Pediatric Neurology 51 (2014) 862e863
Contents lists available at ScienceDirect
Pediatric Neurology journal homepage: www.elsevier.com/locate/pnu
Visual Diagnosis
Neurodegeneration With Brain Iron Accumulation Disorder Mimics Autism Montida Veeravigrom MD a, b, *, Tayard Desudchit MD a, b, Krisnachai Chomtho MD a, b, Wiroje Pongpunlert MD a, b a
Division of Neurology, Department of Pediatrics, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand Division of Neurology, Department of Pediatrics, King Chulalongkorn Memorial Hospital/Thai Red Cross Society, Bangkok, Thailand
b
This 15-year-old Thai girl who was diagnosed with autism by a child psychiatrist at 3 years of age. She was born to healthy, nonconsanguineous parents. Pregnancy, labor, and delivery were normal, and her neonatal period was uneventful. The patient had normal development until 3 months of age and had a global delay of 12 months compared with normal milestones. When she was one year old, she began to crawl. Her parents noticed her walking on the tips of her toes with ataxia and frequent falls. At 18 months, she spoke only a few words. When she entered the prekindergarten level, her teacher reported that she had a poor attention span, remarking that she could finish her work quickly but that the work was filled with mistakes. The child often played by herself and demonstrated repetitive and stereotypic behavior without imaginative play. Her speech development was slow. She began talking in broken sentences with poor pronunciation and comprehension. At age 3 years, a child psychiatrist diagnosed autism. Six months later, a pediatric neurologist diagnosed autism with spastic diplegia as spasticity increased in her lower extremities. Normal investigations included electroencephalography, auditory brainstem responses, and thyroid function tests. She received physical, occupational, and speech therapy and along with botulinum toxin injections for spasticity. Her first in a series of magnetic resonance imaging (MRI) examinations was performed 18 months after her presentation; it demonstrated abnormally low signal intensity in the globus pallidus, posterior limb of the internal capsule, substantia nigra, and pontine corticospinal tract (Fig 1). The findings were consistent with iron deposition in the brain. The diagnosis of neurodegeneration with brain iron accumulation (NBIA) was made in spite of a lack of the * Communications should be addressed to: Dr. Veeravigrom; Division of Neurology; Department of Pediatrics; Chulalongkorn University; Bangkok 10330, Thailand. E-mail address: [email protected] 0887-8994/$ - see front matter Ó 2014 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.pediatrneurol.2014.08.033
FIGURE 1. The initial T2 brain magnetic resonance imaging demonstrated abnormal low signal intensity in globus pallidus and posterior limb of internal capsule.
“eye-of-the-tiger” sign. At 5 years 10 months, her spasticity increased, and she lost her ability to walk. Two years later, she lost her sitting balance and developed dysphonia and dysphagia. At 10 years of age, she developed dystonic movements and tonic seizures. At 14 years, her condition
M. Veeravigrom et al. / Pediatric Neurology 51 (2014) 862e863
863
Discussion
NBIA is a complex heterogeneous age-dependent disease entity presenting with a wide spectrum of extrapyramidal features including spasticity and, more recently, neuropsychiatric features.1 Hallervorden and Spatz first described high levels of brain iron in five sisters with progressive neurological dysfunction in 1922. Hallervorden became a controversial figure because of his subsequent wartime activities.2 With the discovery of PANK2 (pantothenate kinase 2) gene, the syndrome was renamed “pantothenate kinase associated neurodegeneration syndrome.”3 The development of high-field MRI in the 1980s led to the first identification of the characteristic “eye-ofthe-tiger” imaging sign.4 In recent years, advanced genetic innovations have broadened clinical knowledge and spectrum of NBIA. NBIA often presents as a series of developmental disorders. In our patient, autism was the predominant initial manifestation preceding the progression of the disease over a course of 12 years.
FIGURE 2. Axial T2 brain magnetic resonance imaging at 15 years of age demonstrated cortical atrophy and progressive iron deposition in the globus pallidus.
progressed, and she developed spastic quadriparesis. Her second MRI at age 15 years, revealed symmetrical abnormal signal intensity in the globus pallidi and, to a lesser degree, in substantia nigra, caudate nuclei, and putamina associated with atrophic changes of both caudate nuclei which had progressed from previous MRI findings (Fig 2).
References 1. Gregory A, Polster BJ, Hayflick SJ. Clinical and genetic delineation of neurodegeneration with brain iron accumulation. J Med Genet. 2009; 46:73-80. 2. Shevell MI, Peiffer J. Julius Hallervorden’s wartime activities: implications for science under dictatorship. Pediatr Neurol. 2001;25: 162-165. 3. Zhou B, Westaway SK, Levinson B, Johnson MA, Gitschier J, Hayflick SJ. A novel pantothenate kinase gene (PANK2) is defective in Hallervorden-Spatz syndrome. Nat Genet. 2001;28:345-349. 4. Brass SD, Chen NK, Mulkern RV, Bakshi R. Magnetic resonance imaging of iron deposition in neurological disorders. Top Magn Reson Imaging. 2006;17:31-40.
Contents lists available at ScienceDirect
Pediatric Neurology journal homepage: www.elsevier.com/locate/pnu
Visual Diagnosis
Neurodegeneration With Brain Iron Accumulation Disorder Mimics Autism Montida Veeravigrom MD a, b, *, Tayard Desudchit MD a, b, Krisnachai Chomtho MD a, b, Wiroje Pongpunlert MD a, b a
Division of Neurology, Department of Pediatrics, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand Division of Neurology, Department of Pediatrics, King Chulalongkorn Memorial Hospital/Thai Red Cross Society, Bangkok, Thailand
b
This 15-year-old Thai girl who was diagnosed with autism by a child psychiatrist at 3 years of age. She was born to healthy, nonconsanguineous parents. Pregnancy, labor, and delivery were normal, and her neonatal period was uneventful. The patient had normal development until 3 months of age and had a global delay of 12 months compared with normal milestones. When she was one year old, she began to crawl. Her parents noticed her walking on the tips of her toes with ataxia and frequent falls. At 18 months, she spoke only a few words. When she entered the prekindergarten level, her teacher reported that she had a poor attention span, remarking that she could finish her work quickly but that the work was filled with mistakes. The child often played by herself and demonstrated repetitive and stereotypic behavior without imaginative play. Her speech development was slow. She began talking in broken sentences with poor pronunciation and comprehension. At age 3 years, a child psychiatrist diagnosed autism. Six months later, a pediatric neurologist diagnosed autism with spastic diplegia as spasticity increased in her lower extremities. Normal investigations included electroencephalography, auditory brainstem responses, and thyroid function tests. She received physical, occupational, and speech therapy and along with botulinum toxin injections for spasticity. Her first in a series of magnetic resonance imaging (MRI) examinations was performed 18 months after her presentation; it demonstrated abnormally low signal intensity in the globus pallidus, posterior limb of the internal capsule, substantia nigra, and pontine corticospinal tract (Fig 1). The findings were consistent with iron deposition in the brain. The diagnosis of neurodegeneration with brain iron accumulation (NBIA) was made in spite of a lack of the * Communications should be addressed to: Dr. Veeravigrom; Division of Neurology; Department of Pediatrics; Chulalongkorn University; Bangkok 10330, Thailand. E-mail address: [email protected] 0887-8994/$ - see front matter Ó 2014 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.pediatrneurol.2014.08.033
FIGURE 1. The initial T2 brain magnetic resonance imaging demonstrated abnormal low signal intensity in globus pallidus and posterior limb of internal capsule.
“eye-of-the-tiger” sign. At 5 years 10 months, her spasticity increased, and she lost her ability to walk. Two years later, she lost her sitting balance and developed dysphonia and dysphagia. At 10 years of age, she developed dystonic movements and tonic seizures. At 14 years, her condition
M. Veeravigrom et al. / Pediatric Neurology 51 (2014) 862e863
863
Discussion
NBIA is a complex heterogeneous age-dependent disease entity presenting with a wide spectrum of extrapyramidal features including spasticity and, more recently, neuropsychiatric features.1 Hallervorden and Spatz first described high levels of brain iron in five sisters with progressive neurological dysfunction in 1922. Hallervorden became a controversial figure because of his subsequent wartime activities.2 With the discovery of PANK2 (pantothenate kinase 2) gene, the syndrome was renamed “pantothenate kinase associated neurodegeneration syndrome.”3 The development of high-field MRI in the 1980s led to the first identification of the characteristic “eye-ofthe-tiger” imaging sign.4 In recent years, advanced genetic innovations have broadened clinical knowledge and spectrum of NBIA. NBIA often presents as a series of developmental disorders. In our patient, autism was the predominant initial manifestation preceding the progression of the disease over a course of 12 years.
FIGURE 2. Axial T2 brain magnetic resonance imaging at 15 years of age demonstrated cortical atrophy and progressive iron deposition in the globus pallidus.
progressed, and she developed spastic quadriparesis. Her second MRI at age 15 years, revealed symmetrical abnormal signal intensity in the globus pallidi and, to a lesser degree, in substantia nigra, caudate nuclei, and putamina associated with atrophic changes of both caudate nuclei which had progressed from previous MRI findings (Fig 2).
References 1. Gregory A, Polster BJ, Hayflick SJ. Clinical and genetic delineation of neurodegeneration with brain iron accumulation. J Med Genet. 2009; 46:73-80. 2. Shevell MI, Peiffer J. Julius Hallervorden’s wartime activities: implications for science under dictatorship. Pediatr Neurol. 2001;25: 162-165. 3. Zhou B, Westaway SK, Levinson B, Johnson MA, Gitschier J, Hayflick SJ. A novel pantothenate kinase gene (PANK2) is defective in Hallervorden-Spatz syndrome. Nat Genet. 2001;28:345-349. 4. Brass SD, Chen NK, Mulkern RV, Bakshi R. Magnetic resonance imaging of iron deposition in neurological disorders. Top Magn Reson Imaging. 2006;17:31-40.
