Clinical outcomes after MRI connectivity-guided radiofrequency thalamotomy for tremor.

OBJECTIVE: Radiofrequency thalamotomy (RF-T) is an established treatment for refractory tremor. It is unclear whether connectivity-guided targeting strategies could further augment outcomes. The aim of this study was to evaluate the efficacy and safety of MRI connectivity-guided RF-T in severe tremor. METHODS: Twenty-one consecutive patients with severe tremor (14 with essential tremor [ET], 7 with Parkinson's disease [PD]) underwent unilateral RF-T at a single institution between 2017 and 2020. Connectivity-derived thalamic segmentation was used to guide targeting. Changes in the Fahn-Tolosa-Marin Rating Scale (FTMRS) were recorded in treated and nontreated hands as well as procedure-related side effects. RESULTS: Twenty-three thalamotomies were performed (with 2 patients receiving a repeated intervention). The mean postoperative assessment time point was 14.1 months. Treated-hand tremor scores improved by 63.8%, whereas nontreated-hand scores deteriorated by 10.1% (p < 0.01). Total FTMRS scores were significantly better at follow-up compared with baseline (mean 34.7 vs 51.7, p = 0.016). Baseline treated-hand tremor severity (rho = 0.786, p < 0.01) and total FTMRS score (rho = 0.64, p < 0.01) best correlated with tremor improvement. The most reported side effect was mild gait ataxia (n = 11 patients). CONCLUSIONS: RF-T guided by connectivity-derived segmentation is a safe and effective option for severe tremor in both PD and ET.

Effects of deep brain stimulation frequency on eye movements and cognitive control.

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is an effective treatment for Parkinson's disease (PD). Varying the frequency DBS has differential effects on axial and distal limb functions, suggesting differing modulation of relevant pathways. The STN is also a critical node in oculomotor and associative networks, but the effect of stimulation frequency on these networks remains unknown. This study aimed to investigate the effects of 80 hz vs. 130 Hz frequency STN-DBS on eye movements and executive control. Twenty-one STN-DBS PD patients receiving 130 Hz vs. 80 Hz stimulation were compared to a healthy control group (n = 16). All participants were tested twice in a double-blind manner. We examined prosaccades (latency and gain) and antisaccades (latency of correct and incorrect antisaccades, error rate and gain of the correct antisaccades). Executive function was tested with the Stroop task. The motor condition was assessed using Unified Parkinson's Disease Rating Scale part III. The antisaccadic error rate was higher in patients (p = 0.0113), more so in patients on 80 Hz compared to 130 Hz (p = 0.001) stimulation. The differences between patients and controls and between frequencies for all other eye-movements or cognitive measures were not statistically significant. We show that 80 Hz STN-DBS in PD reduces the ability to maintain stable fixation but does not alter inhibition, resulting in a higher antisaccade error rate presumably due to less efficient fixation, without altering the motor state. This provides a wider range of stimulation parameters that can reduce specific DBS-related effects without affecting motor outcomes.

Pedunculopontine Nucleus Deep Brain Stimulation for Parkinsonian Disorders: A Case Series.

BACKGROUND: Deep brain stimulation (DBS) of the pedunculopontine nucleus (PPN) has been investigated for the treatment of levodopa-refractory gait dysfunction in parkinsonian disorders, with equivocal results so far. OBJECTIVES: To summarize the clinical outcomes of PPN-DBS-treated patients at our centre and elicit any patterns that may guide future research. MATERIALS AND METHODS: Pre- and post-operative objective overall motor and gait subsection scores as well as patient-reported outcomes were recorded for 6 PPN-DBS-treated patients, 3 with Parkinson's disease (PD), and 3 with progressive supranuclear palsy (PSP). Electrodes were implanted unilaterally in the first 3 patients and bilaterally in the latter 3, using an MRI-guided MRI-verified technique. Stimulation was initiated at 20-30 Hz and optimized in an iterative manner. RESULTS: Unilaterally treated patients did not demonstrate significant improvements in gait questionnaires, UPDRS-III or PSPRS scores or their respective gait subsections. This contrasted with at least an initial response in bilaterally treated patients. Diurnal cycling of stimulation in a PD patient with habituation to the initial benefit reproduced substantial improvements in freezing of gait (FOG) 3 years post-operatively. Among the PSP patients, 1 with a parkinsonian subtype had a sustained improvement in FOG while another with Richardson syndrome (PSP-RS) did not benefit. CONCLUSIONS: PPN-DBS remains an investigational treatment for levodopa-refractory FOG. This series corroborates some previously reported findings: bilateral stimulation may be more effective than unilateral stimulation; the response in PSP patients may depend on the disease subtype; and diurnal cycling of stimulation to overcome habituation merits further investigation.

Endurance of Short Pulse Width Thalamic Stimulation Efficacy in Intention Tremor.

The benefit of short pulse width stimulation in patients suffering from essential tremor (ET) refractory to thalamic deep brain stimulation remains controversial. Here, we add to the minimal body of evidence available by reporting the effect of this type of stimulation in 3 patients with a persistent and severe intention tremor component despite iterative DBS setting adjustments. While a reduction in pulse width to 30 µs initially showed promise in these patients by improving tremor control and mitigating cerebellar side effects arguably by widening the therapeutic window, these benefits seemed to dissipate during early follow-up. Our experience supports the need for measuring longer-term outcomes when reporting the usefulness of this mode of stimulation in ET.

Novel Programming Features Help Alleviate Subthalamic Nucleus Stimulation-Induced Side Effects.

BACKGROUND: Subthalamic nucleus deep brain stimulation (STN-DBS) is a widely used treatment for Parkinson's disease (PD) patients with motor complications, but can result in adverse effects (AEs) in a significant proportion of treated patients. The use of novel programming features including short pulse width (PW) and directional steering in alleviating stimulation-induced AEs has not been explored. OBJECTIVE: To determine if programming with short PW, directional steering, or the combination of these novel techniques can improve stimulation-induced dysarthria, dyskinesia, and pyramidal AEs. METHODS: Thirty-two consecutive PD patients who experienced reversible AEs of STN-DBS had optimization of their settings using either short PW, directional steering, or the combination, while ensuring equivalent control of motor symptoms. Pairwise comparisons of pre- and post-optimization adverse effect ratings were made. Patients were left on the alternative setting with the greatest benefit and followed up at 6 months. Modeling of volume of tissue activated (VTA) and charge per pulse (Qp) calculations were used to explore potential underlying mechanisms of any differences found. RESULTS: There were significant improvements in stimulation-induced dysarthria, dyskinesia, and pyramidal side effects after optimization. At 6 months, mean AE ratings remained significantly improved compared to pre-optimization ratings. Different patterns of shift in VTA for each AE, and Qp could be used to explain improvements using novel techniques. CONCLUSIONS: Stimulation-induced dysarthria, dyskinesia, and pyramidal AEs induced by STN-DBS can be improved by using novel programming techniques. These represent additional tools to conventional methods that can be used to address these AEs. © 2020 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Subthalamic Nucleus Deep Brain Stimulation in Parkinson's Disease: Valuable Programming Insights from Anecdotal Observations.

In this article, we use a case to illustrate and discuss some practically important learning points about programming subthalamic nucleus deep brain stimulation for Parkinson's disease patients and highlight clinically relevant issues resulting from anatomical and device-related anomalies. These include the phenomenon of a dominant subthalamic nucleus, clinical variability with delayed response to stimulation, equivalence of electrical charge when using short-pulse settings, and issues regarding conversion of settings between constant-current and constant-voltage devices that are increasingly common with the use of device components from multiple manufacturers.

Short Versus Conventional Pulse-Width Deep Brain Stimulation in Parkinson's Disease: A Randomized Crossover Comparison.

BACKGROUND: Subthalamic nucleus deep brain stimulation (STN-DBS) is an effective therapy for selected Parkinson's disease patients with motor fluctuations, but can adversely affect speech and axial symptoms. The use of short pulse width (PW) has been shown to expand the therapeutic window acutely, but its utility in reducing side effects in chronic STN-DBS patients has not been evaluated. OBJECTIVE: To compare the effect of short PW settings using 30-µs with conventional 60-µs settings on stimulation-induced dysarthria in Parkinson's disease patients with previously implanted STN-DBS systems. METHODS: In this single-center, double-blind, randomized crossover trial, we assigned 16 Parkinson's disease patients who had been on STN-DBS for a mean of 6.5 years and exhibited moderate dysarthria to 30-µs or 60-µs settings for 4 weeks followed by the alternative PW setting for a further 4 weeks. The primary outcome was difference in dysarthric speech measured by the Sentence Intelligibility Test between study baseline and the 2 PW conditions. Secondary outcomes included motor, nonmotor, and quality of life measures. RESULTS: There was no difference in the Sentence Intelligibility Test scores between baseline and the 2 treatment conditions (P = 0.25). There were also no differences noted in motor, nonmotor, or quality of life scores. The 30-µs settings were well tolerated, and adverse event rates were similar to those at conventional PW settings. Post hoc analysis indicated that patients with dysarthria and a shorter duration of DBS may be improved by short PW stimulation. CONCLUSIONS: Short PW settings using 30 µs did not alter dysarthric speech in chronic STN-DBS patients. A future study should evaluate whether patients with shorter duration of DBS may be helped by short PW settings. © 2019 International Parkinson and Movement Disorder Society.

Globus pallidal deep brain stimulation for Tourette syndrome: Effects on cognitive function.

INTRODUCTION: In a double-blind randomized crossover trial, we previously established that bilateral deep brain stimulation of the anteromedial globus pallidus internus (GPiam-DBS) is effective in significantly reducing tic severity in patients with refractory Tourette syndrome (TS). Here, we report the effects of bilateral GPiam-DBS on cognitive function in 11 of the 13 patients who had participated in our double-blind cross-over trial of GPi-DBS. METHODS: Patients were assessed at baseline (4 weeks prior to surgery) and at the end of each of the three-month blinded periods, with stimulation either ON or OFF. The patients were evaluated on tests of memory (California Verbal Learning Test-II (CVLT-II); Corsi blocks; Short Recognition Memory for Faces), executive function (D-KEFS Stroop color-word interference, verbal fluency, Trail-making test, Hayling Sentence Completion test), and attention (Paced Auditory Serial Addition Test, Numbers and Letters Test). RESULTS: GPiam-DBS did not produce any significant change in global cognition. Relative to pre-operative baseline assessment verbal episodic memory on the CVLT-II and set-shifting on the Trail-making Test were improved with DBS OFF. Performance on the cognitive tests were not different with DBS ON versus DBS OFF. GPiam-DBS did not alter aspects of cognition that are impaired in TS such as inhibition on the Stroop interference task or the Hayling Sentence Completion test. CONCLUSIONS: This study extends previous findings providing data showing that GPiam-DBS does not adversely affect cognitive domains such as memory, executive function, verbal fluency, attention, psychomotor speed, and information processing. These results indicate that GPiam-DBS does not produce any cognitive deficits in TS.

The Effect of Short Pulse Width Settings on the Therapeutic Window in Subthalamic Nucleus Deep Brain Stimulation for Parkinson's disease.

BACKGROUND: Subthalamic nucleus deep brain stimulation (STN-DBS) is an established treatment for selected Parkinson's disease (PD) patients, but therapy is often limited by side effects. Previous studies indicate an inverse relationship of the therapeutic window (TW) to pulse width (PW) settings down to 60µs, but there is limited data available on the effect of shorter PWs. OBJECTIVE: To define the TW of STN-DBS in PD at PW of 30µs (PW30) relative to standard PW settings at 60µs (PW60), and to compare speed of gait and speech intelligibility on the two PW conditions. METHODS: Monopolar review data of 15 consecutive PD patients who had screening of contacts performed at PW60 and PW30 was used to calculate the TW at each contact. We compared the TWs of the most efficacious contact per STN, and a secondary analysis was performed comparing all contacts. Speed of gait with a timed 10 metre walk test, speech intelligibility, and perceptual characteristics of speech were also compared at the efficacy thresholds for PW60 and PW30. RESULTS: The TW was significantly greater at PW30 [3.8±1.6mA] than at PW60 [1.7±1.1mA]. In the secondary analysis, 110 TWs could be calculated and these remained significantly higher at PW30. The timed 10 metre walk at PW30 was faster than at PW60, and perceptual rating scores of speech were significantly improved at PW30. CONCLUSIONS: STN-DBS in PD patients using a PW of 30µs significantly increases the TW compared to standard PW settings, and this effect is consistent across all contacts of an electrode. Speed of gait and perceptual speech scores are also improved at 30µs settings.

Connectivity derived thalamic segmentation in deep brain stimulation for tremor.

The ventral intermediate nucleus (VIM) of the thalamus is an established surgical target for stereotactic ablation and deep brain stimulation (DBS) in the treatment of tremor in Parkinson's disease (PD) and essential tremor (ET). It is centrally placed on a cerebello-thalamo-cortical network connecting the primary motor cortex, to the dentate nucleus of the contralateral cerebellum through the dentato-rubro-thalamic tract (DRT). The VIM is not readily visible on conventional MR imaging, so identifying the surgical target traditionally involved indirect targeting that relies on atlas-defined coordinates. Unfortunately, this approach does not fully account for individual variability and requires surgery to be performed with the patient awake to allow for intraoperative targeting confirmation. The aim of this study is to identify the VIM and the DRT using probabilistic tractography in patients that will undergo thalamic DBS for tremor. Four male patients with tremor dominant PD and five patients (three female) with ET underwent high angular resolution diffusion imaging (HARDI) (128 diffusion directions, 1.5 mm isotropic voxels and b value = 1500) preoperatively. Patients received VIM-DBS using an MR image guided and MR image verified approach with indirect targeting. Postoperatively, using parallel Graphical Processing Unit (GPU) processing, thalamic areas with the highest diffusion connectivity to the primary motor area (M1), supplementary motor area (SMA), primary sensory area (S1) and contralateral dentate nucleus were identified. Additionally, volume of tissue activation (VTA) corresponding to active DBS contacts were modelled. Response to treatment was defined as 40% reduction in the total Fahn-Tolosa-Martin Tremor Rating Score (FTMTRS) with DBS-ON, one year from surgery. Three out of nine patients had a suboptimal, long-term response to treatment. The segmented thalamic areas corresponded well to anatomically known counterparts in the ventrolateral (VL) and ventroposterior (VP) thalamus. The dentate-thalamic area, lay within the M1-thalamic area in a ventral and lateral location. Streamlines corresponding to the DRT connected M1 to the contralateral dentate nucleus via the dentate-thalamic area, clearly crossing the midline in the mesencephalon. Good response was seen when the active contact VTA was in the thalamic area with highest connectivity to the contralateral dentate nucleus. Non-responders had active contact VTAs outside the dentate-thalamic area. We conclude that probabilistic tractography techniques can be used to segment the VL and VP thalamus based on cortical and cerebellar connectivity. The thalamic area, best representing the VIM, is connected to the contralateral dentate cerebellar nucleus. Connectivity based segmentation of the VIM can be achieved in individual patients in a clinically feasible timescale, using HARDI and high performance computing with parallel GPU processing. This same technique can map out the DRT tract with clear mesencephalic crossing.

Subthalamic Nucleus Deep Brain Stimulation in Parkinson's Disease: The Effect of Varying Stimulation Parameters.

Subthalamic Nucleus Deep Brain Stimulation (STN DBS) is a well-established and effective treatment modality for selected patients with Parkinson's disease (PD). Since its advent, systematic exploration of the effect of stimulation parameters including the stimulation intensity, frequency, and pulse width have been carried out to establish optimal therapeutic ranges. This review examines published data on these stimulation parameters in terms of efficacy of treatment and adverse effects. Altering stimulation intensity is the mainstay of titration in DBS programming via alterations in voltage or current settings, and is characterised by a lower efficacy threshold and a higher side effect threshold which define the therapeutic window. In addition, much work has been done in exploring the effects of frequency modulation, which may help patients with gait freezing and other axial symptoms. However, there is a paucity of data on the use of ultra-short pulse width settings which are now possible with technological advances. We also discuss current evidence for the use of novel programming techniques including directional and adaptive stimulation, and highlight areas for future research.

Motor neurone disease in the greater Wellington region: an observational study.

AIMS: This study investigated the demographic and disease characteristics of motor neurone disease (MND), as well as specific aspects of healthcare provision for MND patients in the greater Wellington region. METHODS: Data was collected from clinical records of all known patients with a diagnosis of Motor Neurone Disease MND in the Capital and Coast and Hutt Valley district health board catchment zones over a 12-month period. Survival data was collected at 2-year follow-up. RESULTS: The study population consisted of 40 patients. The mean age at diagnosis was 66.2 years (SD of 13.2). Thirty patients (75%) were New Zealand European. Predominantly limb signs were present in 12 (30%), and 11 (27.5%) had bulbar signs, while 14 (35%) had a mixed pattern and a further 3 (7.5%) had respiratory muscle weakness. At 2-year follow-up, the median survival time following symptom onset in the 32 deceased patients was 29 months (range 6-126 months). CONCLUSIONS: The demographics and disease characteristics of MND in this cohort of patients from the Wellington region is similar to those found in overseas studies. The majority of patients received care in accordance with established guidelines, although certain aspects of healthcare delivery could be further improved.

Pulmonary arteriovenous malformation: a rare anterior mediastinal mass.

Pulmonary arteriovenous malformations are rare pulmonary vascular lesions which are associated with Osler Weber Rendu syndrome (hereditary haemorrhagic telangectasia). They act as right-to-left shunts and have cardiovascular and embolic complications. We present a patient with an apparent anterior mediastinal mass secondary to a pulmonary arteriovenous malformations which was successfully treated percutaneously.

In sight, in mind: retailer compliance with legislation on limiting retail tobacco displays.

We investigated retailer compliance with point-of-sale display legislation, using a New Zealand region as a case study. An observational survey was conducted of nonspecialist tobacco retailers in the lower North Island of New Zealand during 2006. Compliance was assessed in relation to store type (dairies, convenience stores, supermarkets, and service stations) and by characteristics of the population of the census area unit in which the store was situated. These characteristics include the level of socioeconomic deprivation and proportions of Maori (indigenous New Zealanders), Pacific Islanders, and children aged less than 19 years. Out of the 288 stores surveyed, 185 (64%) had at least one breach of the point-of-sale regulations. The most common breaches were a failure to display a "Smoking Kills" sign, visibility of tobacco from outside the premises, and displaying tobacco less than 1 m from children's products. Compliance was significantly worse in dairies (small local general stores) and convenience stores. Stores situated in areas in the top quartile for the proportion of children were much more likely to have high levels of noncompliance (> or =3 breaches) and to display tobacco products close to children's products. This study is one of very few to systematically investigate retailer compliance with point-of-sale display regulations for tobacco products. The results suggest that the implementation of legislation to partly limit retail displays of tobacco products can be difficult. A ban on retail displays of tobacco products is likely to be a more effective and enforceable policy.