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Table of Contents    
Year : 2018  |  Volume : 66  |  Issue : 6  |  Page : 1810-1812

Celiac disease presenting as motor neuron disease

Department of Neurology, College of Medicine, The Catholic University of Korea, Seoul, Korea

Date of Web Publication28-Nov-2018

Correspondence Address:
Dr. Jee Eun Lee
Department of Neurology, St. Vincent's Hospital, The Catholic University of Korea, 93-6, Ji-dong, Paldal-gu, Suwon, Gyeonggi-do, 442-723
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0028-3886.246268

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How to cite this article:
Lee JE, Ryu DW, Kim JS, An JY. Celiac disease presenting as motor neuron disease. Neurol India 2018;66:1810-2

How to cite this URL:
Lee JE, Ryu DW, Kim JS, An JY. Celiac disease presenting as motor neuron disease. Neurol India [serial online] 2018 [cited 2022 May 26];66:1810-2. Available from: https://www.neurologyindia.com/text.asp?2018/66/6/1810/246268


Celiac disease (CD) is an autoimmune disorder that affects genetically predisposed individuals upon ingestion of gluten. Many extra-intestinal manifestations of CD, such as neuropathy, ataxia, and psychiatric alterations, have been reported in the literature.[1],[2],[3] We report a case of motor neuron disease (MND) syndrome due to CD, in which a gluten-free diet improved neurologic symptoms.

A 60-year-old man was diagnosed with MND at another hospital 6 months before presentation. He had a 4-year history of slowly progressive, generalized weakness and cramping of proximal legs. Weakness started from the left leg, but there was little progression of weakness during the first 2 years. Over the next 2 years, weakness gradually progressed to all four limbs and there was a 10% loss (6 kg) of total body weight. The patient complained of abdominal pain and diarrhea but did not have sensory or bulbar symptoms. There was no significant medical history except for emphysema, and the family history was unremarkable. The referring neurologist had treated the patient with intravenous immunoglobulin (IVIgG) considering the possibility of multifocal motor neuropathy. There was no improvement and so he diagnosed the patient with amyotrophic lateral sclerosis (ALS) and started riluzole. The patient visited our clinic for a second opinion. Neurologic examination revealed generalized weakness (Medical Research Council Grade 4+/4+ in shoulder abduction, 4/4 in elbow extension, 4/4 in wrist extension, 4+/4+ in hip flexion, 4/4 in knee flexion, and 3/2 in ankle dorsiflexion) and diffuse fasciculations. The biceps jerk and knee jerk were diminished and ankle jerk was absent. Cranial nerve, cerebellar function, and sensory examinations were normal, and there were no pathologic reflexes. Needle electromyography showed active denervation and neurogenic changes in motor unit potentials in the sternocleidomastoid, biceps brachii, triceps, first dorsal interosseous, vastus lateralis, tibialis anterior, and gastrocnemius muscles. Active denervation was recorded in the thoracic paraspinal muscles. Nerve conduction studies were normal except for the low amplitude of the left peroneal nerve compound muscle action potential. Routine blood tests, electrolytes, liver functions, renal functions, vitamin B12, and serum folate tests were normal. Tests for human immunodeficiency virus (HIV) antibodies and autoimmune diseases were negative. The cerebrospinal fluid analysis was normal. Cervical spine magnetic resonance imaging showed no signal changes in the spinal cord. Gastroduodenoscopy for abdominal pain and weight loss revealed scattered erythemata in the stomach and loss of villi, engorgement of intraepithelial capillaries, and macrogranularity in the duodenum. Capsule endoscopy showed villous atrophy and a mosaic pattern of micronodularity and scalloping layered folds at the proximal small intestine [Figure 1]a. The biopsy showed flattened villi with lymphocyte infiltration at the duodenum and severe lymphoplasma cell infiltration with lymphoid aggregates at the ascending colon and rectum [Figure 1]b,[Figure 1]c,[Figure 1]d. Endomysial antibody IgA was positive (1:160) and transglutaminase antibody IgA was more than 100 U/mL (normal reference value <4 U/mL). The patient was diagnosed with CD and was started on a gluten-free diet without riluzole. Three months later, diffuse fasciculations and gastrointestinal symptoms had resolved and there was mild improvement in muscle weakness. There was still a persisting ankle weakness.
Figure 1: Capsule endoscopy (a) showed diffuse atrophic villous mucosal changes with blunting of villi, mosaic patterns of micronodularity, and scalloping layered folds in the proximal small intestine. Biopsy findings showed villous atrophy (b) (hematoxylin and eosin [H and E], ×200), increased intraepithelial lymphoplasma cells (c) (H and E, ×400) in the duodenum, and severe lymphocyte infiltration with lymphoid aggregates in the ascending colon (H and E, ×400) (d)

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MND can be classified into several types depending on whether the disease involves the upper or the lower motor neurons or both. There are no biomarkers for the diagnosis of MND, so the establishment of diagnosis of MND is entirely clinical through exclusion of possible alternative diseases. Our patient only had symptoms and signs of lower motor neuron dysfunction and his symptoms progressed gradually despite treatment with IVIgG. These were compatible with the manifestations of progressive muscular atrophy variant of MND. However, there were atypical presentations such as weight loss with gastrointestinal symptoms and a 2-year rest period without progression after the development of initial weakness. We accidently discovered CD in the course of a work-up and observed improvement of weakness and fasciculations associated with a gluten-free diet, albeit for a short-term follow-up duration. We finally diagnosed MND-mimicking syndrome associated with CD because MND is progressive and there is no effective treatment to halt or reverse the progression of the disease. CD is a gluten-sensitive enteropathy and the pathological trigger is gluten, a protein commonly found in rye, barley, and wheat. The diagnosis of CD is made by antibody testing and duodenal biopsy. Endomysial IgA antibody and transglutaminase antibody are highly sensitive and specific markers for gluten-sensitive enteropathy, and duodenal biopsy analysis demonstrated the triad of villous atrophy, crypt hyperplasia, and an increase in the number of intraepithelial lymphocytes that characterize CD.[4],[5] The most common neurological manifestations of CD are ataxia and neuropathy such as chronic inflammatory demyelinating neuropathy, autonomic neuropathy, and mononeuritis multiplex.[6],[7] The mechanism of neuronal damage in CD is still unclear. One hypothesis is that perivascular inflammation may lead to the breakdown of blood–brain barrier, allowing an influx of antibodies that cross-react with neural tissue in the brain.[3] Immunological and autoimmune factors may be the cause of neuropathy through a molecular mimesis mechanism.[8] A few case studies have reported CD mimicking ALS,[3],[9],[10] and all these disorders were relieved following the administration of a gluten-free diet [Table 1]. However, there have been no reports similar to our case showing only pure lower motor neuron symptoms and active denervation of all muscles including the bulbar, cervical, thoracic, and lumbar spinal segments. The mechanism of neurologic improvement due to a gluten-free diet is unknown. Some authors hypothesize that a gluten-free diet could reverse malabsorption of trace elements as a cause of neurologic dysfunction.[8]
Table 1: Celiac disease mimicking amyotrophic lateral sclerosis

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CD appears to be rare in Southeast Asia because of rice as the staple diet and a low frequency of specific human leukocyte antigen type. However, there is the potential for a rising incidence of CD as traditional rice-based diets are being replaced by Western-style diets. Given the lack of awareness and low suspicion of CD in Asia, there is a possibility that our insights may not be useful to those patients who have not yet been diagnosed with CD. It is also important to consider all potentially treatable neurological diseases, although some diseases may have a very low incidence, before diagnosing MND in a patient.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

  References Top

Cooke WT, Smith WT. Neurological disorders associated with adult coeliac disease. Brain 1966;89:683-722.  Back to cited text no. 1
Jackson JR, Eaton WW, Cascella NG, Fasano A, Kelly DL. Neurologic and psychiatric manifestations of celiac disease and gluten sensitivity. Psychiatr Q 2012;83:91-102.  Back to cited text no. 2
Turner MR, Chohan G, Quaghebeur G, Greenhall RC, Hadjivassiliou M, Talbot K. A case of celiac disease mimicking amyotrophic lateral sclerosis. Nat Clin Pract Neurol 2007;3:581-4.  Back to cited text no. 3
Brocchi E, Corazza GR, Caletti G, Treggiari EA, Barbara L, Gasbarrini G. Endoscopic demonstration of loss of duodenal folds in the diagnosis of celiac disease. N Engl J Med 1988;319:741-4.  Back to cited text no. 4
Sollid LM. Intraepithelial lymphocytes in celiac disease: License to kill revealed. Immunity 2004;21:303-4.  Back to cited text no. 5
Hadjivassiliou M, Grunewald RA, Chattopadhyay AK, Davies-Jones GA, Gibson A, Jarratt JA, et al. Clinical, radiological, neurophysiological, and neuropathological characteristics of gluten ataxia. Lancet 1998;352:1582-5.  Back to cited text no. 6
Thawani SP, Brannagan TH 3rd, Lebwohl B, Green PH, Ludvigsson JF. Risk of neuropathy among 28,232 patients with biopsy-verified celiac disease. JAMA Neurol 2015;72:806-11.  Back to cited text no. 7
McKeon A, Lennon VA, Pittock SJ, Kryzer TJ, Murray J. The neurologic significance of celiac disease biomarkers. Neurology 2014;83:1789-96.  Back to cited text no. 8
Bersano E, Stecco A, D'Alfonso S, Corrado L, Sarnelli MF, Solara V, et al. Coeliac disease mimicking amyotrophic lateral sclerosis. Amyotroph Lateral Scler Frontotemporal Degener 2015;16:277-9.  Back to cited text no. 9
Brown KJ, Jewells V, Herfarth H, Castillo M. White matter lesions suggestive of amyotrophic lateral sclerosis attributed to celiac disease. AJNR Am J Neuroradiol 2010;31:880-1.  Back to cited text no. 10


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