Brain Advance Access originally published online on September 1, 2004
Brain 2004 127(10):2360-2372; doi:10.1093/brain/awh262
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Brain Vol. 127 No. 10 © Guarantors of Brain 2004; all rights reserved
The syndrome of fixed dystonia: an evaluation of 103 patients
1 University Department of Clinical Neurosciences, Royal Free and University College Medical School and 2 Institute of Neurology, University College London, London, UK
Correspondence to: Dr Anette Schrag, University Department of Clinical Neurosciences, Royal Free and University College Medical School, London NW3 2PF, UK E-mail: a.schrag{at}medsch.ucl.ac.uk
Received November 19, 2003. Revised May 10, 2004. Second revision on June 2, 2004. Accepted June 4, 2004.
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Summary |
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We describe the clinical features of 103 patients presenting with fixed dystonia and report the prospective assessment and investigation of 41 of them. Most patients were female (84%) and had a young age of onset [mean 29.7 (SD 13.1) years]. A peripheral injury preceded onset in 63% and spread of dystonia to other body regions occurred in 56%. After an average follow-up of 3.3 years (overall disease duration 8.6 years), partial (19%) or complete (8%) remission had occurred in a minority of patients. The fixed postures affected predominantly the limbs (90%), and rarely the neck/shoulder region (6%) or jaw (4%). In the prospectively studied group, pain was present in most patients and was a major complaint in 41%. Twenty percent of patients fulfilled criteria for Complex Regional Pain Syndrome (CRPS). No consistent investigational abnormalities were found and no patient tested (n = 25) had a mutation in the DYT1 gene. Thirty-seven percent of patients fulfilled classification criteria for documented or clinically established psychogenic dystonia; 29% fulfilled DSM-IV (Diagnostic and statistical manual of mental disorders, 4th edition) criteria for somatization disorder, which was diagnosed only after examination of the primary care records in many cases; and 24% fulfilled both sets of criteria. Ten percent of the prospectively studied and 45% of the retrospectively studied patients did not have any evidence of psychogenic dystonia, and detailed investigation failed to reveal an alternative explanation for their clinical presentation. Detailed, semi-structured neuropsychiatric assessments in a subgroup of 26 patients with fixed dystonia and in a control group of 20 patients with classical dystonia revealed dissociative (42 versus 0%, P = 0.001) and affective disorders (85 versus 50%, P = 0.01) significantly more commonly in the fixed dystonia group. Medical and surgical treatment was largely unsuccessful. However, seven patients who underwent multidisciplinary treatment, including physiotherapy and psychotherapy, experienced partial or complete remission. We conclude that fixed dystonia usually, but not always, occurs after a peripheral injury and overlaps with CRPS. Investigations are typically normal, but many patients fulfil strict criteria for a somatoform disorder/psychogenic dystonia. In a proportion of patients, however, no conclusive features of somatoform disorder or psychogenic disorder can be found and, in these patients, whether this disorder is primarily neurological or psychiatric remains an open question. Whilst the prognosis is overall poor, remissions do occur, particularly in those patients who are willing and able to undergo multidisciplinary treatment including physiotherapy and psychotherapy, suggesting that this type of treatment should be recommended to these patients.
Key Words: fixed dystonia; trauma; psychogenic; complex regional pain syndrome
Abbreviations: CRPS = complex regional pain syndrome; DSM-IV = Diagnostic and statistical manual of mental disorders, 4th edition; SCAN = Schedules of Assessment in Neuropsychiatry
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Introduction |
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Dystonia is defined as abnormal muscle contractions frequently holding a body part in an abnormal position, often associated with tremor (Fahn et al., 1998
). Primary or idiopathic dystonia has no identifiable cause although it can be due to a genetic abnormality (Bressman et al., 1998), whereas secondary or symptomatic dystonia can result from numerous environmental and neurodegenerative causes (Calne and Lang, 1988). Primary or idiopathic dystonia is typically mobile, brought on by attempts to move (action dystonia) and in others by specific tasks (e.g. writing); the abnormal posture can frequently be overcome by using sensory tricks (gestes antagonistes), e.g. touching the face in torticollis. Immobile, fixed dystonic postures are not part of the presentation of primary dystonia until the advanced stages, and even then are uncommon (Marsden, 1976). Fixed dystonic postures may, however, occur in secondary dystonia, for example due to acquired basal ganglia lesions or neurodegenerative disorders such as corticobasal degeneration. They can also occur in conditions that can resemble dystonia such as stiff limb syndrome and abnormal postures due to a mechanical cause (e.g. atlanto-axial dislocation) (Suchowersky and Calne, 1988). A problematic group of patients develops post-traumatic fixed dystonia (Jankovic and Van der Linden, 1988; Tarsy, 1998), which may also be associated with complex regional pain syndrome (CRPS; Table 1), when it has been termed causalgia-dystonia syndrome (Bhatia et al., 1993).
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The history, clinical examination and appropriate investigations may reveal the origin of the fixed dystonic postures in some cases. In a proportion of patients with isolated fixed dystonia, however, no such cause is found and some believe that this is a form of psychogenic condition (Lang, 1995
). There is ongoing controversy as to whether isolated fixed dystonia with or without preceding peripheral injury is due to an organic or psychogenic cause (Goldman and Ahlskog, 1993; Weiner, 2001; Sa et al., 2003). To date, only small series of cases of fixed dystonia, with or without preceding peripheral injury, have been published and the clinical features, associated comorbidity and risk factors underlying this syndrome have not been delineated. We therefore undertook a study to describe the clinical characteristics of a large number of patients with fixed dystonia without evidence of basal ganglia lesions or a progressive neurodegenerative disorder, and to study its associated features, risk factors and psychiatric comorbidity.
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Methods |
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Patients
The clinical information on all patients with fixed dystonia who had been seen previously by the authors (or the late Professor David Marsden) was extracted from their medical records. Fixed dystonia was defined as immobile dystonic postures that did not return to the neutral position at rest; patients with fixed dystonia due to an identifiable cause or fixed dystonia in the context of advanced generalized dystonia or parkinsonism were excluded. Eighty-eight patients seen between 1981 and 1999 were identified. Of these we chose to contact 46 patients who had been seen more recently (1989–1999), 31 of whom (67%) agreed to be reviewed. Three of these 31 were subsequently not able to participate and another reported the symptoms had resolved spontaneously. We also saw another 15 patients with fixed dystonia between 1999 and 2002, of whom 14 agreed to participate. Thus, from the overall group of 103 patients whose records we reviewed (retrospective group), we were able to study 41 subjects personally for the purpose of this study (henceforth called the prospective group; Fig. 1). Twenty-seven patients who participated in the prospective part of the study were also invited to participate in a neuropsychiatric evaluation, which only one patient refused. There was no difference between participants and non-participants with regard to gender, age or disease duration.
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Twenty patients with classical, mobile dystonia matched for degree of disability (according to overall clinical judgement and to the Functional Disability score (Jahanshahi and Marsden, 1990
) (Table 2) were recruited as controls, and also underwent neuropsychiatric assessment. Seven of these had dystonia due to a brain injury or stroke in the basal ganglia, six due to perinatal injury, three had childhood onset generalized dystonia due to a mutation in the DYT1 gene, and four had classical cervical dystonia (Fig. 1).
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Assessment
For the prospective assessments, all 41 patients underwent a neurological examination and semi-structured interview that assessed clinical features, precipitating events, potential risk factors, evolution, treatment responses and clinical course. Standard investigations for secondary dystonia (Calne and Lang, 1988
) were normal in all patients; 18 patients had additionally undergone CSF examination, and genetic tests for mutations in the DYT1 gene were performed in 25 patients. MRI of the brain and spine, nerve conduction studies and electromyography were performed in all prospectively studied patients; somatosensory evoked potentials in 22 patients; central motor conduction time to affected muscles in eight patients; and in three patients with stimulus-sensitive movements cutaneomuscular reflexes were examined.
In 26 patients, a neuropsychiatric assessment was performed by a neurologist with several years training in neuropsychiatry (A.S.) using the Schedules of Assessment in Neuropsychiatry (SCAN; Aboraya et al., 1998). SCAN is a computer-based, comprehensive and validated psychiatric assessment tool (Brugha et al., 1999), which is administered by a clinically trained interviewer and includes a section on medically unexplained symptoms. All symptoms that gave rise to multiple consultations with doctors, self-medication and/or change of lifestyle that were not fully explained by any detectable organic pathology following appropriate investigations were recorded. The primary care records were examined in 17 patients who gave consent; these were used to confirm the results from the SCAN interview section on medically unexplained symptoms. Sixteen patients also agreed to be tested using the Structured Assessment of Personality Disorder. This is a standardized telephone interview, validated in patients with psychiatric disorders (Pilgrim et al., 1993), conducted with a person named by the subject who has known them for at least 5 years. The subjects' consent was obtained according to the Declaration of Helsinki and the study was approved by the Joint Research Ethics Committee of the National Hospital for Neurology and Neurosurgery and the Institute of Neurology.
Diagnostic criteria
All psychiatric diagnoses were made according to the Diagnostic and statistical manual of mental disorders, 4th edition (DSM-IV; American Psychiatric Association, 1994). Thus, a diagnosis of somatization disorder was based on the DSM-IV criteria of somatization disorder, which requires a history of at least eight unexplained symptoms in four or more body systems with onset before the age of 30 years. A diagnosis of psychogenic dystonia was made according to the criteria of Fahn and Williams (1988), which classify dystonia as psychogenic based on degree of certainty into: (i) documented; (ii) clinically established; (iii) probable; and (iv) possible (Table 3). As only the first two categories provide a clinically useful degree of diagnostic certainty, they have been combined to one category of ‘clinically definite’ (Williams et al., 1995). Fixed dystonic postures are considered incongruent with typical primary dystonia and can be seen in patients with unequivocal psychogenic dystonia. However, in order to avoid a circular argument (i.e. a priori presumption of a diagnosis of psychogenic dystonia), we excluded fixed dystonia and related pain or sensory symptoms as prima facie evidence of psychogenic dystonia or somatoform disorder.
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Statistical analysis
The majority of data are reported as percentages of the overall total sample of 103 patients or of the subgroups of 41 prospectively or 62 retrospectively assessed patients, as appropriate. Comparisons between categorical data were made using
2 or Fisher's Exact test (if numbers were small); continuous data were compared using t-tests if the data were parametric, and Mann–Whitney tests, if the data were non-parametric. |
Results |
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Among the total 103 patients, 41 were studied prospectively and 62 retrospectively. Their demographic and clinical characteristics were comparable (Table 4). Most patients had already had symptoms for several years before they were first assessed at our hospital.
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Demographics and potential risk factors
In the prospective group, 83% of patients were female and mean age of onset was 30.5 (SD 13) years (Table 4). Only three patients (7%) had onset after the age of 50 years, but onset in teenage years was not uncommon (seven patients; 17%). No patient reported the use of dopamine receptor blockers before onset. Nine (22%) reported a possible family history of a movement disorder and one of complex regional pain syndrome (Table 5B; this table is available as supplementary material at Brain Online). However, none of the 25 patients tested was positive for the DYT1 mutation. Eight prospectively studied patients (20%) reported a previous episode of a movement disorder and 17 patients (41%) reported previous disturbance of the affected limb (Table 5B).
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In the retrospective group, the demographic distribution was similar with 85% female patients with an average age of onset of 29.2 (SD 13) years. Only five patients (8%) had developed symptoms after the age of 50 years, but 18 patients (29%) had onset before age 20 with the youngest at 11 years.
Precipitating event
In the prospectively studied fixed dystonia group, the onset of dystonia occurred after an injury in 28 (68%), significantly more than the 5% in the dystonia control group (P < 0.0001). The injuries were mainly of soft tissues, but limb overuse, fractures and operations (mainly for existing pain) were also reported (Table 5A). Deterioration of dystonia after a further injury, vigorous manipulation or operation was reported by ten patients—even if no injury had occurred before the onset (n = 4). In 15% of patients, dystonia first started or deteriorated markedly during or after immobilization in a plaster cast. In no patient treated with immobilization in a plaster cast did this result in a lasting improvement of symptoms. Other symptoms prior to onset included abscesses or sensory symptoms in the affected limb, back pain or an asthma attack (Table 5A). A psychological stressor, psychotherapeutic treatment or a severe psychiatric illness with clear temporal relationship to the onset of dystonia was reported in five patients, two of whom also reported an injury before onset. In four patients (10%), no precipitating event could be identified (Table 5A).
In the retrospectively analysed group, the pattern of injuries was similar, with injury before onset in 60% (including two whiplash and one mild head-injury; Table 4), flu-like illness in two, Bell's palsy in one, focal paraesthesiae in three, spontaneous pain in six (including one with a radiculopathy), psychological trauma in one, and no precipitating event in 19% of patients. In 8% of these patients, dystonia first started or deteriorated markedly during or after immobilization in a plaster cast.
Characteristics of dystonia
In the prospective group, the right side was involved in 51% at the onset, the left in 44% and both sides in some patients (5%). The distal limb was more commonly affected (n = 40, 98%) than the proximal limb (n = 8, 20%), and one patient had fixed dystonia of the shoulder (Table 4). The dystonia typically developed subacutely over days or weeks (Table 5b). The maximum delay to onset of dystonia in one patient was 1 year. Typically, in initial stages, it had still been possible to return the limb to the neutral position but soon afterwards the limb would become fixed and painful to attempt to return to the neutral position. In 61%, dystonia spread further; whereby spread could occur to more proximal parts of the same limb, the contralateral limb, an ipsilateral limb, the neck or the dystonia could become generalized (Tables 5A and B). The most common pattern of abnormal posture in the arms was flexion of the fingers at the metacarpophalangal or interphalangeal joints. Typically, digits 4 and 5 were more affected than digits 2 and 3, and the thumb was least affected or not affected. In the legs inversion and plantar-flexion of the foot and curling of toes were most common (Figs 2 and 3), but other postures occurred. No patient had a geste antagoniste, and dystonia was never action-induced. No patient displayed overflow dystonia in other limbs when attempting to move the affected body part. Eight patients had had manipulation under general anaesthesia: two had persistent contractures but the remaining six had a full range of motion.
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In the retrospective sample, the pattern of distribution was similar, but four patients had non-mechanical jaw occlusion and deviation. In only half of these patients, who had been followed for a shorter period, spread of the dystonia beyond the site of onset had occurred.
Associated features
Other movement disorders seen or reported in the prospective sample included additional painful spasms (n = 26, 63%), tremor in the affected (n = 10, 24%) or other body parts (n = 6, 15%), and reported involuntary jerks (n = 4, 10%). When seen, the tremor was often irregular and jerky, and had clear features of psychogenic tremor (entrainment, distractibility, variable amplitude and frequency) in four patients (10%). Six patients had additional movement disorders (15%, Table 5B). All patients had severely restricted range of movement. Weakness in the affected limb was seen in 18 (44%), but power in the affected limb was often difficult to test due to the fixed posture associated with spasms and pain. In 10 patients (24%), there was clear ‘give-way’ weakness and, typically, there was increased tone on passive movements in muscles that could not be moved actively (Table 5B). Secondary wasting was, perhaps surprisingly, uncommon (17%). Reflexes were normal or only slightly increased and symmetrical, and the plantar responses were flexor in all patients. Infections secondary to abnormal hand position were a problem in some patients, particularly those whose fingers pressed into their palms. One patient had developed severe recurrent infections of the affected leg.
Continuous pain at rest was a feature in all but three prospectively studied patients, and a major component in 41%. Features of CRPS—including allodynia/hyperpathia, trophic or sudomotor changes, and temperature or colour changes—were seen in 18 (44%), but only eight patients (20%) fulfilled criteria for CRPS (Stanton-Hicks et al., 1995) (Tables 1 and 5). Hypoaesthesia was present in 25 patients (61%), mostly not in a dermatomal or peripheral nerve distribution; however, one patient had a mild residual median and ulnar nerve neuropathy following previous carpal tunnel decompression and ulnar release operation before the onset of dystonia, and one patient had a longstanding radiculopathy (with onset many years before dystonia).
In the records of the retrospective group, similar clinical findings had been noted with no additional features. One patient had experienced severe recurrent infections in one leg, which led to severe gangrene eventually necessitating amputation. There had been some suggestion that these severe infections were due to self-inflicted injuries.
Investigations
In the prospectively studied patients, abnormalities were seen on brain or spine imaging in five patients—a small temporal meningioma, a small temporal pole cavity, a left frontal focal dysplasia, a small middle cerebellar peduncle lesion and a small lumbar spina bifida occulta. None of these findings was felt to be causative for the dystonia. CSF examinations (n = 18) did not reveal any abnormality in any patient. Routine EMG studies revealed active contraction in affected muscles, although this was minimal in the patients with contractures, and as electrical silence could be achieved, there was no continuous motor unit activity. Nerve conduction studies were normal in all but the two patients previously mentioned. Somatosensory evoked potentials (n = 22), central motor conduction time (n = 8) and cutaneomuscular reflexes (n = 3) were normal in all patients in whom these were tested. Radiographs revealed local osteoporosis compatible with a diagnosis of CRPS in 50% of those in whom it was performed (n = 10). None of the 25 fixed dystonia patients tested was positive for the DYT1 mutation.
No additional abnormalities were detected in the patients studied retrospectively.
Prevalence of psychiatric disorders in fixed dystonia and dystonia controls
Twenty-six prospectively studied patients with fixed dystonia and 20 patients with classic dystonia underwent structured and detailed neuropsychiatric evaluation using the SCAN interview. The groups did not differ with regard to gender ratio, age or degree of disability, but patients in the dystonia control group had had longer disease duration (Table 2).
Psychiatric comorbidity
Among those who underwent the detailed SCAN interviews, a higher rate of affective disorders since the onset of dystonia was found in the fixed dystonia group compared with the control group (50 verus 15%, P = 0.01; Table 6). Furthermore, 11 patients (42%) with fixed dystonia but none in the control group reported dissociative symptoms according to DSM-IV criteria (Table 6).
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Conversion or somatoform disorder
Clear evidence for conversion with a history of psychological distress or psychiatric disorder at the onset of the dystonia was found in two of the 26 patients with fixed dystonia who underwent the SCAN interviews (8%), and in five patients in the overall prospective group of 41 patients with fixed dystonia (12%). In addition, nine of the 41 patients with fixed dystonia (22%), but no patient with typical dystonia, reported a history of sexual trauma (P = 0.02).
A DSM-IV diagnosis of somatization disorder was made in 29% of the 41 patients in the prospective fixed dystonia group, in 38.5% of the 26 who underwent structured and detailed SCAN interviews, and in 41% of the 17 whose general practice notes were examined (Table 6). This diagnosis had been previously made in only two patients with fixed dystonia. In the remainder, the diagnosis was made only after the interview and examination of previous general practice notes (83% of the 12 patients in whom this diagnosis was made). Among the 20 control patients, this diagnosis was made in only one patient, who also suffered from a generalized anxiety disorder (5%, P = 0.01), and in none of the control patients whose general practice notes were available (P = 0.005).
Psychogenic dystonia
In the prospective group, 10 patients (24%) fulfilled criteria for ‘documented’ psychogenic dystonia, and five (12%) for ‘clinically established’ psychogenic dystonia. In four patients (10%), there was no suggestion of a psychogenic movement disorder (Tables 5B and 6).
In the retrospective sample who had not had structured assessments and examination of their primary care notes, there was a higher percentage of patients with no evidence of psychogenic dystonia (P < 0.0001; Table 7).
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Factitious disorder and litigation
In the prospective fixed dystonia group, a suspicion of factitious origin was raised in one patient with recurrent abscesses. We did not find convincing evidence for malingering in any patient, but secret video-surveillance was not used in our study. However, in one patient, a lawsuit was settled for a low sum on the advice of the patient's solicitor after he had viewed a secret video-recording recording obtained by the defence (Patient 26). Litigation concerning an initial injury was reported on direct questioning by six patients (15%) and no patient in the control group (not significant). The clinical characteristics of these patients did not differ from those not reporting litigation other than reporting more colour and temperature changes (both P <0.05). However, we did not seek to confirm litigation status by outside sources. All patients in the fixed dystonia group were on disability allowances and no patient received significant insurance payouts (by self-report).
In the retrospective group, there was suspicion in one patient of factitious origin of non-healing abscesses leading to leg amputation following gangrene.
Prognosis and treatment
The progression over time varied widely (Table 4).
In the prospective group, one third did not deteriorate further after initial progression over the first weeks or months. However, in others the dystonia spread to involve the whole limb, spread contralaterally or ipsilaterally, or became generalized—often within a short period (Table 4). In six patients (15%), dystonia deteriorated and other problems occurred such as urinary dysfunction or medically unexplained symptoms (Table 5B). In four patients (10%), the course fluctuated with relapses, often associated with a deterioration in their psychological state. Nineteen patients (46%) experienced remissions (Tables 5A and B).
In the retrospective sample, the dystonia remained focal in a higher percentage (60%; Table 4) and 10 patients had remission of symptoms (16%); however, follow-up was shorter in this patient group (Table 5A).
Treatments included a plethora of drugs, surgical treatments and non-drug treatments, often in multiple combinations. Significant, lasting improvement was seen in the prospective group following a multidisciplinary inpatient treatment combining cognitive behavioural therapy, physiotherapy, occupational therapy and psychotherapy in seven out of the seven patients who underwent this treatment. Marked improvement was also seen with a combination of physiotherapy and suggestion, and oral mexiletine, each in one patient (Table 5A). Improvement was also reported following botulinum toxin injections in eight patients, but the response ranged from no or transient improvement, to almost complete remission (when combined with positive suggestion). One patient, who had already improved considerably following a change of relationship, underwent bilateral tibial nerve neurolysis with complete remission of symptoms. Another patient who underwent subtalar fusion, however, experienced further deterioration of symptoms. Partial relief of dystonia was reported by a few patients on benzodiazepines (n = 4), baclofen (n = 3), dopaminergic drugs (n = 2), anticholinergics (n = 2) and self-medicated cannabis (n = 2). Opiates (n = 5), antiepileptic drugs (n = 1) and neuroleptics (n = 1) resulted in partial pain relief. Antidepressants were effective for the treatment of pain or depression in two patients and transcutaneous electrical nerve stimulation (TENS) was helpful in a further two. Although two of five patients experienced temporary relief of their pain following sympathectomy or sympathetic blocks, this was not sustained and two patients experienced permanent side effects including urinary dysfunction and sensory loss. Two patients derived significant improvement of pain from a spinal cord stimulator. Many patients, however, were on a large number of drugs particularly for pain including high doses of opiates, benzhexol, baclofen, and benzodiazepines, and attempts to reduce opiates were generally unsuccessful.
In the retrospective sample, the response to treatments was similar, but in four patients surgical procedures including tendon resection or transplantation, division of motor nerves and selective denervations were performed with improvement of dystonia and pain for limited periods of time. Arthrodesis to stabilize fixed foot dystonia led to initial improvement in two patients, but spread to other body parts occurred in both patients.
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Discussion |
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Clinical aspects
Fixed dystonia is an uncommon, but severely disabling condition, that usually affects young people, predominantly young women. The pattern of muscle groups involved varies widely, but limb onset is most frequent and, while the condition remains focal in a proportion of cases, spread to other muscle groups occurs in the majority. Pain is present in most patients and the abnormal posture may be accompanied by a variety of other movement disorders, sensory disturbances and features of CRPS. The overall prognosis is poor, but remissions can occur either with treatment or spontaneously.
Fixed dystonia differs from typical dystonia in a variety of ways, including the fixed posture at rest, the distribution and age at onset, the rate of progression and spread, the lack of characteristic features such as sensory tricks and action-specificity, the presence of associated features and the lack of response to traditional treatment for dystonia (see Bhatia et al., 1993). Other disorders including neurodegenerative conditions like corticobasal degeneration or stiff person syndrome can sometimes present with a fixed dystonic posture, but lack of other typical features of these conditions and normal investigations such as the absence of anti-GAD (glutamic acid decarboxylase) antibodies and continuous motor unit activity on EMG exclude these diagnoses in this cohort. However, we found considerable overlap of fixed dystonia with somatoform disorders/psychogenic dystonia. In this discussion, we will attempt to analyse the overlap of the syndrome of fixed dystonia with post-traumatic dystonia and CRPS, and somatoform and psychogenic disorders.
Overlap with post-traumatic dystonia and CRPS
Fixed dystonia most commonly occurs (or exacerbates) after a minor peripheral trauma, including operations or immobilization in a plaster cast, and these cases have been termed ‘post-traumatic dystonia’ in the past (Jankovic and Van der Linden C., 1988; Tarsy, 1998). However, fixed dystonia may also occur spontaneously without obvious precipitating factors or in association with a psychological stressor, suggesting that this may play a role in the aetiology of this condition at least in some patients. There is also considerable overlap of fixed dystonia with CRPS (for a review see Schott, 2001). Fixed dystonic postures are one of the movement disorders associated with CRPS, and the combination of dystonia with CRPS has been termed the causalgia-dystonia syndrome (Bhatia et al., 1993). The features of some of the patients in our series resemble those previously reported in dystonia with CRPS; these include age of onset, female preponderance, weakness, spasms, occasional tremor or myoclonus, difficulty initiating movement, pain and sensory disturbances (Schwartzman and Kerrigan, 1990; Veldman et al., 1993; Birklein et al., 2000; van Hilten et al., 2001). Not all patients with fixed dystonia, however, had features of CRPS and, in many cases, whilst some features of CRPS were present (hyperaesthesia, colour change or coldness of the limb), these were not sufficient to fulfil the full criteria for CRPS (Stanton-Hicks et al., 1995). Only two patients had abnormalities on nerve conduction studies, with a clear temporal relationship to onset of symptoms suggesting CRPS type II (CRPS with nerve injury) in only one. Nevertheless, there appeared to be significant overlap between these conditions in at least some of these patients.
Mechanism/pathophysiology
The mechanism by which dystonia may be related to post-traumatic movement disorders and CRPS is poorly understood. Although reports about effectiveness of sympathectomies in CRPS have suggested that this condition is mediated through the sympathetic nervous system, this view has recently been called into question (Schott, 1995; Baron et al., 1999). Inflammation has also been reported to be involved in the development of CRPS following injury, at least in the early stages (Birklein et al., 2001). Other peripheral mechanisms such as sensitization of peripheral nociceptors, or ectopic or ephaptic transmission of nerve impulses, have been suggested as a possible mechanism of CRPS and post-traumatic movement disorders (Jankovic, 1994; Schott, 1986b, 2001). However, spread to ipsilateral, axial, and contralateral muscles may occur in fixed dystonia, as in CRPS and post-traumatic dystonia. This suggests that, at least in these cases, such peripheral mechanisms are unlikely to explain the development of abnormal movements after injury. Impairment of interneuronal circuits at the spinal or brainstem level and central synaptic reorganization analogous to that following amputation have been suggested as possible mechanisms that may lead to such sequelae even after a minor peripheral injury (van Hilten et al., 2001). However, none of these mechanisms can explain the occurrence of dystonia or CRPS in the absence of an injury. It is well known that a variety of systemic or central causes—including pregnancy and CNS disorders such as stroke or multiple sclerosis (Greene et al., 1990; Butler et al., 2000; Schott, 2001)—can lead to CRPS, and that other reported causes of CRPS with abnormal movements also include somatoform disorders and even malingering (Kurlan et al., 1997; Verdugo and Ochoa, 2000). Verdugo and Ochoa (2000) found that none of 58 patients fulfilling criteria for CRPS with abnormal movements had evidence of structural nerve, spinal cord or intracranial damage; all their patients exhibited non-organic signs and, in some cases, malingering was documented. They concluded that abnormal movements in CRPS indicate a somatoform or malingering origin. However, others have reported conflicting results (Birklein et al., 2000) and have disputed an association between CRPS and psychological disorders (Lynch, 1992; Ciccone et al., 1997). The finding of abnormalities of reciprocal inhibition of H-reflexes, usually seen in typical dystonia (Koelman et al., 1999; van de Beek et al., 2002a,b), abnormal stretch reflexes (van Hilten et al., 2001; van de Beek et al., 2002b), a high prevalence of HLA-DR 13 (van Hilten et al., 2000b) in dystonia associated with CRPS, and changes in contralateral thalamic perfusion on 123iodine-labelled single photon emission computed tomography (SPECT) imaging in cases of CRPS (Fukumoto et al., 1999) have been interpreted as evidence for an organic aetiology in dystonia in CRPS. However, whether these central or peripheral changes are primary or secondary to the clinical abnormalities remains a matter of dispute, and the finding of a HLA-DR 13 association has yet to be replicated in other studies. In addition, functional neuroimaging can demonstrate changes in both classic dystonia and somatoform disorders (Vuilleumier et al., 2001; Hakala et al., 2002) and, at present, this technique has not been useful in allowing an aetiological classification of this disorder.
Overlap with somatoform and psychogenic disorders
In this study, we have examined whether patients with fixed dystonia (with or without CRPS) have a psychogenic disorder after alternative secondary causes were excluded. The results show that a substantial proportion of patients with fixed dystonia clearly fulfil criteria for a psychogenic dystonia (37%) or somatization disorder (29%). Although fixed dystonia sometimes developed in patients in whom a diagnosis of somatization disorder had already been made, a history of somatization was often unrecognized and, in many cases, only became evident after examination of primary care records. What is now recognized as classical dystonia has often been misdiagnosed as a psychiatric disorder in the past (Eldridge et al., 1969). In this study, we were therefore careful not to wrongly attribute fixed dystonia to a psychiatric cause or malingering, and diagnosed somatoform disorder only if full DSM-IV criteria for somatization disorder, the most severe type of somatoform disorder, were met. There may have been additional patients who did not fulfil the full criteria for somatization disorder but, nevertheless, may have had a somatoform disorder. In addition, whilst five patients fulfilled criteria for conversion disorder, it is possible that others, in whom a psychological stressor was not identified, may have been missed. In this context, it is relevant that the rate of dissociative disorders, which has been reported to be higher in conversion disorders (Spitzer et al., 1999), was significantly higher in the group of patients with fixed dystonia than in the control group. Thus, the percentage of patients with fixed dystonia due to a somatoform or conversion disorder is likely to be an underestimate (29 and 12% in this study). In addition, a proportion of patients (37%) fulfilled the criteria for clinically definite psychogenic dystonia (Fahn and Williams, 1988). However, this figure is again likely to be an underestimate for two reasons. First, one of the core feature of psychogenic movement disorder, distractibility, is less likely to be seen in patients with a psychogenic dystonia, as it is easier to maintain an unchanged posture when attention is diverted than to maintain for example psychogenic tremor. Secondly, in order to avoid a circular argument, we excluded fixed dystonic postures, pain or non-anatomical sensory loss from the diagnostic features ‘incongruent with organic dystonia’. Fixed dystonic postures are, nevertheless, commonly seen in psychogenic dystonia (Fahn and Williams, 1988; Lang, 1995; Lees, 2002) and the syndrome shares other characteristics of psychogenic dystonia such as onset in the lower limbs and spread to other body parts in an adult, female preponderance, young age of onset, lack of sensory tricks and overflow-dystonia, unresponsiveness to appropriate medications and non-anatomical sensory impairment (Fahn and Williams, 1988; Lang, 1995; Mailis et al., 2000; Lees, 2002). Thus, we believe that our estimates of somatoform disorder or psychogenic disorder are likely to be conservative and that a considerable proportion of patients with fixed dystonia develop this disorder in the context of a somatoform illness. This is supported to some extent by the considerable improvement experienced by the small number of patients who underwent multidisciplinary treatment including psychotherapy. This therapeutic success, which is similar to that reported in psychogenic movement disorders by Williams et al. (1995), compares favourably with the otherwise poor prognosis of this condition.
Features of CRPS were seen both in patients fulfilling criteria for somatoform illness or psychogenic dystonia and those who did not (Table 5A). One patient with CRPS lost the abnormal limb posture as well as the associated features of CRPS when she became manic after a suicide attempt with opiates, at which time a number of psychological conflicts were uncovered. This is in keeping with the reports of CRPS in conversion disorder (Verdugo and Ochoa, 2000) or malingering (Kurlan et al., 1997), and suggests that the presence of CRPS is not an unequivocal indicator of organicity.
In this study, there remains a proportion of cases (10% in the prospective and 45% in the retrospective sample) in whom there is no suggestion of a psychogenic disorder and in whom the diagnosis remains unclear. It is notable that this number was significantly smaller in the prospective group: as it was possible to study these patients in more detail, the figure of 10% may be more accurate. In these patients, there was no conclusive reason to suggest a psychiatric disorder. Whilst there was a history of previous, but transient, movement disorder and a positive family history in a quarter of the prospectively studied patients, these did not occur in a consistent pattern and it is therefore difficult to postulate a single physiological or genetic cause for these findings. Mutations in the DYT1 gene were excluded in all patients tested, but as focal dystonia is not usually associated with this mutation (Jarman et al., 1999), an, as yet unidentified, genetic predisposition cannot be excluded. In addition, the possibility that a proportion of these patients have an autoimmune disorder related to stiff limb syndrome, as suggest by van Hilten et al. (2000b), cannot be excluded. However, it is also possible that these patients have an, as yet unrecognized, psychiatric disorder—although not fulfilling the strict diagnostic criteria we used. At present, this question cannot be answered and, until further evidence emerges, the aetiology of the disorder in a proportion of these cases remains unclear.
Outcome and treatment
Given the poor overall outcome of this patient group, it is noteworthy that the best outcome was seen in patients who underwent multidisciplinary treatment which incorporated rehabilitation with physiotherapy and occupational therapy, as well as psychotherapy and psychiatric treatment as appropriate. Whilst we recognize that availability of such intensive treatment is limited and that only some patients will be willing and suitable for such treatment, this appeared to be the most successful therapeutic approach in this patient group. Pharmacological treatment was largely unsuccessful and invasive procedures, including lumbar spinal blocks and sympathectomies, did not provide sustained benefit in any patient and resulted in further problems in some. Despite the reported benefit of sympathectomies for CRPS, particularly early in the course of the syndrome (Schwartzman et al., 1997), the findings of this study are in agreement with previous reports that sympathectomies have not been demonstrated to produce convincing benefit in CRPS (Verdugo and Ochoa, 1994; Schott, 2001). On current evidence, we therefore conclude that such procedures should be avoided in fixed dystonia. In addition, we found that immobilization in a plaster cast, which has been reported to be beneficial for some patients with occupational dystonia (Priori et al., 2001) and was a procedure applied to some patients in this study, did not result in benefit to any patient and was associated with the onset or deterioration of dystonia in a proportion of patients. Tibial nerve neurolysis resulted in improvement in one patient, but a placebo response cannot be excluded as this patient had reported previous improvement of dystonia following change of a relationship and there was evidence for the presence of a somatoform disorder. Other operative orthopaedic procedures resulted in further deterioration of dystonia in three patients; in one patient, amputation had become inevitable due to gangrene, but did not prevent the progression to the contralateral side. Finally, addiction to high doses of opiates, but also to anticholinergics or baclofen, was not uncommon, and polypharmacy was frequent. We conclude that management of this condition should therefore remain conservative and that non-medical treatment such as physiotherapy and pain management techniques and, if possible, multidisciplinary treatment incorporating psychotherapy, should be offered to these patients. Botulinum toxin, anticholinergics, baclofen and benzodiazepines may be tried, but should only be used on a long-term basis if there is evidence of definite benefit. We have no experience with the use of corticosteroids in patients with pseudoinflammatory changes, or biphosphonates in those with osteoporosis (Schott, 2001), or intrathecal baclofen (van Hilten et al., 2000a) in fixed dystonia.
Conclusions
Fixed dystonia often follows peripheral trauma and, in some cases, has features overlapping with those of CRPS. Whilst an underlying basal ganglia, spinal cord or peripheral neurological abnormality needs to be excluded, careful evaluation often reveals evidence of a somatoform disorder or psychogenic dystonia. Thus we believe that, once a primary or secondary cause has been excluded, patients with fixed dystonia should be screened for a psychiatric or somatoform illness, and a diagnosis of psychogenic dystonia should be considered. In a minority of patients, however, no features of somatoform disorder or psychogenic disorder can be found, and whether their disorder is primarily neurological or psychiatric remains unclear. Whilst the prognosis in this condition overall is poor, a multidisciplinary treatment approach including physiotherapy and psychotherapy appears to produce considerable improvement in some patients.
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Acknowledgements |
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We are grateful to the patients for their participation in the study and to our colleagues for referring these patients. We also wish to thank Dr Geoffrey Schott and Dr Jonathan Schott for their helpful comments on the final version of this paper.
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