- Email: [email protected]
Opsoclonus-Myoclonus Syndrome, Neuroblastoma, and Insulin-Dependent Diabetes Mellitus in a Child: A Unique Patient
Pediatric Neurology 55 (2016) 68e70
Contents lists available at ScienceDirect
Pediatric Neurology journal homepage: www.elsevier.com/locate/pnu
Clinical Observations
Opsoclonus-Myoclonus Syndrome, Neuroblastoma, and Insulin-Dependent Diabetes Mellitus in a Child: A Unique Patient Twinkle Ghia FRACP a, Manoj Kanhangad MBBS a, Angela Jane Alessandri FRACP b, Glynis Price FRACP c, Parshotam Gera FRACS d, Lakshmi Nagarajan FRACP a, e, * a
Department of Neurology, Princess Margaret Hospital, Perth, Western Australia, Australia Department of Oncology, Princess Margaret Hospital, Perth, Western Australia, Australia c Department of Endocrinology, Princess Margaret Hospital, Perth, Western Australia, Australia d Department of Paediatric Surgery, Princess Margaret Hospital, Perth, Western Australia, Australia e School of Paediatrics and Child Health, University of Western Australia, Princess Margaret Hospital, Perth, Western Australia, Australia b
abstract AIM: We present a new and unique association of opsoclonus-myoclonus-ataxia syndrome with neuroblastoma and type 1 diabetes mellitus. PATIENT DESCRIPTION: This 17-month-old child presented with opsoclonusmyoclonus-ataxia syndrome. Investigations revealed a thoracic neuroblastoma. Eleven days later, she represented with diabetic ketoacidosis. The neuroblastoma was resected, and she was given immunotherapy. At 12 months’ follow-up, her neurological signs and symptoms have significantly improved, but she continues to be insulin dependent. DISCUSSION: This child expands the clinical spectrum of autoimmune disorders associated with opsoclonus-myoclonus-ataxia syndrome. Keywords: opsoclonus myoclonus ataxia, type I diabetes mellitus, neuroblastoma, anti-GAD antibodies
Pediatr Neurol 2016; 55: 68-70 Ó 2016 Elsevier Inc. All rights reserved.
Introduction
Opsoclonus-myoclonus-ataxia syndrome is a rare neurological disorder. It is also called the dancing eyes syndrome or the Kinsbourne syndrome and is characterized by three main features: opsoclonus, myoclonus, and ataxia. It is often associated with behavior disturbances and sleep problems. Opsoclonus-myoclonus-ataxia syndrome affects mainly young children (mean age 1.5-2 years) and has an estimated incidence of 0.18 cases per million per year.1,2 The association of opsoclonus-myoclonus-ataxia with neuroblastoma in childhood is well known: neuroblastoma is detected in 40%-80% of children with opsoclonus-myoclonus-ataxia, and about 3% of children
Article History: Received June 28, 2015; Accepted in final form September 26, 2015 * Communications should be addressed to: Dr. Nagarajan; Department of Neurology; Princess Margaret Hospital for Children; Roberts Road; Subiaco, Perth, Western Australia 6008, Australia. E-mail address: [email protected] 0887-8994/$ e see front matter Ó 2016 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.pediatrneurol.2015.09.021
with neuroblastoma develop opsoclonus-myoclonusataxia.1-3 Opsoclonus-myoclonus-ataxia may also occur with viral infections, immune-mediated encephalitides, and other autoimmune conditions.4-6 Opsoclonusmyoclonus-ataxia syndrome has recently been reported with vanishing white matter disease.7 Autoimmunity is believed to underlie paraneoplastic and nonparaneoplastic opsoclonus-myoclonus-ataxia syndrome. When opsoclonus-myoclonus-ataxia is associated with neuroblastoma, pathogenesis is thought to be secondary to an immune response generated by tumor-associated antigens with cross-reactivity to the structures of the central nervous system.6 The long-term neurological prognosis for children with neuroblastoma-related and neuroblastoma-unrelated opsoclonus-myoclonus-ataxia remains poor, despite many advances in this area.6,8 We report a new association of opsoclonusmyoclonus-ataxia and neuroblastoma with type 1 diabetes mellitus in a 17-month-old girl who developed diabetic ketoacidosis 11 days after her initial neurological presentation.
T. Ghia et al. / Pediatric Neurology 55 (2016) 68e70
Patient Description A 17-month-old girl presented with a 2-week history of unsteady gait, irritability, and slurring of speech. Her parents also reported progressive reluctance and refusal to walk. There was history of mild gastroenteritis three weeks prior. There was no significant perinatal or neonatal history. Developmentally she had been progressing appropriately apart from mild language delay. The family history was negative for autoimmune disorders. On clinical examination, she had opsoclonus (not noticed by parents), myoclonus, and ataxiadshe was tremulous with trunk, head, and limb involvement. The child was distressed and reluctant to walk or crawl. The rest of the clinical examination was unremarkable. A presumptive diagnosis of opsoclonus-myoclonus-ataxia syndrome was made and investigations initiated. Chest x-ray showed a large right posterior mediastinal mass; computed tomography scan and magnetic resonance imaging (Figure) confirmed the presence of the right paraspinal mass extending from mid thoracic T3 down to upper T8 level with calcification and necrosis. Intense metaiodobenzylguanidine uptake within the mass supported the diagnosis of neuroblastoma. No other focal abnormalities were demonstrated to suggest metastatic disease. Lumbar puncture was not undertaken and brain magnetic resonance imaging was normal. Catecholamines (dopamine to creatinine, homovanillic acid to creatinine, and hydroxymethylmandelic acid to creatinine ratios) in the urine were elevated. Serum, stool, or urine testing did not identify any infectious pathogen. A computed tomographyeguided biopsy confirmed neuroblastoma on histopathology. Her immunoglobulin levels were normal, and autoimmune investigations including paraneoplastic (Hu, Ri, Yo, amphiphysin, CV2, MA-1, and MA-2), Purkinje cell, thyroid peroxidase, antinuclear, and celiacassociated antibodies, as well as protein tyrosine phosphatase-2 were negative. Neuron-specific enolase was elevated at 29.7 mg/L (normal < 20 mg/L). While awaiting surgical resection of the neuroblastoma, the child re-presented (11 days from initial presentation) with what her parents thought to be respiratory distress. She was not on immunotherapy at that stage. On evaluation she was found to be in diabetic ketoacidosis: arterial blood pH 6.97 (7.35-7.45); HCO3, 1 mol/L (normal 19-28 mol/L); glucose, 19.8 mmol/L (normal 3-5.4 mmol/L); sodium, 139 mol/L (normal 134-143 mol/L); and potassium, 3.5 mol/L (normal 3.5-5 mol/L). This condition was managed initially in the intensive care unit by an insulin infusion. Complete thoracoscopic resection of the neuroblastoma (day 24) after her metabolic status was stabilized did not ameliorate her need for insulin therapy or her opsoclonus-myoclonus-ataxia syndrome. Subsequently insulin was administered via an insulin pump, and she remains on this at
FIGURE. Magnetic resonance image showing the thoracic neuroblastoma.
69
12 months’ follow-up. At the time of presentation with diabetes ketoacidosis (day 11), her glutamic acid decarboxylase (GAD) antibody level was 0.8 units/mL (normal <1 units/mL); on repeat test (day 24) it was elevated at 3.5 units/mL. Immunotherapy was initiated in the form of intravenous immunoglobulin (IVIg) (first dose given on day 12) and steroids (initially prednisolone 2 mg/kg for 5 days, changed to pulse dexamethasone 4 mg twice daily for 3 days, followed by weaning doses). The administration of steroids was ceased because of significant persistent side effects (insomnia, irritability, and cushingoid features). IVIg was continued at monthly intervals, and four doses of rituximab (weekly dose of 375 mg/m2) were given. Currently she is on 6 weekly IVIg infusions. Opsoclonus-myoclonus-ataxia in our child has improved significantly, with only intermittent mild ataxia still being present; she is making developmental gains, but her glycemic control remains challenging.
Discussion
Our patient is unique because of her constellation of opsoclonus-myoclonus-ataxia, type 1 diabetes mellitus, and neuroblastoma. Although the mechanism is speculative, it is intuitive that autoimmunity underpins this association in this child. In neuroblastoma-related opsoclonus-myoclonus syndrome, various autoantibodies against neurons and cerebellar Purkinje cells have been detected but the antigen specificity of these autoantibodies is low and identification of a specific autoantigen remains elusive. In this child, apart from weakly positive anti-GAD antibody titers, no other markers of autoimmunity were seen. GAD is an enzyme that catalyzes the production of g-aminobutyric acid, a major neurotransmitter of the central nervous system. GAD is expressed both in pancreatic b-cells and cerebellar Purkinje cells. Anti-GAD antibodies indicate islet cell autoimmunity that may progress to insulin-dependent diabetes. Antigenbased therapy with GAD vaccine for type 1 diabetes is being evaluated.9 There is a spectrum of neurological syndromes associated with GAD antibodies including stiff person syndrome, cerebellar ataxia, epilepsy, and limbic encephalitis.10 Intrathecal synthesis of GAD is important to confirm that GAD autoimmunity is related to the neurological syndrome particularly with concomitant type 1 diabetes that could justify the presence of high GAD antibody levels.10 The clinical significance of anti-GAD autoantibodies in our patient remains uncertain; it is possible that GAD autoimmunity might underlie both type 1 diabetes mellitus and opsoclonus-myoclonus-ataxia. However, anti-GAD antibody levels were not elevated at the onset of type 1 diabetes mellitus and only became weakly positive on repeat testing in the context of IVIg treatment. Falsepositive autoantibody to GAD in opsoclonus-myoclonus syndrome after treatment with IVIg has been previously reported.11 There is only one report of an 18-month-old child with type 1 diabetes mellitus who developed opsoclonusmyoclonus-ataxia 8 months later; this was not associated with a neuroblastoma.12 In this patient, anti-GAD antibodies were present at the onset of type 1 diabetes mellitus, and the titers increased when myoclonic encephalopathy occurred and decreased with corticosteroid treatment; this also coincided with the disappearance of neurological disturbances. There are also case reports of adult patients
70
T. Ghia et al. / Pediatric Neurology 55 (2016) 68e70
with a diagnosis of diabetes mellitus who developed opsoclonus-myoclonus-ataxia syndrome many years later; the opsoclonus-myoclonus-ataxia in these instances was temporally associated to other pathology, such as septic shock or mycoplasma infection.13,14 The neurological features in this patient have significantly improved, but the diabetes continues to be problematic due to suboptimal glycemic control. The longterm neurodevelopmental outcome is uncertain; we shall remain hopeful and cautiously optimistic as early aggressive immunotherapy is thought to result in a better outcome.15 In conclusion, as far as we can ascertain this is the first report of opsoclonus-myoclonus-ataxia with neuroblastoma and type 1 diabetes mellitus in a child. Our report adds to the emerging literature on the spectrum of autoimmune disorders associated with this rare disorder and the challenges of prognostication. Author contributions: TG prepared the first draft of the manuscript and revised it. MK helped with the first draft. AJA contributed to the clinical details, cared for the patient, and reviewed the final manuscript. GP contributed to the clinical details, cared for the patient, and reviewed the final manuscript. PG contributed to the clinical details, performed the surgery, and reviewed the final manuscript. LN cared for the patient, initiated the case report, and revised the manuscript. Declaration of conflicting interests: None. The authors thank all the clinicians and professionals involved in the care of this child. Funding: None. Ethical approval: Consent obtained from the child’s parents and submitted to the Ethics Committee as required by our organization.
References 1. Pang KK, de Sousa C, Lang B, Pike MG. A prospective study of the presentation and management of dancing eye syndrome/ opsoclonus-myoclonus syndrome in the United Kingdom. Eur J Paediatr Neurol. 2010;14:156.
2. Tate ED, Allison TJ, Pranzatelli MR, Verhulst SJ. Neuroepidemiologic trends in 105 US cases of pediatric opsoclonus-myoclonus syndrome. J Pediatr Oncol Nurs. 2005;22:8. 3. Rudnick E, Khakoo Y, Antunes NL, et al. Opsoclonus-myoclonusataxia syndrome in neuroblastoma: clinical outcome and antineuronal antibodies - a report from the Children’s Cancer Group Study. Med Pediatr Oncol. 2001;36:612. 4. McMinn P, Stratov I, Nagarajan L, Davis S. Neurological manifestations of enterovirus 71 infection in children during an outbreak of hand, foot, and mouth disease in Western Australia. Clin Infect Dis. 2001;32:236-242. 5. Klaas JP, Ahlskog JE, Pittock SJ, et al. Adult-onset opsoclonusmyoclonus syndrome. Arch Neurol. 2012;69:1598-1607. 6. Hero B, Schleiermacher G. Update on pediatric opsoclonus myoclonus syndrome. Neuropediatrics. 2013;44:324-329. 7. Klingelhoefer L, Misbahuddin A, Jawad T, et al. Vanishing white matter disease presenting as opsoclonus myoclonus syndrome in childhood e a case report and review of the literature. Pediatr Neurol. 2014;51:157-164. 8. Brunklaus A, Pohl K, Zuberi SM, de Sousa C. Outcome and prognostic features in opsoclonus-myoclonus syndrome from infancy to adult life. Pediatrics. 2011;128:388-394. 9. Wherrett DK, Bundy B, Becker DJ, et al. Antigen-based therapy with glutamic acid decarboxylase (GAD) vaccine in patients with recentonset type 1 diabetes: a randomised double-blind trial. Lancet. 2011;378:319-327. 10. Saiz A, Blanco Y, Sabater L, et al. Spectrum of neurological syndromes associated with glutamic acid decarboxylase antibodies: diagnostic clues for this association. Brain. 2008;131: 2553-2563. 11. de Beera F, Schreursb MW, Fonckec EM. False positive autoantibodies to glutamic acid decarboxylase in opsoclonuse myoclonuseataxia syndrome after intravenous treatment with immunoglobulin. Clin Neurol Neurosurg. 2009;111:643-644. 12. Lenti C, Bognetti E, Bonfanti R, et al. Myoclonic encephalopathy and diabetes mellitus in a boy. Dev Med Child Neurol. 1999;41:489-490. 13. Nunes JC, Bruscato AM, Walz R, Lin K. Opsoclonus-myoclonus syndrome associated with Mycoplasma pneumoniae infection in an elderly patient. J Neurol Sci. 2011;305:147-148. 14. Daumas A, Gayet S, Bensa P, et al. A case of opsoclonus-myoclonus syndrome following a septic shock. Anaesth Intensive Care. 2013;41: 810-811. 15. Mitchell WG, Wooten AA, O’Neil SH, et al. Effect of increased immunosuppression on developmental outcome of opsoclonus myoclonus syndrome (OMS). J Child Neurol. 2015;30:976-982.
Contents lists available at ScienceDirect
Pediatric Neurology journal homepage: www.elsevier.com/locate/pnu
Clinical Observations
Opsoclonus-Myoclonus Syndrome, Neuroblastoma, and Insulin-Dependent Diabetes Mellitus in a Child: A Unique Patient Twinkle Ghia FRACP a, Manoj Kanhangad MBBS a, Angela Jane Alessandri FRACP b, Glynis Price FRACP c, Parshotam Gera FRACS d, Lakshmi Nagarajan FRACP a, e, * a
Department of Neurology, Princess Margaret Hospital, Perth, Western Australia, Australia Department of Oncology, Princess Margaret Hospital, Perth, Western Australia, Australia c Department of Endocrinology, Princess Margaret Hospital, Perth, Western Australia, Australia d Department of Paediatric Surgery, Princess Margaret Hospital, Perth, Western Australia, Australia e School of Paediatrics and Child Health, University of Western Australia, Princess Margaret Hospital, Perth, Western Australia, Australia b
abstract AIM: We present a new and unique association of opsoclonus-myoclonus-ataxia syndrome with neuroblastoma and type 1 diabetes mellitus. PATIENT DESCRIPTION: This 17-month-old child presented with opsoclonusmyoclonus-ataxia syndrome. Investigations revealed a thoracic neuroblastoma. Eleven days later, she represented with diabetic ketoacidosis. The neuroblastoma was resected, and she was given immunotherapy. At 12 months’ follow-up, her neurological signs and symptoms have significantly improved, but she continues to be insulin dependent. DISCUSSION: This child expands the clinical spectrum of autoimmune disorders associated with opsoclonus-myoclonus-ataxia syndrome. Keywords: opsoclonus myoclonus ataxia, type I diabetes mellitus, neuroblastoma, anti-GAD antibodies
Pediatr Neurol 2016; 55: 68-70 Ó 2016 Elsevier Inc. All rights reserved.
Introduction
Opsoclonus-myoclonus-ataxia syndrome is a rare neurological disorder. It is also called the dancing eyes syndrome or the Kinsbourne syndrome and is characterized by three main features: opsoclonus, myoclonus, and ataxia. It is often associated with behavior disturbances and sleep problems. Opsoclonus-myoclonus-ataxia syndrome affects mainly young children (mean age 1.5-2 years) and has an estimated incidence of 0.18 cases per million per year.1,2 The association of opsoclonus-myoclonus-ataxia with neuroblastoma in childhood is well known: neuroblastoma is detected in 40%-80% of children with opsoclonus-myoclonus-ataxia, and about 3% of children
Article History: Received June 28, 2015; Accepted in final form September 26, 2015 * Communications should be addressed to: Dr. Nagarajan; Department of Neurology; Princess Margaret Hospital for Children; Roberts Road; Subiaco, Perth, Western Australia 6008, Australia. E-mail address: [email protected] 0887-8994/$ e see front matter Ó 2016 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.pediatrneurol.2015.09.021
with neuroblastoma develop opsoclonus-myoclonusataxia.1-3 Opsoclonus-myoclonus-ataxia may also occur with viral infections, immune-mediated encephalitides, and other autoimmune conditions.4-6 Opsoclonusmyoclonus-ataxia syndrome has recently been reported with vanishing white matter disease.7 Autoimmunity is believed to underlie paraneoplastic and nonparaneoplastic opsoclonus-myoclonus-ataxia syndrome. When opsoclonus-myoclonus-ataxia is associated with neuroblastoma, pathogenesis is thought to be secondary to an immune response generated by tumor-associated antigens with cross-reactivity to the structures of the central nervous system.6 The long-term neurological prognosis for children with neuroblastoma-related and neuroblastoma-unrelated opsoclonus-myoclonus-ataxia remains poor, despite many advances in this area.6,8 We report a new association of opsoclonusmyoclonus-ataxia and neuroblastoma with type 1 diabetes mellitus in a 17-month-old girl who developed diabetic ketoacidosis 11 days after her initial neurological presentation.
T. Ghia et al. / Pediatric Neurology 55 (2016) 68e70
Patient Description A 17-month-old girl presented with a 2-week history of unsteady gait, irritability, and slurring of speech. Her parents also reported progressive reluctance and refusal to walk. There was history of mild gastroenteritis three weeks prior. There was no significant perinatal or neonatal history. Developmentally she had been progressing appropriately apart from mild language delay. The family history was negative for autoimmune disorders. On clinical examination, she had opsoclonus (not noticed by parents), myoclonus, and ataxiadshe was tremulous with trunk, head, and limb involvement. The child was distressed and reluctant to walk or crawl. The rest of the clinical examination was unremarkable. A presumptive diagnosis of opsoclonus-myoclonus-ataxia syndrome was made and investigations initiated. Chest x-ray showed a large right posterior mediastinal mass; computed tomography scan and magnetic resonance imaging (Figure) confirmed the presence of the right paraspinal mass extending from mid thoracic T3 down to upper T8 level with calcification and necrosis. Intense metaiodobenzylguanidine uptake within the mass supported the diagnosis of neuroblastoma. No other focal abnormalities were demonstrated to suggest metastatic disease. Lumbar puncture was not undertaken and brain magnetic resonance imaging was normal. Catecholamines (dopamine to creatinine, homovanillic acid to creatinine, and hydroxymethylmandelic acid to creatinine ratios) in the urine were elevated. Serum, stool, or urine testing did not identify any infectious pathogen. A computed tomographyeguided biopsy confirmed neuroblastoma on histopathology. Her immunoglobulin levels were normal, and autoimmune investigations including paraneoplastic (Hu, Ri, Yo, amphiphysin, CV2, MA-1, and MA-2), Purkinje cell, thyroid peroxidase, antinuclear, and celiacassociated antibodies, as well as protein tyrosine phosphatase-2 were negative. Neuron-specific enolase was elevated at 29.7 mg/L (normal < 20 mg/L). While awaiting surgical resection of the neuroblastoma, the child re-presented (11 days from initial presentation) with what her parents thought to be respiratory distress. She was not on immunotherapy at that stage. On evaluation she was found to be in diabetic ketoacidosis: arterial blood pH 6.97 (7.35-7.45); HCO3, 1 mol/L (normal 19-28 mol/L); glucose, 19.8 mmol/L (normal 3-5.4 mmol/L); sodium, 139 mol/L (normal 134-143 mol/L); and potassium, 3.5 mol/L (normal 3.5-5 mol/L). This condition was managed initially in the intensive care unit by an insulin infusion. Complete thoracoscopic resection of the neuroblastoma (day 24) after her metabolic status was stabilized did not ameliorate her need for insulin therapy or her opsoclonus-myoclonus-ataxia syndrome. Subsequently insulin was administered via an insulin pump, and she remains on this at
FIGURE. Magnetic resonance image showing the thoracic neuroblastoma.
69
12 months’ follow-up. At the time of presentation with diabetes ketoacidosis (day 11), her glutamic acid decarboxylase (GAD) antibody level was 0.8 units/mL (normal <1 units/mL); on repeat test (day 24) it was elevated at 3.5 units/mL. Immunotherapy was initiated in the form of intravenous immunoglobulin (IVIg) (first dose given on day 12) and steroids (initially prednisolone 2 mg/kg for 5 days, changed to pulse dexamethasone 4 mg twice daily for 3 days, followed by weaning doses). The administration of steroids was ceased because of significant persistent side effects (insomnia, irritability, and cushingoid features). IVIg was continued at monthly intervals, and four doses of rituximab (weekly dose of 375 mg/m2) were given. Currently she is on 6 weekly IVIg infusions. Opsoclonus-myoclonus-ataxia in our child has improved significantly, with only intermittent mild ataxia still being present; she is making developmental gains, but her glycemic control remains challenging.
Discussion
Our patient is unique because of her constellation of opsoclonus-myoclonus-ataxia, type 1 diabetes mellitus, and neuroblastoma. Although the mechanism is speculative, it is intuitive that autoimmunity underpins this association in this child. In neuroblastoma-related opsoclonus-myoclonus syndrome, various autoantibodies against neurons and cerebellar Purkinje cells have been detected but the antigen specificity of these autoantibodies is low and identification of a specific autoantigen remains elusive. In this child, apart from weakly positive anti-GAD antibody titers, no other markers of autoimmunity were seen. GAD is an enzyme that catalyzes the production of g-aminobutyric acid, a major neurotransmitter of the central nervous system. GAD is expressed both in pancreatic b-cells and cerebellar Purkinje cells. Anti-GAD antibodies indicate islet cell autoimmunity that may progress to insulin-dependent diabetes. Antigenbased therapy with GAD vaccine for type 1 diabetes is being evaluated.9 There is a spectrum of neurological syndromes associated with GAD antibodies including stiff person syndrome, cerebellar ataxia, epilepsy, and limbic encephalitis.10 Intrathecal synthesis of GAD is important to confirm that GAD autoimmunity is related to the neurological syndrome particularly with concomitant type 1 diabetes that could justify the presence of high GAD antibody levels.10 The clinical significance of anti-GAD autoantibodies in our patient remains uncertain; it is possible that GAD autoimmunity might underlie both type 1 diabetes mellitus and opsoclonus-myoclonus-ataxia. However, anti-GAD antibody levels were not elevated at the onset of type 1 diabetes mellitus and only became weakly positive on repeat testing in the context of IVIg treatment. Falsepositive autoantibody to GAD in opsoclonus-myoclonus syndrome after treatment with IVIg has been previously reported.11 There is only one report of an 18-month-old child with type 1 diabetes mellitus who developed opsoclonusmyoclonus-ataxia 8 months later; this was not associated with a neuroblastoma.12 In this patient, anti-GAD antibodies were present at the onset of type 1 diabetes mellitus, and the titers increased when myoclonic encephalopathy occurred and decreased with corticosteroid treatment; this also coincided with the disappearance of neurological disturbances. There are also case reports of adult patients
70
T. Ghia et al. / Pediatric Neurology 55 (2016) 68e70
with a diagnosis of diabetes mellitus who developed opsoclonus-myoclonus-ataxia syndrome many years later; the opsoclonus-myoclonus-ataxia in these instances was temporally associated to other pathology, such as septic shock or mycoplasma infection.13,14 The neurological features in this patient have significantly improved, but the diabetes continues to be problematic due to suboptimal glycemic control. The longterm neurodevelopmental outcome is uncertain; we shall remain hopeful and cautiously optimistic as early aggressive immunotherapy is thought to result in a better outcome.15 In conclusion, as far as we can ascertain this is the first report of opsoclonus-myoclonus-ataxia with neuroblastoma and type 1 diabetes mellitus in a child. Our report adds to the emerging literature on the spectrum of autoimmune disorders associated with this rare disorder and the challenges of prognostication. Author contributions: TG prepared the first draft of the manuscript and revised it. MK helped with the first draft. AJA contributed to the clinical details, cared for the patient, and reviewed the final manuscript. GP contributed to the clinical details, cared for the patient, and reviewed the final manuscript. PG contributed to the clinical details, performed the surgery, and reviewed the final manuscript. LN cared for the patient, initiated the case report, and revised the manuscript. Declaration of conflicting interests: None. The authors thank all the clinicians and professionals involved in the care of this child. Funding: None. Ethical approval: Consent obtained from the child’s parents and submitted to the Ethics Committee as required by our organization.
References 1. Pang KK, de Sousa C, Lang B, Pike MG. A prospective study of the presentation and management of dancing eye syndrome/ opsoclonus-myoclonus syndrome in the United Kingdom. Eur J Paediatr Neurol. 2010;14:156.
2. Tate ED, Allison TJ, Pranzatelli MR, Verhulst SJ. Neuroepidemiologic trends in 105 US cases of pediatric opsoclonus-myoclonus syndrome. J Pediatr Oncol Nurs. 2005;22:8. 3. Rudnick E, Khakoo Y, Antunes NL, et al. Opsoclonus-myoclonusataxia syndrome in neuroblastoma: clinical outcome and antineuronal antibodies - a report from the Children’s Cancer Group Study. Med Pediatr Oncol. 2001;36:612. 4. McMinn P, Stratov I, Nagarajan L, Davis S. Neurological manifestations of enterovirus 71 infection in children during an outbreak of hand, foot, and mouth disease in Western Australia. Clin Infect Dis. 2001;32:236-242. 5. Klaas JP, Ahlskog JE, Pittock SJ, et al. Adult-onset opsoclonusmyoclonus syndrome. Arch Neurol. 2012;69:1598-1607. 6. Hero B, Schleiermacher G. Update on pediatric opsoclonus myoclonus syndrome. Neuropediatrics. 2013;44:324-329. 7. Klingelhoefer L, Misbahuddin A, Jawad T, et al. Vanishing white matter disease presenting as opsoclonus myoclonus syndrome in childhood e a case report and review of the literature. Pediatr Neurol. 2014;51:157-164. 8. Brunklaus A, Pohl K, Zuberi SM, de Sousa C. Outcome and prognostic features in opsoclonus-myoclonus syndrome from infancy to adult life. Pediatrics. 2011;128:388-394. 9. Wherrett DK, Bundy B, Becker DJ, et al. Antigen-based therapy with glutamic acid decarboxylase (GAD) vaccine in patients with recentonset type 1 diabetes: a randomised double-blind trial. Lancet. 2011;378:319-327. 10. Saiz A, Blanco Y, Sabater L, et al. Spectrum of neurological syndromes associated with glutamic acid decarboxylase antibodies: diagnostic clues for this association. Brain. 2008;131: 2553-2563. 11. de Beera F, Schreursb MW, Fonckec EM. False positive autoantibodies to glutamic acid decarboxylase in opsoclonuse myoclonuseataxia syndrome after intravenous treatment with immunoglobulin. Clin Neurol Neurosurg. 2009;111:643-644. 12. Lenti C, Bognetti E, Bonfanti R, et al. Myoclonic encephalopathy and diabetes mellitus in a boy. Dev Med Child Neurol. 1999;41:489-490. 13. Nunes JC, Bruscato AM, Walz R, Lin K. Opsoclonus-myoclonus syndrome associated with Mycoplasma pneumoniae infection in an elderly patient. J Neurol Sci. 2011;305:147-148. 14. Daumas A, Gayet S, Bensa P, et al. A case of opsoclonus-myoclonus syndrome following a septic shock. Anaesth Intensive Care. 2013;41: 810-811. 15. Mitchell WG, Wooten AA, O’Neil SH, et al. Effect of increased immunosuppression on developmental outcome of opsoclonus myoclonus syndrome (OMS). J Child Neurol. 2015;30:976-982.