Original Article

Acute Movement Disorders in Children: Experience from a Developing Country

Journal of Child Neurology 2015, Vol. 30(4) 406-411 ª The Author(s) 2014 Reprints and permission: sagepub.com/journalsPermissions.nav DOI: 10.1177/0883073814550828 jcn.sagepub.com

Jatinder Singh Goraya, MD, FRCPC1

Abstract We describe acute movement disorders in 92 children, aged 5 days to 15 years, from an Indian tertiary hospital. Eighty-nine children had hyperkinetic movement disorders, with myoclonus in 25, dystonia in 21, choreoathetosis in 19, tremors in 15, and tics in 2. Tetany and tetanus were seen in 5 and 2 children, respectively. Hypokinetic movement disorders included acute parkinsonism in 3 children. Noninflammatory and inflammatory etiology were present in 60 and 32 children, respectively. Benign neonatal sleep myoclonus in 16 and opsoclonus myoclonus syndrome in 7 accounted for the majority of myoclonus cases. Vitamin B12 deficiency in 13 infants was the most common cause of tremors. Rheumatic fever and encephalitis were the most common causes of acute choreoathetosis. Acute dystonia had metabolic etiology in 6 and encephalitis and drugs in 3 each. Psychogenic movement disorders were seen in 4 cases only, although these patients may be underreported. Keywords acute movement disorders, children, developing country Received May 24, 2014. Received revised August 14, 2014. Accepted for publication August 17, 2014.

Movement disorders are encountered in clinical practice as chronic progressive or nonprogressive neurologic disorders, generally evaluated and treated on an outpatient basis. Movement disorders presenting acutely as a mediconeurologic emergency are, however, not entirely uncommon. Acute movement disorders are the conditions in which a movement disorder forms the dominant clinical manifestation that evolves over hours to days, and if not recognized and treated promptly may result in significant morbidity or even mortality.1 Occurrence of an acute movement disorder points to underlying systemic, neurologic, or sometimes psychogenic processes and not infrequently may be an adverse effect of a drug. Intercurrent acute worsening of a chronic movement disorder can also present as an emergency. Likelihood of a serious underlying disorder and potential for harm from the excessive and severe movements determines the emergent nature of these movement disorders. Both hypokinetic and hyperkinetic disorders can present acutely requiring emergent evaluation and treatment.2,3 There has been a recent growth of interest in movement disorder emergencies as is evident from publication of several reviews in the last few years.2-4 Studies on the relative frequency of different movement disorders (as a clinical phenomenon) and their underlying diseases are, however, very limited. This is especially true of acute movement disorders in children. A literature search revealed 1 review5 and 1 prospective study6 describing acute movement disorders in children. Therefore, in the present study, we aim to describe our experience with acute movement disorders in children in the

epidemiologic settings of a developing country with an aim to determine the nature and spectrum of various movement disorders in children presenting acutely and to study the relative frequency of various diseases underlying these acutely occurring movement disorders. We also compare our results with those from previous published studies from the developed world.

Methods The study was done in a tertiary care hospital of North India. The subspecialty of pediatric neurology was recently established in the hospital to provide specialized care to children with neurologic disorders. A retrospective review was done of the charts of all children up to 18 years who were evaluated and treated by the author between February 2010 and January 2014 for an acutely emerging movement disorder. An acute movement disorder was defined as any neurologic disorder evolving acutely or subacutely over hours or days (maximum 4 weeks) in which a movement disorder was the only or the

1

Division of Pediatric Neurology, Department of Pediatrics, Dayanand Medical College & Hospital, Ludhiana, Punjab, India

Corresponding Author: Jatinder Singh Goraya, MD, FRCPC, Division of Pediatric Neurology, Department of Pediatrics, Dayanand Medical College & Hospital, Civil Lines, Ludhiana 141001, Punjab, India. Email: [email protected]

Goraya dominant feature of the illness and required emergent evaluation and treatment. Individual movement disorders were defined according to standard clinical criteria. In cases with a mixed movement disorder, only the predominant movement disorder was counted for classification. The diagnosis of underlying disease was inferred from clinical history, physical examination, and laboratory and neuroimaging findings. Children with acute-onset pure cerebellar syndromes such as cerebellitis, paroxysmal dyskinesias, and nonepileptic seizures were excluded. Data for relevant clinical, laboratory, and radiologic parameters were collected and analyzed. The study was approved by the institutional review board.

Results Ninety-two children met the inclusion criteria for acute movement disorder. There were 63 boys and 29 girls. Mean age at presentation was 4 years 9 months (median 2 years; range from 5 days to 15 years). Forty-eight (52%) children were aged 2 years or younger.

Movement Disorder Phenomenology Hyperkinetic movement disorders as a group accounted for majority of the cases, occurring in 89 of total 92 patients (Table 1). Myoclonus was the most common movement disorder seen in 25 (27%) children, followed by dystonia in 21 (23%), choreoathetosis in 19 (21%), and tremors in 15 (16%). Two children had explosive-onset tics, possibly postinfectious. Involuntary muscle spasms (due to tetany in 5 and tetanus in 2) causing muscle stiffness and abnormal posturing occurred in 7 patients. Acute-onset parkinsonism (n ¼ 3) was the only hypokinetic movement disorder seen. Six children had mixed movement disorder, with co-occurrence of more than 1 kind of movement disorders. Twenty-two patients had life-threatening illnesses requiring intensive care management.

407 with spasms and trismus attributable to infectious tetanus. Distribution of various acute movement disorders attributable to inflammatory, autoimmune, and infectious etiology is summarized in Table 1.

Non-inflammatory Group Etiologically, this was the largest group of 60 children with acute movement disorders. Physiological (meant here to indicate absence of any organic structural brain disorder and likely representing an aberration in the maturational neurophysiological processes in the growing brain) mechanisms underlying acute movement disorders accounted for the condition in 17 children, with benign neonatal sleep myoclonus being the most common cause (n ¼ 16). One child had benign myoclonus of infancy. Nutritional/metabolic group was the largest group (n ¼ 25). Thirteen children in this group presented with infantile tremor syndrome (a term used to describe nutritional B12 deficiency syndrome in infants and young children in the Indian subcontinent). Eight children had underlying inborn errors of metabolism (glutaric aciduria type 1 in 3, Leigh disease in 2, mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes (MELAS) in 1, pantothenate kinase–associated neurodegeneration (PKAN) in 1, and an unspecified leukodystrophy in 1). Three children had hypocalcemia (vitamin D deficiency in 1, hypoparathyroidism in 1, and unknown in 1), and 1 child had basal ganglia calcification secondary to primary hypoparathyroidism. Other important noninflammatory causes of acute movement disorders included psychogenic in 4 and drugs (metoclopramide induced dystonia) in 3. Table 1 summarizes the distribution of various acute movement disorders attributable to noninflammatory etiologies. We also compared the results of our study with those of a study by Dale et al,6 the only other study on the subject, as depicted in Table 2.

Underlying Etiology

Discussion

We classified the etiologies underlying the acute movement disorders into 2 groups, inflammatory and noninflammatory, according to a previously reported study6 and for ease of comparison. The autoimmune and infectious groups were included in the inflammatory category.

This study reveals that acute movement disorders form an important clinical entity in pediatric neurology practice in a busy tertiary care hospital even though literature on the frequency of various acute movement disorders and their underlying etiologies in children is sparse and scattered at best. There is only one previous study on the subject of acute movement disorders in children.6 Our study, therefore, is a significant addition to the field of acute movement disorders in children. Though retrospective in nature, it is the largest reported to date, and describes children with acute movement disorders in the epidemiologic setting of the developing world.

Inflammatory Group Inflammatory, autoimmune, and infectious etiology of an acute movement disorder was present in 32 of 92 (35%) children. Seventeen children in this group had an underlying autoimmune basis for their acute movement disorders. Of these, 7 had opsoclonus myoclonus syndrome (3 had underlying neuroblastoma) and rheumatic chorea occurred in 6. In 3 children, acute movement disorder was caused by acute demyelinating encephalomyelitis. Infectious etiology was responsible for acute movement disorders in 13, largely accounted by encephalitis of presumed viral etiology. Two children presented

Acute Movement Disorders From a phenomenological point of view, all kinds of common movement disorders, for example, choreoathetosis, dystonia, myoclonus, tremors, and parkinsonism, were seen but not necessarily in that order, in our patients. The relative frequency

408

2 Tetanus (2) 13 Tics (2) 2 17

ADEM (1) 17

Benign neonatal sleep myoclonus (16), benign myoclonus of infancy (1)

Physiological

Metabolic/nutritional

Psychogenic (1)

Miscellaneous

4

Mercury poisoning (1)

Hypocalcemic tetany (3) 25

Psychogenic tetany (2) 14

Vitamin B12 deficiency (13) Traumatic brain injury (1)

Metoclopramide Glutaric aciduria type 1(3), Benign paroxysmal torticollis (2), PAID (2), ataxia- telangiectasia (1), (3) PKAN (1), psychogenic (1), cryptogenic (1), Leukodystrophy (1), BGH (1) hypoparathyroidism (1) Leigh disease (2) MELAS (1) Traumatic brain injury (1), cryptogenic (1)

Drugs/toxins

Noninflammatory

Abbreviations: ADEM, acute demyelinating encephalomyelitis; BGH, basal ganglia hemorrhage; MELAS, mitochondrial encephalomyopathy, lactic acidosis, and strokelike episodes; NMDARE, N-methyl-D-aspartate receptor encephalitis; PKAN, pantothenate kinase-associated neurodegeneration; PAID, paroxysmal autonomic instability with dystonia.

Parkinsonism (3) Others (9) Total (92)

Tremors (15)

6

Choreo-athetosis (19)

Rheumatic chorea (6), NMDARE (1), ADEM (1)

ADEM (1)

3

Dystonia (21)

Postinfectious Autoimmune Opsoclonus myoclonus syndrome (7)

Infectious/ encephalitis

Inflammatory

Myoclonus (25)

Movement disorder

Table 1. Acute Movement Disorders and the Underlying Etiology.

Goraya

409

Table 2. Comparison of Studies on Acute Movement Disorders in Children

Number of patients Age Gender (male:female) Types of AMD

Dale et al6

Present study

52 2 mo-15 y 21:31 Hyperkinetica (n ¼ 59) Chorea (n ¼ 20), dystonia(n ¼ 17), tremors (n ¼ 12), myoclonus (n ¼ 10)

92 5 d-15 y 63:29 Hyperkinetic (n ¼ 89) Myoclonus (n ¼ 25), dystonia (n ¼ 21), choreoathetosis (n ¼ 19), tremors (n ¼ 15), tics (n ¼ 2), tetany (n ¼ 5), tetanus (n ¼ 2)

Hypokinetic (n ¼ 10) Parkinsonism (n ¼ 10) Etiology

Inflammatory/immune/infectious (n ¼ 22) NMDAR encephalitis (n ¼ 5), opsoclonus myoclonus syndrome (n ¼ 4), rheumatic (n ¼ 3), lupus (n ¼ 3), acute necrotizing encephalopathy (n ¼ 3), other encephalitis (n ¼ 4) Noninflammatory (n ¼ 18) Drug induced (n ¼ 7), postpump chorea (n ¼ 5), metabolic (n ¼ 3), vascular (n ¼ 2) Psychogenic (n ¼ 12)

Hypokinetic (n ¼ 3) Parkinsonism (n ¼ 3) Inflammatory/immune/infectious (n ¼ 32) Encephalitis (n ¼ 11), opsoclonus myoclonus syndrome (n ¼ 7), rheumatic (n ¼ 6), acute demyelinating encephalomyelitis (n ¼ 3), tetanus (n ¼ 2), postinfectious tics (n ¼ 2), NMDAR encephalitis (n ¼ 1) Noninflammatory (n ¼ 56) Metabolic/nutritional (n ¼ 25), physiological (n ¼ 17), drugs/toxins (n ¼ 4), vascular (n ¼ 1), traumatic brain injury (n ¼ 2), benign paroxysmal torticollis (n ¼ 2), paroxysmal autonomic instability with dystonia (n ¼ 2), cryptogenic (n ¼ 2), ataxia-telangiectasia (n ¼ 1) Psychogenic (n ¼ 4)

Abbreviations: AMD, acute movement disorder; NMDAR, N-methyl-D-aspartate disorder receptor. a Some patients had more than 1 type of movement disorders.

of various acute movement disorders in our study is different from that reported by Dale et al.6 This is most likely due to demographic, epidemiologic, and methodologic differences. For example, myoclonus was the most common acute movement disorder in our patients because of inclusion of benign neonatal sleep myoclonus in our study. Neonates were, however, excluded from the study by Dale et al.6 Infantile tremor syndrome is an entity almost exclusively described from the Indian subcontinent7-9 and was responsible for the majority of cases of tremors in our study. We also included children with tetanus and tetany. A male preponderance in our study likely represents the gender bias that is quite common in India as far as access to health care services is concerned.

Etiologic Considerations Both inflammatory and noninflammatory etiologies were encountered. Unlike in the study by Dale et al,6 where inflammatory causes outnumbered the noninflammatory, the reverse was seen in our patients. This was because of causes such as nutritional deficiencies and benign neonatal sleep myoclonus, which were seen in relatively large numbers of children in our cohort. We had underrepresentation of psychogenic movement disorders10,11 and N-methyl-D-aspartate (NMDA) receptor encephalitis–associated movement disorder.12-14 In the inflammatory causes, majority of the cases were contributed by encephalitis. Various forms of encephalitides are common in developing countries, and infections by

viruses such as Japanese encephalitis are particularly common in our country and are frequently associated with extrapyramidal symptomatology. In the absence of access to virologic confirmation of diagnosis, we grouped the cases under the category of ‘‘presumed viral etiology.’’ Nonspecific encephalitis was also seen as a significant contributor to the causes of acute movement disorders in the study by Dale et al.6 Other inflammatory/autoimmune etiologies such as rheumatic chorea, opsoclonus myoclonus syndrome, and acute demyelinating encephalomyelitis reported by Dale et al6 were also predominantly seen in our study. In contrast to 5 cases of NMDA receptor encephalitis reported by Dale et al,6 we had only 1 patient with NMDA receptor encephalitis. This child was a 3-year-old boy with insomnia, encephalopathy, and severe generalized dyskinesia with a self-injurious behavior of tongue biting. Serum was positive for NMDA receptor antibodies. It is only recently that NMDA receptor is being recognized as the cause of encephalitic presentation in children and we have very likely underrecognized this entity in the past in the absence of easy access to NMDA receptor antibody testing. We did not encounter any cases of systemic lupus erythematosus causing acute movement disorders, but rheumatic chorea was a major contributor to the etiology of choreoathetosis. We diagnosed tetanus in 2 children with spontaneous as well as stimulus-induced body spasms and trismus. These children (along with children with tetany) presented for emergent evaluation. Because these entities are not seizures but cause involuntary muscle spasms resulting in abnormal

410 postures, we included them in our cohort. Absence of tetanus from the Western literature on (acute) movement disorders is probably related to its virtual elimination from these countries as a result of effective vaccination. By including these entities in our cohort, we have tried to expand the scope of acute movement disorders in children. Of the noninflammatory etiologies, drugs, vascular causes, as well as metabolic disorders such as glutaric aciduria type 1 and Leigh disease were similar to those reported by Dale et al.6 Pantothenate-kinase associated neurodegeneration and unspecified leukodystrophy though typically do not cause acute movement disorders but were included in the study because the affected children presented with acute dystonia of very short duration. Certain noninflammatory etiologies, however, were conspicuously prominent in our children with acute movement disorders. These were the benign neonatal sleep myoclonus, and nutritional deficiency syndromes. Benign neonatal sleep myoclonus, as the name suggests, refers to the occurrence of multifocal myoclonus in neonates in the first few days of life during sleep and its disappearance with arousal.15,16 The disorder tends to resolve with age but often is confused with neonatal seizures. From the phenomenological viewpoint, these abnormal movements are myoclonus, and nonepileptic in nature, and hence qualify as a movement disorder. We included it in our study because it frequently had dramatic presentation requiring emergency visits, and most of the cases were (mis)treated as seizures before referral. Neurologists need to be aware of this disorder to avoid unnecessary investigations and potentially harmful treatments. The second and the largest category of acute movement disorders in noninflammatory etiologies was the nutritional group. Most of these cases were due to nutritional B12 deficiency in infants who were being exclusively breastfed by mother who themselves had B12 deficiency because of vegetarianism either by choice or forced by poverty. These infants are labeled as having infantile tremor syndrome.7-9 The tremors in such infants can be so severe at times that they persist in sleep and also interfere with feeding. The movement disorder in infantile tremor syndrome is generally termed tremor though in its severest form it appears as a combination of tremors and multifocal myoclonus. In fullblown cases, tremors become the dominant clinical concern, overshadowing the other clinical manifestations of the syndrome. The tremors usually begin asymmetrically with the upper extremities but soon become generalized. Involvement of oral-lingual-facial musculature is quite characteristic, giving rise to a distinctive tremulous character to the vocalizations or crying (goat’s cry). The tremors sometimes are triggered or made worse by treatment with vitamin B12 before getting better. Persistent neurodevelopmental deficits can result in cases where there is delay in recognition and treatment of this disorder. We also had 2 children who had nutritional vitamin D deficiency causing hypocalcemic tetany with carpopedal spasm. Psychogenic movement disorders were uncommon in our study. It is quite likely that some of the children with abnormal movements of psychogenic

Journal of Child Neurology 30(4) origin in our study were labelled as non-epileptic seizures rather than a specific movement disorder. Acute movement disorders can be associated with considerable morbidity and mortality, largely because of the serious nature of the underlying disorder. In some cases, the movement disorder per se may be very disabling and potentially fatal, causing exhaustion, rhabdomyolysis, acute renal shutdown, and other systemic metabolic derangements, requiring admission to intensive care units.5,6 As many as 22 children in our cohort were admitted to the intensive care unit. A perusal of the different etiologies reported in our study and also described by Dale et al6 shows that majority of the disorders underlying acute movement disorders are potentially treatable with good outcome. Inflammatory disorders are especially amenable to treatment with immunomodulatory interventions such as steroids and immunoglobulins.5,6 A major limitation of the study is its retrospective nature. Additional confounding factors include gender bias and selection bias as the cases included were derived from the experience of a single author. We are beginning to recognize the autoimmune encephalitis secondary to NMDA receptor antibodies, and acute movement disorders of psychogenic origin. These entities are less represented in our current cohort. The incidence of rheumatic chorea seems declining even in the developing countries like ours. These factors are expected to alter the relative contribution of different etiologies in the causation of acute movement disorders in future studies.

Conclusions Movement disorders of all the common types can be seen presenting acutely in children. The relative frequency of these acute movement disorders and their causative diseases is presented and contrasts with that reported from the West. Certain etiologies specific to the Indian subcontinent were seen. More studies are needed to further our knowledge on the epidemiology, clinical presentation, treatment, and outcome of acute movement disorders in children. Author’s Note Part of the data were presented at the 17th International Congress of Parkinson’s Disease and Movement disorders in Sydney, Australia 2013. [Goraya, JS. Acute Movement Disorders in Children: Experience from a Developing Country. Mov Disord. 2013;28:S330-S330.]

Declaration of Conflicting Interests The author declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding The author received no financial support for the research, authorship, and/or publication of this article.

Ethical Approval The study was approved by the institutional ethical review board, DMCH/R&D/2014/125.

Goraya References 1. Frucht SJ, Fahn S. A brief introduction to movement disorders. In: Frucht SJ, Fahn S, eds. Movement Disorder Emergencies: Diagnosis and Treatment. Totowa, NJ: Humana Press;2005:1-7. 2. Robottom BJ, Weiner WJ, Factor SA. Movement disorders emergencies, Part 1: Hypokinetic disorders. Arch Neurol. 2011;68: 567-572. 3. Robottom BJ, Factor SA, Weiner WJ. Movement disorders emergencies, Part 2: Hyperkinetic disorders. Arch Neurol. 2011;68: 719-724. 4. Kipps CM, Fung VSC, Grattan-Smith P, et al. Movement disorder emergencies. Mov Disord. 2005;20:322-334. 5. Kirkham FJ, Haywood P, Kashyape P, et al. Movement disorder emergencies in childhood. Eur J Paed Neurol. 2011;15:390-404. 6. Dale RC, Singh H, Troedson C, et al. A prospective study of acute movement disorders in children. Dev Med Child Neurol. 2010;52:739-748. 7. Sharda B, Bhandari B. Infantile tremor syndrome. Indian Pediatr. 1987;24:415-421. 8. Garewal G, Narang A, Das KC. Infantile tremor syndrome: a vitamin B12 deficiency syndrome in infants. J Trop Pediatr. 1988;34: 174-178.

411 9. Goraya JS. Vitamin B12 deficiency in childhood and adolescence. J Pediatr. 2002;140:636. 10. Ferrara J, Jankovic J. Psychogenic movement disorders in children. Mov Disord. 2008;23:1875-1881. 11. Schwingenschhu P, Pont-Sunyer C, Surtees R, et al. Psychogenic movement disorders in children: a report of 15 cases and a review of the literature. Mov Disord. 2008;23:1882-1888. 12. Armangue T, Petit-Pedrol M, Dalmau J. Autoimmune encephalitis. J Child Neurol. 2012;27:1460-1469. 13. Chakraborty B, Tripathy M, Gulati S, et al. Pediatric anti-Nmethyl-D-aspartate (NMDA) receptor encephalitis: experience of a tertiary care teaching center from North India. J Child Neurol. Oct 4, 2013 [Epub ahead of print]. 14. Goldberg EM, Titulaer M, de Blank PM, et al. Anti-N-methyl-Daspartate receptor-mediated encephalitis in infants and toddlers: case report and review of the literature. Pediatr Neurol. 2014; 50:181-184. 15. Kaddurah AK, Holmes GL. Benign neonatal sleep myoclonus: history and semiology. Pediatr Neurol. 2009;40:343-346. 16. Maurer VO, Rizzi M, Bianchetti MG, Ramelli GP. Benign neonatal sleep myoclonus: a review of the literature. Pediatrics. 2010; 125:e919-e924.

Acute movement disorders in children: experience from a developing country.

We describe acute movement disorders in 92 children, aged 5 days to 15 years, from an Indian tertiary hospital. Eighty-nine children had hyperkinetic ...
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