Review

Clinical presentation and management of dyskinetic cerebral

palsy
Elegast Monbaliu, Kate Himmelmann, Jean-Pierre Lin, Els Ortibus, Laura Bonouvrié, Hilde Feys, R Jeroen Vermeulen, Bernard Dan

Cerebral palsy is the most frequent cause of severe physical disability in childhood. Dyskinetic cerebral palsy (DCP) is Lancet Neurol 2017; 16: 741–49
the second most common type of cerebral palsy after spastic forms. DCP is typically caused by non-progressive Department of Rehabilitation
lesions to the basal ganglia or thalamus, or both, and is characterised by abnormal postures or movements associated Sciences (E Monbaliu PhD,
Prof H Feys PhD) and
with impaired tone regulation or movement coordination. In DCP, two major movement disorders, dystonia and Department of Development
choreoathetosis, are present together most of the time. Dystonia is often more pronounced and severe than and Regeneration
choreoathetosis, with a major effect on daily activity, quality of life, and societal participation. The pathophysiology of (E Ortibus PhD), KU Leuven,
both movement disorders is largely unknown. Some emerging hypotheses are an imbalance between indirect and Leuven, Belgium; Dominiek
Savio Instituut, Gits, Belgium
direct basal ganglia pathways, disturbed sensory processing, and impaired plasticity in the basal ganglia. Rehabilitation (E Monbaliu); Department of
strategies are typically multidisciplinary. Use of oral drugs to provide symptomatic relief of the movement disorders Pediatrics, Sahlgrenska
is limited by adverse effects and the scarcity of evidence that the drugs are effective. Neuromodulation interventions, Academy, University of
such as intrathecal baclofen and deep brain stimulation, are promising options. Gothenburg, Gothenburg,
Sweden (K Himmelmann PhD);
Evelina Children’s Hospital,
Introduction We critically reviewed the literature to provide an Guy’s and St Thomas’ NHS
Cerebral palsy comprises a group of developmental update on the diagnosis and management of DCP, and Foundation Trust, King’s
disorders of movement and posture, attributed to non- identify research priorities. This Review will focus on the Health Partners, London, UK
(J-P Lin MD); Department of
progressive disturbances that occurred in the developing clinical presentation, the management, and emerging Rehabilitation Medicine,
fetal or infant brain. The motor impairments are often therapeutic approaches of this motor disorder. VU University Medical Center
accompanied by disturbances of sensation, perception, Amsterdam, Amsterdam,
cognition, communication, and behaviour, by epilepsy, Clinical presentation Netherlands (L Bonouvrié MD);
Department of Neurology,
and by secondary musculoskeletal problems.1 Motor impairments are often more severe in people Maastricht University Medical
Cerebral palsy is the most common cause of severe with DCP than in patients with the other types of Center, Maastricht,
physical disability in early childhood, with a prevalence of cerebral palsy.7 Non-motor comorbidities are also Netherlands
(Prof R J Vermeulen MD);
1·7–3·1 per 1000 livebirths in high-income countries, and common; more than half of patients with DCP have a
Department of Neurology,
higher prevalence in low-income countries.2,3 Cerebral combination of severe intellectual impairment, Université Libre de Bruxelles,
palsy is clinically categorised into spastic, dyskinetic, and anarthria, and epilepsy.4,5,7 Visual and hearing Brussels, Belgium
ataxic cerebral palsy on the basis of the predominant impairments are also common.5 Despite normal (Prof B Dan PhD); and Inkendaal
Rehabilitation Hospital,
motor disorder.1 Dyskinetic cerebral palsy (DCP) is birthweight in most cases, more than half of patients
Vlezenbeek, Belgium
characterised by abnormal postures or movements became underweight at follow-up in a population-based (Prof B Dan)
associated with impaired muscle tone regulation, study from western Sweden, presumably as a result of Correspondence to:
movement control, and coordination comprising two high energy expenditure due to involuntary movements Prof Bernard Dan, Department of
major movement disorder patterns: dystonia and combined with poor feeding, dysphagia, gastro- Neurology, Université Libre de
Bruxelles, Brussels CP122,
choreoathetosis.4 DCP is sometimes referred to as oesophageal reflux, and suboptimal nutritional intake.7,8
Belgium
dystonic, athetoid, extrapyramidal, choreoathetotic, or Sleep and respiratory function are often disturbed. [email protected]
choreoathetoid cerebral palsy. DCP accounts for up to Drooling, dental problems, constipation, faecal and
15% of cerebral palsy cases, making it the second most urinary incontinence, pain, and musculoskeletal
common type after spastic cerebral palsy.2,5 deformities9 (including scoliosis) are common, and
DCP can have many causes, including perinatal degenerative cervical changes causing myelopathy and
hypoxia–ischaemia in infants born near to term, neonatal motor deterioration have been described in adults.10
hyperbilirubinaemia, brain maldevelopment, intracranial Mental health problems, including depression, are
haemorrhage, stroke, or cerebral infection.5 Hyper­ increasingly recognised. The risk for early death in
bilirubinaemia-induced kernicterus (ie, deposition of these patients is higher than in other types of cerebral
bilirubin in the basal ganglia) can occur during the palsy,11 and in the general population, most commonly
preterm and term period. This condition has become less through respiratory failure due to aspiration and
common in high-income countries because of preventive pneumonia.
strategies, but is still a notable issue in low-income
countries. In addition to primary prevention of Dystonia and choreoathetosis
hyperbilirubinaemia, postnatal monitoring remains Dystonia and choreoathetosis are present in most DCP
essential, and promising prevention approaches have cases (figure 1; videos 1–4),4,12 but they can be identified as See Online for videos
been developed in resource-constrained settings.6 Causes distinct movement disorders.1,13,14 Both movement
outside the neonatal period, such as cardiorespiratory disorders occur independently, but dystonia pre­
arrest or near drowning in the first year, are rarer. dominates in most patients with DCP.4 In childhood,

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 Review

dystonia refers to abnormal postures, involuntary choreoathetosis and other hyperkinetic movement
twisting, and repetitive movements due to sustained or disorders. Several video-based measurement scales can be
intermittent muscle contractions.11–13 Choreoathetosis in used to evaluate the severity of dystonia in DCP, such as
cerebral palsy is characterised by hyperkinesia and the Burke-Fahn-Marsden Dystonia Rating Scale (BFMS),18
muscle tone fluctuation. Although choreoathetosis can the Barry-Albright Dystonia Rating Scale,19 and the
be separated into chorea (ie, rapid, involuntary, jerky, and Dyskinesia Impairment Scale.20 The BFMS and Barry-
often fragmented movements) and athetosis (ie, slower, Albright Dystonia Rating Scale show good reliability in
constantly changing, writhing, or contorting move­ DCP but have limited sensitivity.21 These limitations and
ments), this distinction does not appear to be clinically the absence of choreoathetosis measurements are resolved
useful in people with DCP.13,14 in the Dyskinesia Impairment Scale (DIS), which was
Dystonia and choreoathetosis are complex and difficult specifically developed for the assessment of people with
to measure. However, reliable measurement is crucial for DCP.20,22 The DIS consists of dystonia (DIS-D) and
the characterisation of clinical patterns and evaluation of choreoathetosis (DIS-CA) subscales that determine the
the effects of targeted management. Clinical measures presence of and rate the severity (amplitude and duration)
can be used for discriminative, predictive, or evaluative of either movement disorder in various regions of the
purposes. The Hypertonia Assessment Tool15,16 body during activity and rest. The BFMS and DIS are used
distinguishes dystonia from other hypertonic movement as outcome measures in intervention studies, such as
disorders, such as spasticity and rigidity. However, the those investigating deep brain stimulation (DBS)23 or
current evidence base is insufficient to precisely intrathecal baclofen.24
differentiate between different types of cerebral palsy or Dystonia is often more noticeable and severe than
between motor disorders, such as dystonia and choreoathetosis.4 Both are generalised over all body
choreoathetosis, in so-called pure DCP and spasticity. regions (arms, legs, trunk, neck, mouth, and eyes), with
Dystonia can be exacerbated by non-specific stimuli, higher severity in the upper limbs than in the lower
including emotion, cognitive tasks, stress, pain, and the limbs, and both substantially increase with activity.
intention to move, and is always relieved by sleep; by Dystonia has a major effect on the daily activity, quality of
contrast, spasticity is a velocity-dependent increase in life, and societal participation of individuals with DCP.8,25
muscle tone.17 To date, no established clinical measure can Dystonia particularly affects posture, mobility, hand and
discriminate between hyperkinetic movement disorders. oral-motor function, and—to a lesser extent—non-verbal
Therefore, good familiarity with the operational consensus communication.4 By contrast, no functional associations
definitions is crucial for the reliable recognition of with choreoathetosis have been found, which suggests
that the sustained muscle contractions typical of dystonia
restrict functional abilities to a much greater extent than
A B
the hyperkinetic hallmarks of choreoathetosis.4
Occasionally, status dystonicus can occur, which is
characterised by prolonged or increasingly frequent
generalised dystonia and requires early detection and
urgent management.26
Around 70% of patients with DCP have lesions in the
basal ganglia or thalamus, or both on MRI (figures 2, 3);
other brain lesions can also occur and few patients have
apparently normal scans.4,7,28–30 The basal ganglia and
thalamic lesions can be associated with the higher
vulnerability of these regions because of high metabolic
C D demand during the late third trimester of pregnancy27 or
the perinatal period. In neonates with kernicterus, often
associated with high-frequency deafness, the globus
pallidus is usually involved,31 but brain lesions are not
always seen in the years following development of
kernicterus. More severe presentations in DCP include
cortical-subcortical involvement with increased dystonia
and spasticity.27,32 A pattern of increasing clinical severity
has been described based on an MRI classification
system.33 MRI does not necessarily detect the full extent
Figure 1: Abnormal posture and movements in dyskinetic cerebral palsy of the affected brain region, therefore research with more
(A) Primitive asymmetric tonic neck reflex typically present in patients with dyskinetic cerebral palsy. (B) Lack of
advanced imaging techniques is recommended; however,
coordination when in an upright position and grasping objects. (C) Large, uncontrolled involuntary
choreoathetosis movements during activities. (D) Dystonic postures and movements due to sustained or imaging is difficult to perform in these patients because
intermittent muscle contraction. of the involuntary movements and postures.

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At present, it is unclear how brain abnormalities

A B
produce dystonia and choreoathetosis. Emerging
hypotheses based on inherited or primary (mainly focal)
dystonia studies highlight three pathophysiological
aspects, namely loss of inhibition, sensory dysfunction,
and impaired plasticity in basal ganglia circuits.34 Briefly,
two basal ganglia pathways exist: a direct, excitatory
pathway (from the striatum, through the globu-s pallidus
internus, and to the thalamus) and an indirect, inhibitory
pathway (from the striatum, through the globus pallidus
externus, the subthalamic nucleus, and the globus
pallidus internus to the thalamus). The direct pathway
controls voluntary movements, whereas the indirect
pathway inhibits unwanted movements. Imbalance
between the direct and indirect pathways, for example
because of over­ activity in the direct pathway or
underactivity in the indirect pathway, causes excessive
Figure 2: Basal ganglia and thalamic lesions after hypoxic-ischaemic encephalopathy
movement and a loss of inhibition.35 T2-weighted MRI images of the transverse plane (A) and coronal plane (B) show bilateral focal hyperintensity in
Abnormal sensorimotor integration is a key feature in posterior putamen (blue arrow), mediolateral thalamus (red arrow), and central region. Images are courtesy of
the pathogenesis of many movement disorders,36 and the Kate Himmelmann (Department of Pediatrics, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden).
basal ganglia might function as a gate for sensory input.
Abnormal plasticity during motor learning might lead to Choreoathetosis has been underexplored in clinical
abnormal sensorimotor integration, resulting in studies, except in selected conditions (ie, not DCP).
consolidation of abnormal motor engrams.34 According Recent findings have shown a stronger association of
to this hypothesis, therapeutic management might have selective thalamus and basal ganglia lesions for
little immediate effect on dystonia because so-called bad choreoathetosis than for dystonia,4 suggesting that
motor memories are difficult to erase.34 This hypothesis further research on choreoathetosis in DCP is warranted.
suggests that living longer with dystonia makes clinical Combined approaches can further advance under­
management more difficult.37 However, based on the standing of dystonia and choreoathetosis in people with
different underlying causes of the condition, whether DCP. High-resolution MRI and voxel-based morphometry
this hypothesis also applies to dystonia in DCP is might improve understanding of structural injury, and
questionable. clarify the implication of selected deep grey matter nuclei
A study in patients with DCP found no significant and other brain lesions, including the motor cortex and
association between the severity of dystonia and brain the cerebelllum, and their correlation with appropriately
lesions in the basal ganglia and thalamus.4 Some findings described motor phenotypes. The current description of
suggest that different brain regions that are involved in DCP might not be relevant to a pathophysiological
motor control can cause or contribute to dystonia, explanation of the motor manifestations; therefore, it may
including the cerebellum, brainstem, cerebral cortex, be necessary to define several motor phenotypes.
and other motor and sensory thalamo-cortical Diffusion tensor imaging provides information about
pathways.38,39 Therefore, dystonia might be most connectivity and might help to predict the likelihood of
accurately described as a neuronal network disorder, responsiveness to DBS.42 Electrophysiological assessment,
with different phenotypes possibly reflecting different including transcranial magnetic stimulation,43 central
pathophysiological states triggered by various insults or motor conduction time44 and somatosensory evoked
abnormalities.40 This network model provides testable potentials,45,46 might also contribute towards diagnosis and
hypotheses that are directly relevant to new treatment management of DCP.
strategies that extend beyond the basal ganglia.41 From
this perspective, we hypothesise that the pathophysiology Management
of dystonia caused by an inherited disorder (ie, primary Management of dystonia and choreoathetosis should be
dystonia) differs from that of secondary dystonia in DCP, timed and targeted to maximise the potential for cerebral
as supported by different responses to treatment and by plasticity in people with DCP.47 As suggested by the
differences in motor cortex plasticity and cerebellar WHO International Classification of Functioning,
function in the modulation of dystonic features.40,41 Disability and Health, management should aim to
Therefore, further research is needed to unravel the improve daily activity and quality of life by improving
pathophysiology of dystonia, specifically in DCP, because movement and posture and relieving any associated
the focus of pathophysiological studies over the past two disability, pain, and discomfort.25
decades has been almost exclusively placed on inherited Non-motor comorbidities, such as epilepsy or
(primary) dystonia. depression, require specific treatment. To ensure optimal

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 Review

patients with DCP.52 Less research has been done

A B C
concerning treatment for choreoathetosis. Dopamine-
depleting agents can influence the hyperkinetic
component of dyskinesia.51 Other studies have reported a
positive effect of levetiracetam in children with
choreoathetosis.53,54
The table provides an overview of medications used to
manage dystonia and choreoathetosis in people with
DCP. Oral baclofen, a GABA-B agonist used for spasticity
management, is the most commonly used oral drug for
DCP despite its low efficacy.51 The efficacy of
D E F trihexyphenidyl, an anticholinergic drug, on dystonia is
also low61,62 and its use in people with DCP is often
restricted by the risk of adverse effects. Adverse effects
can include worsening of choreoathetosis, possibly
owing to so-called unmasking when severe dystonia is
reduced (ie, dystonia prevented the full expression of
choreoathetosis).4
Intrathecal baclofen treatment was introduced as an
alternative to oral administration with fewer side-effects,
and much lower dosage. Many studies of intrathecal
baclofen treatment have reported significant decreases in
G H I dystonia63–65 and subjective im­prove­ments in mobility,66,67
speech and communication, swallowing,59 head control,68
sleep,66 pain and mood,64 comfort,66,68–71 and ease of care.66
Patient satisfaction and attained goals are generally
high.71 Although intrathecal baclofen decreases dystonia
in most patients, the treatment usually leads to no
changes in functional independence for daily activities64
Therefore, treatment goals mainly focus on improving
pain and preventing deformities.64,69,71,72 Such therapy
Figure 3: Mild, moderate, and severe MRI patterns of basal ganglia and thalamus lesions could be particularly appropriate in patients with both
(A–C) Mild pattern of basal ganglia and thalamus lesions (T2-weighted, red and green arrows; T1-weighted, blue dystonia and spasticity.72 Whereas the benefits to improve
arrow); central region not involved (T2-weighted, white arrow). Clinical outcome: dyskinetic cerebral palsy. (D–F) dystonia are well known, the effect of intrathecal baclofen
Moderate pattern: Basal ganglia and thalamus lesions (T2-weighted, red and green arrows); central cortical and on choreoathetosis has not been investigated.
subcortical lesions (FLAIR, white arrow); and hippocampus not involved (T2-weighted, blue arrow). Clinical
outcome: dyskinetic cerebral palsy with spastic traits, or spastic cerebral palsy with dyskinetic trait, depending on In people with DCP, the intrathecal baclofen catheter tip
the involvement of the motor cortex. (G–I) Severe pattern of basal ganglia and thalamus lesions (T2-weighted, is often placed high at the cervical spinal level, because
red arrow); central cortical and subcortical lesion (T2-weighted, white arrow); and hippocampus lesions major sites of action of baclofen are likely to be
(T2-weighted, blue arrow). Clinical outcome: severe bilateral spastic cerebral palsy. Images are courtesy of
intracranial.65 The response cannot be fully predicted and
Krägeloh-Mann and colleagues.27
the dosage must be individualised.73 If the effect of a
continuous dose is not sufficient or has a gradually reduced
nutrition, gastrostomy tube feeding can be considered on effect, intermittent bolus dosing can be used.73
the basis of a comprehensive assessment by a Complications after intrathecal baclofen implantation are
multidisciplinary team.48,49 Management should also common. Infection risk is high (33–44%),71,74 particularly in
focus on prevention of contractures and orthopaedic the first month after surgery,73,75 and infection treatment
complications.49 always requires pump removal. CSF leaks occur in 0–21%
Little evidence supports the use of pharmacological of cases,64,71 with an increased risk during patient transfers
treatment of dystonia and choreoathetosis in people with and mobilisation. Extended bed rest usually resolves the
DCP.50 Many patients with DCP take multiple oral drugs leak and accompanying light-headedness, but surgery is
with low efficacy and unwanted side-effects.51 Never­ sometimes needed.65 Catheter-related problems, such as
theless, in some patients, oral drugs can be useful. Before migration, disconnection, and blockage, often manifest
considering medical treatment of dystonia, it is important with signs of baclofen withdrawal, for example an increase
to determine whether the patient also shows spasticity, as in spasticity or dystonia, or both, generalised itching and
this requires a specific approach. Particularly in patients agitation, and hypertension.73 These issues occur in 5–33%
without MRI abnormalities, the possibility of dopamine- of patients with catheter-related problems.63,64,71 When
responsive dystonia as a mimic DCP should be patients are awaiting surgery, oral baclofen can be given to
considered. However, levodopa shows limited efficacy in decrease the severity of withdrawal symptoms.

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Mechanism of action Dystonia Chorea Side-effects

Dopamine agonists (levodopa)55 Enhances the activity of dopamine Used .. Nausea, orthostatic hypotension, and constipation
Anticholinergic (trihexiphenidyl, Blocks acetylcholine muscarinic receptor Used .. Drowsiness, confusion, memory difficulty, blurred
benzatropine) 51,55 vision, hallucinations, urinary retention,
and worsening chorea
Benzodiazepine receptor agonists Enhances GABA-A inhibition Used Used Sedation, confusion, depression, ataxia,
(diazepam, clonazepam)55,56 and dependence
GABA-B receptor agonist Enhances the activity of GABA-B receptor Used ·· Worsening chorea, incontinence, sedation,
(baclofen)51,55–57 dizziness, dry mouth, and increased blood glucose
Dopamine and serotonin Binds to serotonin and dopamine receptors Used ·· Decreased white blood cell count, sedation,
antagonist (clozapine)56 and prevents release hypotension, myocarditis, cardiomyopathy,
drooling, arrhythmia, seizures, and diabetes mellitus
Pre-synaptic α2 receptor agonist Enhances the activity of pre-synaptic α2 Used ·· Orthostatic hypotension, bradycardia, sedation,
(clonidine)58 receptor fatigue, and headache
Dopamine antagonists Antagonist of the D2, D3, and D4 dopamine ·· Used Hypotension, sedation, QT interval prolongation,
(pimozide, haloperidol)55 receptors, and the 5-HT7 receptor and ventricular arrhythmias (including torsades
de pointes); overdose causes severe extrapyramidal
symptoms
Monoamine blockers Inhibits vesicular monoamine transporter 2, Used Used Drowsiness, parkinsonism, depression, insomnia,
(tetrabenazine)51,55,56 resulting in decreased uptake of anxiety, and akathisia
monoamines into synaptic vesicles and
depletion of monoamine storage
Monoamine depleters Blocks the vesicular monoamine transporter .. Used Nasal congestion, nausea, vomiting, weight gain,
(reserpine)51 gastric intolerance, gastric ulceration, stomach
cramps and diarrhoea, hypotension, bradycardia,
and worsening of asthma
Voltage-gated sodium and Blocks voltage-sensitive sodium channels Used ·· Decreased white blood cell count and platelets;
calcium channel blocker increased risk of suicide
(carbamazepine)55
Calcium channel blocker Binds to a synaptic vesicle glycoprotein and ·· Used Somnolence, decreased energy, headache,
(levetiracetam)53,54 inhibits presynaptic calcium channels, dizziness, and (mild) ataxia
reducing neurotransmitter release and
acting as a neuromodulator
Muscle tone reducer Reduces skeletal muscle tone at the muscle Used ·· Speech and visual disturbances; depression and
(dantrolene)59 fibre level confusion; hallucinations; headache; insomnia and
exacerbation or precipitation of seizures, and
increased nervousness
Voltage-gated calcium channel Antagonises binding of thrombospondin to Used ·· Dizziness, drowsiness, sedation, fever, fatigue, viral
blocker (gabapentin)60 voltage-gated calcium channel a2d-1 infection, ataxia, and nystagmus
receptors and inhibits synthesis of
glutaminergic excitatory synapses

Table: Medications used to manage dystonia and choreoathetosis in patients with dyskinetic cerebral palsy

On the basis of dramatic positive outcomes in patients development, in people with DCP, dystonia presents in
with inherited (primary) dystonia,76,77 DBS has been early life before functional motor patterns have developed
increasingly used in people with DCP over the past and, when they do, those movements and postures are
decade.23,37,78–81 Studies of DBS in people with DCP often often abnormal.37,88
describe the reduction of dystonia rather than its effects Currently, the globus pallidus internus is the target of
on functionality, quality of life, or choreoathetosis.25,82–84 choice for electrode implantation in people with DCP.56
The responsiveness of dystonia to DBS treatment is DBS programming is personalised based on subjective
variable85 and usually less beneficial than in patients with evaluations of clinical benefit; an objective approach to
inherited (primary) dystonia.86 Long-term data are rare, parameter selection would require better understanding
but a case series follow-up study in Italy that of the underlying pathophysiology. DBS is generally safe,
included 15 patients reported that improvements in and a reversible method of treatment. Complications
BFMS values were sustained for up to 2 years after such as intracerebral haemorrhage or ischaemic
implant.79 infarction are rare, but infection and hardware problems
The relatively modest and often delayed effects of DBS of the implanted pulse generator can occur.89 More severe
in people with DCP might be due to abnormal plasticity adverse events of DBS have been reported in children
and an altered neuronal cortex-basal ganglia network.34,87 than in adults;23 however, large cohort studies have
Whereas in inherited (primary) movement disorders, reported low infection rates of less than 5% in children
dystonia becomes symptomatic after a period of normal younger than 7 years.90

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Responsiveness of choreoathetosis to DBS has not focus on goal-directed strategies that consider general
been documented, and little is known about the effect of guidelines to handle postural asymmetry and individual
DBS on daily activity, societal participation, or quality of needs.49 Verbal communication is almost always affected
life. Various collaborative efforts are underway to in people with DCP,100,101 therefore augmentative and
systematically collect data on individuals with DBS, alternative com­munication intervention is often needed.
including age of implantation, history of eventual Without appropriate communication intervention, the
musculoskeletal changes, activity levels, and inclusion in intellectual level of the individual with DCP could be
an international registry.23,91 underestimated.7 In addition, given the potential for
Botulinum toxin is often used to decrease dystonia in brain plasticity, cognitive training and motor learning
people with DCP.92 Botulinum toxin causes selective research is warranted in DCP management.
(focal) muscular denervation that is temporary and
reversible. Its therapeutic value has been much more Conclusions and future directions
extensively assessed in inherited (primary) dystonia than Many epidemiological studies2,102 are currently underway;
in people with DCP. Botulinum toxin is also used in these studies are mostly population-based or registry-
individuals with hip dislocation or disabling limb based and focus on the identification of risk factors that
dystonia. A few small studies have indicated that will eventually lead to the implementation of preventive
botulinum toxin has an effect on dystonia and pain in strategies. Hypothermia for term and near-term neonates
people with DCP.93,94 Many issues remain unresolved with hypoxia–ischaemia,103 and magnesium sulphate and
because of variation in injection methods and a shortage other agents as neuroprotective approaches for fetuses are
of knowledge of the determinants of local spread and promising approaches under investigation.104 Population-
distant effects.55 To date, no specific indication is available based follow-up programmes and studies will add to
for choreoathetosis. the evidence base regarding long-term secondary
As musculoskeletal deformities seen in patients with complications and results of management.
DCP and those with other childhood dystonias9 are often Current management options are mainly based on
associated with pain, patients might undergo orthopaedic clinical presentation. To evaluate the efficacy of therapy
surgery.49 However, before orthopaedic surgery is done, it and to adjust and delineate management, well designed
is recommended that attempts are made to control studies and systematic use of meaningful outcome
dystonia and choreoathetosis with oral drugs, intrathecal measures are needed. Future research should include
baclofen, or DBS. Furthermore, based on our clinical additional objective and quantitative tools to assess
experience, the results of soft tissue orthopaedic surgery dystonia and choreoathetosis. Moreover, owing to the
in patients with DCP are not as predictable as in patients relatively small population of patients with DCP,
with spastic cerebral palsy, and adverse outcomes can multicentre studies are crucial for the development of
easily occur. By contrast, orthopaedic procedures can be evidence-based guidelines for the management of
carried out more safely in patients with DCP than in dystonia and choreoathetosis. Specific evaluation of
those with spastic CP. rehabilitation strategies, including physical, occupational,
The medical management options discussed are not and speech and language therapy, is urgently required.101
appropriate as standalone treatment. Combinations with Robotics and other emerging technologies have the
rehabilitation approaches carried out by physiotherapists, potential to increase independent mobility. Better
occupational therapists, and speech and language understanding of motor learning processes is needed to
therapists are key components of the management of implement these new technologies.
dystonia and choreoathetosis. Evidence for rehabilitative To date, medical interventions in DCP (eg, intrathecal
strategies is mostly based on studies in spastic cerebral baclofen, DBS, and botulinum toxin) have mainly
palsy and remains scarce in DCP.95,96 Current practice is targeted dystonia but not choreoathetosis, which requires
therefore mainly based on clinical expertise. This expertise more research attention. Further research into the effect
is usually offered by dedicated multidisciplinary rehab­ of interventions on daily activities, societal participation,
ilitation teams designing individualised management quality of life, pain, nutrition, and sleep is also required.
programmes that begin as early as possible in the life of The clinical interrelationship between dystonia and
the patient. Use of a family-centred approach and the choreoathetosis after different interventions is also worth
concepts developed in WHO’s International Classification further research.
of Functioning, Disability, and Health can ensure the The neurophysiological basis of dystonia and choreo­
development of skills and good quality of life.97–99 athetosis should be explored. To date, there are no
Most patients have substantial motor disability, animal models for DCP.105 Increased insight into the
therefore optimal seating and positioning should be neurophysiological circuits in patients with DCP can be
ensured to increase stability and the coordination of obtained during intraoperative pallidal recordings of
movements for mobility (including electronic local field potentials and microelectrode recordings.
wheelchair use) and hand function. Combined with Neuronal firing frequencies have been shown to
medical management, rehabilitative research should correlate with dystonia phenotype and the timing of the

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6 Olusanya B, Osibanjo F, Mabogunje C, Slusher T, Olowe S.

Search strategy and selection criteria The burden and management of neonatal jaundice in Nigeria:
a scoping review of the literature. Niger J Clin Pract 2016; 19: 1–17.
We identified references for this Review by searching PubMed 7 Himmelmann K, Hagberg G, Wiklund L, Eek MN, Uvebrant P.
for reports published between Jan 1, 2006 and March 31, Dyskinetic cerebral palsy: a population-based study of children born
between 1991 and 1998. Dev Med Child Neurol 2007; 49: 246–51.
2017, and references from relevant articles. Search terms used 8 Monbaliu E, De Cock P, Mailleux L, Dan B, Feys H.
were “dyskinetic cerebral palsy” and “dystonic cerebral palsy”, The relationship of dystonia and choreoathetosis with activity,
“hypoxic-ischemic encephalopathy” and “dystonia”, and participation and quality of life in children and youth with
dyskinetic cerebral palsy. Eur J Paediatr Neurol 2017; 21: 327–35.
“choreoathetosis” and “pathophysiology” in combination 9 Lumsden DE, Gimeno H, Elze M, Tustin K, Kaminska M, Lin JP.
with “management” or “therapy”, or “treatment”. We only Progression to musculoskeletal deformity in childhood dystonia.
considered peer-reviewed reports in English. Eur J Paediatr Neurol 2016; 20: 339–45.
10 Kim KN, Ahn PG, Ryu MJ, Shin DA, Yi S, Ha Y. Long-term surgical
outcomes of cervical myelopathy with athetoid cerebral palsy.
Eur Spine J 2014; 23: 1464–71.
insult, which could be partially predictive of DBS 11 Himmelmann K, Sundh V. Survival with cerebral palsy over
outcome.43 Other non-invasive neurophysiological five decades in western Sweden. Dev Med Child Neurol 2015;
57: 762–67.
models in children and adults with DCP and their
12 Sanger TD, Chen D, Fehlings DL, et al. Definition and classification of
neuroimaging findings are needed to explore cerebral hyperkinetic movements in childhood. Mov Disord 2010; 25: 1538–49.
plasticity.106,107 13 Krägeloh-Mann I, Petruch U, Weber P. SCPE reference and training
In conclusion, although DCP is the second most manual (R&TM). Grenoble: Surveillance of Cerebral Palsy in
Europe, 2005.
common type of cerebral palsy, the condition is under- 14 Cans C, Dolk H, Platt M, Colver A, Prasauskiene A,
reported7 and management remains empirical and largely Krägeloh-Mann. Recommendations from the SCPE collaborative
unsatisfactory. Therefore, a better scientific foundation to group for defining and classifying cerebral palsy.
Dev Med Child Neurol 2007; 49: 35–38.
therapeutic approaches is urgently required. Early 15 Jethwa A, Mink J, Macarthur C, Knights S, Fehlings T, Fehlings D.
detection, improved neuroimaging, and improved Development of the Hypertonia Assessment Tool (HAT):
neurophysiological characterisation of dystonia and a discriminative tool for hypertonia in children.
Dev Med Child Neurol 2010; 52: e83–87.
choreoathetosis in DCP are needed. Increased
16 Knights S, Datoo N, Kawamura A, et al. Further evaluation of the
understanding of the affected brain structures could scoring, reliability, and validity of the Hypertonia Assessment Tool
contribute to better targeted therapeutic management. (HAT). J Child Neurol 2014; 29: 500–04.
17 Lin JP, Nardocci N. Recognizing the common origins of dystonia
Contributors and the development of human movement: a manifesto of unmet
All authors contributed significantly to the work, have read the needs in isolated childhood dystonias. Front Neurol 2016; 7: 226.
manuscript, attest to the validity of the data and its interpretation, and 18 Burke RE, Fahn S, Marsden CD, Bressman SB, Moskowitz C,
agree to its submission. EM provided the videos and figure 1 images and Friedman J. Validity and reliability of a rating scale for the primary
KH provided the images in figures 2 and 3. torsion dystonias. Neurology 1985; 35: 73–76.
Declaration of interests 19 Barry MJ, VanSwearingen JM, Albright AL. Reliability and
J-PL has received a Guy’s and St Thomas Charity New Services and responsiveness of the Barry-Albright dystonia scale.
Dev Med Child Neurol 1999; 41: 404–11.
Innovation Grant (G060708), grants from The Dystonia Society UK
(01/2011, 07/2013) and Action Medical Research (GN2097), is a 20 Monbaliu E, Ortibus E, De Cat J, et al. The Dyskinesia Impairment
Scale: a new instrument to measure dystonia and choreoathetosis
consultant for Medtronic Ltd, and has received unrestricted educational
in dyskinetic cerebral palsy. Dev Med Child Neurol 2012; 54: 278–83.
grants from Medtronic Ltd for delivering courses and attending
21 Monbaliu E, Ortibus E, Roelens F, et al. Rating scales for dystonia
conferences. RJV has received unrestricted educational grants from
in cerebral palsy: reliability and validity. Dev Med Child Neurol 2010;
Medtronic Ltd for delivering courses and from Ipsen International 52: 570–75.
GmbH for his advisory board role. All other authors declare no
22 Monbaliu E, Ortibus E, Prinzie P, et al. Can the Dyskinesia
competing interests. Impairment Scale be used by inexperienced raters? A reliability
Acknowledgments study. Eur J Paediatr Neurol 2013; 17: 238–47.
We would like to thank Marc Vermandere (Dominiek Savio Instituut, 23 Koy A, Timmermann L. Deep brain stimulation in cerebral palsy:
Gits, Belgium) for his support in compiling the videos. Challenges and opportunities. Eur J Paediatr Neurol 2017; 21: 118–21.
24 Bonouvrie LA, Becher JG, Vles JS, et al. Intrathecal baclofen
References treatment in dystonic cerebral palsy: a randomized clinical trial: the
1 Rosenbaum P, Paneth N, Leviton A, et al. A report: the definition IDYS trial. BMC Pediatr 2013; 13: 175.
and classification of cerebral palsy April 2006. Dev Med Child Neurol
25 Gimeno H, Lin JP. The International Classification of Functioning
2007; 49: 8–14.
(ICF) to evaluate deep brain stimulation neuromodulation in
2 Sellier E, Platt MJ, Andersen GL, Krägeloh-Mann I, De La Cruz J, childhood dystonia-hyperkinesia informs future clinical & research
Cans C. Decreasing prevalence in cerebral palsy: a multi-site priorities in a multidisciplinary model of care. Eur J Paediatr Neurol
European population-based study, 1980 to 2003. 2017; 21: 147–67.
Dev Med Child Neurol 2016; 58: 85–92.
26 Allen NM, Lin JP, Lynch T, King MD. Status dystonicus: a practice
3 Yeargin-Allsopp M, Braun KVN, Doernberg NS, Benedict RE, guide. Dev Med Child Neurol 2014; 56: 105–12.
Kirby RS, Durkin MS. Prevalence of cerebral palsy in 8-year-old
27 Krägeloh-Mann I, Helber A, Mader I, et al. Bilateral lesions of
children in three areas of the United States in 2002: a multisite
thalamus and basal ganglia: origin and outcome.
collaboration. Pediatrics 2008; 121: 547–54.
Dev Med Child Neurol 2002; 44: 477–84.
4 Monbaliu E, De Cock P, Ortibus E, Heyrman L, Klingels K, Feys H.
28 Aravamuthan BR, Waugh JL. Localization of basal ganglia and
Clinical patterns of dystonia and choreoathetosis in participants with
thalamic damage in dyskinetic cerebral palsy. Pediatr Neurol 2016;
dyskinetic cerebral palsy. Dev Med Child Neurol 2016; 58: 138–44.
54: 11–21.
5 Himmelmann K, McManus V, Hagberg G, Uvebrant P,
29 Himmelmann K. Dyskinetic cerebral palsy: challenges and new
Krägeloh-Mann I, Cans C. Dyskinetic cerebral palsy in Europe:
approaches. Dev Med Child Neurol 2011; 53: 10–11.
trends in prevalence and severity. Arch Dis Child 2009; 94: 921–26.

www.thelancet.com/neurology Vol 16 September 2017 747

 Review

30 Benini R, Dagenais L, Shevell MI, for the Consortium RdlPCaQ. 55 Roubertie A, Mariani LL, Fernandez-Alvarez E, Doummar D,
Normal imaging in patients with cerebral palsy: what does it tell us? Roze E. Treatment for dystonia in childhood. Eur J Neurol 2012;
J Pediatr 2013; 162: 369–74. 19: 1292–99.
31 Yilmaz Y, Alper G, Kiliçoglu G, Çelik L, Karadeniz L, 56 Jankovic J. Treatment of dystonia. Lancet Neurol 2006; 5: 864–72.
Yilmaz-Degirmenci S. Magnetic resonance imaging findings in 57 Kolker S, Christensen E, Leonard JV, et al. Diagnosis and
patients with severe neonatal indirect hyperbilirubinemia. management of glutaric aciduria type I—revised recommendations.
J Child Neurol 2001; 16: 452–55. J Inherit Metab Dis 2011; 34: 677–94.
32 Platt MJ, Krageloh-Mann I, Cans C. Surveillance of cerebral palsy in 58 Sayer C, Lumsden D, Kaminska M, Lin JP. Clonidine use in the
Europe: reference and training manual. Med Educ 2009; 43: 495–96. outpatient management of severe secondary dystonia.
33 Himmelmann K, Horber V, De La Cruz J, et al. MRI classification Eur J Paediatr Neurol 2017; 21: 621–26.
system (MRICS) for children with cerebral palsy: development, 59 van Karnebeek C, Horvath G, Murphy T, et al. Deep brain
reliability, and recommendations. Dev Med Child Neurol 2017; stimulation and dantrolene for secondary dystonia in x-linked
59: 57–64 adrenoleukodystrophy. JIMD Rep 2015; 15: 113–16.
34 Quartarone A, Hallett M. Emerging concepts in the physiological 60 Liow NY, Gimeno H, Lumsden D, et al. Gabapentin can
basis of dystonia. Mov Disord 2013; 28: 958–67. significantly improve dystonia severity and quality of life in
35 Hallett M. Neurophysiology of dystonia: the role of inhibition. children. Eur J Paediatr Neurol 2016; 20: 100–07.
Neurobiol Dis 2011; 42: 177–84. 61 Rice J, Waugh Mary-Clare MC. Pilot study on trihexyphenidyl in the
36 Patel N, Jankovic J, Hallett M. Sensory aspects of movement treatment of dystonia in children with cerebral palsy. J Child Neurol
disorders. Lancet Neurol 2014; 13: 100–12. 2009; 24: 176–82.
37 Lumsden D, Kaminska M, Gimeno H, et al. Proportion of life lived 62 Sanger TD, Bastian A, Brunstrom J, et al. Prospective open-label
with dystonia inversely correlates with response to pallidal deep clinical trial of trihexyphenidyl in children with secondary dystonia
brain stimulation in both primary and secondary childhood due to cerebral palsy. J Child Neurol 2007; 22: 530–37.
dystonia. Dev Med Child Neurol 2013; 55: 567–74. 63 Motta F, Antonello CE, Stignani C. Upper limbs function after
38 Filip P, Lungu OV, Bareš M. Dystonia and the cerebellum: a new intrathecal baclofen therapy in children with secondary dystonia.
field of interest in movement disorders? Clin Neurophysiol 2013; J Pediatr Orthop 2009; 29: 817–21.
124: 1269–76. 64 Motta F, Stignani C, Antonello CE. Effect of intrathecal baclofen on
39 Stoessl AJ, Lehericy S, Strafella AP. Imaging insights into basal dystonia in children with cerebral palsy and the use of functional
ganglia function, Parkinson’s disease, and dystonia. Lancet 2014; scales. J Pediatr Orthop 2008; 28: 213–17.
384: 532–44. 65 Albright AL, Barry MJ, Shafton DH, Ferson SS. Intrathecal baclofen
40 Kojovic M, Pareés I, Kassavetis P, et al. Secondary and primary for generalized dystonia. Dev Med Child Neurol 2001; 43: 652–57.
dystonia: pathophysiological differences. Brain 2013; 136: 2038–49. 66 Bonouvrie L, Becher J, Soudant D, et al. The effect of intrathecal
41 Neychev VK, Gross RE, Lehéricy S, Hess EJ, Jinnah H. baclofen treatment on activities of daily life in children and young
The functional neuroanatomy of dystonia. Neurobiol Dis 2011; adults with cerebral palsy and progressive neurological disorders.
42: 185–201. Eur J Paediatr Neurol 2016; 20: 538–44
42 Lumsden DE, McClelland V, Ashmore J, Charles-Edwards G, 67 Motta F, Antonello CE, Stignani C. Intrathecal baclofen and motor
Mills K, Lin JP. Central Motor Conduction Time and Diffusion function in cerebral palsy. Dev Med Child Neurol 2011; 53: 443–48.
Tensor Imaging metrics in children with complex motor disorders. 68 Woon K, Tsegaye M, Vloeberghs M. The role of intrathecal baclofen
Clin Neurophysiol 2015; 126: 140–46. in the management of primary and secondary dystonia in children.
43 Dachy B, Dan B. Electrophysiological assessment of the effect of Br J Neurosurg 2007; 21: 355–58.
intrathecal baclofen in dystonic children. Clin Neurophysiol 2004; 69 Bonouvrie LA, van Schie PE, Becher JG, van Ouwerkerk WJ,
115: 774–78. Reeuwijk A, Vermeulen JR. Effects of intrathecal baclofen on daily
44 McClelland V, Mills K, Siddiqui A, Selway R, Lin JP. Central motor care in children with secondary generalized dystonia: a pilot study.
conduction studies and diagnostic magnetic resonance imaging in Eur J Paediatr Neurol 2011; 15: 539–43.
children with severe primary and secondary dystonia. 70 Motta F, Buonaguro V, Stignani C. The use of intrathecal baclofen
Dev Med Child Neurol 2011; 53: 757–63. pump implants in children and adolescents: safety and complications
45 McClelland VM, Cvetkovic Z, Mills KR. Modulation of in 200 consecutive cases. J Neurosurg 2007; 107: 32–35.
corticomuscular coherence by peripheral stimuli. Exp Brain Res 71 Ward A, Hayden S, Dexter M, Scheinberg A. Continuous intrathecal
2012; 219: 275–92. baclofen for children with spasticity and/or dystonia: goal
46 McClelland V, Valentin A, Rey HG, et al. Differences in globus attainment and complications associated with treatment.
pallidus neuronal firing rates and patterns relate to different disease J Paediatr Child H 2009; 45: 720–26.
biology in children with dystonia. J Neurol Neurosurg Psychiatry 2016; 72 Dan B, Motta F, Vles JS, et al. Consensus on the appropriate use of
87: 958–67. intrathecal baclofen (ITB) therapy in paediatric spasticity.
47 Ismail FY, Fatemi SA, Johnston MV. Cerebral plasticity: windows of Eur J Paediatr Neurol 2010; 14: 19–28.
opportunity in the developing brain. Eur J Paediatr Neurol 2017; 73 Albright AL. Intrathecal baclofen for childhood hypertonia.
21: 23–48. Child Nerv Syst 2007; 23: 971–79.
48 Dahlseng MO, Andersen GL, Da Graca Andrada M, et al. 74 Albright AL, Barry MJ, Fasick P, Barron W, Shultz B.
Gastrostomy tube feeding of children with cerebral palsy: variation Continuous intrathecal baclofen infusion for symptomatic
across six European countries. Dev Med Child Neurol 2012; 54: 938–44. generalized dystonia. Neurosurgery 1996; 38: 934–39.
49 Dan B, Mayston M, Paneth N, Rosenbloom L. Cerebral palsy: 75 Ghosh D, Mainali G, Khera J, Luciano M. Complications of
science and clinical practice. London: Wiley; 2015. intrathecal baclofen pumps in children: experience from a tertiary
50 Koy A, Lin J-P, Sanger TD, Marks WA, Mink JW, Timmermann L. care center. Pediatr Neurosurg 2014; 49: 138–44.
Advances in management of movement disorders in children. 76 Coubes P, Roubertie A, Vayssiere N, Hemm S, Echenne B.
Lancet Neurol 2016; 15: 719–35. Treatment of DYT1-generalised dystonia by stimulation of the
51 Lumsden D, Kaminska M, Tomlin S, Lin JP. Medication use in internal globus pallidus. Lancet 2000; 355: 2220–21.
childhood dystonia. Eur J Paediatr Neurol 2016; 20: 625–29. 77 Krauss JK, Pohle T, Weber S, Ozdoba C, Burgunder J-M.
52 Maas RP, Wassenberg T, Lin JP, van de Warrenburg BP, Bilateral stimulation of globus pallidus internus for treatment of
Willemsen MA. L-Dopa in dystonia: a modern perspective. cervical dystonia. Lancet 1999; 354: 837–38.
Neurology 2017 88: 1865–71. 78 Vidailhet M, Yelnik J, Lagrange C, et al. Bilateral pallidal deep brain
53 Vles GF, Hendriksen JG, Visschers A, Speth L, Nicolai J, Vles JS. stimulation for the treatment of patients with
Levetiracetam therapy for treatment of choreoathetosis in dyskinetic dystonia-choreoathetosis cerebral palsy: a prospective pilot study.
cerebral palsy. Dev Med Child Neurol 2009; 51: 487–90. Lancet Neurol 2009; 8: 709–17.
54 Recio MV, Hauser RA, Louis ED, Radhashakar H, Sullivan KL, 79 Romito L, Zorzi G, Marras C, Franzini A, Nardocci N, Albanese A.
Zesiewicz TA. Chorea in a patient with cerebral palsy: treatment Pallidal stimulation for acquired dystonia due to cerebral palsy:
with levetiracetam. Mov Disord 2005; 20: 762–64. beyond 5 years. Eur J Neurol 2015; 22: 426–e32.

748 www.thelancet.com/neurology Vol 16 September 2017

 Review

80 Marks WA, Honeycutt J, Acosta F, et al. Dystonia due to cerebral 94 Lundy CT, Doherty GM, Fairhurst CB. Botulinum toxin type A
palsy responds to deep brain stimulation of the globus pallidus injections can be an effective treatment for pain in children with
internus. Mov Disord 2011; 26: 1748–51. hip spasms and cerebral palsy. Dev Med Child Neurol 2009;
81 Koy A, Hellmich M, Pauls KA, et al. Effects of deep brain 51: 705–10.
stimulation in dyskinetic cerebral palsy: a meta-analysis. Mov Disord 95 Hägglund GA, Alriksson-Schmidt A, Lauge-Pedersen H,
2013; 28: 647–54. Rodby-Bousquet E, Wagner PL, Westbom L. Prevention of
82 Gimeno H, Tustin K, Selway R, Lin J-P. Beyond the dislocation of the hip in children with cerebral palsy: 20-year results
Burke–Fahn–Marsden Dystonia Rating Scale: deep brain stimulation of a population-based prevention programme. Bone Joint J 2014;
in childhood secondary dystonia. Eur J Paediatr Neurol 2012; 16: 501–08. 96: 1546–52.
83 Gimeno H, Gordon A, Tustin K, Lin JP. Functional priorities in 96 Novak I, Mcintyre S, Morgan C, et al. A systematic review of
daily life for children and young people with dystonic movement interventions for children with cerebral palsy: state of the evidence.
disorders and their families. Eur J Paediatr Neurol 2013; 17: 161–68. Dev Med Child Neurol 2013; 55: 885–910.
84 Lumsden DE, Gimeno H, Tustin K, Kaminska M, Lin JP. 97 Capelovitch S. The Bobath concept—did globalization reduce it to a
Interventional studies in childhood dystonia do not address the Chinese whisper? Dev Med Child Neurol 2017; 59: 557.
concerns of children and their carers. Eur J Paediatr Neurol 2015; 98 WHO. International Classification of Functioning, Disability and
19: 327–36. Health. WHO, Geneva, Switzerland, 2001. Jan 27, 2017.
85 Lin J. Deep brain stimulation in children: clinical considerations. http://www.who.int/classifications/icf/en/ (accessed May 24, 2017).
In: Kirton A, Gilbert D eds. Pediatric brain stimulation. Mapping and 99 National Institute for Health and Excellence. Cerebral palsy in
modulating the developing brain, 1st edn. London: Elsevier, 2016: under 25s: assessment and management. 2017. https://www.nice.
401–19. org.uk/guidance/ng62 (accessed May 24, 2017).
86 Marks W, Bailey L, Reed M, et al. Pallidal stimulation in children: 100 Nordberg A, Miniscalco C, Lohmander A, Himmelmann K.
Comparison between cerebral palsy and DYT1 dystonia. Speech problems affect more than one in two children with cerebral
J Child Neurol 2013; 28: 840–48. palsy: Swedish population-based study. Acta Paediatr 2013;
87 Barow E, Neumann W-J, Brücke C, et al. Deep brain stimulation 102: 161–66.
suppresses pallidal low frequency activity in patients with phasic 101 Monbaliu E, De La Peña MG, Ortibus E, Molenaers G, Feys H.
dystonic movements. Brain 2014; 137: 3012–24. Functional outcomes in children and young people with dyskinetic
88 Lin J-P, Lumsden DE, Gimeno H, Kaminska M. The impact and cerebral palsy. Dev Med Child Neurol 2017; 59: 634–40.
prognosis for dystonia in childhood including dystonic cerebral 102 Reid SM, Meehan E, McIntyre S, Goldsmith S, Badawi N,
palsy: a clinical and demographic tertiary cohort study. Reddihough DS. Temporal trends in cerebral palsy by impairment
J Neurol Neurosurg Ps 2014; 85: 1239–44. severity and birth gestation. Dev Med Child Neurol 2016; 58: 25–35.
89 Fenoy AJ, Simpson RK Jr. Risks of common complications in deep 103 Jacobs S, Berg M, Hunt R, Tarnow-Mordi W, Inder T, Davis P.
brain stimulation surgery: management and avoidance: clinical Cooling for newborns with hypoxic ischaemic encephalopathy.
article. J Neurosurg 2014; 120: 132–39. Cochrane Database Syst Rev 2013; CD003311.
90 Kaminska M, Perides S, Lumsden D, et al. Complications of Deep 104 Costantine MM, Weiner SJ. Effects of antenatal exposure to
Brain Stimulation (DBS) for dystonia in children—the challenges magnesium sulfate on neuroprotection and mortality in preterm
and 10 year experience in a large paediatric cohort. infants: a meta-analysis. Obstet Gynecol 2009; 114: 354.
Eur J Paediatr Neurol 2017; 21: 168–75. 105 Graham HK, Rosenbaum P, Paneth N, et al. Cerebral palsy.
91 Marks W, Bailey L, Sanger TD. PEDiDBS: the pediatric Nature Rev Dis Primers 2016; 2: 16005.
international deep brain stimulation registry project. 106 Damji O, Keess J, Kirton A. Evaluating developmental motor
Eur J Paediatr Neurol 2017; 21: 218–22. plasticity with paired afferent stimulation. Dev Med Child Neurol
92 Elkamil AI, Andersen GL, Skranes J, Lamvik T, Vik T. 2015; 57: 548–55.
Botulinum neurotoxin treatment in children with cerebral palsy: 107 Young SJ, Sanger TD. Cathodal transcranial direct current
a population-based study in Norway. Eur J Paediatr Neurol 2012; stimulation in children with dystonia: a sham-controlled study.
16: 522–27. J Child Neurol 2014; 29: 232–39.
93 Jankovic J. Medical treatment of dystonia. Mov Disord 2013;
28: 1001–12.

www.thelancet.com/neurology Vol 16 September 2017 749