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Background: Subthalamic deep brain stimulation (STN-DBS) is a well-established therapy to treat Parkinson's disease (PD). However, the STN-DBS sub-target remains debated. Recently, a white matter tract termed the hyperdirect pathway (HDP), directly connecting the motor cortex to STN, has gained interest as HDP stimulation is hypothesized to drive DBS therapeutic effects. Previously, we have investigated EEG-based evoked potentials (EPs) to better understand the neuroanatomical origins of the DBS clinical effect. We found a 3-ms peak (P3) relating to clinical benefit, and a 10-ms peak (P10) suggesting nigral side effects. Here, we aimed to investigate the neuroanatomical origins of DBS EPs using probabilistic mapping., Methods: EPs were recorded using EEG whilst low-frequency stimulation was delivered at all DBS-contacts individually. Next, EPs were mapped onto the patients' individual space and then transformed to MNI standard space. Using voxel-wise and fiber-wise probabilistic mapping, we determined hotspots/hottracts and coldspots/coldtracts for P3 and P10. Topography analysis was also performed to determine the spatial distribution of the DBS EPs., Results: In all 13 patients (18 hemispheres), voxel- and fiber-wise probabilistic mapping resulted in a P3-hotspot/hottract centered on the posterodorsomedial STN border indicative of HDP stimulation, while the P10-hotspot/hottract covered large parts of the substantia nigra., Conclusion: This study investigated EP-based probabilistic mapping in PD patients during STN-DBS, revealing a P3-hotspot/hottract in line with HDP stimulation and P10-hotspot/hottract related to nigral stimulation. Results from this study provide key evidence for an electrophysiological measure of HDP and nigral stimulation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Introduction: Symmetric biphasic pulses have been shown to increase the therapeutic window compared to standard cathodic pulses in ET Vim-DBS patients. Furthermore, three hours of stimulation with biphasic pulses caused less stimulation-induced ataxia compared to cathodic pulses. Therefore, an investigation of the longer-term safety of biphasic pulses is warranted., Methods: Seven ET patients were included in a randomized double-blind, cross-over design of one week home-use of symmetric biphasic stimulation (anodic phase first) versus cathodic stimulation. Amplitude was set in a double-blinded way, at the tremor arrest threshold. The primary outcome was safety assessed by documenting the adverse events. Secondary outcome parameters were stimulation amplitude, tremor (Fahn-Tolosa-Marin Tremor Rating Scale) and ataxia (International Cooperative Ataxia Rating Scale) severity, quality of life (Quality of Life in Essential Tremor Questionnaire) and cognition (Montreal Cognitive Assessment). Three patients continued in the open-label extension phase for 3 months, during which biphasic stimulation-only was further assessed by the same outcome parameters., Results: During the 1 week testing, no adverse effects were reported. To obtain equivalent tremor control, the amplitude of the biphasic pulse was significantly higher compared to that of the cathodic pulse ( p  = 0.003). The other outcome parameters were not significantly different. During the open-label study, one patient used the remote control to increase the amplitude, leading to two falls caused by stimulation-induced ataxia. No other adverse effects occurred., Discussion and Conclusion: In a small cohort, when tested for one week, symmetric biphasic pulses suggest to be safe, but require higher stimulation amplitudes. Further follow-up studies are needed to investigate long-term effects and safety., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The study was partly funded by Boston Scientific., (Copyright © 2024 Boogers, Peeters, Van Bogaert, De Vloo, Vandenberghe, Nuttin and Mc Laughlin.)

Objectives: Guanine nucleotide-binding protein alpha-activating activity polypeptide O (GNAO1) syndrome, a rare congenital monogenetic disorder, is characterized by a neurodevelopmental syndrome and the presence of dystonia. Dystonia can be very pronounced and even lead to a life-threatening status dystonicus. In a small number of pharmaco-refractory cases, deep brain stimulation (DBS) has been attempted to reduce dystonia. In this study, we summarize the current literature on outcome, safety, and outcome predictors of DBS for GNAO1-associated dystonia., Materials and Methods: We conducted a systematic review and meta-analysis on individual patient data. We included 18 studies describing 28 unique patients., Results: The mean age of onset of symptoms was 2.4 years (SD 3.8); 16 of 28 patients were male, and dystonia was nearly always generalized (20/22 patients). Symptoms were present before DBS for a median duration of 19.5 months, although highly variable, occurring between 3 and 168 months. The exact phenotype, genotype, and radiologic abnormalities varied and seemed to be of little importance in terms of DBS outcome. All studies described an improvement in dystonia. Our meta-analysis focused on pallidal DBS and found an absolute and relative improvement in Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) of 32.5 points (37.9%; motor part; p = 0.001) and 5.8 points (21.5%; disability part; p = 0.043) at last follow-up compared with preoperative state; 80% of patients were considered responders (BFMDRS-M reduction by ≥25%). Although worsening over time does occur, an improvement was still observed in patients after >10 years. All reported cases of status dystonicus resolved after DBS surgery. Skin erosion and infection were observed in 18% of patients., Conclusion: Pallidal DBS can be efficacious and safe in GNAO1-associated dystonia., Competing Interests: Conflict of Interest The authors reported no conflict of interest., (Copyright © 2023 International Neuromodulation Society. Published by Elsevier Inc. All rights reserved.)

Introduction: Fetal surgery for open spina bifida (OSB) requires comprehensive preoperative assessment using imaging for appropriate patient selection and to evaluate postoperative efficacy and complications. We explored patient access and conduct of fetal magnetic resonance imaging (MRI) for prenatal assessment of OSB patients eligible for fetal surgery. We compared imaging acquisition and reporting to the International Society of Ultrasound in Obstetrics and Gynecology MRI performance guidelines., Material and Methods: We surveyed access to fetal MRI for OSB in referring fetal medicine units (FMUs) in the UK and Ireland, and two NHS England specialist commissioned fetal surgery centers (FSCs) at University College London Hospital, and University Hospitals KU Leuven Belgium. To study MRI acquisition protocols, we retrospectively analyzed fetal MRI images before and after fetal surgery for OSB., Results: MRI for fetal OSB was accessible with appropriate specialists available to supervise, perform, and report scans. The average time to arrange a fetal MRI appointment from request was 4 ± 3 days (range, 0-10), the average scan time available was 37 ± 16 min (range, 20-80 min), with 15 ± 11 min (range, 0-30 min) extra time to repeat sequences as required. Specific MRI acquisition protocols, and MRI reporting templates were available in only 32% and 18% of units, respectively. Satisfactory T2-weighted (T2W) brain imaging acquired in three orthogonal planes was achieved preoperatively in all centers, and 6 weeks postoperatively in 96% of FSCs and 78% of referring FMUs. However, for T2W spine image acquisition referring FMUs were less able to provide three orthogonal planes presurgery (98% FSC vs. 50% FMU, p < 0.001), and 6 weeks post-surgery (100% FSC vs. 48% FMU, p < 0.001). Other standard imaging recommendations such as T1-weighted (T1W), gradient echo (GE) or echoplanar fetal brain and spine imaging in one or two orthogonal planes were more likely available in FSCs compared to FMUs pre- and post-surgery (p < 0.001)., Conclusions: There was timely access to supervised MRI for OSB fetal surgery assessment. However, the provision of images of the fetal brain and spine in sufficient orthogonal planes, which are required for determining eligibility and to determine the reversal of hindbrain herniation after fetal surgery, were less frequently acquired. Our evidence suggests the need for specific guidance in relation to fetal MRI for OSB. We propose an example guidance for MRI acquisition and reporting., (© 2023 The Authors. Acta Obstetricia et Gynecologica Scandinavica published by John Wiley & Sons Ltd on behalf of Nordic Federation of Societies of Obstetrics and Gynecology (NFOG).)

Background: Preserved cycling capabilities in patients with Parkinson's disease, especially in those with freezing of gait are still poorly understood. Previous research with invasive local field potential recordings in the subthalamic nucleus has shown that cycling causes a stronger suppression of β oscillations compared to walking, which facilitates motor continuation., Methods: We recorded local field potentials from 12 patients with Parkinson's disease (six without freezing of gait, six with freezing of gait) who were bilaterally implanted with deep brain stimulation electrodes in the subthalamic nucleus. We investigated β (13-30 Hz) and high γ (60-100 Hz) power during both active and passive cycling with different cadences and compared patients with and without freezing of gait. The passive cycling experiment, where a motor provided a fixed cadence, allowed us to study the effect of isolated sensory inputs without physical exercise., Results: We found similarly strong suppression of pathological β activity for both active and passive cycling. In contrast, there was stronger high γ band activity for active cycling. Notably, the effects of active and passive cycling were all independent of cadence. Finally, β suppression was stronger for patients with freezing of gait, especially during passive cycling., Conclusions: Our results provide evidence for a link between proprioceptive input during cycling and β suppression. These findings support the role of continuous external sensory input and proprioceptive feedback during rhythmic passive cycling movements and suggest that systematic passive mobilization might hold therapeutic potential. © 2023 International Parkinson and Movement Disorder Society., (© 2023 International Parkinson and Movement Disorder Society.)

Background: To maximize clinical benefit and minimize stimulation-induced side effects, optimising deep brain stimulation (DBS) parameters is paramount. Recent literature suggests a potential benefit of short pulse width DBS (spDBS; ≤40 μs) over conventional pulse width DBS (cDBS; ≥60 μs) in movement disorders., Objective: To compare therapeutic window (TW), therapeutic and side effects and energy consumption of spDBS and cDBS in movement disorders., Methods: We systematically searched Medline, Embase, Cochrane Library and Web of Science. Appropriate paired analyses were performed., Results: Nine Parkinson's disease (PD) (143 patients), 4 essential tremor (ET) (26 patients) and no dystonia studies were included in the meta-analysis. TW defined as therapeutic amplitude range was larger with spDBS vs. cDBS in PD (standardized mean difference (SMD) = -1.04, p < 0.001) and ET (SMD = -0.71, p < 0.001), but the TW in terms of charge per pulse (CPP) did not differ. In PD, no differences were found in therapeutic and side effects (MDS-UPDRS-III, speech and gait, dyskinesia, non-motor symptoms and quality of life). In ET, Fahn-Tolosa-Marin Tremor Rating Scale was lower with spDBS vs. cDBS (SMD = 0.36, p < 0.001). A qualitative analysis suggested fewer stimulation-induced side effects with spDBS. CPP was lower with spDBS vs. cDBS in PD (SMD = 0.79, p < 0.001) and ET (MD = 46.46 nC, p < 0.001), but real-world data on battery longevity are lacking., Conclusion: Although spDBS enlarges the TW as a wider amplitude range in both PD and ET, it does not alter TW defined by CPP. The therapeutic efficacy of spDBS is not different from cDBS in PD, but spDBS apparently induces more tremor reduction in ET., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:SS, TVB, JP, MM and WV have no relevant financial or non-financial interests to disclose. AB received consultancy fees from Abbvie, Abbott and Boston Scientific. BN holds the Chair Neuromodulation an endowment from Medtronic, and Boston Scientific Chair Neuromodulation for Stroke. PDV and TT are both Research Fund Flanders Senior Clinical Investigators and both received an Educational Chair from Medtronic., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction: Symmetric biphasic pulses enlarge the therapeutic window in thalamic deep brain stimulation in patients with essential tremor. Adding an interphase gap to these symmetric biphasic pulses may further affect the therapeutic window., Materials and Methods: Nine patients (16 hemispheres) were included in this study. Biphasic pulses (anodic phase first) with interphase gaps of 0, 10, 20, 50, and 100 μs were tested, in random order. The outcome parameters were the therapeutic threshold (TT) and side-effect threshold (SET), and thus also the therapeutic window (TW)., Results: Increasing interphase gaps lowered both SET and TT (linear mixed-effects model; p < 0.001 and p < 0.001). Because SET decreased predominantly, increasing interphase gaps resulted in smaller TWs (linear mixed-effects model; p < 0.001)., Discussion and Conclusions: Introducing an interphase gap in a symmetric biphasic pulse may lead to less selectivity in fiber or neuronal activation. Our findings show that, in the context of anode-first biphasic pulses, the use of zero-interphase gaps results in the largest TW., Clinical Trial Registration: The Clinicaltrials.gov registration number for the study is NCT05177900., (Copyright © 2022 International Neuromodulation Society. Published by Elsevier Inc. All rights reserved.)

Objective: To determine the medium-term maternal impact of open fetal spina bifida repair., Design: Prospective cohort study., Setting: University Hospitals Leuven, Belgium., Population: Mothers who had open maternal-fetal spina bifida repair between March 2012 and December 2021., Methods: A patient-reported survey on subsequent fertility, pregnancy, and gynaecological and psychological outcomes., Main Outcome Measures: Complications during subsequent pregnancies, and gynaecological and psychological problems., Results: Seventy-two out of 100 invited women completed the questionnaire (72%). Despite being advised not to, seven of 13 women attempting to conceive became pregnant within 2 years after fetal surgery and one woman delivered vaginally. Two of the 16 subsequent pregnancies were complicated by an open neural tube defect. One pregnancy was complicated by a placenta accreta and one pregnancy was complicated by a uterine rupture, both with good neonatal outcomes. Nearly half of respondents who did not attempt to conceive reported that this was because of their experience of the index pregnancy and caring for the index child. Three out of four respondents reported medium-term psychological problems, mostly anxiety for the health of the index child, fear for recurrence in subsequent pregnancies and feelings of guilt., Conclusions: Open maternal-fetal surgery for spina bifida did not appear to affect fertility in our cohort. Half of the attempts to conceive took place within 2 years. One uterine rupture and one placenta accreta occurred in 16 subsequent pregnancies. Most respondents reported psychological problems linked to the index pregnancy, which reinforces the need for long-term psychological support., (© 2023 John Wiley & Sons Ltd.)

Objective: Subthalamic deep brain stimulation (STN-DBS) is a neurosurgical therapy to treat Parkinson's disease (PD). Optimal therapeutic outcomes are not achieved in all patients due to increased DBS technological complexity; programming time constraints; and delayed clinical response of some symptoms. To streamline the programming process, biomarkers could be used to accurately predict the most effective stimulation configuration. Therefore, we investigated if DBS-evoked potentials (EPs) combined with imaging to perform prediction analyses could predict the best contact configuration., Methods: In 10 patients, EPs were recorded in response to stimulation at 10 Hz for 50 s on each DBS-contact. In two patients, we recorded from both hemispheres, resulting in recordings from a total of 12 hemispheres. A monopolar review was performed by stimulating on each contact and measuring the therapeutic window. CT and MRI data were collected. Prediction models were created to assess how well the EPs and imaging could predict the best contact configuration., Results: EPs at 3 ms and at 10 ms were recorded. The prediction models showed that EPs can be combined with imaging data to predict the best contact configuration and hence, significantly outperformed random contact selection during a monopolar review., Conclusion: EPs can predict the best contact configuration. Ultimately, these prediction tools could be implemented into daily practice to ease the DBS programming of PD patients., Competing Interests: JP, TB, and AB’s research were funded by Boston Scientific, VLAIO, and EIT Health. TD received speaker honoraria and travel grants from Boston Scientific and Medtronic, outside of the submitted work. PV is a senior clinical investigator of Research Fund-Flanders (FWO 18B2322N). BN has received grants from Medtronic and Boston Scientific. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2023 Peeters, Van Bogaert, Boogers, Dembek, Gransier, Wouters, Vandenberghe, De Vloo, Nuttin and Mc Laughlin.)

Objectives: To define and grade fetal and maternal adverse events following fetal surgery for spina bifida and to report on the impact of engaging patients in collecting follow-up data., Methods: This prospective single-center audit included 100 consecutive patients undergoing fetal surgery for spina bifida between January 2012 and December 2021. In our setting, patients return to their referring unit for further pregnancy care and delivery. On discharge, referring hospitals were requested to return outcome data. For this audit, we prompted patients and referring hospitals to provide data in cases of missing outcomes. Outcomes were categorized as missing, returned spontaneously or returned following additional request, by the patient and/or referring center. Postoperative maternal and fetal complications until delivery were defined and graded according to Maternal and Fetal Adverse Event Terminology (MFAET) and the Clavien-Dindo classification., Results: There were no maternal deaths, but severe maternal complications occurred in seven women (anemia in pregnancy, postpartum hemorrhage, pulmonary edema, lung atelectasis, urinary tract obstruction and placental abruption). No cases of uterine rupture were reported. Perinatal death occurred in 3% of fetuses and other severe fetal complications in 15% (perioperative fetal bradycardia/cardiac dysfunction, fistula-related oligohydramnios, chorioamnionitis and preterm prelabor rupture of membranes (PPROM) before 32 weeks). PPROM occurred in 42% of patients and, overall, delivery took place at a median gestational age of 35.3 weeks (interquartile range, 34.0-36.6 weeks). Information provided following additional request, from both centers and patients but mainly from the latter, reduced missing data by 21% for gestational age at delivery, 56% for uterine-scar status at birth and 67% for shunt insertion at 12 months. Compared with the generic Clavien-Dindo classification, the MFAET system ranked complications in a more clinically relevant way., Conclusions: The nature and rate of severe complications following fetal surgery for spina bifida were similar to those reported in other large series. Spontaneous return of outcome data by referring centers was low, yet patient empowerment improved data collection. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology., (© 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.)

Objective: Lumbosacral selective dorsal rhizotomy is a neurosurgical treatment option to reduce spasticity in the lower extremities in children with cerebral palsy. Surprisingly, concomitant improvement of spasticity in the upper extremities and functionality of the hands has been sporadically reported postoperatively. In this systematic review, the authors aimed to quantify the postoperative improvement in upper-extremity spasticity and functionality, identify predictors, and discuss underlying mechanisms., Methods: The authors searched the MEDLINE and Embase databases for studies reporting upper-extremity outcomes in cerebral palsy patients after selective dorsal rhizotomy that reported one or more of the following clinical scales: the Ashworth Scale (AS), the Modified AS (MAS), the fine motor skills domain of the Peabody Developmental Motor Scales (PDMS), the Quality of Upper Extremity Skills Test (QUEST), the self-care domain of the Functional Independence Measure for Children (WeeFIM), or the self-care domain of the Pediatric Evaluation of Disability Inventory (PEDI). The authors arbitrarily divided postoperative follow-up into short-term (< 6 months), medium-term (6-24 months), and long-term (> 24 months) follow-up. A 1-point change in MAS score has been reported as clinically significant. To assess bias, the Cochrane Collaboration's tool and ROBINS-I tool were used., Results: The authors included 24 articles describing 752 patients. Spasticity reduction of the upper extremities ranged from 0.30 to 0.55 (AS) and between 0 and 2.9 (MAS) at medium-term follow-up. This large variability may partially be attributed to a floor effect since patients with normal upper-extremity function would not be expected to have further improvement. QUEST improvement ranged from 2.7% to 4.5% at medium-term follow-up. The mean improvements in functional skills of the self-care domain of the PEDI were 4.3 at short-term and 7 at medium-term follow-ups and ranged from 10.8 to 34.7 at long-term follow-up. There are insufficient data to draw meaningful conclusions regarding the PDMS fine motor skills and the WeeFIM self-care domains., Conclusions: The literature suggests that a pronounced postoperative spasticity reduction in the lower extremities and a moderately severe preoperative upper-extremity spasticity may positively predict postoperative reduction in upper-extremity spasticity. There are at least 5 hypotheses that may explain the postoperative reduction in upper-extremity spasticity and functionality: 1) a somatosensory cortex reorganization favoring the hand region over the leg region, 2) a decrease in abnormal electrical transmission throughout the spinal cord, 3) an indirect result of improved posture due to improved truncal and leg stability, 4) an indirect consequence of occupational/physical therapy intensification, and 5) a maturation effect. However, all remain unproven to date.

Background: Subthalamic deep brain stimulation (DBS) is an established therapy to treat Parkinson's disease (PD). To maximize therapeutic outcome, optimal DBS settings must be carefully selected for each patient. Unfortunately, this is not always achieved because of: (1) increased technological complexity of DBS devices, (2) time restraints, or lack of expertise, and (3) delayed therapeutic response of some symptoms. Biomarkers to accurately predict the most effective stimulation settings for each patient could streamline this process and improve DBS outcomes., Objective: To investigate the use of evoked potentials (EPs) to predict clinical outcomes in PD patients with DBS., Methods: In ten patients (12 hemispheres), a monopolar review was performed by systematically stimulating on each DBS contact and measuring the therapeutic window. Standard imaging data were collected. EEG-based EPs were then recorded in response to stimulation at 10 Hz for 50 s on each DBS-contact. Linear mixed models were used to assess how well both EPs and image-derived information predicted the clinical data., Results: Evoked potential peaks at 3 ms (P3) and at 10 ms (P10) were observed in nine and eleven hemispheres, respectively. Clinical data were well predicted using either P3 or P10. A separate model showed that the image-derived information also predicted clinical data with similar accuracy. Combining both EPs and image-derived information in one model yielded the highest predictive value., Conclusion: Evoked potentials can accurately predict clinical DBS responses. Combining EPs with imaging data further improves this prediction. Future refinement of this approach may streamline DBS programming, thereby improving therapeutic outcomes., Clinical Trial Registration: ClinicalTrials.gov, identifier NCT04658641., Competing Interests: The authors declare that this study received funding from Boston Scientific, this funder was involved in the study design, collection and interpretation of the data. TD received speaker honoraria and travel grants from Boston Scientific and Medtronic, outside of the submitted work. PD was a junior clinical investigator of Research Fund-Flanders (FWO). BN has received grants from Medtronic and Boston Scientific. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Peeters, Boogers, Van Bogaert, Dembek, Gransier, Wouters, Vandenberghe, De Vloo, Nuttin and Mc Laughlin.)

More than 30 years have elapsed since it was recognised that folic acid supplementation could substantially reduce the risk of open neural tube defects (ONTDs). During that time, many countries have adopted policies of food fortification with demonstrable reduction in the incidence of both cranial and spinal ONTDs. Improved prenatal detection and termination has also resulted in a reduction in the number of affected live births. Nonetheless, in the USA about 1500 children, and in the UK around 500 children are born each year with myelomeningocele (MMC) and so the management of MMC and its complications continues to constitute a significant clinical workload for many paediatric neurosurgical units around the world.Until recently, the options available following antenatal diagnosis of MMC were termination of pregnancy or postnatal repair. As a result of the MOMS trial, prenatal repair has become an additional option in selected cases (Adzick et al., N Engl J Med 364(11):993-1004, 2011). Fetal surgery for myelomeningocele is now offered in more than 30 centres worldwide. The aim of this chapter is to review the experimental basis of prenatal repair of MMC, to critically evaluate the neurosurgical implications of this intervention and to describe the technique of 'open' repair, comparing this with emerging minimally invasive alternatives., (© 2023. The Author(s), under exclusive license to Springer Nature Switzerland AG.)

Background: Orthostatic tremor is a rare and debilitating movement disorder. Its first-line treatment is pharmacological. For pharmaco-refractory patients, surgical treatment options such as deep brain stimulation (DBS) and spinal cord stimulation (SCS) have been investigated recently., Objectives: We conducted a systematic review of all published outcome and safety data on DBS and SCS for orthostatic tremor patients., Methods: We searched Pubmed and Embase for studies describing orthostatic tremor patients treated with DBS or SCS. We collected all available outcome and safety data and our primary endpoint was the change in unsupported stance duration 1 year postoperatively (±6 months)., Results: We included 15 studies, reporting on 32 orthostatic tremor patients who underwent DBS, 4 patients SCS and 2 both. The ventral intermediate nucleus and the zona incerta were targeted in 25/34 and 9/34 DBS cases, respectively. The median stance time at 1 year follow-up was 240 s compared to 30 s pre-operatively (p < 0.001). Stimulation-induced side effects occurred in the majority of patients, but were often transient. Bilateral stimulation appeared more effective than unilateral and stimulation settings were comparable to thalamic DBS for essential tremor. There were insufficient data available to draw meaningful conclusions on the long-term effects of DBS. Due to insufficient data, no conclusions could be drawn on the effects of SCS on orthostatic tremor., Conclusion: DBS may be effective to increase stance time in orthostatic tremor patients in the first year, but further research is necessary to evaluate the long-term effects and the role of spinal cord stimulation., Competing Interests: Declaration of competing interest Alexine Billet reports no relevant disclosures. Alexandra Boogers received consultancy fees from Abbvie, Abbott and Boston Scientific. Wim Vandenberghe reports no relevant disclosures. Bart Nuttin received grants from Medtronic and Boston Scientific. Tom Theys is Senior Clinical Investigator of FWO Flanders (FWO 1830722N). Tom Theys holds a Medtronic learning chair. Myles Mc Laughlin reports no disclosures relevant to the manuscript. Philippe De Vloo received a grant from the Helaers Foundation., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Purpose: In 2009, Pang described a radical resection technique for congenital lumbosacral lipomas, with lower long-term symptomatic re-tethering rates compared with partial resections and conservative management, and low surgical morbidity. We adopted this technique in 2011, and aim to describe our first results., Methods: In this monocentric retrospective audit, we included dorsal, transitional, chaotic, and caudal-type lumbosacral lipomas. Exclusion criteria were previously operated lipomas, pure filar lipomas, and concomitant major congenital anatomical urogenital/gastrointestinal abnormalities. Neuro-uro-orthopaedic status at presentation and at three months, one year and last postoperative follow-up, intraoperative electrophysiology, and extent of resection were collected., Results: From January 2011 to September 2019, 91 patients were operated (median age 2y2m; 63 transitional; 14 caudal; 8 dorsal; 6 chaotic). Preoperatively, 67% were symptomatic. Preoperative and one-year postoperative rates of impaired ambulation (44% to 43%), hypoesthesia (8% to 5%), urodynamic/uroradiological abnormalities (49% to 37%), and foot/ankle deformities (8% to 5%) were comparable, whilst pain improved (25% to 5%) but catheterisation rates increased (21% to 36%). 23/92 (25%) suffered wound-related complications. 2/91 (2%) developed symptomatic re-tethering requiring second surgery. Mean cord/sac ratio was 0.47. 43% had > 20 mm 3 residual fat, which improved with increasing surgical experience., Conclusion: Radical lipoma resection, guided by intraoperative neuromonitoring, with reconstruction of the neural placode and expansion duraplasty is technically feasible and results in low rates of late deterioration and re-tethering. Lipoma-type and pre-operative status are important outcome predictors. Operative risks are not insignificant. Future studies need to determine appropriate selection criteria for surgery., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Patients with hypermobile Ehlers-Danlos syndrome (hEDS), a heritable connective tissue disorder, present frequently with symptoms of tethered cord syndrome (TCS) but without a low-lying conus. Currently, surgical treatment of such cases is controversial. Because connective tissue disorder affects fibrous structures, we hypothesized that a diseased filum terminale (FT) might cause TCS in hEDS, justifying surgical transection for treatment., Methods: We investigated FT pathology, FT biomechanics, clinical presentation, and outcome following FT excision in 78 radiologically occult hEDS-TCS cases and for comparison in 38 typical TCS cases with low-lying conus and/or fatty FT infiltration but without hEDS., Results: In hEDS-TCS, electron microscopy revealed inherited collagen fibril abnormalities and acquired fibril damage. Biomechanical tension tests revealed elastic properties of the FT in both study groups, but they were impaired in the hEDS TCS. Follow-up examinations at 3 and 12 months after FT excision showed statistically significant improvement of urinary, bowel, and neurologic symptoms in both study groups; intergroup comparison revealed no differences in outcome except more pronounced neurologic improvement in the hEDS-TCS group., Conclusions: Both morphologic findings and biomechanical tests indicate limited elastic properties of the FT in hEDS, which is no more able to dampen but still transmitting spine movement-related stretch forces. That mechanism exposes the conus medullaris to unphysiologic stretch forces, causing TCS, especially when considering the hypermobile spine in hEDS. This notion is supported by the observed clinical improvement following FT resection in hEDS-TCS cases without a low-lying conus., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Since the inception of DBS, cathodic pulses have been used., Objective: To investigate the effect of anodic and symmetric biphasic pulses on the therapeutic window (TW) in essential tremor (ET) patients., Methods: A randomized, doubled-blinded, cross-over design was used to test the effect of cathodic, anodic and symmetric biphasic pulses (cathode-first and anode-first) on the TW in an acute clinical setting. TW was defined as the difference between the minimal stimulation amplitude provoking side effects and minimal stimulation amplitude inducing tremor arrest., Results: 9 ET patients (10 hemispheres) were included. Anodic stimulation induced a significantly larger TW compared to cathodic stimulation (p = 0.008). Symmetric biphasic stimulation also widened the TW compared to cathodic stimulation for both cathode- (p = 0.047) and anode-first (p = 0.008) biphasic pulses. For both anodic and biphasic pulses, the effect on TW was mainly driven by the change in side effect threshold. The order of the phases in the biphasic pulse had a significant effect on the side effect threshold (p = 0.039), with biphasic-anode first having the highest value. All pulse shapes were safe in the acute setting., Conclusion: Anodic and symmetric biphasic pulses increase TW in ET patients., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction: Programmable shunt valve settings can sometimes be difficult to assess using classic read-out tools, warranting a skull X-ray., Research Question: Can we use available head computed tomography (CT) scans to determine the valve settings, in order to obviate the need for additional skull X-rays?, Material and Methods: The valve setting of two different programmable shunts (Codman Certas Plus® and Sophysa Polaris®) were assessed by two blinded observers in 24 patients using 65 head CT scans (slice thickness ≤2 ​mm). Using multi-planar reconstruction (MPR) tools, images were resliced according to the direction of the valve, allowing a direct readout of the valve settings. We validated our CT based method against 32 available skull X-rays., Results: For all CT scans it was possible to assess the valve setting. No interobserver variability was found and there was a 100 ​% concordance between the CT based method and skull X-rays., Discussion: CT based assessment of programmable shunt valve settings is feasible and reliable. It may obviate the need for additional skull x-rays when a head CT scan is available., Conclusions: This technique can reduce radiation exposure and can be applied to historical CT imaging with unknown valve settings., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2021 The Authors.)

Background: Parkinson's disease (PD) is a common neurodegenerative disorder that results in movement-related dysfunction and has variable cognitive impairment. Deep brain stimulation (DBS) of the dorsal subthalamic nucleus (STN) has been shown to be effective in improving motor symptoms; however, cognitive impairment is often unchanged, and in some cases, worsened particularly on tasks of verbal fluency. Traditional DBS strategies use high frequency gamma stimulation for motor symptoms (∼130 Hz), but there is evidence that low frequency theta oscillations (5-12 Hz) are important in cognition., Methods: We tested the effects of stimulation frequency and location on verbal fluency among patients who underwent STN DBS implantation with externalized leads. During baseline cognitive testing, STN field potentials were recorded and the individual patients' peak theta frequency power was identified during each cognitive task. Patients repeated cognitive testing at five different stimulation settings: no stimulation, dorsal contact gamma (130 Hz), ventral contact gamma, dorsal theta (peak baseline theta) and ventral theta (peak baseline theta) frequency stimulation., Results: Acute left dorsal peak theta frequency STN stimulation improves overall verbal fluency compared to no stimulation and to either dorsal or ventral gamma stimulation. Stratifying by type of verbal fluency probes, verbal fluency in episodic categories was improved with dorsal theta stimulation compared to all other conditions, while there were no differences between stimulation conditions in non-episodic probe conditions., Conclusion: Here, we provide evidence that dorsal STN theta stimulation may improve verbal fluency, suggesting a potential possibility of integrating theta stimulation into current DBS paradigms to improve cognitive outcomes., Competing Interests: Declaration of competing interest Dr. De Vloo reports grants from Helaers Foundation. Dr. Fasano reports personal fees and other from Abbott, grants and personal fees from Boston Scientific, personal fees from Brainlab, personal fees from Ceregate, grants, personal fees, non-financial support and other from Medtronic. Dr. Chen reports grants from Canadian Institutes of Health Research, during the conduct of the study; personal fees from Allergan, personal fees from Merz, personal fees from Ipsen. Dr. Kalia reports other support from Medtronic. Dr. Lozano reports other support from Medtronic, other from Abbott, other from Boston Scientific, other from Insightec, other from Functional Neuromodulation, during the conduct of the study., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: To explore the concepts and strategies parents employ when considering maternal-fetal surgery (MFS) as an option for the management of spina bifida (SB) in their fetus, and how this determines the acceptability of the intervention., Methods: A two-centre interview study enrolling parents whose fetuses with SB were eligible for MFS. To assess differences in acceptability, parents opting for MFS (n = 24) were interviewed at three different moments in time: prior to the intervention, directly after the intervention and 3-6 months after birth. Parents opting for termination of pregnancy (n = 5) were interviewed only once. Themes were identified and organised in line with the framework of acceptability., Results: To parents opting for MFS, the intervention was perceived as an opportunity that needed to be taken. Feelings of parental responsibility drove them to do anything in their power to improve their future child's situation. Expectations seemed to be realistic yet were driven by hope for the best outcome. None expressed decisional regret at any stage, despite substantial impact and, at times, disappointing outcomes. For the small group of participants, who decided to opt for termination of pregnancy (TOP), MFS was not perceived as an intervention that substantially could improve the quality of their future child's life., Conclusion: Prospective parents opting for MFS were driven by their feelings of parental responsibility. They recognise the fetus as their future child and value information and care focusing on optimising the child's future health. In the small group of parents opting for TOP, MFS was felt to offer insufficient certainty of substantial improvement in quality of life and the perceived severe impact of SB drove their decision to end the pregnancy., (© 2021 John Wiley & Sons Ltd.)

Central poststroke pain (CPSP) is a debilitating and often treatment-refractory condition that affects numerous stroke patients. The location of lesions most likely to cause pain and the identity of the functional brain networks that they impinge upon remain incompletely understood. We aimed to (1) elucidate which lesion locations are most frequently accompanied by pain; (2) explore CPSP-associated functional networks; and (3) examine how neuromodulation interacts with these networks. This multisite study investigated 17 CPSP patients who received deep brain stimulation (DBS; n = 12) or motor cortex stimulation (MCS; n = 5). Pain-causing lesions were manually segmented and normalized to standard space. To identify areas linked to high risk of pain, the locations of CPSP lesions and 220 control lesions were compared using voxelwise odds ratio mapping. The functional connectivity of pain-causing lesions was obtained using a large (n = 1000) normative resting-state functional MRI connectome and compared to that of control lesions and therapeutic DBS activation volumes. Brain regions most associated with CPSP risk (highest value = 63 times) were located along the ascending somatosensory pathways. These areas and the majority of individual CPSP lesions were functionally connected to anterior/middle cingulate cortex, insula, thalamus, and inferior parietal lobule (PBonferroni < 0.05). The extent of connectivity to the thalamus, inferior parietal lobule, and precuneus also differed between CPSP and control lesions (PBonferroni < 0.05). Posterior insula and thalamus shared connectivity with both CPSP lesions and pain-alleviating DBS activation volumes (PBonferroni < 0.05). These findings further clarify the topography and functional connectivity of pain-causing brain lesions, and provide new insights into the network-level mechanism of CPSP neuromodulation.

Objective : To reveal clinical characteristics of suboptimal responses to deep brain stimulation (DBS) in a multi-country DYT1 dystonia cohort. Methods : In this multi-country multi-center retrospective study, we analyzed the clinical data of DYT1 patients who experienced suboptimal responses to DBS defined as <30% improvement in dystonia scales at the last follow-up compared with baseline. We used a literature-driven historical cohort of 112 DYT1 patients for comparison. Results : Approximately 8% of our study cohort (11 out of 132) experienced suboptimal responses to DBS. Compared with the historical cohort, the multi-country cohort with suboptimal responses had a significantly younger age at onset (mean, 7.0 vs. 8.4 years; p = 0.025) and younger age at DBS (mean, 12.0 vs. 18.6 years; p = 0.019). Additionally, cranial involvement was more common in the multi-country cohort (before DBS, 64% vs. 45%, p = 0.074; before or after DBS, 91% vs. 47%, p = 0.001). Mean motor improvement at the last follow-up from baseline were 0% and 66% for the multi-country and historical cohorts, respectively. All 11 patients of the multi-country cohort had generalization of dystonia within 2.5 years after disease onset. All patients experienced dystonia improvement of >30% postoperatively; however, secondary worsening of dystonia commenced between 6 months and 3 years following DBS. The improvement at the last follow-up was less than 30% despite optimally-placed leads, a trial of multiple programming settings, and additional DBS surgeries in all patients. The on-/off-stimulation comparison at the long-term follow-up demonstrated beneficial effects of DBS despite missing the threshold of 30% improvement over baseline. Conclusion : Approximately 8% of patients represent a more aggressive phenotype of DYT1 dystonia characterized by younger age at onset, faster disease progression, and cranial involvement, which seems to be associated with long-term suboptimal responses to DBS (e.g., secondary worsening). This information could be useful for both clinicians and patients in clinical decision making and patient counseling before and following DBS implantations. Patients with this phenotype may have different neuroplasticity, neurogenetics, or possibly distinct neurophysiology., (Copyright © 2020 Tsuboi, Cif, Coubes, Ostrem, Romero, Miyagi, Lozano, De Vloo, Haq, Meng, Sharma, Ozelius, Wagle Shukla, Cauraugh, Foote and Okun.)

Objective: Selective dorsal rhizotomy (SDR) is effective at permanently reducing spasticity in children with spastic cerebral palsy. The value of intraoperative neurophysiological monitoring in this procedure remains controversial, and its robustness has been questioned. This study describes the authors' institutional electrophysiological technique (based on the technique of Park et al.), intraoperative findings, robustness, value to the procedure, and occurrence of new motor or sphincter deficits., Methods: The authors analyzed electrophysiological data of all children who underwent SDR at their center between September 2013 and February 2019. All patients underwent bilateral SDR through a single-level laminotomy at the conus and with transection of about 60% of the L2-S2 afferent rootlets (guided by intraoperative electrophysiology) and about 50% of L1 afferent roots (nonselectively)., Results: One hundred forty-five patients underwent SDR (64% male, mean age 6 years and 7 months, range 2 years and 9 months to 14 years and 10 months). Dorsal roots were distinguished from ventral roots anatomically and electrophysiologically, by assessing responses on free-running electromyography (EMG) and determining stimulation thresholds (≥ 0.2 mA in all dorsal rootlets). Root level was determined anatomically and electrophysiologically by assessing electromyographic response to stimulation. Median stimulation threshold was lower in sacral compared to lumbar roots (p < 0.001), and 16% higher on the first operated (right) side (p = 0.023), but unrelated to age, sex, or functional status. Similarly, responses to tetanic stimulation were consistent: 87% were graded 3+ or 4+, with similar distributions between sides. This was also unrelated to age, sex, and functional status. The L2-S2 rootlets were divided (median 60%, range 50%-67%), guided by response to tetanic stimulation at threshold amplitude. No new motor or sphincter deficits were observed, suggesting sparing of ventral roots and sphincteric innervation, respectively., Conclusions: This electrophysiological technique appears robust and reproducible, allowing reliable identification of afferent nerve roots, definition of root levels, and guidance for rootlet division. Only a direct comparative study will establish whether intraoperative electrophysiology during SDR minimizes risk of new motor or sphincter worsening and/or maximizes functional outcome.

Objective: Although deep brain stimulation (DBS) is an accepted treatment for childhood dystonia, there is significant heterogeneity in treatment response and few data are available to identify ideal surgical candidates., Methods: Data were derived from a systematic review and individual patient data meta-analysis of DBS for dystonia in children that was previously published. Outcomes were assessed using the Burke-Fahn-Marsden Dystonia Rating Scale for movement (BFMDRS-M) and for disability (BFMDRS-D). The authors used partial least squares, bootstrapping, and permutation statistics to extract patterns of contributions of specific preoperative characteristics to relationship with distinct outcomes, in all patients and in patients with primary and secondary dystonia separately., Results: Of 301 children undergoing DBS for dystonia, 167 had primary dystonia, 125 secondary dystonia, and 9 myoclonus dystonia. Three dissociable preoperative phenotypes (latent variables) were identified and associated with the following: 1) BFMDRS-M at last follow-up; 2) relative change in BFMDRS-M score; and 3) relative change in BFMDRS-D score. The phenotype of patients with secondary dystonia, with a high BFMDRS-M score and truncal involvement, undergoing DBS at a younger age, was associated with a worse postoperative BFMDRS-M score. Children with primary dystonia involving the trunk had greater improvement in BFMDRS-M and -D scores. Those with primary dystonia of shorter duration and proportion of life with disease, undergoing globus pallidus DBS, had greater improvements in BFMDRS-D scores at long-term follow-up., Conclusions: In a comprehensive, data-driven, multivariate analysis of DBS for childhood dystonia, the authors identified novel and dissociable patient phenotypes associated with distinct outcomes. The findings of this report may inform surgical candidacy for DBS.

Background: Stereotaxy is frequently employed in rodent models for precise brain injections or implantations. We intended to map the current practice in rat stereotaxy and list proposals to improve targeting accuracy., Methods: We selected 235 publications on rat stereotaxy from the last 5 years. We collected data on the subjects, targets, coordinate system used, postoperative implant verification and analysis of subjects with off-target implants., Results: Approximately 10,000 rats, mostly Sprague-Dawley and Wistar, were subjected to stereotaxy. Although referenced in 57% of the studies, only 10% of the subjects resembled those used in the Paxinos atlas. Popular procedures were injections (62%) and implantation of cannulas (20%) and electrodes (8%). Right-sided and bilateral targets were more often used than left-sided targets. Bregma served as a stereotaxic origin in 96% of the publications, although for 27% of the targets, the entry was closer to lambda. The Euclidian distance from the target to the interaural line midpoint and to lambda was shorter than to bregma in 38% and 5% of the cases, respectively. Bregma and the dura/brain surface were the most popular dorsoventral References Implantation accuracy was assessed almost exclusively histologically. 39% of the studies did not perform any accuracy check. The number of on-target implants was reported in only 8% of the studies. Only 15% of the publications reported that they excluded subjects with off-target implants., Conclusions: Although well-established, rat stereotaxy could be improved, mainly in acquiring target coordinates, selecting a stereotaxic origin and verifying and reporting accuracy., (Copyright © 2017 Elsevier B.V. All rights reserved.)

There are several different surgical procedures that are used to treat essential tremor (ET), including deep brain stimulation (DBS) and thalamotomy procedures with radiofrequency (RF), radiosurgery (RS) and most recently, focused ultrasound (FUS). Choosing a surgical treatment requires a careful presentation and discussion of the benefits and drawbacks of each. We conducted a literature review to compare the attributes and make an appraisal of these various procedures. DBS was the most commonly reported treatment for ET. One-year tremor reductions ranged from 53% to 63% with unilateral Vim DBS. Similar improvements were demonstrated with RF (range, 74%-90%), RS (range, 48%-63%) and FUS thalamotomy (range, 35%-75%). Overall, bilateral Vim DBS demonstrated more improvement in tremor reduction since both upper extremities were treated (range, 66%-78%). Several studies show continued beneficial effects from DBS up to five years. Long-term follow-up data also support RF and gamma knife radiosurgical thalamotomy treatments. Quality of life measures were similarly improved among patients who received all treatments. Paraesthesias, dysarthria and ataxia were commonly reported adverse effects in all treatment modalities and were more common with bilateral DBS surgery. Many of the neurological complications were transient and resolved after surgery. DBS surgery had the added benefit of programming adjustments to minimise stimulation-related complications. Permanent neurological complications were most commonly reported for RF thalamotomy. Thalamic DBS is an effective, safe treatment with a long history. For patients who are medically unfit or reluctant to undergo DBS, several thalamic lesioning methods have parallel benefits to unilateral DBS surgery. Each of these surgical modalities has its own nuance for treatment and patient selection. These factors should be carefully considered by both neurosurgeons and patients when selecting an appropriate treatment for ET., Competing Interests: Competing interests: PDV has received grants for research from Research Fund Flanders (FWO) and the European Society for Stereotactic and Functional Neurosurgery (ESSFN) and grants for education and travel from the World Society of Stereotactic and Functional Neurosurgery (WSSFN), Medtronic and St. Jude-Abbott. AML is a consultant for Medtronic, Boston Scientific and Insightech. Alfonso Fasano is a consultant for Abbvie, Medtronic, Boston Scientific, Sunovion, Chiesi farmaceutici, UCB, Ipsen., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Several different surgical procedures targeting the limbic circuit have been utilized for severe, treatment resistant obsessive-compulsive disorder; however, there has only been limited exploration of the inferior thalamic peduncle (ITP). The aim of this study was to determine the safety and initial efficacy of ITP deep brain stimulation (DBS) in patients with severe obsessive-compulsive disorder., Methods: Patients with severe, treatment-refractory obsessive-compulsive disorder were enrolled into this open-label phase 1 DBS pilot study. Bilateral ITP DBS devices were implanted between November 2010 and December 2015. The primary outcome was safety. The initial efficacy was determined by Yale-Brown Obsessive-Compulsive scale (YBOCs) scores. Component Y-BOCs scores, Hamilton Depression Severity Scale, Quality of Life Assessment (SF-36), Oxford Happiness Questionnaire, Warwick-Edinburgh Mental Well-Being Scale, and Sheehan Disability Scale were also analyzed for a minimum of 2 years after surgery. Additionally, preoperative and three-month postoperative FDG-PET studies were performed on two patients., Results: Five patients (2 males, 3 females; age range 25-48 years) received ITP DBS. All five patients were considered responders at one year (52% improvement in YBOCs scores compared to baseline (range 39-73%, p < 0.01) and last follow-up (54% improvement; range 38-85%; p < 0.01). At two years follow-up, there were three adverse events that occurred in two patients. One patient had his DBS system removed after one year due to the device becoming the object of his obsession. The other two adverse events were not related to the device. Post-operative FDG-PET imaging in two patients demonstrated decreased glucose uptake within the right caudate, right putamen, right supplementary motor area, and right cingulum and increased glucose uptake in bilateral motor areas, left temporal pole, and left orbitfrontal cortex., Conclusions: ITP DBS has a favorable safety profile and is potentially an efficacious treatment for severe obsessive-compulsive disorder. Larger clinical trials are necessary to determine efficacy., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Objective: Neuronal loss within the cholinergic nucleus basalis of Meynert (nbM) correlates with cognitive decline in dementing disorders such as Alzheimer's disease and Parkinson's disease (PD). In nonhuman primates, the nbM firing pattern (5-40 Hz) has also been correlated with working memory and sustained attention. In this study, authors performed microelectrode recordings of the globus pallidus pars interna (GPi) and the nbM immediately prior to the implantation of bilateral deep brain stimulation (DBS) electrodes in PD patients to treat motor symptoms and cognitive impairment, respectively. Here, the authors evaluate the electrophysiological properties of the nbM in patients with PD., Methods: Five patients (4 male, mean age 66 ± 4 years) with PD and mild cognitive impairment underwent bilateral GPi and nbM DBS lead implantation. Microelectrode recordings were performed through the GPi and nbM along a single trajectory. Firing rates and burst indices were characterized for each neuronal population with the patient at rest and performing a sustained-attention auditory oddball task. Action potential (AP) depolarization and repolarization widths were measured for each neuronal population at rest., Results: In PD patients off medication, the authors identified neuronal discharge rates that were specific to each area populated by GPi cells (92.6 ± 46.1 Hz), border cells (34 ± 21 Hz), and nbM cells (13 ± 10 Hz). During the oddball task, firing rates of nbM cells decreased (2.9 ± 0.9 to 2.0 ± 1.1 Hz, p < 0.05). During baseline recordings, the burst index for nbM cells (1.7 ± 0.6) was significantly greater than those for GPi cells (1.2 ± 0.2, p < 0.05) and border cells (1.1 ± 0.1, p < 0.05). There was no significant difference in the nbM burst index during the oddball task relative to baseline (3.4 ± 1.7, p = 0.20). With the patient at rest, the width of the depolarization phase of APs did not differ among the GPi cells, border cells, and nbM cells (p = 0.60); however, during the repolarization phase, the nbM spikes were significantly longer than those for GPi high-frequency discharge cells (p < 0.05) but not the border cells (p = 0.20)., Conclusions: Neurons along the trajectory through the GPi and nbM have distinct firing patterns. The profile of nbM activity is similar to that observed in nonhuman primates and is altered during a cognitive task associated with cholinergic activation. These findings will serve to identify these targets intraoperatively and form the basis for further research to characterize the role of the nbM in cognition.

Background: Pantothenate kinase-associated neurodegeneration is a rare autosomal-recessive disorder, characterized by progressive neurodegeneration associated with brain iron accumulation. DBS has been trialed to treat related movement disorders, particularly dystonia. The objective of this study was to determine the outcome and safety of DBS for pantothenate kinase-associated neurodegeneration., Methods: We performed a meta-analysis using independent participant data (n = 99) from 38 articles. Primary outcome was change in movement and disability scores of the Burke-Fahn-Marsden Dystonia Rating Scale 1 year postoperatively. Secondary outcomes were response rate and complications., Results: Patients with classic-type (n = 58) and atypical-type (n = 15) pantothenate kinase-associated neurodegeneration were operated on at a median age of 11 and 31 years, respectively (P < 0.001). GPi was primarily targeted (n = 87). Mean dystonia movement score improved 1 year following GPi-DBS (-26%; 95% confidence interval, -37% to -15%), particularly in atypical versus classic cases (-45% vs -16%; P < 0.001). At least 30% improvement was observed in 34% of classic versus 73% of atypical cases (P = 0.04). Higher preoperative score and atypical type predicted larger improvement. GPi-DBS improved dystonia disability score in atypical (-31%; 95% confidence interval, -49% to -13%) but not classic (-5%; 95% confidence interval, -17% to 8%) cases. Prevalence of surgical infections (6%) and hardware failure (7%) was similar to other dystonia etiologies. Two patients died within 3 months. There was insufficient data to describe outcome > 1 year following GPi-DBS or with other DBS targets. Overall, small sample sizes limited generalizability., Conclusions: This meta-analysis provides level 4 evidence that GPi-DBS for pantothenate kinase-associated neurodegeneration may improve dystonia movement scores in classic type and atypical type and disability scores in atypical type 1 year postoperatively. © 2019 International Parkinson and Movement Disorder Society., (© 2019 International Parkinson and Movement Disorder Society.)

Introduction: Dystonia, one of the most common childhood movement disorders, is often medically refractory and can lead to profound impacts on the child and their caretakers' quality of life. Limited efficacy of pharmacological treatments has fueled enthusiasm for innovative neurosurgical approaches, notably deep brain stimulation (DBS) as a treatment for refractory dystonia. Areas covered: DBS is increasingly applied to successfully treat childhood dystonia. While generally safe and effective, results vary widely depending on underlying dystonia etiology. The current work synthesizes and highlights advances in research pertaining to the use of DBS for childhood dystonia. The efficacy of DBS for children and youth with dystonia is discussed, with analysis divided among etiological subtypes. The role of DBS as a lifesaving treatment for status dystonicus is also reviewed. Expert commentary: When carefully selected, certain children and youth with dystonia experience significant symptomatic improvement after DBS. Beyond dystonic symptoms, DBS can improve quality of life and reduce caretaker burden.

Currently, the most common surgical treatment for Parkinson's disease is deep brain stimulation (DBS). This treatment strategy is typically reserved for bradykinesia, rigidity and tremor in patients who no longer respond to medication in a predictable manner or who suffer medication-induced dyskinesias. In addition to DBS, ablative procedures like radiofrequency, radiosurgery and focused ultrasound are also utilized for select tremor symptoms. In this review, we discuss evolving surgical techniques, targets, and emerging technology. In addition, we evaluate potential paradigm shifts in treatment, including gene therapy, immunotherapy and cell transplantation. While these new techniques and treatment options are still in their infancy, advances in Parkinson's disease treatment are rapidly expanding., Competing Interests: AML is the consultant for Medtronic, St Jude, Boston Scientific, and Functional Neuromodulation

Objective: This study describes the design and microfabrication of a foldable thin-film neural implant and investigates its suitability for electrical recording of deep-lying brain cavity walls., Approach: A new type of foldable neural electrode array is presented, which can be inserted through a cannula. The microfabricated electrode is specifically designed for electrical recording of the cavity wall of thalamic lesions resulting from stroke. The proof-of-concept is demonstrated by measurements in rat brain cavities. On implantation, the electrode array unfolds in the brain cavity, contacting the cavity walls and allowing recording at multiple anatomical locations. A three-layer microfabrication process based on UV-lithography and Reactive Ion Etching is described. Electrochemical characterization of the electrode is performed in addition to an in vivo experiment in which the implantation procedure and the unfolding of the electrode are tested and visualized., Main Results: Electrochemical characterization validated the suitability of the electrode for in vivo use. CT imaging confirmed the unfolding of the electrode in the brain cavity and analysis of recorded local field potentials showed the ability to record neural signals of biological origin., Significance: The conducted research confirms that it is possible to record neural activity from the inside wall of brain cavities at various anatomical locations after a single implantation procedure. This opens up possibilities towards research of abnormal brain cavities and the clinical conditions associated with them, such as central post-stroke pain.