Neurologic Complications of Celiac Disease

Abstract

Source: Zelnik N, Pacht A, Obeid R, et al. Range of neurologic disorders in patients with celiac disease. Pediatrics. 2004;113:1672–1676.Investigators at the Carmel Medical Center in Haifa, Israel, sought to study the neurologic complications of celiac disease (CD) among a cohort of patients evaluated between 1977 and 2001. Patients with celiac disease [n=111] and controls [n=211] matched for age and gender were questioned regarding neurologic disorders, had their charts reviewed, and received neurologic evaluations, including brain imaging or electroencephalography, if indicated. Prior to 1988, diagnosis of CD was based on 3 consecutive intestinal biopsies. After 1988, the diagnostic approach was simplified and was based on immunoglobulin A antiendomysial antibodies and 1 intestinal biopsy. The mean age of patients and controls was 20.1 ± 9 years, and the male to female ratio was 2:3. The CD was classical infantile (diagnosed at 1.8 years) in 58 (52.3%) patients and later in onset (diagnosed at 14.8 years) in 53 (47.7%) patients. Neurologic disorders were found in 57/111 (51.4%) of patients with CD, whereas only 42/211 (19.9%) control subjects had abnormal neurologic findings. Patients with late-onset CD had more neurologic complications than the classical CD group (54.7% versus 48.3%), but the difference was not significant. Neurologic abnormalities and their frequency compared to controls included: hypotonia, 21.6% versus 3.8% (P<.01); developmental delay, 15.5% versus 3.3% (P<.01); seizures, 7.2% versus 0.8% (P<.09); learning disabilities and ADHD, 20.7% versus 10.5% (P<.01); headache, 27.9% versus 8.1% (P<.01); ataxia, 5.4% versus 0% (P<.01); and tics, 0.9% versus 2.4% (P=.67). Seizure disorders were more frequent with CD but not significantly, and tic disorders showed no increased prevalence. The gluten-free diet only benefited those CD patients with infantile hypotonia and migraine headache.The range of neurologic disorders associated with CD is wider than previously reported and includes chronic migraine headache, developmental delay, hypotonia in infants, learning disabilities, ADHD,1,2 and seizures. Apart from cases of epilepsy with occipital calcifications, recurrent seizures were not significantly correlated with CD.In occipital lobe seizures related to CD, the CD may be clinically asymptomatic.3 The incidence of silent CD in children with idiopathic localization epilepsies and the indications for routine CD screening were established in a study of 72 patients (mean age, 12.6 years) observed over a 5-year period.4 Two (8%) of 25 patients with childhood partial epilepsy with occipital paroxysms (CPEO) had positive IgA-antiendomysium antibodies, and jejunal biopsies showed villous atrophy and crypt hyperplasia, confirming the diagnosis of CD. Brain CT showed occipital calcifications in one. Seizures were controlled by treatment with a gluten-free diet, and no brain calcifications developed in the patient with a normal CT after a 3-year follow-up on a gluten-free diet.Forty-seven patients with childhood partial epilepsy with centrotemporal spikes (CPEC) had negative antibody tests for CD.4 CD screening is recommended in children with CPEO but not in those with CPEC and extraoccipital spikes. Early diagnosis and dietary intervention may reverse the tendency to seizures and brain calcifications. The gluten-free diet was also successful in the relief of migraine headaches. Wheat cereal is a known migraine trigger in some children5 and positive reactors should be screened for CD.The underlying pathophysiology linking gluten to neurologic disorders is not well characterized in this study, which refers only to its non-specific immunologic and inflammatory effects. Nonetheless, the association between gluten and brain disorders appears to be very strong, and some patients’ neurologic symptoms remit when gluten is removed from their diet. Thus, to separate the wheat of celiac disease-associated neurologic disorders from the chaff of the truly idiopathic, we must consider celiac disease as a possible etiology for a variety of neurologic presentations.