Polyneuropathy while on duodenal levodopa infusion in Parkinson’s disease patients: we must be alert

submitted by Hicivilmiff

Some reports have emerged describing the occurrence of Guillain-Barré syndrome and polyneuropathy related to vitamin B12 deficiency in some patients with Parkinson’s disease (PD) treated with continuous duodenal levodopa infusion. We describe five PD patients who developed axonal polyneuropathy and vitamin B12 deficiency while on treatment with duodenal levodopa infusion... One case of Guillain-Barré syndrome and at least 12 cases of polyneuropathy related to vitamin B12 deficiency have been reported in PD patients treated with duodenal levodopa infusion. Levodopa gel infusion may induce a decrease in vitamin B12 levels, leading to peripheral neuropathy. Additional pathogenetic mechanisms include alterations related to the metabolism of l-dopa, abnormal l-dopa absorption, and direct neurotoxicity of l-dopa at high doses.... Vitamin B12 deficiency in patients on duodenal levodopa infusion therapy may be more frequent than the published data suggest..

http://scienceindex.com/stories/2081..._be_alert.html


Rajabally YA, Martey J. Neuropathy in Parkinson disease: prevalence and determinants. Neurology 77(22), 1947–1950 (2011).

Sections:

Peripheral neuropathy and levodopa therapy in Parkinson’s disease (PD) are two unlikely bedfellows. Despite decades of levodopa use in thousands of patients, this association has not previously been noted until recently [1]. Case reports of Guillain–Barré syndrome (acute demyelinating neuropathy) have been reported in subjects with intraduodenal infusions of levodopa. The potential pathogenesis may be due to catabolic pathways involving levodopa that could reduce S-adenosylmethionine and lead to lowered vitamin B12, elevated methylmalonic acid and elevated homocysteine.

This is a second cross-sectional case–control study in 37 PD patients (with no risk factors for neuropathy). Of these PD subjects, 37.8% had a predominantly axonal peripheral neuropathy (measured with the Utah Early Neuropathy Scale) versus 8.1% in non-PD neurological controls. Ten out of 14 PD subjects with neuropathy reported symptoms. Low vitamin B12 levels were found in 57% of these PD subjects with neuropathy, which was more likely to be the sole cause in 50%, compared with <25% in a second control group of consecutive non-PD subjects with neuropathy. Cumulative levodopa exposure was inversely correlated with vitamin B12 levels in PD patients with neuropathy.

The issue of peripheral neuropathy in PD remains unresolved and larger studies are needed. At present, measuring vitamin B12 in PD subjects complaining of sensory symptoms or with clinical features of a peripheral neuropathy, appears to be a sensible approach, but whether all PD subjects need to be screened remains unanswered.

– Article suggested and written by Susan Fox

http://www.futuremedicine.com/doi/fu...2217/nmt.12.10

From previous post:

Folic acid and B 12
there are a number of studies noting use of supplements Vitamin B 12 and folic acid in instances of B 12 deficiencies to decrease homocysteine levels that result from use of Levodopa. Levodopa reportedly interferes with folate metabolism and B 12 function.

Parkinsonism Relat Disord. 2008;14(4):321-5. Epub 2007 Dec 4.
Folate and vitamin B12 levels in levodopa-treated Parkinson's disease patients: their relationship to clinical manifestations, mood and cognition.

Abstract
We tested the hypothesis that mood, clinical manifestations and cognitive impairment of levodopa-treated Parkinson's disease (PD) patients are associated with vitamin B12 and folate deficiency...Levodopa-treated PD patients showed significantly lower serum levels of folate and vitamin B12 than neurological controls, while depressed patients had significantly lower serum folate levels as compared to non-depressed. Cognitively impaired PD patients exhibited significantly lower serum vitamin B12 levels as compared to cognitively non-impaired. In conclusion, lower folate levels were associated with depression, while lower vitamin B12 levels were associated with cognitive impairment. The effects of vitamin supplementation merit further attention and investigation.
PMID: 18055246 [PubMed - indexed for MEDLINE]


The influence of levodopa and the COMT inhibitor on serum vitamin B12 and folate levels in Parkinson's disease patients.
...Our findings show that levodopa-treated Parkinson's disease patients have low folate (p < 0.0007) and vitamin B12 levels (p < 0.0003). They also demonstrate that the addition of a COMT-i to levodopa + DDC-i treatment causes lower serum vitamin B12 (p < 0.03) and folate levels (p < 0.005) than levodopa + DDC-i treatment alone. We suggest supplementary treatment with vitamin B12 and folic acid in these situations.
http://www.ncbi.nlm.nih.gov/pubmed/17565222

Neurol Neurosurg Psychiatry 2003;74:549 doi:10.1136/jnnp.74.4.549
Correspondence
Benefit of folic acid supplementation in parkinsonian patients treated with levodopa
T Müller, D Woitalla, W Kuhn
+ Author Affiliations

Department of Neurology, St Josef Hospital, Ruhr University Bochum, Gudrunstrasse 56, 44791 Bochum, Germany
Correspondence to:
 Dr T Müller; 
 thomas.mueller@ruhr-uni-bochum.de
We read with interest the recent excellent review by Reynolds on the role of folic acid and the risks and benefits of its supplementation in the nervous system.1 It emphasises the beneficial importance of folate on the numerous methylation processes in combination with S-adenosylmethionine (SAM), which donates its methyl group to prevent hyperhomocysteinaemia.1 However SAM deficiency, which is associated with, for example, cognitive decline and/or mood disturbances, and increased total homocysteine levels, which support onset of vascular disease, may also caused by drugs, for example, levodopa.2,3 Levodopa is administered with dopa decarboxylase inhibitors (DDI) to prevent its peripheral degradation. This increases conversion of levodopa to 3-O-methyldopa (3-OMD) by the ubiquitious enzyme catechol-O-methyltransferase (COMT) in blood, peripheral tissues and in nigrostriatal neurons.2,3 COMT requires Mg2+ as cofactor and SAM as methyl donor. Thus O-methylation of levodopa to 3-OMD is associated with conversion of SAM to S-adenosylhomocysteine and subsequently homocysteine.

http://jnnp.bmj.com/content/74/4/549.1.full


For those individuals who have had DNA profiling, check for polymorphisms of the methylenetetrahydrofolate reductase (MTHFR C677T), methyltetrahydrofolate-homocysteine methyltransferase (MTR A2756G), and 5-methyltetrahydrofolate-homocysteine methyltransferase reductase both associated with folate metabolism and in addition, check (MTRR A1049G and C1783T) associated with processing of B12 in the bodY. If you have mutations in the MTHFR gene, must use a breakdown product of folic acid, methyl folate, and folinic acid if one has the other mutation. Mutations in MTRR requires a B 12 supplement.
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This whole folate & Vit. B thing is of great interest to me, but I can't seem to get a clear idea anywhere of exactly how you find out your levels of each, what actually constitutes a deficiency, and how much supplementation to take if deficient. I participated in a very interesting & informative forum discussion related to the MTHFR mutations (which I do have) , but ended up with no clear answer of what to do. Anybody here have any answers? Many thanks.

You can start here:

http://neurotalk.psychcentral.com/thread85103.html

Basically you will need methylated B12 and methylated folate if you have the MTHFR mutation, for life.

A blood test for MMA and/or homocysteine will show elevations that B12 (non-methylated-- cyano form) is not working for you properly.

methylcobalamin 1mg or 5 mg daily on an empty stomach.

methylfolate called Metafolin by Solgar, 800mcg daily or more if you are seriously low. (should be advised by a doctor in higher than 800mcg doses daily. Can be taken with food.

Both are available at iherb.com and neither is expensive.

Thanks so much for your clear response, MrsD. I recently had testing with these results: Vitamin B12 was 908 pg/mL and Folate RBC was 658 ng/mL. My G.P. doctor says these are fine, but 23andMe forum participants say I may still need supplementation, esp. for folate, due to my MTHFR "compound heterozygous" status, but type, source, dosage were unclear. Sounds like I should also request homocysteine testing. Thanks again!

If you are not using methylB12 already, and had that test routinely for B12, and it measured other B12 in the serum not being converted... you could still be low in ACTIVE B12.

An MMA and/or homocysteine test will be high when B12 is not being utilized by the body correctly... and is more definitive for those who have the MTHFR mutation. There are several types of MTHFR also ,, which is beyond me, I am sorry to say.