European Journal of Neurology 2012, 19: 12921299

doi:10.1111/j.1468-1331.2011.03649.x

REVIEW ARTICLE

Treatment for dystonia in childhood

A. Roubertiea,b,c,d, L. L. Marianie, E. Fernandez-Alvarezf, D. Doummara,g and E. Rozea,e,h
a

Commission mouvements anormaux de la Societe Franc aise de Neurologie Pediatrique; bDepartement de Neurologie Pediatrique, Hopital

Gui de Chauliac, Montpellier; cINSERM U827, Institut Universitaire de Recherche Clinique, Montpellier; dINSERM U1051, Institut des Neurosciences de Montpellier, Montpellier; eDepartement de Neurologie, Hopital Pitie-Salpetrie`re, AP-HP, Paris, France; fServicio de pital Armand Trousseau, AP-HP, Paris; and Neuropediatr`a, Hospital Sant Joan de Deu, Barcelona, Spain; gService de Neuropediatrie, Ho
h

INSERM, UMRS 975, and CNRS 7225 CRICM, CHU Pitie-Salpetrie`re, Universite Pierre et Marie Curie-Paris-6, Paris, France

Keywords:

anticholinergics, botulinum toxin, deep brain stimulation, dystonia, levodopa, tetrabenazine, therapy
Received 27 July 2011 Accepted 9 December 2011

Management of childhood dystonia diers in certain respects from that of adult dystonia: (i) childhood dystonia is more often secondary than primary; (ii) mixed motor disorders are frequent; (iii) in children, the course of dystonia may be inuenced by ongoing brain maturation and by the remarkable plasticity of the young brain; (iv) drug tolerability and eectiveness can be dierent in children; (v) the therapeutic strategy must be discussed with both the patient and his or her parents; and (vi) the childs education must be taken into account. Based on a systematic review of the literature through June 2011 and on our personal experience, we propose a therapeutic approach to childhood dystonia. After a detailed clinical evaluation and a comprehensive work-up to rule out a treatable cause of dystonia, symptomatic treatment may include various drugs, local botulinum toxin injections, and deep brain stimulation, in addition to rehabilitation.

Introduction
Childhood dystonia can result in lifelong disability and thus represents a signicant health care and rehabilitation challenge. The management of childhood dystonia diers in certain respects from that of adult dystonia: (i) childhood dystonia is more often secondary than primary; (ii) mixed motor disorders are frequent (e.g., dystonia associated with spasticity); (iii) in children, the course of dystonia may be inuenced by ongoing brain maturation and by the remarkable plasticity of young brain; (iv) drug tolerability and eectiveness can be dierent in children; (v) the therapeutic strategy must be discussed with both the patient (when their age allows it) and his or her parents; and (vi) the childs education must be taken into account. Recent experimental and clinical studies have enhanced our understanding of the pathophysiology of dystonia, and deep brain stimulation (DBS) has opened a new area regarding its management [13]. Several authors have made detailed recommendations on the treatment for adult dystonia, but pediatric guidelines are lacking. In particular, treatment options for children (including the daily dosage) are rarely discussed in

the literature [4]. Here, we propose a therapeutic approach to childhood dystonia based on a systematic review of the literature through June 2011 and on our personal experience.

Childhood dystonia: therapeutic strategy

A careful physical examination and comprehensive work-up are mandatory for the elaboration of a therapeutic strategy [5,6]. Secondary dystonia is frequent in childhood [7], and the rst therapeutic step is to rule out a disorder qualifying for specic treatment, especially childhood-onset metabolic disorders, in particular dopa-responsive dystonia (DRD), creatine deciency, glucose transporter disorders, organic aciduria or, rarely, Wilsons disease [5,8,9]. Clinical evaluation is the starting point when dening the therapeutic strategy, focusing on the topography, type (hyperkinetic/xed dystonia) and severity of the dystonic manifestations, and the nature and degree of functional impairment in daily life. Special attention should be paid to any motor disorders associated with the dystonia, as mixed motor disorders are common in childhood, especially in secondary dystonia: dystonic movements associated with chorea, athetosis, cerebellar signs, or spasticity may require specic treatment. It is also crucial to evaluate other neurological disorders and comorbidities. In particular, pain, anxiety, depression, sleep disorders, cognitive decits, orthopedic complications, swallowing

partement de Neurologie Pe diatriCorrespondence: A. Roubertie, De que, Ho pital Gui de Chauliac, Montpellier France (tel.: +33 4 67 33 01 83; fax: +33 4 67 33 77 33; e-mail: a-roubertie@chu-montpellier. fr).

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diculties, and digestive disorders may be observed in dystonic children. These non-motor manifestations may inuence the course of the dystonia and are major determinants of quality of life in this setting. It is important to remember that children are not miniature adults and that childhood dystonia is a dynamic disorder. The course of movement disorders may be aected by ongoing brain maturation and by the remarkable plasticity of childrens brains. For example, onset of dystonia may occur only several years after basal ganglia stroke, and spontaneous recovery from dystonia is rarely seen in some patients with childhoodonset primary dystonia [10]. A background of hypotonia, which is frequent in this setting, can alter the expression of the movement disorders, particularly in choreodystonic cerebral palsy (for example, dystonia may become clinically obvious only when the child has gained enough ton). Finally, pharmacokinetics, pharmacodynamics, and tolerability may dier markedly between children and adults and may change as children grow. After a thorough clinical evaluation, the therapeutic options must be discussed with the child (when age allows it) and the family. Most therapies for dystonia are purely symptomatic, and the treatment aim (functional improvement, quality of life, etc.) should rst be dened, ideally by setting qualitative, individual, and realistic goals with the child and his or her parents. Rehabilitation methods are often highly specic and individually tailored in patients with dystonia and may thus require particular skills [11,12]. These include physiotherapy, speech therapy and occupational therapy, and psychosocial support for both the patient and the family. Rehabilitation will prevent orthopedic complications of dystonia and will also optimize the childs psychomotor development and prepare his or her adolescence and adulthood. Adapted equipment and procedures (special computer keyboards, pictograms, voice synthesizers, ergonomic eating utensils, school note-taking by peers, personalized educational programs, etc.) can improve the childs autonomy with respect to daily life activities, school integration, and mixing with peers. The pharmacological treatment schedule should be clearly explained, including the reasons for very gradual dose titration and the need for a 3-month trial to assess the ecacy of most drugs. Possible adverse eects, such as an increased risk of swallowing diculties in severely disabled children treated with benzodiazepines, must be taken into account when estimating the likely riskbenet ratio of a given treatment. Psychiatric and cognitive adverse eects, which are frequent and might interfere with psychomotor development or academic achievement, must be avoided as often as possible.

Although the therapeutic strategy should be tailored to the individual patient in clinical practice, we propose a simple therapeutic algorithm (not a ow chart) to help the clinician (Fig. 1). Pediatric drug doses and side eects are shown in Table 1. L-dopa should always be tried rst in children with dystonia of unknown or as-yet undiagnosed etiology and in children with presumed cerebral palsy but no clear history of perinatal brain hypoxic insult. L-dopa ecacy points to a diagnosis of DRD and prompts further biochemical and molecular analyses. Anticholinergic drugs should be tried if L-dopa fails. If both these treatments are unsuccessful, options depend partly on the clinical picture: tetrabenazine for mobile dystonia; baclofen or a low-dose benzodiazepine for patients with associated spasticity; amitriptyline or a benzodiazepine for patients with acute exacerbations and/or painful dystonic spasms; and botulinum toxin injection for patients with focal dystonia. For children with severe drug-resistant primary generalized dystonia, early pallidal DBS is recommended, before the onset of xed skeletal deformities and major educational or social setbacks. For patients with drug-resistant and disabling secondary dystonia, DBS should be discussed by a multidisciplinary team. Regardless of the chosen treatment, dystonic children must be monitored very closely, for dose adjustment, detection of adverse eects, and evaluation of improvement toward pre-dened goals.

Pharmacological treatment
L-dopa

L-dopa is the rst-line drug for childhood-onset dystonia, as its ecacy provides a clue for the diagnosis of DRD. L-dopa should be combined with an inhibitor of peripheral decarboxylation [13]. In patients with classical DRD [autosomal dominant guanosine triphosphate cyclohydrolase 1 (GCH1) deciency)] the L-dopa dose is increased on a weekly basis until the minimal eective dosage is obtained, usually after 56 weeks; low L-dopa doses rapidly provide complete or nearcomplete responses persisting for decades [5,8]. The same daily dosage is usually maintained for several years. L-dopa should be tried as a rst-line treatment in all situations that may be consistent with DRD: childhood-onset dystonic syndrome with or without diurnal uctuations, childhood-onset akineto-rigid syndrome, and clinical syndromes mimicking cerebral palsy. In DRD, the ecacy of L-dopa is often but not always rapidly obvious or might be canceled by other events during the period of introduction (as worsening phenomenon owing to drug induced dyskinesias) [13]. As this L-dopa therapeutic trial is a fundamental dividing

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Diagnostic confirmation by neurotransmitter, metabolite & pterin profile in CSF, and/or genetic studies

Childhood dystonia
Etiological investigations

L-DOPA* Not effective

Etiological investigations

Improvement : Probable dopa-responsive dystonia

Clues to a specific disease

Specific treatment

Focal dystonia Botulinum toxin

Multifocal dystonia, functional disability Trihexiphenidyl

Spasticity ?

Tetrabenazine

Baclofen

Generalized or multifocal dystonia with exacerbation, focal pain or functional disability

Limited response, Worsening of dystonia or functional disability

Combination with benzodiazepines, muscle relaxants

Primary dystonia Pallidal stimulation

Cerebral palsy Discuss Intrathecal baclofen or pallidal stimulation

Other secondary dystonia Discuss Pallidal stimulation on an ad hoc basis

*Ldopa should be tried in dystonia of unknown etiology and in dopa

responsive dystonia, but is rarely useful in most genetic primary dystonias (DYT1, DYT6, DYT11)

Figure 1 Therapeutic algorithm for childhood dystonia.

line in the management of the patients, response to L-dopa should only be judged after a three-month trial period, and tolerance, observance, and clues for ecacy should be closely monitored. Management of L-dopa therapy in particular conditions including autosomal recessive GCH1 deciency, sepiapterin reductase (SR) deciency, tyrosine hydroxylase (TH) deciency and aromatic L-amino-acid decarboxylase (AADC) deciency is outlined in Table 2. L-dopa is also useful in dystonia related to juvenile Parkinsons disease but is disappointing in patients with primary dystonia and in patients with secondary dystonia (dyskinetic cerebral palsy for example) [5,14]. Commercial drug preparations used to treat adults with Parkinsons disease are easily administered to school-aged children and adolescents. For younger children, dilutions prepared from dispersible tablets (NB: this is a potential source of dosing error) or individualized single low-dose tablets combining the required L-dopa dosage with a peripheral decarboxylase inhibitor can be manufactured [13].
Other dopaminergic drugs

been reported [15]. Bromocriptine has been used in children with various dopamine synthesis pathway defects and in patients with juvenile Parkinsons disease [16]. However, given the risk of heart valve, pleuropulmonary and retroperitoneal brosis reported in patients receiving chronic treatment with various ergolinic dopamine agonists [17], ergot agonists should never be used in children. Non-ergolinic agonists such as ropinirole or pramipexole might be useful, but neither the dosage nor the ecacy is clearly established in childhood.
Anticholinergic therapy

There are no controlled trials of dopamine agonists, MAO inhibitors, or COMT inhibitors in children, but the use of bromocriptine or lisuride (a dopamine ergolinic agonist), and selegiline (an MAO inhibitor) has

According to a recent meta-analysis, trihexiphenidyl is the only drug with demonstrated ecacy on dystonic children who do not respond to L-dopa [15]. Between one- and two-thirds of dystonic children are responsive to this treatment, regardless of the cause of dystonia [18]. Ecacy is higher in younger children and when treatment begins rapidly after diagnosis, and trihexiphenidyl is more eective on speech and upper-limb function than on lower-limb function in children with mixed movement disorders [5,15]. The trihexiphenidyl dosage is initially increased on a weekly basis, depending on ecacy and tolerability. A 3-month trial period at a dose of around 0.3 mg/kg is generally

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Table 1 Main drugs used in the treatment for childhood dystonia, including daily dosages and main side effects Initial daily dosage 1 mg/kg/day of levodopa for classical DRD 0.2 mg/kg/day for TH, SR or ADCC deciencies TH or ADCC deciencies ADCC deciency 0.50.8 mg/kg/ day in two to three intakes Vertigo Sleep disorders Behaviour disorders 35 mg/kg/day, or even 810 mg/kg/day by increments of 1 mg/kg/week, in three intakes/day for classical DRD 220 mg/kg/day proceeding by very small increments and six intakes/day for TH, SR and ADCC deciencies 0.51.1 mg/kg/day in two to three intakes Gastrointestinal disorders Target daily dosage Main side effects Precautions for use

Drug group

Drug

Dopaminergic drugs

L-dopa

Tyramine-rich food (risk of hypertension)

ADCC deciency 0.030.06 mg/kg/day 0.050.7 mg/kg/day by increments of 0.030.05 mg/kg/week in two to three intakes

0.10.5 mg/kg/day in one or two intakes

Drowsiness

Anticholinergic drugs

Selegiline (MAO-B inhibitor) Tranylcypromine (non-selective MAO inhibitor) Bromocriptine (Dopamine agonist) Trihexiphenidyl

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GABAb receptor agonists

Baclofen

0.3 mg/kg/day

0.5 to 1.5 mg/kg/day, by increments of 0.1 mg/kg/week, in two to three intakes

Worsening of axial hypotonia, Possible potentiation of epileptic seizures Hypotonia, Respiratory depression

Benzodiazepines

Clonazepam Diazepam

0.01 mg/kg/day 0.1 mg/kg/day

Variable, sometimes one intake in the evening, or two to three intakes, proceeding by increments of 34 days 215 mg/day in two intakes

Neuroleptics 0.05 mg/kg/day 2 mg/kg/day 0.25 to 0.5 mg/day 0.5 mg/kg/day

Pimozide

0.5 to 1 mg/day

Drowsiness, Memory impairment, Blurred vision, Dry mouth, Urinary retention, Constipation Drowsiness, Gastrointestinal disorders, Rash, Epileptic seizures Drowsiness, Behavioral changes (irritability, nervousness) Drowsiness, Weight gain

Presynaptic dopamine-depleting drugs

Haloperidol Tiapride Risperidone Tetrabenazine

0.0750.15 mg/kg/day in two to three intakes 36 mg/kg/day in two intakes 25 mg/day in one or two intakes 45 mg/kg/day (without exceeding 150200 mg/day) by increments of 0.5 mg/kg/week, beginning with one intake then two. 48 mg/day in two to four intakes

Long QT syndrome Tardive syndrome Not to be combined with L-dopa or Dopamine agonists Drowsiness, Asthenia, Parkinsonian syndrome, Depression

Muscle relaxants

Thiocolchicoside

2 mg/day

Caution in patients with akinetic-rigid syndome. Not to be combined with L-dopa or Dopamine agonists Not under 15 years old

Treatment for dystonia in childhood

Tricyclic antidepressants

Amitriptyline

0.1 mg/kg/day

0.51 mg/kg/day in two intakes

Drowsiness, Gastrointestinal disorders Drowsiness

Combination with MAO inhibitors contraindicated

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DRD, Dopa-responsive dyskinesia; TH, tyrosine hydroxylase; SR, sepiapterin reductase; ADCC, aromatic L-amino acid decarboxylase; MAO, monoamine oxidase; GABA, gamma-aminobutyric acid.

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Table 2 L-dopa treatment of patients with rare neurotransmitter deciencies Patients with other forms of DRD (tyrosine hydroxylase deciency, autosomal recessive GCH1 deciency or sepiapterine reductase (SR) deciency) or with aromatic L-amino-acid decarboxylase (AADC) deciency are very prone to L-dopa adverse effects, especially dyskinesia, agitation, and extreme irritability, even at very low doses. This is likely related to an increased sensitivity of dopaminergic receptors resulting from the chronic dopamine decit. Treatment must therefore be initiated very carefully, starting at a very low dosage divided into two to six daily fractions. The nal dosage may be reached within 312 months. The response to treatment is highly variable. In patients with autosomal recessive GTP cyclohydrolase deciency or sepiapterin reductase deciency, treatment is based on a combination of L-dopa with 5-hydroxytryptophan, a serotonin precursor (daily dosages ranging from 1 to 16 mg/kg in one to four fractions). 5-hydroxytryptophan should be administered at the same time as L-dopa, which is combined with a dopa-decarboxylase inhibitor. The dopa-decarboxylase inhibitor prevents peripheral decarboxylation of the serotonin precursor, thus limiting its peripheral serotoninergic adverse effects and allowing more of the drug to enter the brain. Efcacy is monitored clinically and, if possible, by CSF neurotransmitter assays. Adjunctive therapy with tetrahydrobiopterin, dopamine agonists, COMT inhibitors, or folinic acid may be useful in some patients. L-dopa treatment is proposed for patients with AADC deciency but has limited benets. Dopamine agonists (selegeline) may be added or be used instead of L-dopa in this setting.

Table 3 Adverse effects of surgical procedures used in childhoodonset dystonia Intrathecal baclofen therapy One-third of patients experience adverse events, including skin lesions at the entry point of the pump or catheter, rupture, or migration of the material, and CSF leakage, due mainly to the mode of administration. Intrathecal baclofen (ITB) withdrawal syndrome (altered mental status, fever, tachycardia, hypertension or hypotension, seizures, and rebound spasticity) may occur when drug delivery is disrupted for any reason and represent a rare but life-threatening complication. Deep brain stimulation Although specic data are limited, surgical complications, including post-operative infection, intracranial hemorrhage, and seizures, are likely to be rare in children and usually result in good outcomes without sequelae. Adverse events related to the hardware (mainly lead fracture and implantable pulse-generator dysfunction) and to stimulation (mainly dysarthria) are also rare.

injection [21]. However, a recent systematic review concludes that there is no evidence to support the use of intrathecal baclofen in ambulant children or adolescents with dystonia without further rigorous longitudinal studies [23]. The main side eects are listed in Table 3.
Antidopaminergic drugs

required to evaluate the ecacy of this drug [19]. The anticholinergics should be escalated slowly (high dosage might be reached only after a few years) until there is either signicant improvement in dystonia or the emergence of intolerable side eects (mainly cognitive and antimuscarinic side eects); there is no real target dosage, but rather a balance to nd between improvement and tolerance [9,10]. It is noteworthy that extremely high dosages, greater than 50 mg, may be required.
Baclofen

This gamma-aminobutyric acid (GABA) B receptor agonist has been widely used in the treatment for spasticity. It has been reported to improve gait and lower-limb dystonia in only one series of children with primary dystonia [20]. Therefore, scientic evidence for baclofen ecacy in the treatment for dystonia is scarce. Moreover, it often worsens preexisting axial hypotonia in children with secondary dystonia. Intrathecal pump delivery of baclofen can be helpful in children with secondary dystonia, especially when associated with spasticity [21,22]. It improved the quality of life and ease of care in most patients, in a series of 77 patients with secondary generalized dystonia of various origin, initially selected for their response to a screening

The use of neuroleptics (mainly tiapride, haloperidol, and risperidone) to treat patients with dystonia is controversial [5,8,15], and these drugs have not been studied in children. We do not consider neuroleptics to be a standard therapeutic option. However, pimozide and haloperidol may be considered for patients with status dystonicus [24]. Tetrabenazine is another dopamine-depleting drug with a unique pharmacological prole: It is a presynaptic dopamine-depleting agent, a post-synaptic dopamine receptor blocker, and it also inhibits vesicular monoamine transporter 2. Although used in the treatment for adult hyperkinetic movement disorders (mostly tardive dyskinesia, Huntingtons disease, ballism and tics) for more than 30 years, data on the use of tetrabenazine in dystonic children are anecdotic and open-labeled [25]. The potential for use of tetrabenazine in childhood dystonia needs further controlled clinical trials to be clearly assessed. In our experience, tetrabenazine can improve both isolated dystonia and mixed motor disorders including dystonia and seem to be more eective on mobile dystonia than on xed postures. It should thus be used cautiously in patients with xed postures or great akinesia and should be avoided in patients with mixed dystoniaparkinsonism syndromes. Titration must be very gradual, mostly based on tolerability.

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Benzodiazepines

These drugs potentiate gabaergic inhibition by enhancing GABA anity for its receptor (GABA-A). Despite the lack of controlled trials, benzodiazepines (especially diazepam and clonazepam) are commonly used in childhood dystonia, particularly in patients with symptomatic dystonia associated with spasticity [5,15]. High dosages are often necessary, although their use may be limited by adverse eects. Intravenous midazolam at a dose of 30100 lg/kg/h can be used for dystonic storms [24].
Analgesics and antidepressant

Analgesics are commonly used to treat pain related to dystonia, although their use has never been specically evaluated. Analgesics can be eective both on pain associated with dystonia exacerbations and on dystonic movements themselves [5]. Codeine and slow-release morphine sulfate or morphine hydrochloride were found to be eective in a small unblinded adult trial [26]. In our experience, the sedative, analgesic, and antidepressant eects of amitriptyline can be very useful; intravenous administration is particularly recommended in case of hospitalization for subacute worsening of dystonia or dystonic storm. Gabapentin has also been tried, based on the same reasoning [5].
Other pharmacological treatments

can be given to children under conscious sedation. Although dystonic and spastic children may benet from botulinum toxin injection, it is worth mentioning that the Food and Drug Administration (FDA) issued a black box warning regarding the use of botulinum toxin, indicating a risk of severe injury or death. The goal of the FDA warning was to better inform physicians and patients about the potential risks associated with botulinum toxin injections. Children with cerebral palsy treated for spasticity with high doses of botulinum toxin may be more prone to severe adverse effects. However, the concerns about botulinum toxin use in this group of patients were derived from reports demonstrating some worrying associations without proving causality [30]. By contrast, a recent pre-post cohort study on 334 consecutive children with cerebral palsy receiving botulinum toxin (with patients being used as their own control) found that their health status was similar before and after botulinum toxin injection and concluded that there was insucient evidence to support restrictions on the administration of botulinum toxin in this group of patients [31]. We recommend that the use of botulinum toxin in dystonic children should be driven by a balanced consideration of benets and risks. Specic pediatric studies are needed to clarify the ecacy, safety, and optimal dose of botulinum toxin in this setting.

Deep brain stimulation

The following medications are often used in children or adults, despite a lack of proven ecacy. Muscle relaxants like clonidine, tizanidine, and thiocolchicoside can be useful, especially in patients with spastic or painful dystonia. Some muscle relaxants, such as cyclobenzaprine, are not recommended in children, whilst others, such as mexiletine, are unavailable in some countries [5]. Anticonvulsants (carbamazepine, sodium valproate, vigabatrin, etc.) are recommended for paroxysmal kinesigenic dyskinesia but have little eect on permanent dystonia [8,15]. DBS has been used to treat severe childhood dystonia since the late 1990s [3234]. The posteroventral part of the internal globus pallidus (GPi) is the target of choice in dystonic children. Although purely symptomatic, bilateral GPi DBS is a conservative, reversible, safe, and eective treatment for primary dystonia in children, providing a signicant functional benet [1820]. Possible complications are described in Table 3. The results may vary signicantly from one patient to another: the improvement in the motor score in primary generalized dystonic children ranges from 65% (meta-analysis; n = 44) to 8090% (open-label study, n = 6), depending on the method [32,33]. There is no reliable way of predicting outcome, but mobile dystonia, DYT1-positive genetic status, greater right pallidal volume, shorter disease duration, a lower severity score, and the absence of skeletal deformities may be associated with a better response to bilateral GPi DBS [32,3437]. The maximal impact on dystonic symptoms is usually obtained after 36 months and persists for years [3840]. The use of DBS is more controversial in children with secondary dystonia. A mean improvement in the dystonic motor score of 1530%, with variable functional consequences (partly depending on the underlying

Botulinum toxin
Botulinum toxin is widely used to treat children with spasticity and particularly cerebral palsy [27], but there are few data on its use in dystonic children [28,29]. Botulinum toxin can occasionally be used to treat a focal dystonia as limb dystonia. In generalized dystonia, botulinum toxin might be used in targeting a specic problematic region (to limit pain or to provide functional benet, by facilitating dressing for example). The injections must be repeated every 1425 weeks and

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etiology), has been reported in small series including patients with dystonia owing to neurodegeneration with brain iron accumulation [41], dystonic cerebral palsy [42,43], and miscellaneous secondary dystonia [44]. Signicant benets have also been reported in adults with myoclonus dystonia [45]. Finally, good results have been reported in patients with abrupt exacerbations of their abnormal movements, resulting in lifethreatening status dystonicus [24].

caregivers. Better understanding of the pathophysiology of dystonia might open a new eld for the development of more adapted therapies.

Acknowledgements
We thank Dr David Grabli for critical review of the manuscript and Constance Flamand-Roze for her help in preparing the manuscript.

Conicts of interest Status dystonicus: therapeutic strategy

Status dystonicus (SD) is a rare condition that raises specic therapeutic issues. It can occur in patients with either primary or secondary dystonia and is characterized by acute worsening of dystonic or dystonic/choreic abnormal movements with severe, generalized, and continuous muscle contraction. The muscle spasms are painful and may have life-threatening complications such as hyperpyrexia, dehydration, respiratory failure, and acute renal failure secondary to rhabdomyolysis. SD is a medical emergency, and an attempt should be made to identify and treat a possible precipitating factor (trauma, surgery, infection, fever, or an abrupt change in medical treatment). Patients with SD must be rapidly admitted to an intensive care unit to monitor vital functions and metabolic parameters (creatine phosphokinase, renal function, etc.). Tracheal intubation and mechanical ventilation may be needed by bulbar and respiratory failures related to neurological status, or to allow the patient to be sedated. There are no widely accepted guidelines on drug therapy of SD [24]. In our experience, intravenous amitriptyline can be useful to alleviate painful muscle spasms. A combination of tetrabenazine, trihexyphenidyl, and pimozide has also been reported to be eective in several patients [46]. When sedation is required, increasing doses of midazolam are recommended (30100 lg/kg/h); propofol can be added when deeper sedation is needed [24], although its use in this setting is controversial given the risk of propofol infusion syndrome in children. In refractory cases, pallidal stimulation should be considered before the onset of secondary complications (malnutrition, infections, etc.), depending on the etiology of the dystonia [24,46]. Dr Roubertie, Dr Mariani, Dr Fernandez-Alvarez, and Dr Doummar have no disclosures to make. Dr Roze received research support from INSERM (COSSEC), AP-HP (DRC-PHRC), the Dystonia Coalition (Pilot project), IPSEN, and MERZ-Pharma, served on scientic advisory boards for ORKYN, IPSEN, and MERZ-pharma and received travel funding from TEVA Pharma, the Dystonia Coalition, the Dystonia Medical Research Foundation, the Movement Disorders Society, the World Federation of Neurology Association of Parkinsonism and Related Disorders, and the Bachmann and Strauss Foundation.

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Conclusion
Dystonia management in childhood is usually a challenge for the clinicians and has specicities related to this age group. Although there are various available drugs, controlled trials are dramatically lacking and the therapeutic strategy is more empirical than evidence based. The ecacy of the drugs is often disappointing, and DBS provides new therapeutic option for the

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2012 The Author(s) European Journal of Neurology 2012 EFNS European Journal of Neurology