Tag: letter

Correspondence: Inaccurate reference leads to tripling of reported FND prevalence

Highlights:

  • Perez et al asserted that FND is the “2nd most common” diagnosis in outpatient neurology.
  • Stone et al (2010), cited by Perez et al, does not support the “2nd most common” claim.
  • In Stone et al, a broad “functional/psychological” category was the second most common
  • •

    FND is not synonymous with the “functional/psychological” category in Stone et al.

To the editor:

An article in NeuroImage: Clinical, “Neuroimaging in functional neurological disorder: state of the field and research agenda” (Perez et al., 2021), cited a prominent paper (Stone et al., 2010) as evidence for the assertion that functional neurological disorder (FND) is the “2nd most common outpatient neurologic diagnosis.” Although studies have yielded varying FND prevalence rates, the claim that it is the second-most common diagnosis at outpatient neurology clinics represents an erroneous interpretation of the findings of the referenced 2010 paper.

FND is the current name for what was formerly called conversion disorder, the diagnosis previously given to patients believed to have psychogenic motor and gait dysfunctions, sensory deficits, and non-epileptic seizures. According to the 2013 edition of the Diagnostic and Statistical Manual of Mental Disorders and as noted in Perez et al, FND is not a diagnosis of exclusion but requires the presence of specific “rule-in” clinical signs believed to be incompatible with known neurological disease. Some of these clinical signs have long been used by neurologists and other clinicians to help them identify cases of conversion disorder.

Stone et al.,’s (2010) paper was one of several arising from the Scottish Neurological Symptoms Study (SNSS). The study reviewed records from multiple outpatient neurology clinics and reported that 209 of 3781 attendees, or less than 6 %, received diagnoses compatible with conversion disorder–in other words, what would now be called FND. In terms of ranking, this group of patients—labeled in the SNSS as having “functional” symptoms or diagnoses–was far down the list. The study found higher rates of many other conditions, including headache (19 %), epilepsy (14 %), peripheral nerve disorders (11 %), miscellaneous neurological disorders (10 %), multiple sclerosis/demyelination (7 %), spinal disorders (6 %) and Parkinson’s disease/movement disorders (6 %).

Earlier this year, a paper in the European Journal of Neurology (Mason et al., 2023) cited a different SNSS paper (Stone et al., 2009) to support the assertion that FND prevalence at outpatient neurology clinics was 5.4 %—far lower than the percentage needed to be the “2nd most common” diagnosis. Moreover, the authors of another paper (Foley et al., 2022) have recently issued a correction for the same misstatement of FND prevalence from the SNSS findings as the one identified in Perez et al.

The assertion that the SNSS found FND to be the “2nd most common” diagnosis at outpatient neurology clinics is based on a parallel and commonly repeated claim that the study found the prevalence in these settings to be 16 % (e.g. Ludwig et al., 2018). That rate is almost three times the 5.4 % prevalence recently highlighted in Mason et al. The extra patients included in this greatly expanded FND category were another 10 % collectively identified in the SNSS as having “psychological” symptoms or diagnoses. These “psychological” patients fell into a range of clinical sub-categories, among them hyperventilation, anxiety and depression, atypical facial/temporomandibular joint pain, post-head injury symptoms, fibromyalgia, repetitive strain injury, and alcohol excess. The SNSS paper cited in Perez et al reported that a combined grouping of the patients with “functional and psychological” symptoms or diagnoses had a prevalence of 16 % but did not provide any evidence that the 10 % included under the “psychological” label met, or could have met, the explicit FND requirement for rule-in clinical signs.

FND is not synonymous with the broader “functional and psychological” category in the SNSS and should not be presented as if it were. The post-hoc reinterpretation of previously reported data in a way that conflates FND with other complex conditions—almost tripling its apparent prevalence in the process–is an example of the phenomenon known as diagnostic creep. In any event, the SNSS results are a matter of record. Whatever future studies might determine about FND rates, the published findings cited by Perez et al and addressed in this letter do not support either the claim that it is the “2nd most common” diagnosis in outpatient neurology clinics or the related claim that its prevalence at these venues is 16 %.

Sincerely–

David Tuller (corresponding author)

Center for Global Public Health

School of Public Health

University of California, Berkeley

Berkeley, CA, USA

David Davies-Payne

Department of Radiology

Starship Children’s Hospital

Auckland, New Zealand

Jonathan Edwards

Department of Medicine

University College London

London, England, UK

Keith Geraghty

Centre for Primary Care and Health Services Research

Faculty of Biology, Medicine and Health

University of Manchester

Manchester, England, UK

Calliope Hollingue

Center for Autism and Related Disorders/Kennedy Krieger Institute

Department of Mental Health/Johns Hopkins Bloomberg School of Public Health

Johns Hopkins University

Baltimore, MD, USA

Mady Hornig

Department of Epidemiology

Columbia University Mailman School of Public Health

New York, NY, USA

Brian Hughes

School of Psychology

University of Galway

Galway, Ireland

Asad Khan

North West Lung Centre

Manchester University Hospitals

Manchester, England, UK

David Putrino

Department of Rehabilitation Medicine

Icahn School of Medicine at Mt Sinai

New York, NY, USA

John Swartzberg

Division of Infectious Diseases and Vaccinology

School of Public Health

University of California, Berkeley

Berkeley, CA, USA

Source: Correspondence: Inaccurate reference leads to tripling of reported FND prevalence. Neuroimage Clin. 2024 Feb 7;41:103537. doi: 10.1016/j.nicl.2023.103537. Epub ahead of print. PMID: 38330816. https://www.sciencedirect.com/science/article/pii/S2213158223002280 (Full text)

Re: What happens inside a long covid clinic?

Dear Editor

As a patient with severe long covid and myalgic encephalomyelitis (M.E.), I was pleased to see the article ‘What happens in a long covid clinic?’ [1] raising awareness of the scale and impact of long covid and the importance of long covid clinics. According to a recent estimate by Altmann et al, 1 in 10 people who contract COVID-19 will be affected by long covid, whilst the oncoming impact of long covid on health systems, populations and economies will be “so large as to be unfathomable”.[2]

Around 2-14% of patients with long covid develop orthostatic tachycardia six to eight months after COVID infection and as many as 60% show some symptoms of POTS. [3] Yet there remain no agreed guidelines for POTS in long covid, making the early diagnosis and management of the condition in primary care challenging. NICE guidance on long covid only mentions POTS in passing with no information on management.[4] The approach outlined by Espinosa-Gonzalez and colleagues to diagnose and manage POTS in primary care could greatly improve function and health for people with POTS.[5]

While I commend the excellent NHS services highlighted in the feature [1], as a patient with severe long covid I would question how prevalent this integrated medically-led care model is across the country despite it being in the ‘The NHS plan for improving long covid services’.[6] Many patients I speak to in long covid support groups report long waits, only to then be offered basic wellbeing classes or rehabilitation without any active treatment for symptoms.

Access to clinics for the most severely affected is variable with not all services offering remote consultations or home visits. It is imperative that long covid clinics are medically led, inter-disciplinary and able to prescribe medications. Additionally, we need the same standard of care for patients with ME/CFS, who are still waiting for NICE guidance from 2021[7] to be implemented. A recent survey noted there remain significant gaps in provision for patients with ME/CFS.[8]

Previously young fit and healthy patients with severe long covid and ME are being left bed-bound without adequate diagnosis, support, care or treatment as there is no specialty or service that is set up to provide this. I went from climbing mountains and working on-call to unable to stand or feed myself in the space of 8 weeks with long covid – I am still severely affected a year later. Given the multi-system complexity of long covid and ME/CFS it is time for an interdisciplinary patient-centred service for post-viral illnesses that recognises the biological nature of the disease and the unique challenges patients with severe long covid and ME have with safely accessing services given their limited energy available, severe cognitive effects, physical immobility and range of complications across bodily systems.

The Department of Health and Social Care are currently seeking views on the interim delivery plan for ME/CFS care in an online consultation [9], which is relevant to both patient groups and professionals and could lay the groundwork for more comprehensive care of post-viral illnesses in the UK.

Yours sincerely,

Dr Alexis Gilbert BSc MBBS MPH FFPH

Source: MJ 2023;382:p1791 https://www.bmj.com/content/382/bmj.p1791/rr (Full text)

Mast cell activation may contribute to adverse health transitions in COVID-19 patients with frailty

Abstract:

A prominent aspect of the post-coronavirus disease-2019 (post-COVID-19) era is long-COVID. Therefore, precise patient classification and exploration of the corresponding factors affecting long-COVID are crucial for tailored treatment strategies. Frailty is a common age-related clinical syndrome characterized by deteriorated physiological functions of multiple organ systems, which increases susceptibility to stressors.

Herein, we performed an inclusion and exclusion analysis (definite COVID-19 infection diagnosis, clear underlying disease information, ≥60 years old, and repeated sampling of clinical cases) of 10,613 blood samples and identified frailty cases for further investigation. RNA-Seq data were used for differential gene expression and functional and pathway analyses.

The results revealed that patients with frailty were more prone to poor health conversions and more sequelae, and the blood transcriptome had obvious disturbances in pathways associated with immune regulation, metabolism, and stress response. These adverse health transitions were significantly associated with mast cell activation. Additionally, NCAPG, MCM10, and CDC25C were identified as hub genes in the peripheral blood differential gene cluster, which could be used as diagnostic markers of poor health conversion.

Our results indicate that healthcare measures should be prioritized to mitigate adverse health outcomes in this vulnerable patient group, COVID-19 patients with frailty, in post-COVID era.

Source: Xiangqi Li, Chaobao Zhang & Zhijun Bao (2023) Mast cell activation may contribute to adverse health transitions in COVID-19 patients with frailty, Emerging Microbes & Infections, 12:2, DOI: 10.1080/22221751.2023.2251589 https://www.tandfonline.com/doi/pdf/10.1080/22221751.2023.2251589 (Full text)

Long COVID, linking etiopathogenic theories

Abstract:

In this letter we discuss the various theories involved in the pathogenesis of Long COVID and how they are closely interrelated, conditioning the full range of symptoms and signs presented by patients affected by this condition, as well as calling for the recognition of the disease by the health authorities that must begin to streamline their health processes to limit the burden of this disease, which tends to be chronic and degenerative.

Source: Luis del Carpio-Orantes, Andrés Aguilar-Silva. Long COVID, linking etiopathogenic theories. Qeios, CC-BY 4.0. https://www.qeios.com/read/A7TYBN (Full text)

Prevalence of Post–COVID-19 Conditions Depends on the Method of Assessment

To the Editor—In their systematic review and meta-analysis on the global prevalence of long coronavirus disease 2019 (COVID-19), Chen et al report that a significant share of patients with COVID-19 suffer from sequelae of acute severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection [1]. The authors performed a database search in PubMed, Embase, and iSearch and included 50 studies comprising hospitalized and nonhospitalized patients from the Americas, Europe, and Asia, of which 41 studies were meta-analyzed. The estimated pooled prevalence of a post–COVID-19 condition was 0.43 (95% confidence interval, .39–.46) [1].

Concerning a post–COVID-19 condition, or long COVID, and their global burden of disease, we think it is important to bear in mind that many studies (including our own [2], which was in the meta-analysis) assess long COVID symptoms via self-report/questionnaires. Self-reported outcomes do not necessarily match clinical reports that are based on physical and/or technical examinations. Thus, there is a difference between functional impairment based on objective medical findings and self-estimation, giving rise to potential detection bias, as the authors briefly mention in the supplement. Moreover, possible bias through elevated media attention, resulting in potentially altered response behavior, must be considered.

Making causal links between nonspecific symptoms, such as dizziness, headache, or fatigue, to SARS-CoV-2 or acute COVID-19 remains challenging [3]. Furthermore, precise pathophysiological mechanisms underlying specific long COVID symptoms have not been fully elucidated [4, 5]. Fatigue, for example, is associated with several chronic conditions and its prevalence in the population is estimated to be in the same range as found in SARS-CoV-2 cases in the present meta-analysis [6]. With regard to the World Health Organization definition, a post–COVID-19 condition may represent a diagnosis per exclusion in many cases [7]. Nonetheless, even if the prevalence of long COVID was overestimated in the underlying studies, COVID-19 sequelae pose a considerable burden on health, social insurance systems, and economies worldwide given the high attack rate of SARS-CoV-2 [8].

Source: Lampl BMJ, Leitzmann MF, Salzberger B. Prevalence of Post-COVID-19 Conditions Depends on the Method of Assessment. J Infect Dis. 2023 Jan 11;227(2):306. doi: 10.1093/infdis/jiac467. PMID: 36546758. https://academic.oup.com/jid/article/227/2/306/6853665 (Full text)

Long-haul COVID: heed the lessons from other infection-triggered illnesses

According to the Johns Hopkins Coronavirus Resource Center, more than 115 million people worldwide have been infected with SARS-CoV-2 during the COVID-19 pandemic, with extensive implications for morbidity and mortality. Description of long-term effects of COVID-19 are apparing in the medical literature; the first large cohort study with 6-months’ follow-up has been published, and more data are sure to follow. A small number of studies point not only to persistent imaging and testing abnormalities across several organ systems in the postacute period, but to a high frequency of patient-reported symptoms such as fatigue, insomnia, anxiety and depression, autonomic disturbances, cognitive difficulties, pain, and others. The presence of patient support groups, and the rapid expansion of clinics to manage or treat these symptoms, validate further their existence and impact.
Although the frequency, severity, and potentially the etiology of persistent symptoms can vary, sequelae after COVID-19 appears poised to join the range of other postinfectious syndromes described in the field of infectious diseases.

These often share a common symptom phenotype, which might also meet case definitions for myalgic encephalomyelitis/chronic fatigue syndrome, fibromyalgia, or post-treatment Lyme disease. We hope that researchers and clinicians will draw on these other conditions as they continue to advance scientific understanding of so-called long-haul or persistent COVID-19. We would also argue that there are important lessons to learn and pitfalls to avoid; our specific area of clinical care and research (post-treatment Lyme disease) has remained a fiercely contentious condition for more than 30 years.

Read the rest of this article HERE.
Source: John N Aucott, Alison W Rebman. Long-haul COVID: heed the lessons from other infection-triggered illnesses. The Lancet, CORRESPONDENCE| VOLUME 397, ISSUE 10278, P967-968, MARCH 13, 2021 https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(21)00446-3/fulltext (Full text) 

Bias in Exercise Trials for ME/CFS: the Importance of Objective Outcomes and Long-term Follow-up

Sharpe and colleagues recommend that patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) be offered cognitive behavior therapy (CBT) and graded exercise therapy (GET)1, advice that contrasts with recent NICE guidance on ME/CFS.2 The authors argue that “there are many randomized trials indicating the safety and efficacy of these treatments.”1

All of these trials, however, were nonblinded and relied on subjective symptom questionnaires as their main outcomes, a combination that creates a high risk of response bias. Treatment manuals used in these trials included explicit encouragements to raise patients’ expectations of GET and CBT. One patient booklet, for example, informed patients: “You will experience a snowballing effect as increasing fitness leads to increasing confidence in your ability. You will have conquered CFS by your own effort and you will be back in control of your body again.”3 These encouragements were not provided to participants in the control group and might have influenced how patients rated their health. In contrast to what Sharpe and colleagues claim, measuring the expectations of patients before the trial begins, does not address how therapists might have influenced symptom reporting during the trial.

There are further arguments that suggest these trials might have measured response bias rather than improvements in health. There were, for example, no clinically significant differences on objective outcome measures that are less prone to response bias such as employment figures, activity levels, or fitness tests.3 In addition, at long-term follow-up, the control group seemed to perform just as well as participants who received GET or CBT. This could not be explained by additional treatment received after the trial ended.4 These findings are difficult to interpret if patients did indeed rehabilitate successfully following GET or CBT. It is unfortunate that the authors, who were primary researchers in many of these trials, do not address these concerns.

Lastly, Sharpe and colleagues argue that “harm reported from patient community surveys reflects poorly implemented therapy.”1 Patient surveys, however, indicate that ME/CFS patients report harm of GET even if prescribed by a specialist or physiotherapist.5 The authors have previously been challenged for misrepresenting the findings of these surveys.5 Post-exertional malaise or a marked worsening of symptoms when patients exceed their energy limit, is a characteristic feature of ME/CFS.2 There are therefore reasonable safety concerns about treatments such as GET and CBT that try to push patients to exceed their limits.

Read the full article HERE.

Source: Tack, M. Bias in Exercise Trials for ME/CFS: the Importance of Objective Outcomes and Long-term Follow-up. J GEN INTERN MED 37, 3193 (2022). https://doi.org/10.1007/s11606-022-07704-0  (Full text)

Microvascular Injury in the Brains of Patients with Covid-19

To the Editor:

We conducted postmortem high-resolution magnetic resonance imaging (magnetic resonance microscopy) of the brains of patients with coronavirus disease 2019 (Covid-19) (median age, 50 years) and histopathological examination that focused on microvascular changes in the olfactory bulb and brain stem. (See the Materials and Methods section in the Supplementary Appendix, available with the full text of this letter at NEJM.org.) Images were obtained from the brains of 13 patients with the use of an 11.7-Tesla scanner at a resolution of 25 μm for the olfactory bulb and at a resolution of 100 μm for the brain. Abnormalities were seen in the brains of 10 patients.

We examined the brains of patients that showed abnormalities by means of multiplex fluorescence imaging (in 5 patients) and by means of chromogenic immunostaining (in 10 patients). We performed conventional histopathological examination of the brains of 18 patients. Fourteen patients had chronic illnesses, including diabetes and hypertension, and 11 had been found dead or had died suddenly and unexpectedly. Of the 16 patients with available medical histories, 1 had delirium, 5 had mild respiratory symptoms, 4 had acute respiratory distress syndrome, 2 had pulmonary embolism, and the symptoms were not known in 3.

Read the rest of this letter HERE.

Source: Lee MH, Perl DP, Nair G, Li W, Maric D, Murray H, Dodd SJ, Koretsky AP, Watts JA, Cheung V, Masliah E, Horkayne-Szakaly I, Jones R, Stram MN, Moncur J, Hefti M, Folkerth RD, Nath A. Microvascular Injury in the Brains of Patients with Covid-19. N Engl J Med. 2021 Feb 4;384(5):481-483. doi: 10.1056/NEJMc2033369. Epub 2020 Dec 30. PMID: 33378608; PMCID: PMC7787217. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7787217/ (Full text)

Post-acute COVID-19 syndrome presented as a cerebral and systemic vasculitis: a case report

To the Editor,

Post-acute Coronavirus Disease of 2019 (COVID-19) syndrome is defined as the appearance of symptoms or an organ dysfunction, which occurs at least 4 weeks after the first COVID-19 manifestations and cannot be explained by any alternative diagnosis []. Neurological complications are also well recognized, and include acute cerebrovascular events, encephalopathy, meningoencephalitis, Guillain–Barre syndrome, demyelination, dementia, parkinsonism, and others []. On the other hand, cerebral vasculitis is one of the causes which can lead to brain damage related to COVID-19 infection []. We present a 69-year-old male with systemic vasculitis and central nervous system (CNS) involvement as a manifestation of post-acute COVID-19 syndrome.

Read the rest of this article HERE.

Source: Ivanovic, Jovana et al. “Post-acute COVID-19 syndrome presented as a cerebral and systemic vasculitis: a case report.” Acta neurologica Belgica, 1–3. 13 Mar. 2022, doi:10.1007/s13760-022-01923-2 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8918071/ (Full text)

Immunological dysfunction persists for 8 months following initial mild-to-moderate SARS-CoV-2 infection

Abstract:

A proportion of patients surviving acute coronavirus disease 2019 (COVID-19) infection develop post-acute COVID syndrome (long COVID (LC)) lasting longer than 12 weeks. Here, we studied individuals with LC compared to age- and gender-matched recovered individuals without LC, unexposed donors and individuals infected with other coronaviruses. Patients with LC had highly activated innate immune cells, lacked naive T and B cells and showed elevated expression of type I IFN (IFN-β) and type III IFN (IFN-λ1) that remained persistently high at 8 months after infection.

Using a log-linear classification model, we defined an optimal set of analytes that had the strongest association with LC among the 28 analytes measured. Combinations of the inflammatory mediators IFN-β, PTX3, IFN-γ, IFN-λ2/3 and IL-6 associated with LC with 78.5–81.6% accuracy. This work defines immunological parameters associated with LC and suggests future opportunities for prevention and treatment.

Source: Phetsouphanh, C., Darley, D.R., Wilson, D.B. et al. Immunological dysfunction persists for 8 months following initial mild-to-moderate SARS-CoV-2 infection. Nat Immunol (2022). https://doi.org/10.1038/s41590-021-01113-x  (Full article)