TGI Friday! Our weekly roundup of recently published research abstracts and related items | 4 April 2014

Journal of Nuclear Medicine, 24 March 2014. Epub ahead of print].

Neuroinflammation in Patients with Chronic Fatigue Syndrome/Myalgic Encephalomyelitis: An 11C-(R)-PK11195 PET Study.

Nakatomi Y(1), Mizuno K, Ishii A, Wada Y, Tanaka M, Tazawa S, Onoe K, Fukuda S, Kawabe J, Takahashi K, Kataoka Y, Shiomi S, Yamaguti K, Inaba M, Kuratsune H, Watanabe Y.
(1) Department of Metabolism, Endocrinology and Molecular Medicine, Osaka
City University Graduate School of Medicine, Osaka, Japan.

Abstract

Chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) is a disease characterized by chronic, profound, disabling, and unexplained fatigue. Although it is hypothesized that brain inflammation is involved in the pathophysiology of CFS/ME, there is no direct evidence of neuroinflammation in patients with CFS/ME. Activation of microglia or astrocytes is related to neuroinflammation.

11C-(R)-(2-chlorophenyl)-N-methyl-N-(1-methylpropyl)-3-isoquinoline-carboxamide (11C-(R)-PK11195) is a ligand of PET for a translocator protein that is expressed by activated microglia or astrocytes. We used 11C-(R)-PK11195 and PET to investigate the existence of neuroinflammation in CFS/ME patients.

METHODS

Nine CFS/ME patients and 10 healthy controls underwent 11C-(R)-PK11195 PET and completed questionnaires about fatigue, fatigue sensation, cognitive impairments, pain, and depression. To measure the density of translocator protein, non displaceable binding potential (BPND) values were determined using linear graphical analysis with the cerebellum as a reference region.

RESULTS

The BPND values of 11C-(R)-PK11195 in the cingulate cortex, hippocampus, amygdala, thalamus, midbrain, and pons were 45%-199% higher in CFS/ME patients than in healthy controls. In CFS/ME patients, the BPND values of 11C-(R)-PK11195 in the amygdala, thalamus, and midbrain positively correlated with cognitive impairment score, the BPND values in the cingulate cortex and thalamus positively correlated with pain score, and the BPND value in the hippocampus positively correlated with depression score.

CONCLUSION

Neuroinflammation is present in widespread brain areas in CFS/ME patients and was associated with the severity of neuropsychologic symptoms. Evaluation of neuroinflammation in CFS/ME patients may be essential for understanding the core pathophysiology and for developing objective diagnostic criteria and effective medical treatments.

From the Journal of Investigative Medicine: high impact care reports, 18 March 2014 (Downloads full report).

Postural Orthostatic Tachycardia With Chronic Fatigue After HPV Vaccination as Part of the “Autoimmune/Auto-inflammatory Syndrome Induced by Adjuvants

Case Report and Literature Review

Lucija Tomljenovic, PhD(1,2), Serena Colafrancesco, MD(1,3), Carlo Perricone, MD(1,3). Yehuda Shoenfeld, MD, FRCP (Hon), MaACR(1,4).
1) Sheba Medical Center, Tel-Hashomer, Israel
2) University of British Columbia, Vancouver, British Columbia, Canada
3) Sapienza University of Rome, Rome, Italy
4) Tel Aviv University, Tel Aviv, Israel

Yehuda Shoenfeld, The Zabludowicz Center for Autoimmune Diseases, Sheba Medical Center, Tel Hashomer 52621, Israel. Email: Shoenfel@post.tau.ac.il

Abstract

We report the case of a 14-year-old girl who developed postural orthostatic tachycardia syndrome (POTS) with chronic fatigue 2 months following Gardasil vaccination.

The patient suffered from persistent headaches, dizziness, recurrent syncope, poor motor coordination, weakness, fatigue, myalgias, numbness, tachycardia, dyspnea, visual disturbances, phonophobia, cognitive impairment, insomnia, gastrointestinal disturbances, and a weight loss of 20 pounds.

The psychiatric evaluation ruled out the possibility that her symptoms were psychogenic or related to anxiety disorders. Furthermore, the patient tested positive for ANA (1:1280), lupus anticoagulant, and antiphospholipid.

On clinical examination she presented lived reticularis and was diagnosed with Raynaud's syndrome. This case
fulfills the criteria for the autoimmune/auto-inflammatory syndrome induced by adjuvants (ASIA). Because human papillomavirus vaccination is universally recommended to teenagers and because POTS frequently results in long-term disabilities (as was the case in our patient), a thorough follow-up of patients who present with relevant complaints after vaccination is strongly recommended.

From Journal of Military and Veterans' Health, Australian Military Medicine Association, 1 May 2013.

Method Issues in Epidemiological Studies of Medically Unexplained Symptom-based Conditions in Veterans.

Coughlin SS(1), McNeil RB(2), Provenzale DT(3), Dursa EK(4), Thomas CM(2).
1) Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, GA.
2) Durham Epidemiologic Research and Information Center, Veterans Affairs Medical Center, Durham, NC.
3) Durham Epidemiologic Research and Information Center, Veterans Affairs Medical Center, Durham, NC ; Division of Gastroenterology, Duke University Medical Center, Durham, NC.
4) Epidemiology Program, Post-deployment Health Group, Office of Public Health, Department of Veterans Affairs, Washington, DC.

Abstract

Symptom-based conditions such as chronic fatigue syndrome (CFS) and medically unexplained multi-symptom illness (MSI) are fairly common in the general population and are also important veteran's health concerns due to their higher frequency among U.S. veterans who served during the 1990-1991 Gulf War.

CFS, MSI, and other symptom-based conditions are often associated with considerable morbidity due to fatigue, chronic pain, neurologic symptoms, and other symptoms that can impair the quality of life.

This article discusses several important issues of methodology that arise in population studies of CFS and MSI. These include the exclusion criteria that have been used in population studies to define CFS-like illness and unexplained MSI, the potential for false positive and false negative assessments of illness status, the potential for sex differences, and the poorly understood natural history of these symptom-based conditions across the life span.

As an empirical example of these methodology issues, we examined existing data from a 2005 follow-up survey. We found that 64.9% (762 of 1,175) of female Gulf War veterans and 53.4% (2,530 of 4,739) of male Gulf War veterans had 1 or more exclusionary medical conditions. The prevalence among veterans with one or more exclusionary medical conditions increased markedly by age among females and those with a low income.