Faculty Bibliography
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Department/Unit:Neurology
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24267
Machine Learning-Based Prediction of Independent Ambulation Following Intramedullary Spinal Cord Tumor Resection
BACKGROUND AND OBJECTIVES/OBJECTIVE:Intramedullary spinal cord tumor (IMSCT) resection carries a high risk of postoperative neurological deficit because of neural tract manipulation and myelotomy. Although short-term and long-term neurological recovery represent key treatment outcomes, current prognostication methods are lacking and would benefit from further complex analysis. METHODS:From March 2009 to August 2025, all adult IMSCT resections at our institution were reviewed. Demographic, oncologic, and perioperative data were extracted from electronic medical records. This included preoperative and follow-up neurological examination data in the form of American Spinal Injury Association Impairment Scale (AIS) grading, Modified McCormick Scale (MMCS), and ambulatory status. Independent ambulation served as the primary outcome for 4 machine learning models. Each model was sequentially evaluated using area under the receiver operating characteristic curve (AUROC). RESULTS:Fifty-four patients underwent 55 surgeries for IMSCT resection. Encapsulated lesions predominated IMSCT pathology, with grade II ependymoma comprising 28 (50.9%) resections, 5 hemangioblastomas (9.1%), and 5 cavernous hemangiomas (9.1%). Gross total resection was achieved in 36 cases (65.5%), with encapsulated tumors more readily achieving gross total resection vs unencapsulated (84.6% vs 18.8%, P < .01). By 4 weeks, conversion of MMCS, but not AIS grade, significantly correlated with concurrent ambulatory conversion (P < .01 vs P = .15). At 6 months, both AIS grade conversion (P < .01) and MMCS conversion (P < .01) significantly correlated with ambulatory conversion. For predicting ambulation at latest follow-up from 4 weeks postoperatively, the comprehensive granular model achieved an AUROC of 0.833, outperforming the AIS grade (0.583), American Spinal Injury Association Motor Score (0.667), and MMCS (0.667) models. By the 6-month follow-up, the comprehensive granular model achieved strong discrimination (AUROC 1.00). CONCLUSION/CONCLUSIONS:Follow-up IMSCT data demonstrate a postoperative lability that stabilizes by 6 months into a reliably modeled outcome. By enhancing the granularity of recovery data, accurate independent ambulation modeling may improve counseling for patients with IMSCT.
PMID: 42240329
ISSN: 1524-4040
CID: 6044392
Hippocampal Long Axis Differentiation in Memory and Seizure Networks
The structure-function gradient along the hippocampal long axis is recognized but poorly understood. Rodent recordings mainly sample the dorsal hippocampus (posterior), while surgical recordings in epilepsy patients typically sample from the ventral hippocampus (anterior), because of greater known involvement in seizure networks. These divergent recording practices imply that the mechanisms of rodent spatial navigation may not directly apply to human episodic memory. In general, the role of the posterior hippocampus in human memory and seizure networks is under-appreciated. We survey the basic, translational, and clinical research accounting for long-axis differentiation and outline future research directions.
PMCID:13229910
PMID: 42245820
ISSN: 1535-7597
CID: 6044632
On-site exposure to clinical epilepsy practice for experimental scientists engaged in epilepsy research: A pilot study by the ILAE commission on neurobiology
Educational initiatives that address the gap between basic/preclinical and clinical practices are important to effectively translate basic science discoveries to benefit patients. The ILAE Neurobiology Commission conducted a pilot project aimed at exposing basic and preclinical scientists engaged in epilepsy research to general clinical issues pertaining to the diagnosis and care of people with epilepsy. This aim was addressed through a two-week-long, on-site clinical training program for 50 basic scientists in 21 epilepsy centers across 18 countries in the six ILAE regions (with a maximum of 3 basic scientists per center). The learning objectives and the training module were discussed and defined by the project organizing committee, which consisted of Neurobiology Commission members and a team of epileptologists representing different geographical regions. The training activities were conducted at each epilepsy center under the local supervision of clinical tutors. Each basic scientist was exposed to 50.3 ± 23.3 (range 16-89) hours of intensive and dedicated clinical training, coordinated by 2-3 tutors per center, assisted by 6.8 ± 3.6 colleagues. A structured test consisting of 17 general clinical epilepsy questions was completed by the trainees before and after the training activity. The learning assessment was based on the comparison between responses to the exit and entry tests. After the on-site clinical exposure, the proportion of correct answers increased to 87% compared to 61% in the entry test. Structured post-training questionnaires demonstrated very high satisfaction of trainees and all involved tutors across the different aspects of the training module. This global pilot study demonstrated that on-site attendance by basic scientists in specialized clinical settings up-scaled their knowledge of clinical epileptology and facilitated networking with clinicians. Expansion of this pilot to further centers should be considered to understand how exposure to clinical practice affects research direction and quality of translational epilepsy research. PLAIN LANGUAGE SUMMARY: Epilepsy research has long benefitted from collaboration between scientists and clinicians. Early exposure of researchers to people with epilepsy and their care teams may strengthen future impact. This pilot study tested a two-week immersive experience where small teams of basic scientists shadowed clinicians during their work at hospitals around the world. Questionnaires showed high satisfaction among both groups. Results support expanding such training, with the backing of the International League Against epilepsy and aligned centers, to build understanding, interest, and long-term commitment, ensuring bench research is informed by and translates to clinical practice and improved quality of life for patients.
PMID: 42220231
ISSN: 2470-9239
CID: 6043402
Markerless 3D hand tracking for analysis of pediatric eye-hand coordination
Precise quantification of eye-hand coordination (EHC) during pediatric dexterity tasks is limited by the lack of practical, high-resolution hand tracking methods suitable for children with brain injury or neurodegenerative disease. Traditional marker-based motion capture systems and instrumented gloves can interfere with natural grasp patterns and are often difficult to implement in clinical pediatric settings. We describe an adaptation of the Anipose markerless 3D pose estimation framework to enable synchronized three-dimensional hand kinematics and eye tracking during the Nine-Hole Peg Test (9HPT). The method integrates multi-camera video acquisition with task-specific neural network training optimized to detect fine finger movements across diverse pediatric hand sizes and grasp configurations. Camera placement and recording geometry were configured to reduce occlusion during peg manipulation and maintain multi-view visibility of hand landmarks. Model validation demonstrated low pixel error and stable three-dimensional reconstruction following confidence-based thresholding. The resulting workflow generates synchronized 2D and 3D visualizations, spatial coordinate outputs, reprojection-error metrics, and landmark confidence scores without requiring wearable sensors. This approach broadens the applicability of eye-hand coordination research within pediatric clinical populations and facilitates the development of more precise, quantitatively informed diagnostic assessments and targeted neurorehabilitation strategies for children with neurologic injury. • Markerless multi-camera 3D reconstruction of pediatric hand kinematics during the 9HPT • Integration of synchronized eye tracking and task-specific neural network training • Output of validated 3D coordinates, confidence metrics, and visualization files suitable for clinical research.
PMCID:13231014
PMID: 42244785
ISSN: 2215-0161
CID: 6044592
Subthalamic versus Posterior Subthalamic Stimulation for Optimal Tremor Control in Parkinson's Disease
UNLABELLED:<p>Introduction: Tremor-predominant Parkinson's disease (TPPD) generally responds favorably to deep brain stimulation (DBS) targeting the subthalamic nucleus (STN). However, traditional stereotactic targeting of the STN does not universally yield the anticipated intraoperative improvement, prompting exploration of additional targets to achieve optimal results prior to permanent implantation of electrodes. The posterior subthalamic area (PSA), including the caudal zona incerta (cZI), have been associated with tremor suppression and can be easily compared to the neighboring STN intraoperatively. METHODS:We retrospectively compared intraoperative and clinical outcomes in tremor-dominant PD patients who prospectively underwent dual trajectory microelectrode monitor targeting the STN and PSA/cZI. We compared the neurophysiology and tremor response of both the central (STN) and posterior (PSA) trajectories in 22 patients and analyzed outcomes in those who ultimately received traditional STN (16) or PSA/cZI lead implantation (12). RESULTS:While both groups achieved substantial overall motor improvement under chronic stimulation, intraoperative test stimulation through the posterior path produced more consistent tremor arrest compared with STN. These findings suggest that positioning the DBS lead further posteriorly to engage the PSA can augment tremor suppression in select cases of TPPD without compromising other parkinsonian symptom relief. CONCLUSION/CONCLUSIONS:Our results emphasize the value of intraoperative physiological feedback in trajectory selection in tremor-predominant patients and are consistent with emerging literature that PSA/cZI DBS is an effective and potentially superior target for management of tremor in PD. </p>.
PMCID:12810967
PMID: 41411220
ISSN: 1423-0372
CID: 6043352
Investigating the analytical robustness of the social and behavioural sciences
The same dataset can be analysed in different justifiable ways to answer the same research question, potentially challenging the robustness of empirical science1-3. In this crowd initiative, we investigated the degree to which research findings in the social and behavioural sciences are contingent on analysts' choices. We examined a stratified random sample of 100 studies published between 2009 and 2018, in which, for one claim per study, at least five reanalysts independently reanalysed the original data. The statistical appropriateness of the reanalyses was assessed in peer evaluations, and the robustness indicators were inspected along a range of research characteristics and study designs. We found that 34% of the independent reanalyses yielded the same result (within a tolerance region of ±0.05 Cohen's d) as the original report; with a four times broader tolerance region, this indicator increased to 57%. Of the reanalyses conducted, 74% reached the same conclusion as the original investigation, 24% yielded no effects or inconclusive results and 2% reported the opposite effect. This exploratory study indicates that the common single-path analyses in social and behavioural research should not be simply assumed to be robust to alternative analyses4. Therefore, we recommend the development and use of practices to explore and communicate this neglected source of uncertainty.
PMID: 41922703
ISSN: 1476-4687
CID: 6041172
Trends in Vascular Risk Factor Control Among US Adults With Prior Stroke: 1999 to 2023
BACKGROUND:Management of modifiable risk factors is key in the prevention of recurrent stroke. We investigated trends in vascular risk factors (hyperglycemia, hyperlipidemia, hypertension, and smoking) control among US adults with stroke. METHODS:, low-density lipoprotein, and blood pressure and prevalence of meeting each recommended target were calculated for each epoch (1999 through 2002, 2003 through 2006, 2007 through 2010, 2011 through 2014, 2015 through 2020, and 2021 through 2023). RESULTS:-trend=0.002). The prevalence of meeting smoking and blood pressure guidelines was stable. Fewer than 10% of individuals met guidelines for all 4 risk factors over the study. CONCLUSIONS:In this nationally representative sample of US adults with stroke, <10% met guideline recommendations for all risk factors with an overall stable trend. These results suggest that efforts aimed at glycemia, blood pressure, and lipid control and smoking cessation could be improved to reduce the burden of recurrent stroke.
PMID: 42179268
ISSN: 2047-9980
CID: 6039212
Neocortical tau burden determines the degree of cognitive impairment in individuals with Braak stage V neurofibrillary degeneration
Alzheimer disease neuropathologic change (ADNC) is considered to be the most common cause of cognitive decline and dementia worldwide. ADNC level is determined using the density of neuritic plaques in combination with the topographical distribution of β-amyloid (Aβ) plaques and hyperphosphorylated tau (p-tau)-positive neurofibrillary tangles (NFTs). While cognitive decline correlates with the level of ADNC, there remains a great deal of variation in cognitive outcomes between individuals that is unaccounted for by current neuropathologic evaluation metrics. We leveraged quantitative computer-assisted positive pixel assessments to establish the neocortical p-tau burden in the middle frontal and superior temporal gyri of 61 individuals with Braak NFT stage V who had a wide range of cognitive outcomes and trajectories. Frontal and temporal neocortical p-tau burden varied between 0.2% and 53.7%. Both frontal and temporal p-tau burden directly affected cognitive outcome and correlated with function of multiple cognitive domains, including measures of language/semantic memory and attention/working memory. In multivariable analysis, only p-tau burden and microinfarcts significantly impacted cognitive decline, while Aβ, limbic-predominant age-related TDP-43 encephalopathy, Lewy body pathology, and other measures of cerebrovascular disease did not. Additionally, individuals with low mean neocortical p-tau burden (≤ 13%) had significantly better longitudinal cognitive trajectories over the final 15 years of life compared to those with high burden (≥ 23.5%). These results suggest that while all individuals with Braak stage V have some degree of neurofibrillary degeneration in the neocortex, the significant variation in cognitive decline observed between these individuals can be partially understood as a reflection of the variation in quantitatively assessed neocortical p-tau burden, which had a greater impact on progression to dementia than common comorbid neuropathologies associated with dementia risk. This argues for the incorporation of the density of ADNC-related pathology, in addition to its regional location, as an adjunct to future staging systems for Alzheimer disease.
PMCID:13201366
PMID: 42184025
ISSN: 1432-0533
CID: 6039352
Prenatal Substance Exposure and Birth Weight: Findings From the HEALthy Brain and Child Development Study
OBJECTIVE:To estimate associations of more than minimal prenatal nicotine, alcohol, cannabis, and opioid exposures with gestational age, birth weight, and birth weight for gestational age. METHODS:Data were drawn from the HEALthy Brain and Child Development (HBCD) Study, a multisite, longitudinal study in the United States. Predefined recruitment thresholds for each substance were assessed using maternal self-report, maternal toxicology results, and newborn substance exposure-related diagnoses. Birth outcomes included gestational age at delivery (weeks), birth weight (grams), and birth weight for gestational age (centiles). Mean differences and risk ratios for the associations between substance exposure and birth outcomes were estimated using multilevel mixed-effect linear regression or multilevel mixed-effect Poisson regression. RESULTS:Among 660 mother-infant dyads, 17% (n = 115) of participants met recruitment thresholds for prenatal cannabis, 15% for nicotine (n = 102), 13% for alcohol (n = 86), and 5% for opioids (n = 32). In adjusted models, prenatal cannabis and opioid exposures were each associated with lower birth weight (cannabis: -272.2 [95% CI -444.6 to -99.8] g; opioids: -295.4 [95% CI -574.9 to -15.9] g) and birth weight centiles (cannabis: -8.2 [95% CI -15.3 to -1.1] centiles; opioids: -14.4 [95% CI -25.5, -3.4] centiles), although the results were sensitive to model specifications. Prenatal nicotine and alcohol estimates were in similar directions but not statistically significant. No significant associations between exposures and gestational age at delivery were detected. CONCLUSIONS:In this initial HBCD Study data release, more than minimal exposure to cannabis and opioids was associated with smaller birth size, adding evidence to an inconsistent literature. Future studies from HBCD can more deeply interrogate timing and dose of each substance and expand to childhood outcomes.
PMID: 42184970
ISSN: 1098-4275
CID: 6039422
Hemispherotomy for Drug-Resistant Epilepsy in a Low-Resource Setting: Surgical Outcomes and Quality of Life in 23 Children Treated in a Hybrid Program in Panama
INTRODUCTION/BACKGROUND:Hemispherotomy is an effective treatment for children with drug-resistant epilepsy (DRE). While hemispherotomy techniques and indications have evolved, access remains predominantly constrained to high-resource settings. METHODS:We performed a retrospective analysis of children who underwent hemispherotomy from 2011 to 2023 by a hybrid team, including local Panamanian and US neurologists, neurosurgeons, and EEG technicians and analyzed surgical, epilepsy, and quality of life (QoL) parameters. Follow-up data were collected according to the International Consortium for Health Outcomes Measurement (ICHOM) guidelines for children with epilepsy. RESULTS:Twenty-three children underwent hemispherotomy. The median age at surgery was 10 years (range 2-20). The median follow-up time was 6 years (range 1-13). The etiology of DRE included malformations of cortical development in 14 children (60.8%), including 8 (34.8%) with schizencephaly, and secondary causes in 9 children (39.1%). Seizure frequency improved for all 23 children (100%): Engel I was achieved in 15 children (65.2%), Engel II (26.1%) in six children, and Engel III (8.7%) in two children. Patients with seizure freedom had significantly fewer preoperative seizures per day than patients with seizure recurrence. Complications occurred in six children (26.1%): 2 wound infections, 2 meningitis, 1 femoral vein thrombosis, and 1 wound hematoma with return to OR. There were no perioperative mortality and no postoperative hydrocephalus or CSF diversion. QoL-related outcomes were available for 16 children: 16/16 (100%) reported that the surgery was a worthwhile and repeatable choice, 14 (87.5%) reported improved cognitive function, the median QOLCE-16 score was 62.5 ± 21. CONCLUSION/CONCLUSIONS:Hemispherotomy for DRE in selected children is a safe and effective surgery in a public children's hospital in a low-resource setting. At last follow-up, the majority of children were seizure-free, and all children had decreased seizure frequency. Families reported improved cognitive function, improved QoL and high satisfaction with their decision to pursue this surgery.
PMCID:13218697
PMID: 41037508
ISSN: 1423-0305
CID: 6039162
