In recognition of Parkinson’s Awareness Month this April, Dr. Jim Bennett has written an essay about James Parkinson.
The son of a London “chemist” (pharmacist), James Parkinson was an early nineteenth century suburban London physician who in some ways is the victim of the eponym. He was much more than the describer of a movement disorder that bears his name.
His first two loves were paleontology and social justice. He owned one of the largest fossil collections in the Western world and studied it intensely. Between 1804 and 1812 he published, at his own expense, three volumes of a 1200 page work “Organic Remains of a Former World,” in which he advanced the novel idea that these fossils represented former carbon-based creatures. He included 52 of his own hand drawn plates. His work was so popular that it was re-published in a second edition.
Figure 1. An illustration by Parkinson of one of his fossils, presented in his “Organic Remains of a Former World”
Parkinson was a tireless advocate for the welfare of poor women and children. He tried to convince parents that childhood epilepsy would be reduced if parents stopped disciplining their children by hitting them on the side of the head. He was one of the first physicians to embrace the importance of oxygen, that had been described 30 years earlier, as essential to life. He developed resuscitation techniques and described successful resuscitations after drowning, hanging and lightning strikes.
We remember Parkinson because of his description of a movement disorder detailed in a small monograph “An Essay on the Shaking Palsy” that he published (again, at his own expense) in 1817. In it he described the abnormal movements of six individuals whom he had observed, three of whom he had examined briefly. His clinical descriptions of the movement disorder have not changed over time, although we now know much more about the nature of the brain disease he described (see below). In the 19th century, the famous French neurologist Jean-Pierre Charcot described the “maladie de Parkinson,” thus creating the eponym that remains to this day. In the early 20th century, the famous British neurologist William Gowers described 80 patients who had “Parkinson’s disease.”
Parkinson did not know what caused the movement disorder he observed, and believed it to be a disease of the upper spinal cord. He recommended application of mustard plasters to the back of the neck.
- In the early 1960′s Swedish neuroanatomists discovered a method of exposing dried brain sections to hot formaldehyde vapors that caused neurons containing dopamine (and other “biogenic amines”) to fluoresce under a microscope. They described paired groups (“nuclei”) of nerve cells in the midbrain that fluoresced and soon found to contain dopamine. These nerve cells were located in the substantia nigra, or “black substance,” so named because early anatomists noted that when sections through this area were exposed to air, they turned black. We now understand that the dopamine neurons contain a golden pigment called neuromelanin that is oxidized when exposed to air and is responsible for the black color.
- By the mid 1960′s it was becoming known that brains from Parkinson’s patients suffered great losses of these dopamine nerve cells and had dopamine deficiencies in the pathways innervated by these neurons. Use of L-DOPA to replace dopamine quickly followed, creating one of the mainstays of symptomatic therapy that persists to this day.
- Until the early 21st century our understanding of Parkinson’s disease in the brain advanced little beyond problems with dopamine neurons and dopamine deficiency states. Therapies advanced to include multiple formulations of L-DOPA, drugs that mimicked dopamine (agonists), drugs that boosted L-DOPA actions and deep brain stimulation surgery that developed as a reversible technique following successful reintroduction of lesion surgery (pallidotomy).
- Between 2003-2006, the neuropathology group led by Heiko Braak at the University of Frankfurt published a series of papers that resulted from their studies of hundreds of patients at all stages of clinical Parkinson’s disease, and many who were comparably aged but did not have a movement disorder. What the Braak group described was a preclinical progression of aggregated protein pathology that begins in enteric neurons of the gastrointestinal system, then spreads into the neurons allowing smell, those in the spinal cord that control blood pressure and heart rate, followed by neurons in the lower brainstem.
Figure 3. Shown are nerve cells from the gastrointestinal system that contain aggregated alpha synuclein protein. These abnormal protein aggregates can be found many years before the neurological signs of Parkinson’s disease appear. Similar protein aggregates appear in brain nerve cells as Parkinson’s disease progresses. From Braak, et. al. Neuroscience Letters 396 (2006) 67-72.
- The pathology then slowly spreads forward in the brain, ultimately involving the substantia nigra (Figure 2), leading to progressive death of the nigral neurons. After approximately two-thirds of those neurons die, the individual develops the earliest signs of Parkinson’s disease movement disorder. But by that time the pathology has already spread forward into the limbic (emotional) brain, and ultimately the entire front lobes of the brain experience the advance of the disease.
Figure 4. Sections from frontal lobe showing aggregates of alpha synuclein protein in someone who died with early (a), moderate (b, c) and advanced (d) Parkinson’s disease. From Braak et al. Cell and Tissue Research 318:121-134(2004).
Figure 5. Summary diagram of the Braak model of Parkinson’s as it progresses pathologically from the pre-clinical stages (1-3), across the threshold into early neurological symptoms (4) and continues into moderate (5) and advanced (6) stages. From Braak et al. Cell and Tissue Research 318:121-134 (2004).
- The Braak findings tell us that Parkinson’s is much more than a disease of dopamine neurons. Death of those specific neurons causes much of the movement disorder difficulties experienced by those afflicted. Other important groups of nerve cells experience premature death, increasing risks of depression and decreased motivation. Spread of disease into the limbic system further increases risk of emotional disorders, hallucinations and memory difficulties, and involvement of the frontal lobes impairs “executive function,” the ability to organize complex tasks. Clearly, Parkinson’s disease is a “complex” disease, and solving its many problems represents a complex task.
I believe James Parkinson would be amazed by what we have learned about the disease that bears his name and by the tools of inquiry and therapy we have acquired. However, he would likely be embarrassed by the eponym attached to the disease he described. He was a product of the Enlightenment and believed in the power of rational inquiry to help us understand the world around us and the nature of diseases. He and his contemporaries eventually won the battle with those who embraced “vitalism,” a quasi-religious explanation of life, but that struggle was long and occasionally vitriolic.
Ultimately, Parkinson, who died in 1824, was a devoted and compassionate physician who was beloved by those who knew him. The nurses at the hospital where he attended patients erected a plaque in his honor, which was particularly remarkable given the very low wages of nurses at that time in history.
His is definitely a path to emulate, as Parkinson successfully combined insatiable curiosity about the world around him with keen powers of observation, rejection of prejudices of existing ideas, experimentation to create new knowledge, and immense concern for the welfare of his fellow man. The eponym of Parkinson’s disease is as much about the character of the man who made the observations as it is about a neurological illness.
April 1, 2011
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