- Email: [email protected]
Prevalence of Celiac Disease in Children With Idiopathic Epilepsy in Southeast Turkey
Pediatric Neurology 50 (2014) 479e481
Contents lists available at ScienceDirect
Pediatric Neurology journal homepage: www.elsevier.com/locate/pnu
Original Article
Prevalence of Celiac Disease in Children With Idiopathic Epilepsy in Southeast Turkey Sedat Is¸ıkay MD a, *, Halil Kocamaz MD b a b
Division of Pediatric Neurology, Gaziantep Children’s Hospital, Gaziantep, Turkey Division of Pediatric Gastroenterology, Gaziantep Children’s Hospital, Gaziantep, Turkey
abstract BACKGROUND: We examined the prevalence of celiac disease in children with idiopathic epilepsy. METHODS: Pa-
tients were screened for celiac disease using the immunoglobulin A anti-tissue transglutaminase antibody. Upper gastrointestinal endoscopy and small intestinal biopsy were offered to all antibody-positive patients. The control group consisted of 400 healthy children. RESULTS: A total of 600 patients (332 boys, 268 girls; 8 months-15 years; 9.40 4.09 years) were studied. In 38 patients, the diagnosis was childhood partial epilepsy with occipital paroxysms. Six of the 38 patients with childhood partial epilepsy with occipital paroxysms (15.7%) had positive immunoglobulin A anti-tissue transglutaminase antibody. The frequency of biopsy-proven celiac disease was 15.7% (6/38) among children with childhood partial epilepsy with occipital paroxysms. None of the control patients had positive immunoglobulin A anti-tissue transglutaminase antibody results. CONCLUSIONS: These findings suggest that the prevalence of celiac disease in children with partial epilepsy with occipital paroxysms may be higher than with other types of epilepsies. It may be reasonable to screen individuals with this type of epilepsy for celiac disease. Keywords: celiac disease, epilepsy, childhood partial epilepsy with occipital paroxysm, children
Pediatr Neurol 2014; 50: 479-481 Ó 2014 Elsevier Inc. All rights reserved.
Introduction
Materials and Methods
Celiac disease (CD) is a chronic autoimmune disease seen in genetically predisposed individuals that is associated with wheat, rye, and barley, which are gluten-containing cereals. Celiac disease has been associated with neurological disorders such as cerebellar ataxia, polyneuropathy, headache, and epilepsy.1-3 The prevalence of CD among epileptic patients has been reported as 0.5-9.1% in different studies; this range may be due to the differences in epilepsy definitions or regional variations of CD prevalence.4-10 In this study, we investigated the prevalence of celiac disease in Turkish children with idiopathic epilepsy.
Patients
Article History: Received October 29, 2013; Accepted in final form January 5, 2014 * Communications should be addressed to: Dr. Is¸ıkay; Department of Pediatric Neurology; Gaziantep Children’s Hospital; 27500; S¸ehitkamil; Gaziantep, Turkey. 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.2014.01.021
A total of 600 children with idiopathic epilepsy (425 children with generalized, 175 with partial epilepsy) were studied over a period of 1 year (2012-2013). Neurological examination and intellectual level were normal in all patients. The 1989 classification of epilepsy by the International League Against Epilepsy was used for diagnostic classification of study patients.10 Children with secondary epilepsy (involving cerebral malformations, metabolic disorders, infections, head injury, tumors, or cerebral palsy) were excluded. A control group comprised 400 gender- and age-matched children who were evaluated at pediatric clinics for mild upper respiratory tract infection. None of the control subjects had a history of seizures. Demographic characteristics, medication histories, and clinical findings of all of participants were recorded. None of the patients had other medical disorders. All patients were screened with immunoglobulin (Ig)A anti-tissue transglutaminase (tTG) antibody. Patients with confirmed positive IgA tTG antibody were offered an endoscopic small intestinal biopsy. Biopsy specimens were assessed according to a modified Marsh classification.11
S. Is¸ıkay, H. Kocamaz / Pediatric Neurology 50 (2014) 479e481
480
Discussion
Laboratory methods
A commercially available microplate enzyme-linked immune sorbent assay (Euroimmune, GmbH, Lübeck, Germany) was used to test for IgA tTG. The threshold for a positive assay result was set at 20 RU/mL. The diagnosis of CD was based on the ESPGHAN guideline.12 To confirm the diagnosis of CD, mucosal biopsy was performed endoscopically from the second part of the duodenum (Olympus GIF P230 videogastroscope, Olympus Optical Corporation, Tokyo, Japan). The ethics committee of Gaziantep University Faculty of Medicine approved the study, which was performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki. Additionally, informed consent was obtained from the parents of all children. Statistical analysis
Statistical analyses were performed with SPSS for Windows version 16.0 (SPSS, Inc, Chicago, IL). c2 and Student t test were used for group comparisons. A P value of <0.05 was considered statistically significant.
Results
Patients and control groups were similar in gender and age (Table 1). None of the 400 control patients had positive IgA tTG. A total of 600 children with epilepsy (332 boys, 268 girls; age range: 8 months-15 years; mean age: 9.40 4.09 years) were studied. Of the 600 patients, 70.8% had generalized epilepsy and 29.2% had partial epilepsy. In 38 patients with partial epilepsy, the electroclinical features were consistent with a diagnosis of childhood partial epilepsy with occipital paroxysms (CPEO). Six of the 38 patients with CPEO (15.7%) had positive IgA tTG (Table 2). Upper gastrointestinal endoscopy and pathological examination of duodenal biopsy of those six children reported total villous atrophy (Marsh type 3). The frequency of biopsy-proven CD was 15.7% (6/38) in children with CPEO. None of the patients in epilepsy group other than patients with CPEO was positive for IgA tTG. Plasma levels of vitamin B12, vitamin E, and folate were all normal among patients diagnosed with CD but all patients were diagnosed with iron deficiency anemia. Additionally, brain computed tomography and brain magnetic resonance imaging of children with celiac disease revealed no intracranial calcifications. Following diagnosis, all of patients have maintained a gluten-free dietary regimen. None of the patients had IgA deficiency. There was a statistically significant difference in IgA tTG positivity percentages between generalized and focal epilepsy groups (P ¼ 0.001). Moreover, there were also significant differences in IgA tTG positivity percentages between the CPEO group and other focal epilepsy patients (P ¼ 0.001) and between the CPEO group and generalized epilepsy group (P ¼ 0.001). TABLE 1. Patient characteristics of children with epilepsy and control group
Age, yr Sex Male Female
Patients, n ¼ 600 Mean SD
Control, n ¼ 400 Mean SD
P Value
9.40 4.09
9.01 3.59
0.214 0.338
332 268
209 191
Abbreviation: SD ¼ Standard deviation
We have studied 600 children with idiopathic epilepsy and determined the CD prevalence as 1% in this heterogeneous group. However, more importantly, when we have grouped the patients according to the type of epilepsy, we have determined that, the CD prevalence was as high as 15.7% in children with CPEO. In fact we have determined CD in only six patients with epilepsy, all of which were in the CPEO group. This finding is very important and should be kept in mind because CD is a treatable disease, and treating CD may result in the improvement of epilepsy.13-15 The prevalence of CD in European countries is reported as between 1/99 and 1/133.16 Previous studies have reported different rates of CD in epileptic children. Zelnik et al.,4 Kieslich et al.,5 Fois et al.,6 and Ruggieri et al.7 reported the rates of CD as7.2%, 1.3%, 1%, and 0.5%, respectively, among patients with epilepsy. In Turkey, Ertekin et al.8 and Dalgıç et al.9 reported the CD ratio among epileptic patients as 9.1% and 1.17%, respectively. This large range of prevalence may be due to the different definitions of epilepsy groups or regional variations in CD prevalence in those studies. In our study group, CD prevalence was 6:600 (1%), whereas none of the control patients was diagnosed with CD. In fact, in a study by Ertekin et al., the seropositivity of healthy school children between the ages of 6 and 17 for IgA t TG was determined as 0.87% in our region.17 In that aspect, it was surprising not to determine any positive results for IgA t TG among control patients, though their age range were also similar. However, we especially took the patients without any gastrointestinal symptoms as control group. Those patients admitted to the hospital with only mild upper airway infections without any symptoms of CD were taken to the control group, which may be the reason for no seropositivity for IgA t TG in control group. In general, CD is an insidious disease, and clinicians must be suspicious about it to be able to diagnose it. The classic symptoms of CD include chronic diarrhea, fatigue, iron deficiency anemia, and failure to thrive, though it may be asymptomatic.12 In our study, when the patients were evaluated retrospectively, all six were diagnosed with iron deficiency anemia, three were having abdominal pain, and one was having diarrhea (Table 2). Although all patients in the epilepsy or control groups were not investigated for iron deficiency anemia; because of this, we cannot compare the prevalence of IDA among patients with or without CD. Because IDA was present in all patients with CD, we can conclude that at least CPEO patients with IDA deserve a screening for CD. Occipital calcification18 and focal white matter changes5 are observed in central nervous system imaging of CD patients. In our study, central imaging of patients showed no pathology. The observation that central involvement was not reported in similar studies in Turkey but was prevalent in European countries such as Italy suggests that racial and individual differences may be associated with central calcification. Gobbi et al.18 defined the association of epilepsy, cerebral calcification, and CD as CEC syndrome, and found that 61% of their patients had occipital epilepsy. Furthermore, Labate et al.19 reported CD in 8% of CPEO patients. We found CD in as high as 15.7% of CPEO patients. These similar findings
S. Is¸ıkay, H. Kocamaz / Pediatric Neurology 50 (2014) 479e481
481
TABLE 2. Outcome of investigation of children with positive antitissue transglutaminase immunoglobulin A
Patient No
Age (yr)
Gender
Iron Deficiency Anemia
Abdominal Pain
Diarrhea
Histology of Jejunum (Marsh)
1 2 3 4 5 6
13 9 9 8 4 10
M M M M M F
þ þ þ þ þ þ
þ þ þ
þ
3b 3b 3c 3c 3b 3b
Abbreviations: F ¼ Female M ¼ Male
about the association of CD with CPEO are important; molecular studies determining the association of both diseases are warranted to elucidate this relationship. It is clearly known that CD has some neurological manifestations including peripheral neuropathy, cerebellar ataxia, myelopathy, and dementia that are reported in 7% to 10% of patients.20 Although the association of CD with epilepsy was reported years ago,21 the direct association of epilepsy with CD is not yet elucidated. Some mechanisms including vitamin deficiencies, gluten toxic effects, and/or autoimmune mechanisms have been suggested as the etiologic factors22; but still the exact mechanisms are not clear. Interestingly in a recent population based cohort study,23 it was determined that individuals with CD were at a 1.4-fold increased risk of future epilepsy. Moreover, in that study, an increased risk of epilepsy before and after the onset of CD has been determined. The authors, with these findings, have suggested a common underlying etiology or predisposition to epilepsy. However, in that study, the data about the subtypes of epilepsy were not present. This study has some limitations. This is a cross-sectional study and the cause and relationship association cannot be performed with this type of study. However, the coexistence and association of CD, especially CPEO, can clearly be concluded. Moreover, the follow-up of patients with a gluten-free diet gains more importance and may be the topic of another study. Our study suggests an increased prevalence of CD in individuals with CPEO. Our data suggest that CD screening of most epilepsy patients is warranted only for those with suggestive symptoms such as malnutrition, gastrointestinal symptoms, and growth retardation, but screening may be appropriate for individuals with CPEO. Because treatment of CD might result in improvement of CPEO symptoms, this association of CD with CPEO should be kept in mind. Molecular studies are warranted to clarify this association.
6. 7.
8.
9.
10.
11.
12.
13.
14.
15.
16. 17. 18. 19.
References 1. Luostarinen L, Pirttila T, Collin P. Coeliac disease presenting with neurological disorders. Eur Neurol. 1999;42:132-135. 2. Lionetti E, Francavilla R, Pavone P, et al. The neurology of coeliac disease in childhood: what is the evidence? A systematic review and meta-analysis. Dev Med Child Neurol. 2010;52:700-707. lu C, Karabiber H, Selimog lu MA. Atypical presentations of 3. Celilog celiac disease. Turk J Pediatr. 2011;53:241-249. 4. Zelnik N, Pacht A, Obeid R, et al. Range of neurologic disorders in patients with celiac disease. Pediatrics. 2004;113:1672-1676. 5. Kieslich M, Errázuriz G, Posselt HG, Moeller-Hartmann W, Zanella F, Boehles H. Brain white-matter lesions in celiac disease:
20.
21.
22. 23.
a prospective study of 75 diet-treated patients. Pediatrics. 2001; 108:E21. Fois A, Vascotto M, Di Bartolo RM, Di Marco V. Celiac disease and epilepsy in pediatric patients. Childs Nerv Syst. 1994;10:450-454. Ruggieri M, Incorpora G, Polizzi A, Parano E, Spina M, Pavone P. Low prevalence of neurologic and psychiatric manifestations in children with gluten sensitivity. J Pediatr. 2008;152:244-249. lu MA, Tan H, Konak M. Prevalence of celiac Ertekin V, Selimog disease in a sample of Turkish children with epilepsy. Pediatr Neurol. 2010;42:380. lu A, Dursun A. Latent and potential Dalgiç B, Dursun I, Serdarog celiac disease in epileptic Turkish children. J Child Neurol. 2006; 21:6-7. Proposal for revised classification of epilepsies and epileptic syndromes. Commission on Classification and Terminology of the International League Against Epilepsy. Epilepsia. 1989;30: 389-399. Marsh MN. Gluten, major histocompatibility complex, and the small intestine: a molecular and immunobiologic approach to the spectrum of gluten sensitivity (celiac sprue). Gastroenterology. 1992; 102:330-354. Husby S, Koletzko S, Korponay-Szabó IR, et al, ESPGHAN Working Group on Coeliac Disease Diagnosis, ESPGHAN Gastroenterology Committee, European Society for Pediatric Gastroenterology, Hepatology, and Nutrition. European Society for Pediatric Gastroenterology, Hepatology, and Nutrition guidelines for the diagnosis of coeliac disease. J Pediatr Gastroenterol Nutr. 2012;54: 136-160. Canales P, Mery VP, Larrondo FJ, Bravo FL, Godoy J. Epilepsy and celiac disease: favorable outcome with a gluten-free diet in a patient refractory to antiepileptic drugs. Neurologist. 2006;12: 318-321. Harper E, Moses H, Lagrange A. Occult celiac disease presenting as epilepsy and MRI changes that responded to gluten-free diet. Neurology. 2007;68:533-534. Mavroudi A, Karatza E, Papastavrou T, Panteliadis C, Spiroglou K. Successful treatment of epilepsy and celiac disease with a glutenfree diet. Pediatr Neurol. 2005;33:292-295. Maki M, Mustalahti K, Kokkonen J, et al. Prevalence of celiac disease among children in Finland. N. Engl J Med. 2003;348:2517-2524. lu MA, Kardas¸ F, Aktas¸ E. Prevalence of celiac Ertekin V, Selimog disease in Turkish children. J Clin Gastroenterol. 2005;39:689-691. Gobbi G, Bouquet F, Greco L, et al. Coeliac disease, epilepsy and cerebral calcifications. Lancet. 1992;340:439-443. Labate A, Gambardella A, Messina D, et al. Silent celiac disease in patients with childhood localization-related epilepsies. Epilepsia. 2001;42:1153-1155. Djuric Z, Kamenov B, Katic V. Celiac disease manifested by polyneuropathy and swollen ankles. World J Gastroenterol. 2007;13: 2636-2638. Chapman RW, Laidlow JM, Colin-Jones O, Eade OE, Smith CL. Increased prevalence of epilepsy in celiac disease. Br Med J. 1978;2: 250-251. Chin RL, Sander HW, Brannagan TH, et al. Celiac neuropathy. Neurology. 2003;60:1581-1585. Ludvigsson JF, Zingone F, Tomson T, Ekbom A, Ciacci C. Increased risk of epilepsy in biopsy-verified celiac disease. A population-based cohort study. Neurology. 2012;78:1401-1407.
Contents lists available at ScienceDirect
Pediatric Neurology journal homepage: www.elsevier.com/locate/pnu
Original Article
Prevalence of Celiac Disease in Children With Idiopathic Epilepsy in Southeast Turkey Sedat Is¸ıkay MD a, *, Halil Kocamaz MD b a b
Division of Pediatric Neurology, Gaziantep Children’s Hospital, Gaziantep, Turkey Division of Pediatric Gastroenterology, Gaziantep Children’s Hospital, Gaziantep, Turkey
abstract BACKGROUND: We examined the prevalence of celiac disease in children with idiopathic epilepsy. METHODS: Pa-
tients were screened for celiac disease using the immunoglobulin A anti-tissue transglutaminase antibody. Upper gastrointestinal endoscopy and small intestinal biopsy were offered to all antibody-positive patients. The control group consisted of 400 healthy children. RESULTS: A total of 600 patients (332 boys, 268 girls; 8 months-15 years; 9.40 4.09 years) were studied. In 38 patients, the diagnosis was childhood partial epilepsy with occipital paroxysms. Six of the 38 patients with childhood partial epilepsy with occipital paroxysms (15.7%) had positive immunoglobulin A anti-tissue transglutaminase antibody. The frequency of biopsy-proven celiac disease was 15.7% (6/38) among children with childhood partial epilepsy with occipital paroxysms. None of the control patients had positive immunoglobulin A anti-tissue transglutaminase antibody results. CONCLUSIONS: These findings suggest that the prevalence of celiac disease in children with partial epilepsy with occipital paroxysms may be higher than with other types of epilepsies. It may be reasonable to screen individuals with this type of epilepsy for celiac disease. Keywords: celiac disease, epilepsy, childhood partial epilepsy with occipital paroxysm, children
Pediatr Neurol 2014; 50: 479-481 Ó 2014 Elsevier Inc. All rights reserved.
Introduction
Materials and Methods
Celiac disease (CD) is a chronic autoimmune disease seen in genetically predisposed individuals that is associated with wheat, rye, and barley, which are gluten-containing cereals. Celiac disease has been associated with neurological disorders such as cerebellar ataxia, polyneuropathy, headache, and epilepsy.1-3 The prevalence of CD among epileptic patients has been reported as 0.5-9.1% in different studies; this range may be due to the differences in epilepsy definitions or regional variations of CD prevalence.4-10 In this study, we investigated the prevalence of celiac disease in Turkish children with idiopathic epilepsy.
Patients
Article History: Received October 29, 2013; Accepted in final form January 5, 2014 * Communications should be addressed to: Dr. Is¸ıkay; Department of Pediatric Neurology; Gaziantep Children’s Hospital; 27500; S¸ehitkamil; Gaziantep, Turkey. 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.2014.01.021
A total of 600 children with idiopathic epilepsy (425 children with generalized, 175 with partial epilepsy) were studied over a period of 1 year (2012-2013). Neurological examination and intellectual level were normal in all patients. The 1989 classification of epilepsy by the International League Against Epilepsy was used for diagnostic classification of study patients.10 Children with secondary epilepsy (involving cerebral malformations, metabolic disorders, infections, head injury, tumors, or cerebral palsy) were excluded. A control group comprised 400 gender- and age-matched children who were evaluated at pediatric clinics for mild upper respiratory tract infection. None of the control subjects had a history of seizures. Demographic characteristics, medication histories, and clinical findings of all of participants were recorded. None of the patients had other medical disorders. All patients were screened with immunoglobulin (Ig)A anti-tissue transglutaminase (tTG) antibody. Patients with confirmed positive IgA tTG antibody were offered an endoscopic small intestinal biopsy. Biopsy specimens were assessed according to a modified Marsh classification.11
S. Is¸ıkay, H. Kocamaz / Pediatric Neurology 50 (2014) 479e481
480
Discussion
Laboratory methods
A commercially available microplate enzyme-linked immune sorbent assay (Euroimmune, GmbH, Lübeck, Germany) was used to test for IgA tTG. The threshold for a positive assay result was set at 20 RU/mL. The diagnosis of CD was based on the ESPGHAN guideline.12 To confirm the diagnosis of CD, mucosal biopsy was performed endoscopically from the second part of the duodenum (Olympus GIF P230 videogastroscope, Olympus Optical Corporation, Tokyo, Japan). The ethics committee of Gaziantep University Faculty of Medicine approved the study, which was performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki. Additionally, informed consent was obtained from the parents of all children. Statistical analysis
Statistical analyses were performed with SPSS for Windows version 16.0 (SPSS, Inc, Chicago, IL). c2 and Student t test were used for group comparisons. A P value of <0.05 was considered statistically significant.
Results
Patients and control groups were similar in gender and age (Table 1). None of the 400 control patients had positive IgA tTG. A total of 600 children with epilepsy (332 boys, 268 girls; age range: 8 months-15 years; mean age: 9.40 4.09 years) were studied. Of the 600 patients, 70.8% had generalized epilepsy and 29.2% had partial epilepsy. In 38 patients with partial epilepsy, the electroclinical features were consistent with a diagnosis of childhood partial epilepsy with occipital paroxysms (CPEO). Six of the 38 patients with CPEO (15.7%) had positive IgA tTG (Table 2). Upper gastrointestinal endoscopy and pathological examination of duodenal biopsy of those six children reported total villous atrophy (Marsh type 3). The frequency of biopsy-proven CD was 15.7% (6/38) in children with CPEO. None of the patients in epilepsy group other than patients with CPEO was positive for IgA tTG. Plasma levels of vitamin B12, vitamin E, and folate were all normal among patients diagnosed with CD but all patients were diagnosed with iron deficiency anemia. Additionally, brain computed tomography and brain magnetic resonance imaging of children with celiac disease revealed no intracranial calcifications. Following diagnosis, all of patients have maintained a gluten-free dietary regimen. None of the patients had IgA deficiency. There was a statistically significant difference in IgA tTG positivity percentages between generalized and focal epilepsy groups (P ¼ 0.001). Moreover, there were also significant differences in IgA tTG positivity percentages between the CPEO group and other focal epilepsy patients (P ¼ 0.001) and between the CPEO group and generalized epilepsy group (P ¼ 0.001). TABLE 1. Patient characteristics of children with epilepsy and control group
Age, yr Sex Male Female
Patients, n ¼ 600 Mean SD
Control, n ¼ 400 Mean SD
P Value
9.40 4.09
9.01 3.59
0.214 0.338
332 268
209 191
Abbreviation: SD ¼ Standard deviation
We have studied 600 children with idiopathic epilepsy and determined the CD prevalence as 1% in this heterogeneous group. However, more importantly, when we have grouped the patients according to the type of epilepsy, we have determined that, the CD prevalence was as high as 15.7% in children with CPEO. In fact we have determined CD in only six patients with epilepsy, all of which were in the CPEO group. This finding is very important and should be kept in mind because CD is a treatable disease, and treating CD may result in the improvement of epilepsy.13-15 The prevalence of CD in European countries is reported as between 1/99 and 1/133.16 Previous studies have reported different rates of CD in epileptic children. Zelnik et al.,4 Kieslich et al.,5 Fois et al.,6 and Ruggieri et al.7 reported the rates of CD as7.2%, 1.3%, 1%, and 0.5%, respectively, among patients with epilepsy. In Turkey, Ertekin et al.8 and Dalgıç et al.9 reported the CD ratio among epileptic patients as 9.1% and 1.17%, respectively. This large range of prevalence may be due to the different definitions of epilepsy groups or regional variations in CD prevalence in those studies. In our study group, CD prevalence was 6:600 (1%), whereas none of the control patients was diagnosed with CD. In fact, in a study by Ertekin et al., the seropositivity of healthy school children between the ages of 6 and 17 for IgA t TG was determined as 0.87% in our region.17 In that aspect, it was surprising not to determine any positive results for IgA t TG among control patients, though their age range were also similar. However, we especially took the patients without any gastrointestinal symptoms as control group. Those patients admitted to the hospital with only mild upper airway infections without any symptoms of CD were taken to the control group, which may be the reason for no seropositivity for IgA t TG in control group. In general, CD is an insidious disease, and clinicians must be suspicious about it to be able to diagnose it. The classic symptoms of CD include chronic diarrhea, fatigue, iron deficiency anemia, and failure to thrive, though it may be asymptomatic.12 In our study, when the patients were evaluated retrospectively, all six were diagnosed with iron deficiency anemia, three were having abdominal pain, and one was having diarrhea (Table 2). Although all patients in the epilepsy or control groups were not investigated for iron deficiency anemia; because of this, we cannot compare the prevalence of IDA among patients with or without CD. Because IDA was present in all patients with CD, we can conclude that at least CPEO patients with IDA deserve a screening for CD. Occipital calcification18 and focal white matter changes5 are observed in central nervous system imaging of CD patients. In our study, central imaging of patients showed no pathology. The observation that central involvement was not reported in similar studies in Turkey but was prevalent in European countries such as Italy suggests that racial and individual differences may be associated with central calcification. Gobbi et al.18 defined the association of epilepsy, cerebral calcification, and CD as CEC syndrome, and found that 61% of their patients had occipital epilepsy. Furthermore, Labate et al.19 reported CD in 8% of CPEO patients. We found CD in as high as 15.7% of CPEO patients. These similar findings
S. Is¸ıkay, H. Kocamaz / Pediatric Neurology 50 (2014) 479e481
481
TABLE 2. Outcome of investigation of children with positive antitissue transglutaminase immunoglobulin A
Patient No
Age (yr)
Gender
Iron Deficiency Anemia
Abdominal Pain
Diarrhea
Histology of Jejunum (Marsh)
1 2 3 4 5 6
13 9 9 8 4 10
M M M M M F
þ þ þ þ þ þ
þ þ þ
þ
3b 3b 3c 3c 3b 3b
Abbreviations: F ¼ Female M ¼ Male
about the association of CD with CPEO are important; molecular studies determining the association of both diseases are warranted to elucidate this relationship. It is clearly known that CD has some neurological manifestations including peripheral neuropathy, cerebellar ataxia, myelopathy, and dementia that are reported in 7% to 10% of patients.20 Although the association of CD with epilepsy was reported years ago,21 the direct association of epilepsy with CD is not yet elucidated. Some mechanisms including vitamin deficiencies, gluten toxic effects, and/or autoimmune mechanisms have been suggested as the etiologic factors22; but still the exact mechanisms are not clear. Interestingly in a recent population based cohort study,23 it was determined that individuals with CD were at a 1.4-fold increased risk of future epilepsy. Moreover, in that study, an increased risk of epilepsy before and after the onset of CD has been determined. The authors, with these findings, have suggested a common underlying etiology or predisposition to epilepsy. However, in that study, the data about the subtypes of epilepsy were not present. This study has some limitations. This is a cross-sectional study and the cause and relationship association cannot be performed with this type of study. However, the coexistence and association of CD, especially CPEO, can clearly be concluded. Moreover, the follow-up of patients with a gluten-free diet gains more importance and may be the topic of another study. Our study suggests an increased prevalence of CD in individuals with CPEO. Our data suggest that CD screening of most epilepsy patients is warranted only for those with suggestive symptoms such as malnutrition, gastrointestinal symptoms, and growth retardation, but screening may be appropriate for individuals with CPEO. Because treatment of CD might result in improvement of CPEO symptoms, this association of CD with CPEO should be kept in mind. Molecular studies are warranted to clarify this association.
6. 7.
8.
9.
10.
11.
12.
13.
14.
15.
16. 17. 18. 19.
References 1. Luostarinen L, Pirttila T, Collin P. Coeliac disease presenting with neurological disorders. Eur Neurol. 1999;42:132-135. 2. Lionetti E, Francavilla R, Pavone P, et al. The neurology of coeliac disease in childhood: what is the evidence? A systematic review and meta-analysis. Dev Med Child Neurol. 2010;52:700-707. lu C, Karabiber H, Selimog lu MA. Atypical presentations of 3. Celilog celiac disease. Turk J Pediatr. 2011;53:241-249. 4. Zelnik N, Pacht A, Obeid R, et al. Range of neurologic disorders in patients with celiac disease. Pediatrics. 2004;113:1672-1676. 5. Kieslich M, Errázuriz G, Posselt HG, Moeller-Hartmann W, Zanella F, Boehles H. Brain white-matter lesions in celiac disease:
20.
21.
22. 23.
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