Dopamine Receptor Agonist Drugs and Impulse Control Disorders

Dopamine Receptor Agonist Drugs and Impulse Control Disorders
JAMA Intern Med. October 20, 2014

The discovery of striatal dopamine deficiency and the introduction of levodopa in the 1960s as treatment for the motor symptoms of Parkinson disease revolutionized neurology and neurotherapeutics.
For the first time, patients with an apparently hopeless chronic degenerative brain disorder were able to regain function and return to the mainstream of life.
Levodopa was subsequently combined with carbidopa, as the latter prevented the adverse effects associated with peripheral dopamine synthesis without blocking central dopamine synthesis.

journalistic version:


Liftware: 70% tremor cancellation

A Spoon That Shakes To Counteract Hand Tremors
May 13, 2014

1 million Americans struggle with the tremors of Parkinson’s disease.

There are also as many as 10 million Americans who have a disorder called essential tremor which, when severe, also can make eating a struggle.

“There’s a little motion sensor right near the spoon,” Pathak explains. “If I had tremor, it’s going to move opposite to what the shaking is doing. So, if I move to the left, it’ll physically move the spoon to the right.”

And that cancels out the tremor as the spoon moves from plate to mouth. In a clinical trial, the Liftware spoon canceled out more than 70 percent of a user’s tremor.

Tourette’s syndrome: improvement after DBS of the GPe

Behavioral and motor improvement after deep brain stimulation of the globus pallidus externus in a case of Tourette’s syndrome.
Neuromodulation. 2013 Jan-Feb;16(1):55-8; discussion 58.
Piedimonte F, et al.

The objective of our paper is to show the partial decrease of therapeutic effect with battery exhaustion in a previously successfully treated patient with refractory Tourette’s syndrome (TS).

We present a 47-year-old patient diagnosed with TS based on the TS Study Group Criteria and Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition. Surgery was considered based on refractoriness to conservative management. Presurgical evaluation included magnetic resonance imaging (MRI), positron emission tomography scan, and neuropsychologic, neurologic, and psychiatric tests utilizing Yale Brown Obsessive Compulsive Scale, Yale Global Tics Severity Scale, Hamilton Depression Rating Scale, Hamilton Anxiety Rating Scale, Global Assessment of Functioning Scale, and Mini-mental State Examination. Target coordinates were obtained from inversion recovery MRI. Quadripolar deep brain stimulation (DBS) electrodes were implanted bilaterally in the globus pallidus externus (GPe) and connected to the pulse generator in the same procedure. To determine the clinical response to DBS, the scores of the scales obtained preoperatively were compared with those obtained postoperatively.

No surgical complications were detected and according to the clinical scales the patient experienced a marked improvement of his symptoms, although he never showed obsessive-compulsive disorder components of any type. The battery was exhausted after two years with the subsequent significant partial loss of therapeutic effect.

GPe seems to be a highly promising target of DBS for the treatment of medically refractory TS. After battery exhaustion, the patient experienced a marked partial decrease in the therapeutic effect, which confirms the beneficial action of this method.

Contrasting changes in cortical activation induced by acute high-frequency stimulation within the globus pallidus in Parkinson’s disease
Journal of Cerebral Blood Flow & Metabolism (2009) 29, 235–243

My life with Parkinson’s

Striatal dopamine innervation assessed by 18F-dopa positron emission tomography.

My life with Parkinson’s
Nature. 06 November 2013

A neuroscientist reflects on his experience of studying the circuits that control neural activity while his own brain began slowly failing him.

The first signs
I remember the first time I noticed that something was wrong.
Four years ago, I was filling out a mountain of order forms for new lab equipment. After a few pages, my hand became a quaking lump of flesh and bone, locked uselessly in a tense rigor.
A few days later, I noticed my walk was changing: rather than swinging my arm at my side, I held it in front of me rigidly, even grabbing the bottom edge of my shirt. I also had an occasional twitch in the last two fingers of my hand.

Take the very peculiar symptom known as ‘freezing’. Occasionally, when I attempt to lift my hand it well … won’t. Notice that I didn’t say can’t. There is nothing wrong with my arm. It is still strong and capable of moving, but I have to put effort, even focus, into getting it to move — frequently to such a degree that I have to pause whatever else my brain is doing (including talking or thinking). Sometimes, when no one else is around, I use my other hand to move it.

Deep brain stimulation in Parkinson disease.

Adaptive deep brain stimulation in advanced Parkinson disease.
Ann Neurol. 2013 Sep;74(3):449-57.
Little S, et al.
Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford.

Brain-computer interfaces (BCIs) could potentially be used to interact with pathological brain signals to intervene and ameliorate their effects in disease states. Here, we provide proof-of-principle of this approach by using a BCI to interpret pathological brain activity in patients with advanced Parkinson disease (PD) and to use this feedback to control when therapeutic deep brain stimulation (DBS) is delivered. Our goal was to demonstrate that by personalizing and optimizing stimulation in real time, we could improve on both the efficacy and efficiency of conventional continuous DBS.

We tested BCI-controlled adaptive DBS (aDBS) of the subthalamic nucleus in 8 PD patients. Feedback was provided by processing of the local field potentials recorded directly from the stimulation electrodes. The results were compared to no stimulation, conventional continuous stimulation (cDBS), and random intermittent stimulation. Both unblinded and blinded clinical assessments of motor effect were performed using the Unified Parkinson’s Disease Rating Scale.

Motor scores improved by 66% (unblinded) and 50% (blinded) during aDBS, which were 29% (p = 0.03) and 27% (p = 0.005) better than cDBS, respectively. These improvements were achieved with a 56% reduction in stimulation time compared to cDBS, and a corresponding reduction in energy requirements (p < 0.001). aDBS was also more effective than no stimulation and random intermittent stimulation.

BCI-controlled DBS is tractable and can be more efficient and efficacious than conventional continuous neuromodulation for PD.


A Novel Brain-Computer Interface Approach to Deep Brain Stimulation for Parkinson’s Disease
October 31, 2013
S. Andrew Josephson, M.D.
Department of Neurology, UCSF, San Francisco, USA
Related To:  Chapter 372. Parkinson’s Disease and Other Movement Disorders


Deep brain stimulation hinders Parkinson’s for ten years and counting
08 Aug 2011

Multiple sclerosis: An old drug (benztropine) plays a new trick

a, rat oligodendrocyte progenitor cells … agents that would induce differentiation of oligodendrocytes, which produce myelin basic protein (MBP). b, Benztropine enhanced axon myelination when added to a co-culture of oligodendrocyte progenitors and neurons. c, Benztropine promoted remyelination, … alleviated disease symptoms such as hind-leg and tail paralysis.

Multiple sclerosis: An old drug plays a new trick
Nature 502, 314–315 (17 October 2013)
Hartmut Wekerle & Edgar Meinl

A drug already used to treat Parkinson’s disease induces repair of the damage that occurs to the myelin sheath around nerve fibres during multiple sclerosis.
The finding offers new therapeutic avenues for this disease.


Stem cell therapy in Parkinson’s disease

Protocols for dopaminergic neuroblasts from stem cells for transplantation in PD.

Prospects of stem cell therapy for replacing dopamine neurons in Parkinson’s disease
Trends in Pharmacological Sciences, May 2009, 30(5):260–267.
Olle Lindvall, Zaal Kokaia.

In Parkinson’s disease (PD), the main pathology is a loss of nigrostriatal dopamine (DA) neurons. Clinical trials with intrastriatal transplantation of human embryonic mesencephalic tissue have shown that grafted DA neurons reinnervate the striatum, restore striatal DA release and, in some patients, induce major clinical benefit. Stem cells could provide an unlimited source of DA neurons for transplantation. Recent studies demonstrate that cells with properties of mesencephalic DA neurons can be produced from stem cells of different sources including reprogrammed somatic cells.

However, as we discuss here, it remains to be shown that these cells can provide efficient functional reinnervation and behavioral recovery in animal PD models.
… strategies to prevent dyskinesias and tumor formation.

The effects of DBS on the motor symptoms of Parkinson’s Disease

The effects of DBS on the motor symptoms of Parkinson’s Disease
Jun 12, 2013
Andrew was diagnosed with Early Onset Parkinson’s Disease in 2009 when he was 35 years old.
He lives with his wife and two children in Auckland, New Zealand. In November 2012 and February 2013 he underwent a surgical procedure, Deep Brain Stimulation surgery, to help control his motor symptoms.
This has been hugely beneficial to his quality of life. He is the author of a blog which he created to raise awareness of the effects of Parkinson’s Disease. This is his experience of how DBS has helped him and in the usual manner, results may vary.

The Man With A ‘Battery Operated Brain’
by Robert Krulwich
June 25, 2013


Neurology – Topic 14 – Parkinsons disease – examining a patient
UCD Medicine