Parkinson's Essay on the Shaking Palsy (1817) is often thought to represent his greatest contribution to medi-cine.26 27 The study is based on six cases, some never actually examined by Parkinson but observed on the streets. The five chapters of this 66-page octavo volume include
I. Definition—History—Illustrative Cases, II. Pathognomic symptoms examined—Tremor Coactus—Scelotyrbe Festinians, III. Shaking Palsy distinguished from other disease with which it may be confounded, IV. Proximate cause—Remote causes—Illustrative cases, V. Considerations respecting the means of cure.
Apologizing for mere conjecture regarding the etiology of the shaking palsy, Parkinson states his "duty to submit his opinions to the examination of others, even in their present state of immaturity and imperfection" and mission to inspire research on this disease.26
Parkinson recognized the long duration and slowly progressive nature of the disease. His first chapter commences with an often-quoted definition of shaking palsy:
...involuntary tremulous motion, with lessened muscular power, in parts not in action and even when supported; with a propensity to bend the trunk forward, and to pass from a walking to a running pace: the senses and intellect being uninjured.26
Similar tremors were noted years before by Galen, Sylvius de la Boe, Juncker, and Cullen, and these different types of tremor are further discussed in his second chapter. Parkinson illustrates the insidious onset and progression of this condition:
So slight and nearly imperceptible are the first inroads of this malady, and so extremely slow is its progress, that it rarely happens, that the patient can form any recollection of the precise period of its commencement. The first symptoms perceived are, a slight sense of weakness, with a proneness to trembling in some particular part; sometimes in the head, but most commonly in one of the hands and arms.26
As the disease progresses, other features appear:
After a few more months the patient is found to be less strict than usual in preserving an upright posture: this being the most observable whilst walking, but sometimes whilst sitting or standing. Sometime after the appearance of this symptom, and during its slow increase, one of the legs is discovered slightly to tremble, and is also found to suffer fatigue sooner than the leg of the other side.26
Inevitably, a state of immobility and dependence occurs with disturbances of sleep and bodily functions of bowels, speech, and swallowing. Parkinson's descriptions quite accurately elaborate on the cardinal symptoms associated with the disease. He also comments on the asymmetric onset of disease, patients' perceptions of weakness, and problems with sleep, constipation, hypo-phonia, and sialorrhea. Observations in years following his publication would lead to recognition of other features such as hypomimia, rigidity, and dementia.
The six cases reported differ in severity as well as depth of Parkinson's observation. The first case features a man older than 50 years, with left upper extremity tremor, who we are told succinctly had almost all symptoms reported in Parkinson's first chapter. Parkinson actually examined only three of the six cases directly. Of those observed casually in the street, he includes the following cases:
...a sixty-two year old man with an eight to ten year history of symptoms of tremor, interrupted speech, flexed posture, and gait impairment; a sixty-five year old man with agitation of his whole body, flexed posture, and fes-tinating gait; and a man with "inability for motion except in a running pace."26
Case four, a 55-year-old man with trembling of his arms for 5 years and costal inflammation necessitating drainage, was examined but lost to follow-up. The sixth case provides a more comprehensive account of the patient's afflictions—gradually progressive tremor, interrupted speech, constipation, intelligible handwriting, gait disturbance, and inability to feed himself. More striking was the occurrence of a stroke in this patient, which suppressed his tremor while his affected arm was paralyzed.
Parkinson systematically dissects each symptom described in his first chapter. Past distinctions between tremors occurring during terror, anger, advanced age, or palsy were explored. Parkinson comments on the useful classification of tremor at rest (tremor coactus) and action by Sylvius de la Boe (1614-1672) and Sauvages (1706-1767). It is possible that he learned about tremors during his study of Latin and Greek and attendance at John Hunter's lectures.10 He examines the origins of flexed posture and running gait. Sauvages described this gait as Scelotyrbe festinans, "a peculiar species of scelo-tyrbe, in which the patients, whilst wishing to walk in the ordinary mode, are forced to run" and differentiated it from Chorea Viti:
.the patients make shorter steps, and strive with a more than common exertion or impetus to overcome the resistance; walking with a quick and hastened step, as if hurried along against their will. Chorea Viti. attacks the youth of both sexes, but this disease only those advanced in years.26
Parkinson differentiated tremor observed in the shaking palsy from that seen in apoplexy, epilepsy, worms, alcohol and caffeine use, and advanced age. He used the term "palsy" as a synonym for weakness and did not appreciate the unique quality of bradykinesia. He did not discuss rigidity. These distinctions were added later by Trousseau in his "Fifteenth Lecture on Clinical Medicine."28
The medulla spinalis and medulla oblongata were the proposed neuroanatomical localization of this disease. Cases with features similar to the shaking palsy were suspected to have involvement of the medulla with "some slow morbid change in the structure of the medulla, or its investing membranes, or theca, occasioned by simple inflammation, or rheumatic or scrophulous affection."26 Despite contributions of spine fractures, venereal disease, and rheumatism in these cases, Parkinson suggests how pathology in the medulla might underlie the weakness, gait disturbance, and bulbar symptoms seen in these examples. Parkinson's arguments for involvement of the medulla spinalis and oblongata reflect understanding of the nervous system in the eighteenth and nineteenth centuries. It was not until the latter part of the nineteenth century, with observations and anatomo-clinical correlates on amyotrophic lateral sclerosis, tabes dorsalis, and multiple sclerosis from physicians such as Charcot, that functions of the brain and spinal cord were better understood.29 The nigral degeneration implicit to Parkinson's disease was not suggested until the late nineteenth century and not systematically studied until Tretiakoff in his 1919 the-sis.1,30 Parkinson's belief, however, in clinical and pathological correlations to understand disease mechanisms is clearly stated:
Before concluding these pages, it may be proper to observe once more, that an important object proposed to be obtained by them is, the leading of the attention of those who humanely employ anatomical examination in detecting the causes and nature of diseases, particularly to this malady. By their benevolent labours its real nature may be ascertained, and appropriate modes, of relief, or even of cure, pointed out.26
In his final chapter, Parkinson enumerates treatments for the shaking palsy. He expresses the potential for neuroprotection as
. „it seldom happens that the agitation extends beyond the arms within the first two years. in this period, it is very probable, that remedial means might be employed with success: and even, if unfortunately deferred to a later period, they might then arrest the farther progress of the disease, although the removing of the effects already produced, might be hardly to be expected.26
Recommended treatments were bleeding from the upper part of the neck, application of vesicatories, and resultant drainage of purulent discharge; the use of internal medicines was not justified until more knowledge of the disease was available.
Overall, his essay was well received in the English medical community. The first review, appearing in The London Medical and Physical Journal in 1818, did criticize his speculation on localization and causes but largely recommended it for reading.31 Other reviews in The London Medical Repository and The Medico-chirurgical Journal praised his observations and excused his speculations on the basis of his respectable reputation.31 It was not until the 1860s that Charcot and Vulpian coined Parkinson's disease as an eponym for paralysis agitans.
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