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Browsing by Author "Raskin, Jeffrey"
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Item Connectomic profiling and Vagus nerve stimulation Outcomes Study (CONNECTiVOS): a prospective observational protocol to identify biomarkers of seizure response in children and youth(BMJ, 2022-04-08) Siegel, Lauren; Yan, Han; Warsi, Nebras; Wong, Simeon; Suresh, Hrishikesh; Weil, Alexander G.; Ragheb, John; Wang, Shelly; Rozzelle, Curtis; Albert, Gregory W.; Raskin, Jeffrey; Abel, Taylor; Hauptman, Jason; Schrader, Dewi V.; Bollo, Robert; Smyth, Matthew D.; Lew, Sean M.; Lopresti, Melissa; Kizek, Dominic J.; Weiner, Howard L.; Fallah, Aria; Widjaja, Elysa; Ibrahim, George M.; Neurological Surgery, School of MedicineIntroduction: Vagus nerve stimulation (VNS) is a neuromodulation therapy that can reduce the seizure burden of children with medically intractable epilepsy. Despite the widespread use of VNS to treat epilepsy, there are currently no means to preoperatively identify patients who will benefit from treatment. The objective of the present study is to determine clinical and neural network-based correlates of treatment outcome to better identify candidates for VNS therapy. Methods and analysis: In this multi-institutional North American study, children undergoing VNS and their caregivers will be prospectively recruited. All patients will have documentation of clinical history, physical and neurological examination and video electroencephalography as part of the standard clinical workup for VNS. Neuroimaging data including resting-state functional MRI, diffusion-tensor imaging and magnetoencephalography will be collected before surgery. MR-based measures will also be repeated 12 months after implantation. Outcomes of VNS, including seizure control and health-related quality of life of both patient and primary caregiver, will be prospectively measured up to 2 years postoperatively. All data will be collected electronically using Research Electronic Data Capture. Ethics and dissemination: This study was approved by the Hospital for Sick Children Research Ethics Board (REB number 1000061744). All participants, or substitute decision-makers, will provide informed consent prior to be enrolled in the study. Institutional Research Ethics Board approval will be obtained from each additional participating site prior to inclusion. This study is funded through a Canadian Institutes of Health Research grant (PJT-159561) and an investigator-initiated funding grant from LivaNova USA (Houston, TX; FF01803B IIR).Item Hydrocephalus: historical analysis and considerations for treatment(Springer, 2022) Hochstetler, Alejandra; Raskin, Jeffrey; Blazer-Yost, Bonnie L.; Biology, School of ScienceHydrocephalus is a serious condition that affects patients of all ages, resulting from a multitude of causes. While the etiologies of hydrocephalus are numerous, many of the acute and chronic symptoms of the condition are shared. These symptoms include disorientation and pain (headaches), cognitive and developmental changes, vision and sleep disturbances, and gait abnormalities. This collective group of symptoms combined with the effectiveness of CSF diversion as a surgical intervention for many types of the condition suggest that the various etiologies may share common cellular and molecular dysfunctions. The incidence rate of pediatric hydrocephalus is approximately 0.1–0.6% of live births, making it as common as Down syndrome in infants. Diagnosis and treatment of various forms of adult hydrocephalus remain understudied and underreported. Surgical interventions to treat hydrocephalus, though lifesaving, have a high incidence of failure. Previously tested pharmacotherapies for the treatment of hydrocephalus have resulted in net zero or negative outcomes for patients potentially due to the lack of understanding of the cellular and molecular mechanisms that contribute to the development of hydrocephalus. Very few well-validated drug targets have been proposed for therapy; most of these have been within the last 5 years. Within the last 50 years, there have been only incremental improvements in surgical treatments for hydrocephalus, and there has been little progress made towards prevention or cure. This demonstrates the need to develop nonsurgical interventions for the treatment of hydrocephalus regardless of etiology. The development of new treatment paradigms relies heavily on investment in researching the common molecular mechanisms that contribute to all of the forms of hydrocephalus, and requires the concerted support of patient advocacy organizations, government- and private-funded research, biotechnology and pharmaceutical companies, the medical device industry, and the vast network of healthcare professionals.Item Predictors of Seizure Freedom in Pediatric Low-Grade Gliomas(Springer Nature, 2022-11-26) Budnick, Hailey C.; Baygani, Shawyon; Easwaran, Teresa; Vortmeyer, Alexander; Jea, Andrew; Desai, Virendra; Raskin, Jeffrey; Neurological Surgery, School of MedicineObjective: Pediatric low-grade gliomas (LGGs) are found in approximately one to three percent of patients with childhood epilepsy. Epilepsy in these patients is often medically refractory and therefore represents a unique cohort with significant morbidity from concomitant pathology. Similar studies in adult patients with low-grade gliomas have identified predictors of seizure freedom including gross-total resection, preoperative seizure control on antiepileptic medication and duration of seizures of less than one year. This study aims to identify similar predictors of seizure freedom in operatively managed pediatric LGGs. Methods: A retrospective chart review was performed for patients diagnosed with World Health Organization (WHO) Grade I and II gliomas in patients ≤18 years old at a single institution (Indiana University School of Medicine at Riley Hospital for Children in Indianapolis, IN) from 2007-2017. Infratentorial and purely intraventricular lesions were excluded. WHO classification and histologic diagnosis were based on surgical pathology. Tumor grade, location, laterality, seizure status at presentation, and AED requirements pre- and post-operatively were recorded. Chi-squared analyses for independence were performed controlling for age at presentation, resection extent, seizure type, and Engel Class for seizure freedom post-operatively. Results: Forty-two patients met the inclusion criteria. Preoperative seizures were observed in 23 patients (55%). Presentation with preoperative seizures was highly associated with continued seizure burden post-operatively, independent of the extent of surgical resection. Supratentorial location and the administration of prophylactic pre- and post-operative AEDs were associated with Engel Class I seizure freedom. Temporal location was not significantly associated with medically refractory epilepsy compared with extra-temporal locations. Conclusions: In our cohort of pediatric LGGs, we find that patients that did not initially present with seizures and those who were treated with prophylactic pre- and post-operative AEDs, were more likely to achieve Engel Class I seizure freedom post-operatively. Tumors located in the temporal location were not significantly associated with a higher seizure burden than other supratentorial, extra-temporal tumors. Neither extent of resection nor electrocorticography-guided resection correlated with improved seizure freedom outcomes during glioma resection.Item Role of Choroid Plexus TRPV4 Channel in Health and Disease(2022-08) Hochstetler, Alexandra; Blazer-Yost, Bonnie L; Berbari, Nicolas; Baucum II, AJ; Roper, Randall; Raskin, JeffreyPediatric hydrocephalus is a complex neurological condition associated with a pathological accumulation of cerebrospinal fluid (CSF), typically within the brain ventricular system. Pediatric hydrocephalus can be primary (due to genetic abnormalities or idiopathic causes), or secondary to injuries such as hemorrhage, trauma, or infection. The current permanent treatment paradigms for pediatric hydrocephalus are exclusively surgical and include the diversion of CSF via shunt or ventriculostomy. These surgical interventions are wrought with failures, burdening both the United States healthcare system and patients with repeat neurosurgical procedures. Thus, the development of nonsurgical interventions to treat hydrocephalus represents a clinically unmet need. To study hydrocephalus, we use a genetic rat model of primary neonatal hydrocephalus, the Tmem67P394L mutant. In several proof-of-concept studies, we identify antagonism of the transient receptor potential vanilloid 4 (TRPV4) channel and associated upstream regulatory kinase, serum-andglucocorticoid-induced kinase 1 (SGK1) as therapeutics for the treatment of hydrocephalus. Using in vitro models of the choroid plexus epithelium, the tissue which produces CSF, we show compelling proof-of-mechanism for TRPV4 antagonism and SGK1 inhibition at preventing CSF production. Therefore, the studies in this dissertation provide substantive evidence on the role of TRPV4 in the choroid plexus in health and disease.Item Single-Institution Comparative Study of MR-guided Laser Interstitial Thermal Therapy and Open Corpus Callosotomy(Elsevier, 2023-07) Ordaz, Josue D.; Vishnubhotla, Ramana; Alfonso, Anthony; Budnick, Hailey; Wen, Qiuting; Radhakrishnan, Rupa; Raskin, Jeffrey; Neurological Surgery, School of MedicineObjective Open corpus callosotomy (CC) poses a higher risk of perioperative morbidity than does magnetic resonance–guided laser interstitial thermal therapy (MRgLITT) for treatment of drop and generalized seizures without documented superiority. We present a single-institution comparison between open and MRgLITT CC. Methods A 2-year retrospective review was performed of patients who underwent open and MRgLITT CC (January 2019–January 2021). Demographics, surgical outcome data, hospital costs, and interhemispheric connectivity with diffusion tensor imaging were compared. Results The average age in years was 9.3 and 11.4 for CC (n = 4) and MRgLITT (n = 9), respectively. Preoperative drop seizure frequency was higher in CC (25 vs. 14.5 seizures/day; P = 0.59). At 10 months follow-up, the reduction in drop seizure frequency was better in open CC, but not statistically significant (93.8% vs. 64.3%; P = 0.21). The extent of CC ablation did not correlate with seizure reduction (Pearson coefficient = 0.09). An inverse correlation between interhemispheric connectivity change (diffusion tensor imaging analysis) and drop seizure frequency reduction was noted (Pearson coefficient = –0.97). Total hospital cost was significantly lower in MRgLITT ($67,754 vs. $107,111; P = 0.004), attributed to lower intensive care unit (1.1 vs. 4 days; P= 0.004) and total hospital stay (1.8 vs. 10.5 days; P = 0.0001). Postoperative hydrocephalus was present in 75% of patients in the CC group compared with zero in the MRgLITT group. Conclusions Our middle-volume single-institution experience shows the safety, efficacy, and cost-effective benefit of MRgLITT compared with the traditional CC with therapeutic equipoise. This study is limited by the number of patients and, hence, further patient enrollment or multicenter study is warranted.Item Thermal Damage Estimate Artifact Following Antecedent Biopsy: A Case Report(Springer Nature, 2022-11-26) Bakr, Salma M.; Kantak, Pranish A.; Jimenez, Med Jimson D.; Budnick, Hailey C.; Raskin, Jeffrey; Neurological Surgery, School of MedicineMR-guided laser interstitial therapy (MRgLITT) is becoming more commonly used for minimal access approaches to intracranial lesions of all etiologies. The short-term safety profile of MRgLITT is favorable compared with sweeping incisions and open craniotomies, especially for lesions located in deep, periventricular, and highly eloquent areas. The Visualase software (Medtronic Inc., Minneapolis, MN, USA) has multiple adaptations to assist with this safety margin, including the thermal damage estimate (TDE), which applies predictive mathematical modeling to a two-dimensional (2D) graphical representation. TDE has been shown to highly correlate with actual tissue destruction in a priori MRgLITT cases and to anecdotally be imprecise when MRgLITT is combined with biopsy. We present a case regarding a 17-year-old male patient with intractable focal epilepsy. He underwent stereotactic biopsy and then ablation where it was shown that TDE is ~35% larger in the coronal plane than in the actual ablation zone. Air may have caused this artifact in the biopsy cavity, which affected the proton resonance frequency (PRF) and caused TDE pigment deposition. We believe in the need for a more comprehensive understanding and investigation regarding this TDE artifact. Future prospective studies into MRgLITT should attend carefully in cases where it is combined with biopsy.