DOI: 10.1590/0004-282X20160109 VIEW AND REVIEW Abnormal eye movements in three types of chorea Anormalidades dos movimentos oculares em três tipos de coreia Tiago Attoni1, Rogério Beato2, Serge Pinto3, Francisco Cardoso2 ABSTRACT Chorea is an abnormal movement characterized by a continuous flow of random muscle contractions. This phenomenon has several causes, such as infectious and degenerative processes. Chorea results from basal ganglia dysfunction. As the control of the eye movements is related to the basal ganglia, it is expected, therefore, that is altered in diseases related to chorea. Sydenham’s chorea, Huntington’s disease and neuroacanthocytosis are described in this review as basal ganglia illnesses that can present with abnormal eye movements. Ocular changes resulting from dysfunction of the basal ganglia are apparent in saccade tasks, slow pursuit, setting a target and anti-saccade tasks. The purpose of this article is to review the main characteristics of eye motion in these three forms of chorea. Keywords: chorea; eye movements; Huntington disease; neuroacanthocytosis. RESUMO Coreia é um movimento anormal caracterizado pelo fluxo contínuo de contrações musculares ao acaso. Este fenômeno possui variadas causas, como processos infecciosos e degenerativos. A coreia resulta de disfunção dos núcleos da base, os quais estão envolvidos no controle da motricidade ocular. É esperado, então, que esta esteja alterada em doenças com coreia. A coreia de Sydenham, a doença de Huntington e a neuroacantocitose são apresentadas como modelos que têm por característica este distúrbio do movimento, por ocorrência de processos que acometem os núcleos da base. As alterações oculares decorrentes de disfunção dos núcleos da base se manifestam em tarefas de sacadas, perseguição lenta, fixação de um alvo e em tarefas de antissacadas. O objetivo deste artigo é revisar as principais características dos movimentos oculares nestas três formas de coreias. Palavras-chave: coreia; movimentos oculares; doença de Huntington; neuroacantocitose. Chorea is an abnormal movement characterized by a contin- A beta-hemolytic streptococci, which cross-react with the epi- uous flow of random involuntary muscle contractions. This phe- topes of the basal ganglia3. There has been an overall decline in nomenon has several causes, such as infectious and degenerative the incidence of SC, even in developing countries, where it used conditions. Chorea results from dysfunction of the basal ganglia, to be endemic. However, it remains the most common cause of which are involved in the control of eye movements. It is, there- chorea in children, worldwide4. The SC patients show a combi- fore, expected that the control of eye movements is changed in nation of motor disorders (chorea, decreased muscle tone, tics diseases with chorea. Frontal areas are often abnormal in chore- and others) and cognitive and behavioral changes. Among the atic diseases due to the connections between the basal ganglia latter are obsessions, hyperactivity and executive dysfunction5. and frontal lobe. The causes of chorea are varied, but its presen- Huntington’s disease is a neurodegenerative disorder tation does not change, even in different pathologies. There are inherited in an autosomal dominant pattern, whose gene was non-genetic and genetic causes for chorea1. Among the former mapped in the region of the gene IT-15 on chromosome 4p16.3. is Sydenham’s chorea (SC), the most common cause of chorea in Although the underlying mechanism responsible for cell death children, while Huntington’s disease (HD) and neuroacanthocy- has not been determined, there is an unstable expansion of the tosis (NA) chorea are of genetic origin1,2. trinucleotide CAG that leads to the production of an abnor- Sydenham’s chorea is the neurologic manifestation of rheu- mally large protein, huntingtin6. The onset of the disease can matic fever (RF), presumably caused by antibodies against group occur at any age; however, in most cases, patients develop early 1Universidade Federal de Minas Gerais, Programa de Pós-Graduação em Neurociências, Belo Horizonte MG, Brasil; 2Universidade Federal de Minas Gerais, Departamento de Medicina Interna, Serviço de Neurologia, Belo Horizonte MG, Brasil; 3Aix-Marseille Université /CNRS, Laboratoire Parole et Langage, Aix-en-Provence, France. Correspondence: Francisco Cardoso; Av Pasteur 89/1107; 30150-290 Belo Horizonte MG, Brasil; E-mail: [email protected] Support: Dr Cardoso has received honoraria from Boehringer-Ingelheim, UCB, and TEVA. Conflict of interest: There is no conflict of interest to declare. Received 21 March 2016; Accepted 16 May 2016. 761 symptoms around 35 years of age. Typically, patients present which is to look for a moving point; and an antisaccade with a triad of movement disorders (chorea, dystonia and oth- task, which consists of deletion or inhibition of a stimulus. ers), cognitive decline and behavioral changes7,8 . With the appearance of the target, the subject has to look to The term NA encompasses a heterogeneous group of rare the opposite side. Such tasks require a more refined cogni- genetic diseases. The most common diseases in this group are tive performance as they involve a preparatory phase, inhi- chorea, acanthocytosis, McLeod syndrome, Huntington’s dis- bition and decision phase13. Munoz and Coe21, produced a ease-like 2 and pantothenate kinase-associated neurodegen- model of the neural control of eye movements that can be eration. Most NA cases are inherited in an autosomal reces- seen in the Figure. sive manner, but some of the diseases are transmitted as a dominant trait linked to X chromosomes or are even autoso- mal dominant. Clinically, patients often have the triad found SYDENHAM’S CHOREA in HD, but other symptoms, such as orofacial self-mutilating dyskinesia, seizures and peripheral neuropathy are also occa- There are very few studies of ocular movements in SC. sionally found in these patients9. We highlight two studies that identified abnormalities in Despite the heterogeneous clinical features of these con- tasks requiring eye movement in patients with SC. ditions, the basal ganglia are the site of dysfunction in all of Cardoso et al.5 examined 50 children with a confirmed them. This anatomical area is involved not only with motor diagnosis of RF, including 13 who developed SC. The aver- control but also in other functions, such as cognition, behav- age age of the 50 patients with RF was 8.4 years. Using clini- ior and eye motion. Therefore, it is no surprise that patients cal evaluation, the authors found the presence of hypomet- with basal ganglia disorders often display a multitude of clini- ric saccade in 80% of patients with chorea, 13% in patients cal characteristics in all these domains. Although the cogni- without chorea, 25% in patients with chorea in remission tive and behavioral disturbances associated with chorea have and in 13.5% of patients without RF chorea. Based on these been thoroughly investigated, there are few data on disorders results, the authors suggest that abnormalities of the ocu- of ocular motility in chorea10,11,12,13. lar motility found in their study may reflect dysfunction of The structures involved in eye motion are able to pro- the connections between the basal ganglia and the superior vide important information about the disease, but it is also colliculi. Considering the results in patients in remission, necessary to investigate the function of these areas and their it is thought that this dysfunction may be transient, disap- connections. It is known that the vertical and horizontal sac- pearing in most patients with chorea who go into remis- cades are impaired in HD14. The superior colliculus plays an sion. However, the presence of saccadic abnormalities in important role in the final execution of these movements, patients in SC remission supports the notion that the ocu- maintaining connections with the basal ganglia and corti- lomotor system damage may be persistent in some individ- cal structures that exert a regulatory role on voluntary and uals. Furthermore, hypometric saccades found in patients reflexive saccades. The frontal cortex and the parietal cor- with RF without chorea, suggests that dysfunction of eye 15 tex work together, allowing voluntary movement . There is movement may occur independently of the movement no involvement of the frontal cortex for the reflexive action, disorder. Furthermore, the authors found an association 16 and its control is exerted solely by subcortical structures . between SC, carditis and alterations in eye movements. The frontal cortex has projections directed to the caudate The antisaccades task has also been explored in SC in nucleus, sending this information to the superior collicu- another article by Cairney et al.22. This study explored the lus. Atrophy in these circuits explains part of the eye motion dysfunction present in HD14,17. The caudate seems to partici- pate in the initiation and inhibition of saccadic movement in Frontal cortex Parietal cortex Visual the horizontal and vertical planes. Imaging studies indicate PFC FEF SEF PEF cortex involvement of the eye field cortex, the inferior parietal cor- tex and caudate nucleus18. Inhibitory Excititory The study of eye motions in a progressive disease may Basal ganglia reveal more insight into the structural dysfunction and pro- Thalamus Striatum LGN vide information about the effectiveness of new treatments19,20. t c y e r a The purpose of this article is to review ocular motility in i w d r h GPe t SC, HD and NA, with emphasis on clinical and pathophys- e SCi SCs Retina a Direct p y p pathway iological aspects. Before we start describing the results of H Eye muscles studies related to each of these conditions, there are terms Indirect pathway Cerebellum PPRF that need to be defined: rapid eye movements are called STN SNr riMLF saccadic or saccades. Eye movements to detect a target Figure. The neural control of eye movements (Munoz and Coe. in motion can be tested through the task of slow pursuit, EJN, 2011). 762 Arq Neuropsiquiatr 2016;74(9):761-766 possibility of residual neurological dysfunction in two SC using EOG, recording with pairs of silver chloride electrodes patients in remission.