Faculty Bibliography
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Department/Unit:Neurology
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24309
Quantitative Analysis of Parenchymal Effects and Flow of Large Arteriovenous Malformations Managed With Stereotactic Radiosurgery
BACKGROUND AND OBJECTIVES/OBJECTIVE:Stereotactic radiosurgery (SRS) of larger arteriovenous malformations (AVM) is associated with an elevated incidence of adverse radiation effects (ARE). To date, volume-response and dose-response models have been used to predict such effects. To understand radiological outcomes and their hemodynamic effects on the regional brain. METHODS:A retrospective analysis was conducted at our institution using a prospective registry of patients managed between 2014 and 2020. We included patients with AVM with a nidus larger than 5 cc who received either single-session or volume-staged Gamma Knife radiosurgery. AVM volume changes, volumes of parenchymal response, and obliteration were analyzed and correlated with transit times and diameters of feeding arteries and draining veins. RESULTS:Sixteen patients underwent single-session SRS, and 9 patients underwent volume-staged SRS. The average AVM volume was 12.6 cc (5.5-23). The AVM locations were predominantly lobar (80%) and 17 (68%) were in critical locations. The mean margin dose was 17.2 Gy (15-21), and the median V12Gy was 25.5 cc. Fourteen (56%) AVMs had a transit time shorter than 1 second. The median vein-artery ratio (sum diameter of the veins/sum diameter of feeding arteries) was 1.63 (range, 0.60-4.19). Asymptomatic parenchymal effects were detected in 13 (52%) patients and were symptomatic in 4 (16%) patients. The median time to ARE was 12 months (95% CI 7.6-16.4). On univariate analysis, significant predictors of ARE were lower vein-artery ratio (P = .024), longer transit time (P = .05), higher mean dose (P = .028), and higher D95 (P = .036). CONCLUSION/CONCLUSIONS:Transit times and vessel diameters are valuable predictors of the subsequent parenchymal response after SRS. A more quantitative understanding of blood flow is critical for predicting the effects on the regional brain after AVM radiosurgery.
PMID: 37235978
ISSN: 1524-4040
CID: 5508662
Hand Dexterity Improves in Patients with Progressive Multiple Sclerosis (MS) with Telerehabilitation Using Transcranial Direct Current Stimulation (tDCS) [Meeting Abstract]
Abstract Background: Loss of hand dexterity is disabling and reduces quality of life. People living with progressive forms of MS have marked neurologic disabilities but limited rehabilitation options. Transcranial direct current stimulation (tDCS) is a method of noninvasive brain stimulation in which stimulation delivered during motor training can strengthen outcomes. We have established a remotely supervised tDCS (RS-tDCS) protocol that delivers multiple stimulation sessions paired with training to participants at home.
Objective(s): To evaluate a blinded randomized sham-controlled clinical trial of active vs. sham tDCS paired with manual dexterity training for people with progressive MS.
Method(s): We recruited right-hand dominant individuals with progressive MS and hand dexterity impairment. Participants completed 20 sessions of daily (M-F) manual dexterity and were randomized to either active (2.0 mA) or sham primary motor cortex (M1-SO) tDCS. Manual dexterity was measured with the Nine-Hole Peg Test (9HPT) and Dellon-Modified Moberg Pick-Up test (MMPUT) at baseline and study end and transformed to normative z-scores for comparison.
Result(s): Participants were n=60 with primary (32%) or secondary (68%) progressive MS (52% female, ages 37-72 years, and a median Expanded Disability Status Scale (EDSS) score of 5.0 [1.5-7.5]). The intervention was safe and well tolerated, with n=59/60 (98%) completing 18/20 daily sessions. Combining hands and tasks, the full group improved following the manual dexterity training (mean z-score improvement 1.64+/-9.53, p=0.016). Active tDCS led to greater improvement (mean z-score improvement 4.51+/-8.78, p=0.001). Analyzing those with right- or left-hand impairment at baseline, the active tDCS group had significant improvement on the 9HPT (Right: p=0.036, Left: p=0.028) and trended towards significant improvement for the MMPUT (Right: p=0.071, Left: p=0.079).
Conclusion(s): At-home manual dexterity training paired with tDCS is a safe, tolerable, and feasible intervention for people with progressive MS and hand impairment. Training outcomes are augmented with simultaneous M1-SO tDCS. Research Category and Technology and Methods Clinical Research: 9. Transcranial Direct Current Stimulation (tDCS) Keywords: tDCS, motor training, multiple sclerosis, teleintervention
Copyright
Objective(s): To evaluate a blinded randomized sham-controlled clinical trial of active vs. sham tDCS paired with manual dexterity training for people with progressive MS.
Method(s): We recruited right-hand dominant individuals with progressive MS and hand dexterity impairment. Participants completed 20 sessions of daily (M-F) manual dexterity and were randomized to either active (2.0 mA) or sham primary motor cortex (M1-SO) tDCS. Manual dexterity was measured with the Nine-Hole Peg Test (9HPT) and Dellon-Modified Moberg Pick-Up test (MMPUT) at baseline and study end and transformed to normative z-scores for comparison.
Result(s): Participants were n=60 with primary (32%) or secondary (68%) progressive MS (52% female, ages 37-72 years, and a median Expanded Disability Status Scale (EDSS) score of 5.0 [1.5-7.5]). The intervention was safe and well tolerated, with n=59/60 (98%) completing 18/20 daily sessions. Combining hands and tasks, the full group improved following the manual dexterity training (mean z-score improvement 1.64+/-9.53, p=0.016). Active tDCS led to greater improvement (mean z-score improvement 4.51+/-8.78, p=0.001). Analyzing those with right- or left-hand impairment at baseline, the active tDCS group had significant improvement on the 9HPT (Right: p=0.036, Left: p=0.028) and trended towards significant improvement for the MMPUT (Right: p=0.071, Left: p=0.079).
Conclusion(s): At-home manual dexterity training paired with tDCS is a safe, tolerable, and feasible intervention for people with progressive MS and hand impairment. Training outcomes are augmented with simultaneous M1-SO tDCS. Research Category and Technology and Methods Clinical Research: 9. Transcranial Direct Current Stimulation (tDCS) Keywords: tDCS, motor training, multiple sclerosis, teleintervention
Copyright
EMBASE:2022769993
ISSN: 1876-4754
CID: 5511542
Safety and Immunogenicity of Radiation-Attenuated PfSPZ Vaccine in Equatoguinean Infants, Children, and Adults
The radiation-attenuated Plasmodium falciparum sporozoites (PfSPZ) Vaccine has demonstrated safety and immunogenicity in 5-month-old to 50-year-old Africans in multiple trials. Except for one, each trial has restricted enrollment to either infants and children or adults < 50 years old. This trial was conducted in Equatorial Guinea and assessed the safety, tolerability, and immunogenicity of three direct venous inoculations of 1.8 × 106 or 2.7 × 106 PfSPZ, of PfSPZ Vaccine, or normal saline administered at 8-week intervals in a randomized, double-blind, placebo-controlled trial stratified by age (6-11 months and 1-5, 6-10, 11-17, 18-35, and 36-61 years). All doses were successfully administered. In all, 192/207 injections (93%) in those aged 6-61 years were rated as causing no or mild pain. There were no significant differences in solicited adverse events (AEs) between vaccinees and controls in any age group (P ≥ 0.17). There were no significant differences between vaccinees and controls with respect to the rates or severity of unsolicited AEs or laboratory abnormalities. Development of antibodies to P. falciparum circumsporozoite protein occurred in 67/69 vaccinees (97%) and 0/15 controls. Median antibody levels were highest in infants and 1-5-year-olds and declined progressively with age. Antibody responses in children were greater than in adults protected against controlled human malaria infection. Robust immunogenicity, combined with a benign AE profile, indicates children are an ideal target for immunization with PfSPZ Vaccine.
PMID: 37160281
ISSN: 1476-1645
CID: 5509312
Author Correction: Global dietary quality in 185 countries from 1990 to 2018 show wide differences by nation, age, education, and urbanicity (Nature Food, (2022), 3, 9, (694-702), 10.1038/s43016-022-00594-9)
EMBASE:2021228968
ISSN: 2662-1355
CID: 5513812
Headache clinicians' perspectives on the remote monitoring of patients' electronic diary data: A qualitative study
OBJECTIVE:We assessed headache clinicians' viewpoints on potential remote access to patients' digital headache diary data and the practicalities of data utilization. BACKGROUND:With the ubiquitous nature of electronic medical records and the existence of remote monitoring (RM) for many medical conditions, there is now the potential for remote symptom monitoring for patients with headache disorders. While patients are asked to utilize headache diaries, clinicians may or may not have access to the data before patient visits, and their perspectives regarding this emerging technology are currently unknown. METHODS:After recruiting participants from the National Institutes of Health Pain Consortium Network, the American Headache Society Special Interest Section listservs, and Twitter and Facebook social media platforms, we conducted 20 semi-structured qualitative interviews of headache providers across the United States from various types of institutions and asked them their perspectives on remote access to patient headache diary data. We transcribed the interviews, which were then coded by two independent coders. Themes and sub-themes were developed using inductive content analysis. RESULTS:All clinicians felt the RM data needed to be integrated into the electronic medical record. Six themes emerged from the interviews: (i) Clinician perspectives on how RM could be beneficial but at other times could create obstacles/challenges, (ii) operationally, data integration could benefit headache care, (iii) there should be initial logistical considerations for bringing RM into clinical care, (iv) education may need to be provided to both patients and clinicians, (v) there are likely research benefits associated with RM, and (vi) additional suggestions for considering potential integration of RM into practice. CONCLUSIONS:While headache clinicians had mixed opinions on the benefits/challenges that RM presents to patient care, patient satisfaction, and visit time, new ideas emerged that may help advance the field.
PMID: 37313636
ISSN: 1526-4610
CID: 5506912
A brain-based definition of death and criteria for its determination after arrest of circulation or neurologic function in Canada: a 2023 clinical practice guideline
This 2023 Clinical Practice Guideline provides the biomedical definition of death based on permanent cessation of brain function that applies to all persons, as well as recommendations for death determination by circulatory criteria for potential organ donors and death determination by neurologic criteria for all mechanically ventilated patients regardless of organ donation potential. This Guideline is endorsed by the Canadian Critical Care Society, the Canadian Medical Association, the Canadian Association of Critical Care Nurses, Canadian Anesthesiologists' Society, the Canadian Neurological Sciences Federation (representing the Canadian Neurological Society, Canadian Neurosurgical Society, Canadian Society of Clinical Neurophysiologists, Canadian Association of Child Neurology, Canadian Society of Neuroradiology, and Canadian Stroke Consortium), Canadian Blood Services, the Canadian Donation and Transplantation Research Program, the Canadian Association of Emergency Physicians, the Nurse Practitioners Association of Canada, and the Canadian Cardiovascular Critical Care Society.
PMID: 37131020
ISSN: 1496-8975
CID: 5503012
What does "brainstem death" mean? A review of international protocols
PURPOSE:The term "brainstem death" is ambiguous; it can be used to refer either exclusively to loss of function of the brainstem or loss of function of the whole brain. We aimed to establish the term's intended meaning in national protocols for the determination of brain death/death by neurologic criteria (BD/DNC) from around the world. METHODS:Of 78 unique international protocols on determination of BD/DNC, we identified eight that referred exclusively to loss of function of the brainstem in the definition of death. Each protocol was reviewed to ascertain whether it 1) required assessment for loss of function of the whole brain, 2) required assessment only for loss of function of the brainstem, or 3) was ambiguous about whether loss of function of the higher brain was required to declare DNC. RESULTS:Of the eight protocols, two (25%) required assessment for loss of function of the whole brain, three (37.5%) only required assessment for loss of function of the brainstem, and three (37.5%) were ambiguous about whether loss of function of the higher brain was required to declare death. The overall agreement between raters was 94% (κ = 0.91). CONCLUSIONS:There is international variability in the intended meaning of the terms "brainstem death" and "whole brain death" resulting in ambiguity and potentially inaccurate or inconsistent diagnosis. Regardless of the nomenclature, we advocate for national protocols to be clear regarding any requirement for ancillary testing in cases of primary infratentorial brain injury who may fulfill clinical criteria for BD/DNC.
PMID: 37131037
ISSN: 1496-8975
CID: 5503022
Flexible, high-resolution cortical arrays with large coverage capture microscale high-frequency oscillations in patients with epilepsy
OBJECTIVE:Effective surgical treatment of drug-resistant epilepsy depends on accurate localization of the epileptogenic zone (EZ). High-frequency oscillations (HFOs) are potential biomarkers of the EZ. Previous research has shown that HFOs often occur within submillimeter areas of brain tissue and that the coarse spatial sampling of clinical intracranial electrode arrays may limit the accurate capture of HFO activity. In this study, we sought to characterize microscale HFO activity captured on thin, flexible microelectrocorticographic (μECoG) arrays, which provide high spatial resolution over large cortical surface areas. METHODS:We used novel liquid crystal polymer thin-film μECoG arrays (.76-1.72-mm intercontact spacing) to capture HFOs in eight intraoperative recordings from seven patients with epilepsy. We identified ripple (80-250 Hz) and fast ripple (250-600 Hz) HFOs using a common energy thresholding detection algorithm along with two stages of artifact rejection. We visualized microscale subregions of HFO activity using spatial maps of HFO rate, signal-to-noise ratio, and mean peak frequency. We quantified the spatial extent of HFO events by measuring covariance between detected HFOs and surrounding activity. We also compared HFO detection rates on microcontacts to simulated macrocontacts by spatially averaging data. RESULTS:We found visually delineable subregions of elevated HFO activity within each μECoG recording. Forty-seven percent of HFOs occurred on single 200-μm-diameter recording contacts, with minimal high-frequency activity on surrounding contacts. Other HFO events occurred across multiple contacts simultaneously, with covarying activity most often limited to a .95-mm radius. Through spatial averaging, we estimated that macrocontacts with 2-3-mm diameter would only capture 44% of the HFOs detected in our μECoG recordings. SIGNIFICANCE/CONCLUSIONS:These results demonstrate that thin-film microcontact surface arrays with both highresolution and large coverage accurately capture microscale HFO activity and may improve the utility of HFOs to localize the EZ for treatment of drug-resistant epilepsy.
PMID: 37150937
ISSN: 1528-1167
CID: 5503242
Common Chronic Daily Headaches in Pediatrics
[S.l.] : Springer International Publishing, 2023
pp. 67-80
ISBN: 9783031139307
CID: 5500732
Disparities associated with Medicare Part D Star Ratings measures among patients with Alzheimer's disease and related dementias
The Medicare Parts C and D Star Ratings system was established to improve care quality in Medicare. Previous studies reported racial/ethnic disparities in the calculation of medication adherence measures of Star Ratings in patients with diabetes, hypertension, and hyperlipidemia. This study aimed to identify possible racial/ethnic disparities in the calculation of adherence measures of Medicare Part D Star Ratings among patients with Alzheimer's disease and related dementias (ADRD) and diabetes, hypertension, or hyperlipidemia. This retrospective study analyzed the 2017 Medicare data and Area Health Resources Files. Non-Hispanic White (White) patients were compared to Black, Hispanic, Asian/Pacific Islander (Asian), and other patients on their likelihood of being included in the calculation of adherence measures for diabetes, hypertension, and/or hyperlipidemia. To adjust for the individual/community characteristics, logistic regression was used when the outcome is the inclusion in the calculation of one adherence measure; multinomial regression was used when examining the inclusion in the calculation of multiple adherence measures. Analyzing the data of 1438,076 Medicare beneficiaries with ADRD, this study found that Black (adjusted odds ratio, or OR = 0.79, 95% confidence interval, or 95% CI = 0.73-0.84) and Hispanic (OR = 0.82, 95% CI = 0.75-0.89) patients were less likely than White patients to be included in the calculation of adherence measure for diabetes medications. Further, Black patients were less likely to be included in the calculation of the adherence measure for hypertension medications than White patients (OR = 0.81, 95% CI = 0.78-0.84). All minorities were less likely to be included in calculating the adherence measure for hyperlipidemia medications than Whites. The ORs for Black, Hispanic, and Asian patients were 0.57 (95% CI = 0.55-0.58), 0.69 (95% CI = 0.64-0.74), and 0.83 (95% CI = 0.76-0.91), respectively. Minority patients were generally likely to be included in the measure calculation of fewer measures than White patients. Racial/ethnic disparities were observed in the calculation of Star Ratings measures among patients with ADRD and diabetes, hypertension, and/or hyperlipidemia. Future studies should explore possible causes of and solutions to these disparities.
PMCID:10158876
PMID: 37144996
ISSN: 1536-5964
CID: 5503142
