Parkinson’s Disease
By Dr. Rizwana Rahim
Chicago, IL

Parkinson’s disease (PD) is basically a chronic and progressive condition of the central nervous system (CNS), named after the British doctor, James P., who described the disorder in considerable detail in 1817.
In PD, cells (neurons) in a certain section of the brain called substantia nigra that produce a chemical messenger called Dopamine (DA), are damaged or are increasingly lost. DA is a brain chemical that signals/transmits or carries messages (neurotransmitter) that ultimately directs movement in different parts of the body, including the limbs. Along with DA loss, the affected neurons also carry clumps called Lewy bodies, the pathological evidence of PD, and these toxic bodies contain a mysterious protein, alpha-synuclein.
Loss of DP causes motor-system disorders, including PD, that make the patients unable to direct or control their normal movements. Early PD symptoms may be confused with various age-related conditions and vary from individual to individual, and may take time to appear but are often quite unmistakably noticeable, and include trembling or tremors in hands and legs, difficulty in simple tasks like walking or keeping balance and talking, stiffness in body and limbs, with a progressive overall slowing down of movements (or bradykinesia).
Progressive damage to neural cells is a feature that PD shares with other neurodegenerative diseases, such as Alzheimer’s and Lou Gehrig’s (Amyotrophic lateral sclerosis; ALS). In Alzheimer’s, the cerebral cortex and hippocampus are atrophied (lose mass), which results in loss of cognitive functions (memory, reasoning) and pattern recognition, (neuritic plaques, neurofibrillary tangles and reduced acetylcholine levels being the distinguishing features). ALS is a neuromuscular disease in which the motor neurons are destroyed, resulting in problems with skeletal muscles (walking etc).
About 50,000 people are diagnosed with PD every year. Since in some, it goes unrecognized for a long time or early symptoms are not noticeable, or are not diagnosed as PD, it is suspected that a million Americans may have this disease. PD seems to be an equalizer of a sort: it occurs in every race, ethnic group, economic class, geographical region or country, and strikes women and men almost equally.
Age seems to be a major risk factor for PD. Most PD patients are 50 years or older (average age 60), but it is also known to strike people younger than 40 (e.g., actor Michael J. Fox, an early on-set case). Another risk factor may be genetic (‘runs in the family’ situation), because 15-20% of PD patients also had a close relative with the same disease.
Long-term exposure to pesticides seems to be an environmental factor that increases the risk of PD. In a recent survey of 143,000 people, a Harvard team found that, regardless of occupation, pesticide exposure boosted long-term Parkinson's risk by 70 percent over the long-term. Another survey of possible dietary role in PD suggested that increased vitamin B6 or pyridoxine consumption may lower the risk of PD. Several studies also showed that smoking can reduce the risk of getting PD, which is attributed to the protection of brain cells by nicotine. Another study published this year in ‘Neurology’ found that smokers who also took higher doses of B6 had a lower risk of developing PD, and this protective effect wasn’t seen in non-smokers.
However, most scientists believe PD may be due to a combination of genetic and environmental factors. Among the genetic leads for PD, the most promising seems to be the gene that produces alpha-synuclein. Abnormal quantities of this protein are found in the affected neurons. Over-expression of this gene (i.e., over-production of alpha-synuclein) and its variants is also a rare cause of PD; a three-fold increase in alpha-synuclein was seen in a recent study. There is some association between the amount of the gene (1 or 2x the normal) and PD’s on-set age, rate of its progression and severity. Rarely (in 1% cases), several mutations in this gene also cause PD. In a large collaborative study published in the 9 August issue of Journal of Medical Association, the length of the REP1-promoter in the gene was found to vary with the increase in PD risk and the age of its onset.
No cure exists for PD, except that some drugs now in use tend to slow down or stop its progress and severity. The first drug approved (in 1970s) against PD was levo-dopa (L-Dopa), which is still used (in the brand, ‘Sinemet’). L-Dopa is taken up by the neurons and is metabolically converted there into DA. Increased DA level significantly improves the PD symptoms, but as the diseases progresses, L-Dopa dose will have to also increase. L-Dopa has some side effects, including involuntary movements and tics (dyskinesia) and hallucinations. Carbi-dopa slows down the enzymatic conversion of L-Dopa to DA in the blood, increasing the DA supply to the brain, which prolongs the effects of L-Dopa and reduces the side effects. A few other drugs (Comtan, Deprenyl, Tasmar) inhibit this enzymatic conversion of L-Dopa to DA, which also helps maintain a high DA supply in the brain. Other drugs (Parlodel, Requip, Permax, Mirapex) imitate DA (i.e., its agonists), and are used along with L-Dopa. Some muscarinic antagonists like Artane, Cogentin are particularly effective for tremors. Symmetrel also helps the tremors and increases L-Dopa effects. But all drugs have adverse side effects, like mental confusion, hallucinations, and dyskinesia.
There are some surgical options too, but after all the non-invasive therapeutic approaches are exhausted, and mostly depending on the patients’ physical condition. Pallidotomy, i.e., a tiny hole drilled into the skull to electrically destroy a small part of the global pallidus that is believed to be overactive in PD patients may help reduce dyskinesia caused in some people by the drugs. Thalamotomy (destruction of a group of cells in the thalamus) could help disabling tremors, but not any other symptoms. Instead of destroying tissue, a relatively new but less-used technique, deep brain stimulation (DBS), can send electric pulses (like pacemakers for the heart), via electrodes implanted in the pallidus or subthalamic nucleus, to block PD signals. Fetal tissue transplants have been tried, but they are very risky, and face ethical objections. Human stem cells (both embryonic and adult) offer a lot of hope but the research on it is mired in a lot of political, ethical debate, and it may take many years before it can be of any clinical use.
Despite a few advances in PD therapies and research so far, PD remains, unfortunately, an irreversibly degenerative CNS disease.
For more information, see the website of the National Institutes of Neurological Disorders & Stroke:


Editor: Akhtar M. Faruqui
2004 . All Rights Reserved.