D’you remember the good ol’ days gang when we used to argue into the night about whether one should begin Levadopa earlier or later and whether Mucuna was better cause it didn’t cause dyskinesia and that the carbidopa was the agent that caused the dyskinesia etc. At some point, some wise person threw the Nigeria study into the mix, which for those of you unacquainted read like this: 2 groups were assessed: one who started early with CL and another who used agonists, presumably some MP too? Well the latter got dyskinesia at roughly the same time as the CL group. For me another thing that swung it was I thought that the CL was at least pharmaceutical grade. I was having success with MP but it was all from China. I feared that all sorts of ‘fillers’ could be in there. Anyway, to come to my point, I was flicking through Eric Ahlskog’s excellent book the other day when I saw a heading ‘Why dyskinesia occurs’. I didn’t know that the neurologists understood this but here’s what - very my paraphrasing - Ahlskog claims: at the start of the disease our neurons are able to ‘suck’ excess Levadopa back up. So when we flood our brains, the neurons sense this and get to work to redress this imbalance . How cool? Unfortunately, as the disease progresses and the neurons become fewer and more tired they aren’t able to carry on this duty and the floods of Levadopa just sit there causing all sorts of mischief. (not so cool 😂).
Anyway, I thought I’d pass this on and so you can make an informed choice on what substance to take.
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Hey Marc. Well ‘sort of’ 😂. I’m sure that in many ways it’s going to be very liberating but tbh I slightly fear some of the possible trade offs such as vocal corruption. It’s pretty par for the course for me to catastrophise: hopefully in reality it will turn out okay.
in one of my favorite books that I always refer to, nutritional lithium supplementation helps control dyskinesia. Must be true, because I take a ton of CL and never once dyskinesed!
“Uses of Lithium for Parkinson’s Disease
In psychiatry, lithium is commonly used to regulate dopamine activity in disorders where the system is known to be out of control, such as in schizophrenia, ADHD, addiction, and affective disorders. Based on this concept, a couple of researchers hypothesized that lithium salts may work to reduce Levodopa side effects by correcting dopamine receptor super-sensitivity (Dalen & Steg, 1973). If the trial worked, lithium could be used together with Levodopa to prolong its benefits and provide more lasting relief to Parkinson’s sufferers. Researchers selected two individuals suffering from Levodopa side effects whose symptoms were not relieved when the medication dosage was lowered. Lithium was administered to each patient, and they were monitored for two months. In order to reduce the risk of layering on additional adverse effects from the lithium, prescriptions were kept below what is considered the therapeutic dose (serum levels at or below 0.6 mEq/L). During the observation period of the study, both individuals experienced a reduction in Levodopa-induced dys-kinesias or tics. The authors concluded that their findings in favor of lithium were positive, but recognized that the small case study design was not sufficient to prove that lithium salts would be useful to remediate Levodopa side effects in Parkinson’s patients.…”
“…Six patients with severe Parkinsonism for whom medications had stopped working consistently were treated with lithium carbonate in addition to their regular medications in a randomized double-blind crossover trial. Lithium was individually adjusted to ensure serum levels stayed between 0.6-1.2 mEg/L and no higher. Five of the lithium-treated patients experienced marked reductions in muscle rigidity (akinesia) and an easing of painful dystonic cramps. The resulting improvements in mobility were so striking that responders regained an average of one full grade in Parkinson staging. Benefits were maintained throughout the full 36 weeks of follow-up. In contrast, there was no reported progress during placebo treatment. The authors of the study concluded that “lithium carbonate appears to offer a new and potentially effective approach to treatment” (Coffey et al., 1982). While previous studies had focused primarily on lithium’s uses for ameliorating the tic-like dyskinesia side effects of Levodopa, research was ignoring lithium as a viable treatment to target Parkinson’s symptoms directly. A double-blind, placebo-controlled study completed shortly thereafter added to this new string of investigation. A single daily dose of 600 mg slow release lithium was administered to seven patients with disabling dystonia, a type of uncontrollable, sustained muscle contraction that is characteristic of progressing Parkinson’s disease. This pharmacological dose was shown to produce therapeutic lithium levels between 0.5-1.2mEq/L. Participants were involved in multiple phases of the study, and alternated between receiving lithium treatment and transitioning to placebo. At the study conclusion researchers reported that painful Parkinsonian cramps were reduced or abolished in the majority of treatment periods with lithium. What’s more, these dystonic cramps consistently returned to pretreatment severity between 1-14 days after stopping lithium (Quinn & Marsden, 1986).“
Nutritional Lithium: A Cinderella Story: The Untold Tale of a Mineral That Transforms Lives and Heals the Brain a.co/d/9SR97IO
How very interesting Bass. Luckily, dyskinesia has never really been part of my story thank the Lord. But I’ll remember this piece of advice and if I ever DO need it, I’ll say ‘thanks’ ahead of usage my friend.
And just for reference, A typical prescription for bipolar disorder might be written as 900 mg of lithium per day but that’s 900 mg of lithium-carbonate not 900 mg of lithium, it contains 170 mg of actual lithium attached to 730 mg of carbonate.
A typical dose for lithium-orotate for comparison might be 260 mg of lithium orotate which contains just 10 mg of elemental lithium attached to 250 mg of orotate
As far as Im aware the African study is the only study pointed to supporting levodopa not leading to dyskinesia. And Its the least controlled study I've ever read.The study itself admits to 3 limitations:
"First, we used a control Parkinson’s disease population with a different genetic and environmental background"
"Second, the different access to medications between the two populations forced us to add a control subgroup of patients with Parkinson’s disease...and thus complicated the design of study analyses."
"Finally, this study was not designed as a community-based trial and inclusion bias might have occurred"
Others have also pointed out that
- the compensatory measures were not clear; overcomplicated the results and created confusion.
- the method of retrospectively assessing the African onset date may have lead to different dates to the Italian cohort.
- the Africans were predominantly presenting because they had tremor therefore people with no tremor were not properly represented in the African group.
So far from convincing.
I do wonder why they haven't tried other studies with both groups at least on the same continent .
Interesting analysis but if Ahlskog is right in his thinking, I’d say it was pretty convincing that duration of disease was key and not how much Cl had been taken?
Are there any studies which establish that ldopa diskenesias are avoided by delaying ldopa therapy initiation? Or is it another case of "it always rains when the pavements are wet"?
No one has spoken of proving anything apart from you. There is no 'proof either way. I've pointed out known flaws with the African study so you've gone off on à few benders😀.
I suggest you make a cup of hot tea, sit outside, listen to the leaves and birds and relax.
If only I could. I have 4 sets of accounts and tax returns to file by Friday, have changed software (back to the one I used previously), can't get support before Monday...
And the pool pump had siezed on return from 2 weeks in the UK, and was an essential urgent fix
And having joined Marc's chat group on Sunday, and been asked by Dave how I knew my vCR gloves operated correctly I found 2 faults on each hand - which also called for urgent rectification.
You have correctly diagnosed stress - and whilst I like your proposed therapy, it's going to be tough to implement. Next week, I will be Mr chilled!
But the African study is the nearest we've got to an answer to your question, is consistent with Ahlskogs explanation, and there is nothing available to contradict it
You were offering links to MJF and assorted studies, in support of your contention that there was evidence that duration of ldopa usage was relevant to dyskenesia severity, and there is no such evidence - just anecdotal popularity, based on the confusion of duration of disease - time since diagnosis. For sure, high doses of ldopa cause dyskenesia in patients who have had the disease a long time (and used ldopa during that time) but there is no evidence it is the ldopa usage, and not time since diagnosis which is responsible
There is also an element of "Groundhog day" for those of us who've been on the forum a while
Ahlskogs book is a cracker - thoroughly recommended. Goes well with a cup of tea
“Yes, there have been studies that suggest delaying the initiation of L-DOPA therapy can help reduce the risk of developing dyskinesias. One such study published in the New England Journal of Medicine in 2009 demonstrated that delaying L-DOPA treatment in patients with early Parkinson's disease reduced the incidence of dyskinesias. However, it's important to consult with a medical professional to get a comprehensive understanding of your specific situation and treatment options.”
I would Ethin, but I've run out of free questions for today. 🤷🏻♂️
Remind me tomorrow.
maybe someone else can help us. If you are interested you can download the app and ask for information yourself, it is called AI CHAT for smartphones, but there are others, all based on chatgpt and all have a free trial period. At the moment I can only ask five questions a day as it is beyond the trial period and today I ran out of them.
ChatOn: I apologize, but as an AI language model, I don't have real-time access to specific study details such as DOIs (Digital Object Identifiers). Additionally, I cannot browse the internet or access external sources. To obtain the DOI or any specific information about the study you mentioned, I recommend referring to the New England Journal of Medicine or conducting a search on their website using relevant keywords or the study's authors and publication year.
"While dyskinetic responses are common with sustained LD therapy, the proportion of patients actually developing disabling and severe dyskinesia has been below 10% in a recent four-year randomized trial2 and below 20% in a 10-year follow-up series.17 This should be taken into account when the physician discusses the potential use of LD with the patient, particularly in patients who require enhanced symptomatic control despite optimized treatment with DAs. Moreover, when making individual decisions on how to initiate dopaminergic treatment, the weighing of relative risks and benefits of starting with a DA or LD should not only consider dyskinesia risks but also risks for other side effects, including daytime somnolence, impulse-control disorders and...."
"It is not definitely established why the UPDRS scores of the pramipexole group never caught up with the LD group, despite the option of open-label LD and other antiparkinsonian therapies, but it might be related to the lower dose of LD used in the supplemented pramipexole patients (434 ± 498 mg/day) compared with those on LD monotherapy (702 ± 461 mg/day)"This indicates that combined treatment with a lower dose of LD and a DA is not equivalent to higher dose LD monotherapy in terms of symptomatic control, calling into question the concept of LD-equivalent doses of DAs.
The study is about various aspects of levodopa including its link to Dyskinesia. You've extracted a quote comparing pramipexole to levodopa?Not sure how this supports the value of the African study.
The African study uniquely had the opportunity to compare PWP who were at the same late stage of progression, using levadopa, but one group had been using it a long time, and the other group had only recently started. It found levadopa induced dyskenesia , but the severity of the side effect was dependant on the length of time since diagnosis, and not on the duration of ldopa use. Nothing I have seen elsewhere invalidates that.
The other studies don't get these control groups. Since they measure dyskenesia which might be worse due to duration of disease or might be worse due to duration of ldopa therapy. It's not possible to distinguish
This study distinguishes the group using ldopa as having worse dyskenesia than the group initially using d agonists. But the ldopa group are using half as much again as the d agonist group, who are not achieving the same level of symptom relief , and therefore not on a reliable ldopa equivalent
Apples and Pears
Note - dyskenesia is likely to be due to the dopamine the ldopa has been converted into, since stem cell grafts have also induced dyskenesia.
Still not sure what pramipexole has to do with it.But if you choose to ignore the listed weaknesses of the African study then that's your choice. The 2 cohorts in that study were definitely Apple's and pears.
So where do you think there is a study comparing 2 groups on the same dose of ldopa, at the same time post diagnosis where one group has been using ldopa for significantly less time than the other group?
I came across Ahlskog’s book last year, when I started having important on’s and off’s. Its really good at explaining what’s going on, distinguishing features, dos and don’ts etc. Very helpful on the long days and nights between neuro appointements.
The New Parkinson's Disease Treatment Book. Partnering with Your Doctor To Get the Most from Your Medications
True enough. By the way you can still write him a letter at Mayo Clinic in rochester, he was still pattering around there about 15 months ago anyway , I was lucky enough to have my annual up there and his name was up on the board too I assume it was him he looks to be about 85, chief of dept. of neurology. I don't know if they accept emails.
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