Authored by MCN Neurologists
Parkinson’s disease is a slowly progressive neurologic disorder characterized by difficulty with balance and shuffling gait, rigidity (abnormal muscle stiffness) of the extremities, resting tremor, slowed and stiff movements (called bradykinesia), decreased facial expressiveness and blinking, and alteration in the sense of smell. Other symptoms may include changes in writing (micrographia), difficulty swallowing, and an excessively soft voice.
Causes of Parkinson’s Disease
Parkinson’s disease is caused by a progressive loss of cells in the substantia nigra, a part of the brain that produces the dopamine and sends it to the basal ganglia. Dopamine is an important neurotransmitter, a chemical used by the brain to communicate information, and the basal ganglia is a part of the brain that controls movement. Therefore, when the substantia nigra is unable to produce enough dopamine, the basal ganglia begins to malfunction, producing the slowed movements, decreased facial expressiveness, difficulties with balance, and shuffling gait characteristic of Parkinson’s disease. Projections of dopamine cells to other parts of the brain probably are responsible for the non-motor aspects of Parkinson’s disease.
The loss of dopamine cells has many causes, but usually none of which are the sole cause. Abnormal deposition or misfolding of Alpha-synuclein form Lewy bodies, inclusions in the substantia nigra cells, leading to their death. Genetic factors play a small role in the development of Parkinson’s disease, but in general, the vast majority of cases are not directly genetically inherited. Only very few patients with early-onset Parkinson’s disease (less than 50) may have an inherited abnormality in the Parkin genes. Exposure to manganese, sometimes used in welding, or organophosphate insecticides, used in commercial farming, has modestly increased people’s risk of developing Parkinson’s disease.
A byproduct of and artificially produced recreational drug called MPTP directly attacks the substantia nigra dopamine producing cells, and caused an outbreak of severe Parkinson’s disease in young drug using individuals. This has led to the development of an animal model for Parkinson’s disease, which was previously unavailable. Additionally, investigations for other avoidable environmental exposures that may be related to MPTP are underway.
Conditions Similar to Parkinson’s Disease
There are related neurologic diseases that can mimic Parkinson’s disease, such as Lewy body disease, progressive supranuclear palsy, multiple system atrophy and cortical basilar degeneration. These disorders have components of their clinical presentation that mimic Parkinson’s, but have different causes, accompanying symptoms, responses to therapy, and long-term prognosis.
Treatment of Parkinson’s Disease
Parkinson’s disease is a slowly progressive disorder, and if identified in the early stages, may not require treatment at all, particularly if the patient is not troubled socially or occupationally by mild symptoms. Once the symptoms of Parkinson’s disease compromise safety, threaten employment, or diminish the ability to carry out social/household activities or activities of daily living, treatment should be considered. Treatment for Parkinson’s disease consists of pharmacologic and non-pharmacologic intervention.
Non-pharmacologic treatments include physical therapy, primarily for balance and gait, occupational therapy, primarily to overcome limitations caused by tremor, tiny writing (micrographia) and slowed movements, and speech therapy to address symptoms of soft voice and difficulty swallowing.
When the amount of dopamine produced by the substantia nigra available to the basal ganglia starts to diminish, the brain attempts to make compensatory changes in other chemicals in the brain to optimize function. Medications aim to improve the amount of dopamine available in the brain, and balance the compensatory mechanisms the brain has adopted to cope with the decreased dopamine.
The most straightforward treatment for the motor symptoms of Parkinson’s disease is the use of carbidopa – levodopa, also called Sinemet or Rytary. Levodopa is converted directly by the residual substantia nigra cells to dopamine, taking advantage of the brain’s own mechanism in making dopamine. Carbidopa blocks the conversion of levodopa to dopamine in the body, forcing more of the levodopa into the brain. Typically, carbidopa — levodopa is instituted at low doses, and gradually increased over time to control the Parkinsonian symptoms as needed. Complications with the use of carbidopa – levodopa, including on-off phenomenon and peak dose dyskinesias, can develop. Rytary, a long-acting form of carbidopa-levodopa, as well as continuous infusions of levodopa, have been effective in controlling some of the variability in dopamine stimulation, further reducing potential side effects.
Another strategy for treatment of Parkinson’s is to use Pramipexole and Ropinirole, medications that mimic dopamine in the brain (also called dopamine agonists) and, therefore, increase the amount of dopamine activity in the substantia nigra. Both levodopa and dopamine agonists can induce decreases in blood pressure, hallucinations, or obsessive compulsive behaviors, and therefore their use must be monitored closely.
Another way to increase the amount of dopamine in the brain is to inhibit the breakdown of dopamine in the basal ganglia. Medications such as Entacapone, Selegiline or Rasageline inhibit one of the the enzymes responsible for the breakdown of dopamine, thereby increasing the amount of dopamine in the basal ganglia. These are used in combination with levodopa and dopamine agonists.
Other medications that had been helpful in special circumstances include trihexyphenidyl (acetylcholine antagonist), amantadine or apomorphine.
Surgical intervention in the past included stem cell transplantation into the basal ganglia, and electrode ablation (destruction) of some of the basal ganglia pathways that produce some of the undesired Parkinsonian symptoms. These have experienced limited success. Currently, surgical treatment predominately consists of deep brain stimulation. Deep brain stimulation involves the implantation of electrodes into the basal ganglia, essentially serving as a “pacemaker” for the brain. Adjustments in the delivery of tiny electrical currents permit improved control of tremor, mobility and dyskinesias associated with Parkinson’s disease. The success of deep brain stimulation has prompted many physicians to use this intervention at the intermediate stages of Parkinson’s disease rather than in the very late stages.