Glioblastoma in Beckwith-Wiedemann syndrome: first case report and review of potential pathomechanisms.

Beckwith-Wiedemann syndrome (BWS) is a rare congenital overgrowth syndrome associated with certain childhood tumours. We present the case of a 36-year-old lady with BWS who developed a left frontoinsular secondary glioblastoma. This is the first case report in the literature of glioblastoma associated with BWS. We explore similarities in the molecular pathomechanisms of BWS and glioblastoma.

Characterising the Analgesic Effect of Different Targets for Deep Brain Stimulation in Trigeminal Anaesthesia Dolorosa.

BACKGROUND: Several deep brain stimulation (DBS) targets have been explored for the alleviation of trigeminal anaesthesia dolorosa. We aimed to characterise the analgesia produced from the periaqueductal grey (PAG) and centromedian-parafascicular (CmPf) nucleus using a within-subject design. METHOD: We report a case series of 3 subjects implanted with PAG and CmPf DBS systems for the treatment of anaesthesia dolorosa. At follow-up, testing of onset and offset times, magnitude, and thermal and mechanical sensitivity was performed. RESULTS: The mean pain score of the cohort was acutely reduced by 56% (p < 0.05) with PAG and 67% (p < 0.01) with CmPf stimulation at mean time intervals of 38 and 16 min, respectively. The onset time was 12.5 min (p < 0.05) for PAG stimulation and 2.5 min (p < 0.01) for CmPf. The offset time was 2.5 min (p < 0.05) for PAG and 12.5 min (p < 0.01) for CmPf. The two targets were effective at different stimulation frequencies and were not antagonistic in effect. CONCLUSION: The mechanisms by which stimulation at these two targets produces analgesia are likely to be different. Certain pain qualities may respond more favourably to specific targets. Knowledge of onset and offset times for the targets can guide optimisation of stimulation settings. The use of more than one stimulation target may be beneficial and should be considered in anaesthesia dolorosa patients.

Implementing novel trial methods to evaluate surgery for essential tremor.

INTRODUCTION: Deep brain stimulation (DBS) can provide dramatic essential tremor (ET) relief, however no Class I evidence exists. MATERIALS AND METHODS: Analysis methods: I) traditional cohort analysis; II) N-of-1 single patient randomised control trial and III) signal-to-noise (S/N) analysis. 20 DBS electrodes in ET patients were switched on and off for 3-min periods. Six pairs of on and off periods in each case, with the pair order determined randomly. Tremor severity was quantified with tremor evaluator and patient was blinded to stimulation. Patients also stated whether they perceived the stimulation to be on after each trial. RESULTS: I) Mean end-of-trial tremor severity 0.84 out of 10 on, 6.62 Off, t = - 13.218, p < 0.0005. II) N-of-1: 60% of cases had 12 correct perceptions (p = 0.001), 20% had 11 correct perceptions (p = 0.013). III) S/N: > 80% tremor reduction occurred in 99/114 'On' trials (87%), and 3/114 'Off' trials (3%). S/N ratio for 80% improvement with DBS versus spontaneous improvement was 487,757-to-1. CONCLUSIONS: DBS treatment effect on ET is too large for bias to be a plausible explanation. Formal N-of-1 trial design, and S/N ratio method for presenting results, allows this to be demonstrated convincingly where conventional randomised controlled trials are not possible. CLASSIFICATION OF EVIDENCE: This study is the first to provide Class I evidence for the efficacy of DBS for ET.

A stochastic total least squares solution of adaptive filtering problem.

An efficient and computationally linear algorithm is derived for total least squares solution of adaptive filtering problem, when both input and output signals are contaminated by noise. The proposed total least mean squares (TLMS) algorithm is designed by recursively computing an optimal solution of adaptive TLS problem by minimizing instantaneous value of weighted cost function. Convergence analysis of the algorithm is given to show the global convergence of the proposed algorithm, provided that the stepsize parameter is appropriately chosen. The TLMS algorithm is computationally simpler than the other TLS algorithms and demonstrates a better performance as compared with the least mean square (LMS) and normalized least mean square (NLMS) algorithms. It provides minimum mean square deviation by exhibiting better convergence in misalignment for unknown system identification under noisy inputs.

Enhancing curve and surface applications with trigonometric polynomial basis functions.

This article primarily focuses on the utilization and importance of parametric curves in surface design. It delves into the construction and applications of parametric curves, exploring the implementation of trigonometric polynomial basis functions that possess two shape parameters. Initially, these basis functions are employed in constructing both rational and non-rational curves. Later, they are employed to define the surfaces generated by these curves. The discussion includes rational surfaces, tensor product surfaces, and various specialized surfaces. The aim is to provide a comprehensive understanding of the role and potential of parametric curves in surface design.

Distinct roles of dopamine and subthalamic nucleus in learning and probabilistic decision making.

Even simple behaviour requires us to make decisions based on combining multiple pieces of learned and new information. Making such decisions requires both learning the optimal response to each given stimulus as well as combining probabilistic information from multiple stimuli before selecting a response. Computational theories of decision making predict that learning individual stimulus-response associations and rapid combination of information from multiple stimuli are dependent on different components of basal ganglia circuitry. In particular, learning and retention of memory, required for optimal response choice, are significantly reliant on dopamine, whereas integrating information probabilistically is critically dependent upon functioning of the glutamatergic subthalamic nucleus (computing the 'normalization term' in Bayes' theorem). Here, we test these theories by investigating 22 patients with Parkinson's disease either treated with deep brain stimulation to the subthalamic nucleus and dopaminergic therapy or managed with dopaminergic therapy alone. We use computerized tasks that probe three cognitive functions-information acquisition (learning), memory over a delay and information integration when multiple pieces of sequentially presented information have to be combined. Patients performed the tasks ON or OFF deep brain stimulation and/or ON or OFF dopaminergic therapy. Consistent with the computational theories, we show that stopping dopaminergic therapy impairs memory for probabilistic information over a delay, whereas deep brain stimulation to the region of the subthalamic nucleus disrupts decision making when multiple pieces of acquired information must be combined. Furthermore, we found that when participants needed to update their decision on the basis of the last piece of information presented in the decision-making task, patients with deep brain stimulation of the subthalamic nucleus region did not slow down appropriately to revise their plan, a pattern of behaviour that mirrors the impulsivity described clinically in some patients with subthalamic nucleus deep brain stimulation. Thus, we demonstrate distinct mechanisms for two important facets of human decision making: first, a role for dopamine in memory consolidation, and second, the critical importance of the subthalamic nucleus in successful decision making when multiple pieces of information must be combined.

Clinical outcomes from bilateral versus unilateral stimulation of the pedunculopontine nucleus with and without concomitant caudal zona incerta region stimulation in Parkinson's disease.

INTRODUCTION: The Pedunculopontine nucleus is a novel target for deep brain stimulation and this may improve postural instability and gait dysfunction in Parkinson's disease. If unilateral Pedunculopontine nucleus stimulation is as efficacious as bilateral stimulation this would lead to less surgical risk. METHODS: 5 Parkinson's disease patients with bilateral caudal Zona Incerta region and Pedunculopontine nucleus electrodes were assessed using the motor component of the Unified Parkinson's Disease Rating Scale. Patients were assessed in the on-medication state to determine the optimal combination of stimulation setting for axial symptom control. RESULTS: The on-medication composite axial-subscore only showed a statistically significant improvement when bilateral Pedunculopontine nucleus and caudal Zona Incerta region stimulation was used. CONCLUSIONS: In the on-medication state bilateral Pedunculopontine nucleus and caudal Zona Incerta region stimulation is required in order to produce a significant change in the motor Unified Parkinson's Disease Rating Scale axial-subscore from baseline.

Bilateral caudal zona incerta nucleus stimulation for essential tremor: outcome and quality of life.

BACKGROUND: Over the past few years, bilateral stimulation of the caudal or motor part of the zona incerta nucleus (cZI) has been performed by the authors in patients with essential tremor (ET). Outcomes including quality of life data in 15 patients with a follow-up period of up to 84 months (mean 31.7 ± 28.6 months) are presented. METHODS: 15 consecutive ET patients underwent MRI guided bilateral cZI deep brain stimulation implantation. Patients were assessed by applying the Fahn-Tolosa-Marin Tremor Rating Scale and the Short Form Health Survey-36 (SF-36) to assess quality of life. RESULTS: The total tremor score improved by 73.8% (p<0.0001). The part A score (items 1-9) improved by 86.6% (p<0.0001). Postural tremor improved by 88.2% (p<0.0001) and action tremor by 82.2% (p<0.0001). The part B score, which evaluates the functional activities of the upper limbs, improved by 60.1% (p<0.0001). Part C score, which evaluates the activities of daily living, improved by 80.0% (p<0.0001). The SF-36 physical component score improved by 23.7% (p<0.0001) and the mental component score by 22.4% (p<0.0001). There was one wound infection and three patients developed stimulation related transient dysarthria. None developed any disequilibrium or tolerance to stimulation. CONCLUSION: Bilateral cZI stimulation is safe and effective in suppressing the postural and action component of ET. It is associated with a low incidence of stimulation related complications and patients do not develop tolerance to stimulation with maintained clinical benefit over a follow-up period of up to 7 years.

Outcomes from stimulation of the caudal zona incerta and pedunculopontine nucleus in patients with Parkinson's disease.

INTRODUCTION: Axial symptoms including postural instability, falls and failure of gait initiation are some of the most disabling motor symptoms of Parkinson's disease (PD). We performed bilateral deep brain stimulation (DBS) of the pedunculopontine nucleus (PPN) in combination with the caudal zona incerta (cZi) in order to determine their efficacy in alleviating these symptoms. METHODS: Seven patients with predominant axial symptoms in both the 'on' and 'off' medication states underwent bilateral cZi and PPN DBS. Motor outcomes were assessed using the motor component of the Unified Parkinson's Disease Rating Scale (UPDRS 3) and a composite axial subscore was derived from items 27, 28, 29 and 30 (arising from chair, posture, gait and postural stability). Quality of life was measured using the PDQ39. Comparisons were made between scores obtained at baseline and those at a mean follow-up of 12 months. RESULTS: In both the off and on medication states, a statistically significant improvement in the UPDRS part 3 score was achieved by stimulation of the PPN, cZi and both in combination. In the off medication state, our composite axial subscore of the UPDRS part 3 improved with stimulation of the PPN, cZi and both in combination. The composite axial subscore, in the 'on' medication state, however, only showed a statistically significant improvement when a combination of cZi and PPN stimulation was used. CONCLUSIONS: This study provides evidence that a combination of PPN and cZi stimulation can achieve a significant improvement in the hitherto untreatable 'on' medication axial symptoms of PD.

High frequency stimulation of the mamillothalamic tract for the treatment of resistant seizures associated with hypothalamic hamartoma.

We investigate the clinical outcome from stimulation of the mamillothalamic tract in two patients with intractable epilepsy secondary to hypothalamic hamartomas. One patient has a left-sided and the other a right-sided tumor. Both patients presented with a history of gelastic and complex partial seizures resistant to multiple antiepileptic drugs. Both patients underwent insertion of a single deep brain-stimulating electrode ipsilateral to the site of the tumor, lying adjacent to the mamillothalamic tract. Postoperatively they both had a significant reduction in seizure frequency, with one patient being seizure free for the last 10 months. An improvement in mood was reported by the patient's primary carers and demonstrated on quality of life questionnaires.

Subcortical evoked activity and motor enhancement in Parkinson's disease.

Enhancements in motor performance have been demonstrated in response to intense stimuli both in healthy subjects and in the form of 'paradoxical kinesis' in patients with Parkinson's disease. Here we identify a mid-latency evoked potential in local field potential recordings from the region of the subthalamic nucleus, which scales in amplitude with both the intensity of the stimulus delivered and corresponding enhancements in biomechanical measures of maximal handgrips, independent of the dopaminergic state of our subjects with Parkinson's disease. Recordings of a similar evoked potential in the related pedunculopontine nucleus - a key component of the reticular activating system - provide support for this neural signature in the subthalmic nucleus being a novel correlate of ascending arousal, propagated from the reticular activating system to exert an 'energizing' influence on motor circuitry. Future manipulation of this system linking arousal and motor performance may provide a novel approach for the non-dopaminergic enhancement of motor performance in patients with hypokinetic disorders such as Parkinson's disease.

Benefits of putaminal GDNF infusion in Parkinson disease are maintained after GDNF cessation.

We previously reported clinical improvement, increase in putamen [(18)F]-dopa uptake on PET imaging, and neuropathologic evidence of sprouting of dopaminergic fibers following chronic intraputaminal delivery of glial cell line-derived neurotrophic factor (GDNF) in idiopathic Parkinson disease (PD).(1-3) We now provide clinical and PET evidence of persistent efficacy lasting for at least 3 years following cessation of GDNF infusion in a patient with PD. This is a single-case observational study, providing Class IV evidence.

A magnetic resonance imaging-directed method for transventricular targeting of midline structures for deep brain stimulation using implantable guide tubes.

OBJECTIVE: The periventricular gray/periaqueductal gray (PVG/PAG) is a target site for deep brain stimulation for chronic pain. The pedunculopontine nucleus (PPN) is a target for the treatment of axial disturbance in Parkinson's disease. Conventionally, a trajectory lateral to the ventricle is used in targeting deep subcortical structures; however, this limits the number of active contacts that can be placed in these midline targets. To maximize the number of contacts within these targets, a trajectory traversing the ventricles may be used; however, this is avoided because lead placement remains unpredictable with problems including ventricular lead migration and hemorrhage. We describe a novel method for accurate and safe transventricular targeting. METHODS: Magnetic resonance imaging is used for visualizing the target structure. A trajectory traversing the lateral ventricle is planned, avoiding blood vessels. The guide tube is inserted through the ventricle to a position short of the target site and its proximal end is fixed. A stylet is inserted in the guide tube with its distal end at the target site. After intraoperative radiological confirmation of placement, the indwelling stylet is removed and the guide tube acts as a port for delivering the stimulating electrode. RESULTS: The PVG/PAG matter and the PPN were targeted, taking a transventricular trajectory. We implanted unilateral PVG/PAG matter electrodes in 10 patients and bilateral PPN electrodes in 3 patients. All electrodes were implanted accurately within the desired target with no complications. CONCLUSION: The use of an implanted guide tube enables the safe and accurate transventricular targeting of the PVG/PAG matter and the PPN.