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Article ; Online: HIV in the Brain: From Devastating Dementia to White Matter Hyperintensities.

Robinson-Papp, Jessica / Saylor, Deanna

2021 Volume 96, Issue 14, Page(s) 645–646

MeSH term(s)	Alzheimer Disease ; Brain/diagnostic imaging ; HIV Infections/complications ; HIV Infections/diagnostic imaging ; Humans ; Risk Factors ; White Matter/diagnostic imaging
Language	English
Publishing date	2021-02-26
Publishing country	United States
Document type	Editorial ; Comment
ZDB-ID	207147-2
ISSN	1526-632X ; 0028-3878
ISSN (online)	1526-632X
ISSN	0028-3878
DOI	10.1212/WNL.0000000000011735
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Article: Reduced cardiovagal baroreflex sensitivity is associated with postural orthostatic tachycardia syndrome (POTS) and pain chronification in patients with headache.

Mueller, Bridget R / Ray, Carly / Benitez, Alyha / Robinson-Papp, Jessica

Frontiers in human neuroscience

2023 Volume 17, Page(s) 1068410

Abstract: Background: Non-cephalgic symptoms including orthostatic intolerance, fatigue, and cognitive impairment, are common in patients with chronic headache disorders and may result from alterations in the autonomic nervous system. However, little is known ... ...

Abstract	Background: Non-cephalgic symptoms including orthostatic intolerance, fatigue, and cognitive impairment, are common in patients with chronic headache disorders and may result from alterations in the autonomic nervous system. However, little is known about the function of autonomic reflexes, which regulate cardiovascular homeostasis and cerebral perfusion in patients with headache. Methods: Autonomic function testing data from patients with headache collected between January 2018 and April 2022 was retrospectively analyzed. Through review of EMR we determined headache pain chronicity and patient self-report of orthostatic intolerance, fatigue, and cognitive impairment. Composite Autonomic Severity Score (CASS), CASS subscale scores, and cardiovagal and adrenergic baroreflex sensitivities were used to quantify autonomic reflex dysfunction. Descriptive analyses (Mann-Whitney- Results: We identified 34 patients meeting inclusion criteria, of whom there were 16 (47.0%) with orthostatic intolerance, 17 (50.0%) with fatigue, 11 (32.4%) with cognitive complaints, and 11 (32.4%) with Postural Orthostatic Tachycardia Syndrome (POTS). The majority of participants had migraine ( Conclusion: Abnormal autonomic reflexes may play an important role in pain chronification and the development of POTS in patients with headache.
Language	English
Publishing date	2023-03-13
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2425477-0
ISSN	1662-5161
ISSN	1662-5161
DOI	10.3389/fnhum.2023.1068410
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Article: Autonomic Neuropathy as a Predictor of Morbidity and Mortality in People Living With HIV: A Retrospective, Longitudinal Cohort Study.

Kwon, Patrick M / Lawrence, Steven / Figueroa, Antonio / Robinson-Papp, Jessica

Neurology. Clinical practice

2023 Volume 13, Issue 3, Page(s) e200141

Abstract: Background and objectives: HIV-associated autonomic neuropathy (HIV-AN) is common; however, its clinical effect is unclear. Previously, it was shown that the composite autonomic severity score is associated with markers of morbidity such as the Veterans ...

Abstract	Background and objectives: HIV-associated autonomic neuropathy (HIV-AN) is common; however, its clinical effect is unclear. Previously, it was shown that the composite autonomic severity score is associated with markers of morbidity such as the Veterans Affair Cohort Study index. In addition, it is known that cardiovascular autonomic neuropathy due to diabetes is associated with poor cardiovascular outcomes. This study aimed to evaluate whether HIV-AN is predictive of important adverse clinical outcomes. Method: The electronic medical records of HIV-infected participants who underwent autonomic function tests at the Mount Sinai Hospital between April 2011 and August 2012 were reviewed. The cohort was stratified into those who had no or mild autonomic neuropathy (HIV-AN [-], CASS ≤3) and those with moderate or severe autonomic neuropathy (HIV-AN [+], CASS >3). The primary outcome was a composite of the incidence of death from any cause, new major cardiovascular or cerebrovascular event, or development of severe renal or hepatic disease. Time-to-event analysis was performed using Kaplan-Meier analysis and multivariate Cox proportional hazards regression models. Results: One hundred eleven of 114 participants had follow-up data (median follow-up for HIV-AN (-) was 94.00 months, and HIV-AN (+) was 81.29 months) and were included in the analysis. Participants were followed until March 1, 2020. The HIV-AN (+) group (N = 42) was significantly associated with the presence of hypertension, higher HIV-1 viral load, and more abnormal liver function. Seventeen (40.48%) events occurred in the HIV-AN (+) group, and 11 (15.94%) occurred in the HIV-AN (-) group. Six (14.29%) cardiac events occurred in the HIV-AN (+) group, whereas 1 (1.45%) occurred in the HIV-AN (-) group. The other subgroups of the composite outcome had a similar trend. The adjusted Cox proportional hazards model showed that the presence of HIV-AN predicted our composite outcome (HR 3.85, CI 1.61-9.20). Discussion: These findings suggest that HIV-AN is associated with the development of severe morbidity and mortality in people living with HIV. People living with HIV with autonomic neuropathy may benefit from closer cardiac, renal, and hepatic surveillance.
Language	English
Publishing date	2023-03-27
Publishing country	United States
Document type	Journal Article
ZDB-ID	2645818-4
ISSN	2163-0933 ; 2163-0402
ISSN (online)	2163-0933
ISSN	2163-0402
DOI	10.1212/CPJ.0000000000200141
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Article ; Online: Postural orthostatic tachycardia syndrome and migraine: A narrative review.

Mueller, Bridget R / Robinson-Papp, Jessica

Headache

2022 Volume 62, Issue 7, Page(s) 792–800

Abstract: Objective: In this narrative review, we summarize experimental and clinical evidence demonstrating mechanistic connections between POTS and migraine.: Background: Migraine is the most common comorbidity in patients with POTS, a heterogenous disorder ... ...

Abstract	Objective: In this narrative review, we summarize experimental and clinical evidence demonstrating mechanistic connections between POTS and migraine. Background: Migraine is the most common comorbidity in patients with POTS, a heterogenous disorder of the autonomic nervous system characterized by orthostatic intolerance and positional tachycardia. POTS is a debilitating illness with few effective treatments. We aim for this narrative review to increase awareness of the mechanistic connections between POTS and migraine providing foundational information that optimizes clinical care and advances the development of pathophysiologic-based treatments. Methods: We used the PubMed and Medline databases in November 2021 to perform a literature review and searched for the following keywords: "postural orthostatic tachycardia syndrome," "POTS," "autonomic nervous system," AND "migraine," "headache." Results: The high prevalence of migraine in patients with POTS may be explained by common pathologic mechanisms. There is evidence that dysregulation of the sympathetic nervous system, alterations in central and peripheral hemodynamics, and central sensitization increase vulnerability to both POTS and migraine. Non-pharmacologic and pharmacologic treatments that target these shared mechanisms may provide significant benefit for the patient with POTS and migraine. Conclusions: Identification of common affected pathways may provide important insight that advances our understanding and treatment of both migraine and POTS.
MeSH term(s)	Autonomic Nervous System ; Heart Rate/physiology ; Hemodynamics ; Humans ; Migraine Disorders/epidemiology ; Migraine Disorders/therapy ; Postural Orthostatic Tachycardia Syndrome/complications ; Postural Orthostatic Tachycardia Syndrome/epidemiology ; Postural Orthostatic Tachycardia Syndrome/therapy ; Sympathetic Nervous System
Language	English
Publishing date	2022-07-19
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	410130-3
ISSN	1526-4610 ; 0017-8748
ISSN (online)	1526-4610
ISSN	0017-8748
DOI	10.1111/head.14365
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Article ; Online: Structural and functional connections between the autonomic nervous system, hypothalamic-pituitary-adrenal axis, and the immune system: a context and time dependent stress response network.

Mueller, Bridget / Figueroa, Alex / Robinson-Papp, Jessica

Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology

2022 Volume 43, Issue 2, Page(s) 951–960

Abstract: The autonomic nervous system (ANS), hypothalamic-pituitary-adrenal (HPA) axis, and immune system are connected anatomically and functionally. These three systems coordinate the central and peripheral response to perceived and systemic stress signals. ... ...

Abstract	The autonomic nervous system (ANS), hypothalamic-pituitary-adrenal (HPA) axis, and immune system are connected anatomically and functionally. These three systems coordinate the central and peripheral response to perceived and systemic stress signals. Both the parasympathetic and sympathetic components of the autonomic nervous system rapidly respond to stress signals, while the hypothalamic-pituitary-adrenal axis and immune system have delayed but prolonged actions. In vitro, animal, and human studies have demonstrated consistent anti-inflammatory effects of parasympathetic activity. In contrast, sympathetic activity exerts context-dependent effects on immune signaling and has been associated with both increased and decreased inflammation. The location of sympathetic action, adrenergic receptor subtype, and timing of activity in relation to disease progression all influence the ultimate impact on immune signaling. This article reviews the brain circuitry, peripheral connections, and chemical messengers that enable communication between the ANS, HPA axis, and immune system. We describe findings of in vitro and animal studies that challenge the immune system with lipopolysaccharide. Next, neuroimmune connections in animal models of chronic inflammatory disease are reviewed. Finally, we discuss how a greater understanding of the ANS-HPA-immune network may lead to the development of novel therapeutic strategies that are focused on modulation of the sympathetic and parasympathetic nervous system.
MeSH term(s)	Animals ; Autonomic Nervous System ; Humans ; Hypothalamo-Hypophyseal System ; Immune System ; Inflammation ; Pituitary-Adrenal System
Language	English
Publishing date	2022-01-16
Publishing country	Italy
Document type	Journal Article ; Review
ZDB-ID	2016546-8
ISSN	1590-3478 ; 1590-1874
ISSN (online)	1590-3478
ISSN	1590-1874
DOI	10.1007/s10072-021-05810-1
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Article ; Online: Phenotyping autonomic neuropathy using principal component analysis.

Lawrence, Steven / Mueller, Bridget R / Kwon, Patrick / Robinson-Papp, Jessica

Autonomic neuroscience : basic & clinical

2022 Volume 245, Page(s) 103056

Abstract: To identify autonomic neuropathy (AN) phenotypes, we used principal component analysis on data from participants (N = 209) who underwent standardized autonomic testing including quantitative sudomotor axon reflex testing, and heart rate and blood ... ...

Abstract	To identify autonomic neuropathy (AN) phenotypes, we used principal component analysis on data from participants (N = 209) who underwent standardized autonomic testing including quantitative sudomotor axon reflex testing, and heart rate and blood pressure at rest and during tilt, Valsalva, and standardized deep breathing. The analysis identified seven clusters: 1) normal, 2) hyperadrenergic features without AN, 3) mild AN with hyperadrenergic features, 4) moderate AN, 5) mild AN with hypoadrenergic features, 6) borderline AN with hypoadrenergic features, 7) mild balanced deficits across parasympathetic, sympathetic and sudomotor domains. These findings demonstrate a complex relationship between adrenergic and other aspects of autonomic function.
MeSH term(s)	Humans ; Principal Component Analysis ; Autonomic Nervous System ; Autonomic Nervous System Diseases/diagnosis ; Blood Pressure/physiology ; Heart Rate/physiology ; Valsalva Maneuver
Language	English
Publishing date	2022-12-10
Publishing country	Netherlands
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2020105-9
ISSN	1872-7484 ; 1566-0702
ISSN (online)	1872-7484
ISSN	1566-0702
DOI	10.1016/j.autneu.2022.103056
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Article ; Online: Neuropathogenesis of HIV and emerging therapeutic targets.

Siddiqui, Alina / He, Celestine / Lee, Gina / Figueroa, Alex / Slaughter, Alexander / Robinson-Papp, Jessica

Expert opinion on therapeutic targets

2022 Volume 26, Issue 7, Page(s) 603–615

Abstract: Introduction: HIV infection causes a wide range of neurological complications, many of which are among the most common complications of chronic HIV infection in the era of combined antiretroviral therapy. These neurological conditions arise due to ... ...

Abstract	Introduction: HIV infection causes a wide range of neurological complications, many of which are among the most common complications of chronic HIV infection in the era of combined antiretroviral therapy. These neurological conditions arise due to complex interactions between HIV viral proteins and neuronal and glial cells that lead to the activation of various inflammatory and neurotoxic pathways across the nervous system. Areas covered: This review summarizes the current literature on the pathogenesis and clinical manifestations of neurological injuries associated with HIV in the brain, spinal cord, and peripheral nervous system. Molecular pathways relevant for possible therapeutic targets or advancements are emphasized. Gaps in knowledge and current challenges in therapeutic design are also discussed. Expert opinion: Several challenges exist in the development of therapeutic targets for HIV-associated cognitive impairments. However, recent developments in drug delivery systems and treatment strategies are encouraging. Treatments for HIV-associated pain and peripheral sensory neuropathies currently consist of symptomatic management, but a greater understanding of their pathogenesis can lead to the development of targeted molecular therapies and disease-modifying therapies. HIV-associated autonomic dysfunction may affect the course of systemic disease via disrupted neuro-immune interactions; however, more research is needed to facilitate our understanding of how these processes present clinically.
MeSH term(s)	Brain ; HIV Infections/complications ; HIV Infections/drug therapy ; Humans ; Nervous System Diseases/complications ; Neuroimmunomodulation ; Peripheral Nervous System Diseases
Language	English
Publishing date	2022-07-18
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	2055208-7
ISSN	1744-7631 ; 1472-8222
ISSN (online)	1744-7631
ISSN	1472-8222
DOI	10.1080/14728222.2022.2100253
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Article: Autonomic Neuropathy is Associated with More Densely Interconnected Cytokine Networks in People with HIV.

Lawrence, Steven / Mueller, Bridget R / Benn, Emma K T / Kim-Schulze, Seunghee / Kwon, Patrick / Robinson-Papp, Jessica

Research square

2023

Abstract: Introduction: The autonomic nervous system (ANS) plays a complex role in the regulation of the immune system, with generally inhibitory effects via activation of β-adrenergic receptors on immune cells. We hypothesized that HIV-associated autonomic ... ...

Abstract	Introduction: The autonomic nervous system (ANS) plays a complex role in the regulation of the immune system, with generally inhibitory effects via activation of β-adrenergic receptors on immune cells. We hypothesized that HIV-associated autonomic neuropathy (HIV-AN) would result in immune hyperresponsiveness which could be depicted using network analyses. Methods: Forty-two adults with well-controlled HIV underwent autonomic testing to yield the Composite Autonomic Severity Score (CASS). The observed range of CASS was 2-5, consistent with normal to moderate HIV-AN. To construct the networks, participants were divided into 4 groups based on the CASS (i.e., 2, 3, 4 or 5). Forty-four blood-based immune markers were included as nodes in all networks and the connections (i.e., edges) between pairs of nodes were determined by their bivariate Spearman's Rank Correlation Coefficient. Four centrality measures (strength, closeness, betweenness and expected influence) were calculated for each node in each network. The median value of each centrality measure across all nodes in each network was calculated as a quantitative representation of network complexity. Results: Graphical representation of the four networks revealed greater complexity with increasing HIV-AN severity. This was confirmed by significant differences in the median value of all four centrality measures across the networks (p≤0.025 for each). Conclusion: Among people with HIV, HIV-AN is associated with stronger and more numerous positive correlations between blood-based immune markers. Findings from this secondary analysis can be used to generate hypotheses for future studies investigating HIV-AN as a mechanism contributing to the chronic immune activation observed in HIV.
Language	English
Publishing date	2023-03-17
Publishing country	United States
Document type	Preprint
DOI	10.21203/rs.3.rs-2670770/v1
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Article ; Online: Baroreflex sensitivity is associated with markers of hippocampal gliosis and dysmyelination in patients with psychosis.

Mueller, Bridget / Robinson-Papp, Jessica / Suprun, Maria / Suarez-Farinas, Mayte / Lotan, Eyal / Gonen, Oded / Malaspina, Dolores

Clinical autonomic research : official journal of the Clinical Autonomic Research Society

2023 Volume 33, Issue 2, Page(s) 101–110

Abstract: Purpose: Hippocampal dysfunction plays a key role in the pathology of psychosis. Given hippocampal sensitivity to changes in cerebral perfusion, decreased baroreflex function could contribute to psychosis pathogenesis. This study had two aims: (1) To ... ...

Abstract	Purpose: Hippocampal dysfunction plays a key role in the pathology of psychosis. Given hippocampal sensitivity to changes in cerebral perfusion, decreased baroreflex function could contribute to psychosis pathogenesis. This study had two aims: (1) To compare baroreflex sensitivity in participants with psychosis to two control groups: participants with a nonpsychotic affective disorder and participants with no history of psychiatric disease; (2) to examine the relationship between hippocampal neurometabolites and baroreflex sensitivities in these three groups. We hypothesized that baroreflex sensitivity would be reduced and correlated with hippocampal neurometabolite levels in participants with psychosis, but not in the control groups. Methods: We assessed baroreflex sensitivity during the Valsalva maneuver separated into vagal and adrenergic components. Metabolite concentrations for cellular processes were quantitated in the entire multivoxel hippocampus using H Results: Vagal baroreflex sensitivity (BRS-V) was reduced in a significantly larger proportion of participants with psychosis compared with patients with nonpsychotic affective disorders, whereas participants with psychosis had increased adrenergic baroreflex sensitivity (BRS-A) compared with participants with no history of psychiatric disease. Only in psychotic cases were baroreflex sensitivities associated with hippocampal metabolite concentrations. Specifically, BRS-V was inversely correlated with myo-inositol, a marker of gliosis, and BRS-A was positively correlated with energy dependent dysmyelination (choline, creatine) and excitatory activity (GLX). Conclusions: Abnormal baroreflex sensitivity is common in participants with psychosis and is associated with MRS markers of hippocampal pathology. Future longitudinal studies are needed to examine causality.
MeSH term(s)	Humans ; Baroreflex ; Blood Pressure ; Gliosis ; Heart Rate ; Psychotic Disorders ; Hippocampus ; Adrenergic Agents
Chemical Substances	Adrenergic Agents
Language	English
Publishing date	2023-03-06
Publishing country	Germany
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	1080007-4
ISSN	1619-1560 ; 0959-9851
ISSN (online)	1619-1560
ISSN	0959-9851
DOI	10.1007/s10286-023-00929-x
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Article ; Online: Autonomic Neuropathy is Associated with More Densely Interconnected Cytokine Networks in People with HIV.

Lawrence, Steven / Mueller, Bridget R / Benn, Emma K T / Kim-Schulze, Seunghee / Kwon, Patrick / Robinson-Papp, Jessica

Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology

2023 Volume 18, Issue 4, Page(s) 563–572

Abstract: The autonomic nervous system (ANS) plays a complex role in the regulation of the immune system, with generally inhibitory effects via activation of β-adrenergic receptors on immune cells. We hypothesized that HIV-associated autonomic neuropathy (HIV-AN) ... ...

Abstract	The autonomic nervous system (ANS) plays a complex role in the regulation of the immune system, with generally inhibitory effects via activation of β-adrenergic receptors on immune cells. We hypothesized that HIV-associated autonomic neuropathy (HIV-AN) would result in immune hyperresponsiveness which could be depicted using network analyses. Forty-two adults with well-controlled HIV underwent autonomic testing to yield the Composite Autonomic Severity Score (CASS). The observed range of CASS was 2-5, consistent with normal to moderate HIV-AN. To construct the networks, participants were divided into 4 groups based on the CASS (i.e., 2, 3, 4 or 5). Forty-four blood-based immune markers were included as nodes in all networks and the connections (i.e., edges) between pairs of nodes were determined by their bivariate Spearman's Rank Correlation Coefficient. Four centrality measures (strength, closeness, betweenness and expected influence) were calculated for each node in each network. The median value of each centrality measure across all nodes in each network was calculated as a quantitative representation of network complexity. Graphical representation of the four networks revealed greater complexity with increasing HIV-AN severity. This was confirmed by significant differences in the median value of all four centrality measures across the networks (p ≤ 0.025 for each). Among people with HIV, HIV-AN is associated with stronger and more numerous positive correlations between blood-based immune markers. Findings from this secondary analysis can be used to generate hypotheses for future studies investigating HIV-AN as a mechanism contributing to the chronic immune activation observed in HIV.
MeSH term(s)	Adult ; Humans ; HIV ; Autonomic Nervous System ; HIV Infections ; Nervous System Diseases ; Biomarkers
Chemical Substances	6-chloropenicillanic acid S-sulfoxide (97729-66-3) ; Biomarkers
Language	English
Publishing date	2023-11-04
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2227405-4
ISSN	1557-1904 ; 1557-1890
ISSN (online)	1557-1904
ISSN	1557-1890
DOI	10.1007/s11481-023-10088-5
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