Cortical involvement in celiac disease before and after long-term gluten-free diet: A Transcranial Magnetic Stimulation study

OBJECTIVE: Transcranial Magnetic Stimulation in de novo patients with Celiac Disease previously revealed an imbalance in the excitability of cortical facilitatory and inhibitory circuits. After a median period of 16 months of gluten-free diet, a global increase of cortical excitability was reported, suggesting a glutamate-mediated compensation for disease progression. We have now evaluated cross-sectionally the changes of cortical excitability to TMS after a much longer gluten-free diet. METHODS: Twenty patients on adequate gluten-free diet for a mean period of 8.35 years were enrolled and compared with 20 de novo patients and 20 healthy controls. Transcranial Magnetic Stimulation measures, recorded from the first dorsal interosseous muscle of the dominant hand, consisted of: resting motor threshold, cortical silent period, motor evoked potentials, central motor conduction time, mean short-latency intracortical inhibition and intracortical facilitation. RESULTS: The cortical silent period was shorter in de novo patients, whereas in gluten-free diet participants it was similar to controls. The amplitude of motor responses was significantly smaller in all patients than in controls, regardless of the dietary regimen. Notwithstanding the diet, all patients exhibited a statistically significant decrease of mean short-latency intracortical inhibition and enhancement of intracortical facilitation with respect to controls; more intracortical facilitation in gluten-restricted compared to non-restricted patients was also observed. Neurological examination and celiac disease-related antibodies were negative. CONCLUSIONS: In this new investigation, the length of dietary regimen was able to modulate the electrocortical changes in celiac disease. Nevertheless, an intracortical synaptic dysfunction, mostly involving excitatory and inhibitory interneurons within the motor cortex, may persist. The clinical significance of subtle neurophysiological changes in celiac disease needs to be further investigated.