Celiac disease presenting As recurrent encephalopathy and seizures

Authors: Dhruvi Shah, Adwait Bendre, Darsita Jatakia, Vishrutha Poojari, Ira Shah

Abstract

Objectives: Celiac disease is an immune-mediated enteropathy triggered by gluten in genetically predisposed individuals. Although gastrointestinal manifestations predominate, neurological features such as seizures, ataxia, and encephalopathy may occur and are often under-recognized in children, particularly in the absence of intestinal symptoms. Case Summary: A 12-year-old girl presented with recurrent generalized seizures and episodic encephalopathy since age 10. Extensive evaluation including cerebrospinal fluid analysis, autoimmune encephalitis panel, MRI brain, and infectious workup was unremarkable. She was treated as MIS-C and autoimmune encephalitis during multiple hospitalizations, with persistent breakthrough seizures despite antiepileptic therapy. Autoimmune screening revealed positive anti-endomysial IgA. Duodenal biopsy showed Marsh 3B changes, confirming celiac disease. A strict gluten-free diet was initiated. Conclusion: The child remained seizure-free over two years with significant clinical improvement, highlighting gluten-sensitive epilepsy as an important, treatable extraintestinal manifestation of pediatric celiac disease.

Introduction

Celiac disease, also known as gluten-sensitive enteropathy (GSE), is a chronic autoimmune disease occurring due to an inflammatory response to dietary gluten in genetically predisposed individuals. It is characterised by villous atrophy, malabsorption and a wide variety of systemic manifestations [1]. Along with gastrointestinal symptoms, celiac disease can cause neurological complications in up to 20% of patients, including ataxia and peripheral neuropathy [2]. Gluten ataxia is characterized by isolated, unexplained ataxia in individuals who test positive for coeliac antibodies, irrespective of intestinal histopathology [3]. The prevalence of gluten ataxia in the pediatric population is not well understood due to insufficient data, making diagnosis and treatment challenging [2]. Here, we present the case of a 12-year-old girl with recurrent seizures and encephalopathy, highlighting this uncommon but important manifestation of celiac disease.

Case presentation

A-12-year old girl was referred to us in May 2023 with recurrent episodes of seizures and encephalopathy, and giddiness and positive anti-endomysial IgA. She had recurrent abdominal pain and constipation for a year. At 10 years age, she had multiple episodes of seizures. Her first episode of seizure was in February 2021 when she was hospitalized with fever, difficulty in maintaining balance and decreased oral intake for 3 days. She had no altered sensorium or focal neurological deficits. Cerebrospinal fluid (CSF) analysis was normal and CSF Xpert/Rif assay did not grow Mycobacterium tuberculosis (MTB). CSF autoimmune encephalitis panel was negative. MRI brain was normal. Covid spike antibody was positive and she was treated with methylprednisolone, intravenous immunoglobulin (IVIG) and low molecular weight heparin (LMWH) for suspected multi-system inflammatory syndrome in children (MISC). She received risperidone and escitalopram for behavioural changes. She was hospitalized in March 2021, April 2021, June 2021 and April 2022 for breakthrough seizures. The patient was treated outside for her seizures and details for ruling out MISC are not available. In July 2022, she had pain in abdomen for 3 days and jejunojejunal intussusception (managed conservatively). In November 2022, she was hospitalized with dengue and had hypotension, ecchymotic patches, thrombocytopenia and was put on ventilator. CT abdomen was normal. The patient had dengue which was confirmed serologically and treated symptomatically. Antinuclear antibody (ANA) was weakly positive with titre of 100. ANA blot was normal. She was suspected to have autoimmune encephalitis and was treated with IV antibiotics, methylprednisolone and required hospital stay for 1 month and was discharged on oral leviracetam and clobazam. Autoimmune encephalitis was excluded on the basis of negative autoimmune panel repeated twice. In December 2022, a detailed autoimmune workup was done which detected positive anti-endomysial IgA (1:10), negative anti-gliadin IgA (1:10) and IgG, and negative anti-tissue transglutaminase (TTG) IgA [2.81RU/ml (Negative < 20 RU/ml)]. In April 2023, she again was hospitalised in another hospital for encephalopathy. She was referred to us in July 2023 for upper gastrointestinal (UGI) endoscopy. On presentation, weight was 39 kg [50th percentile according to Indian Academy of Pediatrics (IAP)], and height was 147 cm (50th percentile according to IAP). Systemic examination was normal. Investigations are depicted in Table 1. UGI scopy was normal (Fig. 1). Histopathological evaluation of the duodenum revealed reduced villous to crypt ratio, partial villous atrophy, crypt hyperplasia, chronic inflammatory changes with lymphocyte predominance and 30 intraepithelial lymphocytes/100 hpf, findings consistent with Marsh 3B classification for Celiac disease (Fig. 2). She was started on gluten free diet. She has been on regular follow up and has been symptom free. In November 2025, weight was 55 kg and the child had no breakthrough seizure or encephalopathy.

Discussion

Celiac disease is an immune-mediated enteropathy that primarily presents with gastrointestinal symptoms such as steatorrhea, flatulence, and malabsorption leading to growth failure, anemia, delayed puberty, weight loss, and nutrient deficiency–related neurological symptoms, including those secondary to low vitamin B1, B12, and E levels [4]. Extraintestinal manifestations include arthritis, bone pain, dermatitis herpetiformis, infertility, ataxia, seizures, and psychiatric complaints. Their prevalence is estimated at 1%–15% and is even rarer in the absence of gastrointestinal symptoms [2, 4].

Gluten sensitivity is associated with neurological manifestations including cerebellar ataxia, peripheral neuropathy, headaches, white matter abnormalities on MRI, epilepsy, cognitive impairment, and depression [5]. Epilepsy is 1.8 times more prevalent in patients with celiac disease than in the general population [6]. Certain epilepsy syndromes have a higher association with gluten sensitivity, and the mean age of presentation is 12 years [6]. Seizures may be generalized tonic–clonic (61.9%), myoclonic (16.7%), or absence (14.3%) [7]. Proposed mechanisms include gluten toxicity, autoimmune processes, and malabsorption, though no definitive cause is established [8]. Gliadin peptides activate cellular signaling pathways, increase oxidative stress, and impair antioxidant capacity, leading to tissue damage [8].

Our patient presented with altered sensorium, recurrent generalized tonic–clonic seizures, and gait imbalance since age 10, with anemia as the only manifestation of celiac disease and no gastrointestinal symptoms. Other causes of seizures and cerebellar ataxia should be excluded, particularly in the absence of enteropathy [2]. Serological markers support diagnosis but have variable sensitivity, with anti-endomysial and anti-tissue transglutaminase antibodies being more specific for enteropathy than neurological disease [9]. There are no established diagnostic criteria for gluten-associated epilepsy, though resistance to antiepileptic drugs may raise suspicion [10]. Vitamin deficiency–related neurological causes must also be excluded [10]. In our patient, the total IgA antibody was 170 mg/dl which is well within the normal range. The positive EMA IgA and TTG IgA are standards documented for cases with predominant gastrointestinal symptoms in cases of gluten sensitivity. Our patient has had abdominal pain only once during the entire duration of the disease [7]. Most of the times there is a discrepancy in antibody levels, it is due to poor sensitivity or specificity of the testing done in the respective laboratories [9], and the test was not repeated as the child was already kept on gluten free diet. EEG changes in cases of gluten encephalopathy are seen in 47.4% cases, which includes focal sharp waves, spikes or slow waves, often in posterior temporal–parietal-occipital region, or focal spike and wave discharges or general epilieptiform activity [11]. Our patient did not show any abnormal findings in her EEG.

A gluten-free diet combined with antiepileptic therapy is most effective, with 53% showing good response, while antiepileptics alone often fail [5, 6]. Gluten-free diet reduces antibody titers over 6–24 months and improves neurological outcomes [9]. Our patient remains seizure-free on levetiracetam, clobazam, and a gluten-free diet for two years.

Consent

Taken.

Guarantor

Dr. Dhruvi Shah, Dr. Adwait Bendre.