Functional Neurological Disorder in people with Long-Covid: A Systematic Review

Abstract:

Background: Acute health events, including infections, can trigger the onset of functional neurological disorder (FND). We hypothesised that a proportion of people with long-COVID might be experiencing functional symptoms.

Methods: We performed a systematic review of studies containing original data on long-COVID. We reviewed the frequency and characteristics of neurological symptoms, looking for positive evidence suggesting an underlying functional disorder, and the hypothesised causes of long-COVID.

Results: We included 102 studies in our narrative synthesis. The most consistently reported neurological symptoms were cognitive difficulties, headaches, pain, dizziness, fatigue, sleep-related symptoms, and ageusia/anosmia. Overall, we found no evidence that any authors had systematically looked for positive features of FND. An exception were three studies describing temporal inconsistency. In general, the neurological symptoms were insufficiently characterised in order to support or refute a diagnosis of FND. Moreover, only 13 studies specifically focussed on long-COVID after mild infection, where the impact of confounders from the general effects of severe illness would be mitigated. Only one study hypothesised that some people with long-COVID might have a functional disorder, and another 8 studies a chronic fatigue syndrome-like response.

Discussion: Neurological symptoms are prevalent in long-COVID, but poorly characterised. We are struck by the similarities between some manifestations of long-COVID and functional disorders triggered by acute illnesses. Unfortunately, the current literature is plagued by confounders, including the mixing of patients with initial mild infection with those with severe acute medical complications. The hypothesis that long-COVID might in part correspond to a functional disorder remains untested.

Source: Teodoro T, Chen J, Gelauff J, Edwards MJ. Functional Neurological Disorder in people with Long-Covid: A Systematic Review. Eur J Neurol. 2023 Jan 31. doi: 10.1111/ene.15721. Epub ahead of print. PMID: 36719069. https://onlinelibrary.wiley.com/doi/10.1111/ene.15721 (Full text available as PDF file)

Functional neurological disorder: new subtypes and shared mechanisms

Abstract:

Functional neurological disorder is common in neurological practice. A new approach to the positive diagnosis of this disorder focuses on recognisable patterns of genuinely experienced symptoms and signs that show variability within the same task and between different tasks over time.

Psychological stressors are common risk factors for functional neurological disorder, but are often absent.

Four entities—functional seizures, functional movement disorders, persistent perceptual postural dizziness, and functional cognitive disorder—show similarities in aetiology and pathophysiology and are variants of a disorder at the interface between neurology and psychiatry.

All four entities have distinctive features and can be diagnosed with the support of clinical neurophysiological studies and other biomarkers. The pathophysiology of functional neurological disorder includes overactivity of the limbic system, the development of an internal symptom model as part of a predictive coding framework, and dysfunction of brain networks that gives movement the sense of voluntariness.

Evidence supports tailored multidisciplinary treatment that can involve physical and psychological therapy approaches.

Source: Prof Mark Hallett, Selma Aybek, Prof Barbara A Dworetzky, Laura McWhirter, Prof Jeffrey P Staab, Prof Jon Stone.  Functional neurological disorder: new subtypes and shared mechanisms. The Lancet- Neurology 21 (6): 537-550 https://www.thelancet.com/journals/laneur/article/PIIS1474-4422(21)00422-1/fulltext 

Functional neurological disorder and other unexplained syndromes

Abstract:

Functional neurological disorder is a syndrome of medically unexplained neurological symptoms. In The Lancet Neurology, Mark Hallett and colleagues review some of the potential explanations for functional neurological disorder and the evidence that supports these explanations.

The paper by Hallett and colleagues, however, is more than a Review: it is also a territorial claim, seeking to expand the boundaries of what should be considered functional neurological disorder. The details of this claim are unlikely to be controversial to any clinician working in the field: the presentations Hallett and colleagues describe are not new, even if they do not fall within the current classifications of the disorder. But the claim is nonetheless remarkable, as even a decade ago it would have been thought to be sheer folly. A good argument could then have been made that functional neurological disorder (or conversion disorder, as it was more formally known) was the most stigmatised of all disorders, even compared with other unexplained syndromes. What would have been the point of expanding the scope of a diagnosis that patients went to such lengths to avoid?

The expansive mood in the Review by Hallett and colleagues therefore reflects a striking transformation in the status of functional neurological disorder. Functional neurological disorder has become a diagnosis that a neurologist might be comfortable to give, and that a patient might be glad to receive.

Source: Kanaan, RA . Functional neurological disorder and other unexplained syndromes. The Lancet- Neurology 21 (6):499-500. https://www.thelancet.com/journals/laneur/article/PIIS1474-4422(22)00095-3/fulltext

A distinctive profile of family genetic risk scores in a Swedish national sample of cases of fibromyalgia, irritable bowel syndrome, and chronic fatigue syndrome compared to rheumatoid arthritis and major depression

Abstract:

Background: Functional somatic disorders (FSD) feature medical symptoms of unclear etiology. Attempts to clarify their origin have been hampered by a lack of rigorous research designs. We sought to clarify the etiology of the FSD by examining the genetic risk patterns for FSD and other related disorders.

Methods: This study was performed in 5 829 186 individuals from Swedish national registers. We quantified familial genetic risk for FSD, internalizing disorders, and somatic disorders in cases of chronic fatigue syndrome (CFS), fibromyalgia (FM), and irritable bowel syndrome (IBS), using a novel method based on aggregate risk in first to fifth degree relatives, adjusting for cohabitation. We compared these profiles with those of a prototypic internalizing psychiatric – major depression (MD) – and a somatic/autoimmune disorder: rheumatoid arthritis (RA).

Results: Patients with FM carry substantial genetic risks not only for FM, but also for pain syndromes and internalizing, autoimmune and sleep disorders. The genetic risk profiles for IBS and CFS are also widely distributed although with lower average risks. By contrast, genetic risk profiles of MD and RA are much more restricted to related conditions.

Conclusion: Patients with FM have a relatively unique family genetic risk score profile with elevated genetic risk across a range of disorders that differs markedly from the profiles of a classic autoimmune disorder (RA) and internalizing disorder (MD). A similar less marked pattern of genetic risks was seen for IBS and CFS. FSD arise from a distinctive pattern of genetic liability for a diversity of psychiatric, autoimmune, pain, sleep, and functional somatic disorders.

Source: Kendler KS, Rosmalen JGM, Ohlsson H, Sundquist J, Sundquist K. A distinctive profile of family genetic risk scores in a Swedish national sample of cases of fibromyalgia, irritable bowel syndrome, and chronic fatigue syndrome compared to rheumatoid arthritis and major depression. Psychol Med. 2022 Mar 31:1-8. doi: 10.1017/S0033291722000526. Epub ahead of print. PMID: 35354508.