Anaesthesia and the development of functional neurological disorder: A systematic review and case series, 2022, Huepe-Artigasa et al

[Andy]

Abstract

Objective
There are reports of functional neurological disorder (FND) developing after anaesthesia, though separating any aetiological role from other possible factors is challenging. We aimed to systematically review all published cases of post-anaesthetic FND to see if any common factors supported an anaesthetic role. We also aimed to identify all cases of post-anaesthetic FND arising in our FND clinic, to obtain an estimate of its frequency.

Methods
For the review, a systematic search for published cases of FND developing within 48 h of anaesthesia was conducted in June 2022. For the case series, the medical records of all patients attending an FND clinic in Melbourne between 2017 and 2019 were examined, and all cases with FND within 48 h of anaesthesia extracted.

Results
36 published cases were identified for the review. Sixteen described preceding stressors and 16 psychiatric diagnoses, including 8 with previous FND. Thirty-two (92%) had undergone general anaesthesia, most commonly for obstetric procedures. Motor/sensory loss was the most common presentation, followed by seizures and coma. Most (80.5%) developed symptoms immediately on induction or cessation of anaesthesia. For the case series, 8 of 107 clinic patients (7.5%), developed FND within 48 h of anaesthesia. All had previous psychiatric diagnoses, including 3 with previous FND. Three underwent general anaesthesia and 3 procedural sedation, with seizures the most common presentation. All developed symptoms immediately on induction or cessation of anaesthesia.

Conclusion
These cases provide some support for an aetiological role for anaesthesia: there is evidence for an anaesthetic ‘model’ for the symptoms of FND that arise, they largely arise with the onset or termination of anaesthesia, and they arise most frequently during general anaesthesia or sedation.

Paywall, https://www.sciencedirect.com/science/article/abs/pii/S0163834322000949

 

[Sid]

Motor/sensory loss was the most common presentation, followed by seizures and coma.

Sounds like incompetent anaesthesiologists trying to chalk up serious adverse events to FND.

 

[Sid]

This paper is pretty obscene to be honest. First you suffer medical malpractice, then you get told it’s all in your mind.

 

[Hutan]

This paper is pretty obscene to be honest. First you suffer medical malpractice, then you get told it’s all in your mind.

The FND labelling is obscene. It looks as though a prior psychiatric diagnosis in a patient provides surgeons/anaesthetists with a 'get out of jail free' card when it comes to post-surgery issues.

It's possible that this is actually progress - someone suggesting that some of these FND symptoms might be being caused by anaesthesia. It's a shame it is paywalled.

a Melbourne School of Psychological Sciences, University of Melbourne, VIC 3010, Australia
b Alfred Health, Department of Psychiatry, VIC 3084, Australia
c Department of Anaesthesia, Austin Health, Heidelberg, VIC 3084, Australia
d The University of Melbourne, Department of Surgery, Austin Health, Heidelberg, VIC 3084, Australia
e The University of Melbourne, Department of Psychiatry, Austin Health, Heidelberg, VIC 3084, Australia
f The Florey Institute of Neuroscience and Mental Health, Heidelberg, VIC 3084, Australia

 

[Cheshire]

It's possible that this is actually progress - someone suggesting that some of these FND symptoms might be being caused by anaesthesia. It's a shame it is paywalled.

there is evidence for an anaesthetic ‘model’ for the symptoms of FND

I am not sure the quote marks indicate that the symptoms may be caused by anaesthesia per se, but that the ‘model’ may be one with causing, precipitating and perpetuating factors directly linked with false illness beliefs of some kind about anaesthesia.

 

[Hutan]

I am not sure the quote marks indicate that the symptoms may be caused by anaesthesia per se, but that the ‘model’ may be one with causing, precipitating and perpetuating factors directly linked with false illness beliefs of some kind about anaesthesia.

It could be, the abstract is unhelpfully vague. Does anyone have access to the paper?

 

[Art Vandelay]

a Melbourne School of Psychological Sciences, University of Melbourne, VIC 3010, Australia
b Alfred Health, Department of Psychiatry, VIC 3084, Australia
c Department of Anaesthesia, Austin Health, Heidelberg, VIC 3084, Australia
d The University of Melbourne, Department of Surgery, Austin Health, Heidelberg, VIC 3084, Australia
e The University of Melbourne, Department of Psychiatry, Austin Health, Heidelberg, VIC 3084, Australia
f The Florey Institute of Neuroscience and Mental Health, Heidelberg, VIC 3084, Australia

e f Richard A.A. Kanaan

He's an old colleague of Wessely and a promoter of the "secondary benefits" model. I'm not in the least bit surprised to see his name on this garbage.

 

[Hutan]

I've added tags to some of the threads relevant to Kanaan.

 

[Sid]

It's possible that this is actually progress - someone suggesting that some of these FND symptoms might be being caused by anaesthesia. It's a shame it is paywalled.

The paper claims that symptoms caused by surgery are psychiatric.

 

[Hutan]

'Psychiatric' as in 'psychogenic' as opposed to 'affecting brain function'?

 

[Sid]

Abreaction – the release of functional symptoms during sedation – is one possible mechanism by which sedation might have its effects. Abreaction was one of the mainstays of treatment of FND for decades, typically with barbiturates, or more recently with benzodiazepines [41]. Critically, however, it was considered to potentially be a possible cause of symptoms, as well as a potential cure. While the mechanism of abreaction is far from clear, it is likely that suggestion is a key part of many successful cases [41]: one possible mechanism in sedation might therefore be an induced state of heightened suggestibility fulfilling whatever expectations or fears were induced by the process of consent.

Dissociation – the separation of aspects of awareness - has long been considered by some to be the primary mechanism of FND [42], though it is perhaps best considered a group of related concepts [43]. Dissociation also occurs in anaesthesia. Though some anaesthetics, notably ketamine and nitrous oxide, achieve their effects through inducing a state of ‘dissociative anaesthesia’, this state may also occur with the kind of procedural sedation employed in several of our cases, and may be a state that all patients pass through as they recover from a general anaesthetic, albeit briefly. Many anaesthetised patients may thus have a state of dissociation induced, a state which may either serve as another ‘model’ for their FND, or perhaps directly produce it.

Another aspect of anaesthesia is of course the vulnerability it induces, and several cases described this as evoking previous traumatic experiences. For example in, Nelson et al. a patient described a sense of helplessness under anaesthesia, experienced as similar to when she was previously abducted [22]. One of our clinic cases described emerging from anaesthesia and feeling intensely scared: though they had previously had FND symptoms, they promptly had their first non-epileptic seizure. Indeed, all of the genito-urinary procedures presented with non-epileptic seizures, sometimes considered to be a response to reminders of past trauma [37,44]. Panic is often considered part of the mechanism of non-epileptic seizures [45]. Perhaps emergence from GA leads to feelings of panic and hyperventilation, precipitating FND in those predisposed.

 

[Hutan]

Oh dear.

Risk of epilepsy in surgical patients undergoing general or neuraxial anaesthesia
Chang et al 2017

I found this study: it used the Taiwanese health insurance research database, looking at the chances of patients developing epilepsy in the year following operations with general anaesthetic or neuraxial anaesthetic (e.g. epidural). I think it has been done well - patients were matched on age and sex, it's a huge sample, patients with epilepsy risk-factors such as those who experienced traumatic brain injury during that year were excluded.

The one-year incidence of postoperative epilepsy for patients with general anaesthesia and neuraxial anaesthesia were 0.41 and 0.32 per 1000 persons, respectively, and the corresponding RR was 1.27 (95%CI 1.15–1.41).

So, the chance of developing epilepsy was much higher after a general anaesthetic than after neuraxial anaesthetic, and it was the case both for men and for women. There were 38 people with multiple sclerosis in the 230,000+ sample of patients who underwent a general anaesthetic; remarkably, 2 of them developed new-onset epilepsy in the year following surgery.

There's some discussion as to why the risk might be higher in people who had a general anaesthetic. They do not mention the evoking of previous traumatic experiences or heightened suggestibility.
e.g.

First, many general anaesthetic drugs have been reported to induce epileptiform seizure activity 29. Synaptic transmission and interaction of excitatory and inhibitory neurons in the neocortex are involved with these proconvulsant effects. Neuro-inflammation is another plausible mechanism 30. Evidence obtained from animal models suggests that exposure to inhalation general anaesthetics may increase levels of proinflammatory cytokines that may cause neuroinflammation 31, 32. The stress response to surgery also triggers the inflammatory cascade, releasing neuro-endocrine mediators and cytokines in a pattern that peaks postoperatively 33. General anaesthesia does not block sympathetic responses completely and will result in higher levels of stress hormones that also may contribute to epileptogenesis 34. There seems to be an interaction with epilepsy risk between general anaesthesia and various neurological disorders or symptoms, such as Parkinson's disease, migraine, sleep apnoea and multiple sclerosis.

Inhaled general anaesthetics and intravenous (i.v.) opioids may interfere with immune cell number and response 35, thereby increasing the risk of both postoperative central nervous system infections and progression of epilepsy. In the absence of regional analgesia, total peri-operative opioid consumption may be increased when propofol-based total i.v. anaesthesia (TIVA) is used for surgery compared with inhalational anaesthesia.

Neuraxial anaesthesia may preserve postoperative immune function by avoiding inhalational anaesthetics and parenteral opioids 36, reducing the risk of postoperative epilepsy. Reductions in the incidence of postoperative infections have been reported in patients treated with regional compared with general anaesthesia 37-39. In our data, a higher incidence of postoperative epilepsy was observed among general anaesthesia recipients compared with those receiving neuraxial anaesthesia when HIV infection co-existed or peri-operative infection developed, such as pneumonia, deep wound infection, septicaemia or urinary tract infection.

Thromboembolic events in the postoperative period can result in cerebral infarction, which may cause epilepsy. Neuraxial anaesthesia has been thought to attenuate the hypercoagulable state and decrease the incidence of thromboembolic complications by blunting the sympathetic response and improving regional blood flow peri-operatively 40-42. This may explain why, in this study, the risk of developing epilepsy was higher in patients underwent general anaesthesia complicated by pulmonary embolism.

A final possible explanation is that general anaesthesia is often used in patients who have contraindications to neuraxial anaesthesia, such as the use of anticoagulants or coagulopathy.

So, lots of reasons why the risk of developing new onset epilepsy might be increased after having a general anaesthetic, with those possibilities creating opportunities for research, learning and a subsequent improving of health outcomes. I am aware that epilepsy is different to what is diagnosed as FND, including the "non-epileptic seizures", but perhaps the same mechanisms are operating. At the very least, there are possibilities that are worth looking at and excluding before labelling patients with FND. That FND labelling and associated speculation is harmful, as it damages the patients' credibility without any off-setting benefit of allowing access to effective treatment.

 

[Hutan]

Thanks to a member for access to the paper.

Functional neurological disorder (FND), also known as conversion disorder, is a syndrome of neurological symptoms unexplained by neuropathology

Cases of adults or children of any age were included where neuro- logical symptoms were defined by the study authors as medically un- explained, functional, psychogenic, conversion, hysterical or dissociative, with onset within 48 h of anaesthesia.

A search was conducted using MEDLINE, PubMed and OVID® on 20 June 2022. Serial searches included the terms ‘anaesthesia’ or ‘anes- thesia’ and ‘functional neurolog*’ or ‘conversion disorder’ or ‘pseudo- seizures’ or ‘psychogenic non-epileptic seizures’ or ‘hysteric*’ or ‘hysteria’.

The authors do not make clear how long the FND symptoms lasted, which surely is of substantial interest. A number of the published case studies they reference involve short-lived symptoms that occurred upon induction of anaesthesia or upon return to consciousness after the operation. Surely the suggestion that these are FND's need to be treated with a high level of skepticism. There are plenty of accounts of seizures during anaesthesia in the veterinary literature, where, unlike here, dosage and other information is typically reported in great detail and the case studies contribute to guidance on safer administration of anaesthesia.

There's a passing reference to the poor quality of the published case reports and to the medical records but they have not let that get in the way.

Conflicts of interest

RAK is a former director of the FND Society, has received grants for research into FND and provided expert testimony on FND in court. The other authors declare no conflicts of interest. There was no funding for this project.

Daniela Huepe-Artigas: Data curation, Formal analysis, Writing – original draft. Parramajaypal Singh: Conceptualization, Data curation, Formal analysis, Writing – original draft. Laurence Weinberg: Super- vision, Writing – review & editing. Richard A.A. Kanaan: Conceptu- alization, Formal analysis, Methodology, Project administration, Supervision, Writing – review & editing.

That's a lot of people reviewing and editing to produce a report that is so muddled and vague. But, probably the paper achieves what its authors wanted it to do; its purpose may well be related to Kanaan's work providing expert testimony on FND in court.