Celiac crisis presenting with status epilepticus and encephalopathy

Abstract

Celiac crisis is a life-threatening presentation of celiac disease which is described in the context of classic gastrointestinal (GI) symptoms of diarrhea, leading to dehydration and electrolyte imbalance. Neurologic manifestations are atypical symptoms of celiac crisis. To the best of our knowledge, there is no published report on seizure or encephalopathy as the presenting manifestation of celiac crisis. We describe a 2-year-old boy presenting with acute status epilepticus and lethargy. Prior to presentation, he had mild abdominal distention and intermittent diarrhea. Laboratory analysis revealed hyponatremia, anemia, hypocalcemia, transaminitis, and hyperglycemia. Electroencephalography revealed severe diffuse encephalopathy, and complete infectious work-up was negative. Initial brain magnetic resonance imaging was normal; however, repeat imaging showed osmotic demyelination syndrome. Given the history of GI symptoms and hyperglycemia, celiac serology was obtained revealing elevated tissue transglutaminase, and a diagnosis was confirmed by Marsh 3c lesions in the duodenum. He significantly improved with steroid therapy in addition to adequate nutrition, fluids, and initiation of a gluten-free diet. Conclusion: We report herein on the first case of celiac crisis presenting with status epilepticus and encephalopathy in the absence of profound GI symptoms. Our case suggests that celiac crisis should be considered in the differential of seizures and encephalopathy in children.

Introduction

Celiac crisis is a rare life-threatening cause of acute diarrhea with subsequent complications of multiple metabolic and systemic emergencies of celiac disease. Most cases of celiac crisis described affect mainly children even though it may present late in life. It is usually described by worsening gastrointestinal symptoms like profuse diarrhea leading to dehydration, metabolic derangements like hypokalemia, hyponatremia, and acidosis. Neurologic manifestations are atypical symptoms of celiac disease and rarely reported in CC. Current case reports on ataxia, paralysis, and quadriplegia secondary to hypokalemia exist in the literature with concomitant acute GI symptoms. We report on the first case of celiac crisis presenting with status epilepticus and encephalopathy in the absence of profound GI symptoms.

Case summary

A previously healthy 2-year-old boy presented with lethargy and status epilepticus in the form of neck and limb stiffening with abnormal eye movements that continued vigorously until he was treated by the emergency department. He had few episodes of vomiting on the day of presentation, and he did not pass any bowel movement 48 h prior to that. He was noticed to have abdominal distention all his life, and occasionally, he complained of abdominal pain. His previous medical history is known to have chronic constipation, rare intermittent diarrhea, and failure to thrive. There was no family history of celiac disease, inflammatory disease, food allergies, diabetes mellitus, thyroid disorder, or seizure disorders.

On general examination, he was lethargic, tachycardic, and mildly dehydrated in postictal status. His weight was 10.4 kg (below the fifth percentile). His abdomen was moderately distended, with sluggish bowel sounds. His skin was dry, warm, and pale. He had generalized hypertonicity and decreased deep tendon reflexes. There was no sensory or cranial deficit, cerebellar or meningeal signs, or any signs of increased intracranial pressure. He did not have papilledema on fundoscopic examination. Following fluid resuscitation, his vital signs stabilized, but he remained in depressed mental status; EEG performed thereafter showed slowing suggestive of encephalopathy without evidence of epileptiform discharges.

His initial work-up showed hyponatremia (125 meq/L), hypochloremia (91 meq/L), normokalemia (4.5 meq/L), hyperglycemia (126 mg/dL), and normal anion gap metabolic acidosis (17 meq/L). His hemogram revealed microcytic microchromic anemia (hemoglobin 95 g/L), normal total white blood cells (11 × 109/L), and differential leukocyte count (polymorph 71 %, lymphocyte 18 %) and platelets (368 × 109/L). Iron and vitamin D levels were noticed to be low, supporting the suspicion of a malabsorptive process. Liver function showed elevated aspartate transaminase (111 U/L) and alanine aminotransferase (89 U/L). His kidney function test, urine electrolyte test, and urine and serum drug screen were normal. Urine tests for ketones and sugars were negative. Central spinal fluid, urine, and blood cultures were all sterile. PCR of HSV in blood and CSF were negative, too. Initial brain magnetic resonance imaging revealed normal-appearing structures.

The metabolic disturbances including hyponatremia and metabolic acidosis were all corrected within 48 h. His encephalopathy was managed in the intensive care unit by using ventilator support. Extensive encephalitis infectious serology work-up was negative. Further metabolic work-up testing included serum amino acids, ammonia, coagulopathy profile, and urine organic acid, and all were unremarkable. Thyroid function, autoimmune diabetes serology, and celiac serology were sent for the concerns of persistent hyperglycemia and history of intermittent diarrhea. Upon positive serologic markers of tissue transglutaminase antibodies (TTG) more than 150 U/mL, the diagnosis of CD was established by endoscopic biopsy of the duodenum. Visualization of the mucosa of the duodenum showed typical blunting of the duodenal villi with paucity of mucosal folds. Biopsies of the duodenum revealed the presence of partial and total villous atrophy, intraepithelial lymphocytes, and increased length of crypts (celiac disease Marsh 3b to 3c) (Fig. 1). Genetic HLA testing was not performed in the patient.

Fig. 1
figure1

Micrograph of the second part of the duodenum showing total loss of villi, crypt hyperplasia, and intraepithelial lymphocytic infiltration

Because of his prolonged encephalopathy, MRI was repeated. It showed pontine changes suggestive of osmotic demyelination syndrome, and it could be explained by metabolic consequence of treating his hyponatremia (Fig. 2). He was started on intravenously administered methylprednisone on day 4 (2 mg/kg per day) upon the return of his elevated TTG serology. The initiation of steroids was supported by previous case reports in order to improve his neurological status with the help of electrolyte and parenteral nutrition support. Vitamins, iron, and folic acid were also introduced. His neurological alertness was achieved on day 10, and steroid was tapered accordingly. After introduction of gluten-free diet, when enterally tolerated, he progressively regained most of his neurological function. He started communicating and ambulating on day 12 and was subsequently discharged from the hospital. On follow-up visit, the patient demonstrated complete reversal of neurological function without developing any sequelae or seizures. He had adequate weight gain within few weeks after starting gluten-free diet.

Fig. 2
figure2

MRI T2 axial images showing pontine myelinosis; hyperintense T2/FLAIR signal in the right anterior central pons. No restricted diffusion

Discussion

Central nervous system (CNS) manifestation of celiac disease develops in about 8–10 % of adults, or it may be the initial symptom of this disease [3]. In childhood, cerebellar ataxia (gluten ataxia) is the most frequent neurological symptom [2, 9], followed by epileptic seizures, neuropathy, myopathy, and multifocal leucoencephalopathy that can be associated with celiac disease. CNS manifestation takes indolent course with most of these changes present later in life into adulthood [2, 9]. Risk of developing neuropsychiatric complications is less in children due to short disease duration, early elimination of gluten from the diet, or different susceptibility to immune-mediated disorders [7].

The reported CNS changes in celiac disease are usually classified as atypical, and extra-intestinal manifestation of gluten sensitivity rarely can present in acute celiac crisis [10]. Most of celiac crisis cases are reported with ataxia [9], paralysis [4], or quadriplegia secondary to hypokalemia [1] with concomitant GI gastrointestinal symptoms. Gupta et al. first described a celiac crisis in a 30-year-old woman who presented with acute quadriparesis, secondary to refractory hypokalemia. Oba et al. had reported on a child with cerebellar ataxia before the onset of diarrhea and metabolic abnormalities [9]. It was suggested that gluten sensitivity (as evidenced by high antigliadin antibodies) has a possible neurotoxic effects caused by the increased ingestion of gluten and, in conjunction with the metabolic effects, may be the cause of the cerebellar ataxia and muscle weakness. To date, there have been no cases of seizure and encephalopathy as a presenting manifestation of celiac crisis with metabolic complications in the absence of severe GI symptoms.

The pathophysiology of neurological disturbances in cases of CD is unknown, but immunological, nutritional, toxic, and metabolic mechanisms have been suggested. However, more evidence points to gluten that can cause direct neurological harm through a combination of cross-reacting antibodies, immune complex disease, and direct gluten toxicity (gluten ataxia). Hadjivassiliou and colleagues detected antibodies against Purkinje cells in sera from individuals with coeliac ataxia as well as cross-reactivity between antigliadin antibodies and epitopes on Purkinje cells [5]. He suggested different neuronal transglutaminase isozymes as markers for gluten sensitivity in relation with the development of neurological disease. Neurological complications may be secondary to vitamin B12 deficiency (e.g., myelopathy and neuropathy), vitamin D malabsorption (e.g., myopathy), or vitamin E deficiency (e.g., cerebellar ataxia and myopathy) [7]. It has been undetermined in our patient if his pontine demyelination is secondary to gluten toxicity or best explained by osmotic demyelination syndrome secondary to the management of his hyponatremia. This suggests that multiple metabolic and autoimmune mechanisms contribute to the development of his seizure.

As with all celiac disease, a gluten-free diet with nutritional support is the treatment of choice. Fifty percent of patients with celiac crisis respond quickly to these interventions alone [6]. Treatment with steroids should be considered in the acute celiac crisis with great expectation to rapid reversal of neurological manifestation, as demonstrated in our patient using methylprednisone of 2 mg/kg. Steroid therapy is considered life-saving especially in terms of celiac crisis complications [8]. Steroids are also suggested in individuals who are not responding promptly to gluten restriction [6]. Steroids can be weaned off completely within few months (within 2 months in our patient) with eventual good response to a gluten-free diet alone with complete reversal of neurological abnormalities.

In conclusion, herein we reported on a case of celiac crisis presenting with status epilepticus in the absence of profound acute GI symptoms. Our case suggests that celiac crisis should be considered in the differential of status epilepticus even in the absence of classical symptoms of celiac disease. Immunological, nutritional, toxic, and metabolic mechanisms have been suggested in the pathophysiology of neurological disturbances. Steroids should be considered in the acute phase of celiac crisis with great results of reversal of neurological manifestation.

Abbreviations

CD:

Celiac disease

CC:

Celiac crisis

MRI:

Magnetic resonance imaging

TTG:

Tissue transglutaminase

GI:

Gastrointestinal

CNS:

Central nervous system

HSV:

Herpes simplex virus

PCR:

Polymerase chain reaction

EEG:

Electroencephalogram

References

  1. 1.

    Bhattacharya M, Kappr S (2012) Quadriplegia due to celiac crisis with hypokalemia as initial presentation of celiac disease: a case report. J Trop Pediatr 58:74–76. doi:10.1093/tropej/fmr034

    PubMed  Article  Google Scholar 

  2. 2.

    Bürk K, Farecki ML, Lamprecht G, Roth G, Decker P, Weller M, Rammensee HG, Oertel W (2009) Neurological symptoms in patients with biopsy proven celiac disease. Mov Disord 24:2358–2362. doi:10.1002/mds.22821

    PubMed  Article  Google Scholar 

  3. 3.

    Gordon N (2000) Cerebellar ataxia and gluten sensitivity: a rare but possible cause of ataxia even in childhood. Dev Med Child Neurol 42:283–286. doi:10.1017/S0012162200000499

    CAS  PubMed  Article  Google Scholar 

  4. 4.

    Gupta T, Mandot A, Desai D, Joshi A (2006) Celiac crisis with hypokalemic paralysis in a young lady. J Gastroenterol 25:259–260

    Google Scholar 

  5. 5.

    Hadjivassiliou M, Aeschlimann P, Strigun A, Sanders DS, Woodroofe N, Aeschlimann D (2008) Autoantibodies in gluten ataxia recognize a novel neuronal transglutaminase. Ann Neurol 64:332–43. doi:10.1002/ana.21450

    CAS  PubMed  Article  Google Scholar 

  6. 6.

    Jamma S, Rubio-Tapia A et al (2010) Celiac crisis is a rare but serious complication of celiac disease in adults. Clin Gastroenterol Hepatol 7:587–590. doi:10.1016/j.cgh.2010.04.009

    Article  Google Scholar 

  7. 7.

    Lionetti E, Francavilla R, Pavone P, Pavone L, Francavilla T, Pulvirenti A, Giugno R, Ruggieri M (2010) The neurology of coeliac disease in childhood: what is the evidence? A systematic review and meta-analysis. Dev Med Child Neurol 52:700–707. doi:10.1111/j.1469-8749.2010.03647.x

    PubMed  Article  Google Scholar 

  8. 8.

    Lloyd-Still J, Grand RJ, Khaw KT, Shwachman H (1972) The use of corticosteroids in celiac crisis. J Pediatr 81:1074–1081. doi:10.1016/S0022-3476(72)80234-8

    CAS  PubMed  Article  Google Scholar 

  9. 9.

    Oba J, Escobar AM, Schvartsman BG, Gherpelli JL (2011) Celiac crisis with ataxia in a child. Clinics 66:173–175. doi:10.1590/S1807-59322011000100031

    PubMed Central  PubMed  Article  Google Scholar 

  10. 10.

    Ozaslan E, Köseoğlu T, Kayhan B (2004) Coeliac crisis in adults: report of two cases. Eur J Emerg Med 11:363–365

    PubMed  Article  Google Scholar 

Download references

Acknowledgments

We would like to acknowledge Dr. Atif Ahmed, pediatric pathologist at Children’s Mercy Hospital, Kansas City, USA, for support in providing histological microphotographs. The abstract has been accepted as a poster presentation at the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition (NASPGHAN) Meeting at Salt Lake City, UT, in October 2012.

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We report no conflict of interest.

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Correspondence to Nadia M. Hijaz.

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Hijaz, N.M., Bracken, J.M. & Chandratre, S.R. Celiac crisis presenting with status epilepticus and encephalopathy. Eur J Pediatr 173, 1561–1564 (2014). https://doi.org/10.1007/s00431-013-2097-1

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Keywords

  • Celiac disease
  • Pediatric
  • Celiac crisis
  • Encephalopathy
  • Seizures