TGI Friday! Our weekly round-up of recently published research abstracts | 7 February 2014

February 7, 2014

From Journal of the Royal Society of Medicine Short Reports, 21 November 2013.

Lumbar puncture, chronic fatigue syndrome and idiopathic intracranial hypertension: a cross-sectional study.

Higgins N(1), Pickard J(2), Lever A(3).
1) Department of Radiology, Addenbrooke's Hospital, Cambridge CB2 0QQ, UK.
2) Academic Department of Neurosurgery, Addenbrooke's Hospital, Cambridge CB2 0QQ, UK.
3) Department of Infectious diseases, Addenbrooke's Hospital, Cambridge CB2 0QQ, UK.



Unsuspected idiopathic intracranial hypertension (IIH) is found in a significant minority of patients attending clinics with named headache syndromes, if it is specifically sought out. Chronic fatigue syndrome is frequently associated with headache. Could the same be true of chronic fatigue? Moreover, there are striking similarities between the two conditions. Could they be related?

Attempting to answer these questions, we describe the results of a change in clinical practice aimed at capturing patients with chronic fatigue who might have IIH.




Hospital outpatient and radiology departments.


Patients attending a specialist clinic with chronic fatigue syndrome and headache who had lumbar puncture to exclude raised intracranial pressure.


Intracranial pressure measured at lumbar puncture and the effect on headache of cerebrospinal fluid drainage.


Mean cerebrospinal fluid pressure was 19 cm H2O (range 12-41 cm H2O). Four patients fulfilled the criteria for IIH. Thirteen others did not have pressures high enough to diagnose IIH but still reported an improvement in headache after drainage of cerebrospinal fluid. Some patients also volunteered an improvement in other symptoms, including fatigue. No patient had any clinical signs of raised intracranial pressure.


An unknown, but possibly substantial, minority of patients with chronic fatigue syndrome may actually have IIH. An unknown, but much larger, proportion of patients with chronic fatigue syndrome do not have IIH by current criteria but respond to lumbar puncture in the same way as patients who do. This suggests that the two conditions may be related.

From the Journal of Anxiety, Stress and Coping, 30 January 2014 2014 Jan 30. [Epub ahead of print].

Living with the unexplained: Coping, distress, and depression among women with chronic fatigue syndrome (CFS) and/or fibromyalgia compared to an autoimmune disorder.

Opal A. McInnis(a,*), Kimberly Matheson(b) & Hymie Anisman(a)
a) Department of Neuroscience, Carleton University, Ottawa, ON, Canada
b) Department of Neuroscience & Department of Psychology, Carleton University, Ottawa, ON, Canada
* Corresponding author, KIS SB6, Tel.:1(613)520-2600 ext. 2692, Fax: 1(613)520-4052. E-mail:


Chronic fatigue syndrome (CFS) and fibromyalgia are disabling conditions without objective diagnostic tests, clear-cut treatments, or established etiologies. Those with the disorders are viewed suspiciously, and claims of malingering are common, thus promoting further distress.

It was hypothesized in the current study that levels of unsupportive social interactions and the coping styles used among those with CFS/fibromyalgia would be associated with perceived distress and depressive symptoms. Women with CFS/fibromyalgia (n=39), in fact, reported higher depression scores, greater perceived distress and more frequent unsupportive relationships than healthy women (n=55), whereas those with a chronic, but medically accepted illness comprising an autoimmune disorder (lupus erythematosus, multiple sclerosis, rheumatoid arthritis) (n=28), displayed intermediate

High problem-focused coping was associated with low levels of depression and perceived distress in those with an autoimmune condition. In contrast, although CFS/fibromyalgia was also accompanied by higher depression scores and higher perceived distress, this occurred irrespective of problem-focused coping. It is suggested that because the veracity of ambiguous illnesses is often questioned, this might represent a potent stressor in women with such illnesses, and even coping methods typically thought to be useful in other conditions, are not associated with diminished distress among those with CFS/fibromyalgia.

From JAMA Pediatrics, 3 February 2014 (published before print).

Disease Mechanisms and Clonidine Treatment in Adolescent Chronic Fatigue Syndrome

Dag Sulheim, MD(1,2); Even Fagermoen, MD(3,4); Anette Winger, RN, MA(3,5); Anders Mikal Andersen, BSc(6); Kristin Godang, BSc(7); Fredrik Müller, MD, PhD(8); Peter C. Rowe, MD, PhD(9); J. Philip Saul, MD(10); Eva Skovlund, PhD(11,12); Merete Glenne Øie, PhD(13,14); Vegard Bruun Wyller, MD, PhD(1,15,16).
1) Department of Paediatrics, Oslo University Hospital, Oslo, Norway
2) Department of Paediatrics, Lillehammer County Hospital, Lillehammer, Norway
3) Institute of Clinical Medicine, Medical Faculty, University of Oslo, Oslo, Norway
4) Department of Anesthesiology and Critical Care, Oslo University Hospital, Oslo, Norway
5) Institute of Nursing Sciences, Oslo and Akershus University College of Applied Sciences, Oslo, Norway
6) Department of Pharmacology, Oslo University Hospital, Oslo, Norway
7) Section of Specialized Endocrinology, Department of Endocrinology, Oslo University Hospital Rikshospitalet, Oslo, Norway
8) Department of Microbiology, Oslo University Hospital, Oslo, Norway
9) Department of Pediatrics, the Johns Hopkins University School of Medicine, Baltimore, Maryland
10) Department of Pediatrics, Medical University of South Carolina, Charleston
11) School of Pharmacy, University of Oslo, Oslo, Norway
12) Norwegian Institute of Public Health, Oslo, Norway
13) Department of Psychology, University of Oslo, Oslo, Norway
14) Innlandet Hospital Trust, Lillehammer, Norway
15) Division of Medicine and Laboratory Sciences, Medical Faculty, University of Oslo, Oslo, Norway
16) Department of Paediatrics, Akershus University Hospital, Nordbyhagen, Norway



Chronic fatigue syndrome (CFS) is a disabling condition with unknown disease mechanisms and few treatment options.


To explore the pathophysiology of CFS and assess clonidine hydrochloride pharmacotherapy in adolescents with CFS by using a hypothesis that patients with CFS have enhanced sympathetic activity and that sympatho-inhibition by clonidine would improve symptoms and function.


Participants were enrolled from a single referral center recruiting nationwide in Norway. A referred sample of 176 adolescents with CFS was assessed for eligibility; 120 were included (34 males and 86 females; mean age, 15.4 years). A volunteer sample of 68 healthy adolescents serving as controls was included (22 males and 46 females; mean age, 15.1 years). The CSF patients and healthy controls were assessed cross-sectionally at baseline. Thereafter, patients with CFS were randomized 1:1 to treatment with low-dose clonidine or placebo for 9 weeks and monitored for 30 weeks; double-blinding was provided. Data were collected from March 2010 until October 2012 as part of the Norwegian Study of Chronic Fatigue Syndrome in Adolescents: Pathophysiology and Intervention Trial.


Clonidine hydrochloride capsules (25 µg or 50 µg twice daily for body weight <35 kg or >35 kg, respectively) vs placebo capsules for 9 weeks.


Number of steps per day.


At baseline, patients with CFS had a lower number of steps per day (P < .001), digit span backward score (P = .002), and urinary cortisol to creatinine ratio (P = .001), and a higher fatigue score (P < .001), heart rate responsiveness (P = .02), plasma norepinephrine level (P < .001), and serum C-reactive protein concentration (P = .04) compared with healthy controls. There were no significant differences regarding blood microbiology evaluation. During intervention, the clonidine group had a lower number of steps per day (mean difference, −637 steps; P = .07), lower plasma norepinephrine level (mean difference, −42 pg/mL; P = .01), and lower serum C-reactive protein concentration (mean ratio, 0.69; P = .02) compared with the CFS placebo group.CONCLUSIONS AND RELEVANVCEAdolescent CFS is associated with enhanced sympathetic nervous activity, low-grade systemic inflammation, attenuated hypothalamus-pituitary-adrenal axis function, cognitive impairment, and large activity reduction, but not with common microorganisms. Low-dose clonidine attenuates sympathetic outflow and systemic inflammation in CFS but has a concomitant negative effect on physical activity; thus, sympathetic and inflammatory enhancement may be compensatory mechanisms. Low-dose clonidine is not clinically useful in CFS.Trial Registration Identifier: NCT01040429

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