Detecting Dopamine Loss for Parkinson’s Diagnosis and Monitoring

Parkinson’s disease is a neurodegenerative disease characterized by a gradual and progressive loss of dopamine nerve cells (dopaminergic neurons) in the substantia nigra region of brain. Dopamine loss is the characteristic hallmark of the disease and is the main culprit behind the signs and symptoms and complications associated with it.

Although there is no specific test for Parkinson’s disease, and the accuracy of clinical diagnosis of parkinsonism is still limited, however recent advances in a diagnostic imaging technique known as  SPECT  molecular imaging technique, may help doctors identify high risk patients even before the symptoms of Parkinson’s disease appear. It may also serve as a tool to monitor the disease progression.

Currently Parkinson’s disease is identified by a clinical diagnosis where the medical history and clinical presentation allows a doctor to reach the diagnosis. However, the new diagnostic technique may allow for conclusive diagnosis and even help prevent misdiagnosis of the disease. It is a functional neuroimaging technique, which helps in the early differential diagnosis of Parkinson’s disease. It is a potential sensitive tool to accurately assess the pathophysiology and disease progression, as well as to assess the therapeutic efficacy of the dopamine drugs. It effectively detects the in – vivo metabolic and biochemical changes in the Parkinson’s disease.

Low Dopamine Levels in Parkinson’s Disease

As explained under Parkinson’s disease brain chemistry,  dopamine is a brain hormone (neurotransmitter) that is deficient in PD patients. This is accompanied by a loss of dopaminergic neurons. When more than 60% of these neurons in the substantia nigra and corpus striatum of the brain are lost, then the motor signs of Parkinson’s disease becomes evident.

L-dopa may therefore help to counteract these symptoms by restoring dopamine levels. When dopaminergic neurons are stimulated, dopamine is released at the nerve terminal into the gap junction known as the synapse. This dopamine is recycled by dopamine transporters (DaT) which pumps it back into the nerve cells and stored for use at a later stage. Parkinson’s patients have a significantly reduced level of Dat activity in the striatum, and it correlates with the progression and severity of disease.

 

Detection of DaT Activity

The binding ligands which are used in the SPECT scan are a group of compounds which are derived from cocaine, which binds to dopamine transporter.

A substance developed by GE Healthcare known as DaTscan can help to detect these dopamine transporters. If the transporters are working then it indicates the presence of healthy dopaminergic neurons. Thus, a decrease in the levels of the Dat Transporter would indicate a possibility of the impending development of Parkinson’s disease. Until now there was no significant structural change in the brain that were detectable by conventional imaging techniques.

Therefore the loss of these dopaminergic neurons could not be isolated in the living patient. Since the advent of the in – vivo molecular imaging techniques like SPECT, The diagnosis of Parkinson’s disease has become more reliable by assessing the dopaminergic as well as the non dopaminergic neurons, and is useful for identifying individuals with dopaminergic loss in the impending Parkinson’s disease even before the onset of motor symptoms. It thus helps in the early diagnosis as the Dat scan results are abnormal even in the earliest clinical presentation of the disease. The test is sensitive enough to detect the loss of dopaminergic neurons even in the preclinical phases of the non-genetic or sporadic cases of Parkinson’s disease.

Although microscopic evaluation of brain tissue post mortem noted pallor of the substantia nigra and the loss of these neurons.  With the use of DaTscan, dopaminergic neurons are highlighted on a SPECT scan. This is a type of nuclear imaging study that stands for single-photon emission computerized tomography (abbreviation~ SPECT). DaTscan is a contrast agent that is visible on a SPECT scan.

 

DaTscan Results

With DaTscan, the brain function can be evaluated rather than just the structural changes associated with Parkinson’s disease.  Healthy dopaminergic neurons are illuminated on a SPECT scan with the use of the DaTscan contrast agent. Therefore higher the number of illuminated areas, the greater the number of healthy neurons. Conversely, dark areas indicate low dopamine activity.

This test holds much promise for accurately identifying patients with Parkinson’s disease or other parkinsonism syndromes. It removes uncertainty associated with undiagnosed or even misdiagnosed cases. It is a well known fact that the symptoms associated with Parkinson’s disease are overlapped with other similar neurological disorders, in other words the differential diagnosis of this disease is extensive, and often various atypical Parkinsonian syndromes are confused with PD. The examples of atypical Parkinson’s syndromes include multiple system atrophy (MSA), progressive supranuclear palsy (PSP), and cortico basal degeneration. Other diseases like drug induced Parkinsonism, vascular parkinsonism, dementia with lewy bodies, and essential tremors also carry a close resemblance to Parkinson’s disease, which is one of the culprits of misdiagnosed or incorrectly diagnosed cases.

The results shown upon functional imaging of Dat scan confirms the integrity of the nigro-striatal dopaminergic neurons. The presence of Parkinson’s like symptoms and a “normal” Dat scan, rules out the possibility of Parkinson’s disease, and suggests an alternative diagnosis of the overlapping diseases mentioned above. In other words, an abnormal Dat scan is the marker of loss of dopaminergic neurons, and hence is a confirmed diagnostic technique of Parkinson’s disease.

While it may not be necessary for every PD patient to get a confirmed diagnosis, it is hoped that this scan will be a reliable technique to monitor the progression of disease and therefore evaluate the efficacy of any treatment that can slow its progression. The rate at which the dopaminergic damage progresses is extremely high in PD patients as compared to the normal aging process. The Dat scan can evaluate the rate of damage and hence the progression of disease. It has been shown in various Dat scan results that PD patients first present with overlapping symptoms, that gradually progress to involve both sides.  This test can even assess the non motor symptoms of the Parkinson’s disease, like urinary dysfunction.
Currently (August 2011) clinical trials are underway by some 14 medical centers in the United States to evaluate DaTscan as a means to monitor the disease progression. This is part of the biomarkers study by the Michael J. Fox Foundation known as the Parkinson’s Progression Markers Initiative. (read more)

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