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BRIEF COMMUNICATIONS: Connie D.S.N.A. Pengiran Tengah, Robert J. Lock, D. Joseph Unsworth, and Adrian J. Wills Multiple sclerosis and occult gluten sensitivity Neurology 2004; 62: 2326-2327 [Abstract] [Full text] [PDF]

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Reply to Hadjivassiliou et al

Adrian J Wills, DJ Unsworth, RJ Lock, C Tengah   (27 October 2004)

Multiple sclerosis and occult gluten sensitivity

Marios Hadjivassiliou, David S. Sanders, Richard A. Grunewald   (27 October 2004)

Reply to Hadjivassiliou et al 27 October 2004
Adrian J Wills, Queen's Medical Centre Nottingham, UK NG7 2UH, DJ Unsworth, RJ Lock, C Tengah Send Correspondence to journal: Re: Reply to Hadjivassiliou et al adewills61{at}hotmail.com Adrian J Wills, et al.	We have read Hadjivassiliou et al's comments with interest. There is a fundamental difference of opinion regarding the significance of finding serum anti-gliadin antibodies (especially of IgG isotype). Given that over 10% of normals[1] are AGA positive, it would appear that positive serology of this nature has a very low positive predictive value. Assuming that the healthy seropositive subjects are not "gluten sensitive", which neurology patients (patients with multiple sclerosis or other conditions) are "gluten sensitive" and which are "false" positive? Why is positive serology always significant in an ataxic case but not significant in a healthy individual? How do we know which ataxic cases are within the 10% we can ignore and which are significant? The finding of anti-gliadin antibodies in hereditary ataxias[2] and Huntington’s disease[3] can only be interpreted as an epiphenomenon. By way of analogy, in the investigation of suspected syphilis, the VDRL test is regarded as having low specificity. Better follow-up tests are necessary. In celiac disease, experts in the field regard anti- gliadin positivity (especially IgG) as so non-specific as to require further tests (IgA anti-tissue transglutaminase for example). In neurology, patients with suspected "gluten sensitivity", the anti- gliadin antibody test is apparently 100% reliable. Our views regarding gluten ataxia have been detailed. [4] Whether a gluten excluding diet is an effective treatment awaits further study. Our results relating to unselected idiopathic ataxia and peripheral neuropathy cases (in preparation) are very different than Dr Hadjivassiliou’s. We have found few cases of occult celiac disease (no different to the general population) and we have had difficulty finding more than a handful of idiopathic patients in our clinics who are anti-gliadin antibody seropositive, with HLA DQ2 or DQ8. By contrast, there seems to be an epidemic of similar cases in Dr Hadjivassiliou’s series. Finally, neither of our atypical MS cases had evidence of peripheral neuropathy and one of the patients has developed further relapses since the paper was written, suggesting that she does have relapsing-remitting multiple sclerosis. References 1. Hadjivassiliou M, Grunewald R, Sharrack B, et al. Gluten ataxia in perspective: epidemiology, genetic susceptibility and clinical characteristics. Brain 2003;126(Pt 3):685-91. 2. Bushara KO, Goebel SU, Shill H, Goldfarb LG, Hallett M. Gluten sensitivity in sporadic and hereditary cerebellar ataxia. Ann Neurol 2001;49(4):540-3. 3. Bushara KO, Nance M, Gomez CM. Antigliadin antibodies in Huntington's disease. Neurology 2004;62(1):132-3. 4. Wills AJ, Unsworth DJ. The neurology of gluten sensitivity: separating the wheat from the chaff. Curr Opin Neurol 2002;15(5):519-23.
Multiple sclerosis and occult gluten sensitivity 27 October 2004
Marios Hadjivassiliou, Department of Neurology, The Royal Hallamshire Hospital, Sheffield UK Glossop Rd, Sheffield S10 2JF, United Kingdom, David S. Sanders, Richard A. Grunewald Send Correspondence to journal: Re: Multiple sclerosis and occult gluten sensitivity m.hadjivassiliou{at}sheffield.ac.uk Marios Hadjivassiliou, et al.	We agree that gluten sensitivity is not etiologically linked to MS.[1] We screened 100 patients with relapsing-remitting, secondary progressive MS, or both, and found the prevalence of antigliadin antibodies to be 10%; the same as in the healthy population (1200 healthy volunteers, prevalence of 12.5%). [2] Involvement of the white matter of the brain and spinal cord in the context of gluten sensitivity has been reported.[3] However, the MRI changes in those cases were different than seen in MS, being more peripherally situated and often confluent. The authors describe two patients with apparent "atypical" MS-like illness both having ataxia in addition to other neurological deficits. We encountered five patients labeled as having primary progressive or atypical MS-like illness who had gluten sensitivity. The predominant feature was ataxia but other focal neurological deficits were also present. MR imaging of the brain showed changes confined to the white matter, indistinguishable from those seen MS patients. Two of them also had spinal lesions. In three, there was neurophysiological evidence of an axonal peripheral neuropathy a finding distinguishes them from patients with MS. The presence of oligoclonal bands cannot be used as a distinguishing feature as their presence has been reported in up to 50% of patients with gluten ataxia.[4] Gluten -free diet resulted in the stabilization of their neurology but no alteration of the MRI findings. Gluten sensitivity may be considered as the etiology of "atypical" primary progressive MS particularly where ataxia is a prominent feature. The authors' conclusion that "antigliadin antibody (especially IgG isotype) can be a nonspecific finding" should be clarified.[1] There is nothing in their report to support this. The existence of gluten sensitivity even in the absence of an enteropathy is now well established. The neurological manifestations of gluten sensitivity have been shown to improve with gluten free diet even in the absence of an enteropathy.[5] The authors also mention, "poor disease specificity for IgG antigliadin antibodies" which is meaningless given that enteropathy is not a prerequisite for the diagnosis of gluten sensitivity. A third of patients with neurological manifestations of gluten sensitivity have enteropathy, antigliadin antibodies (particularly IgG) remain the best available markers of the whole spectrum of gluten sensitivity of which enteropathy (coeliac disease) is only one part. References 1. Tengah CP, Lock RJ, Unsworth DJ, Wills A. Multiple sclerosis and occult gluten sensitivity. Neurology 2004;62:2326-7. 2. Sanders DS, Patel D, Stephenson TJ et al. A primary care cross-sectional study of undiagnosed adult coeliac disease. European J Gastro & Hep 2003;15:407-413. 3. Hadjivassiliou M, Grünewald RAG, Lawden M, Davies-Jones GAB, Powell T, Smith CML. Headache and CNS white matter abnormalities associated with gluten sensitivity. Neurology 2001;56:385-388. 4. Hadjivassiliou M, Williamson CA, Woodroofe NM. The humoral response in the pathogenesis of gluten ataxia: Reply from authors. Neurology 2003; 60: 1397-1399. 5. Hadjivassiliou M, Davies-Jones GAB, Sanders DS, Grünewald RAG. Dietary treatment of gluten ataxia. J