Deep Brain Stimulation with Double Targeting of the VIM and PSA for the Treatment of Rare Tremor Syndromes.

INTRODUCTION: In tremor syndromes, pharmacological therapy is the primary treatment, but deep brain stimulation (DBS) is used when it is insufficient. We explore the use of DBS, focusing on the globus pallidus internus for dystonia and the ventral intermediate nucleus (VIM) for tremor conditions. We introduce the posterior subthalamic area (PSA) as a potential target, suggesting its efficacy in tremor reduction, particularly in rare tremor syndromes. We aim to evaluate the efficacy and safety of double targeting the VIM and PSA in rare tremor conditions, highlighting the limited existing data on this. METHODS: Between 2019 and 2023, 22 patients with rare tremor syndromes were treated with bilateral DBS of the VIM and PSA. This case series consisted of 7 isolated head tremor, 1 hepatic encephalopathic tremor due to Abernethy syndrome, 2 voice tremor, 4 dystonic tremor, and 8 Holmes tremor (2 multiple sclerosis, 2 cerebellar insult, and 4 posttraumatic) patients. Patients' preoperative and 12-month postoperative tremor scores were compared, and the optimum VIM and PSA stimulation areas were investigated. RESULTS: There was a significant reduction in the mean TRS score from 3.70 (±0.57) to 0.45 (±0.68) after 12 months of surgery. Specific outcomes for different indications were observed: for head tremor, 6 of 7 patients showed a reduction in TRS scores to 0 points; the vocal tremor patients demonstrated improvement; this change was not statistically significant, which is likely to be due to the low number of patients in this subgroup; the dystonic tremor patients showed either complete tremor abolition or a reduction in TRS scores; the Holmes tremor patients showed an 80% reduction in TRS scores; and the hepatic encephalopathy tremor and Abernethy syndrome patients showed a 75% improvement in TRS scores. The stimulation parameters converged on the VIM and dorsal PSA. Complications included the need for electrode repositioning, infections requiring electrode removal and re-implantation, dysarthria, and stimulation-induced ataxia, which was resolved by adjusting the stimulation parameters. DISCUSSION: The literature on DBS for rare tremors is limited. Double targeting of the VIM and PSA appears to produce promising improvements on the outcomes reported in the existing literature on VIM-only DBS. The proximity of the VIM and PSA allows for flexible electrode placement, contributing to the potential success of the dual-target approach. We also discuss the theoretical advantages of targeting the PSA based on the distribution of tremor circuits, emphasizing the need for further research and electrophysiological studies.

Thirty Years of Global Deep Brain Stimulation: "Plus ça change, plus c'est la même chose"?

BACKGROUND: The advent of deep brain stimulation (DBS) of the subthalamic nucleus (STN) for Parkinson's disease 30 years ago has ushered a global breakthrough of DBS as a universal method for therapy and research in wide areas of neurology and psychiatry. The literature of the last three decades has described numerous concepts and practices of DBS, often branded as novelties or discoveries. However, reading the contemporary publications often elicits a sense of déjà vu in relation to several methods, attributes, and practices of DBS. Here, we review various applications and techniques of the modern-era DBS and compare them with practices of the past. SUMMARY: Compared with modern literature, publications of the old-era functional stereotactic neurosurgery, including old-era DBS, show that from the very beginning multidisciplinarity and teamwork were often prevalent and insisted upon, ethical concerns were recognized, brain circuitries and rational for brain targets were discussed, surgical indications were similar, closed-loop stimulation was attempted, evaluations of surgical results were debated, and controversies were common. Thus, it appears that virtually everything done today in the field of DBS bears resemblance to old-time practices, or has been done before, albeit with partly other tools and techniques. Movement disorders remain the main indications for modern DBS as was the case for lesional surgery and old-era DBS. The novelties today consist of the STN as the dominant target for DBS, the tremendous advances in computerized brain imaging, the sophistication and versatility of implantable DBS hardware, and the large potential for research. KEY MESSAGES: Many aspects of contemporary DBS bear strong resemblance to practices of the past. The dominant clinical indications remain movement disorders with virtually the same brain targets as in the past, with one exception: the STN. Other novel brain targets - that are so far subject to DBS trials - are the pedunculopontine nucleus for gait freezing, the anteromedial internal pallidum for Gilles de la Tourette and the fornix for Alzheimer's disease. The major innovations and novelties compared to the past concern mainly the unmatched level of research activity, its high degree of sponsorship, and the outstanding advances in technology that have enabled multimodal brain imaging and the miniaturization, versatility, and sophistication of implantable hardware. The greatest benefit for patients today, compared to the past, is the higher level of precision and safety of DBS, and of all functional stereotactic neurosurgery.

Long-Term Follow-Up of Unilateral Deep Brain Stimulation Targeting the Caudal Zona Incerta in 13 Patients with Parkinsonian Tremor.

INTRODUCTION: Deep brain stimulation (DBS) is an established treatment for Parkinson's disease (PD) and other movement disorders. The ventral intermediate nucleus of the thalamus is considered as the target of choice for tremor disorders, including tremor-dominant PD not suitable for DBS in the subthalamic nucleus (STN). In the last decade, several studies have shown promising results on tremor from DBS in the posterior subthalamic area (PSA), including the caudal zona incerta (cZi) located posteromedial to the STN. The aim of this study was to evaluate the long-term effect of unilateral cZi/PSA-DBS in patients with tremor-dominant PD. METHODS: Thirteen patients with PD with medically refractory tremor were included. The patients were evaluated using the motor part of the Unified Parkinson Disease Rating Scale (UPDRS) off/on medication before surgery and off/on medication and stimulation 1-2 years (short-term) after surgery and at a minimum of 3 years after surgery (long-term). RESULTS: At short-term follow-up, DBS improved contralateral tremor by 88% in the off-medication state. This improvement persisted after a mean of 62 months. Contralateral bradykinesia was improved by 40% at short-term and 20% at long-term follow-up, and the total UPDRS-III by 33% at short-term and by 22% at long-term follow-up with stimulation alone. CONCLUSIONS: Unilateral cZi/PSA-DBS seems to remain an effective treatment for patients with severe Parkinsonian tremor several years after surgery. There was also a modest improvement on bradykinesia.

Advances in Technical Aspects of Deep Brain Stimulation Surgery.

BACKGROUND: Deep brain stimulation has become an established technology for the treatment of patients with a wide variety of conditions, including movement disorders, psychiatric disorders, epilepsy, and pain. Surgery for implantation of DBS devices has enhanced our understanding of human physiology, which in turn has led to advances in DBS technology. Our group has previously published on these advances, proposed future developments, and examined evolving indications for DBS. SUMMARY: The crucial roles of structural MR imaging pre-, intra-, and post-DBS procedure in target visualization and confirmation of targeting are described, with discussion of new MR sequences and higher field strength MRI enabling direct visualization of brain targets. The incorporation of functional and connectivity imaging in procedural workup and their contribution to anatomical modelling is reviewed. Various tools for targeting and implanting electrodes, including frame-based, frameless, and robot-assisted, are surveyed, and their pros and cons are described. Updates on brain atlases and various software used for planning target coordinates and trajectories are presented. The pros and cons of asleep versus awake surgery are discussed. The role and value of microelectrode recording and local field potentials are described, as well as the role of intraoperative stimulation. Technical aspects of novel electrode designs and implantable pulse generators are presented and compared.

Deep brain stimulation in the ALIC-BNST region targeting the bed nucleus of stria terminalis in patients with obsessive-compulsive disorder: effects on cognition after 12 months.

PURPOSE: The aim of this study was to evaluate cognitive effects 12 months after Deep Brain Stimulation (DBS) of the Bed Nucleus of Stria Terminalis (BNST) in patients with refractory Obsessive-Compulsive Disorder (OCD). METHODS: Eight patients (5 female; mean ± SD age 36 ± 15) with OCD were included. A neuropsychological test battery covering verbal and spatial episodic memory, executive function, and attention was administered preoperatively and 12 months after surgery. Medical records were used as a source for descriptive data to probe for any changes not covered by standardized checklists and the Yale-Brown Obsessive Compulsive Scale (Y-BOCS), the primary outcome measure. RESULTS: At 12 months, seven patients showed response to DBS: three were full responders (i.e., Y-BOCS ≥ 35% improvement), and four were partial responders (Y-BOCS 25-34% improvement). Relative to baseline, there was a slight decline on visuo-spatial learning (p = 0.027), and improved performance on the Color-Word Interference inhibition/switching subtest (p = 0.041), suggesting improvement in cognitive flexibility. CONCLUSIONS: DBS in the BNST for treatment refractory OCD generates very few adverse cognitive effects and improves cognitive flexibility after 12 months of stimulation. The improvement in Y-BOCS and the absence of major cognitive side effects support the BNST as a potential target for DBS in severe OCD.

Deep brain stimulation for Parkinson's disease.

Parkinson's disease (PD) is a progressive neurodegenerative illness with both motor and nonmotor symptoms. Deep brain stimulation (DBS) is an established safe neurosurgical symptomatic therapy for eligible patients with advanced disease in whom medical treatment fails to provide adequate symptom control and good quality of life, or in whom dopaminergic medications induce severe side effects such as dyskinesias. DBS can be tailored to the patient's symptoms and targeted to various nodes along the basal ganglia-thalamus circuitry, which mediates the various symptoms of the illness; DBS in the thalamus is most efficient for tremors, and DBS in the pallidum most efficient for rigidity and dyskinesias, whereas DBS in the subthalamic nucleus (STN) can treat both tremors, akinesia, rigidity and dyskinesias, and allows for decrease in doses of medications even in patients with advanced stages of the disease, which makes it the preferred target for DBS. However, DBS in the STN assumes that the patient is not too old, with no cognitive decline or relevant depression, and does not exhibit severe and medically resistant axial symptoms such as balance and gait disturbances, and falls. Dysarthria is the most common side effect of DBS, regardless of the brain target. DBS has a long-lasting effect on appendicular symptoms, but with progression of disease, nondopaminergic axial features become less responsive to DBS. DBS for PD is highly specialised; to enable adequate selection and follow-up of patients, DBS requires dedicated multidisciplinary teams of movement disorder neurologists, functional neurosurgeons, specialised DBS nurses and neuropsychologists.

Deep brain stimulation for refractory obsessive-compulsive disorder (OCD): emerging or established therapy?

A consensus has yet to emerge whether deep brain stimulation (DBS) for treatment-refractory obsessive-compulsive disorder (OCD) can be considered an established therapy. In 2014, the World Society for Stereotactic and Functional Neurosurgery (WSSFN) published consensus guidelines stating that a therapy becomes established when "at least two blinded randomized controlled clinical trials from two different groups of researchers are published, both reporting an acceptable risk-benefit ratio, at least comparable with other existing therapies. The clinical trials should be on the same brain area for the same psychiatric indication." The authors have now compiled the available evidence to make a clear statement on whether DBS for OCD is established therapy. Two blinded randomized controlled trials have been published, one with level I evidence (Yale-Brown Obsessive Compulsive Scale (Y-BOCS) score improved 37% during stimulation on), the other with level II evidence (25% improvement). A clinical cohort study (N = 70) showed 40% Y-BOCS score improvement during DBS, and a prospective international multi-center study 42% improvement (N = 30). The WSSFN states that electrical stimulation for otherwise treatment refractory OCD using a multipolar electrode implanted in the ventral anterior capsule region (including bed nucleus of stria terminalis and nucleus accumbens) remains investigational. It represents an emerging, but not yet established therapy. A multidisciplinary team involving psychiatrists and neurosurgeons is a prerequisite for such therapy, and the future of surgical treatment of psychiatric patients remains in the realm of the psychiatrist.

Ipsilateral Effects of Unilateral Deep Brain Stimulation for Essential Tremor.

BACKGROUND: Essential tremor (ET) is the most common adult movement disorder. For the relatively large group of patients who do not respond adequately to pharmacological therapy, deep brain stimulation (DBS) is a well-established treatment option. Most ET patients will have bilateral symptoms, and many of them receive bilateral DBS. Unilateral DBS is however still the most common procedure, and some papers suggest an ipsilateral effect in these patients. OBJECTIVES: The aim of this study was to analyze if there is an ipsilateral effect of DBS for ET. METHOD: We retrospectively analyzed our patient cohort with DBS surgery from 1996 to 2017, selecting patients with ET that underwent surgery with unilateral DBS without previous DBS or lesional surgery. A total number of 68 patients (39 males, 29 females) were identified. The patients were evaluated twice: first, at a mean time of 12 months after surgery defined as short-term follow-up and then again at a mean time of 49 months after surgery defined as long-term follow-up, using the clinical rating scale for tremor (CRST). RESULTS: The total CRST score was reduced from mean 49.5 points at baseline before surgery to 20.2 (p < 0.001) at short-term and 28.3 (p < 0.001) at long-term follow-up. Contralateral tremor was reduced from mean 6.1 to 0.4 (p < 0.001) and 1.2 (p < 0.001), respectively. Contralateral hand function was reduced from 11.5 to 2.6 (p < 0.001) and 4.6 (p < 0.001), respectively. Ipsilateral hand function scored 9 at baseline, 8.3 at 1 year, and then again 9.4 at long-term follow-up. Ipsilateral tremor scored 4.0 at baseline, 3.7 at 1 year, and 4.3 at long-term follow-up. Neither ipsilateral hand function nor ipsilateral tremor showed significant difference. CONCLUSIONS: There was no difference in severity of ipsilateral tremor, neither at 1 year nor in the long term. We believe ipsilateral effects of DBS for ET merits limited consideration regarding decision-making or patient counseling before surgery.

Serendipity and Observations in Functional Neurosurgery: From James Parkinson's Stroke to Hamani's & Lozano's Flashbacks.

BACKGROUND: Serendipity and observations have a noble tradition in medicine, including neurology, and are responsible for many medical treatments (carbamazepine for tic douloureux, amantadine for Parkinson's disease, gabapentin for restless legs…). We aimed at examining the contribution of serendipity and observations to functional neurosurgery. Scholarly publications relevant to the history of functional neurosurgery for movement and psychiatric disorders were reviewed, starting from the pre-stereotactic era. The documents were scrutinized with respect to indications for surgery, surgical methods, and brain targets, in view of determining whether serendipitous discoveries and other observations contributed to various functional neurosurgical procedures. SUMMARY: James Parkinson's observation that tremors disappeared in the arm of a person with shaking palsy after a hemiparetic stroke encouraged neurosurgeons in the first half of the 20th century to perform ablative procedures on central motor pathways. Following a lobotomy performed by Browder that extended too far medially in a psychiatric patient with coexisting Parkinson's disease (PD), it was noted that the Parkinsonian signs improved. This encouraged Russel Meyers to carry out open surgery on the caudate nucleus and basal ganglia in PD. Cooper introduced ligation of the anterior choroidal artery as a treatment for PD following a surgical accident during a pedunculotomy. Cooper later started to perform stereotactic surgery on the ventrolateral thalamus following the pathological finding that an intended pallidal lesion had in fact targeted the thalamus. Leksell discovered the ideal location of a pallidal lesion being in the posteroventral area empirically, long before the advent of the basal ganglia model of PD. Modern Deep Brain Stimulation (DBS) that started in the thalamus for tremor was the result of an observation by Benabid that intraoperative high-frequency stimulation during a thalamotomy reduced tremor. Both the discoveries of the anterior limbic subthalamic nucleus as a DBS target for OCD and the medial forebrain bundle as a DBS target for depression occurred by chance. Hamani and Lozano observed memory flashbacks in a patient who was undergoing DBS for obesity, which led to the discovery of the fornix as a potential DBS target for Alzheimer's disease. KEY MESSAGES: In the history of functional neurosurgery, serendipity and observations have resulted in discoveries of several procedures, brain targets for lesioning or DBS as well as new clinical surgical indications. In this era of neuromodulation, this technology should be exquisite in allowing potential serendipitous discoveries, provided that clinicians remain both observant and prepared.

Distribution of electric field in patients with obsessive compulsive disorder treated with deep brain stimulation of the bed nucleus of stria terminalis.

BACKGROUND: Deep brain stimulation (DBS) is being investigated as a treatment for therapy-refractory obsessive compulsive disorder (OCD). Many different brain targets are being trialled. Several of these targets such as the ventral striatum (including the nucleus accumbens (NAc)), the ventral capsule, the inferior thalamic peduncle, and the bed nucleus of stria terminalis (BNST)) belong to the same network, are anatomically very close to one another, or even overlap. Data is still missing on how various stimulation parameters in a given target will affect surrounding anatomical areas and impact the clinical outcome of DBS. METHODS: In a pilot study of eleven participants with DBS of the BNST, we investigate through patient-specific simulation of electric field, which anatomical areas are affected by the electric field, and if this can be related to the clinical results. Our study combined individual patient's stimulation parameters at 12- and 24-month follow-up with image data from the preoperative MRI and postoperative CT. These data were used to calculate the distribution of electric field and create individual anatomical models of the field of stimulation. RESULTS: The individual electric stimulation fields by stimulation in the BNST were similar at both the 12- and 24-month follow-up, involving mainly anterior limb of the internal capsule (ALIC), genu of the internal capsule (IC), BNST, fornix, anteromedial globus pallidus externa (GPe), and the anterior commissure. A statistical significant correlation (p < 0.05) between clinical effect measured by the Yale-Brown Obsessive Compulsive Scale and stimulation was found at the 12-month follow-up in the ventral ALIC and anteromedial GPe. CONCLUSIONS: Many of the targets under investigation for OCD are in anatomical proximity. As seen in our study, off-target effects are overlapping. Therefore, DBS in the region of ALIC, NAc, and BNST may perhaps be considered to be stimulation of the same target.

Deep Brain Stimulation of Caudal Zona Incerta for Parkinson's Disease: One-Year Follow-Up and Electric Field Simulations.

OBJECTIVE: To evaluate the effects of bilateral caudal zona incerta (cZi) deep brain stimulation (DBS) for Parkinson's disease (PD) one year after surgery and to create anatomical improvement maps based on patient-specific simulation of the electric field. MATERIALS AND METHODS: We report the one-year results of bilateral cZi-DBS in 15 patients with PD. Patients were evaluated on/off medication and stimulation using the Unified Parkinson's Disease Rating Scale (UPDRS). Main outcomes were changes in motor symptoms (UPDRS-III) and quality of life according to Parkinson's Disease Questionnaire-39 (PDQ-39). Secondary outcomes included efficacy profile according to sub-items of UPDRS-III and simulation of the electric field distribution around the DBS lead using the finite element method. Simulations from all patients were transformed to one common magnetic resonance imaging template space for the creation of improvement maps and anatomical evaluation. RESULTS: Median UPDRS-III score off medication improved from 40 at baseline to 21 on stimulation at one-year follow-up (48%, p < 0.0005). PDQ-39 summary index did not change, but the subdomain activities of daily living (ADL) and stigma improved (25%, p < 0.03 and 75%, p < 0.01), whereas communication worsened (p < 0.03). For UPDRS-III sub-items, stimulation alone reduced median tremor score by 9 points, akinesia by 3, and rigidity by 2 points at one-year follow-up in comparison to baseline (90%, 25%, and 29%, respectively, p < 0.01). Visual analysis of the anatomical improvement maps based on simulated electrical fields showed no evident relation with the degree of symptom improvement and neither did statistical analysis show any significant correlation. CONCLUSIONS: Bilateral cZi-DBS alleviates motor symptoms, especially tremor, and improves ADL and stigma in PD patients one year after surgery. Improvement maps may be a useful tool for visualizing the spread of the electric field. However, there was no clear-cut relation between anatomical location of the electric field and the degree of symptom relief.

Deep brain stimulation in the caudal zona incerta modulates the sensorimotor cerebello-cerebral circuit in essential tremor.

Essential tremor is effectively treated with deep brain stimulation (DBS), but the neural mechanisms underlying the treatment effect are poorly understood. Essential tremor is driven by a dysfunctional cerebello-thalamo-cerebral circuit resulting in pathological tremor oscillations. DBS is hypothesised to interfere with these oscillations at the stimulated target level, but it is unknown whether the stimulation modulates the activity of the cerebello-thalamo-cerebral circuit during different task states (with and without tremor) in awake essential tremor patients. To address this issue, we used functional MRI in 16 essential tremor patients chronically implanted with DBS in the caudal zona incerta. During scanning, the patients performed unilateral tremor-inducing postural holding and pointing tasks as well as rest, with contralateral stimulation turned On and Off. We show that DBS exerts both task-dependent as well as task-independent modulation of the sensorimotor cerebello-cerebral regions (p â€‹≤ â€‹0.05, FWE cluster-corrected for multiple comparisons). Task-dependent modulation (DBS â€‹× â€‹task interaction) resulted in two patterns of stimulation effects. Firstly, activity decreases (blood oxygen level-dependent signal) during tremor-inducing postural holding in the primary sensorimotor cortex and cerebellar lobule VIII, and activity increases in the supplementary motor area and cerebellar lobule V during rest (p â€‹≤ â€‹0.05, post hoc two-tailed t-test). These effects represent differences at the effector level and may reflect DBS-induced tremor reduction since the primary sensorimotor cortex, cerebellum and supplementary motor area exhibit less motor task-activity as compared to the resting condition during On stimulation. Secondly, task-independent modulation (main effect of DBS) was observed as activity increase in the lateral premotor cortex during all motor tasks, and also during rest (p â€‹≤ â€‹0.05, post hoc two-tailed t-test). This task-independent effect may mediate the therapeutic effects of DBS through the facilitation of the premotor control over the sensorimotor circuit, making it less susceptible to tremor entrainment. Our findings support the notion that DBS in essential tremor is modulating the sensorimotor cerebello-cerebral circuit, distant to the stimulated target, and illustrate the complexity of stimulation mechanisms by demonstrating task-dependent as well as task-independent actions in cerebello-cerebral regions.

Cerebral Impaludation - An Ignoble Procedure between Two Nobel Prizes: Frontal Lobe Lesions before the Introduction of Leucotomy.

During the 20th century, only two persons have been awarded the Nobel Prize for psychiatric discoveries, Julius Wagner-Jauregg in 1927 for the introduction of malaria inoculation in dementia paralytica and Egas Moniz in 1949 for prefrontal leucotomy. According to traditional narrative, Moniz was inspired by a presentation by Carlyle Jacobsen on prefrontal lesions in chimpanzees at a congress in London in 1935. A few months later, he performed the first operations with the help of a young neurosurgeon. These leucotomies were done using injections of a small amount of alcohol into each frontal lobe through a single burr hole on each side of the skull, and the findings from the first 20 patients were published soon after that in 1936. It has, however, been difficult to reconstruct the path leading Moniz to frontal leucotomy, due to his unwillingness to acknowledge contributions from others. Maurice Ducosté, psychiatrist at Villejuif in Paris, France, started his work with psychiatric patients in the early 1920s with mechanical lesions in schizophrenia and continued with injections into the frontal lobes. Later, he focused on general paresis of the insane in neurosyphilis. Here, he introduced injections of malaria-infested blood into the frontal lobes - cerebral impaludation. Injections were used also in schizophrenia, mania, melancholia, and other psychiatric conditions. These injections were up to 5 mL in volume and could be repeated up to 12 times in an individual patient, which must have created significant lesions. Ducosté performed his procedure in hundreds of psychiatric patients before Moniz attempted leucotomy, and his work was presented in several publications before that by Moniz. Moniz basically used the same entry point, target depth, and technique in his first leucotomies. The major difference was that Moniz used alcohol with the clear intent of producing a lesion. Further, Moniz must have been aware of the work of Ducosté, since they presented papers, one after the other, at a meeting of the French Academy of Medicine in 1932. Even so, Moniz never acknowledged any contribution by Ducosté. In my opinion, it would be appropriate to acknowledge the contribution of Maurice Ducosté to the introduction of lobotomy.

Pulse Width and Implantable Pulse Generator Longevity in Pallidal Deep Brain Stimulation for Dystonia: A Population-Based Comparative Effectiveness Study.

INTRODUCTION: A wide range of pulse widths (PWs) has been used in globus pallidus internus (GPi) deep brain stimulation (DBS) for dystonia. However, no specific PW has demonstrated clinical superiority, and the paradigm may differ among DBS centers. OBJECTIVE: To investigate how different paradigms of PWs in GPi DBS for dystonia affect implantable pulse generator (IPG) longevities and energy consumption. METHODS: Thirty-nine patients with dystonia treated with bilateral GPi DBS at 2 Swedish DBS centers from 2005 to 2015 were included. Different PW paradigms were used at the 2 centers, 60-90 µs (short PWs) and 450 µs (long PW), respectively. The frequency of IPG replacements, pulse effective voltage (PEV), IPG model, pre-/postoperative imaging, and clinical outcome based on the clinical global impression (CGI) scale were collected from the medical charts and compared between the 2 groups. RESULTS: The average IPG longevity was extended for the short PWs (1,129 ± 50 days) compared to the long PW (925 ± 32 days; χ2 = 12.31, p = 0.0005, log-rank test). IPG longevity correlated inversely with PEV (Pearson's r = -0.667, p < 0.0001). IPG longevities did not differ between Kinetra® and Activa® PC in the short (p = 0.319) or long PW group (p = 0.858). Electrode distances to the central sensorimotor region of the GPi did not differ between the short or long PW groups (p = 0.595). Pre- and postoperative CGI did not differ between groups. CONCLUSIONS: Short PWs were associated with decreased energy consumption and increased IPG longevity. These effects were not dependent on the IPG model or the anatomic location of the electrodes. PWs did not correlate with symptom severities or clinical outcomes. The results suggest that the use of short PWs might be more energy efficient and could therefore be preferred initially when programming patients with GPi DBS for dystonia.

Deep brain stimulation in the caudal zona incerta versus best medical treatment in patients with Parkinson's disease: a randomised blinded evaluation.

BACKGROUND: Several open-label studies have shown good effect of deep brain stimulation (DBS) in the caudal zona incerta (cZi) on tremor, including parkinsonian tremor, and in some cases also a benefit on akinesia and axial symptoms. The aim of this study was to evaluate objectively the effect of cZi DBS in patients with Parkinson's disease (PD). METHOD: 25 patients with PD were randomised to either cZi DBS or best medical treatment. The primary outcomes were differences between the groups in the motor scores of the Unified Parkinson's Disease Rating Scale (UPDRS-III) rated single-blindly at 6 months and differences in the Parkinson's Disease Questionnaire 39 items (PDQ-39). 19 patients, 10 in the medical arm and 9 in the DBS arm, fulfilled the study. RESULTS: The DBS group had 41% better UPDRS-III scores off-medication on-stimulation compared with baseline, whereas the scores of the non-surgical patients off-medication were unchanged. In the on-medication condition, there were no differences between the groups, neither at baseline nor at 6 months. Subitems of the UPDRS-III showed a robust effect of cZi DBS on tremor. The PDQ-39 domains 'stigma' and 'ADL' improved only in the DBS group. The PDQ-39 summary index improved in both groups. CONCLUSION: This is the first randomised blinded evaluation of cZi DBS showing its efficacy on PD symptoms. The most striking effect was on tremor; however, the doses of dopaminergic medications could not be decreased. cZi DBS in PD may be an addition to existing established targets, enabling tailoring the surgery to the needs of the individual patient.

Unilateral Left Deep Brain Stimulation of the Caudal Zona Incerta Is Equally Effective on Voice Tremor as Bilateral Stimulation: Evidence from 7 Patients with Essential Tremor.

BACKGROUND/AIMS: Deep brain stimulation (DBS) is less effective on voice tremor than arm tremor, and it is generally assumed that successful voice tremor treatment requires bilateral DBS and possibly more precise thalamic stimulation. However, recent findings suggest that these assumptions should be reconsidered. OBJECTIVES: To evaluate whether unilateral DBS targeting the caudal zona incerta (cZi) may be sufficient to alleviate voice tremor in patients with essential tremor, or whether bilateral stimulation is needed. METHODS: Seven patients with voice tremor off stimulation were evaluated during bilateral stimulation using their clinical settings, and during unilateral left stimulation in iterations with increasing stimulation amplitude. Two expert listeners assessed voice tremor severity in all samples in a blinded procedure. RESULTS: Six patients had comparable or better effects with unilateral left stimulation compared to bilateral stimulation. For the seventh patient, unilateral DBS at a slightly higher amplitude achieved similar results as bilateral DBS. Overall, high-amplitude stimulation did not appear to be beneficial on voice tremor. CONCLUSIONS: Unilateral left and bilateral cZi-DBS had comparable effects on voice tremor in the investigated group of 7 patients. This finding suggests that the assumption that bilateral DBS is required to treat voice tremor may need to be reconsidered.

Prediction of Electrode Contacts for Clinically Effective Deep Brain Stimulation in Essential Tremor.

BACKGROUND/AIM: Deep brain stimulation (DBS) is an established neurosurgical treatment that can be used to alleviate symptoms in essential tremor (ET) and other movement disorders. The aim was to develop a method and software tool for the prediction of effective DBS electrode contacts based on probabilistic stimulation maps (PSMs) in patients with ET treated with caudal zona incerta (cZi) DBS. METHODS: A total of 33 patients (37 leads) treated with DBS were evaluated with the Essential Tremor Rating Scale (ETRS) 12 months after surgery. In addition, hand tremor and hand function (ETRS items 5/6 and 11-14) were evaluated for every contact during stimulation with best possible outcome without inducing side effects. Prediction of effective DBS electrode contacts was carried out in a retrospective leave-one-out manner based on PSMs, simulated stimulation fields, and a scoring function. Electrode contacts were ranked according to their likelihood of being included in the clinical setting. Ranked electrode contacts were compared to actual clinical settings. RESULTS: Predictions made by the software tool showed that electrode contacts with rank 1 matched the clinically used contacts in 60% of the cases. Contacts with a rank of 1-2 and 1-3 matched the clinical contacts in 83 and 94% of the cases, respectively. Mean improvement of hand tremor and hand function was 79 ± 21% and 77 ± 22% for the clinically used and the predicted electrode contacts, respectively. CONCLUSIONS: Effective electrode contacts can be predicted based on PSMs in patients treated with cZi DBS for ET. Predictions may in the future be used to reduce the number of clinical assessments that are carried out before a satisfying stimulation setting is defined.

Acute severe depression induced by stimulation of the right globus pallidus internus.

Depressive symptoms may occur after Deep Brain Stimulation (DBS) in the subthalamic nucleus. This is often explained by reduced pharmacological treatment after surgery, and not as a direct effect of DBS. Pallidal DBS seems not to be associated with such side effects and have not, to our knowledge, previously been reported. We present a patient with acute depressive symptoms induced by pallidal DBS. We believe this case strengthen the hypothesis that the basal ganglia and structures involved in the functional connectome of these nucleuses play a role not only in regulation of movement but also in regulation of mood.