Journal of Neurology J Neurol (1986) 233 : 25-29 © Springer-Verlag 1986 Bilateral ballism: A rare syndrome Review of the literature and presentation of a case M. C. Hoogstraten, J. P. W. F. Lakke, and M.J. Zwarts Department of Neurology, University Hospital, Oostersingel 59, 9713 EZ Groningen, The Netherlands Summary. Ballism rarely occurs as a bilateral phenomenon and only 12 such cases have been reported so far in the literature. A further case is reported in the present paper. The definition of bilateral ballism is discussed, its movements described and the differences from chorea outlined. The most important difference from hemiballism is in the pathological substrate where, in most bilateral cases, diffuse lesions have been reported on both sides of the basal ganglia, without preferential involvement of the subthalamic nucleus. In our case, a frontotemporal infarction was found. In the cases reported to date, the outcome had varied from death to complete recovery, partly depending on the aetiology, which is most frequently vascular. Although relevant data are scarce, dopamine antagonists appear to be the treatment of choice. We stress the role of the dopaminergic system and co-existing factors influencing the abnormal involuntary movements. Key words: Ballism, bilateral - Aetiology - Pathological substrate - Dopamine antagonists Introduction Abnormal involuntary movements are commonly associated with lesions in the basal ganglia complex. Jakob [11] established the relationship of the subthalamic nucleus to hemiballism in 1923, and called it "the syndrome of the corpus Luysii". In 1957, Martin [19] described three patients with hemiballism, without lesions in the subthalamic nucleus. In the same publication he stated that there is no distinct clinical difference between hemichorea and hemiballism. Although the problems concerning the semiology and the neuro-anatomical substrate are generally still unresolved, those with regard to bilateral ballism are even greater. Indeed, it has been questioned whether bilateral ballism as a clinical entity exists. A collection of 12 cases from the literature and the observation of a woman with bilateral ballism form the basis of our discussion of the problems of definition and description of ballistic movements, the clinico-pathological correlation, treatment and outcome. Case report A 20-year-old woman was hospitalized because of forceful involuntary movements occurring for the past 3 weeks. Nine Offprint requests to: M. J. Zwarts (address see above) weeks previously she had given birth to a dysmature, but otherwise healthy child. From her 12th year onwards, she had been treated elsewhere for headaches. During this time the results of neurological examinations had been normal; the E E G showed some minor disorder in the temporal regions. She was treated with phenytoin and phenobarbitone, although she had never suffered from seizures. This medication was discontinued during the second trimester of her pregnancy. Neither the patient nor her family had a history of abnormal involuntary movements or rheumatic fever. The patient's disorder started insidiously 6 weeks postpartum and her general practitioner reinstituted the earlier antiepileptic regimen, but without effect. Neurological examination upon admission revealed rapidly executed flinging movements with both arms, combined with athetoid movements of the hands, turning of the head, grimacing with bizarre facial expressions and restlessness of the legs (Fig. 1). During the rotational and occasional opisthotonic head movements, the eyes deviated both laterally and upwards. The arm movements were almost continuously present during wakefulness and absent during sleep. The ballistic movements were poorly patterned, the left arm moving more vigorously than the right, both independently and congruently. The excursions started with abduction or adduction. Although voluntary action and emotion increased the abnormal movements, she retained some control in executing voluntary movements. There was moderate muscular weakness of the left arm and muscle tone in this arm was slightly reduced during rest. Once the flinging movements commenced, muscle tone on both sides increased. Subcutaneous haemorrhages were seen as a result of forceful contact with the bedside. Consciousness was mostly clear, but sometimes slightly clouded. Further physical and neurological examinations were unremarkable. Normal diagnostic studies included complete blood cell count, urinalysis, routine blood chemistry, ceruloplasmin level and serology for rheumatoid disorder. The CSF was normal except for a slightly increased gammaglobulin level. Radiographs of the skull and brain scintigraphy were normal. The E E G showed bilateral synchronous intermittent delta activity but returned to normal by the 2nd week. Treatment with 2 mg haloperidol b.i.d, was started and in the course of the next 3 weeks the movements disappeared. The patient was discharged with the same haloperidol dosage. Over the next 6 years she was free from symptoms, although several attempts to discontinue the haloperidol medication led to the recurrence of the abnormal involuntary movements. After this period she was readmitted because of spontaneous recurrence 26 Fig.1. Photographs from cinematographic recording of the patient with bilateral ballism, demonstrating the changing synchronous and asynchronous character of the movements. Column A: flinging of the left arm. Column B: both arms abduct in a raised position. Column C: the left arm swings around; note the facial expression and the dystonic posture of the right hand 27 Table 1. Summary of the reported cases of bilateral ballism Reference no./year Age (years)/ Duration/ outcome Additional clinical features Aetiology Morphological findings of the brain sex 30/1920 25/1929 65/F 72/F ? 2 weeks/t Vascular Vascular Bilateral atrophy of striatum and STN Generalized atrophy, including striatum, less in the STN; several occipital haemorrhages 26/1933 40/M 66/F Disorientation Heredodegenerative Vascular ? 2/1939 12 years/slowly progressive 3 months/t 28/1946 47/M 5 years/t Dysarthria ? 12/1957 34/M 11 years/t Chorea and hypotonia Vascular 16/1975 2/F 4 months/? Postictal ? 16/1975 17/1981 1.5/M 75/F Postictal Vascular ? 4/1923a 13/1925a 50/F 52/M ? 2 weeks/ favourable ? 1.5 years/t Psychomotor retardation chorea, apallic Dysmaturity, epilepsy Diabetic, congestive heart failure, atrial fibrillation Hallucinations initially Convulsions Vascular Necrotic lesions diffusely throughout the CNS, including both basal ganglia 24/1978a 28/M Some days/ favourable Cerebellar signs, alcohol abuse and withdrawalseizures Phenytoin intoxication ? Generalized senile changes, atrophy of both pallida, STN and n. ruber Bilateral atrophy of the globus pallidus, STN, n. ruber and n. dentatus Bilateral atrophy of the striatum, only slightly of the STN Bilateral haemorrhagic infarctionof n. caudatus and putamen Feverish illness ? t Deceased; ? not mentioned; STN, subthalamic nucleus a Only paraballism of the abnormal movements, which were this time limited to the left arm. The CT scan now available unexpectedly revealed a sharply demarcated hypodense area in the right frontotemporal region, not extending to the basal ganglia. The ventricular system was symmetrical. The CT abnormality was interpreted as an arachnoidal cyst and no further action was taken. Without the haloperidol medication being changed, the abnormal movements gradually subsided. In the course of the following year, a craniotomy was performed because the patient complained of increasing headaches and three generalized convulsions occurred. A 5-cmdeep spongy cavity was found, which on histological examination proved to be an old infarction and not an arachnoidal cyst. The postoperative recovery was uneventful. A further 3 years later, i.e. 10 years after the onset, she again had a recurrence of only left-sided ballistic movements during the 3rd month of her second pregnancy. After readmission, the abnormal movements gradually subsided again without the haloperidol treatment being changed. At present, 1 year after discharge, she is functioning without symptoms on low-dose haloperidol. Discussion In the literature we found 12 cases of bilateral ballism or paraballism [2, 4, 12, 13, 16, 17, 24-26, 28, 30]. The data are summarized in Table 1. There has been much controversy arising from attempts to differentiate between ballism and chorea. Some authors focus on the site of the lesion, other on the age of the patient [5, 7, 20, 22, 31]. In our opinion, ballism should be differentiated from chorea on phenomenological grounds, just as von Santha [27], Balthasar [1] and, more recently, Meyers [21] have done. In chorea movements are intermittent, fragmentary and simple, with predominant involvement of the distal muscles. In contrast, in ballism movements are almost ceaseless, complex and combined, involving the proximal muscles and resulting in excursions of the entire limb. Hemiballism has been defined [15] as "involuntary movements of the limbs (which) are unilateral, proximal, violent and flinging in character". Although the terminology used in the literature is often poorly defined and used interchangeably, the following classification emerges: monoballism, ballism concerning one extremity; hemiballism, ballism concerning one side of the body; paraballism, ballism concerning the lower limbs; bilateral ballism, ballism concerning both sides of the body. Symptomatology In reporting our case we were faced with the problem of outlining the abnormal involuntary movements in such a way that the reader would be able to visualize these movements. The description is therefore illustrated by means of pictures taken with a motion film (Fig. 1). Previous publications on bilateral ballism or paraballism [2, 4, 12, 13, 16, 17, 24-26, 28, 30] have sometimes simply defined the abnormal movements as "ballistic". Others have placed emphasis on the crude, fast, flinging character of the movements, consisting of flexion and extension, abduction and adduction of the extremities. In many cases, grimacing as well as waltzing and torsion of the trunk are mentioned. It is seldom mentioned whether the movements were congruently, simultaneously or independently present on both sides and whether they were stereotype or irregular. As in our case, 28 As in hemiballism [32], vascular disorders are often seen. A hereditary case was reported by Rakonitz [26]. Although case 5 of Titica and van Bogaert [28] did show a familial preponderance of movement disorders, the clinical picture of the affected members varied (a sister suffered from a cerebellar syndrome, a daughter from a facial tic). Both children in the series of Lesny [16], cases 7 and 8, suffered from generalized convulsions. dopaminergic system [18], as seen in the cases of Opida et al. [24] and of Toru et al. [29]. In our case the abnormal movements occurred twice during a changing hormonal status, postpartum and pregnancy, which suggests that oestrogens could have played a role. The majority of data regarding the relationship between oestrogens and dopamine function indicate a suppressive effect of oestrogens on dopamine function and a supersensitive response after cessation of oestrogen administration. However, a reverse relationship is also wellknown, for example in chorea gravidarum and in chorea induced by oral contraceptives [23]. A definite conclusion regarding the role played by changing hormonal status in the abnormal movements of our patient can therefore not be reached. Anatomical substrate and pathophysiology Treatment and outcome In most cases of hemiballism a lesion is found in the subthalamic nucleus. In 1947, Whittier [32] critically reviewed this relationship and stated: "hemiballism may appear without demonstrable pathologic change in the subthalamic nucleus or its connections, although such cases are relatively rare". The relationship between the subthalamic nucleus and hemiballism has also been confirmed by animal experiments [6, 9, 33, 34]. Lesions of the nucleus in the Rhesus monkey cause contralateral hyperkinesia, sometimes manifesting as ballism, sometimes as chorea. It was assumed that this was due to a release of inhibition of the globus pallidus, to which the subthalamic nucleus has its most important afferent and efferent connections. The anatomical lesions in the reported cases of bilateral ballism are not uniform. The common denominator is more or less extensive damage to both sides of the basal ganglia in the majority of cases, including the subthalamic nucleus, though not preferentially. The basal ganglia appeared normal in our patients when a CT scan of the brain was performed; of course, the possibility of a small infarction cannot wholly be excluded. A frontotemporal lesion, which proved to be an infarction, was clearly present. Although is remained uncertain when this infarction occurred, it might have been at the onset of the abnormal movements in the postpartum period, when there is a heightened risk of cerebrovascular accidents in young women. Isotope brain scintigraphy showed no abnormalities, but was performed at admission, 3 weeks after the initiation of the abnormal movements and too late to definitely exclude the possibility of a recent infarction. A similar lesion in hemiballism has been reported by Martin [19] and by Toru et al. [29]. In these cases the ballistic movements were contralateral to the side of the lesion and, in those of Toru et al. [29], combined with phenytoin intoxication. The relationship between the abnormal movements and this frontotemporal lesion can be disputed. A projection of the precentral motor cortex (the Brodmann areas 6, 8 and 9 of the frontal lobe) to the subthalamic nucleus in the monkey has recently been recognized [10]. One might speculate that a dysregulation in this cortico-subthalamic nucleus circuit could give rise to ballistic movements on the opposite side. The lesions responsible for (hemi)ballism are supposed to increase the dopaminergic activity in the basal ganglia complex. This pathophysiological concept is supported by the fact that neuroleptics can eliminate abnormal involuntary movements [14], while on the other hand, these movements can be induced by phenytoin, which has a stimulating effect on the Therapy for hemiballism is aimed at diminishing pallidal outflow, either by surgical interruption [21] or by blocking dopaminergic receptors in the neostriatum 14. Surgical intervention has not yet been reported in cases of bilateral ballism. Such treatment would require a bilateral pallidal stereotactic lesion, risking a high complication rate. Dopamine antagonists seem to be the treatment of choice (by analogy with hemiballism), but the data are too few to draw any firm conclusions. Up to now, in only two cases of bilateral ballism (including ours) has treatment with haloperidol been reported, both with a favourable response. The outcome in the 12 previously reported cases has varied widely (Table 1) partly depending on the aetiology. In five cases the abnormal movements were unchanged; two patients died within 3 months and two recovered without residual defects. For three patients no data are available. some authors describe a decrease in symptoms when patients are at rest and an increase when in emotional situations or performing voluntary movements. Aetiology Conclusions In clinical neurology bilateral ballism is a rare occurrence. The ballistic movements have to be phenomenologically differentiated from other abnormal involuntary movements, especially chorea. Increased dopaminergic activity in the basal ganglia complex seems to be the underlying pathophysiological mechanism, as in hemiballism. In contrast with hemiballism, in the reported cases of bilateral ballism both basal ganglia are structurally affected, without predominant involvement of the subthalamic nucleus. In our patient, we found a unilateral frontotemporal infarction, which presented in the postpartum period with bilateral ballism. On the left side, i.e. contralateral to the lesion, the ballism was more vigorous than on the right and there were two hemiballistic recurrences on the left. We assume that the initial bilateral manifestation could have been caused by an interaction between the structural lesion and hormonal factors influencing the dopaminergic activity. To date, haloperidol is the only treatment reported to have been successful. 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