Cerebellar Motor Syndrome Research Articles

Immune Ataxias: The Continuum of Latent Ataxia, Primary Ataxia and Clinical Ataxia.

The clinical category of immune-mediated cerebellar ataxias (IMCAs) is now recognized after 3 decades of clinical and experimental research. The cerebellum gathers about 60% of neurons in the brain, is enriched in numerous plasticity mechanisms, and presents a large variety of antigens at the neuroglial level: ion channels and related proteins, synaptic adhesion/organizing proteins, transmitter receptors, and glial cells. Cerebellar circuitry is especially vulnerable to immune attacks. After the loss of immune tolerance, IMCAs present in an acute or subacute manner with various combinations of a vestibulocerebellar syndrome (VCS), a cerebellar motor syndrome (CMS), and a cerebellar cognitive affective syndrome/Schmahmann's syndrome (CCAS/SS). IMCAs include gluten ataxia (GA), post-infectious cerebellitis (PIC), Miller Fisher syndrome (MFS), paraneoplastic cerebellar degeneration (PCD), opsoclonus myoclonus syndrome (OMS), anti-glutamic acid decarboxylase (anti-GAD) ataxia, and glial fibrillary acidic protein (GFAP) astrocytopathy (GFAP-A). In addition, multiple sclerosis (MS), acute disseminated encephalomyelitis (ADEM), Behçet disease, and collagen-vascular disorders may also present with cerebellar symptoms when lesions involve cerebellar afferences/efferences. Patients whose clinical profiles do not fit with IMCAs are now gathered in the group of primary autoimmune cerebellar ataxias (PACAs). Latent auto-immune cerebellar ataxia (LACA) refers to a clinical stage with a slow progressive course and a lack of obvious auto-immune background. At a pre-symptomatic stage, patients remain asymptomatic, whereas at the prodromal stage aspecific symptoms occur, announcing the symptomatic neuronal loss. LACA corresponds to a time-window where an intervention could lead to preservation of plasticity mechanisms. Patients may evolve from LACA to PACA and typical IMCAs, highlighting a continuum. Immune ataxias represent a model to elucidate the sequence of events leading to destruction of cerebellar neuronal reserve and develop novel strategies aiming to restore plasticity mechanisms.

Postoperative pediatric cerebellar mutism syndrome: A literature review

Introduction: Postoperative pediatric cerebellar mutism syndrome (POPCMS) is a significant complication observed after posterior fossa surgery for tumors, particularly in pediatric neurosurgery. This paper presents a literature review on the physiopathology, diagnosis, treatment, and long-term outcomes of POPCMS.
 Methods: A systematic review following PRISMA guidelines, searching for articles published in PubMed, Web of Science, and Lilacs in the last ten years. Inclusion criteria involved studies on human subjects under 18 years of age, focusing on the pathophysiology, diagnosis, treatment, and outcome of POPCMS.
 Results: The review identified 34 studies on POPCMS for final inclusion. Preoperative risk factors commonly associated with cerebellar mutism included midline tumor location, diagnosis of medulloblastoma, younger age at diagnosis, preoperative language impairment, brainstem infiltration, and tumor histology. The SHH subgroup was found to reduce the risk of CMS. Diagnostic criteria for POPCMS included language impairment, emotional lability, hypotonia, oropharyngeal dysfunction, dysphagia, cerebellar motor syndrome, cerebellar cognitive affective syndrome, and brainstem dysfunction. Treatment approaches varied, with medications showing potential benefits. Rehabilitation options for speech and language deficits were limited. Cognitive remediation programs showed promise in improving academic achievement and attention. A significant proportion of patients experienced clinical improvement. 
 Conclusion: POPCMS remains a challenging complication following posterior fossa surgery. Further research is needed to develop standardized diagnostic criteria, effective treatments, and rehabilitation strategies to improve long-term outcomes for patients with POPCMS.

Chapter 8 - Cerebellum: From the identification of the cerebellar motor syndrome to the internal models

Cerebellar circuitry is topographically arranged in closed loops with the cerebral cortex. The three cornerstones of clinical ataxia have emerged from studies on connectional anatomy and from clinical/neuropsychological observations, leading to the definition of clinical syndromes encountered in daily practice: (a) the cerebellar motor syndrome (CMS), (b) the vestibulocerebellar syndrome (VCS), and (c) the cerebellar cognitive affective syndrome/Schmahmann syndrome (CCAS/SS). These syndromes are either isolated or coexist, depending on the underlying pathological process and its degree of extension within the cerebellum. Dysmetria is the core feature of cerebellar deficits, encompassing motor dysmetria (hypermetria, hypometria) in CMS, oculomotor dysmetria in VCS, and dysmetria of thought in CCAS/SS. The leading hypothesis is that dysmetria results from errors in building or maintaining internal models, which are inherent to predictive behavior. Errors in prediction would lead to clumsiness and incoordination of limbs, oculomotor impairments, and aberrant cognitive/affective behavior. The cerebellum is currently viewed as a learning machine enriched with multiple plasticity mechanisms, allowing the permanent adaptation to the external world by generating and maintaining predictive operations, from motor to cognitive, affective, emotional, and social operations essential for daily human life.

Ataxia Rating Scales Reflect Patient Experience: an Examination of the Relationship Between Clinician Assessments of Cerebellar Ataxia and Patient-Reported Outcomes

Ataxia rating scales are observer administered clinical outcome assessments (COAs) of the cerebellar motor syndrome. It is not known whether these COAs mirror patient experience of their disease. Here we test the hypothesis that ataxia COAs are related to and reflect patient reported symptoms and impact of illness. A concept library of symptoms and activities impacted by ataxia was created by reviewing (a) concept elicitation data from surveys completed by 147 ataxia patients and 80 family members and (b) cognitive debrief data from focus groups of 17 ataxia patients used to develop the Patient Reported Outcome Measure of Ataxia. These findings were mapped across the items on 4 clinical measures of ataxia (SARA, BARS, ICARS and FARS). Symptoms reported most commonly related to balance, gait or walking, speech, tremor and involuntary movements, and vision impairment. Symptoms reported less frequently related to hand coordination, loss of muscle control, dizziness and vertigo, muscle discomfort or pain, swallowing, and incontinence. There was a mosaic mapping of items in the observer-derived ataxia COAs with the subjective reports by ataxia patients/families of the relevance of these items to their daily lives. Most COA item mapped onto multiple real-life manifestations; and most of the real-life impact of disease mapped onto multiple COA items. The 4 common ataxia COAs reflect patient reported symptoms and impact of illness. These results validate the relevance of the COAs to patients’ lives and underscore the inadvisability of singling out any one COA item to represent the totality of the patient experience.

Cerebellar ataxias: an update.

Providing an update on the pathophysiology, cause, diagnosis and treatment of cerebellar ataxias. This is a group of sporadic or inherited disorders with heterogeneous clinical presentation and notorious impact on activities of daily life in many cases. Patients may exhibit a pure cerebellar phenotype or various combinations of cerebellar deficits and extracerebellar deficits affecting the central/peripheral nervous system. Relevant animal models have paved the way for rationale therapies of numerous disorders affecting the cerebellum. Clinically, the cerebellar syndrome is now divided into a cerebellar motor syndrome, vestibulocerebellar syndrome and cerebellar cognitive affective syndrome with a novel clinical scale. This subdivision on three cornerstones is supported by anatomical findings and neuroimaging. It is now established that the basal ganglia and cerebellum, two major subcortical nodes, are linked by disynaptic pathways ensuring bidirectional communication. Inherited ataxias include autosomal recessive cerebellar ataxias (ARCAs), autosomal dominant spinocerebellar ataxias and episodic ataxias and X-linked ataxias. In addition to the Movement Disorders Society genetic classification of ARCAs, the classification of ARCAs by the Society for Research on the Cerebellum and Ataxias represents major progress for this complex subgroup of cerebellar ataxias. The advent of next-generation sequencing has broadened the spectrum of cerebellar ataxias. Cerebellar ataxias require a multidisciplinary approach for diagnosis and management. The demonstration of anatomical relationships between the cerebellum and basal ganglia impacts on the understanding of the cerebello-basal ganglia-thalamo-cortical system. Novel therapies targeting deleterious pathways, such as therapies acting on RNA, are under development.

Pediatric post-operative cerebellar mutism syndrome, cerebellar cognitive affective syndrome, and posterior fossa syndrome: historical review and proposed resolution to guide future study.

Cerebellar mutism (CM), pseudobulbar palsy, posterior fossa syndrome (PFS), and cerebellar cognitive affective syndrome (CCAS) are terms that have been used, sometimes interchangeably, to refer to the complex neurological constellation that occurs following surgical removal of cerebellar and fourth ventricular tumors, mostly in children, but also sometimes in adults. This paper reviews the origins of what is now regarded as pediatric post-operative cerebellar mutism, the cerebellar cognitive affective syndrome, and the neurological manifestations of injury to or disruption of brainstem and cerebellar structures. It examines the specific components of each of these phenomena in the context of the evolving understanding of the role of the cerebellum in nervous system function. Children undergoing surgical management of tumors in the posterior cranial fossa are at risk of experiencing cranial neuropathies, corticospinal damage, cerebellar ataxia and related motor disorders, neuropsychiatric and cognitive changes, and in some patients, mutism. These clinical presentations are differentiated from each other and examined in the context of the relevant anatomical structures and distributed neural circuits. The term posterior fossa syndrome is not sufficiently helpful in distinguishing the different elements of the clinical phenomena from each other, and because of this lack of precision and specificity, there is consensus among investigators in the international Posterior Fossa Society that the designation be retired. Using contemporary brain imaging methods and guided by careful clinical observation and meticulous definition of clinical phenomenology, it is now feasible to perform detailed structure function correlation analyses to achieve two critical goals in the care of children with tumors in the posterior cranial fossa. The first goal is to identify and understand the neural circuits responsible for the different manifestations-arousal, cranial neuropathies, long tract signs, cerebellar motor syndrome, cerebellar vestibular syndrome, cerebellar cognitive affective syndrome including emotional dyscontrol, and mutism. The second goal is to transform this knowledge into practical clinical intervention, preventing the complications inherent in the necessary surgery whenever possible, and develop new approaches to treatment with methods including brain modulation targeting interconnected nodes of the damaged neural circuits.

A.04 The classification of autosomal recessive cerebellar ataxias: a consensus statement from the society for research on the cerebellum and ataxias task force

Background: There is currently no accepted classification of recessive cerebellar ataxias, a group of disorders characterized by important genetic heterogeneity and complex phenotypes. The objective of this task force was to build a consensus and develop a clinical and pathophysiological classification for recessive ataxias. Methods: The work of this task force was based on a scoping systematic review of the literature that identified recessive disorders characterized primarily by a cerebellar motor syndrome and cerebellar degeneration. The task force regrouped 12 international ataxia experts who decided on general orientation and specific issues. Results: We identified 59 disorders that are classified as primary recessive ataxias. For each of these disorders, we present geographical and ethnical specificities along with distinctive clinical and imagery features. The primary recessive ataxias were organized in a clinical and a pathophysiological classification, and we present a general clinical approach to the patient presenting with ataxia. We also identified a list of 48 complex multisystem disorders in which ataxia is a secondary feature. Conclusions: This classification is based on a scoping systematic review of the literature and results from a sconsensus among a panel of international experts. It promotes a unified understanding of recessive cerebellar disorders for clinicians and researchers.

The Theory and Neuroscience of Cerebellar Cognition.

Cerebellar neuroscience has undergone a paradigm shift. The theories of the universal cerebellar transform and dysmetria of thought and the principles of organization of cerebral cortical connections, together with neuroanatomical, brain imaging, and clinical observations, have recontextualized the cerebellum as a critical node in the distributed neural circuits subserving behavior. The framework for cerebellar cognition stems from the identification of three cognitive representations in the posterior lobe, which are interconnected with cerebral association areas and distinct from the primary and secondary cerebellar sensorimotor representations linked with the spinal cord and cerebral motor areas. Lesions of the anterior lobe primary sensorimotor representations produce dysmetria of movement, the cerebellar motor syndrome. Lesions of the posterior lobe cognitive-emotional cerebellum produce dysmetria of thought and emotion, the cerebellar cognitive affective/Schmahmann syndrome. The notion that the cerebellum modulates thought and emotion in the same way that it modulates motor control advances the understanding of the mechanisms of cognition and opens new therapeutic opportunities in behavioral neurology and neuropsychiatry.

Chapter 4 - Functional topography of the human cerebellum

Accumulating evidence points to a critical role for the human cerebellum in both motor and nonmotor behaviors. A core tenet of this new understanding of cerebellar function is the existence of functional subregions within the cerebellum that differentially support motor, cognitive, and affective behaviors. This cerebellar functional topography - based on converging evidence from neuroanatomic, neuroimaging, and clinical studies - is evident in both adult and pediatric populations. The sensorimotor homunculi in the anterior lobe and lobule VIII established in early tract tracing and electrophysiologic studies are evident in both task-based and resting-state human functional imaging studies. In patients, damage to the anterior cerebellum, extending into medial lobule VI, is associated with the cerebellar motor syndrome. The cerebellar posterior lobe, including vermal and hemispheric regions of lobules VI and VII, is reciprocally interconnected with cerebral association and paralimbic cortices. Resting-state and task-based neuroimaging studies show functional activation patterns in these regions during higher-level cognitive tasks, and lesions of the posterior cerebellum lead to the cerebellar cognitive affective/Schmahmann syndrome with its characteristic intellectual and emotional impairments. The existence of cerebellar connectional and functional topography provides the critical anatomic substrate for a cerebellar role in both motor and nonmotor functions. It also establishes a framework for interpreting cerebellar activation patterns, cognitive and behavioral outcomes following cerebellar damage, and the cerebellar structural and functional differences reported in a range of neurodevelopmental and neuropsychiatric disorders.

Chapter 27 - The cerebellum from the fetus to the elderly: history, advances, and future challenges

The cerebellum is now at the forefront of research in neuroscience. This is not just a coincidence, occurring about 250 years after the first description of the human cerebellum. The cerebellum contains the majority of neurons in the central nervous system and it is heavily connected with almost all cortical and subcortical areas of the supratentorial region as well as with the brainstem and the spinal cord. Cerebellar circuits are embedded in large-scale networks contributing to motor control and neurocognition. From a phenotypic standpoint, damage to cerebellar lobules interconnected with the sensorimotor cortices leads to a cerebellar motor syndrome, whereas lesions of the posterolateral cerebellum cause cognitive and neuropsychiatric impairments which may or may not be subtle. This topographic rule is valid in children and adults. Midline posterior vermal lesions cause behavioral/affective dysregulation, especially in kids. The extent of the spectrum of human cerebellar disorders is increasingly recognized from the fetus to the elderly, with recognition of consequences for the quality of life and socioeconomic costs due to lifelong morbidity of many cerebellar ataxias/pathologies. The prolonged duration of human cerebellar development makes the cerebellum especially susceptible to developmental disruption, both genetic and nongenetic. This explains the current emphasis on the clarification of the developmental course and impact of the cerebellum. The understanding of how germinal matrix zones and migration of neurons and glial cells end in a highly organized and foliated human cerebellum is essential. This is greatly accelerated by inputs from rodent developmental studies, in particular because cerebellar anatomy is conserved across species. Still, numerous questions on human fetal development remain unanswered. Although both advanced neuroimaging and genetic studies are currently leading to a better definition and understanding of the multitude of cerebellar symptoms, there is a gap, with a great need to develop therapies aiming at first, protection of the cerebellum during development, and second, restoration of cerebellar function in children and in adults. Dynamic profiles of the compensatory processes from newborns to elderly require specific studies.

Cerebellum in Alzheimer's disease and frontotemporal dementia: not a silent bystander.

This scientific commentary refers to ‘Network-selective vulnerability of the human cerebellum to Alzheimer’s disease and frontotemporal dementia’ by Guo et al. (doi: 10.1093/brain/aww003) The network theory of neurodegeneration builds upon the Hebbian notion that neurons that fire together wire together. In this vein, they also die together. Interconnected neural networks in the non-human primate were identified initially with physiological and lesion-degeneration techniques, and refined through anatomical tract tracing studies. Interconnected networks are now identified in the human brain through resting state functional connectivity MRI, and intrinsic connectivity networks have been defined that bind distributed neural hubs according to putative functional relevance (Fox et al. , 2005). At the mechanistic level, it has been proposed that neurodegeneration occurs within these interconnected networks as a result of self-propagating/prion-like spread of neurotoxic agents along neural pathways linking distributed nodes into functional modules (Prusiner, 2013). In this issue of Brain , Guo and co-workers provide evidence that network-based degeneration in Alzheimer's disease and frontotemporal dementia also extends to the cerebellum (Guo et al. , 2016). The cerebellum is a critical node in the distributed neural circuits subserving not only motor function but also autonomic, limbic and cognitive behaviours. Dysmetria of movement that characterizes the cerebellar motor syndrome results from lesions of the motor cerebellum, mostly in lobules III–V in the anterior lobe and the secondary sensorimotor region in lobule VIII. Dysmetria of thought in the realms of intellect and emotion (Schmahmann, 1991, 1996) manifests as the cerebellar cognitive affective syndrome (Schmahmann and Sherman, 1998), which occurs following lesions of the cognitive and limbic cerebellum in the posterior lobe, represented in lobules VI, VIIA (including lobules VIIAf and VIIAt at the vermis, and crus I and crus II in the hemispheres) and VIIB, and possibly in lobule IX as well. The vestibular …

Location of lesion determines motor vs. cognitive consequences in patients with cerebellar stroke.

Cerebellar lesions can cause motor deficits and/or the cerebellar cognitive affective syndrome (CCAS; Schmahmann's syndrome). We used voxel-based lesion-symptom mapping to test the hypothesis that the cerebellar motor syndrome results from anterior lobe damage whereas lesions in the posterolateral cerebellum produce the CCAS. Eighteen patients with isolated cerebellar stroke (13 males, 5 females; 20–66 years old) were evaluated using measures of ataxia and neurocognitive ability. Patients showed a wide range of motor and cognitive performance, from normal to severely impaired; individual deficits varied according to lesion location within the cerebellum. Patients with damage to cerebellar lobules III–VI had worse ataxia scores: as predicted, the cerebellar motor syndrome resulted from lesions involving the anterior cerebellum. Poorer performance on fine motor tasks was associated primarily with strokes affecting the anterior lobe extending into lobule VI, with right-handed finger tapping and peg-placement associated with damage to the right cerebellum, and left-handed finger tapping associated with left cerebellar damage. Patients with the CCAS in the absence of cerebellar motor syndrome had damage to posterior lobe regions, with lesions leading to significantly poorer scores on language (e.g. right Crus I and II extending through IX), spatial (bilateral Crus I, Crus II, and right lobule VIII), and executive function measures (lobules VII–VIII). These data reveal clinically significant functional regions underpinning movement and cognition in the cerebellum, with a broad anterior-posterior distinction. Motor and cognitive outcomes following cerebellar damage appear to reflect the disruption of different cerebro-cerebellar motor and cognitive loops.

Schmahmann's syndrome - identification of the third cornerstone of clinical ataxiology.

Schmahmann’s syndrome represents a novel clinical condition consisting of a constellation of cognitive and affective deficits following cerebellar disease. The complex was first described in 1998 as cerebellar cognitive affective syndrome (CCAS) on the basis of a careful neurological examination, detailed bedside mental state tests, neuropsychological investigations and anatomical neuroimaging of a group of 20 patients with focal cerebellar disorders. The syndrome was characterized by four clusters of symptoms including: (a) impairment of executive functions such as planning, set-shifting, verbal fluency, abstract reasoning and working memory, (b) impaired visuo-spatial cognition, (c) personality changes with blunting of affect or abnormal behaviour, and (d) language deficits including agrammatism, wordfinding disturbances, disruption of language dynamics and dysprosodia. This complex of neurocognitive and behavioural-affective symptoms was ascribed to a functional disruption of the reciprocal pathways that connect the cerebellum with the limbic circuitry and the prefrontal, temporal and parietal association cortices. With the introduction of Schmahmann’s syndrome, clinical ataxiology has found its third cornerstone, the two others being the cerebellar motor syndrome (CMS) mainly delineated by the pioneer French and English neurologists of the 19th and early 20th century, and the vestibulo-cerebellar syndrome (VCS) consisting of ocular instability, deficits of oculomotor movements and ocular misalignment.

Мозочковий руховий синдром при гострих ізольованих інфарктах мозочка: клінічні прояви, діагностика та лікування

Мета роботи — підвищення ефективності діагностики ступеня тяжкості мозочкового рухового синдрому у пацієнтів із гострим ізольованим інфарктом мозочка шляхом використання Міжнародної кооперативної шкали атаксії та визначення особливостей відновлення рухових функцій на тлі комплексної терапії. У дослідження були залучені 20 пацієнтів з доброякісним інфарктом мозочка. Аналіз результатів показав, що клінічні прояви і тяжкість мозочкового рухового дефіциту після інфаркту мозочка залежали від локалізації уражених анатомічних утворень і артеріальних територій васкуляризації. Об’єм рухового дефіциту за Міжнародною шкалою атаксії при інфарктах на території верхньої артерії мозочка (38,30 ± 3,16 бала) і задньої нижньої артерії мозочка (73,80 ± 3,97 бала) відповідав атаксії середньої тяжкості; інфаркти на території васкуляризації передньої нижньої артерії мозочка проявлялись легким атаксичним дефіцитом (18,00 ± 3,41 бала). Комплексна терапія з використанням традиційних засобів і препаратів протекторної та нейрометаболічної дії Цераксону (цитиколіну) та Актовегіну істотно підвищувала ефективність відновлення рухових функцій протягом перших 2 тижнів після розвитку інфаркту. Найстійкішими до лікувальних заходів були такі прояви атаксичного синдрому, як запаморочення, дизартрія і хиткість при ході.

Evidence for topographic organization in the cerebellum of motor control versus cognitive and affective processing

Patients with cerebellar damage often present with the cerebellar motor syndrome of dysmetria, dysarthria and ataxia, yet cerebellar lesions can also result in the cerebellar cognitive affective syndrome (CCAS), including executive, visual spatial, and linguistic impairments, and affective dysregulation. We have hypothesized that there is topographic organization in the human cerebellum such that the anterior lobe and lobule VIII contain the representation of the sensorimotor cerebellum; lobules VI and VII of the posterior lobe comprise the cognitive cerebellum; and the posterior vermis is the anatomical substrate of the limbic cerebellum. Here we analyze anatomical, functional neuroimaging, and clinical data to test this hypothesis. We find converging lines of evidence supporting regional organization of motor, cognitive, and limbic behaviors in the cerebellum. The cerebellar motor syndrome results when lesions involve the anterior lobe and parts of lobule VI, interrupting cerebellar communication with cerebral and spinal motor systems. Cognitive impairments occur when posterior lobe lesions affect lobules VI and VII (including Crus I, Crus II, and lobule VIIB), disrupting cerebellar modulation of cognitive loops with cerebral association cortices. Neuropsychiatric disorders manifest when vermis lesions deprive cerebro-cerebellar-limbic loops of cerebellar input. We consider this functional topography to be a consequence of the differential arrangement of connections of the cerebellum with the spinal cord, brainstem, and cerebral hemispheres, reflecting cerebellar incorporation into the distributed neural circuits subserving movement, cognition, and emotion. These observations provide testable hypotheses for future investigations.

Cerebellar stroke without motor deficit: clinical evidence for motor and non-motor domains within the human cerebellum

Objective. To determine whether there are non-motor regions of cerebellum in which sizeable infarcts have little or no impact on motor control. Experimental procedures. We evaluated motor deficits in patients following cerebellar stroke using a modified version of the International Cooperative Ataxia Rating Scale (MICARS). Lesion location was determined using magnetic resonance imaging (MRI) and computerized axial tomography (CT). Patients were grouped by stroke location—Group I, stroke within the anterior lobe (lobules I–V); Group 2, anterior lobe and lobule VI; Group 3, posterior lobe (lobules VI–IX; including flocculonodular lobe, lobule X); Group 4, posterior lobe but excluding lobule VI (i.e. lobules VII–X); Group 5, stroke within anterior lobe plus posterior lobe. Results. Thirty-nine patients were examined 8.0±6.0 days following stroke. There were no Group 1 patients. As mean MICARS scores for Groups 2 through 5 differed significantly (one-way analysis of variance, F(3,35)=10.9, P=0.000 03), post hoc Tukey's least significant difference tests were used to compare individual groups. Group 2 MICARS scores (n=6; mean±SD, 20.2±6.9) differed from Group 3 (n=6; 7.2±3.8; P=0.01) and Group 4 (n=13; 2.5±2.0; P=0.000 02); Group 5 (n=14; 18.6±12.8) also differed from Group 3 (P=0.009) and Group 4 (P=0.000 02). There were no differences between Groups 2 and 5 (P=0.71), or between Group 3 and Group 4 (P=0.273). However, Group 3 differed from Group 4 when analyzed with a two-sample t-test unadjusted for multiple comparisons (P=0.03). Thus, the cerebellar motor syndrome resulted from stroke in the anterior lobe, but not from stroke in lobules VII−X (Groups 2 plus 5, n=20, MICARS 19.1±11.2, vs. Group 4; P=0.000 002). Strokes involving lobule VI produced minimal motor impairment. Conclusion. These findings demonstrate that cerebellar stroke does not always result in motor impairment, and they provide clinical evidence for topographic organization of motor versus nonmotor functions in the human cerebellum.