J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.52.Suppl.6 on 1 June 1989. Downloaded from

Journal ofNeurology, Neurosurgery, and Psychiatry. Special Supplement 1989:6-10 Aspects of the history of Parkinson's disease

J M S PEARCE From the Department ofNeurology and Parkinson's disease Clinic, Hull Royal Infirmary, Hull, UK

ASPECTS OF THE HISTORY OF PARKINSON'S AN DISEASE Aspects ofthe history ofParkinson's disease E S SAY Before James Parkinson's classic' "An Essay on the Shaking Palsy" (1817) ancient books recorded many types of paralytic disorders and tremors. None fully ON THa described the distinctive features of the syndrome which so justly perpetuates Parkinson's name. His essay (fig 1) mentioned the earlier writings of Juncker who distinguished tremors, either "Active- SHAKING PALSY. sudden affections of the mind, terror, anger or, Passive

-dependant on debilitating causes such as advanced Protected by copyright. age, palsy etc." He credited Sylvius de la Boe for showing the important difference between rest (tremor coactus) and action tremor in 1680. Parkin- BY son cites Sauvages "the tremulous parts leap, and as it wereL vibrate, even when supported: whilst every other JAMES PARKINSON, tremor, he observes, ceases, when the voluntary exer- HUSER OI THE ROYTAL COLLEGE of SUEGEOHI tionfor moving the limb stops ... but returns when we will the limb to move;" He also referred to van Swieten (1749) who had made similar observations about rest tremor. Sauvages had described the festi- LONDON: hant gait which "I think cannot be more fitly named PRINTtD BY WHIrTIGHAW AND ROWLAND. than hastening or hurrying Scelotyrbe (scelotyrbem festinantem, seufestiniam) ", as did Gaubius some ten FOR SHERWOOD, NEELY, AND JONES, years earlier (1758). IATERNORSTER ROW. 1817.

James Parkinson Figure 1 http://jnnp.bmj.com/ This brief essay can neither replace nor do justice to the scholarly writings devoted to James Parkinson, his life and work. The reader is referred to McMenemey's essay,2 was Anatomical Warden of the Surgeon's Company Gardner-Thorpe's introduction to the reprint of The which had replaced the Barber's Company in 1745 Shaking Palsy3 and to Kenneth Tyler's comprehen- and was succeeded by the Royal College of Surgeons sive review.4 Cleevely and Cooper' outline his work in 1800. In addition to his substantial medical con- as a social reformer and geologist and append an tributions James was variously described as a radical on September 28, 2021 by guest. extensive bibliography. political pamphleteer (under the pseudonym of "Old James was born on 11 April 1755, the first child of Hubert"), a pacifist, an agitator for parliamentary Mary and John Parkinson. John was an apothecary reform, a member of secret societies and, a campaig- and surgeon who lived and worked at 1 Hoxton ner for social welfare. Interestingly, no verified Square in the district of Shoreditch in London. He portrait of him exists. His writing was prolific. His first work was a Address for reprint requests: Dr J M S Pearce, Department of critical account of medical practice Observations on Neurology, Hull Royal Infirmary, Hull HU3 2JZ, UK. Dr Hugh Smith's Philosophy of Physic etc in 1780. 6 J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.52.Suppl.6 on 1 June 1989. Downloaded from

Aspects ofthe history ofParkinson's disease 7 The text ofthe Memorial reads: AN

IN PIAM MEMORIAM ESSAY

JAMES PARKINSON oi TUE OF HOXTON SURGEON AND APOTHECARY DIPLOMATE OF THE COMPANY OF SURGEONS SHAKING PALSY. MEMBER AND THE FIRST HONORARY MEDALLIST OF THE ROYAL COLLEGE OF SURGEONS IN HIS 'ESSAY ON THE SHAKING PALSY' HE FIRST DESCRIBED THE DISEASE CHAPTER I. SINCE KNOWN BYHIS NAME FOUNDER MEMBER OF THE GEOLOGICAL SOCIETY OF LONDON DEFENmON-HISTORY-ILLUSTRATIvE CASES. AND AUTHOR OF *ORGANIC REMAINS OF A FORMER WORLD' HONORARY MEDALLIST OF THE ROYAL HUMANE SOCIETY

POLITICAL AND SOCIAL REFORMER Agitans,? BORN AT I HOXTON SQUARE II APRIL 1755 SHAKING PALSY. (Paralysis WHERE HE PRACTISED FOR FORTY YEARS motion, with lessened DIED AT 3 PLEASANT ROW HOXTON Involuntary tremulous 21 DECEMBER 1824 muscular power, in parts not in action and BAPTIZED AND MARRIED IN THIS CHURCH AND BURIED IN THE CHURCHYARD even when supported; with a l)ropensity A LIFE LONG WORSHIPER AT THE PARISH CHURCH to bend the trunk forward, and to pass ERECTED BY THE NURSING STAFF from a walking to a running pace: the

OF ST LEONARD'S HOSPITAL Protected by copyright. senses and intellects being uninjured. Figure 2 Figure 3 His most famous book was a palaeontologoical escape." He stressed the need for "a continuance of study Organic Remains of a Former World in 3 vols observation of the same case, or at least a correct (1804-1811) which ran to three editions. His medical history of its symptoms, even for several years. He works included: some accounts of the effects of regretted that "the disease had escaped particular lightning, a case of diseased vermiform appendix notice and the task of ascertaining its nature by (possibly the first account of appendicitis), typhoid anatomical investigation." He hoped pathologists fever, hydrophobia, hints for the improvement of might "be excited to extend their researches to this trusses, gout, and the Essay on the Shaking Palsy. A malady." crinoid Apiocrinuxs parkinsoni, a gastropod Parkinson's inquiring mind shines throughout the Rostellaria parkinsoni, an ammonite Parkinsonia essay in an array of acute clinical observations and parkinsoni and a stemless palm Nipa parkinsoni are inferences. His descriptions leave one in doubt as to other commemorative tokens5 to this phenomenal whether he examined his patients in the conventional and scholarly scientist. fashion, but the sharpness of his eye and his qualities James married Mary Dale in May 1781 and they as a naturalist are self evident. As in his quixotic http://jnnp.bmj.com/ had six children; two died in infancy, one son John excursions into contemporary politics and the right- qualified in medicine and shared his practice. James ing of social ills, the essay betrays his deep compas- was afflicted with gout for many years, but is said to sion and humanitarian qualities. have died of a stroke3 on 21 December 1824. He was Chapter I opens with his classic summary (fig 3). baptised, married and was finally buried in St Leon- The words shaking palsy had been used before, but ard's church where a marble plaque (fig 2) was imprecisely; tremors had been described by Galen, unveiled in September 1955. Juncker (tremores paralytoidei), and by Cullen. "So on September 28, 2021 by guest. slight and nearly imperceptible are the inroads of this The shaking palsy malady, and so extremely slow its progress ... that the The essay spans 66 pages and five chapters. A preface patient cannot recall the onset. The first symptoms offers the reader a conciliatory explanation for a perceived are, a slight sense of weakness with a prone- "publication in which mere conjecture takes the ness to trembling ... most commonly in one of the place of experiment". "It has not yet obtained a hands and arms." ". .. in less than twelvemonths or place in the classification of the nosologists ...; more, the morbid influence is felt in some other part." whilst the unhappy sufferer has considered it an evil, After afew more months the patient isfound to be less from the domination of which he had no prospect of strict than usual in preserving an upright posture." J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.52.Suppl.6 on 1 June 1989. Downloaded from

8 Pearce ... As the disease proceeds ... the hand fails to but not initiated by Marshall Hall, as is often stated). answer the dictates of the will. Walking becomes a A man with paralysis and venereal infection, palsies task which cannot be performed without considerable occasioned by injury to the brain, medulla and upper attention. ... care is necessary to prevent frequent cord, and Pott's carious disease of the spine are falls." "The disease proceeds, difficulties increase: mentioned. This chapter fully portrays the state of writing can now be hardly at all accomplished; and knowledge, the limitations of medical practice and reading, from the tremulous motion, is accomplished the grave difficulties which beset physicians of the with some difficulty." Later, "the propensity to lean day. forward becomes invincible, and the patient isforced to Similarly, chapter 5 devoted to means of cure, step on the toes andfore part of the feet, ... irresis- shows us how frustrating attempts at treatment were tibly impelled to take much quicker and shorter steps, at that time. Optimism prevails however, "there and thereby to adopt unwillingly a running pace. appears to be sufficient reason for hoping that some ... "The bowels which had all along been torpid, the remedial process may ere long be discovered." He expulsion offaeces requiring mechanical aid." Finally discusses in turn: "blood takenfrom the upper part of "his words are now scarcely intelligible ... no longer the neck, . . . vesicatories applied to the same part and able to feed himself... saliva is continually draining a purulent discharge obtained by use of the Sabine from the mouth, mixed with particles offood he is no Liniment;". Later he remarks "Until we are better longer able to clear from the inside of the mouth." informed regarding the nature of this disease, the Terminally he describes sleepy exhaustion with employment of internal medicines is scarcely warran- incontinence and loss of articulation. table;". Parkinson then provides six beautifully illustrative This classic and exemplary essay ends by case histories of men aged 50, 62, 65, 55, 72 years and generously extolling the virtues of his colleagues a gentleman, the particulars of which could not be professional ardour and devotion and "the benefits

obtained ("the lamented subject of which was only bestowed on mankind by the labours of a Morgagni,Protected by copyright. seen at a distance'). It is curious that no women were Hunter, or Baillie." described. The symptoms-tremor coactus and scelotyrbe Later developments festinans, their nature and the opinions of preceding The essay was well received and cited in Cooke's writers are considered in chapter 2 (vide supra). Treatise on Nervous Disease,6 and in Marshall Hall's Differential diagnosis is considered in the third chap- celebrated Lectures on the Nervous System' and by ter. Parkinson emphasised that this "disease does not Robert Bentley Todd (ofTodd's palsy) in a paper and accord with any which are marked in the systematic in his clinical lectures on paralysis.8 Marshall Hall had arrangements of the nosologists." He refers to palsy access to necropsy on a 28 year old patient with consequent to compression of the brain, or exhaus- "hemiParkinsonism" and concluded that the disease tion of that organ. He decries the use of the term was related to a lesion ofthe corpora quadrigemina; he "shaking palsy" in convulsive affections, including noted a resemblance to tremor mercurialis. By the mid those of a lady with what we would now call ballistic 1850s the disease was well established and described in attacks, and convulsions. Another case cited might the works of Stokes and Robert Graves;4 and, it is be an example of torsion dystonia. He finally des- confounded with a description of action tremor in

cribes "the trembling consequent to the indulgence in Romberg's Lehrbuch.9 But little new was added. http://jnnp.bmj.com/ the drinking of spirituous liquors and the immoderate Trousseau's 15th Lecture on Clinical Medicine'° was employment oftea and coffee-tremor temulentus." on senile trembling and paralysis agitans. He des- The proximate and remote causes are considered cribed rigidity, a sign Parkinson did not pay attention in chapter 4 along with illustrative cases. "A diseased to, and, he explained the scelotyrbe festinans "as his state of the medulla spinalis, in that part which is centre ofgravity is thus displaced, he is obliged to run contained in the canal, formed by the superior cervical after himself, as it were, so that he keeps trotting and vertebrae, and extending, as the disease proceeds, to hopping on. " Trousseau-also described the progressive

the medulla oblongata" is the proximate cause. slowing of repeated hand opening, the first clear on September 28, 2021 by guest. Parkinson again expresses his uncertainty, lacking account of bradykinesia. Although James Parkinson anatomical observations, but postulates injury to the had said "the senses and intellects being uninjured", medulla or theca related to the mobility of the Trousseau was aware that "the intellect ... gets cervical spine "which must render it and the contained weakened at last; the patient loses his memory, and his parts, liable to injury from sudden distortions. " His friends notice soon that his mind is not as clear; cases in,jis. chapter.,arc. described for analogy; he prococious caducity sets in." Trousseau was a realist: realises they differ substantially from paralysis he had, he said, not cured a single patient with agitans (a term used by Parkinson in his title page, medicaments; pneumonia was the common exitus J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.52.Suppl.6 on 1 June 1989. Downloaded from

Aspects ofthe history ofParkinson's disease 9 lethalis, but he was not aware of any necropsy inferior peduncle, destroying the locus niger, he performed in France. remarked "a lesion ofthe locus niger could very well be Charcot, Vulpian and Ordenstein wrote extensively the anatomical basis of Parkinson's disease." At that on the Salpetriere experience which is crystallised" in time nothing was known ofthe structure or physiology Lecture 5 of Charcot's Lecons sur les malades du of the substantia nigra and this was a remarkable and systeme nerveux (1877). Their views leaned heavily on prophetic comment of Brissaud's. Todd's work. Cold, damp and "emotions morales Gowers characteristically surveyed'3 the scene in vives" were held important. Charcot described the masterly fashion, reviewing 80 patients of his own. He affliction as one of the over 50s and classed it as a noted a male preponderance, age of onset 50-60 years neurosis that is, with no proper structural cause. in half the cases and a hereditary influence (now Tremor was the cardinal symptom "limited atfirst to disputed) in 15%. Like Charcot he had seldom seen one member, then little by little becoming generalised. " tremor in the face or head. The gait, speech, writing, Later "almost pathognomonic, the patient closes the and the propensity for mental weakness, loss of fingers on the thumb as though in the act of spinning memory and a tendency to delusions were clearly wool ... or crumbling bread ..." The movements are enunciated. A mixture of "arsenic, Indian hemp (can- slow and seem feeble, although dynamometrical nabis), sometimes combined with opium" were experiments prove that this diminution is not real." He advocated. partly ascribed the weakness to "the rigidity which prevails in the muscles." Charcot recognised "a tendency to propulsion and Pathology retropulsion ... the individual is unable to stop-being Parkinson's disease was considered a syndrome of the apparentlyforced to follow aflying centre ofgravity. " motor cortex by Gowers and his predecessors, the He referred to the "peculiar attitude ofthe body and its function and pathophysiology of the basal ganglia

members, a fixed look, and immobile features." He being then obscure. Tretiakoff in 1919 examined the Protected by copyright. analysed the writing, noting the tremulous fine up- brains of nine Parkinsonian patients and noted'4 a strokes when the down-stroke was firm and relatively variety of degenerative lesions, but pointed out normal. Speech was "slow, jerky and short ofphrase reduced numbers of pigmented cells in the locus niger ... jolted out as it were, like an inexperienced rider on which he related to disorder of the muscular tone in horseback, when the animal is trotting. " Parkinson had Parkinson's disease. He also found peculiar concentric not commented on the rigidity of neck, trunk and inclusions in the cytoplasm of these nigral cells which extremities; Charcot elucidated these signs and said had been described by FW Lewy in 1913. A more Parkinson had overlooked them. Bradykinesia was complete study of the mesencephalon and its neuro- not dependent on rigidity "dependent neither on the pathology formed the basis of a classic paper by Foix existence oftremors, nor on that ofmuscular rigidity." and Nicolesco'5 in 1925, by which time the essential He shrewdly anticipated modem concepts of the anatomical substrate, which so frustratingly had movement disorder: a lapse of time between the eluded James Parkinson, was more or less complete. thought and the act. Terminally "the mind becomes The pandemic of encephalitis lethargica of von clouded and memory is lost. " Tremor faded late in the Economo between 1917 and 1926 left in its wake a new disease and the final event, as Trousseau had noted, variety of disease: post-encephalitic Parkinsonism. was often pneumonia. His pathological studies added This was the first of the symptomatic causes of the http://jnnp.bmj.com/ little, but therapeutically he noted the palliative effect syndrome recognised, but the clinical features and of hyoscyamine, the precursor of other belladonna natural history were substantially different from alkaloids. paralysis agitans. Rare sporadic cases are still des- In Pathogenie et Symptoms de la Maladie de Parkin- cribed, and its historical importance may be as an son in 1895, Brissaud'2 made significant contributions. indicator of the possibility of slow viral infections of He remarked on speech as "murmured an interminable the brain, their epidemiology and sequelae. Critchley littany", the voice weakened without intonation. "The had attempted to separate "arteriosclerotic Parkinson- eyelids were rigid, fashion of trembling, ... pupils ism" from paralysis agitans; and a galaxy of striatal on September 28, 2021 by guest. stenosed and rigid." "At the idea ofmovement, tremor Parkinson-like syndromes, bearing a variety of epon- worsened, with movement itself, tremor ceased." The yms, have been recognised and demarcated from synchrony of tremor led him to favour a central origin idiopathic paralysis agitans. of the disease. He also observed "psychic disorders" the same repugnance to emit their ideas as to move Recent advances their limbs. Paying attention to a crucial paper of The disease was a commonplace in clinical practice Blocq and Marinesco in which hemiplegic Parkinson- between the Great Wars. My undergraduate textbook ism resulted from a tuberculoma of the contralateral (Davidson, 3rd edn, 1956) mentions tinct belladonna, J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.52.Suppl.6 on 1 June 1989. Downloaded from

10 Pearce tinct stramonium and hyoscine hydrobromide and 2 McMenemey WH. James Parkinson (1755-1824). A "newer synthetic preparations Artane, Lysivane and biographical essay. In: Critchley M, ed. James Parkin- Pipanol." Great strides have taken place since this son. London: MacMillan, 1955. time, and since they are well known, I shall mention 3 Gardner-Thorpe C. James Parkinson. Exeter: A Wheaton in outline. & Co, 1987. them only 4 Tyler KL. A History of Parkinson's Disease. In: WC Irving Cooper's serendipitous damage to the Woller, ed. Handbook of Parkinson's Disease. New anterior choroidal artery whilst ligating an aneurysm York, Basel: Marcel Dekker Inc. 1987:1-34. in a Parkinsonian subject spectacularly controlled 5 Cleevely RJ, Cooper J. James Parkinson (1755-1824). A contralateral signs; this led to deliberate surgical significant English 18th Century Doctor and Fossil lesions first in the globus pallidus, then in ventrolateral Collector. Leiden. Tertiary Research. 1987;8(4): nucleus of thalamus, effected by the ingenious 133-45. stereotactic devices of the 1950s with which I failed to 6 Cooke R. History of the method of cure of the various cope as a neurosurgical house surgeon. Chemo- species of palsy, p.207, vol 2, part 1, In: A treatise of and other destructive Nervous Diseases. London: Longman, 1821. pallidectomy employed alcohol 7 Hall Marshall. On the Diseases and Derangements of the agents; later thernal and cryogenic physical methods Nervous System. London: Balliere, 1841. were used. Unilateral tremor and rigidity were often 8 Todd RB. Certain Diseases of the Brain and other abolished with striking benefit, but the central features Affections of the Nervous System. Philadelphia, affecting speech, gait, posture and balance were Lindsay & Blakiston, 1855. unaffected, and sometimes worsened by these 9 Romberg M. Lehrbuch der Nervenkrankheriten des procedures. Menschen. Berlin: A Duncker, 1840-6. The levodopa story, starting in the laboratories of 10 Trousseau A. Lecture XV: Senile trembling and Paralysis Ehringer and Hornykiewicz in 1960 is too well known Agitans. In: Lectures on Clinical Medicine delivered at The late Cotzias the Hotel-Dieu, Paris. trans: PV Bazire. London: New to merit repetition here. George 1868. Sydenham Society, Protected by copyright. showed that large doses oforal d-l-dopa were clinically 1 1 Charcot JM. On Paralysis Agitans (lecture V). In: highly effective, but I well remember the vomiting, Lectures on the Diseases of the Nervous System. pp. fainting and delay of two to three months before a 129-156. trans: G Sigerson. London: New Sydenham stable response was obtained. The pure 1-isomer Society, 1877. lessened toxicity and the addition of a dopa-decar- 12 Brissaud E. Vingt-Deuxieme Lecon: Pathogenie et symp- boxylase inhibitor was an important step forward. toms de la maladie de Parkinson. pp. 488-501. In: Bob Schwab's discovery ofamantadine and the advent Merge H, ed. LeVons sur les maladies nerveuses of dopamine agonists followed. But the most signi- (Salpetriere 1893-1894). Paris: G Masson, 1895. recent advance has been the model 13 Gowers WR. A Manual of Diseases of the Nervous ficant experimental System. 2nd ed. pp. 589-607. London: Churchill, 1888. afforded by the (I-methyl-4-phenyl-1,2,3,6-tetra- 14 Tretiakoff C. Contributions a l'etude de L'anatomie hydropyridine) MPTP contaminants. This was dis- pathologique du locus niger de soemmering avec quelques covered in 1976 when a 23 year old American addict deductions relatives a lapathogenie des troubles de tonus took a shortcut to synthesising his own pethidine musculaire et de la maladie de Parkinson. Paris: Thesis, analogue. One byproduct was MPTP'6 causing severe 1919. and pure Parkinsonism on the third day, which 15 Foix C, Nicolesco J. Anatomie cerebrale: les Noyaux Gris responded to levodopa till his suicide 18 months later. Centraux et la Region Mesencephalo-soux-optique. The current excitement concerning foetal nigral trans- Paris: Masson, 1925. http://jnnp.bmj.com/ plants awaits the validation of time and future 16 Langston WJ. Mechanism of MPTP toxicity: more research. answers, more questions. Trends in Pharmacological David Marsden has in the last 20 years been the pre- Sciences 1985;6:375-8. eminent figure in Parkinson's disease research. Pre- eminent, not only in Great Britain, but throughout Europe and North America. His enormous personal industry, organising capacity and eloquence are now

Additional bibliography on September 28, 2021 by guest. near legendary. Of the recent advances, none has Rowntree LG. James Parkinson. Bulletin of the Johns escaped the golden touch ofthe Marsden research unit Hopkins Hospital 1912;23:33-45. at Kings, and more recently at Queen Square. We hope Morris AD. James Parkinson. Born April 11, 1755. Lancet these recent investigative problems and ultimately 1955;269:761-3. their solution will be the objects of future histories. Knight DM. Chemistry in Palaeontology: The work ofJames Parkinson (1755-1824). Ambyx 1974;21:78-85. References Eyles JM. James Parkinson (1755-1824). Nature 1955; 176:580-1. 1 Parkinson J. An Essay on the Shaking Palsy. London: Jefferson M. James Parkinson (1755-1824). Br Med J 1973; Sherwood, Neely, and Jones 1817. 2:601-4.