|Year : 2021 | Volume
| Issue : 3 | Page : 136-142
Spectrum of childhood dystonia evaluated at a tertiary care center from south India
Ganaraja V H1, Netravathi M1, Nitish Kamble1, Vikram V Holla1, Dwarakanath Srinivas2, Ravi Yadav1, Pramod Kumar Pal1
1 Department of Neurology, National Institute of Mental Health and Neurosciences (NIMHANS), Bengaluru, Karnataka, India
2 Department of Neurosurgery, National Institute of Mental Health and Neurosciences (NIMHANS), Bengaluru, Karnataka, India
|Date of Submission||10-Mar-2021|
|Date of Decision||17-May-2021|
|Date of Acceptance||14-Jun-2021|
|Date of Web Publication||22-Dec-2021|
Dr. Pramod Kumar Pal
Department of Neurology, National Institute of Mental Health & Neurosciences (NIMHANS), Hosur Road, Bengaluru 560029, Karnataka.
Source of Support: None, Conflict of Interest: None
INTRODUCTION: Dystonia is one of the most common hyperkinetic movement disorders observed in children with neurological disorders. The objective of this study was to evaluate the demographic, etiological, and radiological profile of childhood dystonia. METHODS: This study is a retrospective chart review of children with dystonia (onset ≤18 years) who were admitted to our hospital from 2013 to 2017. All the relevant demographic data including the ethnicity, socioeconomic and cultural background, examination findings, electrophysiological, and other investigations were retrieved from the medical records. RESULTS: A total of 814 children were admitted and evaluated in the pediatric ward, of which 85 (38 girls) children had dystonia. Mean age at onset was 6.21 ± 5.21 years. Mean duration of illness was 3.51 ± 4.23 years. Generalized dystonia was noticed in 83.5% followed by focal dystonia in 8.2%. Hemidystonia and segmental dystonia were less commonly seen with 4.7% and 3.5% of cases, respectively. Brain magnetic resonance imaging (MRI) was available in 82 patients; and diagnostic in 56.1% in the form of Wilson’s disease (14.1%) neurodegeneration with brain iron accumulation (14.1%), perinatal insult (8.2%), encephalitis (7.1%), mitochondrial cytopathy (3.5%), glutaric aciduria (2.4%), isovaleric acidemia (1.2%), metachromatic leukodystrophy (1.2%), acute disseminated encephalomyelitis (1.2%), and neuronal ceroid lipofuscinosis (1.2%). Two patients underwent surgical therapy in the form of deep brain stimulation and bilateral pallidotomy. CONCLUSION: Dystonia constitutes 10.4% of pediatric neurological admissions in our study cohort. Generalized dystonia is the commonest subtype. Brain MRI is useful in identifying etiology and it was diagnostic in nearly half of the patients (56.1%).
Keywords: Childhood dystonia, dystonia, neurodegeneration with brain iron accumulation, primary dystonia, Wilson’s disease
|How to cite this article:|
V H G, Netravathi, Kamble N, Holla VV, Srinivas D, Yadav R, Pal PK. Spectrum of childhood dystonia evaluated at a tertiary care center from south India. Ann Mov Disord 2021;4:136-42
|How to cite this URL:|
V H G, Netravathi, Kamble N, Holla VV, Srinivas D, Yadav R, Pal PK. Spectrum of childhood dystonia evaluated at a tertiary care center from south India. Ann Mov Disord [serial online] 2021 [cited 2022 Sep 30];4:136-42. Available from: https://www.aomd.in/text.asp?2021/4/3/136/333369
| Introduction|| |
Dystonia is a movement disorder characterized by sustained or intermittent muscle contractions producing twisting, repetitive, and patterned movements or abnormal postures. It has a wide clinical spectrum that may range from minimal or self-limiting to severe fixed dystonia. Childhood dystonia is one of the most common hyperkinetic movement disorders with heterogenous etiology such as primary or secondary. It is also classified based on the body part/region affected.
Primary dystonia is further classified into pure dystonia in which dystonia is the only sign of the disease (with the exception of tremor), dystonia plus syndromes that are associated with an additional movement disorder (e.g., myoclonus or Parkinsonism More Details) and paroxysmal disorders that include conditions characterized by brief episodes of dystonia with normality in between.
Secondary dystonic forms have an underlying heredodegenerative etiology, or exogenous factors (e.g., perinatal injury, medications, brain tumor, infections).
Dystonia presenting at or before 18 years of age is distinguished as childhood dystonia and dystonia occurring after 19 years is termed as adult-onset dystonia.
It is widely recognized that the causes and associated features in pediatric dystonia are different from those seen in adulthood. As dystonia in childhood may be symptomatic or “secondary” disorders, there are no clear descriptions of the natural history of dystonia in children to explain about prognosis, but the data on frequency of this association are again limited. Hence, it is important to study the course of dystonia in pediatric population. The objective of this study is to evaluate the demographic, etiological, and radiological profile of pediatric dystonia.
| Methods|| |
The present study is a retrospective chart review of children with dystonia (onset ≤18 years) who were admitted and evaluated in the pediatric unit of the department of Neurology at the National Institute of Mental Health and Neuro Sciences, Bangalore, India over a period of 5 years (from 2013 to 2017). The study was approved by the Institute’s ethics committee. All these children were examined by the senior movement disorder specialist (PKP). The case records were retrieved from the hospital’s medical records department. All the relevant demographic data, clinical history, examination findings, imaging, and other investigation details and treatment were noted. Classification of dystonia was done using the MDS consensus update used to categorize the patients. Data were captured from the records using a structured pro forma. The clinical information included age, age at onset, duration of illness, family history, aggravating factors or task specificity, distribution of dystonia, associated other movement disorders, and other neurological signs was recorded. Clinical videos of patients were also reviewed whenever possible.
We used the R software for statistical analysis which is a free software environment for statistical computing and graphics as it compiles and runs on a wide variety of UNIX platforms, Windows, and MacOS and is user friendly and provides accurate results.
| Results|| |
A total of 814 children were evaluated in the pediatric unit over a period of 5 years (2013–2017). Among them, 85 (10.4%, M:F––47:38) children had dystonia and were included for the retrospective study. Mean age at onset was 6.21 ± 5.21years and age at presentation was 9.72 ± 5.41 years. Median duration of illness was 2 years with a range of 10 days to 18 years. Delayed developmental milestones were observed in 43.5% and regression of milestones in 11.8%. History of dystonia in the siblings was noted in 7% [Table 1].
As per Axis 1 definitions, almost half (51%) of cases had onset of dystonia in childhood age group (2–12 years), followed by infantile onset (0–2 years) in 33% and adolescent dystonia (13–18 years) in 17%. Based on body distribution, generalized dystonia was noticed in 83.5% followed by focal dystonia in 8.2%. Hemidystonia (4.7%) and segmental dystonia (3.5%) were less commonly seen. Pure dystonia was noted in 74.1% of cases, others had associated movement disorders, such as choreoathetoid movements (8.2%), tremors (7.1%), cerebellar ataxia (4.7%), and myoclonus (2.3%). Mixed phenotype (combination of 3 or more) was seen in 3.5%. In patients with pure dystonia, approximately two-thirds of them had onset of symptoms before 12 years of age with almost 90% of them had generalized dystonia, followed by hemidystonia (6.3%), and segmental dystonia (3.1%) [Table 2].
Based on Axis 2 classification, evidence of neurodegeneration was noticed in 51.7% and structural lesions in 20%. In 28% of children, there was neither degeneration nor structural changes in brain. Approximately 52.9% of children had inherited cause of dystonia with autosomal recessive pattern (43.5%) being the commonest. Idiopathic primary dystonia was seen in 20% of cases, of which 17.6% were sporadic and 2.3% had familial inheritance. Among acquired causes, perinatal insult was the commonest cause (12.9%) of children; other causes were neuroinfections (7%) and immune-mediated disorders (5.8%). The neuroinfections were Japanese encephalitis (3.6%), dengue encephalitis (2.3%), and viral meningoencephalitis (1.1%). The immune-mediated disorders were seronegative autoimmune encephalitis (3.6%), anti NMDA receptor encephalitis (1.1%), and ADEM (1.1%). Psychogenic dystonia was seen in 1.2%.
Etiologically, Wilson’s disease (WD) and Neurodegeneration and Brain Iron Accumulation (NBIA) accounted for 15.3% of cases, followed by perinatal hypoxic injury in 10.6% of cases [Table 3]. Majority of the children with WD and NBIA had generalized dystonia at presentation; however, approximately 16% of NBIA had focal dystonia and 8.3% of WD had hemidysonia.
Approximately 16.6% of WD had additional tremors, and those with NBIA had tremor (7.7%), ataxia (7.7%), chorea (7.7%), myoclonus (7.7%), and mixed phenomenology (7.7%) in addition to dystonia. Reduced levels of serum copper and ceruloplasmin was observed in children with WD (100%).
Among children with perinatal insult, onset of dystonia was within 2 years of age and all of them had delay in developmental milestones. Approximately 91% of these children had generalized dystonia and remaining 9% had focal dystonia. Brain imaging was suggestive of hypoxic changes in 72.7% and Kernicterus in 27.3%.
In children with encephalitis, all had generalized dystonia at presentation. Seizures (80%) and behavioral changes (50%) were also observed. All children with mitochondrial cytopathy had presented with pure generalized dystonia and brain imaging was consistent with Leigh disease in 50%. Muscle biopsy was suggestive of mitochondrial cytopathy in two patients. Overall clinical, blood investigations (ammonia and lactate), imaging and muscle biopsy was taken into consideration for the diagnosis of mitochondrial cytopathy.
Children with dopa responsive dystonia had normal brain imaging and in 50% (n = 2) the diagnosis was genetically confirmed (Tyrosine hydroxylase (TH gene) mutation). In the other two children, there was no genetic testing done; however, they had a very good response to small doses of levodopa. In children with ataxia telangiectasia, all had conjunctival telangiectasia along with generalized dystonia (100%) and 66% of them had elevated serum alpha fetoprotein and cerebellar atrophy on brain imaging. Among children with glutaric acidurias, developmental delay with macrocephaly was noticed in all (100%), along with pure dystonia [Table 4].
|Table 4: Profile of different neurological disorders presenting with dystonia|
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Brain magnetic resonance imaging (MRI) was available for 82 patients; and diagnostic in 56.1% in the form of WD and NBIA with 14.1% each, perinatal insult (8.2%), encephalitis (7.1%), mitochondrial cytopathy (3.5%), glutaric aciduria (2.4%), isovaleric acidemia (1.2%), metachromatic leukodystrophy (1.2%), acute disseminated encephalomyelitis (1.2%), and neuronal ceroid lipofuscinosis (1.2%) [Figure 1]. Brain MRI was showing nonspecific changes in 22.3% of cases and was normal in 20% of cases.
|Figure 1: (A) Eye of tiger sign in NBIA, (B) midbrain showing mini panda sign in Wilson’s disease, (C) Tigroid pattern in metachromatic leukodystrophy, (D) basal ganglia hyperintensities in mitochondrial disorder, (E) posterior occipital gliosis in perinatal insult, (F) thalamic hyperintensities in Japanese Encephalitis, (G) multifocal white matter signal changes in ADEM, (I) widened sylvian fissure in glutaric aciduria, and (J) inferior putamen hyperintensity in isovaleric acidemia|
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All patients were treated with medical line of management which included Levodopa, trihexyphenidyl, baclofen, tetrabenazine, benzodiazepines, and others, of which 72.9% of patients required polytherapy with two or more medications. Children with dystonia secondary to perinatal insult were the most refractory to medical therapy and required polytherapy. Two (2.3%) patients underwent surgical therapy (Bilateral pallidotomy in a case of ataxia telangiectasia and deep brain stimulation in one child with NBIA), both had severe disabling dystonia refractory to medical therapy. Botulinum toxin was not administered to any of our patients. It was mainly due to the financial constraints and lack of consent by the parents.
| Discussion|| |
Dystonia is the second most common movement disorder, after tics in children. However, data on profile of dystonia in this pediatric population is limited. Our study provides a detailed profile of dystonia observed in 85 children.
In our cohort, dystonia accounts for approximately 10% of pedicatric neurological admissions and 83.5% of them present with generalized dystonia. The most common causes for childhood dystonia were NBIA and WD, which are mainly childhood-onset disorders.
In a hospital-based study from north India, almost half of patients aged ≤ 26 years had focal dystonia and generalized dystonia was noticed in 42.10%. The most common type of dystonia was writer’s cramp. Among the children with generalized dystonia WD, was the most common type similar to our study. In the western population, genetically mediated dystonia (DYT1) is found to be the most common cause for early-onset generalized dystonia, and it constitutes up to 90% in Ashkenazi Jewish population.
In another hospital-based study, secondary dystonia was the most common and constituted 72% of cases and approximately 65% were due to cerebral palsy. This difference could be due to lesser proportion of cerebral palsy children in our inpatient cohort. Overall definitive diagnosis could be made in approximately 82.4% of cases which are similar to other studies. In another hospital-based study, 44% were of primary dystonia and 21% of cases were due to metabolic causes. Only 20% were due to secondary causes. These differences in the etiology of dystonia could be due to selection bias.
Imaging findings of NBIA showing “eye of tiger” sign was observed in all cases. A similar observation was noted in a previous study where 11/13 patients had this feature and one case had acanthocytes in peripheral smear.
Approximately 73% of cases required two or more anti dystonia medications, suggesting refractoriness of dystonia to treatment, more so with secondary dystonia. Use of these polytherapy may also cause a significant burden to caregivers and also may result in poor compliance. In one study, approximately 22% of children were receiving three or more anti- dystonia medication, even with this, there was no sufficient dystonia control. Hence, it requires clinical discussion and shared decision with caregivers about risk of side effects, benefits, and drug interactions. One case of pharmacological resistant dystonic storm in ataxia-telangiectasia underwent bilateral pallidotomy.
In comparison, in another hospital-based study focal dystonia was observed in approximately 48.8% of cases and features of degenerative dystonia in only 10% of cases. However, in their study, all patients attending movement disorder clinic were included, unlike ours where only children from inpatient care were included.
The strength of the present study is that we have provided the detailed demographic, clinical, and therapeutic profile of pediatric dystonia. It also gives an account of various disorders that can present as dystonia in the pediatric population. This will help the treating clinician with an approach and manage pediatric dystonia
Our study had limitations. Our hospital is a tertiary care center and hence there could be a referral bias with more severe and difficult cases seeking in-patient care. There are a number of cases who present with focal and segmental dystonias in the out-patient department. Hence, the distribution of dystonia may not be representative of our community. In addition, the genetic diagnosis was done for only a few patients mostly due to the financial constraints. Genetics analysis for other primary dystonia could have helped us in better understanding of the disease and also in genetic counseling.
| Conclusion|| |
Dystonia is prevalent in 10.9% of neurological inpatient cases in pediatric population. Generalized dystonia was the most common subtype of dystonia. Brain MRI is a useful imaging modality in identifying etiology and it was diagnostic in nearly half of the patients (56.1%). WD and NBIA are common causes of dystonia. Majority of children are refractory to treatment requiring two or more anti dystonia medications.
Ganaraja VH: Research conception, organization and execution, statistical analysis design and execution, writing of first draft; Netravathi M and Nitish Kamble: Research conception, organization and execution, manuscript review and critique; Vikram V. Holla, Dwarakanath Srinivas and Ravi Yadav: manuscript review and critique; Pramod Kumar Pal: Research conception and supervision, statistical analysis review and critique, manuscript review and critique.
Ethical compliance statement
Ethical approval for this study was waived by the Institute Ethics Committee owing to the retrospective nature of the study (No. NIMH/DO/DEAN (Basic Science)/2020-21).
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Table 1], [Table 2], [Table 3], [Table 4]