Striatal deformities of the hand and foot in Parkinson’s disease.pdf

Review Striatal deformities of the hand and foot in Parkinson’s disease Ramsey Ashour, Ron Tintner, Joseph Jankovic Striatal deformit...

Review Striatal deformities of the hand and foot in Parkinson’s disease Ramsey Ashour, Ron Tintner, Joseph Jankovic Striatal deformities of the hand and foot are abnormal postures that are common in patients with advanced Lancet Neurol 2005; 4: 423–31 Parkinson’s disease (PD); they can present in the early stages of PD and in other parkinsonian disorders. Over a Parkinson’s Disease Center and century ago, Charcot and Purves-Stewart recognised these deformities, which cause substantial functional disability Movement Disorders Clinic, Department of Neurology, and discomfort. The term striatal is used because pathology in the neostriatum (putamen and caudate) has been Baylor College of Medicine, suggested to cause the deformities, but the pathogenesis is unknown. Misdiagnosis of the deformities is common— Houston, TX, USA (R Ashour BS, particularly when they occur early and in the absence of cardinal parkinsonian signs, such as tremor, bradykinesia, R Tintner MD, J Jankovic MD) and rigidity—because the hand deformities are similar to those in rheumatoid arthritis, equinovarus foot deformity Correspondence to: typically suggests an orthopaedic problem, and toe extension may be thought to be the Babinski sign of upper-motor- Prof Joseph Jankovic, Director of Parkinson’s Disease Center and neuron syndromes. Here we review the background and clinical features of these deformities to highlight these Movement Disorders Clinic, commonly unrecognised and poorly understood parkinsonian signs. Department of Neurology, Baylor College of Medicine, Suite 1801, Introduction noted that the deformities in his “paralysis agitans” 6550 Fannin, Houston, TX 77030, USA Various abnormal postures and movements have been patients were “neither the articular tumefaction and [email protected] associated with pathology in the neostriatum, a stiffness, nor the osseous deposits and cracking sounds combination of putamen and caudate.1 The terms of nodose rheumatism”. Indeed, unlike rheumatoid “striatal hand” and “striatal foot” were originally used by arthritis, local signs of joint involvement, such as pain, Charcot2 and Purves-Stewart3 to report the distal limb tenderness, heat, and swelling, are absent in striatal deformities typically associated with Parkinson’s disease hand. Also, rheumatoid arthritis tends to occur (PD). Striatal limb deformities might not be easily bilaterally, whereas focal dystonia before PD tends to be differentiated from dystonia, a well-recognised unilateral, with tremor, rigidity, and bradykinesia movement disorder in patients with PD and other developing on the ipsilateral side (table 1).1,9 parkinsonian disorders.1 By contrast with fixed striatal In the “paralysis agitans” section of his Manual of hand and foot deformity, dystonia commonly begins Diseases of the Nervous System, Gowers10 included during activity and can be associated with dystonic illustrations of striatal hand accompanied by a tremor. In patients with PD who are treated with description of the abnormal posture: “...[the fingers] are levodopa and have motor fluctuations, dystonia, such as flexed at the metacarpophalangeal joints and extended at painful fixed inversion of the foot and flexion of the toes, the others...the digits deviate toward the ulnar side, as can be part of the wearing-off process.4 If untreated, in chronic rheumatoid arthritis”. Purves-Stewart also dystonia can develop into a fixed contracture, although briefly mentioned the “interosseal attitude” of the hands the fixed posture is generally different from that of in his patients.3 Many years later, Gortvai11 expanded on striatal hand or foot. Fixed deformity is rarely isolated, the early observations, describing four stages of hand except for complex regional pain syndrome, particularly deformity in PD—progression from moderate after trauma.5 Although striatal deformities have been metacarpophalangeal flexion and interphalangeal reported in 10% of patients with untreated, advanced extension to severe proximal interphalangeal PD,1 prevalence has not been systematically studied. Because the deformities are commonly wrongly Features Rheumatoid arthritis Striatal abnormalities diagnosed—eg, rheumatoid arthritis, Dupuytren’s Pathophysiological Proliferative synovitis, autoimmunity, Non-inflammatory, dystonic features, contractures,6,7 flexor tendon entrapment of the digits features microbial initiator soft-tissue elastic changes (also referred to as trigger finger and trigger thumb or de Joints Swollen, warm, painful, pannus formation Painful, contractures Quervain’s tenosynovitis8), Babinski sign, and other Radiographic changes Joint effusions, juxta-articular osteopenia Normal pseudodystonic disorders—we discuss the clinical with erosions, narrowed joint space with loss of cartilage associations of striatal deformities. The primary aim of Mobility Morning stiffness, decreased range of Fixed deformity, may respond to levodopa this review is to draw attention to these commonly motion (active and passive) or botulinum toxin unrecognised signs and to consider possible Distribution Generally symmetrical joint involvement, In most cases develops on one side with polyarticular ipsilateral emergence of cardinal PD signs pathogenetic mechanisms and treatment. Genetics Association with HLA DR4 or DR1 Seems to be more common in juvenile-onset PD Striatal hand Extra-articular features Cutaneous and visceral rheumatoid Rigidity, bradykinesia, tremor In the late 19th century, Charcot described a “digital nodules, increased serum rheumatoid factor, synovial cysts, vasculitis, episcleritis deformation simulating that of primitive chronic articular rheumatism” in which fingers were “alternately Table 1: Striatal deformity and rheumatoid arthritis9 flexed and extended at their several articulations”.2 He http://neurology.thelancet.com Vol 4 July 2005 423  Review hyperextension with distal phalangeal subluxation, flexion of the fingers can lead to pressing of fingernails leading to distal interphalangeal flexion. Clinical and into the palm of the hand, causing abrasion and radiological findings prompted Gortvai to comment that secondary infection (figure 2). Such contractures are the hand joints of his patients with PD were healthy, typical in advanced PD and other parkinsonian even after many years of deformed posture.11 He showed disorders, but they can occur even in early stages and the role of small muscle contraction in the production of also secondary to reactive fibrosis resulting from the deformities, observing that ulnar-nerve block with a treatment with an ergot dopamine agonist (eg, local anaesthetic stopped the deformity in patients bromocriptine, pergolide),14 which can also cause whereas ulnar-nerve stimulation produced the abnormal fibrosis in the lungs, heart, and other tissues.27 posture in healthy people. Since Gortvai’s research, Although hand deformities are accepted as a several reports have described many “typical” hand common complication in patients with advanced, deformities associated with parkinsonism with different treated PD, less attention has been given to the patterns of flexion or extension at the various digital frequency of striatal hand as an early sign in patients articulations.12–18 The most typical deformity associated who have not been treated.18 We have seen a mild with striatal hand is characterised by flexion of the flexion of the metacarpophalangeal joint in the hands metacarpophalangeal joints, extension of the proximal of many patients with early PD, even before other interphalangeal joints, flexion of the distal parkinsonian features present. This flexion is typically interphalangeal joints, and ulnar deviation (figure 1).19 on the side initially affected by tremor, rigidity, Some features of striatal hand in patients with or bradykinesia. Although prospective studies untreated PD are common to other well-described forms must validate this observation, clinicians should of dystonia. Striatal hand must be differentiated from: search for this sign as evidence of the side of the dystonia in primary dystonic states; dystonia initial presentation. contributing to a differential phenotypic expression of the same disease, as in dystonia-parkinsonism Striatal foot syndromes; dystonia as a complication of pharma- In a lecture on the symptoms of “paralysis agitans” in cotherapy;4,20–22 and dystonia associated with an ablative 1877, Charcot gave an account of two patients whose feet lesion or high-frequency, deep-brain stimulation.23–25 were “stiff, extended, and turned in, simulating the In addition, striatal hand must be differentiated from malformation known as talipes equines (varus) entrapment neuropathies and cervical myelopathies.26 clubfoot”.2 Claw-like “extension of the first and Although striatal hand (metacarpophalangeal flexion, concomitant flexion of the second phalanges” were seen interphalangeal extension, ulnar deviation) is similar to in both patients. Gowers10 also noted in his discussion of the swan-neck deformities that occur in some arthritic “paralysis agitans” that “[rigidity] may extend to the feet, disorders, other postures have been described that more and even cause talipes equinovarus, and distortion of the closely parallel the opposite boutonnière deformity toes—extension of the first, and flexion of the other (metacarpophalangeal extension, proximal inter- phalanges so as to cause a claw-like deformity”. Similar phalangeal flexion, distal interphalangeal extension). posturing (hallucal hyperextension, flexion of the other Postures with features intermediate between these two toes, ankle inversion) was described 10 years later in five prototypical positions also occur and are common in of 28 patients with “paralysis agitans” who were advanced disease.12,13,15,17 A claw-hand deformity has also observed for 2 years.3 This “toe curling” symptom with been described in PD.13 Whereas metacarpophalangeal pain and cramps was unpredictably associated with flexion and interphalangeal extension, due to walking and preceded all other symptoms by up to contraction of the lumbricals and interossei respectively, 2 years in three of the five patients. seem to be the earliest signs of striatal hand, Several studies done before the era of levodopa hyperextension and subluxation of the terminal treatment attributed foot and other deformities to PD.11,12 phalanges are thought to be signs of more advanced In 1972, Duvoisin and colleagues28 noted that “this deformity.11 In addition to disfigurement, striatal hand dystonic phenomenon is an intrinsic feature of PD”. By can cause pain or discomfort and can affect daily use of the term “striatal foot”, they described the typical activities such as writing, eating, and buttoning. Severe features, including big-toe extension, flexion of the other toes, equinovarus foot positioning, and pain.28 Striatal foot deformity can cause pain and impair the ability to stand, walk, and wear shoes. If untreated, skin ulceration and bone erosion can happen (figure 3). Equinovarus foot positioning produces inadequate support, hinders early and mid-stance dorsiflexion, and prevents the tibia from moving over the stationary foot.29,30 Thus, the stance phase of gait is shortened, and Figure 1: Striatal hand in a patient with typical PD push-off propulsion and forward propulsion are 424 http://neurology.thelancet.com Vol 4 July 2005  Review Figure 2: Typical striatal hand deformity and severe flexion contracture Left and middle: typical striatal hand deformity in the right hand. Right: marked flexion of fingers resulting in severe flexion-contracture in the left hand. hindered.31 Early swing-phase limb advancement and however, the exact differences need further study. foot clearance are also affected. Pressure is increased Striatal toe has been differentiated from the Babinski over the lateral aspect of the foot and ankle instability sign according to toe fanning and flexion synergy of occurs.29,31 other muscles in the same leg, which are both features Over the years, different terms have been used to of the Babinski response.35 Other disorders with limb describe the striatal foot deformity, including the abnormalities similar to striatal foot include peripheral dystonic foot response of parkinsonism,32 dystonic vascular disease, lumbar canal stenosis, familial claudication,33 striatal toe,34,35 hitchhiker’s great toe,29 paroxysmal exercise-induced dystonia, and exercise- pseudo-rheumatoid deformity,36 and pseudo-Babinski.35 induced hypocalcaemic-tetanic spasms.43 The all-encompassing term foot dystonia is commonly used to describe dystonic posturing of the legs and feet Classification and diagnosis that happens in various clinical settings including PD Although the term striatal is used to describe these and other Parkinson-plus syndromes.19,33,37–43 deformities, it is inaccurate because it implies a non- Furthermore, striatal toe and equinovarus foot are used specific lesion in the striatum (eg, neostriatum, to describe clinical patterns of motor dysfunction, such paleostriatum, and corpus striatum) even though there as upper-motor-neuron syndrome, that are visually similar or identical to but aetiologically distinct from striatal foot in PD.29 As with striatal hand, striatal foot must be differentiated from other well-described forms of dystonia commonly attributed to dopaminergic therapy, such as off-period and biphasic dystonia.4 Striatal foot in PD is part of the primary disease process and can be one of the earliest signs in untreated patients.1,3,19,28,32,33,36–45 When striatal foot is a secondary (symptomatic) dystonia in patients with PD, it might be mistaken for a primary dystonic state (sporadic or familial), particularly when the classic parkinsonian signs are absent. Primary adult-onset dystonia rarely involves the feet, and thus the possibility of PD should be considered in all adults who present with isolated foot dystonia.1 Striatal toe is a type of striatal foot, but without the equinovarus foot. Electromyographic analyses have shown a different pattern of muscle contraction in striatal foot from that in the Babinski response;28 Figure 3: Striatal foot with severe skin ulceration and bone erosion http://neurology.thelancet.com Vol 4 July 2005 425  Review is little evidence that a striatal lesion is needed to 86 parkinsonian patients, which was done before produce the posture. Furthermore, traumatic, vascular, levodopa treatment was available, 34 (~40%) had some or other lesions in the striatum rarely produce striatal deformity of the hands, including 14 (~24%) of deformities.46 Moreover, the term does not adequately 58 patients with PD.12 By contrast with this finding, account for the range of extrastriatal lesions that could only three cases of hand deformity in patients with PD lead to these postural deformities. We suggest use of the were recorded during 12 months in a “busy” neurology terms striatal hand and striatal foot to help with department; however, a formal epidemiological study recognition of the clinical entity of distal limb deformity was not done.15 in parkinsonism. Although in this review we focus on striatal hand and Pathophysiology striatal foot associated with PD, there are many other Early reports attributed the characteristic postural parkinsonian disorders in which striatal hand occurs, deformities in PD to muscular rigidity.2,3 Later studies including multiple system atrophy,40,47,48 corticobasal on striatal foot suggested an extrapyramidal origin, degeneration,49 progressive supranuclear palsy,50–52 NBIA differentiating the deformity from similar but (neurodegeneration of the brain with iron unrelated frontal release, such as the “grasp”, and accumulation),53 and parkinsonism-dementia seen in proprioceptively mediated flexion synergy in mesial western Pacific regions.54 frontal-lobe lesions.32,69 The relation between parkinsonism and coexistent Various lesions disrupting striatopallidothalamic abnormal postures, such as striatal hand, striatal foot, projections produce focal dystonia in human bent spine, scoliosis, and camptocormia, is not well beings;20,46,70–72 research with animal models has given understood. Camptocormia—a disorder characterised insights as well. For example, foot dystonia similar to by pronounced flexion of the thoracolumbar spine, that seen in early PD has been reported in studies of which is most prominent on standing and walking and parkinsonism in monkeys induced by 1-methyl-4- relieved in the supine position—is associated with phenyl-1,2,3,6-tetrahydropyridine (MPTP).73 Also, the various musculoskeletal and neurological causes, abnormal posture and compulsive circling behaviour in including parkinsonism, dystonia, and other dogs74 and cats75,76 after unilateral ablation of the caudate neurological and non-neurological disorders.55 In nucleus77 suggest that asymmetrical degenerative patients with idiopathic PD, camptocormia is changes in the caudate—through disruption of its tonic increasingly identified and should not be confused with effect on posture and locomotion—contribute to bent spine syndrome seen in axial myopathies.1,55–59 the development of scoliosis in patients with PD and Camptocormia associated with active contraction of the in patients with postencephalitic parkinsonism. rectus abdominus can be treated with injection of Furthermore, rats with hemiparkinsonism, induced by botulinum toxin into that muscle.60 Scoliosis is a lateral unilateral injection of 6-hydroxydopamine into the left curvature of the spine accompanied by vertebral rotation ventralis tegmenti, showed strong ipsilateral deviation;78 that results in asymmetrical deformity of the trunk. the severity of scoliosis was closely related to the Scoliosis is more common in patients with PD61–63 than decrease in extracellular striatal dopamine and to the in elderly people of similar age to those with PD.63–65 development of postsynaptic dopamine receptor supersensitivity. A similar mouse model showed the Epidemiology development of dyskinesias and abnormal posture after Striatal hand and foot deformities might present in up 6-OHDA injection into the sensorimotor striatum.79 to 10% of untreated patients with advanced PD;1 Of the basal ganglia, the lentiform nucleus (putamen however, neither the true prevalence nor the relation of and globus pallidus) is commonly involved when these deformities with age and sex has been dystonia and parkinsonism coexist.1 Lenticular systematically studied. Although many reports support lesions are also associated with the development the high prevalence of dystonia in patients with of camptocormia.55,59 Thalamic relay nuclei have idiopathic, untreated PD,1,19,20,37,66 few have questioned been associated with contralateral symptomatic the relation, some even noting a similar prevalence of hemidystonia,20,69 and lesions in the posterior and focal dystonia in untreated PD and the general posteriolateral thalamus, red nucleus, and subthalamic population.38 Patients who develop dystonia before or nucleus have been reported to cause various with PD tend to be younger than the general population dystonias.1,23–25,46,50–52,70–72 of patients with PD.1 Similarly, patients with early-onset Dystonia in PD includes a range of focal dystonias— PD, particularly those with PARKIN mutations, are eg, cervical dystonia, limb dystonia, blepharospasm and more likely to have dystonia.67 other cranial dystonias, and hemidystonia.1,19–21,37,38,80,81 Foot dystonia develops in 20–40% of patients Although striatal hand and foot overlap with other forms with PD receiving sustained levodopa treatment,42 and of dystonia, comparison of the clinical features of these some studies have found that striatal foot precedes deformities with those in primary (idiopathic) dystonia treatment in 2·4–8·0% of patients.32,68 In a series of shows substantial differences (table 2).19,38,80 426 http://neurology.thelancet.com Vol 4 July 2005  Review Why some patients with PD develop striatal deformity Distinguishing Striatal deformities Primary idiopathic dystonia and others do not is not clear, and there is no predictor features* of striatal deformity in patients with PD. In one study,12 Fixed or mobile Relatively fixed Mobile, but can evolve into contractures if left untreated the frequency of striatal hand was associated with the Pain Typically painless Typically painless, but some dystonias (eg, cervical) are amount of generalised rigidity but not with the amount associated with local pain When present Typically Commonly induced by action or duration of tremor. Severe rigidity has also been present at rest suggested to contribute.15 Study of limb contractures in Other symptoms Concomitant parkinsonism Commonly other dystonic features are present patients with PD by use of transcranial magnetic signs and symptoms stimulation found that central motor conduction time is (tremor, rigidity, bradykinesia) Anatomy Typically affects the hands, Dystonia affecting legs and feet is very rare at onset in adults; if lower in the limb that is more severely affected; shorter but can also affect the feet present, dystonia is commonly associated with parkinsonism central motor conduction time reflects decreased and other parts of the body excitability in cortical-inhibitory circuits and has been Sleep association Typically persists during sleep Not present during sleep, except when associated with suggested to contribute to overactive and inappropriate contractures muscle contraction in the hand.17 *These features are not absolute and are given as a guide. Qualitative research findings that striatal hand is more common in women than in men could be explained by Table 2: Striatal deformities and primary idiopathic dystonia19,38,80 more ligament laxity in women than in men—ie, by an interaction between a central tone disturbance and a peripheral, predisposing state.16 Epidemiological Progression of striatal-limb deformities from studies82–84 reporting much higher rates of anterior cruciate abnormal contraction to fixed contracture results in ligament injury in females than males participating in the further functional disability in patients already coping same sports have prompted investigation of non-contact with PD symptoms. Particularly distressing is the rapid, mechanisms and risk factors to explain the difference.85–87 unpredictable development of contractures in levodopa- The effects of female hormones on connective-tissue responsive patients. In previous studies on hand structure have been studied,82,83,88,89 and some have shown contractures in PD, the progression of deformity to fixed that collagen structure and tensile properties vary with contracture happened over periods of 2 weeks,14 hormonal fluctuations in women.90,91 Similarly, studies 2 months,15 2 weeks to 2 months,17 and 6 months.98 In have identified transcripts for oestrogen and progesterone most of the patients with PD in these studies, receptors in normal connective tissue in women.90,92 In contractures developed after several years of disease rats, oestrogen increases elastin in connective tissue93–95 with a strong (but not fully understood) female and decreases collagen in tendons and fascias.88 The preponderance. cyclically released hormone relaxin changes collagen The combination of long-lasting, fixed posture, and metabolism through an effect on the secretion of sustained muscle contraction associated with hypertonia procollagenases by tissue fibroblasts.96,97 Although these reduces the number of sarcomeres in the affected findings provide clues to the sex-specific factors that muscle groups.99 Furthermore, torque measurements predispose or perhaps contribute to joint and soft-tissue during imposed constant-velocity muscle-contraction pathology, particularly for sports-related trauma, their role cycles have been used to show secondary changes in the in the development of striatal-limb deformities in PD is mechanical properties of affected muscles and their speculative. Observations that these deformities are surrounding tissues in patients with long-standing associated with sex must be substantiated by formal spasticity.100 In particular, alterations in soft-tissue epidemiological studies; the deformities could be caused plasticity and viscoelasticity are thought to cause atrophy by many factors with anatomical, sociological, and and fibrosis in both muscle and connective tissue98–100 hormonal differences modifying the course of disease in and could thus compound the effect of sarcomere-loss individual patients. and muscle shortening in the overall progression of A pathophysiological model for parkinsonism and deformity to fixed contracture. Although contracture dystonia, such as observed in levodopa-related, off- development has been well characterised in patients period dystonic processes, has been proposed to involve with long-standing spasticity, similar changes seem dopaminergic hypofunction with concurrent or possible in patients with PD—electromyographic compensatory cholinergic hyperfunction.42 Improve- analyses show excessive, involuntary motor-unit ment in patients treated with baclofen has led some to recruitment in rigid muscles apparently at rest that is posit a contributory role for other neurotransmitter not suppressible, and the average area of surface systems (specifically glutamate and GABA) in dystonia electromyographic readings relates to clinical as well.32 Furthermore, a hypothesised rostrocaudal assessment of rigidity.101 gradient of decreased dopaminergic and increased The rapid development of limb contractures in patients GABA-ergic function across a somatotopically organised with PD taking the ergot dopamine agonist bromocriptine striatum42 might underlie the dystonic complications in mesilate14 suggests drug-induced reactive fibrosis as a the feet of patients with PD. pathogenetic mechanism of contracture. Indeed, in most http://neurology.thelancet.com Vol 4 July 2005 427  Review have striatal hand with varying amounts of contracture.98 Search strategy and selection criteria However, the large muscle groups contributing to References for this review were identified from searches of dystonia in the foot as well as the associated contracture MEDLINE up to March 1, 2005. The keywords “Parkinson’s can make botulinum-toxin injections less effective disease”, “parkinsonism”, “dystonia”, “primary”, “secondary”, in striatal deformities than in more mobile forms “focal”, “hand deformity”, “foot deformity”, “musculoskeletal of dystonia.123 Also, chemodenervation of extensor deformity”, “striatum”, “contractures”, “dyskinesias”, and hallucis longus for striatal toe might unmask “levodopa” were entered in various combinations with the co-contraction of flexor hallucis longus29 and therefore inclusion of all subheadings. The references of each paper necessitate further treatment. were studied for pertinent papers for follow-up, and many If conventional, non-operative treatments are additional searches were done up to April 15, 2005. No limits unsuccessful, orthopaedic surgical interventions can be were placed on the dates of publication. Only articles attempted. Split anterior tibial-tendon transfer with published in English were consulted in the initial review. extrinsic toe-flexor release and percutaneous achilles- Other references followed up were reviewed in English only; tendon lengthening has been reported to result in papers written in other languages in this category were substantial functional improvement and plantigrade foot allowed only if an English translation was available. in patients with idiopathic foot dystonia.123 Z-lengthening procedures and capsulotomy have also been used in the treatment of hand deformities in PD.13 reports of patients with PD who rapidly developed Neurosurgical treatments that have been assessed for contractures, the patients were being treated with ergot the treatment of PD and dystonia include stereotactic dopamine agonists14,17 or ergolines.98 Furthermore, digital pallidotomy, thalamotomy, and deep-brain stimula- vasospasm,102,103 pleuropulmonary fibrosis,27,104–107 and tion.1,11,25,125–128 Cooper125–127 described improvement and retroperitoneal fibrosis107–110 have all been reported in even complete resolution of striatal hand and foot patients treated with bromocriptine mesilate as well as deformities after occlusion of the anterior choroidal other ergot compounds. An interaction between ergot artery and stereotactic thalamotomy in patients with PD. compounds and serotonin receptors could explain the Patients with PD who had combined thalamic lesion in production of tissue fibrosis,14,111–114 and both the ventralis intermedius and ventralis oralis nuclei bromocriptine mesilate and methylsergide are known to (selective Vim-Vo thalamotomy) for the treatment of interact with 5-HT1 and 5-HT2 receptors.114,115 Serotonin- dyskinesias showed improvement in limb dystonia.128 secreting carcinoid tumours have been linked to Nevertheless, the role of neurosurgery in the treatment endocardial and pulmonary fibrosis.114,116,117 Other of striatal hand and foot requires further study; surgery fibroblast-modulating substances have been researched, is generally reserved for patients with other severe including tachykinins (eg, substance P and substance K)118 symptoms refractory to non-surgical treatments. and growth factors, including platelet-derived growth factor,119,120 insulin-like growth factors,121 and the Conclusion transforming growth factor  family.117,122 Investigation of the temporal relation between the early development of striatal hand and foot deformities, Treatment initially shown with slight flexion of the Dystonia responds variably to treatment with systemic metacarpophalangeal joint, and the natural history of PD drugs in parkinsonism. The response to anti- might give insight into the pathogenesis of this sign and parkinsonian drugs is less predictable in striatal hand its relation to underlying pathology. Future studies and foot than in primary dystonia, although levodopa should assess whether there are predictors for the and anticholinergic agents have improved dystonia in development of deformity and whether the deformities some cases.32,33,35,36,42–44 We have observed cases in which a are associated with disease severity and progression, complete resolution of striatal-hand dystonia was symptom laterality, age, sex, and other clinical markers. achieved with levodopa treatment. Anticholinergics, baclofen, and benzodiazepines have also been variously Acknowledgments We thank the staff at the Mary Moody Medical Library in Galveston, successful in treating foot dystonia in parkinsonism, TX, USA, for providing copies of papers published before 1975 for including striatal foot in PD.123,124 this review. We also thank the National Parkinson Foundation for Botulinum-toxin injection is a treatment option. In their support. combination with systemic drugs, botulinum toxin is the Authors’ contributions preferred treatment for focal dystonias and has been used All authors contributed equally to this review. in the treatment of striatal toes.34,60 The dose injected is Conflicts of interest guided by electromyographic activity in the affected We have no conflicts of interest. muscles. Botulinum-toxin injection into the lumbricals Role of the funding source and short adductors of the thumb has led to functional No funding source had a role in the preparation of this paper or in the decision to submit it for publication. improvement and pain relief in patients with PD who 428 http://neurology.thelancet.com Vol 4 July 2005  Review References 28 Duvoisin RC, Yahr MD, Lieberman J, Antunes J, Rhee S. 1 Jankovic J, Tintner R. Dystonia and parkinsonism. The striatal foot. 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