Topography of Cerebellar Deficits in Humans

Grimaldi, Giuliana; Manto, Mario

doi:10.1007/s12311-011-0247-4

Cited by 147 publications

(106 citation statements)

References 94 publications

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“…18 Axons of Purkinje cells are the sole efferent output from the cerebellum, and their pattern of connections in the cerebellar nuclei roughly maintains the temporal and spatial features conserved within the cerebellum itself. 15 The dorsal portion of the lateral cerebellar nucleus sends projections to the primary motor and premotor areas of the cerebral cortex, which have a key role in modulating voluntary movement of the extremities. 11,19 Lesions in the lateral dentate nucleus in human patients (roughly corresponding to the nucleus lateralis in animals) are characterized by decomposition of multijoint movement manifested by errors in the direction and rate of slow movements.…”

Section: Discussionmentioning

confidence: 99%

The Equine Movement Disorder “Shivers” Is Associated With Selective Cerebellar Purkinje Cell Axonal Degeneration

et al. 2015

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''Shivers'' is a progressive equine movement disorder of unknown etiology. Clinically, horses with shivers show difficulty walking backward, assume hyperflexed limb postures, and have hind limb tremors during backward movement that resembles shivering. At least initially, forward movements are normal. Given that neither the neurophysiologic nor the pathologic mechanisms of the disease is known, nor has a neuroanatomic locus been identified, we undertook a detailed neuroanatomic and neuropathologic analysis of the complete sensorimotor system in horses with shivers and clinically normal control horses. No abnormalities were identified in the examined hind limb and forelimb skeletal muscles nor the associated peripheral nerves. Eosinophilic segmented axonal spheroids were a common lesion. Calretinin-positive axonal spheroids were present in many regions of the central nervous system, particularly the nucleus cuneatus lateralis; however, their numbers did not differ significantly from those of control horses. When compared to controls, calretinin-negative, calbindin-positive, and glutamic acid decarboxylase-positive spheroids were increased 80-fold in Purkinje cell axons within the deep cerebellar nuclei of horses with shivers. Unusual lamellar or membranous structures resembling marked myelin decompaction were present between myelin sheaths of presumed Purkinje cell axons in the deep cerebellar nuclei of shivers but not control horses. The immunohistochemical and ultrastructural characteristics of the lesions combined with their functional neuroanatomic distribution indicate, for the first time, that shivers is characterized by end-terminal neuroaxonal degeneration in the deep cerebellar nuclei, which results in context-specific hypermetria and myoclonus.

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Section: Discussionmentioning

confidence: 99%

The Equine Movement Disorder “Shivers” Is Associated With Selective Cerebellar Purkinje Cell Axonal Degeneration

et al. 2015

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“…Recent studies have linked the cerebellum with both cognitive and emotional processes as well. Moreover, there is now evidence for a topographic organization of cerebellar functions [9]. A dichotomy between motor and nonmotor functions has been found in the cerebellum based on anatomical, functional and neuropsychological studies [10].…”

Section: Anatomymentioning

confidence: 99%

Very Small Cerebellar Infarcts: Integration of Recent Insights into a Functional Topographic Classification

et al. 2013

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Background: Very small cerebellar infarcts (diameter <2 cm) are a frequent finding on MRI. With an increasing scientific interest in cerebral microinfarcts, very small infarcts in the cerebellum deserve more of our attention as well. The goal of the present article was to review infarct terminology and mechanisms, as well as to critically appraise the current classification system for very small cerebellar infarcts. Methods: A search strategy was designed to identify all relevant studies on very small cerebellar infarcts in the English language. This search was restricted to papers published up to February 21, 2013. Studies were initially identified from the MEDLINE/PubMed database using the search terms ‘small cerebellar infarct', ‘lacunar infarct', ‘microinfarct', ‘end zone infarct', ‘border zone infarct', ‘watershed infarct', ‘territorial infarct', and ‘nonterritorial infarct'. Furthermore, a similar search strategy was directed to identify all relevant articles on (descriptive and functional) neuroanatomy and neuroimaging of the cerebellum. Results: Very small cerebellar infarcts have been referred to as lacunar infarcts, as junctional, border zone or watershed infarcts, as nonterritorial infarcts, as very small territorial or end zone infarcts, or simply as (very) small cerebellar infarcts. Since the original clinicoradiological study on these small infarcts, the classification into border zones remains in common use. This classification is based upon the assumption that these infarcts occur secondary to low flow in between arterial perfusion territories, where flow is believed to be the lowest. Later studies, however, have suggested occlusion of small (end-) arteries as a prerequisite for the pathogenesis of even small cerebellar infarcts, with low flow merely as a potential contributor. Therefore, it is likely that infarcts may as well occur in a nonborder zone distribution. Moreover, the classification into border zones may be considered unreliable since the location of border zones is highly variable among individuals and is not known in a particular patient. Recently, a functional topographic organization has been found in the cerebellum with evidence for a motor-nonmotor dichotomy between the anterior and posterior lobe. Since the cerebellar lobes can be easily and reliably distinguished with both CT and MRI, we recommend the classification of very small cerebellar infarcts according to topographic location. Conclusion: There are several fundamental concerns with the current classification of very small cerebellar infarcts according to border zones, which we would like to overcome by recommending a new classification system based on topography. This will allow for a reliable and reproducible way of classifying very small cerebellar infarcts and is expected to improve clinicoradiological correlation.

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“…Deficits were most prominent in those patients with olivo-ponto-cerebellar atrophy and lesions of the posterior cerebellum. The posterior cerebellum is generally regarded as the critical area for cognitive functions (Grimaldi and Manto 2012). Although cognitive dysfunction is relatively broad, visuospatial abilities appear to be over-represented (M. Molinari et al 2004a;Marco Molinari and Leggio 2007).…”

Section: Cerebellum and Spatial Cognitionmentioning

confidence: 99%

A theory inspired proposal for a novel medical treatment in autism. The cerebellar model of autism and the hypothesis of dorsal stream dysfunction: evidence from idiopathic and syndromic cases.

Vakalopoulos¹

2017

Preprint

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The cerebellum figures prominently in the pathophysiology of idiopathic autism. Many syndromic comorbid cases and animal studies also highlight cerebellar involvement. The role of the cerebellum is implicated in cognitive and affective disorders. However, there remains a profound gap in understanding the route from genes, the effect of mutations on Purkinje cells and ultimately the behavioural phenotype. Given that conditions like autism are disorders of consciousness it is likely that progress will be made beyond the data generating enterprise, by improved theoretical models of the mind-body gap. A way forward is the proposal of consciousness as embodiment of a process of world discovery through motor efference copy. The cerebellum and basal ganglia are essential to a component theory of motor efference copy, providing a heuristic for understanding the structure of cortical dorsal and ventral stream pathways of a sensory modality. This then, further suggests that autism results from a selective dorsal stream dysfunction with all the attendant and hierarchical features that follow such a model and lead to both high level social and attentional deficits as well as lower level motor and restrictive interests. The paper aims to present evidence for dorsal stream dysfunction and how it may relate to a primary cerebellar pathology. The involvement of the cerebellum in most if not all syndromic cases of comorbid ASD is then presented. Finally, it is shown how such insights can be used to propose a general medical intervention based on the use of cerebellar rTMS across the disorder spectrum.

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Topography of Cerebellar Deficits in Humans

Cited by 147 publications

References 94 publications

The Equine Movement Disorder “Shivers” Is Associated With Selective Cerebellar Purkinje Cell Axonal Degeneration

The Equine Movement Disorder “Shivers” Is Associated With Selective Cerebellar Purkinje Cell Axonal Degeneration

Very Small Cerebellar Infarcts: Integration of Recent Insights into a Functional Topographic Classification

A theory inspired proposal for a novel medical treatment in autism. The cerebellar model of autism and the hypothesis of dorsal stream dysfunction: evidence from idiopathic and syndromic cases.

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