Trial By Error: Update on Efforts to Correct False Statements about FND Prevalence

By David Tuller, DrPH

I have continued writing my letter-writing effort to alert journals about papers on functional neurological disorder (FND) that have included false statements regarding the prevalence of the condition reported by a seminal study in the field the reported prevalence of the condition. (I was going to refer to this as a “letter-writing campaign” until I remembered that in British English the word “campaigner” is somewhat of a slur designating a pesky, unreasonable and perhaps belligerent promoter of a questionable cause. In the US, that word is more of a neutral term applied mainly to people engaged in political races.)

The study in question, Stone et al, published in 2010, was one of several papers arising from the authoritative research project known as the Scottish Neurological Symptoms Study (SNSS). It found that 209 out of 3781 patients (5.5%) at outpatient neurology clinics were diagnosed with what was then called conversion disorder—the former name for FND. Through some weird alchemy, this very clear finding has been tripled to yield the assertion that the exact same study found an FND prevalence of 16%, which would make it the second-most-common presentation at outpatient neurology clinics.

A valued colleague has pulled together a list of at least four dozen papers, many in high-impact journals, that have categorically declared that FND is the #2 diagnosis at outpatient neurology clinics and/or that 16% of patients were given such a diagnosis. The persistence of this self-evident error is unacceptable and extremely troubling. Apparently the FND field is suffering from a severe case of group-think; not only are top investigators replicating these claims in paper after paper, but neither peer-reviewers nor journal editors have noticed. Or perhaps they have noticed and don’t care because they sincerely believe the prevalence is higher than 5.5%.

I mean, who wouldn’t want their specialty to be the second-most-common problem rather than the eighth-most common at 5.5%, as Stone et al actually found? I assume some of those repeating this misinformation are ignorant of the statistical sleight-of-hand at play here and haven’t bothered to scrutinize the original source. But others undoubtedly know of the discrepancy and have actively perpetuated it; I guess they believe it’s no big deal. In any event, I assume more are aware of it now that our group has started sending letters seeking corrections.

Since the error is indisputable, it is somewhat perplexing that none of the leaders in the FND field have publicly acknowledged the issue. I have seen no sign that any of them have themselves begun to initiate the process of correcting their papers. Of course, everyone can make mistakes. I would suggest that not taking affirmative steps to fix them once they have been highlighted by others suggests that the investigators involved have a malfunctioning or missing integrity chip. Perhaps they need to contact the factory or Amazon.com to see if a replacement for implantation can be shipped immediately.

The editorial team at the first journal to whom we sent our letter, NeuroImage: Clinical, was quick to respond with news that a correction was forthcoming. We aren’t thrilled with the phrasing of the correction, which allows the authors to fudge and obscure the issue and suggest that the statistic might be correct anyway even if not supported by the 2010 study. (I haven’t posted the correction since it is not ours to publish.) Still, a correction is a correction is a correction—which I’m sure Gertrude Stein would have written had she focused her attention on the academic literature rather than roses.

The lead author of the NeuroImage: Clinical study was Dr David Perez, a neuropsychiatrist at Massachusetts General Hospital and Harvard Medical School. After we received news about the forthcoming correction, I alerted him that our group intended next to contact journals that published FND papers for which he was the lead or senior author. I didn’t hear back from him, and I assume that he did not initiate any further corrections—although of course I could be wrong. In any event, I haven’t yet received a response from the three other journals in that category.

Why did I start with Dr Perez? Not long ago, I posted an interview with Dr David Putrino, a neuroscientist and physical therapist at Mt Sinai, in which he offered his views about the relationship, if any, between long Covid and FND. In response, Dr Perez tweeted at him, informing him that there were clinical rule-in signs that could identify FND and distinguish it from other neurological conditions. He added links to several studies.

Next, Dr Perez tweeted out his thread to a who’s who of FND experts and proponents. I interpreted this as an effort to alert them that danger was afoot, given that their hegemony over this domain was being challenged by a highly reputable source. Since Dr Perez is based in Boston, it struck me that perhaps he was having his Paul Revere moment (“Putrino is coming! Putrino is coming!”). I took the opportunity to tweet back to the FND group, noting not only the misstatements related to prevalence rates but also some questionable claims regarding the high specificity of the rule-in signs.

So all things considered, it seemed like Dr Perez’ oeuvre was a good place to start. Since receiving word from NeuroImage: Clinical of the forthcoming correction, I’ve written to three more journals regarding his papers. Now it’s time to move on to studies from other authors. This might seem like a tedious prospect. But it’s really just a cut-and-paste job, with minor adjustments for each letter. It’s actually kind of fun!

In fact, I mis-numbered the list of references in these three letters. Oops! Embarrassing! Because of this mistake, I re-sent them with the list of references rendered accurately and included the following explanation:

“In the previous version of this letter, the references were inadvertently mis-numbered. That has been corrected in this version–the rest of the letter remains the same. As authors, we felt it necessary to correct this citation mistake as soon as we noticed it. We apologize for the error.”

In the end, no harm done. I acknowledged and apologized for the mistake, and fixed it.

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Is FND a feminist issue?

Today, I sent a letter to yet another publication, the Journal of Neurology, Neurosurgery, and Psychiatry, about a paper called “Functional neurological disorder is a feminist issue,” which stated that Stone et al found FND to be the second-most-common diagnosis. Since this was a recent paper, I almost sent this letter first. Then I thought better of it, given the feminist angle. I figured it would have been easy for the authors to dismiss my concerns as somehow representing an anti-feminist agenda, even though this would have been an unfair interpretation.

Having already sent out five other letters, I assume at this point that no one will try to make that assertion. I sent it to Dr Karen Furie, a neurologist in Rhode Island. I have posted this letter below—even though it’s not much different from the previous iterations. And the list of references is correct this time!!

Dear Dr Furie:

For years, leading neurologists have noted that functional neurological disorder (FND), the new term for what was formerly called conversion disorder, is not a diagnosis of exclusion but a rule-in diagnosis requiring positive signs found during clinical examination. This approach was enshrined in the fifth iteration of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5), which was published in 2013. Nonetheless, FND experts appear to be overlooking this definition when making claims about rates of the diagnosis at neurology clinics.

For example, an article published earlier this year in the Journal of Neurology, Neurosurgery, and Psychiatry from McLoughlin et al, “Functional neurological disorder is a feminist issue,” included the following sentence: “FND is the second most common reason for patients to attend neurology clinics, estimated to have an incidence of 4–5 per 100 000 and therefore to be present in the population at a similar frequency to multiple sclerosis and Parkinson’s disease.” (1). The reference for the assertion that FND is the “second most common reason for patients to attend neurology clinics” was a seminal and widely cited paper from Stone et al called “Who is referred to neurology clinics?—the diagnoses made in 3781 new patients,” which was published in 2010 in Clinical Neurology and Neurosurgery” (2). 

Yet Stone et al, one of several papers arising from a research project called the Scottish Neurological Symptoms Study (SNSS), does not support the claim. The journal NeuroImage: Clinical has recently agreed to issue a corrigendum regarding the exact same assertion and reference in a paper called “Neuroimaging in functional neurological disorder: state of the field and research agenda” (3). 

According to Stone et al, the second-most-common category of presentations at neurology clinics, after headache, was a grouping called “functional and psychological symptoms,” at 16%. An examination of this heterogeneous grab-bag of conditions indicates that it does not easily equate to what is called FND, per the DSM-5 criteria.

In the SNSS, 209 of the 3781 patients, or 5.5%, were diagnosed with “functional” symptoms such as sensory or motor disorders or non-epileptic seizures. These were identified in a related 2009 paper as cases of “conversion” symptoms (4); they would now be indisputably classified as FND. At the 5.5% rate, FND would be way down on the list of diagnoses mentioned in Stone et al, after 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%).

Moreover, the problematic sentence in the paper under discussion further argues that FND has a similar prevalence in the population to multiple sclerosis and Parkinson’s disease. Stone et al reported that these diagnoses were identified, respectively, in 7% and 6% of outpatients at neurology clinics; at those rates, multiple sclerosis was the fifth-most-common diagnosis, and Parkinson’s was tied for sixth. If the population prevalence of FND is comparable, as the article noted, then it is hard to understand why this clinical entity would be so much higher on the list of diagnoses at outpatient neurology clinics. The authors provide no explanation for this discrepancy.

The other 10% of the 16% in Stone et al’s second-most-common grouping, who were defined collectively as having “psychological” symptoms, fell into a hodge-podge of sub-groups, including hyperventilation, anxiety and depression, atypical facial/temporomandibular joint pain, post-head injury symptoms, fibromyalgia, repetitive strain injury, and alcohol excess, among others. Also lumped in with this “psychological” cohort were cases identified as “non-organic” and “no diagnosis.” Stone et al presented no evidence that any of these patients met or could have met the rule-in criteria for a more strictly defined FND diagnosis. Arguments that members of this 10% also had FND are grounded in speculation and assumption, not fact.

In subsequent articles, two of the co-authors of Stone et al have repeatedly endorsed the much lower rate for the specific clinical entity known as FND. In the 2016 publication cited by McLoughlin et al for the population prevalence rates of multiple sclerosis, Parkinson’s and FND, Professor Alan Carson, the second author of Stone et al, contradicted the claim that FND had a prevalence at neurology clinics of 16%–the basis for the assertion that it was the second-most-common diagnosis. Here is what wrote Professor Carson and a co-author wrote in the abstract of the paper, which was published as a chapter of the Handbook of Clinical Neurology (5):

“The recent changes in DSM-5 to a definition based on positive identification of physical symptoms which are incongruent and inconsistent with neurologic disease and the lack of need for any psychopathology represent a significant step forward in clarifying the disorder. On this basis, FND account for approximately 6% of neurology outpatient contacts.” The text of the chapter mentioned the SNSS data and gave the exact rate for “typical FND cases” as 5.4%. (Since this “typical FND” group included 209 out of the 3781 study participants, it is unclear why the figure given was 5.4% and not 5.5%.)

In 2018, several FND experts, including Professor Carson and Professor Jon Stone, the lead author of Stone et al, published a paper in JAMA Neurology called “Current concepts in diagnosis and treatment of functional neurological disorders” (6). Referencing the SNSS, the paper included the following statement: “In a well-designed consecutive series of 3781 outpatients of neurology clinics, 5.4% had a primary diagnosis of FND.” (Again, it is not clear why this figure was not 5.5%.)

More recently, Professor Carson and Professor Stone were co-authors of a paper called “Functional neurological disorder is common in patients attending chronic pain clinics,” published on May 23rd in the European Journal of Neurology (7). Citing the SNSS findings, this article reported that “the prevalence of typical FND in patients attending neurology outpatient clinics is 5.4%.” (Again, we believe the proper figure is 5.5%.)

Incidentally, Dr McWhirter was a co-author of the European Journal of Neurology paper, and the senior and corresponding author was Dr Ingrid Hoeritzauer, the second author of “Functional neurological disorder is a feminist issue.” That means both are on record as supporting two conflicting claims—that FND has a 5.4% prevalence at outpatient neurology clinics and that it is the second-most-common presentation at outpatient neurology clinics.

Finally, Professor Stone is one of two co-authors of the section about conversion disorder on the medical education site UpToDate. (It is unclear why UpToDate is still using this outdated term for the diagnosis.) The section indicates that it was last updated in June of 2022. 

In the epidemiology sub-section, the article states that “the point prevalence of conversion symptoms in clinical settings ranges from 2 to 6 percent.” The section cites three studies, including Stone et al. Here’s what it notes about the latter: “A prospective study of 3781 neurology outpatients found that conversion disorder was present in 6 percent.” This statement is obviously inconsistent with any claim that the same study found FND to be the second-most-common presentation, with a 16% prevalence.

While unexplained symptoms or ailments found among SNSS participants who did not have a conversion disorder diagnosis might be called “functional” in the current lexicon, they cannot reasonably be said to be equivalent to FND. Functional disorders are diagnoses of exclusion; FND is definitively not, given the DSM-5 requirement for rule-in clinical signs. The data from Stone et al have not changed since 2010. So why has this research since been framed, in et al and other publications, as evidence that FND is the second-most-common presentation at neurology clinics?

The popular site neurosymptoms.org, maintained by Professor Stone, sheds some light on how a claim of “second commonest reason to see a neurologist,” at a rate of 16%, could be derived from the SNSS data. According to the “frequently asked questions” section of the site:

“In [an] older study of 3781 new appointments across Scotland, there were 209 patients who had clear FND and another 200 who had additional functional disorder diagnoses including dizziness and cognitive symptoms which could also be included now within FND. Other patients presented with diagnoses like migraine, but the neurologists thought the main issue was an associated functional disorder. So, anything from 6-16% of patients could be said to have a functional disorder depending on how that was defined. The upper limit of that estimate would make it the second commonest reason to see a neurologist.”

First, this passage confirms the relevant point. Only 209 patients out of 3781, or 5.5%, had “clear FND”–way below the level that would be required for this diagnosis to be the second-most common. Second, the 16% figure represents merely the “upper limit” of a broad possible range of estimated rates—and not rates for “clear FND” but for the fuzzier and more expansive construct of “functional disorder depending on how that was defined.”

It is not appropriate to retroactively re-interpret the data from the SNSS and effectively triple the reported rate of “clear FND” from 5.5% to 16%–thus vaulting this diagnosis into second place on the list. FND experts presumably believe the higher number is a better reflection of current diagnostic rates. Neurosymptoms.org notes, for example, that recruitment of patients for the SNSS occurred two decades ago and that “recognition of FND has improved” since then. But this argument, even if valid, does not justify the decision to inflate the study’s reported FND rate beyond what the data indicated.  

 
Professor Stone made a salient observation during a 2021 podcast produced by the Encephalitis Society: “Some people think that FND is a condition you diagnose when someone has neurological symptoms but you can’t find a brain disease to go along with it. And that’s absolutely not the case. Some people [i.e. clinicians] do that, but if they’re doing it like that then they’re doing it wrong.”

If clinicians who regard FND as a diagnosis of exclusion and ignore the need for rule-in signs are “doing it wrong,” per Professor Stone, then surely those who cite Stone et al or other SNSS papers to assert that FND is the second-most-common reason to see a neurologist, with a 16% rate, are also “doing it wrong.” It is confusing, not to mention epidemiologically incoherent, when FND experts report divergent rates in different papers while citing the exact same set of data.

This is especially so when the lead and second authors of Stone et al have on multiple occasions endorsed statements about the rate of “typical FND” in the SNSS that do not support the greater claims disseminated in dozens of publications, such as McLoughlin et al. It is particularly perplexing that these same investigators have also been co-authors of studies endorsing the inaccurate but higher prevalence claims, and that Dr McWhirter and Dr Hoeritzauer have similarly professed agreement with both assertions. 

It is self-evident, but perhaps bears repeating given the persistent confusion, that the prevalence of FND at outpatient neurology clinics cannot simultaneously be the eighth-most-common presentation at 5.4% (or 5.5%) and the second-most-common at 16%. Unless the changes in the DSM-5 and the requirement for positive rule-in clinical signs are meaningless, the statement that Stone et al or the SNSS found FND to be the second-most-common diagnosis is categorically untrue. The citation in McLoughlin et al—or rather, the mis-citation–needs to be corrected.

Thank you for your attention to this matter. (I have cc’d the paper’s second author and corresponding author as well as the co-signatories of this letter.)

Sincerely,

Todd Davenport
Department of Physical Therapy
University of the Pacific
Stockton, 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
Dept 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.

David Tuller (corresponding author)
Center for Global Public Health
School of Public Health
University of California, Berkeley
Berkeley, CA, USA
davetuller@berkeley.edu

***** 

1. McLoughlin C, Hoeritzauer I, Cabreira V, et al. Functional neurological disorder is a feminist issue. J Neurol Neurosurg Psychiatry 2023;0:1–8. Epub ahead of print. DOI: doi:10.1136/jnnp-2022-330192

2. Stone J, Carson A, Duncan R, et al. Who is referred to neurology clinics?—The diagnoses made in 3781 new patients. Clinical Neurology and Neurosurgery 2010; 112: 747–751.

3. Perez D, Nicholson T, Asadi-Pooya A, et al. Neuroimaging in functional neurological disorder: state of the field and research agenda. NeuroImage: Clinical 2021; 30: 102623.

4. Stone J, Carson A, Duncan R, et al. Symptoms ‘unexplained by organic disease’ in 1144 new neurology out-patients: how often does the diagnosis change at follow-up? Brain 2009; 132: 2878-88.

5. Carson A, Lehn A. Epidemiology. Handbook of Clinical Neurology 2016; 139: 47–60.

6. Espay A, Aybek S, Carson A, et al. Current concepts in diagnosis and treatment of functional neurological disorder. JAMA Neurology 2018; 75(9): 1132–1141.

7. Mason I, Renee J, Marples I, et al. Functional neurological disorder is common in patients attending chronic pain clinics. Eur J Neurol 2023;00: 1-6. DOI: 10.1136/jnnp-2022-330192

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