Dyskinesia
 

Ron-
I've been scratching around for a couple of hours and found nothing to make me wonder about either curcumin or citicholine.

Research is sparse, but I did find a promising few old friends and I'll list them individually.

-Rick

Dextromethorphan for dyskinesia
 

In true white rat fashion, I am testing this one even as we type. It is presently 4:18 PM here and I've been dyskinetic for the last couple of hours and expect to be so for a couple more. So, I took a quarter teaspoon at 4:15 and will report later.


1. Mov Disord. 1998 May;13(3):414-7.

A trial of dextromethorphan in parkinsonian patients with motor response
complications.

Verhagen Metman L, Blanchet PJ, van den Munckhof P, Del Dotto P, Natté R, Chase
TN.

Experimental Therapeutics Branch, National Institute of Neurological Diseases and
Stroke, National Institutes of Health, Bethesda, Maryland 20892-1406, USA.

The effects of the NMDA antagonist dextromethorphan (DM) on levodopa-associated
dyskinesias and motor fluctuations were studied in patients with advanced
Parkinson's disease. During initial open-label dose escalation, 6 of 18 patients
reported a beneficial effect at their individually determined optimal DM dose
(range, 60-120 mg/day). The 12 remaining patients either experienced reversible
side effects, particularly mild drowsiness, or decreased levodopa efficacy, and
were therefore excluded from the study. The six responders entered the
double-blind, placebo-controlled, crossover study with two 2-week arms separated
by 1 week wash-out. On the last day of each arm, motor ratings were performed
every 20 minutes for 8 consecutive hours. In addition, motor complications and
Activities of Daily Living (ADL) were assessed using the Unified Parkinson's
Disease Rating Scale (UPDRS) and patient diaries. With DM, dyskinesias improved
by 25% according to physician's ratings and by 40% according to UPDRS interviews,
without compromising the anti-Parkinson effect of levodopa. Motor fluctuations
and ADL scores also improved significantly. Although the narrow therapeutic index
of DM limits its clinical usefulness, these findings support the view that drugs
acting to inhibit glutamatergic transmission at the NMDA receptor can ameliorate
levodopa-associated motor complications.

PMID: 9613730 [PubMed - indexed for MEDLINE]


1. Amino Acids. 1998;14(1-3):75-82.

Blockade of glutamatergic transmission as treatment for dyskinesias and motor
fluctuations in Parkinson's disease.

Verhagen Metman L, Del Dotto P, Blanchet PJ, van den Munckhof P, Chase TN.

National Institute of Neurological Diseases and Stroke, National Institutes of
Health, Bethesda, Maryland, USA.

In animal models of Parkinson's disease (PD), glutamate antagonists diminish
levodopa (LD)-associated motor fluctuations and dyskinesias. We sought to
investigate if these preclinical observations can be extended to the human
disease, by evaluating the effects of three non-competitive NMDA antagonists
(dextrorphan, dextromethorphan and amantadine) on the motor response to LD in
patients with advanced PD. In four separate trials, adjuvant therapy with these
drugs reduced LD-induced dyskinesias and motor fluctuations. These findings
support the view that drugs acting to inhibit glutamatergic transmission at the
NMDA receptor can ameliorate LD associated motor response complications.

PMID: 9871445 [PubMed - indexed for MEDLINE]


1. Neurology. 1998 Jul;51(1):203-6.

Dextromethorphan improves levodopa-induced dyskinesias in Parkinson's disease.

Verhagen Metman L, Del Dotto P, Natté R, van den Munckhof P, Chase TN.

Experimental Therapeutics Branch, National Institute of Neurological Diseases and
Stroke, National Institutes of Health, Bethesda, MD 20892-1406, USA.

OBJECTIVE: This study assessed the effects of the N-methyl-D-aspartate (NMDA)
antagonist dextromethorphan (DM) on levodopa-induced dyskinesias in Parkinson's
disease (PD). BACKGROUND: Recent experimental evidence suggests that increased
synaptic efficacy of NMDA receptors expressed on basal ganglia neurons may play a
role in the pathophysiology of levodopa-induced motor response complications.
METHODS: DM was given to six PD patients with motor fluctuations in a
double-blind, placebo-controlled, cross-over study. At the end of each 3-week
study arm, patients received several brief i.v. levodopa infusions while
parkinsonian symptoms and dyskinesias were frequently scored. Levodopa
dose-response curves for antiparkinsonian and dyskinetic effects were then
compared for each study arm. RESULTS: With DM, average and maximum dyskinesia
scores improved by >50%, without compromising the antiparkinsonian response
magnitude or duration of levodopa, although in some subjects the levodopa
threshold dose was slightly higher with DM than with placebo. CONCLUSIONS: These
findings support the view that drugs acting to inhibit glutamatergic transmission
at the NMDA receptors can ameliorate levodopa-associated dyskinesias.

PMID: 9674803 [PubMed - indexed for MEDLINE]

Remember a couple of things about dextromethorphan-
1- Less is more. Take the least dose that gives you the effect as a little more will reverse the effect.
2- When you do your research, be aware that dextromethorphan gives the Drug Warriors apoplexy because it is so readily available and has so few side effects. So they put out a lot of lies about it.

BTW, it is now 4:41 PM and my dk is down by a third. :)

Mucuna pruriens for dyskinesia
 

Some recent work


1. Nat Prod Res. 2010 Jul 13:1-8. [Epub ahead of print]

Mucuna pruriens attenuates haloperidol-induced orofacial dyskinesia in rats.

Pathan AA, Mohan M, Kasture AS, Kasture SB.

Department of Pharmacology, MGV's Pharmacy College, Panchavati, Nashik,
Maharashtra, India.

Neuroleptic-induced tardive dyskinesia (TD) is a motor disorder of the orofacial
region resulting from chronic neuroleptic treatment. The agents improving
dopaminergic transmission improve TD. Mucuna pruriens seed contains levodopa and
amino acids. The effect of methanolic extract of M. pruriens seeds (MEMP) was
studied on haloperidol-induced TD, alongside the changes in lipid peroxidation,
reduced glutathione, superoxide dismutase (SOD) and catalase levels. The effect
of MEMP was also evaluated in terms of the generation of hydroxyl and
1,1-diphenyl,2-picrylhydrazyl (DPPH) radical. MEMP (100 and 200 mg kg(-1))
inhibited haloperidol-induced vacuous chewing movements, orofacial bursts and
biochemical changes. MEMP also inhibited hydroxyl radical generation and DPPH.
The results of the present study suggest that MEMP by virtue of its free radical
scavenging activity prevents neuroleptic-induced TD.

PMID: 20635303 [PubMed - as supplied by publisher]

Creatine and dyskinesia
 

Creatine is the "Poor Man's CoQ10 and is in trials somewhere. It is widely used in the sports world-


1. Behav Brain Res. 2009 Jan 30;197(1):90-6. Epub 2008 Aug 12.

Oral creatine supplementation attenuates L-DOPA-induced dyskinesia in
6-hydroxydopamine-lesioned rats.

Valastro B, Dekundy A, Danysz W, Quack G.

Preclinical Research and Development, In Vitro Screening, Merz Pharmaceuticals
GmbH, Altenhöferallee 3, 60438 Frankfurt am Main, Germany.

L-DOPA-induced dyskinesia (LID) is among the motor complications that arise in
Parkinson patients after a prolonged treatment with levodopa (L-DOPA). Since
previous transcriptome and proteomic studies performed in the rat model of LID
suggested important changes in striatal energy-related components, we hypothesize
that oral creatine supplementation could prevent or attenuate the occurrence of
LID. In this study, 6-hydroxydopamine-lesioned rats received a 2%
creatine-supplemented diet for 1 month prior to L-DOPA therapy. During the 21
days of L-DOPA treatment, significant reductions in abnormal involuntary
movements (AIMs) have been observed in the creatine-supplemented group, without
any worsening of parkinsonism. In situ hybridization histochemistry and
immunohistochemistry analysis of the striatum also showed a reduction in the
levels of prodynorphin mRNA and FosB/DeltaFosB-immunopositive cells in
creatine-supplemented diet group, an effect that was dependant on the development
of AIMs. Further investigation of the bioenergetics' status of the denervated
striatum revealed significant changes in the levels of creatine both after L-DOPA
alone and with the supplemented diet. In conclusion, we demonstrated that
combining L-DOPA therapy with a diet enriched in creatine could attenuate LID,
which may represent a new way to control the motor complications associated with
L-DOPA therapy.

PMID: 18762218 [PubMed - indexed for MEDLINE]

Vitamin B6
 

1. J Clin Psychiatry. 2007 Nov;68(11):1648-54.

Vitamin B6 treatment for tardive dyskinesia: a randomized, double-blind,
placebo-controlled, crossover study.

Lerner V, Miodownik C, Kaptsan A, Bersudsky Y, Libov I, Sela BA, Witztum E.

Division of Psychiatry, Ministry of Health Be'er Sheva Mental Health Center,
Faculty of Health Sciences, Ben-Gurion University of the Negev, Be'er-Sheva,
Israel. lernervld@yahoo.com

BACKGROUND: Tardive dyskinesia (TD) is a significant clinical problem. Vitamin
B(6) is a potent antioxidant and takes part in almost all of the possible
mechanisms that are suggested as being associated with appearance of TD. The aims
of this study were (1) to reexamine the efficacy and safety of higher doses of
vitamin B(6) versus placebo in a greater sample of patients for a longer time and
(2) to evaluate the carryover effect of vitamin B(6). METHOD: A 26-week,
double-blind, placebo-controlled trial was conducted in a university-based
research clinic from August 2002 to January 2005 on 50 inpatients with DSM-IV
diagnoses of schizophrenia or schizoaffective disorder and TD. In a double-blind
crossover paradigm, all study subjects were randomly assigned to start treatment
with either vitamin B(6) (daily dose of 1200 mg) or placebo. After 12 weeks of
treatment and then a 2-week washout, subjects were crossed over to receive the
other treatment for 12 weeks. The primary outcome measure was the change from
baseline in Extra-pyramidal Symptom Rating Scale (ESRS) scores. RESULTS: The mean
decrease in ESRS clinical global impression scores from baseline to endpoint was
2.4 points in patients treated with vitamin B(6) and 0.2 points in patients
treated with placebo (p < .0001). The mean decrease in the parkinsonism subscale
score was 18.5 points and 1.4 points, respectively (p < .00001), and the mean
decrease in the dyskinesia subscale score was 5.2 points and -0.8 points,
respectively (p < .0001). CONCLUSION: Vitamin B(6) appears to be effective in
reducing symptoms of TD. The specific mechanisms by which vitamin B(6) attenuates
symptoms of TD are not clear.

PMID: 18052557 [PubMed - indexed for MEDLINE]

Quercetin
 

1. Neuropharmacology. 2003 Jun;44(8):1100-6.

Quercetin, a bioflavonoid, attenuates haloperidol-induced orofacial dyskinesia.

Naidu PS, Singh A, Kulkarni SK.

Pharmacology Division, University Institute of Pharmaceutical Sciences, Panjab
University, -160014, Chandigarh, India.

Chronic treatment with neuroleptics leads to the development of abnormal
orofacial movements described as vacuous chewing movements (VCMs) in rats.
Vacuous chewing movements in rodents are widely accepted as one of the animal
models of tardive dyskinesia. Oxidative stress and the products of lipid
peroxidation are implicated in the pathophysiology of various neurological
disorders including tardive dyskinesia. In the present study chronic haloperidol
(1.0 mg kg(-1) for 21 days) treatment induced vacuous chewing movements and
tongue protrusions in rats. Co-administration of quercetin, a bioflavonoid, dose
dependently (25-100 mg kg(-1)) reduced haloperidol-induced vacuous chewing
movements and tongue protrusions. Biochemical analysis revealed that chronic
haloperidol treatment induces lipid peroxidation and decreases the glutathione
(GSH) levels in the forebrains of rats. The antioxidant defense enzymes,
superoxide dismutase (SOD) and catalase were also decreased due to chronic
haloperidol treatment. Co-administration of quercetin (25-100 mg kg(-1))
significantly reduced the lipid peroxidation and restored the decreased
glutathione levels in these animals. Further quercetin (50-100 mg kg(-1)) also
reversed the haloperidol-induced decrease in forebrain SOD and catalase levels in
rats. The major findings of the present study suggested that oxidative stress
plays a significant role in neuroleptic-induced orofacial dyskinesia and
quercetin co-administration reverses these behavioral and biochemical changes.
Quercetin, a naturally occurring bioflavonoid could prove to be a useful agent in
neuroleptic-induced orofacial dyskinesia.

PMID: 12763102 [PubMed - indexed for MEDLINE]

Melatonin
 

1. Arch Gen Psychiatry. 2001 Nov;58(11):1049-52.

Melatonin treatment for tardive dyskinesia: a double-blind, placebo-controlled,
crossover study.

Shamir E, Barak Y, Shalman I, Laudon M, Zisapel N, Tarrasch R, Elizur A, Weizman
R.

Abarbanel Mental Health Center, 15 KKL St, Bat-Yam 59100, Israel.
drshamir@hotmail.com

Comment in:
Arch Gen Psychiatry. 2001 Nov;58(11):1054-5.

BACKGROUND: Antipsychotics remain the mainstay of drug intervention in the
management of schizophrenia. However, long-term treatment with antipsychotics is
associated with a variety of movement disorders, the most disabling of which is
tardive dyskinesia (TD), which occurs in up to 50% of patients hospitalized with
chronic schizophrenia. The pathophysiology of TD is still unclear and no definite
treatment exists. Both dopamine receptor supersensitivity and oxidative
stress-induced neurotoxicity in the nigrostriatal system are apparently
implicated. The pineal hormone melatonin is a potent antioxidant and attenuates
dopaminergic activity in the striatum and dopamine release from the hypothalamus.
Thus, it may have a beneficial effect for both the treatment and prevention of
TD. METHODS: Using a double-blind, placebo-controlled, crossover study, we
evaluated the efficacy of 10 mg/d of melatonin for 6 weeks in 22 patients with
schizophrenia and TD. The primary outcome measure was the change from baseline in
Abnormal Involuntary Movement Scale (AIMS) score. RESULTS: The decrease (mean +/-
SD) in AIMS score was 2.45 +/- 1.92 for the melatonin and 0.77 +/- 1.11 for the
placebo treatment groups (P<.001). No adverse events or side effects were noted.
CONCLUSION: This is the first clinical evidence for efficacy of melatonin in the
treatment of TD.

PMID: 11695951 [PubMed - indexed for MEDLINE]

6:20 Dk down to 25% level. Feel no need for meds.

Dyskinesia,
 

Rick,
I take my hat off to you, that is an incredible amount of work. These days, I just never seem to have the time. However I am still doing a lot of work for Kings College Hospital London, literature searches, fundraising etc.
Looking at the prescription drugs for dyskinesia, amantadine is effective , but looses its effectiveness after around 6 months of use. It is an antiviral drug, and a very similar drug is Rimantadine, with a similar structure.
Yesterday, I went to a Christening, and took half a 50mg Stavelo (25mg L-dopa) at 12-30pm. I writhed with dyskinesia until nearly 4-00pm. I can't take less than 25mg L-dopa!! Some time ago, there was no way 50mg would switch me on.
It must mean my threshold level of sensitivity to L-dopa has reduced.
Is it caused by prolonged use of curcumin, (it repairs BBB), and will I eventually not need L-dopa?
Ron

Ron,
Just a thought, have you changed the way your l-dopa is delivered?

Lindy

Good thinking Lindy, yes I have. As far as I can gather from my records, I was using 50mg tablets of Sinamet up to 1st May this year, then switched to Stavelo. I think that ties in roughly to the increase in dyskinesia.
I had tried Stavelo before, but did not like the lack of control over the amount of entacapone I was getting. If I rememer correctly, entacapone has a reputation for increasing dyskinesia
I fly to Scotland for a week, at the end of next week, so I won't be able to keep posting.

Ron

Dyskinesia is my biggest problem. When my meds kick in, I'm dyskinetic ALL THE TIME. Doesn't matter if I cut the pill in half or not. It just wears off sooner.

Hypnosis
 

Strictly from my own experience this morning. No research on it in so far as I can tell. Which is odd since the French neuro Charcot was big on it and also named PD.

Anyway, I seemed to banish a moderate case of dk this morning with a very simple image involving a thermostat ("Turn it down, Luke." :D ) and it seems to have done the trick. I'm going to work on this one some more. If anyone else wants to try it let me know and I'll post the text I used. You can simply read it into your computer and voila!

Ron,
As any form of entacapone will increase the available amount of l-dopa to the brain it may be the culprit. I think it is interesting though that some people do less well on stalevo only, and some do less well on entacapone + ldopa, EVEN at the same dose........... so it may be your culprit..... I declined to go on stalevo because I wouldn't be able to control my intake the way I want to.

Good luck finding a balance....... and enjoy your holiday.

Lindy

Rick,

I'll give it a go if you don't mind posting it.

'Atta' Girl...
 

Self Hypnosis 101
First of all, ditch all preconceptions. It is not what you've seen on television. It is simply you using a script to help your mind to focus. No one else is involved and there are no tricks.

You can do this one of two ways- either with a recorder or with your computer. I prefer the latter because it is easy to edit and can be used to generate "modules" that can be combined in moments to deal with something that just came up. The downside is that you have to learn the software. I use a free program called "Audacity" but I think there is one that comes with Windows, too.

A voice recorder is much simpler but only if you rehearse a little and correct mistakes as you go.

Safety- Use it in the safety of your home and you have nothing to worry about. Do I have to say it? DON'T DO THIS AND DRIVE! Sheesh...

If you forget to tell yourself to wake up, you will anyway. it just might be the next morning.

There are three modules- the induction, the suggestion, and the awakening.

The induction is when the guy in the bad movie says "Look into my eyez!" You will do it a bit different. It is not so much what you say but how you say it. You should try for a soothing monotone. Imagine that you are trying to calm your dog during a thunderstorm. Now record the following-

"Let yourself relax as you slip into hypnosis. Listening to my voice. Ignoring all other sounds. Breathing slowly. Easily. Your body growing heavier as you relax more and more.

Be aware of the weight of your body as you relax more and more. Breathing slowly. Easily. Growing heavier and more and more relaxed. Ignoring all other sounds but my voice. Calmer and calmer.

Now, as I count, feel yourself sinking gently down into hypnosis. More and more relaxed. Heavier and heavier.

Five.

Four.

Three.

Two.

One.

Zero.

Sleep.

Relaxing more and more. Your body growing heavier. Your mind growing calmer.

Five.

Four.

Three.

Two.

One.

Zero.

Sleep."

When you are counting, allow about one normal breath for each number. Remember that you are calming your pet. That part above should be about two to two and a half minutes but don't stress about it.

Now, record it again. And if needed, a third time. You want about five minutes of this. When finished, you have your induction.

I'm not sure what limits are on length of post so will adjourn to the next post.

Continue to record the following-

"Your dyskinesias result from the sensitivity you have to your medications. You are able to influence that sensitivity and your dyskinesias. I am going to give you an image to use as a tool to do this anytime you wish. It will not be necessary that you enter hypnosis to usethis image, only that you close your eyes and take two slow breaths to begin. This approach will get more and more effective each time you use it, allowing you great control over your sensitivity and the dyskinesia.

Now, imagine that you are standing facing a wall at arm's length in front of you. On that wall and at eye level is an old fashioned, round thermostat. Picture your hand reaching out and turning the control counter-clockwise to reduce your dyskinesias.

<repeat that last paragraph a total of three times>

This approach will get more and more effective each time you use it, allowing you great control over your sensitivity and the dyskinesia."

Finally, record this to awken-

"Now, you may awaken by silently counting from one to ten, becoming more alert with each count and fully awake at th count of ten."

Will give this a try. Thank you so much!

some hypno-tips
 

In general, the more intelligent and imaginative you are the more readily hypnotizeable you are. Add in the well known placebo response and we have a potential major tool here. Keep in mind that you haven't heard of it from your doc not because science has found it lacking but, rather, that the studies have not been done.

Symptom relief is an obvious avenue, but it could be more as well. An example- my wife has fought depression all her life. Twenty years or so ago, as she struggled with Churchill's "black dog", I hypnotized her and simply instructed her to rebalance her brain chemistry and banish the depression. It worked. Also, the thing that led me into the subject were terrible monthly cramping that she had endured for years. Using an image similar to the one used here, the cramping was eliminated with a single session!

The power of suggestion is just that - suggestion. We don't necessarily have to know the details. This wonderous melon-sized lump of jelly holds miracles we cannot imagine. Who is to say that the proper approach will not increase levels of GDNF where needed or reduce inflammation? This part of us is an idiot savant and is capable of great things but only if asked.

In trying this, it is best done by day and while sitting quietly. Falling asleep is counter productive. Turn offthe phone. Put out the cat. etc.

While you may be surprised, don't expect results right away. Go through it ten times before making any judgements. Don't do it more than once a day and take every fourth day off. You are persuading, not coercing.

An added advantage- record one without the middle part.You can get profoundly relaxed without suggesting anything. It soothes those weary muscles quite well.

I hope that some of you will get interested in this. It has been neglected for a century and it is a great patient empowerment tool.

Nicotine
 

I figure once I pass 60 I willbe entitled to smoke, drink, and chase women. I figure that I will be shuffling after my wife demanding to know where she hid my pipe and wine. :)


1. Biochem Pharmacol. 2009 Oct 1;78(7):677-85. Epub 2009 May 9.

Multiple roles for nicotine in Parkinson's disease.

Quik M, Huang LZ, Parameswaran N, Bordia T, Campos C, Perez XA.

The Parkinson's Institute, Sunnyvale, CA 94085, United States.
mquik@parkinsonsinstitute.org

There exists a remarkable diversity of neurotransmitter compounds in the
striatum, a pivotal brain region in the pathology of Parkinson's disease, a
movement disorder characterized by rigidity, tremor and bradykinesia. The
striatal dopaminergic system, which is particularly vulnerable to
neurodegeneration in this disorder, appears to be the major contributor to these
motor problems. However, numerous other neurotransmitter systems in the striatum
most likely also play a significant role, including the nicotinic cholinergic
system. Indeed, there is an extensive anatomical overlap between dopaminergic and
cholinergic neurons, and acetylcholine is well known to modulate striatal
dopamine release both in vitro and in vivo. Nicotine, a drug that stimulates
nicotinic acetylcholine receptors (nAChRs), influences several functions relevant
to Parkinson's disease. Extensive studies in parkinsonian animals show that
nicotine protects against nigrostriatal damage, findings that may explain the
well-established decline in Parkinson's disease incidence with tobacco use. In
addition, recent work shows that nicotine reduces l-dopa-induced abnormal
involuntary movements, a debilitating complication of l-dopa therapy for
Parkinson's disease. These combined observations suggest that nAChR stimulation
may represent a useful treatment strategy for Parkinson's disease for
neuroprotection and symptomatic treatment. Importantly, only selective nAChR
subtypes are present in the striatum including the alpha4beta2*, alpha6beta2* and
alpha7 nAChR populations. Treatment with nAChR ligands directed to these subtypes
may thus yield optimal therapeutic benefit for Parkinson's disease, with a
minimum of adverse side effects.

PMCID: PMC2815339 [Available on 2010/10/1]
PMID: 19433069 [PubMed - indexed for MEDLINE]

anti-action and its fallout.......
 

Thinking about it I never DID fell good after quitting! :D

There is now so much I SHOULDN'T do that I'm not sure what's left!