White Matter Lesions Suggestive of
Amyotrophic Lateral Sclerosis Attributed to
Celiac Disease
K.J. Brown, V. Jewells, H. Herfarth and M. Castillo
This information is current as
of April 12, 2024.

AJNR Am J Neuroradiol 2010, 31 (5) 880-881
doi: https://doi.org/10.3174/ajnr.A1826
http://www.ajnr.org/content/31/5/880

CASE REPORT
K.J. Brown
V. Jewells
H. Herfarth
M. Castillo

White Matter Lesions Suggestive of Amyotrophic
Lateral Sclerosis Attributed to Celiac Disease
SUMMARY: CD is an autoimmune-mediated disorder of the gastrointestinal tract. Initial symptom
presentation is variable and can include neurologic manifestations that may comprise ataxia, neuropathy, dizziness, epilepsy, and cortical calcifications rather than gastrointestinal-hindering diagnosis and
management. We present a case of a young man with progressive neurologic symptoms and brain MR
imaging findings worrisome for ALS. During the diagnostic work-up, endomysium antibodies were
discovered, and CD was confirmed by upper gastrointestinal endoscopy with duodenal biopsies. MR
imaging findings suggestive of ALS improved after gluten-free diet institution.
ABBREVIATIONS: ALS ⫽ amyotrophic lateral sclerosis; CD ⫽ celiac disease; FLAIR ⫽ fluid-attenu-

ated inversion recovery; IgA ⫽ immunoglobulin A

C

D is an inflammatory condition of the small intestine also
called celiac sprue, nontropical sprue, and gluten-sensitive
enteropathy. The most common presenting symptoms include diarrhea, steatorrhea, weight loss, iron deficiency anemia, and abdominal distension. Imaging findings specific to
the brain have been reported primarily involving the periventricular white matter.
Case Report
A 32-year-old man with a 1-year history of balance difficulties presented with 1 week of worsening symptoms, including hand tremors
and gait disturbance. Admission review of systems revealed a 60pound (27.22 kg) weight loss during the past year, which he attributed
to diarrhea consisting of 3– 4 loose stools per day. Physical examination showed a broad-based gait leaning to the right, dysmetria with
right finger-to-nose, hyperreflexia, an upgoing right toe, right lower
extremity weakness, and right foot drop. Sensation was normal. Laboratory studies revealed a slightly elevated phosphorus concentration
(4.8 mg/dL), but findings were otherwise normal. Brain MR imaging
showed abnormal increased signal intensity on T2 and FLAIR in the
bilateral corona radiata, extending inferiorly into the corticospinal
tracts without contrast enhancement (Fig 1).
Initial diagnostic considerations included ALS and Friedrich
ataxia. Electromyelography findings of the right upper and lower extremities were normal. Total spine MR imaging and CT findings of
the chest, abdomen, and pelvis were normal. CSF findings for herpes
simplex virus, human herpesvirus 6 cytomegalovirus, varicella-zoster
virus, Epstein-Barr virus, and Venereal Disease Research Laboratory
test were negative, but ⫹4 oligoclonal bands were noted. Findings
were negative for paraneoplastic antibodies. Ataxia work-up included
a positive antiendomysial antibody titer of 1:160. Duodenal biopsies
yielded crypt hyperplastic villous atrophy with numerous intraepithelial lymphocytes, most consistent with gluten-sensitive enteropathy.
The patient started a strict gluten-free diet with improvement of
symptoms during the next several months. Repeat brain MR imaging
(23 months after initial presentation) revealed resolution of initial
Received June 23, 2009; accepted July 3.
From the Department of Radiology (K.J.B., V.J., M.C.) and Division of Gastroenterology and
Hepatology (H.H.), University of North Carolina, Chapel Hill, North Carolina.
Please address correspondence to Kelan J. Brown, MD, Department of Radiology, University of North Carolina, 2036 Old Clinic Bldg, CB 7510, Chapel Hill, NC, 27599-7510; e-mail:
kelanbrown@gmail.com
DOI 10.3174/ajnr.A1826

880

Brown 兩 AJNR 31 兩 May 2010 兩 www.ajnr.org

abnormalities (Fig 2). Continued physical therapy and a gluten-free
diet have been prescribed.

Discussion
CD is an inflammatory condition of the small intestine also
called celiac sprue, nontropical sprue, and gluten-sensitive enteropathy.1 The disease appears in early childhood and has a
second peak in the third-to-fourth decades. Males and females
are equally affected, and its incidence has increased in Northern Europe and the United States.2,3 Multiple other disorders
have been associated with CD, including Down syndrome,
insulin-dependent diabetes mellitus, IgA deficiency, and
rheumatoid arthritis.1
Symptoms are precipitated in genetically predisposed individuals by ingestion of foods containing gluten, such as wheat,
rye, and barley. Consumption of triggering foods leads to an
autoimmune-mediated inflammatory response in the small
intestine, resulting in villous atrophy and malabsorption.3 The
most common presenting symptoms include diarrhea, steatorrhea, weight loss, iron deficiency anemia, and abdominal
distension.
The diagnosis is sometimes difficult to make given that not
all patients present in the same manner and that symptoms
overlap other gastrointestinal disorders. Half of patients have
iron deficiency anemia or osteoporosis, without diarrhea. Diagnostic evaluation for CD consists of antibody testing and
duodenal biopsy.4 The most sensitive and specific antibodies
for its confirmation are tissue transglutaminase IgA and endomysial IgA antibodies. Due to the low specificity compared
with tissue transglutaminase and endomysium antibodies, gliadin antibodies should no longer be used in the diagnostic
work-up for CD. Duodenal biopsies are still the criterion standard for tissue diagnosis and reveal villous atrophy5 and increased intraepithelial lymphocytes.6
Neurologic findings associated with CD disease were initially reported in 1966 by Cooke and Smith.7 Most common
symptoms are ataxia and neuropathy, followed by epilepsy,
ALS and multiple sclerosis-like symptoms, isolated motor
neuron disorders, sensory ataxia, and dizziness. These complications may arise as consequences of vitamin and mineral deficiencies. Other authors discuss a potential pathophysiologic
role of antigliadin antibodies in a neurotoxic autoimmune
process.8

Fig 1. FLAIR images from initial brain MR imaging demonstrate abnormal increased signal intensity in the white matter of the centra semiovale and bilateral corticospinal tracts.

Fig 2. Follow-up FLAIR images after a gluten-free diet show complete resolution of signal-intensity abnormalities.

1. Green PH, Cellier C. Celiac disease. N Engl J Med 2007;357:1731– 43
2. Collin P, Kaukinen K, Vogelsang H, et al. Antiendomysial and antihuman

AJNR Am J Neuroradiol 31:880 – 81 兩 May 2010 兩 www.ajnr.org

881

CASE REPORT

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BRAIN

MR imaging is used primarily in the diagnostic work-up of
CD-associated conditions. Nonspecific periventricular white
matter lesions of various sizes with increased T2/FLAIR signal
intensity and without enhancement have been described.9,10
The lesions may be unilateral and bilateral.11 Occipital calcifications have also been reported. In 2007, Turner et al12 reported a case of CD mimicking ALS with T2/FLAIR signalintensity abnormalities in the left corticospinal tract, which
improved on a gluten-free diet. Our patient also showed abnormal signal intensity involving both corticospinal tracts on
MR imaging. His symptoms and MR imaging lesions improved and resolved, respectively, on appropriate treatment of
CD. Ours is the second patient reported with this group of
findings. Because ALS is a progressive and untreatable disease
while CD is easily treatable, considering the latter as a cause of
neurologic disorders in patients with ALS-like symptoms may
be indicated.