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Trial By Error: An FND Patient’s View–and More on Those Inflated Prevalence Rates

22 June 2022 12 Comments

By David Tuller, DrPH

In a post last week, I noted that experts in FND have a tendency to assert prevalence rates that ignore their own diagnostic criteria. Before offering further thoughts on that score, I want to make one point very explicit: I am in no way questioning whether people with the diagnosis have serious disorders and very debilitating symptoms. Of course they do! And of course they deserve the best medical care available, like everyone does.

I have not suggested and do not believe that FND patients are hypochondriacs, hysterics, fakers or whiners. Perhaps that hasn’t been clear from previous posts. If anyone has interpreted my work that way or has criticized FND patients based on my posts, I really apologize for the misunderstanding. That has never been my intention. It has, of course, been my intention to raise concerns about how experts in the field have themselves generated confusion with contradictory statements about FND diagnoses and prevalence.

In talks and presentations, FND experts come across as sensitive and caring clinicians who clearly want the best for their patients. I have zero reason to doubt that. But whether doctors demonstrate compassion is a separate issue from whether it is acceptable to disseminate prevalence claims that go way beyond the established clinical criteria. Perhaps someone raised this problematic issue at the recent gathering, in Boston, of the Functional Neurological Disorder Society—but I doubt it.

It is true, as some have noted, that I haven’t included the voices of FND patients in my half dozen or so posts on this issue. While my focus is on questionable claims in the medical literature, I understand why this absence has bothered some patients. I’d like to rectify the omission by recommending an excellent, recently posted essay called “Cadenza for Fractured Consciousness: A Personal History of the World’s Most Misunderstood Illness.”

The author, a patient who goes by @FNDPortal, provides an overview of the history and development of the construct as well as a harrowing account of his own condition. Here’s an excerpt from the opening section:

“Late in 2013, I inexplicably lost my ability to walk. It happened over the course of just a few weeks; fast enough to be terrifying, slow enough to feel everything in crystalline detail…First, I could no longer manage my usual walk across town. Then I couldn’t reach the end of the parking lot. Then the other end of the house.”

Yikes! Terrifying indeed!  

If anyone believes FND patients are not struggling with something really awful, this essay will quickly alleviate them of their misconceptions. They will also learn a great deal about the FND patient perspective—or at least this particular FND patient’s perspective. He describes his search for answers, his appreciation of the FND diagnosis and related treatment approaches, and the improvements he has experienced over time. However, as enlightening as the essay is about many aspects of the issue, it does not resolve some of the questions I have raised since I first posted on FND in December, 2019.

**********  

A “rule-in” diagnosis, or not?

My post last week examined how FND experts have presented inconsistent information about prevalence rates of the condition. Based on the requirement that FND is now a “rule-in” diagnosis relying on positive clinical findings and not a diagnosis of exclusion, these cases account for close to 6% of outpatient visits to neurology clinics—per an exhaustive study into attendance at Scottish neurology clinics. Here, as I noted in my previous post, is a 2016 statement on the numbers from FND experts Alan Carson and Alexander Lehn, from UK and Australia, respectively:

“The recent changes…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.”

Yet FND experts themselves routinely declare that prevalence in outpatient neurology clinics is 16%, or even a third. These numbers represent either a tripling or heptupling (is that a word?) of the rule-in rate. 

Here’s just one example, from Richard Grunewald, formerly the clinical director of neurosciences at Central Sheffield University Hospitals NHS Trust, in a recent blog for an organization called Inneg. (Inneg describes itself as “a leading agency specialising in providing Clinical Negligence, Serious Injury and Complex Case reports.” In other words, if you’re involved in litigation related to FND, better call these folks for help.) Grunewald’s post is called “The Challenge of Distinguishing Unusual Neurological Symptoms from. Malingering.”

Here’s what he writes:

“One common problem in neurological medicolegal practice is diagnosing Functional Neurological Disorder (FND), sometimes known as somatization, conversion disorder, hysteria or medically unexplained neurological symptoms…It is common, and has been estimated that it comprises about one third of the workload of most neurologists, yet is poorly understood.”

Is Grunewald aware that FND is now a rule-in diagnosis and not simply a placeholder term for anything unexplained by current neurological understanding? He seems not to know that the established prevalence via positive identification is “approximately 6%”–as Carson and Lehn reported. Whether Grunewald is familiar with these data or not, he and other experts in the field continue to fudge the diagnostic boundaries by citing prevalence rates of 16% or a third.

In a 2021 article, the authors described confusion among neurologists about how and when to code patients as having FND and noted that a major factor was “the outdated belief that FND is a diagnosis of exclusion.” (In other words, some or many neurologists do not understand that FND is now considered a diagnosis of inclusion, based on the rule-in signs.) The authors also stated that FND “accounts for 16% of consultations”—even thought that number combines both the “approximately 6%” identified by rule-in signs, per Carson and Lehn, plus another 10% who were assessed as having “psychological symptoms,” according to the data from Scottish neurology clinics.

Yet having “psychological symptoms” is not considered a clinical rule-in sign for FND, as is required for the diagnosis. So what is the authors’ rationale for combining these two smaller groups into one larger FND category? They provide no explanation. Perhaps they don’t recognize that they are contradicting themselves. The FND literature is full of examples of this sort of internal inconsistency and epidemiological incoherence.

People, this is not rocket science! (Or perhaps that should be: “People, this is not neuroscience!”) It is basic statistics, logic, and public health. After all, investigating disease prevalence rates is a core public health function. I have never pretended to have a medical education or an advanced degree in biology–much less neuroscience. But such training is not needed in order to notice that experts are citing multiple prevalence rates for the condition.

If FND is now a rule-in condition, I would argue that anyone without rule-in signs who has been given the label has been misdiagnosed. Much clinical guidance in recent years has focused on how to execute these rule-in strategies and why positive identification through such incongruities in clinical presentation is necessary to render the diagnosis accurately. Don’t take my word for it. Here is Jon Stone, a colleague of Alan Carson’s from the University of Edinburgh, in a 2021 presentation to 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 they’re doing it wrong.”

From my interpretation of this authoritative statement, anyone claiming that the prevalence of FND is greater than the “approximately 6%” cited by Carson and Lehn is “doing it wrong.” Yet Stone and Carson themselves wrote in a 2020 paper that FND is the “second commonest reason for new neurology consultations”—a claim based on the 16% prevalence rate. In contrast, based on the “approximately 6%” prevalence, FND is much farther down the list of common neurological presentations.

This is all kind of weird. Why aren’t neurologists following their own FND criteria in their prevalence pronouncements?

******

Rebranding and reframing FND

Here’s how this confusion might have developed over time. By all or most accounts, it seems that around a third of outpatient neurology attendees present with symptoms that do not conform to known patterns of neurological disease, as currently understood. The Scottish neurology clinic study, for example, reported that 30% of outpatient consultations–not quite a third–involved cases that could not not be explained by “organic disease.” Rather than identifying some or all such unexplained symptoms and conditions by old standbys like conversion disorder, hysteria or other terms often perceived as insulting, neurologists began decades ago promoting the need to call them “functional” instead.

Ok, rebranding a disorder with a less stigmatizing term is a step forward. And many patients report that they feel more respected, believed and cared for than when the condition was called something else. (Other patients report that, in their experience, doctors have changed their language but not their dismissive attitudes toward the illness.)

Along with the new name, neurologists pushed for a revision of the diagnostic criteria. They recognized that not every patient in this cohort had identifiable psychological distress or trauma that could, in their view, account for the symptoms—a requirement under the longstanding definition of conversion disorder. That requirement was therefore removed in the description of the illness enshrined in the fifth iteration of the so-called psychiatric bible known as the Diagnostic and Statistical Manual (DSM).

The experts further posited that certain clinical tests provide affirmative evidence of the “functional” rather than “organic” nature of the symptoms—Hoover’s sign being the most prominent. (The essay from @FNDPortal provides a helpful discussion of these strategies.) So the updated description in DSM-5 also noted that evidence from such rule-in signs is necessary for rendering an accurate diagnosis.

It would be a significant improvement if patients with symptoms not consistent with standard neurological understanding but without the mandated rule-in signs were said to have idiopathic neurological disorders or neurological disorders of unknown etiology. But perhaps because the field has become so used to regarding all unexplained symptoms as “functional” rather than “organic,” experts still seem to use the FND label when writing or talking about this larger group of patients without rule-in signs.

So who cares? Don’t all these patients need medical care and treatment, whether their illness is called FND or neurological disorder of unknown etiology?

Of course they do. But clinicians conduct medical investigations so that they can render a diagnosis. Once they have rendered the diagnosis, they move on to providing care and treatment based on that assessment. The literature on “medically unexplained symptoms,” a larger category of which FND is a major subset, is replete with warnings that once the diagnosis has been established, continuing to investigate possible medical causes of somatic complaints serves to feed patients’ purportedly unjustified fears that they have underlying but undiscovered pathophysiological dysfunctions.

I don’t know exactly how this dynamic is playing out in clinical care. But it is indisputable that those referencing prevalence rates of 16% and a third, whether in the medical literature or in public presentations, are not adhering to the rule-in rule they have themselves promoted. In medicine, as in public health, consistency in communication and messaging on core issues like disease prevalence is essential. The FND field so far has fared poorly on this front.

FND is either a diagnosis of inclusion, or it isn’t. Citing prevalence rates far higher than the “approximately 6%” identified by rule-in signs risks turning FND into another wastebasket diagnosis of exclusion—a dumping ground for any symptoms as yet unexplained.

TWiV 911: Antibody can get vaccinated now

20 June 2022 1 Comment

TWiV provides an update on hepatitis of unknown etiology in children, an experimental nanoparticle vaccine for Epstein-Barr virus, and minimal impact of bamlanivimab therapy on antiviral antibodies induced by vaccination.

Hosts: Vincent Racaniello, Rich Condit, Kathy Spindler, and Brianne Barker

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Show notes at microbe.tv/twiv

TWiV 910: COVID-19 clinical update #119 with Dr. Daniel Griffin

18 June 2022 Leave a Comment

In COVID-19 clinical update #119, Dr. Griffin reviews tixagevimab for infection prevention, ivermectin for outpatient infection treatment, symptom rebound after PAXLOVID treatment, bamlanivimab minimally impacting immune response to vaccination, in-hospital mortality among infection patients, residual viral antigen in patients following infection, usage of Casirvimab/Imdevimab and Remdesivir in infected patients with depleted B-cells, and rheumatic symptoms following infection.

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Trial By Error: Does Functional Neurology Disorder Account for a Third of Outpatient Neurology Consults?

16 June 2022 16 Comments

By David Tuller, DrPH

Functional neurological disorder, or FND, is the new-ish name for the hoary Freudian construct known as conversion disorder. For decades, psychiatrists informed patients that they were “converting” their emotional distress and anxieties into physical symptoms like tremors, seizures, sensory and cognitive deficits, a halting gait, or other physical dysfunctions. The impossibility of proving such claims did not seem to impact psychiatry’s acceptance of the concept or the certainty with which it was applied to patients with unexplained conditions.

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Trial By Error: A Reprise of an Earlier Blog Post About Godwin’s Law on Nazi Analogies and Simon Wessely

6 June 2022 5 Comments

By David Tuller, DrPH

In a new book, Fiona Fox, the head of the London-based Science Media Centre, has compared critics of the GET/CBT ideological brigades and the PACE trial to Nazis, as I noted recently on Virology Blog. In response to her unfortunate reference to the Holocaust in this context, some on social media have invoked the popular meme known as “Godwin’s Law.”

Here’s the Wikipedia definition: “Godwin’s law, short for Godwin’s law (or rule) of Nazi analogies, is an Internet adage asserting that as an online discussion grows longer (regardless of topic or scope), the probability of a comparison to Nazis or Adolph Hitler approaches 1.”

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TWiV 906: Long COVID, giant viruses, and smallish pox

5 June 2022 2 Comments

TWiV reviews human monkeypox infections, evidence for human Mimivrus infections, and incidence of long COVID in post-vaccine SARS-CoV-2 infections.

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Dickson – Lake Mead water level very low
Brianne – Transplantation of a 3D printed ear made out of human cells
Rich – nderstanding Vaccine Safety and the Roles of the FDA and the CDC and The Facts About Vaccine Safety
Vincent – My new favorite backpack

Show notes at microbe.tv/twiv

Trial By Error: Science Media Centre Chief Fiona Fox Compares ME/CFS Patient Advocates to Nazis

4 June 2022 13 Comments

By David Tuller, DrPH

I have called the PACE trial of graded exercise therapy (GET) and cognitive behavior therapy (CBT) for ME/CFS “a piece of crap.” As I have indicated over the years, I think the trial is an example of serious research misconduct. (Whether it meets legal definitions of “fraud” is beyond my professional expertise, but I wouldn’t be surprised if it does.) According to Fiona Fox, director of the Science Media Centre (SMC) in London, these public expressions of my distaste for PACE make me a Nazi. Or Nazi-like. Or legitimately comparable to Nazis.

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TWiV 905: COVID-19 clinical update #117 with Dr. Daniel Griffin

4 June 2022 Leave a Comment

In COVID-19 clinical update #117, Dr. Griffin discusses duration of virus shedding, association between pre-exposure to steroids and infection outcome, post-infection subtypes, rehabilitation for post-acute infection, Tixagevimab/Cilgavimab for infection prevention, antibody prophylaxis and vaccination in kidney transplant recipients, remdesivir and bebtelovimab fact sheets for providers, the updated guidelines on treatment with Famotidine, Paxlovid rebound symptom characterizations, antigen test positivity duration, viral dynamics of variants and isolation, association of inflammation in CS fluid, and transmission dynamics in Ghana. 

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Herd Immunity and this Pandemic

2 June 2022 6 Comments

by Gertrud U. Rey

Photo courtesy of Andrea Lightfoot photography

Herd immunity occurs when a large enough percentage of the population has acquired either natural or vaccine-induced immunity against an infectious disease, thereby indirectly protecting a minority of non-immune individuals who are dispersed throughout the population. During this pandemic, many prominent scientists have stated that it is impossible to achieve herd immunity in the context of COVID-19, leading some to conclude that a mass SARS-CoV-2 vaccination campaign would be pointless. However, this thinking is flawed, and I want to explain why.

Traditionally, herd immunity is thought to create a barrier for the transmission of infectious agents, resulting not only in prevention of disease, but also prevention of infection. This understanding was based on previous observations that vaccination against poliovirus, measles virus, and other pathogens led to drastic reductions in the incidence of disease burden. It is reasonable to assume that if there is no disease, there is probably also no virus; and hence no viral infection or transmission of virus. However, past vaccination campaigns were not followed up with regular testing programs, so we actually have no way of knowing whether vaccination prevented infection and transmission! Considering that the vast majority of poliovirus infections are asymptomatic, it is possible that some polio virus infections and transmission occurred even after vaccination, despite the fact that those infections did not lead to disease.

The widespread testing measures adopted during the present pandemic have revealed the approximate frequency of asymptomatic SARS-CoV-2 infections, giving us a clearer understanding of the difference and dynamics between disease and infection. The type of immunity that prevents both disease and infection is called sterilizing immunity, and it is mostly thought to be induced by neutralizing antibodies, which inactivate infectious agents before they have a chance to infect a cell, thereby directly neutralizing the biological effect of the agent. However, any immune activity that prevents replication of a pathogen directly or indirectly necessarily induces sterilizing immunity, including the activity of non-neutralizing antibodies, whose binding can trigger other immune functions that can also prevent infection and replication.

Do SARS-CoV-2 vaccines induce sterilizing immunity? The answer to this question is complicated. There are many studies showing that most people have high levels of antibodies in the months following vaccination, and this large proportion of circulating antibodies could likely sequester an incoming virus before it has a chance to enter cells, infect them, and replicate. In this sense, the SARS-CoV-2 vaccines do induce sterilizing immunity, but only within a certain time period after vaccination. As antibody levels contract over time (a normal process), they leave behind a baseline population of memory B cells that can quickly expand and mass-produce new antibodies upon a subsequent encounter with SARS-CoV-2. Likewise, memory T cells can quickly react to incoming virus and virus-triggered signals, and destroy infected cells. Therefore, it is likely that when circulating SARS-CoV-2-specific antibody levels decline months and years after vaccination, the collective activity of memory immune cells will protect one from disease, but probably not infection, meaning that the SARS-CoV-2 vaccines no longer induce sterilizing immunity at that time. In other words, vaccinated people could briefly replicate and transmit low levels of virus, at least until memory immune responses kick in, which then prevent illness and additional viral replication and spread.

The emergence of new variants that are not as well recognized by existing vaccine-induced antibodies may also allow for some increased viral transmission, thus slowing down the establishment of immunity in the population. However, immune responses are not binary, and even a low level immune response that doesn’t protect against infection and spread but prevents serious disease can play a critical role in slowing down the pandemic. Vaccination has historically been very effective at suppressing community outbreaks, despite the fact that most vaccines do not induce sterilizing immunity.

Vaccination or natural immunity do not have to prevent all infections, and immunity does not have to last a lifetime for a pandemic to end. Pediatrician and vaccinologist Paul Offit defines herd immunity as the point where the serious disease burden is reduced sufficiently so as to no longer overwhelm the healthcare system. It’s becoming pretty clear that the pandemic is slowing down in the US, especially in the context of severe disease, hospitalization, and death; and that this is likely due to increased SARS-CoV-2 immunity among US residents. It is therefore likely that reduced illness and a shortened period of transmission from immune individuals will also reduce the overall rate of community infection and transmission. And in the end, it doesn’t matter whether we call it herd immunity, community immunity or some other name; the pandemic will end because a majority of the population is no longer susceptible to severe COVID-19.

[Please check out my video Catch This Episode 29 for an explanation of sterilizing immunity.]

Trial By Error: Deja Vu All Over Again with Proposed Lightning Process Study in Norway

31 May 2022 4 Comments

By David Tuller, DrPH

It’s déjà vu all over again in Norway with the Lightning Process (LP). Earlier this month, a national research ethics authority, NEM, postponed a decision on a proposed LP trial until at least June. The trial has already been approved by a regional committee. The NEM had been expected to decide at its May meeting but did not.

This is the second go-round for this saga. Last year, a previous and also inadequate trial proposal was approved at the regional level but rejected by NEM—and after a similar delay from the expected decision date till a subsequent meeting. At that point, NEM determined that the proposed trial was fraught with conflicts of interest and potential bias. However, this year’s designated committee has new members who might assess the project differently, despite its ongoing deficiencies.

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