Ventricular cerebrospinal fluid lactate is increased in [CFS] compared with generalized anxiety disorder, 2009, Mathew et al.

Ventricular cerebrospinal fluid lactate is increased in chronic fatigue syndrome compared with generalized anxiety disorder: an in vivo 3.0 T 1H MRS imaging study
Sanjay J. Mathew; Xiangling Mao; Kathryn A. Keegan; Susan M. Levine; Eric L. P. Smith; Linda A. Heier; Viktor Otcheretko; Jeremy D. Coplan; Dikoma C. Shungu

Chronic fatigue syndrome (CFS) is a controversial diagnosis because of the lack of biomarkers for the illness and its symptom overlap with neuropsychiatric, infectious, and rheumatological disorders.

We compared lateral ventricular volumes derived from tissue-segmented T1 -weighted volumetric MRI data and cerebrospinal fluid (CSF) lactate concentrations measured by proton MRS imaging (1 H MRSI) in 16 subjects with CFS (modified US Centers for Disease Control and Prevention criteria) with those in 14 patients with generalized anxiety disorder (GAD) and in 15 healthy volunteers, matched group-wise for age, sex, body mass index, handedness, and IQ.

Mean lateral ventricular lactate concentrations measured by 1H MRSI in CFS were increased by 297% compared with those in GAD (P < 0.001) and by 348% compared with those in healthy volunteers (P < 0.001), even after controlling for ventricular volume, which did not differ significantly between the groups. Regression analysis revealed that diagnosis accounted for 43% of the variance in ventricular lactate.

CFS is associated with significantly raised concentrations of ventricular lactate, potentially consistent with recent evidence of decreased cortical blood flow, secondary mitochondrial dysfunction, and/or oxidative stress abnormalities in the disorder.

Link | PDF (NMR in Biomedicine)

 

I don't think we have a thread for this paper. They used Fukuda criteria and manually segmented the ventricles from brain parenchyma (the latter recognised in their limitations). I think this could be worth replicating in LC and non-Covid ME/CFS, using modern automated segmentation tools.

I've circled below the doublet-peak at 1.33 ppm for lactate, seen only in the CFS group. Note that all groups also had a smaller NAA peak at 2.0 ppm which means their segmentation wasn't perfect and included some brain parenchyma. I don't think that matters as all that might indicate is that lactate is increased in the brain parenchyma as well as the CSF (which it presumably is).

Also another example where the term "CFS" is so unhelpful, with CSF -> CFS typos in the manuscript, which is the opposite of what we often see!

 

Maybe that reflects the presence or degree of cognitive dysfunction / brain fog. I hope the NIH intramural study reports on ventricular and muscle lactate findings in the small cohort, and includes this in the GWI and any LC studies.

 

Other ME/CFS studies are generally neuroimaging using 1H MR spectroscopy, measuring intraventricular CSF, but I don't think they did that in Walitt et al. The legend for the most significant metabolites heat map above is —

So they are indicating that lactate was downregulated in ME/CFS CSF samples, which is counter to other studies I've seen but those have used MRS.

Eg in Multimodal and simultaneous assessments of brain and spinal fluid abnormalities in chronic fatigue syndrome and the effects of psychiatric comorbidity (2017, Journal of the Neurological Sciences) —

It would have been ideal if Walitt et al had done ventricular CSF MRS — they had the patients in the MRI scanner doing functional MRI. Perhaps ventricular lactate is high but direct lumbar cistern CSF sampling is normal or (genuinely?) low in ME/CFS.

Do we have older papers with direct measurements of CSF lactate?