Parkinson’s disorder (PD) is a movement disorder where dopaminergic (dopamine producing) neurons in the substantia nigra of the brain undergo neurodegeneration (deterioration of neurons). This causes the individual to produce less dopamine(a neurotransmitter that controls motivation factor).The substantia nigra is a region of the brain that is darker than the others and is composed of two sub-regions, one on each side of the midbrain. The substantia nigra is part of the basal ganglia which is a collection of brain regions that control movement due to connections with the motor cortex. Parkinson’s is a type of Lewy body dementia. Darkened areas of the substantia nigra gradually disappear in Parkinson’s due to the formation of Lewy bodies (misfolded alpha-synuclein in neurons). Lewy bodies are also found in other diseases such as dementia with Lewy bodies (DLB) and Multiple System Atrophy. Individuals with PD also lose endings of nerves that produce the neurotransmitter norepinephrine (part of the sympathetic nervous system and controls automatic functions: heart rate, blood pressure, sweating). Fatigue and irregular blood pressure are some of the non-movement related symptoms of PD that can be explained due to a lack of norepinephrine.The exact cause of PD is unknown, however scientists are discovering that there might be a genetic component involved. Mutations in the gene PINK 1, PARKIN, or alpha-synuclein genes are a possible explanation for the onset of Parkinson’s.
James Parkinson was a London doctor who the disorder is named after. It was after his essay titled, “An Essay on the Shaking Palsy” that Parkinson’s was established as a medical condition. There are numerous risk factors for developing Parkinson’s. One risk factor is age. Individuals usually develop PD after 60 years however five to ten percent of individuals develop it by the age of 50 which is known as “early-onset” disease. Another risk factor is genetics. Individuals with family members who have Parkinson’s have a greater chance of developing the disorder. The next risk factor is age. PD is 1.5 times more likely to occur in men as compared to women. The last risk factor is the environment. Exposure to toxins such as pesticides slightly increases an individual's risk of developing PD. More research is being conducted in this field to determine the extent risk factors play into the onset of the disorder.
Clinical Symptoms:
Tremors: Tremors are involuntary shakes which are most noticeable when they occur in an individual’s hands. When tremors occur in the hands it known as “pill-rolling tremor”. Pill-rolling tremors along with other tremors occur at rest. It progressively gets worse as long as the person is not in motion, and diminishes with movement.
Rigidity: Muscles can be stiff and often this causes a lot of pain. This limits the individual’s range of motion. This symptom is responsible for a hunched posture and expressionless face which an individual might display.
Changes in Speech: Speech might become slurred. An individual might also become hesitant to speak. Tone variation may not be present.
Automatic Movement Dysfunction: A decrease in ability to perform everyday functions such as smiling or waving a hand.
Problems with Stability: There might be an imbalance while walking or even while standing in place.
Bradykinesia: Slow movement
Hypokinesia: lessened movement
Akinesia: Absence of movement
Non-Motor Symptoms:
Symptoms which have no regards to movement include:
Depression
Emotional Changes
Difficulty Sleeping
Constipation
Decreased Ability of Smell
Memory Difficulties
Fatigue
The significance of PD symptoms is that it does not cause weakness, and symptoms gradually get better with movement. These key characteristics helps differentiate Parkinson’s from other disorders that affect the motor cortex.
Treatment:
There currently is no cure for Parkinson’s however, treatments exist that help relieve symptoms. One method of treatment involves increasing the amount of dopamine being signaled in the brain. In the brain, a protective tissue known as the blood-brain barrier (BBB) is made up of endothelial cells, and protects the brain from toxins and constant fluctuations in the blood. Dopamine cannot cross the BBB however, it’s precursor levodopa can. Levodopa is converted by decarboxylase to dopamine once it enters the brain. However, peripheral dopa decarboxylase exists in the bloodstream and it breaks down levodopa before it enters the brain. That’s why levodopa is always administered to an individual with carbidopa which prevents peripheral dopa decarboxylase from breaking levodopa down. This promotes the production of dopamine as levodopa is able to cross the BBB and be converted. Another form of treatment includes administering dopamine agonists which trick receptors of dopamine in the brain to think that there is more dopamine than what is present. In the brain there is a balance of dopamine and acetylcholine which reaches the striatum (a region of the substantia nigra). In individuals with PD, there is more acetylcholine reaching the striatum as compared to dopamine. Therefore, anticholinergic medication can be given to the individuals to balance the amount of dopamine and acetylcholine reaching the striatum. Anticholinergics also reduce stiffness in the muscles as well as reduce tremors. Catecholamine-o- methyltransferase (COMT) and Monoamine Oxidase B (MAO-B) inhibitors should be administered to promote production of dopamine as these two enzymes degrade the neurotransmitter.
For certain individuals, drugs do not prove to be an effective form of treatment. In this case, they might respond better to deep brain stimulation (DBS). DBS is a type of surgery where electrodes are implanted in the basal ganglia (collection of brain regions that control movement: substantia nigra is part of it) which is connected to a device that is placed in the chest. These electrodes counteract the diverging signals present in individuals dealing with Parkinson’s, and helps alleviate symptoms such as stiffness, tremors and bradykinesia. Talk to your loved one’s doctor to find out the type of treatment that is right for them.
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