Faculty Bibliography
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Department/Unit:Neurology
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24330
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
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
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
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
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
Predicting seizure freedom in the postpartum period: Findings from the Maternal Outcomes and Neurodevelopmental Effects of Antiepileptic Drugs study
OBJECTIVE:This study was undertaken to evaluate whether seizure freedom in pregnancy predicts seizure freedom in the postpartum period in women with epilepsy (WWE). Prior studies have shown that seizure freedom prior to conception strongly predicts seizure freedom during pregnancy. The postpartum period is considered especially vulnerable to recurrent seizures given rapid hormonal changes, shifting antiseizure medication pharmacokinetics, and disrupted sleep. There is a lack of sufficient data on whether seizure freedom during pregnancy predicts postpartum outcomes. METHODS:Pregnant WWE (aged 14-45 years) were enrolled at <20 weeks gestation in the prospective Maternal Outcomes and Neurodevelopmental Effects of Antiepileptic Drugs study. Participants completed electronic daily seizure and medication diaries with study visits each trimester, and at 6-12 weeks and 6 and 9 months postpartum. Participants also reported retrospective seizure frequency for the 9 months preconception. We used logistic regression to assess whether seizure freedom during pregnancy predicted seizure freedom postpartum, with additional analyses by seizure types. In participants with seizures during pregnancy, we evaluated median percent change in seizure frequency. RESULTS:This analysis included 331 pregnant WWE. Overall, 60.7% were seizure-free during pregnancy and 61.0% postpartum. Seizure freedom during pregnancy strongly predicted seizure freedom postpartum (odds ratio [OR] = 6.78, 95% confidence interval [CI] = 4.15-11.1, p < .0001), with a predictive value of 78% (95% CI = 72%-84%). Retrospectively reported preconception seizure freedom was also independently associated with postpartum seizure freedom (OR = 5.84, 95% CI = 3.57-9.58, p < .0001). Long-term seizure freedom during pregnancy and preconception was associated with 85% postpartum seizure freedom, whereas long-term presence of seizures was associated with only 36% postpartum seizure freedom. There were no significant differences by seizure type. Among participants with seizures during pregnancy, median postpartum seizure frequency declined by 77% (interquartile range = seizure-free to 31% reduced). SIGNIFICANCE/CONCLUSIONS:Our data demonstrated that seizure freedom during pregnancy was a robust predictor of seizure freedom during the postpartum period. These data can be used to counsel patients about seizure risk in the postpartum period.
PMID: 42159064
ISSN: 1528-1167
CID: 6038182
Common Consent Elements for Research Involving Persons with Disorders of Consciousness (CCE-DOC)
Persons with disorders of consciousness (DoC) occupy an ethically charged space in modern medicine and biomedical research. Their decisional capacity is characteristically absent or limited or unpredictably fluctuates, requiring clinicians and investigators to rely on surrogates. Although there is general guidance for informed consent (IC) for research studies, there is no specific guidance for research involving persons with DoC. There are inconsistencies in IC forms for these studies related to explanation of a DoC, evaluation of capacity, description of risks/benefits, and sharing investigational results. This is problematic for persons with DoC, their surrogates, researchers, and institutional review boards (IRBs)/research ethics boards (REBs). To address these issues, the Curing Coma Campaign (CCC) Ethics Workgroup developed the Common Consent Elements for Research Involving Persons with Disorders of Consciousness (CCE-DoC). This practical framework aims to clarify and standardize consent processes in this complex and ethically sensitive research area. Through this structured, adaptable approach, CCE-DoC may have the potential to enhance participant protections, strengthen trust, help families and decision-makers understand studies, reduce duplicative efforts across research groups, and guide investigators and IRBs/REBs in navigating the complex ethical terrain of consent in DoC research. In so doing, CCE-DoC seeks to extend respect for autonomy and trust and promote responsible research urgently needed to advance paradigms of diagnosis, prognosis, and treatment for individuals with disorders of consciousness. The framework offers example language to encourage standardization, while allowing teams flexibility to customize to local needs.
PMID: 42156702
ISSN: 1556-0961
CID: 6038132
A systematic review on pharmacotherapy of post-traumatic attention impairments
BACKGROUND/UNASSIGNED:Attention impairment is common in post-traumatic brain injury. We synthesized evidence on pharmacological treatments for adults with attention deficits in the acute-to-chronic phases. METHODS/UNASSIGNED:We searched Ovid MEDLINE and Cochrane Library (1946-December 2024). Two reviewers screened studies, extracted data, and assessed study quality. Risk of bias was assessed using the Cochrane Risk of Bias tool and the PEDro scale for RCTs. Levels of evidence (LoE) were determined by the Sackett framework. RESULTS/UNASSIGNED:Twenty-nine studies met inclusion criteria across five drug classes and 14 medications. Results of LoE 1 were mixed: Methylphenidate improved classroom attention/processing speed, and exhibited neutral outcome; amantadine showed no improvement (LoE 1, 4, 5). MLC901 (a multi-herb antioxidant) improved complex attention (LoE 1). Donepezil improved sustained (LoE 1) and divided attention (LoE 4). Physostigmine/lecithin (LoE 1) and antidepressants (LoE 1, 3, 5) had mixed effects; growth hormone (LoE 4), and L-carnitine (LoE 1) showed no effect. Anticonvulsants impaired cognition (LoE 1). CONCLUSION/UNASSIGNED:Methylphenidate showed the strongest evidence at lower doses. Donepezil and MLC901 showed potential benefits. Phenytoin and carbamazepine showed adverse effects on cognition. Standardized attention outcome measures and other high-quality alternative clinical trials with larger study samples are recommended to overcome the current limitations.
PMID: 42165308
ISSN: 1362-301x
CID: 6038472
Word finding difficulties in multiple sclerosis and its relation to cognitive impairment, fatigue and depression
INTRODUCTION/BACKGROUND:Although word-finding difficulties (WFD) are prevalent in multiple sclerosis (MS), they remain poorly understood. This cross-sectional study aimed to identify several important practical and theoretical challenges, including key knowledge gaps related to understanding and measuring aspects of language deficit in MS (i.e., WFD). Further investigations of possible correlates of deficits with other symptoms of MS (i.e., such as depression, fatigue and cognitive impairment) were also carried out as part of this study to find out if WFD is a standalone symptom or is a part of a broader and complex symptom of MS. METHODS:In this cohort study, all data from 586 consecutive Persons with MS (PwMS) (137 males and 449 females), with a mean age of 47.1 (SD±10.34) and a median EDSS score of 2.0, were included. A standardized naming task was used as part of a computerized cognitive assessment battery (CAB, NeuroTrax™) with computer-based administration and off-site scoring that has been validated for use in PwMS to determine the associations between cognitive impairment (CI), fatigue, and depression in WFD. RESULTS:A significant correlation (r = 0.327) was noted in this study between cognitive impairment and WFD (p < 0.001). PwMS with CI had a higher rate of WFD (i.e., 43.2%) as compared to individuals with WFD despite not having CI (i.e., 13.9%). Disability (EDSS), disease duration, depression and fatigue, were not correlated with WFD. CONCLUSION/CONCLUSIONS:WFD are most likely part of a larger underlying problem (i.e., CI), but there is a small group of persons with MS and WFD who have isolated WFD. Findings of this study have implications for activities of daily living (ADLs) and therapy for rehabilitation professionals working with PwMS.
PMID: 42155383
ISSN: 2211-0356
CID: 6038062
Evaluating OCR performance for assistive technology: effects of walking speed, camera placement, and camera type
PURPOSE/UNASSIGNED:Optical character recognition (OCR), a process that converts printed or handwritten text into machine-readable form, is widely used in assistive technology for people with blindness and low vision. Yet most evaluations rely on static datasets that do not reflect the challenges of mobile use. This study evaluated how OCR performance changes under static and walking conditions relevant to real-world navigation. METHODS/UNASSIGNED:Static tests varied distance from 1-7 metres and viewing angle from 0°-75°. Dynamic tests examined the impact of motion by varying walking speed from 0.8 m/s to 1.8 m/s and compared head-mounted, shoulder-mounted, and handheld positions. We evaluated a smartphone and smart glasses, including the phone's main and ultra-wide cameras, across four OCR engines: Google Vision, PaddleOCR 3.0, EasyOCR, and Tesseract. Dynamic tests used PaddleOCR 3.0. Accuracy was computed at the character level using the Levenshtein ratio against manually defined ground truth. RESULTS/UNASSIGNED:Recognition accuracy declined with increased walking speed and wider viewing angles. Google Vision achieved the highest overall accuracy, with PaddleOCR close behind as the strongest open-source alternative. Across devices, the phone's main camera achieved the highest accuracy, and a shoulder-mounted placement yielded the highest average among body positions; however, differences among shoulder, head, and hand were not statistically significant. CONCLUSION/UNASSIGNED:OCR performance depends on the recognition engine, camera hardware, field of view, device placement, and user motion. OCR systems for navigation should be evaluated under dynamic, mobility-relevant conditions rather than static images alone and designed to balance coverage, recognition accuracy, and practical deployment.
PMID: 42154989
ISSN: 1748-3115
CID: 6038042
