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A P E D I G R E E O F P A R A L Y S I S AGITANS

BY JULIA BELL AND PROFESSOR A. J. CLARK, M.D.

(1) Introductory. This disease was first described by Parkinson in 1817 in his famous treatise entitled A n Essay on the Shaking Palsy; previously to this date the two most prominent symptoms of the disease had been noted and commented on by a number of writers, but their association as a definite clinical entity had not been recognised until Parkinson drew attention to it: he defines the disease as being characterised by “ Involuntary tremulous motion, with lessened muscular power in parts not in action and even when supported; with a propensity to bend the trunk forwards and to pass from a walking to a running pace: the senses and intellect being uninjured.” “Paralysis agitans” was the name given to the disease by Parkinson because of the agitation produced by the peculiar species of tremor (Bibl. No. 5).

Much of historic interest occurs in this essay; we read of Galen’s differentiation between types of tremor, of how Sylvius divides tremors into those produced by attempts a t voluntary motion and those which occur whilst the body is at rest; also we read of the interesting observation of Gaubius describing the gait now well known as a characteristic of Paralysis agitans translated by Parkinson thus: “Cases occur in which the muscles duly excited into action by the impulse of the will, do then, with an unbidden agility and with an impetus not to be repressed, accelerate their motion and run before the unwilling mind. It is a frequent fault of the muscles belonging to speech, nor yet of these alone: I have seen one who was able to run but not to walk” (Bibl. No. 2). Parkinson’s classical description of the onset and course of the disease is as follows:

So slight and nearly imperceptible are the first inroads of this malady and so extremely slow 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. These symptoms gradually increase in the part first affected, and at an uncertain period, but seldom in less than twelve months or more, the morbid influence is felt in some other part. Thus assuming one of the hands and arms to be first attacked the other a t this period becomes similarly affected. After a few more months the patient is found to be less strict than usual in preserving an upright posture: this being most observable whilst walking, but sometimes whilst sitting or standing. Some time 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 : and in a few months this limb becomes agitated by similar trembling and suffers a similar loss of power.

Hitherto the patient will have experienced but little inconvenience, and befriended by the strong influence of habitual endurance, would perhaps seldom think of his being the subject of disease, except when reminded of it by the un- steadiness of his hand, whilst writing or employing himself in any nicer kind of manipulation. But as the disease proceeds, similar employments are accomplished with considerable difficulty, the hand failing to answer with exactness to the dictatea of the will. Walking becomes a task which cannot be performed without considerable attention. The legs are not raised to that height or with that promptitude which the will directs, so that the utmost care is necessary to prevent frequent falls.

At this period the patient experiences much inconvenience, which unhappily is found daily to increase. The sub- mission of the limbs to the directions of the will can hardly ever be obtained in the performance of the most ordinary offices of life. The fingers cannot be disposed of in the proposed directions, and applied with certainty to any proposed point. As time and the disease proceed, difficulties increase, writing can now be hardly at all accomplished; and reading, from the tremulous motion, is accomplished with some difficulty. Whilst at meals the fork not being duly directed frequently fails to raise the morsel from the plate which when seized is with much difficulty conveyed to the mouth. At this period the patient seldom experiences a suspension of the agitation of his limbs. Commencing for instance in one arm, the wearisome agitation is borne until beyond sufferance, when by suddenly changing the posture it is for a time stopped in that limb, to commence, generally in less than a minute, in one of the legs or in the arm of the other side. Harassed by this tormenting round, the patient has recourse to walking, a mode of exercise to which the sufferers from this malady are in general partial, owing to their attention being thereby somewhat diverted from their unpleasant feelings, by the care and exertion required to ensure its safe performance.

456 A P E D I G R E E O F PARALYSIS AGITANS But as the maladv Droceeds. even this temDorarv mitigation of suffering from the agitation of the limbs is denied. The

U I

propensity to lean forward becomes invincible, and the patient is thereby forced to step on the toes and forepart of the feet, whilst the upper part of the body is thrown so far forward as to render it difficult to avoid falling on the face. In some cases, when this state of the malady is attained, the patient can no longer exercise himself by walking in his usual manner but is thrown on the toes and forepart of the feet, being at the same time irresistibly impelled to take much quicker and shorter steps, and thereby to adopt unwillingly a running pace. In some cases .it is found necessary entirely to substitute running for walking, since otherwise the patient, on pro- ceeding only a very few paces, would inevitably fall.

In this stage, the sleep becomes much disturbed. The tremulous motions of the limbs occur during sleep and augment until they awaken the patient, and frequently with much agitation and alarm. The power of conveying the food to the mouth is a t length so much impeded that he is obliged to con- sent to be fed by others. The bowels, which had been all along torpid, now, in most cases, demand stimulating medicines of very considerable power. . . .As the disease proceeds towards its last stage the trunk is almost permanently bowed, the mus- cular power is more decidedly diminished, and the tremulous agitation becomes violent. The patient walks now with great difficulty and unable any longer to support himself with his stick he dares not venture on this exercise unless assisted by an attendant who, walking backwards before him, prevents his falling forwards by the pressure of his hands against the fore part of his shoulders.. . .

As the debility increases and the influence of the will over the muscles fades away the tremulous agitation becomes more vehement. It now seldom leaves him for a moment but even when exhausted nature seizes a small portion of sleep the motion becomes so violent as not only to shake the bed- hangings but even the floor and sashes of the room. The chin is now almost immoveably bent down upon the sternum. . .a t the last, constant sleepiness, with slight delirium and other marks of extreme exhaus- tion, announce the wished-for release.

A

B Fig. 1. Showing characteristic gait and posture in Paralysis agitans. A, flexed

type, B, extended type. (After Richer and Meige, Nouvelle Iconogruphie de la Salp&trit?re, T. I, pp. 214-15, Park 1888.)

This vivid and painful picture described from an individual example of the disease portrays undoubtedly the worst that may happen in a severe case of Paralysis agitans, but no less certainly a, large number of cases never experience so terrible a state of disability; cases occur accompanied by no tremor and very rarely cases occur in which no rigidity is present; again, in some cases the typical localised tremor and rigidity develop but the progress of the disability is so slow that little change is noted after a period of years and the patient retains his independence until death occurs from some intercurrent disease. Parkinson does not emphasise in his account what has become one of the best known features of the disease, which indeed frequently suggests the diagnosis to the physician as the patient appears before him, namely, the lack of facial expression following from the rigidity of the facial muscles and of the neck, and known as the Parkinsonian mask.

Since the day of Parkinson a number of post-mortem examinations of these cases have been made and it has become apparent from these and from a more refined clinical analysis that the

JULIA BELL A N D A. J. CLARK 457

syndrome known as Paralysis agitans probably constitutes a group of diseases exhibiting certain common clinical features but having very different underlying pathological conditions. Ramsay Hunt in his most valuable contribution to the subject (Bibl. No. 29) distinguishes between the presenile and senile, the symptomatic, and a rare juvenile form of the disease: he demonstrates that the characteristic features of Paralysis agitans may be produced by a progressive atrophy of the motor neurons of the globus pallidus mechanism, and he believes this to be the lesion at the basis of the juvenile form of the disease which, he states, is often familial.

We have met with no definition as to the age of onset which may be taken to characterise the case as being “juvenile” in type. The relative smoothness of the frequency distributions taken from Hart, Patrick and Levy, and from Busch, shown below, does not lead to the suggestion that

Author ... Age of onset

Under 30 30-40 4&50 5 M O 60-70

Over 70

Totals

Hart’s Series

$ ?

2 0 10 9 38 16 49 39 30 12 5 4

134 80

Busch 1 ... 1 Patrick and Levy

d + Q 1 Age of onset I 6 +? 1 6

15 24 16 2

20-30 3 1 4 0

51-60 41-50

61-70 7 1-80

5 20 41 49 27 4

63 I I 146

the age of onset is of any significance from the etiological point of view, nevertheless it is an undoubted fact that the average age of onset in hereditary cases only is considerably younger than the average age given by these series and the frequency distribution for hereditary cases does, judging from the literature, differ markedly from those here given; for example we find among histories of fifty-four hereditary cases in which the age of onset is given, no fewer than thirteen individuals who developed the disease before the age of 20 years.

It may be deduced from the work of those who have considered the question that probably heredity as an etiological factor is responsible for the disease in 10 to 15 yo of cases and possibly a neuropathic stock exhibiting other forms of degeneration of the nervous system may be found to be associated with the occurrence of Paralysis agitans in some 25 to 30 Yo of cases; Ramsay Hunt writes that “one very striking feature of the juvenile cases is the unusual frequency of familial incidence”; hence it would appear to be a fact that hereditary cases of Paralysis agitans do tend to occur relatively early in life, but whether such cases differ in any essential manner from those whose onset is attributed to trauma, emotional shock, overwork, infection, arterio- sclerosis, etc. we have at present no means of judging.

(2) New Pedigree. The present pedigree, Fig. 1 on p. 458, investigated some years ago by one *of the authors (A. J. Clark), shows Paralysis agitans in two or three males and in three or four females of two generations. I, 1 died aged 85 and was said to have been perfectly healthy with no tremor. 11,l and 2 died aged 75 and 60 respectively were said to have been healthy and to have had no tremor. 11, 1 and 2 had two sons and three daughters of whom 111, 1, a daughter, died aged 40; tremor and weakness of muscles developed at the age of 28 years and during the last part of her life she was bedridden. 111, 2, a son, was seen aged 70 when he kept an ironmonger’s shop; from his history difficulty in walking commenced at the age of 14, tremor commenced at the age of 55; he was then (1910) a healthy old man with Parkinsonian mask, rigid features, forward stoop, marked pill-rolling tremor in both hands but most marked in the right hand, and weakness of hands; his gait was spastic and the patient could only walk a short distance and then became tired; he got stiffness and pain in the back and neck if he lay long in one position,

EUGENICS I, 111 & IV 59

458

I

A PEDIGREE OF PARALYSIS AGITANS

PARALVSIS AGITANS

1 CJuk

V No consanguinity recorded

e No information i Died in infancy

7 I

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II

111

T

I I I' A

-+- Ill 46 A 3946

_____* 0 Chorea and epilepsy

No consmguinity recorded e Hyslem-epllepg

*story for Nationai Eugenics.

J U L I A BELL A N D A. J. CLARK 459 111, 2 was married and had eight children of whom one daughter suffered from Paralysis agitans.

111, 4 died aged 73; her brother 111, 2 said that she was healthy until her death and never developed a tremor, but her son and daughter said that during the last few years of her life she had tremor in her arms, an immobile face and shuffling gait; she was married and had five children of whom two had Paralysis agitans; one of her eighteen grandchildren was showing signs of the disease. 111, 6 and 8 were normal and had normal children.

Of the children of 111, 2, IV, 1 died in infancy; IV, 2 was normal, aged 47; IV, 3 and 4, aged 45 and 43 respectively, were also normal; IV, 5, aged 40, found difficulty in walking at the age of 38; she tended to lean towards her right side and this became worse after walking some distance; she was seen by Dr Miller of Cambridge who noted her mask-like expression and monotonous voice; electrical reactions were normal. In 1910 the patient was seen by Dr Batten who found her suffering from weakness, fixed expression, loss of control over her emotions, pain after writing and slight rigidity of the limbs; she had an extensor response of the left plantar reflex; no tremor is described and the case was then diagnosed as incipient Paralysis agitans.

We hear from inquiries made by Dr Moore of Great Chesterford that IV, 5 died about the age of 47; she was unmarried and apparently no further cases of the disease occurred in members of her sibship.

IV, 6, twin brother of IV, 5, aged 40, was in West Africa; he was said to be quite healthy and did not complain of tremor or weakness. IV, 7, aged 35, was believed to be normal. IV, 8 died in infancy.

Of the children of 111,4, IV, 9, aged 63, was healthy, she was married and had eight children of whom the eldest was aged 43; none of them showed signs of tremor. IV, 11, aged 58, was an agricultural labourer; tremor of his right arm commenced at the age of 40 and during the last few years the right arm had become weak and showed some wasting of the muscles; A. J. Clark noted immobility of features, forward stoop, coarse tremor of both hands most marked on the right side and ceasing on voluntary effort; gait was only slightly affected, the patient was able to walk a fair distance and work in the fields. Dr Moore kindly called in 1925 to see the patient, now aged 73, and reports of his present condition (13. XII. 25) as follows-the whole body shakes which prevents sleep at night; he can only walk about 20 yards at a time owing to shortness of breath; the right hand is tightly clenched but can be opened with the left and made to carry things; uses a feeding cup and can feed himself with a spoon; the patient falls about a good deal owing to lack of balance; he gets headache at the occipital region.

IV, 11 was married and had seven children; one daughter died of carcinoma of the uterus, another daughter died of heart failure and the other five children are normal.

IV, 14 commenced to have tremor at the age of 27; when seen by A. J. Clark at the age of 50 (1910) this patient presented a typical case of advanced Paralysis agitans; she had mask-like features and violent tremor of both arms which was partially controlled during voluntary effort; she could scarcely walk and propulsion was readily induced. We hear through Dr Moore that this patient is still alive (1925) and now aged 64; her mental condition is very poor.

IV, 14 was married and had three children of whom A. J. Clark saw V, 5 and 6; he found that the latter, aged 18, was healthy, the former, aged 26, was a healthy young man of apparently very good physique but he complained that his arms became easily tired and his family said that his hands developed a tremor when he became excited. Dr Moore reports that V, 5 died of some other complaint at the age of 29. V, 6 and 7 have apparently remained normal.

59-2

460 A PEDIGREE OF PARALYSIS AGITANS A. J. Clark personally examined 111,2, IV, 3 , l l and 14, and V, 5 and 6; infor$lation as to other

members of the family was obtained chiefly from 111, 2 and IV, 11, 12 and 14. The details of the case of IV, 5 were kindly supplied to the authors by Dr Miller of Cambridge, and we are indebted to Dr Yorke Moore of Great Chesterford for the account of the present condition of IV, 11.

ACCOUNTS OF PREVIOUSLY PUBLISHED PEDIGREES. Fig. 2. Paralysis agitans in two brothers and in their mother; the mother became affected at about the age of 50;

a sister of the affected brothers suffered from severe migraine and had a generalised tremor of her limbs following the slightest psychical excitement ; a niece also was epileptic : we are not told whether this niece was daughter of one of the affected brothers or of their sister. Berger, 1882 (Bibl. No. 8).

Fig. 3. Paralysis agitans or tremor affecting seven members of a sibship of nine; three of the affected members had each an affected child. The precise nature of this case is a little uncertain. I, 1 died aged 84; a t 50 she had a tremor affecting her upper limbs, moderate a t first, later much more severe especially after emotional disturbance; other parts of the body remained free from the affection. I, 2 died aged 78; a t 60 he had a tremor of the upper limbs which was emphasised by psychical tension. I, 4 died aged 84; a t 40 tremor affected his upper limbs, after some time the lower limbs and trunk also became affected and he reached a severe state of disability. I, 5 died a t 84; a t the age of 38 she suffered from some form of mania; at 50 years she had tremor of her arms to which it remained limited but she suffered from considerable disability. I, 7 died at 74; she had tremor a t 35 which started in her upper limbs and later spread to the lower limbs, trunk and head; she is said to have presented a true form of Paralysis agitans. I, 9 died at 60; tremor commenced at 50 and affected only hands and forearm; he died from some other malady. I, 10 died a t 70; a t one period of her life she suffered from a form of mania; a t the age of 50 she had tremor of her upper limbs which spread to other parts and was associated with a general loss of power; this was believed to be a definite example of Paralysis agitans. 11, 1 commenced to suffer at 40 from tremor and was believed to have had Paralysis agitans. 11, 3 died aged 40 from some acute malady; she had suffered from tremor of her upper limbs for five years. 11, 5 was believed to have suffered from a form of essential tremor. Borgherini, 1889 (Bibl. No. 11).

Fig. 4. Paralysis agitans in a brother and sister. II,2, aged 60, had a severe affection of the right arm only; her brother, aged 66, became affected at the age of 62; parents and one brother were healthy Berger, 1882 (Bibl. No. 8).

Fig. 5. Paralysis agitans in a brother and sister; two other sisters possibly affected. 11, 1 had to give up his work as a mill spinner a t the age of 35 owing to weakness in his legs and a tendency to fall upon his face; these were the earliest symptoms to attract his attention, a year later he noticed that his legs were shaking, after a few months his arms began to tremble and subsequently tremor affected his head also a t times. I I ,2 stated that her illness commenced a t about the age of 18, the tremors came on so gradually that she could not be sure definitely when they commenced; a t the age of 19 she had to give up her work a t the mill upon which she had been engaged for several years. The father suffered from asthma; the mother was dead and the cause of her death was not known; one brother died from phthisis at the age of 24, another brother died from influenza. The patients stated that two sisters had also suffered from Paralysis agitans but the recorder was able to get no confirmation of this statement; one of these sisters died aged 16, the other died a t the age of 26. Bury, 1902 (Bibl. No. 17).

Fig. 6. Paralysis agitans in four siblings: the onset was early in each case, parents were normal and unrelated and there was no hereditary syphilis; three siblings were adult and healthy. 11,3, Robert S., aged 21, was healthy until the age of 14 since when he has gradually reached his present condition: he cannot stand steadily and walks in a trembling, tottering manner; the unsteadiness is but little increased when his eyes are shut, the movements cease when he lies down and the limbs are supported; his face lacks expression and attempts to speak usually cause some quivering of lips, his words are slurred. 11, 1, aged 36, and 11, 2, aged 26, both became affected at the age of 14, they were only now able to get about with great difficulty but their condition had remained stationary for some years. 11, 4, aged 17, was just beginning to be seriously troubled with the same symptoms; the recorder describes the tremor as choreiform with considerable jactitations. Moxon, 1879 (Bibl. No. 6).

Fig. 7. Paralysis agitans in four males and five females of a very fully worked out family history showing much intermarriage throughout the stock : other significant characteristics of the family are its considerable fertility with a high infant mortality. Many other signs of degeneracy occur in members unaffected by Paralysis agitans, such as myoclonus epilepsy, alcoholism, mental defect, chorea and tuberculosis.

Five of the affected members were seen by the recorder and there would appear to be no doubt of the diagnosis in the cases which were not personally examined by him; i t is of interest that there is never more than one case of Paralysis agitans in any sibship of this pedigree; two affected females have an affected child, and one affected male has an affected son. 111, 9 died aged 74 from cancer of the stomach: she had suffered from Paralysis agitans during the later years of her life; we are not told at what age her son IV, 2 became affected but he died aged 56 and was said to have become very helpless; he suffered also from epileptic attacks and had hallucinations. V, 3, the son of IV, 2, became affected at 28 and appears to have been a typical case showing all the classical symptoms, IV, 14, whose mother had myoclonus epilepsy, became affected late in life. 111,20 died aged 75 and was described as suffering in her later years from Paralysis agitans. IV, 24 died aged 61 and suffered during her last ten years from the disease which rendered her completely helpless. III,30 died aged 66 having suffered from the disease for many years; her daughter, IV, 27, who died aged 55,

JULIA J. CLARK 461 was also said to have been affected for many years. 111, 39 died aged 55; he became affected shortly after the age of 32 and became completely helpless.

Thus there is great variation in the age of onset of the disease in the different members of this family. Lundborg, 1913 (Bibl. No. 27).

Fig. 8. Five definite cases of Paralysis agitans and three further probable cases in a fully worked-out pedigree: three members of the family were known to have suffered from tremor but information was too incomplete to determine whether these members also suffered from Paralysis agitans or whether they were cases of senile tremor.

I, 1 died aged 82; his grandson, 111, 10, says that in old age he had tremors of his hand and head; he had eight children of whom seven were affected with Paralysis agitans or with tremor. II ,2 died aged 66; he had a hunchback and according to reports suffered from limitation of movements and tremor; his son, aged 61, was healthy and had six daughters of whom four died, two were healthy. 11, 4 died aged 77; he had a localised tremor of the hands and head which started at about the age of 60; he had ten children of whom four died in infancy, one died young from phthisis. 11, 5 died aged 60 from kidney disease, he had a coarse tremor which started towards the end of his life and remained chiefly localised in his hands; he had four children of whom one, 111, 13, had Paralysis agitans.

111, 13 was seen aged 61 when he complained that three months previously his right hand and right foot had begun to tremble and had got worse each month; now he could only write with difficulty; rigidity and sluggishness of voluntary movements are described and the case appears to be a typical example of the disease; the patient was married but had no children owing to organic defects in his wife. 11, 7 died aged 70; he had suffered from tremor during the last fifteen years of his life which was especially marked in his head; he had seven children several of whom were married and all of whom appeared to be normal. 11, 9 died in old age; a t the end of her sixties her speech became markedly slurred and she developed tremors; she had four children, one of whom had an affected son, IV, 4.

IV, 4 died of typhus, aged 20; in childhood before the age of six he had a fall from some considerable height; a coarse tremor developed in his hands whilst he was still a t school; when standing he could only initiate movement with difficulty and when walking he could only with difficulty stop. 11, 11 died aged 72 ; she had a tremor which was localised in her head; her son, 111, 26, was diagnosed as a case of Paralysis agitans sine agitatione, for he had no tremor but had the rigidity and bowed head typical of the disease; he was married and had ten children of whom two died young. 11, 13 died aged 46 from tuberculosis; she suffered from tremor; three of her six children died young. Thus only one of the eight children of I, 1 remained free from Paralysis agitans or from tremor. Benedek and Csorsz, 1923 (Bibl. No. 30).

Fig. 9. Paralysis agitans with symptoms extending over a wide area of the body in father and son; the son had four children of whom two sons had an incurable chorea with epilepsy, a daughter suffered from hystero-epilepsy, and only one child, a son, remained healthy. Berger, 1882 (Bibl. No. 8).

Fig. 10. Paralysis agitans in four males and three or four females. The recorder’s patient, IV, 7, is examined fully and described in detail, other cases are reported upon. The patient’s paternal grandfather, 11, 1, his father, 111, 2, his two aunts, 111, 3 and 5 , one brother, IV, 2, and one sister, IV, 5, were all affected and the disease was believed to have come through the mother, I, 1, of the affected grandfather, I1,l; the disease was looked upon as a family curse and healthy members suffered from the dread of symptoms developing in them also. Probably most or all of the members of Generation V are still below the age at which the disease most frequently shows itself. We are told that the symptoms were alike in all; each case showed the typical tremor, rigidity, lack of facial expression, and posture characteristic of the disease. 11, 1 died at about the age of 55 years; the onset in 111, 2 was at the age of 42, he died at 47; 111, 3 died a t the age of 47, the age of onset of the disease was not known; the onset in 111,5 was at the age of 32, she died at 39; IV, 2 died aged 40 and became affected at the age of 35; IV, 5 died aged 40, the age of onset was unknown; IV, 7 developed the disease a t the age of 36. Thus for the affected cases the onset occurred rather early in life and they died rather young. Giinther, 1913 (Bibl. No. 26).

Fig. 11. Paralysis agitans in a brother and sister; the father, I, 5, had attacks of acute articular rheumatism and died from heart disease aged 72; the mother, I, 6, was nervous and died aged 62 from pneumonia. Of the eight children of I, 5 and 6, two sons died young, one son died aged 33, one daughter suffered from the age of about 28 from arthritis deformans and two daughters were well; the son, 11, 3, had Paralysis agitans, the disease being first noticed a t the age of 55; he was married and had five children. The affected daughter, 11, 6 , was of a nervous temperament, always very impressionable and readily developed phobias and ideas of persecution ; the symptoms of Paralysis agitans showed themselves a t the age of 37. Ricca, 1908 (Bibl. No. 22).

*

BIBLIOGRAPHY. * Indicates that the original publication has not been seen.

GALEN. Opera Omnia. Lipsiae, 1824. [De tremore, Cap. nr and IV, in which species of tremor are differentiated, occurs in Vol. w, pp. 586893.1 GAUBIIJS, H. D. Institutiones Pat?wbgiae medicinalis. Leiden, 1758. [Gives probably the first description of the gait characteristic of Paralysis agitans, p. 398: “Est et, ubi musculi, recte quidem ad voluntatis nutum in actum concitati, injussa dein agilitate atque impetu non reprimendo motus suos accelerant, mentemque invitam praecurrunt. Vitium, loquelae musculis frequens, nec his solis tamen proprium: vidi enim, qui currere, non gradi, poterat.”] SAUVAOES, F. B. DE. Nosologie me‘thodique. Paris, 1771. [Translated from the Latin by Nicolas. In the section entitled “Des Maladies Convulsives” the following occurs: “I1 paroit qu’on doit rapporter au m6me genre de maladie une autre espece trbs-rare que les auteurs n’ont pas aperpue, et que je ne crois pas pouvoir mieux appeller que du nom de scblotyrbe festinante ou festinie.” T. I, p. 798.1

462 A P E D I G R E E O F P A R A L Y S I S A G I T A N S 4. SYL~US, F. DELEBOE. Opera Mediea. Amstelodami, 1780. [Sections v, XIX and xxv of the Section entitled “Praxeos Medicae

5. 6. 7*. 8.

9*.

10.

11.

12*.

13.

14*.

15.

16*.

17.

18.

19.

20.

21.

22.

23.

24*.

25.

26. 27. 28. 29.

30.

31.

Idea Nova,” pp. 291, 292, refer to the author’s differentiation between tremorswhich occur on attempts a t voluntary motion and those which occur whilst the body is a t rest.] PARKINSON, J. A n Essay on the Shaking Palsy. London, 1817. MOXON, W. “A Form of Trembling Palsy.” Lancet, Vol. I for 1879, pp. 3-5. London, 1879. Plate, fig. 6. LEROUX, P. D. ContriWion b l ’ l h aka cawles de la paralysie agitante. Paris, 1880. BERQER. “Paralysis agitans” in Eulenburg’a Real-E~lcyclqxidie der gesammten Heilkunde, Bd. x. Wien and Leipzig, 1882. [Here- ditary cases of the disease are described, p. 323.1 Plate, figs. 2, 4, 9. L’HIRONDEL, G. Anihtiienis et causes de la maladie de Parkinsbn. Paris, 1883. [Said to ref& to a case of Paralysis agitans in mother and daughter.] WEBER, L. “Paralysis agitans and a Consideration of some Cases of this Disease.” Journal of Nenxvusand Menial Diseases, Vol. XV, pp. 356-365. New York, 1888. [Tho hereditary element, it is said, does not seem to play any r6le in Paralysis agitans, yet one case is reported in a male whose father and two brothers were similarly affected, also a second case in a male whose brother was affected.] BORQHERINI, A. “Della Paralisi Agitante.” Rivista Sperimentale di Freniatria e di Medicinu Legale, Vol. XV, pp. 149. Reggio- Emilia, 1889. Plate, fig. 3. BBCHET, E. Contribution b I’e‘twle clinique d a formes de la maladie de Parkinson. Paris, 1892. [Describes a case of Paralysis agitans in two sisters.] GOWERS, W. R. A Manual of Diseases of the Nervous System. 2nd Edn. London, 1893. [For observations concerning the heredity of Paralysis agitans see Vol. 11, p. 637. “Heredity can seldom be traced, perhaps in not more than 15 yo. In one case. . .the patient’s father and uncle had suffered from it.. . .The sister of one patient and the mother of another and in two othcr cases the father suffered also from Paralysis agitans.” CLERICI, A. and MEDEA, E. “La malattia di Parkinson e l’eredo-familiarit.” Bollettino clinieo-scientijieo dellu Poliambulunzu di Mklano, Vol. XII, pp. 33-51. Milan, 1899. [Two sisters became affected a t the ages of 12 and 28 years respectively; probably other members of the family were also affected.] COLLINS, J. and MUSEENS, L. J. J. “A clinical study of twenty-four cases of Paralysis agitans.” New Y&k Medical Jouml , Vol. LXX, pp. 41-46. New York, 1899. [The following hereditary cases are reported: (1) An affected male had a father with Paralysis agitans, his mother and a maternal uncle died with some form of paralysis. (2) Paralysis agitans in a mother and in her son. (3) An affected male had a father and possibly a paternal unclc similarly affected. (4) An affected female had a father and a paternal aunt with Paralysis agitans.] SIEHR, P. H. Zwei Fdlle w n Paralysis agitans im jugendlichen Alter. Dissertation, Konigsberg, 1899. [A brother and sister were affected, the onset of tremor being a t the age of 13 for the brother and a t 16 for the sister: the mother was hysterical.] BURY, J. S. “Two cases of Paralysis agitans in the same family in which improvement followed the administration of Hyoscine.” Lancet, Vol. I for 1902, p. 1097. London, 1902. Plate, fig. 5. TERRIEN. “Une famille de Parkinsonniens.” Gazette mtiiicale de Nantes, T. XXI, pp. 594-598. Nantes, 1903. [Describes Paralysis agitans in a brother and sister and in a male first cousin; two nephews were showing certain symptoms which the recorder thought might well be the forerunners of the disease in them also.] HART, T. S. “Paralysis agitans: some clinical observations based on the study of 219 cases seen a t the Clinic of Professor M. Allen Starr.” Journal of Nervowl and Mental Diseases, Vol. XXXI, pp. 177-188. New York, 1904. [In 16 % of cams the disease was found to have occurred in relatives-in the mother six times, in the father three times, in three cases a sister was affected, in one case a brother and in one case a cousin.] OPPENHEIM, H. Lehrbuch der Nervenkrankheiten. 4te Aufl. Berlin, 1905. [Paralysis agitans is described Bd. n, S. 1313-1329; the following hereditary cases are reported: (1) Two sisters with Paralysis agitans a t a comparatively early age. (2) Patient and brother affected. (3) (in 5th Edn) Three sisters affected.] PENNATO, P. “Morbo di Parkinson post-infettivo e famigliare.” La Riforma medica, Vol. XXI, pp. 1.50-154. Napoli, 1905. [A brother and sister were affected, no information is given of other members of the family.] RICCA, S. “Due casi di morbo di Parkinson atipici in fratello e sorella.” La Riforma medica, Vol. x n v , pp. 1067-70. Napoli, 1908. Plate, fig. 11. BONHOEFRER, K. “Demonstration eines Kranken mit juveniler Paralysis agitans.” Berliner klinieche Wmhenschrift, Bd. XLm, S. 1250. Berlin, 1911. [Two siblings were affected, the onset in each case was a t the age of 18 years.] MENDEL, K. Ueber Paralysis agituns. Berlin, 1911. [Four hereditary cases are described in thie monograph: (1) The patient and two of the grandfather’s brothers were affected. (2) The patient, father and uncle were affected. (3 and 4) In both cases the disease occurred in patient and sister.] WILLIQE, H. “tfber Paralysis agitans im jugendlichen Alter.” Zeitschrift f . d . ges. Neurologie u. Pqchiatrie, Bd. IV, S. 520687. Berlin, 1911. GUNTHER, H. “tfber Paralysis agitans.” Deulsche Zeitschrift f . Nervenheilkunde, Bd. XLW, S. 192-206. Leipzig, 1913. Plate, fig. 10. LuNDBoRa, H. Medizinisch-biologische Familien-Forschungen. Jena, 1913. [Sea Text, pp. 4614, Atlas Plate xxXv.1 Plate, fig. 7. BUSCH, P. Parkinsonache Krankheit und Unfall. Dissertation. Zerbst, 1914. HUNT, J. RAMSAY. “Progressive Atrophy of the Globus pallidus. A system disease of the Paralysis agitans type characterised by atrophy of the motor cells of the corpus striatum.” Brain, Vol. XL, pp. 58-148. London, 1917. BENEDEE, L. and CSORSZ, K. “Heredofamiliaritiit bei Paralysis agitans.” Deutsche Zeitschrift f. Nervenheilkud, Bd. Lxnx, S. 367-373. Leipzig, 1923. Pbte, fig. 8. PATRKIK, H. T. and LEVY, D. M. “Parkinson’s Disease. A Clinical Study of one hundred and forty-six caaes.” Archives of Neurology and Psychiatry, Vol. w, pp. 711-720. Chicago, 1923.

THE POPULATION PROBLEM.

The Biobqy of Population Growth. By RAYMOND PEARL. New York: Alfred A. Knopf. Now that Professor Raymond Pearl has added another study to his already extensive work on the growth of popu-

lations, it may seem not inopportune to consider briefly what are the essential principles which underlie his theories of growth.

One of the di&culties with which the statistician has occasionally to contend is the possibility of getting two quite different analytical forms of curve which give equally good graduations of statistical data over a given range. If the graduations are equally good it is probably justifiable to choose the form of curve to use on “ a priori grounds” and this is what Profemor Pearl has done. As stated in his “Studies in Human Biology,” his postulates are the following:

(1) There is an upper finite limit to the area on which populations can grow (e.g. for human populations, the habitable area of the earth).

(2) As a consequence of (1) there is a finite upper limit to the population itself. (3) The lower limit to population is zero, negative populations being impossible. (4) Each geographical unit which has been inhabited for any long time has, so far as the evidence available indicates,

had a succession of waves or eras of population-growth, each superposed upon the last, and each marking the duration of a more or less definite cultural epoch.

(5) Within each cultural epoch there has been first a slow rise gradually getting faster until a point of inflexion is reached after which the rate of growth becomes progressively slower and the curve stretches along nearly horizontally in close approach to the upper asymptote which belongs to the particular cultural epoch and area involved.

Postulates (l), (2) and (3) are almost indisputable, (4) and (5) are however more speculative and their validity must depend on how far they are borne out by the evidence, a great deal of which has already been given by Professor Pearl.

The assumptions are satisfied (though not necessarily uniquely) by

............ (4

(B)

k

k

= 1 + mekax

............ Y = 1 + meaix+arzg+ ...+ a,* for one cycle, while the more general form

is capable of describing a whole series of cycles.

The form ........... (Y) is particularly useful as it will give rise to a single cycle (provided the roots of a, + 2~ + 3aga are imaginary) which is more general than (a) as it is asymmetrical.

These curves had already been fitted by Professor Pearl to a great variety of data before the publication of the present volume. Satisfactory fits were obtained for the growth of the pumpkin, of the tadpole’s tail and of yeast cells and for populations of the fruit fly (Drosophila) in the grtificial universe of pint or half-pint bottles.

The populations of many countries in the world had also been fitted and the results published in “Studies of Human Biology,” but the results could not in many cases be regarded as altogether conclusive because observations were not available over the whole of one cycle in any one case, the position over which censuses extended being either in the middle of the cycle as in the case of England and Wales, at the beginning as in the United States, or a t the end as in fiance, and in one or two cases, as in Germany and Japan, the censuses appeared to extend from the end of one cycle to the beginning of another.

The present volume is an attempt to remedy the deficiency by a study of the indigenous native population of Algeria which appears to have gone through the whole of a cycle since census records were first taken. In the first chapter the reader is introduced to Pearl’s theory of growth, in the second the theory is illustrated by the growth of Drosophila in pint or half-pint bottles and then follows the careful study, occupying much of the book, of the native population of Algeria. A great deal of trouble seems to have been taken to ascertain the reliability of the data used and, whether the census figures from 1856 to 1886 (which were probably too low) are included or excluded from the calculation, much the same logistic curve is shown to result giving an upper limit of about five millions, probably slightly more, for the native population of Algeria during its present cycle of growth.

We are then led to an analysis of the mortality of the native Algerian population which leads to the conclusion that its death rate has declined at a speed quite as rapid as that of either of the European groups living in the same environment or of the populations of the United States and England and Wales in spite of the absence of adequate public health and sanitary measures in the Algerian population. The birth rate is then considered and its fall between the years 1900 and 1914 in a population known to be essentially uninfluenced by the intentional practice of contraceptive measures itj noted as being of the character which has been theoretically shown by Yule to be a necessary concomitant of the logistic population curve.

464 THE POPULATION PROBLEM Since the form of the growth curve must be regarded as a consequence rather than a cause of the birth and death

rates, the author, who agrees with Yule in regarding the former as the more fundamental in this connection, devotes the remaining chapters to a discussion of the reasons for the falling birth rate “not with the thought of completely solving it, but rather with the view of putting upon the record some new and pertinent bits of evidence concerning it.”

And thus we are introduced to the three most intereating chapters of the book dealing respectively with the influence of density of population, of class and of human behaviour, on the birth rate. In the first, we are shown by ingenious studies of Drosophila, of fowls and of human beings, that population density and the birth rate are negatively corre- lated and the author considers that here is one “Vera causa” for the damping off of the growth of population as the upper limit of the logistic is reached. In the second, further evidence is given to show, as is already well known, that the birth rate is negatively correlated with wealth, while in the third we are given data as to sex habits in normal men of a kind which we are not aware have been published before Only about 250 cases were available and we imagine that there would be a difference of opinion among physiologists as to whether men ultimately undergoing operations for hypertrophy of the prostate gland have a sex history which may be regarded as normal even in early years; but it is interesting to find (though the number of cases is very small), that different classes of society occupy the same order when classified by sexual activity as by the birth rate. These data are a step in the right direction and were more of their kind about normal men available, they would have more value than much pathological literature.

Professor Pearl seems to have reached the position that population in a relatively constant environment will have a law of growth which is given approximately by equations (a) and ( y ) above and that a Sufficiently great change of environmental conditions will switch the law of growth from one curve to another of the same kind and that this logistic curve is really biologically significant. As far aa “Drosophila” is concerned his case seems to be fully made out and the hypothesis could at any time be confirmed by further experiments, but with regard to human populations the position is rather more difficult. A critical reader might hazard the suggezltion that the human population data, even that of the native population of Algeria, could have been equally well fitted with cubic or in one or two cases biquadratic curves, but even. were the graduations as good as Professor Pearl’s we think the logistic is to be preferred as a graduation because it satisfies the postulates (I), (2) and (3) above, which we think are incontestable. Postulates (4) and (5) can only be established by means of the evidence, and the present study adds considerably to their plausi- bility. Whether we actually have here a biological law or not with regard to human populations must in our view remain undecided, nor will it be easy to establish; for if the law be true predictions may be falsified by a change in the en- vironmental conditions. Should however these conditions fortunately remain sufficiently steady for the verification of some of the more daring prophecies by extrapolation on which the author (not without pointing out the environmental limitation) has ventured, the time may come when his insight will have its reward. To conclude, we are indeed grateful to the author for his contributions to a subject whose interest did not start with

Malthus and will not end with Pearl and whose contemplation must awaken the hopes and fears of all minds capable of reflecting on what the past was and what the future may be.

J. 0. I.

OAMBBIDOE: PRINTED BY W. LEWIS, ?d.A., AT TEE UNNERSITY PRESS