A prospective study of acute movement disorders in children

Authors

  • RUSSELL C DALE,

    1.  Neuroimmunology Group, Institute of Neuroscience and Muscle Research, Kids Research Institute at the Children’s Hospital at Westmead, Sydney, NSW, Australia
    2.  Faculty of Medicine, University of Sydney, Sydney, NSW, Australia
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  • HARRY SINGH,

    1.  TY Nelson Department of Neurology, the Children’s Hospital at Westmead, Sydney, NSW, Australia
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  • CHRISTOPHER TROEDSON,

    1.  TY Nelson Department of Neurology, the Children’s Hospital at Westmead, Sydney, NSW, Australia
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  • SEKHAR PILLAI,

    1.  Neuroimmunology Group, Institute of Neuroscience and Muscle Research, Kids Research Institute at the Children’s Hospital at Westmead, Sydney, NSW, Australia
    2.  TY Nelson Department of Neurology, the Children’s Hospital at Westmead, Sydney, NSW, Australia
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  • SHILPA GAIKIWARI,

    1.  Department of Psychological Medicine, Children’s Hospital at Westmead, Sydney, NSW, Australia
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  • KASIA KOZLOWSKA

    1.  Faculty of Medicine, University of Sydney, Sydney, NSW, Australia
    2.  Department of Psychological Medicine, Children’s Hospital at Westmead, Sydney, NSW, Australia
    3.  Brain Dynamics Centre, Westmead Hospital, Sydney, NSW, Australia.
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Dr Russell C Dale at Neuroimmunology Group, Institute of Neuroscience and Muscle Research, Kids Research Institute at Children’s Hospital at Westmead 2145, Sydney, NSW 2006, Australia. E-mail: russelld@chw.edu.au

Abstract

Aim  The purpose of this study was to report a prospective cohort of children with acute-onset movement disorders.

Method  We report on 52 individuals (31 females, 21 males; mean age 6y 5mo, range 2mo–15y) with acute-onset movement disorders managed at a busy tertiary paediatric referral hospital over a 40-month period.

Results  In descending order of frequency, the movement disorders reported were chorea, dystonia, tremor, myoclonus, and parkinsonism. It was possible to divide the participants into three groups: (1) those with inflammatory or autoimmune disorders (n=22), (2) those with non-inflammatory disorders (n=18), and (3) those with psychogenic disorders (n=12). The inflammatory or autoimmune aetiologies included N-methyl-d-aspartate receptor encephalitis (n=5), opsoclonus–myoclonus syndrome (n=4), Sydenham chorea (n=3), systemic lupus erythematosus (n=3), acute necrotizing encephalopathy (n=3), and other types of encephalitis (n=4). Other important non-inflammatory movement disorder aetiologies included drug-induced movement disorder (n=6), post-pump chorea (n=5), metabolic (n=3) and vascular (n=2) disease. The participants with psychogenic movement disorders (n=12) were all over 10 years of age and were more likely to be female. Tremor and myoclonus were significantly over-represented in the psychogenic movement disorder subgroup. The outcomes of the total cohort were variable, and included full recovery, severe morbidity, and death.

Interpretation  Acute-onset movement disorders in children are important and may be treatable. Management should focus upon identifying the cause and treating the underlying disease process, as symptomatic treatment of the abnormal movements is variably effective.

Abbreviations
APS

Anti-phospholipid syndrome

NMDAR

N-methyl-d-aspartate receptor

PMD

Psychogenic movement disorder

SLE

Systemic lupus erythematosus

Movement disorders can be separated into hyperkinetic (also termed dyskinetic) or hypokinetic subgroups. Depending on the clinical phenomenology, the hyperkinetic group can be further classified into chorea, dystonia, tremor, myoclonus, and tics. The classic hypokinetic movement disorder is parkinsonism. Acute movement disorders may occur as a manifestation of many different neurological or psychogenic processes. Acute movement disorders present a particular diagnostic challenge. The first step is to classify the specific movement disorder: this is particularly important if there is no specific biomarker and diagnosis is dependent upon clinical phenomenology alone (as is the case with opsoclonus–myoclonus syndrome). The next step is to try to define the causative mechanism of the disease, which is important in treatable or life-threatening disorders such as N-methyl-d-aspartate receptor (NMDAR) encephalitis, systemic lupus erythematosus (SLE), acute necrotizing encephalopathy (ANE), and glutaric aciduria type 1.

Acute movement disorders present a further challenge as psychogenic or ‘functional’ disorders can present with abnormal movements. It is now possible to make ‘positive’ diagnoses of a psychogenic movement disorder, rather than a ‘diagnosis of exclusion’.1 Early diagnosis and implementation of appropriate therapies may improve long-term outcome in psychogenic movement disorders (PMDs).1,2

We aimed to prospectively record all individuals with acute movement disorder referred to a neurology service at a busy tertiary referral hospital. We further aimed to determine the relative frequency of different diseases and to test previously reported clinical phenomenology and associations.

Method

The Children’s Hospital at Westmead is the largest paediatric hospital in New South Wales, Australia, with a referral population of approximately 5 000 000. The hospital has a busy emergency department and manages a full spectrum of general and subspecialty paediatric conditions. The hospital offers a multiorgan transplant service, an oncology service, and cardiothoracic surgery, and has a 30-bed paediatric intensive care unit. To represent a typical paediatric neurology practice, all neurology referrals from local health practitioners, the emergency department, or hospital consultations fulfilling the inclusion criteria were added to a prospective database by the first author (RCD). Fifty-two individuals were seen by the three clinical neurology fellows (RCD, CT, HS) in post between February 2006 and June 2009. The majority of participants were seen by RCD, as part of the paediatric movement disorder service. Videos of 25 participants were available for confirmation of clinical phenomenology and movement disorder definition. The study’s primary aim was to document the relative frequency of different diseases causing acute movement disorder. This study obtained approval from the hospital ethics committee.

Inclusion criteria and definitions

All individuals presenting with an acute movement disorder were included (except isolated tics – see exclusion criteria below). All individuals with movement disorders as a dominant feature of the illness were included, although sometimes other clinical features were more prescient (such as encephalopathy in acute necrotizing encephalopathy). Movement disorders were defined according to clinical criteria as described on website of the Movement Disorders Society (http://www.movementdisorders.org/disorders). Abbreviated summaries are as follows. (1) ‘Chorea is an abnormal involuntary movement disorder derived from the Greek word to “dance”. Chorea is characterized by brief, abrupt, irregular, unpredictable, non-stereotyped movements’. (2) ‘Dystonia is a syndrome of abnormal, involuntary muscle movements due to sustained muscle contractions resulting in twisting and/or repetitive, patterned movements’. (3) Myoclonus is a sudden, fast, arrhythmic movement (electric shock-like), generally repeated in the same part of the body. (4) ‘Tremor is an unintentional, rhythmic, oscillation of a body part in a fixed plane’. (5) Parkinsonism is defined by ‘bradykinesias, or slowness with decrement and degradation of repetitive movements.’ Associated features can include rigidity, rest tremor, and loss of postural reflexes.

A thorough examination for a cause was sought in all cases, based on evidence-based practice. Some diagnoses, such as NMDAR encephalitis, were made retrospectively based on findings in stored serum and cerebrospinal fluid.3 Individuals were defined as having a life-threatening movement disorder if they were admitted to the intensive care unit as a consequence of their movement disorder, or if the movement disorder was symptomatic of a life-threatening neurological illness. Participants were followed up as part of routine clinical care.

Psychogenic movement disorders

Patients with psychogenic movement disorders were included in the acute movement disorder cohort. Participants were typically admitted as in-patients for a number of days to make a positive diagnosis of psychogenic movement disorder, perform important exclusion investigations as necessary, and implement a multidisciplinary treatment approach. Participants were watched and videoed, and the movement phenomenology, based on previously reported psychogenic movement characteristics,1,4 and the time until maximum symptom severity were recorded. A positive diagnosis of a psychogenic movement disorder (chorea, dystonia, tremor, myoclonus, parkinsonism) was then made, rather than a ‘diagnosis of exclusion’, and was based on the ‘best fit’ of the overall clinical picture.

Other features compatible with psychogenic movement disorders included:1 (1) abnormal movements incongruent with an organic movement disorder; (2) variability; (3) distractibility; (4) selective or inconsistent disability; (5) the disappearance of movements when the patient was unaware that he or she was being observed; (6) entrainment with psychogenic tremor (the presence of entrainment was determined by asking the patient to perform voluntary movements at a frequency determined by the examiner, who was performing the movements simultaneously – psychogenic tremor will assume the frequency of the contralateral voluntary movement if entrainment is present);1 (7) suggestibility; and (8) the simultaneous occurrence of multiple abnormal movements and dysfunctions (gait disturbance, exaggerated effort or slowness, near falling, false weakness).1

Participants were given a PMD diagnostic certainty as previously proposed1,4 and graded as follows: (1) ‘Documented psychogenic movement disorder. Movements relieved by psychotherapy, suggestion, or spontaneous symptom resolution when the patient feels unobserved’. (2) ‘Clinically established psychogenic movement disorder. Movements incongruent with organic disease or inconsistent symptoms, in addition to the presence of false localizing signs, or a documented psychiatric illness’. (3) ‘Probable psychogenic movement disorder. Movements are incongruent with organic disease or inconsistent, but no other supportive features are present’. (4) ‘Possible psychogenic movement disorder. Suspicion for disorder is based on the patient’s obvious emotional disturbance alone’. In addition, the acute and chronic psychological factors plus any acute physical stressors were defined by SG and KK, as part of psychological medicine service provision. Participants were followed up to define the outcome of the movement disorder and psychological impairments for a variable period dependent upon family engagement with therapy.

Exclusion criteria

The following disorders were excluded. Participants with tics were not included as it is frequently difficult to define the absolute onset of tic disorders, and acute dramatic presentations (‘Tourette storm’) are rare. During the same period, around 150 participants with tics and Tourette syndrome were reviewed through the movement disorder/Tourette service. Individuals with paroxysmal movement disorder, chronic and insidious onset of movement disorder due to genetic or metabolic causes, and acquired brain injuries to the developing brain (dystonic cerebral palsy) were excluded. Neonates and infants with transient or benign movement disorders were also excluded, as they present a different diagnostic challenge. Individuals with acute-onset cerebellar syndromes (postinfectious cerebellar ataxia and cerebellitis) and those with pseudoseizures or pseudoataxia (including psychogenic astasia abasia without coexistent movement disorder) were also excluded.

Results

Total cohort (n=52)

Fifty-two individuals (31 females, 21 males) with a mean age of 6 years 5 months (median age 5y; range 2mo–15y) were included. The participants were subdivided into a subgroup with inflammatory, autoimmune, and infectious disorders (n=22; 13 females, 9 males; mean age 7y 5.5mo; range 1–14y), a subgroup with movement disorders of non-inflammatory cause (drug-induced, post-pump chorea, metabolic, vascular, other; n=18, 8 females, 10 males; mean age 5y 0.7mo; range 2mo–15y), and a subgroup with psychogenic movement disorders (n=12, 10 females, 2 males; mean age 12y 7mo; range 10–15y).

Thirty-six participants had one movement disorder only, and 16 had two or more coexistent movement disorders. The movement disorders in descending order of frequency were chorea, dystonia, tremor, myoclonus, and parkinsonism (Table I). Thirteen participants had a severe or life-threatening illness that required intensive care management, and four participants died of their disease.

Table I.   Summary of different movement disorders, by aetiology, presented in descending order of frequencya
Chorea (n=20)Dystonia (n=17)Tremor (n=12)Myoclonus (n=10)Parkinsonism (n=10)
  1. aSome participants had more than one movement disorder, (69 movement disorders in 52 participants). ADEM, acute disseminated encephalomyelitis; ANE, acute necrotizing encephalopathy; NMDAR, N-methyl-d-aspartate receptor; SLE/APS, systemic lupus erythematosus/anti-phospholipid syndrome.

Post-pump chorea (n=5)NMDAR encephalitis (n=4)Psychogenic (n=10)Psychogenic (n=5)NMDAR encephalitis (n=3)
NMDAR encephalitis (n=3)Drug induced (n=3)SLE/APS (n=1)Opsoclonus–myoclonus (n=4)Encephalitis/ADEM (n=3)
Sydenham chorea (n=3)ANE (n=3)Unknown (n=1)Drug induced (n=1)SLE/APS (n=1)
Vascular (n=2)Psychogenic (n=3)  Drug induced (n=1)
ANE (n=2)Metabolic (n=2)  Metabolic (n=1)
Drug induced (n=2)Encephalitis, other (n=2)  Psychiatric (catatonia) (n=1)
Metabolic (n=1)    
SLE/APS (n=1)    
Encephalitis, other (n=1)    

Inflammatory, autoimmune and infectious subgroup (n=22; Table II)

Table II.   Acute-onset movement disorders: organic causes of inflammatory, autoimmune, or infectious origin (n=22)
DiseaseAge (y), sexMovement disorderPsychiatryOther featuresNeurological outcome (follow-up)Diagnostic features or investigations
  1. aCL Ab, anti-cardiolipin antibody; ADEM, acute disseminated encephalomyelitis; AML, acute myeloid leukaemia; BMT, bone marrow transplant; MRI, magnetic resonance imaging; NMDAR, N-methyl-d-aspartate receptor; OGC, oculogyric crises; SIB, self-injurious behaviour; CSF, cerebrospinal fluid.

NMDAR encephalitis2, FChorea, late parkinsonismAgitation, SIB, trichotillomaniaEncephalopathy, mutism, seizures, insomniaRelapse. Mild motor and cognitive impairment (2y)CSF and serum NMDAR antibodies
7, FChorea, dystonia, OGC, late parkinsonismCatatonia, agitation, trichotillomaniaEncephalopathy, mutism, seizures, memory loss, insomniaRelapse, moderate motor, psychiatric and cognitive impairment (2y 6mo)
8, MChorea, status dystonicus, OGC, stereotypiesSIB, agitation, echolaliaInsomniaComplete recovery (3y)
8, FDystoniaAgitation, emotional labilityMutism, seizure, insomniaMood disorder (2y)
13, MDystonia, stereotypies, late parkinsonismCatatonia, agitation, delusionsInsomnia, neuroleptic malignant syndrome, mutismComplete recovery (3y)
Opsoclonus–myoclonus syndrome1, MOpsoclonus–myoclonusNoneIrritability, ataxia neuroblastomaRemission (1y)Clinical phenomenology, tumour imaging
3, FOpsoclonus–myoclonusNoneAtaxia, neuroblastomaDied of tumour complications
4, MOpsoclonus–myoclonusNoneAtaxiaRemission (1y)
13, MOpsoclonus–myoclonusNoneRemission (2y)
Sydenham chorea10, FChoreaNoneCarditisComplete recovery (1y 6mo)Clinical phenomenology, anti-streptolysin titre, echocardiography
13, FChorea (hemi)Anger, emotional labilityCarditisComplete recovery (2y 6mo)
14, FChorea (hemi)AngerComplete recovery (6mo)
Systemic lupus erythematosus/anti-phospholipid syndrome (n=3)13, FChoreaChorea relapse In remission (3y)Anti-double-stranded DNA Ab, anti-nuclear antibody, aCL Ab, American Rheumatology association criteria
13, FTremorGait disorder, dysarthria, headache, nephritis, arthritisCNS relapse, depression (1y 6mo)
14 FParkinsonismDelusions, paranoia, psychosis, agitationCognitive decline, cutaneous lupusMild parkinsonism only (1y)
Acute necrotizing encephalopathy1.7, FDystoniaFever, encephalopathy, locked-in, brainstem, pyramidal signsMixed dystonic and spastic quadriplegia (1y)Classical MRI features, clotting and liver dysfunction
1.8, MDystonia, hemiballismusEncephalopathyMild motor deficit (2y)
3.7, FDystonia and choreaEncephalopathy, locked-in, pyramidal and autonomic signsMild motor deficit (1y)
Encephalitis, unspecified2, MChorea, status dystonicusAgitation, aggression, SIBEncephalopathyComplete recovery (6mo)Inflammatory CSF, otherwise negative investigation
5, FDystonia, parkinsonismEmotional labilityMild pyramidal signsAttention deficit (2y)
6, MParkinsonism (immunosuppressed)AML and BMT, pyramidal signsDeafness
Basal ganglia encephalitis/ADEM8, MParkinsonismSomnolenceComplete recovery (3y)Classic MRI imaging

NMDAR encephalitis

Five individuals with NMDAR encephalitis presented with early chorea and/or dystonia and late parkinsonism. There was dominant behavioural alteration in all participants, and sleep disorder, encephalopathy, and seizures in some participants (Table II). Most participants were diagnosed retrospectively using a cell-based assay to detect the presence of antibodies against NMDAR in serum and cerebrospinal fluid.3 Steroids and intravenous immunoglobulin were used in some participants with benefit, but the outcome was variable.

Opsoclonus–myoclonus syndrome

Four individuals with opsoclonus–myoclonus syndrome were diagnosed based on the typical clinical phenomenology alone; two had associated neuroblastoma.5 All participants received steroids and intravenous immunoglobulin monthly for 6 to 12 months. One patient with neuroblastoma died. The other three are in remission and are neurologically healthy to date.

Sydenham chorea

Three females, all of Aboriginal Australian origin, were diagnosed as having Sydenham chorea; two also had associated rheumatic carditis (mitral and aortic regurgitation). All participants were managed conservatively and have made a good recovery.

Systemic lupus erythematosus

SLE was diagnosed in three adolescent females with variable movement disorders (Table II). One participant with chorea had secondary anti-phospholipid syndrome (APS). Two participants relapsed and one has ongoing mild residual parkinsonism. All participants had typical SLE serology (elevated anti-nuclear antibody, anti-double-stranded DNA antibody) and all fulfilled the American Rheumatology Association criteria for SLE or APS. Participants have received steroids, and they receive ongoing immunosuppression with mycophenylate, cyclophosphamide, and rituximab.

Acute necrotizing encephalopathy

ANE was diagnosed in three young children who had profound encephalopathy and severe central nervous system dysfunction, including movement disorders. Diagnosis was based on identification of the classic features on magnetic resonance imaging (MRI; Fig. 1a and b), plus acute clotting and liver dysfunction.6 Management was with steroids to reduce the inflammatory cascade plus intensive care management, but the outcome was variable.

Figure 1.

 Diagnostically important magnetic resonance imaging (MRI) findings in selected participants with acute-onset extrapyramidal movement disorders. (a, b) Patient with acute necrotizing encephalopathy (ANE) presenting with encephalopathy, dystonia, and brainstem and pyramidal signs. The axial T2-weighted MRI shows the classic features of ANE with swelling and enhancement of (a) the thalami and posterior putamen and (b) the brainstem and cerebellar white matter. Follow-up imaging showed ’holes’ in the thalami as previously described.6 (c, d) Patient with basal ganglia encephalitis/acute disseminated encephalomyelitis presenting with parkinsonism showing (c) bilateral basal ganglia enhancement, with (d) significant resolution on repeat imaging. (e, f) Patient with known glutaric aciduria type 1, presenting with acute dystonia–parkinsonism as part of an acute ’encephalitic’ decompensation. The T2-weighted axial MRI shows (e) swollen basal ganglia with (f) diffusion restriction on diffusion-weighted imaging. There is additional frontotemporal atrophy. Patient with Leigh syndrome and preceding developmental delay presents with infection-induced relapse with dystonia. MRI shows typical Leigh syndrome imaging features of T2-weighted lesions in brainstem (g) and basal ganglia (h).

Encephalitis (unspecified)

Unspecified encephalitis occurred in four participants, who were given the diagnosis encephalitis lethargica, postencephalitic parkinsonism, or basal ganglia acute disseminated encephalomyelitis (Fig. 1c and d).7,8 No diagnostic marker exists, and participants were empirically treated with steroids, antibiotics, and antiviral drugs with a variable outcome (Table II).

Non-inflammatory movement disorders subgroup (n=18) (Table III)

Table III.   Acute-onset movement disorders: non-inflammatory causes (drug-induced, metabolic, or vascular aetiologies; n=18)
DiseaseAge (y), sexAetiologyMovement disorderOther featuresNeurological outcome (follow-up)Diagnostic features or investigations
  1. AED, antiepileptic drug; ALL, acute lymphoblastic leukaemia; CNS, central nervous system; DD, developmental delay; MD, movement disorder; MRI, magnetic resonance imaging; MRA, magnetic resonance angiography; SBE, subacute bacterial endocarditis; SSRI, serotonin reuptake inhibitor.

Drug induced0.8, FPhenytoin for refractory epilepsy on two AEDsChorea and dystoniaEncephalopathy and regressionRecovery of MD in 2wk, ongoing epilepsy and DD (2y)Clinical history
1, MKetamine and analgesia withdrawal for burns analgesiaMyoclonusHypotoniaRecovery of MD in 1wk, mild DD (7.2mo)
4, MCyclizine and metochlopramide for chemotherapy-induced nauseaDystonic crisisRecovery of MD in 3d (1y)
5, MPhenytoin for refractory epilepsy on two AEDsDystoniaDrowsy, hypotoniaRecovery of MD in 1wk, ongoing refractory epilepsy (3y)
5, MMethotrexate, cytarabine, amphotericin for CNS relapse of ALLChoreaAkathisiaPartial recovery of MD, ongoing neurotoxicity of therapy, died of ALL (1y)
15, FRisperidone plus two SSRIs for psychosisNeuroleptic malignant syndrome: ParkinsonismFever, hypertension, rhabdomyolysisComplete recovery in 3d, ongoing psychiatric disturbance (3y)
Post-pump chorea0.2, FPost transposition bypass surgeryChoreaRight Horner syndromeRecovery of MD, normal development (0.6y)Clinical phenomenology
0.4, MPost tetralogy of Fallot bypass surgeryChoreaHypotoniaRecovery of MD in 1mo, moderate DD (1y)
0.5, MPost mitral valve bypass surgeryChoreaRecovery of MD in 2wks, mild DD (8.4mo)
0.8, MPost tetralogy of Fallot bypass surgeryChoreaEncephalopathyRecovery of MD in 1wk, normal development (3.6mo)
15, MPost aortic valve bypass surgery then SBEHemichoreaEncephalopathy, multiple strokesDied of SBE (3.6mo)
Metabolic0.8, MGlutaric aciduria type 1 (infection-induced attack)Dystonia–parkinsonismEncephalopathy, irritabilityIntractable status dystonicus, died (6mo)Urine organic acids (newborn screening), MRI
1.4, MGlutaric aciduria type 1 (infection-induced attack)ChoreaEncephalopathy, irritable, mild pyramidal signsMild motor delay (2y)
5, FLeigh syndrome (cytochrome oxidase deficiency) (infection induced attack)DystoniaIrritable, encephalopathyDD, dystonia, regression (6mo)
Vascular4.5, FCerebral vasculitis and caudate strokeHemichoreaMild hemiplegiaComplete recovery with steroid treatment (1y 6mo)MRI, MRA
11, FCaudate strokeHemichoreaMild hemiplegia and focal seizuresComplete recovery of MD, deterioration in school performance (1y)
Psychiatric11, FCatatoniaParkinsonismAgitation, mutismNear-complete recovery, remains anxious and withdrawn (1y)Psychiatric history
Unknown10, FUnknown encephalopathyTremorEncephalopathy, catastrophic status epilepticusSevere acute brain injury related to status epilepticus (3y)Unknown

The participants with non-inflammatory disorders (Table III) were subgrouped into those with drug-induced movement disorders, those with post-pump chorea, and those with disorders of metabolic, vascular, or any other cause.

Drug-induced movement disorders

Out of six participants with drug-induced movement disorders, two had reactions to dopamine receptor blockers – one in the form of an acute dystonic crisis, and one neuroleptic malignant syndrome. Two further participants with refractory epilepsy taking multiple antiepileptic drugs had movement disorders induced by phenytoin loading. A further oncology participant had chorea in the week after intense chemotherapy and antifungal treatments (Table III), and another had myoclonus secondary to anaesthetic and analgesic withdrawal. The movement disorder resolved on withdrawal or modification of the causative drug.

Post-pump chorea

Post-pump chorea (n=5) occurred in four infants and one adolescent, 2 weeks after cardiac bypass surgery, usually noted when the participants were weaned from sedating agents. The chorea usually resolved, but one patient died and two have developmental problems, suggesting that post-pump chorea may be symptomatic of a significant brain injury in some participants.

Metabolic disorders

There were three participants with metabolic disorders. Two participants who were diagnosed with glutaric aciduria type 1 on neonatal screening presented with an ‘encephalitic’ basal ganglia metabolic decompensation, despite dietary management and emergency planning. These participants exhibited typical encephalopathy and irritability, and the MRI findings were characteristic (Fig. 1e,f); one participant died of intractable status dystonicus with associated medical complications. Another participant with known Leigh syndrome had an infection-induced decompensation with dystonia and characteristic imaging findings (Fig. 1g,h).

Vascular causes

Two participants with vascular diseases presented with hemichorea with subtle hemiplegic weakness. Both participants had strokes close to, or involving, the caudate; one had cerebral vasculitis (as evidenced by magnetic resonance angiography plus inflammatory cerebrospinal fluid). This patient received steroid treatment, and the vasculitis resolved clinically and radiologically.

Other

Two participants were placed in the ‘other’ group. One had an agitated catatonia of presumed psychiatric aetiology with profound bradykinesia; she responded to psychiatric management. The other participant in this group presented with a tremor of unknown aetiology and developed a catastrophic status epilepticus with secondary severe brain injury (Table III).

Psychogenic movement disorders (n=12; Table IV)

Table IV.   Psychogenic movement disorders (n=12)
CaseAge (y), sexTime until maximum severityMovement disordersOther featuresDuration of MD until treatment startedPMD diagnostic certaintyMD outcome (follow-up, y)
  1. MD, movement disorder; PMD, psychogenic movement disorder.

110, F0.5wkTremor (all limbs)Pelvic thrusting, gait instability2.5wksDocumentedResolution, relapse when anxious (9.6mo)
210, F4wksTremor (all limbs)Gait instability, dizziness, headache, false sensory signs, abnormal eating8wksProbableResolution (6mo)
310, F1wksTremor (generalized)Pelvic thrusting, unable to walk, headache2wksDocumentedResolution (6mo)
411, F0.5wkTremor, tics (dominant arm)Shouting tic, la belle indifference, gait instability1.5wkDocumentedResolution, prone to short relapses (1y 6mo)
511, F0.7wkMyoclonus (generalized)Weakness, gait instability, exhaustion2wksClinically establishedResolution, prone to stress-induced short relapses (3.6mo)
613, M4wksTremor, dystonia (generalized)Mumbling speech, bizarre gait8wksDocumentedResolution (1y)
714, F26wksTremor (head and legs)False sensory signs, headache, hyperventilation12wksPossibleUnchanged (1y)
814, F0.5wkMyoclonus (generalized)Gait instability, headache, dizziness, hyperventilation1.5wksDocumentedResolution (6mo)
914, F2wksTremor and myoclonus (dominant arm)Dizziness, headache3wksDocumentedResolution after minor relapse (1y)
1014, F2wksDystonia and tremor (limb then generalized)Gait instability, memory loss, pseudoseizures4wksClinically establishedImproved but ongoing relapses (1y)
1115, M1wkMyoclonus, dystonia, tremor (generalized)Reduced memory1wkDocumentedResolution (4.8mo)
1215, F0.7wkMyoclonus, tremor, dystonia (episodic, generalized)Pelvic thrusting, headache, dizziness, flushing1wkProbableResolution (2.4mo)

Twelve participants, two males and 10 females aged 10 to 15 years (mean 12y 7mo), had a PMD. In terms of psychiatric comorbidity, both male participants had autism and mild learning difficulties and one also suffered from Tourette syndrome. Seven of the 10 females suffered from anxiety (n=4) or depression (n=2), or both (n=1); in four cases, one or both parents met the criteria for anxiety or depression. All children presented in the context of one or more psychosocial or physical stressor, with the most common being a minor physical illness or medical procedure experienced by the child, such as minor head injury, immunization, tooth extraction (n=9), bullying (n=7), parental conflict, separation, or divorce (n=5), parent psychiatric illness (n=4), or parental physical illness (n=3). Chronic medical or neurological problems were present in two children, in one case epilepsy due to glucose transporter 1 deficiency and in the other chronic eczema.

The onset of the PMD was often dramatic, with a short time until maximum severity: seven children experienced maximum severity of the movement disorder within a week of movement disorder onset, and five had more subacute onset (>14wks). Six had two or more types of movement disorder. Tremor was the most common movement disorder (n=10), followed by myoclonus (n=5), dystonia (n=4), and tics (n=1). The movement disorder was often generalized, but when it was localized it usually affected the dominant arm. The movement disorders were often incongruent with an organic movement disorder (n=12), variable (n=12), distractible (n=11), and showed selective or inconsistent disability (n=10). Distractibility was common when the participant was asked to perform motor or cognitive tasks such as counting the months of the year backwards. The PMD was entrainable (for tremor; n=5), and was suggestible (n=4). The participants were typically admitted for diagnostic and therapeutic purposes. All participants were observed, and in some cases the movement disorder disappeared when the patient thought that he or she was not being watched (n=7).

Other features were common, particularly bizarre or unstable gait (n=8), pelvic thrusting (n=3), dizziness (n=4), headache (n=6), and reduced memory (n=2; Table IV). An attempt was made to make an early and positive diagnosis of PMD at a mean of 3.8 weeks after onset (range 1–12wks); it was possible to make a ‘documented PMD’ diagnosis in seven. Two participants had ‘clinically established PMD’, two had ‘probable PMD’, and one ‘possible PMD’.

Psychological interventions were tailored to individual children and the needs of their families. All 12 families received psycho-education during the acute assessment. Broadly, intervention aimed to reduce the levels of stress within the child’s relationship context, to coach the child to better manage stress-related symptoms, and to treat comorbid psychological disorders. Six families agreed to ongoing psychological therapy on an in-patient basis. This included physiotherapy (n=4), hospital school attendance (n=4), and management of conflict, grief, or treatment of a family member (family intervention; n=4). Five participants received a specific individual intervention, such as relaxation therapy, cognitive behavioural therapy, or ‘talking therapy’. One patient agreed to pharmacotherapy for comorbid psychiatric conditions, but three participants declined pharmacological treatment of comorbid depression or anxiety disorder. Three families refused to engage with psychological therapy altogether.

The outcome in the PMD group was often good, with nine having complete or near-complete resolution (often over the following weeks). Despite resolution of the movement disorder in many participants, five of the children experienced multiple relapses in the context of families declining treatment of comorbid anxiety or depression, or being unwilling to address ongoing psychological stressors. Three had intractable PMD over a period of 6 to 18 months. These three children also suffered from chronic psychiatric disorders (depression, n=2, and obsessive–compulsive disorder, n=1) and refused treatment.

Discussion

The study aimed to review the different aetiologies and outcomes of acute movement disorders in childhood. We believe this cohort is representative of typical paediatric neurological practice in an industrialized country. We suspect that drug-induced movement disorders are probably underrepresented, as this diagnosis is often obvious, and the treatment (drug modification) may not require referral to neurological services. This is particularly true for dystonic reactions caused by dopamine receptor antagonists, as psychiatrists and oncologists are very familiar with these potential side effects.9,10 We also suspect that the use of the antiemetic ondansetron has reduced the incidence of acute dystonic crises in paediatric practice. Drug-induced movement disorders are classically induced by dopaminergic or dopamine antagonists, serotonin reuptake inhibitors, stimulants, antiepileptic drugs, chemotherapeutics, antifungals, or drug withdrawal.9–13 Drug-induced movement disorders are reviewed in detail elsewhere.9,13

Acute-onset movement disorders can occur as a life-threatening illness or a movement disorder emergency, such as status dystonicus or neuroleptic malignant syndrome. Among our cohort, 25% of participants had a life-threatening illness and 8% died.

Other causes of acute movement disorder not described in this cohort include toxic causes such as carbon monoxide poisoning13 and the newly described acute-onset dystonia–parkinsonism due to a mutation in the gene coding for NaK-ATPase.14

The treatment of acute movement disorder depends on identifying the underlying cause. Many autoimmune causes of acute movement disorders, such as NMDAR encephalitis, opsoclonus–myoclonus syndrome, and SLE, are modifiable with immune therapies. There is increasing emphasis on early diagnosis and early treatment of autoimmune central nervous system conditions, as these disorders will result in morbidity or mortality if untreated or undertreated.3,5,15 If treating the cause of the abnormal movements is inadequate, or the abnormal movements are causing life-threatening complications such as rhabdomyolysis or multiorgan dysfunction,13 then symptomatic treatment of the movement disorder may be required.16 Symptomatic treatment of movement disorders aims to redress the chemical imbalance in dopaminergic, GABAergic, or cholinergic systems, or to reduce excitotoxicity.16 Symptomatic treatment of movement disorders may be difficult or ineffective, particularly in status dystonicus, and sometimes extreme sedation or anaesthesia is required.

This cohort confirmed a number of features previously described in acute movement disorders. Chorea was the most common acute movement disorder and was only seen in the ‘organic’ groups, whereas tremor was most commonly due to PMDs.1 Tremor, dystonia, and myoclonus are the most commonly described PMDs in both adults and children.1,2,17 However, caution is required as tremor was also a feature in two participants with ‘organic’ disorders.

PMDs accounted for 23% of the acute movement disorders in our cohort, a significant proportion and much higher than the 2 to 3% incidence in children described in outpatient settings.2,17 As anticipated, PMDs were more common in female adolescents. Interestingly, 9 of 12 children with PMDs had comorbid psychiatric diagnoses. We reproduced a number of previously described clinical phenomena and associations in PMD. Chronic and acute psychosocial stressors were common in the participants with PMDs. These typically involved the child being distressed secondary to acute physical stressors, relationship conflicts, the loss or illness of a loved one, and a variety of other commonplace stressors. Two children had histories of sexual abuse in the distant past, and two suffered from chronic neurological or medical illness.2

As previously reported, the following features were common in our cohort and are typical of PMD: fast progression to maximum severity, incongruous signs, distractibility, variability, selective or inconsistent disability, and entrainment (with tremor). PMD assumed a generalized distribution in many participants, but when localized affected the dominant limb.2,17 PMD is also associated with a high incidence of gait disturbance, headache, and other neurological symptoms.17 The diagnosis of PMD requires a constellation of these characteristics because the diagnosis based on the existence of a single feature is not infallible. It is often more straightforward to make a confident diagnosis of psychogenic tremor than of psychogenic dystonia, which often requires extensive testing for organic causes.2

In-patient admission allowed the opportunity to observe the participants with PMD performing different motor and cognitive tasks in different environments surrounded by various friends and family members. Observing the disappearance of the movement disorder in different circumstances made it possible to be more diagnostically certain of a PMD diagnosis. As with other paediatric cohorts, we found the diagnostic confidence levels of PMD to be applicable to our paediatric population, and were able to make a documented PMD diagnosis in 7 out of 12 participants. However, we were able to make only a probable or possible diagnosis of PMD in three participants. One of these participants had glucose transporter 1 deficiency and presented a particular diagnostic difficulty; we believe that she had a pre-existing organic movement disorder and developed a new PMD. Acute onset, short duration of symptoms, and psychogenic tremor are the best predictors of remission in childhood.2,18 It is hoped that prompt diagnosis and intervention will improve the outcome of PMD, but this cannot be determined by this descriptive study.2 The interventions for the PMD were tailored to the individual needs. Acceptance of the diagnosis by the family is essential to treatment success. Sometimes reassuring the family that there is no organic illness and creating a positive environment can result in rapid early improvements. A number of families failed to take up psychological therapy, or attended only transiently, despite comorbid psychiatric disorders and ongoing psychosocial impairments. Extended follow-up of these participants would be valuable to determine whether they have ongoing physical or psychological problems as adults. In adults, untreated PMD often becomes chronic, with symptoms persisting in 65 to 95% of affected individuals.1

Conclusions

In conclusion, to our knowledge this is the first prospective study of acute movement disorders in children aiming to define aetiological subgroups and short-term outcomes. Autoimmune and inflammatory causes were the most significant subgroup of acute movement disorders. We were surprised that PMDs were so prevalent in this acute movement disorder population. We have highlighted the importance of early diagnosis, early intervention, and anticipation of potentially life-threatening complications.

What this paper adds:

  • • Autoimmune and inflammatory disorders are the most common cause of acute movement disorders.
  • • Psychogenic movement disorders represent a significant percentage of acute movement disorders in childhood (23% in this cohort).
  • • The outcome is extremely variable, and is dependent upon the underlying disease mechanism.

Acknowledgement

This paper is dedicated to the late Dr Elizabeth (Liz) Fagan, previous head of the TY Nelson Department of Neurology, and founder of the Movement Disorder Group at the Children’s Hospital at Westmead.

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