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J Neurol Neurosurg Psychiatry 68:104-105 doi:10.1136/jnnp.68.1.104
  • Letters to the editor

Recurrent peripheral neuropathy in a girl with celiac disease

  1. AGATA POLIZZI,
  2. MARIA FINOCCHIARO,
  3. ENRICO PARANO,
  4. PIERO PAVONE
  1. Division of Paediatric Neurology, Department of Paediatrics, University of Catania
  2. Catania, Italy
  3. Department of Paediatrics, University of Sassari, Sassari, Italy
  4. Neurosciences Group, Institute of Molecular Medicine, Department of Clinical Neurology, University of Oxford, Oxford, UK
  1. Dr Agata Polizzi, Division of Paediatric Neurology, Department of Paediatrics, University of Catania, Viale A Doria 6, 95125 Catania, Italy email: rupo{at}ctonline.it
  1. SALVATORE MUSUMECI
  1. Division of Paediatric Neurology, Department of Paediatrics, University of Catania
  2. Catania, Italy
  3. Department of Paediatrics, University of Sassari, Sassari, Italy
  4. Neurosciences Group, Institute of Molecular Medicine, Department of Clinical Neurology, University of Oxford, Oxford, UK
  1. Dr Agata Polizzi, Division of Paediatric Neurology, Department of Paediatrics, University of Catania, Viale A Doria 6, 95125 Catania, Italy email: rupo{at}ctonline.it
  1. AGATA POLIZZI
  1. Division of Paediatric Neurology, Department of Paediatrics, University of Catania
  2. Catania, Italy
  3. Department of Paediatrics, University of Sassari, Sassari, Italy
  4. Neurosciences Group, Institute of Molecular Medicine, Department of Clinical Neurology, University of Oxford, Oxford, UK
  1. Dr Agata Polizzi, Division of Paediatric Neurology, Department of Paediatrics, University of Catania, Viale A Doria 6, 95125 Catania, Italy email: rupo{at}ctonline.it

    The involvement of the peripheral nervous system (PNS) in children with celiac disease is particularly rare. Furthermore, in both children and adults with celiac disease, neurological complications are chronic and progressive.1

    We report on a 12 year old girl affected by celiac disease, who on two separate occasions presented with an acute peripheral neurological syndrome after accidental reintroduction of gluten in her diet.

    This patient was born uneventfully to healthy non-consanguineous parents with no family history of neurological or metabolic diseases. At the age of 6 months she was diagnosed as having celiac disease according to the European Society of Paediatric Gastroenterology and Nutrition (ESPGAN) criteria. Since then she was on a strict gluten free diet and was asymptomatic until the age of 10 years when severe diarrhoea, vomiting, and abdominal pain manifested 6 days after the intake of corn flakes erroneously thought to be gluten free. No previous infections had been noticed. One week after the onset of these symptoms she experienced acute weakness and pins and needles sensation confined to her legs. At that time her parents stopped her intake of corn flakes on the suspicion that these were responsible for the symptoms. Despite this, symptoms worsened during the next 2 days, confining her to bed.

    At hospital admission, she was alert and mentally stable. Results of general physical examination were unremarkable. Neurological examination disclosed symmetric, predominantly distal, weakness of the legs; the knee jerks and ankle reflexes were depressed; plantar reflexes were flexor. Distal stocking glove decreased in pin prick and temperature with sparing of propioception and light touch. Coordination tests were normal.

    Laboratory investigations showed a white cell count of 9300/mm3. The results of the following investigations were within the normal limits: haemogram, erythrocyte sedimentation rate, serum urea, nitrogen, electrolytes, creatinine, glucose, transaminase, bilirubin, immunoglobulins (Igs), lead, iron, copper, urinalysis, urinary porphyrin, folic acid, and vitamins A, B1, B6, B12, and E. Antibodies toCampylobacter jejuni, neurotropic antivirus antibodies, specific and non-specific organ autoantibodies, IgA and IgG antigliadin antibodies (AGAs), IgA antiendomesium antibodies (EMAs), and IgA antireticulum antibodies (ARA), assayed by enzyme linked immunoadsorbent assay (ELISA) and immunofluorescence (IF) were also negative. Lumbar puncture was not performed. Antibodies against gangliosides GM1 and GQ1b, myelin associated glycoprotein and myelin basic protein were not tested. Nerve conduction studies were consistent with a predominately motor demyelinating peripheral neuropathy (table). Her symptoms improved spontaneously and she was discharged home after 2 weeks. For 2 years she was asymptomatic on a gluten free diet.

    Electrophysiological study suggestive in both episodes of an acute demyelinating peripheral neuropathy confined to the lower limbs. Values were within normal limits in the upper limbs

    At the age of 12 she presented acutely with severe abdominal pain 8 days after a weekly intake of bread meant to be gluten free. Two weeks later, due to persisting gastrointestinal symptoms, her parents excluded the bread from her diet. After 2 further weeks, while the abdominal pain was gradually improving, she had a new episode of acute weakness in the lower limbs and sensory abnormalities including burning paraesthesiae. On neurological examination the legs showed marked diminution in muscle power; absent deep tendon reflexes, and a reduction in pain and temperature; light touch, perception of position, and vibration were preserved. Walking was impaired and the patient was bedridden. Otherwise the examination was normal.

    A haemogram showed white cell counts of 9700/mm3. Laboratory investigations were within normal values as in the past. IgA and IgG AGA, IgA EMA, and IgA ARA assayed by ELISA and IF were again negative. Nerve conduction studies confirmed the presence of a predominantly motor demyelinating neuropathy (table). The parents refused consent for a lumbar puncture or nerve biopsy.

    Over the next 2 weeks her neurological disabilities spontaneously improved until full recovery was complete. After 4 weeks, AGA, EMA, and ARA were still negative.

    On her most recent admission, 1 year after the onset of her first neurological symptoms, she is still on a strict gluten free diet and has no residual symptoms or signs.

    The natural history of celiac disease is well known and the typical celiac enteropathy is often associated with several other disorders. However, as celiac disease is a relatively common and lifelong condition, it is likely that some of these associations may occur by chance.

    This patient, who was diagnosed as having frank celiac disease at the age of 6 months, experienced two episodes of acute peripheral neuropathy, at the age of 10 and 12 years, respectively. Two major pieces of evidence strongly support the assumption of a gluten derived disease: (1) the episodes occurred on both occasions when gluten was accidentally reintroduced in the diet; and (2) the response to a gluten free diet was reasonably rapid, occurring within weeks.

    The present case, however, differs clinically from those with neurological involvement previously reported. In the paediatric age group, in fact, neurological complications of celiac disease are rarely encountered and are mostly confined to the CNS2: to the best of our knowledge, there are only two previously reported cases of PNS involvement in children with celiac disease. In both cases, however, these were chronic axonal polyneuropathies presenting during a gluten free diet.3 4

    In both episodes in the present case neurophysiology was strongly supportive of a demyelinating peripheral neuropathy, which is most commonly attributed to a direct immune mediated attack to the myelin. By contrast, wallerian and axonal degeneration may be caused by vasculitis, and nutritional, metabolic, and toxic factors.

    An autoimmune pathogenesis in association with strong evidence of a genetic susceptibility has been proposed for celiac disease. Although it is well established that AGA, EMA, and ARA are reliable indicators of sensitisation to gluten at least at the time of diagnosis, in the clinical practice at follow up, during a gluten challenge, pathological values of these antibodies may not be detected.5 In the present case the time course of the disease might be suggestive of an antibody mediated response. However, we could not detect pathological concentrations of AGA, EMA, or ARA antibodies either during the course of the disease or at follow up.

    It is known that in celiac disease many immunological perturbations can occur outside the gastrointestinal tract. Crossing of the antigens through a damaged small intestinal mucosa, deposition of immune complexes in target organs, a reduction in immune surveillance, mechanism of molecular mimicry, and activated T cell response may contribute to the pathogenesis of the diseases associated with celiac disease. Direct toxic effects of gliadin and vitamin deficiency are other possible pathogenic mechanisms of damage to the nervous system. Although we ruled out a vitamin deficiency it is still questionable whether a toxic neuropathy can be the case.

    In conclusion, this case shows two major issues: an acute polyneuropathy can be a complication of celiac disease in childhood and its benign course could help in the understanding of the underlying pathogenic mechanisms.

    Acknowledgments

    We are grateful to Professor Angela Vincent (Oxford) for her helpful suggestions in reviewing the manuscript.

    References

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