TGI Friday! Our weekly round-up of recently published research abstracts | 1 February 2013

February 1, 2013

From the European Journal of Clinical Investigation, 24 January 2013.

Is Chronic Fatigue Syndrome in Older Patients a different disease? – a clinical cohort study

Ieuan Lewis(1), Jessie Pairman(2), Gavin Spickett(2), Julia L Newton(1,2,3)
(1) Institute for Ageing & Health, Newcastle University, Newcastle
(2) Northern CFS Clinical Network, Newcastle Hospitals NHS Foundation Trust, Newcastle
(3) UK NIHR Biomedical Research Centre in Ageing, Newcastle University, Newcastle



Chronic Fatigue Syndrome (CFS) is a disabling disorder characterised by persistent fatigue with a typical age of diagnosis of 35-50 years. CFS doespresent in those aged over 50 but whether this is a different disease in older age groups has not been considered. Therefore we performed a clinical cohort study to examine and differentiate the clinical and autonomic features in CFS patients aged over 50.


179 Fukuda diagnosed CFS patients were recruited and 25 older CFS patients (50+ years) were matched case by case for gender and length of history to 25 younger CFS patients (16-29 years). A range of symptomatic based questionnaires were used in addition to heart rate variability and baroreceptor sensitivity to assess autonomic function.


CFS can present for the first time in an older population. Older CFS patients demonstrate increased fatigue (Fatigue impact scale; 85±33 vs. 107±27, p=0.02) (Chalder fatigue scale; 9±3 vs. 11±1, p=0.002) and caseness for depression (Hospital Anxiety and Depression scale; 7±3 vs. 10±4; p=0.005).

There is greater autonomic dysfunction in older CFS patients, with reduced parasympathetic function (HFnu; 49.1±18 vs. 36.2±18, p=0.01, RR30:15; ±, p=0.02) and increased sympathetic function (LFnu; 51.5±17 vs. 63.8±18, p=0.01).

Baroreflex sensitivity was substantially reduced (BRS; 19.7±12 vs. 9.9±5, p=0.0004) and left ventricular ejection time prolonged (LVET; 274.6±16 vs. 285.8±9, p=0.004).


Older CFS patients demonstrate a disease phenotype very different from younger patients. The combination of differing underlying pathogenic mechanisms and the physiological aspects of ageing, result in a greater disease impact in older CFS patients.

From the Annals of the Indian Academy of Neurology, 15 October 2012. Full paper available.

The therapeutic value of yoga in neurological disorders.

Mishra SK, Singh P, Bunch SJ, Zhang R.
Department of Neurology, Keck School of Medicine, USC, Neurology Department, GLA and Olive-View UCLA Medical Center, CA, USA.



The ancient mind and body healing methods of yoga recently sparked fervor in the scientific community as an alternative and complementary means of therapy. Since the World Health Organization officially began promoting yoga in developing countries in 1978, yoga has been cited for its therapeutic potential and has been widely recognized in Western culture. However, as an increasing number of people practice yoga for remedial purposes, researchers raise two important questions: 1) Is yoga a valid complementary management and rehabilitation treatment modality? 2) What conditions show promise of treatment with this intervention?.


This review article uses comprehensive scientific, evidence-based studies to analyze the efficacy of various basic and applied aspects of yoga in disease prevention and health promotion. It specifically intends to expose the effects of yoga in neurological disorders, particularly epilepsy, stroke, multiple sclerosis, Alzheimer's disease, peripheral nervous system disease, and fibromyalgia.


Information was gathered from various resources including PubMed, Ovid, MD-Consult, USC, and U.C.L.A. libraries. Studies were selected and reviewed on the basis of sample size, control, randomization, double-blinding, and statistical analysis of results.


The practice of yoga and meditation demonstrates statistically encouraging physiological and psychological improvements in the aforementioned neurological disorders. However, there were certain flaws and inadequacies in the study designs employed to evaluate the same. A critical analysis of these studies is presented.


With the aim to focus attention on this widespread yet largely unexamined treatment modality, this paper seeks to provide direction and support for further research necessary to validate yoga as an integrative, alternative, and complementary therapy.

From Neurology, 22 January 2013.

Fatigue and fatigability in neurologic illnesses: Proposal for a unified taxonomy.

Kluger BM, Krupp LB, Enoka RM.
From the Departments of Neurology and Psychiatry (B.M.K.), University of Colorado Denver, Aurora; Departments of Neurology and Psychology (L.B.K.), Stony Brook University Medicine Stony Brook, Stony Brook, NY; and the Department of Integrative Physiology (R.M.E.), University of Colorado Boulder, Boulder.


Fatigue is commonly reported in many neurologic illnesses, including multiple sclerosis, Parkinson disease, myasthenia gravis, traumatic brain injury, and stroke. Fatigue contributes substantially to decrements in quality of life and disability in these illnesses.

Despite the clear impact of fatigue as a disabling symptom, our understanding of fatigue pathophysiology is limited and current treatment options rarely lead to meaningful improvements in fatigue. Progress continues to be hampered by issues related to terminology and assessment.

In this article, we propose a unified taxonomy and a novel assessment approach to addressing distinct aspects of fatigue and fatigability in clinical and research settings. This taxonomy is based on our current knowledge of the pathophysiology and phenomenology of fatigue and fatigability.

Application of our approach indicates that the assessment and reporting of fatigue can be clarified and improved by utilizing this taxonomy and creating measures to address distinct aspects of fatigue and fatigability.

We review the strengths and weaknesses of several common measures of fatigue and suggest, based on our model, that many research questions may be better addressed by using multiple measures. We also provide examples of how to apply and validate the taxonomy and suggest directions for future research.

From the American journal of Translational Research, 30 January 2013 (linking to full text download).

A Chronic Fatigue Syndrome (CFS) severity score based on case designation criteria

James N Baraniuk(1), Oluwatoyin Adewuyi(1), Samantha Jean Merck(2), Mushtaq Ali(3), Murugan K Ravindran(4), Christian R Timbol(5), Rakib Rayhan(1), Yin Zheng(6), Uyenphuong Le(1), Rania Esteitie(1), Kristina N Petrie(1)
(1) Division of Rheumatology, Immunology and Allergy, Georgetown University, Washington, DC, USA;
(2) School of Medicine, University of Pennsylvania, Philadelphia, PA, USA;
(3) Internal Medicine Residency Program, 1415 Woodland Ave, Suite 140, Des Moines, IA 50309, USA;
(4) Department of Internal Medicine, Norwalk Hospital, Norwalk, CT, USA;
(5) School of Medicine, Georgetown University, Washington, DC, USA;
(6) School of Medicine University of South Florida, Tampa, FL, USA



Chronic Fatigue Syndrome case designation criteria are scored as physicians’ subjective, nominal interpretations of patient fatigue, pain (headaches, myalgia, arthralgia, sore throat and lymph nodes), cognitive dysfunction, sleep and exertional exhaustion.


Subjects self-reported symptoms using an anchored ordinal scale of 0 (no symptom), 1 (trivial complaints), 2 (mild), 3 (moderate), and 4 (severe). Fatigue of 3 or 4 dis- tinguished “Fatigued” from “Not Fatigued” subjects. The sum of the 8(Sum8) ancillary criteria was tested as a proxy for fatigue. All subjects had history and physical examinations to exclude medical fatigue, and ensure categorization as healthy or CFS subjects.


Fatigued subjects were divided into CFS with ≥4 symptoms or Chronic Idiopathic Fatigue (CIF) with ≤3 symptoms. ROC of Sum8 for CFS and Not Fatigued subjects generated a threshold of 14 (speci- ficity=0.934; sensitivity=0.928). CFS (n=256) and CIF (n=55) criteria were refined to include Sum8≥14 and ≤13, respectively. Not Fatigued subjects had highly skewed Sum8 responses. Healthy Controls (HC; n=269) were defined by fatigue≤2 and Sum8≤13. Those with Sum8≥14 were defined as CFS–Like With Insufficient Fatigue Syndrome (CFSLWIFS; n=20). Sum8 and Fatigue were highly correlated (R2=0.977; Cronbach’s alpha=0.924) indicating an intimate relationship between symptom constructs. Cluster analysis suggested 4 clades each in CFS and HC. Translational utility was inferred from the clustering of proteomics from cerebrospinal fluid.


Plotting Fatigue severity versus Sum8 produced an internally consistent classifying system. This is a necessary step for translating symptom profiles into fatigue phenotypes and their pathophysiological mechanisms.

From PLosOne Clinical Trials, 17 January 2013 (open access journal).

Effects of Oral L-Carnitine Administration in Narcolepsy Patients: A Randomized, Double-Blind, Cross-Over and Placebo-Controlled Trial

Taku Miyagawa, Hiromi Kawamura, Mariko Obuchi, Asuka Ikesaki, Akiko Ozaki, Katsushi Tokunaga, Yuichi Inoue, Makoto Honda
Japan Somnology Center, Neuropsychiatric Research Institute, Tokyo, Japan, Sleep Disorders Project, Department of Psychiatry and Behavioral Sciences, Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan


Narcolepsy is a sleep disorder characterized by excessive daytime sleepiness, cataplexy, and rapid eye movement (REM) sleep abnormalities. A genome-wide association study (GWAS) identified a novel narcolepsy-related single nucleotide polymorphism (SNP), which is located adjacent to the carnitine palmitoyltransferase 1B (CPT1B) gene encoding an enzyme involved in β-oxidation of long-chain fatty acids. The mRNA expression levels of CPT1B were associated with this SNP.

In addition, we recently reported that acylcarnitine levels were abnormally low in narcolepsy patients. To assess the efficacy of oral l-carnitine for the treatment of narcolepsy, we performed a clinical trial administering l-carnitine (510 mg/day) to patients with the disease. The study design was a randomized, double-blind, cross-over and placebo-controlled trial.

Thirty narcolepsy patients were enrolled in our study. Two patients were withdrawn and 28 patients were included in the statistical analysis (15 males and 13 females, all with HLA-DQB1*06:02). l-carnitine treatment significantly improved the total time for dozing off during the daytime, calculated from the sleep logs, compared with that of placebo-treated periods. l-carnitine efficiently increased serum acylcarnitine levels, and reduced serum triglycerides concentration.

Differences in the Japanese version of the Epworth Sleepiness Scale (ESS) and the Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36) vitality and mental health subscales did not reach statistical significance between l-carnitine and placebo. This study suggests that oral l-carnitine can be effective in reducing excessive daytime sleepiness in narcolepsy patients.

While we are thinking of L-carnitine, here is an abstract taken from Psychosomatic Medicine in 2004:

Taken from Psychosomatic Medicine, March-April 2004

Exploratory open label, randomized study of acetyl- and propionylcarnitine in chronic fatigue syndrome

Vermeulen RC, Scholte HR.
Research Center Amsterdam, Amsterdam, Netherlands



We compared the effects of acetylcarnitine, propionylcarnitine and both compounds on the symptoms of chronic fatigue syndrome (CFS).


In an open, randomized fashion we compared 2 g/d acetyl-L-carnitine, 2 g/d propionyl-L-carnitine, and its combination in 3 groups of 30 CFS patients during 24 weeks. Effects were rated by clinical global impression of change. Secondary endpoints were the Multidimensional Fatigue Inventory, McGill Pain Questionnaire, and the Stroop attention concentration test. Scores were assessed 8 weeks before treatment; at randomization; after 8, 16, and 24 weeks of treatment; and 2 weeks later.


Clinical global impression of change after treatment showed considerable improvement in 59% of the patients in the acetylcarnitine group and 63% in the propionylcarnitine group, but less in the acetylcarnitine plus propionylcarnitine group (37%). Acetylcarnitine significantly improved mental fatigue (p =.015) and propionylcarnitine improved general fatigue (p =.004). Attention concentration improved in all groups, whereas pain complaints did not decrease in any group. Two weeks after treatment, worsening of fatigue was experienced by 52%, 50%, and 37% in the acetylcarnitine, propionylcarnitine, and combined group, respectively. In the acetylcarnitine group, but not in the other groups, the changes in plasma carnitine levels correlated with clinical improvement.


Acetylcarnitine and propionylcarnitine showed beneficial effect on fatigue and attention concentration. Less improvement was found by the combined treatment. Acetylcarnitine had main effect on mental fatigue and propionylcarnitine on general fatigue.

From Annals of Behavioural Medicine, 30 January 2013.

Chronic Fatigue and Personality: A Twin Study of Causal Pathways and Shared Liabilities.

Poeschla B, Strachan E, Dansie E, Buchwald DS, Afari N.
Department of Psychiatry and Behavioral Sciences, School of Medicine, University of Washington, Box 359911, Seattle, WA, 98104-2499, USA,



The etiology of chronic fatigue syndrome (CFS) remains unknown. Personality traits influence well-being and may play a role in CFS and unexplained chronic fatigue.

This study aimed to examine the association of emotional instability and extraversion with chronic fatigue and CFS in a genetically informative sample.


We evaluated 245 twin pairs for two definitions of chronic fatigue. They completed the Neuroticism and Extraversion subscales of the NEO Five Factor Inventory. Using a co-twin control design, we examined the association between personality and chronic fatigue.


Higher emotional instability was associated with both definitions of chronic fatigue and was confounded by shared genetics. Lower extraversion was also associated with both definitions of fatigue, but was not confounded by familial factors.


Both emotional instability and extraversion are related to chronic fatigue and CFS. Whereas emotional instability and chronic fatigue are linked by shared genetic mechanisms, the relationship with extraversion may be causal and bidirectional.

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