Recognising and explaining functional neurological disorder

Dear Editor,
I was pleased to see this helpful practice pointer on Functional Neurological Disorders (FNDs) (1). Especially useful to emphasise the importance of neuroscience, not requiring a history of trauma and allowing for expecting co-existing disease.
I would argue however that they have gone too far in suggesting that FNDs should be positively diagnosed as definitive disorders and not far enough in helping patients and clinicians understand the varied and likely complex multicomponent origins of symptoms. At the heart of our dis-ease as doctors at ‘functional’ presentations is our as yet primitive understanding of how they come to be. The little we do know in terms of patho-physiology does not allow us to pin point what is happening for the individual. While the specific symptom suggests an imbalance of functioning of the relevant part of the brain-body, it does not help us understand what combination of insults, or genetic predispositions are relevant for the patient in front of us.
However, we do know that Adverse Childhood Events, viral infections (most recently COVID-19), and prescribed and other substances acting on the brain (or being suddenly withdrawn) can contribute to the symptoms found in FND and other ‘functional’ conditions. And that there are a number of potential pathological pathways from viral or emotional insult, (e.g. HPA axis dysfunction, cytokines, glial cell changes) which together can be seen as Psycho-immuno-neuro-endocrine dysfunction(2,3,4). Furthermore there are good arguments and increasing evidence (eg re depression and inflammation) for a unified approach not just to all ‘functional’ ‘disorders’ but also to many psychiatric ‘disorders’. While confident doctors and diagnostic labels are appreciated by some patients, many of my patients appear to prefer to understand their Emotionally Unstable Personality Disorder as an imbalanced amygdala resultant from years of trauma. Technically disorder does mean a disordered physiology (as opposed to disease), but I would argue we too often present disorders as substantive fixed entities.
So, I would go further than the authors in bringing in neuroscience to help patients understand their conditions as complex but real, and propose we work across primary care, out-patient specialties and psychiatry and psychology to agree on some scientifically accurate ways to describe (bio-psycho-social) aetiology, underlying brain-body dysfunction and rationale for the array of management strategies we are in early stages of developing for what is a very wide range of overlapping and changing syndromes.

1. Stone J, Burton C, Carson A. Recognising and explaining functional neurological disorder. BMJ. 2020;371:m3745. doi: 10.1136/bmj.m3745.
2. Anda RF, Felitti VJ, Bremner JD, et al. The enduring effects of abuse and related adverse experiences in childhood. A convergence of evidence from neurobiology and epidemiology. Eur Arch Psychiatry Clin Neurosci. 2006;256(3):174-186. doi:10.1007/s00406-005-0624-4
3. Rasa, S., Nora-Krukle, Z., Henning, N. et al. Chronic viral infections in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). J Transl Med 16, 268 (2018). https://doi.org/10.1186/s12967-018-1644-y
4. Danese, A., J Lewis, S. Psychoneuroimmunology of Early-Life Stress: The Hidden Wounds of Childhood Trauma?. Neuropsychopharmacol 42, 99–114 (2017). https://doi.org/10.1038/npp.2016.198

Dear Editor,

Stone et al. describe a common and important clinical syndrome, with a large impact on the patients and everyone around them. They have often had unsatisfactory experiences of healthcare and changing this is important for all involved.

The old fashioned named GP who regularly checks in with the person affected has incredible value, ensuring different consultants and hospitals talk and write to each other, that the management plans are enacted and links to local OT and physiotherapy and in particular between physical and mental health services are made. Ideally an empowered patient or secondary care do this automatically but too often it does not occur.

In my work as a general neurologist and doing a tertiary FND clinic I find that monitoring for newly emergent disorders is extremely important for quality of life, and the feeling that any new and persistent symptom is taken seriously. General practice has an extremely important role to play in this.

A common scenario is weight gain with medication and immobility and other causes and its complications. I frequently diagnose OSAS in this context. Another common scenario is evolving musculoskeletal problems as a result of altered movement, and frozen shoulder, carpal tunnel, trochanteric bursitis and many other tendonitis and bursitis are common.

A previous response raises the issue of akathisia. As discussed by Stone et al. co-morbid neurological and psychiatric conditions are common and it is important not to diagnose FND just based on distractibility, but in, for example, tremor (a regular oscillation) this is extremely helpful. An experienced movement disorder neurologist should be able to differentiate however if patient has one or the other or both.

Another response raises the important issue of side-effects of medication. I agree this can be sometimes be the trigger of FND (small literature on levatiracetam inducing functional seizures, and functional seizures can improve with stopping this and other antiepileptics) but more commonly possible side effects co-exist with FND. Certainty is however hard and nocebo and placebo rates are high in many neurological and psychiatric conditions. Medication use however can be an important perpetuating factor. It requires a slow approach and thorough conversation with patients but I have seen dramatic improvements in patients with FND when stopping e.g. valproate (sleepiness/weight gain/cognitive), topiramate (word fluency/cognitive/mood), pizotifen (mood, weight gain and sedation) and often a very slow reduction of pregabalin, opiates and gabapentinoids are helpful (or no change occurs, but benefit of medication reduction regardless) since people have often tried a fast withdrawal and conclude they can't come of the medication. Being positive to patients about the potential to feel better with medication reduction is important in this context and general practice has an extremely important role to play. Changing and stopping TCA/SSRIs and other psychiatric medications are often possible, but sometimes might need more discussion with neurologists, pain management and psychiatrists.

All these examples illustrate that in this often complex biopsychosocial condition close relationships between general practice and secondary care are of vital importance and I thank Stone et al. for their open-minded and comprehensive review of this.

Dear Editor,

The purpose of this response is to shed light on the significant harm that can be caused by a functional neurological disorder (FND) misdiagnosis, especially in the case of akathisia, and to challenge the authors' claim that it is rarely misdiagnosed.

In Psychogenic Explanations of Physical Illness: Time to Examine the Evidence (2016) [1], Wilshire and Ward state what should be obvious, “Medical practitioners simply cannot assume that the current knowledge of disease and its markers is 100% perfect or that all complaints not otherwise accounted for must have a psychological origin.” Stone, et al. cite a "systematic review" from 2005 [2], also co-authored by Stone, which concluded that only 4% of patients diagnosed with FND are misdiagnosed. This was based upon the fact that the patients included in the study had not later been diagnosed with an established organic neurological disorder. Although the authors seemingly use this statistic to purport the accuracy of the FND clinical assessment, it simply proves there was still no medical explanation for the patients' symptoms years later, not that one did not exist.

As founder of the Akathisia Alliance for Education and Research, I represent thousands of people who are being misdiagnosed with FND by clinicians who have little to no knowledge of medication-induced akathisia. This is causing catastrophic harm in many cases. Already suffering from the suicidality inherent in akathisia, the FND misdiagnosis can result in loss of family support, abandonment, mistreatment, homelessness, involuntary hospitalizations, and forced drugging with medications that exacerbate the symptoms and increase the likelihood of suicide.

Patients with akathisia are being misdiagnosed by neurology as psychogenic/functional primarily because their motor symptoms can be distractible and suppressible, yet these are positive, documented features of this medication-induced disorder (Factor, Jankovic, 2020) [3]. It is well documented that certain neurotransmitters and neuropeptides affect physiological as well as psychological processes (Shu-Heng, Li-Peng, Xu, et al., 2020; Bamalan, Al-Khalili, 2020) [4,5]. Thus, it stands to reason that side effects and withdrawal symptoms of commonly prescribed medications such as antiemetics, antipsychotics, antidepressants, benzodiazepines, etc., could be multi-systemic and organic, and undetectable upon clinical assessment.

On behalf of the many people being harmed by the FND diagnosis, I hope the authors and their colleagues will begin spending more time looking for an explanation for "medically unexplained symptoms" and less time training clinicians based on the assumption that every possible neurological disorder has already been discovered. Many lives could be saved.

References

1. Wilshire CE, Ward T. Psychogenic explanations of physical illness: time to examine the evidence. Perspect Psychol Sci. 2016 11(5) 606-631

2. Stone J, Smyth R, Carson A, et al. Systematic review of misdiagnosis of conversion symptoms and “hysteria". BMJ 2005 331(7523):989

3. Factor S, Jankovic J. Akathisia. 2020. https://medlink.com/article/akathisia

4. Shu-Heng J, Li-Peng H, Xu W, et al. Neurotransmitters: emerging targets in cancer. Oncogene 2020 39(3):503-515

5. Bamalan OA, Al-Khalili Y. Physiology, serotonin. StatPearls Publishing, 2020