J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.46.4.289 on 1 April 1983. Downloaded from Journal ofNeurology, Neurosurgery, and Psychiatry 1983;46:289-298 Occasional Review The athetoid syndrome. A review of a personal series JOHN FOLEY* From the Cheyne Centre for Spastic Children, London, UK "This class of ataxic persons has an interest of its own in the large amount of sympathy and patience it calls for, appearances being so very adverse" (Shaw, 1873). Athetosis is a disorder of movement, not a disease "most cases of the athetoid group belong to the However, it forms the main feature of a familiai quadriplegias". syndrome, but its definition is difficult because oux The athetoid syndrome is here defined as a non- concept of the condition has expanded far beyond progressive but evolving disorder, due to damage to the terms of the original description. Some authors the basal ganglia of the full-term brain, character- confine athetosis to involuntary movements of a par- ised by impairment of postural reflexes, arhythmical ticular kind involving the limbs. Others prefer the involuntary movements, and dysarthria, with spar- terms dyskinesia in relation to the limbs and dys- ing of sensation, ocular movements and, often, intel- Protected by copyright. tonia in relation to the trunk,'2 though these terms ligence. The layman, untroubled by neurophysiolog- offer no advantage in clarifying the nature of the ical niceties, sees the problem more simply-they disorder of function. Hammond, in 1871, originally can't sit, can't move at will, can't talk, and yet take used athetosis to describe involuntary movements of everything in. the limbs appearing in previously normal adults, a Athetoids form about a quarter of the cerebral- condition as rare to-day as "post-hemiplegic palsied population and, because of their latent chorea". Shaw3 described athetosis as "ataxia with abilities, are the cause of the emotive concern for imbecility" (the latter meaning in those days children with brain-damage. Not only were the ear- incapability) but emphasised its onset shortly after lier definitions concerned mainly with involuntary birth, the involvement of the facial and trunk mus- movements of the limbs, but many of the reviews did cles, speechlessness in some cases, and often preser- not include severe cases. Some of Carpenter's9 and vation of intelligence. Twitchell's8 cases could walk and talk and would The variety of synonyms makes for confusion- have been classed as mild in our present series. "double athetosis" ,45 "Little's disease with involun- tary movements", "infantile partial striatal Pathology sclerosis", "congenital chorea",6 and "distal dys- http://jnnp.bmj.com/ tonia".' The greatest cause of confusion is the The responsible lesions are mainly in the basal gang- occurrence in some cases of signs thought to be lia3 s'1-1 and result in most cases either from purely "cortical". Some authors8 feel that the term is intranatal asphyxia9 or neonatal jaundice.'0 It is used too loosely, that pure athetosis is rare, and that curious that Carpenter9 in his review of athetosis did bilateral athetoid movements often complicate dip- not mention kernicterus, while Gerrard'5 in his legia and quadriplegia. Many authors have referred study of kernicterus did not mention asphyxia as the to a few "signs of spasticity" in some cases.389 cause of an identical syndrome. Polani'6 gave equal Plum'0 was unperturbed by the occurrence of weight to kernicterus and abnormal labour. Plum'0 on September 25, 2021 by guest. pyramidal signs in some of his cases of kernicterus, was unable to distinguish between the two varieties while Bobath"I avoided a definition by stating that except in respect of deafness, though he found some "spastic" signs slightly more often in cases due to asphyxia. Exsanguination-transfusion, first done by Address for reprint requests: Dr John Foley, The Cheyne Centre Hart'7 in 1925, before the description of the main for Spastic Children, 61 Cheyne Walk, London SW3, UK. blood-groups, and the use of anti-D globulin, first Received 20 April 1982 and in revised form 30 October 1982. proposed by Finn'8 and developed- by Clarke et al'9 Accepted 20 November 1982 have now made kernicterus a rare disease, and have 289 J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.46.4.289 on 1 April 1983. Downloaded from 290 Foley spared countless individuals a lifetime of misery. Though the asphyxial and kernicteric varieties The aetiological and pathological features of the seem clinically indistinguishable, the distribution of diplegias and quadriplegias20 are quite different lesions is different. In the former, the caudate nuc- from those of the athetoid syndrome, and the differ- leus and putamen are most involved, and this has ence in pathology is reflected in outstanding differ- also usually been the case in the athetoid syndrome ences in both the main clinical features and the following rotational head-injuries in childhood.2527 commonly associated phenomena. The quadrip- In kernicterus, due usually to Rh-iso- legias, having multiple and disseminated lesions, immunisation, and less commonly to ABO incom- show in general perceptual defects due to involve- patibility or glucose-6-phosphate-dehydrogenase ment of the parietal association areas, intellectual deficiency, there is characteristic yellow staining of impairment, an abnormal EEG and CT scan, and a the dead nerve cells followed by gliosis and poverty high incidence of epilepsy. In the athetoid group, in of myelination. Schmorl,28 who coined the term, contrast, in which the damage is almost limited to considered involvement of the caudate nucleus to be the basal ganglia, perceptual difficulties are rare, rare. The putamen is less severely damaged than in intelligence can be high, the CT scan and EEG are etat marbre, and the cortex is rarely affected. normal2' 22 and epilepsy is rare. Schmorl found the main lesions in the globus The best-known pathological feature of athetosis pallidus, subthalamic nucleus, cornu ammonis, is marbling, or etat marbre, of the basal ganglia in dentate nucleus, inferior olives, vermis, flocculus, cases due to abnormal birth (presumably with and the cranial nerve nuclei of the fourth ventricle asphyxia). Originally described by the Vogts'2 as a floor; to which Gerrard'5 added the putamen and congenital malformation, it consists of a coarse net- caudate. Gerrard found the vestibular nuclei as work, or even bundles, of myelinated nerve-fibres often affected as the cochlear. The crucial level of disturbing the normal radial pattern of the striatum. unconjugated bilirubin necessary for the causation Denny-Brown6 denied the relationship to asphyxia of kernicterus is 18 mgs.% or 308 ,umoL/l, though a Protected by copyright. postulated by the Vogts, while Alexander,"4 concen- lower level is injurious if the infant is premature, trating on the abnormal myelinated fibres, denied hypoxic, anaemic or febrile. Gerrard's aphorisms the occurrence of significant cell-loss or gliosis, are noteworthy: "no kernicteric infant is ever though he pointed out the sharp watershed running normal"; "it is to those who feed, handle and hold through the striatum between the vascular ter- these infants during the first ten days of life, rather ritories of the anterior choroidal and the striate than to those who subject them to a full neurological branches of the middle cerebral artery.'3 Alexander examination that, in mild cases, the presence of was emphatic that the marbling fibres ("tractus kernicterus is revealed." He was aware of high-tone marmoratus") come from the frontopontine tract deafness as an important accompaniment of and are of prenatal origin, and are thus not ascrib- kernicterus but was wrong in supposing that affected able to intranatal factors; Byers23 refuted him. Cell- children are usually mentally subnormal. One of his loss, if not gliosis, is widespread, and the globus pal- mothers commented "the deafness is so perceptive lidus may even show "status dysmyelinatus". An you can't perceive it". alternative is "etat fibreux", a diffuse loss of nerve Athetosis also occurs in many other conditions. cells giving a false impression of hypermyelination. Apart from the drug-induced dyskinesias there are a Marbling of the striatum is sometimes associated number of conditions in which the lesion is, or is http://jnnp.bmj.com/ with abnormalities elsewhere in the brain, ulegyria thought to be, biochemical rather than anatomical, or periventricular softening. Though marbling may such as familial kinesigenic choroathetosis,29-32 occur near vascular lesions in adult brains, wide- paroxysmal dystonic choreoathetosis,3334 chorea with spread marbling of the basal ganglia has no counter- thyrotoxicosis35 and choreoacanthocytosis;36 a part in the pathology of later life. Generally speak- number of metabolic disorders, usually with severe ing the striatum is marbled while the thalamus is mental retardation, may also show progressive spared. An inherited factor may be involved as there athetosis,37 including Lesch-Nyhan disease38 with its on September 25, 2021 by guest. is occasionally a familial incidence. Other aetiologi- combination of self-mutilation and hyperuricaemia. cal factors are responsible in a proportion of cases. The pathological processes at work in the athetoid Malamud24 described cases following meningitis in syndrome and spastic diplegia would at first sight infancy, and 2% of our cases had this history. Of appear to be widely different, but anatomically the Christensen and Melchior's20 six cases of the relationship between them is not as obscure as might athetoid syndrome, including three with rigidity, all be supposed. Greenfield39 mentioned "periventricu- had a history of perinatal difficulties, and four had lar rarefaction" as the commonest sequel of birth been jaundiced, but one, with a similarly affected injury. In a proportion of the very premature, sister, had a major central malformation. haemorrhage occurs into the germinal subepen- J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.46.4.289 on 1 April 1983.