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Abstract

  1. Top of page
  2. Abstract
  3. What this paper adds
  4. Method
  5. Results
  6. Discussion
  7. Supporting Information
  8. References
  9. Supporting Information

Aim  The cognitive and psychiatric aspects of adult movement disorders are well established, but specific behavioural profiles for paediatric movement disorders have not been delineated. Knowledge of non-motor phenotypes may guide treatment and determine which symptoms are suggestive of a specific movement disorder and which indicate medication effects.

Method  The goal of this review is to outline the known cognitive and psychiatric symptoms associated with paediatric movement disorders. We used a systematic approach, via PubMed, and reviewed over 400 abstracts of studies of selected disorders, of which 88 papers reporting paediatric non-motor symptoms are summarized.

Results  Obsessive–compulsive disorder was manifest in children with paediatric autoimmune neuropsychiatric disorders associated with streptococcal infections and Sydenham chorea. Children with opsoclonus–myoclonus syndrome had, for the most part, cognitive and behavioural problems, and attention-deficit–hyperactivity disorder was reported as a major comorbidity in Tourette syndrome, stereotypies, and restless legs syndrome. Symptoms of depression and anxiety were more frequent in individuals with idiopathic dystonia. Affective disorders were suggestive of Wilson disease. Cognitive decline was common in children with juvenile Huntington disease. A limitation of this review was the lack of systematic assessment in paediatric movement disorders for evaluation and uniform definitions.

Interpretation  Although the literature in non-motor phenomena is still emerging, recognition of salient cognitive and psychiatric phenomena may facilitate management of paediatric movement disorders.


Abbreviations
OCD

Obsessive–compulsive disorder

ODD

Oppositional defiant disorder

PANDAS

Paediatric autoimmune neuropsychiatric disorders associated with streptococcal infections

RLS

Restless legs syndrome

What this paper adds

  1. Top of page
  2. Abstract
  3. What this paper adds
  4. Method
  5. Results
  6. Discussion
  7. Supporting Information
  8. References
  9. Supporting Information
  • • 
    Cognitive and psychiatric symptoms are common in paediatric movement disorders and should be diagnosed and treated accordingly.
  • • 
    Non-motor manifestations may be the presenting symptoms of basal ganglia dysfunction.
  • • 
    Medication may induce cognitive and psychiatric symptoms similar to the underlying movement disorder.

In adults, an association between movement disorders and psychiatric syndromes is well established. Movement disorders have distinct psychiatric phenotypes, and in some, such as Huntington disease, behavioural changes or psychiatric illness herald the onset of motor signs. Anxiety and depression are prevalent in individuals with Parkinson disease,1 while essential tremor has been associated with dementia, specific personality traits, anxiety, social phobia, and depressive symptoms.2 Individuals with dementia and those with untreated psychiatric disorders often diagnosed with primary movement disorders.3,4 Whereas dementia has been associated with parkinsonian signs,4 parkinsonism and spontaneous dyskinesia have been documented in first-episode psychosis. These motor signs were reported in individuals who had never received neuroleptics, indicating that the motor disorder is not necessarily an adverse effect of medication.3 The prevalence of cognitive and psychiatric symptoms in adult movement disorders suggests that they share a similar neurological substrate.

Delineation of salient cognitive and psychiatric (non-motor) manifestations in paediatric movement disorders is still emerging; case reports, population studies, and clinical reviews on these disorders have not been systematically analysed. In this review, we examined whether individual paediatric movement disorders are accompanied by a characteristic cognitive and psychiatric phenotype.

Method

  1. Top of page
  2. Abstract
  3. What this paper adds
  4. Method
  5. Results
  6. Discussion
  7. Supporting Information
  8. References
  9. Supporting Information

We performed a search using MEDLINE via the PubMed interface for cognitive and psychiatric manifestations in paediatric movement disorders. We chose distinct entities of movement disorders in the paediatric population and reviewed all studies containing non-motor neuropsychiatric manifestations. The movement disorders reviewed were Sydenham chorea, benign hereditary chorea, opsoclonus–myoclonus syndrome, Tourette syndrome, paediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS), stereotypies, restless legs syndrome (RLS), idiopathic dystonia, torsion dystonia, dopa-responsive dystonia, myoclonus–dystonia, Wilson disease, juvenile Huntington disease, and genetic parkinsonism. This review does not cover mixed movement disorders such as cerebral palsy or multi-organ disorders, brain dysplasia, and systemic inflammatory diseases because of extensive non-specific neuroanatomical damage in these entities. A search was conducted for each disorder in conjunction with the following cognitive and psychiatric keywords: cog*, psych*, anxiety, depression, obsessive–compulsive disorder, and attention-deficit–hyperactivity disorder. We rechecked our findings (last search March 2011) using limits (all children, human, English, and title) for the following expanded movement disorder vocabulary: essential tremor, Sydenham chorea, rheumatic chorea, benign hereditary chorea, TIFF-1, opsoclonus–myoclonus syndrome, myoclonic encephalopathy, paediatric autoimmune neuropsychiatric disorders associated with streptococcal infection, PANDAS, stereotypies, restless legs, idiopathic dystonia, torsion dystonia, torsion dystonia, dopa-responsive dystonia, dopa-responsive dystonia, myoclonus dystonia, myoclonus–dystonia, Wilson disease, juvenile Huntington disease, genetic parkinsonism, and juvenile Parkinson disease. We contacted authors to identify additional studies and individual information (Segawa – dopa-responsive dystonia; Bressman, Giladi, and Mink – torsion dystonia; Bhatia – cervical dystonia; Dening – Wilson disease). We found 1661 papers, from which more than 400 abstracts were initially reviewed for this systematic approach of non-motor symptoms report in children (age <18y); from these, 88 were identified as potentially pertinent. Relevant papers were summarized within tables indicating manifestations, ages of affected children, and the number of cases reported. Essential tremor was not mentioned in the results since we found no study of non-motor signs in children with this disorder. As a large number of studies are available for Tourette syndrome, we incorporated only those with more than 30 cases or those delineating special phenotypes. In this review the term ‘cognitive’ refers to overall cognitive impairment or specific deficits such those in speech, verbal memory, visuospatial function, learning, and attention-deficit–hyperactivity disorder (ADHD). The term ‘psychiatric’ refers to irritability, behavioural problems, aggression, oppositional defiant disorder (ODD), substance abuse, obsessive–compulsive disorder (OCD), anxiety, bipolar disorder, depression, and psychosis. Percentages in the text were used only for sample sizes over 20.

Results

  1. Top of page
  2. Abstract
  3. What this paper adds
  4. Method
  5. Results
  6. Discussion
  7. Supporting Information
  8. References
  9. Supporting Information

We screened over 1600 papers and assessed over 400 abstracts for systematic non-motor reports of the selected paediatric movement disorders and found 88 clinical studies reporting cognitive and psychiatric symptoms. For some disorders there were several large studies, whereas for others only single studies or small samples were available (Table SI, supporting information published online). Main symptoms are outlined in Table I and in summarized detail in Table SII (supporting information published online).

Table I.   Overview of cognitive and psychiatric symptoms in paediatric movement disorders
 Cognitive impairmentSpeechVerbal memoryVisuospatial functionLearning disabilitiesADHDIrritabilityBehaviour disorderAggressionODDSubstance abuseOCDAnxietyAffective disorderBipolar disorderDepressionPsychosis
  1. aDifficult to detect data by age for children under the age of 18 years. Average prevalence reported: −, none reported; +/−, <10%; +, ∼10 to 30%; ++, ∼30 to 50%; +++, ∼50 to 70%; ++++, ∼70 to 90%. ADHD, attention-deficit–hyperactivity disorder; ODD, oppositional defiant disorder; OCD, obsessive–compulsive disorder; BHC, benign hereditary chorea; DYT11, myoclonus–dystonia; OMS, opsoclonus–myoclonus syndrome; PANDAS, paediatric autoimmune neuropsychiatric disorders associated with streptococcal infections; RLS, restless legs syndrome; DYT5, dopa-responsive dystonia; HD, Huntington disease.

Sydenham chorea+++++++++−/+
BHC−/+−/+
DYT11+++++++++++++++++−/+
OMS++++++++++++++++++++++ +++
Tourette syndrome+++++−/++++++−/+−/+
PANDAS+++++++++++
Stereotypies++++−/++
RLS++++++++++
Idiopathic dystoniaa+++
DYT5−/++++
Wilson diseasea++++−/+−/+++++++
Juvenile HD++++−/+−/++++++−/+
Genetic parkinsonism−/+−/+−/+

Chorea is an ongoing random-appearing sequence of one or more discrete involuntary movements.5

Sydenham chorea

Sydenham chorea is a neuropsychiatric disorder occurring in 10 to 30% of children with rheumatic fever. Retrospective studies based on file reviews indicate that 46% of children exhibit behavioural change (n=144).6 Parents described emotional liability, irritability, and age-regressed behaviour.7

Psychiatric aspects:  OCD has been extensively described in Sydenham chorea with different time courses. Two prospective studies using formal psychiatric evaluation, Diagnostic and Statistical Manual of Mental Disorders, 3rd Edition, Revised (DSM-IIIR; n=11)8 and Leyton Obsessional Inventory – Child Version (n=30),9 found that most children with Sydenham chorea had obsessive–compulsive symptoms (70–81%) and some met OCD criteria (17–27%).7,10 These symptoms were present only in children with Sydenham chorea (n=30) and not in children with rheumatic fever (n=20); symptoms peaked after the first 2 months and then waned, disappearing at 6 months.10 However, another systematic controlled study (50 children with rheumatic fever, 50 children with Sydenham chorea, and 50 comparison children) using DSM-IV criteria reported that OCD was not significant in the acute phase but was found in 50% of children with persistent Sydenham chorea.8 It is important to be aware that that obsessive–compulsive spectrum disorders may not be specific to the movement disorder since they were also reported at a similar rate in children after rheumatic fever without Sydenham chorea9,11 as well as in first-degree relatives of children with rheumatic fever.12 A characteristic obsessive and compulsive profile was delineated in 73 children using the Yale–Brown Obsessive Compulsive Scale, child version; 34% met DSM-IV criteria for OCD but disease stage during testing was not specified. Checking (56%), cleaning (42%), and repeating (36%) were common compulsions; the two most commonly reported symptoms were aggressive (63%) and contamination obsessions (34%), similar to the primary OCD profile but different from obsessions commonly seen in tic disorders.13

In a retrospective study (n=14),14 depression increased dramatically during and after Sydenham chorea symptoms while anxiety was reported in most cases before, during, and after clinical symptoms. In a controlled study (n=32) of young adults with non-acute Sydenham chorea, rates of anxiety and depression were the same as in a comparison group.15 In other studies, generalized anxiety disorder was found at higher rates in first-degree relatives of children with a history of rheumatic fever.16 Psychosis was reported in one case;17 however, retrospective studies in 369 individuals with psychosis have shown a higher than expected incidence of a history of Sydenham chorea,18 and a prospective controlled study found that individuals with Sydenham chorea (n=29) have a significantly higher risk of developing schizophrenia.19

Cognitive aspects:  In one study,14 ADHD symptoms in children with Sydenham chorea were reported even before the appearance of chorea (4 of 14) and did not increase significantly during the acute phase (5 of 148), suggesting an underlying predilection. In another study, the prevalence of ADHD approached 60% among children with persistent Sydenham chorea.8 In controlled studies, lower scores on the Wechsler Intelligence Scale for Children-Revised (WISC-R)7 and impaired verbal fluency20 were reported and attributed to frontal lobe dysfunction. After Sydenham chorea, adults were found to perform at a lower level of attention, and information processing, executive functions, and working memory were impaired.21

Benign hereditary chorea

Benign hereditary chorea is a familial dominant disorder related to a mutation in the thyroid transcription factor 1 (TIFF1) gene with thyroid and lung involvement. Affected family members have lower IQ than unaffected relatives, which may explain, at least in part, early termination of formal education. Low–average IQ was reported in isolated cases (5%) but was not assessed systematically. There are no reports of cognitive decline.22–24 Adult-onset psychosis was reported in several families,22,23 but no systematic studies were found.

Myoclonus is a sequence of repeated, often non-rhythmic, brief shock-like jerks due to sudden involuntary contraction or relaxation of one or more muscles.5

Opsoclonus-myoclonus syndrome

Opsoclonus–myoclonus syndrome, originally described as a myoclonic encephalopathy, is a paraneoplastic disorder presenting in infancy with erratic eye movements (opsoclonus) and generalized myoclonus. Most studies, although small or non-systematic, reported cognitive impairment presenting initially as developmental delay but ultimately as lower intellectual performance (60–80%), speech impairments (41–75%), and behavioural problems (17–90%).25–27 Over half of all children who recovered from opsoclonus–myoclonus syndrome required special education.28,29 Small systematic cognitive studies reported low–borderline IQ levels of 50 to 70 in the majority of cases.30 Verbal fluency and articulation were impaired (13 of 14), whereas verbal comprehension and language pragmatics were preserved. Memory, executive functions, and goal-directed motor activity were relative strengths.30

Systemic psychiatric evaluation demonstrated persistent irritability, dysphoric mood and poor affective regulation (10 of 17), disruptive behaviour problems with severe tantrums, restiveness, and aggressive and/or self-injurious behaviours (8 of 17).29,31 There was an inconsistent correlation between behavioural problems and low cognitive function.29,32 Attention problems were noted in most studies but could be attributed to other behavioural or emotional issues.28,29,32

According to a large retrospective non-controlled study based on parent questionnaires (n=105),28 only 50% of the language produced by their children was understandable according to half of the parents. Psychiatric problems reported by parents were rage attacks (79%), ODD (65%), obsessive or compulsive symptoms (58%), hyperactivity (47%), depression (29%), and ADHD (19%). Language impairment and behavioural problems were considered the most disruptive by parents.28 Unfortunately, cognitive and behavioural outcome is generally poor regardless of early treatment.28,29 Although this may change with the recent use of more aggressive immunomodulatory treatment, including immunosuppression with cyclophosphamide, only a single study has been published so far monitoring long-term non-motor outcome. Most children had impaired cognitive function (median IQ was found in 8 of 14 [3 of 14 had borderline and 5 of 14 had mild and moderate learning disability*], 10 of 14 had language impairment, 7 of 10 had behavioural problems). Although this small study did not demonstrate a significant change from previous reports, the outcome was better for children who received early treatment.33

Tics are repeated intermittent movements which are briefly suppressible and usually associated with a premonitory urge.5

Tourette syndrome

Tourette syndrome is defined as the presence of vocal and motor tics for over a year. Emotional comorbidities associated with Tourette syndrome have been extensively studied and are often more disturbing than the tics themselves. Some of the variety in symptoms may be attributed to the sample source; community populations generally have lower non-motor symptom percentages than clinical and referral centres. Comorbid conditions are ADHD (70%), ODD (30%), OCD (26%), separation anxiety (14%), bipolar disorder (11%), depression (2–9%), schizophrenia (3%), and pervasive developmental disorder (5%).34–36 Bizarre behaviours, personality disorders, self-injurious behaviour, and criminal activity have all been described.34

OCD has been closely associated with tics and differs from the characteristic OCD profile without tics.37 Children with Tourette syndrome and OCD have more somatosensory and symmetry obsessions and less anxiety than children with OCD alone; they have excessive concern with appearance, and have compulsive touching and counting.37

The intelligence level of children with Tourette syndrome is, for the most part, within the normal range; however, learning disability is common and were found to be associated with an earlier age at manifestation and a familial history of tics.38 Children with Tourette syndrome and ADHD have a cognitive profile similar to children with ADHD alone, manifested by impaired inhibition and executive function, abnormal visuospatial construction, and learning disabilities.39 Children with Tourette syndrome without ADHD exhibit better motor coordination and a higher IQ than children with ADHD alone or Tourette syndrome comorbid with ADHD.40 Because the studies we found did not differentiate between Tourette syndrome and chronic tic disorder, it is not possible to discuss cognitive and psychiatric profiles in chronic tic disorder.41,42

Paediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS)

The existence of PANDAS as a separate entity remains the subject of debate as dyskinesias and psychiatric disorders are known to follow streptococcal infections.43 PANDAS is defined as an abrupt presentation of OCD or tic disorder following streptococcal infection. Current diagnostic criteria include OCD and/or a tic disorder, paediatric age at onset, episodic course, association with streptococcal infection, and association with neurological abnormalities. Abrupt changes in attention, impaired executive functions, and deterioration in maths skills have been reported. Only one study delineates psychiatric manifestations, which were similar to those seen in Tourette syndrome: OCD (56%), ADHD (40%), ODD (40%), depression (36%), and anxiety (28%); aggressiveness, catatonia, eating disorder, enuresis, and encopresis have also been reported.44

Stereotypies

Stereotypies are patterned, repetitive, purposeless, involuntary movements that also are rhythmic and continual; they tend to change little over time and can be voluntarily suppressed.45 Stereotypies are typically, but not exclusively, observed in children on the autistic spectrum.46 Although most (54%) non-autistic children with stereotypies do not have neuropsychiatric disabilities, ADHD (25–30%), learning disabilities (20%), OCD (10%), mild speech (6 of 10), and motor delay (3 of 10) have all been reported.46–48 Children with autistic disorders and learning disabilities display similar stereotypies, albeit more frequent and variable.49 For instance, children with low functioning autism were found to have the highest prevalence of stereotypies (71%), followed by the high-functioning autism group (64%). Stereotypies were observed in lower rates in children without autism with a low IQ (31%) and in those with developmental language disorder (18%).50 Stereotypies were associated with a lower non-verbal IQ, especially in females, and correlated with low socialization and communication scores.50

Restless legs syndrome

RLS is a sensorimotor disorder characterized by a desire to relieve leg discomfort by movement, mainly at night. RLS is a common movement disorder in children and is comorbid with ADHD in up to 90% of cases. The severity of RLS symptoms is correlated with the severity of ADHD symptoms and is not attributed only to sleep disruption.51 Anxiety and/or depression occur in affected children, but at rates lower than in adults (8 of 18), and only after onset of sleep disturbance.52 Iron supplementation improves motor symptoms but not those of ADHD,53 whereas dopaminergic agonists have been found to improve both RLS and ADHD.54

Dystonia is an involuntary sustained or intermittent muscle contraction causing twisting and repetitive movements and abnormal postures.5

Idiopathic dystonia

Idiopathic dystonia, or primary dystonia, is a form of generalized dystonia with no known genetic mutation and includes focal (i.e. cervical dystonia), segmental (i.e. writer’s cramp), and generalized dystonia. Adults with idiopathic focal dystonia evaluated by a structured clinical interview (DSM-IV) were found to have a fivefold increased risk of any psychiatric disorder, and for the most part presented before motor manifestations.1 Among a group of young people (aged 3–28y) with cervical dystonia, 23% had anxiety or depression before the onset of motor signs. Symptoms were identified by clinical history and not by any formal assessment,55 nor was the developmental pattern delineated.

Torsion dystonia

Torsion dystonia is a primary genetic cause of dystonia in children, prevalent in the Ashkenazi Jewish population and caused by torsion dystonia mutation. Dystonia can be focal, segmental, or generalized. Cognitive and psychiatric aspects in children have not been published, but the clinical impression is that these children have typical cognition and have an increased incidence of anxiety and depression (Bressman S and Mink J, personal communications 2009). Depression is also seen in asymptomatic carriers, indicating that dysphoria may be a comorbid condition.56

Dopa-responsive dystonia

Dopa-responsive dystonia, also known as Segawa syndrome, is a genetic disorder characterized by low monoamine and pterin metabolites. Dystonic symptoms exhibit diurnal fluctuation and respond dramatically to l-dopa. Some 20% of affected children suffer from learning diability.57 Depression was reported in one child (one of four).58

Myoclonus-dystonia

Myoclonus–dystonia is characterized by involuntary jerks and dystonia alleviated by alcohol ingestion; phenotypic variations in symptomatology correlate with pedigree-dependent mutations in the epsilon sarcoglycan gene.59,60 The only psychiatric symptom reported to have an onset in childhood was OCD appearing after motor signs. OCD was seen in four of 16 individuals, in three of whom onset occurred in childhood.61

Rigidity is a constant resistance to movement that is detected even at very low speed of movement.62

Wilson disease

Wilson disease is caused by malfunction of the copper-transporting adenosine triphosphatase leading to copper accumulation.63 Psychiatric, neurological, or hepatic symptoms appear in the second to fourth decade. The most common movement disorder in children is dystonia, but rigidity and tremor are also prevalent; chorea is less common.63,64 Most studies report cognitive impairments, but time of onset is not certain.65 Psychiatric symptoms appear in 30 to 50% of adults before diagnosis and treatment.66 Depression accompanied by suicidal ideation is common.67 In addition, anxiety, bipolar affective disorder, incongruous behaviour, excessive talkativeness, apathy, abusiveness, irritability, aggression, hostility, and personality change have all been reported. Psychosis is rare.66–69 Damage subsequent to copper accumulation in different brain areas may explain, at least in part, the diversity in reported symptoms.70

A survey of presenting symptoms and natural history of Wilson disease in childhood (n=96) found that more than half of children with Wilson disease suffered from psychiatric issues,71 a higher percentage than that seen in adults.68 Recognizing the cause of the psychiatric manifestations is crucial as chelating therapy may reverse symptoms including psychiatric illness resistant to conventional symptomatic psychiatric therapy.63,65

Juvenile Huntington disease

Juvenile Huntington disease is a neurodegenerative disease caused by large CAG expansions in the Huntington disease gene; the classical presentation of rigidity, parkinsonian signs, and rapid cognitive deterioration was found in 18 of 33 participants in one study.72 Psychiatric symptoms in school-age children are ODD, aggression, hyperactivity, depression (2 of 20), addictions (4 of 37), psychotic disorders (3 of 37), and suicide attempts (1 of 37).73,74

Genetic parkinsonism

The triad of bradykinesia, tremor, and rigidity with onset before the age of 21 years is usually termed genetic parkinsonism. Cognitive impairment and depression have been reported, but at a lower rate than in adults.75–78

Psychogenic movement disorder

Psychogenic movement disorder is a conversion reaction manifested by involuntary movements. Generally dominant limbs are involved and movements are multiple and difficult to categorize to a specific movement disorder.79–81 Onset is rare before the age of 10 years and there is a female predominance.79,80 Movements do not cause pain or injury or disturb performance of desired tasks, but can be precipitated by a minor injury or stressful event and often disappear when the child is distracted. In most cases an underlying psychiatric disorder could be found (9 of 12)82 and recovery may occur after psychotherapy.79,82 The shorter the time from symptom onset to diagnosis and treatment, the better the prognosis.79

Discussion

  1. Top of page
  2. Abstract
  3. What this paper adds
  4. Method
  5. Results
  6. Discussion
  7. Supporting Information
  8. References
  9. Supporting Information

This review of the literature allows us, albeit cautiously, to draw associations between non-motor manifestations and specific movement disorders. OCD is manifest in children with Sydenham chorea and PANDAS. Children with opsoclonus–myoclonus syndrome have cognitive and behavioural problems. ADHD has been reported as a major comorbidity in Tourette syndrome, stereotypies, and RLS. Symptoms of depression and anxiety are more frequent in dystonia. Affective disorders are suggestive of Wilson disease. Cognitive decline is common in juvenile Huntington disease. Thus, at least for some disorders, evidence is available linking motor and non-motor manifestations.

Developmental aspects of non-motor symptoms, for the most part, are still unclear as studies do not always provide the age of participants, age at onset, or details of symptom progression. However, existing information suggests that non-motor deficits in movement disorders differ according to age. For example, ADHD is seen in children with RLS whereas adults with this disorder tend to have anxiety and depression.83 Cognitive impairment is already seen at presentation in childhood-onset Huntington disease. Differences in non-motor symptoms with age may reflect brain development and age-specific physiology as well as being a function of disease severity and progression. Age-specific differences are found in Huntington disease, with CAG expansions being larger in children than in adults, and in Wilson disease, in which copper accumulation is lower in children than in adults.

The neuropsychiatric symptomatology may become apparent only with pharmacological treatment, so it may not be self-evident if psychiatric symptoms are part of the disease or an adverse drug effect (Table II). In some instances it becomes evident only after discontinuing medication that the emerging psychiatric symptoms were not an adverse drug effect. Once a child is diagnosed with a movement disorder, cognitive and psychiatric aspects should be evaluated since neuroanatomical underpinnings of both the motor and non-motor pathways are closely related.84

Table II.   Cognitive and psychiatric adverse effects of drug treatment in movement disorders
 DrugMechanismCognitive and psychiatric adverse effect
ChoreaTetrabenazineDopamine depletionDepression
HaloperidolDopamine antagonistLethargy, restlessness, depression
MyoclonusClonazepamBenzodiazepineImpaired cognition, somnolence, irritability, aggression, hallucinations, amnesia
TremorPropranololBeta blockerHallucinations, insomnia, nightmares, depression
TicsClonidineAlpha-2 agonistDrowsiness
RisperdalSerotonin antagonistAnxiety, drowsiness, fatigue, restlessness
DystoniaTrihexiphenidylAnticholinergicIrritability, somnolence, anxiety, confusion
l-dopaDopamine precursorDepression, anxiety, confusion, hallucinations

In children, as in adults, non-motor and motor symptoms may result, at least in part, from a neurotransmitter imbalance and both types of symptoms are observed even in carriers. Dopamine depletion, but also abnormalities of other neurotransmitters, is thought to lead to both rigidity and depression, while excessive dopaminergic input contributes to chorea and psychosis. Serotonin dysregulation is related to OCD and tics.85 One individual with idiopathic dystonia also had low cerebrospinal fluid serotonin levels, a finding that may have a causal role for depression.86 The neurotransmitters involved in the pathogenesis of myoclonus are unknown; however, clonazepam – the treatment of choice in certain types of myoclonus – is used as a mood stabilizer and to control anxiety. Although their underlying neuropathology remains unknown, symptomatic treatment for both movement disorders and psychiatric illnesses often targets neurotransmitters and basal ganglia circuitry. For example, l-dopa and dopamine agonists are the drugs of choice for the treatment dystonia, rigidity, and parkinsonism, while dopamine antagonists are used to ameliorate tics and chorea. Psychiatric illnesses can be treated by altering neurotransmitter balance using selective serotonin reuptake inhibitors or dopamine antagonists. Deep-brain stimulation of basal ganglia structures is used for treating Parkinson disease, essential tremor, and certain forms of dystonia, and can be effective in refractory depression and OCD.

Limitations to the review:  Difficulties encountered in this review were the small number of studies for some of the disorders and studies that included only small numbers of participants or did not differentiate between adults and children (Table SI). Also, information was often descriptive or impressionistic and not based on standardized cognitive tools or psychiatric questionnaires. The terms ‘acute state’ and ‘chronic state’ were not well defined and may overlap between studies. Most findings were presented as the prevalence of symptoms and do not indicate the severity of disability; none of the studies assessed symptom impact on quality of life.

In summary, non-motor symptoms in children with movement disorders cause major disability and their treatment requires clinical expertise; these cognitive and psychiatric manifestations may result from the disease process itself or be a consequence of therapy, and often it is the clinical course that is instructive in resolving the diagnostic dilemma. This review of non-motor characteristics may serve as a reference, assisting the clinician in management and treatment of paediatric movement disorders, and creates a basis for further systematic research.

Footnotes
  • *

    North American usage: mental retardation.

Supporting Information

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  3. What this paper adds
  4. Method
  5. Results
  6. Discussion
  7. Supporting Information
  8. References
  9. Supporting Information

Additional material and supporting information for this paper may be found online.

References

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  7. Supporting Information
  8. References
  9. Supporting Information

Supporting Information

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  6. Discussion
  7. Supporting Information
  8. References
  9. Supporting Information
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