Cerebellar Abnormalities on Proton MR Spectroscopy and Imaging in Patients With Gluten Ataxia: A Pilot Study

Abstract

Gluten ataxia is a rare immune-mediated neurological disorder caused by the ingestion of gluten. The diagnosis is not straightforward as antibodies are present in only up to 38% of patients, but often at lower titers. The symptoms of ataxia may be mild at the onset but lead to permanent damage if remain untreated. It is characterized by damage to the cerebellum however, the pathophysiology of the disease is not clearly understood. The present study investigated the neurochemical profile of vermis and right cerebellum and structural changes in various brain regions of patients with gluten ataxia (n = 6, age range 40–65 years) and compared it with healthy controls (n = 10, 40–55 years). Volumetric 3-D T1 and T1-weighted magnetic resonance imaging (MRI) in the three planes (axial, coronal, and sagittal) of the whole brain and single-voxel 1H- magnetic resonance spectroscopy (MRS) of the vermis and right cerebellum were acquired on 3 T human MR scanner. The metabolite concentrations were estimated using LC Model (6.1–4A) while brain volumes were estimated using the online tool volBrain pipeline and CERES and corrected for partial volumes. The levels of neuro-metabolites (N-acetyl aspartate + N-acetyl aspartate glutamate, glycerophosphocholine + phosphocholine, and total creatine) were found to be significantly lower in vermis, while N-acetyl aspartate + N-acetyl aspartate glutamate and glycerophosphocholine + phosphocholine was lower in cerebellum regions in the patients with gluten ataxia compared to healthy controls. A significant reduction in the white matter of (total brain, cerebellum, and cerebrum); reduction in the volumes of cerebellum lobe (X) and thalamus while lateral ventricles were increased in the patients with gluten ataxia compared to healthy controls. The reduced neuronal metabolites along with structural changes in the brain suggested neuronal degeneration in the patients with gluten ataxia. Our preliminary findings may be useful in understanding the gluten-induced cerebral damage and indicated that MRI and MRS may serve as a non-invasive useful tool in the early diagnosis, thereby enabling better management of these patients.

Applications of magnetic resonance spectroscopy in diagnosis of neurodegenerative diseases: A systematic review

“…In the study of Rawat et al on GA, there were lower N-acetyl aspartate (tNAA: N-acetylaspartate + N-acetylaspartate glutamate) and choline (tCho: glycerylphosphorylcholine + phophocholine) amounts in the vermis and right cerebellum [ 8 ].…”

“…SCAs primarily affect the cerebellum and spinal cord but may also cause degeneration in other parts of the central nervous system [ 7 ]. Gluten ataxia (GA), a rare immune-mediated cerebellar ataxia (IMCA), is a neurological presentation of gluten sensitivity enteropathy and can be demonstrated (although non-specifically) through the concentration of antigliadin antibodies in the blood serum [ 8 ].…”

Psychiatric and Neurological Manifestations of Celiac Disease in Adults

“…Ataxia's early signs may be subtle, but worsen if left untreated. In a study by Rawat et al (2022), patients with gluten ataxia were analyzed for structural alterations in different parts of the brain as well as their neurochemical profile in the vermis and right cerebellum. Patients with gluten ataxia had smaller lobes (X) of the cerebellum and thalamus, as well as larger lateral ventricles, compared to healthy controls.…”

“…Patients with gluten ataxia had smaller lobes (X) of the cerebellum and thalamus, as well as larger lateral ventricles, compared to healthy controls. Neuronal degeneration was likely present in patients with gluten ataxia, as evidenced by decreased neuronal metabolites and anatomical alterations in the brain [24].…”

Trends in biological and genetic markers of gluten-related disorders research

“…On the other hand, anti-TG6 antibodies were presented in 32% of patients with negative tests for other serological markers of GRD, which makes diagnosis a challenge. Because of this great variation in the prevalence of serological evidence or even its absence, the evaluation of the presence of cerebellar atrophy, usually present in up 60% of GA patients, has been more frequently performed for GA diagnosis through magnetic resonance imaging (MRI) and spectroscopy (MRS) (Hadjivassiliou et al, 2015), that was the focus of the study carried out by Rawat et al (2022) (Rawat et al, 2022). This eligible study showed cerebellar atrophy in all GA patients (aged from 40-60 years) with no neurological/psychiatric diseases and no medical or family history of ataxia and with weak serological evidence for GRD (66.6% positive IgA anti-AGA and 16.6% positive anti-TG6 and anti-tTG2).…”