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2011EFNS+原发性肌张力障碍的诊断和治疗指南

2011EFNS+原发性肌张力障碍的诊断和治疗指南
2011EFNS+原发性肌张力障碍的诊断和治疗指南

EFNS GUIDELINES

EFNS guidelines on diagnosis and treatment of primary dystonias A.Albanese a,b,F.Asmus c,K.P.Bhatia d,A.E.Elia a,b,B.Elibol e,G.Filippini a,T.Gasser c,

J.K.Krauss f,N.Nardocci a,A.Newton g and J.Valls-Sole′h

a Istituto Neurologico Carlo Besta,Milan,Italy;

b Universita`Cattolica del Sacro Cuore,Milan,Italy;

c Department of Neurodegenerative Diseases,Hertie-Institute for Clinical Brain Research,University of Tubingen,Germany;

d Institut

e o

f Neurology,University College London, Queen Square,London,UK;e Hacettepe University Hospitals,Department of Neurology,Ankara,Turkey;f Department of Neurosurgery, Medical School Hannover,MHH,Hannover,Germany;

g European Dystonia Federation,Brussels,Belgium;and

h Neurology Department, Hospital Cl?′n ic,Barcelona,Spain

Keywords:

classi?cation,diagnosis, dystonia,genetics, guidelines,treatment Received6February2010 Accepted11March2010Objectives:To provide a revised version of earlier guidelines published in2006. Background:Primary dystonias are chronic and often disabling conditions with a widespread spectrum mainly in young people.

Diagnosis:Primary dystonias are classi?ed as pure dystonia,dystonia plus or par-oxysmal dystonia syndromes.Assessment should be performed using a validated rating scale for dystonia.Genetic testing may be performed after establishing the clinical diagnosis.DYT1testing is recommended for patients with primary dystonia with limb onset before age30,and in those with an a?ected relative with early-onset dystonia.DYT6testing is recommended in early-onset or familial cases with cranio-cervical dystonia or after exclusion of DYT1.Individuals with early-onset myoclonus should be tested for mutations in the DYT11gene.If direct sequencing of the DYT11 gene is negative,additional gene dosage is required to improve the proportion of mutations detected.A levodopa trial is warranted in every patient with early-onset primary dystonia without an alternative diagnosis.In patients with idiopathic dysto-nia,neurophysiological tests can help with describing the pathophysiological mecha-nisms underlying the disorder.

Treatment:Botulinum toxin(BoNT)type A is the?rst-line treatment for primary cranial(excluding oromandibular)or cervical dystonia;it is also e?ective on writing dystonia.BoNT/B is not inferior to BoNT/A in cervical dystonia.Pallidal deep brain stimulation(DBS)is considered a good option,particularly for primary generalized or cervical dystonia,after medication or BoNT have failed.DBS is less e?ective in sec-ondary dystonia.This treatment requires a specialized expertise and a multidisci-plinary team.

Background

Dystonia is characterized by sustained muscle con-tractions,frequently causing repetitive twisting move-ments or abnormal postures[1,2].Although thought to be rare,dystonia may be more common than currently evidenced because of underdiagnosis or misdiagnosis [3].Adult onset primary dystonia can present mainly with tremor,which could be misdiagnosed as Parkin-son?s disease[4].In such cases,imaging of dopaminergic terminals with dopamine transporter(DAT)scan or F-DOPA PET may help with the di?erential diagnosis.

Primary dystonias are diseases where torsion dystonia is the only or the largely prevalent clinical feature.To improve clarity of de?nitions and exchange of clinical information,this EFNS committee proposes to intro-duce a new terminology for the etiological classi?cation of primary forms,which encompass pure dystonia, dystonia plus and paroxysmal dystonia syndromes (Table1).Areas of speci?c concern include clinical diagnosis,di?erential diagnosis with other movement disorders,aetiology,genetic counselling,drug treat-ment,surgical interventions and rehabilitation. Search strategy

Computerized MEDLINE and EMBASE searches (2005–July2009)were conducted using a combination of textwords,MeSH and EMTREE terms?dystonia?,

Correspondence:A.Albanese,Fondazione Istituto Neurologico Carlo

Besta,Via G.Celoria,11,20133Milano,Italy(tel.:

+390223942552;fax+390223942539;e-mail alberto.albanese@

unicatt.it).

ó2010The Author(s)

European Journal of Neurologyó2010EFNS5 European Journal of Neurology2011,18:5–18doi:10.1111/j.1468-1331.2010.03042.x

?blepharospasm?,?torticollis?,?writer?s cramp?,?Meige syndrome?,?dysphonia?and?sensitivity and speci?city?or?diagnosis?,and?clinical trial?or?random allocation?or?therapeutic use?limited to human studies.The Cochrane Library and the reference lists of all known primary and review articles were searched for relevant citations.No language restrictions were applied.Studies of diagnosis,diagnostic test and various treatments for patients su?ering from dystonia were considered and rated as level A to C according to the recommendations for EFNS scienti?c task forces[5].Where only class IV evidence was available but consensus could be achieved, we have proposed good practice points.

Method for reaching consensus

The results of the literature searches were circulated by e-mail to the task force members for comments.The task force chairman prepared a?rst draft of the man-uscript based on the results of the literature review,data synthesis and comments from the task force members. The draft and the recommendations were discussed during a conference held in Florence on12September 2009,until consensus was reached within the task force. Results

In addition to the previously published literature screen [6],we found299papers,amongst whom191were primary diagnostic studies,and108were e?cacy studies.

Clinical features of dystonia

Literature search on the clinical features of dystonia identi?ed a report of a multidisciplinary working group [7],one workshop report[8],64primary studies on clinically based diagnosis and125primary studies on the diagnostic accuracy of di?erent laboratory tests. The primary clinical studies encompassed4cohort studies,15case–control studies,12cross-sectional and 33clinical series.

The clinical features of dystonia have been summa-rized in the previous guidelines edition[6].More recent reviews and new primary studies have focused on spe-ci?c diagnostic features;a recent review has assembled the features of dystonia into a diagnostic?owchart[9]. Dystonia is a dynamic condition that often changes in severity depending on the posture assumed and on vol-untary activity of the involved body area.The changing nature of dystonia makes the development of rating scales with acceptable clinimetric properties problematic. Three clinical scales are available for generalized dystonia:the Fahn–Marsden rating scale[10],the Uni?ed Dystonia Rating Scale and the global dystonia rating scale[11].The total scores of these three scales correlate well,they have excellent internal consistency, from good to excellent inter-rater correlation and from

Table1Classi?cation of dystonia based on three axes

1.By cause(aetiology)

Primary dystonias

Primary pure dystonias:torsion dystonia is the only clinical sign(apart from tremor),and there is no identi?able exogenous cause or other inherited or degenerative disease.Examples are DYT1and DYT6dystonias.

Primary plus dystonias:torsion dystonia is a prominent sign but is associated with another movement disorder,for example myoclonus or parkinsonism.There is no evidence of neurodegeneration.For example,DOPA-responsive dystonia(DYT5)and myoclonus-dystonia(DYT11) belong to this category.

Primary paroxysmal dystonias:torsion dystonia occurs in brief episodes with normalcy in between.These disorders are classi?ed as idiopathic (often familial although sporadic cases also occur)and symptomatic because of a variety of causes.Three main forms are known depending on the triggering factor.In paroxysmal kinesigenic dyskinesia(PKD;DYT9),attacks are induced by sudden movement;in paroxysmal exercise-induced dystonia(PED)by exercise such as walking or swimming and in the non-kinesigenic form(PNKD;DYT8)by alcohol,coffee,tea,etc.A complicated familial form with PNKD and spasticity(DYT10)has also been described.

Heredodegenerative dystonias:dystonia is a feature,amongst other neurological signs,of a heredodegenerative disorder.Example:Wilson?s disease. Secondary dystonias:dystonia is a symptom of an identi?ed neurological condition,such as a focal brain lesion,exposure to drugs or chemicals. Examples:dystonia because of a brain tumour,off-period dystonia in Parkinson?s disease.

2.By age at onset

Early-onset(variably de?ned as£20–30years):usually starts in a leg or arm and frequently progresses to involve other limbs and the trunk. Late onset:usually starts in the neck(including the larynx),the cranial muscles or one arm.Tends to remain localized with restricted progression to adjacent muscles.

3.By distribution

Focal:single body region(e.g.,writer?s cramp,blepharospasm)

Segmental:contiguous body regions(e.g.,cranial and cervical,cervical and upper limb)

Multifocal:non-contiguous body regions(e.g.,upper and lower limb,cranial and upper limb)

Generalized:both legs and at least one other body region(usually one or both arms)

Hemidystonia:half of the body(usually secondary to a structural lesion in the contralateral basal ganglia)

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fair to excellent inter-rater agreement[11].An evidence-based review identi?ed more than10rating scales for cervical dystonia[12].However,the most frequently used ones are the Toronto Western Spasmodic Torti-collis Rating Scale[13],the Tsui scale[14]and the Cervical Dystonia Severity Scale[15].

Dystonia in?uences various aspects of quality of life, particularly those related to physical and social func-tioning.Class IV studies have evaluated the predictors of quality of life in dystonia[12,16].Functional dis-ability,body concept and depression were important predictors of quality of life in dystonia.

Classi?cation

The classi?cation is based on three axes:(i)aetiology, (ii)age at onset of symptoms,and(iii)distribution of body regions a?ected(Table1).The etiological axis de?nes primary(idiopathic)dystonia with no identi?-able exogenous cause or evidence of neurodegeneration (i.e.,no progressive loss of neural cells).In the pure form,dystonia is the only clinical sign(apart from dystonic tremor).We propose to call these forms?pri-mary pure dystonia?(PPD).In dystonia plus,instead, usually there are additional movement disorders(e.g., myoclonus or parkinsonism).In the paroxysmal form, symptoms are intermittent and provoked by identi?able triggers(e.g.,kinesigenic because of sudden movement, exercise-induced or non-kinesigenic).Non-primary dystonia is because of heredodegenerative diseases or secondary(symptomatic)to known causes;these forms are characterized by the presence of additional symp-toms or signs,apart from movement disorders.A number of genes and gene loci have been identi?ed for primary as well as for other forms. Recommendations and good practice points

1.The diagnosis of dystonia is clinical,the core being abnormal postures(with or without tremor)and the recognition of speci?c features,e.g.gestes antagonistes, over?ow and mirror movements(good practice point).

2.The classi?cation of dystonia is important for pro-viding appropriate management,prognostic informa-tion,genetic counselling and treatment(good practice point).

3.Because of the lack of speci?c diagnostic tests,expert observation is https://www.doczj.com/doc/5714900774.html,ing a structured?ow chart[9]may increase diagnostic accuracy(good prac-tice point).

4.Appropriate investigations are required if the initial presentation or the course suggests heredodegenerative or secondary(symptomatic)dystonia(good practice point).

5.Assessment of dystonia should be performed using a validated rating scale(good practice point).

Use of genetic test in diagnosis and counselling

Two genes for PPD have been identi?ed:DYT1and DYT6[17,18].Three other gene loci for autosomal-dominant PPD(DYT4,DYT7and DYT13)and two forms of recessive PPD(DYT2and DYT17)have been described with phenotypes ranging from cranial to generalized dystonia;however,the speci?c gene abnormality has not yet been identi?ed[19].

All known DYT1mutations reside in exon5of the TorsinA gene,except for one in exon3[20].Screening for a GAG-deletion at position302/303is su?cient for clinical testing(class II)[21].Only two patients with PPD have been described with missense mutations in exon3(p.F205I)and exon5(p.R288Q),and the pathogenicity of this variant has not been proven,as no familial cosegregation has been demonstrated[20,22]. Early-onset DYT1dystonia typically presents in childhood and usually starts in a limb,gradually and in many patients rapidly progressing to a generalized form (class II)[21].Many exceptions to this typical presen-tation have been reported,especially in mutation car-riers from DYT1families with focal or segmental dystonia of adult onset(class IV)[23,24].Family studies have assessed that the penetrance of DYT1dystonia is around30%.

DYT1mutations are the most important genetic cause of early-onset PPD worldwide.Phenotype-genotype correlations have been assessed in di?erent DYT1dys-tonia populations(class II and III)[21,25].In Ashkenazi Jews,DYT1testing is positive in close to100%in patients with limb onset dystonia before age26.Rec-ommendation1below is based on such evidence[21,26]. In the western-European population,the proportion of DYT1mutation negative dystonia is considered higher than in North America[25].Patients with early-onset PPD not caused by the DYT1gene tend to have later age at onset,less commonly limb onset,more frequent cer-vical involvement,and a slower progression than DYT1 PPD cases(class IV)[27]In patients with generalized dystonia with cranio-cervical onset DYT6mutations should be considered[28].thanatos associated protein (THAP1)has been identi?ed to cause autosomal-domi-nant DYT6,?mixed?-type dystonia,in Amish-Mennonite families with cranial or limb onset at young age(from5 to48years)[18,29].DYT6mutations have been described in other populations with clinical presenta-tions from focal to generalized dystonia in a few per cent of cases.In particular,early-onset generalized PPD with spasmodic dysphonia is a characteristic phenotype caused by DYT6mutations(class IV)[28].

EFNS dystonia guidelines7

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European Journal of Neurologyó2010EFNS European Journal of Neurology18,5–18

Four dystonia-plus syndromes have been character-ized genetically:dopa-responsive dystonia(DRD, DYT5),myoclonus-dystonia(M-D,DYT11),rapid-onset dystonia-parkinsonism(RDP,DYT12)and auto-somal-recessive(AR)dystonia-parkinsonism(DYT16). The most common form is DRD linked to the GTPcyclohydrolase I(GCH1)gene.As this is a treat-able and often misdiagnosed condition,a particular e?ort should be made to establish a correct diagnosis. The classical phenotype comprises onset with walking di?culties before20years,and progression to seg-mental or generalized dystonia,sometimes with addi-tional parkinsonism and sustained response to levodopa[30,31].Three additional DRD categories with di?erent courses have been recognized:(i)young-onset(<20years)cases with episodic dystonia,toe walking or progressive scoliosis throughout life; (ii)compound heterozygous GCH1mutation carriers, who develop young-onset severe DRD with initial hypotonia similar to AR-DRD caused by tyrosine hydroxylase(TH)mutations;and(iii)adult-onset DRD patients manifesting above age30with mild dystonia or resting tremor or non-tremulous parkinsonism[31,32]. To date numerous GCH1mutations but no phenotype-genotype correlations to speci?c heterozygous GCH1 mutations have been detected.

Inclusion of screening for gene dosage alterations of GCH1[33,34]in addition to direct sequencing has in-creased the rate of detected mutations to over80% [35,36].

If genetic testing of GCH1is negative,other genes of the tetrahyhdrobiopterin and dopamine synthesis pathways like TH and sepiapterin reductase should be considered,especially if inheritance is recessive or atypical features like mental retardation or oculogyric crises are present(class IV)[36,37].Parkin mutations are a rare di?erential diagnosis of DRD,and the diagnosis can be made by dopamine transporter imag-ing(class IV)[38].For the TH gene,sequencing of the 3¢-promoter sequence is recommended to increase mutation detection(class IV)[39].

A therapeutic trial with levodopa has been proposed for diagnostic purposes(class IV)[40].Alternatively, studies on pterin and dopamine metabolites from cer-ebrospinal?uid(CSF)or a phenylalanine loading test have been suggested as diagnostic complements[41–43], but there is no clear evidence regarding their diagnostic accuracy and both may only be performed in special-ized centres.Hence,the practical recommendation still remains that every patient with early-onset dystonia without an alternative diagnosis should have a trial with levodopa.The initial symptoms at the onset of M-D emerge in childhood and usually consist of light-ning jerks and dystonia mostly a?ecting the neck and the upper limbs,with a prevalent proximal involvement and slow progression[44].In a subset of patients,M-D presents as a gait disorder with lower limb onset and evolves into the typical clinical presentation until ado-lescence[45,46].Myoclonus and dystonia are strikingly alleviated by alcohol in many but not in all patients [47].However,a response to alcohol is not speci?c for DYT11(class IV)[48–50].In patients with the typical M-D phenotype,mutations in the epsilon-sarcoglycan gene(DYT11)may be detected in over50%with an age at onset generally below20[51–54].As in DRD,the rate of mutation detection in the epsilon-sarcoglycan gene is increased by screening for exon or whole gene deletions(gene dosage)[50,55–57].Complex pheno-types with additional features may be related to chro-mosomal deletions and rearrangements of the7q21 region[50,57–59].

In DYT12,RDP,the mutated gene is ATP1A3.RDP is an extremely rare disease with onset in childhood or early adulthood in which patients develop dystonia, bradykinesia,postural instability,dysarthria and dys-phagia over a period ranging from several hours to weeks with triggering factors[60].In addition to rapid onset,features suggesting an ATP1A3mutation are prominent bulbar symptoms and a gradient of dystonia severity with the cranial region being more severely a?ected than arms and legs.Tremor at onset or prominent pain could not be found in ATP1A3muta-tion-positive patients[61].

Protein-kinase RNA-dependent activator(PRKRA) has been identi?ed as the DYT16gene on chromosome 2q31.2.Mutations cause a novel form of non-degener-ative,early-onset AR dystonia-parkinsonism[62].The phenotypic spectrum of DYT16has not been deter-mined yet.

Four forms of paroxysmal dystonias have been genetically de?ned to date.In two,only the locus has been mapped:paroxysmal dystonic choreoathetosis with episodic ataxia and spasticity(DYT9)and par-oxysmal familial kinesigenic dyskinesia(DYT10). Paroxysmal non-kinesigenic dystonia(PNKD,DYT8) is caused by mutations in the myo?brillogenesis regulator1(MR-1)gene in all families with a typical PNKD phenotype[63–65].This condition is charac-terized by episodes of choreodystonia with onset in infancy or early childhood.Attacks typically last 10min–1h and are induced by ca?eine or alcohol [66].

Paroxysmal exertion-induced dyskinesia(PED)is caused by mutations in the gene for the glucose trans-porter1(SLC2A1,DYT18).In addition to PED, patients with DYT18gene may present with epilepsy (absence or generalized tonic-clonic seizures),migraine, cognitive de?cits,haemolytic anaemia or developmental

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delay.A diagnostic marker is a decreased CSF/serum glucose ratio below0.5(class III)[67,68]. Recommendations and good practice points

1.Genetic testing should be performed after establish-ing the clinical diagnosis.Genetic testing is not su?-cient to make a diagnosis of dystonia without clinical features of dystonia[26,69,70](level B).Genetic coun-selling is recommended.

2.DYT1testing is recommended for patients with limb-onset,primary dystonia with onset before age30[70] (level B),as well as in those with onset after age30if they have an a?ected relative with early-onset dystonia [26,70](level B).

3.In dystonia families,DYT1testing is not recom-mended in asymptomatic individuals(good practice point).

4.DYT6testing is recommended in early-onset dystonia or familial dystonia with cranio-cervical predominance [28,29]or after exclusion of DYT1(good practice point).

5.A diagnostic levodopa trial is warranted in every patient with early-onset dystonia without an alternative diagnosis[40](good practice point).

6.Individuals with early-onset myoclonus a?ecting the arms or neck,particularly if positive for autosomal-dominant inheritance and if triggered by action,should be tested for the DYT11gene[51](good practice point). If direct sequencing of the SGCE gene is negative,gene dosage studies increase the proportion of mutation-positives(level C).

7.Diagnostic testing for the PNKD gene(DYT8)is recommended in symptomatic individuals with PNKD (good practice point).

8.Gene testing for mutation in GLUT1is recom-mended in patients with paroxysmal exercise-induced dyskinesias,especially if involvement of GLUT1is suggested by low CSF/serum glucose ratio,epileptic seizures or haemolytic anaemia(good practice point). Use of neurophysiology in the diagnosis and

classi?cation of dystonia

Neurophysiological tests are helpful in the character-ization of functional abnormalities in patients with dystonia.However,all neurophysiology studies are class IV,not providing evidence-based results.The need for standardized study designs and methods to investi-gate the diagnostic sensitivity and speci?city of neuro-physiological tests in dystonia has been emphasized in a recent review[71].A number of studies have been reviewed previously[6]and will not be dealt with here. Alterations in cerebellar functions suggest a role of the cerebellum in the pathophysiology of dystonia[72,73].Cortical excitability is abnormally enhanced in symp-tomatic and non-symptomatic DYT1carriers,whilst this is not the case in DYT11M-D syndrome[74].The induction of plastic changes in the motor cortex by repetitive transcranial magnetic stimulation(rTMS)at theta burst frequency has been found to be excessive in patients with dystonia(either genetic or sporadic)and abnormally reduced in asymptomatic DYT1carriers [75].It is possible that such decrease in gene carriers with no symptoms indicates a form of protection against the propensity or susceptibility of DYT1 patients to undergo plastic changes that could eventu-ally lead to clinical manifestations of dystonia. Disturbed sensory processing has been for the past years recognized as one of the main pathophysiological agents of dystonia[76,77].Many authors have contrib-uted recently to con?rm these?ndings and expand in the implication of altered sensory processing in the disor-dered motor control of patients with dystonia:abnormal sensory perception has been reported with studies of mental rotation and two point discrimination[78]. Several reports have shown abnormal enhancement of sensory evoked potentials(SEP)in patients with dys-tonia[79].Notably,however,the only study in which the assessment was carried out blindly showed that di?er-ences in the size of the SEPs were not signi?cant between patients and controls or between patients before and after botulinum toxin treatment[80].Somatosensory stimuli cause abnormally reduced inhibitory e?ects on the motor evoked potentials(MEP)to TMS,regardless of whether the stimulus is applied on homotopic or heterotopic peripheral nerves[81].A recent study indi-cates that somatosensory temporal discrimination threshold abnormalities are a generalized feature of patients with primary focal dystonias and are a valid tool for screening subclinical sensory abnormalities[82]. Using the paradigm of paired associative stimulation (PAS),i.e.,applying a sensory stimulus followed15–20ms later by a single pulse TMS,Tamura et al.[79] reported a transient enhancement of cortical excitabil-ity,manifested by an increase in the P27of the somatosensory evoked potentials tested15min after PAS.The same intervention was reported to cause an abnormal increase in the MEP,which is not only limited to the territory depending on the nerve stimulated but includes other muscles as well[83].

In most instances,neurophysiological abnormalities are not speci?c but,rather,they reveal a trend towards functional defects that may or may not become clini-cally relevant.This is the case in non-a?ected relatives of patients with dystonia[78]or in non-dystonic sites of patients with focal dystonia.Changes in neuronal excitability have been found in patients with forms of dystonia akin to psychogenicity[84,85].

EFNS dystonia guidelines9

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European Journal of Neurologyó2010EFNS European Journal of Neurology18,5–18

Recommendations and good practice points

1.Neurophysiological tests are not routinely recom-mended for the diagnosis or classi?cation of dystonia; however,multiple simultaneous electromyography (EMG)recordings from various muscles may contri-bute to the clinical assessment by showing characteristic features of dystonia[9](good practice point).

Use of brain imaging in the diagnosis of dystonia Conventional or structural MRI studies in primary dystonia are normal,and a normal MRI study is usu-ally considered a pre-requisite to state that a patient?s dystonia is primary.Recent class III[86]and class IV [87–89]di?usion magnetic resonance studies found signal abnormalities in various brain areas(including corpus callosum,basal ganglia,pontine brainstem and pre-frontal cortical areas)in cervical dystonia,writer?s cramp and generalized dystonia,but not in blepharos-pam.

Interesting prospects of understanding the patho-physiological mechanisms of primary and secondary dystonia are o?ered by functional MRI studies.Class IV studies conducted in series of patients with blepha-rospasm[90],writer?s cramp[91–93]or other focal dystonia of the arm[94]demonstrated that several deep structures and cortical areas may be activated in pri-mary dystonia,depending on the di?erent modalities of examination.A class II study on blepharospasm and cervical dystonia demonstrated increased basal ganglia activation in a task not primarily involving the dystonic musculature[95].

Recent class II[96]and class IV[97–100]voxel-based morphometry studies demonstrated an increase in grey matter density or volume in various areas,including cerebellum,basal ganglia and primary somatosensory cortex.This increase might represent plastic changes secondary to overuse,but di?erent interpretations have been considered.Another class IV study found that non-DYT1adult-onset patients with dystonia and asymptomatic DYT1carriers have signi?cantly larger basal ganglia compared to symptomatic DYT1muta-tion carriers,with a signi?cant negative correlation between severity of dystonia and basal ganglia size in DYT1patients[101].

Positron emission tomography studies with di?erent tracers have provided information about areas of abnormal metabolism in di?erent types of dystonia and in di?erent conditions(e.g.during active involuntary movement or during sleep),providing insight on the role of cerebellar and subcortical structures versus cortical areas in the pathophysiology of dystonia(all class IV studies)[102,103].A signi?cant reduction in caudate and putamen D2receptor availability and re-duced[11C]raclopride binding in the ventrolateral thalamus were evident in DYT6and DYT1dystonia in a class III study[104].The changes were greater in DYT6than DYT1carriers without di?erence between manifesting and non-manifesting carriers of either genotype.

A practical approach to di?erentiate patients with dystonia-plus syndromes from patients with parkin-sonism and secondary dystonia is to obtain a single photon emission computerized tomography study with ligands for dopamine transporter;this is readily avail-able and less expensive than positron emission tomog-raphy.Patients with DRD have normal studies, whereas patients with early-onset Parkinson?s disease show reduction of striatal ligand uptake(class IV)[105]. It has been suggested that patients with tremor resem-bling parkinsonian tremor who have normal DAT scans may be a?ected by dystonia[4]. Recommendations and good practice points

1.Structural brain imaging is not routinely required when there is a con?dent diagnosis of primary dystonia in adult patients,because a normal study is expected in primary dystonia[106](good practice point).

2.Structural brain imaging(MRI)is necessary for screening of secondary forms of dystonia[107](good practice point).Computed tomography may be required to di?erentiate between calcium and iron accumulation.

3.Pre-synaptic dopaminergic scan(DAT or18F-DOPA)is useful to di?erentiate between DRD and juvenile Parkinson?s disease presenting with dystonia (good practice point).This can also be useful to dis-tinguish dystonic tremor from parkinsonian tremor (good practice point).

Treatment

Botulinum toxin(BoNT)treatment continues to be the ?rst choice treatment for most types of focal dystonia. Pharmacological and neurosurgical treatments have also a role in the treatment algorithm.

Medical treatments:BoNT

It is established that BoNT,in properly adjusted doses, are e?ective and safe treatments of cranial(excluding oromandibular)and cervical dystonia[6].In the last years long-term studies on the e?cacy and safety of BoNT/A have become available,a new formulation of BoNT/A has been marketed,and new studies on BoNT/ B have been performed.Further to systematic reviews already reported in the previous guidelines version,a new evidence-based systematic review released by the

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American Academy of Neurology[108]recommended that BoNT injections should be o?ered as a treatment option for cervical dystonia(established as e?ective)and may be o?ered for blepharospasm,focal upper extre-mity dystonia,adductor laryngeal dystonia(probably e?ective).A lower level of evidence was detected for focal lower limb dystonia(possibly e?ective).

The e?cacy and safety pro?le of BoNT treatment has been evaluated in long-term observational studies. In patients with di?erent dystonia types followed for >12years,there was no decline of e?cacy and the main side e?ects consisted in muscle weakness in or around the injected region[109].Also,immunogenicity was found to be low for BoTN/A in long-term use, although might be higher for BoTN/B(Class III, [110]).Four class I[111–114],two class II[115,116], two class III[80,117]and29class IV new studies on BoNT were identi?ed.These reports have con?rmed the long-term safety of BoNT products for dystonia and other conditions.A meta-analysis performed on children with cerebral palsy found that adverse events are more frequent amongst children with cerebral palsy than in individuals with other conditions[118]. Occasional occurrences of botulism-like symptoms have been reported in children and in adults treated with BoNT products;therefore,the United States Food and Drug Administration has ordered the manufacturers to add a boxed warning to the pre-scribing information for each product about the po-tential for serious side e?ects at sites distant from injection[119].No similar initiative has been taken by the European Medicines Agency.Furthermore,the possible occurrence of central e?ect following BoNT because of axonal migration and neuronal transcytosis has been recently suggested[120],but not unequivo-cally demonstrated.

Three recent studies compared di?erent BoNT/A products and three compared the A and B serotypes. Two class II trials reported that Xeomin is as e?ective and safe as Botox for the treatment for cervical dysto-nia[115]and blepharospasm[121].A class IV trial found that in cervical dystonia and blepharospasm, Botox is more e?cacious than Dysport and has a longer duration of e?ect[122].A class IV study with longer follow-up reported that in blepharospasm the mean duration of improvement was higher for Dysport than for Botox[123].Two class I studies found that improvement of cervical dystonia was comparable following BoNT/A and B treatments,but dry mouth and dysphagia were more frequent with BoNT/B [112,114].A class II study reported that patients treated with BoNT/B had less saliva production and more severe constipation than those treated with BoNT/A [116].

A class IV study reported that using EMG guidance can improve outcome in patients with cervical dystonia [124].A class III trial evaluated that the association of ad hoc rehabilitative programme with BoNT injections in patients with cervical dystonia[117]provided more marked improvement and a longer duration e?ect than BoNT injections alone.

Recommendations and good practice points

1.BoNT/A(or type B if there is resistance to type A) can be regarded as?rst-line treatment for primary cranial(excluding oromandibular)or cervical dystonia [125,126](level A).

2.BoNT/A is e?ective for writer?s cramp[113](level A) and is possibly e?ective in other types of upper limb dystonia,but controlled dose adjustments are needed because of frequent muscle weakness(good practice point).

3.BoNT/A is probably e?ective for adductor-type lar-yngeal dystonia,but there is insu?cient evidence to support e?cacy in abductor-type laryngeal dystonia and in muscular tension dysphonia(good practice point).

4.BoNT are safe and e?cacious when repeated treat-ments are performed over many years(good practice point),but doctors and patients should be aware that excessive cumulative doses may be dangerous,particu-larly in children(good practice point).

5.BoNT injections can be performed by direct inspec-tion;EMG-or ultrasound-assisted targeting may improve clinical outcome(good practice point).

6.BoNT should not be used in patients a?ected by a disorder of neuromuscular transmission or in presence of local infection at the injection site.The recom-mended dosage should not be exceeded(good practice point).

Other medical treatments

No new class A or B data are available for oral medi-cations.Therefore,the previously reported recommen-dations and good practice points are retained[6]. Neurosurgical procedures:Deep brain stimulation

Long-term electrical stimulation of the globus pallidus internus(GPi)is now established as an e?ective treat-ment for various types of dystonia[127].The use of deep brain stimulation(DBS)for dystonia currently addresses in particular primary generalized or segmen-tal forms,complex cervical dystonia and tardive dys-tonia in patients who do not achieve su?cient relief with conservative approaches[128].Other manifesta-tions are still being explored,such as status dystonicus, task-speci?c dystonia,camptocormia and secondary

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dystonias including hemidystonia,pantothenate kinase-associated neurodegeneration,Lesch-Nyhan and cere-bral palsy-related dystonia-choreoathetosis.DBS for dystonia is widely available in Western countries and in Japan.After it received FDA approval in the form of a humanitarian device exemption in the United States and CE certi?cation in Europe,it is uniformly being reimbursed by health-insurance carriers.

In August2006,the National Institute for Clinical Excellence(NICE),UK,published a guideline for treatment of tremor and dystonia with DBS[129], which was based on data from a systematic review and two primary studies.According to this evidence,GPi DBS provided marked bene?t of dystonia,with improvement of dystonia motor scores ranging between34and88%and disability scores between40 and50%.A meta-analysis using a regression analysis published in2006revealed that longer duration of dystonia correlated negatively with surgical outcome [130].The German DBS Working Group recently pro-vided recommendations on several practical issues[131]. One class I randomized sham-controlled study with a crossover design at3months found that in patients with primary generalized and segmental dystonia the change from baseline in the mean dystonia motor score was signi?cantly greater in the neurostimulation group ()15.8±14.1points)than in the sham-stimulation group()1.4±3.8points)[132].In addition,patients in the sham-stimulation group had a similar bene?t when they switched to active treatment during the open label phase of the study.A total of22adverse events occurred in19patients(the most frequent adverse event was dysarthria)during an overall follow-up of 6months.

There are several studies with some form of blinded assessment,including either blinded video evaluation or double-blind assessment randomized to o?or on DBS [133–136]which provide class II-III evidence and sup-port the e?cacy and safety of DBS GPi in selected patients with primary generalized or segmental dystonia [133,134],primary cervical dystonia[135]or tardive dystonia[136].

Numerous class IV studies with either prospective or retrospective design have been published over the past few years.The e?cacy of GPi DBS was related to dis-ease duration in one study[137].Quality of life was shown to improve both in patients with primary seg-mental and generalized dystonia[138–141].Stimulation via contacts located directly within the posteroventral portion of the GPi provided the best overall e?ect[142]. Whilst high-frequency stimulation at130Hz or higher has been used in most studies,stimulation<100Hz has been shown to be a possible alternative in selected patients with dystonia[143,144].

It is clear that improvement of dystonia after DBS frequently follows a particular pattern,with phasic, myoclonic and tremulous elements improving earlier than tonic elements,the latter often with a delay of weeks or months[145–147].More recently,it has also been shown that upon recurrence of dystonia after switching o?DBS,phasic elements manifest again within minutes and tonic elements within hours[148]. The GPi has been used in most studies on chronic stimulation,whilst there is limited experience with other targets[128]such as thalamus[149],STN[150]and cortex[151].

Overall,the most bene?cial results with pallidal DBS were reported in children with primary generalized dystonia.DYT1dystonia was shown to improve in the range of40%to90%[152–154]and also,adult patients with non-DYT1primary generalized dystonia can achieve equivalent bene?t[145,146,155].The French Spidy Study on patients with primary generalized dys-tonia reported a mean motor improvement of54%,and a mean improvement of disability of44%at1-year follow-up[133].

Long-term e?cacy was reported to be sustained after more than5years of follow-up[156–159].Bilateral pallidal stimulation did not negatively a?ect cognitive performance[160].

In patients with cervical dystonia,GPi DBS has been used primarily in those who were thought not to be ideal candidates for peripheral denervation,including patients with head tremor and myoclonus,or marked phasic dystonic movements[147,161,162].In the past few years,however,indications have been widened.In a recent class II trial,the Toronto Western Spasmodic Torticollis Rating Scale(TWSTRS)dystonia severity score improved from a mean of14.7±4.2before surgery to8.4±4.4at12months post-operatively [135].Disability and pain scores improved similarly. Patients with primary craniofacial dystonia may achieve similar bene?t than patients with other seg-mental dystonia with regard to the severity score.In a study on six patients with Meige syndrome,a mean improvement of72%of dystonia motor scores was seen at6months post-operatively[163].The impact of GPi on secondary dystonia,in general,is much less pro-nounced.Patients with dystonia and choreoathetosis because of cerebral palsy may achieve limited bene?t with motor scores improving between10–40%,but nevertheless yielding acceptable patient satisfaction in some patients[164].Tardive dystonia,as opposed to other dystonias appears also a good indication for Gpi DBS with bene?ts similar to those seen in primary dystonia[136].

Safety aspects which have to be considered include surgery-related complications,stimulation-induced side

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e?ects and hardware-related problems.Recently,it was noted that Gpi DBS in patients with segmental dystonia may induce a parkinsonian gait or bradykinesia in extremities which were not a?ected by dystonia at chronic stimulation with high voltage[163,165]. Chronic stimulation in dystonia uses both higher pulse width and voltage than in PD which results in earlier battery depletion;replacement may be needed sometimes every2years or less.Sudden battery deple-tion may induce acute recurrence of dystonia,some-times resulting in a medical emergency.No study,thus far,has evaluated if rechargeable pulse generators are more useful than non-rechargeable ones for patients with dystonia.

Recommendations and good practice points

1.Pallidal DBS is considered a good option,particu-larly for primary generalized or segmental dystonia, after medication or BoNT has failed to provide ade-quate improvement[132](level A).

2.Pallidal DBS can be considered a good option for cervical dystonia,after medication or BoNT has failed to provide adequate improvement[135](level B).

3.Pallidal DBS,in general,is less e?ective in secondary dystonia with the exception of tardive dystonia [164,166](level C).

4.This procedure requires a specialized expertise and a multidisciplinary team and is not without side e?ects (good practice point).

Other surgical procedures

In the past5years,there have been no new studies providing class I or II evidence for selective peripheral denervation,myectomy and myotomy,intrathecal baclofen or radiofrequency lesioning.Therefore,the previously reported recommendations and good prac-tice points are retained[6].

Physical therapy and rehabilitation

Recently,there have been an increased number of publications showing that physical therapy and reha-bilitation procedures have an important role in the care of patients with dystonia[167,168].A number of studies have reported motor improvement in patients with writer?s cramp and other forms of focal dystonia fol-lowing physical treatment,and sensory and motor retraining[169–171].

A class II study showed that transcutaneous electrical nerve stimulation caused a signi?cant bene?cial e?ect in patients with writer?s cramp[172].A class IV study of patients with primary writing tremor showed bene?cial e?ect of writing after training with a device that sup-ported the hand and held the pen[173].This evidence adds to the already reported class III study[117]where physical therapy was combined with BoNT/A injections in patients with cervical dystonia.

Musicians with dystonia may have speci?c bene?t from motor retraining.A class IV study reported the long-term subjective outcome in a large series of musi-cians with focal dystonia after treatment with di?erent medical and physical options:54%of patients reported an alleviation of symptoms,33%improved with trih-exiphenidyl,49%with BoNT,50%with pedagogical retraining,56%with unmonitored technical exercises and63%with ergonomic changes[167]. Recommendations and good practice points

1.Transcutaneous electrical nerve stimulation to fore-arm?exor muscles administered is probably e?ective in patients with writer?s cramp[172](level B).

2.We encourage the conduction of new randomized controlled studies on these potentially useful interven-tions,particularly for patients with upper limb dystonia (good practice point).

References

1.Fahn S,Marsden CD,Calne DB.Classi?cation and

investigation of dystonia.In:Marsden CD,Fahn S eds.

Movement disorders2.London:Butterworths,1987:332–358.

2.Fahn S,Bressman S,Marsden CD.Classi?cation of

dystonia.Adv Neurol1998;78:1–10.

https://www.doczj.com/doc/5714900774.html,lli S,Albanese A.The diagnostic challenge of primary

dystonia:evidence from misdiagnosis.Mov Disord2010;

in press.

4.Schneider SA,Edwards MJ,Mir P,et al.Patients with

adult-onset dystonic tremor resembling parkinsonian tremor have scans without evidence of dopaminergic de?cit(SWEDDs).Mov Disord2007;22:2210–2215. 5.Brainin M,Barnes M,Baron JC,et al.Guidance for the

preparation of neurological management guidelines by EFNS scienti?c task forces–revised recommendations 2004.Eur J Neurol2004;11:577–581.

6.Albanese A,Barnes MP,Bhatia KP,et al.A systematic

review on the diagnosis and treatment of primary(idio-pathic)dystonia and dystonia plus syndromes:report of an EFNS/MDS-ES Task Force.Eur J Neurol2006;13: 433–444.

7.Ludlow CL,Adler CH,Berke GS,et al.Research pri-

orities in spasmodic dysphonia.Otolaryngol Head Neck Surg2008;139:495–505.

8.Hallett M,Evinger C,Jankovic J,Stacy M.Update on

blepharospasm:report from the BEBRF International Workshop.Neurology2008;71:1275–82.

9.Albanese A,Lalli S.Is this dystonia?Mov Disord2009;

24:1725–1731.

10.Burke RE,Fahn S,Marsden CD,Bressman SB,

Moskowitz C,Friedman J.Validity and reliability of a rating scale for the primary torsion dystonias.Neurology 1985;35:73–77.

EFNS dystonia guidelines13

ó2010The Author(s)

European Journal of Neurologyó2010EFNS European Journal of Neurology18,5–18

https://www.doczj.com/doc/5714900774.html,ella CL,Leurgans S,Wuu J,Stebbins GT,Chmura

T.Rating scales for dystonia:a multicenter assessment.

Mov Disord2003;18:303–312.

12.Cano SJ,Hobart JC,Fitzpatrick R,Bhatia K,Thompson

AJ,Warner TT.Patient-based outcomes of cervical dystonia:a review of rating scales.Mov Disord2004;19: 1054–1059.

13.Consky ES,Lang AE.Clinical assessments of patients

with cervical dystonia.In:Jankovic J,Hallett M eds.

Therapy with botulinum toxin.New York,NY:Marcel Dekker,1994:211–237.

14.Tsui JK,Eisen A,Stoessl AJ,Calne S,Calne DB.

Double-blind study of botulinum toxin in spasmodic https://www.doczj.com/doc/5714900774.html,ncet1986;2:245–247.

15.O?Brien C,Brashear A,Cullis P,et al.Cervical dystonia

severity scale reliability study.Mov Disord2001;16: 1086–1090.

16.Lim VK.Health related quality of life in patients with

dystonia and their caregivers in New Zealand and Aus-tralia.Mov Disord2007;22:998–1003.

17.Ozelius LJ,Hewett JW,Page CE,et al.The early-onset

torsion dystonia gene(DYT1)encodes an ATP-binding protein.Nat Genet1997;17:40–48.

18.Fuchs T,Gavarini S,Saunders-Pullman R,et al.Muta-

tions in the THAP1gene are responsible for DYT6pri-mary torsion dystonia.Nat Genet2009;41:286–288. 19.Muller U.The monogenic primary dystonias.Brain2009;

132:2005–2025.

20.Calakos N,Patel V,Gottron M,et al.Functional

evidence implicating a novel TOR1A mutation in idio-pathic,late-onset focal dystonia.J Med Genet2009;

in press.

21.Bressman SB,Raymond D,Wendt K,et al.Diagnostic

criteria for dystonia in DYT1families.Neurology2002;

59:1780–1782.

22.Zirn B,Grundmann K,Huppke P,et al.Novel TOR1A

mutation p.Arg288Gln in early-onset dystonia(DYT1).

J Neurol Neurosurg Psychiatry2008;79:1327–1330. 23.Edwards M,Wood N,Bhatia K.Unusual phenotypes in

DYT1dystonia:a report of?ve cases and a review of the literature.Mov Disord2003;18:706–711.

24.Gambarin M,Valente EM,Liberini P,et al.Atypical

phenotypes and clinical variability in a large Italian family with DYT1-primary torsion dystonia.Mov Disord 2006;21:1782–1784.

25.Valente EM,Warner TT,Jarman PR,et al.The role of

DYT1in primary torsion dystonia in Europe.Brain 1998;121:2335–2339.

26.Bressman SB,Sabatti C,Raymond D,et al.The DYT1

phenotype and guidelines for diagnostic testing.Neurol-ogy2000;54:1746–1752.

27.Fasano A,Nardocci N,Elia AE,Zorzi G,Bentivoglio

AR,Albanese A.Non-DYT1early-onset primary torsion dystonia:comparison with DYT1phenotype and review of the literature.Mov Disord2006;21:1411–1418.

28.Djarmati A,Schneider SA,Lohmann K,et al.Mutations

in THAP1(DYT6)and generalised dystonia with prominent spasmodic dysphonia:a genetic screening https://www.doczj.com/doc/5714900774.html,ncet Neurol2009;8:447–452.

29.Bressman SB,Raymond D,Fuchs T,Heiman GA,

Ozelius LJ,Saunders-Pullman R.Mutations in THAP1 (DYT6)in early-onset dystonia:a genetic screening https://www.doczj.com/doc/5714900774.html,ncet Neurol2009;8:441–446.30.Segawa M,Hosaka A,Miyagawa F,Nomura Y,Imai H.

Hereditary progressive dystonia with marked diurnal ?uctuation.Adv Neurol1976;14:215–233.

31.Trender-Gerhard I,Sweeney MG,Schwingenschuh P,

et al.Autosomal-dominant GTPCH1-de?cient DRD: clinical characteristics and long-term outcome of34 patients.J Neurol Neurosurg Psychiatry2009;80:839–845.

32.Bandmann O,Wood NW.Dopa-responsive dystonia.

The story so far.Neuropediatrics2002;33:1–5.

33.Hagenah J,Saunders-Pullman R,Hedrich K,et al.High

mutation rate in dopa-responsive dystonia:detection with comprehensive GCHI screening.Neurology2005;

64:908–811.

34.Steinberger D,Trubenbach J,Zirn B,Leube B,Wild-

hardt G,Muller U.Utility of MLPA in deletion analysis of GCH1in dopa-responsive dystonia.Neurogenetics 2007;8:51–55.

35.Zirn B,Steinberger D,Troidl C,et al.Frequency of

GCH1deletions in Dopa-responsive dystonia.J Neurol Neurosurg Psychiatry2008;79:183–186.

36.Clot F,Grabli D,Cazeneuve C,et al.Exhaustive analysis

of BH4and dopamine biosynthesis genes in patients with Dopa-responsive dystonia.Brain2009;132:1753–1763.

37.Tassin J,Durr A,Bonnet AM,et al.Levodopa-respon-

sive dystonia.GTP cyclohydrolase I or parkin mutations.

Brain2000;123:1112–1121.

38.Jeon BS,Jeong JM,Park SS,et al.Dopamine trans-

porter density measured by[123I]beta-CIT single-photon emission computed tomography is normal in dopa-responsive dystonia.Ann Neurol1998;43:792–800. 39.Verbeek MM,Steenbergen-Spanjers GC,Willemsen

MA,et al.Mutations in the cyclic adenosine mono-phosphate response element of the tyrosine hydroxylase gene.Ann Neurol2007;62:422–426.

40.Robinson R,McCarthy GT,Bandmann O,Dobbie M,

Surtees R,Wood NW.GTP cyclohydrolase de?ciency;

intrafamilial variation in clinical phenotype,including levodopa responsiveness.J Neurol Neurosurg Psychiatry 1999;66:86–89.

41.Bandmann O,Goertz M,Zschocke J,et al.The phen-

ylalanine loading test in the differential diagnosis of dystonia.Neurology2003;60:700–702.

42.Hyland K,Fryburg JS,Wilson WG,et al.Oral phenyl-

alanine loading in dopa-responsive dystonia:a possible diagnostic test.Neurology1997;48:1290–1297.

43.Hyland K,Nygaard TG,Trugman JM,Swoboda KJ,

Arnold LA,Sparagana SP.Oral phenylalanine loading pro?les in symptomatic and asymptomatic gene carriers with dopa-responsive dystonia due to dominantly inher-ited GTP cyclohydrolase de?ciency.J Inherit Metab Dis 1999;22:213–215.

44.Asmus F,Gasser T.Inherited myoclonus-dystonia.Adv

Neurol2004;94:113–119.

45.Foncke EM,Gerrits MC,van RF,et al.Distal myoclo-

nus and late onset in a large Dutch family with myoc-lonus-dystonia.Neurology2006;67:1677–1680.

46.Asmus F,Langseth A,Doherty E,et al.‘‘Jerky’’dysto-

nia in children:spectrum of phenotypes and genetic testing.Mov Disord2009;24:702–709.

47.Vidailhet M,Tassin J,Durif F,et al.A major locus for

several phenotypes of myoclonus–dystonia on chromo-some7q.Neurology2001;56:1213–1216.

14 A.Albanese et al.

ó2010The Author(s)

European Journal of Neurologyó2010EFNS European Journal of Neurology18,5–18

48.Tezenas du Montcel S,Clot F,Vidailhet M,et al.Epsi-

lon sarcoglycan mutations and phenotype in French patients with myoclonic syndromes.J Med Genet2006;

43:394–400.

49.Ritz K,Gerrits MC,Foncke EM,et al.Myoclonus-

dystonia:clinical and genetic evaluation of a large cohort.J Neurol Neurosurg Psychiatry2009;80:653–658.

50.Grunewald A,Djarmati A,Lohmann-Hedrich K,et al.

Myoclonus-dystonia:signi?cance of large SGCE dele-tions.Hum Mutat2008;29:331–332.

51.Valente EM,Edwards MJ,Mir P,et al.The epsilon-

sarcoglycan gene in myoclonic syndromes.Neurology 2005;64:737–739.

52.Klein C,Schilling K,Saunders-Pullman RJ,et al.A major

locus for myoclonus-dystonia maps to chromosome7q in eight families.Am J Hum Genet2000;67:1314–1319. 53.Leung JC,Klein C,Friedman J,et al.Novel mutation in

the TOR1A(DYT1)gene in atypical early onset dystonia and polymorphisms in dystonia and early onset parkin-sonism.Neurogenetics2001;3:133–143.

54.Asmus F,Zimprich A,Tezenas du MS,et al.Myoclonus-

dystonia syndrome:epsilon-sarcoglycan mutations and phenotype.Ann Neurol2002;52:489–492.

55.Asmus F,Salih F,Hjermind LE,et al.Myoclonus-dys-

tonia due to genomic deletions in the epsilon-sarcoglycan gene.Ann Neurol2005;58:792–797.

56.Han F,Racacho L,Yang H,et https://www.doczj.com/doc/5714900774.html,rge deletions ac-

count for an increasing number of mutations in SGCE.

Mov Disord2008;23:456–460.

57.Asmus F,Hjermind LE,Dupont E,et al.Genomic

deletion size at the epsilon-sarcoglycan locus determines the clinical phenotype.Brain2007;130:2736–2745. 58.Bonnet C,Gregoire MJ,Vibert M,Raffo E,Leheup B,

Jonveaux P.Cryptic7q21and9p23deletions in a patient with apparently balanced de novo reciprocal transloca-tion t(7;9)(q21;p23)associated with a dystonia-plus syn-drome:paternal deletion of the epsilon-sarcoglycan (SGCE)gene.J Hum Genet2008;53:876–885.

59.Guettard E,Portnoi MF,Lohmann-Hedrich K,et al.

Myoclonus-dystonia due to maternal uniparental disomy.Arch Neurol2008;65:1380–1385.

60.Dobyns WB,Ozelius LJ,Kramer PL,et al.Rapid-onset

dystonia-parkinsonism.Neurology1993;43:2596–2602.

61.Brashear A,Dobyns WB,de Carvalho Aguiar P,et al.

The phenotypic spectrum of rapid-onset dystonia-par-kinsonism(RDP)and mutations in the ATP1A3gene.

Brain2007;130:828–835.

62.Camargos S,Scholz S,Simon-Sanchez J,et al.DYT16,a

novel young-onset dystonia-parkinsonism disorder: identi?cation of a segregating mutation in the stress-response protein https://www.doczj.com/doc/5714900774.html,ncet Neurol2008;7:207–215.

63.Rainier S,Thomas D,Tokarz D,et al.Myo?brillo-

genesis regulator1gene mutations cause paroxysmal dystonic choreoathetosis.Arch Neurol2004;61:1025–1029.

64.Lee HY,Xu Y,Huang Y,et al.The gene for paroxysmal

non-kinesigenic dyskinesia encodes an enzyme in a stress response pathway.Hum Mol Genet2004;13:3161–3170.

65.Chen DH,Matsushita M,Rainier S,et al.Presence of

alanine-to-valine substitutions in myo?brillogenesis regulator1in paroxysmal nonkinesigenic dyskinesia: con?rmation in2kindreds.Arch Neurol2005;62:597–600.66.Bruno MK,Lee HY,Auburger GW,et al.Genotype-

phenotype correlation of paroxysmal nonkinesigenic dyskinesia.Neurology2007;68:1782–1789.

67.Weber YG,Storch A,Wuttke TV,et al.GLUT1muta-

tions are a cause of paroxysmal exertion-induced dyski-nesias and induce hemolytic anemia by a cation leak.

J Clin Invest2008;118:2157–2168.

68.Suls A,Dedeken P,Gof?n K,et al.Paroxysmal exercise-

induced dyskinesia and epilepsy is due to mutations in SLC2A1,encoding the glucose transporter GLUT1.

Brain2008;131:1831–1844.

69.American Society of Human Genetics Board of

Directors,American College of Medical Genetics Board of Directors.Points to consider:ethical,legal, and psychosocial implications of genetic testing in chil-dren and adolescents.Am J Hum Genet1995;57:1233–1241.

70.Klein C,Friedman J,Bressman S,et al.Genetic testing

for early-onset torsion dystonia(DYT1):introduction of

a simple screening method,experiences from testing of a

large patient cohort,and ethical aspects.Genet Test1999;

3:323–328.

71.Tinazzi M,Squintani G,Berardelli A.Does neurophys-

iological testing provide the information we need to improve the clinical management of primary dystonia?

Clin Neurophysiol2009;120:1424–1432.

72.Brighina F,Romano M,Giglia G,et al.Effects of cer-

ebellar TMS on motor cortex of patients with focal dystonia:a preliminary report.Exp Brain Res2009;192: 651–656.

73.Teo JT,van De Warrenburg BP,Schneider SA,Rothwell

JC,Bhatia KP.Neurophysiological evidence for cere-bellar dysfunction in primary focal dystonia.J Neurol Neurosurg Psychiatry2009;80:80–83.

74.Marelli C,Canafoglia L,Zibordi F,et al.A neurophys-

iological study of myoclonus in patients with DYT11 myoclonus-dystonia syndrome.Mov Disord2008;23: 2041–2048.

75.Edwards MJ,Huang YZ,Mir P,Rothwell JC,Bhatia

KP.Abnormalities in motor cortical plasticity differen-tiate manifesting and nonmanifesting DYT1carriers.

Mov Disord2006;21:2181–2186.

76.Murase N,Kaji R,Shimazu H,et al.Abnormal pre-

movement gating of somatosensory input in writer?s cramp.Brain2000;123:1813–1829.

77.Sohn YH,Hallett M.Disturbed surround inhibition in

focal hand dystonia.Ann Neurol2004;56:595–599. 78.Fiorio M,Gambarin M,Valente EM,et al.Defective

temporal processing of sensory stimuli in DYT1muta-tion carriers:a new endophenotype of dystonia?Brain 2007;130:134–142.

79.Tamura Y,Ueki Y,Lin P,et al.Disordered plasticity in

the primary somatosensory cortex in focal hand dystonia.

Brain2009;132:749–755.

80.Contarino MF,Kruisdijk JJ,Koster L,Ongerboer de

Visser BW,Speelman JD,Koelman JH.Sensory inte-gration in writer?s cramp:comparison with controls and evaluation of botulinum toxin effect.Clin Neurophysiol 2007;118:2195–2206.

81.Lourenco G,Meunier S,Vidailhet M,Simonetta-

Moreau M.Impaired modulation of motor cortex excitability by homonymous and heteronymous muscle afferents in focal hand dystonia.Mov Disord2007;22: 523–527.

EFNS dystonia guidelines15

ó2010The Author(s)

European Journal of Neurologyó2010EFNS European Journal of Neurology18,5–18

82.Scontrini A,Conte A,Defazio G,et al.Somatosensory

temporal discrimination in patients with primary focal dystonia.J Neurol Neurosurg Psychiatry2009;80:1315–1319.

83.Quartarone A,Morgante F,Sant?angelo A,et al.

Abnormal plasticity of sensorimotor circuits extends beyond the affected body part in focal dystonia.J Neurol Neurosurg Psychiatry2008;79:985–990.

84.Espay AJ,Morgante F,Purzner J,Gunraj CA,Lang AE,

Chen R.Cortical and spinal abnormalities in psycho-genic dystonia.Ann Neurol2006;59:825–834.

85.Avanzino L,Martino D,van De Warrenburg BP,et al.

Cortical excitability is abnormal in patients with the ‘‘?xed dystonia’’syndrome.Mov Disord2008;23:646–652.

86.Fabbrini G,Pantano P,Totaro P,et al.Diffusion tensor

imaging in patients with primary cervical dystonia and in patients with blepharospasm.Eur J Neurol2008;15:185–189.

87.Carbon M,Kingsley PB,Tang C,Bressman S,Eidelberg

D.Microstructural white matter changes in primary

torsion dystonia.Mov Disord2008;23:234–239.

88.Delmaire C,Vidailhet M,Wassermann D,et al.Diffu-

sion abnormalities in the primary sensorimotor pathways in writer?s cramp.Arch Neurol2009;66:502–508.

89.Bonilha L,de Vries PM,Vincent DJ,et al.Structural

white matter abnormalities in patients with idiopathic dystonia.Mov Disord2007;22:1110–1116.

90.Schmidt KE,Linden DE,Goebel R,Zanella FE,Lan-

fermann H,Zubcov AA.Striatal activation during blepharospasm revealed by fMRI.Neurology2003;60: 1738–1743.

91.Preibisch C,Berg D,Hofmann E,Solymosi L,Naumann

M.Cerebral activation patterns in patients with writer?s cramp:a functional magnetic resonance imaging study.

J Neurol2001;248:10–17.

92.Oga T,Honda M,Toma K,et al.Abnormal cortical

mechanisms of voluntary muscle relaxation in patients with writer?s cramp:an fMRI study.Brain2002;125: 895–903.

93.Peller M,Zeuner KE,Munchau A,et al.The basal

ganglia are hyperactive during the discrimination of tactile stimuli in writer?s cramp.Brain2006;129:2697–2708.

94.Butterworth S,Francis S,Kelly E,McGlone F,Bowtell

R,Sawle GV.Abnormal cortical sensory activation in dystonia:an fMRI study.Mov Disord2003;18:673–682.

95.Obermann M,Yaldizli O,De GA,et al.Increased basal-

ganglia activation performing a non-dystonia-related task in focal dystonia.Eur J Neurol2008;15:831–838.

96.Obermann M,Yaldizli O,De GA,et al.Morphometric

changes of sensorimotor structures in focal dystonia.

Mov Disord2007;22:1117–1123.

97.Draganski B,Thun-Hohenstein C,Bogdahn U,Winkler

J,May A.‘‘Motor circuit’’gray matter changes in idiopathic cervical dystonia.Neurology2003;61:1228–1231.

98.Garraux G,Bauer A,Hanakawa T,Wu T,Kansaku K,

Hallett M.Changes in brain anatomy in focal hand dystonia.Ann Neurol2004;55:736–739.

99.Egger K,Mueller J,Schocke M,et al.Voxel based

morphometry reveals speci?c gray matter changes in primary dystonia.Mov Disord2007;22:1538–1542.100.Delmaire C,Vidailhet M,Elbaz A,et al.Structural abnormalities in the cerebellum and sensorimotor circuit in writer?s cramp.Neurology2007;69:376–380.

101.Draganski B,Schneider SA,Fiorio M,et al.Genotype-phenotype interactions in primary dystonias revealed by differential changes in brain structure.Neuroimage2009;

47:1141–1147.

102.Hutchinson M,Nakamura T,Moeller JR,et al.The metabolic topography of essential blepharospasm:a focal dystonia with general implications.Neurology2000;55: 673–677.

103.Asanuma K,Ma Y,Huang C,et al.The metabolic pathology of dopa-responsive dystonia.Ann Neurol2005;

57:596–600.

104.Carbon M,Niethammer M,Peng S,et al.Abnormal striatal and thalamic dopamine neurotransmission: genotype-related features of dystonia.Neurology2009;

72:2097–2103.

105.Marshall V,Grosset D.Role of dopamine transporter imaging in routine clinical practice.Mov Disord2003;18: 1415–1423.

106.Rutledge JN,Hilal SK,Silver AJ,Defendini R,Fahn S.

Magnetic resonance imaging of dystonic states.Adv Neurol1988;50:265–275.

107.Meunier S,Lehericy S,Garnero L,Vidailhet M.Dysto-nia:lessons from brain mapping.Neuroscientist2003;9: 76–81.

108.Simpson DM,Blitzer A,Brashear A,et al.Assessment: Botulinum neurotoxin for the treatment of movement disorders(an evidence-based review):report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology.Neurology 2008;70:1699–1706.

109.Mejia NI,Vuong KD,Jankovic J.Long-term botulinum toxin ef?cacy,safety,and immunogenicity.Mov Disord 2005;20:592–597.

110.Brin MF,Comella CL,Jankovic J,Lai F,Naumann M.

Long-term treatment with botulinum toxin type A in cervical dystonia has low immunogenicity by mouse protection assay.Mov Disord2008;23:1353–1360. 111.Truong D,Duane DD,Jankovic J,et al.Ef?cacy and safety of botulinum type A toxin(Dysport)in cervical dystonia:results of the?rst US randomized,double-blind,placebo-controlled study.Mov Disord2005;20: 783–791.

https://www.doczj.com/doc/5714900774.html,ella CL,Jankovic J,Shannon KM,et https://www.doczj.com/doc/5714900774.html,pari-son of botulinum toxin serotypes A and B for the treatment of cervical dystonia.Neurology2005;65:1423–1429.

113.Kruisdijk JJ,Koelman JH,Ongerboer de Visser BW,De Haan RJ,Speelman JD.Botulinum toxin for writer?s cramp:a randomised,placebo-controlled trial and1-year follow-up.J Neurol Neurosurg Psychiatry2007;78:264–270.

114.Pappert EJ,Germanson T.Botulinum toxin type B vs.

type A in toxin-naive patients with cervical dystonia: randomized,double-blind,noninferiority trial.Mov Disord2008;23:510–517.

115.Benecke R,Jost WH,Kanovsky P,Ruzicka E,Comes G, Grafe S.A new botulinum toxin type A free of com-plexing proteins for treatment of cervical dystonia.

Neurology2005;64:1949–1951.

116.Tintner R,Gross R,Winzer UF,Smalky KA,Jankovic J.

Autonomic function after botulinum toxin type A or B:a

16 A.Albanese et al.

ó2010The Author(s)

European Journal of Neurologyó2010EFNS European Journal of Neurology18,5–18

double-blind,randomized trial.Neurology2005;65:765–767.

117.Tassorelli C,Mancini F,Balloni L,et al.Botulinum toxin and neuromotor rehabilitation:an integrated ap-proach to idiopathic cervical dystonia.Mov Disord2006;

21:2240–2243.

118.Albavera-Hernandez C,Rodriguez JM,Idrovo AJ.Safety of botulinum toxin type A among children with spasticity secondary to cerebral palsy:a systematic review of ran-domized clinical trials.Clin Rehabil2009;23:394–407. 119.Kuehn BM.FDA requires black box warnings on labeling for botulinum toxin products.JAMA2009;301: 2316.

120.Antonucci F,Rossi C,Gianfranceschi L,Rossetto O, Caleo M.Long-distance retrograde effects of botulinum neurotoxin A.J Neurosci2008;28:3689–3696.

121.Roggenkamper P,Jost WH,Bihari K,Comes G,Grafe S.Ef?cacy and safety of a new Botulinum Toxin Type A free of complexing proteins in the treatment of blepha-rospasm.J Neural Transm2006;113:303–312.

122.Bihari K.Safety,effectiveness,and duration of effect of BOTOX after switching from Dysport for blepharo-spasm,cervical dystonia,and hemifacial spasm dystonia, and hemifacial spasm.Curr Med Res Opin2005;21:433–438.

123.Bentivoglio AR,Fasano A,Ialongo T,Soleti F,Lo Fermo S,Albanese A.Fifteen-year experience in treating blepharospasm with Botox or Dysport:same toxin,two drugs.Neurotox Res2009;15:224–231.

124.Cordivari C,Misra VP,Vincent A,Catania S,Bhatia KP,Lees AJ.Secondary nonresponsiveness to botulinum toxin A in cervical dystonia:the role of electromyogram-guided injections,botulinum toxin A antibody assay,and the extensor digitorum brevis test.Mov Disord2006;21: 1737–1741.

125.Costa J,Espirito-Santo C,Borges A,et al.Botulinum toxin type A therapy for blepharospasm.Cochrane Database Syst Rev2005;CD004900.

126.American Academy of Ophthalmology.Botulinum toxin therapy of eye muscle disorders.Safety and effectiveness.

Ophthalmology1989;96(Pt2):37–41.

127.Krauss JK,Yianni J,Loher TJ,Aziz TZ.Deep brain stimulation for dystonia.J Clin Neurophysiol2004;21: 18–30.

128.Capelle HH,Krauss JK.Neuromodulation in Dystonia: current Aspects of Deep Brain Stimulation.Neuromod-ulation2009;12:8–21.

129.National Institute for Health and Clinical Excellence.

Deep brain stimulation for tremor and dystonia(ex-cluding Parkinson?s disease).https://www.doczj.com/doc/5714900774.html,/ IPG188(accessed5/4/2010).

130.Holloway KL,Baron MS,Brown R,Cifu DX,Carne W, Ramakrishnan V.Deep brain stimulation for dystonia:a meta-analysis.Neuromodulation2006;9:253–261. 131.Schrader C,Benecke R,Deuschl G,et al.Tiefe Hirnsti-mulation bei Dystonie.Empfehlungen der Deutschen Arbeitsgemeinschaft Tiefe Hirnstimulation.Nervenarzt 2009;80:656–661.

132.Kupsch A,Benecke R,Muller J,et al.Pallidal deep-brain stimulation in primary generalized or segmental dysto-nia.N Engl J Med2006;355:1978–1990.

133.Vidailhet M,Vercueil L,Houeto JL,et al.Bilateral deep-brain stimulation of the globus pallidus in primary gen-eralized dystonia.N Engl J Med2005;352:459–467.134.Diamond A,Shahed J,Azher S,Dat-Vuong K,Jankovic J.Globus pallidus deep brain stimulation in dystonia.

Mov Disord2006;21:692–695.

135.Kiss ZH,Doig-Beyaert K,Eliasziw M,Tsui J,Haffenden A,Suchowersky O.The Canadian multicentre study of deep brain stimulation for cervical dystonia.Brain2007;

130:2879–2886.

136.Damier P,Thobois S,Witjas T,et al.Bilateral deep brain stimulation of the globus pallidus to treat tardive dyski-nesia.Arch Gen Psychiatry2007;64:170–176.

137.Isaias IU,Alterman RL,Tagliati M.Outcome predictors of pallidal stimulation in patients with primary dystonia: the role of disease duration.Brain2008;131:1895–1902. 138.Pretto TE,Dalvi A,Kang UJ,Penn RD.A prospective blinded evaluation of deep brain stimulation for the treatment of secondary dystonia and primary torticollis syndromes.J Neurosurg2008;109:405–409.

139.Blahak C,Wohrle JC,Capelle HH,et al.Health-related quality of life in segmental dystonia is improved by bilateral pallidal stimulation.J Neurol2008;255:178–182.

140.Mueller J,Skogseid IM,Benecke R,et al.Pallidal deep brain stimulation improves quality of life in segmental and generalized dystonia:results from a prospective, randomized sham-controlled trial.Mov Disord2008;23: 131–134.

141.Skogseid IM.Pallidal deep brain stimulation is effective, and improves quality of life in primary segmental and generalized dystonia.Acta Neurol Scand Suppl2008;188: 51–55.

142.Tisch S,Zrinzo L,Limousin P,et al.Effect of electrode contact location on clinical ef?cacy of pallidal deep brain stimulation in primary generalised dystonia.J Neurol Neurosurg Psychiatry2007;78:1314–1319.

143.Alterman RL,Miravite J,Weisz D,Shils JL,Bressman SB,Tagliati M.Sixty Hertz pallidal deep brain stimula-tion for primary torsion dystonia.Neurology2007;69: 681–688.

144.Alterman RL,Shils JL,Miravite J,Tagliati M.Lower stimulation frequency can enhance tolerability and ef?-cacy of pallidal deep brain stimulation for dystonia.Mov Disord2007;22:366–368.

145.Coubes P,Cif L,El Fertit H,et al.Electrical stimulation of the globus pallidus internus in patients with primary generalized dystonia:long-term results.J Neurosurg 2004;101:189–194.

146.Krause M,Fogel W,Kloss M,Rasche D,Volkmann J, Tronnier V.Pallidal stimulation for dystonia.Neurosur-gery2004;55:1361–1370.

147.Krauss JK,Pohle T,Weber S,Ozdoba C,Burgunder JM.Bilateral stimulation of globus pallidus internus for treatment of cervical https://www.doczj.com/doc/5714900774.html,ncet1999;354: 837–838.

148.Grips E,Blahak C,Capelle HH,et al.Patterns of reoc-currence of segmental dystonia after discontinuation of deep brain stimulation.J Neurol Neurosurg Psychiatry 2007;78:318–320.

149.Woehrle JC,Blahak C,Kekelia K,et al.Chronic Deep Brain Stimulation for Segmental Dystonia.Stereotact Funct Neurosurg2009;87:379–384.

150.Sun B,Chen S,Zhan S,Le W,Krahl SE.Subthalamic nucleus stimulation for primary dystonia and tardive dystonia.Acta Neurochir Suppl2007;97:207–214.

EFNS dystonia guidelines17

ó2010The Author(s)

European Journal of Neurologyó2010EFNS European Journal of Neurology18,5–18

151.Romito LM,Franzini A,Perani D,et al.Fixed dystonia unresponsive to pallidal stimulation improved by motor cortex stimulation.Neurology2007;68:875–876.

152.Coubes P,Roubertie A,Vayssiere N,Hemm S,Echenne

B.Treatment of DYT1-generalised dystonia by stimula-

tion of the internal globus https://www.doczj.com/doc/5714900774.html,ncet2000;355: 2220–2221.

153.Egidi M,Franzini A,Marras C,et al.A survey of Italian cases of dystonia treated by deep brain stimulation.

J Neurosurg Sci2007;51:153–158.

154.Borggraefe I,Mehrkens JH,Telegravciska M,et al.

Bilateral pallidal stimulation in children and adolescents with primary generalized dystonia-Report of six patients and literature-based analysis of predictive outcomes variables.Brain Dev2010;32:223–228.

155.Yianni J,Bain P,Giladi N,et al.Globus pallidus inter-nus deep brain stimulation for dystonic conditions:a prospective audit.Mov Disord2003;18:436–442. 156.Cersosimo MG,Raina GB,Piedimonte F,Antico J, Graff P,Micheli FE.Pallidal surgery for the treatment of primary generalized dystonia:long-term follow-up.Clin Neurol Neurosurg2008;110:145–150.

157.Isaias IU,Alterman RL,Tagliati M.Deep brain stimu-lation for primary generalized dystonia:long-term out-comes.Arch Neurol2009;66:465–470.

158.Loher TJ,Capelle HH,Kaelin-Lang A,et al.Deep brain stimulation for dystonia:outcome at long-term follow-up.J Neurol2008;255:881–884.

159.Mehrkens JH,Botzel K,Steude U,et al.Long-term ef?cacy and safety of chronic globus pallidus internus stimulation in different types of primary dystonia.Ste-reotact Funct Neurosurg2009;87:8–17.

160.Pillon B,Ardouin C,Dujardin K,et al.Preservation of cognitive function in dystonia treated by pallidal stimu-lation.Neurology2006;66:1556–1558.

161.Krauss JK.Deep brain stimulation for cervical dystonia.

J Neurol Neurosurg Psychiatry2003;74:1598.

162.Eltahawy HA,Saint-Cyr J,Poon YY,Moro E,Lang AE, Lozano AM.Pallidal deep brain stimulation in cervical dystonia:clinical outcome in four cases.Can J Neurol Sci 2004;31:328–332.163.Ostrem JL,Marks WJ Jr,Volz MM,Heath SL,Starr PA.

Pallidal deep brain stimulation in patients with cranial-cervical dystonia(Meige syndrome).Mov Disord2007;

22:1885–1891.

164.Vidailhet M,Yelnik J,Lagrange C,et al.Bilateral pal-lidal deep brain stimulation for the treatment of patients with dystonia-choreoathetosis cerebral palsy:a prospec-tive pilot https://www.doczj.com/doc/5714900774.html,ncet Neurol2009;8:709–717.

165.Berman BD,Starr PA,Marks WJ,Ostrem JL.Induction of bradykinesia with pallidal deep brain stimulation in patients with cranial-cervical dystonia.Stereotact Funct Neurosurg2009;87:37–44.

166.Gruber D,Trottenberg T,Kivi A,et al.Long-term effects of pallidal deep brain stimulation in tardive dys-tonia.Neurology2009;73:53–58.

167.Jabusch HC,Zschucke D,Schmidt A,Schuele S,Alten-muller E.Focal dystonia in musicians:treatment strate-gies and long-term outcome in144patients.Mov Disord 2005;20:1623–1626.

168.Candia V,Rosset-Llobet J,Elbert T,Pascual-Leone A.

Changing the brain through therapy for musicians?hand dystonia.Ann N Y Acad Sci2005;1060:335–342. 169.McKenzie AL,Goldman S,Barrango C,Shrime M, Wong T,Byl N.Differences in physical characteristics and response to rehabilitation for patients with hand dystonia:musicians?cramp compared to writers?cramp.

J Hand Ther2009;22:172–181.

170.Zetterberg L,Halvorsen K,Farnstrand C,Aquilonius SM,Lindmark B.Physiotherapy in cervical dystonia:six experimental single-case studies.Physiother Theory Pract 2008;24:275–290.

171.Byl NN,Archer ES,McKenzie A.Focal hand dystonia: effectiveness of a home program of?tness and learning-based sensorimotor and memory training.J Hand Ther 2009;22:183–197.

172.Tinazzi M,Farina S,Bhatia K,et al.TENS for the treatment of writer?s cramp dystonia:a randomized, placebo-controlled study.Neurology2005;64:1946–1978. 173.Espay AJ,Hung SW,Sanger TD,Moro E,Fox SH,Lang AE.A writing device improves writing in primary writing tremor.Neurology2005;64:1648–1650.

18 A.Albanese et al.

ó2010The Author(s)

European Journal of Neurologyó2010EFNS European Journal of Neurology18,5–18

肌张力障碍的发病机理是什么

肌张力障碍的发病机理是什么 看到有很多人在网上打听及张力障碍的发病机理,我恰好知道一些,就跟大家分享一下。肌张力障碍(dystonia)是主动肌与拮抗肌收缩不协调或过度收缩引起的以肌张力异常的动作和 姿势为特征的运动障碍综合征,具有不自主性和持续性的特点。依据病因可分为原发性和继发性。肌张力障碍的发病原因是什么呢? 原发性肌张力障碍多为散发,少数有家族史,呈常染色体显性或隐性遗传,或X染色体连锁遗传,最多见于7~15岁儿童或少年。常染色体显性遗传的原发性扭转痉挛绝大部分是由定位在9q32-34的DYTl基因突变所致,外显率为30%~50%。多巴反应性肌张力障碍也是常染色体显性遗传,为三磷酸鸟苷环化水解酶-1(GCH-1)基因突变所致。有研究证实,外周创伤可诱发原发性肌张力障碍基因携带者发生肌张力障碍,如口-下颌肌张力障碍,病前有发生面部或牙损伤史。另外,过度作用一侧肢体也可诱发肌张力障碍。如各种职业性的肌张力障碍,书写痉挛、打字员痉挛、乐器演奏家和运动员肢体痉挛等,其外周因素常被认为是主要作用。故推测其病因是由于脊髓运动环路的重组或脊髓水平以

上运动感觉联系的改变导致基底节功能改变所致。 继发性(症状性)肌张力障碍指凡是累及新纹状体、旧纹状体、丘脑、蓝斑、脑干网状结构等处的病变,均可引发肌张力障碍的症状出现,如肝豆状核变性、核黄疸、神经节苷脂沉积症、苍白球黑质色素变性、进行性核上性眼肌麻痹、双侧基底节钙化、甲状旁腺功能低下、中毒、脑血管病变、脑外伤、脑炎、脑裂畸形、药物诱发(L-DOPA、酚噻嗪类、丁酰苯类、胃复安、化疗药物)等。 肌张力障碍这是一种危害性比较大的疾病,所以还是要做好疾病的预防。有遗传背景的疾病,预防措施包括避免近亲结婚,推行遗传咨询、携带者基因检测及产前诊断等。早期诊断、早期治疗、加强临床护理,对改善患者的生活质量有重要意义

运动诱发性肌张力障碍

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3. 多灶型肌张力障碍(multifocal dystonia) 2个以上非相邻部位肌群受累。 4. 全身型肌张力障碍(generalized dystonia) 下肢与其他任何节段型肌张力障碍的组合,如扭转痉挛。 5. 偏身型肌张力障碍(hemi-dystonia) 半侧身体受累,一般都是继发性肌张力障碍,常为对侧半球、尤其是基底节损害所致。 (三)根据病因分型 1. 原发性或特发性肌张力障碍是临床上仅有的异常表现,没有已知病因或其他遗传变性病,如DYT-1、DYT-2、DYT-4、DYT-6、DYT-7、DYT-13型肌张力障碍。 2. 肌张力障碍叠加肌张力障碍是主要的临床表现之一,但与其他的运动障碍疾病有关,没有神经变性病的证据,如DYT-3、DYT-5、DYT-11、DYT-12、DYT-14、DYT-15型肌张力障碍。 3. 遗传变性病肌张力障碍是主要的临床表现之一,伴有一种遗传变性病的其他特征,如Wilson病、脊髓小脑性共济失调、亨廷顿舞蹈病、帕金森综合征等。 4. 发作性肌张力障碍表现为突然出现且反复发作的运动障碍,发作间期表现正常。

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肌张力障碍 疾病概述 肌张力障碍是肌肉过度收缩导致身体一部分或全部出现持续性扭转或姿势 异常为主要表现的一组综合征。其特点是主动肌和拮抗肌同时收缩,运动时症状加剧,严重的病人安静时也出现肌肉的异常活动。 疾病病因 特发性扭转性肌张力障碍迄今病因不明,可能与遗传有关,可为常染色体显性(30%-40%外显率)、常染色体隐性或X连锁隐蔽形成遗传,显性遗传的缺损基因DYT1已定位于9号常染色体长臂9q32-34,编码一种ATP结合蛋白扭转蛋白A,有些病例可发生在散发基础上。环境因素如创伤或高劳等可诱发特发性肌张力障碍基因携带者发病,如口-下颌肌张力障碍病前有面部或牙损伤史,一侧肢体过劳可诱发肌张力障碍如书写痉挛、打字员痉挛和运动员肢体痉挛等。继发性肌张力障碍是纹状体、丘脑、蓝斑、脑干网状结构等病变所致,如肝豆状核变性、核黄疸、神经节苷脂沉积症、苍白球黑质红核色素变性、进行性核上性麻痹、特发性基底节钙化、甲状旁腺功能低下、中毒、脑血管病变、脑外伤、脑炎、药物(左旋多巴、酚噻嗪类、丁酰苯类、胃复安)诱发等。 病理生理 特发性扭转痉挛可见非特异性病理改变,包括壳核、丘脑及尾状核小神经元变性,基底节脂质及脂色素增多。继发性扭转痉挛病理学特征随原发病不同而异;痉挛性斜颈、Meige综合征、书写痉挛和职业性痉挛等局限性肌张力障碍病理上无特意性改变。 临床分型 临床上肌张力障碍可以表现为全身性或局灶性,后者包括眼睑痉挛、Meige综合征、口舌综合征、痉挛性斜颈、书写痉挛以及其他节段性肌张力障碍。根据原因可以分为: (1)原发性肌张力障碍:该类病人没有明确的中枢神经系统构造异常,表现为全身性异常如特发性扭转痉挛或局灶性异常如书写痉挛、眼睑痉挛和痉挛性

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原发性肌张力障碍的病因迄今不明,认为可能与遗传有关,呈常染色体显性遗传(AD)、常染色体隐性遗传(AR)或X染色体连锁隐性遗传。遗传的原发性扭转痉挛大多由于DYT1基因突变所致,基因定位于9q32~34。另外在6个具有不同单倍体型的患者中均发现有一GAG缺失,不论是否是Ashkenazi犹太人,典型早期起病的ITD大多是由于此种GAG缺失引起。 环境因素如创伤或过度劳累等可诱发原发性肌张力障碍的基因携带者发病,如口‐下颌肌张力障碍病可有面部或牙齿损伤史;一侧肢体的过度劳累也可诱发肌张力障碍,如书写痉挛、打字员痉挛、乐器演奏家和运动员肢体痉挛等。ITD的发病机制很可能是由于某种原因引起了脑内一些神经递质的传导及代谢方面的障碍,导致皮质及皮质下结构对运动系统的抑制减弱而致病。几项研究均证明改变了的多巴胺能对基底核的输入可导致肌张力障碍,典型例子为多巴反应性肌张力障碍(DRD,IDT5),但也有部分ITD患者对多巴胺没有反应,故推测是否由于多巴胺释放缺陷多于多巴的合成障碍。进一步了解DYT1基因新的ATP结合蛋白的作用,将有可能从基底核环路方面来阐明ITD的发病机制。 ITD一般没有明显的病理改变,一些病例研究发现蓝斑、黑质致密层、脑桥脚核和背缝神经核有病理改变,但其他病例并没有发现类似的改变。据McNaught等(2004)的研究,在4个(男3女1,33~86岁)的DYT1‐阳性患者以及4个对照病例的尸检中用泛素‐蛋白结合体等多重抗体作为标记,进行染色,结果发现在中脑的神经元、脑桥网状系统、中脑水管周围灰质等处有蛋白沉积和包涵体,包涵体在核周明显,其内未见‐醩ynuclein。受累均为胆碱能神经元,而多巴胺能、五羟色胺能神经元以及星形细胞均未累及。脑部其他部位如皮质、纹状体、海马、黑质致密带等都未发现有这些改变。4名对照组均未见到这些病理改变。 作者的结论是他们的研究提出了这样的可能性:DYT1型肌张力障碍是一种蛋白结构疾病,在脑干特别是在大脑脚、蓝斑、中脑水管周围灰质等的细胞核内所见表明了这就是DYT1型肌张力障碍的病理改变。这是有关蛋白在肌张力障碍病例聚集的首个报道。然而,Holton 等(2008)对6例肌张力障碍(男2女4,眼睑痉挛2例;轴性肌张力障碍1例;颈肌张力障碍3例)和对照4例,在死后剖检中进行了免疫组织化学和神经病理学检查,在中脑神经元内并未发现上述作者提到的ubiquitin,torsinA,laminA/C或p62阳性包涵体,也无证据表明纹状体间隔内有神经元丢失。作者认为他们的研究进一步肯定以前某些关于成人起病的原发性肌张力障碍病例并无确定的结构异常,大多数病例显示正常的脑结构。

肌张力障碍的临床特点及诊治要点

肌张力障碍的临床特点及诊治要点 万新年 关键词:张力失调;临床;治疗 中图分类号:R741.04 文献标识码:C 文章编号:1006—2963(2010)02—0167-03 作者单位:100730中国医学科学院北京协和医院神经科通讯作者:万新年 肌张力障碍(dystonia)是一种病理生理复杂、 机制未明的运动障碍病,既往因缺乏有效治疗手段 而常被忽视。国外有关调查结果显示原发性肌张 力障碍的患病率约为370/100万,据此推算,世界 约有超过300万人罹患该病,同时存在认识不足造 成的漏诊、误诊,实际患病人数可能更多。继发性 肌张力障碍患者人数更难统计,如约1/3的脑瘫儿 童可有肌张力障碍,且某些患儿肌张力障碍是运动 障碍的主要表现;约i/3的帕金森病可在病程中伴 有或某个阶段(早期或治疗后)出现肌张力障碍。 原发性肌张力障碍与诸多遗传变异有关。痉 挛性斜颈和眼睑痉挛的发病可能与多巴胺转运体 和/或D5受体的基因多态性有关,关于遗传易感 性或保护性机制的研究近来颇受关注。一般认为,

皮质一纹状体一苍白球一皮质运动环路的功能失调可能在原发性肌张力障碍的病理生理中起主要作用,至少部分肌张力障碍是易感者神经元对某些刺激 或负荷诱发的蛋白结构变化不能适时反应的结果。目前应用电生理、生化、人类基因和脑功能显 像技术对肌张力障碍的病理生理机制有了更多认识,拓展了肌张力障碍系基底节功能异常所致的传统观念,有助于阐明肌张力障碍神经功能紊乱的病理机制,为研究肌张力障碍治疗的新方法提供了基础。 l肌张力障碍的临床特点 肌张力障碍是一种不自主、持续性肌肉收缩引 起的扭曲、重复运动或姿势异常的综合征。如仅从中文名称字面理解容易产生歧义,可将此病误解为一般意义上的肌张力异常,如肌张力增高(如锥体 束损害时出现的痉挛状态)或减低。实际上dystonia 用于疾病诊断的术语是特指一种具有特殊表现 形式的不自主运动,患者多以异常的表情、姿势或不自主的变换动作为突出表现。 肌张力障碍的临床表现取决于受累肌肉的部 位、收缩强度和不同肌肉的组合。轻度的肌张力障碍可能仅表现为基本正常的动作而略有夸张;稍重

肌张力障碍翻译 - 副本

第135章局限性手部肌张力障碍 提纲 历史 病因 临床表现 诊断 治疗 总结 本章要点: 目前公认手部肌张力障碍为原发疾病,病因不明,为多因素致病。 手部肌张力障碍包括手指及腕部的姿势异常。由于主动肌和拮抗肌同时协同收缩异常,使得手指和腕关节不自主的呈扭转姿态。这个病的发病很隐匿,可能表现为弹奏乐器时的错音,做事是错误增加,异常疲劳或感觉无力,在做某些动作时一个或者多个手指不自主地活动范围过度。 患者治疗的目的在于保持手的正常形态,增强感受-运功反馈的精确性,保证手部运动的效率和效果。 治疗手部肌张力障碍需要综合多学科方法。这些方法包括患者教育、心理管理、健康管理、良好的力学环境、合理的人体工学环境、药物治疗(比如肉毒素)、社会支持、脑功能训练,有时候还需要脑部刺激。 由于工作需要,人们经常不断重复某个动作。比如:打字、演奏乐器和写字等。在这些工作中,人们经常遭受反复的疲劳损伤,使得创伤障碍不断积累。为了解决这个问题,可以在工作中抽时间休息,或者缩短工作时间、减轻劳动强度、改善工作本身或者环境的人体工程学特性。如果人体工程学环境长时间不能得到改善,将可能罹患手部肌张力障碍,将引起慢性疼痛,或者导致虽然不痛但可导致功能丧失的不自主运动(职业性手痉挛,比如演奏家、键盘手、作家、特殊工种)。这些情况是由于内在因素和外在因素长期积累导致的。本章总结了此病的历史、病因、诊断和治疗方面的内容。本章的目的有:(1)提高大家对此病的认识(2)鼓励医生对患者进行健康教育以最大程度预防此病(3)让医生能早期诊断此病(4)提倡多学科联合干预提供患者支持并促进康复(5)鼓励医生及理疗师对此病进行深入研究,最大程度恢复患者功能,以使患者能够自理(6)激励临床工作者对此病进行基础研究,明确其病因,并改进治疗,提高疗效。 历史 肌张力障碍医学研究基金(Dystonia Medical Research Fundation)下属的特别学术委员会(Ad hoc committe)为肌张力障碍下了定义:肌张力障碍是一种综合征,由于肌肉持久反复的不协调收缩,导致关节扭转和肢体的姿势异常1。肌张力障碍累及到身体的某个具体部位,就以肢体部位命名。如果肌张力障碍仅仅在做某个特定在动作是才发生,就叫做动作特异性肌张力障碍或者运动性肌张力障碍2。Fahn1和他的团队补充到,在运动性肌张力

肌张力障碍诊断及鉴别诊断

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