I am fed up. I can deal with this disorder, but I can no longer hack the medical "professionals" who just wash their hands of us. I can give in to the sense of physical helplessness but not the psychological one. Do doctors really expect us to passively accept all this and not probe or push them farther to actually do something meaningful for a change like actually condone; for example, low -dose Naltrexone. I just cannot sit idly by on the sidelines while other people and this disease run the course for me. If any of our doctors had this, can you see them kicking back with DBS and the status quo?

I recall back two years ago, Vicky asked me "what kind of Parkinson's do you have?" She accused me of not knowing what kind of PD I have and how to best treat it. I recall feeling pretty insulted. Now I get it. She has clearly genetic PD and knew way before any of that PD does not have one cause.

My goal is to establish that I have frank PD as defined by PET scan. If that shows positive, my next route is to be tested for 1-2 common YO gene mutations. If I do have one of those, there is so much written on their pathogenesis and prognosis that I can likely fine tune my treatment. If the genetic tests fall through I will pursue an MRI to rule out vascular lesions.

I am atypical enough for this and to top it all off, I have something metabolic happening that now looks like untreated diabetes or diabetes insipidus. The latter is known for altering sodium and potassium levels to the point where I have episodes of periodic paralysis. It is not normal PD freezing. This has been going on for two years now and the diabetes symptoms are rather scary. Saw an endocrinologist early on and was dismissed. This profile below is essentially me minus 42 years. I presentated with dystonic foot and action tremor in my thirties. The rapidly escalating ldopa fits too.

Late onset dopa-responsive dystonia with tremor, gait freezing and behavioural disturbance and a normal dopamine transporter scan.


This may be crazy and I am not sure how I will convince my doctor of any of this, but if I am going to be bankrupt by disability; why not? I will pay for tests; it is worth it for peace of mind.

Question is how do I get doctor(s) on board? Also, has anyone else felt insulin and blood sugars off post treatment with l-dopa?

Thanks,

Laura

Laura said-
"I am atypical enough for this and to top it all off, I have something metabolic happening that now looks like untreated diabetes or diabetes insipidus. The latter is known for altering sodium and potassium levels to the point where I have episodes of periodic paralysis. It is not normal PD freezing. This has been going on for two years now and the diabetes symptoms are rather scary. Saw an endocrinologist early on and was dismissed. This profile below is essentially me minus 42 years. I presentated with dystonic foot and action tremor in my thirties. The rapidly escalating ldopa fits too.

Late onset dopa-responsive dystonia with tremor, gait freezing and behavioural disturbance and a normal dopamine transporter scan.


This may be crazy and I am not sure how I will convince my doctor of any of this, but if I am going to be bankrupt by disability; why not? I will pay for tests; it is worth it for peace of mind.

Question is how do I get doctor(s) on board? Also, has anyone else felt insulin and blood sugars off post treatment with l-dopa?"


First, about our common problem of "something metabolic happening" I have good news and bad news. The good is that I am doing so much better and the bad is that I'm not sure why. But I will tell you what I can.

My own manifestation of this problem had extreme spikes of blood pressure as an effect. I think now that it was a cause resulting from "neurogenic hypertension" (NH). The NH (IMHO) was the result of my childhood stress due to my alcoholic father and affected my response to stress hormones. I had my GP change my hypertension medications to a beta blocker and an ACE inhibitor. The first (perindropril) inhibits the production of angiotensen and the next softens the action of adrenaline. Both these also have positive effects on PD.

Other things that I *think* helped include: potassium gluconate (15 - 20 mEq) and a B-complex. Both these are vital for nerves to functiom and both are lost in the urine.

What I think is happening is that our autonomic nervous system getting out of control.

This one has full text available


1. J Appl Physiol. 2004 Dec;97(6):2339-46. Epub 2004 Jul 16.

Levodopa with carbidopa diminishes glycogen concentration, glycogen synthase
activity, and insulin-stimulated glucose transport in rat skeletal muscle.

Smith JL, Ju JS, Saha BM, Racette BA, Fisher JS.

Dept. of Biology, St. Louis University, 3507 Laclede Ave., St. Louis, MO 63103,
USA. smithjl@slu.edu

We hypothesized that levodopa with carbidopa, a common therapy for patients with
Parkinson's disease, might contribute to the high prevalence of insulin
resistance reported in patients with Parkinson's disease. We examined the effects
of levodopa-carbidopa on glycogen concentration, glycogen synthase activity, and
insulin-stimulated glucose transport in skeletal muscle, the predominant
insulin-responsive tissue. In isolated muscle, levodopa-carbidopa completely
prevented insulin-stimulated glycogen accumulation and glucose transport. The
levodopa-carbidopa effects were blocked by propranolol, a beta-adrenergic
antagonist. Levodopa-carbidopa also inhibited the insulin-stimulated increase in
glycogen synthase activity, whereas propranolol attenuated this effect.
Insulin-stimulated tyrosine phosphorylation of insulin receptor substrate (IRS)-1
was reduced by levodopa-carbidopa, although Akt phosphorylation was unaffected by
levodopa-carbidopa. A single in vivo dose of levodopa-carbidopa increased
skeletal muscle cAMP concentrations, diminished glycogen synthase activity, and
reduced tyrosine phosphorylation of IRS-1. A separate set of rats was treated
intragastrically twice daily for 4 wk with levodopa-carbidopa. After 4 wk of
treatment, oral glucose tolerance was reduced in rats treated with drugs compared
with control animals. Muscles from drug-treated rats contained at least 15% less
glycogen and approximately 50% lower glycogen synthase activity compared with
muscles from control rats. The data demonstrate beta-adrenergic-dependent
inhibition of insulin action by levodopa-carbidopa and suggest that unrecognized
insulin resistance may exist in chronically treated patients with Parkinson's
disease.

PMID: 15258132 [PubMed - indexed for MEDLINE]

It saddens me to see this was done EIGHT years ago and docs so casually script ldopa without any warning that it may have these effects. We've seen FIVE neuros (one at a world class teaching facility-and famous doc too) and not one word about sugar or insulin or metabolic change. Ugh.

It would be nice if docs said "I'm going to give you ldopa because it is the gold standard...side effects might include...." and share with the patient this information. Then at least the patient would know that maybe, just maybe, some of the issues being experienced were not necessarily progression. And, in fact, might be reversible...as Rick has indicated. Keep us posted, Rick, on how things are going for you, and glad to hear you are doing better!

Thanks for responding, Rick. I should have just PMed you but I already vent so much there; was thinking that some other oddball with symptoms we share might have joined us. Safety in numbers

My short term solution until I can find a patient oriented endocrinologist is to buy a glucose monitor and see where I am at in a 24-48 hour period.

I agree that our autonomic systems are definitely out of whack but is it PD, just meds, or a combo?

Worse is you can take a list of citations with abstracts on both this issue and thyroid (levodopa skews TSH levels on thyroid tests) and they will acknowledge it by stating that the effect of levodopa may slightly impact test results but not enough to it to keep me within normal range. How does he know? The meager handful of studies say otherwise!

Further, my thyroid level was way off prior to my PD diagnosis signaling hypothryoidism. I didn't pursue treatment because doctor and I were overly focused on my tremor. How could my thyroid spontaneously rebound to normal? Still if anything falls in that norm range even if still at high end, they dismiss all your symptoms.

This is just a perfect example of why we our conditon should be managed between a team of specialists who treat PD. I went to make an appt with the endo who works in same dept as my neuro and was told that I was too young because the team treated geriatric patients only- well, I guess looking and feeling 85 when off meds does not count

Laura

Laura writes:
"I am fed up. I can deal with this disorder, but I can no longer hack the medical "professionals" who just wash their hands of us. I can give in to the sense of physical helplessness but not the psychological one. Do doctors really expect us to passively accept all this and not probe or push them farther to actually do something meaningful for a change like actually condone; for example, low -dose Naltrexone. I just cannot sit idly by on the sidelines while other people and this disease run the course for me. If any of our doctors had this, can you see them kicking back with DBS and the status quo?"

It seems common that once a person is diagnosed with PD:
- doctors automatically assume there is no cure (at least at present) for this person;
- treatment is limited to symptom reduction (stiffness, tremor etc.);
- treatment is limited to officially sanctioned therapies (levodopa, DBS etc.).

The problem with this approach is that at a number of places it handles opinion as fact and, wrongly, assumes the most likely option is the best one to take.

A doctor can reasonably claim to have done a good job if he or she had, in a timely and sympathetic way, made the same diagnosis as experts in the field. In other words, the diagnosis is often more to do with matching the opinion of doctors than finding out what is really wrong with the patient. The patient has been given the "expert" diagnosis, but it may not be the correct one.

At this stage what is uncertain is often treated as certain: the diagnosis is probably correct, but not certainly. But now, the patient is officially deemed to have PD and PD has no known cure, therefore, the patient cannot be cured, therefore look no further. From the patient's perspective things are different.

Not only is it uncertain as to what Parkinson's is (I go for the multiple variants view), it's uncertain how best to treat these variants. This raises another problem: risk is asymmetrically distributed between the patient and the doctor. The patient can see the PD progressing and is prepared to take some risks trying different treatments. The doctor is at risk if the guidelines are not followed.

John

This is waaaay off the topic of PD but tort reform would fix a lot of these problems. Problem is, lawyers are a huge lobbying group and, having written the laws themselves, know how to play better than anyone. Consider: the lawyers for BOTH sides win in a lawsuit, because they are both getting paid regardless of who "wins". Some of the most pro-consumer legislation has been worked on by defense lawyers because they knew when the slew of consumers inevitably sued under the law, the defendants would come running for counsel. It worked, and the lawyers on both sides made a lot of money...money which I would argue would probably never had been made if the law had not been created out of thin air in the first place.

Not until we have legitimate tort reform will this change. And by legitimate, I mean, look to Germany. Guess what they have? Yep, loser pays. Books have been written about the merits of that system but you mention that in the US and it's like asking to be shot.

My current neuro whom I have been seeing for 18 months now made the statement, "If you like, I can send you to some of the Big Boys, but they'll just tell us that we've been doing it wrong without offering anything better."

But back to our subject-

L-DOPA: From a biologically inactive amino acid
to a successful therapeutic agent Historical review article
by
Hornykiewicz O.
Institute for Brain Research,
University of Vienna, Vienna, Austria.
Amino Acids 2002;23(1-3):65-70

ABSTRACT

The article traces the development of research on the naturally occurring amino acid L-3,4-dihydroxyphenylalanine (L-dopa), from the first synthesis of its D,L racemate in 1911, and the isolation of its L-isomer from seedling of Vicia faba beans to the amino acid's successful application, from 1961 onward, as the most efficacious drug treatment of Parkinson's disease (PD). Upon its isolation from legumes in 1913, L-dopa was declared to be biologically inactive. However, two early pharmacological studies, published in 1927 and 1930 respectively, proved (in the rabbit) that D,L-dopa exerted significant effects on glucose metabolism (causing marked hyperglycemia) and on arterial blood pressure. Interest in L-dopa's biological activity increased considerably following the discovery, in 1938, of the enzyme L-dopa decarboxylase and the demonstration that in the animal and human body L-dopa was enzymatically converted to dopamine (DA), the first biologically active amine in the biosynthetic chain of tissue catecholamines. This prompted, in the 1940s, many studies, both in animals and in humans, especially concerned with the vasopressor potential of L-dopa/DA. In the 1950s, the focus of L-dopa research shifted to its potential for replenishing the experimentally depleted (by insulin or reserpine) peripheral and brain catecholamine stores and the concomitant restoration of normal function. During that period, of special interest were the observations that L-dopa reversed the reserpine-induced state of "tranquilisation" and that its decarboxylation product DA occurred in high amounts in animal and human brain, with a preferential localization in the basal ganglia. These observations set the stage for the beginning of DA studies in PD brain. In 1960, the severe brain DA deficit, confined to patients with PD was discovered, and a year later L-dopa's strong therapeutic effect in patients with PD was demonstrated. In 1967, the chronic high-dose oral L-dopa regimen was successfully introduced into clinical practice. Despite some initial doubts about L-dopa's mechanism of action in PD, it is now generally recognized that L-dopa use in PD is a classic example of a brain neurotransmitter replacement therapy. However, the DA replacement potential of L-dopa may not be its sole action of interest, as suggested by recent evidence that L-dopa may also have its own biological activity in the CNS, independent of DA.

Found this doc in my dusty closet.

Attached Files

Annotated Ldopa induced hyperglycemia in PD.pdf (193.2 KB, 1951 views)