Contemporary positive signs of functional limb weakness in post-acute sequelae of SARS-CoV-2: an exploratory analysis…, 2025, Osada et al.

[SNT Gatchaman]

Contemporary positive signs of functional limb weakness in post-acute sequelae of SARS-CoV-2: an exploratory analysis of their utility in diagnosis and follow-up
Takashi Osada; Hiroaki Kimura; Terunori Sano; Masaki Takao


BACKGROUND
Sequelae of the acute phase of coronavirus disease-19, termed long COVID, are characterised by numerous indicators, including neurological symptoms. Functional neurological disorder (FND) can occur with or without various structural diseases. No previous study has examined the relationship between long COVID and FND, with positive signs for FND. This study confirmed positive signs of functional limb weakness (hereafter positive signs) in patients with long COVID.

METHODS
This was an observational, retrospective, single-centre study at an outpatient clinic conducted from 1 June 2021 to 31 May 2024. We collected patients’ clinical data, including positive signs. The primary outcome was the prevalence of positive signs. Patients with positive signs were followed up over 2 months, and subjective patient perceptions of symptomatic improvements and changes in positive signs were analysed.

RESULTS
Overall, 502 were diagnosed with long COVID, and 100 assessed patients had positive signs. Female sex, time of infection after 2022, comorbidity of psychiatric diseases, fatigue, headache and muscle weakness were statistically significant in patients with positive signs compared with those in patients without positive signs. 89 patients (41 with positive signs and 48 without positive signs) were followed up, and 28 (68.3%) with positive signs and 33 (68.8%) without positive signs reported improvements. Positive signs disappeared in patients with symptomatic improvements but not in patients without symptomatic improvements (p=0.0001).

CONCLUSIONS
Positive signs were found in over one-third of patients (33.9%) who were investigated in this study. Some positive signs disappeared concurrently with their symptomatic improvement.

Link | PDF | BMJ Neurology Open [Open Access]

 

[SNT Gatchaman]

I've chosen to put this FND paper in the main LC forum rather than the purely psychosomatic one. It's open access, useful in that it describes their use of positive signs. While it includes some of the inevitable problematic framing, it does report on spontaneous recovery.

And as these authors write there's always the possibility that some of long Covid is FND — at least in as much as those labels are useful, and recognising that we don't adequately understand the mechanisms behind either label.

 

[SNT Gatchaman]

FND has multiple clinical subtypes and is now a rule-in diagnosis using bedside clinical tests, which are called ‘positive signs’. Recently, reliable and easy-to-implement tests for positive signs with good sensitivity and specificity have been developed.

Previous studies have reported that female sex, younger age and personality disorders are predisposing factors for FND.

Patients at the clinic underwent neurological examinations unless their neurologist deemed it unnecessary. For example, in a case with long COVID symptoms that only encompassed hair loss, a neurological examination was sometimes not performed. Checking for positive signs was at the discretion of each neurologist. Positive signs in this study consisted of drift without pronation, give-way weakness, paradoxical wrist flexion, ‘gluteus maximus weakness and weak iliopsoas with normal gluteus maximus’ sign (weak gluteus maximus), Hoover’s sign and Sonoo abductor sign (for a detailed feature of each positive sign, see the online supplemental material).

Combinations of these signs were used because they are easily checked during routine neurological examination; moreover, their positivity or functional features can be determined easily by general neurologists. In addition, recently reported positive signs, including paradoxical wrist flexion and weak gluteus maximus, were demonstrated to have high sensitivity and specificity for diagnosing functional weakness without a precondition of symptomatic laterality.

variables that are generally considered predictors for FND, such as female sex, young age and psychiatric disease, were analysed using multivariate logistic regression analysis to determine factors associated with the presence of positive signs in patients with long COVID.

Overall, 892 patients (412 men and 480 women) visited the clinic from 1 June 2021 to 31 May 2023. Of these, 502 patients (246 men and 256 women) were diagnosed with long COVID according to the WHO criteria with confirmation of previous infection of COVID-19, and 390 patients were excluded because they did not fulfil the WHO criteria or lacked confirmation of previous infection. Of the 502 patients, 295 long COVID patients (58.8%) were assessed for positive signs, and 207 (41.2%) were excluded. These patients were excluded because, in 18 patients (3.6%), positive signs were not confirmed, and a neurological examination was not conducted. Furthermore, positive signs were not checked in the remaining 189 excluded patients (37.6%).

We excluded 207 patients (41.2%) who fulfilled the WHO criteria for long COVID in this study. First, checking for positive signs was overlooked in 189 patients because the physician did not know about the possibility of or forgot to check for comorbid FND. Second, 17 patients experienced symptoms that were not neurological.

 

[Utsikt]

And as these authors write there's always the possibility that some of long Covid is FND — at least in as much as those labels are useful, and recognising that we don't adequately understand the mechanisms behind either label.

I don’t understand how this paper adds any value, because I don’t understand how FND as a concept adds any value. They might as well study the number or unicorns in Wales..

 

[SNT Gatchaman]

Some of the patients in this study exhibited positive signs. In general, positive signs do not directly indicate that a patient has FND. However, when patients who fulfil the WHO criteria used to define a post-COVID-19 condition (ie, muscle weakness and/or muscle fatigue) show positive signs of FND, they are highly likely to fulfil the Diagnostic and Statistical Manual of Mental Disorders-5 criteria for FND. The reason for this is unclear. One possible explanation is that FND can coexist alongside long COVID, which leads to the modification or exacerbation of FND symptoms, similarly to other comorbid neurological conditions. An alternative explanation is a common pathological mechanism underlying FND and long COVID.

Several dominant features of patients with positive signs are compatible with FND, including female sex. 13 In Japan, the Omicron variant of COVID was dominant, and the number of COVID-19 cases increased dramatically after January 2022. 29 The prevalence of post-Omicron COVID-19 conditions was lower than that of the other strains before 2022. 30 Assuming that patients with positive signs had FND, the prevalence of FND coexisting with long COVID is likely to not depend on which variant of COVID patients were infected with but solely on the number of patients infected with COVID-19, as observed in this study. The reason for the significant difference in duration between the end of infection and the first visit to the clinic is unclear. One possibility is that long COVID symptoms affected by FND might be more persistent than those unrelated to FND.

BPS flags flying strongly here though:

We postulate that long COVID might trigger, or be overlaid by, FND more frequently in patients with psychiatric illnesses, including abnormal illness beliefs and a perception of symptoms being irreversible, than in those without psychiatric illnesses.

we speculate that FND contributes to some of the symptoms of long COVID, one of the most common being chronic fatigue.

Interestingly, some these supposed abnormal illness beliefs seem to be absence of symptoms —

The number of patients who claimed muscle weakness was 24, whereas the number of patients with positive signs was 100. Among the 24 patients who noticed weakness, 16 had positive signs and eight did not (OR 4.43, 95% CI 1.71 to 12.4, p=0.001).

Fatigue, headache and muscle weakness were more common in patients with positive signs than in those without positive signs. The dominance of muscle weakness in patients with positive signs is natural because positive signs are used to form a diagnosis of functional limb weakness.

Many recovered with no treatment —

89 patients were followed up with supportive care only or without any medication. Of these, 41 patients with positive signs were followed up for 13.0 months (range 7–20 months), and 48 patients without positive signs were followed up for 6.5 months (range 4–14.25 months). The difference in follow-up duration was significantly different (p=0.01; figure 1). Of the patients with positive signs who were followed up, 41 were positive for paradoxical wrist flexion, 38 (92.7%) had give-way weakness, 31 (75.6%) had a weak gluteus maximus, 11 (26.8%) had Sonoo abductor sign, 3 (7.3%) had Hoover’s sign, 3 (7.3%) had Sonoo abductor sign and 1 (2.4%) had drift without pronation. There was no significant difference in the noted improvements between patients with (n=28) and without positive signs (n=33; OR 0.98, 95% CI 0.36 to 2.66, p=1).

In this study, we verified the disappearance of positive signs in some patients during the follow-up period of 2 months and found that positive signs were associated with the perceived symptomatic improvement in patients, even though they were treated with supportive care alone.

 

[Sean]

Functional neurological disorder (FND) can occur with or without various structural diseases.

Unfalisifiable, then. Alleged positive signs not withstanding.

 

[Sean]

We postulate...
we speculate...

Yeah, we know.

 

[Jonathan Edwards]

A physician looking for positive signs is almost certainly a positive sign of a psychosomatic physician - someone who seems to be a physician but in fact it is all in their mind.

 

[Eleanor]

I'd love to do a Rosenhan-style experiment sending 100 healthy people to these neurologists with a letter saying their GP suspects they have FND, and see 1) how many of them show "positive signs", 2) how many of them don't show "positive signs" but come away with an FND diagnosis anyway.