TGI Friday! Our weekly round-up of recently published research abstracts | 19 December 2014

December 19, 2014

From Cytokine, 13 December 2014 (published before print).

Cytokine expression provides clues to the pathophysiology of Gulf War illness and myalgic encephalomyelitis

Svetlana F. Khaiboullina(a,b), Kenny L. DeMeirleir(b), Shanti Rawat(b), Grady S. Berk(b), Rory S. Gaynor-Berk©, Tatjana Mijatovic(d), Natalia Blatt(b,e), 1, Albert A. Rizvanovb,(e), Sheila G. Young©, Vincent C. Lombardi(a,b)
a) Department of Biochemistry and Molecular Biology, University of Nevada School of Medicine, Reno, NV, USA
b) WPI, Reno, NV, USA
c) Sierra Veterans Research and Education Foundation, VA Sierra Nevada Health Care System, Reno, NV, USA
d) R.E.D Laboratories, Zellik, Belgium
e) Institute of Fundamental Medicine and Biology, Kazan Federal University, Kazan, Republic of Tatarstan, Russian Federatio


• Gulf War illness (GWI) is characterized by a Th1/Th17 shift.
• Th1, Th2 and inflammatory cytokines characterize myalgic encephalomyelitis (ME).
• Cytokine importance by Random Forest were IL-7, IL-4, TNF-α, IL-13, and IL-17F.
• GWI and ME have distinct cytokine profiles despite similar symptomology.


Gulf War illness (GWI) is a chronic disease of unknown etiology characterized by persistent symptoms such as cognitive impairment, unexplained fatigue, pervasive pain, headaches, and gastrointestinal abnormalities. Current reports suggest that as many as 200,000 veterans who served in the 1990–1991 Persian Gulf War were afflicted.

Several potential triggers of GWI have been proposed including chemical exposure, toxins, vaccines, and unknown infectious agents. However, a definitive cause of GWI has not been identified and a specific biological marker that can consistently delineate the disease has not been defined.

Myalgic encephalomyelitis (ME) is a disease with similar and overlapping symptomology, and subjects diagnosed with GWI typically fit the diagnostic criteria for ME. For these reasons, GWI is often considered a subgroup of ME.

To explore this possibility and identify immune parameters that may help to understand GWI pathophysiology, we measured 77 serum cytokines in subjects with GWI and compared these data to that of subjects with ME as well as healthy controls.

Our analysis identified a group of cytokines that identified ME and GWI cases with sensitivities of 92.5% and 64.9%, respectively. The five most significant cytokines in decreasing order of importance were IL-7, IL-4, TNF-α, IL-13, and IL-17F. When delineating GWI and ME cases from healthy controls, the observed specificity was only 33.3%, suggesting that with respect to cytokine expression, GWI cases resemble control subjects to a greater extent than ME cases across a number of parameters.

These results imply that serum cytokines are representative of ME pathology to a greater extent than GWI and further suggest that the two diseases have distinct immune profiles despite their overlapping symptomology.

From Reviews in Medical Virology, May 2014.

Neurological aspects of human parvovirus B19 infection: a systematic review.

Barah F, Whiteside S, Batista S, Morris J.
Center for Neuroscience and Cell Biology, Faculty of Medicine, University of Coimbra, Coimbra, Portugal.


Parvovirus B19 has been linked with various clinical syndromesincluding neurological manifestations. However, its role in the latter
remains not completely understood. Although the last 10 years witnessed a surge of case reports on B19-associated neurological
aspects, the literature data remains scattered and heterogeneous, and epidemiological information on the incidence of B19-associated
neurological aspects cannot be accurately extrapolated.

The aim of this review is to identify the characteristics of cases of B19-associated neurological manifestations. A computerized systematic review of existing literature concerning cases of B19-related neurological aspects revealed 89 articles describing 129 patients; 79 (61.2%) were associated with CNS manifestations, 41 (31.8%) were associated with peripheral nervous system manifestations, and 9 (7.0%) were linked with myalgic encephalomyelitis.

The majority of the cases (50/129) had encephalitis. Clinical characteristic features of these cases were analyzed, and possible pathological mechanisms were also described.

In conclusion, B19 should be included in differential diagnosis of encephalitic syndromes of unknown etiology in all age groups. Diagnosis should rely on investigation of anti-B19 IgM antibodies and detection of B19 DNA in serum or CSF.

Treatment of severe cases might benefit from a combined regime of intravenous immunoglobulins and steroids. To confirm these outcomes, goal-targeted studies are recommended to exactly identify epidemiological scenarios and explore potential pathogenic mechanisms of these complications.

Performing retrospective and prospective and multicenter studies concerning B19 and neurological aspects in general, and B19 and
encephalitic syndromes in particular, are required.

From The Clinical Journal of Pain, 11 December 2014 (e-published before print).

The process of change in pain during Cognitive Behavior Therapy for Chronic Fatigue Syndrome

Bloot, Lotte Msc; Heins, Marianne J. Msc, PhD; Donders, Rogier PhD; Bleijenberg, Gijs PhD; Knoop, Hans PhD
Radboud University, Nijmegen, The Netherlands



Cognitive behavior therapy (CBT) leads to a reduction of fatigue and pain in chronic fatigue syndrome (CFS). The processes underlying the reduction in pain have not been investigated. Recently, it was shown that increased self-efficacy, decreased focusing on symptoms, increased physical functioning and a change in beliefs about activity contribute to the decrease in fatigue.


The present study has two objectives: (1) to determine the relationship between the reduction of fatigue and pain during CBT; (2) test to what extent the model for change in fatigue is applicable to the reduction in pain.


142 patients meeting US center for disease criteria for CFS, currently reporting pain, and starting CBT were included. A cross-lagged analysis was performed to study the causal direction of change between pain and fatigue. Pain and process variables were assessed before therapy, three times during CBT and after therapy. Actual physical activity was also assessed. The model was tested with multiple regression analyses.


The direction of change between pain and fatigue could not be determined. An increase in physical functioning and decrease in focusing on symptoms explained 4 to 14% of the change in pain.


Pain and fatigue most probably decrease simultaneously during CBT. Pain reduction can partly be explained by a reduction of symptom focusing and increased physical functioning. Additional, yet unknown cognitive-behavioral factors also play a role in the reduction of pain.

From the Annals of Medical and Health Services Research, November 2014.

Hepatitis B vaccination and associated oral manifestations: a non-systematic review of literature and case reports.

Tarakji B(1), Ashok N(1), Alakeel R(2), Azzeghaibi S(1), Umair A(1), Darwish S(1), Mahmoud R(3), Elkhatat E(3).
1) Department of Oral Maxillofacial Sciences, Alfarabi College of Dentistry and Nursing, Riyadh, Saudi Arabia.
2) Department of Clinical Laboratory Sciences, King Saud University, Alfarabi College of Medicine, Riyadh, Saudi Arabia.
3) Department of Restorative Dentistry Sciences, Alfarabi College of Dentistry and Nursing, Saudi Arabia.


Hepatitis B vaccine has been administered in children and adults routinely to reduce the incidence of the disease. Even though, hepatitis B vaccine is considered as highly safe, some adverse reactions have been reported.

A literature search was carried out in PubMed, accessed via the National Library of Medicine PubMed interface, searching used the following keywords: Hepatitis B vaccine and complications from 1980 to 2014.

A total of 1147 articles were obtained out of which articles, which discuss the complications occurring orally or occurring elsewhere in the body, which have the potential to manifest orally after hepatitis B vaccination were selected. A total of 82 articles were identified which included 58 case series or case reports, 15 review articles, 4 cross sectional studies, 3 prospective cohort studies, one retrospective cohort study and a case control study.

After reviewing the literature, we observed that complications seen after Hepatitis B vaccination are sudden infant death syndrome, multiple sclerosis, chronic fatigue syndrome, idiopathic thrombocytopenic purpura, vasculititis optic neuritis, anaphylaxis, systemic lupus erytymatosus, lichen planus and neuro-muscular disorder. Of these complications, some are manifested orally or have the potential to manifest orally. Although, most of the complications are self-limiting, some are very serious conditions, which require hospitalization with immediate medical attention.

From Frontiers in Neurology, 28 November 2014.

Clinical features in patients with long-lasting macrophagic myofasciitis.

Rigolet M(1), Aouizerate J(2), Couette M(3), Ragunathan-Thangarajah N(2), Aoun-Sebaiti M(3), Gherardi RK(4), Cadusseau J(5), Authier FJ(4).
1) Faculty of Medicine, INSERM U955-Team 10, Créteil, France.
2) Faculty of Medicine, INSERM U955-Team 10, Créteil, France; Reference Center for Neuromuscular Diseases, Garches-Necker-Mondor-Hendaye, Créteil, France.
3) Neurology Department, Henri Mondor University Hospital, Créteil, France.
4) Faculty of Medicine, INSERM U955-Team 10, Créteil, France;
Reference Center for Neuromuscular Diseases. Garches-Necker-Mondor-Hendaye, Créteil, France; Paris Est-Créteil
University, Créteil, France.
5) Reference Center for Neuromuscular Diseases, Garches-Necker-Mondor-Hendaye, Créteil, France; Paris Est-Créteil
University, Créteil, France.


Macrophagic myofasciitis (MMF) is an emerging condition characterized by specific muscle lesions assessing abnormal long-term persistence of aluminum hydroxide within macrophages at the site of previous immunization. Affected patients usually are middle-aged adults, mainly presenting with diffuse arthromyalgias, chronic fatigue, and marked cognitive deficits, not related to pain, fatigue, or depression.

Clinical features usually correspond to that observed in chronic fatigue syndrome/myalgic encephalomyelitis.

Representative features of MMF-associated cognitive dysfunction include dysexecutive syndrome, visual memory impairment, and left ear extinction at dichotic listening test. Most patients fulfill criteria for non-amnestic/dysexecutive mild cognitive impairment, even if some cognitive deficits appear unusually severe.

Cognitive dysfunction seems stable over time despite marked fluctuations. Evoked potentials may show abnormalities in keeping with central nervous system involvement, with a neurophysiological pattern suggestive of demyelination. Brain perfusion SPECT shows a pattern of diffuse cortical and subcortical abnormalities, with hypoperfusions correlating with cognitive deficiencies.

The combination of musculoskeletal pain, chronic fatigue, and cognitive disturbance generates chronic disability with possible social exclusion. Classical therapeutic approaches are usually unsatisfactory making patient care difficult.

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