I went to a talk today hosted by GIG of Marin (the gluten intolerance group of Marin) entitled:
How Gluten can affect the brain: from seizures and headaches to anxiety and inattention. Julie A Griffith, MD, MS, CMT (Neurologist – San Rafael)
Caveat: This was not written by Angela. It was written by me, her husband. I am by no means a Celiac disease expert, but I am a neurologist. I am still trying to learn about celiac disease as my children have been formally diagnosed. That was the impetus for coming to the talk tonight.
My take home: Raising awareness of the neurologic complications of celiac disease is always a good thing, and Dr. Griffith surely accomplished that goal.
1) Try not to over interpret data – always consider the quality of the data. Just because it is published in a “medical journal” isn’t enough. The quality of the study is key.
A few pointers – case reports are by definition a single case. They are usually very bizarre and unusual, which is why the story is worth writing about.
Big name medical journals have a much higher level of quality than lesser known journals as the process of peer review is much more stringent (i.e. Brain, Neurology, Annals of Neurology, Archives of Neurology are much more reputable that the Psychiatra Polska).
Side note - This is a Polish journal that was used tonight to back up a claim that Celiac Disease is linked to temporal lobe epilepsy. First off, this article is written in Polish. Second, it is an old article and not available online (even to doctors). This makes determining the quality of the study very difficult. From my search, there is one good recent article on this topic, which is a small group of patients (only 7) from a respectable neurological journal. Here is the reference:
Peltola M, et al. Hippocampal sclerosis in refractory temporal lobe epilepsy is associated with gluten sensitivity. J Neurol Neurosurg Psychiatry. 2009 Jun;80(6):626-30. Epub 2009 Feb 24.
Lastly, the usual seizures associated with celiac disease (which are very rare) are visual in nature manifesting as geometric shapes or lights in the visual field, and are thought to be caused by calcifications in the occipital lobe (which is the vision center). In truth, this could feel very similar to a visual aura for a migraine. They are not the grand mal seizures that you are probably thinking of and are terrified of witnessing or suffering.
Larger numbers are better – again, a case report is not good evidence and you should be very careful drawing any conclusions from such evidence. A study with hundreds or thousands of patients that were randomized to a treatment and then rated by an expert evaluator that was blinded to their treatment… that is a good study.
Positive take home point – consider the source, this is no slight on Dr. Griffith. I am referring to the data itself. Consider the quality of the data before drawing any conclusions. As it turns out, all that hoopla about Autism and vaccines was proven to be falsified research. The one who wrote the original article will never be able to publish research in a medical journal again. Just take a step back and consider the source.
2) Take a step back and take a deep breath - As a Neurologist and a father of twins with Celiac disease, I was troubled by the fear that I saw in the faces of some around me. The information about the risks of neurological illness presented in this talk were at times very misleading. Let me illustrate:
One of the slides included a long list of neurological symptoms that have been associated with celiac disease including Attention deficit, Encephalopathy, Epilepsy (especially temporal lobe) – see above for this poor level of evidence, Neuropathy (conflicting evidence), Sleep disorders, Myopathy, Autonomic neuropathy, Multiple systems atrophy (a rare a fatal neurodegenerative disease), Dystonia, Childhood stroke and White matter lesions on the brain.
As a lay person, I would have left this talk thinking that my child is doomed or at least wondering when one of these awful things was going to happen to my child. This same kind of list was also applied to adults within the talk.
What are the actual risks? Are these one in a million or is this a very common problem? How worried should I actually be?
This was presented a couple of times in different ways, and the crowd in attendance at times reacted with the appropriate exclamations of fear and dismay at hearing this terrifying list.
My advice, take a step back and look at the evidence. Then take a deep breath and realize that your child is most likely going to be OK.
In the talk she stated that Celiac disease is found in about 1% of people. That is roughly 3 million Americans (1% of 300 million). The vast majority of people with celiac disease will never get any of these symptoms. In one of the first slides it estimated that 10-22% get a neurological symptom. Sure, that is 300,000-600,000 people, but the other 2.4-2.7 million Americans with diagnosed celiac disease are going to be just fine.
Positive take home point – don’t freak out. Just be aware of the possibility, and if something pops up, think about Celiac disease as a cause and talk about it with your Doc.
3) Be cautious about extensive and expensive testing. The first rule of medicine in the Hippocratic oath is “Primum non nocere” or “First, do no harm.” Spending a lot of time, money and energy getting tested can be harmful to your pocketbook, your relationships and your sanity.
The work-up that was suggested for celiac disease in this talk would run you into the thousands and possibly tens of thousands in cost. I am pretty sure that she was not actually suggesting that all of this be done, but it was a bit unclear.
The list of labs that was presented as “to do” is not necessarily mainstream, as was alluded to by one of the organizers in the back of the room.
One of the labs was touted as being 100% sensitive, which was reiterated twice in the talk. Specificity was not mentioned. What am I talking about? Let me explain. From good ol’ Wikipedia:
Sensitivity measures the proportion of actual positives, which are correctly identified as such (e.g. the percentage of sick people who are correctly identified as having the condition).
Specificity measures the proportion of negatives, which are correctly identified (e.g. the percentage of healthy people who are correctly identified as not having the condition).
Put another way, a sensitivity of 100% means that the test recognizes all actual positives and a specificity of 100% means that the test recognizes all actual negatives.
Let me illustrate this principle: It would be correct to say that testing to see if someone has intestines is 100% sensitive for detecting patients with celiac disease. This is true because everyone who has celiac disease, also has intestines. There will be no false negatives (or in other words, you will not miss a single person with celiac disease when you check to see if they have intestines by this measurement). However, the specificity of this test is hideously bad. Everyone has intestines, so the false positive rate is going to be sky high making it a useless test for the diagnosis of celiac disease.
Take home point – It is easier said than done, but try not to spend to much time, money or energy getting tested only to find out later that the test is essentially uninterpretable. Find out how good the test is (Sensitivity and Specificity) before going ahead with it. In other words, before getting tested, know how to interpret your result.
Again, per the conversation in the room, this point is going to be addressed in a talk within the group this coming April, so tune in for more.
My NOTES from the Talk:
- Celiac Disease is 1% of the population
- 10-23% have neurological symptom
- 70% had abnormalities on EEG in an Israel cohort
- Those with neuro symptoms usually don’t have GI symptoms.
- Hadjivassilou et al 2010 – many other gluten sensitivity syndromes can affect the brain?
- Gut and Neuro disease 10-22.5% (Holmes et al, 1997 Brain)
- Ataxia is the most common neuro symptom of celiac
- Commonly in autism, there is elevated urine gluteomorphin which binds to opioid receptors in the brain.
Neuro symptoms in Celiac – Grossman 2008, Zingone 2010
- Attention deficit
- Headache – check Mg++, give magnesium glycinate (helps to make GABA)
- Epilepsy (especially temporal lobe)
- Neuropathy (conflicting evidence) – periph sensory/motor
- Sleep disorders
- Myopathy ???
- Autonomic neuropathy
- Childhood stroke
- White matter lesions on the brain
Gluten and Anxiety –
- Prevalence of 17% in Celiac - Hauser et al (germany 2010), 14% in IBS, 6% in general population
- GF diet has been associated with decreased anxiety in celiac disease – Collins 2008 (Sca J Gastroentereology)
- She proposes that this is due to poor perfusion due to leaky blood vessels (dubious!), she also proposes vitamin deficiency and anemia as etiology (possible)
- B12 and folate lowered anxiety in Celiac (Hallert et al, 2009)
- Omega 3, 6, 9 which increases prostaglandin 3 (anti-inflammatory)
Gluten and Ataxia –
- 500 patients in UK with progressive ataxia, ~100 were positive for anti-TTG Iga and IgG
- Those who also had gut disease had elevated anti-TTG and gliadin abs
- If no GI symptoms the titers were positive but lower
Gluten and ADD –
- J Atten Disorder 2006 Nov, Niederhofer
- 1 study – unclear number of patients
Gluten and Encephalopathy –
- A case report with wide spread white matter changes.
Epilepsy and Gluten –
- Psyciatria Polska 1991 Kozlowska
- Study of 41 patients associting celiac disease with temporal lobe epilepsy.
Gluten and Hypoperfusion ????? -
- Am J Med, 2004, Addolorato (need to look this one up)
Gluten induced sensory neuropathy (vs. B12)
- Hadjivassilou, Neurology, 2010 Sep
- This is a large study, in a very good journal
Gluten and sleep disorders
- Poor quality paper?!? Hmmm.
Labs to test
- IgE and IgG type 4 to gluten, barley, rye
- Urine for gluteomorphin level
- HLA-DQ testing
- Anti TTG2 IgA and IgG
- Anti-TTG6 bind to the brain (purkinje cells in the cerebellum, pons) – leads to loss in purkinje cells
- Some lab that apparently has 100% sensitivity for Celiac… what is the specificity?
- Duodenal gut biopsy (gold standard) – buccal swab for genetic predisposition
- IgA level
- IgE level
- GI bacterial search
Pathophysiology of gluten-induced neuro disease
- Hadjivassilou Neurology Sep 2010 (need to look this up, Neurology is a good journal)
- Nutritional supplementation
- Supplement amino acids
- Vit A, D, E, K
- B vitamins
- Removing other food allergens
- Checking stool for other disease
- Consider supplementing mitochondira – i.e., ribose 5 phosphate, L-carnitine, co-enzyme Q10, NADH (data?????)
- Steroids can help???? – in neurologic condition
Verbal apraxia and autism –
- Morris and Agin 2009
- Received vitamin E, polyunsaturated
- Had low carnitine, deficiencies in zinc
Neurological symptoms in Adults with Celiac
- Cerebral calcifications
- Depression in the elderly
- NMO – need to look up
- MS – need to look up
She recommended taking Quercetin 500-3000mg PO daily – can help with joint arthritis (data?????)
Celiac disease with spastic paraparesis, diplopia and decreased visual acuity
- Haddou et al 2009 –
- Required steroids to treat
Warned that MNGIE can mimic the symptoms of celiac disease (devastating mitochondrial disease)
- abdominal pain, diarrhea, eye muscle weakness, peripheral neuropathy, weakness
- pathology had ragged red fibers in the muscle and a leukodystrophy of the brain