We read with great interest the review by Grossman on neurologic
complications of celiac disease in a recent issue of Pract Neurol.(1)
Using an evidence-based approach, the author has carefully and critically
analyzed articles published in the last decade on the most common
neurologic manifestations associated with celiac disease, namely ataxia,
epilepsy, and peripheral neur...
We read with great interest the review by Grossman on neurologic
complications of celiac disease in a recent issue of Pract Neurol.(1)
Using an evidence-based approach, the author has carefully and critically
analyzed articles published in the last decade on the most common
neurologic manifestations associated with celiac disease, namely ataxia,
epilepsy, and peripheral neuropathy.
Grossman has rigorously dissected the evidence for, and against, the
possible association of celiac disease with neurological manifestations.
The association, the review concludes, does not seem to hold up when
referral bias is considered or when strict criteria are applied.
While still leaving open the possibility of an association between celiac
disease and certain neurologic disorders, the author calls for well-
controlled and prospective studies to help clarify the issue.
We would like to call attention to a 2-year prospective study, which was
recently published.(2)
After a retrospective study of a cohort of celiac children, where we did
not find a correlation between neurologic manifestations and improvement
on gluten-free diet (3), we undertook a prospective study in an adult
celiac population in order to evaluate the incidence of neurologic
symptoms and examine the response to gluten-free diet.
Our prospective study enrolled 71 patients with histologically proven
celiac disease, who were prospectively followed for up to 28 months.
Of the 71 patients, 69 were consecutively referred to our centre from the
university’s gastroenterology department, whereas 2 directly sought
treatment at our clinic for neuropathic symptoms. Forty-two patients were
on gluten-free diet at recruitment. Adherence to the diet was assessed by
testing for anti-transglutaminase antibodies. All patients underwent
neurological and electrophysiological evaluation at recruitment and at
every follow-up visit.
The results of the prospective study showed that 3 patients were affected
by sensory-motor polyneuropathy. However, 2 of the 3 patients with
polyneuropathy had sought treatment at our clinic for neuropathic
symptoms. Considering this referral bias, only one of the 69 celiac
patients referred for evaluation was affected by neuropathy. Several other
manifestations affecting the nervous system were detected in our celiac
population (4 with headache, 4 with depression, 4 with entrapment
syndromes, 1 with facial hemispasm, and one of the 3 patients with
neuropathy was also affected by epilepsy). However, the relatively common
occurrence in the general population of headache, depression, and
entrapment neuropathies makes it difficult to conclude a likely
association with celiac disease.
Antibody reactivity to neural antigens was detected in 30/71 (42.2%)
patients, but there was no clear correlation between anti-neural
reactivity and active neurologic dysfunction.
Follow-up of 62 patients during gluten-free diet did not reveal
significant changes in electrophysiology. However, in 2 patients with
neuropathy, improvement in symptoms did correlate with the diet.
In conclusion, the results of our prospective study do not seem to support
a causal relationship between biopsy-proven celiac disease and neurologic
disease in the studied group of patients.
We agree with Grossman that further well-controlled studies are warranted
in order to clarify the relationship, as well as the effect of diet.
The use of proper outcome measures should be considered when evaluating
therapeutic efficacy of any intervention (e.g. diet) in such a
heterogeneous disease.(4)
While further research may end up refuting an association between celiac
disease and neurologic dysfunction, gluten sensitivity, as defined only on
the basis of presence of anti-gluten antibodies, might prove to have a
connection with certain neurologic and psychiatric deficits.(5)
The potential relevance and significance of elevated levels of these
antibodies in the absence of celiac disease deserve proper attention as
well and should not be overlooked.
References
1. Grossman G. Neurological complications of coeliac disease: what is
the evidence?
Pract Neurol. 2008;8:77-89.
2. Briani C, Zara G, Alaedini A, Grassivaro F, Ruggero S, Toffanin
E, Albergoni MP, Luca M, Giometto B, Ermani M, De Lazzari F, D’Odorico A,
Battistin L. Neurological complications of celiac disease and autoimmune
mechanisms: a prospective study.
J Neurommunol. 2008;195(1-2):171-5.
3. Briani C, Ruggero S, Zara G, Toffanin E, Ermani M, Betterle C,
Guariso G. Anti-ganglioside antibodies in children with celiac disease: correlation
with gluten-free diet and neurological complications.
Alimentary
Pharmacology and Therapeutics, 2004;20:231-235.
4. Hobart JC, Cano SJ, Zajicek JP, Thompson AJ. Rating scales as
outcome measures for clinical trials in neurology: problems, solutions,
and recommendations.
Lancet Neurol. 2007;6:1094-105.
5. Briani C, Samario D, Alaedini A. Celiac disease: from gluten to
autoimmunity.
Autoimmun Rev. 2008;7(8):644-50.
I read with interest the important case report of Turner and Talbot
describing clinical subacute combined degeneration in a patient with
“functional” vitamin B12 deficiency (defined by elevated levels of the B12
-dependent metabolites, methylmalonic acid and homocysteine, despite
normal serum B12 values).1 It is important to note that although their
patient did not improve with hydroxycobalamin the...
I read with interest the important case report of Turner and Talbot
describing clinical subacute combined degeneration in a patient with
“functional” vitamin B12 deficiency (defined by elevated levels of the B12
-dependent metabolites, methylmalonic acid and homocysteine, despite
normal serum B12 values).1 It is important to note that although their
patient did not improve with hydroxycobalamin therapy, progression of her
disease was halted. This pattern is consistent with B12 deficiency since
neurologic changes become irreversible if B12 therapy is delayed for more
than 6 months.2
Importantly, functional vitamin B12 deficiency may be far more
prevalent than classic B12 deficiency where serum vitamin B12 levels are
clearly depressed.3 Moreover, recent reports suggest that vitamin B12
therapy can indeed improve neuropathy in some patients with functional B12
deficiency as well as in some patients with normal B12, methylmalonic acid
and homocysteine values.3-5 Finally, B12, methylmalonic acid and
homocysteine values have been shown to fluctuate widely in untreated
individuals.3 Thus, when the clinical picture is consistent with B12
deficiency, therapeutic trials of B12 should be considered regardless of
the results of B12 and metabolite testing.
2. Chanarin I. The Megaloblastic Anaemias, 2nd Edition, Oxford, UK.
Blackwell Scientific Publications, 1979:287-290.
3. Solomon LR. Cobalamin-responsive disorders in the ambulatory care
setting” unreliability of cobalamin, methylmalonic acid and homocysteine
testing.
Blood 2005; 105:978-985.
4. Solomon LR. Disorders of cobalamin (vitamin B12) metabolism:
emerging concepts in pathophysiology, diagnosis and treatment.
Blood
Reviews 2007; 21:113-130.
5. Nardin RA, Amick ANH, Raynor EM. Vitamin B12 and methylmalonic acid
levels in patients presenting with polyneuropathy.
Muscle Nerve 2007;
36:532-535.
Dear Editor,
We read with great interest the review by Grossman on neurologic complications of celiac disease in a recent issue of Pract Neurol.(1)
Using an evidence-based approach, the author has carefully and critically analyzed articles published in the last decade on the most common neurologic manifestations associated with celiac disease, namely ataxia, epilepsy, and peripheral neur...
Dear Editor,
I read with interest the important case report of Turner and Talbot describing clinical subacute combined degeneration in a patient with “functional” vitamin B12 deficiency (defined by elevated levels of the B12 -dependent metabolites, methylmalonic acid and homocysteine, despite normal serum B12 values).1 It is important to note that although their patient did not improve with hydroxycobalamin the...
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