TGI Friday! Our weekly round-up of recently published research abstracts | 11 September 2015

From the Journal of Pain, 31 August 2015. [Epub ahead of print]

Effect of Milnacipran Treatment on Ventricular Lactate in Fibromyalgia : A Randomized, Double-blind, Placebo-controlled Trial

Natelson BH(1), Vu D(2), Mao X(3), Weiduschat N(3), Togo F(4), Lange G(2), Blate M(2), Kang G(3), Coplan JD(5), Shungu DC(3).
1) Department of Neurology, Mount Sinai Beth Israel, New York, NY. Electronic address:
2) Department of Neurology, Mount Sinai Beth Israel, New York, NY.
3) Department of Radiology, Weill Medical College of Cornell University, New York, NY.
4) Educational Physiology Laboratory, Graduate School of Education, The University of Tokyo.
5) Department of Psychiatry & Behavioral Sciences, State University of New York- Downstate Medical Center, Brooklyn NY.


Milnacipran, a serotonin/norepinephrine reuptake inhibitor (SNRI), is FDA-approved for the treatment of fibromyalgia (FM). This report presents the results of a randomized, double-blind, placebo-controlled trial of milnacipran conducted to test the hypotheses that (a) similar to patients with chronic fatigue syndrome, FM patients have elevated ventricular lactate at baseline; (b) 8 weeks of treatment with milnacipran will lower ventricular lactate levels compared to both baseline and to placebo; and (c) treatment with milnacipran will improve attention and executive function in the Attention Network Test compared to placebo.

In addition, we examined the results for potential associations between ventricular lactate and pain. Baseline ventricular lactate measured by proton magnetic resonance spectroscopic imaging (1H MRSI) was found to be higher in FM than in healthy controls [F(1,37) = 22.11; p < 0.0001, partial η2 = 0.37]. Milnacipran reduced pain in FM relative to placebo but had no effect on cognitive processing. At study end, ventricular lactate in the milnacipran-treated group decreased significantly compared to baseline and to placebo [F1,18 = 8.18, p = 0.01, partial η2 = 0.31]. A significantly larger proportion of milnacipran-treated patients showed decreases in both ventricular lactate and in pain than placebo [p = 0.03]. These results suggest that 1H MRSI measurements of lactate may serve as a potential biomarker for therapeutic response in FM and that milnacipran may act, at least in part, by targeting the brain response to glial activation and neuroinflammation. PERSPECTIVE Patients treated with milnacipran showed decreases in both pain and ventricular lactate compared to those treated with placebo, but, even after treatment, levels of ventricular lactate remained higher than in controls. The hypothesized mechanism for these decreases is via drug-induced reductions of a central inflammatory state.

From the European Journal on Paediatrics, 3 September 2015. [Epub ahead of print]

The impact of chronic fatigue syndrome on cognitive functioning in adolescents.

Nijhof LN, Nijhof SL, Bleijenberg G, Stellato RK, Kimpen JL, Pol HE, van de Putte EM.
Department of Pediatrics, Wilhelmina Children’s Hospital, University Medical Centre Utrecht, HP KE.04.133.1, Post box 85090, 3508 AB, Utrecht, The Netherlands,


Chronic fatigue syndrome (CFS) is characterized by persistent fatigue and severe disability. Most adolescent patients report attention and concentration problems, with subsequent poor performance at school.

This study investigated the impact of CFS on intellectual capacity by (1) assessing discrepancies between current intelligence quotient (IQ) and school level and (2) exploring differences in current IQ and pre-CFS school performance, compared with healthy individuals.

Current data was cross-sectionally gathered and compared with retrospective pre-CFS school performance data. Fifty-nine CFS adolescents and 40 controls were evaluated on performance on age-appropriate intelligence tests and school level. Current IQ scores of CFS adolescents were lower than expected on the basis of their school level.

Furthermore, there was a difference in intelligence performance across time when current IQ scores were compared with pre-CFS cognitive achievement. Healthy controls did not show any discrepancies.


According to their pre-CFS intelligence assessments, CFS patients started with appropriate secondary school levels at the age of 12.

Our data suggest that CFS may be accompanied by a decline in general cognitive functioning.

Given the critical age for intellectual development, we recommend a timely diagnosis followed by appropriate treatment of CFS in adolescents.


• Adolescent chronicfatigue syndrome (CFS) is a debilitating condition with major impact on social and intellectual development.

• Most patients report concentration problems, with subsequent poor performance at school. Little is known about the influence of CFS on intellectual


• IQ scores of CFS adolescents are lower than the IQ scores of healthy peers with an equivalent school level.

• There is a decrease in intelligence performance across time when current IQ scores are compared with pre-CFS cognitive achievement. Healthy controls do not show any discrepancies between their current IQ, school level and previous cognitive functioning. This suggest that adolescent CFS may be accompanied by a decline in general cognitive functioning.