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

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.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.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.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

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

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.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.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.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

Improving the diagnostic approach to celiac disease: Experience from a regional network

Background: Celiac disease (CD) is still underestimated. To close this diagnostic gap, the Health Sicilian Authorities have constituted the "Sicilian Network for CD". Aims: A) To verify the quality of the current diagnostic approach using the data sheet of the Network. B) To evaluate the clinical, serologic and histologic data of new diagnoses in the context of the Network METHODS: We retrospectively evaluated the data collection forms of 369 patients with CD from three Centers within the Sicilian Network. All the Centers used a standard data collection form. Results: A non-classical CD presentation was more frequent than the classical one, anemia being the most frequent symptom (50%). An IBS-like presentation was found in one third of the cases. A diagnostic delay of about 9 years following the onset of symptoms was observed. Almost half of the patients had not undergone multiple duodenal biopsies; unrecommended CD serology assays were prescribed in 59.9% of the cases. Conclusions: The regional data sheets allowed an assessment of the diagnostic delay. We recorded a frequent use of unrecommended tests prescribed before referring patients to the regional Centers. Updating the education of physicians regarding CD is necessary to avoid unwarranted health expenditure

Excitability of the motor cortex in de novo patients with celiac disease.

INTRODUCTION: Celiac disease (CD) may initially present as a neurological disorder or may be complicated by neurological changes. To date, neurophysiological studies aiming to an objective evaluation of the potential central nervous system involvement in CD are lacking. OBJECTIVE: To assess the profile of cortical excitability to Transcranial Magnetic Stimulation (TMS) in a group of de novo CD patients. MATERIALS AND METHODS: Twenty CD patients underwent a screening for cognitive and neuropsychiatric symptoms by means of the Mini Mental State Examination and the Structured Clinical Interview for DSM-IV Axis I Disorders, respectively. Instrumental exams, including electroencephalography and brain computed tomography, were also performed. Cortico-spinal excitability was assessed by means of single and paired-pulse TMS using the first dorsal interosseus muscle of the dominant hand. TMS measures consisted of resting motor threshold, motor evoked potentials, cortical silent period (CSP), intracortical inhibition (ICI) and facilitation (ICF). None of the CD was on gluten-free diet. A group of 20 age-matched healthy controls was used for comparisons. RESULTS: CD showed a significantly shorter CSP (78.0 vs 125.0 ms, p<0.025), a reduced ICI (0.3 vs 0.2, p<0.045) and an enhanced ICF (1.1 vs 0.7, p<0.042) compared to controls. A dysthymic disorder was identified in five patients. The effect size between dysthymic and non-dysthymic CD patients indicated a low probability of interference with the CSP (Cohen's d -0.414), ICI (-0.278) and ICF (-0.292) measurements. CONCLUSION: A pattern of cortical excitability characterized by "disinhibition" and "hyperfacilitation" was found in CD patients. Immune system dysregulation might play a central role in triggering changes of the motor cortex excitability

Comparison of electrophysiological data in patients with celiac disease and controls.

<p>rMT  =  resting motor threshold; CSP  =  cortical silent period; MEP  =  Motor Evoked Potentials; CMCT  =  central motor conduction time; CMCTF  =  central motor conduction time estimated by F wave; A ratio  =  amplitude ratio.</p

Intracortical excitability at different interstimuls intervals obtained from patients and controls.

<p>ISI  =  interstimuls interval; MEP  =  Motor Evoked Potential.</p

Clinical features of the subjects included in this study.

<p>MMSE  =  Mini Mental State Examination; HDRS  =  Hamilton Depression Rating Scale; SCID-I  =  Structured Clinical Interview for DSM-IV Axis I.</p

Diagnostic delay in adult coeliac disease: An Italian multicentre study

Background: There are few data regarding the diagnostic delay and its predisposing factors in coeliac disease (CD). Aims: To investigate the overall, the patient-dependant, and the physician-dependant diagnostic delays in CD. Methods: CD adult patients were retrospectively enroled at 19 Italian CD outpatient clinics (2011-2021). Overall, patient-dependant, and physician-dependant diagnostic delays were assessed. Extreme diagnostic, i.e., lying above the third quartile of our population, was also analysed. Multivariable regression models for factors affecting the delay were fitted. Results: Overall, 2362 CD patients (median age at diagnosis 38 years, IQR 27-46; M:F ratio=1:3) were included. The median overall diagnostic delay was 8 months (IQR 5-14), while patient- and physician-dependant delays were 3 (IQR 2-6) and 4 (IQR 2-6) months, respectively. Previous misdiagnosis was associated with greater physician-dependant (1.076, p = 0.005) and overall (0.659, p = 0.001) diagnostic delays. Neurological symptoms (odds ratio 2.311, p = 0.005) and a previous misdiagnosis (coefficient 9.807, p = 0.000) were associated with a greater extreme physician-dependant delay. Gastrointestinal symptoms (OR 1.880, p = 0.004), neurological symptoms (OR 2.313, p = 0.042), and previous misdiagnosis (OR 4.265, p = 0.000) were associated with increased extreme overall diagnostic delay. Conclusion: We identified some factors that hamper CD diagnosis. A proper screening strategy for CD should be implemented