Longterm course of neuropsychological symptoms and ME/CFS after SARS-CoV-2-infection: a prospective registry study

Abstract:

A significant proportion of patients after SARS-CoV-2 infection suffer from long-lasting symptoms. Although many different symptoms are described, the majority of patients complains about neuropsychological symptoms. Additionally, a subgroup of patients fulfills diagnostic criteria for ME/CFS. We analyzed a registry of all patients presenting in the out-patients clinic at a German university center. For patients with more than one visit, changes in reported symptoms from first to second visit were analyzed.

A total of 1022 patients were included in the study, 411 of them had more than one visit. 95.5% of the patients reported a polysymptomatic disease. At the first visit 31.3% of the patients fulfilled ME/CFS criteria after a median time of 255 days post infection and and at the second visit after a median of 402 days, 19.4% still suffered from ME/CFS. Self-reported fatigue (83.7-72.7%) and concentration impairment (66.2-57.9%) decreased from first to second visit contrasting non-significant changes in the structured screening.

A significant proportion of SARS-CoV-2 survivors presenting with ongoing symptoms present with ME/CFS. Although the proportion of subjective reported symptoms and their severity reduce over time, a significant proportion of patients suffer from long-lasting symptoms necessitating new therapeutic concepts.

Source: Reuken PA, Besteher B, Finke K, Fischer A, Holl A, Katzer K, Lehmann-Pohl K, Lemhöfer C, Nowka M, Puta C, Walter M, Weißenborn C, Stallmach A. Longterm course of neuropsychological symptoms and ME/CFS after SARS-CoV-2-infection: a prospective registry study. Eur Arch Psychiatry Clin Neurosci. 2023 Aug 16. doi: 10.1007/s00406-023-01661-3. Epub ahead of print. PMID: 37587244. https://link.springer.com/article/10.1007/s00406-023-01661-3 (Full text)

Neuropsychological impairment in female patients with chronic fatigue syndrome: a preliminary study

Abstract:

This study examines neuropsychological impairments associated with chronic fatigue syndrome (CFS) and explores their association with related clinical factors.

Sixty-eight women with CFS were assessed with a neuropsychological battery. Raw scores were adjusted for age and gender and were converted to T scores according to normative data extracted from a local sample of 250 healthy subjects. Neuropsychological dysfunction was calculated using summary impairment indexes (proportion of test scores outside normal limits-T score <40-for each cognitive domain). Finally, a linear regression was calculated to identify predictors of cognitive deficit, including intrinsic factors of the disease (level of fatigue and length of illness) and extrinsic factors (emotional factors, age, and education).

Approximately 50% of scores showed impairment in attention and motor functioning, and nearly 40% showed impairment in speed information processing and executive functioning. Fatigue predicted attention and executive functioning impairment, and emotional factors predicted verbal memory dysfunction.

According to our findings, cognitive dysfunction in CFS could be explained by pathophysiological processes of the disease. One implication of this would be the need to identify homogeneous subgroups of patients with CFS by taking into account common factors, which, in turn, would help to identify more specific cognitive profiles, which could then serve to implement appropriate therapeutic measures accordingly.

 

Source: Santamarina-Perez P, Eiroa-Orosa FJ, Rodriguez-Urrutia A, Qureshi A, Alegre J. Neuropsychological impairment in female patients with chronic fatigue syndrome: a preliminary study. Appl Neuropsychol Adult. 2014;21(2):120-7. doi: 10.1080/09084282.2013.771264. Epub 2013 Aug 13. https://www.ncbi.nlm.nih.gov/pubmed/24826505

 

Does neuropsychological test performance predict outcome of cognitive behavior therapy for Chronic Fatigue Syndrome and what is the role of underperformance?

Abstract:

OBJECTIVE: A subgroup of patients with Chronic Fatigue Syndrome (CFS) has cognitive impairments, reflected by deviant neuropsychological test performance. However, abnormal test scores can also be caused by suboptimal effort. We hypothesized that worse neuropsychological test performance and underperformance were related to each other and to a smaller reduction in fatigue, functional impairments, physical limitations and higher dropout rates following cognitive behavior therapy (CBT) for CFS.

METHODS: Data were drawn from a previous trial, in which CFS patients were randomized to two conditions; 1) guided self-instruction and additional CBT (n=84) or 2) waiting period followed by regular CBT for CFS (n=85). Underperformance was assessed using the Amsterdam Short Term Memory Test (<84). To test neuropsychological test performance, the Symbol Digit Modalities Task, a simple reaction time task and a choice reaction time task were used. Interaction effects were determined between underperformance and neuropsychological test performance on therapy outcomes.

RESULTS: Underperformance was associated to worse neuropsychological test performance, but there were no significant interaction effects of these two factors by therapy on fatigue severity, functional impairments and physical limitations, but there was a significant main effect of underperformance on functional impairments, physical limitations and dropout rates.

CONCLUSION: Underperformance or neuropsychological test performance was not related to the change in fatigue, functional impairments, and physical limitations following CBT for CFS. However, underperforming patients did drop out more often. Therapists should pay attention to beliefs and behavioral or environmental factors that might maintain underperformance and increase the risk of dropout.

© 2013

Comment in

Source: Goedendorp MM, van der Werf SP, Bleijenberg G, Tummers M, Knoop H. Does neuropsychological test performance predict outcome of cognitive behavior therapy for Chronic Fatigue Syndrome and what is the role of underperformance? J Psychosom Res. 2013 Sep;75(3):242-8. doi: 10.1016/j.jpsychores.2013.07.011. Epub 2013 Jul 26. https://www.ncbi.nlm.nih.gov/pubmed/23972413

 

Neuropsychological performance in persons with chronic fatigue syndrome: results from a population-based study

Abstract:

OBJECTIVE: To examine the neuropsychological function characterized in subjects with chronic fatigue syndrome (CFS) at the same time controlling for relevant confounding factors. CFS is associated with symptoms of neuropsychological dysfunction. Objective measures of neuropsychological performance have yielded inconsistent results possibly due to sample selection bias, diagnostic heterogeneity, comorbid psychiatric disorders, and medication usage.

METHOD: CFS subjects (n = 58) and well controls (n = 104) from a population-based sample were evaluated, using standardized symptom severity criteria. Subjects who had major psychiatric disorders or took medications known to influence cognition were excluded. Neuropsychological function was measured using the Cambridge Neuropsychological Test Automated Battery (CANTAB).

RESULTS: Compared with controls, CFS subjects exhibited significant decreases in motor speed as measured in the simple and five-choice movement segments of the CANTAB reaction time task. CFS subjects also exhibited alterations in working memory as manifested by a less efficient search strategy on the spatial working memory task, fewer % correct responses on the spatial recognition task, and prolonged latency to a correct response on the pattern recognition task. A significantly higher percentage of CFS subjects versus controls exhibited evidence of neuropsychological impairment (defined by performance 1 standard deviation below the CANTAB normative mean) in tasks of motor speed and spatial working memory. Impairment in CFS subjects versus control subjects ranged from 20% versus 4.8% in five-choice movement time (p = .002) to 27.8% versus 10.6% in search strategy on the spatial working memory task (p = .006).

CONCLUSIONS: These results confirm and quantify alterations in motor speed and working memory in CFS subjects independent of comorbid psychiatric disease and medication usage.

 

Source: Majer M, Welberg LA, Capuron L, Miller AH, Pagnoni G, Reeves WC. Neuropsychological performance in persons with chronic fatigue syndrome: results from a population-based study. Psychosom Med. 2008 Sep;70(7):829-36. doi: 10.1097/PSY.0b013e31817b9793. Epub 2008 Jul 7. https://www.ncbi.nlm.nih.gov/pubmed/18606722

 

Neuropsychiatric sequelae of Nipah virus encephalitis

Abstract:

The authors followed nine patients with Nipah virus encephalitis over the course of 24 months. Eight of the nine developed psychiatric features assigned to the encephalitis. Three patients developed major depressive disorder immediately after recovering from the encephalitis, and two developed depression approximately 1 year after the outbreak. Two patients developed personality changes, and two suffered chronic fatigue syndrome.

Neuropsychological testing was accomplished in eight of the nine patients. Deficits in attention, verbal, and/or visual memory were substantial in seven of the eight patients tested. Verbal memory was more impaired than visual memory in these patients. Comparison between psychiatric and cognitive impairment and total number of brain lesions showed no discernible trends.

 

Source: Ng BY, Lim CC, Yeoh A, Lee WL. Neuropsychiatric sequelae of Nipah virus encephalitis. J Neuropsychiatry Clin Neurosci. 2004 Fall;16(4):500-4. http://www.ncbi.nlm.nih.gov/pubmed/15616178

 

Longitudinal assessment of neuropsychological functioning, psychiatric status, functional disability and employment status in chronic fatigue syndrome

Abstract:

The longitudinal course of subjective and objective neuropsychological functioning, psychological functioning, disability level, and employment status in chronic fatigue syndrome (CFS) was examined. The relations among several key outcomes at follow-up, as well as the baseline characteristics that predict change (e.g., improvement), were also evaluated.

The study sample consisted of 35 individuals who met the 1988 and 1994 CFS case definition criteria of the Centers for Disease Control (CDC) at intake. Participants were evaluated a mean of 41.9 (SEM = 1.7) months following their initial visit (range = 24-63 months).

Results indicated that objective and subjective attention abilities, mood, level of fatigue, and disability improve over time in individuals with CFS. Moreover, improvements in these areas were found to be interrelated at follow-up. Finally, psychiatric status, age, and between-test duration were significant predictors of outcome. Overall, the prognosis for CFS appears to be poor, as the majority of participants remained functionally impaired over time and were unemployed at follow-up, despite the noted improvements.

 

Source: Tiersky LA, DeLuca J, Hill N, Dhar SK, Johnson SK, Lange G, Rappolt G, Natelson BH. Longitudinal assessment of neuropsychological functioning, psychiatric status, functional disability and employment status in chronic fatigue syndrome. Appl Neuropsychol. 2001;8(1):41-50. http://www.ncbi.nlm.nih.gov/pubmed/11388123

 

Neuropsychological function in patients with chronic fatigue syndrome, multiple sclerosis, and depression

Abstract:

Patients with chronic fatigue syndrome (CFS), multiple sclerosis (MS), and major depression were compared with controls and with each other on a neuropsychological battery that included standard neuropsychological tests and a computerized set of tasks that spanned the same areas of ability.

A total of 101 participants were examined, including 29 participants with CFS, 24 with MS, 23 with major depressive disorder, and 25 healthy controls. There were significant differences among the groups in 3 out of 5 cognitive domains: memory, language, and spatial ability. Assessment of psychiatric symptoms indicated that all 3 patient groups had a higher prevalence of depression than the controls. A total measure of psychiatric symptomatology also differentiated the patients from the controls.

After covarying the cognitive test scores by a measure of depression, the patient groups continued to differ from controls primarily in the area of memory. The findings support the view that the cognitive deficits found in CFS cannot be attributed solely to the presence of depressive symptomatology in the patients.

 

Source: Daly E, Komaroff AL, Bloomingdale K, Wilson S, Albert MS. Neuropsychological function in patients with chronic fatigue syndrome, multiple sclerosis, and depression. Appl Neuropsychol. 2001;8(1):12-22. http://www.ncbi.nlm.nih.gov/pubmed/11388119

 

Neuropsychological functioning in chronic fatigue syndrome: a review

Abstract:

OBJECTIVE: In this paper we review critically the current status of neurocognitive studies in patients with chronic fatigue syndrome (CFS).

METHOD: CFS literature was monitored as part of a large research project which involved several neuropsychological and psychopathological studies. The literature survey was the result of several consecutive searches on Medline and PsycInfo databases.

RESULTS: The neurocognitive studies are reviewed in terms of scientifically accepted aspects of attention and memory. In addition, we review possible explanations for cognitive dysfunction in CFS. This is preceded with a discussion of the methodological limitations that are considered to explain inconsistencies across neuropsychological studies in CFS.

CONCLUSION: The current research shows that slowed processing speed, impaired working memory and poor learning of information are the most prominent features of cognitive dysfunctioning in patients with CFS. Furthermore, to this date no specific pattern of cerebral abnormalities has been found that uniquely characterizes CFS patients. There is no overwhelming evidence that fatigue is related to cognitive performance in CFS, and researchers agree that their performance on neuropsychological tasks is unlikely to be accounted solely by the severity of the depression and anxiety.

 

Source: Michiels V, Cluydts R. Neuropsychological functioning in chronic fatigue syndrome: a review. Acta Psychiatr Scand. 2001 Feb;103(2):84-93. http://www.ncbi.nlm.nih.gov/pubmed/11167310

 

Parallels between post-polio fatigue and chronic fatigue syndrome: a common pathophysiology?

Abstract:

Fatigue is the most commonly reported and most debilitating of post-polio sequelae affecting the >1.8 million North American polio survivors. Post-polio fatigue is characterized by subjective reports of difficulty with attention, cognition, and maintaining wakefulness. These symptoms resemble those reported in nearly 2 dozen outbreaks of post-viral fatigue syndromes (PVFS) that have recurred during this century and that are related clinically, historically, anatomically, or physiologically to poliovirus infections.

This article reviews recent studies that relate the symptoms of post-polio fatigue and chronic fatigue syndrome (CFS) to clinically significant deficits on neuropsychologic tests of attention, histopathologic and neuroradiologic evidence of brain lesions, impaired activation of the hypothalamic-pituitary-adrenal axis, increased prolactin secretion, and electroencephalogram (EEG) slow-wave activity.

A possible common pathophysiology for post-polio fatigue and CFS, based on the Brain Fatigue Generator Model of PVFS, and a possible pharmacotherapy for PVFS based on replacement of depleted brain dopamine, will be described.

 

Source: Bruno RL, Creange SJ, Frick NM. Parallels between post-polio fatigue and chronic fatigue syndrome: a common pathophysiology? Am J Med. 1998 Sep 28;105(3A):66S-73S. http://www.ncbi.nlm.nih.gov/pubmed/9790485

 

Relation between neuropsychological impairment and functional disability in patients with chronic fatigue syndrome

Abstract:

OBJECTIVES: To examine the relation between neuropsychological impairment and functional disability in patients with chronic fatigue syndrome, and determine whether the relation is independent of psychiatric factors.

METHODS: The subjects were 53 patients with chronic fatigue syndrome and 32 healthy controls who did not exercise regularly. Subjects were administered a structured psychiatric interview and completed questionnaires focusing on depression and functional disability. They also completed a battery of standardised neuropsychological tasks focusing on the cognitive domains that patients with chronic fatigue syndrome experience as particularly difficult: memory (verbal and visual), and attention/concentration. A test score was defined as failing when it was > or =2 SD below the mean of the healthy controls after controlling for demographic factors.

RESULTS: Those patients with chronic fatigue syndrome with higher numbers of failing neuropsychological test scores reported significantly more days of general inactivity in the past month than those with fewer failing scores. This result remained significant even after partialling out the contribution of the presence of a comorbid axis I psychiatric episode and the overall level of depressive symptomology. Patients with failing verbal memory scores were particularly functionally disabled compared with those with passing scores.

CONCLUSION: A relation was found between cognitive impairment and functional disability which could not be explained entirely on the basis of psychiatric factors.

Comment in: The importance of mental fatigue. [J Neurol Neurosurg Psychiatry. 1998]

 

Source: Christodoulou C, DeLuca J, Lange G, Johnson SK, Sisto SA, Korn L, Natelson BH. Relation between neuropsychological impairment and functional disability in patients with chronic fatigue syndrome. J Neurol Neurosurg Psychiatry. 1998 Apr;64(4):431-4. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2170049/