Electroencephalographic Abnormalities in a Patient Suffering from Long-Term Neuropsychological Complications following SARS-CoV-2 Infection

Abstract:

Introduction: Emotional apathy has recently been identified as a common symptom of long COVID. While recent meta-analyses have demonstrated generalized EEG slowing with the emergence of delta rhythms in patients hospitalized for severe SARS-CoV-2 infection, no EEG study or dopamine transporter scintigraphy (DaTSCAN) has been performed in patients with long COVID presenting with apathy. The objective of this case report was to explore the pathophysiology of neuropsychological symptoms in long COVID.

Case presentation: A 47-year-old patient who developed a long COVID with prominent apathy following an initially clinically mild SARS-CoV-2 infection underwent neuropsychological assessment, cerebral MRI, DaTSCAN, and resting-state high-density EEG 7 months after SARS-CoV-2 infection. The EEG data were compared to those of 21 healthy participants. The patient presented with apathy, cognitive difficulties with dysexecutive syndrome, moderate attentional and verbal episodic memory disturbances, and resolution of premorbid mild gaming disorder, mild mood disturbances, and sleep disturbances. His MRI and DaTSCAN were unremarkable. EEG revealed a complex pattern of oscillatory abnormalities compared to the control group, with a strong increase in whole-scalp delta and beta band activity, as well as a decrease in alpha band activity. Overall, these effects were more prominent in the frontal-central-temporal region.

Conclusion: These results suggest widespread changes in EEG oscillatory patterns in a patient with long COVID characterized by neuropsychological complications with prominent apathy. Despite the inherent limitations of a case report, these results suggest dysfunction in the cortical networks involved in motivation and emotion.

Source: Benis D, Voruz P, Chiuve SC, Garibotto V, Assal F, Krack P, Péron J, Fleury V. Electroencephalographic Abnormalities in a Patient Suffering from Long-Term Neuropsychological Complications following SARS-CoV-2 Infection. Case Rep Neurol. 2023 Dec 5;16(1):6-17. doi: 10.1159/000535241. PMID: 38179211; PMCID: PMC10764086. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10764086/ (Full text)

Neuroinflammation After COVID-19 With Persistent Depressive and Cognitive Symptoms

Abstract:

Importance: Persistent depressive symptoms, often accompanied by cognitive symptoms, commonly occur after COVID-19 illness (hereinafter termed COVID-DC, DC for depressive and/or cognitive symptoms). In patients with COVID-DC, gliosis, an inflammatory change, was suspected, but measurements of gliosis had not been studied in the brain for this condition.

Objective: To determine whether translocator protein total distribution volume (TSPO VT), a marker of gliosis that is quantifiable with positron emission tomography (PET), is elevated in the dorsal putamen, ventral striatum, prefrontal cortex, anterior cingulate cortex, and hippocampus of persons with COVID-DC.

Design, setting, and participants: This case-control study conducted at a tertiary care psychiatric hospital in Canada from April 1, 2021, to June 30, 2022, compared TSPO VT of specific brain regions in 20 participants with COVID-DC with that in 20 healthy controls. The TSPO VT was measured with fluorine F 18-labeled N-(2-(2-fluoroethoxy)benzyl)-N-(4-phenoxypyridin-3-yl)acetamide ([18F]FEPPA) PET.

Main outcomes and measures: The TSPO VT was measured in the dorsal putamen, ventral striatum, prefrontal cortex, anterior cingulate cortex, and hippocampus. Symptoms were measured with neuropsychological and psychological tests, prioritizing outcomes related to striatal function.

Results: The study population included 40 participants (mean [SD] age, 32.9 [12.3] years). The TSPO VT across the regions of interest was greater in persons with COVID-DC (mean [SD] age, 32.7 [11.4] years; 12 [60%] women) compared with healthy control participants (mean [SD] age, 33.3 [13.9] years; 11 [55%] women): mean (SD) difference, 1.51 (4.47); 95% CI, 0.04-2.98; 1.51 divided by 9.20 (17%). The difference was most prominent in the ventral striatum (mean [SD] difference, 1.97 [4.88]; 95% CI, 0.36-3.58; 1.97 divided by 8.87 [22%]) and dorsal putamen (mean difference, 1.70 [4.25]; 95% CI, 0.34-3.06; 1.70 divided by 8.37 [20%]). Motor speed on the finger-tapping test negatively correlated with dorsal putamen TSPO VT (r, -0.53; 95% CI, -0.79 to -0.09), and the 10 persons with the slowest speed among those with COVID-DC had higher dorsal putamen TSPO VT than healthy persons by 2.3 (2.30 divided by 8.37 [27%]; SD, 2.46; 95% CI, 0.92-3.68).

Conclusions and relevance: In this case-control study, TSPO VT was higher in patients with COVID-DC. Greater TSPO VT is evidence for an inflammatory change of elevated gliosis in the brain of an individual with COVID-DC. Gliosis may be consequent to inflammation, injury, or both, particularly in the ventral striatum and dorsal putamen, which may explain some persistent depressive and cognitive symptoms, including slowed motor speed, low motivation or energy, and anhedonia, after initially mild to moderate COVID-19 illness.

Source: Braga J, Lepra M, Kish SJ, Rusjan PM, Nasser Z, Verhoeff N, Vasdev N, Bagby M, Boileau I, Husain MI, Kolla N, Garcia A, Chao T, Mizrahi R, Faiz K, Vieira EL, Meyer JH. Neuroinflammation After COVID-19 With Persistent Depressive and Cognitive Symptoms. JAMA Psychiatry. 2023 May 31:e231321. doi: 10.1001/jamapsychiatry.2023.1321. Epub ahead of print. PMID: 37256580; PMCID: PMC10233457. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10233457/ (Full text)

Cortical Hypoactivation During Resting EEG Suggests Central Nervous System Pathology in Patients with Chronic Fatigue Syndrome

Abstract:

We investigated cognitive impairment to executive function in 50 patients with chronic fatigue syndrome (CFS) and 50 matched healthy controls (HC). Resting state EEG was collected from 19 scalp locations during a 3 minute, eyes-closed condition. Current densities were localized using exact low-resolution electromagnetic tomography (eLORETA). The Multidimensional Fatigue Inventory (MFI-20) and the Fatigue Severity Scale (FSS) were administered to all participants. Independent t-tests and linear regression analyses were used to evaluate group differences in current densities, followed by statistical non-parametric mapping (SnPM) correction procedures.

Significant differences were found in the delta (1-3 Hz) and beta-2 (19-21 Hz) frequency bands. Delta sources were found predominately in the frontal lobe, while beta-2 sources were found in the medial and superior parietal lobe. Left-lateralized, frontal delta sources were associated with a clinical reduction in motivation. The implications of abnormal cortical sources in patients with CFS are discussed.

Source: Zinn MA, Zinn ML, Valencia I, Jason LA, Montoya JG. Cortical Hypoactivation During Resting EEG Suggests Central Nervous System Pathology in Patients with Chronic Fatigue Syndrome. Biol Psychol. 2018 May 23. pii: S0301-0511(18)30407-1. doi: 10.1016/j.biopsycho.2018.05.016. [Epub ahead of print] https://www.ncbi.nlm.nih.gov/pubmed/29802861

Low putamen activity associated with poor reward sensitivity in childhood chronic fatigue syndrome

Abstract:

Motivational signals influence a wide variety of cognitive processes and components of behavioral performance. Cognitive dysfunction in patients with childhood chronic fatigue syndrome (CCFS) may be closely associated with a low motivation to learn induced by impaired neural reward processing. However, the extent to which reward processing is impaired in CCFS patients is unclear.

The aim of the present functional magnetic resonance imaging (fMRI) study was to determine whether brain activity in regions related to reward sensitivity is impaired in CCFS patients. fMRI data were collected from 13 CCFS patients (mean age, 13.6 ± 1.0 years) and 13 healthy children and adolescents (HCA) (mean age, 13.7 ± 1.3 years) performing a monetary reward task. Neural activity in high- and low-monetary-reward conditions was compared between CCFS and HCA groups. Severity of fatigue and the reward obtained from learning in daily life were evaluated by questionnaires.

Activity of the putamen was lower in the CCFS group than in the HCA group in the low-reward condition, but not in the high-reward condition. Activity of the putamen in the low-reward condition in CCFS patients was negatively and positively correlated with severity of fatigue and the reward from learning in daily life, respectively.

We previously revealed that motivation to learn was correlated with striatal activity, particularly the neural activity in the putamen. This suggests that in CCFS patients low putamen activity, associated with altered dopaminergic function, decreases reward sensitivity and lowers motivation to learn.

 

Source: Mizuno K, Kawatani J, Tajima K, Sasaki AT, Yoneda T, Komi M, Hirai T, Tomoda A, Joudoi T, Watanabe Y. Low putamen activity associated with poor reward sensitivity in childhood chronic fatigue syndrome. Neuroimage Clin. 2016 Sep 26;12:600-606. eCollection 2016. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5043413/ (Full article)

 

Chronic fatigue in complementary rehabilitative medicine–predictors of the outcomes

Abstract:

Chronic exhaustion and fatigue are increasingly important in rehabilitation medicine. Objectives of this study were (a) to describe the effects of in-patient rehabilitation on patients with chronic fatigue syndromes, (b) to identify predictors for treatment outcome, and (c) to analyze the impact of comprehensive diagnosing on these issues.

A total of 171 patients with chronic exhaustion or fatigue (90 % female, mean age 55 +/- 10 yrs) from a rehabilitation hospital with a complementary medicine-based treatment concept were included in a prospective observational study. Within the longitudinal study patients were examined three times (on admission to hospital, at discharge as well as six months later). Participation rate of the postal inquiry was 69 %. Besides items constructed ad hoc, Patient questionnaires included the Symptom Checklist and assessment instruments for depression, quality of life, sense of coherence as well as for changes in experience and behaviour. Treatment outcome was defined as sum score of binary-coded response criteria.

The pattern of complaints differed clearly between diagnostic subgroups (neurasthenia, affective disorders, adjustment disorders) before treatment. At discharge from hospital patients showed clinically relevant improvements lasting for six months after rehabilitation. Multiple regression analyses revealed a statistically significant relationship (R (mult) = 0.59) between predictors and outcome at discharge from hospital.

A better result was associated with higher trust in treatment success, active information seeking on complementary medicine, healthier feeding habits, better somatic health and a decreased mental status, with regard to the status before treatment. The prediction of outcome after six months was comparably poorer (R (mult) = 0.42).

Treatment success was higher in the absence of a diagnosis of neurasthenia, in patients accepting the group-oriented treatment concept and in patients not believing that their disease was due to their own way of living. Trust in the success of the treatment was a highly ranked predictor for longer lasting outcome, too. The results underline the importance of motivation aspects for treatment outcome indicating that individual expectations and attitudes should be considered in a more distinct way when allocating patients to rehabilitative programmes.

 

Source: Weidenhammer W, Wessel A, Hutter A, Melchart D, Schröder A. Chronic fatigue in complementary rehabilitative medicine–predictors of the outcomes. Rehabilitation (Stuttg). 2006 Oct;45(5):299-308. [Article in German] https://www.ncbi.nlm.nih.gov/pubmed/17024614