Brain abnormalities found in PoTS

Posted on 01/06/2015 by wames

Postural tachycardia syndrome (PoTS), a form of dysautonomia, is
characterized by orthostatic intolerance, and is frequently  accompanied by a range of symptoms including palpitations,  lightheadedness, clouding of thought, blurred vision, fatigue, anxiety  and depression.

Although the estimated prevalence of PoTS is  approximately 5-10 times as common as the better-known condition orthostatic hypotension, the neural substrates of the syndrome are poorly characterized. In the present study, we used magnetic resonance imaging (MRI) with voxel-based morphometry (VBM) applying the diffeomorphic anatomical registration through exponentiated lie
algebra (DARTEL) procedure to examine variation in regional brain  structure associated with PoTS.

We recruited eleven patients with established PoTS and twenty-three age-matched normal controls. Group comparison of grey matter volume revealed diminished grey matter volume within the left anterior insula, right middle frontal gyrus and right cingulate gyrus in the PoTS group. We also observed lower white matter volume beneath the precentral gyrus and paracentral lobule, right pre- and post-central gyrus, paracentral lobule and superior frontal gyrus in PoTS patients.

Subsequent ROI analyses revealed significant negative correlations between left insula volume and trait anxiety and depression scores. Together, these findings of structural differences, particularly within insular and cingulate components of
the salience network, suggest a link between dysregulated physiological reactions arising from compromised central autonomic control (and interoceptive representation) and increased vulnerability to psychiatric symptoms in PoTS patients.

Structural brain abnormalities in postural tachycardia syndrome: a  VBM-DARTEL study, by  Satoshi Umeda, Neil A. Harrison, Marcus Gray, Christopher Mathias and Hugo Critchley in Frontiers in neuroscience   [Received: 30 Sep 2014; Paper pending published: 01 Dec 2014]

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ME and Gulf War Illness have distinct immune profiles

Posted on 01/06/2015 by wames

Research abstract

Highlights

  • 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-a, 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-a, 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.

Cytokine expression provides clues to the pathophysiology of Gulf War illness and myalgic encephalomyelitis, by F Svetlana et al in Cytokine, Volume 72, Issue 1, March 2015, Pages 1–8, Received 30 September 2014, Revised 16 November 2014, Accepted 19 November 2014, Available online 13 December 2014

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Dantzer on the neuroimmune basis of fatigue and CFS

Posted on 01/05/2015 by wames

Simon McGrath provides an overview of a fascinating lecture that points to
a possible treatment being studied in cancer fatigue that has a more than
intriguing connection with ME/CFS.

Check it out

 

 

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Probiotic B infantis improves immune system in CFS

Posted on 01/01/2015 by wames

Research abstract:

Certain therapeutic microbes, including Bifidobacteria infantis (B. infantis) 35624 exert beneficial immunoregulatory effects by mimicking commensal-immune interactions; however, the value of these effects in patients with non-gastrointestinal inflammatory conditions remains unclear. In this study, we assessed the impact of oral administration of B. infantis 35624, for 6‒8 weeks on inflammatory biomarker and plasma cytokine levels in patients with ulcerative colitis (UC) (n = 22), chronic fatigue syndrome (CFS) (n = 48) and psoriasis (n = 26) in three separate randomized, double-blind, placebo-controlled interventions. Additionally, the effect of B. infantis 35624 on immunological biomarkers in healthy subjects (n = 22) was assessed. At baseline, both gastrointestinal (UC) and non-gastrointestinal (CFS and psoriasis) patients had significantly increased plasma levels of C-reactive protein (CRP) and the pro-inflammatory cytokines tumor necrosis factor α (TNF-α) and interleukin-6 (IL-6) compared with healthy volunteers. B. infantis 35624 feeding resulted in reduced plasma CRP levels in all three inflammatory disorders compared with placebo. Interestingly, plasma TNF-α was reduced in CFS and psoriasis while IL-6 was reduced in UC and CFS. Furthermore, in healthy subjects, LPS-stimulated TNF-α and IL-6 secretion by peripheral blood mononuclear cells (PBMCs) was significantly reduced in the B. infantis 35624-treated groups compared with placebo following eight weeks of feeding. These results demonstrate the ability of this microbe to reduce systemic pro-inflammatory biomarkers in both gastrointestinal and non-gastrointestinal conditions. In conclusion, these data show that the immunomodulatory effects of the microbiota in humans are not limited to the mucosal immune system but extend to the systemic immune system. Bifidobacterium infantis 35624 modulates host inflammatory processes beyond the gut, by David Groeger, Liam O’Mahony, Eileen F. Murphy, John F. Bourke, Timothy G. Dinan, Barry Kiely, Fergus Shanahan and Eamonn M.M. Quigley in Gut Microbes 1 July 2013

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ME/CFS: differential diagnosis of vasovagal syncope

Posted on 12/22/2014 by wames

Abstract
Fatigue is a frequent symptom in the general population, being reported by up to 50 % of the respondents to large-scale surveys. It is attributable to underlying systemic diseases such as diabetes, cardiopulmonary disease, or rheumatoid arthritis, but may also accompany psychiatric conditions such as depression, panic disorder, or somatization.

The etiology of isolated fatigue or fatigue associated with the symptoms of other minor illnesses is often undiagnosed and poorly treated. The word “fatigue” can have various meanings, including exhaustion, a perceived decrease in the ability to undertake mental or physical activities, delayed recovery after demanding physical exertion, or weariness due to unrefreshing sleep. Self-reported fatigue is typically transient, self-limiting, and explained by prevailing circumstances, but a small minority of subjects experience persistent and debilitating fatigue.

When fatigue cannot be explained by a medical condition such as depression, cancer, infections, or inflammatory disorders, it may be due to myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), a clinical diagnosis without any distinguishing physical or routine laboratory findings.

Attempts have been made to establish whether its etiology is infectious, immunological, neuroendocrinological, psychiatric, or sleep- or malignancy-related, but no definite conclusion has yet been reached, and it seems likely that it is a heterogeneous illness that reflects a common pathway of various pathophysiological abnormalities that manifest themselves with similar symptoms.

Differential Diagnosis of Vasovagal Syncope: Myalgic Encephalomyelitis/ Chronic Fatigue Syndrome, by Piercarlo Sarzi-Puttini et al, in Vasovagal Syncope 2015, pp 197-211 Date: 04 Nov 2014 [chapter in book]

Vasovagal syncope definition

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Relationship between idiopathic intracranial hypertension and CFS

Posted on 12/19/2014 by wames

Abstract

Introduction
Similarities between chronic fatigue syndrome and idiopathic intracranial hypertension (IIH) invite speculation that they may be related. Cranial venous outflow obstruction plays a role in the development of IIH. Could it be a factor in chronic fatigue? This paper attempts to evaluate an investigative approach to chronic fatigue syndrome that allows for this possibility.

Methods
Since 2007, patients attending a specialist clinic at our institution diagnosed with chronic fatigue syndrome and with prominent headache have been offered CT venography, lumbar puncture and a trial of cerebrospinal fluid withdrawal looking for IIH. Also, if CT venography revealed focal narrowing of the jugular veins, patients were offered catheter cerebral venography and jugular venoplasty attempting to establish their clinical significance.

Results
In the 29 patients investigated to date, the mean cerebrospinal fluid (CSF) pressure was 19 cm H2O (range 12-41 cm H2O). Twenty-five patients responded positively to CSF withdrawal and in 5 the CSF pressures were high enough to allow an unequivocal diagnosis of IIH while in the remaining 20, symptoms improved with lumbar puncture even though CSF pressures were within the normal range. Twenty-one patients had focal narrowing of one or both internal jugular veins on CT venography. Fourteen of these have had jugular venoplasty, all of whom reported an improvement in symptoms afterwards lasting from a few minutes to more than 1 month.

Conclusions
Chronic fatigue syndrome may represent an incomplete form of IIH. Cranial venous outflow obstruction deserves further investigation as a possible aetiological factor.

What do lumbar puncture and jugular venoplasty say about a connection between chronic fatigue syndrome and idiopathic intracranial hypertension? by Nicholas Higgins, John D Pickard, Andrew M Lever in EJMINT (eJournal of the European Society of Minimally Invasive Neurological Therapy) Article 1448000223, November 24, 2014

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Interleukin-6 levels at rest and in response to exercise

Posted on 12/10/2014 by wames

Research abstract

IL-6 plays a mechanistic role in conditions such as metabolic syndrome, chronic fatigue syndrome and clinical depression and also plays a major role in inflammatory and immune responses to exercise.

The purpose of this study was to investigate the levels of resting and post exercise IL-6 when measured in venous plasma, saliva and capillary plasma.

Five male and five females completed 2 separate exercise trials, both of which involved standardized exercise sessions on a cycle ergometer. Venous blood and saliva samples were taken immediately before and after Trial A, venous and capillary blood samples were taken immediately before and after Trial B. IL-6 values were obtained using a high-sensitivity enzyme-linked immunosorbent assay (ELISA).

In Trial A venous plasma IL-6 increased significantly from 0.4±0.14pg/ml to 0.99±0.29pg/ml (P<0.01) while there was no increase in salivary IL-6. Venous plasma and salivary IL-6 responses were not correlated at rest, post exercise or when expressed as an exercise induced change.

In Trial B venous and capillary plasma IL-6 increased significantly (venous: 0.22±0.18 to 0.74±0.28pg/ml (P⩽0.01); capillary: 0.37±0.22 to 1.08±0.30pg/ml (P<0.01). Venous and capillary plasma responses did not correlate at rest (r=0.59, P=0.07) but did correlate post exercise (r=0.79, P⩾0.001) and when expressed as an exercise induced change (r=0.71, P=0.02).

Saliva does not appear to reflect systemic IL-6 responses, either at rest or in response to exercise. Conversely, capillary plasma responses are reflective of systemic IL-6 responses to exercise.

The relationship between interleukin-6 in saliva, venous and capillary plasma, at rest and in response to exercise, by Cullen T, Thomas AW, Webb R, Hughes MG in Cytokine 2014 Nov 15. pii [Epub ahead of print]

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Q-fever patients suffer long after the acute phase

Posted on 12/09/2014 by wames

Research abstract

OBJECTIVES: During the largest Q-fever outbreak ever reported, a cohort study was established to assess the health status of Q-fever patients over a 24-month period and to identify factors associated with health status.

METHODS: Laboratory-confirmed Q-fever patients participated at six time points after onset of illness. Scores on twelve subdomains from two health status instruments were calculated for each time point to determine progression and compare to reference groups.

RESULTS: The study included 336 Q-fever patients. There is a significant linear improvement over time in nine of the twelve health status subdomains. For example, the proportion of patients with severe fatigue improved from 73.0% at three months to 60.0% at twelve months and 37.0% at twenty-four months, but this was still high compared to a healthy reference group (2.5%).

For the three most severely affected subdomains -‘Fatigue’, ‘General Quality of Life’ and ‘Role Physical’- the baseline characteristics significantly associated with a long-term reduced health status were being female, being a young adult and having pre-existing health problems.

CONCLUSIONS: Despite a significant linear improvement over time in nine of the twelve health status subdomains, more than one out of three patients still suffered from a reduced health status at 24 months.

Q-fever patients suffer from impaired health status long after the acute phase of the illness: Results from a 24-month cohort study, by JA van Loenhout, JL Hautvast, JH Vercoulen, RP Akkermans, CJ Wijkmans, K van der Velden, WJ Paget in J Infect. 2014 Nov 1. pii: S01   [Epub ahead of print]

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CFS and co-morbid conditions

Posted on 12/09/2014 by wames

Research abstract

Background:

Epidemiologic data that inform our understanding of the type, frequency, and burden of co-morbidities with chronic fatigue syndrome is limited.

Purpose:

To elucidate co-morbid and consequent conditions, using data from a clinical epidemiology study of long-term CFS patients.

Methods:

Some 960 adults with CFS were identified at four sites specializing in the diagnosis and treatment of CFS. Patients reported their demographics, CFS course, other medical diagnoses, and current functioning. We determined associations between: co-morbidities and a patient’s current health relative to their health when diagnosed with CFS; CFS symptom severity at onset and subsequent diagnosis with a co-morbid condition; and presence of a co-morbidity and functional ability. We also modeled the change in CFS symptom severity over time as it relates to the presence of a co-morbidity.

Results:

Of the sample, 84% was diagnosed with one or more co-morbid conditions after CFS onset. Fibromyalgia, depression, anxiety, and hypothyroidism were the most common diagnoses. Nearly 60% of the sample reported a mental illness.

Conclusions:

In general, co-morbid conditions reduced functional ability and were associated with the worsening of CFS symptoms over time. This study provides important new information on the prevalence of co-morbid

Chronic fatigue syndrome and co-morbid and consequent conditions: evidence from a multi-site clinical epidemiology study, by Lucinda Bateman, Salima Darakjy, Nancy Klimas, Daniel Peterson, Susan M. Levine, Ali Allen, Shane A. Carlson, Elizabeth Balbin, Gunnar Gottschalk & Dana March in Fatigue: Biomedicine, Health & Behavior [Received: 31 Aug 2014, Accepted: 5 Nov 2014, Published online: 6 Dec 2014]

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Immunoglobulin treatment concerns for Parvovirus B19

Posted on 12/08/2014 by wames

Research highlights

  • Parvovirus B19 infection can be involved in the pathogenesis of CFS.
  • Previous reports described a favourable outcome of CFS associated with B19V by IVIG treatment.
  • In our experience the administration of IVIG to a patient suffering of B19V-associated CFS produced a paradoxical exacerbation of the disease.
  • The indication of IVIG administration in the treatment of B19V-associated CFS should be carefully reconsidered.

Research abstract

We describe a case of chronic fatigue syndrome (CFS) associated to Parvovirus B19 infection where administration of intravenous immunoglobulins (IVIG), previously reported as effective, induced a paradoxical clinical response and increased viral replication. The indication of IVIG administration in the treatment of Parvovirus B19-associated CFS should be carefully reconsidered.

Paradoxical response to intravenous immunoglobulin in a case of Parvovirus B19-associated chronic fatigue syndrome, by Luciano Attard et al in Journal of Clinical Virology, Received: September 24, 2014; Received in revised form: November 14, 2014; Accepted: November 17, 2014; Published Online: November 22, 2014

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