Brain fog of post-COVID-19 condition and Chronic Fatigue Syndrome, same medical disorder?

Abstract:

Background: Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is characterized by persistent physical and mental fatigue. The post-COVID-19 condition patients refer physical fatigue and cognitive impairment sequelae. Given the similarity between both conditions, could it be the same pathology with a different precipitating factor?

Objective: To describe the cognitive impairment, neuropsychiatric symptoms, and general symptomatology in both groups, to find out if it is the same pathology. As well as verify if the affectation of smell is related to cognitive deterioration in patients with post-COVID-19 condition.

Methods: The sample included 42 ME/CFS and 73 post-COVID-19 condition patients. Fatigue, sleep quality, anxiety and depressive symptoms, the frequency and severity of different symptoms, olfactory function and a wide range of cognitive domains were evaluated.

Results: Both syndromes are characterized by excessive physical fatigue, sleep problems and myalgia. Sustained attention and processing speed were impaired in 83.3% and 52.4% of ME/CFS patients while in post-COVID-19 condition were impaired in 56.2% and 41.4% of patients, respectively. Statistically significant differences were found in sustained attention and visuospatial ability, being the ME/CFS group who presented the worst performance. Physical problems and mood issues were the main variables correlating with cognitive performance in post-COVID-19 patients, while in ME/CFS it was anxiety symptoms and physical fatigue.

Conclusions: The symptomatology and cognitive patterns were similar in both groups, with greater impairment in ME/CFS. This disease is characterized by greater physical and neuropsychiatric problems compared to post-COVID-19 condition. Likewise, we also propose the relevance of prolonged hyposmia as a possible marker of cognitive deterioration in patients with post-COVID-19.

Source: Azcue N, Gómez-Esteban JC, Acera M, Tijero B, Fernandez T, Ayo-Mentxakatorre N, Pérez-Concha T, Murueta-Goyena A, Lafuente JV, Prada Á, López de Munain A, Ruiz-Irastorza G, Ribacoba L, Gabilondo I, Del Pino R. Brain fog of post-COVID-19 condition and Chronic Fatigue Syndrome, same medical disorder? J Transl Med. 2022 Dec 6;20(1):569. doi: 10.1186/s12967-022-03764-2. PMID: 36474290. https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-022-03764-2 (Full text)

Cognitive impairments in chronic fatigue syndrome patients: choice reaction time, encoding of new information, response organisation and selective attention

ABSTRACT:

Background: One of the features of Chronic Fatigue Syndrome (CFS) is the reporting of cognitive impairment. Prior research has confirmed this using cognitive performance test batteries. Psychomotor slowing and episodic memory impairments appear to be robust, but little is known about selective attention or the stages of processing leading to slower reaction times. The present study addressed these gaps in the literature.

Methods: CFS patients were recruited from a health service clinic. Sixty-seven patients agreed to carry out cognitive tasks measuring aspects of focused attention and categoric search and the components (encoding and response organisation) of choice reaction time. They were compared with 126 healthy controls. As well as carrying out the performance tasks, the participants also completed symptom checklists and questionnaires measuring fatigue, mental health and cognitive failures.

Results: The questionnaires revealed the typical profile of symptoms of CFS patients. With regards to the objective performance tasks, the CFS patients had significantly slower choice reaction times on both tasks. This is likely to be due to slower motor responses as neither of the measures of stimulus encoding or response organisation showed differences between the groups. There was also little evidence for the groups differing in aspects of selective attention.

Conclusions: CFS patients report greater fatigue, more somatic symptoms, greater mental health issues and more cognitive difficulties. Objective testing revealed slower choice reaction times which probably reflect motor slowing. These measures can now be used to assess the efficacy of the management of CFS.

Source: Smith AP. Cognitive impairments in chronic fatigue syndrome patients: choice reaction time, encoding of new information, response organisation and selective attention. World Journal of Pharmaceutical and Medical Research 8(4): 27-36 https://www.wjpmr.com/home/article_abstract/4110 (Full text available as PDF file)

The maintained attention assessment in patients affected by Myalgic encephalomyelitis/chronic fatigue syndrome: a reliable biomarker?

Abstract:

The maintained attention is the cause of great functional limitations in CFS/ME, a disease that mainly affects women in the central period of life. Cognitive function is explored using the Montreal Cognitive Assessment, the maintained attention using the Toulouse-Piéron test with which the Global Index of Attention and Perception (GIAP) is obtained, the fatigue using the visual analog scale and the perception of effort using the modified Borg scale. The final sample were 84 patients (66 women/18 men) who met diagnostic criteria (Fukuda-1994, Carruthers-2011) and 22 healthy controls (14 women/8 men).

Most of patients maintain normal cognitive function, showing low or very low attention score in the 70% of patients with a marked cognitive fatigue compared to the control group (p < 0.05). There were no significant differences between genders in GIAP or fatigue for CFS/ME; however, sick women perceive cognitive effort higher than men.

Deficits in sustained attention and the perception of fatigue, so effort after performing the proposed test are a sensitive and reliable indicator that allows us to substantiate a clinical suspicion and refer patients for further studies in order to confirm or rule out CFS/ME.

Source: Murga I, Aranburu L, Gargiulo PA, Gómez-Esteban JC, Lafuente JV. The maintained attention assessment in patients affected by Myalgic encephalomyelitis/chronic fatigue syndrome: a reliable biomarker? J Transl Med. 2021 Dec 4;19(1):494. doi: 10.1186/s12967-021-03153-1. PMID: 34863209. https://pubmed.ncbi.nlm.nih.gov/34863209/

Attentional Processing and Interpretative Bias in Functional Neurological Disorder

Abstract:

Objective: Altered attentional processing (automatically attending to negative or illness-relevant information) and interpretative biases (interpreting ambiguous information as negative or illness-relevant) may be mechanistically involved in functional neurological disorder (FND). Common mechanisms between FND and chronic fatigue syndrome (CFS) have been proposed but not compared experimentally.

Methods: We compared cognitive task performance of FND, CFS and healthy control (HC) groups. Tasks assessed attentional bias towards illness-relevant stimuli (visual probe task), attentional control (attention network task) and somatic interpretations (interpretative bias task), alongside self-reported depression, anxiety, fatigue and general health.

Results: Thirty-seven participants diagnosed with FND, 52 participants diagnosed with CFS and 51 HC participants were included. Whilst participants with CFS showed attentional bias for illness-relevant stimuli relative to HC (t = -3.13 p = 0.002, d = 0.624), individuals with FND did not (t = -1.59, p = 0.118, d = 0.379). Both FND (t = 3.08, p = 0.003, d = 0.759) and CFS (t = 2.74, p = 0.007, d = 0.548) groups displayed worse attentional control than HC. Similarly, FND (t = 3.63, p < 0.001, d = 0.801) and CFS groups (t = 4.58, p < 0.001, d = 0.909) showed more somatic interpretative bias than HC.

Conclusions: Similar attentional control deficits and somatic interpretative bias in individuals with FND and CFS support potential shared mechanisms underlying symptoms. Interpretative bias towards somatic and illness-relevant stimuli in functional disorders may prove a therapeutic target.

Source: Keynejad RC, Fenby E, Pick S, et al. Attentional processing and interpretative bias in functional neurological disorder [published online ahead of print, 2020 Jun 12]. Psychosom Med. 2020;10.1097/PSY.0000000000000821. doi:10.1097/PSY.0000000000000821 https://pubmed.ncbi.nlm.nih.gov/32541544/

Neuropsychological dysfunction in chronic fatigue syndrome and the relation between objective and subjective findings

Abstract:

OBJECTIVE: This study aimed to explore the relationship between self-reported cognitive difficulties, objective neuropsychological test performances, and subjective health complaints in chronic fatigue syndrome (CFS) and to examine the degree of impaired cognitive functions.

METHOD: A total of 236 consecutively recruited outpatients, 18-62 years of age, completed the tests. Self-administered questionnaires were used for assessing fatigue, pain, depression, anxiety and subjective cognitive complaints (Everyday Memory Questionnaire [EMQ]). Also, neuropsychological tests, that is, Stroop I-IV, California Verbal Learning Test-Second Edition (CVLT-II) learning and delay, Wechsler Adult Intelligence Scale-Third Edition (WAIS-III) Letter Number (L-N) Sequencing, and the Paced Auditory Serial Addition Task were performed to examine whether these objective measures correlated with subjective complaints and were compared with normative data.

RESULTS: There was a trend of association (p < .05) between the unadjusted EMQ with Stroop IV (inhibition and shifting attention), the CVLT-II learning and delay (verbal learning and memory), and the WAIS-III L-N Sequencing (working memory), but none were statistically significant at the .001 level. The EMQ was positively associated with fatigue, pain, and depression (p < .001). The PASAT (working memory) was negatively associated with pain (p < .001). Between 21% and 38% of the patients performed below the 1.5-SD cutoff for clinically significant impairment on the Stroop tests.

CONCLUSION: The self-reported cognitive performance was not strongly associated with the objective cognitive performances on any domains in patients with CFS. Patients with higher fatigue, pain, and depression levels reported greater subjective cognitive difficulties, as well as higher pain related to lower objective working memory function. The CFS patients had problems mainly in the domains of psychomotor speed and attention measured by the objective neuropsychological tests. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

TRIAL REGISTRATION: ClinicalTrials.gov NCT00920777.

Source: Rasouli O, Gotaas ME, Stensdotter AK, Skovlund E, Landrø NI, Dåstøl P, Fors EA. Neuropsychological dysfunction in chronic fatigue syndrome and the relation between objective and subjective findings. Neuropsychology. 2019 Jun 6. doi: 10.1037/neu0000550. [Epub ahead of print] https://www.ncbi.nlm.nih.gov/pubmed/31169386

Resting-state functional connectivity, cognition, and fatigue in response to cognitive exertion: a novel study in adolescents with chronic fatigue syndrome

Abstract:

Emerging evidence suggests that central nervous system dysfunction may underlie the core symptoms of Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME) in adults, such as cognitive disturbance, fatigue and post-exertional malaise. Research into brain dysfunction in the pediatric CFS/ME context, however, is severely lacking. It is unclear whether the adolescent CFS/ME brain functions differently compared with healthy peers, particularly in situations where significant mental effort is required. This study used resting-state functional MRI in a novel repeated-measures design to evaluate intrinsic connectivity, cognitive function, and subjective fatigue, before and after a period of cognitive exertion in 48 adolescents (25 CFS/ME, 23 healthy controls).

Results revealed little evidence for a differential effect of cognitive exertion in CFS/ME compared with controls. Both groups demonstrated a similar rate of reduced intrinsic functional connectivity within the default mode network (DMN), reduced sustained attentional performance, slower processing speed, and increased subjective fatigue as a result of cognitive exertion.

However, CFS/ME adolescents consistently displayed higher subjective fatigue, and controls outperformed the CFS/ME group overall on cognitive measures of processing speed, sustained attention and new learning. No brain-behavior relationships were observed between DMN connectivity, cognitive function, and fatigue over time.

These findings suggest that effortful cognitive tasks may elicit similar levels of energy expenditure across all individuals in the form of reduced brain functioning and associated fatigue. However, CFS/ME may confer a lower starting threshold from which to access energy reserves and cognitive resources when cognitive effort is required.

Source: Josev EK, Malpas CB, Seal ML, Scheinberg A6, Lubitz L, Rowe K, Knight SJ. Resting-state functional connectivity, cognition, and fatigue in response to cognitive exertion: a novel study in adolescents with chronic fatigue syndrome. Brain Imaging Behav. 2019 May 17. doi: 10.1007/s11682-019-00119-2. [Epub ahead of print] https://www.ncbi.nlm.nih.gov/pubmed/31102168

Less efficient and costly processes of frontal cortex in childhood chronic fatigue syndrome

Abstract:

The ability to divide one’s attention deteriorates in patients with childhood chronic fatigue syndrome (CCFS). We conducted a study using a dual verbal task to assess allocation of attentional resources to two simultaneous activities (picking out vowels and reading for story comprehension) and functional magnetic resonance imaging.

Patients exhibited a much larger area of activation, recruiting additional frontal areas. The right middle frontal gyrus (MFG), which is included in the dorsolateral prefrontal cortex, of CCFS patients was specifically activated in both the single and dual tasks; this activation level was positively correlated with motivation scores for the tasks and accuracy of story comprehension.

In addition, in patients, the dorsal anterior cingulate gyrus (dACC) and left MFG were activated only in the dual task, and activation levels of the dACC and left MFG were positively associated with the motivation and fatigue scores, respectively.

Patients with CCFS exhibited a wider area of activated frontal regions related to attentional resources in order to increase their poorer task performance with massive mental effort. This is likely to be less efficient and costly in terms of energy requirements. It seems to be related to the pathophysiology of patients with CCFS and to cause a vicious cycle of further increases in fatigue.

 

Source: Mizuno K, Tanaka M, Tanabe HC, Joudoi T, Kawatani J, Shigihara Y, Tomoda A, Miike T, Imai-Matsumura K, Sadato N, Watanabe Y. Less efficient and costly processes of frontal cortex in childhood chronic fatigue syndrome. Neuroimage Clin. 2015 Sep 10;9:355-68. doi: 10.1016/j.nicl.2015.09.001. ECollection 2015. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4589845/ (Full article)

 

Patterns of abnormal visual attention in myalgic encephalomyelitis

Abstract:

PURPOSE: To experimentally assess visual attention difficulties commonly reported by those with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS).

METHODS: Twenty-nine ME/CFS patients and 29 controls took part in the study. Performance was assessed using the Useful Field of View (UFOV), a spatial cueing task and visual search.

RESULTS: Patients and controls performed similarly on the processing speed subtest of the UFOV. However, patients exhibited marginally worse performance compared with controls on the divided attention subtest and significantly worse performance on the selective attention subtest. In the spatial cueing task, they were slower than controls to respond to the presence of the target, particularly when cues were invalid. They were also impaired, relative to controls, on visual search tasks.

CONCLUSIONS: We have provided experimental evidence for ME/CFS-related difficulties in directing visual attention. These findings support the subjective reports of those with ME/CFS and could represent a potential means to improve diagnosis.

 

Source: Hutchinson CV, Badham SP. Patterns of abnormal visual attention in myalgic encephalomyelitis. Optom Vis Sci. 2013 Jun;90(6):607-14. doi: 10.1097/OPX.0b013e318294c232. https://www.ncbi.nlm.nih.gov/pubmed/23689679

 

Neurocognitive impairment in childhood chronic fatigue syndrome

Abstract:

Neurocognitive impairment is a feature of childhood chronic fatigue syndrome (CCFS). Several studies have demonstrated reduced attention control in CCFS patients in switching and divided attention tasks. In students, the extent of deterioration in task performance depends on the level of fatigue.

Poor performance in switching and divided attention is common in both fatigued students and CCFS patients. Additionally, attentional functions show dramatic development from childhood to adolescence, suggesting that abnormal development of switching and divided attention may be induced by chronic fatigue.

The brain structures associated with attentional control are situated in the frontal and parietal cortices, which are the last to mature, suggesting that severe fatigue in CCFS patients and students may inhibit normal structural and functional development in these regions. A combination of treatment with cognitive behavioral therapy and antidepressant medication is effective to improve attentional control processing in CCFS patients. Studies identifying the features of neurocognitive impairment in CCFS have improved our current understanding of the neurophysiological mechanisms of CCFS.

 

Source: Mizuno K, Watanabe Y. Neurocognitive impairment in childhood chronic fatigue syndrome. Front Physiol. 2013 Apr 19;4:87. doi: 10.3389/fphys.2013.00087. ECollection 2013. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3630366/ (Full article)

 

The neuropsychiatric and neuropsychological features of chronic fatigue syndrome: revisiting the enigma

Abstract:

The aim of this article is to provide a comprehensive and updated review of the key neuropsychiatric and neuropsychological complaints associated with chronic fatigue syndrome (CFS). Neuropsychiatric and neuropsychological difficulties are common in CFS and are linked primarily to disorders of mood, affect and behaviour.

The neuropsychiatric complaint most frequently encountered amongst CFS patients is depression and in particular major depressive disorder (MDD). Despite decades of research, the precise aetiological relationship between CFS and MDD remains poorly understood. This has resulted in the development of a number of interesting and polarised hypotheses regarding the aetiological nature of CFS. Recent scientific advances have however begun to unravel a number of interesting inflammatory and immunological explanations that suggest CFS and MDD are distinct yet interrelated conditions.

The possibility that the overlap between CFS and MDD might be explained in terms of shared oxidative and nitrosative (IO&NS) pathways is an area of intense research interest and is reviewed in detail in this article. The overlap between CFS and MDD is further differentiated by variations in HPA axis activity between the two disorders. Important immunological differences between MDD and CFS are also reviewed with particular emphasis on antiviral RNase L pathways in CFS.

In addition to the presence of neuropsychiatric complaints, CFS is also associated with neuropsychological symptoms such as impaired attention, memory and reaction time. The key neuropsychological problems reported by CFS patients are also included in the review in an effort to understand the significance of cognitive impairment in CFS.

 

Source: Christley Y, Duffy T, Everall IP, Martin CR. The neuropsychiatric and neuropsychological features of chronic fatigue syndrome: revisiting the enigma. Curr Psychiatry Rep. 2013 Apr;15(4):353. doi: 10.1007/s11920-013-0353-8. https://www.ncbi.nlm.nih.gov/pubmed/23440559