Hostname: page-component-7c8c6479df-xxrs7 Total loading time: 0 Render date: 2024-03-28T18:18:59.753Z Has data issue: false hasContentIssue false

Letter to the Editor: Plausible explanations for neurocognitive deficits in ME/CFS, aggravation of neurocognitive impairment induced by exertion

Published online by Cambridge University Press:  12 April 2010

FRANK N. M. TWISK*
Affiliation:
Zonnedauw 15, 1906 HB Limmen, The Netherlands
ROBERT J. W. ARNOLDUS
Affiliation:
Freesiadal 22, 2317 HN Leiden, The Netherlands
MICHAEL MAES
Affiliation:
Maes@Tria Clinics, Piyavate Hospital, Bangkok, Thailand
*
Address correspondence to: Frank N. M. Twisk, MBA, BEd, BEc ME-de-patiënten Foundation, Zonnedauw 15, 1906 HB Limmen, The Netherlands (Email: frank.twisk@hetnet.nl)
Rights & Permissions [Opens in a new window]

Abstract

Type
Correspondence
Copyright
Copyright © Cambridge University Press 2010

We read the review by Cockshell & Mathias (Reference Cockshell and Mathias2010) with great interest and compliment the authors for their thorough review of cognitive deficits in Chronic Fatigue Syndrome (CFS). As noted by Thomas & Smith (Reference Thomas and Smith2009), cognitive impairments can be identified if the appropriate tests and measures are used. However, we would like to make two comments.

First, many studies have established organic aberrations which, at least partially, could account for the neurocognitive deficits seen in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS).

Many aberrations in brain structures and functions have been established in ME/CFS, like hypoperfusion and hypometabolism of brain regions of interest, impaired cerebral oxygenation during exercise, SPECT scan abnormalities in the cerebral cortex, small discrete lesions in the subcortex, a reduction in grey matter, and immunological abnormalities and aberrant proteins in spinal fluid (Lange et al. Reference Lange, Steffener, Cook, Bly, Christodoulou, Liu, Deluca and Natelson2005; Chen et al. Reference Chen, Liang, Moriya, Yamakawa, Sumino, Kanda and Takahashi2008; Twisk & Maes, Reference Twisk and Maes2009). In ME/CFS brain activity is significantly more diffuse (Chen et al. Reference Chen, Liang, Moriya, Yamakawa, Sumino, Kanda and Takahashi2008), possibly as a compensation mechanism (Lange et al. Reference Lange, Steffener, Cook, Bly, Christodoulou, Liu, Deluca and Natelson2005).

Hypoperfusion and hypometabolism are plausible explanations for the ‘brain fog’ often reported by ME/CFS patients. Moreover, a correlation between neurological abnormalities and neurocognitive functioning has been established (Lange et al. Reference Lange, Steffener, Cook, Bly, Christodoulou, Liu, Deluca and Natelson2005; Chen et al. Reference Chen, Liang, Moriya, Yamakawa, Sumino, Kanda and Takahashi2008).

Second, exercise and graded exercise therapy (GET), proposed as a treatment for ME/CFS, are likely to aggravate the cognitive complaints in ME/CFS. The average increase of the prefrontal cortical volume due to cognitive behavioural therapy/GET (CBT/GET), mentioned by Cockshell & Mathias (Reference Cockshell and Mathias2010), is very modest (+4.8 ml, s.e.=2.3 ml, difference in grey-matter volume before intervention: −38.8 ml). The grey-matter volume even declined in a substantial subpopulation.

Inflammation, immunosuppression, immune dysfunction, oxidative and nitrosative stress, mitochondrial dysfunction, apoptosis, infections, channelopathy and a blunted stress response are key pathways in ME/CFS (Twisk & Maes, Reference Twisk and Maes2009), as has been confirmed by various gene expression studies.

Since exertion and GET increase inflammation, oxidative and nitrosative stress, and channelopathy, it is not surprising that exercise has a negative impact on the pre-existing cognitive impairments, in large subgroups of patients (Twisk & Maes, Reference Twisk and Maes2009).

Several studies show that neurocognitive problems of many ME/CFS patients are aggravated by exercise, e.g. cognitive processing is impaired 24 hours after physically demanding exercise; exertion has a negative effect on simple reaction time and choice reaction time; fatigue-inducing activities cause altered central nervous system signals, which control voluntary muscles; and exertion has a negative impact on perfusion of the left prefrontal lobe and cerebral oxygenation (Twisk & Maes, Reference Twisk and Maes2009). The latter could account for the sustained negative effect of exercise on neurocognitive performance.

We hope that this letter shows the readership that organic aberrations plausibly explain the neurocognitive impairments in ME/CFS, as reported by Thomas & Smith (Reference Thomas and Smith2009) and Cockshell & Mathias (Reference Cockshell and Mathias2010), and that CBT/GET has potential risks, because it can amplify the above-mentioned organic aberrations.

Declaration of Interest

None.

References

Chen, R, Liang, FX, Moriya, J, Yamakawa, J, Sumino, H, Kanda, T, Takahashi, T (2008). Chronic fatigue syndrome and the central nervous system. Journal of International Medical Research 36, 867874.CrossRefGoogle ScholarPubMed
Cockshell, SJ, Mathias, JL (2010). Cognitive functioning in chronic fatigue syndrome: a meta-analysis. Psychological Medicine. Published online: 5 January 2010. doi:10.1017/S0033291709992054.CrossRefGoogle ScholarPubMed
Lange, G, Steffener, J, Cook, DB, Bly, BM, Christodoulou, C, Liu, WC, Deluca, J, Natelson, BH (2005). Objective evidence of cognitive complaints in chronic fatigue syndrome: a BOLD fMRI study of verbal working memory. Neuroimage 26, 513524.CrossRefGoogle ScholarPubMed
Thomas, M, Smith, A (2009). An investigation into the cognitive deficits associated with chronic fatigue syndrome. Open Neurology Journal 3, 1323.CrossRefGoogle ScholarPubMed
Twisk, FNM, Maes, M (2009). A review on cognitive behavorial therapy (CBT) and graded exercise therapy (GET) in myalgic encephalomyelitis (ME)/chronic fatigue syndrome (CFS): CBT/GET is not only ineffective and not evidence-based, but also potentially harmful for many patients with ME/CFS. Neuroendocrinology Letters 30, 284299.Google Scholar