Faculty Bibliography
Searched for:
Department/Unit:Neurology
Total Results:
24282
Structural and functional organization of the lower jaw barrel subfield in rat primary somatosensory cortex
Barrel subfields in rodent primary somatosensory cortex (SI) are important model systems for studying cortical organization and reorganization. During cortical reorganization that follows limb deafferentation, neurons in deafferented forelimb SI become responsive to previously unexpressed inputs from the lower jaw. Although the lower jaw barrel subfield (LJBSF) is a likely source of the input, this subfield has received little attention. Our aim was to describe the structural and functional organization of the normal LJBSF. To investigate LJBSF organization, a nomenclature for lower jaw skin surface was developed, cytochrome oxidase (CO) was used to label flattened-cut LJBSF sections, microelectrodes were used to map the lower jaw skin surface representation in SI, and electrolytic lesions, recovered from electrode penetrations, were used to align the physiological map to the underlying barrel map. LJBSF is a tear-shaped subfield containing approximately 24 barrels, arranged in eight mediolateral rows and a barrel-free zone capping the anterior border. The representation of the lower jaw skin consisting of chin vibrissae and microvibrissae embedded in common fur is somatotopically organized in a single map in the contralateral SI. This physiological map shows that the activity from the vibrissae aligns with the CO-staining of the underlying LJBSF. LJBSF barrels receive topographically ordered barrel-specific input from individual vibrissa and microvibrissae in the lower jaw but not from trident whiskers. The barrel-free zone receives topographically ordered input from the lower lip. These data demonstrating that the LJBSF is a highly organized subfield are essential for understanding its possible role in cortical reorganization.
PMID: 33135168
ISSN: 1096-9861
CID: 4956482
Lessons From Disaster Medicine for the Neurologist in the COVID-19 Era: Going Viral [Editorial]
PMCID:8032430
PMID: 33842059
ISSN: 2163-0402
CID: 4956512
Therapeutic Applications of Botulinum Neurotoxin for Autonomic Symptoms in Parkinson's Disease: An Updated Review
Parkinson's disease is the most common age-related motoric neurodegenerative disease. In addition to the cardinal motor symptoms of tremor, rigidity, bradykinesia, and postural instability, there are numerous non-motor symptoms as well. Among the non-motor symptoms, autonomic nervous system dysfunction is common. Autonomic symptoms associated with Parkinson's disease include sialorrhea, hyperhidrosis, gastrointestinal dysfunction, and urinary dysfunction. Botulinum neurotoxin has been shown to potentially improve these autonomic symptoms. In this review, the varied uses of botulinum neurotoxin for autonomic dysfunction in Parkinson's disease are discussed. This review also includes discussion of some additional indications for the use of botulinum neurotoxin in Parkinson's disease, including pain.
PMCID:8003355
PMID: 33808714
ISSN: 2072-6651
CID: 4954642
The Intersection of Neurology and Religion: A Survey of Hospital Chaplains on Death by Neurologic Criteria
BACKGROUND:To enhance knowledge about religious objections to brain death/death by neurologic criteria (BD/DNC), we surveyed hospital chaplains about their experience with and beliefs about BD/DNC. METHODS:We distributed an online survey to five chaplaincy organizations between February and July 2019. RESULTS:There were 512 respondents from all regions of the USA; they were predominantly Christian (450 of 497; 91%), board certified (413 of 490; 84%), and employed by community hospitals (309 of 511; 61%). Half (274 of 508; 56%) of the respondents had been involved in a case in which a family objected to BD/DNC on the basis of their religious beliefs. In 20% of cases involving a religious objection, the patient was Buddhist, Hindu, Jewish, or Muslim. Most respondents believed that a person who is declared brain dead in accordance with the American Academy of Neurology standard is dead (427 of 510; 84%). A minority of respondents believed that a family should be able to choose whether an assessment for determination of BD/DNC is performed (81 of 512; 16%) or whether organ support is discontinued after BD/DNC (154 of 510; 30%). These beliefs were all significantly related to lack of awareness that BD/DNC is the medical and legal equivalent of cardiopulmonary death throughout the USA and that organ support is routinely discontinued after BD/DNC, outside of organ donation. CONCLUSIONS:Hospital chaplains, who work at the intersection between religion and medicine, commonly encounter religious objections to BD/DNC. To prepare them for these situations, they should receive additional education about BD/DNC and management of religious objections to BD/DNC.
PMID: 34195896
ISSN: 1556-0961
CID: 4951002
3-hydroxy-L-kynurenamine is an immunomodulatory biogenic amine
Tryptophan catabolism is a major metabolic pathway utilized by several professional and non-professional antigen presenting cells to maintain immunological tolerance. Here we report that 3-hydroxy-L-kynurenamine (3-HKA) is a biogenic amine produced via an alternative pathway of tryptophan metabolism. In vitro, 3-HKA has an anti-inflammatory profile by inhibiting the IFN-γ mediated STAT1/NF-κΒ pathway in both mouse and human dendritic cells (DCs) with a consequent decrease in the release of pro-inflammatory chemokines and cytokines, most notably TNF, IL-6, and IL12p70. 3-HKA has protective effects in an experimental mouse model of psoriasis by decreasing skin thickness, erythema, scaling and fissuring, reducing TNF, IL-1β, IFN-γ, and IL-17 production, and inhibiting generation of effector CD8+ T cells. Similarly, in a mouse model of nephrotoxic nephritis, besides reducing inflammatory cytokines, 3-HKA improves proteinuria and serum urea nitrogen, overall ameliorating immune-mediated glomerulonephritis and renal dysfunction. Overall, we propose that this biogenic amine is a crucial component of tryptophan-mediated immune tolerance.
PMID: 34290243
ISSN: 2041-1723
CID: 4951192
Association of Disease Severity and Socioeconomic Status in Black and White Americans With Multiple Sclerosis
OBJECTIVE:To compare clinical and imaging features of multiple sclerosis (MS) severity between Black Americans (BA) and White Americans (WA) and evaluate the role of socioeconomic status. METHODS:We compared BA and WA participants in the Multiple Sclerosis Partners Advancing Technology Health Solutions (MS PATHS) cohort with respect to MS characteristics including self-reported disability, objective neurologic function assessments, and quantitative brain MRI measurements, after covariate adjustment (including education level, employment, or insurance as socioeconomic indicators). In a subgroup, we evaluated within-race, neighborhood-level indicators of socioeconomic status (SES) using 9-digit ZIP codes. RESULTS:Of 1,214 BAs and 7,530 WAs with MS, BAs were younger, had lower education level, and were more likely to have Medicaid insurance or be disabled or unemployed than WAs. BAs had worse self-reported disability (1.47-fold greater odds of severe vs. mild disability, 95% CI 1.18, 1.86) and worse performances on tests of cognitive processing speed (-5.06 fewer correct, CI -5.72, -4.41), walking (0.66 seconds slower, 95% CI 0.36, 0.96) and manual dexterity (2.11 seconds slower, 95% CI 1.69, 2.54). BAs had more brain MRI lesions and lower overall and gray matter brain volumes, including reduced thalamic (-0.77 mL, 95% CI -0.91, -0.64), cortical (-30.63 mL, 95% CI -35.93, -25.33), and deep (-1.58 mL, 95% CI -1.92, -1.23) gray matter volumes. While lower SES correlated with worse neuroperformance scores in WAs, this association was less clear in BA. CONCLUSION/CONCLUSIONS:We observed a greater burden of disease in BAs with MS relative to WAs with MS, despite adjustment for SES indicators. Beyond SES, future longitudinal studies should also consider roles of other societal constructs (e.g., systemic racism). Such studies will be important for identifying prognostic factors and optimal treatment strategies among BAs with MS is warranted.
PMID: 34193590
ISSN: 1526-632x
CID: 4950992
Baseline brain function in the preadolescents of the ABCD Study
The Adolescent Brain Cognitive Development (ABCD) Study® is a 10-year longitudinal study of children recruited at ages 9 and 10. A battery of neuroimaging tasks are administered biennially to track neurodevelopment and identify individual differences in brain function. This study reports activation patterns from functional MRI (fMRI) tasks completed at baseline, which were designed to measure cognitive impulse control with a stop signal task (SST; N = 5,547), reward anticipation and receipt with a monetary incentive delay (MID) task (N = 6,657) and working memory and emotion reactivity with an emotional N-back (EN-back) task (N = 6,009). Further, we report the spatial reproducibility of activation patterns by assessing between-group vertex/voxelwise correlations of blood oxygen level-dependent (BOLD) activation. Analyses reveal robust brain activations that are consistent with the published literature, vary across fMRI tasks/contrasts and slightly correlate with individual behavioral performance on the tasks. These results establish the preadolescent brain function baseline, guide interpretation of cross-sectional analyses and will enable the investigation of longitudinal changes during adolescent development.
PMID: 34099922
ISSN: 1546-1726
CID: 4950912
Long-term safety and efficacy of add-on cannabidiol in patients with Lennox-Gastaut syndrome: Results of a long-term open-label extension trial
OBJECTIVE:Lennox-Gastaut syndrome (LGS) is an epileptic encephalopathy that is often treatment resistant. Efficacy and safety of add-on cannabidiol (CBD) to treat seizures associated with LGS was demonstrated in two randomized controlled trials (RCTs). Patients who completed the RCTs were invited to enroll in this long-term open-label extension (OLE) trial, GWPCARE5 (NCT02224573). We present the final analysis of safety and efficacy outcomes from GWPCARE5. METHODS:Patients received plant-derived highly purified CBD (Epidiolex in the United States; Epidyolex in the European Union; 100 mg/ml oral solution), titrated to a target maintenance dose of 20 mg/kg/day over 2 weeks. Based on response and tolerability, CBD could then be reduced or increased up to 30 mg/kg/day. RESULTS:Of 368 patients with LGS who completed the RCTs, 366 (99.5%) enrolled in this OLE. Median and mean treatment duration were 1090 and 826 days (range = 3-1421), respectively, with a mean modal dose of 24 mg/kg/day. Adverse events (AEs) occurred in 96% of patients, serious AEs in 42%, and AE-related discontinuations in 12%. Common AEs were convulsion (39%), diarrhea (38%), pyrexia (34%), and somnolence (29%). Fifty-five (15%) patients experienced liver transaminase elevations more than three times the upper limit of normal; 40 (73%) were taking concomitant valproic acid. Median percent reductions from baseline ranged 48%-71% for drop seizures and 48%-68% for total seizures through 156 weeks. Across all 12-week visit windows, 87% or more of patients/caregivers reported improvement in the patient's overall condition on the Subject/Caregiver Global Impression of Change scale. SIGNIFICANCE/CONCLUSIONS:Long-term add-on CBD treatment had a similar safety profile as in the original RCTs. Sustained reductions in drop and total seizure frequency were observed for up to 156 weeks, demonstrating long-term benefits of CBD treatment for patients with LGS.
PMID: 34287833
ISSN: 1528-1167
CID: 4948222
Psychiatric and cognitive comorbidities of persistent post-traumatic headache attributed to mild traumatic brain injury
OBJECTIVE:To investigate the association of psychiatric and cognitive comorbidities with persistent post-traumatic headache (PTH) attributed to mild traumatic brain injury (TBI). METHODS:A total of 100 patients with persistent PTH attributed to mild TBI and 100 age- and gender-matched healthy controls free of mild TBI were enrolled between July 2018 and June 2019. Quality of sleep was evaluated using the Pittsburgh Sleep Quality Index, while symptoms of anxiety and depression were assessed using the Hospital Anxiety and Depression Scale. Cognitive impairment was evaluated using the Montreal Cognitive Assessment questionnaire, while post-traumatic stress disorder (PTSD) was assessed using the Harvard Trauma Questionnaire. RESULTS:In 100 patients with persistent PTH, 85% reported poor quality sleep, compared with 42% of healthy controls (P < 0.01). The relative frequency of probable to high risk of anxiety was 52% in the persistent PTH group vs. 8% in healthy controls (P < 0.01), while the relative frequency of probable to high risk of depression was 42% in the persistent PTH group vs. 2% in healthy controls (P < 0.01). Furthermore, 27% of the patients with persistent PTH had mild cognitive impairment while 10% had probable PTSD. CONCLUSIONS:Poor quality of sleep as well as symptoms suggestive of anxiety and depression were more common in patients with persistent PTH than healthy controls. Clinicians should screen patients with persistent PTH for these comorbidities and develop treatment plans that account for their presence.
PMCID:8314480
PMID: 34311696
ISSN: 1129-2377
CID: 4949162
Effect of Alteplase Use on Outcomes in Patients With Atrial Fibrillation: Analysis of the Initiation of Anticoagulation After Cardioembolic Stroke Study
Background Intravenous alteplase improves outcome after acute ischemic stroke without a benefit in 90-day mortality. There are limited data on whether alteplase is associated with reduced mortality in patients with atrial fibrillation (AF)-related ischemic stroke whose mortality rate is relatively high. We sought to determine the association of alteplase with hemorrhagic transformation and mortality in patients with AF. Methods and Results We retrospectively analyzed consecutive patients with acute ischemic stroke between 2015 and 2018 diagnosed with AF included in the IAC (Initiation of Anticoagulation After Cardioembolic Stroke) study, which pooled data from stroke registries at 8 comprehensive stroke centers across the United States. For our primary analysis, we included patients who did not undergo mechanical thrombectomy (MT), and secondary analyses included patients who underwent MT. We used binary logistic regression to determine whether alteplase use was associated with risk of hemorrhagic transformation and 90-day mortality. There were 1889 patients (90.6%) who had 90-day follow-up data available for analyses and were included; 1367 patients (72.4%) did not receive MT, and 522 patients (27.6%) received MT. In our primary analyses we found that alteplase use was independently associated with an increased risk for hemorrhagic transformation (odds ratio [OR], 2.23; 95% CI, 1.57-3.17) but reduced risk of 90-day mortality (OR, 0.58; 95% CI, 0.39-0.87). Among patients undergoing MT, alteplase use was not associated with a significant reduction in 90-day mortality (OR, 0.68; 95% CI, 0.45-1.04). Conclusions Alteplase reduced 90-day mortality of patients with acute ischemic stroke with AF not undergoing MT. Further study is required to assess the efficacy of alteplase in patients with AF undergoing MT.
PMID: 34323120
ISSN: 2047-9980
CID: 4949902
