Focused Ultrasound Thalamotomy for Tremor in Parkinson's Disease: Outcomes in a Large, Prospective Cohort.

BACKGROUND: Magnetic resonance guided focused ultrasound (MRgFUS) is United States Food and Drug Administration approved for the treatment of tremor-dominant Parkinson's disease (TdPD), but only limited studies have been described in practice. OBJECTIVES: To report the largest prospective experience of unilateral MRgFUS thalamotomy for the treatment of medically refractory TdPD. METHODS: Clinical outcomes of 48 patients with medically refractory TdPD who underwent MRgFUS thalamotomy were evaluated. Tremor outcomes were assessed using the Fahn-Tolosa-Marin scale and adverse effects were categorized using a structured questionnaire and clinical exam at 1 month (n = 44), 3 months (n = 34), 1 year (n = 22), 2 years (n = 5), and 3 years (n = 2). Patients underwent magnetic resonance imaging <24 hours post-procedure. RESULTS: Significant tremor control persisted at all follow-ups (P < 0.001). All side effects were mild. At 3 months, these included gait imbalance (38.24%), sensory deficits (26.47%), motor weakness (17.65%), dysgeusia (5.88%), and dysarthria (5.88%), with some persisting at 1 year. CONCLUSIONS: MRgFUS thalamotomy is an effective treatment for sustained tremor control in patients with TdPD. © 2023 International Parkinson and Movement Disorder Society.

The Relationship Between Placental Pathology and Neurodevelopmental Outcomes in Complex Congenital Heart Disease.

Complex congenital heart disease (CCHD) is associated with impaired neurodevelopmental outcomes. Peri- and post-operative factors are known contributors while the impact of the prenatal environment is not yet delineated. Variations in fetal circulation, seen in transposition of the great arteries (TGA) and single ventricular physiology (SVP), are associated with placenta abnormalities. These abnormalities may be associated with placental insufficiency, a risk factor for poor neurodevelopmental outcomes. We hypothesized there is a correlation between placental pathology and impaired neurodevelopmental outcomes in patients with CCHD. We performed a single center retrospective cohort study with patients with TGA and SVP from 2010 to 2017 at Children's Wisconsin. Patient variables were obtained from the medical record. Bayley Scales of Infant Development Third Edition standard scores for cognitive, motor, and language performance were collected from neurodevelopmental visits. Placenta pathology reports were reviewed with tabulation of predetermined anatomical and pathological characteristics. We identified 79 patients in our cohort and 61 (77.2%) had abnormal placentas. There was no significant difference between the two groups in any demographic or clinical variables. For cognitive and motor performance, without adjusting for the covariates, infants with placental abnormalities had significantly lower scores compared to infants without (p = 0.026, p = 0.045 respectively). Conversely, there was no significant difference in language scores between the two groups (p = 0.12). Placenta abnormalities are common in patients with CCHD, and placenta abnormalities are associated with impaired neurodevelopmental outcomes. These results underscore the complex causal pathways of neurodevelopmental impairment in infants with CCHD and offer opportunities for targeted postnatal developmental interventions after discharge.

Clinical Variables Associated with Pre-Fontan Aortopulmonary Collateral Burden.

Aortopulmonary collaterals (APCs) develop universally, but to varying degrees, in patients with single ventricle congenital heart disease (CHD). Despite their ubiquitous presence, APCs remain poorly understood. We sought to evaluate the association between APC burden and common non-invasive clinical variables. We conducted a single center, retrospective study of patients with single ventricle CHD and previous Glenn palliation who underwent pre-Fontan cardiac magnetic resonance (CMR) imaging from 3/2018 to 3/2021. CMR was used to quantify APC flow, which was normalized to aortic (APC/QAo) and pulmonary vein (APC/QPV) blood flow. Univariate, multivariable, and classification and regression tree (CART) analyses were done to investigate the potential relationship between CMR-quantified APC burden and clinical variables. A total of 29 patients were included, all of whom had increased APC flow (APC/QAo: 26.9, [22.0, 39.1]%; APC/QPV: 39.4 [33.3, 46.9]%), but to varying degrees (APC/QAo: range 11.9-44.4%; APC/QPV: range 17.7-60.0%). Pulmonary artery size (Nakata index, at pre-Fontan CMR) was the only variable associated with APC flow on multivariable analysis (APC/QAo: p = 0.020, R2 = 0.19; APC/QPV: p = 0.0006, R2 = 0.36) and was the most important variable associated with APC burden identified by CART analysis (size inversely related to APC flow). APC flow is universally increased but highly variable in patients with single ventricle CHD and Glenn circulation. Small branch pulmonary artery size is a key factor associated with increased APC burden; however, the pathogenesis of APCs is likely multifactorial. Further research is needed to better understand APC pathogenesis, including predisposing and mitigating factors.

Lesion location and lesion creation affect outcomes after focused ultrasound thalamotomy.

MRI-guided focused ultrasound thalamotomy has been shown to be an effective treatment for medication refractory essential tremor. Here, we report a clinical-radiological analysis of 123 cases of MRI-guided focused ultrasound thalamotomy, and explore the relationships between treatment parameters, lesion characteristics and outcomes. All patients undergoing focused ultrasound thalamotomy by a single surgeon were included. The procedure was performed as previously described, and patients were followed for up to 1 year. MRI was performed 24 h post-treatment, and lesion locations and volumes were calculated. We retrospectively evaluated 118 essential tremor patients and five tremor-dominant Parkinson's disease patients who underwent thalamotomy. At 24 h post-procedure, tremor abated completely in the treated hand in 81 essential tremor patients. Imbalance, sensory disturbances and dysarthria were the most frequent acute adverse events. Patients with any adverse event had significantly larger lesions, while inferolateral lesion margins were associated with a higher incidence of motor-related adverse events. Twenty-three lesions were identified with irregular tails, often extending into the internal capsule; 22 of these patients experienced at least one adverse event. Treatment parameters and lesion characteristics changed with increasing surgeon experience. In later cases, treatments used higher maximum power (normalized to skull density ratio), accelerated more quickly to high power, and delivered energy over fewer sonications. Larger lesions were correlated with a rapid rise in both power delivery and temperature, while increased oedema was associated with rapid rise in temperature and the maximum power delivered. Total energy and total power did not significantly affect lesion size. A support vector regression was trained to predict lesion size and confirmed the most valuable predictors of increased lesion size as higher maximum power, rapid rise to high-power delivery, and rapid rise to high tissue temperatures. These findings may relate to a decrease in the energy efficiency of the treatment, potentially due to changes in acoustic properties of skull and tissue at higher powers and temperatures. We report the largest single surgeon series of focused ultrasound thalamotomy to date, demonstrating tremor relief and adverse events consistent with reported literature. Lesion location and volume impacted adverse events, and an irregular lesion tail was strongly associated with adverse events. High-power delivery early in the treatment course, rapid temperature rise, and maximum power were dominant predictors of lesion volume, while total power, total energy, maximum energy and maximum temperature did not improve prediction of lesion volume. These findings have critical implications for treatment planning in future patients.

Transcranial MR-Guided Focused Ultrasound and Hyperostosis Calvariae Diffusa: Case Report and Systematic Review of the Literature.

We describe a 74-year-old male with intractable essential tremor (ET) and hyperostosis calvariae diffusa who was unsuccessfully treated with magnetic resonance-guided focused ultrasound (MRgFUS). A computed tomography performed prior to the procedure demonstrated a skull density ratio (SDR) of 0.37 and tricortical hyperostosis calvariae diffusa. No lesion was evident on post-MRgFUS MRI, and no improvement in the patient's hand tremor was noted clinically. We systematically reviewed the literature to understand outcomes for those patients with hyperostosis who have undergone MRgFUS. A comprehensive literature search using the PubMed, Cochrane, and Google Scholar databases identified 3 ET patients with hyperostosis who failed treatment with MRgFUS. Clinical findings, skull characteristics, treatment parameters, and outcomes were summarized, demonstrating different patterns/degrees of bicortical hyperostosis and variable SDRs (i.e., from 0.38 to ≥0.45). Although we have successfully treated patients with bicortical hyperostosis frontalis interna (n = 50), tricortical hyperostosis calvariae diffusa appears to be a contraindication for MRgFUS despite acceptable SDRs.

Is native aortic valvuloplasty at time of Norwood operation in infants with hypoplastic left heart syndrome and aortic stenosis safe?

In hypoplastic left heart syndrome, the size and function of the left ventricle vary and are dependent on the patency of the aortic valve. A patent native aortic valve, permitting left ventricular ejection, can augment cardiac output. We performed a retrospective chart review of patients with hypoplastic left heart syndrome and a stenotic aortic valve who underwent native aortic valvuloplasty at the time of Norwood and found that none of the eight patients identified had clinically significant aortic insufficiency. This case series suggests that surgical aortic valvuloplasty at Norwood is associated with aortic valve patency/augmented systemic cardiac output without the development of clinically significant aortic regurgitation at intermediate follow-up in a limited cohort.

Two-trajectory laser amygdalohippocampotomy: Anatomic modeling and initial seizure outcomes.

OBJECTIVE: Laser interstitial thermal therapy (LITT) for mesial temporal lobe epilepsy (mTLE) is typically performed with one trajectory to target the medial temporal lobe (MTL). MTL structures such as piriform and entorhinal cortex are epileptogenic, but due to their relative geometry, they are difficult to target with one trajectory while simultaneously maintaining adequate ablation of the amygdala and hippocampus. We hypothesized that a two-trajectory approach could improve ablation of all relevant MTL structures. First, we created large-scale computer simulations to compare idealized one- vs two-trajectory approaches. A two-trajectory approach was then validated in an initial cohort of patients. METHODS: We used magnetic resonance imaging (MRI) from the Human Connectome Project (HCP) to create subject-specific target structures consisting of hippocampus, amygdala, and piriform/entorhinal/perirhinal cortex. An algorithm searched for safe potential trajectories along the hippocampal axis (catheter one) and along the amygdala-piriform axis (catheter two) and compared this to a single trajectory optimized over all structures. The proportion of each structure ablated at various burn radii was evaluated. A cohort of 11 consecutive patients with mTLE received two-trajectory LITT; demographic, operative, and outcome data were collected. RESULTS: The two-trajectory approach was superior to the one-trajectory approach at nearly all burn radii for all hippocampal subfields and amygdala nuclei (p < .05). Two-laser trajectories achieved full ablation of MTL cortical structures at physiologically realistic burn radii, whereas one-laser trajectories could not. Five patients with at least 1 year of follow-up (mean = 21.8 months) experienced Engel class I outcomes; 6 patients with less than 1 year of follow-up (mean = 6.6 months) are on track for Engel class I outcomes. SIGNIFICANCE: Our anatomic analyses and initial clinical results suggest that LITT amygdalohippocampotomy performed via two-laser trajectories may promote excellent seizure outcomes. Future studies are required to validate the long-term clinical efficacy and safety of this approach.

The diagnosis and management of primary and iatrogenic soft tissue sarcomas of the sella.

PURPOSE: Soft tissue sarcoma (STS) of the sella is exceptionally rare. We conducted a case series, literature review, and nationwide analysis of primary and iatrogenic (radiation-associated) STS of the sella to define the clinical course of this entity. METHODS: This study employed a multi-institutional retrospective case review, literature review, and nationwide analysis using the National Cancer Database (NCDB). RESULTS: We report five patients who were diagnosed at three institutions with malignant STS of the sella. All patients presented with symptoms related to mass effect in the sellar region. All tumors extended to the suprasellar space, with the majority displaying extension into the cavernous sinus. All patients underwent an operation via a transsphenoidal approach with a goal of maximal safe tumor resection in four patients and biopsy for 1 patient. Histopathologic evaluation demonstrated STS in all patients. Post-operative adjuvant radiotherapy and chemotherapy were given to 2 and 1 out of 4 patients with known post-operative clinical course, respectively. The 1-year and 5-year overall survival rates were 100% (5/5) and 25% (1/4). Twenty-two additional reports of primary, non-iatrogenic STS of the sella were identified in the literature. Including the three cases from our series, treatment included resection in all cases, and adjuvant radiotherapy and chemotherapy were utilized in 50% (12/24) and 17% (4/24) of cases, respectively. The national prevalence of malignant STS is estimated to be 0.01% among all pituitary and sellar tumors within the NCDB. CONCLUSIONS: We report the prevalence and survival rates of STS of the sella. Multimodal therapy, including maximal safe resection, chemotherapy, and radiotherapy are necessary to optimize outcomes for this uncommon pathology.

Postoperative Changes in Orbital Dysmorphology in Patients With Unicoronal Synostosis.

Orbital asymmetry in unicoronal synostosis impacts craniofacial appearance and can potentiate functional visual disturbances, such as strabismus. Surgical treatment aims to normalize overall cranial morphology, including that of the orbits. The purpose of this study was to compare postoperative changes in orbital asymmetry following 2 common procedures.Preoperative and 1-year postoperative computed tomography scans for patients with isolated, nonsyndromic unicoronal synostosis treated from 2007 to 2012, at 2 academic institutions were analyzed. Only patients treated by endoscopic suturectomy and postoperative helmeting or bilateral fronto-orbital advancement were included. Orbital index, depth, and volume asymmetry were determined for each patient both pre- and 1-year postoperatively. Student's t-tests were used to compare pre- and postoperative asymmetries within each treatment group. Regression analyses were used to examine postoperative change in asymmetry between treatment groups.Scans from 12 patients treated by fronto-orbital advancement and 23 treated by endoscopic suturectomy were analyzed. Differences between synostotic and nonsynostotic orbital index, depth, and volume were statistically significant both pre- and postoperatively. Statistically significant postoperative improvements in asymmetry were observed for orbital index, depth, and volume following suturectomy. Regression analysis indicated that the amount of pre- to postoperative change in all measures of asymmetry did not depend on surgical technique. Residual asymmetry following both procedures was apparent at 1 year postoperatively.Orbital asymmetry is improved, but not resolved following both fronto-orbital advancement and endoscopic suturectomy. Degree of improvement in symmetry is independent of surgical technique used.

Evaluation of Endoscopic Strip Craniectomy and Orthotic Therapy for Bilateral Coronal Craniosynostosis.

BACKGROUND: Bilateral coronal craniosynostosis is the premature fusion of both coronal sutures. Traditionally, this condition is treated by frontal-orbital advancement (FOA). Endoscopic strip craniectomy with cranial orthotic therapy, which has gained popularity in treating single suture craniosynostosis, has recently been adapted for the treatment of bicoronal synostosis. There have been few studies documenting the outcomes of this treatment. The objective of this study is to compare the morphological outcomes of endoscopic strip craniectomy and FOA in patients with bicoronal synostosis. METHODS: A retrospective case series was done on 24 patients with bilateral coronal synostosis treated with endoscopic strip craniectomy or FOA at 2 institutions. Patients with preoperative and 1-year postoperative computed tomography scans were included. Multiple measures of cranial shape and size were assessed: cephalic index, turricephaly index, basofrontal angle, circumference Z-score, and cranial vault volume Z-score. RESULTS: The 2 groups were similar statistically in terms of morphology at preoperative scan. There were no statistical differences between the FOA group and endoscopic group at postoperative scan in any of the morphologic outcomes measured. Cranial vault volume Z-scores increased postoperatively in both the endoscopic (P < 0.001) and FOA (P = 0.034) groups. CONCLUSIONS: One year after repair there were no significant morphological difference between patients with bicoronal synostosis treated with the endoscopic approach and those treated by FOA.

Focused ultrasound in neurosurgery: a historical perspective.

Focused ultrasound (FUS) has been under investigation for neurosurgical applications since the 1940s. Early experiments demonstrated ultrasound as an effective tool for the creation of intracranial lesions; however, they were limited by the need for craniotomy to avoid trajectory damage and wave distortion by the skull, and they also lacked effective techniques for monitoring. Since then, the development and hemispheric distribution of phased arrays has resolved the issue of the skull and allowed for a completely transcranial procedure. Similarly, advances in MR technology have allowed for the real-time guidance of FUS procedures using MR thermometry. MR-guided FUS (MRgFUS) has primarily been investigated for its thermal lesioning capabilities and was recently approved for use in essential tremor. In this capacity, the use of MRgFUS is being investigated for other ablative indications in functional neurosurgery and neurooncology. Other applications of MRgFUS that are under active investigation include opening of the blood-brain barrier to facilitate delivery of therapeutic agents, neuromodulation, and thrombolysis. These recent advances suggest a promising future for MRgFUS as a viable and noninvasive neurosurgical tool, with strong potential for yet-unrealized applications.

Physiological Approach to Sodium Supplementation in Preterm Infants.

OBJECTIVE: To implement and evaluate a clinical practice algorithm to identify preterm infants with sodium deficiency and guide sodium supplementation based on urine sodium concentrations. STUDY DESIGN: Urine sodium concentration was measured in infants born at 260/7 to 296/7 weeks' gestation at 2-week intervals. Sodium supplementation was based on the urine sodium algorithm. Growth and respiratory outcomes in this cohort were compared with a matched cohort cared for in our neonatal intensive care unit prior to algorithm implementation (2014-2015 cohort). RESULTS: Data were compared for 50 infants in the 2014-2015 cohort and 40 infants in the 2016 cohort. Urine sodium concentration met criteria for supplementation in 75% of the 2016 cohort infants within the first 4 weeks after birth. Average daily sodium intake was greater in the 2016 cohort compared with the 2014-2015 cohort (p < 0.05). Caloric, protein, and total fluid intakes were similar between cohorts. The change in weight Z-score between 2 and 8 weeks of age was significantly greater in the 2016 versus 2014-2015 cohort (0.32 ± 0.05 vs. -0.01 ± 0.08; p < 0.01). No impact on respiratory status at 28 days of age or 36 weeks of postmenstrual age was identified. CONCLUSION: Institution of a clinical practice algorithm to instruct clinicians on sodium supplementation in preterm infants may improve growth outcomes.

Deep brain stimulation for the obsessive-compulsive and Tourette-like symptoms of Kleefstra syndrome.

Deep brain stimulation (DBS) has been reported to have beneficial effects in severe, treatment-refractory cases of obsessive-compulsive disorder (OCD) and Tourette syndrome (TS). In this report, the authors present the first case in which DBS was used to treat the neuropsychiatric symptoms of Kleefstra syndrome, a rare genetic disorder characterized by childhood hypotonia, intellectual disability, distinctive facial features, and myriad psychiatric and behavioral disturbances. A 24-year-old female patient with childhood hypotonia, developmental delay, and diagnoses of autism spectrum disorder, OCD, and TS refractory to medical management underwent the placement of bilateral ventral capsule/ventral striatum (VC/VS) DBS leads, with clinical improvement. Medical providers and family observed gradual and progressive improvement in the patient's compulsive behaviors, coprolalia, speech, and social interaction. Symptoms recurred when both DBS electrodes failed because of lead fracture and dislodgement, although the clinical benefits were restored by lead replacement. The symptomatic and functional improvements observed in this case of VC/VS DBS for Kleefstra syndrome suggest a novel indication for DBS worthy of further investigation.

Endoscopic endonasal transclival approach for a ventral brainstem epidermoid cyst: illustrative case.

BACKGROUND: Intracranial epidermoid cysts are benign, slow-growing malformations that most commonly arise at the skull base. Maximizing resection of the cyst contents and the capsule reduces long-term recurrence but can be made difficult by cyst wall adherence to critical neurovascular structures. Expanded endonasal approaches (EEAs) offer an alternative to traditional open transcranial approaches for accessible epidermoid cysts. In this case report, the authors demonstrate a transclival EEA for a large, ventral brainstem epidermoid cyst. OBSERVATIONS: A 41-year-old woman who presented with progressive headaches, diplopia, malaise, and fatigue was found to have a 4.7-cm midline, ventral brainstem epidermoid cyst. She underwent an expanded endonasal transclival approach that exposed the brainstem from the level of the dorsum sella to the tip of the basion. A near-total resection was completed with removal of all cyst contents and most of the capsular wall. Reconstruction was completed with Duragen, an autologous fat graft, and a nasoseptal flap. Postoperatively, she had a partial left cranial nerve VI palsy that remained stable 8 weeks after surgery. LESSONS: The expanded endoscopic transclival approach can facilitate effective resection of midline, ventral epidermoid cysts.

Modeling of intracranial tumor treating fields for the treatment of complex high-grade gliomas.

Increasing the intensity of tumor treating fields (TTF) within a tumor bed improves clinical efficacy, but reaching sufficiently high field intensities to achieve growth arrest remains challenging due in part to the insulating nature of the cranium. Using MRI-derived finite element models (FEMs) and simulations, we optimized an exhaustive set of intracranial electrode locations to obtain maximum TTF intensities in three clinically challenging high-grade glioma (HGG) cases (i.e., thalamic, left temporal, brainstem). Electric field strengths were converted into therapeutic enhancement ratios (TER) to evaluate the predicted impact of stimulation on tumor growth. Concurrently, conventional transcranial configurations were simulated/optimized for comparison. Optimized intracranial TTF were able to achieve field strengths that have previously been shown capable of inducing complete growth arrest, in 98-100% of the tumor volumes using only 0.54-0.64 A current. The reconceptualization of TTF as a targeted, intracranial therapy has the potential to provide a meaningful survival benefit to patients with HGG and other brain tumors, including those in surgically challenging, deep, or anatomically eloquent locations which may preclude surgical resection. Accordingly, such an approach may ultimately represent a paradigm shift in the use of TTFs for the treatment of brain cancer.

Longitudinal MR imaging after unilateral MR-guided focused ultrasound thalamotomy: clinical and radiological correlation.

Introduction: Magnetic-resonance-guided focused ultrasound (MRgFUS) thalamotomy uses multiple converging high-energy ultrasonic beams to produce thermal lesions in the thalamus. Early postoperative MR imaging demonstrates the location and extent of the lesion, but there is no consensus on the utility or frequency of postoperative imaging. We aimed to evaluate the evolution of MRgFUS lesions and describe the incidence, predictors, and clinical effects of lesion persistence in a large patient cohort. Methods: A total of 215 unilateral MRgFUS thalamotomy procedures for essential tremor (ET) by a single surgeon were retrospectively analyzed. All patients had MR imaging 1 day postoperatively; 106 had imaging at 3 months and 32 had imaging at 1 year. Thin cut (2 mm) axial and coronal T2-weighted MRIs at these timepoints were analyzed visually on a binary scale for lesion presence and when visible, lesion volumes were measured. SWI and DWI sequences were also analyzed when available. Clinical outcomes including tremor scores and side effects were recorded at these same time points. We analyzed if patient characteristics (age, skull density ratio), preoperative tremor score, and sonication parameters influenced lesion evolution and if imaging characteristics correlated with clinical outcomes. Results: Visible lesions were present in all patients 1 day post- MRgFUS and measured 307.4 ± 128.7 mm3. At 3 months, residual lesions (excluding patients where lesions were not visible) were 83.6% smaller and detectable in only 54.7% of patients (n = 58). At 1 year, residual lesions were detected in 50.0% of patients (n = 16) and were 90.7% smaller than 24 h and 46.5% smaller than 3 months. Lesions were more frequently visible on SWI (100%, n = 17), DWI (n = 38, 97.4%) and ADC (n = 36, 92.3%). At 3 months, fewer treatment sonications, higher maximum power, and greater distance between individual sonications led to larger lesion volumes. Volume at 24 h did not predict if a lesion was visible later. Lesion visibility at 3 months predicted sensory side effects but was not correlated with tremor outcomes. Discussion: Overall, lesions are visible on T2-weighted MRI in about half of patients at both 3 months and 1 year post-MRgFUS thalamotomy. Certain sonication parameters significantly predicted persistent volume, but residual lesions did not correlate with tremor outcomes.

Focal drug-resistant temporal lobe epilepsy associated with an ipsilateral anterior choroidal artery aneurysm: illustrative case.

BACKGROUND: The occurrence of both an intracranial aneurysm and epilepsy, especially drug-resistant epilepsy (DRE), is rare. Although the overall incidence of aneurysms associated with DRE is unclear, it is thought to be particularly infrequent in the pediatric population. Surgical ligation of the offending aneurysm has been reported in conjunction with resolving seizure activity, although few cases have cited a combined approach of aneurysm ligation and resection of an epileptogenic focus. OBSERVATIONS: We present the case of a 14-year-old female patient with drug-resistant temporal lobe epilepsy and an ipsilateral supraclinoid internal carotid artery aneurysm. Seizure semiology, electroencephalography monitoring, and magnetic resonance imaging all indicated a left temporal epileptogenic focus, in addition to an incidental aneurysm. The authors recommended a combined surgery involving resection of the temporal lesion and surgical clip ligation of the aneurysm. Near-total resection and successful ligation were achieved, and the patient has remained seizure free since surgery at 1 year postoperatively. LESSONS: In patients with focal DRE and an adjacent intracranial aneurysm, a combined surgical approach involving both resection and surgical ligation can be used. Several surgical timing and neuroanesthetic considerations should be made to ensure the overall safety and efficacy of this procedure.

Asleep deep brain stimulation with intraoperative magnetic resonance guidance: a single-institution experience.

OBJECTIVE: Deep brain stimulation (DBS) is traditionally performed on an awake patient with intraoperative recordings and test stimulation. DBS performed under general anesthesia with intraoperative MRI (iMRI) has demonstrated high target accuracy, reduced operative time, direct confirmation of target placement, and the ability to place electrodes without cessation of medications. The authors describe their initial experience with using iMRI to perform asleep DBS and discuss the procedural and radiological outcomes of this procedure. METHODS: All DBS electrodes were implanted under general anesthesia by a single surgeon by using a neuronavigation system with 3-T iMRI guidance. Clinical outcomes, operative duration, complications, and accuracy were retrospectively analyzed. RESULTS: In total, 103 patients treated from 2015 to 2019 were included, and all but 1 patient underwent bilateral implantation. Indications included Parkinson's disease (PD) (65% of patients), essential tremor (ET) (29%), dystonia (5%), and refractory epilepsy (1%). Targets included the globus pallidus pars internus (12.62% of patients), subthalamic nucleus (56.31%), ventral intermedius nucleus of the thalamus (30%), and anterior nucleus of the thalamus (1%). Technically accurate lead placement (radial error ≤ 1 mm) was obtained for 98% of leads, with a mean (95% CI) radial error of 0.50 (0.46-0.54) mm; all leads were placed with a single pass. Predicted radial error was an excellent predictor of real radial error, underestimating real error by only a mean (95% CI) of 0.16 (0.12-0.20) mm. Accuracy remained high irrespective of surgeon experience, but procedure time decreased significantly with increasing institutional and surgeon experience (p = 0.007), with a mean procedure duration of 3.65 hours. Complications included 1 case of intracranial hemorrhage (asymptomatic) and 1 case of venous infarction (symptomatic), and 2 patients had infection at the internal pulse generator site. The mean ± SD voltage was 2.92 ± 0.83 V bilaterally at 1-year follow-up. Analysis of long-term clinical efficacy demonstrated consistent postoperative improvement in clinical symptoms, as well as decreased drug doses across all indications and follow-up time points, including mean decrease in levodopa-equivalent daily dose by 53.57% (p < 0.0001) in PD patients and mean decrease in primidone dose by 61.33% (p < 0.032) in ET patients at 1-year follow-up. CONCLUSIONS: A total of 205 leads were placed in 103 patients by a single surgeon under iMRI guidance with few operative complications. Operative time trended downward with increasing institutional experience, and technical accuracy of radiographic lead placement was consistently high. Asleep DBS implantation with iMRI appears to be a safe and effective alternative to standard awake procedures.

Magnetic Resonance Image Guided Focused Ultrasound Thalamotomy. A Single Center Experience With 160 Procedures.

INTRODUCTION: MRgFUS thalamotomy has gained popularity as an FDA approved, non-invasive treatment for patients with Essential Tremor and tremor predominant Parkinson's Disease. We present our initial clinical experience with 160 consecutive cases of MRgFUS thalamotomy and describe the clinical outcomes with long term follow-up. METHODS: A retrospective chart review of all patients who underwent MRgFUS thalamotomy at our institution was performed. CRST Part A tremor scores were obtained pre-operatively and at each follow-up visit along with an assessment of side effects (SE). All patients had a post-operative MRI within 24 h to determine the location, size, and extent of the MRgFUS lesion. RESULTS: One hundred and sixty unilateral MRgFUS Thalamotomies (Left, n = 128; Right, n = 32) were performed for medically refractory essential Tremor (n = 150) or tremor predominant Parkinson's disease (n = 10). Mean age at surgery was 75 Years (range: 48-93) and the mean skull density ratio (SDR) was 0.48 (range: 0.32-0.75; median: 0.46). In ET patients, both rest and postural tremor was abolished acutely and remained so at follow-up whereas intention tremor was reduced acutely by 93% below baseline, 87% at 3 months, 83.0% at 1-year, and 78% at 2 years. On post-operative day 1, the most common SE's included imbalance (57%), sensory disturbances (25%), and dysmetria (11%). All adverse events were rated as mild on the Clavien-Dindo Scale and improved over time. At 2-years follow-up, imbalance was seen in 18%, sensory disturbance in 10% and dysmetria in 8% patients. Mean clinical follow-up for all patients was 14 months (range: 1-48 months). CONCLUSION: MRgFUS thalamotomy is a safe and effective procedure for long term improvement of unilateral tremor symptoms, with the most common side-effects being imbalance and sensory disturbance.

A national stratification of the global macroeconomic burden of central nervous system cancer.

OBJECTIVE: Country-by-country estimates of the macroeconomic disease burden of central nervous system (CNS) cancers are important when determining the allocation of resources related to neuro-oncology. Accordingly, in this study the authors investigated macroeconomic losses related to CNS cancer in 173 countries and identified pertinent epidemiological trends. METHODS: Data for CNS cancer incidence, mortality, and disability-adjusted life years (DALYs) were collected from the Global Burden of Disease 2019 database. Gross domestic product data were combined with DALY data to estimate economic losses using a value of lost welfare approach. RESULTS: The mortality-to-incidence ratio of CNS cancer in 2019 was 0.60 in high-income regions compared to 0.82 in Sub-Saharan Africa and 0.87 in Central Europe, Eastern Europe, and Central Asia. Welfare losses varied across both high- and low-income countries. Welfare losses attributable to CNS cancer in Japan represented 0.07% of the gross domestic product compared to 0.23% in Germany. In low- and middle-income countries, Iraq reported welfare losses of 0.20% compared to 0.04% in Angola. Globally, the DALY rate in 2019 was the same for CNS cancer as for prostate cancer at 112 per 100,000 person-years, despite a 75% lower incidence rate, equating to CNS cancer welfare losses of 182 billion US dollars. CONCLUSIONS: Macroeconomic losses vary across high- and low-income settings and appear to be region specific. These differences may be explained by differences in regional access to screening and diagnosis, population-level genetic predispositions, and environmental risk factors. Mortality-to-incidence ratios are higher in low- and middle-income countries than in high-income countries, highlighting possible gaps in treatment access. Quantification of macroeconomic losses related to CNS cancer can help to justify the spending of finite resources to improve outcomes for neuro-oncological patients globally.