In 1969, the neurologist Oliver Sacks gave the experimental drug Levodopa (L-DOPA) to patients suffering from encephalitis (inflammation of the brain). These patients suffered from symptoms of Parkinson’s disease and had been trapped in their bodies for decades, unable to move or speak. Miraculously, the drug was a success and the patients regained many of their previously lost abilities; they were able to move and talk like before. This case revolutionised the treatment of Parkinson’s Disease and created a link between Parkinson’s Disease and the neurotransmitter dopamine, which is derived from L-DOPA.
How does dopamine help Parkinson’s patients?
Parkinson’s disease is a type of dementia that primarily affects motor functioning. Patients experience symptoms like slowness of movement, tremors, and rigidity. In Parkinson's Disease, dopamine decreases in multiple areas of the basal ganglia. These areas are all involved in different functions from movement to executive functions (which involve tasks such as planning, inhibitory control, attention, and more). However, the decreases in dopamine are uneven across them, with the motor areas experiencing the largest reduction. When L-DOPA is taken, it increases dopamine to a normal level within the motor areas such as the Putamen, a specific area of the basal ganglia. As a consequence, patients feel a reduction in the difficulties experienced with movement.
Are there consequences of giving dopamine to Parkinson’s patients?
It is important to note that Parkinson’s disease does not cause a high decrease in dopamine throughout the brain. L-DOPA helps to specifically reduce difficulties in movement by increasing dopamine in areas where dopamine levels are low, however, L-DOPA can also lead to dopamine overdose in other brain regions, not involved in directing movement. The relationship between cognitive performance and dopamine can be graphed as an inverted U-shape; where too little and too much dopamine can impair cognitive performance. The graph below shows that performance on some tasks (Task B) increases from higher dopamine, whilst performance in other tasks decreases (Task A). The horizontal black arrow represents how a dopamine-increasing drug like L-DOPA can positively impact performance (Cools & D'Esposito, 2011).
In Parkinson’s disease, areas of the basal ganglia such as the ventral striatum and caudate nucleus experience less dopamine decreases compared to the putamen. As base levels are at a higher level, a dopamine ‘overdose’, or overshoot, can occur. Due to this dopamine overdose, cognitive decline from L-DOPA can include visual hallucinations, distraction, or issues with decision-making.
Circling back to Oliver Sacks’ patients, not all of them responded well to the drug. Although the initial response was positive across patients, the long-term effectiveness of the drug could not be guaranteed. This is because dopamine is an important neurotransmitter that is involved in multiple functions of the brain. Therefore, adjusting the global level of dopamine would cause multiple side-effects across domains. In terms of his patients, many of them struggled to deal with the psychological, emotional, and environmental factors associated with waking up from the multiple decade-long coma. For example, Leonard L. responded very well to L-DOPA but after six weeks, grew very sensitive to it. This also tells us that each individual has their own level of sensitivity and tolerance to a drug. Although this is a very extreme case, it is a good example that one drug cannot be a cure-all for any disease.
Are there other treatments for Parkinson’s Disease?
Although there is still no cure for Parkinson’s disease, L-DOPA remains the most effective treatment in improving the quality of life for patients. In specific cases, surgery or behavioural treatment may be beneficial. For example, Deep Brain Stimulation (DBS) is a procedure that is used mostly for patients who exhibit symptoms that cannot be controlled with medication. DBS involves implanting electrodes in the brain that control the motor aspects of the disease. It has been shown to be very effective and can sometimes also improve non-motor symptoms.
Since research is still ongoing, most therapies focus on improving the quality of life of patients. Most of the time, this involves a combination of medication, behavioural therapies, and psychoeducation of the disease. Ultimately, this discovery of the link between dopamine and Parkinson’s Disease has been important in understanding this disease. It is important to consider multiple factors such as the environment and psychological state when treating a complicated disease like Parkinson’s.
Author: Aisha Humaira Waldi
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