James Parkinson and His Disease

James Parkinson was born in 1755 in Shoreditch, close to the City of London and like his father practised medicine there as an Apothecary and Surgeon. His earlier years in practice were disturbed by a rebellious spirit, roused by the poverty and injustices he saw around him. Inevitably he was drawn into politics and joined the provocative London Corresponding Society. He wrote a number of highly critical pamphlets under the pseudonym of “Old Hubert”. His criticisms of government and administration were at times so bitter and fearless that eventually they led to his being subpoened and examined by the Privy Council. During the course of these examinations he had to answer to the Lord Chancellor, the Prime Minister, Mr. William Pitt and others in high office. Fortunately his explanations impressed his interrogators by their honesty and sincerity and he escaped imprisonment. By the time he was 40, with the increasing demands of a busy practice and a young family, he seemed to turn all his efforts to his own work and writings. His interests were broad. His first book was on “The Organic Remains of a Former World”. Later he wrote on medical education, the preservation of health, and a brilliant criticism “Observations on Doctor Hugh Smith’s Philosophy of Physics”. Nevertheless it was not for another 22 years that he wrote his classic essay on “The Shaking Palsy” which was published in 1817 (Critchley 1955). Copyright Royal Medical Society. All rights reserved. The copyright is retained by the author and the Royal Medical Society, except where explicitly otherwise stated. Scans have been produced by the Digital Imaging Unit at Edinburgh University Library. Res Medica is supported by the University of Edinburgh’s Journal Hosting Service: http://journals.ed.ac.uk ISSN: 2051-7580 (Online) ISSN: 0482-3206 (Print) Res Medica is published by the Royal Medical Society, 5/5 Bristo Square, Edinburgh, EH8 9AL Res Medica, April 1967, 5(4): 8-12 doi: 10.2218/resmedica.v5i4.494 JAMES PARKINSON AND HIS DISEASE John Gillingham. M.B.. B.S.. F.R.C.S.. F.R.O.S.E., F.R.C.P.E. Professor of Surgical Neurology, Royal Infirmary o f Edinburgh, and The Western General Hospital Jam es Parkinson was born in 1755 in Shoreditch, close to the C ity of London and like his father practised m edicine there as an A pothecary and Surgeon. His earlier years in practice were disturbed by a rebellious spirit, roused by the poverty and injustices he saw around him. Inevitably he was drawn into politics and joined the provocative London Corresponding Society. H e wrote a number of highly critical pam phlets under the pseudonym of “ Old H ubert” . H is criticisms of governm ent and administration were at times so bitter and fearless that eventually they led to his being subpoened and examined by the Privy Council. During the course of these examinations he had to answer to the Lord Chancellor, the Prim e M inister, M r. W illiam P itt and others in high office. Fortunately his explanations impressed his interrogators by their honesty and sincerity and he escaped im prisonm ent. B y the time he was 40, with the increasing demands of a busy practice and a young family, he seemed to turn all his efforts to his own work and writings. His interests were broad. His first book was on “ T h e Organic Rem ains of a Form er W o rld ” . Later he wrote on m edical education, the preservation of health, and a brilliant criticism “ Observations on Doctor Hugh Sm ith ’s Philosophy of Physics” . Nevertheless it was not for another 22 years that he wrote his classic essay on “ T h e Shaking Palsy” which was published in 18 17 (Critchley 1955). , It is not surprising that this energetic com passionate man with a keen sense of observation and flair for detailed recording, should turn his attention to that hitherto neglected group of patients suffering from the disease later to be called by his followers “ Parkinsonism ” . O n Pages 15 and 16 of his monograph, (Parkinson 1 8 17) he describes how the tremor of an aged patient disappeared follow ing the onset of a “ stroke” — a capsular hemiplegia. In about a fortnight the lim bs had regained most of their m ovem ent. H e says — “ D uring the tim e of their having remained in this state, neither the arm nor the leg of the paralytic side was in the least affected with the tremulous agitation; but as their paralysed state was re­ moved, the shaking returned.” T h e first surgical attem pts to treat Parkin­ sonian tremor were in the early 19 30 ’s by de­ structive lesions at various levels of the cortical spinal pathways — the m otor cortex, the internal capsule, the cerebral peduncle and later the posterior lateral quadrant of the upper cervical spinal cord. However, had this original observation of Jam es Parkinson been carefully considered, a more successful surgical approach to this problem m ight have been achieved earlier. H e clearly stated “ As their paralysed state was removed, the shaking returned” . These first operations often led to considerable disability from paralysis and neither the results nor their physiological basis encouraged pursuit of the problem in this way. Nevertheless it was his experience with these procedures that led Russell Meyers (1942) to put forward his hypothesis that trem or and rigidity might be relieved by interruption of


Professor of Surgical Neurology, Royal Infirmary of Edinburgh, and The Western General Hospital
Jam es Parkinson was born in 17 5 5 in Shoreditch, close to th e C ity of Lon don and like his father practised m edicine there as an A po th ecary and Surgeon.H is earlier years in practice were disturbed by a rebellious spirit, roused by the poverty and injustices he saw around him .In evitably he was drawn into politics and joined the provocative L on don Corresponding Society.H e wrote a num ber o f highly critical pam phlets under the pseudonym of " O ld H u b ert" .H is criticism s of governm ent and adm inistration were at times so bitter and fearless that eventually they led to his being subpoened and exam ined by the Privy C ou ncil.D uring th e course of these exam inations he had to answer to the L ord C hancellor, the Prim e M inister, M r.W illiam P itt and others in high office.Fortu nately his explanations im pressed his interrogators by their honesty and sincerity and he escaped im prisonm ent.B y the tim e he was 40, with the increasing dem ands of a busy practice and a young fam ily, he seem ed to turn all his efforts to his own work and writings.H is interests were broad.H is first book was on " T h e O rganic R em ains o f a Form er W o rld " .L ater he wrote on m edical education, the preservation o f health, and a brilliant criticism " O bservations on D octor H ugh S m ith 's Philosoph y o f Physics" .N evertheless it was not for another 22 years that he w rote his classic essay on " T h e Shaking P alsy" w hich was published in 1 8 1 7 (C ritch ley 1955).

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It is not surprising that this energetic compassionate m an w ith a keen sense of observation and flair for detailed recording, should turn his attention to that hitherto neglected group of patients suffering from the disease later to be called by his followers " Parkinsonism " .
O n Pages 1 5 and 16 of his m onograph, (Parkinson 1 8 17) he describes how th e trem or of an aged patient disappeared follow in g the onset of a " stroke" -a capsular hem iplegia.In abou t a fortnight the lim bs had regained m ost o f their m ovem ent.H e says -" D u rin g the tim e of their having rem ained in this state, neither the arm nor the leg of the paralytic side was in the least affected w ith the trem ulous agitation; but as their paralysed state was re m oved, the shaking returned." T h e first surgical attem pts to treat Parkin sonian trem or were in the early 19 3 0 's by de structive lesions at various levels o f the cortical spinal pathways -the m otor cortex, the internal capsule, the cerebral peduncle and later the posterior lateral quadrant o f the upper cervical spinal cord.H ow ever, had this original observation of Jam es Parkinson been carefully considered, a m ore successful surgical approach to this problem m ight have been achieved earlier.H e clearly stated " A s their paralysed state was rem oved, the shaking returned" .T h ese first operations often led to considerable disability from paralysis and neither the results nor their physiological basis encouraged pursuit o f the problem in this way.
N evertheless it was his experience with these procedures that led Russell M eyers (194 2) to put forward his hypothesis that trem or and rigidity m ight be relieved by interruption of the pallido-fugal fibres and w ithout any involve m ent of the cortico-spinal tract.T h is marked the great step forward but unfortunately his operation, designed to interrupt these fibres through the lateral wall of the third ventricle, was ill-conceived.T h e results although encour aging in some respects, were disappointing be cause of injury to diencephalic structures adjacent to the third ventricle with stupor and a high m ortality and the operation fell into disrepute.Because of this and preoccupation with the m edical problem s of the Second W orld W ar, nothing m ore was done.Later Fenelon (1949) in Paris took up Russell M eyer's original observation and devised a new operative approach using a sub-frontal route.H e followed the optic tract backwards beneath the frontal lobe to the point where the tract begins to m erge with brain.Using this landm ark and by directing his electrode upwards and slightly laterally for 1 cm., lie was able to create an electro-coagulation lesion of the pallido-fugal fibres -the ansa lenticularis and adjacent globus pallidus.T h e results of this procedure were encouraging.T rem or and rigidity were often reduced and occasionally abolished, yet w ithout any untoward side effects.In particular there was no evidence of stupor, paralysis, sensory deficit or akinesis.T h is work was soon taken up by G u iot who published a series of successful results in 19 5 3 and it was G u io t who dem onstrated this exciting new operation to me in Paris in 1954 (G uiot 19 53).
Early in 19 55 our first patient was treated.A m iner of 50 with post encephalitic Parkinsonism, he had been unable to work for 10 years because of severe trem or and rigidity of left lim bs.A t least half of each week was spent in bed because of an exacerbation of akinesis, sweating and tremor.O ver the years he had lost 2 stones in w eight and had becom e gravely disabled.Follow in g operation which of necessity had to be perform ed under local anaesthesia to observe the effect and effective ness of the lesion, he rapidly im proved.H e lost his tremor and rigidity com pletely and there was no paresis.H is sense of well-being and weight were quickly restored, his kyphosis lessened and he returned to surface work at the pit in two m onths.H e has remained well since although some m ild rigidity in the left lim bs has returned in the last few years.H ow ever for tw elve years h e has been w ithout trem or and a A further patient was treated in the same way shortly afterwards and a sim ilar result obtained which has been m aintained after tw elve years.
In the m eantim e we were becom ing increas ingly interested in the developm ent o f the first stereotaxic human instrum ent devised and used by Spiegel and W y c is o f Philadelphia in 1947 for the treatm ent of psychiatric disorder (Spiegel et al. 1947).T h is was designed very m uch on the pattern of that devised and used by H orsely and C larke w ith such precision for anim al work in 1908 (H orsley and C larke 1908).
T h e open operation of Fenelon, although very' successful, was difficult and hazardous.If a discrete lesion could be sited accurately at a predeterm ined target through a burr hole b y m eans of a suitable guiding apparatus fixed to the head, then m uch w ould have been achieved.T h is was th e great contribution of Spiegel and W y c is for the field of stereotaxic surgery is now one of the m ajor branches of surgical neurology not only in Parkinsonism and the dyskinesias, but also in epilepsy, intractable pain and som e of the psychiatric disorders.
G u io t was soon to follow with a m uch sim pler yet very precise apparatus, a modified version of which has been used in my own departm ent for m any years (Figs.I and II).I rem em ber the early discussions w e had in Paris with great pleasure and how ultim ately we decided that the posterior stereotaxic approach using an occipital burr hole, even though it m eant a longer track, would probably be the best.As subsequent events have shown it was a fortuitous decision not only because th e best results were obtained in this way, but also be cause it led to a greater understanding o f the basic problem s of Parkinsonism and the effec tiveness of the different lesions used.
T h ese early procedures were som etim es inaccurate and we cam e to realise th e stereotaxic method was fallible.T h e problem was not that of im precise instrum entation or lesion m aking bu t of the anatom ical variation of one brain to another and even of one hem isphere to another.W e had to rely upon radiologically determ ined landm arks such as th e septum pellucidum and the third ventricle (the m id sagittal plane) and the anterior and posterior com m issures shown by m eans o f a radio opaque dye or air.T h ese landm arks gave only a reasonable bearing for our target and we began increasingly to look for physiological m ethods such as electric stim ulation and reversible lesions to help us.B y fractionating the electro-coagulation lesion using low heat initially it was possible to show the dam ping down o f trem or or the relief of rigidity and of equal im portance, side-effects such as speech, m otor or sensory disturbances, before the perm anent lesion was created; this m ethod has proved to be m ore reliable in our hands than stim ulation.G rad ually as a result of the m arking of all lesions at operation by detaching the tiny stainless steel tip of the electrode, taking a skull X ray afterwards, then charting them on stereotaxic atlases, the sites o f the m ost effective lesions for the relief of trem or and rigidity were soon determ ined.T h is was further helped by m aking as small a lesion as would be com patible with m aintained improvem ent.W e also began to m ap out fo r the first tim e the various tract systems such as the corticospinal fibres, the parieto-sensory projection w ithin the posterior lim b of the internal capsule and the tract systems concerned with speech.T h e results of this work using scattergram techniques have been published elsewhere (G illingh am 1962).
In 19 55, when m ost o f us were working on the globus pallidus and the pallido-fugal fibres, H assler suggested that the m ost effective lesion for the relief o f trem or should lie in the ventro lateral nucleus o f the thalam us (Hassler 1955).T h is was subsequently proved by R iechert, C ooper, ourselves and m any others as successful operations on the thalam us were reported (R iech ert 19 5 5 , C o op er 1959, G illingham 1 960).N evertheless w ith follow up the lesion o f the globus pallidus rem ained the m ost effective for th e relief of rigidity.B y elevating our posterior track to th e globus pallidus, we found that a double ipsilateral lesion 1 5 mm from the midsagittal plane could be m ade quite successfully with only one insertion of the electrode.T h e posterior lesion for trem or was m ade first in the v e n tro -lateral nucleus posterior to the capsule, and th e second for rigidity in the globus p allidus anterior to the capsule.T h is technique even after som e 700 operations have been perform ed for Parkinsonism has rem ained the m ost effective.
T h ere still seemed to be room for error and our restless search for further accuracy was eventually rewarded.F o r som e years the neurophysiologists had relied on electrical recording rather than stim ulation for locating the elcctrode tip and this was beautifully dem onstrated to m e by Professor D avid W h itteridge during explorations o f the external geniculate ganglion of the cat.T h e borders of grey and white m atter were clearly defined with a degree o f accuracy which so far we had not known.T h e subsequent developm ent of the technique and its value in stereotaxic surgery has been published elsewhere (G aze et al. 1964) and follow ed very closely the work of Albefessard (1962).
Since then, depth microelectrode recording has becom e alm ost standard practice as further inform ation has accum ulated from greater experience and th e use o f smaller electrodes (1 to10 μ tips).T h e borders o f the thalam us and its sensory relay nucleus, of the internal capsule and the globus pallidus, are identified with confidence and target siting is no longer a problem .
D etailed study of electrical activity from the basal ganglia is continuing for there is m uch to learn about sensory m echanism s and the basic pathology o f Parkinsonism .O f particular inter est has been the recognition o f spontaneous rhythm ical activity arising in the thalam us synchronous w ith trem or yet not evoked by any sensory stim ulus.It is not always found and as yet its relation to trem or has not been fully determ ined.T h e m ore sophisticated tech niques o f frequency analysis o f the various patterns o f cell activity m ay give som e of the answers.
Perhaps of equal im portance to the under standing o f the basic pathology of Parkinson ism is the biochem ical changes which occur.R ecen tly B arbeau (1962) and others have shown a disturbance o f dopam ine m etabolism and we have followed this work b y a study of this substance in the cerebro-spinal flu id o f the lateral and third ventricles in patients with Parkinsonism and in controls.T h e team responsible for this study, working in m y departm ent and that of Professor Perry, w ill be reporting about it shortly.F u tu re research in the field o f the D yskinesias w ould seem to depend very' m uch upon the pursuit of the abnorm al electrochem ical changes w hich are present.
T h e surgeon, stum bling as he does, often in an empirical way, responds to each challenge thoughtfully and with the im provem ent of the patient as his prim ary concern.T h e rewards of such an exercise in understanding the problem s of Parkinsonism have been considerable, and in particular perhaps in the ou tlining of a " pathw ay" which lies w ithin the diencephalon, interruption o f which at any point relieves trem or and rigidity and to a greater or lesser extent som e o f the other associated sym ptom s as w ell, such as oculogyric crises and the compulsive thinking th at som etim es go with them .T h is " pathw ay" w hich has been defined by a w hole series of differently sited yet successful lesions b y surgeons across th e world, extends from the inferior aspect o f the globus pallidus anteriorly, upwards and posteriorly through the globus pallidus, across the posterior lim b of the internal capsule at and above the intercom m issural plane into th e ventro-lateral nucleus o f the thalam us.T h e re it turns downwards through the zona incerta ju st lateral to the red nucleus to th e substantia nigra.Its distance from the m id-line and its w idth varies from p oin t to point and there w ould seem to b e " bottlenecks" w ithin it.A lesion placed strategically w ithin it brings im m ediate relief o f sym ptom s and signs but if it is poorly placed the results are inadequate and side effects follow .Its connections w ith the cortex above and spinal cord below have not yet been defined but in the diencephalon we w ould seem to have shown " the p athw ay" to be the ansa and fasciculus lenticularis (G illingham 1966).
M u ch of w hat I have said has been about research and th e solution o f our problem s of accurate placem ent of effective lesions for the relief of this relentlessly progressive disease, but we m ust now look at the results and the indic ations and contraindications o f operation.
N o t all patients are benefitted by stereotaxic surgery.T h ose who arc deteriorating rapidly w ith bilateral trem or and rigidity and who show widespread effects of their disease, notably intellectual im pairm ent, gross reduction o f voice volum e and disturbances o f m icturition, cannot be im proved and are often m ade worse.Fortu nately the m ajority are not so severely affected and in these patients operation will always effect som e increase in independence, and in a reasonably high proportion great im provem ent, particularly in those with strictly unilateral rigidity and trem or.B ilateral oper ations, if staged w ith at least a m onth between them , are being carried out increasingly as precision has increased.(G illingh am 1904).
Post-o perative drugs are usually necessary although the dosage is often progressively reduced as the m onths and years pass.It is the accum ulating evidence, w ith prolonged followup, now of tw elve years in som e patients, of the greatly slowed or halted disease process which is perhaps th e m ost exciting observation o f all and w hich now poses the im portant question " H ow has it happened?" .C.S.. F.R.O.S.E., F.R.C.P.E.

Figure I
Figure I Figure II