Ying Meng and Nir Lipsman
Karim Mithani, Ying Meng, David Pinilla, Nova Thani, Kayee Tung, Richard Leung and Howard J. Ginsberg
A 52-year-old man with a 10-year history of treatment-resistant asthma presented with repeated exacerbations over the course of 10 months. His symptoms were not responsive to salbutamol or inhaled corticosteroid agents, and he developed avascular necrosis of his left hip as a result of prolonged steroid therapy. Physical examination and radiography revealed signs consistent with diffuse idiopathic skeletal hyperostosis (DISH), including a C7–T1 osteophyte causing severe tracheal compression. The patient underwent C6–T1 anterior discectomy and fusion, and the compressive osteophyte was removed, which completely resolved his “asthma.” Postoperative pulmonary function tests showed normalization of his FEV1/FVC ratio, and there was no airway reactivity on methacholine challenge. DISH is a systemic, noninflammatory condition characterized by ossification of spinal entheses, and it can present with respiratory disturbances due to airway compression by anterior cervical osteophytes. The authors present, to the best of their knowledge, the first documented case of asthma as a presentation of DISH.
Benjamin Davidson, Karim Mithani, Yuexi Huang, Ryan M. Jones, Maged Goubran, Ying Meng, John Snell, Kullervo Hynynen, Clement Hamani and Nir Lipsman
Magnetic resonance imaging–guided focused ultrasound (MRgFUS) is an emerging treatment modality that enables incisionless ablative neurosurgical procedures. Bilateral MRgFUS capsulotomy has recently been demonstrated to be safe and effective in treating obsessive-compulsive disorder (OCD) and major depressive disorder (MDD). Preliminary evidence has suggested that bilateral MRgFUS capsulotomy can present increased difficulties in reaching lesional temperatures as compared to unilateral thalamotomy. The authors of this article aimed to study the parameters associated with successful MRgFUS capsulotomy lesioning and to present longitudinal radiographic findings following MRgFUS capsulotomy.
Using data from 22 attempted MRgFUS capsulotomy treatments, the authors investigated the relationship between various sonication parameters and the maximal temperature achieved at the intracranial target. Lesion volume and morphology were analyzed longitudinally using structural and diffusion tensor imaging. A retreatment procedure was attempted in one patient, and their postoperative imaging is presented.
Skull density ratio (SDR), skull thickness, and angle of incidence were significantly correlated with the maximal temperature achieved. MRgFUS capsulotomy lesions appeared similar to those following MRgFUS thalamotomy, with three concentric zones observed on MRI. Lesion volumes regressed substantially over time following MRgFUS. Fractional anisotropy analysis revealed a disruption in white matter integrity, followed by a gradual return to near-baseline levels concurrent with lesion regression. In the patient who underwent retreatment, successful bilateral lesioning was achieved, and there were no adverse clinical or radiographic events.
With the current iteration of MRgFUS technology, skull-related parameters such as SDR, skull thickness, and angle of incidence should be considered when selecting patients suitable for MRgFUS capsulotomy. Lesions appear to follow morphological patterns similar to what is seen following MRgFUS thalamotomy. Retreatment appears to be safe, although additional cases will be necessary to further evaluate the associated safety profile.
Lauren Conova, Jennifer Vernengo, Ying Jin, B. Timothy Himes, Birgit Neuhuber, Itzhak Fischer, Anthony Lowman, Jennifer Vernengo, Ying Jin, B. Timothy Himes, Birgit Neuhuber, Itzhak Fischer and Anthony Lowman
The authors investigated the feasibility of using injectable hydrogels, based on poly(N-isopropylacrylamide) (PNIPAAm), lightly cross-linked with polyethylene glycol (PEG) or methylcellulose (MC), to serve as injectable scaffolds for local delivery of neurotrophins and cellular transplants into the injured spinal cord. The primary aims of this work were to assess the biocompatibility of the scaffolds by evaluating graft cell survival and the host tissue immune response. The scaffolds were also evaluated for their ability to promote axonal growth through the action of released brain-derived neurotrophic factor (BDNF).
The in vivo performance of PNIPAAm-g-PEG and PNIPAAm-g-MC was evaluated using a rodent model of spinal cord injury (SCI). The hydrogels were injected as viscous liquids into the injury site and formed space-filling hydrogels. The host immune response and biocompatibility of the scaffolds were evaluated at 2 weeks by histological and fluorescent immunohistochemical analysis. Commercially available matrices were used as a control and examined for comparison.
Experiments showed that the scaffolds did not contribute to an injury-related inflammatory response. PNIPAAm-g-PEG was also shown to be an effective vehicle for delivery of cellular transplants and supported graft survival. Additionally, PNIPAAm-g-PEG and PNIPAAm-g-MC are permissive to axonal growth and can serve as injectable scaffolds for local delivery of BDNF.
Based on the results, the authors suggest that these copolymers are feasible injectable scaffolds for cell grafting into the injured spinal cord and for delivery of therapeutic factors.
Ying Meng, Christopher B. Pople, Suneil K. Kalia, Lorraine V. Kalia, Benjamin Davidson, Luca Bigioni, Daniel Zhengze Li, Suganth Suppiah, Karim Mithani, Nadia Scantlebury, Michael L. Schwartz, Clement Hamani and Nir Lipsman
The development of transcranial MR-guided focused ultrasound (MRgFUS) has revitalized the practice of lesioning procedures in functional neurosurgery. Previous health economic analysis found MRgFUS thalamotomy to be a cost-effective treatment for patients with essential tremor, supporting its reimbursement. With the publication of level I evidence in support of MRgFUS thalamotomy for patients with tremor-dominant Parkinson’s disease (TDPD), the authors performed a health economic comparison between MRgFUS, deep brain stimulation (DBS), and medical therapy.
The authors used a decision tree model with rollback analysis and one-factor sensitivity analysis. Literature searches of MRgFUS thalamotomy and unilateral DBS of the ventrointermediate nucleus of the thalamus for TDPD were performed to determine the utility and probabilities for the model. Costs in Canadian dollars (CAD) were derived from the Schedule of Benefits and Fees in Ontario, Canada, and expert opinion on usage.
MRgFUS was associated with an expected cost of $14,831 CAD. Adding MRgFUS to continued medical therapy resulted in an incremental cost-effectiveness ratio of $30,078 per quality-adjusted life year (QALY), which remained cost-effective under various scenarios in the sensitivity analysis. Comparing DBS to MRgFUS, while DBS did not achieve the willingness-to-pay threshold ($56,503 per QALY) in the base case scenario, it did so under several scenarios in the sensitivity analysis.
MRgFUS thalamotomy is a cost-effective treatment for patients with TDPD, particularly over continued medical therapy. While MRgFUS remains competitive with DBS, the cost-effectiveness advantage is less substantial. These results will help inform the integration of this technology in the healthcare system.
Ying Meng, Mathew R. Voisin, Suganth Suppiah, Zamir Merali, Ali Moghaddamjou, Naif M. Alotaibi, Arbelle Manicat-Emo, Shelly Weiss, Cristina Go, Blathnaid McCoy, Elizabeth J. Donner and James T. Rutka
Intracranial electroencephalography (iEEG) monitoring is an important method of identifying the seizure focus in patients with medically refractory epilepsy. While previous studies have demonstrated low rates of surgical complications, reported rates of surgical site infection (SSI) are highly variable. To date, no studies have specifically evaluated the patient or operative risk factors contributing to SSI. The goals of this study were to examine the rate of SSI after iEEG monitoring for epilepsy workup in pediatric patients and to determine the variables that might contribute to the development of SSI.
A retrospective analysis of hospital charts at the Hospital for Sick Children was performed for all patients who had undergone iEEG monitoring between 2000 and 2016. Univariate and multivariate analyses were performed to look for statistically significant variables in relation to SSI.
Among 199 patients eligible for analysis, 8 (4.0%) developed SSIs within a period ranging from 21 to 51 days postoperatively. Univariate analysis yielded 4 factors related to SSI: number of people present in the operating room on electrode insertion (p = 0.02), length of insertion surgery (p = 0.04), previous operation at the same surgical site (p = 0.04), and number of depth electrodes inserted (p = 0.01). Multivariate analysis revealed that both the number of people present during the implant operation (OR 0.08, 95% CI 0.01–0.70) and the number of depth electrodes inserted (OR 3.52, 95% CI 1.44–8.59) independently contributed to SSI.
This is the largest case series and the first comprehensive review of both patient and operative risk factors in the development of SSI from iEEG monitoring in a pediatric population. The authors’ institution had a lower rate of infection than those in most other studies, which could be explained by their protocol of administering intravenous antibiotics perioperatively and post–implant removal antibiotics for 14 days. The authors found a correlation between SSI and the number of people present during the implant operation, as well as the number of depth electrodes; both may contribute to breaks in sterility.