Tag: brain fog

Orthostatic Challenge Causes Distinctive Symptomatic, Hemodynamic and Cognitive Responses in Long COVID and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

Abstract:

Background: Some patients with acute COVID-19 are left with persistent, debilitating fatigue, cognitive impairment (“brain fog”), orthostatic intolerance (OI) and other symptoms (“Long COVID”). Many of the symptoms are like those of other post-infectious fatigue syndromes and may meet criteria for myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Common diagnostic laboratory tests are often unrevealing.

Methods: We evaluated whether a simple, standardized, office-based test of OI, the 10-min NASA Lean Test (NLT), would aggravate symptoms and produce objective hemodynamic and cognitive abnormalities, the latter being evaluated by a simple smart phone-based app.

Participants: People with Long COVID (N = 42), ME/CFS (N = 26) and healthy control subjects (N = 20) were studied just before, during, immediately after, 2 and 7 days following completion of the NLT.

Results: The NLT provoked a worsening of symptoms in the two patient groups but not in healthy control subjects, and the severity of all symptoms was similar and significantly worse in the two patient groups than in the control subjects (p < 0.001). In the two patient groups, particularly those with Long COVID, the NLT provoked a marked and progressive narrowing in the pulse pressure. All three cognitive measures of reaction time worsened in the two patient groups immediately following the NLT, compared to the healthy control subjects, particularly in the Procedural Reaction Time (p < 0.01).

Conclusions: A test of orthostatic stress easily performed in an office setting reveals different symptomatic, hemodynamic and cognitive abnormalities in people with Long COVID and ME/CFS, compared to healthy control subjects. Thus, an orthostatic challenge easily performed in an office setting, and the use of a smart phone app to assess cognition, can provide objective confirmation of the orthostatic intolerance and brain fog reported by patients with Long COVID and ME/CFS.

Source: Vernon SD, Funk S, Bateman L, Stoddard GJ, Hammer S, Sullivan K, Bell J, Abbaszadeh S, Lipkin WI, Komaroff AL. Orthostatic Challenge Causes Distinctive Symptomatic, Hemodynamic and Cognitive Responses in Long COVID and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. Front Med (Lausanne). 2022 Jun 23;9:917019. doi: 10.3389/fmed.2022.917019. PMID: 35847821; PMCID: PMC9285104. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9285104/ (Full text)

An online survey of pelvic congestion support group members regarding comorbid symptoms and syndromes

Abstract:

Objectives: Patients with pelvic congestion syndrome (PCS) often report overlapping somatic symptoms and syndromes. The objective of this study was to explore the prevalence of co-existing symptoms and self-reported syndrome diagnoses among women with PCS and to inform future research hypotheses.

Methods: A brief online survey was offered to members of a PCS support group website. Responses were assessed for self-reported co-existing symptoms and formal diagnoses, including: chronic fatigue syndrome, fibromyalgia, postural tachycardia syndrome, irritable bowel syndrome, migraines, interstitial cystitis, and temporomandibular joint dysfunction.

Results: Of a total of 6000 members, there were 398 respondents; 232 (59%) had not yet been treated for PCS. Among these, the most prevalent co-existing symptoms were as follows: severe fatigue (72%), dizziness (63%), IBS symptoms (61%), brain fog (33%), migraines (49%), polyuria or dysuria (41%), excessive sweating (31%), TMJ pain (31%), and loose skin or lax joints (18%). These are much higher than reported for the general female population. The most commonly self-reported comorbid syndrome diagnoses for the overall group of 398 were: irritable bowel syndrome (29%), fibromyalgia (13%), spinal nerve problems (18%), interstitial cystitis (10%), postural tachycardia syndrome (9%), hypertension (11%), chronic fatigue syndrome (10%), and Ehlers-Danlos syndrome (6%). Other than with hypertension, these rates are variably higher than in the general population.

Conclusion: Several self-reported co-existing symptoms and syndromes are more prevalent in members of a PCS support group relative to the reported prevalence in the general population. More formal investigation is warranted to evaluate this finding and to investigate potential etiologic links. Ehlers-Danlos Syndrome appears to be common in self identifying PCS women.

Source: Smith SJ, Sichlau M, Sewall LE, Smith BH, Chen B, Khurana N, Rowe PC. An online survey of pelvic congestion support group members regarding comorbid symptoms and syndromes. Phlebology. 2022 Jul 13:2683555221112567. doi: 10.1177/02683555221112567. Epub ahead of print. PMID: 35831253. https://pubmed.ncbi.nlm.nih.gov/35831253/

Molecular Mechanisms of Neuroinflammation in ME/CFS and Long COVID to Sustain Disease and Promote Relapses

Abstract:

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a disease now well-documented as having arisen commonly from a viral infection, but also from other external stressors, like exposure to agricultural chemicals, other types of infection, surgery, or other severe stress events. Research has shown these events produce a systemic molecular inflammatory response and chronic immune activation and dysregulation. What has been more difficult to establish is the hierarchy of the physiological responses that give rise to the myriad of symptoms that ME/CFS patients experience, and why they do not resolve and are generally life-long.

The severity of the symptoms frequently fluctuates through relapse recovery periods, with brain-centered symptoms of neuroinflammation, loss of homeostatic control, “brain fog” affecting cognitive ability, lack of refreshing sleep, and poor response to even small stresses. How these brain effects develop with ME/CFS from the initiating external effector, whether virus or other cause, is poorly understood and that is what our paper aims to address.

We propose the hypothesis that following the initial stressor event, the subsequent systemic pathology moves to the brain via neurovascular pathways or through a dysfunctional blood-brain barrier (BBB), resulting in chronic neuroinflammation and leading to a sustained illness with chronic relapse recovery cycles. Signaling through recognized pathways from the brain back to body physiology is likely part of the process by which the illness cycle in the peripheral system is sustained and why healing does not occur. By contrast, Long COVID (Post-COVID-19 condition) is a very recent ME/CFS-like illness arising from the single pandemic virus, SARS-CoV-2.

We believe the ME/CFS-like ongoing effects of Long COVID are arising by very similar mechanisms involving neuroinflammation, but likely with some unique signaling, resulting from the pathology of the initial SARS-CoV-2 infection. The fact that there are very similar symptoms in both ongoing diseases, despite the diversity in the nature of the initial stressors, supports the concept of a similar dysfunctional CNS component common to both.

Source: Tate W, Walker M, Sweetman E, Helliwell A, Peppercorn K, Edgar C, Blair A, Chatterjee A. Molecular Mechanisms of Neuroinflammation in ME/CFS and Long COVID to Sustain Disease and Promote Relapses. Front Neurol. 2022 May 25;13:877772. doi: 10.3389/fneur.2022.877772. PMID: 35693009; PMCID: PMC9174654.  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9174654/ (Full text)

Persistent Brain Fog After Mild COVID Infection Tied to CSF Markers

Abstract:

As cases of coronavirus disease 2019 (COVID-19) mount worldwide, attention is needed on potential long-term neurologic impacts for the majority of patients who experience mild to moderate illness managed as outpatients. To date, there has not been discussion of persistent neurocognitive deficits in patients with milder COVID-19. We present two cases of non-hospitalized patients recovering from COVID-19 with persistent neurocognitive symptoms. Commonly used cognitive screens were normal, while more detailed testing revealed working memory and executive functioning deficits.

An observational cohort study of individuals recovering from COVID-19 (14 or more days following symptom onset) identified that among the first 100 individuals enrolled, 14 were non-hospitalized patients reporting persistent cognitive issues. These 14 participants had a median age of 39 years (interquartile range: 35-56), and cognitive symptoms were present for at least a median of 98 days (interquartile range: 71-120 following acute COVID-19 symptoms); no participants with follow-up evaluation reported symptom resolution. We discuss potential mechanisms to be explored in future studies, including direct viral effects, indirect consequences of immune activation, and immune dysregulation causing auto-antibody production.

Source: Hellmuth J, Barnett TA, Asken BM, Kelly JD, Torres L, Stephens ML, Greenhouse B, Martin JN, Chow FC, Deeks SG, Greene M, Miller BL, Annan W, Henrich TJ, Peluso MJ. Persistent COVID-19-associated neurocognitive symptoms in non-hospitalized patients. J Neurovirol. 2021 Feb;27(1):191-195. doi: 10.1007/s13365-021-00954-4. Epub 2021 Feb 2. PMID: 33528824; PMCID: PMC7852463. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7852463/ (Full text)

‘I can’t cope with multiple inputs’: a qualitative study of the lived experience of ‘brain fog’ after COVID-19

Abstract:

Objective: To explore the lived experience of ‘brain fog’-the wide variety of neurocognitive symptoms that can follow COVID-19.

Design and setting: A UK-wide longitudinal qualitative study comprising online focus groups with email follow-up.

Method: 50 participants were recruited from a previous qualitative study of the lived experience of long COVID-19 (n=23) and online support groups for people with persistent neurocognitive symptoms following COVID-19 (n=27). In remotely held focus groups, participants were invited to describe their neurocognitive symptoms and comment on others’ accounts. Individuals were followed up by email 4-6 months later. Data were audiotaped, transcribed, anonymised and coded in NVIVO. They were analysed by an interdisciplinary team with expertise in general practice, clinical neuroscience, the sociology of chronic illness and service delivery, and checked by people with lived experience of brain fog.

Results: Of the 50 participants, 42 were female and 32 white British. Most had never been hospitalised for COVID-19. Qualitative analysis revealed the following themes: mixed views on the appropriateness of the term ‘brain fog’; rich descriptions of the experience of neurocognitive symptoms (especially executive function, attention, memory and language), accounts of how the illness fluctuated-and progressed over time; the profound psychosocial impact of the condition on relationships, personal and professional identity; self-perceptions of guilt, shame and stigma; strategies used for self-management; challenges accessing and navigating the healthcare system; and participants’ search for physical mechanisms to explain their symptoms.

Conclusion: These qualitative findings complement research into the epidemiology and mechanisms of neurocognitive symptoms after COVID-19. Services for such patients should include: an ongoing therapeutic relationship with a clinician who engages with their experience of neurocognitive symptoms in its personal, social and occupational context as well as specialist services that include provision for neurocognitive symptoms, are accessible, easily navigable, comprehensive and interdisciplinary.

Source: Callan C, Ladds E, Husain L, Pattinson K, Greenhalgh T. ‘I can’t cope with multiple inputs’: a qualitative study of the lived experience of ‘brain fog’ after COVID-19. BMJ Open. 2022 Feb 11;12(2):e056366. doi: 10.1136/bmjopen-2021-056366. PMID: 35149572; PMCID: PMC8844964. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8844964/ (Full text)

Neurocognitive Profiles in Patients With Persisting Cognitive Symptoms Associated With COVID-19

Abstract:

Objective: A subset of individuals with coronavirus disease 2019 (COVID-19) appears to develop persisting cognitive and medical symptoms. Research in the acute stages of illness, generally utilizing cognitive screening measures or case reports, suggests presence of deficits in attention and executive function. This observational study investigated cognitive functioning among individuals with persistent cognitive complaints about 5.5 months after COVID-19 infection.

Methods: Patients with polymerase chain reaction confirmed COVID-19 and persistent cognitive complaints underwent comprehensive in-person neuropsychological evaluations. Patients with prior neurological disorders were excluded. When diagnosed, 40% required hospitalization, 15% were in an intensive care unit, 10% needed mechanical ventilation, and 10% experienced delirium.

Results: This sample was predominately women (90%), White non-Hispanic (70%), with average education of 15 years. Mild cognitive deficits were seen on tests involving attention and processing speed or executive function. Seventy percent of patients were diagnosed with a mood disorder prior to COVID-19 infection. At the time of testing, 35%-40% endorsed moderate to severe mood symptoms and 85% noted significant fatigue as measured by the Fatigue Severity Scale.

Conclusions: The pattern of cognitive deficits, although mild, is consistent with prior research at the acute stage of the illness. These findings suggest that psychological factors and other persisting symptoms (e.g., sleep, fatigue) may play a significant role in subjective cognitive complaints in patients with persisting complaints post COVID-19 who did not require intensive treatment. These patients would likely benefit from resources to manage persisting or new mood symptoms and compensatory strategies for the cognitive inefficiencies they experience.

Source: Krishnan K, Miller AK, Reiter K, Bonner-Jackson A. Neurocognitive Profiles in Patients With Persisting Cognitive Symptoms Associated With COVID-19. Arch Clin Neuropsychol. 2022 Feb 5:acac004. doi: 10.1093/arclin/acac004. Epub ahead of print. PMID: 35136912. https://academic.oup.com/acn/advance-article/doi/10.1093/arclin/acac004/6522998 (Full text)

Biomedical Perspectives of Acute and Chronic Neurological and Neuropsychiatric Sequelae of COVID-19

Abstract:

The incidence of infections from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the etiologic agent for coronavirus disease 2019 (COVID-19), has dramatically escalated following the initial outbreak in China in late 2019, resulting in a global pandemic with millions of deaths. Although the majority of infected patients survive, and the rapid advent and deployment of vaccines have afforded increased immunity against SARS-CoV-2, long term sequelae of SARS-CoV-2 infection have become increasingly recognized. These include, but are not limited to, chronic pulmonary disease, cardiovascular disorders, and proinflammatory-associated neurological dysfunction that may lead to psychological and neurocognitive impairment. A major component of cognitive dysfunction is operationally categorized as “brain fog” which comprises difficulty with concentration, forgetfulness, confusion, depression, and fatigue.

Multiple parameters associated with long-term neuropsychiatric sequelae of SARS-CoV-2 infection have been detailed in clinical studies. Empirically elucidated mechanisms associated with the neuropsychiatric manifestations of COVID-19 are by nature complex, but broad based working models have focused on mitochondrial dysregulation leading to systemic reductions of metabolic activity and cellular bioenergetics within CNS structures. Multiple factors underlying the expression of brain fog may facilitate future pathogenic insults leading to repetitive cycles of viral and bacterial propagation. Interestingly, diverse neurocognitive sequelae associated with COVID-19 are not dissimilar from those observed in other historical pandemics, thereby providing a broad and integrative perspective on potential common mechanisms of CNS dysfunction subsequent to viral infection. Poor mental health status may be reciprocally linked to compromised immune processes and enhanced susceptibility to infection by diverse pathogens.

By extrapolation, we contend that COVID-19 may potentiate the severity of neurological/neurocognitive deficits in patients afflicted by well-studied neurodegenerative disorders such as Alzheimer’s disease and Parkinson’s disease. Accordingly, the prevention, diagnosis, and management of sustained neuropsychiatric manifestations of COVID-19 are pivotal health care directives and provide a compelling rationale for careful monitoring of infected patients, as early mitigation efforts may reduce short- and long-term complications.

Source: Stefano GB, Büttiker P, Weissenberger S, Ptacek R, Wang F, Esch T, Bilfinger TV, Kream RM. Biomedical Perspectives of Acute and Chronic Neurological and Neuropsychiatric Sequelae of COVID-19. Curr Neuropharmacol. 2021 Dec 23. doi: 10.2174/1570159X20666211223130228. Epub ahead of print. PMID: 34951387. https://pubmed.ncbi.nlm.nih.gov/34951387/

Long-COVID syndrome-associated brain fog and chemofog: Luteolin to the rescue

Abstract:

COVID-19 leads to severe respiratory problems, but also to long-COVID syndrome associated primarily with cognitive dysfunction and fatigue. Long-COVID syndrome symptoms, especially brain fog, are similar to those experienced by patients undertaking or following chemotherapy for cancer (chemofog or chemobrain), as well in patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) or mast cell activation syndrome (MCAS). The pathogenesis of brain fog in these illnesses is presently unknown but may involve neuroinflammation via mast cells stimulated by pathogenic and stress stimuli to release mediators that activate microglia and lead to inflammation in the hypothalamus. These processes could be mitigated by phytosomal formulation (in olive pomace oil) of the natural flavonoid luteolin.

Source: Theoharides TC, Cholevas C, Polyzoidis K, Politis A. Long-COVID syndrome-associated brain fog and chemofog: Luteolin to the rescue. Biofactors. 2021 Apr 12. doi: 10.1002/biof.1726. Epub ahead of print. PMID: 33847020. https://pubmed.ncbi.nlm.nih.gov/33847020/

Historical Insight into Infections and Disorders Associated with Neurological and Psychiatric Sequelae Similar to Long COVID

Abstract:

Long-term sequelae of coronavirus disease 2019 (COVID-19) due to infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are now recognized. However, there is still a lack of consensus regarding the terminology for this emerging chronic clinical syndrome, which includes long COVID, chronic COVID syndrome, post-COVID-19 syndrome, post-acute COVID-19, and long-hauler COVID-19. In this review, I will use the term “long COVID”. A review of the medical history and epidemiology of past pandemics and epidemics in modern literature review identifies common long-term post-infectious disorders, with the common finding of altered cognition.

In the brain, the cerebral hypoxia induced by SARS-CoV-2 infection may be caused by mitochondrial dysfunction, resulting in “brain fog”. Historically, the common symptom of altered cognition has been reported during earlier pandemics, which include the influenza pandemics of 1889 and 1892 (Russian flu), the Spanish flu pandemic (1918-1919), encephalitis lethargica, diphtheria, and myalgic encephalomyelitis (chronic fatigue syndrome or post-viral fatigue syndrome).

There are similarities between chronic fatigue syndrome and the “brain fog” described in long COVID. During past viral epidemics and pandemics, a commonality of neural targets may have increased viral survival by conformational matching. The neurological and psychiatric sequelae of SARS-CoV-2 infection, or long COVID, may have emerged from neural effects that have emerged from an invertebrate and vertebrate virosphere. This review aims to present a historical overview of infections and disorders associated with neurological and psychiatric sequelae that have shown similarities with long COVID.

Source: Stefano GB. Historical Insight into Infections and Disorders Associated with Neurological and Psychiatric Sequelae Similar to Long COVID. Med Sci Monit. 2021 Feb 26;27:e931447. doi: 10.12659/MSM.931447. PMID: 33633106; PMCID: PMC7924007. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7924007/ (Full text)

Patients with chronic fatigue syndrome do not score higher on the autism-spectrum quotient than healthy controls: Comparison with autism spectrum disorder

Abstract:

Clinically, there is an overlap of several symptoms of chronic fatigue syndrome (CFS) and autism spectrum disorder (ASD), including fatigue; brain “fog”; cognitive impairments; increased sensitivity to sound, light, and odour; increased pain and tenderness; and impaired emotional contact.

Adults with CFS (n = 59) or ASD (n = 50) and healthy controls (HC; n = 53) were assessed with the Autism-Spectrum Quotient (AQ) in a cross-sectional study. Non-parametric analysis was used to compare AQ scores among the groups. Univariate analysis of variance (ANCOVA) was used to identify if age, sex, or diagnostic group influenced the differences in scores. Patients with ASD scored significantly higher on the AQ than the CFS group and the HC group. No differences in AQ scores were found between the CFS and HC groups. AQ results were influenced by the diagnostic group but not by age or sex, according to ANCOVA. Despite clinical observations of symptom overlap between ASD and CFS, adult patients with CFS report few autistic traits in the self-report instrument, the AQ. The choice of instrument to assess autistic traits may influence the results.

Source: Bileviciute-Ljungar I, Maroti D, Bejerot S. Patients with chronic fatigue syndrome do not score higher on the autism-spectrum quotient than healthy controls: Comparison with autism spectrum disorder. Scand J Psychol. 2018 May 8. doi: 10.1111/sjop.12451. [Epub ahead of print] https://www.ncbi.nlm.nih.gov/pubmed/29738079