA-lesioned cases (97%), and to a lesser extent, in the TH+ and calbindin+ cell number in the dorsal tier ( approximately 40%). In conclusion, we show a surprising increase in TH+ and calbindin+ cell number in the dorsal tier in response to MPTP insult; such an increase was not evident after 6OHDA insult. We suggest that the increase in antigen expression relates to the dopaminergic reinnervation of the striatum in MPTP-treated cases. We also suggest that the greater loss of dopaminergic cells in the ventral tier when compared to the dorsal tier relates to glutamate toxicity.

Deep brain stimulation (DBS) was first used for the treatment of pain in 1954. Since that time, remarkable advances have been made in the field of DBS, largely because of the resurgence of DBS for the treatment of movement disorders. Although DBS for pain has largely been supplanted by motor cortex and spinal cord stimulation during the last decade, no solid evidence exists that these alternative modalities truly offer improved outcomes. Furthermore, nuclei not yet fully explored are known to play a role in the transmission and modulation of pain. This article outlines the history of DBS for pain, pain classification, patient selection criteria, DBS target selection, surgical techniques, indications for DBS (versus ablative techniques), putative new DBS targets, complications, and the outcomes associated with DBS for pain.

Since its advent in 1993, high frequency stimulation (HFS) of the subthalamic nucleus (STN) has rapidly developed into the most commonly practiced surgical procedure for the treatment of Parkinson's Disease (PD). Although its exact mechanism of action, be it through an inhibitory depolarization block, desynchronization of neuronal circuits or other means, is not clear, the efficacy and safety of the technique are now well established. HFS of the STN improves the motor function by at least 60%, drastically reduces the levodopa requirement and significantly improves the quality of life in PD. This review updates the recent concepts on the pathophysiology of PD and analyses the basic science principles underlying the clinical practice of the STN HFS. The evolution of the surgical technique and long-term patients' outcome are further discussed.

BACKGROUND: There is an increasing tendency towards sub-specialisation in the larger surgical specialties. The feasibility and effectiveness of this is less clear in the smaller specialties with limited manpower such as neurosurgery. PATIENTS AND METHODS: To evaluate this, we carried out an audit comparing the throughput and outcome of patients treated for intracranial aneurysms in our unit before and after a period of neurovascular sub-specialisation. RESULTS: In the period before sub-specialisation, 68 aneurysms were treated compared to 69 after sub-specialisation. The epidemiological profile of patients, their clinical condition at presentation and the location of aneurysms were not significantly different in the two periods. There was less morbidity and mortality and better long-term functional outcome (P = 0.05) following sub-specialisation. More investigations including cerebral angiograms were performed after sub-specialisation. The added cost, however, was offset against savings made by the shorter length of patient's hospital stay (P = 0.002). CONCLUSIONS: Sub-specialisation appears to confer benefits both in terms of patient outcome and socio-economic gain.

Background What do patients expect from a treatment? A patient-centred approach to treatment is becoming necessary given the choices for invasive treatments for Parkinson’s disease. Patient’s perceptions of severity and expectations from complex therapies have not been studied. We describe the rationale and concept of developing a Patient-Reported Outcome (PRO) tool to assess perceptions of symptom severity and expectations of therapy. We report preliminary findings from use of the tool, association with clinical factors, and illustrate the potential use in individual patients awaiting therapy. Methods Patient symptoms were grouped into four domains, with 8 motor, 7 non-motor, 7 psychological and 4 social questions. For each question, symptom severity was rated on a Likert scale scoring from 0 (no problem) to 7 (perceived as a severe problem). Similarly, the expectation for each symptom to change after therapy was rated on a Likert scale: score −3 (expected to be very much worse) to + 3 (expected to be very much improved). Results 22 consecutive patients, routinely planned to receive one of Deep Brain Stimulation/Intrajejunal Levodopa Infusion/Apomorphine Infusion therapies, were recruited: 13 male, mean (+/−sd) age: 65.6 (+/−9.5) years, mean (+/−sd) disease duration: 14.3 (+/−5.7) years. Subjective severity scores are reported as mean (+/−sd) / maximum possible score: (i) motor 23.5 (+/−7.5) / 56, (ii) non-motor 15.5 (+/−5.6) / 49, (iii) cognitive - psychological 12.4 (+/−5.8) / 49, (iv) social 9.3 (+/−4.1) / 28. Expectation of change (improvement) scores are reported as mean (+/−sd) / maximum possible score of: (i) motor 14.0 (+/−5.6) / 24, (ii) non-motor 8.5 (+/−4.1) / 21, (iii) cognitive - psychological 7.4 (+/−4.4)/ 21, and (iv) social 5.5 (+/−2.8) / 12. For each domain, Spearman correlation coefficient showed significant associations between severity and expectation within-domain. Conclusion This tool (PRO-APD) provides a description of perceived problem severity and expectation of treatments encompassing a holistic patient-driven view of care. PD patients about to receive complex therapy have moderately high perception of symptom load in multiple domains, and expect substantial improvements in multiple domains. These preliminary findings may be useful in documenting multi-domain symptoms, as well as counseling patients to help them reach realistic expectations and reduce potential dissatisfaction following therapy.

We report two young patients with obscure presentations of gliomatosis cerebri. Initial CT scanning was inconclusive and in one case showed intraventricular haemorrhage, a feature not previously described. Magnetic resonance imaging was required to show the lesions with greater definition; however, in both cases, a biopsy was needed to confirm the diagnosis.

In a patient with an old head injury, violent nose-blowing can have dangerous consequences.

A 45 year old previously fit woman presented with a six month history of fatigue, generalised arthralgia, and burning discomfort in both legs. General examination was unremarkable except for a dull percussion …

A 54-year-old man presented with symptoms of cauda equina syndrome, which spontaneously resolved. Initial MRI did not show any compression of the cauda equine; however, an unusual pattern of epidural fat lead to further investigation and ultimately the diagnosis.

Neuropsychology Department, King’s College Hospital, London, UK Division of Neuropsychology, Riyadh Military Hospital, Saudi Arabia Department of Psychological Medicine, South London and Maudsley NHS Foundation Trust, London, UK Department of Neurosurgery, King’s College Hospital, London, UK Department of Clinical Neurology, King’s College Hospital, London, UK Department of Clinical Neurosciences, Institute of Psychiatry, King’s College London, UK

Back pain and sciatica in patients with neurofibromatosis may result from a multitude of pathological processes which include scoliosis, degenerative diseases of the spine, and …

Although pneumothorax is the commonest presentation of pulmonary barotrauma unrelated to mechanical ventilation, systemic air embolism and emphysema within the pulmonary interstitium, mediastinum, retroperitoneum, pericardium, and subcutaneous tissues have all been described.1 We report a case of pulmonary barotrauma after inflation of party balloons. A 24 year old previously healthy, non-smoker presented with a 48 hour history of a sensation of crackling under the skin. His symptoms were initially confined to the neck but within 24 hours had affected his chest wall, trunk, and legs. The next day he developed retrosternal pleuritic chest pain and attended the accident and emergency department. He reported that 24 hours before the onset of symptoms he had inflated about 20 party balloons over one hour. He had not experienced chest pain or shortness of breath at the time or immediately afterwards. …

Parkinson’s disease (PD) is a complex progressive movement disorder leading to motor and non-motor symptoms that become increasingly debilitating as the disease advances, considerably reducing quality of life. Advanced treatment options include deep brain stimulation (DBS). While clinical effectiveness of DBS has been demonstrated in a number of randomised controlled trials (RCT), evidence on cost-effectiveness is limited. The cost-effectiveness of DBS combined with BMT, versus BMT alone, was evaluated from a UK payer perspective. Individual patient-level data on the effect of DBS on PD symptom progression from a large 6-month RCT were used to develop a Markov model representing clinical progression and capture treatment effect and costs. A 5-year time horizon was used, and an incremental cost-effectiveness ratio (ICER) was calculated in terms of cost per quality-adjusted life-years (QALY) and uncertainty assessed in deterministic sensitivity analyses. Total discounted costs in the DBS and BMT groups over 5 years were £68,970 and £48,243, respectively, with QALYs of 2.21 and 1.21, giving an incremental cost-effectiveness ratio of £20,678 per QALY gained. Utility weights in each health state and costs of on-going medication appear to be the key drivers of uncertainty in the model. The results suggest that DBS is a cost-effective intervention in patients with advanced PD who are eligible for surgery, providing good value for money to health care payers.

Local field potential recordings made from the basal ganglia of patients undergoing deep brain stimulation have suggested that frequency specific activity is involved in determining the rate of force development and the peak force at the outset of a movement. However, the extent to which the basal ganglia might be involved in motor performance later on in a sustained contraction is less clear. We therefore recorded from the subthalamic nucleus region (STNr) in patients with Parkinson's disease (PD) as they made maximal voluntary grips. Relative to age-matched controls they had more rapid force decrement when contraction was meant to be sustained and prolonged release reaction time and slower rate of force offset when they were supposed to release the grip. These impairments were independent from medication status. Increased STNr power over 5–12Hz (in the theta/alpha band) independently predicted better performance—reduced force decrement, shortened release reaction time and faster rate of force offset. In contrast, lower mean levels and progressive reduction of STNr power over 55–375Hz (high gamma/high frequency) over the period when contraction was meant to be sustained were both strongly associated with greater force decrement over time. Higher power over 13–23Hz (low beta) was associated with more rapid force decrement during the period when grip should have been sustained, and with a paradoxical shortening of the release reaction time. These observations suggest that STNr activities at 5–12Hz and 55–375Hz are necessary for optimal grip performance and that deficiencies of such activities lead to motor impairments. In contrast, increased levels of 13–25Hz activity both promote force decrement and shorten the release reaction time, consistent with a role in antagonising (and terminating) voluntary movement. Frequency specific oscillatory activities in the STNr impact on motor performance from the beginning to the end of a voluntary grip.

Background/Aim: While neuron-glia 2 (NG2) is well-characterized in the developing brain and in adult high-grade gliomas, little is known about NG2 expression in paediatric brain tumors. Here, NG2 expression was examined in a range of paediatric brain tumors. Materials and Methods: A retrospective immunohistopathological analysis of 57 paediatric brain tumor biopsies of various tumor types was carried out. Paediatric cell lines, including two medulloblastomas and one dysembryoplastic neuroepithelial tumor, in addition to one adult high-grade glioma, were also assessed for NG2 expression. Results: NG2-positive staining was seen in all dysembryoplastic neuroepithelial tumors (DNETs) examined; however, only two of the fourteen medulloblastomas examined were NG2-positive. Compared to adult glioma, there was a lack of NG2 staining in the vasculature of paediatric brain tumors. Conclusion: NG2 expression in paediatric brain tumors differs depending upon type and, unlike adult glioma, includes expression on lower-grade tumors.