Maternal obesity and gestational diabetes reprogram the methylome of offspring beyond birth by inducing epigenetic signatures in metabolic and developmental pathways.

BACKGROUND: Obesity is a negative chronic metabolic health condition that represents an additional risk for the development of multiple pathologies. Epidemiological studies have shown how maternal obesity or gestational diabetes mellitus during pregnancy constitute serious risk factors in relation to the appearance of cardiometabolic diseases in the offspring. Furthermore, epigenetic remodelling may help explain the molecular mechanisms that underlie these epidemiological findings. Thus, in this study we explored the DNA methylation landscape of children born to mothers with obesity and gestational diabetes during their first year of life. METHODS: We used Illumina Infinium MethylationEPIC BeadChip arrays to profile more than 770,000 genome-wide CpG sites in blood samples from a paediatric longitudinal cohort consisting of 26 children born to mothers who suffered from obesity or obesity with gestational diabetes mellitus during pregnancy and 13 healthy controls (measurements taken at 0, 6 and 12 month; total N = 90). We carried out cross-sectional and longitudinal analyses to derive DNA methylation alterations associated with developmental and pathology-related epigenomics. RESULTS: We identified abundant DNA methylation changes during child development from birth to 6 months and, to a lesser extent, up to 12 months of age. Using cross-sectional analyses, we discovered DNA methylation biomarkers maintained across the first year of life that could discriminate children born to mothers who suffered from obesity or obesity with gestational diabetes. Importantly, enrichment analyses suggested that these alterations constitute epigenetic signatures that affect genes and pathways involved in the metabolism of fatty acids, postnatal developmental processes and mitochondrial bioenergetics, such as CPT1B, SLC38A4, SLC35F3 and FN3K. Finally, we observed evidence of an interaction between developmental DNA methylation changes and maternal metabolic condition alterations. CONCLUSIONS: Our observations highlight the first six months of development as being the most crucial for epigenetic remodelling. Furthermore, our results support the existence of systemic intrauterine foetal programming linked to obesity and gestational diabetes that affects the childhood methylome beyond birth, which involves alterations related to metabolic pathways, and which may interact with ordinary postnatal development programmes.

Advances in Technical Aspects of Deep Brain Stimulation Surgery.

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

Mapping autonomic, mood and cognitive effects of hypothalamic region deep brain stimulation.

Because of its involvement in a wide variety of cardiovascular, metabolic and behavioural functions, the hypothalamus constitutes a potential target for neuromodulation in a number of treatment-refractory conditions. The precise neural substrates and circuitry subserving these responses, however, are poorly characterized to date. We sought to retrospectively explore the acute sequelae of hypothalamic region deep brain stimulation and characterize their neuroanatomical correlates. To this end we studied-at multiple international centres-58 patients (mean age: 68.5 ± 7.9 years, 26 females) suffering from mild Alzheimer's disease who underwent stimulation of the fornix region between 2007 and 2019. We catalogued the diverse spectrum of acutely induced clinical responses during electrical stimulation and interrogated their neural substrates using volume of tissue activated modelling, voxel-wise mapping, and supervised machine learning techniques. In total 627 acute clinical responses to stimulation-including tachycardia, hypertension, flushing, sweating, warmth, coldness, nausea, phosphenes, and fear-were recorded and catalogued across patients using standard descriptive methods. The most common manifestations during hypothalamic region stimulation were tachycardia (30.9%) and warmth (24.6%) followed by flushing (9.1%) and hypertension (6.9%). Voxel-wise mapping identified distinct, locally separable clusters for all sequelae that could be mapped to specific hypothalamic and extrahypothalamic grey and white matter structures. K-nearest neighbour classification further validated the clinico-anatomical correlates emphasizing the functional importance of identified neural substrates with area under the receiving operating characteristic curves between 0.67 and 0.91. Overall, we were able to localize acute effects of hypothalamic region stimulation to distinct tracts and nuclei within the hypothalamus and the wider diencephalon providing clinico-anatomical insights that may help to guide future neuromodulation work.

Factors Contributing to Spinal Cord Stimulation Outcomes for Chronic Pain.

OBJECTIVE: Spinal cord stimulation (SCS) has been shown to be a safe and effective therapy for patients with chronic pain. However, some patients do not obtain or maintain adequate pain relief after SCS. The goal of this study was to identify factors that affect patient outcome with regard to SCS. MATERIALS AND METHODS: A retrospective analysis of electronic medical records at a single site was performed. Records for 181 patients who received SCS implants from 2014 through 2016 were collected with follow-up data captured up to August 2019. Patient outcome was measured by device explantation and patient benefit from the SCS. Study parameters included demographic characteristics, history of pain, SCS implant characteristics, and postimplantation events. RESULTS: An earlier diagnosis of radiculopathy was associated with an increased risk of poor benefit (relative risk [RR], 1.81; 95% CI, 1.19-2.74; p = 0.008). Postimplantation falls were associated with an increased risk of poor benefit (RR, 2.17; 95% CI, 1.48-3.17; p = 0.009). Device manufacturer was associated with both patient benefit and explantation. Device 2 was associated with a reduced risk of poor benefit (RR, 0.52; 95% CI, 0.32-0.85; p = 0.009). Device 4 was associated with an increased risk of poor benefit (RR, 1.71; 95% CI, 1.14-2.55; p = 0.02) and increased risk of device explantation (RR, 2.69; 95% CI, 1.2-6.02; p = 0.03). CONCLUSIONS: Patient outcome was associated with diagnosis, postimplantation falls, and device manufacturer. Further investigation is recommended to confirm associations through prospective studies that can more accurately quantify patient outcome over longer periods.

Thalamic Deep Brain Stimulation May Improve Restless Legs Syndrome in Patients With Essential Tremor.

OBJECTIVES: To determine change in restless legs syndrome (RLS) symptoms in essential tremor (ET) patients undergoing bilateral thalamic ventral intermedius (VIM) deep brain stimulation (DBS) surgery. MATERIALS AND METHODS: We retrospectively reviewed our database of ET patients with RLS who had undergone VIM DBS for tremor from 2012 to 2020. We reviewed the patients with available International Restless Leg Syndrome Study Group RLS scale scores before and after DBS. Percentage of responders, defined as proportion of patients experiencing three or more point improvement of RLS scores post-DBS, was calculated. We performed two-tailed t-test of pre-DBS and post-DBS RLS scores. RESULTS: We identified 13 patients with ET and RLS who had undergone bilateral VIM DBS, of whom nine (69%) were responders post-DBS. Five of 13 patients (38%) had complete resolution of RLS post-DBS. For all patients, mean pre-DBS RLS score was 15.8 ± 7.9 which improved by 46% post-DBS to a mean of 8.5 ± 8.8 (p = 0.007). Four patients rated their RLS scale one night with the stimulator OFF and another night with the stimulator ON. The mean RLS score with stimulator ON was 15.5 ± 7.6 which improved by 53% to a mean of 6.25 ± 7.8 (p = 0.008), with two having complete resolution of RLS with stimulator ON. Of the nine responders, six preferred to keep their stimulator ON at night due to relief of RLS and better subjective quality of sleep. CONCLUSIONS: We report for the first time improvement of RLS in patients with ET after bilateral thalamic DBS. Although many ET patients with nonrechargeable DBS systems switch off their stimulator at night to conserve battery life, those with RLS may potentially benefit from keeping their stimulator ON at night to relieve their RLS.

Short-Lasting Unilateral Neuralgiform Headache With Conjunctival Injection and Tearing (SUNCT) Improves With Bilateral Ventral Tegmental Area Deep Brain Stimulation.

BACKGROUND: Short-lasting unilateral neuralgiform headache with conjunctival injection and tearing (SUNCT) is a severe headache disorder characterized by clustered episodes of extreme pain. Refractory to most interventions, ipsilateral unilateral ventral tegmental area (VTA) deep brain stimulation (DBS) has been previously reported to be efficacious in 14 cases. METHODS AND RESULTS: Herein, we report the first case of an individual with medically refractory SUNCT who underwent bilateral VTA DBS. The patient experienced better improvement of his headaches with bilateral stimulation compared to unilateral stimulation. He also had a return of severe headaches within a few hours after his stimulator was switched off during sleep, with rebound worsening of his headaches over several days. The main side effects were double vision and difficulty focusing while reading, which were observed primarily with unipolar stimulation that required high voltages, high frequencies, and multiple negative contacts to control the headaches. The side effects were minimized with bipolar and interleaving stimulation with comparable control of his headaches. CONCLUSION: Bilateral VTA DBS may be effective in alleviating medical refractory SUNCT.

A Multimodal Real-Time Feedback Platform Based on Spoken Interactions for Remote Active Learning Support.

While technology has helped improve process efficiency in several domains, it still has an outstanding debt to education. In this article, we introduce NAIRA, a Multimodal Learning Analytics platform that provides Real-Time Feedback to foster collaborative learning activities' efficiency. NAIRA provides real-time visualizations for students' verbal interactions when working in groups, allowing teachers to perform precise interventions to ensure learning activities' correct execution. We present a case study with 24 undergraduate subjects performing a remote collaborative learning activity based on the Jigsaw learning technique within the COVID-19 pandemic context. The main goals of the study are (1) to qualitatively describe how the teacher used NAIRA's visualizations to perform interventions and (2) to identify quantitative differences in the number and time between students' spoken interactions among two different stages of the activity, one of them supported by NAIRA's visualizations. The case study showed that NAIRA allowed the teacher to monitor and facilitate the learning activity's supervised stage execution, even in a remote learning context, with students working in separate virtual classrooms with their video cameras off. The quantitative comparison of spoken interactions suggests the existence of differences in the distribution between the monitored and unmonitored stages of the activity, with a more homogeneous speaking time distribution in the NAIRA supported stage.

Comparison of Awake and Asleep Deep Brain Stimulation for Parkinson's Disease: A Detailed Analysis Through Literature Review.

OBJECTIVES: Deep brain stimulation (DBS) for Parkinson's disease (PD) has been applied to clinic for approximately 30 years. The goal of this review is to explore the similarities and differences between "awake" and "asleep" DBS techniques. METHODS: A comprehensive literature review was carried out to identify relevant studies and review articles describing applications of "awake" or "asleep" DBS for Parkinson's disease. The surgical procedures, clinical outcomes, costs and complications of each technique were compared in detail through literature review. RESULTS: The surgical procedures of awake and asleep DBS surgeries rely upon different methods for verification of intended target acquisition. The existing research results demonstrated that the stereotactic targeting accuracy of lead placement obtained by either method is reliable. There were no significant differences in clinical outcomes, costs, or complications between the two techniques. CONCLUSION: The surgical and clinical outcomes of asleep DBS for PD are comparable to those of awake DBS.

Accuracy in Deep Brain Stimulation Electrode Placement: A Single-Surgeon Retrospective Analysis of Sterotactic Error in Overlapping and Non-Overlapping Surgical Cases.

BACKGROUND: Many surgeons utilize assistants to perform procedures in more than one operating room at a given time using a practice known as overlapping surgery. Debate has continued as to whether overlapping surgery improves the efficiency and access to care or risks patient safety and outcomes. OBJECTIVE: To examine effects of overlapping surgery in deep brain stimulation (DBS) for movement disorders. METHODS: In this retrospective analysis of overlapping and non-overlapping cases, we evaluated stereotactic accuracy, operative duration, length of hospital stay, and the presence of hemorrhage, wound-related complications, and hardware-related complications requiring revision in adults with movement disorders undergoing DBS. RESULTS: Of 324 cases, 141 (43.5%) were overlapping and 183 (56.5%) non-overlapping. Stereotactic error, number of brain penetrations, and postoperative length of hospitalization did not differ significantly (p ≥ 0.08) between the overlapping and non-overlapping groups. Mean operative duration was significantly longer for overlapping (81/141 [57.4%], 189.5 ± 10.8 min) than for non-overlapping cases (79/183 [43.2%], 169.9 ± 7.6 min; p = 0.004). There were no differences in rates of wound-related complications or hemorrhages, but overlapping cases had a significantly higher rate of hardware-related complications requiring revision (7/141 [5.0%] vs. 0/183 [0%]; p = 0.002). CONCLUSIONS: Overlapping and non-overlapping cases had comparable DBS lead placement accuracy. Overlapping cases had a longer operative duration and had a higher rate of hardware-related complications requiring revision.

Deep brain stimulation for dementias.

OBJECTIVE 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.

Open-loop deep brain stimulation for the treatment of epilepsy: a systematic review of clinical outcomes over the past decade (2008-present).

OBJECTIVE The field of deep brain stimulation (DBS) for epilepsy has grown tremendously since its inception in the 1970s and 1980s. The goal of this review is to identify and evaluate all studies published on the topic of open-loop DBS for epilepsy over the past decade (2008 to present). METHODS A PubMed search was conducted to identify all articles reporting clinical outcomes of open-loop DBS for the treatment of epilepsy published since January 1, 2008. The following composite search terms were used: ("epilepsy" [MeSH] OR "seizures" [MeSH] OR "kindling, neurologic" [MeSH] OR epilep* OR seizure* OR convuls*) AND ("deep brain stimulation" [MeSH] OR "deep brain stimulation" OR "DBS") OR ("electric stimulation therapy" [MeSH] OR "electric stimulation therapy" OR "implantable neurostimulators" [MeSH]). RESULTS The authors identified 41 studies that met the criteria for inclusion. The anterior nucleus of the thalamus, centromedian nucleus of the thalamus, and hippocampus were the most frequently evaluated targets. Among the 41 articles, 19 reported on stimulation of the anterior nucleus of the thalamus, 6 evaluated stimulation of the centromedian nucleus of the thalamus, and 9 evaluated stimulation of the hippocampus. The remaining 7 articles reported on the evaluation of alternative DBS targets, including the posterior hypothalamus, subthalamic nucleus, ventral intermediate nucleus of the thalamus, nucleus accumbens, caudal zone incerta, mammillothalamic tract, and fornix. The authors evaluated each study for overall epilepsy response rates as well as adverse events and other significant, nonepilepsy outcomes. CONCLUSIONS Level I evidence supports the safety and efficacy of stimulating the anterior nucleus of the thalamus and the hippocampus for the treatment of medically refractory epilepsy. Level III and IV evidence supports stimulation of other targets for epilepsy. Ongoing research into the efficacy, adverse effects, and mechanisms of open-loop DBS continues to expand the knowledge supporting the use of these treatment modalities in patients with refractory epilepsy.

Cost of Deep Brain Stimulation Infection Resulting in Explantation.

BACKGROUND: Deep brain stimulation (DBS) hardware infection is a serious complication, often resulting in multiple hardware salvage attempts, hospitalizations, and long-term antibiotic therapy. OBJECTIVES: We aimed to quantify the costs of DBS hardware-related infections in patients undergoing eventual device explantation. METHODS: Of 362 patients who underwent 530 electrode placements (1 January 2010 to 30 December 2014), 16 (4.4%) had at least 2 hardware salvage procedures. Most (n = 15 [93.8%]) required complete explantation due to recurrent infection. Financial data (itemized hospital and physician costs) were available for 13 patients and these were analyzed along with the demographic data. RESULTS: Each patient underwent 1-5 salvage procedures (mean 2.5 ± 1.4; median 2). The mean total cost for a patient undergoing the median number of revisions (n = 2), device explantation, and subsequent reimplantation after infection clearance was USD 75,505; just over half this cost (54.2% [USD 40,960]) was attributable to reimplantation, and nearly one-third (28.9% [USD 21,816]) was attributable to hardware salvage procedures. Operating-room costs were the highest cost category for hardware revision and explantation. Medical and surgical supplies accounted for the highest reimplantation cost. CONCLUSIONS: DBS infection incurs significant health care costs associated with hardware salvage attempts, explantation, and reimplantation. The highest cost categories are operating-room services and medical and surgical supplies.

Cerebral peduncle tumor ablated by novel 3-mm laser tip.

BACKGROUND/OBJECTIVE: Decisions to use open surgery or radiotherapy in pediatric patients with familial neoplastic syndromes must consider not only the symptomatic benefits of treatment, but also future limitations these treatments may impose. Specifically, open surgical resection of noncurable tumors may preclude or encumber future lesion resections, while radiotherapy has detrimental effects on pediatric cognitive development and increases the risk of future malignancy development. We provide the first report of using a novel 3.0-mm diffusing laser tip with laser-induced thermal therapy (LiTT) to treat a pediatric patient with neurofibromatosis type 1 (NF-1). METHODS: A 12-year-old boy with NF-1 presented with a progressively enlarging lesion in the right midbrain. A stereotactic biopsy was performed, followed by LiTT with a novel 3.0-mm laser applicator. RESULTS: MRI 1 week after LiTT showed stable gross total ablation of the lesion with reduction in fluid-attenuated inversion recovery signal. The patient remained neurologically intact 6 months after his procedure, and follow-up MRI showed no evidence of recurrence. CONCLUSION: LiTT is a powerful adjunct to conventional open surgical and radiotherapy modalities in the treatment of patients with familial neoplastic syndromes or incurable lesions. The novel laser applicator tip described expands the treatment scope of this technique.

Proceedings of the Second Annual Deep Brain Stimulation Think Tank: What's in the Pipeline.

The proceedings of the 2nd Annual Deep Brain Stimulation Think Tank summarize the most contemporary clinical, electrophysiological, and computational work on DBS for the treatment of neurological and neuropsychiatric disease and represent the insights of a unique multidisciplinary ensemble of expert neurologists, neurosurgeons, neuropsychologists, psychiatrists, scientists, engineers and members of industry. Presentations and discussions covered a broad range of topics, including advocacy for DBS, improving clinical outcomes, innovations in computational models of DBS, understanding of the neurophysiology of Parkinson's disease (PD) and Tourette syndrome (TS) and evolving sensor and device technologies.

Validation of CT-MRI fusion for intraoperative assessment of stereotactic accuracy in DBS surgery.

Deep brain stimulation is typically performed with intraoperative microelectrode recording and test stimulation for target confirmation. Recent studies have shown accurate, clinically efficacious results after lead placement without microelectrode recording or test stimulation, using interventional magnetic resonance imaging (MRI) or intraoperative computed tomography (CT; iCT) for verification of accuracy. The latter relies on CT-MRI fusion. To validate CT-MRI fusion in this setting, we compared stereotactic coordinates determined intraoperatively using CT-MRI fusion with those obtained on postoperative MRI. Deep brain stimulation electrodes were implanted with patients under general anesthesia. Direct targeting was performed on preoperative MRI, which was merged with preimplantation iCT images for stereotactic registration and postimplantation iCT images for accuracy confirmation. Magnetic resonance imaging was obtained 6 weeks postoperatively for comparison. Postoperative MRI was obtained for 48 patients, with 94 leads placed over a 1-year period. Vector error of the targeted contact relative to the initial plan was 1.1 ± 0.7 mm on iCT and 1.6 ± 0.7 mm on postoperative MRI. Variance comparisons (F-tests) showed that the discrepancy between iCT- and postoperative MRI-determined errors was attributable to measurement error on postoperative MRI, as detected in inter-rater reliability testing. In multivariate analysis, improved lead placement accuracy was associated with frame-based stereotaxy with the head of the bed at 0° compared with frameless stereotaxy with the head of the bed at 30° (P = 0.037). Intraoperative CT can be used to determine lead placement accuracy in deep brain stimulation surgery. The discrepancy between coordinates determined intraoperatively by CT-MRI fusion and postoperatively by MRI can be accounted for by inherent measurement error.

WarpDrive: Improving spatial normalization using manual refinements.

Spatial normalization-the process of mapping subject brain images to an average template brain-has evolved over the last 20+ years into a reliable method that facilitates the comparison of brain imaging results across patients, centers & modalities. While overall successful, sometimes, this automatic process yields suboptimal results, especially when dealing with brains with extensive neurodegeneration and atrophy patterns, or when high accuracy in specific regions is needed. Here we introduce WarpDrive, a novel tool for manual refinements of image alignment after automated registration. We show that the tool applied in a cohort of patients with Alzheimer's disease who underwent deep brain stimulation surgery helps create more accurate representations of the data as well as meaningful models to explain patient outcomes. The tool is built to handle any type of 3D imaging data, also allowing refinements in high-resolution imaging, including histology and multiple modalities to precisely aggregate multiple data sources together.

Deep brain stimulation in PD: risk of complications, morbidity, and hospitalizations: a systematic review.

Introduction: Parkinson's disease (PD) is a progressive and debilitating neurological disorder. While dopaminergic medication improves PD symptoms, continued management is complicated by continued symptom progression, increasing medication fluctuations, and medication-related dyskinesia. Deep brain stimulation (DBS) surgery is a well-accepted and widespread treatment often utilized to address these symptoms in advanced PD. However, DBS may also lead to complications requiring hospitalization. In addition, patients with PD and DBS may have specialized care needs during hospitalization. Methods: This systematic review seeks to characterize the complications and risk of hospitalization following DBS surgery. Patient risk factors and modifications to DBS surgical techniques that may affect surgical risk are also discussed. Results: It is found that, when candidates are carefully screened, DBS is a relatively low-risk procedure, but rate of hospitalization is somewhat increased for DBS patients. Discussion: More research is needed to determine the relative influence of more advanced disease vs. DBS itself in increased rate of hospitalization, but education about DBS and PD is important to insure effective patient care within the hospital.

Management of hangman's fractures using anchored anterior cervical cages.

Background: Hangman's fractures comprise approximately 20% of C2 fractures and often require surgery to correct significant angulation and/or subluxation. Recently, anchored anterior cervical cages (ACCs) have been used to fuse C2-3 as they reduce the risks of soft-tissue dissection, bone drilling, operative time, and postoperative dysphagia. Methods: This single-center and retrospective study (2012-2019) included 12 patients (3 type I, 6 type II, and 3 type IIa fractures) undergoing C2-3 ACCs (zero profile, half plate, full plate). Preoperative and postoperative radiographic and clinical data were analyzed. Results: The 12 patients demonstrated the following findings: a mean operative time of 106 ± 21 min, blood loss averaging 67 ± 58 mL, and mean length of stay of 9.8 ± 7.7 days (6.4 ± 5.5 days in intensive care). The mean differences in preoperative versus postoperative radiographs showed an increase in disc angle (9.0° ± 9.4° vs. 14.0° ± 7.2°), reduction of subluxation (18.5% ± 13.6% vs. 2.6% ± 6.2%), and maintenance of C2-7 lordosis (14.3° ± 9.5° vs. 14.4° ± 9.5°). All patients demonstrated fusion on dynamic films obtained >6 months postoperatively. In addition, only one patient had Grade 0 subsidence, three had transient postoperative dysphagia, whereas none had either intraoperative complications or 90-day readmissions. Conclusion: ACCs proved to be a viable alternative to traditional anterior cervical discectomy/fusion to treat 12 patients with C2-3 hangman's fractures in this preliminary study.