Tag: Deep Brain Stimulation

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The accuracy of 3D fluoroscopy (XT) vs computed tomography (CT) registration in deep brain stimulation (DBS) surgery

Acta Neurochirurgica (2020) 162:1871–1878

Stereotactic registration is the most critical step ensuring accuracy in deep brain stimulation (DBS) surgery. 3D fluoroscopy (XT) is emerging as an alternative to CT. XT has been shown to be safe and effective for intraoperative confirmation of lead position following implantation. However, there is a lack of studies evaluating the suitability ofXT to be used for themore crucial step of registration and its capability of being merged to a preoperative MRI. This is the first study comparing accuracy, efficiency, and radiation exposure of XT- vs CT-based stereotactic registration and XT/MRI merging in deep brain stimulation.

Methods Mean absolute differences and Euclidean distance between planned (adjusted for intraoperative testing) and actual lead trajectories were calculated for accuracy of implantation. The radiation dose from each scan was recorded as the dose length product (DLP). Efficiency was measured as the time between the patient entering the operating room and the initial skin incision. A one-way ANOVA compared these parameters between patients that had either CT- or XT-based registration.

Results Forty-one patients underwent DBS surgery—25 in the CT group and 16 in the XT group. The mean absolute difference between CT and XTwas not statistically significant in the x (p = 0.331), y (p = 0.951), or z (p = 0.807) directions. The Euclidean distance between patient groups did not differ significantly (p = 0.874). The average radiation exposure with XT (220.0 ± 0.1 mGy*cm) was significantly lower than CT (1269.3 ± 112.9 mGy*cm) (p < 0.001). There was no significant difference in registration time between CT (107.8 ± 23.1 min) and XT (106.0 ± 18.2 min) (p = 0.518).

Conclusion XT-based frame registration was shown to result in similar implantation accuracy and significantly less radiation exposure compared with CT. Our results surprisingly showed no significant difference in registration time, but this may be due to a learning curve effect.

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Postmortem Dissections of Common Targets for Lesion and Deep Brain Stimulation Surgeries

Neurosurgery 86:860–872, 2020

The subthalamic nucleus (STN), globus pallidus internus (GPi), and pedunculopontine nucleus (PPN) are effective targets for deep brain stimulation (DBS) in many pathological conditions. Previous literature has focused on appropriate stimulation targets and their relationships with functional neuroanatomic pathways; however, comprehensive anatomic dissections illustrating these nuclei and their connections are lacking. This information will provide insight into the anatomic basis of stimulation-induced DBS benefits and side effects.

OBJECTIVE: To combine advanced cadaveric dissection techniques and ultrahigh field magnetic resonance imaging (MRI) to explore the anatomy of the STN, GPi, and PPN with their associated fiber pathways.

METHODS: A total of 10 cadaveric human brains and 2 hemispheres of a cadaveric head were examined using fiber dissection techniques. The anatomic dissections were compared with 11.1 Tesla (T) structural MRI and 4.7 T MRI fiber tractography.

RESULTS: The extensive connections of the STN (caudate nucleus, putamen, medial frontal cortex, substantia innominata, substantia nigra, PPN, globus pallidus externus (GPe), GPi, olfactory tubercle, hypothalamus, and mammillary body) were demonstrated. The connections of GPi to the thalamus, substantia nigra, STN, amygdala, putamen, PPN, and GPe were also illustrated. The PPN was shown to connect to the STN and GPi anteriorly, to the cerebellum inferiorly, and to the substantia nigra anteriorly and superiorly.

CONCLUSION: This study demonstrates connections using combined anatomic microdissections, ultrahigh field MRI, and MRI tractography. The anatomic findings are analyzed in relation to various stimulation-induced clinical effects. Precise knowledge of neuroanatomy, anatomic relationships, and fiber connections of the STN, GPi, PPN will likely enable more effective targeting and improved DBS outcomes.

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Tractography-Guided Deep Brain Stimulation of the Anteromedial Globus Pallidus Internus for Refractory Obsessive-Compulsive Disorder

Neurosurgery 86:E558–E563, 2020

Obsessive-compulsive disorder (OCD) is a disabling psychiatric disorder, mainly treated with psychotherapy and pharmacotherapy. Surgical intervention may be appropriate for patients with treatment-refractory OCD. Deep brain stimulation (DBS) is an alternative for previously common ablative surgical procedures. Tractography has been proposed as a method for individualizing DBS treatment and may have the potential to improve efficacy.

CLINICAL PRESENTATION: We present a patient with treatment-refractory OCD previously treated with bilateral leucotomies, who underwent DBS surgery with targeting informed by tractography. Preoperative tractography to identify suitable DBS targets was undertaken. Structural images were also utilized for standard stereotactic surgical planning. The anteromedial globus pallidus internus (amGPi) was chosen as the target bilaterally after consideration of white matter projections to frontal cortical regions and neurosurgical approach. Bilateral amGPi DBS surgery was undertaken without adverse events. At 16-mo follow-up, there was a 48.5% reduction in OCD symptom severity as measured by the Yale-Brown Obsessive Compulsive Scale.

CONCLUSION: The amGPi can be a successful DBS target for OCD. This is the first known case to report on DBS surgery postleucotomies for OCD and highlights the utility of tractography for surgical planning in OCD.

 

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The dentato-rubro-thalamic tract as the potential common deep brain stimulation target for tremor of various origin

Acta Neurochirurgica (2020) 162: 1053–1066

Deep brain stimulation alleviates tremor of various origins. The dentato-rubro-thalamic tract (DRT) has been suspected as a common tremor-reducing structure. Statistical evidence has not been obtained. We here report the results of an uncontrolled case series of patients with refractory tremor who underwent deep brain stimulation under tractographic assistance.

Methods A total of 36 patients were enrolled (essential tremor (17), Parkinson’s tremor (8), multiple sclerosis (7), dystonic head tremor (3), tardive dystonia (1)) and received 62 DBS electrodes (26 bilateral; 10 unilateral). Preoperatively, diffusion tensor magnetic resonance imaging sequences were acquired together with high-resolution anatomical T1Wand T2W sequences. The DRTwas individually tracked and used as a direct thalamic or subthalamic target. Intraoperative tremor reduction was graded on a 4-point scale (0 = no tremor reduction to 3 = full tremor control) and recorded together with the current amplitude, respectively. Stimulation point coordinates were recorded and compared to DRT. The relation of the current amplitude needed to reduce tremor was expressed as TiCR (tremor improvement per current ratio).

Results Stimulation points of 241 were available for analysis. A total of 68 trajectories were tested (62 dB leads, 1.1 trajectories tested per implanted lead). Tremor improvement was significantly decreasing (p < 0.01) if the distance to both the border and the center of the DRT was increasing. On the initial trajectory, 56 leads (90.3%) were finally placed. Long-term outcomes were not part of this analysis.

Discussion Tremor of various origins was acutely alleviated at different points along the DRT fiber tract (above and below the MCP plane) despite different tremor diseases. DRT is potentially a common tremor-reducing structure. Individual targeting helps to reduce brain penetrating tracts. TiCR characterizes stimulation efficacy and might help to identify an optimal stimulation point.

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The striking effects of deep cerebellar stimulation on generalized fixed dystonia

J Neurosurg 132:712–716, 2020

Cerebellar neuromodulation could influence the pathological abnormalities of movement disorders through several connections between the cerebellum and the basal ganglia or other cortices. In the present report, the authors demonstrate the effects of cerebellar deep brain stimulation (DBS) on a patient with severe generalized fixed dystonia (FD) that was refractory to bilateral pallidotomy and intrathecal baclofen therapy.

A previously healthy 16-year-old girl presented with generalized FD. Bilateral pallidotomy and intrathecal baclofen therapy had failed to resolve her condition, following which she received DBS through the bilateral superior cerebellar peduncle (SCP) and dentate nucleus (DN). Ipsilateral stimulation of the SCP or DN improved the FD, and the ability of DBS administered via the SCP to relax muscles was better than that of DN DBS.

A considerable improvement of generalized FD, from a bedridden state to a wheelchairbound state, was observed in the patient following 6 months of chronic bilateral DBS via the SCP; moreover, the patient was able to move her arms and legs. The findings in the present case suggest that neuromodulation of deep cerebellar structures is a promising treatment for FD that is refractory to conventional treatments.

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Deep brain stimulation of the globus pallidus internus versus the subthalamic nucleus in isolated dystonia

J Neurosurg 132:721–732, 2020

Surgical procedures involving deep brain stimulation (DBS) of the globus pallidus internus (GPi) or subthalamic nucleus (STN) are well-established treatments for isolated dystonia. However, selection of the best stimulation target remains a matter of debate. The authors’ objective was to compare the effectiveness of DBS of the GPi and the STN in patients with isolated dystonia.

METHODS In this matched retrospective cohort study, the authors searched an institutional database for data on all patients with isolated dystonia who had undergone bilateral implantation of DBS electrodes in either the GPi or STN in the period from January 30, 2014, to June 30, 2017. Standardized assessments of dystonia and health-related quality of life using the Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) and SF-36 were conducted before and at 1, 6, and 12 months after surgery. No patients were lost to the 6-month follow-up; 5 patients were lost to the 12-month follow-up.

RESULTS Both GPi (14 patients) and STN (16 patients) stimulation produced significant improvement in dystonia and quality of life in all 30 patients found in the database search. At the 1-month follow-up, however, the percentage improvement in the BFMDRS total movement score was significantly (p = 0.01) larger after STN DBS (64%) than after GPi DBS (48%). At the 12-month follow-up, the percentage improvement in the axis subscore was significantly (p = 0.03) larger after GPi DBS (93%) than after STN DBS (83%). Also, the total amount of electrical energy delivered was significantly (p = 0.008) lower with STN DBS than with GPi DBS (124 ± 52 vs 192 ± 65 mJ, respectively).

CONCLUSIONS The GPi and STN are both effective targets in alleviating dystonia and improving quality of life. However, GPi stimulation may be better for patients with axial symptoms. Moreover, STN stimulation may produce a larger clinical response within 1 month after surgery and may have a potential economic advantage in terms of lower battery consumption.

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3-Tesla MRI of deep brain stimulation patients: safety assessment of coils and pulse sequences

J Neurosurg 132:586–594, 2020

Physicians are more frequently encountering patients who are treated with deep brain stimulation (DBS), yet many MRI centers do not routinely perform MRI in this population. This warrants a safety assessment to improve DBS patients’ accessibility to MRI, thereby improving their care while simultaneously providing a new tool for neuromodulation research.

METHODS A phantom simulating a patient with a DBS neuromodulation device (DBS lead model 3387 and IPG Activa PC model 37601) was constructed and used. Temperature changes at the most ventral DBS electrode contacts, implantable pulse generator (IPG) voltages, specific absorption rate (SAR), and B1+rms were recorded during 3-T MRI scanning. Safety data were acquired with a transmit body multi-array receive and quadrature transmit-receive head coil during various pulse sequences, using numerous DBS configurations from “the worst” to “the most common.” In addition, 3-T MRI scanning (T1 and fMRI) was performed on 41 patients with fully internalized and active DBS using a quadrature transmit-receive head coil. MR images, neurological examination findings, and stability of the IPG impedances were assessed.

RESULTS In the phantom study, temperature rises at the DBS electrodes were less than 2°C for both coils during 3D SPGR, EPI, DTI, and SWI. Sequences with intense radiofrequency pulses such as T2-weighted sequences may cause higher heating (due to their higher SAR). The IPG did not power off and kept a constant firing rate, and its average voltage output was unchanged. The 41 DBS patients underwent 3-T MRI with no adverse event.

CONCLUSIONS Under the experimental conditions used in this study, 3-T MRI scanning of DBS patients with selected pulse sequences appears to be safe. Generally, T2-weighted sequences (using routine protocols) should be avoided in DBS patients. Complementary 3-T MRI phantom safety data suggest that imaging conditions that are less restrictive than those used in the patients in this study, such as using transmit body multi-array receive coils, may also be safe. Given the interplay between the implanted DBS neuromodulation device and the MRI system, these findings are specific to the experimental conditions in this study.

 

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Somatosensory functional MRI tractography for individualized targeting of deep brain stimulation in patients with chronic pain after brachial plexus injury

Acta Neurochirurgica (2019) 161:2485–2490

The optimal targets for deep brain stimulation (DBS) in patients with refractory chronic pain are not clearly defined. We applied sensory functional MRI (fMRI)- and diffusion tensor imaging (DTI)-based DBS in chronic pain patients into 3 different targets to ascertain the most beneficial individual stimulation site.

Methods Three patients with incapacitating chronic pain underwent DBS into 3 targets (periventricular gray (PVG), ventroposterolateral thalamus (VPL), and posterior limb of the internal capsule according to fMRI and DTI (PLIC). The electrodes were externalized and double-blinded tested for several days. Finally, the two electrodes with the best pain reduction were kept for permanent stimulation. The patients were then followed up for 12 months. Outcome measures comprised the numerical rating scale (NRS), short-form McGill’s score (SF-MPQ), and health-related quality of life (SF-36).

Results Continuous pain (mean NRS 6.6) was reduced to NRS 3.6 after 12 months. Only with stimulation of the PLIC pain attacks, that occurred at least 3 times a week (mean NRS 9.6) resolved in 2 patients and improved in one patient concerning both intensity (NRS 5) and frequency (twice a month). The mean SF-MPQ decreased from 92.7 to 50. The health-related quality of life improved considerably.

Conclusion fMRI- and DTI-based DBS to the PLIC was the only target with a significant effect on pain attacks and seems to be the most promising target in chronic pain patients after brachial plexus injury. The combination with PVG or VPL can further improve patients’ outcome especially in terms of reducing the continuous pain.

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Role of Biomarkers in Adaptive Modulation of Clinical Brain Stimulation

Neurosurgery, Volume 85, Issue 3, September 2019:  E430–E439

Therapeutic brain stimulation has proven efficacious for treatment of nervous system diseases, exerting widespread influence via disease-specific neural networks. Activation or suppression of neural networks could theoretically be assessed by either clinical symptom modification (ie, tremor, rigidity, seizures) or development of specific biomarkers linked to treatment of symptomatic disease states.

For example, biomarkers indicative of disease state could aid improved intraoperative localization of electrode position, optimize device efficacy or efficiency through dynamic control, and eventually serve to guide automatic adjustment of stimulation settings.

Biomarkers to control either extracranial or intracranial stimulation span from continuous physiological brain activity, intermittent pathological activity, and triggered local phenomena or potentials, to wearable devices, blood flow, biochemical or cardiac signals, temperature perturbations, optical or magnetic resonance imaging changes, or optogenetic signals.

The goal of this review is to update new approaches to implement control of stimulation through relevant biomarkers. Critical questions include whether adaptive systems adjusted through biomarkers can optimize efficiency and eventually efficacy, serve as inputs for stimulation adjustment, and consequently broaden our fundamental understanding of abnormal neural networks in pathologic states.

Neurosurgeons are at the forefront of translating and developing biomarkers embedded within improved brain stimulation systems. Thus, criteria for developing and validating biomarkers for clinical use are important for the adaptation of device approaches into clinical practice.

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Machine learning—aided personalized DTI tractographic planning for deep brain stimulation of the superolateral medial forebrain bundle using HAMLET

Acta Neurochirurgica (2019) 161:1559–1569

Growing interest exists for superolateral medial forebrain bundle (slMFB) deep brain stimulation (DBS) in psychiatric disorders. The surgical approach warrants tractographic rendition. Commercial stereotactic planning systems use deterministic tractography which suffers from inherent limitations, is dependent on manual interaction (ROI definition), and has to be regarded as subjective. We aimed to develop an objective but patient-specific tracking of the slMFB which at the same time allows the use of a commercial surgical planning system in the context of deep brain stimulation.

Methods The HAMLET (Hierarchical Harmonic Filters for Learning Tracts from Diffusion MRI) machine learning approach was introduced into the standardized workflow of slMFB DBS tractographic planning on the basis of patientspecific dMRI. Rendition of the slMFB with HAMLET serves as an objective comparison for the refinement of the deterministic tracking procedure. Our application focuses on the tractographic planning of DBS (N = 8) for major depression and OCD.

Results Previous results have shown that only fibers belonging to the ventral tegmental area to prefrontal/orbitofrontal axis should be targeted. With the proposed technique, the deterministic tracking approach, that serves as the surgical planning data, can be refined, over-sprouting fibers are eliminated, bundle thickness is reduced in the target region, and thereby probably a more accurate targeting is facilitated. The HAMLET-driven method is meant to achieve a more objective surgical fiber display of the slMFB with deterministic tractography.

Conclusions The approach allows overlying the results of patient-specific planning from two different approaches (manual deterministic and machine learningHAMLET). HAMLET shows the slMFB as a volume and thus serves as an objective tracking corridor. It helps to refine results from deterministic tracking in the surgical workspace without interfering with any part of the standard software solution. We have now included this workflow in our daily clinical experimental work on slMFB DBS for psychiatric indications.

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Dorsal anterior cingulate cortex (ACC) deep brain stimulation (DBS): a promising surgical option for the treatment of refractory thalamic pain syndrome (TPS)

Acta Neurochirurgica (2019) 161:1579–1588

Neuroimaging evidences and previous successful case series of cingulotomy for cancer pain have disclosed the key- role of the dorsal anterior cingulate cortex (ACC) in the generation of the empathic and affective dimension of pain. The aim of this study is to assess the effectiveness and safety of ACC neuromodulation for the treatment of the thalamic pain syndrome (TPS), a chronic neuropathic disease often complicated by severe affective and emotional distress in the long term.

Method From January 2015 to April 2017, 5 patients with pure drug-refractory TPS underwent ACC deep brain stimulation (DBS) at our institution. Quantitative assessment of pain and health-related quality of life were performed 1 day before surgery and postoperatively at 6 and 18 months by using the numeric rating scale (NRS), the 36-item short-form health survey (SF-36), and the McGill pain and the EuroQol5-domain questionnaires.

Results Mean age at surgery was 56.2 years (range, 47–66). NRS score improved by 37.9% at 6 months (range, − 22.2 to − 80%) and by 35% at 18 months (range, − 11.1 to − 80%). At the last follow-up, one patient reported a relevant pain reduction (NRS 2), only complaining of mild pain poorly interfering with activities of daily living. Concomitant improvements in the McGill and EuroQol5-domain pain questionnaires, SF-36 total and sub-item scores were also noticed at each follow-up. No surgical or stimulation-related complications occurred during the study period.

Conclusions ACC DBS may be a safe and promising surgical option to alleviate discomfort and improve the overall quality of life in a patient affected by drug-resistant TPS. Further prospective, larger, and randomized studies are needed to validate these findings.

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Surgical management of camptocormia in Parkinson’s disease: systematic review and meta-analysis

J Neurosurg 131:368–375, 2019

Camptocormia is a potentially debilitating condition in the progression of Parkinson’s disease (PD). It is described as an abnormal forward flexion while standing that resolves when lying supine. Although the condition is relatively common, the underlying pathophysiology and optimal treatment strategy are unclear. In this study, the authors systematically reviewed the current surgical management strategies for camptocormia.

METHODS PubMed was queried for primary studies involving surgical intervention for camptocormia in PD patients. Studies were excluded if they described nonsurgical interventions, provided only descriptive data, or were case reports. Secondarily, data from studies describing deep brain stimulation (DBS) to the subthalamic nuclei were extracted for potential meta-analysis. Variables showing correlation to improvement in sagittal plane bending angle (i.e., the vertical angle caused by excessive kyphosis) were subjected to formal meta-analysis.

RESULTS The query resulted in 9 studies detailing treatment of camptocormia: 1 study described repetitive trans-spinal magnetic stimulation (rTSMS), 7 studies described DBS, and 1 study described deformity surgery. Five studies were included for meta-analysis. The total number of patients was 66. The percentage of patients with over 50% decrease in sagittal plane imbalance with DBS was 36.4%. A duration of camptocormia of 2 years or less was predictive of better outcomes (OR 4.15).

CONCLUSIONS Surgical options include transient, external spinal stimulation; DBS targeting the subthalamic nuclei; and spinal deformity surgery. Benefit from DBS stimulation was inconsistent. Spine surgery corrected spinal imbalance but was associated with a high complication rate.

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Stimulation of the Anterior nuclei of Thalamus for Epilepsy

Neurosurgical Review (2019) 42:287–296

Despite the use of first-choice anti-epileptic drugs and satisfactory seizure outcome rates after resective epilepsy surgery, a considerable percentage of patients do not become seizure free. ANT-DBS may provide for an alternative treatment option in these patients. This literature review discusses the rationale, mechanism of action, clinical efficacy, safety, and tolerability of ANT-DBS in drug-resistant epilepsy patients.

A review using systematic methods of the available literature was performed using relevant databases including Medline, Embase, and the Cochrane Library pertaining to the different aspects ANT-DBS. ANTDBS for drug-resistant epilepsy is a safe, effective and well-tolerated therapy, where a special emphasis must be given to monitoring and neuropsychological assessment of both depression and memory function.

Three patterns of seizure control by ANT-DBS are recognized, of which a delayed stimulation effect may account for an improved long-term response rate. ANTDBS remotely modulates neuronal network excitability through overriding pathological electrical activity, decrease neuronal cell loss, through immune response inhibition or modulation of neuronal energy metabolism. ANT-DBS is an efficacious treatment modality, even when curative procedures or lesser invasive neuromodulative techniques failed. When compared to VNS, ANTDBS shows slightly superior treatment response, which urges for direct comparative trials. Based on the available evidence ANTDBS and VNS therapies are currently both superior compared to non-invasive neuromodulation techniques such as t-VNS and rTMS. Additional in-vivo research is necessary in order to gain more insight into the mechanism of action of ANT-DBS in localization-related epilepsy which will allow for treatment optimization.

Randomized clinical studies in search of the optimal target in well-defined epilepsy patient populations, will ultimately allow for optimal patient stratification when applying DBS for drug-resistant patients with epilepsy.

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Deep brain stimulation for dementias

Neurosurg Focus 45 (2):E8, 2018

The aim of this article is to review the authors’ and published experience with deep brain stimulation (DBS) therapy for the treatment of patients with Alzheimer’s disease (AD) and Parkinson’s disease dementia (PDD).

METHODS Two targets are current topics of investigation in the treatment of AD and PDD, the fornix and the nucleus basalis of Meynert. The authors reviewed the current published clinical experience with attention to patient selection, biological rationale of therapy, anatomical targeting, and clinical results and adverse events.

RESULTS A total of 7 clinical studies treating 57 AD patients and 7 PDD patients have been reported. Serious adverse events were reported in 6 (9%) patients; none resulted in death or disability. Most studies were case reports or Phase 1/2 investigations and were not designed to assess treatment efficacy. Isolated patient experiences demonstrating improved clinical response after DBS have been reported, but no significant or consistent cognitive benefits associated with DBS treatment could be identified across larger patient populations.

CONCLUSIONS PDD and AD are complex clinical entities, with investigation of DBS intervention still in an early phase. Recently published studies demonstrate acceptable surgical safety. For future studies to have adequate power to detect meaningful clinical changes, further refinement is needed in patient selection, metrics of clinical response, and optimal stimulation parameters.

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Congress of Neurological Surgeons Systematic Review and Evidence-Based Guideline on Subthalamic Nucleus and Globus Pallidus Internus Deep Brain Stimulation for the Treatment of Patients With Parkinson’s Disease

Neurosurgery 82:753–756, 2018

QUESTION 1: Is bilateral subthalamic nucleus deep brain stimulation (STN DBS) more, less, or as effective as bilateral globus pallidus internus deep brain stimulation (GPi DBS) in treating motor symptoms of Parkinson’s disease, as measured by improvements in Unified Parkinson’s Disease Rating Scale, part III (UPDRS-III) scores?

RECOMMENDATION: Given that bilateral STN DBS is at least as effective as bilateral GPi DBS in treating motor symptoms of Parkinson’s disease (as measured by improvements in UPDRS-III scores), consideration can be given to the selection of either target in patients undergoing surgery to treat motor symptoms. (Level I)

QUESTION 2: Is bilateral STN DBS more, less, or as effective as bilateral GPi DBS in allowing reduction of dopaminergic medication in Parkinson’s disease?

RECOMMENDATION: When the main goal of surgery is reduction of dopaminergic medications in a patient with Parkinson’s disease, then bilateral STN DBS should be performed instead of GPi DBS. (Level I)

QUESTION 3: Is bilateral STN DBSmore, less, or as effective as bilateral GPi DBS in treating dyskinesias associated with Parkinson’s disease?

RECOMMENDATION: There is insufficient evidence to make a generalizable recommendation regarding the target selection for reduction of dyskinesias. However, when the reduction of medication is not anticipated and there is a goal to reduce the severity of “on” medication dyskinesias, the GPi should be targeted. (Level I)

QUESTION 4: Is bilateral STN DBS more, less, or as effective as bilateral GPi DBS in improving quality of life measures in Parkinson’s disease?

RECOMMENDATION:When considering improvements in quality of life in a patient undergoing DBS for Parkinson’s disease, there is no basis to recommend bilateral DBS in 1 target over the other. (Level I) QUESTION 5: Is bilateral STN DBS associated with greater, lesser, or a similar impact on neurocognitive function than bilateral GPi DBS in Parkinson disease?

RECOMMENDATION: If there is significant concern about cognitive decline, particularly in regards to processing speed and working memory in a patient undergoing DBS, then the clinician should consider using GPi DBS rather than STN DBS, while taking into consideration other goals of surgery. (Level I)

QUESTION 6: Is bilateral STN DBS associated with a higher, lower, or similar risk of mood disturbance than GPi DBS in Parkinson’s disease?

RECOMMENDATION: If there is significant concern about the risk of depression in a patient undergoing DBS, then the clinician should consider using pallidal rather than STN stimulation, while taking into consideration other goals of surgery. (Level I)

QUESTION 7: Is bilateral STN DBS associated with a higher, lower, or similar risk of adverse events compared to GPi DBS in Parkinson’s disease?

RECOMMENDATION: There is insufficient evidence to recommend bilateral DBS in 1 target over the other in order to minimize the risk of surgical adverse events.

The full guideline can be found at: https://www.cns.org/guidelines/deep-brainstimulation- parkinsons-disease.

 

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Deep brain stimulation for Parkinson’s disease: meta-analysis of results of randomized trials at varying lengths of follow-up

J Neurosurg 128:1199–1213, 2018

Deep brain stimulation (DBS) is effective in the management of patients with advanced Parkinson’s disease (PD). While both the globus pallidus pars interna (GPi) and the subthalamic nucleus (STN) are accepted targets, their relative efficacy in randomized controlled trials (RCTs) has not been established beyond 12 months. The objective of this study was to conduct a meta-analysis of RCTs to compare outcomes among adults with PD undergoing DBS of GPi or STN at various time points, including 36 months of follow-up.

METHODS The MEDLINE, Embase, CENTRAL, Web of Science, and CINAHL databases were searched. Registries for clinical trials, selected conference proceedings, and the table of contents for selected journals were also searched. Screens were conducted independently and in duplicate. Among the 623 studies initially identified (615 through database search, 7 through manual review of bibliographies, and 1 through a repeat screen of literature prior to submission), 19 underwent full-text review; 13 of these were included in the quantitative meta-analysis. Data were extracted independently and in duplicate. The Cochrane Collaboration tool was used to assess the risk of bias. The GRADE evidence profile tool was used to assess the quality of the evidence. Motor scores, medication dosage reduction, activities of daily living, depression, dyskinesias, and adverse events were compared. The influence of disease duration (a priori) and the proportion of male patients within a study (post hoc) were explored as potential subgroups.

RESULTS Thirteen studies (6 original cohorts) were identified. No difference in motor scores or activities of daily living was identified at 36 months. Medications were significantly reduced with STN stimulation (5 studies, weighted mean difference [WMD] -365.46, 95% CI -599.48 to -131.44, p = 0.002). Beck Depression Inventory scores were significantly better with GPi stimulation (3 studies; WMD 2.53, 95% CI 0.99–4.06 p = 0.001). The motor benefits of GPi and STN DBS for PD are similar.

CONCLUSIONS The motor benefits achieved with GPi and STN DBS for PD are similar. DBS of STN allows for a greater reduction of medication, but not as significant an advantage as DBS of GPi with respect to mood. This difference is sustained at 36 months. Further long-term studies are necessary.

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Deep brain stimulation for the early treatment of the minimally conscious state and vegetative state

J Neurosurg 128:1189–1198, 2018

An effective treatment of patients in a minimally conscious state (MCS) or vegetative state (VS) caused by hypoxic encephalopathy or traumatic brain injury (TBI) is not yet available. Deep brain stimulation (DBS) of the thalamic reticular nuclei has been attempted as a therapeutic procedure mainly in patients with TBI. The purpose of this study was to investigate the therapeutic use of DBS for patients in VS or MCS.

METHODS Fourteen of 49 patients in VS or MCS qualified for inclusion in this study and underwent DBS. Of these 14 patients, 4 were in MCS and 10 were in VS. The etiology of VS or MCS was TBI in 4 cases and hypoxic encephalopathy due to cardiac arrest in 10. The selection criteria for DBS, evaluating the status of the cerebral cortex and thalamocortical reticular formation, included: neurological evaluation, electrophysiological evaluation, and the results of positron emission tomography (PET) and MRI examinations. The target for DBS was the centromedian-parafascicular (CM-pf) complex. The duration of follow-up ranged from 38 to 60 months.

RESULTS Two MCS patients regained consciousness and regained their ability to walk, speak fluently, and live independently. One MCS patient reached the level of consciousness, but was still in a wheelchair at the time the article was written. One VS patient (who had suffered a cerebral ischemic lesion) improved to the level of consciousness and currently responds to simple commands. Three VS patients died of respiratory infection, sepsis, or cerebrovascular insult (1 of each). The other 7 patients remained without substantial improvement of consciousness.

CONCLUSIONS Spontaneous recovery from MCS/VS to the level of consciousness with no or minimal need for assistance in everyday life is very rare. Therefore, if a patient in VS or MCS fulfills the selection criteria (presence of somatosensory evoked potentials from upper extremities, motor and brainstem auditory evoked potentials, with cerebral glucose metabolism affected not more than the level of hypometabolism, which is judged using PET), DBS could be a treatment option.

 

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DBS for Tourette syndrome: a single-center series

J Neurosurg 128:596–604, 2018

Tourette syndrome (TS) is a complex neuropsychiatric disorder characterized by multiple motor and phonic tics. While pharmacological and behavioral therapy can be effective in most patients, a subset of patients remains refractory to treatment. Increasing clinical evidence from multiple centers suggests that deep brain stimulation (DBS) of the medial thalamus can be effective in many cases of refractory TS.

METHODS The authors retrospectively reviewed outcomes in 13 patients with refractory TS who underwent medial thalamic DBS performed by their team over a 7-year period. Patients were evaluated by a multidisciplinary team, and preoperative objective assessments were performed using the Yale Global Tic Severity Scale (YGTSS) and Yale-Brown Obsessive Compulsive Scale. YGTSS scores were calculated at visits immediately postoperatively and at the most recent follow-up in patients with a minimum of 6 months of postoperative follow-up. Coordinates of the active DBS contacts were calculated and projected onto each patient’s pre- and postoperative images.

RESULTS Patients showed an average decrease of 37% (p = 0.0063) in the total tic severity at their first postoperative visit. At their latest visit, their scores achieved significance, decreasing from preoperative scores by an average of 50% (p = 0.0014). The average position of the active contact was noted to be at the junction of the posterior ventralis oralis internus/ centromedian-parafascicular nuclei. Device-related complications occurred in 2 patients, necessitating additional surgeries. All patients continued to use the system at last follow-up.

CONCLUSIONS The authors’ data are consistent with the small but growing body of literature supporting DBS of the ventralis oralis internus/centromedian-parafascicular thalamus as an effective and relatively safe treatment for severe, refractory TS.

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Asleep Robot-Assisted Surgery for the Implantation of Subthalamic Electrodes Provides the Same Clinical Improvement and Therapeutic Window as Awake Surgery

OBJECTIVE: To study the impact of not performing awake clinical evaluation during the robot-assisted implantation of subthalamic nucleus deep brain stimulation (STN-DBS) electrodes on the stimulation parameters and clinical outcomes in patients with Parkinson disease (PD).

METHODS: A total of 23 patients with PD underwent robot-assisted surgery for the bilateral implantation of STN-DBS electrodes. Thirteen patients received general anesthesia (GA) and a limited intraoperative evaluation (side effects only), and the other 10 patients received local anesthesia (LA) and a full evaluation. The primary endpoint was the therapeutic window (TW), defined as the difference between the mean voltage threshold for motor improvement and the mean voltage threshold for side effects in the active contacts at 12 months after surgery. Motor scores were measured as well.

RESULTS: The TW was similar in the LA and GA groups, with mean  standard deviation values of 2.06  0.53 V and 2.28  0.99 V, respectively (P [ 0.32). In the short term, the Unified Parkinson Disease Rating Scale (UPDRS) III score in the “off-drug, on-stim” condition fell to a similar extent in the LA and GA groups (by 40.3% and 49%, respectively; P [ 0.336), as did the UPDRS III score in the “on-stim, ondrug” condition (by 57% and 70.7%, respectively; P [ 0.36).

CONCLUSIONS: Asleep, robot-assisted implantation of STN-DBS electrodes (with accurate identification of the STN and positioning of the DBS lead) produced the same motor results and TW as awake surgery.

 

 

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Exploring the brain through posterior hypothalamus surgery for aggressive behavior

Neurosurg Focus 43 (3):E14, 2017

Neurological surgery offers an opportunity to study brain functions, through either resection or implanted neuromodulation devices. Pathological aggressive behavior in patients with intellectual disability is a frequent condition that is difficult to treat using either supportive care or pharmacological therapy.

The bulk of the laboratory studies performed throughout the 19th century enabled the formulation of hypotheses on brain circuits involved in the generation of emotions.

Aggressive behavior was also studied extensively. Lesional radiofrequency surgery of the posterior hypothalamus, which peaked in the 1970s, was shown to be an effective therapy in many reported series. As with other surgical procedures for the treatment of psychiatric disorders, however, this therapy was abandoned for many reasons, including the risk of its misuse.

Deep brain stimulation (DBS) offers the possibility of treating neurological and psychoaffective disorders through relatively reversible and adaptable therapy. Deep brain stimulation of the posterior hypothalamus was proposed and performed successfully in 2005 as a treatment for aggressive behavior. Other groups reported positive outcomes using target and parameter settings similar to those of the original study. Both the lesional and DBS approaches enabled researchers to explore the role of the posterior hypothalamus (or posterior hypothalamic area) in the autonomic and emotional systems.

 

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