Effect of a Gluten-Free Diet on Cortical Excitability in Adults with Celiac Disease

Abstract

IntroductionAn 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.MethodsPatients 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.ResultsCompared 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.DiscussionIn 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.

Serum brain‐derived neurotrophic factor in children with coeliac disease

“…33 Interestingly, when the same patients were re-evaluated after a small period on GFD (approximately 16 months), the phenomenon was accentuated, despite the gastrointestinal symptoms remission. The above studies [33][34][35] are in line with our findings, where BDNF levels were higher in both groups (A and B) than in HC and even higher after long term on GFD. 35 These findings imply that the intrasynaptic cortical changes occurring in patients with CD may require more time on GFD to restore than serological conversion or intestinal remission, while some of them might never be fully restored, despite the patients being on GFD.…”

“…[29][30][31][32][33][34][35][36] A recent report by Pennisi et al explored CNS electrophysiology, using transcranial magnetic stimulation (TMS) in adult CD patients. [29][30][31][32][33][34][35][36] A recent report by Pennisi et al explored CNS electrophysiology, using transcranial magnetic stimulation (TMS) in adult CD patients.…”

“…[29][30][31][32][33][34][35][36] A recent report by Pennisi et al explored CNS electrophysiology, using transcranial magnetic stimulation (TMS) in adult CD patients. 34 Another cross-sectional study by the same authors comparing untreated CD patients 33,34 with a group of patients on a long duration on GFD (mean duration of 8.35 y) found that the cortical changes mentioned above were reversed for the latter, although some specific excitatory findings remained. 33 Interestingly, when the same patients were re-evaluated after a small period on GFD (approximately 16 months), the phenomenon was accentuated, despite the gastrointestinal symptoms remission.…”

Cognitive Impairment and Celiac Disease: Is Transcranial Magnetic Stimulation a Trait d’Union between Gut and Brain?

“…The hypothesis is supported by previous CD-associated epilepsy studies showing that the effectiveness of the diet is directly connected to the duration of neurological disorders and the age where GFD starts [80,81]. Lastly, it is important to note that a degree of improvement of depressive symptoms was observed in the study, confirming the significance of GFD in the management of CD-related neuropsychiatric symptoms [54]. …”

<b><i>Valeriana officinalis</i></b> Root Extract Modulates Cortical Excitatory Circuits in Humans

“…We should acknowledge that calcium-channel agonists consistently increase ICF [30]; nonetheless, the assumption of a top-down regulation of ICF induced by the NE brain concentration is speculative at the moment. Furthermore, previous TMS studies carried out in a clinical context highlighted the electrophysiological role of ICF changes as potential markers of a glutamate-mediated adaptive response or compensatory neuroplastic phenomena [42,43,44,45,46,47]. Thus, we cannot rule out an indirect (adaptive) modulatory effect on ICF.…”