A man now 80 years old presents progressive ataxia amb pendular nystagmus wich began at age 75. A extensive study was negative. He doesn't present malabsorption and diarrhea, Two month ago vomited freqüently and ataxia got worse . Transglutaminase and endomisium antibodies were negative, Recent duodenal biopsy is compatible with celiac disease (MARSH 3), amb HLA-DQ2 is positive. Slight improvement with gluten free diet.
This case, a silent seronegative celiac disease with clinical neuroloy over age 75,is a exception, or is not a true celiac disease, or instead, may be a possible cause of some idiophatic ataxias ?,
Celiac disease can cause ataxia by various means [1] Direct cerebellar affection by antibodies in which case reversal might occur if diagnosed and treated early, [2] By vitamin deficiencies due to malabsorption e.g. B1, B12 and E. B12 deficiency is due to associated autoimmune gastritis (pernicious anemia) and pancreatic atrophy with celiac. These are treatable and needs exclusion. Rarely other intestinopathies with malabsorption like Whipple's disease, abetalipoproteinemia can cause ataxia.
Of course it s clearly possible. You must recommend to start a gluten-free-diet as soon as possible
Ataxia is not rare in old people, and most of them are idiophatic. If transgluminase and endomisium antibodies are negative, do you think is necessary a duodenal biopsy to exclude the possibility of celiac disease, like the present case, a silent seronegative celiac disease?
At the age of this gentleman, an age related brain atrophy may be the principal cause of ataxia which can be excluded by CT/MRI scan of brain. Isolated mucosal atrophy in the absence of antibodies and without malabsorption (at MARSH 3 stage) may also be partly age related or associated with other subtle non gluten food intolerance.
Yes, I am agree with Gatam Ray, but after ataxia got worse with vomits and dysphagia , he has improved significantly with a gluten free diet . Also the duodenal biopsy and HLA are positives. All this suggests that the patient has celiac disease, But our question is whether a seronegative celiac disease can produce neurological disease, like ataxia and dysphagia.
In this old age most of celiac patients present a negative serology for CD
If he has improved significantly with gluten free diet, there is definite possibility of celiac disease.The serology may be negative in old age as antibody generation may be low but also depends on the type and amount of diet that the patient was consuming just before the acute attack as antibody generation depends on the antigen exposure [diet].
The relation of celiac disease and ataxia is certainly not linear. At this age, and without any manifestation of CD before, I would describe this as ataxia in the presence of, at best. Rather, I'd presume some late manifestation of some degenerative ataxia (e.g. SCA, MSA-C) with worsening by intercurrent vomiting. Alternatively, one might consider the vomiting as symptom of MSA... So clinical diagnosis will become more clear at follow-up.
The temporal relationship to improvement with a gluten free diet is significant, in the context of excluding other more common reasons for his symptoms. Vertebrobasilar insufficiency, for example, with MRA (Magnetic resonance angiography) if found to be negative, and as suggested by Dirk Ulbricht 'degenerative ataxia', and by Gautam Ray 'age related brain atrophy' with negative imaging, would strenghten the case for a Coeliac-related causation.
I recommend the addition of the supplements found in Metanx BID, which contains the following active ingredients (per capsule):
L-methylfolate (Metafolin): 3 mg
Pyridoxal 5'-phosphate: 35 mg
Methylcobalamin: 2 mg
And, add Krill oil 3-4grams per day all at once. These help repair the axon and myelin of nerves. Also, he should be oat free due to a similar amino acid sequence as found in wheat.
Yes it can by the pass way of inflammasomes. The long term sub clinical inflammation of the gut will activate these. See the article in Nature I think a year ago. See also: Melanie Uhde et all: Intestinal cell damage and systemic immune activation individuals reporting sensitivity to wheat in the absence of coeliac disease, Gut 2016.
Indeed well established, well known - refer to Hajdivassalou's work from Sheffield. AV