Avindra nath

A workshop titled "Beyond the Symptom: The Biology of Fatigue" was held virtually September 27-28, 2021. It was jointly organized by the Sleep Research Society and the Neurobiology of Fatigue Working Group of the NIH Blueprint Neuroscience Research Program. For access to the presentations and video recordings, see: https : //neuroscienceblueprint.nih.gov/about/event/beyond-symptom-biology-fatigue. The goals of this workshop were to bring together clinicians and scientists who use a variety of research approaches to understand fatigue in multiple conditions and to identify key gaps in our understanding of the biology of fatigue...

BACKGROUND: A central feature of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is post exertional malaise (PEM), which is an acute worsening of symptoms after a physical, emotional and/or mental exertion. PEM is also a feature of Long COVID. Dynamic measures of PEM have historically included scaled questionnaires which have not been validated in ME/CFS. To enhance our understanding of PEM and how best to measure it, we conducted semi-structured qualitative interviews (QIs) at the same intervals as Visual Analog Scale (VAS) measures after a Cardiopulmonary Exercise Test (CPET)...

Over the previous half century, vaccines have shaped human life by eradicating or nearly eradicating infections that were once a major cause of morbidity and mortality. The number of infections for which vaccines are now available has steadily increased. The types of vaccines have evolved over the years from crude extracts to more refined mRNA or protein-based vaccines. With these well-defined manufacturing process, the safety profile has also improved. Despite such measures, vaccines are not without side effects including those that impact the nervous system...

BACKGROUND AND OBJECTIVES: SARS-CoV-2 infection has been associated with a syndrome of long-term neurologic sequelae that is poorly characterized. We aimed to describe and characterize in-depth features of neurologic postacute sequelae of SARS-CoV-2 infection (neuro-PASC). METHODS: Between October 2020 and April 2021, 12 participants were seen at the NIH Clinical Center under an observational study to characterize ongoing neurologic abnormalities after SARS-CoV-2 infection...

BACKGROUND AND OBJECTIVES: Neurologic outcomes in people with HIV (PWH) on long-duration antiretroviral therapy (ART) are not fully understood, and the underlying pathophysiology is unclear. To address this, we established a cohort of such individuals and compared them with HIV-negative controls using a novel matching technique. Both groups underwent extensive cognitive testing, evaluation for psychiatric measures, and MRI and CSF analyses. METHODS: Participants underwent comprehensive neuropsychological testing and completed standardized questionnaires measuring depressive symptoms, perceptions of own functioning, and activities of daily living as part of an observational study...

Recent advances in sequencing technologies and collaborative efforts have led to substantial progress in identifying the genetic causes of amyotrophic lateral sclerosis (ALS). This momentum has, in turn, fostered the development of putative molecular therapies. In this Review, we outline the current genetic knowledge, emphasizing recent discoveries and emerging concepts such as the implication of distinct types of mutation, variability in mutated genes in diverse genetic ancestries and gene-environment interactions...

Chronic, treated HIV and the neurologic effects, both clinically and virologically, is a field with significant potential for research that will have impacts for patients and virologists alike as we seek to better understand HIV reservoirs with the ultimate aim of curing them.

Despite viral suppression with antiretroviral therapy (ART), people with human immunodeficiency virus (HIV) continue to experience central nervous system (CNS) complications, primarily in the form of mild cognitive impairment and mental health disorders (eg, depression, anxiety, other neuropsychiatric problems). The multifactorial pathogenesis and heterogeneity of mechanisms likely underlying CNS complications must be addressed in the development of preventive interventions and effective treatments. The biotyping approach has previously been useful to define phenotypes of other CNS diseases based on underlying mechanisms and could be translated to the field of neuroHIV...

The subspecialty of Experimental Neurotherapeutics trains neurologists in discovering and developing new treatments for neurologic diseases. Based on development of exciting new treatments for genetic and inflammatory diseases, we predict that there will be many other breakthroughs. The job market has expanded rapidly in academia, the pharmaceutical industry, government, and not-for-profit sectors; many new opportunities can be anticipated. The burgeoning opportunities in the field mandate that training address the challenges of overcoming obstacles in therapeutic discovery, implementation science, and development of affordable and equitably available treatments...

PURPOSE OF REVIEW: The purpose of this study was to evaluate demographics, clinical profiles, and outcomes of transverse myelitis (TM) in the setting of COVID-19 infection (iTM) or vaccination (vTM) and to describe a case of spontaneous resolution of iTM. RECENT FINDINGS: Of a total of 158 articles that met our search criteria, 30 articles detailing 65 unique cases were included, of which 48 (73.8%) were iTM and 17 (26.2%) were vTM. The mean age of the iTM group was significantly lower as compared with vTM (43 ± 20...

PURPOSE OF REVIEW: The discipline of experimental neurotherapeutics targets the process and operation of translating scientific discoveries into new treatments for neurologic diseases and has been instrumental in the progression of many areas of neurology. RECENT FINDINGS: From the US Food and Drug Administration (FDA) market approval of the first systemic in vivo gene therapy in neurology to multiple current gene-targeting therapeutics, monoclonal antibodies, and new drugs under development or approved in the last several years, the field of experimental neurotherapeutics has a presence in every neuromuscular clinic in the United States...

BACKGROUND AND OBJECTIVES: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can cause a wide range of neurological complications however its neuropenetrance during the acute phase of the illness is unknown. METHODS: Extracellular vesicles were isolated from brain biopsy tissue from a patient undergoing epilepsy surgery using ultracentrifugation and analyzed by Western blot and qPCR for the presence of virus protein and RNA, respectively. Biopsy tissue was assessed by immunohistochemistry for the presence of microvascular damage and compared to three other non-COVID surgical epilepsy brain tissues...

Transposable elements (TEs) are active in neuronal cells raising the question whether TE insertions contribute to risk of neuropsychiatric disease. While genome-wide association studies (GWAS) serve as a tool to discover genetic loci associated with neuropsychiatric diseases, unfortunately GWAS do not directly detect structural variants such as TEs. To examine the role of TEs in psychiatric and neurologic disease, we evaluated 17,000 polymorphic TEs and find 76 are in linkage disequilibrium with disease haplotypes (P < 10-6 ) defined by GWAS...

No abstract text is available yet for this article.

The etiology of Nodding Syndrome remains unclear, and comprehensive genotyping and phenotyping data from patients remain sparse. Our objectives were to characterize the phenotype of patients with Nodding Syndrome, investigate potential contributors to disease etiology, and evaluate response to immunotherapy. This cohort study investigated members of a single-family unit from Lamwo District, Uganda. The participants for this study were selected by the Ugandan Ministry of Health as representative for Nodding Syndrome and with a conducive family structure for genomic analyses...

IMPORTANCE: Orthopox viruses include smallpox virus, a once feared but now eradicated virus, as well as monkeypox virus. Monkeypox is an emerging virus initially isolated in 1958, previously unrecognized outside sub-Saharan Africa until a worldwide outbreak in May 2022. It is important to review known neurologic consequences of both these viruses, as complications of smallpox may be relevant to monkeypox, though complications of monkeypox may be rarer and perhaps less severe. OBSERVATIONS: This was a literature review of the known neurologic complications of smallpox, which include encephalitis, transverse myelitis, and acute disseminated encephalomyelitis among others; historical complications of smallpox vaccination, including postvaccinal encephalomyelitis; and the known neurologic complications of monkeypox, which include headaches and mood disturbances, as well as rare presentations of encephalitis, transverse myelitis, and seizures...

No abstract text is available yet for this article.

BACKGROUND: Retinal measurements correlate with disease progression in patients with multiple sclerosis; however, whether they associate with neurologic disease in people with controlled HIV is unknown. Using spectral domain optical coherence tomography, we evaluated retinal differences between people with HIV and HIV-negative controls and investigated clinical correlates of retinal thinning. METHODS: People with HIV on antiretroviral therapy for at least 1 year and HIV-negative controls recruited from the same communities underwent spectral domain optical coherence tomography, ophthalmic examination, brain MRI, and neuropsychological testing...

BACKGROUND: HIV persistence during antiretroviral therapy (ART) is the principal obstacle to cure. Lymphoid tissue is a compartment for HIV, but mechanisms of persistence during ART and viral rebound when ART is interrupted are inadequately understood. Metabolic activity in lymphoid tissue of patients on long-term ART is relatively low, and increases when ART is stopped. Increases in metabolic activity can be detected by 18 F-fluorodeoxyglucose Positron Emission Tomography (FDG-PET) and may represent sites of HIV replication or immune activation in response to HIV replication...

OBJECTIVES: Reactivation of HERV-K(HML-2) has been found in subsets of individuals with amyotrophic lateral sclerosis (ALS). This study examines the antibody response against HML-2 in ALS and analyzes its clinical relevance. METHODS: Antibodies to HML-2 envelope (env) were analyzed using a peptide array for epitope mapping and by a peptide enzyme-linked immunosorbent assay (ELISA) in 242 healthy donors, and 243 ALS and 85 multiple sclerosis (MS) individuals. Extracellular levels of HML-2 were analyzed by digital polymerase chain reaction (PCR)...