‘Progressive lenticular degeneration may be defined as a disease which occurs in young people, which is often familial but not congenital or hereditary; it is essentially and chiefly a disease of the extrapyramidal motor system, and is characterised by involuntary movements, usually of the nature of tremor, dysarthria, dysphagia, muscular weakness, spasticity, and contractures with progressive emaciation; with these may be associated emotionalism and certain symptoms of a mental nature. It is progressive, and, after a longer or shorter period, fatal. Pathologically it is characterised predominantly by bilateral degeneration of the lenticular nucleus, and in addition cirrhosis of the liver is constantly found, the latter morbid condition rarely, if ever, giving rise to symptoms during the life of the patient.’ The clinical symptoms can be considered a pure syndrome of the corpus striatum; manifesting as generalized tremor increasing with voluntary movement, spasticity especially of the face, bulbar involvement culminating in anarthria, and increased emotionalism. Balance is lost, despite a lack of paresis; and additional mental symptoms may be present. This is an extra-pyramidal motor disease since the abdominal reflexes are preserved and the plantar responses flexor. The lenticular nucleus, especially the putamen but occasionally also the globus pallidus and caudate, shows neuronal loss and gliosis with eventual cavity formation. But what is striking and curious is the associated profound cirrhosis of the liver which ‘… does not reveal itself by any symptoms during life … clinically, the symptoms are exclusively nervous’. First, Dr Kinnier Wilson addresses the historical background. Under the title of tetanoid chorea, Sir William Gowers wrote in his Manual of Diseases of the Nervous System (1888, Vol. II, p. 656) of Sydney M., a 10-year-old boy, who had a total of four similarly affected relatives. This young patient died after a short illness characterized by chorea, facial grimacing with the mouth held open spasmodically and the tongue forced back, speech reduced to a whining sound, contractures and involuntary movements including dystonia, athetosis and tremor but with the mind clear. At autopsy, despite no apparent abnormality of the nervous system, the child had cirrhosis of the liver—an observation on which Gowers did not comment further. Later his sister, Charlotte M., presents with an identical illness—although the involuntary movements are more rhythmical and tremulous—and she shows the same pathological findings; and a third sibling, Case 5, forms one of Kinnier Wilson's six newly described cases. The description by Joseph Arderne Ormerod (1890) is important for Kinnier Wilson in that, in addition to cirrhosis, passing mention is made of softening in the lenticular nucleus, considered by the author to be inflammatory. Homén from Finland (1890) has described three siblings—Alfred, Wilhelm and Anna K.—each manifesting a gaping mouth, anarthria, incontinence, involuntary movements, contractures and spasticity with lenticular softening or cavity formation, and liver cirrhosis at autopsy. Prior to Kinnier Wilson, no one of these authors has perceived much concerning the nature of their cases—variously considering them (at one time) to have an hysterical illness or congenital syphilis [probably correct in a further case described by Anton of Halle (1908)] and generally ignoring the combination of pathological changes in the liver and lenticular nucleus. In a footnote, Kinnier Wilson identifies a hitherto unrecognized case from 1854, buried in the New Sydenham Society translation of Wilhelm Frerichs Treatise on diseases of the liver (1860). When first encountering the patient ‘S.T.’ (Fig. 1) under the care of Sir David Ferrier in 1905, Dr Kinnier Wilson ‘… was not aware of the cases that have been sketched in the previous chapter … a year later … D.P. came into hospital … and whenever I saw her I recognised that her condition was identical … this case supplied the clue to the mystery for at the post-mortem … an unsuspected cirrhosis of the liver was discovered … (with Gowers's cases) … they at once threw the illuminating ray for which I had been waiting over the darkness that enshrouded the others’. Now, in 12 pages, Kinnier Wilson describes S.T.'s clinical case history: an episode of jaundice followed after some years by progressive involuntary movement (tremor), impaired speech and swallowing, spasticity and contractures, incontinence (‘wet and dirty’: Kinnier Wilson was fond of music hall vernacular and had a penchant for somewhat scatological humour), and with the characteristic open mouth and fatuous silly facial expression, dying aged 29 years after a neurological illness lasting four years. D.P. (Case 2, Fig. 2) presents with untidy handwriting heralding dysarthria and a gaping mouth with sialorrhoea, involuntary movement, spasticity with contractures, emotionalism and intermittent episodes of confusion but an otherwise intact mental state and with no involvement of the pyramidal system or sensory function. She is dead shortly before her 20th birthday, having been ill for almost three years. Her brother, E.P. is admitted to the Bethlem Royal Hospital claiming to have been ‘… hypnotised to do certain things, is quite sure that God is working a miracle on his behalf. Says he has heard God and the devil talking to him simultaneously, and does not know which voice to obey …’ (Fig. 3). Within a few months of recovery one year later, he develops neurological symptoms and is eventually examined at a sanatorium in Lausanne by Kinnier Wilson: ‘… the impression I received was not one to be easily forgotten … a broad smile … his mouth wide open and the saliva dribbling from it … he hardly speaks at all … his arms in a state of contracture … moving ceaselessly with a quick rhythmical tremor … his whole attitude one of vacant complacency … the maintenance of balance was somewhat hazardous and [precipitated] a perfect riot of tremor … and when his reflexes were tested he burst into a loud “rire spasmodique”‘. E.P. shows no symptoms or signs of liver disease but is dead less than four years after the onset of neurological symptoms. M.To., aged 18 years, becomes clumsy four years after an attack of jaundice (Fig. 4). Her speech and swallowing deteriorate. She is rigid with contractures and a never-ceasing generalized rhythmical tremor: ‘… the face is immobile; the corners of the mouth are retracted in a spastic smile; saliva runs from the lips; the mouth is widely open; only the lively and interested expression of the eyes remains to show that the patient's mental condition is one of alertness and intelligence’. After recovering from typhoid fever caught after falling into the Regent's canal in London, Samuel M. starts to shake, cannot walk, speak clearly or swallow and within a year of presentation lies helpless on his bed ‘… anarthric, dysphagic, emaciated and contractured … with all his limbs “constantly on the work”‘, dying in this condition, aged 15 years. And Christopher J., aged 13 years, has ‘… difficulty in walking; his voice alters and he becomes emotional … his mouth is open and saliva dribbles away; his muscles waste … become rigid … and contract … there is rhythmical tremor … emaciation sets in and he dies after an illness of about two years’ duration … he has shown signs at intervals of defect of liver function …’. Photograph of S.T. taken at Virginia Water. Characteristic appearance of face and upper limbs. (For this photograph I am indebted to Dr. G. W. Smith). D.P. (National Hospital, May 1906). Note how patient is leaning over to the right side. E.P. (June 4, 1910). Note vacant expression, open mouth, sialorrhoea, contractures. (Exposure 1/250 s, to counteract effect of constant tremor). M.To. Note characteristic contracture-attitudes, tremor of the right hand (the patient is grasping her nightdress with that hand in the endeavour to keep the limb as steady as possible), open mouth, vacant expression. ‘The harmony in the pathological findings of the personally observed cases is no less convincing than the similarity in their clinical features.’ The liver in Case 1 is intensely cirrhotic and divided into multilobular nodules varying in size ‘from a shilling to a three penny-piece’ interspersed with liver cell necrosis, fatty infiltration, degeneration and regeneration, connective tissue overgrowth and thickening of the portal tracts. On sectioning the brain, ‘the eye was at once caught by a remarkable bilateral and symmetrical cavitation of the lenticular nucleus [measuring 2.5 × 1.25 cm] … the putamen and globus pallidus had almost completely disappeared, and in their place on each side was a crumbling cavity’ (Figs 5 &6). Microscopically, the edges of the cavity are irregular with extensions along fibre tracts that once connected the putamen and globus pallidus to other nuclei, many passing through the internal capsule which is otherwise intact. These secondary degenerations particularly affect the ansa lenticularis, the subthalamic nucleus of Luys and the bundle of Forel but with relative sparing of the caudate and thalamus. The walls consist of a thick interlacing network of neuroglia and their fibres, demyelinated and degenerated axons, and altered blood vessels. But ‘… in view of the almost complete helplessness of the patient and … the spasticity, tremors and contractures, the practically normal condition of the [cerebral] cyto-architectonic structure and … the corticospinal tracts are facts of great importance’. Things have gone awry with the preparation of autopsy material from Case 2 but there is enough information to confirm lenticular degeneration without cavity formation, and microscopic evidence for glial overgrowth, neuronal loss in the putamen, degeneration of connecting fibres, and cirrhosis of the liver (Fig. 7). The pathological findings in Case 3 are dealt with at length (33 printed pages including 36 figures) and include early bilateral cavitation of the lenticular nucleus (3 cm × 1 cm) due mainly to loss of the putamen; the remains of which shows glial overgrowth, extensive neuronal loss and infiltration of macrophages. There is relative sparing of the globus pallidus although many fibre pathways once connecting this and the putamen to the subthalamic nucleus of Luys are degenerate: again, cortical cyoarchitecture is preserved and there is advanced multilobular liver cirrhosis with fatty degeneration and some regeneration of hepatocytes. Case 4 is living, Case 5 lacks pathological examination; and the available details on Case 6 are scanty although extreme cirrhosis is noted. Horizontal section through hemispheres (S.T., Case 1). (They are reversed in the figure, the left being at the right-hand side). Vertico-transverse No. 148. (Case 1.) Weigert-Pal. (About 2/1.) Liver, transverse section (D.P., Case 2). Natural size. The general character of the cirrhosis and the varying appearance of the nodules are well shown. Now, Dr Kinnier Wilson synthesizes the best 12 examples of the disorder, six of which he has himself described, preferring ‘progressive lenticular degeneration’ to the term ‘tetanoid chorea’ suggested by Sir William Gowers; and challenging all three components of the designation ‘dementia chorea-asthenica’ used by Anton. Analysis of age at onset, gender, familial clustering and birth order especially in large sibships, and place of origin of affected individuals (Finland, metropolitan and rural England, and Italy) all do little to illuminate the cause of the disease. It is not related to syphilis, alcohol abuse or prior infection; but the fever and emaciation seen in three cases that followed an accelerated course, and the occurrence of jaundice in others, suggest a toxi-infective aetiology. Symptomatically, despite various prodromes, the condition rapidly evolves into ‘… a motor disorder par excellence’: fine distal tremor at a frequency of 4–8 cycles per second accentuated by attention and effort; spasticity predominantly of flexor muscles that ends in contractures and eventually renders the patient utterly helpless, unable to speak or swallow, and with a fatuous facial expression but sparing movement of the eyes; muscle wasting and emaciation but strength well preserved such that ‘… it may be said, without risk of being misunderstood, that volitional innervation is defective, while involuntary innervation is exaggerated’; there is no evidence for pyramidal disease from examination of the reflexes; mental symptoms, but lacking consistency between cases are present in the early stages, and—not appropriately described as dementia—these consist of ‘narrowing of the mental horizon, facileness, docility and childishness’. As for the pathology, ‘in the seven cases with positive findings … [these] are so similar … bilateral symmetrical degeneration of the putamen and of the globus pallidus to a less extent … the changes in the [rest of] the brain [being] insignificant … that they afford striking proof of the selective action of some morbid agent’. The condition is not inflammatory (no small-cell infiltration) or vascular but: ‘… I do not think that a diagnosis of progressive lenticular degeneration can be made in any case in which the liver is not [cirrhosed]’. Whilst, to the informed observer, the condition cannot be confused with any other condition, the novice may consider disseminated sclerosis, bulbar and pseudobulbar palsy, Parkinson's disease and juvenile general paralysis amongst the differential diagnosis. The prognosis is grim and there is no treatment. But what of the pathogenesis and pathophysiology? Others have favoured a vascular or syphilitic disease mechanism for individual examples of what was clearly progressive lenticular degeneration. Kinnier Wilson discards congenital or abiotrophic influences and—pausing momentarily to ask whether the fluctuating nature of the symptoms in some instances denotes a functional, i.e. hysterical, component—concludes that the condition is acquired and due to a toxin that is not microbial ‘but possibly … chemical and of the nature of a lipoid’, elaborated in the liver and delivered via the blood-stream. Taken together, liver disease precedes and is probably the cause of the lenticular degeneration. Dr Kinnier Wilson is encouraged in this formulation by the example of neonatal kernicterus in which there is selective involvement of the lenticular and subthalamic nuclei (and some other structures) even though jaundice in adults does not appear directly to damage the brain. Involuntary movement indicates disease of the extrapyramidal system with relatively intact pyramidal pathways. But of the two main functional components that might be responsible—the cerebello-rubro-thalamo-cortical and the lenticulo-rubrospinal connections —it is damage to the latter that explains tremor increasing when the intact pyramidal system is activated during voluntary movement: ‘… we can agree that the hypertonus of muscles in progressive lenticular degeneration is clearly also of extrapyramidal origin and different from the ordinary spasticity of pyramidal lesions’. But would we now share Kinnier Wilson's opinion that the views of Charcot and others on spasticity resulting from removal of the inhibitory influence of an intact pyramidal system on the spinal reflex arc are ‘… now somewhat discredited’? This seems a little cavalier since he promptly goes on to claim that: ‘… the suggestion I make … [is that] … disease of the lenticular nucleus … removes a steadying or “inhibitory” influence … normally [exerted] on the corticospinal paths’- and that a mechanism also providing a sufficient explanation for the dysarthria and dysphagia. Anticipating one of his later publications, Kinnier Wilson singles out pathological laughter as a cardinal feature of the disease but he cannot explain it in terms of pathophysiology. Ultimately, Kinnier Wilson is keen to emphasize that his recognition of an organic disease of the nervous system, having predominantly motor manifestations that are not the result of pyramidal disease, creates a precedent for establishing the true nature of some other disorders hitherto designated ‘functional’; and he wants to make clear that all previous accounts of the ‘syndrome of the corpus striatum’ are inadequate by comparison with his own. An appendix describes (in 15 pages) the six cases of Gowers, Ormerod and Homén on which his own conclusions are partly drawn: the 91 references are numbered in groups by topic; and an addendum describes a report appearing ‘within a few days of the publication of this monograph’ by Völsch on ‘Pseudosclerosis’ which is clearly another example of progressive lenticular degeneration. Quite when progressive lenticular degeneration became ‘Wilson's disease’ is unclear. Kinnier Wilson was using the term at the time of his death in 1937, as were J. G. (Godwin) Greenfield and Derek Denny Brown at around that time. Perhaps the origin lies in a remark recorded by Webb Haymaker (The Founders of Neurology, 1953): ‘Derek Denny Brown once asked Wilson his opinion on the essential aspects of “hepatolenticular degeneration” whereupon Wilson eyed him with circumspection and, starting to walk away, asked, perhaps with tongue in cheek, “Do you mean Kinnier Wilson's disease?”‘In Neurology (Vol II, Chapter 35, pp. 787–831; published posthumously in 1940) Kinnier Wilson addresses ‘… the status of the disease and its connexion with one or two others [that have] been in dispute … my monograph of 1912 described a disease unknown to the medical profession at that time … the cases of Westphal and Strümpell [of pseudosclerosis] are … useless for the extraction of any specific clinico-pathological entity … in not one of these cases was allusion made to cirrhosis of the liver, for the simple reason that it did not occur … the pseudosclerosis of Westphal and Strümpell … violates the of And on ‘… be before can be in for extrapyramidal do not influence the of the disease … I have … without any It is the of as the that the liver and lenticular nucleus, the for that and the for its that are by in his on ‘The of Wilson's disease’
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Alastair Compston (2009) studied this question.