functional (psychogenic) movement disorders: merging mind and brain

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Page 1: Functional (psychogenic) movement disorders: merging mind and brain

250 www.thelancet.com/neurology Vol 11 March 2012

Review

IntroductionFunctional (psychogenic) movement disorders (FMD) are part of the spectrum of functional neurological disorders, some of the most prevalent disorders seen in neurological practice.1 In common with other functional disorders, there is an absence of appropriate health-service provision and research interest for FMD, despite their prevalence. These disorders occupy a grey area between neurology and psychiatry—often with neither specialist group willing to take charge—which has resulted in what has been described in relation to FMD as a “crisis for neurology”.2

There are three rationales behind this Review. First, there have been notable developments in diagnostic techniques, pathophysiological understanding, and treat-ments in FMD, which together represent a substantial advance in knowledge. Second, we wish to highlight an important shift that has taken place in approaches to functional disorders in general: the historically infl uential explanation for symptoms triggered by emotional trauma (and the research and treatment agendas that emerge from this explanation) has been challenged. Third, because of the enormous health-care and social-care costs associated with functional symp toms such as FMD, health professionals and medical scientists need to take an active interest in keeping up to date with best practice in diagnosis and management. FMD have traditionally been thought of as the most diffi cult of the functional neurological disorders to diagnose and manage, but we will show that they need not always carry such a reputation.

Terminology and defi nitionWhen experts cannot agree on a unifi ed terminology for a disorder, there is likely to be a fundamental problem with understanding the underlying pathophysiology. This diffi culty in understanding is certainly present for psychogenic disorders, including FMD, for which there are many descriptive terms to choose from (panel 1). The choice of term is not a trivial issue, because it

directly aff ects case defi nition, diagnosis, treatment, research agenda, and explanations of illness that we give to patients.

Some terms, such as psychogenic, conversion, or somatisation, directly suggest that the cause of physical symptoms is psychologically mediated. Conversion and somatisation are operationalised diagnoses that specif-ically need the presence of a psychological triggering factor and exclusion of feigning. However, for most movement disorder clinicians, the presence of a psycho logical triggering factor is not a requirement for diagnosing a patient with FMD,3 and the diffi culties of routinely excluding feigning in clinical practice are complex.4 We also show later that recent epidemiological studies question the relevance of psychological triggers in most patients with FMD.5 However, other terms also have their diffi culties. For example, does a disorder that is medically unexplained simply mean that we have not yet found the medical explanation, and with advance ment of medical knowledge it will become a medically explained disorder? What level of medical explanation do we need for a disorder to be medically explained? The term hysteria comes with substantial historical baggage, but some movement disorder specialists, including the most eminent of recent times, David Marsden, have argued passionately that the term should be retained.6 The term functional also has a long and distinguished neurological history, but some argue that it has lost its meaning over time and is now too broad a term to be helpful.7

Patients are directly aff ected by the diagnostic labels we give them. Stone and colleagues8 explored this issue with unselected neurology outpatients and found that many terms were judged by patients as suggesting that the doctor thought their symptoms were “put on” or “all in the mind”. Hysteria came out badly on this assessment, but so did the term medically unexplained. The term psychogenic was not specifi cally assessed, but psycho-somatic was and was rated negatively. Functional was the term most acceptable to patients.

Functional (psychogenic) movement disorders: merging mind and brainMark J Edwards, Kailash P Bhatia

Functional (psychogenic) movement disorders (FMD) are part of the wide spectrum of functional neurological disorders, which together account for over 16% of patients referred to neurology clinics. FMD have been described as a “crisis for neurology” and cause major challenges in terms of diagnosis and treatment. As with other functional disorders, a key issue is the absence of pathophysiological understanding. There has been an infl uential historical emphasis on causation by emotional trauma, which is not supported by epidemiological studies. The similarity between physical signs in functional disorders and those that occur in feigned illness has also raised important challenges for pathophysiological understanding and has challenged health professionals’ attitudes toward patients with these disorders. However, physical signs and selected investigations can help clinicians to reach a positive diagnosis, and modern pathophysiological research is showing an appreciation of the importance of both physical and psychological factors in FMD.

Lancet Neurol 2012; 11: 250–60

Sobell Department of Motor Neuroscience and Movement

Disorders, UCL Institute of Neurology, London, UK

(M J Edwards PhD, Prof K P Bhatia MD)

Correspondence to:Prof K Bhatia, Sobell

Department, UCL Institute of Neurology, Queen Square,

London WC1N 3BG, [email protected]

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We use the term functional in this Review. The origins and chequered history of this term have been discussed in detail by Trimble.7 He argues that the original physiological use of the term as a disturbance of functioning of the nervous system where the cause has yet to be defi ned has value, in contrast to its use as a “polite eponym” for a psychiatric disorder.7 We accept that there are diffi culties in using this term as a replacement for other terms such as psychogenic. Although in our view this term accurately refl ects the state of the evidence regarding the pathophysiology of psychogenic disorders, this use does also mean that the word functional is used to apply to the functional disturbance that occurs in this patient group only, and not in patients with, for example, headache. Unfortunately, this debate cannot be solved in this Review, and we recognise the insuffi ciency of present terminological options. In clinical practice, we use the term functional, because it is the term most acceptable to patients and does not presuppose a cause for symptoms that is unproven. We specifi cally defi ne this disorder by its clinical appearance, rather than by any causative speculation as a movement disorder that is signifi cantly altered by distraction or non-physiological manoeuvres (including dramatic placebo response) and that is clinically incongruent with movement disorders known to be caused by neurological disease.

Epidemiology, quality of life, and costThe subject of this Review represents an important issue because of its prevalence and eff ect on quality of life and health-care economics. FMD are part of the wide spectrum of functional or psychogenic neurological symptoms, which together account for 16% of new pa-tients attending neurology outpatients’ clinics.1 Accurate estimates of prevalence of FMD are hampered by case defi nition and the setting of the clinic from which cases are ascertained, and range between 2 and 20% of patients attending movement disorder clinics.9,10 These disorders cause an impairment in quality of life that is similar to, and in some aspects worse than, that experienced by patients with Parkinson’s disease.11 No studies have specifi cally addressed the economic burden of FMD but, given the level of disability reported by patients in the long term (see Prognosis section), there are probably substantial associated health and social care costs. In a large study of patients with functional neurological symptoms (n=1144) who were followed up for 1 year, at least 50% had stopped working and more than one-quarter were receiving illness-related fi nancial benefi ts;12 the economic burden for those with FMD is unlikely to diff er from this. UK estimates for the yearly costs associated with working-age patients with “medically un explained symptoms” are approximately £18 billion,13 slightly more than the annual cost associated with dementia for patients of all ages in the UK.14 Women are more often aff ected by

FMD than men, and mean age at onset in diff erent studies ranges from 37 to 50 years.9,10 FMD are also reported, but not commonly, in children15 and in the elderly.9,10

Clinical featuresSeveral historical features and examination fi ndings are commonly noted in patients with FMD regardless of the movement disorder phenomenology. These features are not diagnostic of FMD, but can be helpful as part of the diagnostic process. Patients often describe the sudden onset of symptoms, which might be precipitated by a physical event (eg, injury or illness).9,10 Symptoms can rapidly progress to become severe—a pattern that is unlike the slow progressive course of most movement disorders.9,10 Patients might report marked variability in symptom severity, including complete remissions and sudden recurrences. The phenomenology of the move ment disorder might shift over time. Patients might have a history of other functional symptoms. Neurological signs apart from

Panel 1: Terms commonly used to describe psychogenic disorders and their implications

Psychogenic• Suggests psychological causation

Conversion disorder• Operationalised within DSM: requires an identifi ed

psychological triggering factor for diagnosis

Somatisation disorder• Operationalised within DSM: requires presence of

multiple physical symptoms including one conversion neurological symptom

Medically unexplained symptoms• Suggests that a medical explanation might one day

be apparent• Could refer to many medical symptoms that are not

thought to be psychogenic, but still are not of a known cause

Functional• Broad term suggesting a functional rather than a

structural defi cit, which could apply to several neurological disorders not regarded as psychogenic but where structural pathology is absent, eg, migraine

Hysteria• Historical term that carries substantial stigma in society

and implies a link between symptoms and the uterus

Non-organic• Defi nes the condition by what it is not; the term organic is

itself not well defi ned

DSM=Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, American Psychiatric Association.

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the movement disorder can be consistent with functional illness, for example Hoover’s sign (leg paresis), give-way weakness, and non-anatomical patterns of sensory loss.9,10 The co-occurrence of functional and organic movement disorders might be expected, given the common co-occurrence of other functional disorders with organic disorders, for example epilepsy and non-epileptic seizures.16 However, hard evidence for the prevalence of this phenomenon is limited.17,18

Functional tremorFunctional tremor (FT) is the commonest presentation of FMD, accounting for at least 50% of patients.9 Com monly, the historical features are as outlined earlier, with sudden onset, variability in severity with remissions, and variability in the body part aff ected. Most patients have a tremor that is present (or at least can be present at diff erent times) at rest, in posture, and during action, which is an unusual pattern for organic tremor. Tremor can occur in any body part; the hands and arms are most frequently involved, but tremor of the head, legs, or even palate can also occur. By contrast with patients with organic tremor, patients with FT often direct clear visual attention towards their aff ected limb during examination.19

The key clinical feature that helps to diff erentiate FT from organic tremor is that FT changes with the level of attention towards the aff ected limb. This can be appreciated during history taking as fl uctuation in tremor severity (or even presence) while the patient’s attention is engaged. Conversely, FT commonly worsens during examination. Specifi c examination manoeuvres can be used to distract attention away from the tremoring limb; some formal assessments of specifi city and sensitivity have been done on these manoeuvres clinically,20 and more extensively with electrophysiological tremor recordings.21–25 Thus, tremor may change with cognitive distraction tasks or tapping at diff erent frequencies (it may entrain to the tapping frequency, shift in frequency, or stop altogether; or the patient might inexplicably be unable to undertake the required tapping movement correctly);21,22 pause with ballistic movement of the other limb (fi gure 1);23 or paradoxically worsen with loading.24 The specifi city and sensitivity of some of these tasks have been investigated (without tremor recordings) in patients with FT compared with those with essential tremor; tapping tasks had the highest sensitivity and specifi city (72·7% and 73·3%, respect ively).20 In a head-to-head study, we compared these techniques with tremor recordings in FT and a

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Figure 1: Tremor recordings in a patient with functional tremorTri-axial accelerometry recordings from an accelerometer attached to the tremoring hand (top three traces) and to the unaff ected hand (bottom three traces). The patient is undertaking rapid reaching movements to a target with the unaff ected hand, which produces brief pauses in the tremor in the other hand. Acc=acceleration. X=x axis. Y=y axis. Z=z axis. R=right. L=left.

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range of organic tremor disorders (Parkinson’s disease, essential tremor, dystonic tremor, and neuropathic tremor).25 We found that no single measure had suffi cient specifi city and sensitivity to diff erentiate FT from organic tremor. This fi nding is probably due to the diff erent mechanisms for tremor generation in FT, with some patients generating tremor primarily by co-contraction, which is not readily distractible by tapping tasks.24 Cognitive distracter tasks were poor dis-criminators between organic tremor and FT. A cutoff score was devised by combining several of these measures, which, if validated in a prospective study, could provide a laboratory-supported level of diagnostic certainty (table).

Functional dystoniaFunctional dystonia is the second most common presentation in patients with FMD.9 There are substantial diff erences of opinion between experts regarding the diagnosis of functional dystonia. These diff erences are not helped by the history of dystonia in general: patients now classifi ed as having organic dystonia were, until the 1980s, commonly classifi ed as having hysteria. Advances in genetics have led to recognition of the phenotypes of primary idiopathic dystonia, which have typical ages of onset, courses, and distributions of dystonia. For example, DYT1 gene-related primary dystonia starts before age 25 years, often aff ects the legs at onset, and can spread over a few years after onset to cause generalised dystonia.26 By contrast, late-onset primary dystonia aff ects the cranio-cervical region (spasmodic torticollis is the most common form) and tends to remain focal.26 This identifi cation of distinct phenotypes has made easier the recognition of secondary dystonic (including functional) disorders, which have presentations incongruous with primary dystonia phenotypes. Patients with functional dystonia typically present with fi xed abnormal postures accompanied by severe pain similar to that noted in chronic regional pain syndrome type 1 (CRPS1). Most patients with functional dystonia are young women and the usual trigger is a minor peripheral injury, but the disorder is sometimes spontaneous. Such patients (who might also be classed as having “causalgia-dystonia”27 or “tonic dystonia of chronic regional pain”28) may experience spread of symp toms to other body parts without further injury. Limbs are usually involved, but fi xed dystonia aff ecting the neck or jaw has also been reported.29

Physical examination manoeuvres can be used to show with certainty whether attention is playing a key part in symptom generation in functional tremor; however, to show the same level of certainty in fi xed dystonia is diffi cult. One might argue that this diffi culty occurs because fi xed dystonia is not a functional disorder, but to state that maintenance of postures does not need a similar level of attention as maintenance of

tremor would also be reasonable. However, in some patients a brief give way of muscle activity in the aff ected limb will be felt when the patient is distracted. In support of the functional label for fi xed dystonia, symptoms may resolve with multidisciplinary re-habilitation with an emphasis on cognitive-behavioural therapy,30 the disorder may co-exist with other more clearly defi ned psychogenic disorders,29,30 and marked (curative) placebo responses have been reported.31 However, some,32 but not all,33 research electro-hysiological tests suggest similarities between patients with fi xed dystonia and those with organic dystonia, although these tests are all subject to confounding from muscle activity, attention, and anxiety. Maintenance of a fi xed posture has been hypothesised to produce secondary changes in central body schema,34 and these changes might contribute to pain and other unusual features, such as the seeking of limb amputation by some patients.35

Functional myoclonusFunctional myoclonus is reported in about 20% of patients with FMD.9 As might be expected in patients with intermittent movements, distractibility can be diffi cult to demonstrate on examination. Electro-physiological tests can therefore be of substantial diagnostic help to clinicians.36 Simple electromyography (EMG) recordings can be used to assess EMG burst duration: consistent EMG bursts of less than 75 ms do not occur in functional myoclonus. However, the converse is not true, because some forms of organic myoclonus are associated with long-duration EMG bursts. Electrophysiological features associated with cortical myoclonus (giant somatosensory evoked potentials, electroencephalogram [EEG] spike 20 ms

Points

Incorrect tapping performance at:

1 Hz 1

3 Hz 1

5 Hz 1

Entrainment, suppression, or pathological frequency shift at:

1 Hz 1

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5 Hz 1

Pause or 50% reduction in amplitude of tremor with ballistic movements

1

Tonic activation before tremor onset 1

Coherence of bilateral tremors 1

Increase of TP (as surrogate of tremor amplitude) 1

Cutoff score for functional tremor ≥3

TP=total power of the spectra between 1 and 30 Hz. Data from Schwingenschuh and colleagues.25

Table: Suggested electrophysiological test criteria for diagnosis of functional tremor

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before jerks) would not be expected in functional myoclonus. The most useful diagnostic test in patients with suitable symptoms (see below) is EEG–EMG back-averaging—a method for assessing cortical activity shortly before movement (fi gure 2). In healthy people undertaking a self-paced voluntary movement, a slow rising potential is seen in the EEG starting about 1·5 s before movement and peaking just before movement: this is the pre-movement potential, or Bereitschafts-potential.36 This potential can be recorded in patients with functional myoclonus and is not seen in people with organic myoclonus. There are technical limitations to this test: at least 30 jerks need to be recorded, so patients must have a reasonable number of jerks within the recording time; and pre-movement potentials are often diffi cult to record in patients with very rapid jerks (more than one every 3–5 s), although distractibility is often easy to indentify in such patients clinically. Pre-movement potentials have been reported in patients with tics,37 but not consistently.38 Two groups have inde-pendently reported that most patients diagnosed with idiopathic spinal segmental or propriospinal myoclonus (the latter characterised by fl exion jerks of the abdomen) have pre-movement potentials before jerks and are therefore best characterised as functional.39,40

Other functional movement disordersPure functional gait disturbance accounts for about 6% of patients with functional movement disorders, but an abnormal gait is a common feature in patients with other FMD.41 Various gait patterns are described, but a key feature of most of these patterns is that the patient does not seem to adapt to the gait problem they complain of in an optimum way.42–44 For example, patients who complain of un steadiness might walk with a narrow base or might adopt uneconomic postures, which are apparently compensatory for the gait disturbance but would seem objectively to make it worse.41 Some patients have object ively very good balance while subjectively complaining of poor balance; such patients shift their centre of gravity by pivoting from side to side at the waist on a narrow base without

falling, thus showing excellent balance. This pattern has been termed the “walking on ice” gait.44 Another common pattern of functional gait disturbance is a monoplegic dragging gait, where the aff ected leg is dragged behind the patient, typically with the medial surface of the foot in contact with the fl oor and the leg externally rotated.45 This is quite diff erent from the circumducting gait typically seen in patients with organic hemiplegia. So-called bizarre patterns of gait are seen in organic movement disorders such as Huntington’s disease and generalised dystonia, and care needs to be taken in reaching a diagnosis with regard to unusual gait disturbance.

Functional parkinsonism, chorea, and tics are rarely reported.9 Most patients diagnosed with functional parkinsonism actually have a functional resting tremor rather than other features (such as slowness of move-ment) that mimic parkinsonism.46 Dopamine trans-porter scans can be helpful to a limited extent if diagnostic uncertainty exists. Dopamine transporter scans are normal in patients with functional parkinsonism but also in organic parkinsonism due to postsynaptic dopaminergic defi cit, such as drug-induced parkin sonism. Paroxysmal func tional move-ment disorders are rarely reported but do occur.9 They may be under-recognised because patients might instead be diagnosed with functional non-epileptic seizures. Clinicians need to be familiar with the range of triggers, attack durations, and attack frequencies that occur in organic paroxysmal movement disorders to help them to diff erentiate patients with functional attacks with confi dence and to exclude epilepsy by EEG measurement during an attack if necessary. There is no substitute for seeing an attack, and the video facility available on many modern mobile phones makes it easier for patients’ relatives to record an attack for viewing by the physician.

Diagnostic criteriaWe emphasised earlier that the diagnosis of FMD should as much as possible be a positive diagnosis. It should not be a diagnosis of exclusion, nor a diagnosis

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Figure 2: Electroencephalogram recordings from a patient with functional myoclonus A slow rising potential can be seen, which starts around 1 s before movement.

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made on the basis of co-existence of a movement disorder with psychological disturbance. Co-existent psychological disturbance is common throughout organic neurological disease and is not an adequate symptom on its own to diagnose a psychogenic disorder.47

Operationalised diagnostic criteria for functional move ment disorders include the Fahn-Williams criteria48 (the most widely used), the Shill-Gerber criteria,49 and a recent revision of the Fahn-Williams criteria proposed by Gupta and Lang (panel 2).47 All these criteria have as a key element a gradation of certainty of diagnosis; for example, in the Fahn-Williams criteria the gradation is documented, clinically established, probable, and pos sible. Various alterations to the Fahn-Williams criteria have been suggested, including a merging of documented and clinically established categories into one category of clinically defi nite; the removal of the possible category; and the addition of laboratory tests to produce a category of laboratory supported.47 The Shill-Gerber criteria have been criticised for being so heavily weighted towards historical information that the diagnosis of FMD could possibly be made with little reference to the clinical characteristics of the movement disorder.50 These criteria also place weight on the notion of disease modelling, in which experience of a disease in a family member, acquaintance, or via work provides a model for patients to produce functional symptoms. This notion is diffi cult to investigate (eg, the quantifi cation of all potential disease models to which a person has been exposed would seem to be very diffi cult), and therefore its place in diagnostic criteria seems questionable according to the available evidence.

The Fahn-Williams and Shill-Gerber criteria have recently been subjected to assessment of inter-rater reliability.51 There was only poor (Shill-Gerber) to moderate (Fahn-Williams) inter-rater reliability for probable and possible categories, with good agreement for the clinically defi nite category.

PathophysiologyThe earlier discussion of terminology shows a historical emphasis on psychological causation in FMD, as with other functional disorders. Psychiatric formulations based on late 19th and early 20th century concepts of conversion, somatisation, and dissociation still form the basis for psychiatric diagnoses in these disorders and, by extension, ideas regarding pathophysiology.52 However, patients with psychogenic disorders in general, including those with FMD, do not have the expected rates of psychological trauma, either at the onset of physical symptoms or in the past.5,53 This fi nding presents a problem for those who emphasise such factors as important pathophysiologically. This problem has traditionally been solved, in a rather circular argument, by suggesting that recall of such life events is repressed by patients and therefore is not

available for report. Although this repression may occur in some patients, the suggestion is largely untestable.

Panel 2: Fahn-Williams and Gupta-Lang criteria for diagnosis of psychogenic movement disorders

Fahn-Williams criteria48

DocumentedPersistent relief by psychotherapy, suggestion, or placebo has been demonstrated, which may be helped by physiotherapy; or the patient was seen without the movement disorder when believing himself or herself unobserved.

Clinically establishedThe movement disorder is incongruent with a classical movement disorder or there are inconsistencies in the examination, plus at least one of the following three: other psychogenic signs, multiple somatisations, or an obvious psychiatric disturbance.

ProbableThe movement disorder is incongruent or inconsistent with typical movement disorders or there are psychogenic signs or multiple somatisations.

PossibleEvidence of an emotional disturbance.

Laboratory supported defi niteNot included in this classifi cation.

Gupta and Lang proposed revisions47

Clinically defi niteIncludes Fahn-Williams documented and clinically established categories, and also includes movement disorders that are incongruent with a classical movement disorder or for which there are inconsistencies in the examination, without the need for the additional presence of psychogenic signs, multiple somatisations, or an obvious psychiatric disturbance.

ProbableNot included in this classifi cation.

PossibleGupta and Lang question the utility of this category. They suggest it could be used to include those with movement disorders congruent or consistent with a classical movement disorder but where there are additional psychogenic signs, somatisations, or evidence of emotional disturbance. However, they suggest that this category may then include patients who are diff erent pathophysiologically from those with true psychogenic movement disorders.

Laboratory supported defi nitePresence of data from electrophysiological tests that prove the presence of a psychogenic movement disorder (primarily evidence of pre-movement potentials before jerks or data from tremor studies).

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The key clinical feature that separates patients with FMD from those with organic movement disorders is that the movements have features that one would usually associate with voluntary movement (distractibility, resolution with placebo, and presence of pre-movement potentials), but patients report them as being involuntary and not under their control. There seem to be just two logical explanations for this feature: either movements are deliberately feigned or there must be a brain mechanism that allows voluntary movement to occur but to be experienced subjectively as involuntary. Understanding this mechanism would seem to be key to understanding the development of symptoms and their treatment.

Although study of subjective experience of movement might seem impossible, cognitive neuroscience has revealed the existence of mechanisms within the brain that confer a sense of intention and a sense of agency to movement, and examples of organic brain disease in which such processes are disrupted.54 Functional imaging recorded in patients during an episode of functional tremor or when the same pa tients were voluntarily mimicking their tremor showed hypoactivation of the temporoparietal junction during the psychogenic tremor.55 This area is thought to be an important comparator region, comparing actual with predicted sensory feedback. The suggestion is that hypoactivity might represent a failure to match the actual and predicted sensory feedback, producing a feeling of involuntariness associated with movement.55 Linked with this fi nding, we have reported that patients with functional tremor do not have the normal sense of intention that is associated with voluntary movement.56 Another functional imaging study in FMD noted abnormally strong amygdala–supple mentary motor area connectivity when patients were presented with emotionally valent stimuli and abnormally weak supplementary motor area–prefrontal cortex connectivity in a reaction time task.57 A hypothesis arising from this work and a further functional imaging study in FMD58 is that emotionally arousing events might trigger movement controlled by the supplementary motor area that is functionally disconnected from top–down control by the prefrontal cortex.

In a recent study that compared patients with functional tremor to those with organic tremor, we compared self-completed diaries in which patients rated the amount of the waking day they felt they had tremor with the results of continuous tremor recordings from a wrist-worn actigraph.59 Patients were all aware of the purpose of the study, as confi rmed in a post-study questionnaire. Patients with organic tremor tended to over-rate their tremor (by about 20%) in diaries compared with the tremor watch recordings. Patients with functional tremor over-rated their tremor by a signifi cantly higher amount (more than 65%; p=0·0001), and had on average only 30 min of tremor per day. We

have interpreted this fi nding within a Bayesian framework as a dominance of prior expectancy over sensory data.59

These studies all provide results that would be unexpected in patients feigning symptoms, although they do not amount to an aid to diagnose feigning of symptoms. However, these studies do provide examples of research in functional disorders that look beyond the rigid framework that has provided a causal model for symptoms on the basis of emotional trauma alone. There has been a wider rebalancing of attitudes toward functional disorders, so that they are considered within a biopsychosocial model, not just a psychosocial one. This change in attitude might prompt a search for psychological factors of causative importance that are not solely related to emotional trauma. This type of search has been underway for some decades in other disorders (eg, schizophrenia) once regarded as mental disorders but in which great importance is now given to understanding the biological basis of the disorder. The old dichotomy between mental and brain disorders has increasingly been swept away by the progress of cognitive neuroscience and, although long overdue, this process is now aff ecting views of functional neurological dis orders. To regard FMD and other functional disorders as just brain disorders would also be incorrect, and so a combined approach is necessary that integrates societal and psychological factors with our present knowledge of the biology of brain function. This process might not just lead to better understanding of FMD, but might also improve our understanding of the human brain.

ManagementThere are limited studies available on which to base management decisions in FMD. It seems reasonable to presume that treatment of FMD can be informed by data regarding treatment of other functional neurological conditions, in particular those that involve motor symptoms.

In our view, the most important fi rst steps in a successful treatment approach are eff ective commu-nication of the diagnosis and the provision to patients and their families of a rational model within which to understand the physical symptoms. In light of the earlier discussion regarding diagnosis, we emphasise the positive ways in which the diagnosis has been made rather than falling back on explanations based on normal test results. We try to introduce the role of psychological factors in their proper context and do not insist on extensive exploration for underlying psycho-logical trauma. Patients with FMD are vulnerable to unscrupulous medical and health practitioners, par-ticularly over the internet.60 There are some useful web resources that can help to support understanding of the diagnosis for patients with functional symptoms, and we direct patients towards these.61

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There is no evidence to support the use of drugs traditionally used for the treatment of organic movement disorders in patients with FMD. Medical and surgical interventions are often harmful to patients with FMD,30,35 and part of successful treatment is removal of unne cessary medications and avoidance of unnecessary tests and surgical treatments. The only exception to this is provided by studies of intrathecal baclofen in patients with fi xed dystonia and CRPS1, but these results carry important caveats. An initial controlled study in a small group of patients gave impressive results,62 but a follow-up study of a larger group of patients63 found treatment-related com-plications to be high, although a benefi cial eff ect was seen in many patients. The diffi culty with both studies is that the systemic eff ects of intrathecal baclofen cannot be adequately controlled, and therefore patients are systematically unmasked to the intervention. We would urge caution with the use of this invasive treatment given evidence of dramatic placebo response of patients with fi xed dystonia to other treatments.31 We have highlighted earlier the diff erence of specialist opinion regarding the nature of the disorder in patients with fi xed dystonia. Despite this diff erence in opinion, there is no need to delay eff ective management, because delay is associated with worse outcome and, in some patients, the develop ment of irreversible contractures.30 The key component of treatment is rapid early mobil-isation with suitable holistic manage ment of pain (with emphasis on techniques used in CRPS1 such as desensitisation). Surgical intervention and prolonged immobilisation should be avoided.

There is some evidence that psychological inter vention, in the form of either psychodynamic psycho therapy64 or more pragmatic symptom-based cognitive-behavioural therapy,65 might be helpful for patients with functional motor symptoms, including FMD. These techniques are only applicable to those patients who accept that psychological or behavioural inter ventions are valid methods of treatment for their physical symptoms. Like-wise, there is evidence that a subset of patients who are willing to take antidepressants (in this study, those diagnosed with primary conversion disorder and not those with somatisation disorder) can benefi t from this treatment.66

Physical rehabilitation has face validity as a treatment to manage motor symptoms, but there are few trials upon which to base opinion. There is evidence that a multidisciplinary approach combining physical and psychological treatment can be eff ective for some patients.30 This intensive (often inpatient) treatment is expensive and will always have limited availability. In a retrospective, case-control study, a brief (5 day) intensive inpatient physical therapy programme produced major self-rated improve ment in symptoms in more than 60% of participants (n=48) compared with 22% of control individuals (n=32) after 2 years of follow-up.67 This

study used an explana tory model of symptoms that was deliberately physical (abnormal motor learning) and, although psychological factors were addressed, the focus was maintained on physical symptoms and treatment. Benefi t has also been reported from a simple 12-week programme of supervised low-to-medium intensity walking in patients with FMD.68 Such fi ndings, if confi rmed by further studies, suggest that physical interventions (perhaps combined with symptom-focused cognitive-behavioural techniques65) may provide an eff ective and acceptable means of symptom management.

Placebo interventions can have strong eff ects in patients with FMD,31 but evidence for long-term benefi t is absent and the ethics of such treatments are hotly debated.69 In this vein, transcranial magnetic stimulation has been reported to be of benefi t in patients with FT, with investigators suggesting a possible real eff ect of stimulation.70 However, the unmasked nature of the intervention makes a placebo eff ect likely.

PrognosisLong-term follow-up studies are confounded by the manner in which cases are diagnosed—typically by tertiary movement disorder clinics where patients with brief transient symptoms will be missed. In these studies, about half of patients report some improvement in symptoms at long-term (3–5 years) follow-up, although most patients remain out of work due to illness.71,72 Good prognostic features include a short duration of illness, perception by the patient of eff ective management by the clinician, and the presence of depression or anxiety (which is therefore amenable to psychiatric treat ment).71,72

Future workThis Review reports several areas in which evidence-based knowledge is limited. With specifi c reference to FMD, we wish to highlight the following areas and important questions.

Diagnostic tests and criteriaThe discussion of FT shows how clinical (and simple electrophysiological) tests can be used to make a positive diagnosis. This process urgently needs to be extended to other movement disorders, in particular to patients with abnormal postures. If successful, use of this process could lead to new diagnostic criteria, which would be based on these positive clinical features and rely less on associations with psychological factors or with the notion of (unspecifi ed) incongruity with organic movement disorders.

ResearchBy contrast with some functional disorders in which symptoms are subjective (pain, sensory loss, or disturb-ance), functional motor disorders such as FMD provide

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researchers with a measurable entity that refl ects the underlying symptom. We suggest, therefore, that patients with functional motor disorders, in particular FMD, are the natural group to include in future research studies. Research studies such as those reviewed herein show that such patients can participate in research and that informative results can be obtained.

TreatmentThere is a clear and urgent need for treatment studies in FMD and other functional neurological disorders. The acceptability of treatment approaches and the availability of those who might deliver treatment should be considered when planning clinical trials. In this regard, patients with FMD may not accept that there is an important psychological dimension to their symp-toms, and therefore they might be less likely to accept treatments based solely on psychotherapy or cognitive-behavioural therapy. However, research on symptom-focused cognitive-behavioural therapy approaches and simple physical interventions point towards workable interventions which, if given early in the course of the illness, could produce benefi t in these patients.

EducationNone of the aforementioned suggested changes is likely to happen unless concerted eff orts are made to increase interest and knowledge about FMD among movement disorder specialists. Through this process, patients will be most likely to receive early positive diagnoses, avoid iatrogenic harm by unnecessary investigations and treat-ments, benefi t from world-class research, and receive eff ective treatment in a timely manner.

ConclusionsWe have described here how the correct diagnosis of FMD should rely on positive clinical characteristics and not on the presence of psychological trauma. The historical emphasis on psychological trauma as a triggering factor has perhaps skewed research agendas and neurological interest in these patients, and has certainly alienated many patients who cannot believe that their physical symptoms are related to psycho-logical trauma. We do not aim to minimise the importance of psychological factors (anxiety, depression, arousal, and attention) in such patients, but rather to

Search strategy and selection criteria

For the purposes of this Review, we searched Medline between 1975 and December, 2011, for articles with the keywords “psychogenic”, “functional”, “conversion”, “movement disorder”, “parkinsonism”, “tremor”, “dystonia”, “myoclonus”, “chorea”, “tics”, and “gait”. We selected papers relevant to diagnosis, treatment, and pathophysiology.

point out that a dogmatic and relentless search for a clear triggering psychological trauma may be misguided and unhelpful.

One additional benefi t of rebalancing the approach to FMD and functional disorders in general is that it might allow us to reconsider some of the symptoms that are present in our patients with organic neurological dis-orders. Any practising neurologist would recognise that patients with the same organic disease of apparently similar severity manifest symptoms in diff ering ways, which can have a dramatic eff ect on disability and quality of life. This phenomenon, often called functional overlay, is, we would suggest, often ignored as a non-symptom that interferes with the neurological management of patients. However, under standing the pathophysiology of this overlay and knowing how to treat it—knowledge that is likely to come from research into pure functional disorders—could be of substantial benefi t to patients with organic disease. The common occurrence of physical triggering events such as illness or injury in patients with pure functional symptoms is itself a pointer towards an important overlap between organic and non-organic illness.5

Although we agree that FMD and other functional disorders do represent a crisis for neurology, it is not an unsolvable one. We believe that now is the time for the movement disorder and wider neurological community, in cooperation with psychiatry, psychology, and physical therapy services, to lead the search for solutions.

ContributorsMJE and KPB generated an outline for the paper. MJE wrote the fi rst

draft and MJE and KPB revised this draft.

Confl icts of interestMJE is supported by a National Institute for Health Research (NIHR)

Clinician Scientist Fellowship; has received funding from the UK

Dystonia Society and Parkinson’s UK; receives royalties from The

Oxford Specialist Handbook of Parkinson’s Disease and Other

Movement Disorders (Oxford University Press, 2008); and has received

honoraria for speaking engagements from the Movement Disorders

Society and UCB. KPB has received funding for travel from

GlaxoSmithKline, Orion Corporation, Ipsen, and Merz

Pharmaceuticals; serves on the editorial boards of Movement Disorders and Therapeutic Advances in Neurological Disorders; receives royalties

from the publication of The Oxford Specialist Handbook of

Parkinson’s Disease and Other Movement Disorders (Oxford

University Press, 2008); received speaker honoraria from

GlaxoSmithKline, Ipsen, Merz Pharmaceuticals, and Sun

Pharmaceutical Industries; and has received research support from

Ipsen and the Halley Stewart Trust through the Dystonia Society UK

and the Wellcome Trust MRC strategic neurodegenerative disease

initiative award (reference number WT089698).

AcknowledgmentsMJE is supported by an NIHR Clinician Scientist Grant. NIHR had no

involvement in the writing of the paper or in the decision to submit for

publication.

References1 Stone J, Carson A, Duncan R, et al. Who is referred to neurology

clinics?—the diagnoses made in 3781 new patients. Clin Neurol Neurosurg 2010; 112: 747–51.

2 Hallett M. Psychogenic movement disorders: a crisis for neurology. Curr Neurol Neurosci Rep 2006; 6: 269–71.

Page 10: Functional (psychogenic) movement disorders: merging mind and brain

www.thelancet.com/neurology Vol 11 March 2012 259

Review

3 Espay AJ, Goldenhar LM, Voon V, et al. Opinions and clinical practices related to diagnosing and managing patients with psychogenic movement disorders: an international survey of movement disorder society members. Mov Disord 2009; 24: 1366–74.

4 Kanaan R, Armstrong D, Barnes P, et al. In the psychiatrist’s chair: how neurologists understand conversion disorder. Brain 2009; 132: 2889–96.

5 Stone J, Edwards MJ. How “psychogenic” are psychogenic movement disorders? Mov Disord 2011; 26: 1787–88.

6 Marsden CD. Hysteria—a neurologist’s view. Psychol Med 1986; 16: 277–88.

7 Trimble MR. Functional diseases. BMJ 1982; 285: 1768–70.

8 Stone J, Wojcik W, Durrance D, et al. What should we say to patients with symptoms unexplained by disease? The “number needed to off end”. BMJ 2002; 325: 1449–50.

9 Factor SA, Podskalny GD, Molho ES. Psychogenic movement disorders: frequency, clinical profi le, and characteristics. J Neurol Neurosurg Psychiatry 1995; 59: 406–12.

10 Williams DT, Ford B, Fahn S. Phenomenology and psychopathology related to psychogenic movement disorders. Adv Neurol 1995; 65: 231–57.

11 Anderson KE, Gruber-Baldini AL, Vaughan CG, et al. Impact of psychogenic movement disorders versus Parkinson’s on disability, quality of life, and psychopathology. Mov Disord 2007; 22: 2204–09.

12 Carson A, Stone J, Hibberd C, et al. Disability, distress and unemployment in neurology outpatients with symptoms ‘unexplained by organic disease’. J Neurol Neurosurg Psychiatry 2011; 82: 810–13.

13 Bermingham S, Hague J, Parsonage M. The cost of somatisation among the working age population of England for the year 2008/2009. Mental Health in Family Medicine 2011; 7: 71–84.

14 Knapp M, Prince M, Albanese E, et al. Dementia UK: The Full Report. London: Alzheimer’s Society, 2007.

15 Schwingenschuh P, Pont-Sunyer C, Surtees R, et al. Psychogenic movement disorders in children: a report of 15 cases and a review of the literature. Mov Disord 2008; 23: 1882–88.

16 Benbadis SR, Agrawal V, Tatum WO. How many patients with psychogenic nonepileptic seizures also have epilepsy? Neurology 2001; 57: 915–17.

17 Ranawaya R, Riley D, Lang A. Psychogenic dyskinesias in patients with organic movement disorders. Mov Disord 1990; 5: 127–33.

18 Onofrj M, Bonanni L, Manzoli L, et al. Cohort study on somatoform disorders in Parkinson disease and dementia with Lewy bodies. Neurology 2010; 74: 1598–606.

19 van Poppelen D, Saifee TA, Schwingenschuh P, et al. Attention to self in psychogenic tremor. Mov Disord 2011; 26: 2575–76.

20 Kenney C, Diamond A, Mejia N, et al. Distinguishing psychogenic and essential tremor. J Neurol Sci 2007; 263: 94–99.

21 Zeuner KE, Shoge RO, Goldstein SR, et al. Accelerometry to distinguish psychogenic from essential or parkinsonian tremor. Neurology 2003; 61: 548–50.

22 Kumru H, Begeman M, Tolosa E, et al. Dual task interference in psychogenic tremor. Mov Disord 2007; 22: 2077–82.

23 Kumru H, Valls-Sole J, Valldeoriola F, et al. Transient arrest of psychogenic tremor induced by contralateral ballistic movements. Neurosci Lett 2004; 370: 135–39.

24 Deuschl G, Koster B, Lucking CH, et al. Diagnostic and pathophysiological aspects of psychogenic tremors. Mov Disord 1998; 13: 294–302.

25 Schwingenschuh P, Katschnig P, Seiler S, et al. Moving toward “laboratory-supported” criteria for psychogenic tremor. Mov Disord 2011; 26: 2509–15.

26 Edwards MJ. Dystonia: a clinical approach. Acta Neurol Taiwan 2008; 17: 219–27.

27 Bhatia KP, Bhatt MH, Marsden CD. The causalgia-dystonia syndrome. Brain 1993; 116: 843–51.

28 van Hilten JJ, van de Beek WJ, Roep BO. Multifocal or generalized tonic dystonia of complex regional pain syndrome: a distinct clinical entity associated with HLA-DR13. Ann Neurol 2000; 48: 113–16.

29 Lang AE. Psychogenic dystonia: a review of 18 cases. Can J Neurol Sci 1995; 22: 136–43.

30 Schrag A, Trimble M, Quinn N, et al. The syndrome of fi xed dystonia: an evaluation of 103 patients. Brain 2004; 127: 2360–72.

31 Edwards MJ, Bhatia KP, Cordivari C. Immediate response to botulinum toxin injections in patients with fi xed dystonia. Mov Disord 2011; 26: 917–18.

32 Avanzino L, Martino D, van de Warrenburg BP, et al. Cortical excitability is abnormal in patients with the “fi xed dystonia” syndrome. Mov Disord 2008; 23: 646–52.

33 Quartarone A, Rizzo V, Terranova C, et al. Abnormal sensorimotor plasticity in organic but not in psychogenic dystonia. Brain 2009; 132: 2871–77.

34 Katschnig P, Edwards MJ, Schwingenschuh P, et al. Mental rotation of body parts and sensory temporal discrimination in fi xed dystonia. Mov Disord 2010; 25: 1061–67.

35 Edwards MJ, Alonso-Canovas A, Schrag A, et al. Limb amputations in fi xed dystonia: a form of body integrity identity disorder? Mov Disord 2011; 26: 1410–14.

36 Brown P, Thompson PD. Electrophysiological aids to the diagnosis of psychogenic jerks, spasms, and tremor. Mov Disord 2001; 16: 595–99.

37 Duggal HS, Nizamie SH. Bereitschaftspotential in tic disorders: a preliminary observation. Neurol India 2002; 50: 487–89.

38 Obeso JA, Rothwell JC, Marsden CD. Simple tics in Gilles de la Tourette’s syndrome are not prefaced by a normal premovement EEG potential. J Neurol Neurosurg Psychiatry 1981; 44: 735–38.

39 Esposito M, Edwards MJ, Bhatia KP, et al. Idiopathic spinal myoclonus: a clinical and neurophysiological assessment of a movement disorder of uncertain origin. Mov Disord 2009; 24: 2344–49.

40 van der Salm SM, Koelman JH, Henneke S, et al. Axial jerks: a clinical spectrum ranging from propriospinal to psychogenic myoclonus. J Neurol 2010; 257: 1349–55.

41 Baik JS, Lang AE. Gait abnormalities in psychogenic movement disorders. Mov Disord 2007; 22: 395–99.

42 Jordbru AA, Smedstad LM, Moen VP, Martinsen EW. Identifying patterns of psychogenic gait by video-recording. J Rehabil Med 2012; 44: 31–35.

43 Keane JR. Hysterical gait disorders: 60 cases. Neurology 1989; 39: 586–89.

44 Lempert T, Brandt T, Dieterich M, et al. How to identify psychogenic disorders of stance and gait. A video study in 37 patients. J Neurol 1991; 238: 140–46.

45 Stone J, Warlow C, Sharpe M. The symptom of functional weakness: a controlled study of 107 patients. Brain 2010; 133: 1537–51.

46 Benaderette S, Zanotti FP, Apartis E, et al. Psychogenic parkinsonism: a combination of clinical, electrophysiological, and [(123)I]-FP-CIT SPECT scan explorations improves diagnostic accuracy. Mov Disord 2006; 21: 310–17.

47 Gupta A, Lang AE. Psychogenic movement disorders. Curr Opin Neurol 2009; 22: 430–36.

48 Fahn S, Williams DT. Psychogenic dystonia. Adv Neurol 1988; 50: 431–55.

49 Shill H, Gerber P. Evaluation of clinical diagnostic criteria for psychogenic movement disorders. Mov Disord 2006; 21: 1163–68.

50 Voon V, Lang AE, Hallett M. Diagnosing psychogenic movement disorders—which criteria should be used in clinical practice? Nat Clin Pract Neurol 2007; 3: 134–35.

51 Morgante F, Edwards MJ, Espay AJ, et al. Diagnostic agreement in patients with psychogenic movement disorders. Mov Disord (in press).

52 Brown RJ. Psychological mechanisms of medically unexplained symptoms: an integrative conceptual model. Psychol Bull 2004; 130: 793–812.

53 Kranick S, Ekanayake V, Martinez V, et al. Psychopathology and psychogenic movement disorders. Mov Disord 2011; 26: 1844–50.

54 Haggard P. Human volition: towards a neuroscience of will. Nat Rev Neurosci 2008; 9: 934–46.

55 Voon V, Gallea C, Hattori N, et al. The involuntary nature of conversion disorder. Neurology 2010; 74: 223–28.

56 Edwards MJ, Moretto G, Schwingenschuh P, et al. Abnormal sense of intention preceding voluntary movement in patients with psychogenic tremor. Neuropsychologia 2011; 49: 2791–93.

57 Voon V, Brezing C, Gallea C, et al. Emotional stimuli and motor conversion disorder. Brain 2010; 133: 1526–36.

Page 11: Functional (psychogenic) movement disorders: merging mind and brain

260 www.thelancet.com/neurology Vol 11 March 2012

Review

58 Voon V, Brezing C, Gallea C, et al. Aberrant supplementary motor complex and limbic activity during motor preparation in motor conversion disorder. Mov Disord 2011; 26: 2396–403.

59 Parees I, Saifee TA, Kassavetis P, et al. Believing is perceiving: self-report and actigraphy mismatch in psychogenic tremor. Brain 2011; published online Nov 10. DOI:10.1093/brain/awr292.

60 Stamelou M, Edwards MJ, Espay AJ, et al. Movement disorders on YouTube—caveat spectator. N Engl J Med 2011; 365: 1160–61.

61 Stone J. Functional and dissociative neurological symptoms: a patient’s guide. http://www.neurosymptoms.org/ (accessed Jan 27, 2012).

62 van Hilten BJ, van de Beek WJ, Hoff JI, et al. Intrathecal baclofen for the treatment of dystonia in patients with refl ex sympathetic dystrophy. N Engl J Med 2000; 343: 625–30.

63 van Rijn MA, Munts AG, Marinus J, et al. Intrathecal baclofen for dystonia of complex regional pain syndrome. Pain 2009; 143: 41–47.

64 Hinson VK, Weinstein S, Bernard B, et al. Single-blind clinical trial of psychotherapy for treatment of psychogenic movement disorders. Parkinsonism Relat Disord 2006; 12: 177–80.

65 Sharpe M, Walker J, Williams C, et al. Guided self-help for functional (psychogenic) symptoms: a randomized controlled effi cacy trial. Neurology 2011; 77: 564–72.

66 Voon V, Lang AE. Antidepressant treatment outcomes of psychogenic movement disorder. J Clin Psychiatry 2005; 66: 1529–34.

67 Czarnecki K, Thompson JM, Seime R, et al. Functional movement disorders: successful treatment with a physical therapy rehabilitation protocol. Parkinsonism Relat Disord 2011; published online Nov 21. DOI:10.1016/j.parkreldis.2011.10.011.

68 Dallocchio C, Arbasino C, Klersy C, et al. The eff ects of physical activity on psychogenic movement disorders. Mov Disord 2010; 25: 421–25.

69 Shamy MC. The treatment of psychogenic movement disorders with suggestion is ethically justifi ed. Mov Disord 2010; 25: 260–64.

70 Dafotakis M, Ameli M, Vitinius F, et al. Transcranial magnetic stimulation for psychogenic tremor—a pilot study. Fortschr Neurol Psychiatr 2011; 79: 226–33.

71 Jankovic J, Vuong KD, Thomas M. Psychogenic tremor: long-term outcome. CNS Spectr 2006; 11: 501–08.

72 Thomas M, Vuong KD, Jankovic J. Long-term prognosis of patients with psychogenic movement disorders. Parkinsonism Relat Disord 2006; 12: 382–87.