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Journal of Neurology
Published in: Journal of Neurology 7/2019

Open Access 01-07-2019 | Review

Gluten sensitivity and epilepsy: a systematic review

Authors: Thomas Julian, Marios Hadjivassiliou, Panagiotis Zis

Published in: Journal of Neurology | Issue 7/2019

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Abstract

Objective

The aim of this systematic review was to establish the prevalence of epilepsy in patients with coeliac disease (CD) or gluten sensitivity (GS) and vice versa and to characterise the phenomenology of the epileptic syndromes that these patients present with.

Methodology

A systematic computer-based literature search was conducted on the PubMed database. Information regarding prevalence, demographics and epilepsy phenomenology was extracted.

Results

Epilepsy is 1.8 times more prevalent in patients with CD, compared to the general population. CD is over 2 times more prevalent in patients with epilepsy compared to the general population. Further studies are necessary to assess the prevalence of GS in epilepsy. The data indicate that the prevalence of CD or GS is higher amongst particular epileptic presentations including in childhood partial epilepsy with occipital paroxysms, in adult patients with fixation off sensitivity (FOS) and in those with temporal lobe epilepsy (TLE) with hippocampal sclerosis. A particularly interesting presentation of epilepsy in the context of gluten-related disorders is a syndrome of coeliac disease, epilepsy and cerebral calcification (CEC syndrome) which is frequently described in the literature. Gluten-free diet (GFD) is effective in the management of epilepsy in 53% of cases, either reducing seizure frequency, enabling reduced doses of antiepileptic drugs or even stopping antiepileptic drugs.

Conclusion

Patients with epilepsy of unknown aetiology should be investigated for serological markers of gluten sensitivity as such patients may benefit from a GFD.
Literature
1.
Mustalahti K, Catassi C, Reunanen A et al (2010) The prevalence of celiac disease in Europe: results of a centralized, international mass screening project. Ann Med 42:587–595CrossRefPubMed
2.
Fasano A, Catassi C (2001) Current approaches to diagnosis and treatment of celiac disease: an evolving spectrum. Gastroenterology 120:636–651CrossRefPubMed
3.
4.
Hadjivassiliou M, Sanders DS, Grünewald RA et al (2010) Gluten sensitivity: from gut to brain. Lancet Neurol 9:318–330CrossRefPubMed
5.
6.
Gabrielli M, Cremonini F, Fiore G et al (2003) Association between migraine and Celiac disease: results from a preliminary case-control and therapeutic study. Am J Gastroenterol 98:625–629CrossRefPubMed
7.
Zis P, Rao DG, Sarrigiannis PG et al (2017) Transglutaminase 6 antibodies in gluten neuropathy. Dig Liver Dis 49:1196–1200CrossRefPubMed
8.
Ludvigsson JF, Zingone F, Tomson T et al (2012) Increased risk of epilepsy in biopsy-verified celiac disease: a population-based cohort study. Neurology 78:1401–1407CrossRefPubMed
9.
Guy Daynes (1956) Bread and tears—naughtiness, depression and fits due to wheat sensitivity. Proc R Soc Med 49:391–394PubMedCentral
10.
Gobbi G, Ambrosetto P, Zaniboni MG et al (1992) Celiac disease, posterior cerebral calcifications and epilepsy. Brain Dev 14:23–29CrossRefPubMed
11.
Peltola M, Kaukinen K, Dastidar P et al (2009) Hippocampal sclerosis in refractory temporal lobe epilepsy is associated with gluten sensitivity. J Neurol Neurosurg Psychiatry 80:626–630CrossRefPubMed
12.
Marsh N, Johnson MW, Rostami M (2015) K. Mucosal histopathology in celiac disease: a rebuttal of Oberhuber’s sub-division of Marsh III. Gastroenterol Hepatol Bed Bench 8:99–109
13.
14.
Bonanni P, Negrin S, Antoniazzi L et al (2017) Clinical implications of interictal epileptiform discharges in cognitive functioning in CEC syndrome with evolution into epileptic encephalopathy. Neurocase 23:230–238CrossRefPubMed
15.
Sel ÇG, Aksoy E, Aksoy A et al (2017) Neurological manifestations of atypical celiac disease in childhood. Acta Neurol Belg 117:719–727CrossRefPubMed
16.
Bashiri H, Afshari D, Babaei N et al (2016) Celiac Disease and epilepsy: the effect of gluten-free diet on seizure control. Adv Clin Exp Med 25:751–754CrossRefPubMed
17.
Struck AF, Beinlich BR, Rutecki PA (2015) A case of celiac disease, epilepsy, and cerebral calcifications with temporal lobe epilepsy. WMJ 114:116–117PubMed
18.
Işikay S, Hizli Ş, Kocamaz H (2015) Celiac disease and juvenile absence epilepsy. Pediatr Emerg Care 31:e19–e20CrossRefPubMed
19.
Işikay S, Kocamaz H (2015) The neurological face of celiac disease. Arq Gastroenterol 52:167–170CrossRefPubMed
20.
Işıkay S, Kocamaz H, Sezer S et al (2015) The frequency of epileptiform discharges in celiac disease. Pediatr Neurol 53:78–82CrossRefPubMed
21.
Işikay S, Hizli Ş, Yilmaz K (2014) Prevalence of celiac disease in Turkish children with idiopathic epilepsy. Iran J Pediatr 24:280–284PubMedPubMedCentral
22.
Casciato S, Morano A, Albini M et al (2015) Cryptogenic focal epilepsy and “hidden” celiac disease in adulthood: a causal or accidental link? Int J Neurosci 125:913–917CrossRefPubMed
23.
Nevalainen O, Auvinen A, Ansakorpi H et al (2014) Autoimmunity-related immunological serum markers and survival in a tertiary care cohort of adult patients with epilepsy. Epilepsy Res 108:1675–1679CrossRefPubMed
24.
Soós Z, Salamon M, Erdei K et al (2014) LADA type diabetes, celiac diasease, cerebellar ataxia and stiff person syndrome. A rare association of autoimmune disorders. Ideggyogy Sz 67:205–209PubMed
25.
26.
Işıkay S, Kocamaz H (2014) Prevalence of celiac disease in children with idiopathic epilepsy in southeast Turkey. Pediatr Neurol 50:479–481CrossRefPubMed
27.
Dai AI, Akcali A, Varan C et al (2014) Prevalence of resistant occipital lobe epilepsy associated with celiac disease in children. Childs Nerv Syst 30:1091–1098CrossRefPubMed
28.
Vieira C, Jatobá I, Matos M et al (2013) Prevalence of celiac disease in children with epilepsy. Arq Gastroenterol 50:290–296CrossRefPubMed
29.
Franceschetti S, Michelucci R, Canafoglia L et al (2014) Progressive myoclonic epilepsies: definitive and still undetermined causes. Neurology 82:405–411CrossRefPubMedPubMedCentral
30.
31.
Vitelli O, Miano S, Tabarrini A et al (2014) Epilepsy and sleep-disordered breathing as false friends: a case report. J Child Neurol 29:114–117CrossRef
32.
Fattouch J, Casciato S, Lapenta L et al (2013) The spectrum of epileptic syndromes with fixation off sensitivity persisting in adult life. Epilepsia 7:59–65CrossRef
33.
Djurić Z, Nagorni A, Jocić-Jakubi B et al (2012) Celiac disease prevalence in epileptic children from Serbia. Turk J Pediatr 54:247–250PubMed
34.
Johnson AM, Dale RC, Wienholt L et al (2013) Coeliac disease, epilepsy, and cerebral calcifications: association with TG6 autoantibodies. Dev Med Child Neurol 55:90–93CrossRefPubMed
35.
Javed S, Safdar A, Forster A et al (2012) Refractory coeliac disease associated with late onset epilepsy, ataxia, tremor and progressive myoclonus with giant cortical evoked potentials—a case report and review of literature. Seizure 21:482–485CrossRefPubMed
36.
Licchetta L, Bisulli F, Di Vito L et al (2011) Epilepsy in coeliac disease: not just a matter of calcifications. Neurol Sci 32:1069–1074CrossRefPubMed
37.
Ertekin V, Selimoğlu MA, Tan H et al (2010) Prevalence of celiac disease in a sample of Turkish children with epilepsy. Pediatr Neurol 42:380–381 (380; author reply) CrossRefPubMed
38.
Bürk K, Farecki ML, Lamprecht G et al (2009) Neurological symptoms in patients with biopsy proven celiac disease. Mov Disord 24:2358–2362CrossRefPubMed
39.
Sallem FS, Castro LM, Jorge C et al (2009) Gluten sensitivity presenting as myoclonic epilepsy with cerebellar syndrome. Mov Disord 24:2162–2163CrossRefPubMed
40.
Ryan AM, Ryan J, Wan-Ahmed M et al. (2009) Vacuolar leucoencephalopathy and pulvinar sign in association with coeliac disease. BMJ Case Rep
41.
Emami MH, Taheri H, Kohestani S et al (2008) How frequent is celiac disease among epileptic patients? J Gastrointestin Liver Dis 17:379–382PubMed
42.
Briani C, Zara G, Alaedini A et al (2008) Neurological complications of celiac disease and autoimmune mechanisms: a prospective study. J Neuroimmunol 195:171–175CrossRefPubMed
43.
Ruggieri M, Incorpora G, Polizzi A et al (2008) Low prevalence of neurologic and psychiatric manifestations in children with gluten sensitivity. J Pediatr 152:244–249CrossRefPubMed
44.
Della Nave R, Magaudda A, Michelucci R et al (2007) Whole-brain histogram and voxel-based analyses of apparent diffusion coefficient and magnetization transfer ratio in celiac disease, epilepsy, and cerebral calcifications syndrome. AJNR 28:479–485PubMed
45.
Mavroudi A, Xinias I, Papastavrou T et al (2007) Increased prevalence of silent celiac disease among Greek epileptic children. Pediatr Neurol 36:165–169CrossRefPubMed
46.
Harper E, Moses H, Lagrange A (2007) Occult celiac disease presenting as epilepsy and MRI changes that responded to gluten-free diet. Neurology 68:533–534CrossRefPubMed
47.
Canales P, Mery VP, Larrondo FJ et al (2006) Epilepsy and celiac disease: favorable outcome with a gluten-free diet in a patient refractory to antiepileptic drugs. Neurologist 12:318–321CrossRefPubMed
48.
Dalgiç B, Dursun I, Serdaroğlu A et al (2006) Latent and potential celiac disease in epileptic Turkish children. J Child Neurol 21:6–7CrossRefPubMed
49.
Mavroudi A, Karatza E, Papastavrou T et al (2005) Successful treatment of epilepsy and celiac disease with a gluten-free diet. Pediatr Neurol 33:292–295CrossRefPubMed
50.
Díaz RM, González-Rabelino G, Delfino A (2005) Epilepsy, cerebral calcifications and coeliac disease. The importance of an early diagnosis. Rev Neurol 40:417–420PubMed
51.
Ranua J, Luoma K, Auvinen A et al (2005) Celiac disease-related antibodies in an epilepsy cohort and matched reference population. Epilepsy Behav 6:388–392CrossRefPubMed
52.
Nakken KO, Røste GK, Hauglie-Hanssen E (2005) Coeliac disease, unilateral occipital calcifications, and drug-resistant epilepsy: successful lesionectomy. Acta Neurol Scand 111:202–204CrossRefPubMed
53.
Siqueira Neto JI, Costa AC, Magalhães FG et al (2004) Neurological manifestations of celiac disease. Arq Neuropsiquiatr 62:969–972CrossRefPubMed
54.
Vaknin A, Eliakim R, Ackerman Z et al (2004) Neurological abnormalities associated with celiac disease. J Neurol 251:1393–1397CrossRefPubMed
55.
Pfaender M, D’Souza WJ, Trost N et al (2004) Visual disturbances representing occipital lobe epilepsy in patients with cerebral calcifications and coeliac disease: a case series. J Neurol Neurosurg Psychiatry 75:1623–1625CrossRefPubMedPubMedCentral
56.
Pengiran Tengah DS, Holmes GK, Wills AJ (2004) The prevalence of epilepsy in patients with celiac disease. Epilepsia 45:1291–1293CrossRefPubMed
57.
Zelnik N, Pacht A, Obeid R et al (2004) Range of neurologic disorders in patients with celiac disease. Pediatrics 113:1672–1676CrossRefPubMed
58.
Pratesi R, Modelli IC, Martins RC et al (2003) Celiac disease and epilepsy: favorable outcome in a child with difficult to control seizures. Acta Neurol Scand 108:290–293CrossRefPubMed
59.
Essid M, Trabelsi K, Jerbi E et al (2003) Villous atrophy and idiopathic epilepsy. Tunis Med 81:270–272PubMed
60.
Arroyo HA, De Rosa S, Ruggieri V et al (2002) Epilepsy, occipital calcifications, and oligosymptomatic celiac disease in childhood. J Child Neurol 17:800–806CrossRefPubMed
61.
Volta U, De Giorgio R, Petrolini N et al (2002) Clinical findings and anti-neuronal antibodies in coeliac disease with neurological disorders. Scand J Gastroenterol 37:1276–1281CrossRefPubMed
62.
Santos CH, Almeida IL, Gomes MD et al (2002) Bilateral occipital calcification, epilepsy and coeliac disease: case report. Arq Neuropsiquiatr 60:840–843CrossRefPubMed
63.
Luostarinen L, Dastidar P, Collin P et al (2001) Association between coeliac disease, epilepsy and brain atrophy. Eur Neurol 46:187–191CrossRefPubMed
64.
Labate A, Gambardella A, Messina D et al (2001) Silent celiac disease in patients with childhood localization-related epilepsies. Epilepsia 42:1153–1155CrossRefPubMed
65.
Kieslich M, Errázuriz G, Posselt HG et al (2001) Brain white-matter lesions in celiac disease: a prospective study of 75 diet-treated patients. Pediatrics 108:E21CrossRefPubMed
66.
Calvani M Jr, Parisi P, Guaitolini C et al (2001) Latent coeliac disease in a child with epilepsy, cerebral calcifications, drug-induced systemic lupus erythematosus and intestinal folic acid malabsorption associated with impairment of folic acid transport across the blood-brain barrier. Eur J Pediatr 160:288–292CrossRefPubMed
67.
Salur L, Uibo O, Talvik I et al (2000) The high frequency of coeliac disease among children with neurological disorders. Eur J Neurol 7:707–711CrossRefPubMed
68.
Lahat E, Broide E, Leshem M et al (2000) Prevalence of celiac antibodies in children with neurologic disorders. Pediatr Neurol 22:393–396CrossRefPubMed
69.
70.
Bernasconi A, Bernasconi N, Andermann F et al (1998) Celiac disease, bilateral occipital calcifications and intractable epilepsy: mechanisms of seizure origin. Epilepsia 39:300–306CrossRefPubMed
71.
Hernández MA, Colina G, Ortigosa L (1998) Epilepsy, cerebral calcifications and clinical or subclinical coeliac disease. Course and follow up with gluten-free diet. Seizure 7:49–54CrossRefPubMed
72.
Baquero M, Narciso ML, García M et al (1995) Celiac disease with occipital calcifications: 2 late cases. Med Clin (Barc) 105:781–783
73.
Lea ME, Harbord M, Sage MR (1995) Bilateral occipital calcification associated with celiac disease, folate deficiency, and epilepsy. AJNR Am J Neuroradiol 16:1498–1500PubMed
74.
Fois A, Vascotto M, Di Bartolo RM et al (1994) Celiac disease and epilepsy in pediatric patients. Childs Nerv Syst 10:450–454CrossRefPubMed
75.
76.
Bye AM, Andermann F, Robitaille Y et al (1993) Cortical vascular abnormalities in the syndrome of celiac disease, epilepsy, bilateral occipital calcifications, and folate deficiency. Ann Neurol 34:399–403CrossRefPubMed
77.
Magaudda A, Dalla Bernardina B, De Marco P et al (1993) Bilateral occipital calcification, epilepsy and coeliac disease: clinical and neuroimaging features of a new syndrome. J Neurol Neurosurg Psychiatry 56:885–889CrossRefPubMedPubMedCentral
78.
Piattella L, Zamponi N, Cardinali C et al (1993) Endocranial calcifications, infantile celiac disease, and epilepsy. Childs Nerv Syst 9:172–175PubMed
79.
Tiacci C, D’Alessandro P, Cantisani TA et al (1993) Epilepsy with bilateral occipital calcifications: Sturge-Weber variant or a different encephalopathy? Epilepsia 34:528–539CrossRefPubMed
80.
Fois A, Balestri P, Vascotto M et al (1993) Progressive cerebral calcifications, epilepsy, and celiac disease. Brain Dev 15:79–82CrossRefPubMed
81.
Gobbi G, Bouquet F, Greco L et al (1992) Coeliac disease, epilepsy, and cerebral calcifications. The Italian Working Group on Coeliac Disease and Epilepsy. Lancet 340:439–443CrossRefPubMed
82.
Crosato F, Senter S (1992) Cerebral occipital calcifications in celiac disease. Neuropediatrics 23:214–217CrossRefPubMed
83.
Ambrosetto G, Antonini L, Tassinari CA (1992) Occipital lobe seizures related to clinically asymptomatic celiac disease in adulthood. Epilepsia 33:476–481CrossRefPubMed
84.
Della Cella G, Beluschi C, Cipollina F (1991) Intracranial calcifications–seizures–celiac disease: a case presentation. Pediatr Med Chir 13:427–430PubMed
85.
Ventura A, Bouquet F, Sartorelli C et al (1991) Coeliac disease, folic acid deficiency and epilepsy with cerebral calcifications. Acta Paediatr Scand 80:559–562CrossRefPubMed
86.
87.
Banerji NK, Hurwitz LJ (1971) Neurological manifestations in adult steatorrhoea (probable Gluten enteropathy). J Neurol Sci 14:125–141CrossRefPubMed
88.
89.
Fiest KM, Sauro KM, Wiebe S et al. Prevalence and incidence of epilepsy: A systematic review and meta-analysis of international studies Neurology. 2017; 88:296–303
90.
Kotsopoulos IA, van Merode T, Kessels FG et al (2002) Systematic review and meta-analysis of incidence studies of epilepsy and unprovoked seizures. Epilepsia 43:1402–1409CrossRefPubMed
91.
Hadjivassiliou M, Aeschlimann P, Strigun A et al (2008) Autoantibodies in gluten ataxia recognize a novel neuronal transglutaminase. Ann Neurol 64:332–343CrossRefPubMed
Metadata
Title
Gluten sensitivity and epilepsy: a systematic review
Authors
Thomas Julian
Marios Hadjivassiliou
Panagiotis Zis
Publication date
01-07-2019
Publisher
Springer Berlin Heidelberg
Published in
Journal of Neurology / Issue 7/2019
Print ISSN: 0340-5354
Electronic ISSN: 1432-1459
DOI
https://doi.org/10.1007/s00415-018-9025-2

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