November 1993. European Journal of Pediatrics. Authors Hilhorst MI. Brink M. Wauters EA. Houwen RH. Institution: Department of gastro-enterology, Wilhelmina Childrens Hospital, Utrecht, The Netherlands.

Among 783 patients referred to our institute with different types of seizures as presenting symptom, systematic evaluation of antigliadin and antiendomysial antibodies in the serum has identified nine in whom jejunal biopsy has subsequently confirmed the diagnosis of celiac disease (CD). In three of them brain imaging showed the presence of calcified areas in the occipital region. They had complex partial seizures (CPS), associated in two with transient episodes of blindness.

In another patient with CPS and generalized tonic-clonic seizures (GTCS) progressive multifocal cerebral calcifications were noted. In the other six patients with CPS and/or GTCS cerebral calcifications were absent. Symptoms of celiac disease in all these cases were either not previously taken into account, or they were very mild or completely absent. In a group of 36 patients with clinically manifest CD, regular follow-up, and good compliance with the dietary regimen, no clinical seizures were reported. The pathogenic mechanism and the relationship between epilepsy and an early diagnosis and treatment of celiac disease are discussed (Footnote #1).

Bilateral occipital calcifications, occurring in celiac disease, are factors coming under a particular cerebral syndrome, which also includes epilepsy, migraine-like headache, visual troubles and mental deterioration. They seem to arise from hypofolatemia following gluten-induced enteropathy (Footnote #2).

There have been anecdotal reports of an association between celiac disease and epilepsy with cerebral calcifications that resemble those of the Sturge-Weber syndrome. A series of patients who had epilepsy with calcifications, in whom celiac disease (CD) was incidentally observed, prompted us to study this association. 43 patients (15 male, age range 4.6-30.7 years) were selected from two series. 31 patients with cerebral calcifications of unexplained origin and epilepsy (series A) underwent intestinal biopsy. 12 patients with celiac disease and epilepsy (series B) underwent computed tomography. Antibodies to gluten, folic acid serum concentrations, were measured, and HLA typing was done in most patients. 24 of the series A patients were identified as having celiac disease on the basis of a flat intestinal mucosa (15/22 with a high concentration of serum antigluten), and 5 series B patients showed cerebral calcifications, giving a total of 29 cases with the combination of CD, epilepsy, and cerebral calcifications (CEC). In 27 of these CEC patients, calcifications were located in the parieto-occipital regions. Only 2 of the series A patients had gastrointestinal symptoms at the time of intestinal biopsy; most patients had recurrent diarrhea, anemia, and other symptoms suggestive of celiac disease in the first 3 years of life. The epilepsy in CEC patients was poorly responsive to antiepileptic drugs. Gluten-free diet beneficially affected the course of epilepsy only when started soon after epilepsy onset. Cases of atypical Sturge-Weber syndrome (characterized by serpiginous cerebral calcifications and epilepsy without facial port-wine naevus) should be reviewed, and celiac disease should be ruled out in all cases of epilepsy and cerebral calcifications of unexplained origin (Footnote #3).

4. We report the electroclinical findings of four epileptic patients with clinically asymptomatic celiac disease (CD). Celiac disease diagnosis was suspected by past history and/or computed tomography (CT) findings in all patients and confirmed by laboratory tests and jejunal biopsy. All patients had paroxysmal visual manifestations and ictal EEG discharges arising from the occipital lobe. Epilepsy evolution was favorable in two patients and severe in 2, regardless of CT evidence of occipital corticosubcortical calcifications in 2 patients. Occipital lobe seizures may be characteristic of the epilepsy related to CD, and epileptic patients with these seizures of unknown etiology should be carefully investigated for malabsorption. If past history and/or laboratory tests suggest gastrointestinal (GI) dysfunction they should also undergo small intestinal biopsy even if they do not have GI tract symptoms (Footnote #4).

References:
  • Fois A; Vascotto M; Di Bartolo RM; Di Marco V, Celiac disease and epilepsy in pediatric patients,Childs Nerv Syst; 10 (7) p450-4, Sep 1994.
  • Cerebral occipital calcifications in celiac disease, Crosato F; Senter S, Neuropediatrics; 23 (4) p214-7, Aug 1992.
  • Celiac disease, epilepsy, and cerebral calcifications. The Italian Working Group on Celiac Disease and Epilepsy Gobbi G; Bouquet F; Greco L; Lambertini A; Tassinari CA; Ventura A; Zaniboni MG ,Lancet; 340 (8817) p439-43, Aug 22 1992.
  • Ocipital lobe seizures related to clinically asymptomatic celiac disease in adulthood , mbrosetto G; Antonini L; Tassinari CA, Epilepsia; 33 (3) p476-81, May-Jun 1992.

A MEDLINE search showed these additional articles on celiac and epilepsy:

  • Convulsive disorder in celiac disease, Cohen O; River Y; Zelinger I, Harefuah; 126 (12) p707-10, 763, Jun 15 1994.
  • Need for follow up in celiac disease, Bardella MT; Molteni N; Prampolini L; Giunta AM; Baldassarri AR, Arch Dis Child; 70 (3) p211-3, Mar 1994.
  • Familial unilateral and bilateral occipital calcifications and epilepsy, Tortorella G; Magaudda A; Mercuri E; Longo M; Guzzetta F, Neuropediatrics; 24 (6) p341-2, Dec 1993.
  • Endocranial calcifications, infantile celiac disease, and epilepsy, Piattella L; Zamponi N; Cardinali C; Porfiri L; Tavoni MA, Childs Nerv Syst; 9 (3) p172-5, Jun 1993.
  • Cortical vascular abnormalities in the syndrome of celiac disease, epilepsy, bilateral occipital calcifications, and folate deficiency, Bye AM; Andermann F; Robitaille Y; Oliver M; Bohane T; Andermann E, Ann Neurol; 34 (3) p399-403, Sep 1993.
  • Progressive cerebral calcifications, epilepsy, and celiac disease, AU- Fois A; Balestri P; Vascotto M; Farnetani MA; Di Bartolo RM; Di Marco V; Vindigni C, Brain Dev; 15 (1) p79-82, Jan-Feb 1993.
  • Celiac disease, posterior cerebral calcifications and epilepsy, Gobbi G; Ambrosetto P; Zaniboni MG; Lambertini A; Ambrosioni G; Tassinari CA, Brain Dev; 14 (1) p23-9, Jan 1992.
  • Intracranial calcifications--seizures--celiac disease: a case presentation, Della Cella G; Beluschi C; Cipollina F, Pediatr Med Chir; 13 (4) p427-30, Jul-Aug 1991.
  • Celiac disease, folic acid deficiency and epilepsy with cerebral calcifications, Ventura A; Bouquet F; Sartorelli C; Barbi E; Torre G; Tommasini G, Acta Paediatr Scand; 80 (5) p559-62, May 1991.
  • Ramsay Hunt syndrome and celiac disease: a new association?, Lu CS; Thompson PD; Quinn NP; Parkes JD; Marsden CD, Mov Disord; 1 (3) p209-19, 1986.
  • Celiac disease associated with epilepsy and intracranial calcifications: report of two patients, Molteni N; Bardella MT; Baldassarri AR; Bianchi PA, Am J Gastroenterol; 83 (9) p992-4, Sep 1988.
  • Bilateral cerebral occipital calcifications and migraine-like headache, Battistella PA; Mattesi P; Casara GL; Carollo C; Condini A; Allegri F; Rigon F Cephalalgia; 7 (2) p125-9, Jun 1987.
  • Blood selenium content and glutathione peroxidase activity in children with cystic fibrosis, celiac disease, asthma, and epilepsy, Ward KP; Arthur JR; Russell G; Aggett PJ, Eur J Pediatr; 142 (1) p21-4, Apr 1984.

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