Introduction: Functional motor disorder (FMD) is a common cause of disabling neurological symptoms such as weakness and tremor. Physio4FMD is a pragmatic, multicentre single blind randomised controlled trial to evaluate effectiveness and cost effectiveness of specialist physiotherapy for FMD. Like many other studies this trial was affected by the COVID-19 pandemic. Methods: The planned statistical and health economics analyses for this trial are described, as well as the sensitivity analyses designed to assess the disruption caused by COVID-19. The trial treatment of at least 89 participants (33%) was disrupted due to the pandemic. To account for this, we have extended the trial to increase the sample size. We have identified four groups based on how participants’ involvement in Physio4FMD was affected; A: 25 were unaffected; B: 134 received their trial treatment before the start of the COVID-19 pandemic and were followed up during the pandemic; C: 89 were recruited in early 2020 and had not received any randomised treatment before clinical services closed because of COVID-19; D: 88 participants were recruited after the trial was restarted in July 2021. The primary analysis will involve groups A, B and D. Regression analysis will be used to assess treatment effectiveness. We will conduct descriptive analyses for each of the groups identified and sensitivity regression analyses with participants from all groups, including group C, separately. Discussion: The COVID-19 mitigation strategy and analysis plans are designed to maintain the integrity of the trial while providing meaningful results. Trial registration: ISRCTN56136713.

Adverse life events precede the onset of functional neurological disorder (FND, also known as conversion disorder) more commonly than other neuropsychiatric conditions, but their aetiological role is unclear. We conducted a systematic review and quantitative analysis of the type, timing and number of life events preceding the onset of FND in adults, and a meta-analysis of the proportions of types of events in controlled studies. Fifty-one studies of different designs, covering 4247 patients, were eligible for inclusion. There was no clear majority of any type of preceding event. Family problems were the most common category of events, followed by relationship problems. Females were more likely to experience preceding family/relationship problems than males, who reported more work problems. Family problems were the commonest type of preceding event in studies in developing countries, whereas family and health problems were equally common in developed countries. Abuse was associated with early symptom onset, while patients with later onset were more likely to report family problems. The median number of events was one, and the events occurred closer to onset than in controls. Meta-analysis found that family, relationship and work events were all relatively more common in patients than pathological controls, as were events where symptoms might provide a solution to the stressor. In conclusion, although a range of events precede the onset of FND, they do not appear to do so uniformly. This may support a different aetiological role for stressors than in other disorders, although the support is indirect and the quality generally low.

Cognitive behavioral therapy (CBT) is a widely used therapeutic modality in general psychiatric practice. In this review, we consider its application to neurological disorders. We examine the basic framework of CBT—that symptoms, emotions, thoughts, and behaviors are all interrelated and that therapeutic interventions that lead to change in thoughts or behavior may have the potential to reduce symptoms or emotional distress. We also outline specific methodological issues to consider when reading or planning studies of CBT interventions, highlighting important topics pertaining to quality control, control group selection, dropouts, and generalizability. We then review the evidence base for CBT's use across a range of neurological disorders. In doing so, we highlight where there is a clear evidence base, and where it is a technique with potential. The review is targeted at a general neurology audience as introduction to the topic not as an advanced guide for expert practitioners.

Purpose: The CODES Trial for adults with dissociative seizures had a predesignated 12-month post-randomisation follow-up point for outcome evaluation. We undertook an exploratory, unplanned, secondary analysis to evaluate the effectiveness of cognitive behavioural therapy plus standardised medical care (CBT+SMC) compared to SMC alone at 6 months post-randomisation, i.e., closer to the end of treatment. Methods: The analysis of 6-month data followed our previous method of using multiple imputation and an intention-to-treat approach to analyse variables 12 months post-randomisation. Results: The original trial primary outcome of monthly seizure frequency showed greater benefit from CBT+SMC than SMC-alone at 6 months (at p < 0.05). Of 13 comparable previously-defined secondary outcomes, 12 showed a significant between group effect (p < 0.05) in favour of the CBT intervention at 6 months. The average effect size of the comparable previously-defined primary and secondary continuous outcomes was 0.33 at 6 months vs 0.26 at 12 months. The estimated Incidence Rate Ratio (IRR) quantifying monthly seizure reduction was IRR = 0.72 (95%CI from 0.55 to 0.93) at 6 months compared to IRR = 0.78 at 12 months. Conclusion: DS-specific CBT (plus SMC) produced evidence of significant benefits at 6 months post-randomisation (around which time CBT was complete) compared to SMC alone; for the majority of these outcomes, better results following CBT (plus SMC) had previously been reported at 12 months. Our pattern of results suggests that short- and longer-term follow-ups are necessary to understand treatment effects in this disorder. Studies only providing short-term follow-up data should be interpreted with caution.

Purpose: Little is known about the accuracy of the GAD-7, a self-report anxiety measure, in detecting generalised anxiety disorder (GAD) in people with dissociative seizures (DS). We evaluated the reliability, validity and uniformity of the GAD-7 using a diagnosis of GAD on the Mini-International Neuropsychiatric Interview as a reference.Methods: We assessed 368 adults with DS at the pre-randomisation phase of the CODES trial. Factor analysis for categorical data assessed GAD-7 uniformity. Diagnostic accuracy was assessed by estimating the area under the curve (AUC). We evaluated discriminant validity, reviewed data on convergent validity and calculated internal consistency. We explored correlations between GAD-7 scores and monthly DS frequency, frequency of severe seizures and measures of behavioural and emotional avoidance. Results: Internal consistency of the GAD-7 was high (alpha = 0.92). Factor analysis elicited one main factor and general measurement invariance. Diagnostic accuracy was fair (AUC = 0.72) but the best balance of sensitivity and specificity occurred at a cut-off of >= 12 and still had a specificity rate of only 68%. Discriminant and convergent validity were good. GAD-7 scores correlated positively with DS frequency, severe seizure frequency, behavioural and emotional avoidance (all p < 0.001).Conclusion: Findings regarding internal consistency and factor structure parallel previous psychometric evalua-tions of the GAD-7. Correlations between GAD-7 scores and DS occurrence/severity and avoidance are evidence of the concept validity of GAD-7 and provide further support for a fear-avoidance treatment model for DS. However, the utility of the GAD-7 as a diagnostic instrument for generalised anxiety disorder is limited in pa-tients with DS.

Objective To describe clinical features relevant to diagnosis, mechanism, and etiology in patients with “scan-negative” cauda equina syndrome (CES). Methods We carried out a prospective study of consecutive patients presenting with the clinical features of CES to a regional neurosurgery center comprising semi-structured interview and questionnaires investigating presenting symptoms, neurologic examination, psychiatric and functional disorder comorbidity, bladder/bowel/sexual function, distress, and disability. Results A total of 198 patients presented consecutively over 28 months. A total of 47 were diagnosed with scan-positive CES (mean age 48 years, 43% female). A total of 76 mixed category patients had nerve root compression/displacement without CES compression (mean age 46 years, 71% female) and 61 patients had scan-negative CES (mean age 40 years, 77% female). An alternative neurologic cause of CES emerged in 14/198 patients during admission and 4/151 patients with mean duration 25 months follow-up. Patients with scan-negative CES had more positive clinical signs of a functional neurologic disorder (11% scan-positive CES vs 34% mixed and 68% scan-negative, p < 0.0001), were more likely to describe their current back pain as worst ever (41% vs 46% and 70%, p = 0.005), and were more likely to have symptoms of a panic attack at onset (37% vs 57% and 70%, p = 0.001). Patients with scan-positive CES were more likely to have reduced/absent bilateral ankle jerks (78% vs 30% and 12%, p < 0.0001). There was no significant difference between groups in the frequency of reduced anal tone and urinary retention. Conclusion The first well-phenotyped, prospective study of scan-negative CES supports a model in which acute pain, medication, and mechanisms overlapping with functional neurologic disorders may be relevant.

OBJECTIVE:To describe clinical features relevant to diagnosis, mechanism, and etiology in patients with "scan-negative" cauda equina syndrome (CES).METHODS:We carried out a prospective study of consecutive patients presenting with the clinical features of CES to a regional neurosurgery center comprising semi-structured interview and questionnaires investigating presenting symptoms, neurologic examination, psychiatric and functional disorder comorbidity, bladder/bowel/sexual function, distress, and disability.RESULTS:A total of 198 patients presented consecutively over 28 months. A total of 47 were diagnosed with scan-positive CES (mean age 48 years, 43% female). A total of 76 mixed category patients had nerve root compression/displacement without CES compression (mean age 46 years, 71% female) and 61 patients had scan-negative CES (mean age 40 years, 77% female). An alternative neurologic cause of CES emerged in 14/198 patients during admission and 4/151 patients with mean duration 25 months follow-up. Patients with scan-negative CES had more positive clinical signs of a functional neurologic disorder (11% scan-positive CES vs 34% mixed and 68% scan-negative, p < 0.0001), were more likely to describe their current back pain as worst ever (41% vs 46% and 70%, p = 0.005), and were more likely to have symptoms of a panic attack at onset (37% vs 57% and 70%, p = 0.001). Patients with scan-positive CES were more likely to have reduced/absent bilateral ankle jerks (78% vs 30% and 12%, p < 0.0001). There was no significant difference between groups in the frequency of reduced anal tone and urinary retention.CONCLUSION:The first well-phenotyped, prospective study of scan-negative CES supports a model in which acute pain, medication, and mechanisms overlapping with functional neurologic disorders may be relevant.

Background: The PHQ-9 is a self-administered depression screening instrument. Little is known about its utility and accuracy in detecting depression in adults with dissociative seizures (DS). Objectives: Using the Mini-International Neuropsychiatric Interview as a reference, we evaluated the diagnostic accuracy of the PHQ-9 in adults with DS, and examined its convergent and discriminant validity and uniformity. Methods: Our sample comprised 368 people with DS who completed the pre-randomisation assessment of the CODES trial. The uniformity of the PHQ-9 was determined using factor analysis for categorical data. Optimal cutoffs were determined using the area under the curve (AUC), Youden Index, and diagnostic odds ratio (DOR). Convergent and discriminant validity were assessed against pre-randomisation measures. Results: Internal consistency of the PHQ-9 was high (alpha = 0.87). While the diagnostic odds ratio suggested that a cut-off of >10 had the best predictive performance (DOR = 14.7), specificity at this cut off was only 0.49. AUC (0.74) and Youden Index (0.48) suggested a > 13 cut-off would yield an optimal sensitivity (0.81) and specificity (0.67) balance. However, a cut-off score of >20 would be required to match specificity resulting from a cut-off of >13 in other medical conditions. We found good convergent and discriminant validity and one main factor for the PHQ-9. Conclusions: In terms of internal consistency and structure, our findings were consistent with previous validation studies but indicated that a higher cut-off would be required to identify DS patients with depression with similar specificity achieved with PHQ-9 screening in different clinical and non-clinical populations.

Objective To determine whether self-rated health of patients with motor functional neurologic disorder (FND) can be improved by unguided Internet-based self-help and education. Methods In this nonblinded randomized controlled trial, patients were allocated 1:1 unbiased to an unguided education and self-help website in addition to usual care or usual care only. Patients over 17 years of age with a functional motor symptom that caused distress or disability were included. The primary outcome was self-rated health on the Clinical Global Improvement scale at 3 and 6 months. Secondary outcomes were severity of motor symptoms, other physical and psychiatric symptoms, physical functioning, quality of life, work and social adjustment, illness beliefs, and satisfaction with care. Results A total of 186 patients were randomized, with a follow-up rate of 87% at 6 months. There was no difference in improvement of self-rated health at 3 months (44% vs 40%,p= 0.899) or 6 months (42% vs 43%,p= 0.435). Secondary outcomes did not differ between groups, with a threshold ofp< 0.01. Satisfaction was high, with 86% of patients recommending the website to other patients. Conclusion We found no significant effect of the intervention added to usual care on self-rated health or secondary outcome measures, despite high patient satisfaction with the intervention. These results suggest that online education and nonguided self-help could be valuable additions to stepped care for motor FND, but are not effective treatments as interventions in their own right. Clinicaltrials.gov identifier NCT02589886. Classification of evidence This study provides Class III evidence that for patients with motor FND, online education and self-help intervention does not significantly improve self-rated health.

Functional cognitive disorders are likely to account for a significant proportion of adults presenting with cognitive (memory and thinking) symptoms which are not caused by neurodegenerative disease or structural brain lesions, incorporating those with isolated functional cognitive symptoms, those with primary psychiatric disorders, and those with health anxiety or who attend excessively to normal cognitive lapses. There is a need for improved diagnostic methods to identify those with functional cognitive symptoms so that they might be offered appropriate treatment, protected from iatrogenic harms, and also in order to improve the specificity of prodromal neurodegenerative disease phenotypes. This study aims to identify elements of clinical, neurological, cognitive examination which can, in combination as part of a diagnostic scoring tool, accurately discriminate functional cognitive symptoms from those more likely to be due to neurodegenerative disease. The study will recruit 120 participants with mild or subjective memory symptoms (but not dementia) from memory, neurology, and neuropsychiatry clinics. Each subject will attend for a structured research assessment examining interactional, linguistic, metacognitive features, as well as psychiatric, physical, and sleep disorder comorbidity. Multiple outcomes will be compared with panel consensus diagnosis using discriminant factor analysis. The intention is to follow up medical record / general practice diagnosis at 1-2 years, and ultimately it is hoped that further studies beyond this will re-examine the cohort in the future.

Objective Foreign accent syndrome (FAS) is widely understood as an unusual consequence of structural neurological damage, but may sometimes represent a functional neurological disorder. This observational study aimed to assess the prevalence and utility of positive features of functional FAS in a large group of individuals reporting FAS. Methods Participants self-reporting FAS recruited from informal unmoderated online support forums and via professional networks completed an online survey. Speech samples were analysed in a subgroup. Results Forty-nine respondents (24 UK, 23 North America, 2 Australia) reported FAS of mean duration 3 years (range 2 months to 18 years). Common triggers were: migraine/severe headache (15), stroke (12), surgery or injury to mouth or face (6) and seizure (5, including 3 non-epileptic). High levels of comorbidity included migraine (33), irritable bowel syndrome (17), functional neurological disorder (12) and chronic pain (12). Five reported structural lesions on imaging. Author consensus on aetiology divided into, ‘probably functional (n=35.71%), ‘possibly structural’ (n=4.8%) and ‘probably structural’ (n=10.20%), but positive features of functional FAS were present in all groups. Blinded analysis of speech recordings supplied by 13 respondents correctly categorised 11 (85%) on the basis of probable aetiology (functional vs structural) in agreement with case history assignment. Conclusions This largest case series to date details the experience of individuals with self-reported FAS. Although conclusions are limited by the recruitment methods, high levels of functional disorder comorbidity, symptom variability and additional linguistic and behavioural features suggest that chronic FAS may in some cases represent a functional neurological disorder, even when a structural lesion is present.

A history of head injury is common in patients with psychogenic nonepileptic seizures (PNES). This association has so far been interpreted as either spurious or psychologically mediated. Biased recall and misattribution could foster illness beliefs about brain damage that promote symptom production. Furthermore, the emotional impact of head injury could induce long-term changes in stress responsivity. Lastly, maladaptive cognitive-behavioural processes involving symptom modelling and aversive conditioning, known to play a role in functional neurological disorders, could contribute to the development of PNES after head trauma. Lesional effects of head injury, on the other hand, remain unexplored in the context of PNES. However, even mild traumatic brain injury without structural MRI abnormalities on routine imaging can lead to disruptions of network connectivity that correlate with short-term cognitive impairments and psychiatric symptoms. Since alterations in global functional connectivity have been demonstrated in PNES patients using imaging and electroencephalography, we hypothesize that, in some patients, TBI and the associated disruption of long-range association fibres could contribute to the individual propensity for dissociative experiences in general and PNES in particular. This possibility is explored in the context of new cognitive-behavioural models of PNES pathogenesis, and the concept of a "dissociogenic" brain lesion is introduced.

Background: Akathisia is a common and distressing neuropsychiatric syndrome associated with antipsychotic medication, characterised by subjective and objective psychomotor restlessness. The goal of this guideline is to provide clinicians with recommendations on the assessment and treatment of akathisia. Methods: We performed a systematic review of therapeutic studies assessing the treatment of antipsychotic-induced extrapyramidal symptoms. Forty studies on akathisia and 4 systematic reviews evaluating the adverse effects of antipsychotics were used in the formulation of recommendations. Studies were rated for methodological quality using the American Academy of Neurology Risk of Bias Classification system. The overall level of evidence classifications and grades of recommendation were made using the Scottish Intercollegiate Guidelines Network framework. Results: As a good practice point, clinicians should systematically assess akathisia with a validated scale before starting antipsychotics and during antipsychotic dosage titration. For the management of akathisia, there was adequate evidence to allow recommendations regarding antipsychotic dose reduction, antipsychotic polypharmacy, switching antipsychotic medication, and the use of adjuvant medications including beta-blockers, anticholinergics, 5HT 2A antagonists, benzodiazepines, and vitamin B6. Conclusion: The treatment of antipsychotic-induced akathisia should be personalised, with consideration of antipsychotic dose reduction, cessation of antipsychotic polypharmacy, and switching to an antipsychotic with a perceived lower liability for akathisia, before the use of adjuvant medications. The choice of adjuvant medications should favour the more established treatments, with careful consideration of contraindications and side effects. Limitations in the evidence should be acknowledged and prompt cautious prescribing, particularly with respect to the duration of use of adjuvant medications, is warranted.

The majority of patients presenting with suspected clinical cauda equina syndrome (CES) have no identifiable structural cause for their symptoms (‘scan-negative’ CES). Understanding these patients aids clinical differentiation and management in CES.

Functional, often called psychogenic, disorders are common in neurological practice. We illustrate clinical issues and highlight some recent research findings using six case studies of functional neurological disorders. We discuss dizziness as a functional disorder, describing the relatively new consensus term Persistent Posturo-Perceptual Dizziness (PPPD), axial jerking/myoclonus as a functional movement disorder, functional speech symptoms, post-concussion disorder with functional cognitive symptoms and finally advances in treatment of dissociative seizures and functional motor disorders.

The epidemiology of functional neurologic disorders (FND) is complex and has been hampered over the years by a lack of clear definition, with previous definitions struggling with an uneasy mix of both physical and psychologic components. 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 associated psychopathology represent a significant step forward in clarifying the disorder. On this basis, FND account for approximately 6% of neurology outpatient contacts and putative community incidence rates of 4–12 per 100 000 per annum. Comorbid neurologic disease occurs in around 10% of cases. The diagnosis is reliable, with revision rates less than 5%. Of note, this revision rate was consistent prior to the widespread utilization of computed tomography and magnetic resonance imaging. FND symptoms are disabling and associated with significant distress. They are more common in women and have a peak incidence between the ages of 35 and 50; however the presentation is common in men and throughout the lifespan. The issues surrounding case definition, ascertainment, misdiagnosis, and risk factors are discussed in detail.

The use of electricity in medical treatment has always been technology-driven, rather than aetiology-driven; as new techniques have appeared, clinicians have quickly looked to try them in the treatment of all sorts of conditions where existing treatment options are limited. Functional disorders--as identified anachronistically in our analysis--have been key contenders for emerging electrical treatments: with Leyden jars, with galvanic and electromagnetic machines, and more recently with TMS and TENS. Parallels can be drawn with the history of electrical treatments for migraine and headache (Koehler and Boes, 2010). Regardless of the mode of delivery of electricity, stimulating a limb to produce movement has repeatedly been found to aid and assist recovery in functional motor disorders. This may also be true of non-electrical methods: we have found benefits using both therapeutic sedation and explanatory demonstration of a positive Hoover's sign as therapeutic methods of demonstrating normal movement in functionally weak limbs (Stone et al., 2014). Each surge in enthusiasm for new electrical treatments has been followed by questions about the nature of the disorder and validity of the treatment response. Physicians have tended to attribute therapeutic success initially to powerful biological or even metaphysical effects, but with time and experience these explanations have been replaced by views that the treatment works through suggestion and placebo. Discomfort with these conclusions has in the past discouraged ongoing development of electrical treatments, even if the end result for patients has been encouraging. In Edwards's Bayesian model, functional motor and sensory symptoms are hypothesized to arise when 'pathologically precise prior beliefs' mediated by attentional processes cause experience of symptoms via a hierarchy of false inferences (Edwards, 2012). It can be argued that use of TMS or peripheral stimulation to produce movement of a functionally weak limb has the specific potential to modulate pathological expectations. To reject these treatments as no more than placebo may mean missing an unusual opportunity to manipulate key elements in the mechanism of the disorder. However, changes to these 'priors' may also be dependent upon patient expectations, and as we see through history, this may only happen if the patient believes there is an actual neuromodulatory effect. This may give rise to significant ethical issues in that the treatment may well directly benefit patients but only if they are (mis)informed that there is an underlying biological rationale. We conclude that modern trials of TMS in functional disorders are part of a repeating cycle of experimentation recurring since the mid-18th century. We suspect that emerging technology, including transcranial direct current stimulation, will follow a similar pattern of experimentation, speculation and marginalization. We suggest that considering our modern efforts in a historical context could aid our ability to further expand and maintain our use of electrical therapies that have proven helpful in the past for patients with functional disorders.

“When I use a word,” Humpty Dumpty said in rather a scornful tone, “it means just what I choose it to mean—neither more nor less.” Lewis Carroll Journal editors like themed or special issues. It is a chance to appeal to readers of the paper journal, our subscribers, and produce a stimulating, integrated read that will hopefully have some form of ‘added value’. In an era of computerised search engines to identify individual papers out there in the ether, the special issue seems to speak to a journal's identity. The JNNP 's identity, since its formation by Kinnear Wilson, has always been bound to the idea of coherent integration of differing perspectives from the different disciplines that may be loosely considered as clinical brain sciences . A neuropsychiatry themed issue seems an obvious choice. But what actually is neuropsychiatry? The American Neuropsychiatric Association (ANA) define it ‘as the integrated study of psychiatric and neurologic disorders’ which is wonderfully circular, although they do within their mission statement add a desire ‘for better understanding [of the] links between neuroscience and behaviour’. The International Neuropsychiatric Association echo this with a similar definition describing an ‘increase [in] understanding of brain function and human behaviour’. But in what way is this different from simply viewing mental disorder in general as having a, at least in part, neural basis, and does it matter? The British Neuropsychiatry Association (BPNA) avoid a definition altogether. …

Background: Patients with severe functional (psychogenic) neurological symptoms such as paralysis and fixed dystonia present a therapeutic challenge, particularly if no movement is possible during physiotherapy. Sedation has been discussed as a treatment for functional neurological symptoms for 100 years but technique, use of video and, outcome has not been systematically described.Methods: Therapeutic sedation of patients with severe functional neurological symptoms with propofol and follow up at a neuroscience centre.Results: Of eleven patients (median duration 14 months), five were cured or had major improvement with sedation. At follow up (median 30 months) four were asymptomatic, two were significantly improved and one had minor improvements. We describe a standardized anesthetic and physician technique, refined over consecutive treatments.Conclusion: In carefully chosen patients, therapeutic sedation with propofol can be a useful adjunctive treatment for patients with severe functional neurological symptoms. The treatment deserves randomized evaluation. (C) 2013 Elsevier Inc. All rights reserved.