e u r o p e a n j o u r n a l o f p a e d i a t r i c n e u r o l o g y 1 5 ( 2 0 1 1 ) 3 9 0e4 0 4

Official Journal of the European Paediatric Neurology Society

Invited papers presented at the EPNS 2011 Cavtat meeting

Movement disorder emergencies in childhood

F.J. Kirkhama,b,c,*, P. Haywood a,d, P. Kashyape a, J. Borbone a, A. Lording a, K. Pryde a,M. Cox a, J. Keslake a, M. Smith a,d, L. Cuthbertson a, V. Murugan a, S. Mackie a,N.H. Thomas a, A. Whitney a, K.M. Forrest a, A. Parker e, R. Forsyth f, C.M. Kipps a

aSouthampton University Hospitals NHS Trust, UKbClinical Neurosciences, University of Southampton, UKcUCL Institute of Child Health, London, UKdCommunity Child Health, Southampton, UKeAddenbrooke’s hospital, Cambridge, UKf Institute of Neuroscience, Newcastle University, Newcastle upon Tyne, UK

a r t i c l e i n f o

Article history:

Received 3 April 2011

Accepted 17 April 2011

Keywords:

Chorea

Dystonia

Status dystonicus

Paroxysmal Autonomic Instability

with Dystonia

Sandifer syndrome

Myoclonus

Opsoclonus

Tremor

Parkinsonism

Drugs

Neuroleptic malignant syndrome

Metabolic

Infection

Sydenham’s chorea

Systemic lupus erythematosus

Cardiopulmonary bypass

Wilson’s disease

Organic aciduria

Biotin

Creatine

* Corresponding author. UCL Institute of ChiE-mail address: fk@soton.ac.uk (F.J. Kirkh

1090-3798/$ e see front matter ª 2011 Europdoi:10.1016/j.ejpn.2011.04.005

a b s t r a c t

The literature on paediatric acute-onset movement disorders is scattered. In a prospective

cohort of 52 children (21 male; age range 2mo-15y), the commonest were chorea, dystonia,

tremor, myoclonus, and Parkinsonism in descending order of frequency. In this series of

mainly previously well children with cryptogenic acute movement disorders, three groups

were recognised: (1) Psychogenic disorders (n ¼ 12), typically >10 years of age, more likely

to be female and to have tremor andmyoclonus (2) Inflammatory or autoimmune disorders

(n ¼ 22), including N-methyl-D-aspartate receptor encephalitis, opsoclonus-myoclonus,

Sydenham chorea, systemic lupus erythematosus, acute necrotizing encephalopathy

(which may be autosomal dominant), and other encephalitides and (3) Non-inflammatory

disorders (n ¼ 18), including drug-induced movement disorder, post-pump chorea, meta-

bolic, e.g. glutaric aciduria, and vascular disease, e.g. moyamoya. Other important non-

inflammatory movement disorders, typically seen in symptomatic children with under-

lying aetiologies such as trauma, severe cerebral palsy, epileptic encephalopathy, Down

syndrome and Rett syndrome, include dystonic posturing secondary to gastro-oesophageal

reflux (Sandifer syndrome) and Paroxysmal Autonomic Instability with Dystonia (PAID) or

autonomic ‘storming’. Status dystonicus may present in children with known extrapyra-

midal disorders, such as cerebral palsy or during changes in management e.g. introduction

or withdrawal of neuroleptic drugs or failure of intrathecal baclofen infusion; the main risk

in terms of mortality is renal failure from rhabdomyolysis. Although the evidence base is

weak, as many of the inflammatory/autoimmune conditions are treatable with steroids,

immunoglobulin, plasmapheresis, or cyclophosphamide, it is important to make an early

diagnosis where possible. Outcome in survivors is variable. Using illustrative case histories,

this review draws attention to the practical difficulties in diagnosis and management of

this important group of patients.

ª 2011 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights

reserved.

ld Health, London, UK.am).ean Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

e u r o p e a n j o u r n a l o f p a e d i a t r i c n e u r o l o g y 1 5 ( 2 0 1 1 ) 3 9 0e4 0 4 391

Contents

1. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3912. Dystonia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 392

2.1. Syndromes in patients with previously diagnosed dystonia (symptomatic) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3922.1.1. Status dystonicus . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3922.1.2. Paroxysmal Autonomic Instability with Dystonia (PAID) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3952.1.3. Sandifer syndrome . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3962.1.4. Rett syndrome . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 396

2.2. Cryptogenic acute dystonic syndromes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3962.2.1. Infections . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3962.2.2. Metabolic conditions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3962.2.2.1. Leigh syndrome . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3962.2.2.2. Organic acidaemias . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 396

3. Chorea . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3973.1. Symptomatic chorea . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 397

3.1.1. Post-cardiopulmonary bypass chorea . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3973.1.2. Herpes simplex encephalitis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 398

3.2. Cryptogenic chorea . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3983.2.1. Sydenham’s chorea . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3983.2.2. Systemic lupus erythematosus . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3983.2.3. Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 399

4. Myoclonus . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3994.1. Opsoclonus-myoclonus . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 399

5. Parkinsonism . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4006. Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 400

References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 400

1. Introduction with the multidisciplinary team. Rehabilitation and psycho-

The literature on recognition andmanagement of acute-onset

movement disorders in adult practice is scattered1 and is

very limited for paediatric practice, except for reviews on

drug-induced neuroleptic malignant syndrome which typi-

cally has clinical features of paroxysmal autonomic instability

with dystonia (PAID), and may evolve into life-threatening

status dystonicus.2,3 Some paediatric cases within the spec-

trum of status dystonicus/PAID but unrelated to drug treat-

ment have been published under the term ‘neuroleptic

malignant syndrome’. Chorea, dystonia, tremor, myoclonus,

and Parkinsonism can all present acutely, and since somemay

be treatable, timely recognition and diagnosis is important to

prevent morbidity.

Disorders with a psychological component are relatively

rare in paediatric movement disorder clinics, but are common

acute presentations in practice.4 Patients are more likely to be

female, particularly if >13 years of age, and to have tremor,

dystonia or myoclonus, often after a triggering traumatic or

infectious illness.4,5 Rehabilitation by experienced physio-

therapists and occupational therapists is usually successful

provided that the adolescent and family engage with

psychological input in addition and the search for organic

pathology ceases. It is important to remember this from

a practical point of view despite the increasing evidence for

overlap with organic disorders.6 It is not harmful (and may

even be helpful) to consider low risk treatment strategies such

as antibiotics,7 provided that the family continues to engage

logical support are also important for children where there is

convincing evidence for an organic pathology.

In a prospective4 cohort of 52 children (21 male; age range

2mo-15y), the commonest movement disorders were chorea,

dystonia, tremor, myoclonus, and parkinsonism (Table 1) in

descending order of frequency. In this series of mainly

previously well children with cryptogenic acute movement

disorders, three groups were recognised:

(1) Psychogenic disorders (n ¼ 12)

(2) Inflammatory or autoimmune disorders (n ¼ 22), including

N-methyl-D-aspartate receptor encephalitis (Fig. 1A),

Sydenham chorea and other post-streptococcal movement

disorders (Figs. 1B, 1C1e3) opsoclonus-myoclonus (which

may be paraneoplastic in relation to Neuroblastoma, Fig.

1D), systemic lupus erythematosus, acute necrotizing

encephalopathy (which may be autosomal dominant),

and other encephalitides (Table 2) and

(3) Non-inflammatory disorders (n ¼ 18), including drug-

induced movement disorder, post-pump chorea and

Tourette syndrome (Fig. 1E), metabolic, e.g. Leigh’s disease

(Fig. 1F) glutaric aciduria,8 and vascular disease, e.g.

moyamoya (Fig. 1G).9,10 Other important non-

inflammatory movement disorders, typically seen in

symptomatic children with underlying aetiologies such as

trauma, severe cerebral palsy11, epileptic encephalopathy,

post-hemispherectomy, after shunt dysfunction in

hydrocephalus,12 Down syndrome and Rett syndrome

Table 1 e Acute movement disorders in children: emergency investigation and management.

Movement disorder Definition Essential investigations Treatments to consider

Chorea brief, abrupt, irregular, unpredictable,

non-stereotyped movements

ASO titre

Anti-DNase B

Anticardiolipin antibodies

Lupus anticoagulant

Antibodies against NMDAR in

serum/CSF

MRI/MRA

Antibiotics

Steroids

Immunoglobulin

Plasma exchange

Cyclophosphamide

Dystonia abnormal, involuntary muscle

movements due to sustained muscle

contractions resulting in twisting

and/or repetitive,

patterned movements

Creatine kinase

Urine myoglobin

Urea, creatinine

Lactate in plasma/CSF

Antibodies against NMDAR in

serum/CSF, ASOT, Anti-DNAase B

Serum copper and caeruloplasmin

Organic acids

Mutation Ran-BP & RYR

MRI/MRA

Benzodiazepines

Morphine, Bromocriptine

Beta-blockers, Clonidine

Rx Gastro-oesophageal

reflux & constipation

Botulinum toxin

Baclofen, Anticholinergics

Trihexyphenidyl

Intrathecal Baclofen

Deep brain stimulation

Pallidothalamotomy

Myoclonus sudden, fast, arrhythmic movement

(electric shock-like), generally repeated

in the same part of the body

Urine VMA

Tumour imaging Steroids

Cyclophosphamide

Benzodiazepines

Tremor unintentional, rhythmic, oscillation

of a body part in a fixed plane

Serum copper and caeruloplasmin

Parkinsonism bradykinesia

rigidity

Calcium, magnesium,

carboxyhaemoglobin,

ASO titre, Anti-DNAase B

Antibiotics, Antivirals

Benzodiazepines

L-Dopa, Amantadine

e u r o p e a n j o u r n a l o f p a e d i a t r i c n e u r o l o g y 1 5 ( 2 0 1 1 ) 3 9 0e4 0 4392

include dystonic posturing secondary to gastro-

oesophageal reflux (Sandifer syndrome) and/or con-

stipation as well as PAID or autonomic ‘storming’. Status

dystonicus, whether seen in a child with dystonic cerebral

palsy and an intercurrent infection, drug-induced (neuro-

leptic malignant syndrome) or secondary to withdrawal/

failure of intrathecal baclofen infusion, is a life-

threatening medical emergency because of the risk of

rhabdomyolysis. Some paediatric cases within the spec-

trum of PAID/status dystonicus have been reported as

‘neuroleptic malignant syndrome’ even when drugs were

unlikely to have played a role12 and there is also clinical

overlap with the syndrome of malignant hyperpyrexia.

This review draws attention to the practical difficulties in

diagnosis and management of this important group of

patients with illustrative case histories.

2. Dystonia

2.1. Syndromes in patients with previously diagnoseddystonia (symptomatic)

2.1.1. Status dystonicusThis emergency typically occurs in children already known to

have a dystonic movement disorder such as cerebral palsy,11

acquired brain injury, Wilson’s disease,11 Huntingdon

disease, neurodegeneration with brain iron accumulation e.g.

Pantothenate Kinase-Associated Neurodegeneration (Fig.

1H),13 and severe epilepsies such as infantile spasms

secondary to the ARX mutation epilepsy.14 Triggers include

infection and drugs such as clonezepam, Penicillamine,

Haloperidol, Clozapine, Risperidone, Metachlorpropamide

and Ondansetron or drug withdrawl.15 Increasing muscle

contractions lead to rhabdomyolysis with acute renal failure

secondary to myoglobinuria, which is life-threatening and

should be excluded with regular creatine kinase and urinary

myoglobinmeasurements. Admission to the high dependency

or intensive care unit is important and many patients require

ventilation as well as dialysis if indicated for the renal failure.

Positioning, ideally with trunkal flexion, and treatment of

gastro-oesophageal reflux and constipation are important.

Midazolam may reduce the frequency of muscle contraction

sufficiently to avoid rhabdomyolysis in patients with treatable

dystonias, such as Wilson’s disease, or in those with cerebral

palsy in whom status dystonicus has been precipitated by

infection. The patient can then be gradually weaned from

sedation and ventilation although agitation and tremor may

be a problem for several days. Themortality has beenhigh and

it may be difficult to determine whether death is secondary to

the triggering sepsis, the use of drugs such as Propofol or the

status dystonicus (case 1). Status dystonicus in progressive

dystonias, e.g. Neurodegeneration with brain iron accumula-

tion (Fig. 1H), may require more aggressive management e.g.

intrathecal baclofen infusion,12,15,16 bilateral pallidal deep

brain stimulation12,17,18or pallidothalamotomy.13

Case 1. A girlwith severedystonia secondary to birthasphyxia

had had a fundoplication for severe gastro-oesophageal reflux

at the age of 2 years which had been associated with

Table 2 e Cryptogenic acute movement disorders in children: diagnosis and early management.

Primarymovementdisorder

Aetiology Movements Diagnosis MRI Management

Chorea Sydenham chorea Chorea, Dystonia, motor tics, dystonia,

tremor, stereotypies, opsoclonus,

myoclonus

ASOT, anti-

streptolysin B

May show unilateral

or bilateral basal ganglia

& white matter abnormality

Penicillin. More severe

cases may benefit from

steroids. Sodium valproate

or Carbamezepine

Systemic lupus

erythematosus

Chorea lupus anticoagulant,

anti-nuclear antibody,

anti-double-stranded

DNA antibody

Anticoagulation,

immunosuppression

N-methyl-D

-aspartate receptor

encephalitis

Chorea, Dystonia,

Parkinsonism

antibodies against

NMDAR in serum/CSF

May have lesions in

white matter & pons

Steroids, plasma exchange,

cyclophosphamide

Acute necrotizing

encephalopathy

Chorea, Dystonia,

Parkinsonism

Clotting and liver

dysfunction

Swelling & enhancement

thalami, posterior putaminae,

brainstem, cerebellar white

matter

Steroids

Moyamoya Chorea MRA Focal ischaemia Revascularisation

Focal cerebral

arteriopathy

Chorea, dystonia MRA Focal ischaemia Aspirin

Dystonia Mycoplasma

encephalitis

Dystonia, Parkinsonism Thalamic necrosis,

striatal necrosis

Erythromicin, steroids

Glut-1 deficiency Episodic dystonia Low CSF: plasma

glucose; SLC2A1 gene

Ketogenic diet

Biotin dependant

basal ganglia

disease

SLC19A3 gene, Trial

of biotin

Bilateral central

necrosiscaudate

head, involvement putamen

Biotin

Creatine deficiency

syndromes

Plasma creatine, creatinine,

Urine Guanidinoacetate

Proton MRS: absence

of creatine/

phosphocreatine

peak basal ganglia

Oral creatine

supplementation

Dihydrolipoamide

acetyltransferase

deficiency

Episodic dystonia E2 pyruvate dehydrogenase Ketogenic diet

Glutaric aciduria type 1 Dystonia urine organic acids Basal ganglia DWI

abnormality, subdurals,

Low lysine diet,

carnitine supplements

Rapid onset dystoniae

parkinsonism

Dystonia, Parkinsonism ATP1A3 gene

Leigh’s disease Dystonia, hypotonia Mitochondrial DNA,

SURF-1, pyruvate

dehydrogenase, muscle

biopsy for complex I-V

enzymes

brainstem & basal ganglia

(putamen) T2-W abnormality

Avoid hypocapnia

Pantothenate kinasee

neurodegeneration

Dystonia,

Parkinsonism

‘eye of the tiger’ sign Deep brain stimulation

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Table 2 (continued )

Primarymovementdisorder

Aetiology Movements Diagnosis MRI Management

Phospholipase A2 group

6-associated

neurodegeneration

Dystonia,

Parkinsonism

Acanthocytosis;

ERG: retinopathy;

PANK2 gene

Cerebellar atrophy,

hypointensity globus

pallidus, substantia

nigra, subthalamic

Deep brain stimulation?

EEG: high amplitude

fast; EMG: denervation;

Nerve conduction:

axonal sensory

neuropathy; PLAN gene

Myoclonus Opsoclonusemyoclonus

syndrome

Clinical, Urinary VMA,

exclude coeliac

Tumour imaging Steroids,

cyclophosphamide,

Rituximab

Parkinsonism

/rigidity

Hypocalcaemia Low calcium Calcium

Hypomagnesaemia Low magnesium Magnesium

Carbon monoxide Carboxyhaemoglobin White matter

abnormality

Hyperbaric

oxygenation

Acute disseminated

Encephalomyelitis

White matter

abnormality

Methyl

prednisolone

Encephalitis lethargica Sleep disturbance

dyskinesia,

ophthalmoplegia.

Grey matter

abnormality

in 40%

Methyl

prednisolone

Malignant Hyperthermia Gene encoding

for ryanodine

receptor (RYR1) on

chromosome 19q13.1.

Dantrolene

Tetanus Muscle spasms

triggered by stimuli,

autonomic

Instability, trismus,

spasms in limb

History, anti-tetanus

antibody excludes

Tetanus immune

globulin, antibiotics.

Benzodiazepines,

phenobarbitone

and avoidance

excessive sensory

stimulation

baclofen

Rabies High fever, agitation,

hallucinations,

violent behaviour,

autonomic

instability, hydrophobia.

Saliva sample, hair

follicle or nape-of-neck

biopsy for antigen

Prolonged

intensive care

Neuroleptic malignant

syndrome

Drug history Stop drugs, sedation,

intensive

care, dialysis

Hyperekplexia Exaggerated startle Glycine receptor

(GLRA1) gene

Benzodiazepines

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improvement in themovement disorder sufficient to allowher

to be appropriately seated. At the age of 10 years, she had

a febrile illness associated with marked deterioration in the

dystonia. On admission her creatine kinase was significantly

elevated at 15,450 IU/L and she was in renal failure, passing

only small amounts of rusty-coloured urine consistent with

myoglobinuria. Despite ventilation, dialysis and a midazolam

infusion, she died within 24 h of admission.

2.1.2. Paroxysmal Autonomic Instability with Dystonia(PAID)Dystonias are very common in patients with acquired brain

injury (ABI).11,12,19 The term Paroxysmal Autonomic Instability

with Dystonia (PAID) or paroxysmal sympathetic storms20e23

has been suggested to describe a syndrome of intermittent

agitation, diaphoresis, hyperthermia, hypertension, tachy-

cardia and tachypnoea. PAID is commoner in younger

patients24 and is becoming a better recognised phenomenon

in children with congenital syndromes, e.g. Rett25e27 and

Down28e30 (cases 2 and 3) as well as those with ABI20,31,32 who

have prolonged episodes of autonomic instability (case 4).

Children who have neuroleptic malignant syndrome3 on

exposure to drugs such as clozapine, risperidone, metoclo-

pramide hydrochloride and haloperidol have similar features

as well as hyperpyrexia and status dystonicus.

Patients should be adequately hydrated, alternative diag-

noses, e.g. epilepsy and gastrointestinal disorders such as

reflux oesophagitis and constipation, should be excluded and

any triggers, e.g. pain, and drugs should be avoided or actively

managed. The episodes may respond to morphine33 or

nonselective beta-blockers e.g. propranolol.34 Bromocriptine

mesylate has been used successfully in adults33,35,36 and

anticholinergics and gabapentin may have a role.2,37,38 Dan-

trolene sodium has been used in adults with hyperpyrexia but

did not decrease the duration of symptoms in children with

neuroleptic malignant syndrome.3 Although escalation may

be too slow for the acute situation, Trihexiphenydyl can be

tried, starting at a dose of 0.5mg daily in children<7 years or 2

mg daily in children>7 years, increasing by 0.5e2mg every 10

days until an effect or the maximum dose is reached (for an

infant 3 mg tds; for a child 1.5e10 years of age, 10 mg tds and

for a child>10y, 25 mg tds. In our experience, clonidine (orally

test dose 1 mg/kg observing for hypotension, increasing by 1e3

mg/kg/dose to a maximum of 5 mg/kg three times daily; intra-

venous infusion on PICU only 0.25 mg/kg/hour increasing until

sedation achieved to maximum 2 mg/kg/min) is helpful in

some patients with severe PAID in the context of ABI.32 Six

cases (all boys) with ABI sustained at a median of 12.5 (range

0.8e14) years were seen over 2 years. Three had suffered

hypoxic-ischaemic insults (after drowning, pneumococcal

meningitis and sepsis). The other three had septic shock, post

radiotherapy stroke and traumatic brain injury. Neuroimaging

showed global brain ischaemia in one, borderzone ischaemia

in 2, diffuse axonal injury in one,multiple brain infarcts in one

and left basal ganglia infarct with bilateral motor cortex

hyper-intensity in one. All patients had bilateral brain damage

and all remained unconscious when they developed PAID at

a median of 17.5 (range 7e42) days after ABI. Clonidine was

given to a maximum dose of 160 mg/kg/day for a median of 21

(10e90) days and was then weaned over a median of 25

(14e440) days. Five also received benzodiazepines and one

also received Baclofen and Morphine. Four patients had no

PAID at discharge but symptoms remained a problem in two

patients, needing ongoing treatment with Clonidine.

Successful outcome in treating PAID in traumatic brain injury

in these cases suggest that high dose clonidine should be

considered for treating PAID episodes. Intrathecal baclofen

may be effective in refractory cases and Dantrolene and

electroconvulsive therapy have occasionally been used in

children with neuroleptic malignant syndrome, although

there is scanty evidence for a reduction in the duration of

symptoms.2,3

Case 2. A 12 year old girl with classical Rett Syndrome had

a two year history of screaming episodes. Previously, her

seizures were well-controlled with lamotrigine. Aged ten, she

developed prolonged episodes of screaming and posturing.

These episodes persisteddespitenumerous investigations and

interventions, including dental extraction, multiple anticon-

vulsants and optimal treatment of gastro-oesophageal reflux

and constipation. The possibility of PAID was considered and

a trial of labetolol produced remittance of the episodes.

Case 3. A three year old boy with Trisomy 21 was admitted for

management of a reported increase in seizure activity. At

sixteen months of age, his parents reported abnormal move-

ments suggestive of infantile spasms. In retrospect, these

appeared to have started at around 4 months of age. Develop-

ment was static and EEG showed hypsarrhythmia. West

Syndrome was diagnosed and treated aggressively with pred-

nisolone, rapidly rendering him seizure-free. His develop-

mental progress then improved. He remained seizure-free until

aged three when he presented with a two-week history of pro-

longed episodes of stiffening, arching and laboured breathing.

High-dose prednisolone had been commenced with no effect.

Observation of the episodes revealed dystonic posturing,

tachypnoea, upper airway noise, increased work of breathing

and sweating. EEG during the episodes showed no epileptiform

activity. PAID was suspected and propranolol and clonazepam

were commenced with significant reduction in the frequency

of episodes. Two months later clonidine was added for

breakthrough episodes, with a good therapeutic response.

Case 4. A 2 year old boy suffered a near drowning accident

when he was found face down in a swimming pool. MRI of the

head showed extensive bilateral, predominantly posterior,

abnormality in both cerebral hemispheres with involvement

of the cortico-spinal tracts bilaterally, the posterior brainstem

and cerebellum, representing extensive hypoxic-ischaemic

injury. He developed a predominately dystonic movement

disorder with elements of spasticity within the lower limbs.

He received Botulinum toxin bilaterally to his soleus and

gastrocnemius muscles one month after the accident. He was

nasogastrically fed until a gastrostomywas inserted 3months

post-accident for longterm nutrition. He was noted to have

severe gastro-oeophageal reflux and a jejunostomy extension

was performed 5 months after the accident to decrease his

risk of aspiration. Post-operatively, he developed abdominal

distension and poor gastric motility. An abdominal X-Ray

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(when he had had some bilious aspirates) showed pneuma-

tosis intestinalis and was treated with 2 week course of

Metronidazole. Constipationwas treatedwithMovicol. He had

episodes of autonomic instability with dystonia, leading to

increased secretions and raised temperature, diagnosed as

PAID and responding acutely to positioning, oxygen and

gentle physiotherapy. To improve his dystonia and decrease

his episodes of PAID, he was treated with Trihexyphenidyl,

Clonidine and Diazepam with gradual improvement. He was

referred for intrathecal bacofen pump insertion 6 months

after the accident but from an anaesthestic point of view, was

not considered stable enough for the procedure to take place.

He gradually improved and was discharged home 8 months

after the accident with a chair, a wheelchair, a profiling bed,

a sleep system and a hoist.

2.1.3. Sandifer syndromeSandifer syndrome, or dystonia secondary to gastro-

oesophageal reflux, oesophagitis or gastro-oesophageal dys-

motility, is common in children with neurological conditions,

including epilepsy, and it is always worth excluding in

patients with apparently intractable seizures as the dystonic

episodes can be very difficult to distinguish without video-

telemetry.39e41 Medical management of gastro-oesophageal

reflux may be effective, but some patients may need naso-

jejunal, or even intravenous, feeding for a period of time, or

fundoplication.

Case 5. A 3 year old boy with a history of West syndrome

presented with acute spasms considered initially to be

a recurrence. However the EEG did not show hypsarrhythmia

and the spasms were not accompanied by an EEG change. In

addition, the creatine kinase was elevated at 2200 IU/L. During

the admission it became clear that the spasms occurred after

feedingand thathewas inpainduringbolusgastrostomy feeds.

After a month of partial intravenous feeding, the spasms and

pain had settled and he could again be fed through his gastro-

stomy but continuously and with the tube in the jejunum. The

creatine kinase settled back into the normal range.

2.1.4. Rett syndromeIn addition to dysautonomic syndromes (case 2) and gastro-

oesophageal reflux, girls with Rett syndrome may have acute

dystonic life-threatening episodes. Trihexyphenidyl reduced

the frequency in 2 girls in one report; the third had died before

treatment could be offered.42

2.2. Cryptogenic acute dystonic syndromes

2.2.1. InfectionsAcute hemidystonia is typically secondary to arterial ischae-

mic stroke,43 often due to infections such as Varicella zoster or

Mycoplasma pneumoniae.44 These infections may also be asso-

ciated with generalised dystonia.45e47

2.2.2. Metabolic conditionsThere is a long list of metabolic conditions whichmay present

as dystonia, most presenting over a long period of time.8 Table

2 includes some of those which are treatable and present

acutely or episodically.

2.2.2.1. Leigh syndrome. Leigh syndrome commonly presents

as dystonia. Most, but not all, children have an abnormal MRI

(Fig. 1F) and high plasma and CSF lactate. Genetic testing and

muscle biopsy are usually required to make an accurate

diagnosis.48 Hypocapnia should be avoided if possible.49,50

Case 6. This boy presented with dystonia in the first year of

life and was noted to have putaminal abnormality on MRI

consistentwith Leigh’s disease (Fig. 1F), although therewas no

deterioration over a further 18 months of follow-up. However,

he presented encephalopathic with dystonic posturing in the

context of an acute influenzal illness and the MRI changes

were more widespread and characteristic of Leigh’s disease.

He could not be weaned from the ventilator and died in

hospital.

Case 7. At the age of 15 months, this girl was not quite

walking by herself although she did have a lot of words.

Following a febrile upper respiratory tract infection and

tonsillitis, she developed abnormal movements of her hands

and feet. At this stage she was very ill, in hospital and was

not sitting up although it is not certain that she was in coma.

She had a normal CT scan. She then made a good recovery

and was soon sitting alone. She subsequently walked on her

own without support by the age of two, although her speech

remained slurred. She had a further episode at the age of 3

years, again with a sore throat but only lasting a day when

she was unable to sit alone. A further CT scan was normal

and after about a week she returned to making progress at

her previous rate. At the age of five and a half, she developed

fever and an unsteady gait with speech changes. Her muscle

tone decreased, especially in the hip girdle and shoulders,

particularly involving biceps and deltoid. Muscle strength

was normal in the distal muscles of her hands. Her deep

tendon reflexes were sluggish but elicitable, her gait was wide

based and she had a lumber lordosis and a waddling gait with

weak hip girdle muscles. She was also noted to have oral

motor coordination difficulties. Her tandem walking was

normal, although heel toe walking was difficult because she

was weak. Creatine kinase was normal. Again she made an

apparently complete recovery but then presented encepha-

lopathic in the context of Mycoplasma pneumonia. She was

ventilated and on emerging from coma was extending her

arms and legs, although she remained hypotonic for some

time with areflexia. She then became hypertonic after the

first few weeks with severe equinovarus. MRI remained

normal on several occasions but she was found to have

recessive SURF-1 mutations, associated with cytochrome c

oxidase deficiency.

2.2.2.2. Organic acidaemias. Organic acidaemias, primarily

glutaric aciduria type 1, 3-methyl glutaconic aciduria, methyl-

malonic aciduria and propionic aciduria typically present with

dystonia or Parkinsonism8,51, and can usually be excluded by

undertaking urinary organic acids. All of these can presentwith

acute on chronic exacerbations.

Fig. 1 e Imaging in acutemovement disorders. A. Focus of T2-weighted high signal density in the left frontal whitematter in

a child with anti-NMDA receptor antibody encephalitis. High signal on T1-weighted imaging in a child presenting with

hemichorea and a raised antistreptolysin O titre. She recovered within 2 weeks on a combination of Penicillin and

Prednisolone. C1e3. Involvement of basal ganglia, white matter (B1 acute presentation aged 8; B2 3 months later) and

eventually grey matter (B3 representation aged 11) in a girl with positive antistreptolysin O antibodies. D. Radioisotope scan

in a child with opsoclonus-myoclonus. E. Lacunar infarct with in a teenager who developed Tourette syndrome after

cardiopulmonary bypass. F. Bilateral basal ganglia abnormality consistent with Leigh’s disease in a child with dystonia who

became unconscious in the context of H1N1 influenza. G. Moyamoya in a child with acute chorea. H. Eye-of-the-tiger’ sign in

neurogeneration with brain iron accumulation.

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3. Chorea

3.1. Symptomatic chorea

3.1.1. Post-cardiopulmonary bypass choreaChoreiform movements after cardiopulmonary bypass

surgery have been recognised for the past 30 years with an

incidence of 0.6e3% of those undergoing cardiopulmonary

bypass.52,53,54,55,56,57 Oro-facial dyskinesias are typical53,57 and

a Tourette-like syndrome, with simple and complex motor tics

and obsessive-compulsive behaviour, has been described (Fig.

1E).58 The onset is usually delayed by 2e7 days and most

patients have a clear period of normality between the operation

and the presentation with choreiform movements. The post

bypass chorea syndrome is commoner in those who have

undergone deep hypothermic ischaemic arrest,54,55,59 although

there is little evidence that the duration is important and it has

been reported in patients where this has not be the case.60

Relative polycythaemia may be a factor.61 MRI and CT scan in

the cases reported have been either normal, have shown

generalised atrophy or basal ganglia abnormality.54 Recent data

suggests that an alpha-stat method of pH management may

increase the chance of peri-operative complications, including

post bypass chorea, perhaps because the hypocapnia reduces

cerebral blood flow below the ischaemic threshold.56,62 Bron-

chopulmonary collaterals in patients with right ventricular

outflow tract obstruction and VSD also predispose to this

syndrome, and very rapid cooling has also been identified as

a risk factor. However it has been well documented that

patients have had choreoathetosis after cardiopulmonary

bypass without necessarily having any of the risk factors.

Improvement in the choreoathetoid movement is also typical,

although some patients have long term neurological

disability.63,64

Case 8. An 8 year old girl with pulmonary atresia with bron-

chopulmonary collaterals developed choreoathetosis after

palliative surgery. She made a good recovery over a period of

6 months and on neuropsychological testing one year later,

had a full scale IQ of 100, exactly the same as her twin sister

without congenital heart disease.

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3.1.2. Herpes simplex encephalitisChorea is unusual at presentation but may be an early sign of

relapse of Herpes simplex encephalitis. In addition to

continuation of antiviral treatment, plasma exchange,65 and

possibly other immunomodulation, may be considered.

3.2. Cryptogenic chorea

3.2.1. Sydenham’s choreaSydenham’s chorea remains the commonest cause of chorea in

childhood in the developed as well as the developing

World66e69 Between one and two thirds have carditis andmany

also have tics and psychological symptoms, such as anxiety,

sleep problems or obsessive-compulsive disorder.70e72 Neuro-

imaging is typically normal but may show non-specific abnor-

mality, while children with more severe post-streptococcal

acute movement disorders may have white and gray matter

involvement. (Fig. 1B and 1C1e3). Around one third relapse.

Penicillin should be given and bed rest is recommended.73

There is some evidence that immunotherapy with predniso-

lone or immunoglobulin is associated with more rapid resolu-

tion of the chorea.69,73e78 Sodium valproate or carbamezepine

often reduce the chorea.

Case 9. A 6 year old boy presented with choreoathetosis and

tics after a throat infection and had a raised antistreptolysin O

titre and a markedly elevated anti-DNase B level. He woke at

night feeling frightened and anxious and had symptoms

compatible with an obsessive-compulsive disorder. He was

treated with Penicillin and Prednisolone and made a good

recovery but had 3 further relapses with frequent tics during

intercurrent infections which were associated with positive

anti-basal ganglia antibodies and responded to steroids and

clonidine whichwereweaned successfully each time after the

tics resolved, in addition to long-term Penicillin.

Case 10. An 8 year old girl presented with headache, persis-

tent head and eye deviation to the right, left facial weakness,

and ataxia a fewweeks after she had chickenpox. MRI showed

symmetrical T2 high signal and swelling of the basal ganglia,

involvement of midbrain, and cortical signal abnormalities,

but no cerebellar involvement (Fig. 1C1). She was diagnosed as

having acute disseminated encephalomyelitis (ADEM) and

improved slightly after treatment with steroids and immu-

noglobin and substantially after plasma exchange so that she

resumed mainstream school, although she remained ataxic

with some residual left arm dystonia and dysarthric speech.

An interval MRI showed mildly atrophic basal ganglia with

slightly increased signal and a few cortical signal abnormali-

ties (Fig. 1C2). There was sparing of the thalami, midbrain and

cerebellum. At the age of 11 years, she presentedwith a 2week

history of abnormal movements, further regression of motor

skills, and difficulties with feeding, swallowing and speech.

On examination, she had generalised rigidity, dystonia with

choreiform movements , drooling, poor sitting balance, brisk

reflexes, and intermittent restriction of upward eye gaze.

There was no intelligible speech but she had a good level of

comprehension and non-verbal communication initially.

However, she deteriorated in the next few weeks, requiring

nasogastric feeding, and eventually becoming bed ridden and

emotionally labile with increasing rigidity and dystonia.

Further MRIs showed fluctuating grey matter abnormalities

with preferential involvement of the basal ganglia and arterial

watershed zones, very unlike ADEM (Fig. 1C3). There was no

response to further treatment with steroids and immunoglo-

bin. Despite extensive investigation, the only abnormalities

were a raised ASOT and AntiDNAse B and a diagnosis was

made of Poststreptococcal Acute Disseminated Encephalo-

myelitis with Basal Ganglia Involvement.78 She made a partial

recovery after further plasma exchange and continues to

improve during a course of Cyclophosphamide.

3.2.2. Systemic lupus erythematosusNeurological complications are common at presentation with

systemic lupus erythematosus in childhood.79e82 Chorea is

most frequent in childhood but occurs in <10% of cases.83e86

Other typical symptoms include headache, behavioural

disorders including confusion, depression, anxiety and

psychosis, lethargy, diplopia, blurred vision, memory alter-

ation, dizziness and altered consciousness. The most

frequently observed neurological signs in addition to the

possibility of chorea, tremor or rigidity are cranial nerve palsy,

ataxia, papilloedema, nystagmus, meningism, myelopathy,

neuropathy and cortical blindness. Presentation with

seizures, status epilepticus or coma is not uncommon. More

subtle presentations include progressive cognitive dysfunc-

tion and idiopathic intracranial hypertension. Ischaemic or

haemorrhagic stroke is obvious in 15e30% of those with

neurological complications and may be associated with arte-

rial abnormality, but in most of the presentations the possi-

bility of venous sinus thrombosis should be excluded. The

presence of the lupus anticoagulant on laboratory testing is

associated with chorea.87 Anticoagulation is usually appro-

priate for those with antiphospholipid syndrome, particularly

if thrombosis has occurred.87 Prednisolone, hydroxy-

chloroquine and cyclophosphamide may be required.

Case 11. A 15 year old girl presented with poor appetite,

lethargy, weight loss and arthralgia and was diagnosed with

Systemic lupus erythematosus. She developed sudden onset

severe chorea three days after she was commenced on

hydroxychloroquine. Cortical vein thrombosis was considered

and she was commenced on IV heparin infusion but the MRI,

including susceptibility-weighted imaging, did not show

definite evidence. The heparin infusion was changed to

subcutaneous clexane and her anti Xa levels were in the

acceptable range. She was also commenced on levatiracetam

and clonazepam which were gradually weaned off. She

initially received IV methylprednisolone which was changed

to oral prednisolone which was eventually weaned to low

dose on alternate days and she had monthly cyclophospha-

mide infusions for 6 months.

Case 12. A girl presented at the age of 12 years with an

episode of severe headache with bilateral papilloedema. MRI

brain scan was normal and opening pressure on lumbar

puncture was high, so she was diagnosed with idiopathic

intracranial hypertension. Two months later she developed

chorea involving her left sided limbs, mainly her arm, fol-

lowed by right side chorea. The working diagnosis at the time

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was Sydenham’s chorea. Her movements normalised and she

was asked to continue on penicillin prophylaxis. At the age of

16 years, she presented with sudden onset of left sided

weakness and sixth and seventh nerve palsies. MRI and MRA

showed right middle cerebral artery (MCA) occlusion with

MCA territory infarction. Echocardiography was normal with

no intracardiac thrombus. She had a low platelet count and

abnormal clotting so she was investigated for an autoimmune

aetiology. She had a high ESR (42e80) and showed positive

Anti-Nuclear Antibody, anticardiolipin antibody, and lupus

anticoagulant, and low C4 (complement). Direct antiglobulin

test was positive, and although therewas no other evidence of

haemolysis, she was given a short course of low-dose pred-

nisolone. Shewas anticoagulatedwith lowmolecular heparin,

followed by warfarin to keep her INR between 3e4. She was

rehabilitated and has been followed for 5 yearswith no further

neurological complications.

3.2.3. Anti-N-methyl-D-aspartate receptor (NMDAR)encephalitisAn acute encephalopathy with a prominent movement

disorder, typically dyskinesia, dystonia and chorea, has been

recognised for some time.88,89 Recently anti-N-methyl-D-

aspartate receptor (NMDAR) encephalitis has been recognised

in adults, typically women with a mean age of onset of 25.8

years and often (60%) with ovarian teratomas; resolution is

common following removal. Children, the majority girls, have

been described, typically presenting after infections and with

no evidence of malignancy90e92 Clinical features include

psychiatric symptoms including personality change, irrita-

bility, anxiety, aggressive behaviour, delusional thoughts, and

short-termmemory loss. Additional features include partial or

generalized seizure activity and a movement disorder, most

frequently orofacial dyskinesia. Imaging may show non-

specific changes and the diagnosis is made by demonstrating

the antibody in serum, and if necessary, CSF. The prognosis

may be good in many cases but many paediatricians have

treated with steroids, immunoglobulin, plasmapheresis and

cyclophosphamide.93

Case 13. A previously healthy 26 month-old girl presented

with a one-week history of unsteady gait and mood lability

preceded by a viral prodrome several weeks previously.

Clinical progression, with regression of speech and

language and motor skills, ensued leading to a florid

movement disorder by the third week. She developed oro-

facial dyskinesia, choreoathetoid right arm movements,

ballistic leg movements and left upper limb dystonia

requiring frequent sedation. There was a subtle focus of T2

and proton density high signal in the left frontal white

matter (Fig. 1A). EEG demonstrated persistent diffuse,

generalised slow activity. Screening for occult malignancy

was negative. Clonazepam infusion had marginal benefit.

She was subsequently managed with high dose steroids

and immunoglobulin infusions with only partial thera-

peutic response. With confirmation of very high anti-NMDA

serum antibodies, monthly pulsed cyclophosphamide

infusion was commenced. She promptly made an excellent

functional recovery and her neuro-developmental profile is

age-appropriate eighteen months later.

4. Myoclonus

Myoclonus may present acutely days, months or years after

hypoxic insults,94 is sometimes a feature of post-infectious

encephalopathies95 and is a common presentation in those

with a conversion disorder.4,5 The important syndrome in

previously well children is acute opsoclonus-myoclonus and

the priority is to exclude neuroblastoma.

4.1. Opsoclonus-myoclonus

This is a rare condition with an incidence in the United

Kingdom of 0.18 cases per million total population per year.96

Hospital-based series of children with opsoclonus-myoclonus

have found neuroblastoma in over half the cases97,98 but the

population-based study found this condition in just over

a quarter.96 The neuroblastoma is typically stage I/II and may

be cured by surgery alone, suggesting that the opsoclonus-

myoclonus may be an auto-immune phenomenon.99 Urine

for Vanillyl mandelic acid (VMA) and radioisotope imaging

(Figure 1D) should always be undertaken but removing the

neuroblastoma does not cure the opsoclonus-myoclonus.100

The movement disorder may also be triggered by infections

and vaccines101e105 and has been reported as a presentation of

coeliac disease.106 The associated developmental delay and

behavioural disorder is often very prominent and difficult to

manage.96,98,100,107 In patients with or without neuroblastoma,

there is a little evidence for benefit with immunomodulation

using steroids, cyclophosphamide, microphenolate or rit-

uximab,108e115 ideally started as early as possible after

presentation. The results of the planned European trial are

eagerly awaited. Some patients may benefit from

Clonezepam.116

Case 14. A previously well boy presented with opsoclonus-

myoclonus at the age of 18 months in the context of an

upper respiratory tract infection. Neuroblastoma was not

found despite extensive imaging. He was treated initially

with Prednisolone 2 mg/kg which controlled the eye

movements and was therefore weaned. However the

movement disorder returned on weaning and his behav-

iour deteriorated and remained poor when the steroids

were increased again. His developmental progress pla-

teaued. After considerable discussion with the parents, 6

monthly cycles of Cyclophosphamide were given with an

impressive improvement in developmental trajectory and

behaviour.

Case 15. A 2 year old presented with ataxia in the context of

an upper respiratory tract infection and recovered over the

following month without sequelae. Four months later, she

presented with opsoclonus-myoclonus and urinary VMA was

high. Imaging showed a small neuroblastoma which was

surgically removed. The opsoclonus-myoclonus resolved on

Prednisolone and she made normal developmental progress

with no behavioural problems. She had several similar infec-

tions without relapse but had a further episode one year after

the initial presentation, which also responded quickly to

Prednisolone.

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5. Parkinsonism

This is a relatively rare acute presentation, although some

patients with post-infectious movement disorders secondary

to influenza, EpsteineBarr virus, Streptococcus pneumonia and

M. pneumoniae may have features45,117e120 sometimes with

clinical signs and neuroimaging compatible with acute

disseminated encephalomyelitis, encephalitis lethargica121 or

acute necrotizing encephalopathy.122e125 Anti-MMDA

receptor encephalitis should be excluded.126 In the devel-

oping world, Japanese B encephalitis,127 tetatnus and rabies

may be causes. Hypocalcaemia, hypomagnesaemia128 and

carbon monoxide poisoning117,129,130 should be excluded

urgently. There are a number of important genetic conditions

which require exclusion131e133 (Table 2), although as testing is

very expensive, it is wise to ask for clinical advice over likely

diagnoses at an early stage.131e133 Early speech and language

therapy assessment over the method of feeding is advisable,

in addition to physiotherapy and occupational therapy.

Correct diagnosis of Parkinsonism may mean that exacer-

bating drugs are avoided.134,135 Most children do not require

specific drug treatment for the movement disorder in the

acute phase but antibiotics and antivirals and immunosup-

pression should be considered if there is an infectious or

autoimmune cause and benzodiazepines are probably safe.

Amantadine is an antiviral which is no longer used for influ-

enza treatment as there is widespread resistance136 but it may

have a role in acute Parkinsonism in childhood134 and is being

trialled in ABI.137 Levodopa/carbidopa has been used,134,135,138

but gradual spontaneous improvement is common and

dopaminergic drugs may need to be withdrawn rapidly if

other acute movement disorders appear in the convalescent

phase.134,135

Case 16. This previously well 3 year old boy presented

following a short history of temperature, vomiting and diar-

rhoea. He then became encephalopathic, refused to walk,

stopped eating and speaking and required a nasogastric tube

to manage his fluid requirements. On admission he was irri-

table, with a paucity of facial movements and difficulty in

initiating movements, particularly of his left arm. He was

encephalopathic with abnormal interaction with those

around him, no speech and was unable to walk with low

central tone although his peripheral tone, power and reflexes

were normal. Hismother had an admission at a similar age for

a neurological condition which has left her with some subtle

difficulties, including ataxia. Extensive metabolic testing was

negative and genetic testing is in progress.

Case 17. This teenager had an acute deterioration in writing

and began blinking very frequently. Referral was precipitated

because he began to require feeding by hand, taking up to

three hours per meal. He had walked and spoken early but

always had a stammer. On examination, he had blepharo-

spasm and intermittent rigidity and a lot of difficulty in initi-

atingmovement, with a bent head and a shuffling gait. He had

impaired dopamine and serotonin turnover and some

evidence of tetrahydrobiopterin deficiency. There was also

a minimal increase in 3-methyldopa. In view of this, aromatic

amino acid decarboxylase deficiency was briefly considered

but plasma enzyme analysis did not support this diagnosis. A

problem with tetrahydrobiopterin availability was considered

but a phenylalanine loading test was negative. He was anti

basal ganglia antibody positive. He had a partial response to L-

Dopa and is under investigation for genetic causes of juvenile

Parkinsonism.

6. Conclusion

There is a wide differential diagnosis in children presenting

with acute movement disorders. Once drug effects and

presentations related to psychological distress have been

considered, it is essential to investigate previously well chil-

dren for conditions with an infectious and/or immunological

basis so that therapy, including intensive care, can be appro-

priately considered for the individual patient. There should be

a low threshold for antibiotics and immunomodulation

should be discussed early. Feeding disorders are often prom-

inent at presentation, so a multidisciplinary approach to

rehabilitation including speech and language as well as

physiotherapy, occupational therapy, specialist nursing and

access to advice from adult neurologists is essential, whether

or not there is an organic basis. European and International

collaboration will be needed to develop the evidence base for

managing this important group of conditions.

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