Clinical Characteristics and Management of 50 Patients with Anti-GAD Ataxia: Gluten-Free Diet Has a Major Impact

Hadjivassiliou, Marios; Sarrigiannis, Ptolemaios G.; Shanmugarajah, Priya; Sanders, David S.; Grünewald, Richard A.; Zis, Panagiotis; Hoggard, Nigel

doi:10.1007/s12311-020-01203-w

Cited by 23 publications

(20 citation statements)

References 29 publications

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“…In particular, neuropsychiatric disorders are often referred to and greatly impact the quality of life of the patients suffering from them. Ataxia and neuropathy are the disorders most frequently reported in untreated CD [2], with several studies and case reports describing an improvement in neurological symptoms after the start of a glutenfree diet (GFD) [3]. By contrast, depression, anxiety, and somatization disorders, together with headache and fatigue, are commonly referred by patients with IBS [4,5].…”

Section: Introductionmentioning

confidence: 99%

Frequency and Clinical Aspects of Neurological and Psychiatric Symptoms in Patients with Non-Celiac Wheat Sensitivity

et al. 2021

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Background: Non-Celiac Wheat Sensitivity (NCWS) is characterized by both intestinal and extra-intestinal symptoms. The study aims to investigate the frequency of neuropsychiatric manifestations in NCWS patients and identify their clinical and demographic characteristics. Methods: 278 clinical records of NCWS patients, diagnosed by a double-blind placebo-controlled wheat challenge between 2006 and 2020, were retrospectively revised. Fifty-two patients with Celiac Disease (CD) and 54 patients with Irritable Bowel Syndrome (IBS) served as controls. Results: 87% of the NCWS patients had an IBS-like clinical presentation. The NCWS group showed a longer duration of symptoms, a higher frequency of positive serum anti-nuclear antibodies than CD and IBS patients, and a higher frequency of DQ2/DQ8 haplotypes and duodenal mucosa lymphocytosis than IBS controls. In addition, 50% of NCWS patients showed neuropsychiatric manifestations, while lower percentages were observed in CD (25%) and IBS (28%) controls. Neuropsychiatric symptoms in NCWS were more frequently associated with the male sex, longer duration of symptoms, and IBS-diarrhea-like clinical presentation. Conclusions: Our data suggest that in patients with IBS-like symptoms and neuropsychiatric manifestations of unknown cause, it could be useful to investigate a correlation of these symptoms with wheat ingestion to identify NCWS patients with this ‘atypical’ manifestation.

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Section: Introductionmentioning

confidence: 99%

Frequency and Clinical Aspects of Neurological and Psychiatric Symptoms in Patients with Non-Celiac Wheat Sensitivity

et al. 2021

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“…We have previously identified a link between gluten sensitivity and anti-GAD associated SPS as well as anti-GAD ataxia [3,11]. Here we report a link between coeliac disease-related CNS hyperexcitability and GlyR-Abs.…”

Section: Discussionmentioning

confidence: 48%

“…We have previously reported a significant overlap between gluten sensitivity and anti-GAD associated diseases. In our cohort of gluten sensitive patients we found anti-GAD antibodies to be present in a high proportion of patients who also displayed features of stiff person syndrome or ataxia [3,11]. Furthermore, strict gluten-free diet resulted in serological reduction of the anti-GAD titre and in some cases reversal from anti-GAD positive to anti-GAD negative which corresponded to clinical improvement [3].…”

Section: Introductionmentioning

confidence: 58%

Glycine receptor antibodies and coeliac disease-related neurological dysfunction

et al. 2021

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Gluten sensitivity can manifest with a spectrum of neurological dysfunction including ataxia, encephalopathy and neuropathy with or without associated coeliac disease (CD). Gluten sensitivity can also present with central nervous system (CNS) hyperexcitability and cortical myoclonus which is often accompanied with refractory CD. CNS hyperexcitability can also be associated with Glutamic Acid Decarboxylase (GAD) antibodies or much less commonly with Glycine Receptor Antibodies (GlyR-Abs) but the direct pathogenic roles of these antibodies remain debatable. We have previously reported a link between gluten sensitivity and anti-GAD associated ataxia which improves with the adoption of gluten-free diet. It is unclear if a similar link exists between gluten driven CNS hyperexcitability and the presence of GlyR-Abs. We report two cases of CD presenting with CNS hyperexcitability and associated GlyR-Abs. Apart from ataxia and cortical myoclonus, one patient had refractory CD and died from enteropathy-associated T-cell lymphoma. The other patient not only improved with strict gluten-free diet but also showed serological elimination of circulating GlyR-Abs. We conclude that there is an interaction between gluten sensitivity and GlyR-Abs-associated CNS hyperexcitability and in such patients gluten-free diet is an important therapeutic intervention. The elimination of GlyR-Abs by the adoption of gluten free diet suggests that these antibodies may represent an epiphenomenon rather than being directly implicated in the pathogenesis.

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“…We have previously made a connection between anti-GAD associated diseases and gluten sensitivity (GS) including coeliac disease (CD) [5]. We were also able to show considerable overlap between anti-GAD ataxia and gluten ataxia (70% of patients with anti-GAD ataxia are gluten sensitive), and we have demonstrated that gluten free diet (GFD) is an effective therapeutic intervention in such patients [6]. In this report we share our experience in managing and treating patients with SPS and in particular highlighting the overlap between SPS, gluten sensitivity and CD as well as reporting the therapeutic effect of gluten free diet (GFD).…”

Section: Introductionmentioning

confidence: 95%

Stiff Person Syndrome and Gluten Sensitivity

et al. 2021

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Stiff person syndrome (SPS) is a rare autoimmune disease characterised by axial stiffness and episodic painful spasms. It is associated with additional autoimmune diseases and cerebellar ataxia. Most patients with SPS have high levels of glutamic acid decarboxylase (GAD) antibodies. The aetiology of SPS remains unclear but autoimmunity is thought to play a major part. We have previously demonstrated overlap between anti-GAD ataxia and gluten sensitivity. We have also demonstrated the beneficial effect of a gluten-free diet (GFD) in patients with anti-GAD ataxia. Here, we describe our experience in the management of 20 patients with SPS. The mean age at symptom onset was 52 years. Additional autoimmune diseases were seen in 15/20. Nineteen of the 20 patients had serological evidence of gluten sensitivity and 6 had coeliac disease. Fourteen of the 15 patients who had brain imaging had evidence of cerebellar involvement. Twelve patients improved on GFD and in seven GFD alone was the only treatment required long term. Twelve patients had immunosuppression but only three remained on such medication. Gluten sensitivity plays an important part in the pathogenesis of SPS and GFD is an effective therapeutic intervention.

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Clinical Characteristics and Management of 50 Patients with Anti-GAD Ataxia: Gluten-Free Diet Has a Major Impact

Cited by 23 publications

References 29 publications

Frequency and Clinical Aspects of Neurological and Psychiatric Symptoms in Patients with Non-Celiac Wheat Sensitivity

Frequency and Clinical Aspects of Neurological and Psychiatric Symptoms in Patients with Non-Celiac Wheat Sensitivity

Glycine receptor antibodies and coeliac disease-related neurological dysfunction

Stiff Person Syndrome and Gluten Sensitivity

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