Neurocoeliac disease: Prevalence, diagnosis, treatment and follow up

Coeliac disease is an immune mediated, chronic inflammatory enteropathy caused
by gluten ingestion in genetically susceptible individuals. It is a common
disease in Western Europe, with an estimated prevalence of 0.5-1.0%.
(Altobelli, Paduano, Petrocelli, & Di Orio, 2014; Gujral, Freeman, & Thomson,
2012) Neurological symptoms have been reported in 8 up to 50% of the patients
with coeliac disease, with cerebellar ataxia and peripheral neuropathy being
most common. (Burk et al., 2001; Cicarelli et al., 2003) A high prevalence of
coeliac disease related antibodies has been found in ataxia patients.
(Hadjivassiliou et al., 2013) Autopsy performed on a gluten ataxia patient
revealed loss of Purkinje cells throughout the cerebellar cortex, loss of white
matter, astrocytic gliosis and microglial activation. T-cell infiltration was
seen intra-parenchymal and perivascular, mainly dominated by CD8 positive
lymphocytes. (Hadjivassiliou et al., 1998; Mittelbronn et al., 2010) Currently
no data on patients with coeliac disease and related neurological symptoms is
gathered or stocked in the Netherlands. In this study we will approach this
disease as neurocoeliac disease, defined as a neurological illness otherwise
idiopathic in patients with coeliac disease or gluten sensitivity, which
stabilizes or ameliorates on a gluten-free diet.

The primary (research) objective of this project is to determine the magnitude
of the disease burden of neurocoeliac disease in the Netherlands by studying
the prevalence of coeliac disease or gluten sensitivity in ataxia patients.
The secondary objective is to attain a better understanding of this disease
entity by studying and examining different diagnostic tools and studying the
effects of a gluten-free diet in a cohort of patients with sporadic ataxia and
coeliac disease or gluten sensitivity. We hypothesize that coeliac disease
markers (e.g. Transglutaminase 2 and gliadin antibodies) and Transglutaminase 6
antibodies, a proclaimed neurocoeliac disease marker, will be helpful in
diagnosing gluten ataxia, a form of neurocoeliac disease and monitoring the
effect of a gluten-free diet.

This a prospective and partly retrospective longitudinal cohort study. We will
recruit patients with an unexplained ataxia and test them for coeliac disease
or gluten sensitivity, a gluten-free diet will be initiated if necessary, and
we will perform follow up for 12 months. During visits, blood will be analysed
for antibody titres. If there is no bloodsample yet, a venipunture will be
performed for this study specifically. This will also be the case after 12
months. Patients will undergo a magnetic resonance spectroscopy following a
magnetic resonance imaging (MRI) scan if the latter is planned for standard
care.

The risk of participation is considered to be very low to non-existent. This
study is mainly observational. What will be extra: possibly extra blood will be
drawn if no previous bloodsamples are available or if no venipunctures are
performed for standard care. A patient will undergo an MR spectroscopy directly
after a standard care MRI which will lead to 8 minutes of extra scan time. The
patient will be asked to fill in a brief questionnaire on the quality of life
three times.