Celiac disease, a lifelong gluten-sensitive disorder, is well recognized and is characterized by malabsorption, villous atrophy, and crypt hyperplasia. However, the disease is often underdiagnosed, and the classic form constitutes only the tip of the “celiac iceberg” because patients with celiac disease can have very subtle symptoms. Recent population-based serologic surveys showed a prevalence of 1 in 250 to 500 in most countries, including Italy (1). This has caused heightened suspicion and awareness, especially regarding the pediatric population, leading to the description of an extraordinarily wide spectrum of clinical findings that include neurologic signs (2).
Vertigo and nystagmus are nonspecific neurologic signs and require a careful diagnostic workup. Differential diagnosis includes primary central nervous system diseases, vestibular and ocular involvement, and, more rarely, metabolic disorders. The association of celiac disease with nystagmus has been described only rarely in adults (3), whereas vertigo has not been attributed to celiac disease. We describe a patient who had vertigo and nystagmus as the first signs of celiac disease.
An 11-year-old prepubertal girl was admitted to the Department of Paediatrics because of objective vertigo associated with nausea and lack of appetite. Vertigo had appeared for the first time 1 month before admission, increasing during the 2 weeks before admission, when nausea and lack of appetite became more apparent. The symptoms required occasional bedrest. The girl did not report any other symptoms. Loss of weight was not reported, and height (141 cm, 25–50th percentile) and weight (31 kg, 25th percentile) were normal for age and sex. General examination was unremarkable, with the exception of bilateral nystagmus. A complete neurologic examination did not show evidence of cerebellar involvement or other neurologic involvement. Visual acuity and ocular motility were normal. Complete blood count, erythrocyte sedimentation rate, kidney and liver function tests, and glucose and lipid concentrations were normal. No thyroid dysfunction could be detected. Vestibular function testing was performed and excluded vestibular origin of the symptoms. Electroencephalography showed a normal and symmetric rhythm. A cerebral magnetic resonance imaging scan was normal, and a cerebral angiography showed no vascular disorders. Twice tests for antigliadin and antiendomysial antibodies were positive. A small bowel biopsy with multiple specimens taken from the proximal duodenum showed subtotal villous atrophy, elongated crypts with increased mitotic index, increased intraepithelial lymphocytes with infiltrations of plasma cells, and lymphocytes in the lamina propria in the absence of other significant disease (Fig. 1). These histologic features were consistent with gluten-sensitive enteropathy. A gluten-free diet was established, and within 3 months, antigliadin and antiendomysial antibody tests were negative and vertigo disappeared. However, after a short period of poor compliance with the gluten-free diet, vertigo recurred. This was associated with positive serologic markers of celiac disease. Since this episode, the girl has adhered strictly to the gluten-free diet and no further relapse has occurred. After 2 years of good compliance with the diet, the patient still has bilateral nystagmus.
The question of whether the frequency of celiac disease increases in patients with neurologic manifestations of unknown origin has been investigated intensively (4,5). Hadjivassiliou et al. (6) found that among patients with neurologic manifestations of unknown origin, 57% had positive titers for antigliadin and had typical histologic changes in small bowel mucosa consistent with celiac disease. Most of these patients have ataxia, which is progressive in same cases. This finding is mainly true in the adult population and has been confirmed recently in a large population in which cerebellar oculomotor symptoms were relatively common (3), whereas manifestations of cerebellar involvement have only rarely been described in childhood (7). The underlying mechanism of such manifestations is obscure. However, the immune response triggered by sensitivity to gluten may be expressed in organs other than the gut, and the central and peripheral nervous systems may be affected. Most of the damage in gluten ataxia occurs in the cerebellum and the posterior columns of the spinal cord (5,6), which may be reversed by a strict gluten-free diet. In fact, in some of the patients, in whom the diagnosis of gluten ataxia was prompt, a complete resolution of symptoms was achieved after strict adherence to a gluten-free diet (6).
Among the neurologic symptoms of celiac disease in childhood, vertigo has not been described, to the best of our knowledge, either in patients with well-established celiac disease or as the first sign of the disorder, whereas nystagmus has been described only in association with frank gluten ataxia (3). Neither symptom may represent anything other than an early involvement of the cerebellum, which if misdiagnosed could progress to gluten ataxia. Reversible immunologic damage probably is the underlying process. In fact, in our patient, vertigo disappeared with a gluten-free diet, recurred promptly during a period of poor compliance, and thereafter disappeared with a strict gluten-free diet. In contrast, the bilateral nystagmus showed no improvement after 2 years of a gluten-free diet. Permanent neurologic damage or insufficient suppression of the immunologic process, despite strict a gluten-free diet, may explain this, as described earlier (8).
Despite the contentious and not universal recommendation of performing serologic testing for celiac disease in all patients with neurologic dysfunction of unknown origin (4), we think that early screening in childhood is fundamentally important because undiagnosed celiac disease may cause more severe neurologic damage.
1. Greco L, Di Donato F, Ansaldi N. Analysis of incidence trends: an example from the Italian cohort. In: Auricchio S, Visakorpi JK, eds. Common Food Intolerance 1, Epidemiology of Coeliac Disease. Basel, Switzerland: Karger; 1992:25–34.
2. Murray JA. The widening spectrum of celiac disease. Am J Clin Nutr 1999; 69:354–65.
3. Bürk K, Bösch S, Müller CA, et al. Sporadic cerebellar ataxia associates with gluten sensitivity. Brain 2001; 124:1013–9.
4. Wills AJ. The neurology and neuropathology of coeliac disease. Neuropathol Appl Neurobiol 2000; 26:493–6.
5. Cooke WT, Thomas-Smith W. Neurological disorders associated with adult celiac disease. Brain 1966; 89:683–722.
6. Hadjivassiliou M, Gibson A, Davies-Jones GAB, et al. Does cryptic gluten sensitivity play a part in neurological illness? Lancet 1996; 347:369–71.
7. Gordon N. Cerebellar ataxia and gluten sensitivity: a rare but possible cause of ataxia even in childhood. Dev Med Child Neurol 2000; 42:283–6.
8. Hadjivassiliou M, Grünewald RA, Chattopadhyay AK, et al. Clinical, radiological, neurophysiological, and neuropathological characteristics of gluten ataxia. Lancet 1998; 352:1582–4.