I recently heard from a woman via The Gluten File who had narcolepsy that remitted completely on a gluten free diet. She is a medical librarian, and has written this hypothesis paper~ so, I thought I would share it here for anyone who might be interested to read it.



Narcolepsy, Parkinson's Disease, and Lewy Body Dementia:
An Autoimmune Hypothesis

http://www.lindborglabs.com/Hypothesis.html


Cara

Very very interesting. Thank you for the link.

M

So without my having to read each and every link at this time, which I will do, what are the common symptoms of Gluten Sensitivity or Celiac Disease?

How does Gluten Sensitivity or Celiac Disease relate to Parkinson's Disease?

It's not that I'm lazy, I just don't have time to read it right now.

GregD

There are some 250 symptoms associated with celiac disease/ gluten sensitivity, and can affect essentially any organ in the body~ skin, brain, nerves. So... hard to give a comprehensive list.

Here is one fairly comprehensive listing of symptoms.

The most commonly recognized symptoms are GI symptoms (diarrhea, constipation, gas, bloating, GI bleeding, malabsorption).

More common neurological symptoms include neuropathy, ataxia, seizures, cognitive decline, depression. It can also cause neuromuscular symptoms and movement disorders. You can have neurological symptoms with or without having GI symptoms.


From: Neurologic Manifestations of Gastrointestinal Disease by Mark B. Skeen, MD, Neurologic Clinics, Volume 20, Number 1, February 2002

"Neurologic disease associated with gluten sensitivity or celiac disease includes a wide range of manifestations:

Central nervous system (CNS) manifestations include dementia, cerebellar ataxia, myelopathy, encephalopathy, brain stem encephalitis, progressive multifocal leukoencephalopathy,chronic, progressive leukoencephalopathy, progressive myoclonic ataxia, seizures, isolated CNS vasculitis, and a syndrome of celiac disease with encephalopathy and bilateral occipital calcifications.”

“Several reports document the existence of peripheral neuropathy in association with celiac disease.”


How does it relate to Parkinson's Disease? I'm not sure I've seen any hard evidence, although I do see the question arise from time to time. The neurological symptoms of gluten sensitivity are diverse and just starting to be recognized... the connection might be one of potential misdiagnosis in some cases?

There is also the possible zonulin / BBB connection. Zonulin regulates the tight junctions of the intestinal barrier, and the blood brain barrier. It has been shown that those with celiac disease, diabetes, MS, and some other autoimmune diseases have higher levels of zonulin. It has also been shown that the ingestion of gluten actually leads to increased zonulin levels in all people....possibly leading to "leaky gut" and "leaky brain".

Affinity purification and partial characterization of the zonulin/zonula occludens toxin (Zot) receptor from human brain.
PMID: 10617135 Jan 2000

When the finely tuned trafficking of macromolecules is dysregulated in genetically susceptible individuals, both intestinal and extraintestinal autoimmune disorders can occur. This new paradigm subverts traditional theories underlying the development of autoimmunity, which are based on molecular mimicry and/or the bystander effect, and suggests that the autoimmune process can be arrested if the interplay between genes and environmental triggers is prevented by re-establishing intestinal barrier function.
Mechanisms of disease: the role of intestinal barrier function in the pathogenesis of gastrointestinal autoimmune diseases. PMID: 16265432 Sept 2005


CONCLUSIONS: Based on our results, we concluded that gliadin activates zonulin signaling irrespective of the genetic expression of autoimmunity, leading to increased intestinal permeability to macromolecules.
Gliadin, zonulin and gut permeability: Effects on celiac and non-celiac intestinal mucosa and intestinal cell lines. PMID: 16635908 April 2006

There is, however, growing evidence that the loss of the intestinal barrier function typical of celiac disease could be responsible of the onset of other autoimmune disease. This concept implies that the autoimmune response can be theoretically stopped and perhaps reversed if the interplay between autoimmune predisposing genes and trigger(s) is prevented or eliminated by a prompt diagnosis and treatment.
Systemic autoimmune disorders in celiac disease. PMID: 17053448 Nov 2006


Sorry... still gave you a lot to read~

Cara

I just stumbled upon this past post... Narcolepsy and Parkinson's connection?

http://neurotalk.psychcentral.com/sh...ad.php?t=25930

There are definite links between the two. Sorting them out will be a challenge.


http://jnnp.bmjjournals.com/cgi/content/full/72/5/560
THE NEUROLOGY OF COELIAC DISEASE
In 1966 Cooke published a landmark paper on 16 patients with neurological disorders associated with adult CD.8 This was the first systematic review of the subject after the introduction of diagnostic criteria for CD. Ten of these patients had a severe progressive neuropathy. All patients had gait ataxia and some had limb ataxia. Neuropathological data from postmortem examinations showed extensive perivascular inflammatory changes affecting both the central and peripheral nervous systems. A striking feature was the loss of Purkinje cells with atrophy and gliosis of the cerebellum. All 16 patients had evidence of severe malabsorption as evidenced by anaemia and vitamin deficiencies as well as profound weight loss…..

…..A review of all such reports (with biopsy proved CD) from 1964 to date shows that ataxia and peripheral neuropathy are the commonest neurological manifestations seen in patients with established CD…

…Some studies looking at normal populations have shown that the prevalence of CD is much higher than previously thought13,14 (approximating to 1 in 100). Most of such patients have no gastrointestinal symptoms…..

…Systematic screening of 143 patients with so-called "idiopathic sporadic ataxia" showed that 41% had gluten sensitivity as defined by the presence of circulating antigliadin antibodies20 (IgG with or without IgA). The prevalence of antigliadin antibodies in 51 patients with familial ataxia did not differ from that found in normal healthy control subjects (13%). The mean age of onset of the ataxia was 54 but we have recently seen three patients with early onset (under 20 years of age) sporadic idiopathic ataxia and gluten sensitivity. Recently four patients have been described with CD presenting as gait disturbance and ataxia in infancy.21 Alhough the ataxia tends to be slowly progressive, in some cases it can take a very rapid course with the development of cerebellar atrophy within a year of the onset of the illness (fig 1Go). Ataxia and myoclonus is a much less common presentation (only four patients in these series). We have encountered two patients who in addition to ataxia had evidence of chorea but normal genetic testing for Huntington's disease. Gluten ataxia primarily affects the lower limbs and gait. Extrapyramidal or autonomic features are rarely apparent and these features distinguish it from the cerebellar variant of multisystem atrophy (MSA). Screening of patients with clinically probable MSA (cerebellar variant) for the presence of antigliadin antibodies showed the prevalence to be similar to the normal population. Brain MRI usually shows cerebellar atrophy; sometimes with evidence of white matter abnormalities. Up to 40% of patients also have a sensorimotor axonal peripheral neuropathy that can often be subclinical. In a few cases oligoclonal bands are present in the CSF….

….Peripheral neuropathy is the second commonest manifestation of gluten sensitivity. Prospective screening of 101 patients with idiopathic peripheral neuropathy has shown the prevalence of gluten sensitivity to be 40% (unpublished data). The commonest type of peripheral neuropathy we encountered is sensorimotor axonal (26) followed by mononeuropathy multiplex (15), pure motor neuropathy (10), small fibre neuropathy (four) and mixed axonal and demyelinating (two). The neuropathy is usually chronic and of gradual progression. Patients with a pure motor neuropathy may progress to involvement of sensory fibres…..

….Gluten sensitivity is best defined as a state of heightened immunological responsiveness in genetically susceptible people.15 This definition does not imply bowel involvement. That gluten sensitivity is regarded as principally a disease of the small bowel is a historical misconception.28 Gluten sensitivity can be primarily and at times exclusively a neurological disease.

Thanks Cara & Ric,
At least now I have a good idea of what celiac disease/ gluten sensitivity are and do to the body. I can see where there could be a connection to PD.
Hopefully next week I'll be able to sit down and do some reading.

GregD

I also wanted to add that celiac disease and gluten sensitivity cause malabsorption, and therefore widespread symptoms related to vitamin deficiency. Although not widely recognized, nutritional deficiency itself can contribute to wide ranging neurological and neuromuscular symptoms..including depression, dementia, tremors, myoclonus, ataxia, and a whole lot more.

So, in celiac disease/gluten sensitivity, the neurological complications can come from both nutritional deficiency and immune system responses.

I don't know enough about Parkinson's disease to really analyze the possible relationship between these things. I just know that gluten sensitivity can do a lot of neurologic damage that is already well documented, and may be responsible for quite a bit yet undiscovered. For example, I have now heard from two people whose narcolepsy remitted via a gluten free diet. Anecdotal, but I value such evidence.

The problem with gluten related neurological disease is that damage is not as quickly reversed as is damage to the intestines. Sometimes the only hope is to limit further progression. This is the case with gluten ataxia, and also with peripheral neuropathy, and epilepsy (if associated with gluten..not suggesting all is). If caught early enough, there is at least a chance for reversal of symptoms. If identified too late the chances not as good. After removing gluten from the diet, it can take as long as 6-12 months for the immune system to stop reacting, and then those things that can repair do so very slowly.

Cara

I posted recently (and briefly) that I have been on a Gluten Free diet for about 2 months. Afew weeks ago I succumbed to temptation and ate a breaded - with wheat flour - pork chop. Half-way through the meal I began to shake so badly that I couldn't hold the fork. The next morning I was very shakey and my gait was worse than usual. It took almost a week to get back to where I had been pre-breaded chop. Just a few days before that I had noted in my daily log that tremor and gait were both slightly improved.

I was put on this diet by Center IMT in Atlanta. I called to report my experience and the PT there said there could be anywhere from a 10 to 50% reduction in symptom severity when gluten free. She also said that it is not necessary to stay gluten free forwever - but it could take awhile - months to years, depending. Sorry I can't remember her explanations but got that gluten gloms up neuron endings. I also am taking several gluten elimination
supplements.

I don't expect a miracle cure here by anymeans but if eliminating gluten helps - as it seems to - I certainly plan to stick to it. I'm getting used to the diet...sometimes inconvenient and limiting and expensive - but doable.

Do any other PD'ers have gluten-free tales? I have one PD friend who was g-free for 2 years and got rid of all her aches and pains. Now that's encouraging! Come to think of it, I am not hurting as much as I used to either!

Ibby

Great to hear you have had such positive results with a gluten free diet, Ibken! And nothing like an obvious reaction to gluten like the one you had... to confirm to yourself, at least, that gluten is a problem for you. It contradicts any notion that the improvements are placebo affect or coincidental.

How long did it take before you noticed improvement? My young daughter had been exhibiting ataxia like symptoms, but they all resolved within the first couple months... mostly within the first weeks..although we did have a few early oops with the diet that resulted in symptoms showing.

And those little bits of gluten do matter... for some people the slightest cross contamination during food preparation can provoke symptoms, or prevent someone from experiencing meaningful improvement. Live and learn. Even when doing your very best to avoid gluten 100%, there will be some unavoidable mishaps.
I couldn't agree more... and after six years... I don't even notice I'm doing it...except when I go out to eat or I'm traveling. There is still a lot of food in the world that isn't wheat, barley or rye! I just have a little different grocery list than I used to... that has very few boxes.

Did they suggest that you also remove cow's milk? 50% of those with gluten sensitivity also have casein sensitivity, which can do much the same things. Both gluten and casein sensitivity have been suggested to aggravate various neurological and autoimmune diseases. But, it is individual... for some it is one or the other, but sometimes both. OK... corn and soy and yeast for some people, too. Essentially any food can provoke neurologic symptoms depending on the individual, but gluten, casein, soy, corn and yeast top the lists. So... if someone sets out to self experiment, I'd probably follow the dietary guidelines suggested on Direct-MS.


Little is PROVEN in this arena, except for Celiac Disease. And you can definitely have gluten sensitivity without having Celiac Disease... a subject still in hot debate among mainstream medicine... but Dr. Marios Hadjivassiliou has come a far way in proving it during this last ten years. It is proven as far as I'm concerned.

For the most part, gluten sensitivity is thought to be for life. If you stop eating it for long enough, the immune system may calm down and you may be able to tolerate it again for a while...but it will generally catch up with you again.... although it might even take years. That is ABSOLUTELY TRUE in Celiac Disease. There is no question that gluten is out of your diet for life in those who have a Celiac Diagnosis.

However, I do personally believe it might be possible that some gluten sensitivity might be secondary to another condition. For example, if your gut is badly damaged from an h. pyloria infection, parasites, or yeast overgrowth~ that can lead to secondary gluten sensitivity. Sometimes, if you clear those problems and heal the gut, perhaps gluten could reenter your diet. Most people I hang out with, though, would never take that chance.... simply because the risk is to great for recurrence. What if something goes wrong in your gut again? And what if the gluten sensitivity was actually the primary problem and directly responsible for the initial gut damage, and poor nutritional status and poor gut health is why you succumbed to h. pylori infection or yeast overgrowth... something a healthy strong immune system would fight off on its own.

These are just my thoughts... that come from many circular discussions we've had trying to figure this all out. My family doesn't have Celiac Disease (or Parkinson's Disease), but we do have family history of autoimmune diseases (thyroid, pernicious anemia, diabetes) and gluten sensitivity, and we've had a wide variety of neurological problems.

I personally believe anyone with any neurological disease of unknown cause should look closely at nutritional status, potential food sensitivities, and the immune system. Goes true for those with any autoimmune disease.

I pulled these references out of The Gluten File as I thought they might be of interest, especially when talking about whether gluten sensitivity might be secondary to another condition...especially the last one.
There is testing available for gluten sensitivity, but I don't want to get into that now (gone on too long already) except to say you can test negative for IgE wheat allergy and test negative for Celiac Disease... and still have a big problem with gluten. There is a page on diagnostic testing in The Gluten File, and a page on Food Allergy that lists labs that do IgG food allergy testing... also of great debate in the medical community...for anyone interested in pursuing testing.

Cara