REVIEW ARTICLE http://dx.doi.org/10.14802/jmd.16004 / J Mov Disord 2016;9(2):80-88 pISSN 2005-940X / eISSN 2093-4939 Movement Disorders ABSTRACT Cerebellar circuitry is important to controlling and modifying motor activity. It conducts the coordina- Following tion and correction of errors in muscle contractions during active movements. Therefore, cerebrovascu- lar lesions of the cerebellum or its pathways can Cerebrovascular cause diverse movement disorders, such as action tremor, Holmes’ tremor, palatal tremor, asterixis, and dystonia. The pathophysiology of abnormal Lesions in Cerebellar movements after stroke remains poorly under- stood. However, due to the current advances in functional neuroimaging, it has recently been de- Circuits scribed as changes in functional brain networks. This review describes the clinical features and pathophysiological mechanisms in different types of movement disorders following cerebrovascular Seong-Min Choi lesions in the cerebellar circuits. Department of Neurology, Chonnam National University Medical School, Gwangju, Korea Key Words Movement disorder; Cerebellum; Cerebrovascular disorder; Strokes. Received: January 25, 2016 Revised: March 4, 2016 Accepted: March 30, 2016 Corresponding author: Seong-Min Choi, MD, PhD, Department of Neurology, Chonnam National University Medical School, 160 Baekseo-ro, Dong-gu, Gwangju 61469, Korea Tel: +82-62-220-6135 Fax: +82-62-228-3461 E-mail: [email protected] cc This is an Open Access article distributed under the terms of the Creative Commons Attri- bution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0) which per- mits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. 80 Copyright © 2016 The Korean Movement Disorder Society Movement Disorders Following Cerebellar Stroke Choi SM INTRODUCTION lar circuitry is uncertain. Post-stroke movement dis- orders are mostly reported as unusual cases or in Cerebrovascular diseases and strokes are major series of case reports obtained retrospectively from causes of secondary movement disorders, although stroke registries. In addition, stroke in the cerebel- abnormal movements occur infrequently in associa- lar circuitry comprises only a small proportion of tion with stroke. It is important for clinicians to de- these post-stroke movement disorders. Among 2,900 tect abnormal movements in stroke patients in lesion patients with acute stroke in the Lausanne Stroke localizations and to determine basic pathophysiol- Registry, only 29 cases of hyperkinetic movement ogy. Strokes accompanied by abnormal movements disorders were found (1% prevalence), only 3 of which are not limited to a specific vascular territory or le- were related to cerebellar stroke.4 Another stroke sion sites.1 Movement disorders occur frequently registry identified 56 acute or delayed (up to 1 year when strokes involve the basal ganglia or their con- after the stroke) movement disorders from 1,500 pa- nections. However, they can occur with cerebrovas- tients with stroke (3.7% prevalence), and 5 of these cular lesions at diverse locations in the motor cir- cases were related to stroke in the cerebellar circuit- cuits. The cerebellar circuitry, like the basal ganglia ry.5 Therefore, it is no surprise that the natural his- circuitry, is also important for controlling and mod- tory and pathophysiology of movement disorders ifying motor activity. Therefore, cerebrovascular le- in patients with stroke in the cerebellar circuitry are sions of the cerebellum or its pathways can cause di- not well understood. verse movement disorders. These lesions typically In this article, we summarize the current knowl- result in the deterioration of coordination (ataxia, edge about the clinical features and pathophysiologi- asynergia), misjudgment of distance (dysmetria), cal mechanisms of different types of movement dis- and intention tremors.2 In addition to these typical orders following cerebrovascular lesions in the cere- symptoms of cerebellar dysfunction, various abnor- bellar circuits. mal movements can occur in patients with cerebro- vascular lesions of the cerebellum or its pathways. FUNCTIONAL ANATOMY AND Common movement disorders in patients with PATHOPHYSIOLOGY stroke in the cerebellar circuitry are action tremor, Holmes’ tremor, palatal tremor, asterixis, and dysto- Cerebellar motor circuits nia, but other movement disorders, such as stereoty- The motor system, which controls the entire range py, can occur rarely (Table 1). of human activity, encompasses a broad range of ner- Abnormal movements, including both acute and vous system structures and pathways. Two parallel delayed phase complications, can appear in 1–4% pathways, the cerebellar and basal ganglia circuits, of stroke patients.3 However, the prevalence of move- control and modify motor activity. The basal ganglia ment disorders in patients with stroke in the cerebel- are mainly concerned with learned, automatic be- Table 1. Common movement disorders after stroke in the cerebellar circuits Frequent location of stroke Onset Common phenotype Involved circuit (except cerebellum) Cerebellar outflow Intention tremor, w/o postural Dentato-rubro-thalamic Acute Posterior thalamus tremor tremor or dentato-rubro-olivary Both nigrostriatal dopaminergic Delayed Rest and intention tremor, Holmes’ tremor and cerebello-thalamic/ Brainstem or thalamus (1‒24 months) w/o postural tremor cerebello-olivary Delayed Dentato-rubro-olivary Palatal tremor - Brainstem (1 week‒49 months) (Guillain-Mollaret tringle) Unilateral or occasionally Thalamus, basal ganglia, midbrain, Asterixis Acute Dentato-rubro-thalamic bilateral or frontoparietal cortex Delayed Basal ganglia, thalamus, Dystonia Focal or segmental Cerebello-thalamic (1 month‒15 years) or brainstem Stereotypy Delayed (1 month) - - Basal ganglia w/o: with or without. www.e-jmd.org 81 JMD J Mov Disord 2016;9(2):80-88 logic symptoms in patients with lesions in the ce- rebellar circuitry are intention tremor, dysmetria, dysdiadochokinesia, gait ataxia, ataxic dysarthria, and nystagmus. The anatomy of the cerebellar pathways is com- plicated, but there are simplified models.2 In the cur- rent model, there are two circuits that are clinically significant. One is the main cortico-cerebellar-cor- tical circuit, and the other is the modulatory denta- to-rubro-olivary circuit [the Guillain-Mollaret tri- BG Thalamus VLp VLa angle (GMT)] (Figure 1). The cortico-cerebellar-cortical circuit The main afferent fiber of the cerebellum is the SNc RN cortico-ponto-cerebellar tract, which starts from the frontal lobe, creates synapses on the pontine nuclei, and finally arrives at the cerebellar cortex via the Cerebellum middle cerebellar peduncle. The main efferent fiber of the cerebellum is the dentato-rubro-thalamo-cor- DN tical tract, which starts from the dentate nucleus, passes through the superior cerebellar peduncle and PN the contralateral red nucleus, creates synapses with Guillain- Mollaret the ventrolateral thalamus, and finally arrives at the triangle motor cortex. The dentato-rubro-olivary circuit ION (the Guillain-Mollaret triangle) This triangle is composed of a few fibers that con- nect the dentate nucleus with the contralateral red nucleus and inferior olivary nucleus (ION). Efferent fibers from the dentate nucleus pass through the su- Midline perior cerebellar peduncle and create synapses with the contralateral red nucleus. Efferent fibers from the Figure 1. Schematic diagram of the cerebellar circuits involved in movement dis- orders.There are two cerebellar circuits that are clinically significant in movement red nucleus traverse through the central tegmental disorders following cerebrovascular lesions. One is the cortico-cerebellar-corti- tract and create synapses with the ipsilateral ION. cal circuit and the other is the dentato-rubro-olivary circuit (the Guillain-Mollaret triangle). BG: basal ganglia, DN: dentate nucleus, ION: inferior olivary nucleus, Thereafter, efferent fibers from the ION pass through PN: pontine nuclei, RN: red nucleus, SNc: substantia nigra pars compacta, VLa: the inferior cerebellar peduncle and create synapses ventral lateral anterior nucleus of the thalamus, VLp: ventral lateral posterior nu- cleus of the thalamus. with the contralateral cerebellum to complete the triangular circuit. This triangle forms a feedback havior and with maintaining the background sup- loop between the cerebellum and brainstem, and it port or posture needed for voluntary motor activity, serves to control spinal cord motor activity.7 whereas the cerebellum conducts the coordination Both the basal ganglia circuit and the cerebellar and correction of errors in muscle contractions dur- circuit are subcortical loops that largely receive in- ing active movements.6 The cerebellum plays a par- formation from the cortex and provide information ticularly important role in muscle activation at the back to the cortex via the thalamus. Although both correct time. Therefore, pathologic lesions in the loops utilize the thalamus, their relay nuclei are sepa- cerebellum or its pathways can cause a loss of coor- rate, and the loops remain separate.2 The ventral lat- dination and errors in the timing of muscle activa- eral posterior nucleus of the thalamus is a relay nu- tions on the same side of the body. Typical neuro- cleus for the cerebellum, whereas the ventral lateral 82 Movement Disorders Following Cerebellar Stroke Choi SM anterior nucleus of the thalamus is a relay