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Structural Focal Temporal Lobe Seizures in a Child With Lipoproteinosis
Pediatric Neurology 52 (2015) 104e106
Contents lists available at ScienceDirect
Pediatric Neurology journal homepage: www.elsevier.com/locate/pnu
Clinical Observations
Structural Focal Temporal Lobe Seizures in a Child With Lipoproteinosis Martina Balestri MD a, b, *, Simona Cappelletti Psy c, Massimiliano Valeriani MD, PhD a, Federico Vigevano MD a a
Neurology Division, Bambino Gesù Children Hospital, IRCCS, Rome, Italy PhD School in Applied Neurological Sciences, University of Siena, Italy c Unit of Clinical Psychology, Bambino Gesù Children’s Hospital, IRCCS, Rome, Italy b
abstract BACKGROUND: Lipoproteinosis is a rare autosomal recessive disorder caused by a mutation in a gene (ECM1) on chromosome 1q21. Alterations of membrane and vessels in the dermal-epidermal junction represent the pathologic background of the disease. Calcification in the temporal lobes and hippocampi are common and may be associated with epileptic seizures. PATIENT DESCRIPTION: We describe a 7-year-old girl with lipoproteinosis who presented with hoarseness, typical skin lesions, and seizures. RESULTS: Video electroencephalography demonstrated focal temporal lobe seizures. Intelligence quotient was normal, but psychologic tests revealed depressed mood. Neuroimaging revealed bilateral mesial temporal lobe calcifications. CONCLUSIONS: The report reveals that the temporal lobe calcifications and the consequent epileptic seizures can appear even very early. The psychological signs may reflect limbic system dysfunction. Keywords: EEG, temporal seizure, lipoproteinosis, cutaneous and mucosal hyalinosis or Urbach-Wiethe syndrome
Pediatr Neurol 2015; 52: 104-106 Ó 2015 Elsevier Inc. All rights reserved.
Introduction
Lipoproteinosis is a rare autosomal recessive disease; it is also known as cutaneous and mucosal hyalinosis or UrbachWiethe syndrome. Lipoproteinosis is caused by a mutation in a gene on chromosome 1q21 that encodes for a glycoprotein (ECM1),1 expressed in the dermis, basal keratinocytes, endothelial cells, and developing bones, and it is connected to cell differentiation, regulation, collagen composition, and growth-factor binding. Although the protein function is uncertain, it might maintain the dermal homeostasis. The loss of function of the gene leads to a deposition of hyaline-like material and disruption-duplication of the basement membrane, resulting in thickening of the skin and mucous membranes.2 Article History: Received April 30, 2014; Accepted in final form August 26, 2014 * Communications should be addressed to: Dr. Balestri; Division of Neurology; Bambino Gesù Children’s Hospital; IRCCS P.za S. Onofrio; 4 00165 Rome, Italy. E-mail address: [email protected] 0887-8994/$ - see front matter Ó 2015 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.pediatrneurol.2014.08.023
The first clinical sign is often hoarseness, which is caused by infiltration of the vocal cords and usually develops within the first year of life. Later, skin lesions appear, such as pox-like and acneiform scars.1 Treatment with oral steroids, dimethyl sulfoxide, heparin, or laser surgery can rarely improve the mucocutaneous manifestations. Life expectancy of individuals with lipoproteinosis is normal, although there is some risk of respiratory obstruction. Although cutaneous manifestations are the cardinal signs, lipoproteinosis is a multisystemic disease that may involve the eyes, heart, liver, small intestine, lungs, ovary, testes, prostate, pancreas, kidneys, and skeletal muscle.2 Neurological manifestations are also possible, yet rare. Intracranial calcifications are the most often reported findings and can be located anywhere in the brain.1,3 The incidence of epilepsy in lipoproteinosis is unknown.4 In spite of having been described as a common manifestation especially in association with intracerebral calcifications,3,4 childhood onset of epilepsy is rare. There are only five reported patients who experienced epilepsy during childhood.
M. Balestri et al. / Pediatric Neurology 52 (2015) 104e106
105
FIGURE 1. The onset of a focal seizure onset (arrow) is characterized by hypersynchronous rhythmic theta activity arising from the right temporal lobe. (The color version of this figure is available in the online edition.)
Patient Description We describe a girl with regular neuropsychomotor development. She was born by Cesarean delivery, scheduled at 36 weeks of gestation due to repeated threatened miscarriages during pregnancy. Her parents reported third degree consanguinity. She was asymptomatic until the age of 5 months, when she developed hoarseness during crying. In spite of early fiberoptic laryngoscopy that was performed twice, lipoproteinosis was diagnosed at age 4 years, when she manifested the typical skin lesions, such as rash, papules, and scars. Genetic examination revealed an ECM1 mutation. She had taken acitretin (0.5 mg/kg) for 2 years, with poor results. We observed her at age 7 years, when she began to experience seizures. The first episode was characterized by sudden fear, followed by throat constriction and breathing difficulties. Similar episodes, lasting 10-20 seconds each, occurred over the following weeks. She was aware of the impending seizures and was able to inform her parents. Other manifestations that could precede or follow the seizures included “déjà vu,” stomachache, body heat, and drowsiness without any evidence of loss of consciousness. During seizures, the child was able to speak fluently. Seizures were infrequent at onset, but later their frequency increased up to many episodes per week. General and neurological examinations were normal except for hoarseness and skin lesions, as described previously. The girl was right handed. Twenty-one channel video electroencephalography monitoring included both ictal and interictal recordings. A 5-day recording demonstrated interictal sporadic slow and epileptiform discharges arising from the right posterior regions. Sleep structure was normal, and the slow abnormalities were reduced during sleep. Four long-lasting seizures were recorded during both awakefulness and sleep. At seizure onset, she reported a periumbilical undefined feeling, which allowed her to alert the parents. During seizures, she placed one hand on her own abdomen, whereas the other hand was held by that of a parent. She was able to speak and execute simple commands during seizures. During all episodes, the electroencephalograph revealed a paroxysmal discharge, characterized by a hypersynchronous theta rhythmic activity arising from the right temporal region (Fig 1). In some instances, the discharge spread to the ipsilateral parietal region or to the contralateral temporal region.
Carbamazepine did not reduce the seizure frequency. After a few months, clobazam was added, and the number of seizures was reduced. When carbamazepine was replaced by levetiracetam, complete seizure control was achieved. She underwent brain magnetic resonance imaging using a 3-T magnetic resonance imaging scanner, which revealed bilateral mesial temporal lobe calcifications in both amygdala and hippocampus (Fig 2). During neuropsychological assessment, the girl scored a normal intelligence quotient (IQ): 86th percentile to the Progressive Matrices 47 and 103 of total IQ to the Wechsler Intelligence Scale for Children-Third Edition III5 (verbal IQ ¼ 90 and performance IQ ¼ 116). “Memory Task” (Batteria di valutazione neuropsicologica per l’età evolutiva [BVN])6 exploring immediate verbal memory revealed normal profile. The child characterized normal phonological and morphosyntactic abilities (Valutazione delle competenze metafonologiche),7 whereas word fluency (BVN < 2DS)6 and reading performance (Prove di lettura MT)8 were slightly impaired. Behavioral attitudes were explored using the Italian version of the child behavior checklist for children and adolescents.9 The child behavior checklist demonstrated a tendency toward internalizing and depressed mood (Table).
Discussion
Lipoproteinosis is a rare disease characterized by cutaneous and extracutaneous features. Central nervous system (CNS) manifestations can include epilepsy, headache, variable degrees of mental retardation, depression, anxiety, panic episodes, memory dysfunction, abnormal social interaction patterns, and dystonia.10,11 Neurological manifestations may reflect the presence of intracranial calcifications that can be located everywhere in the brain, but especially in the temporal lobes. Amygdala involvement is considered pathognomonic.10,11 Pathophysiologic mechanisms of calcium deposits and their localization are not well understood. CNS infiltration involves especially hippocampal capillaries, resulting in wall
106
M. Balestri et al. / Pediatric Neurology 52 (2015) 104e106
FIGURE 2. T1-weighted (A), T2-weighted (B), and FLAIR (C) magnetic resonance imaging sequences depict bilateral mesial temporal lobe calcifications in the amygdala and hippocampus (arrows). (The color version of this figure is available in the online edition.)
thickening and perivascular calcium deposition.1,3 Cerebral calcifications seem to correlate with the disease duration and occur more frequently after age 10 years.12 This may explain why neurological manifestations are rare in childhood. Only five reported patients presented with epilepsy during childhood.3,4,13-15 Among them, only a 16-year-old boy had a clear neurophysiologic and clinical definition of focal temporal lobe seizures,13 whereas for the other patients the focal temporal lobe seizures were reported retrospectively,3,4,15 or the seizures remained undefined.14 Moreover, none of these individuals exhibited the neuropsychologic or psychological problems that are commonly described adults. 11 Our patient represents the first child with a complete clinical and neurophysiologic definition of focal temporal lobe seizures associated with both psychological (depressed mood) and neuropsychological (reduced word fluency and reading performance) impairment. Although our patient’s cerebral calcifications were bilaterally symmetric, her seizures were unilateral. The lateralization of epileptic seizures may be related with a slightly greater amount of calcium deposit in one hemisphere than in the other. A larger number of patients and a longer follow-up time would be required to verify this hypothesis.
Conclusions
Lipoproteinosis is a rare autosomal recessive multisystemic disease involving CNS. Focal temporal lobe TABLE. Child Behavior Checklist (CBCL) Values in Our Patient
Raw Score (T*) CBCL Scales Internalization Externalization Total problem score CBCL subscales Anxious/depressed Withdrawn/depressed Somatic complaints Social problems Thought problems Attention problems Rule-breaking behavior Aggressive behavior Others *
T values over 60 are considered abnormal.
21 (71) 4 (49) 31 (56) 3 8 10 2 2 0 0 4 2
(52) (73) (75) (52) (54) (50) (50) (52)
seizures along with both psychological and neuropsychological abnormalities, reflecting the presence of mesial temporal calcification lesions, are common but only in adulthood. This may be because brain calcifications are age dependent and related to disease duration. Our patient confirms that the temporal lobe calcifications and the consequent neurological manifestations may appear very early. References 1. Gonçalves FG, de Melo MB, de L Matos V, Barra FR, Figueroa RE. Amygdalae and striatum calcification in lipoid proteinosis. AJNR Am J Neuroradiol. 2010;31:88-90. 2. Hamada T, Wessagowit V, South AP, et al. Extracellular matrix protein 1 gene (ECM1) mutations in lipoid proteinosis and genotypephenotype correlation. J Invest Dermatol. 2003;120:345-350. 3. Appenzeller S, Chaloult E, Velho P, et al. Amygdalae calcifications associated with disease duration in lipoid proteinosis. J Neuroimaging. 2006;16:154-156. 4. Claeys KG, Claes LR, Van Goethem JW, et al. Epilepsy and migraine in a patient with Urbach-Wiethe disease. Seizure. 2007;16:465-468. 5. Wechsler D. Wechsler Intelligence Scale for Children III (WISC III). New York, NY: The Psychological Corporation; 1991. Italian translation: Scala di Intelligenza Wechsler per Bambini-Terza Edizione. Firenze: OS Organizzazioni Speciali; 2006. 6. Bisiacchi PS, Cendron M, Gugliotta M, Tressoldi PE, Vio C. BVN 5-11Batteria di valutazione neuropsicologica per l’età evolutiva, Ed. Erickson. 7. Marotta L, Ronchetti C, Trasciani M, Vicari S. Test CMF Valutazione delle competenze meta fonologiche, Ed.Erickson. 8. Cornoldi C, Colpo G. Prove di lettura MT per la scola primaria-2, Ed. Giunti OS. 9. Achenbach TM, Rescorla LA. Manual for the ASEBA School-Age Forms & Profiles. Burlington, VT: University of Vermont, Research Center for Children, Youth & Families; 2000. 10. Teive HA, Pereira ER, Zavala JA, et al. Generalized dystonia and striatal calcifications with lipoid proteinosis. Neurology. 2004;63: 2168-2169. 11. Thornton HB, Nel D, Thornton D, van Honk J, Baker GA, Stein DJ. The neuropsychiatry and neuropsychology of lipoid proteinosis. J Neuropsychiatry Clin Neurosci. 2008;20:86-92. 12. Newton FH, Rosenberg RN, Lampert PW, O’Brien JS. Neurologic involvement in Urbach-Wiethe’s disease (lipoid proteinosis): a clinical, ultrastructural, and chemical study. Neurology. 1971;21:1205-1213. 13. Nagasaka T, Tanaka M, Ito D, Tanaka K, Shimizu H. Protean manifestations of lipoid proteinosis in a 16-year-old boy. Clin Exp Dermatol. 2000;25:30-32. 14. Kini S, Jain A, Shet TM, Bansode S, Vora IM, Ghorpade K. Lipoid proteinosis in a 12-year-old child: a report from west India. Dermatol Online J. 2006;12:10. 15. Omrani HG, Tajdini M, Ghelichnia B, et al. Should we think of Urbach-Wiethe disease in refractory epilepsy? Case report and review of the literature. J Neurol Sci. 2012;320:149-152.
Contents lists available at ScienceDirect
Pediatric Neurology journal homepage: www.elsevier.com/locate/pnu
Clinical Observations
Structural Focal Temporal Lobe Seizures in a Child With Lipoproteinosis Martina Balestri MD a, b, *, Simona Cappelletti Psy c, Massimiliano Valeriani MD, PhD a, Federico Vigevano MD a a
Neurology Division, Bambino Gesù Children Hospital, IRCCS, Rome, Italy PhD School in Applied Neurological Sciences, University of Siena, Italy c Unit of Clinical Psychology, Bambino Gesù Children’s Hospital, IRCCS, Rome, Italy b
abstract BACKGROUND: Lipoproteinosis is a rare autosomal recessive disorder caused by a mutation in a gene (ECM1) on chromosome 1q21. Alterations of membrane and vessels in the dermal-epidermal junction represent the pathologic background of the disease. Calcification in the temporal lobes and hippocampi are common and may be associated with epileptic seizures. PATIENT DESCRIPTION: We describe a 7-year-old girl with lipoproteinosis who presented with hoarseness, typical skin lesions, and seizures. RESULTS: Video electroencephalography demonstrated focal temporal lobe seizures. Intelligence quotient was normal, but psychologic tests revealed depressed mood. Neuroimaging revealed bilateral mesial temporal lobe calcifications. CONCLUSIONS: The report reveals that the temporal lobe calcifications and the consequent epileptic seizures can appear even very early. The psychological signs may reflect limbic system dysfunction. Keywords: EEG, temporal seizure, lipoproteinosis, cutaneous and mucosal hyalinosis or Urbach-Wiethe syndrome
Pediatr Neurol 2015; 52: 104-106 Ó 2015 Elsevier Inc. All rights reserved.
Introduction
Lipoproteinosis is a rare autosomal recessive disease; it is also known as cutaneous and mucosal hyalinosis or UrbachWiethe syndrome. Lipoproteinosis is caused by a mutation in a gene on chromosome 1q21 that encodes for a glycoprotein (ECM1),1 expressed in the dermis, basal keratinocytes, endothelial cells, and developing bones, and it is connected to cell differentiation, regulation, collagen composition, and growth-factor binding. Although the protein function is uncertain, it might maintain the dermal homeostasis. The loss of function of the gene leads to a deposition of hyaline-like material and disruption-duplication of the basement membrane, resulting in thickening of the skin and mucous membranes.2 Article History: Received April 30, 2014; Accepted in final form August 26, 2014 * Communications should be addressed to: Dr. Balestri; Division of Neurology; Bambino Gesù Children’s Hospital; IRCCS P.za S. Onofrio; 4 00165 Rome, Italy. E-mail address: [email protected] 0887-8994/$ - see front matter Ó 2015 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.pediatrneurol.2014.08.023
The first clinical sign is often hoarseness, which is caused by infiltration of the vocal cords and usually develops within the first year of life. Later, skin lesions appear, such as pox-like and acneiform scars.1 Treatment with oral steroids, dimethyl sulfoxide, heparin, or laser surgery can rarely improve the mucocutaneous manifestations. Life expectancy of individuals with lipoproteinosis is normal, although there is some risk of respiratory obstruction. Although cutaneous manifestations are the cardinal signs, lipoproteinosis is a multisystemic disease that may involve the eyes, heart, liver, small intestine, lungs, ovary, testes, prostate, pancreas, kidneys, and skeletal muscle.2 Neurological manifestations are also possible, yet rare. Intracranial calcifications are the most often reported findings and can be located anywhere in the brain.1,3 The incidence of epilepsy in lipoproteinosis is unknown.4 In spite of having been described as a common manifestation especially in association with intracerebral calcifications,3,4 childhood onset of epilepsy is rare. There are only five reported patients who experienced epilepsy during childhood.
M. Balestri et al. / Pediatric Neurology 52 (2015) 104e106
105
FIGURE 1. The onset of a focal seizure onset (arrow) is characterized by hypersynchronous rhythmic theta activity arising from the right temporal lobe. (The color version of this figure is available in the online edition.)
Patient Description We describe a girl with regular neuropsychomotor development. She was born by Cesarean delivery, scheduled at 36 weeks of gestation due to repeated threatened miscarriages during pregnancy. Her parents reported third degree consanguinity. She was asymptomatic until the age of 5 months, when she developed hoarseness during crying. In spite of early fiberoptic laryngoscopy that was performed twice, lipoproteinosis was diagnosed at age 4 years, when she manifested the typical skin lesions, such as rash, papules, and scars. Genetic examination revealed an ECM1 mutation. She had taken acitretin (0.5 mg/kg) for 2 years, with poor results. We observed her at age 7 years, when she began to experience seizures. The first episode was characterized by sudden fear, followed by throat constriction and breathing difficulties. Similar episodes, lasting 10-20 seconds each, occurred over the following weeks. She was aware of the impending seizures and was able to inform her parents. Other manifestations that could precede or follow the seizures included “déjà vu,” stomachache, body heat, and drowsiness without any evidence of loss of consciousness. During seizures, the child was able to speak fluently. Seizures were infrequent at onset, but later their frequency increased up to many episodes per week. General and neurological examinations were normal except for hoarseness and skin lesions, as described previously. The girl was right handed. Twenty-one channel video electroencephalography monitoring included both ictal and interictal recordings. A 5-day recording demonstrated interictal sporadic slow and epileptiform discharges arising from the right posterior regions. Sleep structure was normal, and the slow abnormalities were reduced during sleep. Four long-lasting seizures were recorded during both awakefulness and sleep. At seizure onset, she reported a periumbilical undefined feeling, which allowed her to alert the parents. During seizures, she placed one hand on her own abdomen, whereas the other hand was held by that of a parent. She was able to speak and execute simple commands during seizures. During all episodes, the electroencephalograph revealed a paroxysmal discharge, characterized by a hypersynchronous theta rhythmic activity arising from the right temporal region (Fig 1). In some instances, the discharge spread to the ipsilateral parietal region or to the contralateral temporal region.
Carbamazepine did not reduce the seizure frequency. After a few months, clobazam was added, and the number of seizures was reduced. When carbamazepine was replaced by levetiracetam, complete seizure control was achieved. She underwent brain magnetic resonance imaging using a 3-T magnetic resonance imaging scanner, which revealed bilateral mesial temporal lobe calcifications in both amygdala and hippocampus (Fig 2). During neuropsychological assessment, the girl scored a normal intelligence quotient (IQ): 86th percentile to the Progressive Matrices 47 and 103 of total IQ to the Wechsler Intelligence Scale for Children-Third Edition III5 (verbal IQ ¼ 90 and performance IQ ¼ 116). “Memory Task” (Batteria di valutazione neuropsicologica per l’età evolutiva [BVN])6 exploring immediate verbal memory revealed normal profile. The child characterized normal phonological and morphosyntactic abilities (Valutazione delle competenze metafonologiche),7 whereas word fluency (BVN < 2DS)6 and reading performance (Prove di lettura MT)8 were slightly impaired. Behavioral attitudes were explored using the Italian version of the child behavior checklist for children and adolescents.9 The child behavior checklist demonstrated a tendency toward internalizing and depressed mood (Table).
Discussion
Lipoproteinosis is a rare disease characterized by cutaneous and extracutaneous features. Central nervous system (CNS) manifestations can include epilepsy, headache, variable degrees of mental retardation, depression, anxiety, panic episodes, memory dysfunction, abnormal social interaction patterns, and dystonia.10,11 Neurological manifestations may reflect the presence of intracranial calcifications that can be located everywhere in the brain, but especially in the temporal lobes. Amygdala involvement is considered pathognomonic.10,11 Pathophysiologic mechanisms of calcium deposits and their localization are not well understood. CNS infiltration involves especially hippocampal capillaries, resulting in wall
106
M. Balestri et al. / Pediatric Neurology 52 (2015) 104e106
FIGURE 2. T1-weighted (A), T2-weighted (B), and FLAIR (C) magnetic resonance imaging sequences depict bilateral mesial temporal lobe calcifications in the amygdala and hippocampus (arrows). (The color version of this figure is available in the online edition.)
thickening and perivascular calcium deposition.1,3 Cerebral calcifications seem to correlate with the disease duration and occur more frequently after age 10 years.12 This may explain why neurological manifestations are rare in childhood. Only five reported patients presented with epilepsy during childhood.3,4,13-15 Among them, only a 16-year-old boy had a clear neurophysiologic and clinical definition of focal temporal lobe seizures,13 whereas for the other patients the focal temporal lobe seizures were reported retrospectively,3,4,15 or the seizures remained undefined.14 Moreover, none of these individuals exhibited the neuropsychologic or psychological problems that are commonly described adults. 11 Our patient represents the first child with a complete clinical and neurophysiologic definition of focal temporal lobe seizures associated with both psychological (depressed mood) and neuropsychological (reduced word fluency and reading performance) impairment. Although our patient’s cerebral calcifications were bilaterally symmetric, her seizures were unilateral. The lateralization of epileptic seizures may be related with a slightly greater amount of calcium deposit in one hemisphere than in the other. A larger number of patients and a longer follow-up time would be required to verify this hypothesis.
Conclusions
Lipoproteinosis is a rare autosomal recessive multisystemic disease involving CNS. Focal temporal lobe TABLE. Child Behavior Checklist (CBCL) Values in Our Patient
Raw Score (T*) CBCL Scales Internalization Externalization Total problem score CBCL subscales Anxious/depressed Withdrawn/depressed Somatic complaints Social problems Thought problems Attention problems Rule-breaking behavior Aggressive behavior Others *
T values over 60 are considered abnormal.
21 (71) 4 (49) 31 (56) 3 8 10 2 2 0 0 4 2
(52) (73) (75) (52) (54) (50) (50) (52)
seizures along with both psychological and neuropsychological abnormalities, reflecting the presence of mesial temporal calcification lesions, are common but only in adulthood. This may be because brain calcifications are age dependent and related to disease duration. Our patient confirms that the temporal lobe calcifications and the consequent neurological manifestations may appear very early. References 1. Gonçalves FG, de Melo MB, de L Matos V, Barra FR, Figueroa RE. Amygdalae and striatum calcification in lipoid proteinosis. AJNR Am J Neuroradiol. 2010;31:88-90. 2. Hamada T, Wessagowit V, South AP, et al. Extracellular matrix protein 1 gene (ECM1) mutations in lipoid proteinosis and genotypephenotype correlation. J Invest Dermatol. 2003;120:345-350. 3. Appenzeller S, Chaloult E, Velho P, et al. Amygdalae calcifications associated with disease duration in lipoid proteinosis. J Neuroimaging. 2006;16:154-156. 4. Claeys KG, Claes LR, Van Goethem JW, et al. Epilepsy and migraine in a patient with Urbach-Wiethe disease. Seizure. 2007;16:465-468. 5. Wechsler D. Wechsler Intelligence Scale for Children III (WISC III). New York, NY: The Psychological Corporation; 1991. Italian translation: Scala di Intelligenza Wechsler per Bambini-Terza Edizione. Firenze: OS Organizzazioni Speciali; 2006. 6. Bisiacchi PS, Cendron M, Gugliotta M, Tressoldi PE, Vio C. BVN 5-11Batteria di valutazione neuropsicologica per l’età evolutiva, Ed. Erickson. 7. Marotta L, Ronchetti C, Trasciani M, Vicari S. Test CMF Valutazione delle competenze meta fonologiche, Ed.Erickson. 8. Cornoldi C, Colpo G. Prove di lettura MT per la scola primaria-2, Ed. Giunti OS. 9. Achenbach TM, Rescorla LA. Manual for the ASEBA School-Age Forms & Profiles. Burlington, VT: University of Vermont, Research Center for Children, Youth & Families; 2000. 10. Teive HA, Pereira ER, Zavala JA, et al. Generalized dystonia and striatal calcifications with lipoid proteinosis. Neurology. 2004;63: 2168-2169. 11. Thornton HB, Nel D, Thornton D, van Honk J, Baker GA, Stein DJ. The neuropsychiatry and neuropsychology of lipoid proteinosis. J Neuropsychiatry Clin Neurosci. 2008;20:86-92. 12. Newton FH, Rosenberg RN, Lampert PW, O’Brien JS. Neurologic involvement in Urbach-Wiethe’s disease (lipoid proteinosis): a clinical, ultrastructural, and chemical study. Neurology. 1971;21:1205-1213. 13. Nagasaka T, Tanaka M, Ito D, Tanaka K, Shimizu H. Protean manifestations of lipoid proteinosis in a 16-year-old boy. Clin Exp Dermatol. 2000;25:30-32. 14. Kini S, Jain A, Shet TM, Bansode S, Vora IM, Ghorpade K. Lipoid proteinosis in a 12-year-old child: a report from west India. Dermatol Online J. 2006;12:10. 15. Omrani HG, Tajdini M, Ghelichnia B, et al. Should we think of Urbach-Wiethe disease in refractory epilepsy? Case report and review of the literature. J Neurol Sci. 2012;320:149-152.