Introduction: An imbalance between excitatory and inhibitory synaptic excitability was observed in de novo patients with celiac disease (CD) in a previous study with Transcranial Magnetic Stimulation (TMS), suggesting a subclinical involvement of GABAergic and glutamatergic neurotransmission in asymptomatic patients. The aim of this investigation was to monitor the eventual changes in the same cohort of patients, evaluated after a period of gluten-free diet.
Methods: Patients were re-evaluated after a median period of 16 months during which an adequate gluten-free diet was maintained. Clinical, cognitive and neuropsychiatric assessment was repeated, as well as cortical excitability by means of single- and paired-pulse TMS from the first dorsal interosseous muscle of the dominant hand.
Results: Compared to baseline, patients showed a significant decrease of the median resting motor threshold (from 35% to 33%, p<0.01). The other single-pulse (cortical silent period, motor evoked potentials latency and amplitude, central motor conduction time) and paired-pulse TMS measures (intracortical inhibition and intracortical facilitation) did not change significantly after the follow-up period. Antibodies were still present in 7 subjects.
Discussion: In patients under a gluten-free diet, a global increase of cortical excitability was observed, suggesting a glutamate-mediated functional reorganization compensating for disease progression. We hypothesize that glutamate receptor activation, probably triggered by CD-related immune system dysregulation, might result in a long-lasting motor cortex hyperexcitability with increased excitatory post-synaptic potentials, probably related to phenomena of long-term plasticity. The impact of the gluten-free diet on subclinical neurological abnormalities needs to be further explored.