Nancy Klimas

Nancy G. Klimas, MD, is an American researcher and physician who is the Director at the Institute for Neuro Immune Medicine at Nova Southeastern University in Miami and Ft. Lauderdale, Florida. She is, also: Director of Clinical Immunology Research, Miami VAMC; Professor of Medicine, Department of Clinical Immunology, College of Osteopathic Medicine, Nova Southeastern University; Chair, Department of Clinical Immunology, College of Osteopathic Medicine, Nova Southeastern University; and Professor Emerita, University of Miami, School of Medicine.

Klimas is one of the authors of the 2011 case definition, International Consensus Criteria, as well as, one of the authors of the 2003 Canadian Consensus Criteria for ME/CFS, published as Myalgic Encephalomyelitis/Chronic Fatigue Syndrome:Clinical Working Case Definition,Diagnostic and Treatment Protocols

Likewise, she was one of the experts on the "Committee on the Diagnostic Criteria for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome" that was convened for the 2015 Institute of Medicine report.

Klimas served as past President of the Board of Directors of the International Association for Chronic Fatigue Syndrome/Myalgic Encephalomyelitis from 2004-2009. She was a voting member of the Health and Human Services's CFSAC committee from 04/01/07-04/01/11.

Awards

• 2014, Rudy Perpich Senior Lectureship Award, presented to a distinguished CFS/FMS scientist, physician or healthcare worker awarded by IACFS/ME
• 2011, Nelson Gantz Outstanding Clinician Award awarded to a physician who emulates Nelson Gantz's clinical acumen, his passion for medicine, and his empathy for persons with CFS/FM awarded by IACFS/ME

Notable studies

• 2017, Telephone-administered versus live group cognitive behavioral stress management for adults with CFS

  Abstract - "OBJECTIVE: Chronic fatigue syndrome (CFS) symptoms have been shown to be exacerbated by stress and ameliorated by group-based psychosocial interventions such as cognitive behavioral stress management (CBSM). Still, patients may have difficulty attending face-to-face groups. This study compared the effects of a telephone-delivered (T-CBSM) vs a live (L-CBSM) group on perceived stress and symptomology in adults with CFS. METHODS: Intervention data from 100 patients with CFS (mean age 50years; 90% female) participating in T-CBSM (N=56) or L-CBSM (N=44) in previously conducted randomized clinical trials were obtained. Perceived Stress Scale (PSS) and the Centers for Disease Control and Prevention symptom checklist scores were compared with repeated measures analyses of variance in adjusted and unadjusted analyses. RESULTS: Participants across groups showed no differences in most demographic and illness variables at study entry and had similar session attendance. Both conditions showed significant reductions in PSS scores, with L-CBSM showing a large effect (partial ε2=0.16) and T-CBSM a medium effect (partial ε2=0.095). For CFS symptom frequency and severity scores, L-CBSM reported large effect size improvements (partial ε2=0.19-0.23), while T-CBSM showed no significant changes over time. CONCLUSIONS: Two different formats for delivering group-based CBSM-live and telephone-showed reductions in perceived stress among patients with CFS. However, only the live format was associated with physical symptom improvements, with specific effects on post-exertional malaise, chills, fever, and restful sleep. The added value of the live group format is discussed, along with implications for future technology-facilitated group interventions in this population.

• 2016, Poor sleep quality is associated with greater circulating pro-inflammatory cytokines and severity and frequency of chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) symptoms in women

  "ABSTRACT: Objective - Poor sleep quality has been linked to inflammatory processes and worse disease outcomes in the context of many chronic illnesses, but less is known in conditions such as chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME). This study examines the relationships between sleep quality, pro-inflammatory cytokines, and CFS/ME symptoms. Methods - Sixty women diagnosed with CFS/ME were assessed using the Pittsburgh Sleep Quality Index (PSQI), Fatigue Symptom Inventory (FSI) and Center for Disease Control and Prevention (CDC)-based CFS/ME symptom questionnaires. Circulating plasma pro-inflammatory cytokine levels were measured by ELISA. Multiple regression analyses examined associations between sleep, cytokines and symptoms, controlling for age, education, and body mass index. Results - Poor sleep quality (PSQI global score) was associated with greater pro-inflammatory cytokine levels: interleukin-1β (IL-1β) (β = 0.258, p = 0.043), IL-6 (β = 0.281, p = 0.033), and tumor necrosis factor-alpha (TNF-α) (β = 0.263, p = 0.044). Worse sleep quality related to greater fatigue severity (β = 0.395, p = 0.003) and fatigue-related interference with daily activities (β = 0.464, p < 0.001), and more severe and frequent CDC-defined core CFS/ME symptoms (β = 0.499, p < 0.001, and β = 0.556, p < 0.001, respectively). Conclusions - Results underscore the importance of managing sleep-related difficulties in this patient population. Further research is needed to identify the etiology of sleep disruptions in CFS/ME and mechanistic factors linking sleep quality to symptom severity and inflammatory processes."

• 2016, Illness progression in chronic fatigue syndrome: a shifting immune baseline
• 2016, Tracking post-infectious fatigue in clinic using routine Lab tests.

  ABSTRACT:"BACKGROUND: While biomarkers for chronic fatigue syndrome (CFS) are beginning to emerge they typically require a highly specialized clinical laboratory. We hypothesized that subsets of commonly measured laboratory markers used in combination could support the diagnosis of post-infectious CFS (PI-CFS) in adolescents following infectious mononucleosis (IM) and help determine who might develop persistence of symptoms. METHODS: Routine clinical laboratory markers were collected prospectively in 301 mono-spot positive adolescents, 4 % of whom developed CFS (n = 13). At 6, 12, and 24 months post-diagnosis with IM, 59 standard tests were performed including metabolic profiling, liver enzyme panel, hormone profiles, complete blood count (CBC), differential white blood count (WBC), salivary cortisol, and urinalysis....RESULTS: Lower ACTH levels at 6 months post-IM diagnosis were highly predictive of CFS (AUC p = 0.02). ACTH levels in CFS overlapped with healthy controls at 12 months, but again showed a trend towards a deficiency at 24 months. Conversely, estradiol levels depart significantly from normal at 12 months only to recover at 24 months (AUC p = 0.02). Finally, relative neutrophil count showed a significant departure from normal at 24 months in CFS (AUC p = 0.01). Expression of these markers evolved differently over time between groups. CONCLUSIONS: Preliminary results suggest that serial assessment of stress and sex hormones as well as the relative proportion of innate immune cells measured using standard clinical laboratory tests may support the diagnosis of PI-CFS in adolescents with IM."

• 2016, Dr. Nancy Klimas, Dr. Irma Rey and several other researchers studied patients who developed gastroparesis following a viral history of flu-like symptoms or gastroenteritis. Nine at of the eleven patients with Idiopathic Gastroparesis studied (82 %) had active enterovirus infection on gastric biopsies. The study conclusion was that "antiviral and/or immune therapies against enterovirus seem to be favorable, as most of our patients had resolution of their gastroparesis symptoms after treatment. This is the first study to identify enterovirus as a possible infectious etiology of idiopathic gastroparesis.
• 2015, Findings from a clinical and laboratory database developed for discovery of pathogenic mechanisms in myalgic encephalomyelitis/chronic fatigue syndrome. Abstract
• 2015, Chronic fatigue syndrome and co-morbid and consequent conditions: evidence from a multi-site clinical epidemiology study. Abstract
• 2015, Distinct plasma immune signatures in ME/CFS are present early in the course of illness FULL TEXT

  "Abstract: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is an unexplained incapacitating illness that may affect up to 4 million people in the United States alone. There are no validated laboratory tests for diagnosis or management despite global efforts to find biomarkers of disease. We considered the possibility that inability to identify such biomarkers reflected variations in diagnostic criteria and laboratory methods as well as the timing of sample collection during the course of the illness. Accordingly, we leveraged two large, multicenter cohort studies of ME/CFS to assess the relationship of immune signatures with diagnosis, illness duration, and other clinical variables. Controls were frequency-matched on key variables known to affect immune status, including season of sampling and geographic site, in addition to age and sex. We report here distinct alterations in plasma immune signatures early in the course of ME/CFS (n = 52) relative to healthy controls (n = 348) that are not present in subjects with longer duration of illness (n = 246). Analyses based on disease duration revealed that early ME/CFS cases had a prominent activation of both pro- and anti-inflammatory cytokines as well as dissociation of intercytokine regulatory networks. We found a stronger correlation of cytokine alterations with illness duration than with measures of illness severity, suggesting that the immunopathology of ME/CFS is not static. These findings have critical implications for discovery of interventional strategies and early diagnosis of ME/CFS."

• 2014, Stress management skills, cortisol awakening response, and post-exertional malaise in Chronic Fatigue Syndrome
• 2012, Minimum data elements for research reports on CFS. Full text

  Abstract: "Chronic fatigue syndrome (CFS) is a debilitating condition that has received increasing attention from researchers in the past decade. However, it has become difficult to compare data collected in different laboratories due to the variability in basic information regarding descriptions of sampling methods, patient characteristics, and clinical assessments. The issue of variability in CFS research was recently highlighted at the NIH's 2011 State of the Knowledge of CFS meeting prompting researchers to consider the critical information that should be included in CFS research reports. To address this problem, we present our consensus on the minimum data elements that should be included in all CFS research reports, along with additional elements that are currently being evaluated in specific research studies that show promise as important patient descriptors for subgrouping of CFS. These recommendations are intended to improve the consistency of reported methods and the interpretability of reported results. Adherence to minimum standards and increased reporting consistency will allow for better comparisons among published CFS articles, provide guidance for future research and foster the generation of knowledge that can directly benefit the patient."

• 2012, Biomarkers for chronic fatigue.
• 2012, Cytokine expression profiles of immune imbalance in post-mononucleosis chronic fatigue
• 2010, Plasma neuropeptide Y: a biomarker for symptom severity in chronic fatigue syndrome
• 2010, A Formal Analysis of Cytokine Networks in Chronic Fatigue Syndrome Full Text
• 2005, Stress-associated changes in the steady state expression of latent Epstein-Barr Virus: Implications for Chronic Fatigue Syndrome and Cancer

  Abstract - "Antibodies to several Epstein-Barr virus (EBV)-encoded enzymes are observed in patients with different EBV-associated diseases. The reason for these antibody patterns and the role these proteins might play in the pathophysiology of disease, separate from their role in virus replication, is unknown. In this series of studies, we found that purified EBV deoxyuridine triphosphate nucleotidohydrolase (dUTPase) can inhibit the replication of human peripheral blood mononuclear cells in vitro and upregulate the production of TNF-alpha, IL-1beta, IL-6, IL-8, and IL-10. It also enhanced the ability of natural killer cells to lyse target cells. The EBV dUTPase also significantly inhibited the replication of mitogen-stimulated lymphocytes and the synthesis of IFN-gamma by cells isolated from lymph nodes and spleens obtained from mice inoculated with the protein. It also produced sickness behaviors known to be induced by some of the cytokines that were studied in the in vitro experiments. These symptoms include an increase in body temperature, a decrease in body mass and in physical activity. The data provide a new perspective on how an early nonstructural EBV-encoded protein can cause immune dysregulation and produce clinical symptoms observed in patients with chronic fatigue syndrome (CFS) separate from its role in virus replication and may serve as a new approach to help identify one of the etiological agents for CFS. The data also provide additional insight into the pathophysiology of EBV infection, inflammation, and cancer."

• 2003, Identification of ambiguities in the 1994 chronic fatigue syndrome research case definition and recommendations for resolution
• 2001, Cytokine and Other Immunologic Markers in Chronic Fatigue Syndrome and Their Relation to Neuropsychological Factors
• 2000, Comparative Analysis of Lymphocytes in Lymph Nodes and Peripheral Blood of Patients with Chronic Fatigue Syndrome
• 1996, Interindividual Immune Status Variation Patterns in Patients with Chronic Fatigue Syndrome: Association with Gender and the Tumor Necrosis Factor System

  Abstract - "Changes in soluble immune mediator levels in association with the chronic fatigue syndrome (CFS) usually occur within normal ranges and are apparent mainly as changes in the skewness of population distributions. The latter finding undermines the usefulness of cytokine levels as clinical tools at the individual level as has been seen in sepsis syndrome where a similar overlap occurs. Nonetheless, changes in cytokine levels at the population level can contribute to an understanding of the disease process. For example, we reported previously that significant proportions of CFS patients showed elevated serum levels of either soluble tumor necrosis factor-receptor I (sTNF-RI, sCD120a) or TNF-a as compared to controls. The latter results could reflect different disease processes or extremes of a common disease process. Using sera collected over a five-year period, we have now studied an extended cohort of 108 CFS patients and our results are consistent with a common graded disease process. When we assessed the effect of gender on the distributions of serum levels of immune mediators, levels of sTNF-RI, sTNF-RII (sCD 12Ob), sIL-6R (sCDl26), and sICAM-1 were found to be consistently higher among males than females and among CFS patients as compared to controls regardless of gender. Moreover, differences in soluble immune mediator levels between CFS and control individuals were more clearly defined when restricting the analysis to the female gender. These observations are consistent with endocrine influences on immunological changes."

• 1995, Physical symptoms of chronic fatigue syndrome are exacerbated by the stress of Hurricane Andrew
• 1995, Relationships of Cognitive Difficulties to Immune Measures, Depression and Illness Burden in Chronic Fatigue Syndrome - Abstract
• 1994, Dysregulated expression of tumor necrosis factor in chronic fatigue syndrome: interrelations with cellular sources and patterns of soluble immune mediator expression

  "ABSTRACT: Among a group of 70 individuals who met the criteria established by the Centers for Disease Control and Prevention (Atlanta) for chronic fatigue syndrome (CFS), 12%-28% had serum levels exceeding 95% of control values for tumor necrosis factor (TNF) alpha, TNF-beta, interleukin (IL) 1 alpha, IL-2, soluble IL-2 receptor (sIL-2R), or neopterin; overall, 60% of patients had elevated levels of one or more of the nine soluble immune mediators tested. Nevertheless, only the distributions for circulating levels of TNF-alpha and TNF-beta differed significantly in the two populations. In patients with CFS--but not in controls--serum levels of TNF-alpha, IL-1 alpha, IL-4, and sIL-2R correlated significantly with one another and (in the 10 cases analyzed) with relative amounts (as compared to beta-globin or beta-actin) of the only mRNAs detectable by reverse transcriptase-coupled polymerase chain reaction in peripheral-blood mononuclear cells: TNF-beta, unspliced and spliced; IL-1 beta, lymphocyte fraction; and IL-6 (in order of appearance). These findings point to polycellular activation and may be relevant to the etiology and nosology of CFS."

Interviews & talks

There are many videos on YouTube of Nancy Klimas speaking about her work.

• Dec 2, 2016, Episode 84 of ME/CFS Alert - Dr Nancy Klimas on ME/CFS Research, Treatment
• Dec 1, 2016 NBCDFW video interview and transcription
• 2014 ME/CFS Diagnosis and Name with Dr. Nancy Klimas
• 2014 ME/CFS Treatment Options Part 1 with Dr. Nancy Klimas
• 2014 ME/CFS Treatment Options Part 2 with Dr. Nancy Klimas
• ME/CFS and Exercise: VO2 Max Testing with Nancy Klimas M.D. PREVIEW
• 2011 ME/CFS Management A Pathogenesis Based Approach (sponsored by ANZMES)
• From Bedside to Bench and Back Again: Untangling the Mystery of Gulf War Illness and Chronic Fatigue Syndrome

Quotations

• "They experience a level of disability equal to that of patients with late-stage AIDS and patients undergoing chemotherapy"

Open Letter to The Lancet

Two open letters to the editor of The Lancet urged the editor to commission a fully independent review of the PACE trial, which the journal had published in 2011. In 2016, Dr. Klimas, along with 41 colleagues in the ME/CFS field, signed the second letter.

• 10 February 2016, An open letter to The Lancet, again - Virology blog

Online presence

• PubMed - Nancy Klimas
• Nova Southeasterm University - Nancy Klimas

See also

• Dr. Gordon Broderick
• Dr. Mary Ann Fletcher
• Dr. Irma Rey
• Dr. Maria Vera
• Institute for Neuro Immune Medicine

myalgic encephalomyelitis (M.E.) - A disease often marked by neurological symptoms, but fatigue is sometimes a symptom as well. Some diagnostic criteria distinguish it from chronic fatigue syndrome, while other diagnostic criteria consider it to be a synonym for chronic fatigue syndrome. A defining characteristic of ME is post-exertional malaise (PEM), or post-exertional neuroimmune exhaustion (PENE), which is a notable exacerbation of symptoms brought on by small exertions. PEM can last for days or weeks. Symptoms can include cognitive impairments, muscle pain (myalgia), trouble remaining upright (orthostatic intolerance), sleep abnormalities, and gastro-intestinal impairments, among others. An estimated 25% of those suffering from ME are housebound or bedbound. The World Health Organization (WHO) classifies ME as a neurological disease.

cognition Thought processes, including attention, reasoning, and memory.

stress Stress can by either physical or psychological, or both. Stress is either 1) a state of emotional or psychological strain or 2) the physical stress (pressure or tension) that a physical object such the human body is placed under, e.g., a stress test is a medical test that monitors the cardiovascular system during strenuous exercise.

Centers for Disease Control and Prevention (CDC) - The Centers for Disease Control and Prevention is a U.S. government agency dedicated to epidemiology and public health. It operates under the auspices of the Department of Health and Human Services.

post-exertional malaise (PEM) - A notable exacerbation of symptoms brought on by small physical or cognitive exertions. PEM may be referred to as a "crash" or "collapse" and can last for days or weeks. Symptoms can include cognitive impairments, muscle pain, trouble remaining upright (orthostatic intolerance), sleep abnormalities, and gastro-intestinal impairments, and others.

chronic illness any long-term illness, regardless of the severity. Chronic illnesses are typically incurable, requiring long-term management.

cytokine any class of immunoregulatory proteins secreted by cells, especially immune cells. Cytokines are small proteins important in cell signaling that modulate the immune system. (Learn more: me-pedia.org)

Centers for Disease Control and Prevention (CDC) - The Centers for Disease Control and Prevention is a U.S. government agency dedicated to epidemiology and public health. It operates under the auspices of the Department of Health and Human Services.

Centers for Disease Control and Prevention (CDC) - The Centers for Disease Control and Prevention is a U.S. government agency dedicated to epidemiology and public health. It operates under the auspices of the Department of Health and Human Services.

cytokine any class of immunoregulatory proteins secreted by cells, especially immune cells. Cytokines are small proteins important in cell signaling that modulate the immune system. (Learn more: me-pedia.org)

β β / Β. Greek letter beta (a symbol used in science), equivalent to "b".

α α / Α. Greek letter alpha or alfa (a symbol used in science), equivalent to "a".

etiology The cause of origin, especially of a disease.

enzyme a substance produced by a living organism which acts as a catalyst to bring about a specific biochemical reaction.

enterovirus A genus of RNA viruses which typically enter the body through the respiratory or gastrointestinal systems and sometimes spread to the central nervous system or other parts of the body, causing neurological, cardiac, and other damage. Since the first reports of myalgic encephalomyelitis (ME), enteroviruses have been suspected as a cause of ME. Enteroviruses have also been implicated as the cause of Type I diabetes, congestive heart failure, and other conditions. Enteroviruses include poliovirus, coxsackieviruses, and many others. New enteroviruses and new strains of existing enteroviruses are continuously being discovered. (Learn more: viralzone.expasy.org)

myalgic encephalomyelitis (M.E.) - A disease often marked by neurological symptoms, but fatigue is sometimes a symptom as well. Some diagnostic criteria distinguish it from chronic fatigue syndrome, while other diagnostic criteria consider it to be a synonym for chronic fatigue syndrome. A defining characteristic of ME is post-exertional malaise (PEM), or post-exertional neuroimmune exhaustion (PENE), which is a notable exacerbation of symptoms brought on by small exertions. PEM can last for days or weeks. Symptoms can include cognitive impairments, muscle pain (myalgia), trouble remaining upright (orthostatic intolerance), sleep abnormalities, and gastro-intestinal impairments, among others. An estimated 25% of those suffering from ME are housebound or bedbound. The World Health Organization (WHO) classifies ME as a neurological disease.

National Institutes of Health (NIH) - A set of biomedical research institutes operated by the U.S. government, under the auspices of the Department of Health and Human Services.

cytokine any class of immunoregulatory proteins secreted by cells, especially immune cells. Cytokines are small proteins important in cell signaling that modulate the immune system. (Learn more: me-pedia.org)

plasma The liquid part of blood, lymph, or milk after removing any suspended material. Most of the time, "plasma" simply refers to blood, after all the blood cells have been removed. If you also remove the clotting factors, then the plasma is referred to as "serum".

antibodies Antibody/immunoglobulin refers to any of a large number of specific proteins produced by B cells that act against an antigen in an immune response.

enzyme a substance produced by a living organism which acts as a catalyst to bring about a specific biochemical reaction.

antibodies Antibody/immunoglobulin refers to any of a large number of specific proteins produced by B cells that act against an antigen in an immune response.

etiology The cause of origin, especially of a disease.

serum The clear yellowish fluid that remains from blood plasma after clotting factors have been removed by clot formation. (Blood plasma is simply blood that has had its blood cells removed.)

serum The clear yellowish fluid that remains from blood plasma after clotting factors have been removed by clot formation. (Blood plasma is simply blood that has had its blood cells removed.)

β β / Β. Greek letter beta (a symbol used in science), equivalent to "b".

enterovirus A genus of RNA viruses which typically enter the body through the respiratory or gastrointestinal systems and sometimes spread to the central nervous system or other parts of the body, causing neurological, cardiac, and other damage. Since the first reports of myalgic encephalomyelitis (ME), enteroviruses have been suspected as a cause of ME. Enteroviruses have also been implicated as the cause of Type I diabetes, congestive heart failure, and other conditions. Enteroviruses include poliovirus, coxsackieviruses, and many others. New enteroviruses and new strains of existing enteroviruses are continuously being discovered. (Learn more: viralzone.expasy.org)

etiology The cause of origin, especially of a disease.

somatic symptom disorder A psychiatric term to describe an alleged condition whereby a person's thoughts somehow cause physical symptoms. The actual existence of such a condition is highly controversial, due to a lack of scientific evidence. It is related to other psychiatric terms, such as "psychosomatic", "neurasthenia", and "hysteria". Older terms include "somatization", "somatoform disorder", and "conversion disorder". Such terms refer to a scientifically-unsupported theory that claims that a wide range of physical symptoms can be created by the human mind, a theory which has been criticized as "mind over matter" parapsychology, a pseudoscience.

cognition Thought processes, including attention, reasoning, and memory.