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Article ; Online: Case-Control Study of Individuals With Small Fiber Neuropathy After COVID-19.

McAlpine, Lindsay / Zubair, Adeel S / Joseph, Phillip / Spudich, Serena

Neurology(R) neuroimmunology & neuroinflammation

2024 Volume 11, Issue 3, Page(s) e200244

Abstract: Objectives: To report a case-control study of new-onset small fiber neuropathy (SFN) after COVID-19 with invasive cardiopulmonary exercise testing (iCPET). SFN is a critical objective finding in long COVID and amenable to treatment.: Methods: A ... ...

Abstract	Objectives: To report a case-control study of new-onset small fiber neuropathy (SFN) after COVID-19 with invasive cardiopulmonary exercise testing (iCPET). SFN is a critical objective finding in long COVID and amenable to treatment. Methods: A retrospective chart review was conducted on patients seen in the NeuroCOVID Clinic at Yale who developed new-onset SFN after a documented COVID-19 illness. We collected demographics, symptoms, skin biopsy, iCPET testing, treatments, and clinical response to treatment or no intervention. Results: Sixteen patients were diagnosed with SFN on skin biopsy (median age 47, 75% female, 75% White). 92% of patients reported postexertional malaise characteristic of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), and 7 patients underwent iCPET, which demonstrated neurovascular dysregulation and dysautonomia consistent with ME/CFS. Nine patients underwent treatment with IVIG, and 7 were not treated with IVIG. The IVIG group experienced significant clinical response in their neuropathic symptoms (9/9) compared with those who did not receive IVIG (3/7; Discussion: Here, we present preliminary evidence that after COVID-19, SFN is responsive to treatment with IVIG and linked with neurovascular dysregulation and dysautonomia on iCPET. A larger clinical trial is indicated to further demonstrate the clinical utility of IVIG in treating postinfectious SFN. Classification of evidence: This study provides Class III evidence. It is a retrospective cohort study.
MeSH term(s)	Humans ; Female ; Middle Aged ; Male ; Small Fiber Neuropathy ; Case-Control Studies ; Retrospective Studies ; Fatigue Syndrome, Chronic ; Post-Acute COVID-19 Syndrome ; Immunoglobulins, Intravenous ; COVID-19 ; Autonomic Nervous System Diseases
Chemical Substances	Immunoglobulins, Intravenous
Language	English
Publishing date	2024-04-17
Publishing country	United States
Document type	Journal Article
ZDB-ID	2767740-0
ISSN	2332-7812 ; 2332-7812
ISSN (online)	2332-7812
ISSN	2332-7812
DOI	10.1212/NXI.0000000000200244
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Article ; Online: Immune activation in the central nervous system throughout the course of HIV infection.

Spudich, Serena S

Current opinion in HIV and AIDS

2016 Volume 11, Issue 2, Page(s) 226–233

Abstract: Purpose of review: Robust and dynamic innate and adaptive responses characterize the acute central nervous system (CNS) response to HIV and other viral infections. In a state of chronic infection or viral latency, persistent immune activation associates ...

Abstract	Purpose of review: Robust and dynamic innate and adaptive responses characterize the acute central nervous system (CNS) response to HIV and other viral infections. In a state of chronic infection or viral latency, persistent immune activation associates with abnormality in the CNS. Understanding this process is critical, as immune-mediated abnormality in nonrenewable CNS cells may result in long-term neurologic sequelae for HIV-infected individuals. Recent findings: In humans, immune activation is reduced by suppressive combination antiretroviral therapy, but persists at abnormally elevated levels on treatment. CNS immune activation is initiated in acute infection and progressively increases until combination antiretroviral therapy is started. Newly identified characteristics of the CNS immune surveillance network include features of homeostasis and function of brain microglial cells, lymphatic drainage from CNS to cervical lymph nodes, and cells in cerebrospinal fluid associated with neurocognitive impairment. Summary: More research is required to determine whether early intervention to reduce infection limits the immunopathology established by sustained immune responses that ultimately fail to resolve infection, and to unravel mechanisms of persistent immune activation during treated HIV so that strategies can be developed to therapeutically protect the brain.
MeSH term(s)	Central Nervous System/immunology ; Cerebrospinal Fluid/immunology ; Encephalitis ; HIV Infections/complications ; HIV Infections/immunology ; HIV-1/immunology ; Humans
Language	English
Publishing date	2016-03
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2502511-9
ISSN	1746-6318 ; 1746-630X
ISSN (online)	1746-6318
ISSN	1746-630X
DOI	10.1097/COH.0000000000000243
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Zs.A 6812: Show issues

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Article ; Online: Neuropathogenesis of HIV-1: insights from across the spectrum of acute through long-term treated infection.

Killingsworth, Lauren / Spudich, Serena

Seminars in immunopathology

2022 Volume 44, Issue 5, Page(s) 709–724

Abstract: This review outlines the neuropathogenesis of HIV, from initial HIV entry into the central nervous system (CNS) to chronic infection, focusing on key advancements in the last 5 years. Discoveries regarding acute HIV infection reveal timing and mechanisms ...

Abstract	This review outlines the neuropathogenesis of HIV, from initial HIV entry into the central nervous system (CNS) to chronic infection, focusing on key advancements in the last 5 years. Discoveries regarding acute HIV infection reveal timing and mechanisms of early HIV entry and replication in the CNS, early inflammatory responses, and establishment of genetically distinct viral reservoirs in the brain. Recent studies additionally explore how chronic HIV infection is maintained in the CNS, examining how the virus remains in a latent "hidden" state in diverse cells in the brain, and how this leads to sustained pathological inflammatory responses. Despite viral suppression with antiretroviral therapy, HIV can persist and even replicate in the CNS, and associate with ongoing neuropathology including CD8 + T-lymphocyte mediated encephalitis. Crucial investigation to advance our understanding of the immune mechanisms that both control viral infection and lead to pathological consequences in the brain is necessary to develop treatments to optimize long-term neurologic health in people living with HIV.
MeSH term(s)	Brain ; CD8-Positive T-Lymphocytes ; Central Nervous System ; HIV Infections/drug therapy ; HIV-1 ; Humans
Language	English
Publishing date	2022-07-26
Publishing country	Germany
Document type	Journal Article ; Review ; Research Support, N.I.H., Extramural
ZDB-ID	2316828-6
ISSN	1863-2300 ; 1863-2297
ISSN (online)	1863-2300
ISSN	1863-2297
DOI	10.1007/s00281-022-00953-5
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Zs.A 1425: Show issues

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Article ; Online: Nervous system consequences of COVID-19.

Spudich, Serena / Nath, Avindra

Science (New York, N.Y.)

2022 Volume 375, Issue 6578, Page(s) 267–269

Abstract: Neurological symptoms highlight the need to understand pathophysiologic mechanisms. ...

Abstract	Neurological symptoms highlight the need to understand pathophysiologic mechanisms.
MeSH term(s)	Autoimmunity ; Brain/immunology ; Brain/pathology ; COVID-19/complications ; COVID-19/immunology ; COVID-19/physiopathology ; COVID-19/virology ; Cerebrospinal Fluid/immunology ; Cerebrospinal Fluid/virology ; Humans ; Mental Disorders/etiology ; Mental Disorders/immunology ; Mental Disorders/physiopathology ; Nervous System Diseases/etiology ; Nervous System Diseases/immunology ; Nervous System Diseases/physiopathology ; Neuroinflammatory Diseases/etiology ; Neuroinflammatory Diseases/immunology ; Neuroinflammatory Diseases/physiopathology ; SARS-CoV-2/isolation & purification
Language	English
Publishing date	2022-01-20
Publishing country	United States
Document type	Journal Article
ZDB-ID	128410-1
ISSN	1095-9203 ; 0036-8075
ISSN (online)	1095-9203
ISSN	0036-8075
DOI	10.1126/science.abm2052
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Zs.A 27: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MG 77: Show issues

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Article ; Online: HIV Compartmentalization in the CNS and Its Impact in Treatment Outcomes and Cure Strategies.

Chan, Phillip / Spudich, Serena

Current HIV/AIDS reports

2022 Volume 19, Issue 3, Page(s) 207–216

Abstract: Purpose of review: This review focuses on the cerebrospinal fluid (CSF) findings in connection to the central nervous system (CNS) reservoir in treatment-naïve and virally suppressed PLWH, followed by the findings in CSF HIV-1 escape and analytical ... ...

Abstract	Purpose of review: This review focuses on the cerebrospinal fluid (CSF) findings in connection to the central nervous system (CNS) reservoir in treatment-naïve and virally suppressed PLWH, followed by the findings in CSF HIV-1 escape and analytical treatment interruption studies. Recent findings: Compared to chronic infection, initiating antiretroviral therapy (ART) during acute HIV-1 infection results in more homogeneous longitudinal benefits in the CNS. Viral variants in CSF HIV-1 escape are independently linked to infected cells from the systemic reservoir and in the CNS, highlighting the phenomenon as a consequence of different mechanisms. HIV-infected cells persist in CSF in nearly half of the individuals on stable ART and are associated with worse neurocognitive performance. Future studies should probe into the origin of the HIV-infected cells in the CSF. Examining the capacity for viral replication would provide new insight into the CNS reservoir and identify strategies to eradicate it or compensate for the insufficiency of ART.
MeSH term(s)	Central Nervous System ; HIV Infections/cerebrospinal fluid ; HIV Infections/drug therapy ; HIV Seropositivity ; HIV-1/genetics ; Humans ; RNA, Viral ; Treatment Outcome ; Viral Load
Chemical Substances	RNA, Viral
Language	English
Publishing date	2022-05-10
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	2151206-1
ISSN	1548-3576 ; 1548-3568
ISSN (online)	1548-3576
ISSN	1548-3568
DOI	10.1007/s11904-022-00605-1
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Zs.A 5920: Show issues

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Article ; Online: Global Health Neurology: HIV/AIDS.

Patel, Payal B / Spudich, Serena S

Seminars in neurology

2018 Volume 38, Issue 2, Page(s) 238–246

Abstract: With the advent of combination antiretroviral therapies, the mortality rate from HIV has declined, while the prevalence of long-term HIV-related neurologic complications continues to rise. Thirty-six million individuals are living with HIV around the ... ...

Abstract	With the advent of combination antiretroviral therapies, the mortality rate from HIV has declined, while the prevalence of long-term HIV-related neurologic complications continues to rise. Thirty-six million individuals are living with HIV around the world, many of whom reside in resource-limited settings. The majority of studies have focused on individuals residing in the developed world, while the impact of HIV disproportionately affects people living in developing countries. This review focuses on recent domestic and international studies regarding neurologic complications related to HIV, including opportunistic infections, peripheral neuropathy, cerebrovascular disease, and HIV-associated neurocognitive disorders, in light of the growing population affected by these conditions.
MeSH term(s)	Global Health/statistics & numerical data ; HIV Infections/complications ; HIV Infections/epidemiology ; HIV Infections/therapy ; Humans ; Nervous System Diseases/epidemiology ; Nervous System Diseases/etiology ; Nervous System Diseases/therapy ; Nervous System Diseases/virology ; Neurology/methods ; Prevalence
Language	English
Publishing date	2018-05-23
Publishing country	United States
Document type	Journal Article
ZDB-ID	603165-1
ISSN	1098-9021 ; 0271-8235
ISSN (online)	1098-9021
ISSN	0271-8235
DOI	10.1055/s-0038-1649334
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Zs.A 1737: Show issues

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Article ; Online: CROI 2014: Neurologic complications of HIV infection.

Spudich, Serena S

Topics in antiviral medicine

2014 Volume 22, Issue 2, Page(s) 594–601

Abstract: A shift in focus in the field of neuroHIV was clearly manifest at the 2014 Conference on Retroviruses and Opportunistic Infections (CROI), where a major emphasis was on the milder forms of neurologic morbidity, including cognitive impairment, seen in ... ...

Abstract	A shift in focus in the field of neuroHIV was clearly manifest at the 2014 Conference on Retroviruses and Opportunistic Infections (CROI), where a major emphasis was on the milder forms of neurologic morbidity, including cognitive impairment, seen in well-treated patients. Mechanisms of this persistent abnormality were investigated, including extensive analysis of the prevalence and associations of persistent HIV detection in cerebrospinal fluid (CSF) and characterization of persistent CNS immune activation. Another key emphasis was the early establishment of HIV replication and inflammation within the central nervous system (CNS) and the potentially salutary effect of very early HIV diagnosis and treatment in protecting the CNS from HIV-related injury. Mitochondrial function was identified as a potential mediator of a number of aspects of HIV-associated CNS dysfunction, including neurotoxicity associated with efavirenz, host genetic determinants of HIV-associated neurocognitive disorders (HAND), associations with direct measures of mitochondria in CSF, and metabolomic screening of CSF in HIV-infected subjects and those with HAND. Many studies employed laboratory rather than neuropsychologic end points, with a major focus on CSF biomarkers. Overall, neuroHIV presentations at CROI 2014 provided new insights into pathogenesis and treatment of the CNS, raising new challenges for researchers and practitioners aiming to optimize the status of the brain in people living with HIV infection.
MeSH term(s)	AIDS Dementia Complex/diagnosis ; AIDS Dementia Complex/epidemiology ; AIDS Dementia Complex/etiology ; AIDS Dementia Complex/therapy ; Anti-HIV Agents/adverse effects ; Anti-HIV Agents/therapeutic use ; Drug-Related Side Effects and Adverse Reactions ; HIV Infections/complications ; HIV Infections/drug therapy ; Humans
Chemical Substances	Anti-HIV Agents
Language	English
Publishing date	2014-06-05
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	2656632-1
ISSN	2161-5853 ; 2161-5853
ISSN (online)	2161-5853
ISSN	2161-5853
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Article ; Online: Investigating vascular diseases in people living with HIV by nuclear imaging.

Chan, Phillip / Spudich, Serena

Journal of nuclear cardiology : official publication of the American Society of Nuclear Cardiology

2021 Volume 29, Issue 4, Page(s) 1576–1582

MeSH term(s)	HIV Infections/complications ; HIV Infections/diagnostic imaging ; Humans ; Vascular Diseases
Language	English
Publishing date	2021-04-21
Publishing country	United States
Document type	Editorial ; Comment
ZDB-ID	1212505-2
ISSN	1532-6551 ; 1071-3581
ISSN (online)	1532-6551
ISSN	1071-3581
DOI	10.1007/s12350-021-02613-x
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Zs.A 4121: Show issues

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Article ; Online: New approaches for understanding the potential role of microbes in Alzheimer's disease.

Whitson, Heather E / Banks, William A / Diaz, Monica M / Frost, Bess / Kellis, Manolis / Lathe, Richard / Schmader, Kenneth E / Spudich, Serena S / Tanzi, Rudolph / Garden, Gwenn

Brain, behavior, & immunity - health

2024 Volume 36, Page(s) 100743

Abstract: Alzheimer's disease (AD) involves a complex pathological process that evolves over years, and its etiology is understood as a classic example of gene-environment interaction. The notion that exposure to microbial organisms may play some role in AD ... ...

Abstract	Alzheimer's disease (AD) involves a complex pathological process that evolves over years, and its etiology is understood as a classic example of gene-environment interaction. The notion that exposure to microbial organisms may play some role in AD pathology has been proposed and debated for decades. New evidence from model organisms and -omic studies, as well as epidemiological data from the recent COVID-19 pandemic and widespread use of vaccines, offers new insights into the "germ hypothesis" of AD. To review new evidence and identify key research questions, the Duke/University of North Carolina (Duke/UNC) Alzheimer's Disease Research Center hosted a virtual symposium and workshop: "New Approaches for Understanding the Potential Role of Microbes in Alzheimer's disease." Discussion centered around the antimicrobial protection hypothesis of amyloid accumulation, and other mechanisms by which microbes could influence AD pathology including immune cell activation, changes in blood-brain barrier, or direct neurotoxicity. This summary of proceedings reviews the content presented in the symposium and provides a summary of major topics and key questions discussed in the workshop.
Language	English
Publishing date	2024-02-21
Publishing country	United States
Document type	Journal Article ; Review
ISSN	2666-3546
ISSN (online)	2666-3546
DOI	10.1016/j.bbih.2024.100743
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Article ; Online: Small Fiber Neuropathy after COVID-19: A Key to Long COVID

McAlpine, Lindsay S. / Zubair, Adeel S. / Joseph, Phillip / Spudich, Serena S.

medRxiv

Abstract: Objectives: Report a case series of new onset small fiber neuropathy (SFN) after COVID-19 treated with intravenous immunoglobulin (IVIG). SFN is a critical objective finding in long COVID and amenable to treatment. Methods: A retrospective chart review ... ...

Abstract	Objectives: Report a case series of new onset small fiber neuropathy (SFN) after COVID-19 treated with intravenous immunoglobulin (IVIG). SFN is a critical objective finding in long COVID and amenable to treatment. Methods: A retrospective chart review was conducted on patients seen in the NeuroCOVID Clinic at Yale who developed new-onset SFN after a documented COVID-19 illness. We documented demographics, symptoms, treatments, diagnostics, and clinical response to treatment. Results: Sixteen patients were diagnosed with length dependent or independent SFN on skin biopsy (median age 47, 75% female, 75% Caucasian). Among the nine patients tested for autoantibodies, six were positive for either trisulfated heparin disaccharide (TS-HDS) or fibroblast growth factor receptor 3 (FGFR3). Eight patients underwent treatment with IVIG and experience significant clinical improvement in their neuropathic symptoms. 92% of patients reported post-exertional malaise characteristic of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and six patients underwent invasive cardiopulmonary exercise testing (iCPET), which demonstrated neurovascular dysregulation and dysautonomia consistent with ME/CFS. Discussion: Here we present preliminary evidence that SFN is responsive to treatment with IVIG and linked with neurovascular dysregulation and dysautonomia. A larger clinical trial is indicated to further demonstrate the clinical utility of IVIG in treating post-infectious small fiber neuropathy.
Keywords	covid19
Language	English
Publishing date	2023-11-08
Publisher	Cold Spring Harbor Laboratory Press
Document type	Article ; Online
DOI	10.1101/2023.11.07.23297764
Database	COVID19

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