Trial By Error: A Letter Regarding Inflated Prevalence Rates for Functional Neurological Disorder

By David Tuller, DrPH

I have posted previously about how papers on functional neurological disorder (FND) have routinely mis-cited a seminal 2010 study in asserting that the diagnosis is the second-most-common presentation at neurology clinics, with a rate of 16%. In fact, the 2010 study found that only 5.5% had FND, the new name for the antiquated Freudian construct of conversion disorder. Many others apparently had symptoms that the neurologists could not explain, but that doesn’t automatically translate to a diagnosis of FND, which requires positive rule-in signs from clinical examinations.

Nonetheless, this claim—that Stone et al found FND to be the second-most-common diagnosis at neurology clinics—has gained credibility through repetition in the medical literature. But repetition doesn’t make it true.

This morning, I sent a letter to the editor of the journal NeuroImage: Clinical, asking for a correction in a 2021 paper claiming that FND is the “2nd most common” presentation at neurology clinics. Several colleagues co-signed the letter.

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Dear Professor Zalesky–

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, a 2021 article from Perez et al in NeuroImage: Clinical, “Neuroimaging in functional neurological disorder: state of the field and research agenda,” highlights the rule-in requirement and then asserts that FND “is the 2nd most common outpatient neurologic diagnosis” (1). The reference for this assertion is 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. According to the study, 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 (3); 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%).

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 endorsed the much lower rate for the specific clinical entity known as FND. In 2016, Professor Alan Carson, the second author of Stone et al, wrote the following with a co-author in the abstract of an account of the epidemiology of FND, published as a chapter of the Handbook of Clinical Neurology (4):

“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%. (It is not clear why the figure was 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” (5). 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%.) The 2018 paper noted that a larger group of patients in Stone et al had “symptoms that were described as only somewhat or not at all explained by disease.”

While these other unexplained symptoms or ailments might be called “functional” disorders in the current lexicon, they cannot reasonably be said to be equivalent to a diagnosis of FND, given the DSM-5 requirement for rule-in clinical signs. Otherwise, the 2016 and 2018 papers would have included these functional disorders as part of the FND total from Stone et al and reported that the rate was 16%, not “approximately 6%” or 5.4%.

The data have not changed since these 2016 and 2018 papers were published. Why is Stone et al now being framed, in Perez et al as well as other publications, as evidence that FND, as defined in DSM-5, 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 data in Stone et al. According to 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 Stone et al 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 Stone et al’s recruitment of patients 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 Stone et al’s reported FND rate beyond what the data showed.  

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 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 previously made statements about the study’s rate of “typical FND” that do not support the greater claims disseminated in more recent publications, such as Perez et al. Unless the changes in the DSM-5 and the requirement for positive rule-in clinical signs are meaningless, the statement that Stone et al found FND to be the second-most-common diagnosis is categorically untrue. The citation in Perez et al—or rather, mis-citation–should be corrected.

Thank you for your attention to this matter. (The paper’s corresponding and senior authors have been cc’d on this letter, as have the co-signatories of the letter and one of the journal’s associate editors.)

Sincerely,

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

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1. 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.

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. 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.

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

5. 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.